ALTERNATIVE THERAPIESI N H E A L T H A N D M E D I C I N E

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2 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Table of Contents

TABLE OF CONTENTSmar/apr 2008, VOL. 14, NO. 2

10 Does Dementia Exist? Dispelling the Myth Mark A. Hyman, MD

16 Does Complementary and Alternative Medicine Represent Only Placebo Therapies? Jeffrey Bland, PhD, FACN, FACB

20 Progress Notes Updated: The Consortium and Other Developments in Education in

Complementary and Integrative Medicine Victor S. Sierpina, MD

24 Effi cacy of Lifestyle Changes in Modifying Practical Markers of Wellness and Aging Steven Cameron Masley, MD, FAAFP, CNS; Wendy Weaver, BA; Gil Peri, MPH, MBA; Sharon E. Phillips, MSPH

32 Cost-Effectiveness of Naturopathic Care for Chronic Low Back Pain Patricia M. Herman, ND, PhD (candidate); Orest Szczurko, ND, MSc (candidate); Kieran Cooley, ND, MSc (candidate); Edward J. Mills, MSc, PhD

40 Discerning the Mauve Factor, Part 1 Woody R. McGinnis, MD; Tapan Audhya, PhD; William J. Walsh, PhD; James A. Jackson, PhD; John McLaren-Howard, DSc, FACN; Allen Lewis, MD; Peter H. Lauda, MD; Douglas M. Bibus, PhD; Frances Jurnak, PhD; Roman Lietha, MD; Abram Hoffer, MD, PhD

52 Increasing Research Capacity at the New England School of Acupuncture Through

Faculty and Student Research Training Initiatives Peter M. Wayne, PhD; Julie E. Buring, ScD; Roger B. Davis, ScD; Sally M. Andrews, MBA; Meredith St John, LicAc; Lisa Conboy, ScD; Catherine E. Kerr, PhD; Ted J. Kaptchuk, OMD; Steven C. Schachter, MD

60 Randomized Controlled Trials as Evidence in Legal Disputes About the Benefi ts of

Complementary and Alternative Medicine Ian D. Coulter, PhD; John Walsh, LLM

w w w . a l t e r n a t i v e - t h e r a p i e s . c o m

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4 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Table of Contents

66 Jacob Liberman, OD, PhD: Change Your Vision, Change Your Life

78 Conference Calendar

78 Advertisers Index

80 Resources

• CAM in US Family Medicine Practices: A Pilot Qualitative Study

• Effect of a High Nutrient Density Diet on Long-Term Weight Loss: A Retrospective Chart Review

• Inhaled Glutathione for the Prevention of Air Pollution-related Health Effects: A Brief Review and Proposal

• Clinical Decision Support Tools: Focus on Dietary Supplement Databases

• Effects of Aqueous Green Tea Extract on Activities of DNA Turn-over Enzymes in Cancerous and

Noncancerous Human Gastric and Colon Tissues

• Discerning the Mauve Factor, Part 2

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aboutthe

cover

This painting was inspired by a Sumerian creation myth dating earlier than 5000 BCE and depicts the god Enki,

often associated with the stag, and Lady Ki, the earth. Together this divine pair created what historians refer to as

the Fertile Crescent, a place now known as Iraq, Iran, Syria, and Turkey. Below is a brief explanation of this paint-

ing, written as if spoken by master magician Enki, patron god of artisans, also known as Sweet Water.

“From the very beginning, when my beloved and I fi rst arrived at this place, we saw possibility. Creatrix and

creator, together we fashioned clay prototypes for all manner of living beings. I assisting, Ki birthed our plant

children and the world became a living tapestry. I then bathed her weary body with fresh fl owing waters and on a

whim, to see her smile, fi lled these with dancing fi sh. My Lady Ki: fertility itself, wherever she steps there springs

forth abundance! We two, the Great Stag and Mother of Earth, populated the earth with all that runs and fl ies.

Ki’s supple energy is replicated in all green and fecund things, and to this day everywhere I look, I see her face.”

Ki and Enki Rest After Their Labors. Watercolor and pencil, Helena Nelson-Reed.

Ki and Enki is available as a fi ne art print. For information on this and other works, please contact Helena at

hnelsonreed@gmail.com or visit her website, www.helenanelsonreed.com.

departments

Conversations

in future issues

Due to the efficacy and the science behind the products, and the experiences in my clinic, I have found Researched Nutritionals® very use-ful. A few of my personal favorites:

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I discovered this product at a medical conference, and was intrigued by the research. One of the published studies reported that patients experienced a 40% decrease in fatigue(1) in eight weeks. The product is formulated to deliver a stabilized unique phospholipid matrix (this is what composes the mitochondrial membranes), wrapped in pre and probiotics as well as Mitochondrial Pro Regulator™ to optimize mitochondrial function, Krebs Cycle Glucose Absorb™ to propel the burning of glucose, creating energy and removal of excess ammonia which can cause fatigue, and RN Fatty Acid Metabolizer™ to maximize ATP

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(1) Journal of the American Nutraceutical Association 2003; 6(1); 23-28. Available only through healthcare professionals. *These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.

production by regulating fatty acid buildup which, if left unchecked reduces mitochondrial function and increases cellular toxins. Normally, cells produce and repair their own mitochondrial membranes. However, these membranes may become compromised during long-term illness or interestingly, intense physical exercise by healthy individuals. This product helps the body help itself. By improving cell membrane potential, nutrients are better able to enter the cells for greater ATP fuel production, toxin removal is improved and oxidative stress is reduced.

CoQ10 Power™ 400mg I actually tested the blood level of a patient on this product versus another well-known CoQ10. The patient using CoQ10 Power™ had three times the CoQ10 in the blood than the other product. As I have come to expect from Re-searched Nutritionals, the raw material is of the highest quality and is imported from Japan.

Transfer Factor Multi-Immune™ People have asked me what differentiates transfer factor from colostrum. I generally reply that it is supercharged colostrum. In every gallon of colostrum, you derive only an ounce or two of pure transfer factor. This is where you find the heart of immune support.

Maintaining natural killer cell function is essential for achieving optimal health. Each capsule of Transfer Factor Multi-Immune™ combines the following complexes to provide optimal natural killer cell support:

NK Maximizer Bioplex™- Super blend of pure transfer factor, larch arabinogalactan, IP-6, shiitake and maitake mushrooms to promote healthy NK cell levels & immune modulation

Macrophage & T-Cell Pro-Blend™ - Proprietary blend of beta glucan, astragulus, and TMG for healthy macrophage and neutrophil support, aiding removal of cellular debris and recovery of damaged tissue. Unique blend also supports proper T-cell function, cellular replication and liver function.

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6 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Masthead

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Editorial Board

EDITOR in chiefMark A. Hyman, MD

Sidney Baker, MD

Co-Chairman of the DAN! Advisory Board

Elizabeth Ann Manhart Barrett, RN, PhD, FAAN Hunter College of CUNY

Harriet Beinfi eld, LAc

Chinese Medicine Works

William Benda, MD

University of California San Francisco

Samuel Benjamin, MD

Phoenix, Arizona

Jeff Bland, PhD

Institute for Functional Medicine

Mark Blumenthal American Botanical Council

Joan Borysenko, PhD

President, Mind Body Health Sciences

Ronald A. Chez, MD

Newport Beach, California

Ian Coulter, PhD RAND; UCLA; Samueli Institute;

Southern University of Health Sciences

Harley Goldberg, DO

Kaiser Permanente

James Gordon, MD The Center for Mind-Body Medicine

Russell Greenfi eld, MD Carolinas Integrative Health

David Hufford, PhD

Pennsylvania State University

Ellen Kamhi, PhD, RN

Stony Brook University

Ted Kaptchuk, OMD

Harvard Medical School

Stanley Krippner, PhD Saybrook Graduate School and Research Center

George Lewith, MD, FRCP

University of Southampton

Peter Libby, MD Brigham and Women’s Hospital

Harvard Medical School

Tieraona Low Dog, MD

University of Arizona

Victoria Maizes, MD University of Arizona

Bill Manahan, MD

American Holistic Medical Association

Woodson C. Merrell, MD

Continuum Center for Health and Healing, Beth Israel Medical Center

Pamela Miles, Reiki master

Institute for the Advancement of Complementary Therapies (I*ACT)

Dean Ornish, MD

Preventive Medicine Research Institute,University of California, San Francisco

Kenneth R. Pelletier, PhD, MD(hc)

University of ArizonaUCSF School of Medicine

Joseph E. Pizzorno, ND President Emeritus, Bastyr University and

President, SaluGenecists, Inc

Anthony L. Rosner, PhD, LLD (Hon)

Parker College of Chiropractic

Robert B. Saper, MD, MPH

Boston University Medical Center

Betsy B. Singh, PhD

Medicus Research, LLC

Leanna Standish, ND, PhD, LAc Bastyr University

Eugene Taylor, PhD

Saybrook Graduate SchoolHarvard University

Roeland van Wijk, PhD

International Institute of Biophysics, Germany

ASSOCIATE EDITORsJames E. Dalen, MD, MPH

Marc DavidMelvyn R. Werbach, MD

CONTRIBUTING EDITORsMichael Balick, PhD

Roberta Lee, MD

w w w . a l t e r n a t i v e - t h e r a p i e s . c o m

MISSION Alternative Therapies in Health and Medicine is an international scientifi c forum for the dissemination of peer-reviewed information to healthcare professionals regarding the use of complementary and alternative therapies in promoting health and healing.

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8 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Masthead

advisory Board

Lise Alschuler, ND, FABNO

Midwestern Regional Medical Center, Cancer Treatment Centers of America

Belinda J. Anderson, PhD, LAc

Pacifi c College of Oriental Medicine

Robert Anderson, MD Bastyr University

American Board of Holistic Medicine

Maira Bes-Rastrollo, PharmD, PhD

University of Navarra, Spain

Clement Bezold, PhD

Institute for Alternative Futures

Felicity L. Bishop, MA, MSc, PhD, CPsychol

University of Southampton School of Medicine, UK

Jeffrey B. Blumberg, PhD, FACN, CNS

Tufts University

Michelle Bowman, BSN, RNC, DiplAc Health Center of Integrated Therapies,A Service of Longmont United Hospital

William Braud, PhD Institute of Transpersonal Psychology

Sarah Brien, PhD

University of Southampton, UK

Jane Buckle, RN, PhD

Thames Valley University, London, UK

Margaret Burkhardt, RN, PhD

West Virginia University School of Nursing

Etzel Cardeña, PhD University of Lund, Sweden

Michael Carlston, MD University of California, San Francisco

Lisa Conboy, MA, MS, ScD

Osher Institute, Harvard Medical School

J. K. Crellin, MD, PhD Newfoundland, Canada

Jonathan Davidson, MD

Duke University

Robert M. Duggan, MA, MAc

Tai Sophia Institute

Charles Elder, MD, MPH, FACP

Kaiser Permanente NW

Henry Emmons, MD

Abbott Northwestern Hospital

Joan Engebretson, DrPH, AHN-BC, RN

University of Texas Health Science Center at Houston

Joel M. Evans, MD

Albert Einstein College of Medicine

Tiffany Field, PhD University of Miami

Peter Fisher, FRCP, FFHom Royal London Homeopathic Hospital

Paula Gardiner, MD, PhD

Boston University

Nicholas J. Gonzalez, MD

New York, New York

Gloria Andrea Gronowicz, PhD

University of Connecticut Health Center

Aviad Haramati, PhD

Georgetown University School of Medicine

Charles Nelson Ross Henderson Palmer Center for Chiropractic Research

Peter Hinderberger, MD, PhD PAM, Baltimore, Md

Mark L. Hoch, MD

Partners in Healing of Minneapolis

Linda L. Isaacs, MD

New York, New York

Randy A. Jones, PhD

University of Virginia School of Nursing

Lynn Keegan, RN, PhD, AHN-BC, FAAN

Holistic Nursing Consultants

Raheleh Khorsan, MA

Samueli Institute

Barry Krakow, MD

Sleep & Human Health Institute

James D. Lane, PhD

Duke University Medical Center

Lixing Lao, PhD, LAc University of Maryland

Dana J. Lawrence, DC, MMedEd

Palmer Center for Chiropractic Research

Larry LeShan, PhD

New York, New York

Karen Lesniak, PhD

Loma Linda University

DeAnn Liska, PhD

Ocean Spray Cranberries, Inc

Patrick B. Massey, MD, PhD

Alexian Brothers Hospital Network

Robert S. McCaleb Herb Research Foundation

Darshan H. Mehta, MD, MPH

Harvard Medical School, Osher Research Center

Melany A. Meier, DC

Southern California University of Health Sciences

Deanna Minich, PhD, CN

Metagenics

Lakshmi Chandra Mishra, PhD

National Institute of Ayurveda and Toxicology Reviews

Ralph W. Moss, PhD

The Cancer Chronicles

Barry S. Oken, MD

Oregon Health and Science University

Karen Olness, MD Case Western Reserve University

Lawrence B. Palevsky, MD

Northport Wellness Center

Michael M. Patterson, PhD, DO(HON)

Nova Southeastern University

Daryl S. Paulson, PhD

BioScience Laboratories, Inc.

Joanne L. Perron, MD, FACOG

Pebble Beach, California

Janice Post-White, RN, PhD, FAAN

University of Minnesota

Satya P. Rao, PhD, CHES

New Mexico State University

Keith Rayburn, MD

Castroville, California

Pamela G. Reed, RN, PhD, FAAN

University of Arizona

Susan W. Ryan, DO

Rose Medical Center

Alexander G. Schauss, PhD

AIBMR Life Sciences, Inc

Mark A. Schroll, PhD

Beatrice, Nebraska

Lai-Chu See, PhD

Chang Gung University, Taiwan

Anees A. Sheikh, PhD Marquette University

Marc A. Silver, MD Advocate Christ Medical Center

Jerry Solfvin, PhD University of Massachusetts

Dartmouth

Suzanne Steinbaum, MD

Lenox Hill Hospital

Jacob Teitelbaum, MD

Fibromyalgia and Fatigue Centers

Vidette Todaro-Franceschi, PhD, RN

Hunter College of CUNY

Carolyn Torkelson, MD

University of Minnesota

Nancy Vuckovic, PhD

Intel Corporation/Digital Health Group

Diane Wind Wardell, PhD, RNC

The University of Texas Health Science Center at Houston

Andrew Weil, MD University of Arizona

Kristine Westrom, MD

Northwestern Health Sciences University

James Whedon, DC

Dartmouth-Hitchcock Medical Center

Eugene R. Zampieron, ND, (MH)AHG

Woodbury, Connecticut

Leonard Zegans, MD University of California, San Francisco

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10 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Does Dementia Exist?

Mark A. Hyman, MD, is the editor in chief of Alternative

Therapies in Health and Medicine. (Altern Ther Health Med.

2008;14(2):10-12.)

The great enemy of truth is very often not the lie—deliberate, contrived

and dishonest—but the myth—persistent, persuasive, and unrealistic.

Too often we hold fast to the clichés of our forebears. We subject all

facts to a prefabricated set of interpretations. We enjoy the comfort of

opinion without the discomfort of thought.

—John F. Kennedy

Obesity is obvious. Just look around the American

landscape. But memory loss and cognitive decline is

invisible—and more fearsome. Alzheimer’s disease

will affect 30% (and some experts say 50%) of people

over 85 years old, which is the fastest growing seg-

ment of the population. The prevalence of Alzheimer’s is expected

to increase 3-fold by 2050 affecting 14 million people, at an annual

cost at $83.9 billion to our healthcare system and society,1 which

doesn’t even begin to account for the untold suffering on families

and caregivers. It is now the seventh leading cause of death.2

With Alzheimer’s we are facing a global problem. It is project-

ed to increase 285% in North America, 534% in South America,

476% in Africa, and 497% in Asia by 2050.3 Even small progress in

preventing the disease and slowing its progression will have a pro-

found impact on the personal and fi nancial costs we will bear.

If we want to do something other than provide palliative care,

we must ask certain questions. What is dementia? What causes it?

Is it uniformly the same disease or the heterogeneous manifestation

of multiple genetic and environmental insults? Can it be prevented?

Can it be slowed, stopped, or even cured? And why are we seeing

growths of epidemic proportions of the incidence of cognitive dys-

function, mild cognitive impairment (MCI), and dementia?

Conventionally dementia falls into 2 main categories—Alzheim-

er’s and vascular dementia, with many other minor variations.

Therapy is limited to 2 main categories of medication—acteylcholin-

esterase inhibitors and NMDA (N-methyl D-aspartate) receptor

antagonists, neither of which addresses the causes of dementia and

both of which are marginally effective (if at all) and have signifi cant

side effects. New treatments such as vaccines are on the horizon.

Emerging research indicates that inflammation, oxidative

stress, insulin resistance, and mitochondrial dysfunction are key

mediators of brain degeneration. But rarely is the question explored

as to why these processes occur. What are the proximal causes? Is

there another clinical model for preventing, treating, and even

reversing cognitive decline and dementia? Even more, mounting

research suggests that loss of cognitive function is not a homoge-

neous process and that Alzheimer’s or dementia is not a single dis-

order but a common clinical manifestation of disordered neuronal

function arising from a multitude of genetic, environmental, and

lifestyle factors unique to each individual. Even if large-scale system-

based clinical trials are yet to be done—or diffi cult to do—if we can

assemble existing data into safe lifestyle-based and nutritional inter-

ventions for optimizing brain function, then we might hold back

the tsunami of broken brains and broken lives we face.

HEALING THE MIND AND REVERSING DEMENTIA: IS IT

POSSIBLE?

New research suggests that focusing on the “disease” called

dementia and fi nding drugs to modify downstream effects of brain

injury such as insuffi ciency of acetylcholine misses the opportunity

to address the real problems. In fact, “dementia” does not exist but

is simply a common collection of symptoms that explain nothing

about the underlying etiology or pathophysiology. These include

infl ammation, oxidative stress, insulin resistance and other hor-

monal dysregulation, mitochondrial dysfunction, nutritional defi -

ciency, and toxic injury. The question is not how to treat dementia,

because it is not a single disorder, but how to fi nd the underlying

reasons for our broken brains and how to fi x them.

The cognitive dysfunction we call dementia is simply the way

the body expresses injury to a myriad of insults that can be quite

different from person to person. No 2 “dementias” are exactly

alike. But how do we apply molecular personalized genomic medi-

cine to such a complex disorder?

The answer is quite simple. Ample science lays out the pat-

terns of dysfunction in dementia and, to a great degree, most of the

precipitating causes. Then our individual genetic differences and

predispositions set us up for biological breakdown from the same

few common insults—toxins such as mercury, digestive imbalanc-

es, nutritional defi ciencies or excesses, stress, allergens, infections.

These in turn, lead to the altered physiological processes we see in

the “dementias”—infl ammation, oxidative stress, mitochondrial

dysfunction, and insulin resistance.

We have to think about individuals, not diseases. In medicine

our differences (genetic predispositions, environmental exposures,

diets, and stresses) are more important than our similarities.

Sometimes the practice of medicine lags behind the science, and

sometimes the practice gets ahead of the science. Genetic testing

DOES DEMENTIA EXIST? DISPELLING THE MYTHMark A. Hyman, MD

Editorial

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 11Does Dementia Exist?

puts us squarely in the middle of that dilemma.

We are at a crossroads where the old ideas we have about dis-

ease and diagnosis become less meaningful as we understand more

and more about the importance of individual differences in deter-

mining illness. This is a time when personalized medicine will

replace medicine based on diagnosis and disease. In fact, disease

and diagnosis as we know it (ICD-9 classifi cation of diseases) will

soon be an obsolete concept, an artifact of medical history like

bloodletting or phrenology (the art of diagnosis based on the shape

of your skull, popular in the 19th century).

AN “N” OF 1: REVERSING DEMENTIA

As a medical student, I participated in a public health research

project in a remote Nepalese village. In exchange for the villagers’ help,

we offered an improvised outdoor medical clinic. One man brought

his mother to our clinic after carrying her on his back for 10 days

through the Himalayas. I asked how we could help. He said his mother

was blind. She had cataracts. There was nothing we could do.

That is how I felt about my patients with dementia until I met

“George.” George presented with dementia. His story is an exam-

ple of how treating a person—not a disease—leads to improved

clinical outcomes; how environmental infl uences on genetic predis-

positions—mostly mercury exposure in this case—can lead to any

number of diseases depending on individual genetic variations.

George presented with a diagnosis of dementia after a com-

prehensive neurological evaluation including neuropsychological

testing, MRI (magnetic resonance imaging), MRA (magnetic reso-

nance angiography), and SPECT (single-photon emission comput-

erized tomography) scanning. When he came with his wife to see

me, he could no longer manage his business affairs, had become

increasingly unable to function at home, and had to withdraw from

family and social relationships.

HOW THE ENVIRONMENT AFFECTS YOUR GENES: A CASE

OF MERCURY POISONING

Chronic diseases, like Alzheimer’s, cardiovascular disease, or

cancer are usually multi-gene disorders. It is not 1 gene but the

interaction between many genes, their variations or single nucle-

otide polymorphisms (SNPs), and the environment that puts

someone at risk for a chronic disease such as dementia. That is why

we will never fi nd “the” gene for Alzheimer’s—or heart disease,

cancer, autism, or depression.

In the case of George, whose mind and life were evaporating, I

looked deeply into his genes and the biochemistry his genes con-

trolled and found places we could improve things. He was homozy-

gous for apo E4, a high-risk gene for Alzheimer’s disease4 that also

predisposes to dyslipidemia and impaired heavy metal detoxifi ca-

tion from the brain.5

A 6-hour DMPS provocation challenge test for heavy metals*

revealed mercury of 350 mg/g creatinine (normal < 3 mg/g creati-

nine). Sources of mercury include vaporization of dental fi llings or

environmental exposures from tuna fi sh or air pollution.6 George

lived his life in an industrial area with large coal burning plants and

had many dental amalgams.7 Mercury toxicity is a potent neuro-

toxin linked to many neurological disorders including dementia.8

In one study of 465 patients with chronic mercury toxicity,

32% had severe fatigue, 88% had memory loss, and almost 30% had

depression. These symptoms and mercury poisoning were much

more common in people with the apo E4 gene. Removal of amal-

gam fillings combined with a mercury detoxification program

resulted in signifi cant symptom reduction.9

Other genes act synergistically with apo E4 to amplify risk.

Common polymorphisms of genes regulating glutathione metabo-

lism, the main detoxifi er of metals in the body, such as glutathione-

S-transferase (GST),10 increase risk of cognitive impairment.

Combinations of GST and apo E4 polymorphisms further increase

risk for dementia.11 George carried the GSTM1 null or absent SNP.

Carriers of the null (or absent) polymorphisms for GST have higher

total body burdens of mercury.12 Genes load the gun, and the envi-

ronment pulls the trigger.

George had an elevated homocysteine and was homozygous

for methylene tetrahydrofolate reductase (MTHFR),13 which

impairs methylation and increases homocysteine, which can dou-

ble the risk of dementia.14 Disruptions of 2 key interdependent,

interconnected biochemical cycles are at the root of the physiologi-

cal dysfunction we see in most chronic diseases. These are the

methylation and trans-sulfuration (glutathione metabolism) cycles.

They are necessary for proper detoxifi cation and redox balance, as

well as modulation of immune response, control of gene expres-

sion, membrane function, and more. Polymorphisms in any of the

enzymes facilitating these cycles may increase the risk of chronic

disease, particularly neurologic and psychiatric disorders such as

dementia, autism, ADHD, and depression. Adequate concentra-

tions and active forms of nutrient cofactors involved in these cycles,

especially methylcobalamin (B12), 5-methyl-tetrahydrofolate

(5-MTHF), and pyridoxine (B6), as well as adequate dietary sources

of sulfur are essential for proper function of the methylation and

sulfation cycles.

Lastly, George had a polymorphism of cholesterol ester trans-

fer protein (CETP). This gene limits HDL reverse transport of cho-

lesterol and increases risk of hyperlipidemia. CETP polymorphisms

act synergistically with apo E4 to increase the risk of dementia.15

For George, those SNPs (apo E4, GSTM1, MTHFR, CETP)

acted synergistically to increase his risk and made him in one way

or another susceptible to environmental insults from mercury

overload, nutritional defi ciencies of folate or B12, and dietary infl u-

ences on cholesterol and insulin sensitivity. Other studies show

similar polymorphisms in autism16 and depression.17 In fact, these

may be simply different manifestations across the age spectrum of

the same “disease.” The genetics, biochemistry, and physiology of

these conditions overlap and arise from common roots. What is

critical to remember is that these genes are highly regulated and

their expression modifi ed by nutrient and lifestyle inputs.

*Blood levels of mercury only refl ect recent exposure from pollution or fi sh consump-tion, but a provocation test identifi es total body burden of mercury. Studies have found that using DMPS increases mercury excretion from 3- to 107-fold. The chelating agents or drugs, DMPS and DMSA, are both used to treat heavy metal toxicity.

12 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Does Dementia Exist?

PERSONALIZED MEDICINE: A CURRENT REALITY OR

FUTURE POSSIBILITY?

Based on George’s unique genotype and his phenotypic

expression (elevated body burden of mercury, hyperlipidemia,

insulin resistance, hyperhomocysteinemia, low glutathione, and

impaired detoxification), a therapeutic plan was developed to

address his entire systemic dysfunction. George also had a 30-year

history of irritable and infl ammatory bowel diseases, which has

been linked to dementia and other neuropathologies.18

The single gene, single disease, single drug model is inappro-

priate for complex multi-gene systemic disorders with common

manifestations but differing etiologies such as dementia. The com-

ponents of his therapeutic plan were design to remove toxic trig-

gers (mercury, poor diet, dysbiosis), while optimizing

nutrient-regulated gene expression. Doing just one thing wouldn’t

help George. Treatment required addressing all the imbalances,

the causative factors, and their effects systematically.

Treatment included careful mercury detoxifi cation including

safe amalgam removal and chelation.19 Phytonutrients and nutrients

that upregulate glutathione, including cruciferous vegetables such as

kale, watercress, and cilantro; herbs such as milk thistle; nutrients

such as selenium and zinc, were added to his diet. His hyperlipi-

demia and insulin resistance were managed with a low glycemic

load, plant-based high-fi ber whole foods, organic diet, and exercise.

To further improve his genetic limitations in methylation and

sulfation, he was treated with high doses of MTHF (methyl-tetra-

hydrofolate),20 methylcobalamin,21 and B6. To address his gut

infl ammation, food allergens were eliminated, small bowel bacteri-

al overgrowth was treated, and enzymes and probiotics were

replaced. Additional basic nutritional support, including a multivi-

tamin and omega 3 fatty acids,22 was provided.

After a year of aggressive therapy that was matched to his

quirky genes and biochemistry—not his diagnosis—George had a

remarkable and dramatic recovery. Before I saw him, he could not

manage his business nor did his grandchildren want to be around

him. After matching his treatment to his genes, he was again to

function able, and his grandchildren loved being with him.

Although this area of genetic testing and nutrigenomics is

new and more research is needed to help us refi ne our understand-

ing and treatment, there are ways to look through new doors into

an entirely new era of medicine—one that no longer focuses on the

disease but on the person and his or her uniqueness. Widespread

gene testing is not ready for primetime, but it can be a helpful

guide in understanding the origins and the risks of some chronic

illnesses. But we have to recognize that it is the interplay of many

genes interacting with the environment that determines our

health. What we do know is that there is no single gene for

Alzheimer’s—or autism, depression, heart disease, or cancer. In

fact, those diseases, as single homogeneous, uniform conditions,

do not exist. We must give up that myth.

Instead, there are common variations in the symphony of our

gene patterns that are integral to many chronic diseases. These

patterns vary from person to person and are highly infl uenced by

diet, stress, infections, allergens, and toxins.

The time has come to focus on systems approaches to com-

plex systems disorders. Treatment based on mechanism, genetics,

biochemistry, and physiology will supplant diagnosis-based treat-

ment. Clinicians can begin to navigate with a different map for the

territory of illness than the one we received in our training and in

the process can become re-enchanted with medicine and the possi-

bility of healing where there was none.

REFERENCES1. Cummings JL. Alzheimer’s disease. N Engl J Med. 2004;351(1):56-67.2. US Department of Health and Human Services. Centers for Disease Control and

Prevention. National Center for Health Statistics. Deaths—Leading Causes. Available at: http://www.cdc.gov/nchs/fastats/lcod.htm. Accessed January 29, 2008.

3. Brookmeyer R, Johnson E, Ziegler-Grahamm K, Arrighi M. Forecasting the global preva-lence and burden of Alzheimer’s disease. Alzheimer’s Dement. 2007;3:S168-S169.

4. Tsai MS, Tangalos EG, Petersen RC, et al. Apolipoprotein E: risk factor for Alzheimer disease. Am J Hum Genet. 1994;54(4):643-649.

5. Godfrey ME, Wojcik DP, Krone CA. Apolipoprotein E genotyping as a potential bio-marker for mercury neurotoxicity. J Alzheimers Dis. 2003;5(3):189-195.

6. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury—current exposures and clinical manifestations. N Engl J Med. 2003;349(18):1731-1737. Review.

7. Mutter J, Naumann J, Schneider R, Walach H. Mercury and Alzheimer’s disease [article in German]. Fortschr Neurol Psychiatr. 2007;75(9):528-538.

8. Mutter J, Naumann J, Sadaghiani C, Schneider R, Walach H. Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator. Neuro Endocrinol Lett. 2004;25(5):331-339. Review.

9. Wojcik DP, Godfrey ME, Christie D, Haley BE. Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994-2006). Neuro Endocrinol Lett. 2006;27(4):415-423.

10. Stroombergen MC, Waring RH. Determination of glutathione S-transferase mu and theta polymorphisms in neurological disease. Hum Exp Toxicol. 1999;18(3):141-145.

11. Bernardini S, Bellincampi L, Ballerini S, et al. Glutathione S transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele. Clin Chem. 2005;51(6):944-951. Epub 2005 Apr 1.

12. Gundacker C, Komarnicki G, Jagiello P, et al. Glutathione-S-transferase polymorphism, metallothionein expression, and mercury levels among students in Austria. Sci Total Environ. 2007;385(1-3):37-47. Epub 2007 Aug 22.

13. Dorszewska J, Florczak J, Rozycka A, et al. Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer’s and Parkinson’s diseases. Acta Neurobiol Exp (Wars). 2007;67(2):113-129.

14. Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenera-tive diseases with special reference to dementia. FEBS Lett. 2006;580(13):2994-3005. Epub 2006 May 6.

15. Rodríguez E, Mateo I, Infante J, Llorca J, Berciano J, Combarros O. Cholesteryl ester transfer protein (CETP) polymorphism modifi es the Alzheimer’s disease risk associated with APOE epsilon4 allele. J Neurol. 2006;253(2):181-185. Epub 2005 Aug 17.

16. James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004;80(6):1611-1617.

17. Kelly CB, McDonnell AP, Johnston TG, et al. The MTHFR C677T polymorphism is asso-ciated with depressive episodes in patients from Northern Ireland. J Psychopharmacol. 2004;18(4):567-571.

18. Dietrich W, Erbguth F. Neurological complications of infl ammatory intestinal diseases [arti-cle in German]. Fortschr Neurol Psychiatr. 2003;71(8):406-414. Review.

19. International Academy of Oral Medicine and Toxicology. The scientifi c case against mercury amalgam. Available at: http://www.iaomt.org/articles/category_view.asp?intReleaseID=193&catid=30. Accessed February 5, 2008.

20. Corrada MM, Kawas CH, Hallfrisch J, Muller D, Brookmeyer R. Reduced risk of Alzheimer’s disease with high folate intake: the Baltimore Longitudinal Study of Aging. Alzheimer’s Dement. 2005;1(1):11-18.

21. Clarke R, Birks J, Nexo E, Ueland PM, Schneede J, Scott J, Molloy A, Evans JG. Low vita-min B-12 status and risk of cognitive decline in older adults. Am J Clin Nutr. 2007;86(5):1384-1391.

22. Dullemeijer C, Durga J, Brouwer IA, van de Rest O, Kok FJ, Brummer RJ, van Boxtel MP, Verhoef P.n 3 fatty acid proportions in plasma and cognitive performance in older adults. Am J Clin Nutr. 2007;86(5):1479-1485.

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16 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Does CAM Represent Only Placebo Therapies?

Jeffrey Bland, PhD, FACN, FACB, is founder of the Institute for

Functional Medicine, Gig Harbor, Washington. Learn more

about Dr Bland at www.JeffreyBland.com. (Altern Ther Health

Med. 2008;14(2):16-18.)

Complementary and alternative medicine (CAM) is

“something you heard about from your hairdresser,

who thinks she saw it on Oprah—a category that . . .

includes acupuncture, homeopathy, healing magnets

and assorted herbs and supplements.”1 This is a quote

from Jerry Adler’s editorial in the December 1, 2007, issue of

Newsweek titled, “A Big Dose of Skepticism.” The editorial repre-

sents a strong “shot across the bow” of the National Center for

Complementary and Alternative Medicine (NCCAM) at the

National Institutes of Health as well as the tens of thousands of

licensed CAM practitioners and millions of their patients who reg-

ularly employ what have been termed “CAM therapies.”

Mr Adler states that his 2008 resolution as a medical writer is

to “not report on any new treatments for anything, unless they

were tested in large, randomized, placebo-controlled, double-blind

clinical trials published in high-quality peer-reviewed medical jour-

nals.” He takes his lead in this advocacy from the recent book,

Snake Oil Science: The Truth About Complementary and Alternative

Medicine by R. Barker Bausell, PhD.2 In essence, Bausell makes a

strong case using his background as a former director of research

for the University of Maryland’s Center of Complementary and

Alternative Medicine that all CAM therapies have an impact on

health only by placebo-related effects. He bases his conclusions on

the effi cacy of CAM therapies on the following 5 criteria:

1. Studies of CAM therapies that show benefi t beyond place-

bo effects have not been done well, whereas studies of CAM

therapies that are methodologically sound have not dem-

onstrated benefi t beyond placebo.

2. Scientists and clinicians engaged in either the administra-

tion or study of CAM therapies have an inherent bias in

support of the positive nature of the therapies, and there-

fore their conclusions are suspect.

3. Scientists and clinicians associated with CAM therapies do not

understand methodological issues in the science of clinical tri-

als such as the placebo effect, attrition/drop-out, the natural

history of the disease in question, the Hawthorne effect, regres-

sion to the mean, or statistical methods of analysis.

4. No scientific mechanism of action for the validity of

CAM therapies has been proven beyond that of the

known mechanism of action of the placebo effect.

5. There is a lack of understanding of the concept of parsi-

mony (ie, Occam’s razor) that results in unusual and

unproven mechanisms beyond placebo effect to be

ascribed to CAM therapies.

In support of his contention that these 5 criteria defi ne the

limitations of CAM studies, Bausell provides evidence using the

Cochrane Collaboration database3-5 of 98 randomized, controlled

CAM studies published in 4 top-tier, peer-reviewed journals: The

New England Journal of Medicine, JAMA, Archives of Internal Medicine,

and the Annals of Internal Medicine. These studies include acupunc-

ture, herbal therapies, chelation therapy, traditional Chinese medi-

cine (TCM), electrical stimulation techniques, hypnotherapy,

homeopathy, intercessory prayer, massage, meditation, manipula-

tive therapies, ultrasound, and nutritional supplements such as glu-

cosamine. As he applies his criteria to the validity of these studies he

shows that only 5% of the 98 published studies demonstrate posi-

tive outcomes beyond that of placebo. It is this analysis that leads to

his conclusion that “after initiating [what appears to be a successful

CAM] therapy, if you begin to experience some fall-off in its bene-

fi ts, discuss the situation immediately with your therapist. Most

experienced CAM therapists will have a menu of new strategies

capable of initiating a new round of placebo effects.”2(p294)

What is wrong with this analysis of the effi cacy of CAM ther-

apies? The analysis is based on well-founded concerns from an

expert in scientifi c methodology. It would seem that Bausell has

offered a fait accompli that wipes away thousands of years of histo-

ry associated with the purported clinical success of many tradi-

tional healing methods with the stroke of one scientifi c eraser.

But there is much more to the story than that which is told. First

of all, he has seemingly lumped all of what is considered non-

traditional medical intervention under the rubric of CAM. He has

selectively chosen issues in the history of science to support his

hypothesis that there is no basis of a clinical benefi t for any CAM

therapy (which many readers might interpret as “non-pharmacologi-

cal therapies”) beyond that of placebo. The implication of Bausell’s

argument is that the success that was witnessed with the develop-

ment in the 1930s of antibiotic therapy ushered in the era of suc-

cessful, non-placebo therapies6 that, unlike CAM therapies, had

demonstrable effects beyond that of placebo. With regard to the

DOES COMPLEMENTARY AND ALTERNATIVE MEDICINE REPRESENT ONLY PLACEBO THERAPIES?

Jeffrey Bland, PhD, FACN, FACB

guest editorial

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 17Does CAM Represent Only Placebo Therapies?

necessity of conducting large randomized clinical trials to deter-

mine non-placebo effects of a specifi c therapy, it is interesting to

note that many accepted surgical procedures have not been tested

by randomized, placebo-controlled trials. They are, however, con-

sidered standards of care based on agreement among trained

medical professionals that they are effi cacious.7

Also interesting is Bausell’s contention that it is essential to

know the mechanism of action of a specifi c therapeutic interven-

tion when it is well known that many of the pharmaceutical prepa-

rations approved for use by the US Food and Drug Administration

do not have known mechanisms of action.8 The defi nitive criteria

that establish the safety and effi cacy of any therapy may be a little

more complicated than Bausell’s analysis implies.

There is another important limitation of using the random-

ized, placebo-controlled trial as the only criterion for determining

the non-placebo value of a therapy. The randomized, placebo-

controlled clinical trial favors the evaluation of an intervention

that can be easily blinded and placebo-controlled. As such, it is an

excellent methodology to evaluate the effect of 1 pill tested against

1 clinical endpoint—for example a new-to-nature angiotensin-

converting enzyme inhibitor for systolic and diastolic blood pres-

sure compared to an identical-looking placebo. This methodology,

however, is not as easily applied when one wants to study the

effect of a CAM therapy involving specifi c diet or lifestyle inter-

vention on blood pressure. Diet and lifestyle interventions are

impossible to completely blind and therefore are more susceptible

to issues related to the Hawthorne effect, compliance, dropout, or

the placebo effect.

The issue of the limitations of control of dietary intervention

trials was discussed in a recent review describing the inter-individual

variation of response that occurs in dietary studies and the need

for managing genetic heterogeneity with large study groups and

specifi c dietary subgroup analysis.9 This criticism can be applied

to important studies such as the Dietary Approach to Stopping

Hypertension (DASH). These studies demonstrated clinical validi-

ty of the effect diet and lifestyle have on hypertension but did not

fulfi ll Bausell’s criteria of an acceptable, randomized, placebo-

controlled trial.10,11 In the end, the well-designed study of a phar-

maceutical product for hypertension has far fewer methodological

issues confounding its results than do the diet-and-lifestyle inter-

vention studies.12,13

Beyond the obvious methodological challenge of how to blind

and develop appropriate placebos for CAM intervention trials is

another thorny issue. How long does it take to demonstrate true

improved patient outcome in a clinical study? Most clinical inter-

vention trials evaluating the effect of a new therapeutic agent for

the management of a chronic health problem will be of a year’s

duration at most. It is assumed that at the end of this period of

time the safety and effectiveness of the agent has been “proven.”

But what if this agent is applied in clinical practice for a much lon-

ger duration than the 1 year it was studied? Many patients with a

chronic disease have their therapies applied indefi nitely, as is the

case with type 2 diabetes, osteoarthritis pain and disability, chron-

ic digestive problems such as esophageal refl ux disease, chronic

depression, benign prostatic hypertrophy, hyperlipidemias, and

hypertension.14,15 In these cases the true safety and effectiveness of

the therapy that had been proven through the administration of a

successful short-term randomized, placebo-controlled trial might

in the longer term prove to either not improve outcome or even

cause serious adverse effects. An example is the recent voluntary

recall of the selective COX-2 inhibitor Rofecoxib by Merck & Co

(Whitehouse Station, New Jersey) due to the number of adverse

drug reactions that occurred after patients had been taking the

drug for an extended period of time.16,17 It wasn’t that the drug had

not been proven to be safe and effective through multiple random-

ized, placebo-controlled trials—rather, the adverse drug reactions

occurred when patients took the drug for a period of time that was

longer than the duration of the clinical trials.

A CAM treatment often is based on a much longer historical

perspective of safe use in indigenous cultures.18,19 It may not “mea-

sure up” in terms of outcome from a short-term placebo-controlled

trial, but it may actually provide for both a safer and more effec-

tive outcome in the longer term. No long-term, head-to-head out-

come studies have been done to compare the safety and

effectiveness of specifi c CAM therapies to those of pharmaceuti-

cally based therapies.20,21 However, population studies of various

diet and lifestyle CAM therapies have shown signifi cant improve-

ments in health outcomes when compared to populations that

have not adopted these habits.22,23 The recent HALE (Healthy

Aging Longitudinal Study in Europe) project, a 10-year study of

health outcomes in individuals aged 70 to 90 years who elected to

consume a Mediterranean diet compared to an age- and gender-

matched control group in the same countries who consumed their

traditional European diet, illustrates this concept.24 The study

reported that “among individuals aged 70 to 90 years, adherence to

a Mediterranean diet and healthful lifestyle is associated with a

more than 50% lower rate of all-cause mortality and cause-specifi c

mortality.”24(p1433) Although this study doesn’t fulfi ll the Bausell cri-

teria of a randomized, placebo-controlled trial, it was published

in a peer-reviewed, tier-one journal, and the results have poten-

tially significant implications on health outcomes of an aging

population. As Ivan Ilich said in his landmark book Medical

Nemesis25 and as suggested by the HALE study, the big break-

throughs in health have not occurred through agents developed

by the application of the randomized controlled clinical trial to

develop new medicines but rather through the effective applica-

tion of nutrition, sanitation, and hygiene, all of which were con-

sidered “CAM therapies” in their time.

The question that emerges from Bausell’s interpretation of

CAM therapies is whether the randomized clinical trial is the

appropriate methodology to address the most important ques-

tions concerning our health where chronic disease is the dominant

form of disease in the developed world.26 What is emerging is a dif-

ferent model for evaluating a therapy’s safety and effectiveness that

is born out of the developing algorithms of systems biology.27,28 It

uses multivariate, non-parametric statistical methods of analysis of

complex data sets. Rather than constructing the experiment to

hold all variables constant except the clinical endpoint that is to be

18 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Does CAM Represent Only Placebo Therapies?

studied, this model allows the study participants to engage in real-

world activities of daily living and then determines how the cap-

tured complex data set clusters into patterns of significant

outcome.29,30 Bausell’s questioning of the non-placebo validity of all

CAM therapies is built on an old model of statistics. It is through

the computing power of the 21st century and new technology that

pattern recognition and cluster analysis of complex data sets can

be routinely accomplished.

Work that is being done on the analysis of complex biological

systems at places such as the Institute for Systems Biology in Seattle,

Washington, has presented an opportunity for new experimental

methodologies to be employed in clinical studies.31 These new meth-

ods of analysis don’t suffer the “one agent for one outcome” bias of

the randomized, placebo-controlled clinical trial. The systems biol-

ogy approach to medicine is now being seriously discussed as part

of the development of an integrated biological approach to health-

care.32 The Institute for Functional Medicine recently published the

Textbook of Functional Medicine, which describes a clinical approach

to applying systems biology to the management of chronic disease.33

The clinical model described in the textbook is built on a founda-

tion of evidence from not only randomized, controlled clinical trials

but also studies published from epidemiology, meta-analyses, case-

controlled studies, basic science discoveries, and complex data set

analyses. The functional medicine approach to chronic disease rep-

resents a new paradigm in healthcare that moves beyond the limita-

tions of CAM described by Bausell.

We are witnessing a new era in which it might be said that we

are “moving back to the future.” The move back is to explore what

makes the greatest impact on improving health outcomes in a soci-

ety burdened with the rising incidence of chronic disease from a

historical perspective. The future holds the development of new

experimental methods of designing studies that can better address

complexity within human populations and the computing and sta-

tistical methodologies to bring clarity from confusion.34,35

It is certainly true that all interventions are “tainted” by meth-

odological issues such as the placebo effect. Some therapies have a

much greater likelihood of a strong placebo effect than others,

such as those for chronic pain. It is also true that some therapies

are much more diffi cult to separate methodologically from that of

the placebo effect. This is the case with a number of CAM therapies

in that it may be virtually impossible to completely blind the par-

ticipants or the practitioners or provide a suitable placebo. Using

the new experimental methods that are based on complexity theo-

ry and systems biology and the statistical methods that support

them, we will be better able to address the long-term safety and

effi cacy of many CAM therapies. It is through this work that stud-

ies will help answer the question of which CAM therapies work via

placebo effect and which therapies will aid us in fi ghting chronic

disease and infi rmity.36

REFERENCES1. Adler J. A big dose of skepticism. Newsweek. December 10, 2007. Available at http://www.

newsweek.com/id/73283/output/print. Accessed January 8, 2008.2. Bausell RB. Snake Oil Science: The Truth About Complementary and Alternative Medicine.

New York: Oxford University Press; 2007.

3. Miyasaka LS, Atallah AN, Soares BG. Valerian for anxiety disorders. Cochrane Database Syst Rev. 2006;4:CD004515.

4. Linde K, Mulrow CD. St John’s wort for depression. Cochrane Database Syst Rev. 2000;2:CD000448.

5. Furlan AD, van Tulder M, Cherkin D, et al. Acupuncture and dry-needling for low back pain: an updated systematic review within the framework of the Cochrane collaboration. Spine. 2005;30(8):944-963.

6. Rolinson G. History of antimicrobial chemotherapy: from Pasteur to penicillin. Chemioterapia. 1987:6(2 Suppl):6-7.

7. Chan S, Bhandari M. The quality of reporting of orthopedic randomized trials with use of a checklist for nonpharmacological therapies. J Bone Joint Surg Am. 2007;89(9):1970-1978.

8. Jones JK. The Institute of Medicine’s report on drug safety: constructive and ambitious, but does it go far enough? Clin Pharmacol Ther. 2007;81(2):156-158.

9. Ordovas JM, Kaput J, Corella D. Nutrition in the genomics era: Cardiovascular disease and the Mediterranean diet. Mol Nutr Food Res. 2007;51(10):1293-1299.

10. Lin PH, Appel LJ, Funk K, et al. The PREMIER intervention trial helps participants follow the Dietary Approaches to Stop Hypertension dietary pattern and current Dietary Reference Intakes recommendations. J Am Diet Assoc. 2007;107(9):1541-1551.

11. O’Shaughnessy KM. Role of diet in hypertension management, Curr Hypertens Rep. 2006;8(4):292-297.

12. Kirpizidis H, Stavrati A, Geleris P. Assessment of quality of life in a randomized clinical trial of candesartan only or in combination with DASH diet for hypertensive patients. J Cardiol. 2005;46(5):177-182.

13. Funk KL, Elmer PJ, Stevens VJ, et al. PREMIER—A trial of lifestyle interventions for blood pressure control: Intervention Design and Rationale. Health Promot Pract. 2006;34:233-239.

14. Nair V, Salmon JW, Kaul AF. Iatrogenic disease management: moderating medication errors and risks in a pharmacy benefi t management environment. Dis Manag. 2007;10(6):337-346.

15. Schmittdiel J, Mosen DM, Glasgow RE, Hibbard J, Remmers C, Bellows J. Patient Assessment of Chronic Illness Ccare (PACIC) and improved patient-centered outcomes for chronic conditions. J Gen Intern Med. 2008;23(1);77-80.

16. Clark RC, Maxwell SR, Kerr S, et al. The infl uence of primary care prescribing rates for new drugs on spontaneous reporting of adverse drug reactions. Drug Saf. 2007;30(4):357-366.

17. Topol EJ, Failing the public health—rofecoxib, Merck and the FDA. N Engl J Med. 2004;351(17):1707-1709.

18. Pearson NJ, Chesney MA. The CAM education program of the National Center for Complementary and Alternative Medicine: an overview. Acad Med. 2007;82(10):921-926.

19. Wong VT, Feichau P. Linking research, policy, and action: evidence-based complementary and alternative medicine. Healthc Manage Forum. 2006;19(1):21-26.

20. Graz B, Falquet J, Morency P. Rapid assessment of alternative medicine through a com-parison of the expected and observed progress of patients: a feasibility study of the prog-nosis/follow-up method. J Altern Complement Med. 2003;9(5):755-761.

21. Eisenberg DM, Cohen MH, Hrbek A, Grayzel J, Van Rompay MI, Cooper RA. Credentialing complementary and alternative medical providers. Ann Intern Med. 2002;137(12):965-973.

22. Villareal DE, Miller BV 3rd, Banks M, Fontana L, Sinacore DR, Klein S. Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults. Am J Clin Nutr. 2006;84(6):1317-1323.

23. Howard BV, Van Horn L, Kotchen JM, et al. Low-fat dietary pattern and risk of cardiovas-cular disease: the Women’s Health Initiative Randomized Controlled Dietary Modifi cation Trial. JAMA. 2006;295(6):655-666.

24. Knoops KT, de Groot LC, Kromhout D, et al. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European mean and women: the HALE project. JAMA. 2004;292(12):1433-1439.

25. Barnet RJ. Ivan Illich and the nemesis of medicine: the man and the message in memori-am. Med Health Care Philos. 2003;6(3):273-286.

26. Holman H. Chronic disease—the need for a new clinical education. JAMA. 2004;292(9):1057-1059.

27. Draghici S, Khatri P, Tarca AL, et al. A systems biology approach to pathway level analy-sis. Genome Res. 2007;17(10):1537-1545.

28. Opgen-Rhein R, Strimmer K. Learning causal networks from systems biology time course data: an effective model selection procedure for the vector autoregressive process. BMC Bioinformatics. 2007;8(Suppl 2):S3.

29. Fitzgerald J, Schoeberi B, Neilsen UB, Sorger PK. Systems biology and combination thera-py in the quest for clinical effi cacy. Nat Chem Biol. 2006;2(9):458-466.

30. Bell IR, Koithan M. Models for the study of whole systems. Integr Cancer Ther. 2006;5(4):293-307.

31. Reitman ML, Schadt EE. Pharmacogenetics of metformin response: a step in the path toward personalized medicine. J Clin Invest. 2007;117(5):1226-1229.

32. Liu ET. Systems biology, integrative biology, predictive biology. Cell. 2005;121(4):505-506.

33. Jones DS, ed. Textbook of Functional Medicine. Gig Harbor, Washington: Institute for Functional Medicine; 2005.

34. Lindgren TG, Fukuouka Y, Rankin SH, Cooper BA, Carroll D, Munn YL. Cluster analysis of elderly cardiac patients’ prehospital symptomatology. Nurs Res. 2008; 57(1):14-23.

35. Spencer L, Roberts G, Irvine F, Jones P, Baker C. Using cluster analysis to explore survey data. Nurse Res. 2007;15(1):37-54.

36. Biobel BG, Pharow P, Norgall T. How to enhance integrated care towards the personal health paradigm? Medinfo. 2007;12:172-176.

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20 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Developments in Education in Complementary and Integrative Medicine

Victor S. Sierpina, MD, is the W.D. and Laura Nell Nicholson

Professor of Integrative Medicine and professor of family medi-

cine at the University of Texas Medical Branch. He is chair of

the Consortium of Academic Health Centers for Integrative

Medicine. His books include 1000 Cures for 200 Ailments (New

York: Harper Collins; 2007) and Integrative Health Care:

Complementary and Alternative Therapies for the Whole Person

(Philadelphia, Pennsylvania: F.A. Davis Co; 2001). (Altern Ther

Health Med. 2008;14(2):20-22.)

From 2000 to 2004 I had the pleasure and opportunity

to write a regular column entitled “Progress Notes in

CAM Education” for this journal. At the time, exciting

new things were happening in the academic world

with the evolution of a wide range of educational ini-

tiatives in complementary and alternative medicine (CAM) edu-

cation. I interviewed educators and documented their projects,

curricular changes, institutional and cultural challenges, evalua-

tion efforts, feedback from learners, funding issues, time and

effort, faculty development, and more. A mid-trajectory summa-

ry article was published that reviewed the major trends in CAM

education at that time.1 It was during an era when the National

Center for Complementary and Alternative Medicine (NCCAM)

of the National Institutes of Health (NIH) was investing more

than $21 million in a series of educational enhancement grants

in CAM education and many of those columns summarized work

that was just starting or underway across the country.

We have come a long way since then. In October 2007,

Academic Medicine: Journal of the Association of American Medical

Colleges, the premier journal for medical educators, published a

theme issue comprised of 9 papers summarizing the outcomes,

methods, processes, evaluation, and impact of the NCCAM-

funded projects.2,3 This was a high watermark for the fi eld in that

it presented the broad academic medicine community with a

solid showing of the state-of-the-art education in CAM and inte-

grative medicine (IM). While any one publication or even a

theme issue rarely makes a tectonic shift in the methods and cul-

ture of academia, the presence of such a theme issue offers us

hope that gradual acceptance and integration of the role of

CAM/IM training is occurring and that sustainable change is

upon us.4 Indeed, surveys of medical schools continue to show

that nearly all of them have some offerings in this area and also

that board examinations are increasingly quizzing students on

this content.

It is, of course, a positive step that ATHM continues to print

new research on CAM/IM education, as in this issue. Our col-

league Peter Wayne is an established, well-respected CAM educa-

tor and researcher. I found his report of developing research

capacity at the New England School of Acupuncture in collabora-

tion with Harvard’s Osher Integrative Medicine Center to be

excellent. His pragmatic approach of introducing research skills

to his faculty and students, starting with the “publishable case

report,” clinical research methods and seminar series, required

courses on research, as well as electives, is highly innovative and

progressive in helping CAM practitioners, faculty, and students

become more oriented to the rules of evidence and the methods

of scientifi c clinical inquiry. This NIH-funded research is doing

much to help develop a culture of scholarship and academic rigor

in his institutions and is helping to bridge the cultures of conven-

tional and CAM researchers.

Another promising development is the rapid growth of the

Consortium of Academic Health Centers for Integrative Medicine.

The Consortium is composed of 39 North American academic

health science centers that have active programs in at least 2 of the

3 areas of education, clinical care, and/or research in IM. This

group started with 8 schools in 1999 and with the generous sup-

port of the Bravewell Philanthropic Collaborative has grown to its

present size. The mission of the Consortium is as follows:

Our mission is to help transform medicine and health-

care through rigorous scientific studies, new models of

clinical care, and innovative educational programs that

integrate biomedicine, the complexity of human beings,

the intrinsic nature of healing and the rich diversity of

therapeutic systems.

With the voice of nearly 30% of US and Canadian medical

schools, the Consortium is poised to advocate within academia

for a relevant role for IM across all institutional missions. The

PROGRESS NOTES UPDATED: THE CONSORTIUM AND OTHER DEVELOPMENTS IN EDUCATION IN

COMPLEMENTARY AND INTEGRATIVE MEDICINEVictor S. Sierpina, MD

guest editorial

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 21Developments in Education in Complementary and Integrative Medicine

Consortium leadership consists of a steering committee member

from each of the 39 schools. An executive committee is composed

of chair (Victor Sierpina, University of Texas Medical Branch),

vice chair (Adam Perlman, University of Medicine and Dentistry

New Jersey), treasurer (John Pan, George Washington University),

secretary (Anne Nedrow, Oregon Health Sciences University), and

the past chair (Susan Folkman, University of California, San

Francisco) and past vice chair (Mary Jo Kreitzer, University of

Minnesota), as well as at-large members (Sara Warber, University

of Michigan; Roberta Lee, Albert Einstein Medical School;

Victoria Maizes, University of Arizona; David Rakel, University of

Wisconsin; Bud Rickhi, University of Calgary; Saki Santorelli,

University of Massachusetts Medical School).

The Consortium has operationalized its mission through its

working groups. The Education Working Group, headed by Mary

Guerrera from the University of Connecticut and Ron Glick from

the University of Pittsburgh is actively involved in several projects,

including proposing a change in educational standards to the

Licensing Commission for Medical Education (LCME). The pro-

posed changes are modifi cations of existing standards to include

requirements for complementary and integrative medicine content

into medical school curricula as well as an exposure to indigenous

systems of care. If approved through the LCME’s established pro-

cess of revising standards, these changes will promote the fi eld of

medical education’s efforts for creative and across-the-board incor-

poration of CAM/IM concepts and content into the educational

programs of all US medical schools. Each school would need to

demonstrate that it teaches this material in some way and evalu-

ates the results of such teaching in order to be accredited by the

LCME. The Education Working Group is also compiling a database

of educational resources in CAM/IM education available in the

United States and Canada for other centers wishing to access such

materials for their own ongoing or nascent programs.

Another initiative of this energetic working group is to create

presentations about the need, rationale, and resources needed for

fostering IM education, which will be presented to educational

deans and other educators at the regional General Education

Association meetings held as part of the Association of American

Medical Colleges annual sessions this spring. Four proposals have

been submitted for these regional meetings. The Education

Working Group also submitted and had published a letter to the

editor of the Journal of Family Practice arguing for incorporating

integrative medicine into the design of residency programs. The

group is also preparing a viewpoint paper on the changes needed

in undergraduate, premedical curriculum in order to introduce

premed students to the broad range of perspectives and skills

needed to understand and practice integratively.

Several member schools (University of Arizona, University

of Connecticut, Albert Einstein Medical School, University of

Texas Medical Branch), led by University of Arizona Program in

Integrative Medicine’s Patricia Lebensohn and Victoria Maizes,

are developing an Integrative Medicine in Residency curriculum.

This pilot started with a 12.5-hour online botanical curriculum

and will be launched in July 2008 at 8 pilot family medicine resi-

dencies (4 Consortium members) as a 250-hour longitudinal,

required curriculum across the 3 years of training. A student

leadership committee is being formed to help foster leadership

training at the American Medical Student Association.

The Clinical Working Group, led by Andy Heyman, an

Integrative Fellow from the University of Michigan, and Jillian

Capodice, Columbia University, has a number of activities in

progress initiated by the previous co-chairs, Mary Hardy from

UCLA and John Pan from George Washington University. Eight

schools have institutional review board approval, and 4 more are

pending to participate in The Outcomes Research Project to

examine patient outcomes related to IM. Enrollment is under-

way. A new initiative involves joint conference calls with the

Society for Integrative Oncology. A pediatric subgroup is also

active with monthly conference calls and a number of initiatives

in their specialty area. The Clinical Working Group also has

developed a Clinical Models Survey, which is an audit of clinical

services of Consortium members. This group also is developing

the infrastructure for a practice-based research network in col-

laboration with the Research Working Group.

The Research Working Group, led by Susan Gould Fogerite,

University of Medicine and Dentistry of New Jersey, and Laurie

Lachance, University of Michigan, is in the process of creating a

network of researchers from the various schools to share their

expertise and patient populations for recruitment in studies in

IM. By developing a membership database with information

about research, practice, areas of expertise, and ongoing projects,

they anticipate fostering collaboration and mentoring among

members. This information also will be used to establish a Rapid

Response and Referral Network for responding to questions from

the media and providing comment on topics related to CAM and

IM. The Research Working Group will be an instrumental part of

a number of Consortium and non-Consortium peer reviewers of

abstracts submitted for the North American Complementary

and Integrative Medicine Research Conference to be held in

Minneapolis in May 2009. This conference offers opportunities

for researchers from the worldwide CAM community to present

their best work on education, clinical, and other research areas in

IM. The last conference, held in Edmonton, Alberta, Canada, in

May 2006 was an enormous success, with over 700 attendees

from 14 countries and hundreds of posters, presentations, theme

sessions, and keynotes. We will soon be inviting proposals and

encourage you to submit your best work. ATHM published the

last conference proceedings.

Another vital activity of the Consortium is the policy

domain, where our stated goal is to “inform national policy that

advances integrative medicine through research, clinical, and

education initiatives.” Mary Jo Kreitzer of the University of

Minnesota is the liaison to the Executive Committee on policy

matters. An attractive, informative “leave behind” describing the

Consortium was developed and is being used to initiate dialogues

with legislators, policy makers, and other opinion leaders. We

are in the process of developing a process and policies for estab-

lishing alliances for collaboration and networking with other

organizations in the CAM community, such as the Academic

Consortium for Complementary and Alternative Health Care

(ACCAHC) and others,5,6 with arranging bi-annual meetings with

NCCAM leadership and developing relationships with campus

Government Relations Offi cers in member schools.

The Consortium is preparing to expand its membership as

more activity is clearly evident at other academic centers. We are

also seeking to expand our revenue streams from membership

dues and new sources of philanthropy and to explore potential

business and intellectual property opportunities. For a complete

list of member schools and other Consortium information, visit

the website at www.imconsortium.org.

While the future of IM education is bright, some major chal-

lenges and opportunities lie ahead for us to prepare the next gen-

eration of integrative medicine practitioners.7 Among these are

1. faculty development in both conventional and CAM

schools regarding the content of the field, teaching

methods, and research expertise;

2. transprofessional collaboration in education, research,

clinical care, and healthcare policy among IM practitio-

ners and colleagues in conventional medicine, allied

health, nursing, pharmacy, and CAM disciplines such as

chiropractic, massage, naturopathy, indigenous health-

care systems, and others;

3. providing learners with critical thinking skills, access to

reliable resources, and role modeling of integrative prac-

tice in consistent, credible, and relevant ways;

4. outcomes-based practice and optimal care pathways

informed by research; and

5. changes in health insurance reimbursement and policy to

provide broader access for underserved patients to inte-

grative medicine.

To forward such an agenda, the Consortium must partner

with other CAM organizations and professional educators,

deans, and course directors in our medical, nursing, and allied

health schools; researchers; health policy and opinion-leaders;

patient advocacy groups; and the scientifi c community. Together,

we can change the world of healthcare.

REFERENCES1. Sierpina V. Progress notes: a review of educational developments in CAM. Altern Ther

Health Med. 2002;8(6):112-114. 2. Acad Med. 2007;82(10):917-1118.3. Sierpina V, Schneeweiss R, Frenkel M, Bulik R, Maypole J. Barriers, strategies, and les-

sons learned from complementary and alternative medicine curricular initiatives. Acad Med. 2007;82(10):946-950.

4. Sierpina V, Bulik R, Frenkel M, et al. Creating sustainable curricular change: Lessons learned from an alternative therapies educational initiative. Acad Med. 2007;82(4):341-350.

5. Kligler B, Maizes V, Schachter S, et al. Core competencies in integrative medicine for medical school curricula: a proposal. Acad Med. 2004;79(6):521-531.

6. Benjamin P, Phllips R, Warren D, et al. Response to a proposal for an integrative medi-cine curriculum. J Altern Complement Med. 2007;13(9):1021-1033.

7. Sierpina V. Teaching integratively: How the next generation of doctors will practice. Integr Cancer Ther. 2004;3(3):1-7.

http://www.metabolicmaintenance.com

24 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Modifying Practical Markers of Wellness and Aging

Steven Masley, MD, FAAFP, CNS, is president of the Masley

Optimal Health Center and a clinical assistant professor in

the Department of Family Medicine at the University of South

Florida, both in St Petersburg. Wendy Weaver, BA, was the

fi tness coordinator at and Gil Peri, MPH, MBA, was director of

the Carillon Wellness Center at St Anthony’s Health Care, St

Petersburg, when this article was written. Sharon E. Phillips,

MSPH, is a biostatistician III in the Department of

Biostatistics, Vanderbilt University School of Medicine,

Nashville, Tennessee.

Increasing obesity, epidemic rates of type 2 diabetes and the

metabolic syndrome, low-nutrient diets, and lack of activity

play key roles in the decline in fi tness, health, and potential

longevity in average Americans.1-3 Evidence-based lifestyle

interventions are indicated to offset this potential decrease

in lifespan and health span. Many diet studies have assessed

weight loss and lipid response, yet few have combined dietary

changes specifi cally addressing fi ber and saturated fat intake with

aerobic exercise and strength training and measured their impact

on various measures of wellness, in particular, body composition

(lean and fat mass), total cholesterol:high-density lipoprotein

(TC:HDL) ratios, strength, fl exibility, maximal rate of oxygen con-

sumption (VO2 max), and cognitive performance.

After age 40, steady physiological changes in age occur year-

ly, with body fat increasing by 1% and body lean mass decreasing

by 1%. These changes are associated with losses in strength and

an increased risk for both morbidity and mortality.4-10 Aerobic fi t-

ness also drops linearly, best noted by a VO2 max decrease of 1%

per year after age 40.11,12 Every decade these measures worsen by

approximately 10% with normal aging; hence, they appear to be

useful measures of wellness.

Total cholesterol levels have been suggested to increase lin-

early through adulthood until age 70, by approximately 1 mg/dL

yearly, with HDL levels changing minimally over this time

frame.13 Studies have shown that low-density lipoprotein (LDL)

receptor activity decreases with advancing age and appears to be

EFFICACY OF LIFESTYLE CHANGES IN MODIFYING PRACTICAL MARKERS OF WELLNESS AND AGING

Steven Cameron Masley, MD, FAAFP, CNS; Wendy Weaver, BA; Gil Peri, MPH, MBA; Sharon E. Phillips, MSPH

original research

Purpose • To determine the effi cacy of asking people to add

fi ber, exercise, and stress management to their lifestyles to

enhance markers of wellness and aging.

Methods • A 10-week, randomized control study conducted in a

wellness center in St Petersburg, Florida. Participants were adults

aged 21 to 65 years who exercised fewer than 3 days per week.

Fifty-six subjects were randomized to a control or an intervention

group. Subjects followed a diet with >30 g of fi ber and <16 g of

saturated fat daily and were taught to reach 70% to 85% of their

maximum heart rate 5 to 6 days per week and to perform strength

training 3 days per week. They were also asked to participate in

10 to 20 minutes of stress management activities daily. The study

was designed to determine changes in body composition, maxi-

mal rate of oxygen consumption (VO2 max), total cholesterol:

high-density lipoprotein (TC:HDL) ratio, and cognition.

Results • Initial analyses with analysis of variance (ANOVA) com-

paring the intervention group to the control group showed signifi -

cant improvements in TC:HDL (8.9% average; P=.02) and change

in weight (2.3 kg average; P=.016). When the groups were com-

pared, the improvements in cognitive fl exibility and VO2 max with

ANOVA were not signifi cant (P=.17 and P=.11, respectively).

Additional independent t tests showed decreases in TC:HDL of

8.9% (P=.02) and TC of 7.3% (P=.001) for the intervention group

compared to the control group. A mean increase of 29% in VO2

max of intervention subjects who exercised aerobically for at least

30 minutes 5 days/week was signifi cant (P=.02) compared to the

control group. Over the 10 weeks, the control group showed no

signifi cant change in lipids, body composition, cognition, and

fi tness, whereas the intervention group showed decreased body

mass index (BMI) of 0.72 (P=.02), weight loss of 2.3 kg (P=.016),

and decreased body fat of 1.6% (P<.0001). In the intervention

group, those with a BMI >24 who exercised 5 to 6 days/week lost

4.8 kg and 4.1 kg in body fat. Also, in the intervention group,

several of the cognitive scores showed statistically signifi cant

improvements from baseline: mental speed (4.6%, P=.014), reac-

tion time (4.5%, P=.023), and cognitive fl exibility (11.7%, P=.019),

but none of these cognitive changes was signifi cant with indepen-

dent t testing when compared to the control group.

Conclusions • A diet high in fi ber and low in saturated fat

combined with strength training, aerobic activity, and stress

management activities improves fi tness and several markers of

wellness and aging. (Altern Ther Health Med. 2008;14(2):24-29.)

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 25Modifying Practical Markers of Wellness and Aging

associated with an increase in LDL and TC levels without impact-

ing HDL levels.14-16 As the TC:HDL ratio is easy to measure and

has been shown to be one of the best predictors for developing

cardiovascular disease (CVD),17 this makes the TC:HDL a practi-

cal predictor of CVD and potentially a useful marker of health.

Lastly, cognitive function as measured by reaction time,

mental speed, and cognitive fl exibility also has been suggested to

decrease linearly over time.18-20 Enhancing cognitive function

would likely also be important in improving overall productivity.

Hence, various outcome markers exist that are potential physio-

logical measures of wellness and can be used to assess the effi cacy

of various lifestyle interventions.

Our hypothesis was that combining aerobic activity and

strength training with a diet emphasizing high fi ber and low sat-

urated fat intake plus a stress-management component could

improve cholesterol profi les, body composition, strength, aero-

bic fi tness, fl exibility, and cognitive performance.

METHODS

St Anthony’s Hospital’s institutional review board approved

this protocol, and all subjects gave written informed consent to

participate. Subjects 21 to 65 years of age, enrolled in a wellness

center in St Petersburg, Florida, and exercising fewer than 3 days

per week were invited to participate. Our aim in enrolling well-

ness center members who were not using the facilities regularly

was to fi nd subjects willing to participate in a study assessing

markers of fi tness and wellness with a diet and exercise regimen;

these subjects would be similar to average Americans in terms of

body mass index (BMI), dietary intake, and fi tness. At entry the

subject’s average BMI was 28.9, daily fi ber intake was 15 g with 22

g of saturated fat, and VO2 max was 41.3, compared to national

American averages of 26.6 BMI,1 fi ber intake of 15.6 g,2 saturated

fat intake of 27.9 g,3 and VO2 max of 38.5.4

Fifty-six subjects were ranked by BMI to help ensure similar

BMI and fi tness levels at entry and randomized to either a control

or an intervention group for 10 weeks. At entry there was no sta-

tistical difference in BMI; gender distribution; age distribution;

body fat percentage; VO2 max; or TC:HDL ratio, TC, or HDL lev-

els between the control and intervention groups (Table 1).

Members of the control group were asked to continue their

current dietary intake and activity level for 10 weeks, and in addi-

tion to the listed outcome measures, their dietary intake was

assessed with NutriBase 5 software (CyberSoft Inc, Phoenix,

Arizona) at entry and end of the study. After the study was complet-

ed, control subjects were invited to participate in the intervention.

The intervention program participants were taught by a

nutritionist and American College of Sports Medicine (ACSM)–

certifi ed exercise instructors during weekly lectures in a group set-

ting using meal plans and recipes for a diet with >30 g of fi ber and

<16 g of saturated fat daily. They were encouraged to reach 70% to

85% of their maximum achieved heart rate 5 to 6 days per week

for 30 minutes and to perform strength training 3 days per week

with 1 to 2 sets of 10 to 15 repetitions for 10 body movements to

smooth-motion lifting exhaustion for a total of 10 weeks. The

emphasis upon adding fi ber and decreasing saturated fat has been

described previously.21 In addition, intervention subjects were

encouraged to create 10 to 20 minutes each day for mentally calm-

ing activities, such as meditation, breathing activities taught in a

yoga class, or enjoying a hot bath by candlelight with soft music.

Outcome measures included body composition, strength

and fl exibility, VO2 max, TC:HDL ratios, and cognitive function.

Body composition was measured with bioelectrical impedance

(Tanita® TBF-310, Tanita Corp of America, Inc, Arlington Heights,

Illinois). Strength and fl exibility data were collected using instruc-

tions from the ACSM for curl-ups (abdominal crunches), push-

ups, and sit-and-reach fl exibility.22 VO2 max was predicted from

peak MET (exercise measure of metabolic equivalent) and heart-

rate levels achieved during a treadmill test using the Bruce proto-

col—a standardized multistage treadmill test for assessing

cardiovascular health—with Physiologic® software (KI Software,

Silver Spring, Maryland). TC and HDL were measured with

Cholestech® (Cholestech Corp, Hayward, California) using refl ec-

tance photometry to measure the amount of cholesterol fractions

in the blood, which is converted to a mg/dL measurement. At

entry and following the 10-week intervention, neurocognitive per-

formance was assessed using a computerized battery, CNS Vital

Signs® (CNS Vital Signs, LLC, Chapel Hill, North Carolina). This

test battery is self-administered in 30 minutes on a PC and

includes tests of visual and verbal memory, fi nger tapping, sym-

bol digit coding, the Stroop test, shifting attention, and continu-

ous performance. The 7 tests generate domain scores for memory,

psychomotor speed, information processing time, attention, and

cognitive fl exibility. The tests in the CNS Vital Signs battery are

standardized and are known to be valid, reliable, and sensitive to

TABLE 1 Demographic Data of Subjects at Entry*

Measures

Mean (SD)

Control

Group

(N=28)

Intervention

Group

(N=28) P values

Gender (% male) 39.3% 53.6% —

Age 43.5 (11.2) 47.1 (9.4) —

Years of education 16.3 15.8 0.79

BMI 28.6 (6.6) 29.3 (6.2) 0.71

Body fat percentage 30.8% (8.8) 33.0% (9.4) 0.37

TC:HDL ratio 4.2 (1.5) 4.5 (1.7) 0.58

VO2 max 41.4 (12.0) 41.2 (9.3) 0.96

Mental speed 171.1 (23.9) 175.9 (25.2) 0.52

Reaction time 692.4 (85.6) 667.3 (101.4) 0.39

Attention 8.2 (5.1) 11.2 (19.5) 0.45

Cognitive fl exibility 43.3 (9.5) 44.4 (14.8) 0.78

*BMI indicates body mass index; TC:HDL, total cholesterol: high-density lipoprotein; VO2 max, maximal rate of oxygen consumption.

26 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Modifying Practical Markers of Wellness and Aging

very small changes in neurocognitive performance.5-8

Dietary adherence was measured using NutriBase 5® soft-

ware, analyzing 3-day food intake records with 2 weekdays and

1 weekend day at entry and after 10 weeks to assess dietary

changes. Subjects were asked to calculate their fi ber and saturat-

ed fat intake 1 day per week using provided tables. Activity lev-

els and stress-management activities were reported verbally

weekly with an exercise physiologist who recorded frequency

and intensity of strength training and aerobic activity and

whether subjects participated in calming activities for 10 to 20

minutes daily over each week.

Power calculations were performed to determine the sample

size, such that an independent t test would be based on a power

of 0.85 to detect a signifi cant difference (P=.05, 2-sided) based on

projected changes in the measures for BMI, the TC:HDL ratio,

and percentage of body fat from previous pilot studies, resulting

in a requirement of 23 patients per group. After allowing for a

20% dropout rate, we planned to enroll 28 patients per group.

We did not have data to assess sample size for changes in

strength, cognitive performance, or VO2 max; hence, the primary

outcome measures would be changes in TC:HDL, BMI, and body

fat. Secondary measures would be changes in strength, VO2 max,

and cognitive performance. ANOVA was used to compare the

intervention group with the control group for changes in

TC:HDL, weight, cognitive fl exibility, and VO2 max.

Between-group and within-group differences were tested

using independent and paired t tests. Weight change was ana-

lyzed for both groups and for overweight subjects (BMI >24,

which is the cut-off for normal weight) in each group. Likewise,

TC:HDL changes were measured in both groups and for group

subjects who started with a TC:HDL >4.8, which is considered

abnormal by some national commercial laboratories. Diet and

exercise compliance was assessed using the weekly data collected

by the exercise physiologists and analyzed. Of the initial 28 inter-

vention subjects, 1 dropped out at the beginning because of a

family emergency, and the remaining 27 completed the study. Of

the 28 control subjects, 2 dropped out immediately for personal

reasons, and 6 were unwilling to complete testing at the end of

10 weeks. Hence, 27 of 28 intervention and 20 of 28 control sub-

jects completed the study.

RESULTS

Over the 10 weeks, the control group showed no signifi cant

change in BMI, total weight, body fat percentage, TC:HDL ratio,

VO2 max, or cognitive performance as assessed by mental speed,

reaction time, and cognitive fl exibility. ANOVA comparing the

intervention group to the control group showed significant

changes in weight loss, an average of 2.3 kg (P=.016, standard

error 5.6), an average 8.9% improvement in the TC:HDL ratio

(P=.02, standard error 1.1), and non-signifi cant changes in cog-

nitive flexibility (P=.17, standard error 12.1) and VO2 max

(P=.11, standard error 9.5).

Compared to the control group over 10 weeks with an inde-

pendent test, the intervention group showed a significant

decrease in BMI (0.72, P=.02), weight (2.3 kg, P=.016), and per-

centage of body fat (1.6%, P<.0001), without a loss in lean mass

with an independent t test. The 16 control subjects with a BMI

>24 at entry noted a 0.2-kg decrease in weight (P=.7); however,

their body fat increased 0.6%. In contrast, the 20 intervention

subjects with a BMI >24 noted a 2.3-kg weight loss (P=.001) with

a 1.7% decrease in body fat. Finally, the 7 in the intervention

group with a BMI >24 and who exercised at least 5 to 6 days per

week lost 4.3 kg in body weight and 4.1 kg in body fat (P=.009),

which represents a 2.6% decrease in body fat and a 12.8% loss in

their total fat mass (Figure 1).

The intervention group also showed an 8.9% decrease in

TC:HDL (P=.02) and a 7.3% decrease in TC (P=.001). Although

not statistically signifi cant, in subjects who had abnormally ele-

vated TC:HDL levels at entry (>4.8), there was an 11.7% (5.97 to

6.73) increase in the 7 control subjects and a 12.7% (6.26 to 5.46)

decrease in 10 intervention subjects (Figure 2).

6

5

4

3

2

1

0

-1

0.4

-0.4

0.2

-0.6

2.3 2.5 2.3 2.5

4.3 4.1

Control Group

Control, BMI >24Group

InterventionGroup

Intervention, BMI >24Group

Intervention, BMI >24,Active 5+

d/wk

Weight Loss (kg) Fat Mass Loss (kg)

FIGURE 1 Changes in Weight and Fat Mass Over 10 Weeks as

Measured With Bioelectrical Impedance

8

7

6

5

4

3

2

1

0

4.2

4.6

66.7

4.54.1

6.3

5.5

Control Group14.3% increase in

TC:HDL(SD 1.03)

Control GroupTC:HDL >4.8

16.7% increase in TC:HDL

(SD 1.7)

Intervention Group

8.9 decrease in TC:HDL(SD 1.08)

Intervention,TC:HDL >4.8

12.7% decrease in TC:HDL

(SD 1.6)

TC:HDL at entry TC:HDL post-10 weeks

FIGURE 2 Changes in the TC:HDL Ratio Over 10 Weeks

TK ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 27

With a paired t test and following ACSM methods, the inter-

vention group noted a 91% increase in the number of curl-ups they

could do, (44.7 to 85.7, P<.0001); a 79% increase in the number of

push-ups they could do (10.1 to 18.1, P<.0001); and a 30% increase

in sit-and-reach fl exibility (20.1 cm to 26.2 cm, P=.0008) over the

10 weeks (Figure 3). Strength and fl exibility testing was used as

part of the intervention and not tested in the control group.

The mean increase of 17% in VO2 max in the intervention

group was not different (P=.11) from the control group. After

comparing only intervention subjects who exercised aerobically

for at least 30 minutes 5 to 6 days per week (n=13), the mean

29% increase in VO2 max in the intervention subjects was signif-

icant (P=.02) compared to the control group (Figure 4). In the

intervention group, increasing fi ber intake to >30 g daily com-

pared to an intake of <30 g also was associated with an increase

in VO2 max (P<.0001).

This study did not show a statistically signifi cant difference

in cognitive function by independent t testing when comparing

the intervention and control groups. For within-group compari-

sons, there were no statistically signifi cant changes in the con-

trol group from baseline to follow-up. Of interest within the

intervention group is that several of the cognitive scores showed

statistically significant improvements from baseline: mental

speed (4.6%, P=.014), reaction time (4.5%, P=.023), and cogni-

tive fl exibility (11.7%, P=.019). The intervention groups’ changes

in attention were not signifi cant (45%, P=.18, Table 2). Hence,

there is a non-signifi cant trend for cognitive improvement for

mental speed, reaction time, and cognitive flexibility in the

intervention group, and further studies with larger samples

sizes are warranted.

In the intervention group, 70% of the subjects reached at

least 30 g of fi ber daily, 78% decreased their saturated fat intake

to <16 g daily, 48% exercised in their aerobic heart rate range at

least 5 to 6 days per week, and 56% engaged in strength training

at least 3 days per week. As evidenced by the average nutritional

intake with the NutriBase 5 software, no significant changes

occurred in the control group. The intervention group reported

a calorie intake decrease from 1898 kcal to 1511, a fi ber intake

increase from 15 to 28 g daily, and a saturated fat intake

decrease from 22 to 11 g daily.

In comparing whether adherence to the various aspects of the

program (dietary change, activity change, or stress management)

achieved signifi cant reduction in these objective measures of well-

ness and aging, we compared the results of the intervention group

who adhered to each intervention against those who did not with

paired t tests. Participating in exercise 5 to 6 days per week

appeared the most important, followed by increasing fi ber intake,

adding strength training, and reducing saturated fat intake.

Adding stress management activities (as defi ned by creating peace-

ful time daily) did not impact the fi nal outcome measures.

DISCUSSION

This intervention combined dietary changes, activity rec-

ommendations, and stress management and then gauged basic

outcome measures that refl ect fi tness and markers for wellness

and aging. Five areas were assessed, including changes in body

fat, strength, aerobic fi tness, cholesterol, and cognitive perfor-

mance. Signifi cant improvements were seen in the fi rst 4 of these

areas, and a trend toward improvement was seen in 3 of the 5

domains of cognitive function that were assessed in this study.

The weight loss noted in this study as a result of adding the

recommended extra 250 kcal in exercise daily (350 calories x 5

days per week) and decreasing caloric intake by 350 calories

would have been expected to decrease body weight by 5.4 kg.

This is close to the 4.8-kg weight loss noted in the study in those

who were adherent and overweight. Overall, the focus on adding

at least 30 g of fi ber daily gained wide adherence and may have

added to the success of this intervention.

Modifying Practical Markers of Wellness and Aging

100

90

80

70

60

50

40

30

20

10

0

10.1

18.1 20.1

Curl-ups(Abdominal crunches)

(SD 43.3)

Push-ups(SD 7.9)

Sit and reach (cm)(SD 3.2)

At entry Post-10 weeks

44.7

85.7

26.2

FIGURE 3 Changes in Strength and Flexibility Measures in

Intervention Subjects

60

50

40

30

20

10

0Control

group6.5% increase

(SD 10.1)

Intervention group

17.9% increase(SD 8.98)

Intervention group

active 5+d/wk29.2% increase

(SD 9.48)

Intervention group

>30gm fiber/d22.6% increase

(SD 8.88)

At entry Post-10 weeks

4143.7

41.2

48.6

40.4

52.2

41.5

50.9

FIGURE 4 Changes in VO2 Max Over the 10-Week Study

28 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Modifying Practical Markers of Wellness and Aging

The general public can easily perform most of the outcome

measures chosen for this study. Strength tests used in this inter-

vention with charts from the ACSM provide comparisons of results

to gender- and age-specifi c groups. The TC:HDL ratio is perhaps

the best predictor of risk for cardiovascular disease and can be

measured easily in a non-fasting state at health fairs, clinics, and

fi tness centers across the country, often for free or for a nominal

fee. The improvement noted in TC:HDL is similar to that in previ-

ous studies.23 Fitness centers and medical professionals across the

country provide body composition testing with skin-fold testing,

and electrical impedance testing is becoming increasingly com-

mon. Aerobic fi tness testing can be performed in a medical facility

when warranted and also can be assessed in almost any fi tness cen-

ter that has treadmill machines. Of these tests, only cognitive test-

ing is not yet practical on a large scale without medical referral and

interpretation, but it too is being used increasingly as a screening

test for cognitive decline and cognitive performance.

The adherence rate to most aspects of this intervention was

good and at least comparable with other studies seeking to change

lifestyle behaviors.24,25 The dietary changes outlined were the easi-

est to follow, with >70% adherence; the ability to reach 5 to 6 days

per week of aerobic activity was the most diffi cult but reached 48%

adherence. However, the greatest benefi t in terms of loss in fat

mass, gains in cognitive performance, and improvements in cho-

lesterol profi les occurred in those who exercised at least 5 to 6 days

per week. These fi ndings support results from the National Weight

Loss Registry, which has noted daily activity to be the best predic-

tor of maintaining weight loss long term26; however, caution is war-

ranted with this comparison as further studies are needed to

confi rm that the short-term results obtained in this trial can be

sustained in long-term clinical trials.

LIMITATIONS

Though study subjects are typically more motivated than

the average American, thus limiting the applicability of the

results, this group of subjects at entry showed similar fiber

intake, saturated fat intake, fi tness levels, and BMI to that of

most Americans. Also, the fact that the randomized control

group showed no signifi cant improvements in weight, body fat

percentage, aerobic fi tness, eating habits, or TC:HDL ratios sug-

gests that this group was not overly motivated. The majority of

subjects in this trial had completed college, were Caucasian, and

were free of serious medical conditions; hence, additional studies

on subjects with varied education levels and ethnicity would be

needed before these results can be applied to the general public.

As is done in most wellness programs, entry results were

shared with subjects in the control and the intervention groups.

Although sharing results adds the potential for bias, it permitted a

realistic look at the effi cacy of this type of intervention in typical

wellness centers, and as no signifi cant changes occurred in the

control group, the study results do not appear to have been biased.

We acknowledge that it would have been preferable to mea-

sure VO2 max directly rather than estimating it and to assess

detailed lipid profi les and other more advanced measures of cardio-

vascular disease risk, including C-reactive protein levels; however,

these additional outcome measures were beyond the scope of this

initial study. We noted an apparent improvement in VO2 max in

subjects who increased their fi ber intake, but this study was not

designed or powered to distinguish between benefi ts from exercise

and benefi ts from nutritional intake. Although it is plausible that

more optimal nutritional intake could improve VO2 max indepen-

dent of exercise, further studies are warranted to assess this fi nding.

Bioelectrical impedance testing has true limits in measuring

TABLE 2 Changes in Cognitive Function*

Mental Speed Reaction Time† Attention† Cognitive Flexibility

Control group at entry

Mean (SD)

171

(23.9)

692

(85.6)

8

(5.1)

43

(9.5)

Control group post-10 wks

Mean (SD)

(% improvement)

176

(20.0)

(3%)

666

(90.7)

(3.7%)

8

(4.7)

(0%)

45

(10.7)

(4.6%)

Intervention group at entry

Mean (SD)

176

(25.2)

667

(101.4)

11

(19.5)

44

(14.8)

Intervention post-10 wks

Mean (SD)

(% improvement)

183

(25.0)

(4.6%)

637

(97.9)

(4.5%)

6

(3.5)

(45%)

50

(9.5)

(11%)

Intervention group at entry, activity 5+ d/wk

Mean (SD)

175

(29.5)

681

(99.7)

9.7

(10.0)

39.9

(20.0)

Intervention group post-10 wks, activity 5+ d/wk

Mean (SD)

(% improvement)

184

(27.5)

(5.1%)

619

(55.5)

(9.1%)

5.4

(3.9)

(44.3%)

49.7

(11.4)

(24.6%)

*Changes were measured using CNS Vital Signs testing.†A decrease in reaction time score and attention score indicates improvement.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 29Modifying Practical Markers of Wellness and Aging

lean mass as it varies with hydration. Measures were taken to

standardize hydration, caffeine, exercise, alcohol, and time-of-day

factors that infl uence hydration and body composition measures.

The dropout rate in the control group did limit the analyses

in this study but fell within the allowable overall rate for our

sample size calculations. However, many members of the control

group who declined to complete their fi nal evaluation noted that

their status had worsened from the starting time in late

September to completion in mid-December and that they did

not want to document their deterioration. Therefore, their inclu-

sion likely would have enhanced the outcome for the interven-

tion group rather than detracted from the results.

CONCLUSION

A 10-week lifestyle program with a diet emphasizing high

fi ber intake (>30 g daily) and <16 g of saturated fat daily (which

are consistent with USDA recommendations) combined with

strength training 2 to 3 times per week, aerobic activity 5 to 6

days per week, and stress management improves multiple mea-

sures of wellness and aging. These enhancements, compared to a

randomized control group, include TC:HDL ratios, VO2 max per-

formance, body fat mass loss, strength gains, and flexibility

gains. This intervention program can also be associated with

gains in cognitive performance.

Although this combination of recommendations requires fur-

ther study, an approach that focuses on implementing a combination

of fi ber, aerobic activity, strength training, and stress management

achieves multiple improvements in wellness and aging.

AcknowledgmentsThis study was funded by St Anthony’s Health Care and conducted at the Carillon Wellness

Center in St Petersburg, Florida.

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Comparison of Calcium Absorption In Healthy Human Adults:

Treatment Groups Supplements No. of Subjects Calcium amino acid chelate (18%) A 15 Dicalcium malate B 15 Calcium amino acid chelate (26%) C 15 Calcium carbonate D 15

Pre-experimental blood samples and physical examination

Study (4 x Calcium Supplements – single dose of 900 mg)

12 hours

0 0.5 2 4 6 9 12

Time in hours

Blood samples are obtained at: 0, 0.5, 2, 4, 6, 9, 12 hours

-7 days

Figure 1.

Table 1.

Table 2.Treatments Time

Point 0 Time Point 0.5

Time Point 2

Time Point 4

Time Point 6

Time Point 9

Time Point 12

Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Supplement

A2.32 0.1 2.32 0.1 2.36 0.11 2.47 0.13 2.44 0.09 2.39 0.09 2.39 0.09

* * * *# *Supplement

B 2.3 0.09 2.29 0.08 2.34 0.09 2.37 0.1 2.4 0.08 2.37 0.09 2.38 0.12

# # # * *+ #

Supplement C

2.3 0.07 2.29 0.08 2.7 0.1 2.38 0.11 2.38 0.1 2.33 0.08 2.36 0.09

$ $ $ #$ * # $

Supplement D

2.38 0.08 2.38 0.1 2.4 0.08 2.45 0.1 2.45 0.1 2.4 0.06 2.43 0.09

* # $ * # $ * # $ * $+ $

The present study was undertaken to compare the bioavailability of calcium after supplementation with four preparations - Calcium AA Chelate (18%; A), Dicalcium malate (B), Calcium AA Chelate (26%; C) and Calcium carbonate (D). After ingestion of a single dose containing 900 mg of elemental calcium, no significant differences were observed in AUC suggesting that bioavailability of all four Supplements is similar. However, there were significant differences between the groups in the maximum concentration (Cmax), time to reach maximum concentration (Tmax) and half-life of elimination. Supplement A showed the maximum increase in serum calcium concentration compared to baseline followed by Supplements B, C and D. Time required to reach the maximum serum concentration was shortest for Supplement D followed by Supplements C, A and B. This suggests that absorption of Supplement D is better compared to the other Supplements. However, the half-life of Supplement D in serum was shortest suggesting that it is cleared from the blood faster than the other Supplements. Supplement B had the longest half-life and seems to be most bioavailable followed by supplement A, C and D. This work was sponsored by Albion Advanced Nutrition.

Abstract

IntroductionAccording to the Osteoporosis Society of Canada, approximately 1.4 million Canadians suffer from osteoporosis (www.osteoporosis.ca). Although more prevalent in older women, older men and younger individuals also get the disease. The cost of treating osteoporosis and the fractures it causes is estimated to be $1.3 billion each year in Canada. Given the increasing proportion of older people in the population over the next few years, these costs, as well as the number of individuals with osteoporosis, will likely rise. Adequate calcium intake is necessary for bone remodeling to take place in healthy individuals. In older adults adequate calcium intake can slow bone loss and lower the risk of fracture (Lin and Lane, 2004). Furthermore, calcium supplementation is an important part of the medical management of osteoporosis in combination with various prescription medications. Calcium bioavailability is important when calcium intakes are low, or when an individual is growing or losing bone (Fairweather-Tait and Teucher, 2002). Calcium absorption is dependent on many dietary and environmental factors, including the level of protein, sodium, caffeine, vitamin D, fructose and phosphorous in the body. Furthermore, one’s genetic makeup, including the vitamin D receptor genotype, may also play a role in calcium absorption (Dawson-Hughes et al., 1995). Supplementation with various calcium preparations is now the most common approach to increase calcium intake in individuals concerned with osteoporosis. However, it has been shown that the bioavailabilities of many commercial calcium preparations are different (Fairweather-Tait and Teucher, 2002). The most common calcium supplement, calcium carbonate, is known to be generally well absorbed but other calcium forms, such as citrate, malate and amino acid chelate, have shown superior efficacy in some studies (Sakhaee et al., 1999, Heaney et al., 1990).

Objective

Methods

The objective of this study was to compare in healthy individuals the bioavailability of calcium from four separate calcium-containing products. This information will increase the overall knowledge of these compounds.

The calcium treatments are identified in the following table:

Individuals were studied for a total of approximately 5 weeks. All subjects were studied as outpatients. The screening process consisted of CBC count, platelets, electrolytes, glucose, BUN, creatinine, liver function tests, total protein, albumin, calcium, phosphorous, PT/PTT, and urinalysis. Women of childbearing age also had a urine pregnancy test. Subjects were asked questions to determine present health and past medical history and underwent a brief physical exam. Those deemed eligible after the screening process were asked to return for the four supplementation days. On the firstsupplementation day, subjects were randomized for receiving the four supplements in a random order. Blood was taken immediately before supplement administration and 0.5, 2, 4, 6, 9 and 12 hours after the dose. Standard low calcium meals, breakfast, lunch and dinner, were provided immediately after the dose, following the 4-h blood sample and following the 9-h blood sample, respectively. Each individual was given 6 capsules containing a total of 900 mg of elemental calcium. This dose of elemental calcium is within the RDI recommended by the United States National Institutes of Health (United States National Institutes of Health 1994. Optimal calcium intake. NIH Consensus Statement, Vol. 12, No. 4. 31 pp.) Each subject returned three more times for supplementation with the identical level of elemental calcium in an alternative form. Each visit was separated by a minimum of 1 week. The identical food was supplied to the subjects on each supplementation day. Blood levels of calcium were determined at each time point. Blood: Peripheral blood was taken by venipuncture prior to baseline to determine overall health. Blood was subsequently taken at 0, 0.5, 2, 4, 6, 9 and 12 hours following each supplementation for measurement of calcium in the blood serum.

The study design is summarized in the following figure:

The data presented in the following table show the changes between the groups in serum calcium concentrations at all the time points after oral supplementation.

It was observed that supplementation with A, B and C elevated the serum calcium levels from baseline. A significant difference from baseline within the Supplement A, B and C-treated groups was observed for all time points except for 0.5 hours. Also in the Supplement B-treated group at 2 hours there was no significant difference from baseline. No Significant difference was observed in the Supplement D-treated group.

Results

Study Outline

The participants, clinical assistants and those assessing the outcome were blinded to the group assignment.

Symbols (*, #, $ and +) represent corresponding groups with statistically significant differences (p<0.05).

Manufacturer-sponsored Poster Board

From Various Calcium-Containing Products A Bioavailability Study

Pratibha Chaturvedi1, Rinee Mukherjee1, Meagan McCorquodale1, Dave Crowley1, Stephen Ashmead2 and Najla Guthrie11KGK Synergize Inc., 2Albion Human Nutrition

Figure 3: Maximum Concentration of Calcium in Serum After

Oral Supplementation

Calcium Supplements

0 1 2 3 4 5

Cm

ax

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Calcium amino acid chelate (18%)Dicalcium malateCalcium amino acid chelate (26%)Calcium Carbonate

Figure 2: Serum Concentration of Calcium At Different Time Points After Supplementation with Different Preparations

Time (hour)

0 2 4 6 8 10 12 14

Seru

m C

alci

um c

once

ntra

tion

(mm

ol/L

)

2.20

2.25

2.30

2.35

2.40

2.45

2.50

Time vs Supplement A Time vs Supplement B Time vs Supplement C Time vs Supplement D

Figure 4: Half Life of Different Calcium Preparations After Absorption

Calcium Supplements0 1 2 3 4 5

Hal

f Life

(Hou

r s)

0

10

20

30

40

50

60

70Calcium amino acid chelate (18%)Dicalcium malateCalcium amino acid chelate (26%)Calcium carbonate

Pratibha ChaturvediKGK Synergise, Inc. Suite 1030, 255 Queens AvenueLondon, ON N6A 5R8Canada(519) 438-9374

Contact InformationStephen D. AshmeadAlbion Advanced Nutrition101 North Main StreetClearfield, Utah 84015USA(801) 773-4631

The results of the pharmacokinetic analysis for serum calcium concentrations demonstrated that the AUC0-12h values were similar for all four Supplements and there was no significant difference.

It was observed that supplementation with different calcium preparations led to different serum concentrations suggesting a difference in absorption. A significantdifference in the maximum concentration of serum calcium (Cmax) was observed between Supplement D and Supplement B groups and also between Supplement D and Supplement C groups (Figure 2)

It was observed that the half-life of elimination was similar for Supplement A and B, but substantially shorter for Supplement D.

In the present study, the pharmacokinetic characteristics and bioavailability of four calcium components were investigated. It was observed that all the supplements had a poor bioavailabiity as suggested by the low values for AUC. This could be due to the elimination of the majority of the supplement after the first pass through the liver. The results demonstrated that an oral administration of Supplement B (900 mg dose) led to more bioavailable calcium compared to the other three supplements.

Remarkably little is known about the relative efficacy of amino acid chelates of calcium. In the only commonly cited trial, absorption was measured for an amino acid chelate called calcium bisglycinate and compared with absorption from citrate, carbonate, and MCHC (Heaney, et al., 1990). In that trial, the amino acid chelate showed the best absorption and MCHC the worst. Although CCM was studied in that trial, it was taken under different circumstances than the chelate (with meals), so drawing definitive conclusions is not possible. In this study, Dicalcium malate was found to be more bioavailable than the amino acid chelate form of calcium with almost similar absorption but with Dicalcium malate having a longer half-life.

The present study was undertaken to compare the bioavailability of calcium after supplementation with four preparations. It was observed that the calcium present in the four Supplements is absorbed and is bioavailable in humans and can be detected in serum after ingestion of a single dose containing 900 mg of elemental calcium.

All the Supplements had a poor bioavailabiity as suggested by the low values for AUC. This is likely due to substantial first-pass elimination. Based on the results of this study, Supplement B seems to be most bioavailable than other Supplements with a longer half-life followed by Supplement A, C and D.

Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calciumsupplementation on bone density in postmenopausal women. N Engl J Med 1990;323:878–83.

Dawson-Hughes B. Calcium absorption on high and low calcium intakes in relation tovitamin D receptor genotype. J Clin Endo Metab, 1995; 80, 3657-3661.

Fairweather-Tait and Teucher, Iron and Calcium Bioavailability of Fortified Foods andDietary Supplements. Nutr. Rev. 2002; 60:360-367.

Heaney RP, Recker RR, Weaver CM. Absorbability of calcium sources: the limited roleof solubility. Calcif Tissue Int 1990;46:300–4.

Heaney RP, Dowell MS, Barger-Lux MJ. Absorption of calcium as the carbonate andcitrate salts, with some observations on method. Osteoporos Int 1999;9:19–23.

Heaney RP. Quantifying human calcium absorption using pharmacokinetic methods. JNutr. 2003;133:1224-6.

Lin JT, Lane JM: Osteoperosis: a review. Clin Orthop 2004;425:126-134.

Sakhaee K, Bhuket T, Adams-Huet B, Rao DS. Meta-analysis of calcium bioavailability:a comparison of calcium citrate with calcium carbonate. Am J Ther.1999;6:313-21.

Discussion

Conclusion

References

Manufacturer-sponsored Poster Board

32 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Naturopathic Care for Chronic Low Back Pain

original research

Patricia M. Herman, ND, PhD (candidate), is a research princi-

pal and graduate student in the Department of Psychology,

University of Arizona, Tucson, Arizona. Orest Szczurko, ND,

MSc (candidate) is a clinical trial coordinator, and Kieran

Cooley, ND, MSc (candidate), is an assistant professor and

research fellow in the Department of Clinical Epidemiology,

Canadian College of Naturopathic Medicine, Toronto,

Ontario, Canada, and both are graduate students in the

Department of Pharmaceutical Sciences, Leslie Dan Faculty

of Pharmacy, University of Toronto. Edward J. Mills, MSc,

PhD, is an assistant professor in the Department of Clinical

Epidemiology, Canadian College of Naturopathic Medicine,

and the Department of Clinical Epidemiology & Biostatistics,

McMaster University, Hamilton, Ontario.

Low back pain poses a major economic burden to society

and to employers.1,2 Back pain is common, and in gen-

eral, prognosis is good, with 60% to 70% of patients

recovering within 6 weeks.3 However, the largest per-

centage of the costs of back pain, including the more

than $28 billion (1998 USD) in productivity losses (which infl ated

to 2007 USD is more than $36 billion), is concentrated in the small

percentage of patients with chronic low back pain.1,4

Conventional treatments for chronic low back pain have been

found to be expensive and ineffective.1,5 Consequently, a signifi cant

number of patients have turned to complementary and alternative

medicine (CAM). One survey of patients eligible for insurance cov-

erage for CAM found that 55% of low back pain patients had at

least 1 visit to a CAM provider in the study year, and 43% used only

CAM for their back pain.6 Whereas chiropractic is the most com-

mon type of CAM used for low back pain,5,6 other CAM therapies

also seem effective.7 In particular, acupuncture has shown promise

as part of a package of care for low back pain.8

This study is an economic evaluation carried out alongside a

pragmatic randomized controlled trial of naturopathic care (includ-

ing acupuncture) vs a standardized physiotherapy education regi-

men for low back pain in a population of warehouse workers.

METHODS

In the trial, workers aged 18 to 65 years with a clinical diagno-

sis of low back pain of at least 6 weeks’ duration and who were not

on sick leave were recruited from a warehouse site of a large North

American corporation. After informed consent, 75 who were eligi-

ble (Figure 1) were randomly assigned (via observed coin toss) to

receive 3 months of 30-minute semi-weekly onsite naturopathic

care visits (acupuncture, exercise and dietary advice, relaxation

training, and a back care educational booklet9,10) or 3 months of

30-minute bi-weekly onsite control group visits (standardized

physiotherapy advice and the back care educational booklet).

COST-EFFECTIVENESS OF NATUROPATHIC CARE FOR CHRONIC LOW BACK PAIN

Patricia M. Herman, ND, PhD (candidate); Orest Szczurko, ND, MSc (candidate); Kieran Cooley, ND, MSc (candidate); Edward J. Mills, MSc, PhD

Objective • To determine the cost-effectiveness of naturopathic

care (acupuncture, relaxation exercises, exercise and dietary

advice, and a back care booklet) compared to standardized phys-

iotherapy education and a back care booklet (control treatment)

for low back pain in a sample (N=70) of warehouse workers.

Design • Economic evaluation based upon the results of a

pragmatic randomized controlled trial to determine the cost-

effectiveness of naturopathic care to society as a whole, to the

employer, and to participants.

Results • Naturopathic care (as compared to the control treat-

ment) signifi cantly improved quality-adjusted life-years over

the 6-month study period (3-month intervention period and

3-month follow-up period) by 0.0256 (95% CI: 0.0075,

0.0437)—roughly equivalent to 9.4 “perfect health” days.

Naturopathic care also signifi cantly reduced societal costs by

$1212 per participant. From the perspective of the employer,

the intervention cost $154 per absentee day avoided (compared

to employer costs of lost productivity of $172 per day) and had

a return on investment of 7.9% under the healthcare coverage

limits set by this employer and assuming the employer paid the

full cost of naturopathic care. Participants experienced savings

in adjunctive care of $1096 per participant.

Conclusions • This economic evaluation alongside a pragmatic

randomized control trial shows naturopathic care to be more

cost-effective than a standardized physiotherapy education

regimen in the treatment of chronic low back pain. Further

studies of the economic impact of naturopathic medicine are

warranted. (Altern Ther Health Med. 2008;14(2):32-39.)

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 33Naturopathic Care for Chronic Low Back Pain

Study participants in both groups were told to continue their usual

pain medications as needed, and this usage was monitored.

Participants’ use of other adjunctive care (chiropractic care, mas-

sage, and physiotherapy) was also monitored but not guided in

any way by the study. The study was approved by the McMaster

University Research Ethics Board, and more detail on the study

design is available in Szczurko et al.11

The cost-effectiveness of naturopathic care over the control

intervention is calculated for 3 perspectives: societal, employer,

and participant. Because the cost-effectiveness of this intervention

to the employer and to participants depends on coverage limits

and the resulting allocation of healthcare costs (both of which can

vary widely across employers), the main perspective for this study

is societal. The effectiveness of the intervention in terms of the

Roland-Morris Disability Questionnaire (RDQ ), the Oswestry

Disability Index (ODI), and a visual analog scale for pain has been

established.11 Here effectiveness for the societal and participants’

perspectives is measured in terms of quality-adjusted life-years

(QALYs) gained over 6 months (3-month treatment period plus

3-month follow-up). The algorithm devised by Brazier et al,12 a sin-

gle index measure of health-related quality of life (HRQoL)—the

SF-6D—is used to calculate QALYs for each participant at baseline,

1 month, 2 months, 3 months, and 6 months from responses to

the SF-36 at each of these time points. Total change in QALYs is

calculated as the area under the SF-6D score curve over the

6-month study period. Cost-effectiveness to the employer is calcu-

lated in terms of cost per day of absenteeism reduced and return

on investment. Given the short time horizon, neither costs nor

effects are discounted.

Absenteeism was not directly measured in this study. However,

because productivity losses are such a large portion of the cost of

low back pain,1 changes in absenteeism are estimated using the

change in the RDQ. A search of the literature revealed several recent

randomized controlled trials of various interventions for low back

pain that measured both days lost from work and the RDQ. A study

by Moffett et al13 proved the best match in terms of average baseline

RDQ levels (6.65 for the treatment group and 5.56 for controls), the

intervention tested (exercise classes added to routine general practi-

tioner care), and sample size (N=183). This study also provided the

most conservative estimate of absentee days reduced per 1-point

reduction (improvement) in the RDQ of 2.32 days per 1-point

reduction in the RDQ maintained over 1 year.

Costs are reported in 2005 US dollars. The patients themselves

reported their use of back pain–related adjunctive care at baseline,

1 month, 2 months, 3 months, and 6 months via 1-week diaries.14

Unfortunately, the unit cost of each type of adjunctive care was not

recorded, and published sources of these costs (other than medica-

tion costs) are sparse. Therefore, the unit costs and resource use are

reported separately to enable decision makers facing different costs

to adjust the study’s results. As shown in Table 1, the best available

source for unit price data for naturopathic care, massage, and phys-

iotherapy was the national association for each type of practice.

Published sources were available to value chiropractic care,15 over-

the-counter and prescription drugs, and productivity losses.16

Published guidelines for the treatment of low back pain gener-

ally consist of patient education and reassurance, discouragement

Screened

for eligibility

(n=84)

Not randomized

(n=9)

Not able to commit time (n=3)No pain at assessment (n=2)

Pregnant (n=2)

Previous spinal surgery (n=1)

Too late in accepting

enrollment (n=1)

Randomized after

informed consent

(n=75)

Control (n=36)

Naturopathic care

(n=39)

Month 1 (n=39)

Month 2 (n=39)

Month 3 (n=37)

Month 1 (n=28)

Month 2 (n=26)

Month 3 (n=23)

Some data (n=31)

Follow-up

Month 6 (n=32)

Follow-up

Month 6 (n=8)

Crossover

Month 4

(n=13)

Dropped

out (n=5)

Dissatisfaction

with care (n=2)

Unable to commit

time (n=3)

FIGURE 1 Flowchart of Subjects Through the Randomized Controlled Trial

34 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Naturopathic Care for Chronic Low Back Pain

of bed rest and recommendations for a gradual increase in activity,

referral for exercise therapy (especially for chronic low back pain),

and pain medication.17 Participants on prescription medications

were assumed to manage those with their regular conventional phy-

sician. Visits to conventional physicians for prescription manage-

ment or for non–back pain-related conditions were not assumed to

vary between groups and were not tracked. The study naturopathic

physicians provided both the naturopathic and control group care.

In the real world, low back pain patients would not likely seek out

naturopathic physicians to obtain physiotherapy advice at the exclu-

sion of other naturopathic care. Therefore, the time the control

group spent with the naturopathic physicians is valued at the cost of

a physiotherapy visit. To account for the protocol-related time spent

by both groups (informed consent and data collection), only half of

the 1-hour screening visit (where histories were taken and initial

exams performed) will be counted and a total of 45 minutes (15

minutes per data collection cycle times 3 cycles) will be subtracted

from practitioner time for each group.

This analysis follows an intent-to-treat principle for partici-

pants who received at least 1 treatment, and missing data are han-

dled using carry-forward imputation. Because the distribution of

cost data tends to be highly skewed, bias-corrected and accelerated

bootstrap estimates are used to determine confi dence intervals for

mean differences in costs (1000 replications).18 The bootstrapped

societal cost-QALY pairs are also graphically represented on a cost-

effectiveness plane.19

Uncertainty in an economic evaluation comes not just from

sample variation, but also from the assumptions made that can

affect generalizability.20 In order to test the robustness of study

results, a univariate sensitivity analysis is conducted. The use of

each resource is varied over its 95% confi dence interval range (Table

2), and in the absence of better data, the unit price of each resource

shown in Table 1 is varied from 50% to 150% its value. In discus-

sions with practitioners, these ranges are possible, especially if they

are allowed to also capture variation in the length and intensity of

each visit. The absenteeism estimate has 3 sources of uncertainty:

labor costs, RDQ scores, and the change in absentee days for each

point change in RDQ. Labor costs will be varied the same way

other unit costs are varied, and RDQ scores are varied over their

95% confidence interval. The change in absentee days for each

point change in RDQ is varied from a low of 0 days per RDQ point

(essentially setting absenteeism to 0) to the higher rate seen in

Kovacs et al21 of 3.59 days per 1-point change in the RDQ. All calcu-

lations are made using Microsoft Excel 2003 SP1 (Microsoft

Corporation, Redmond, Washington).

RESULTS

The 75 workers were randomized to naturopathic care

(n=39) or to a standardized physiotherapy education regimen

(control group care; n=36). Overall, 68 patients (91%) had use-

able data for the 12-week treatment period, and 32 (82%) of the

naturopathic care group and 8 (22%) of the control group had

week 26 follow-up data (Figure 1). The primary reason why the

response rate for the control group at week 26 is so low is because

both groups were offered the opportunity to receive crossover

care for 4 weeks after the treatment period ended (between week

12 and week 16) as an incentive for retention during the treat-

ment period. Thirteen of the control group participants elected

to receive crossover naturopathic treatment and were no longer

able to represent control group outcomes at follow-up. No partic-

ipants in the naturopathic care group elected to receive crossover

control group care. At baseline, minor differences in characteris-

tics are seen between the full treatment and control groups (Table

3). Baseline characteristics for the control group participants

with available 6-month data are also shown in Table 3 to aid in

the interpretation of that portion of the sensitivity analysis,

which is discussed below.

Resource use for the study treatments (net of protocol-related

hours), adjunctive care visits and medication, and estimated

absenteeism days (all net of baseline) are reported in Table 2.

TABLE 1 Unit Prices and Sources for Each Resource Valued

Resource Unit price (USD) Source

Naturopathic visit (per hour) $125.00 Based on a range of $100 to $150 per hour reported via e-mail by

American Association of Naturopathic Physicians staff

Chiropractic visit (per visit) $60.70 Overall average cost of a visit from Segall (2004)15

Massage visit (per visit, assuming a 1-hour visit) $55.00 Based on a range of $50 to $60 per hour reported via e-mail by American

Medical Massage Association staff

Physiotherapy visit (per visit, assuming a 30-minute visit) $61.20 Based on the Canadian Physiotherapy Association’s recommended fee for

private practice of $37.50 CAD per 15 minutes translated to US dollars

using an exchange rate of 1.2254 CAD per USD

Medication costs Varies Medi-Span Master Drug Database* and drugstore.com†

Lost productivity (per hour, assumes productivity value to

employer equals employer outlay for that employee)

$21.44 Employer cost for employee compensation—production, transportation,

and material moving from Bureau of Labor Statistics (2005)18

*Costs according to Medi-Span Master Drug Database (MDDB) v2.5; accessed August 2006.†Costs according to www.drugstore.com; accessed October 2006.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 35Naturopathic Care for Chronic Low Back Pain

TABLE 3 Baseline Characteristics of Patients With at Least One Data Collection Point After Treatment Began and for the Control Group

Participants With Data Available at 6-month Follow-up*

Outcome measure Naturopathic care (n=39) Control (n=31)

Control group participants with

6-month follow-up data (n=8)

Age in years, mean (SD) 45.3 (7.46) 48.2 (8.13) 43.1 (8.84)

Female, number (%) 22 (56) 13 (42) 3 (38)

Work type/shift, number (%)

Day

Afternoon

Night

Package delivery

Truck driver

Sales representative

19 (49)

5 (13)

5 (13)

8 (21)

2 (5)

0 (0)

10 (32)

7 (23)

9 (29)

2 (6)

1 (3)

2 (6)

4 (50)

1 (13)

2 (25)

1 (13)

0 (0)

0 (0)

Roland-Morris Disability Questionnaire Score 8.1 (6.09) 5.4 (3.51) 3.6 (3.20)

Oswestry Disability Index Score 11.9 (8.12) 11.4 (7.70) 8.25 (7.70)

Baseline quality-adjusted life-year 0.70 (0.105) 0.71 (0.102) 0.74 (0.111)

Adjunctive care, visits/week Mean (SD); median (range):

Chiropractic

Massage

Physiotherapy

Pain medication cost/week

0.43 (1.03), 0.0 (0.0 - 4.0)

0.15 (0.32); 0.0 (0.0 - 1.0)

0.28 (0.94); 0.0 (0.0 - 5.0)

$2.72 (4.48);

$0.63 ($0.00 - $19.76)

0.06 (0.16); 0.0 (0.0 - 0.5)

0.17 (0.41); 0.0 (0.0 - 1.5)

0.32 (0.78); 0.0 (0.0 - 3.0)

$18.04 (64.63);

$0.00 ($0.00 - $274.12)

0.03 (0.09); 0.0 (0.0 - 0.3)

0.13 (0.35); 0.0 (0.0 - 1.0)

0.25 (0.46); 0.0 (0.0 - 1.0)

$34.49 (96.82);

$0.00 ($0.00 - $274.12)

*Mean (SD) unless otherwise indicated.

TABLE 2 Average Use of Resources Net of Baseline Use and Health-related Quality of Life (SF-6D)

Resource Naturopathic care (n=39) Control (n=31) Difference

Study treatment 30-minute visits (net of protocol-specifi c hours) 23.5 5.5

Adjunctive care over 6 months Mean (Bootstrap BCa 95% CI)*

Chiropractic visits -6.7 (-14.6, -2.3) 3.2 (0.9, 7.6) -9.9 (-18.5, -4.8)

Massage visits -2.9 (-5.7, -1.4) 2.6 (-0.4, 8.8) -5.5 (-12.3, -2.1)

Physiotherapist visits -3.6 (-10.3, 0.0) 1.6 (-3.7, 10.0) -5.2 (-15.4, 1.5)

Pain medication costs† -$52 (-$84, -$32) -$72 (-$277, -$3.5) $20 (-$53, $219)

Estimated absenteeism days -4.8 (-6.2, -3.6) 1.9 (0.9, 3.1) -6.7 (-8.6, -5.0)

Health-related quality of life (SF-6D, score out of 100) Mean (SD)

Baseline 69.7 (10.5) 70.7 (10.2)

1 month 74.2 (8.2) 72.9 (11.4)

2 months 76.4 (9.2) 71.8 (10.2)

3 months 76.9 (11.7) 70.8 (9.5)

6 months 75.9 (11.0) 71.4 (9.6)

*BCa 95% CI indicates bias corrected and accelerated 95% confi dence interval.†Average medication costs rather than pill counts are reported here because of the wide variety of over-the-counter and prescription medications used.

36 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2

Naturopathic care participants tended to reduce adjunctive care

use and have reduced absenteeism. Conversely, control group

participants tended to increase adjunctive care (except for medi-

cations) and have slightly increased absenteeism. No participant

reported adjunctive use of acupuncture. Table 2 also reports

HRQoL as measured by the SF-6D. The naturopathic care group

experienced a statistically signifi cant (P=.006) increase in QALYs

over the 6-month study period, but the control group did not

(Table 3). The difference between groups in QALY gains was sta-

tistically signifi cant (P=.036). The estimated mean health gain is

0.0256 QALYs, which is equivalent to 9.4 “perfect health” days or

to taking average participants’ health (measured by the SF-6D as

approximately 70% health at baseline, Table 2) to “perfect health”

for 31 days over the 6-month period.

The mean incremental cost to society of naturopathic care is

estimated to be -$1212 (a net savings of $1212) per participant

(Table 4). Figure 2 shows the cost-utility plane for the societal

perspective. The graph represents 1000 bootstrap replications of

the relationship between incremental societal costs and incre-

mental QALY gains. All cost-effect pairs (100%) are in the bottom

right quadrant, suggesting that naturopathic care is dominant

over the control treatment (a standardized physiotherapy educa-

tion regimen)—that is, the use of naturopathic care instead of

the control treatment is associated with both an improvement in

HRQoL and lower costs. Under these assumptions and in this

population, naturopathic care is a cost-effective alternative to

standardized physiotherapy education.

As discussed previously, the portion of these savings that

accrues to the employer (through reductions in medical costs, if

self-insured, and productivity losses avoided) and the portion

that accrues to participants (through out-of-pocket costs avoid-

ed) depend upon the coverage limits specifi ed. Table 4 reports

the breakdown of adjunctive care costs between the employer

and the participant based on employer coverage of 80% of costs

up to $400 annually for chiropractic care and massage and up to

$1000 for physiotherapy. Medications were covered by this

employer at various rates from 0% to 80% with no maximum.

Under these assumptions, the majority of the savings due to

reductions in adjunctive care accrue to participants as reductions

in their out-of-pocket costs.

The other cost that must be allocated before cost-effectiveness

to the employer and to the participant can be determined is the

cost of treatment. In this study participants in both groups

received their treatment at no cost. The employer covered all

Naturopathic Care for Chronic Low Back Pain

TABLE 4 Costs (Net of Baseline) and Quality-adjusted Life-years*

Costs Naturopathic care (n=39) Control (n=31) Difference (Bootstrap BCa 95% CI)†

Study treatment costs $1469 $337 $1132

Adjunctive care costs:

Chiropractic visit costs -$406 ($1146) $196 ($561) -$603 (-$1122, -$292)

Massage visit costs -$161 ($350) $142 ($654) -$303 (-$677, -$116)

Physiotherapist visit costs -$221 ($956) $97 ($1146) -$318 (-$943, $92)

Pain medication costs -$52 ($82) -$72 ($355) $20 (-$53, $219)

Total adjunctive care costs -$840 ($1828) $363 ($1272) -$1203 (-$2097, -$592)

Estimated productivity loss -$817 ($758) $324 ($541) -$1141 (-$1470, -$866)

Total Societal Costs -$188 ($1977) $1024 ($1456) -$1212 (-$2169, -$533)

Adjunctive costs paid by the participant -$857 ($1783) $239 ($1022) -$1096 (-$1959, -$575)

Adjunctive costs paid by the employer $17 ($169) $124 ($430) -$107 (-$264, $55)

Quality-adjusted life-years 0.0293 (0.0409) 0.0036 (0.0332) 0.0256 (0.0075, 0.0437)‡

*Mean (SD) unless otherwise indicated.†BCa 95% CI indicates bias corrected and accelerated 95% confi dence interval.‡95% standard error–based confi dence interval.

$500

$0

-$500

-$1000

-$1500

-$2000

-$2500

-$3000-0.01 0.01 0.03 0.05 0.07

Incr

emen

tal C

ost

s

Incremental QALYs

FIGURE 2 Cost Effectiveness Plane for Societal Costs and Quality-adjusted

Life-year (QALY) Gains for Naturopathic Care Compared to the Control

Treatment (a standardized physiotherapy regimen) Over 6 Months

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 37Naturopathic Care for Chronic Low Back Pain

TABLE 5 Sensitivity Analysis*

Sensitivity analysis scenarios Naturopathic care (n=39) Control (n=31) Difference (Bootstrap BCa 95% CI)†

Absenteeism excluded $629 ($1828) $700 ($1272) -$71 (-$965, $540)

Absenteeism at higher rate -$635 ($2170) $1202 ($1625) -$1836 (-$2886, -$1058)

Analysis using only those participants that reported 6-month data‡

Total societal costs -$192 ($2135) $666 ($1652) -$858 (-$2564, $123)

Quality-adjusted life-years (QALYs) 0.0263 (0.0434) 0.0110 (0.0348) 0.0153 (-0.0182, 0.0488)§

*Mean (SD) unless otherwise indicated.†BCa 95% CI indicates bias corrected and accelerated 95% confi dence interval.‡Naturopathic care (n=32), control (n=8).§95% standard error–based confi dence interval.

study costs. Free onsite naturopathic treatment may not neces-

sarily be continued, however, and it should be noted that some of

the attractiveness to participants of naturopathic care on this

study (possibly affecting retention and outcomes) may have been

due to its accessibility and lack of cost.

Assuming that the employer pays all costs of treatment,

naturopathic care is cost-effective for participants, with savings

in out-of-pocket adjunctive care costs of $1096 and an increase in

QALYs of 0.0256. Employer costs of $1025 ($1132 less $107,

assuming the employer would also have paid for the control

treatment) are compared to a net reduction in absenteeism days

of 6.7 (95% CI: -4.8, -8.6) for an incremental cost-effectiveness

ratio for the employer of $154 per absentee day avoided. If

employer costs per absentee day are $172 ($21.44 per hour times

8 hours) as assumed in this analysis, then under the assumptions

of this study, offering naturopathic care is a cost-effective alterna-

tive to standardized physiotherapy education to employers.

Comparing an investment of $1469 for naturopathic care per

participant to a return of $1585 ($337 + $107 + $1141) gives a

return on investment over the 6 months of 7.9%.

Sensitivity analyses indicate that the incremental societal

cost savings shown in this study are robust to widely differing cost

and resource use assumptions. Varying each resource use category

across its 95% confi dence interval range and varying unit prices

from 50% to 150% in all cases generated incremental societal cost

savings. The largest changes in societal costs came from varying

the cost of the naturopathic care visits (incremental societal costs

ranged from -$1948 to -$479), varying labor costs (incremental

societal costs ranged from -$1784 to -$643), and varying the num-

ber of adjunctive care physiotherapy visits (incremental societal

costs ranged from -$1838 to -$803). However, if absenteeism costs

(productivity losses) are not counted or realized, incremental

societal cost savings drop to near 0 (Table 5). Nevertheless, natur-

opathic care would still be considered to be the cost-effective

alternative even at 0 incremental societal costs as long as its net

increase in health benefi ts (QALYs) remains.

Because of the large number of unavailable data for the con-

trol group, mainly at the 6-month follow-up, total societal costs

and QALY gains were calculated including only those partici-

pants who did not take the crossover naturopathic treatment

option and who reported 6-month data. Comparing results for

the naturopathic care group in Table 5 to those shown in Table 4,

as expected due to the small number of this group lost to follow-

up, there is not much change in their total societal costs (an aver-

age of -$192 for those reporting 6-month data compared to -$188

for the full sample) or QALYs (an average of 0.0263 for those

reporting 6-month data compared to 0.0293 for the full sample).

It seems that those in the naturopathic group who did not pro-

vide 6-month data were doing somewhat better health-wise

(QALYs, when they are included, are higher) and were almost

identical on costs to those who provided data. The control group

participants who took crossover naturopathic treatment and/or

who did not provide 6-month data were doing worse health-wise

(average QALYs decrease from 0.0110 to 0.0036 when they are

included) and had higher costs (average societal costs increase

from $666 to $1024 when they are included) than those who did

not cross over but did provide 6-month data. Therefore, those

lost to 6-month follow-up in the naturopathic group were doing

better than average and those lost to 6-month follow-up in the

control group were doing worse than average in terms of both

HRQoL and costs. Control group participants who did not take

crossover care and did provide 6-month data also were in better

health at baseline than control participants who opted for cross-

over naturopathic care (Table 3).

DISCUSSION

Naturopathic care for the treatment of chronic low back

pain in this population of warehouse workers is a cost-effective

alternative to a standardized physiotherapy education regimen

from a societal perspective. Naturopathic care resulted in signifi -

cantly lower societal costs and signifi cantly better HRQoL than

the control treatment over the 3-month treatment period and

3-month follow-up. Naturopathic care was also cost-effective to

the employer and participants under the coverage assumptions

used in this study.

This is the fi rst economic evaluation of naturopathic medi-

cine and one of the fi rst of a package of care including comple-

mentary and alternative medicine therapies.22 Naturopathic

38 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Naturopathic Care for Chronic Low Back Pain

medicine is practiced as a system of medicine, not as individual

therapies.23 Therefore, it is appropriate that multiple therapies

(here acupuncture, exercise and dietary advice, relaxation train-

ing, and a back care education booklet) applied by trained natur-

opathic physicians be included in an evaluation of naturopathic

medicine. However, this study falls short of an evaluation of the

system of naturopathic medicine in that the physicians were

restricted to these modalities in their treatment of patients.24

Although this study followed published guidelines for eco-

nomic evaluations,25-27 it is not without limitations, and as with

any economic evaluation, the generalizability of the results

depends on the assumptions made. For example, there are a num-

ber of factors that could improve the cost-effectiveness of natur-

opathic care for low back pain offered in other settings. This study

did not measure “presenteeism” (productivity at work) impacts,

which could signifi cantly increase the savings in productivity due

to the intervention. In one study, workers who reported chronic

back or neck disorders as their primary condition also reported

an average reduction of 21.7% over the last month in their at-work

productivity.28 Similarly, if reductions in lost leisure time follow

the same pattern as work-related productivity losses, the inclusion

of the value of quality leisure time regained would also increase

cost-effectiveness. The duration of the intervention also could be

shortened to reduce intervention costs. A recently completed

growth curve analysis of the trial data indicates that although a

3-month intervention period was used in this study, the full

health benefits of the intervention could be achieved after 2

months, and the health benefi ts of naturopathic care are main-

tained at a constant level for the duration of the 3-month follow-

up (Herman and Sechrest, in preparation). If impacts continue

past 6 months, cost-effectiveness analyses taking this longer peri-

od of benefi ts into account would show an even greater increase

in health benefi ts in terms of QALYs.

There are also a number of factors that could reduce the cost-

effectiveness of naturopathic care. Because this study used an

onsite clinic to provide care during work hours, there were no

travel, time-off-work, or child-care costs for visits. Inclusion of

these costs would likely decrease cost-effectiveness. The same 2

naturopathic physicians offered both the naturopathic care and

control group treatment. It is possible that they unconsciously

negatively biased the results of the control group. Lack of blinding

also may have negatively biased the results of the control group,

especially since this was a sample of workers who volunteered for

a study of naturopathic care, albeit with the forewarning that they

may not be randomized to the naturopathic care group.

Participants seemed to show a strong preference for naturopathic

care—all immediate post-randomization dropouts were from the

control group, and 42% of those remaining at 3 months took

advantage of the offer of crossover naturopathic care. Retention in

the naturopathic care group was excellent (82% at 6-month follow-

up), and the participants who left the study, possibly due to time

constraints, tended to be those with the better health outcomes.

In the control group the non-completers and those taking advan-

tage of the crossover tended to be those with worse health out-

comes. A pre-randomization measure of patient preferences may

have provided some insight into these results.

Other limitations include the small sample size, the unavoid-

able reduction in follow-up data for the control group due to the

popularity of the naturopathic care crossover offer, the lack of a

direct measure of absenteeism, and the limits on generalizability

that come from recruiting all participants from 1 worksite.

CONCLUSIONS

This economic evaluation alongside a pragmatic randomized

control trial shows naturopathic care to be more cost-effective than

a standardized physiotherapy education regimen in the treatment

of chronic low back pain from the societal, employer, and partici-

pant perspectives. Further studies of the economic impact of

naturopathic medicine are warranted, especially those that address

the limitations of this study.

AcknowledgmentsThis publication was made possible by Grant Number F32 AT003363 from the National

Center for Complementary and Alternative Medicine (NCCAM). Its contents are solely the

responsibility of the authors and do not necessarily represent the offi cial views of the NCCAM

or the National Institutes of Health. Patricia Herman would like to acknowledge Drs Lee

Sechrest of the University of Arizona and Ben Craig of the University of Wisconsin, Madison,

for their invaluable guidance and support on this project.

REFERENCES1. Maetzel A, Li L. The economic burden of low back pain: a review of studies published

between 1996 and 2001. Best Pract Res Clin Rheumatol. 2002;16(1):23-30.2. Goetzel RZ, Hawkins K, Ozminkowski RJ, Wang S. The health and productivity cost

burden of the “top 10” physical and mental health conditions affecting six large U.S. employers in 1999. J Occup Environ Med. 2003;45(1):5-14.

3. Andersson GB. Epidemiological features of chronic low-back pain. Lancet. 1999;354(9178):581-585.

4. Rizzo JA, Abbott TA 3rd, Berger ML. The labor productivity effects of chronic backache in the United States. Med Care. 1998;36(10):1471-1488.

5. Waddell G. Low back pain: a twentieth century health care enigma. Spine. 1996;21(24):2820-2825.

6. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. St. John’s wort for depression—an overview and meta-analysis of randomised clinical trials. BMJ. 1996;313(7052):253-258.

7. van Tulder MW, Furlan AD, Gagnier JJ. Complementary and alternative therapies for low back pain. Best Pract Res Clin Rheumatol. 2005;19(4):639-654.

8. Furlan AD, van Tulder MW, Cherkin DC, et al. Acupuncture and dry-needling for low back pain. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001351.

9. Frost H, Lamb SE, Doll HA, Carver PT, Stewart-Brown S. Randomised controlled trial of physiotherapy compared with advice for low back pain. BMJ. 2004;329(7468):708.

10. Professors of General Practice O, Physiotherapy, Ergonomics, and Psychology. The Back Book. 2nd ed. London: Stationary Offi ce; 2002.

11. Szczurko O, Cooley K, Busse JW, et al. Naturopathic care for chronic low back pain: a randomized trial. PLoS ONE. 2007;2(9):e919.

12. Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ. 2002;21(2):271-292.

13. Moffett JK, Torgerson D, Bell-Syer S, et al. Randomised controlled trial of exercise for low back pain: clinical outcomes, costs, and preferences. BMJ. 1999;319(7205):279-283.

14. Goossens ME, Rutten-van Mölken MP, Vlaeyen JW, van der Linden SM. The cost diary: a method to measure direct and indirect costs in cost-effectiveness research. J Clin Epidemiol. 2000;53(7):688-695.

15. Segall L. How do your fees compare? Chiropractic Econ. 2004;50(13):23-32. 16. US Department of Labor. Bureau of Labor Statistics. Employer costs for employee com-

pensation--September 2005. Washington, DC: US Department of Labor; 2005. 17. Koes BW, van Tulder MW, Ostelo R, Burton AK, Waddell G. Clinical guidelines for the

management of low back pain in primary care. Spine. 2001;26(22):2504-2513; discus-sion 2513-2514.

18. Thompson SG, Barber JA. How should cost data in pragmatic randomised trials be analysed? BMJ. 2000;320(7243):1197-1200.

19. Drummond MF, O’Brien BJ, Stoddart GL, Torrance GW. Methods for the Economic Evaluation of Health Care Programmes. 2nd ed. Oxford, UK: Oxford University Press; 1997.

20. Briggs A. Economics notes: handling uncertainty in economic evaluation. BMJ. 1999;319(7202):120.

21. Kovacs FM, Llobera J, Abraira V, et al. Effectiveness and cost-effectiveness analysis of

Naturopathic Care for Chronic Low Back Pain

neurorefl exotherapy for subacute and chronic low back pain in routine general practice: a cluster randomized, controlled trial. Spine. 2002;27(11):1149-1159.

22. Herman PM, Craig BM, Caspi O. Is comple-mentary and alternative medicine (CAM) cost-effective? A systematic review. BMC Complement Altern Med. 2005 Jun 2;5:11.

23. National Institutes for Health. National Center for Complementary and Alternative Medicine. What is complementary and alternative medi-cine (CAM)? Available at: http://nccam.nih.gov/health/whatiscam/. Accessed December 18, 2007.

24. Herman PM, Sherman KJ, Erro JH, Cherkin DC, Milliman B, Adams LA. A method for describing and evaluating naturopathic whole p r a c t i c e . A l t e r n T h e r He a l t h M e d . 2006;12(4):20-28.

25. Drummond MF, Davies, L. Economic analysis alongside clinical trials. Revisiting methodolog-ical issues. Int J Technol Assess Health Care. 1991;7(4):561-573.

26. Korthals-de Bos I, van Tulder M, van Dieten H, Bouter L. Economic evaluations and random-ized trials in spinal disorders: principles and methods. Spine. 2004;29(4):442-448.

27. Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic sub-missions to the BMJ. The BMJ Economic E v a l u a t i o n Wo r k i n g P a r t y . B M J . 1996;313(7052):275-283.

28. Collins JJ, Baase CM, Sharda CE, et al. The assessment of chronic health conditions on work performance, absence, and total econom-ic impact for employers. J Occup Environ Med. 2005;47(6):547-557.

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40 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Discerning the Mauve Factor, Part 1

Woody R. McGinnis, MD, directs the Oxidative Stress in

Autism Study, Auckland, New Zealand. Tapan Audhya, PhD,

is a research professor of Endocrinology at New York

University School of Medicine. William J. Walsh, PhD, is

director of research at Pfeiffer Treatment Center, Warrenville,

Illinois. James A. Jackson, PhD, is a retired professor of medi-

cal technology, Wichita Kansas. John McLaren-Howard, DSc,

FACN, is director of BioLab Medical Unit, London. Allen

Lewis, MD, is medical director, Pfeiffer Treatment Center.

Peter H. Lauda, MD, is medical director, Diagnostic and

Therapy Center, Vienna, Austria. Douglas M. Bibus, PhD, is

director of Lipid Technologies, Austin, Minnesota, and a fac-

ulty member at the Center for Spirituality and Healing,

University of Minnesota, Minneapolis. Frances Jurnak, PhD,

is a professor of physiology and biophysics, University of

California School of Medicine, Irvine. Roman Lietha, MD, is

medical director of the Institute for Applied Biology,

Rapperswil, Switzerland. Abram Hoffer, MD, PhD, is presi-

dent emeritus of the International Schizophrenia Foundation

and founder and editor in chief of the Journal of

Orthomolecular Medicine, Victoria, British Columbia.

DisclosureThe following authors affi liate with commercial laboratories that perform HPL assay: Audhya

(Vitamin Diagnostics, Inc, Cliffwood Beach, New Jersey); Jackson (Bio-Center Laboratory,

Wichita, Kansas); and McLaren-Howard (Biolab Medical Unit, London).

Editor’s note: The following is part 1 of a 2-part article. Part 2 will

appear in the May/Jun 2008 issue of Alternative Therapies in

Health and Medicine.

“Mauve Factor,” or “Mauve” (mōv) for brevity, first was

detected in the urine of psychiatric patients by the Hoffer group in

19581-4 and named for its appearance on paper chromatograms.

Irvine extracted the compound from urine,1,5 correctly assigned the

structure to the pyrrole family,1,6 and conferred the common

name.1 Early technology permitted only qualitative assay.2,6-8

Hoffer observed that recovery from acute schizophrenia asso-

ciated with disappearance of Mauve from the urine, regression

with reappearance.2,4,7 Large doses of vitamin B3 suppressed Mauve

in schizophrenics.6,7,9 Pfeiffer reported superior clinical results with

combined vitamin B6 and zinc, which suppressed Mauve and

improved symptoms in many neurobehavioral disorders.10-17

The Pfeiffer group introduced a colorimetric quantitative

assay for Mauve,18 which utilizes kryptopyrrole (KP) as standard.

Structural similarity affords the use of KP as standard for HPL

assay, but the 2 molecules are distinct (Figure 1). Mauve was iden-

tifi ed mistakenly as KP by Irvine in a high-profi le scientifi c journal

in 196919 and again by Sohler in 1970.20 A fl urry of research on the

experimental effects of KP eventuated.3,10,21-33 Improved technology

demonstrated that KP is not found in human urine,34,35 and Mauve

was identifi ed indisputably by synthesis as HPL.36-41

“HPL” and “Mauve” are used synonymously in this article and

REVIEW ARTICLE

DISCERNING THE MAUVE FACTOR, PART 1Woody R. McGinnis, MD, Tapan Audhya, PhD, William J. Walsh, PhD; James A. Jackson, PhD; John McLaren-Howard, DSc, FACN;

Allen Lewis, MD; Peter H. Lauda, MD; Douglas M. Bibus, PhD; Frances Jurnak, PhD; Roman Lietha, MD; Abram Hoffer, MD, PhD

“Mauve Factor” was once mistaken for kryptopyrrole but is the

hydroxylactam of hemopyrrole, hydroxyhemopyrrolin-2-one

(HPL). Treatment with nutrients—particularly vitamin B6 and

zinc—reduces urinary excretion of HPL and improves diverse

neurobehavioral symptoms in subjects with elevated urinary HPL.

Heightened HPL excretion classically associates with emotional

stress, which in turn is known to associate with oxidative stress. For

this review, markers for nutritional status and for oxidative stress

were examined in relationship to urinary HPL.

In cohorts with mixed diagnoses, 24-hour urinary HPL cor-

related negatively with vitamin B6 activity and zinc concentra-

tion in red cells (P<.0001). Above-normal HPL excretion

corresponded to subnormal vitamin B6 activity and subnormal

zinc with remarkable consistency. HPL correlated inversely with

plasma glutathione and red-cell catalase, and correlated directly

with plasma nitric oxide (P<.0001). Thus, besides implying pro-

portionate needs for vitamin B6 and zinc, HPL is a promising

biomarker for oxidative stress. HPL is known to cause non-

erythroid heme depression, which lowers zinc, increases nitric

oxide, and increases oxidative stress.

Administration of prednisone reportedly provoked HPL

excretion in animals. Since adrenocorticoid (and catecholamine)

stress hormones mediate intestinal permeability, urinary HPL was

examined in relationship to urinary indicans, presumptive marker

for intestinal permeability. Urinary HPL associated with higher

levels of indicans (P<.0001). Antibiotics reportedly reduce HPL in

urine, suggesting an enterobic role in production. Potentially, gut

is a reservoir for HPL or its precursor, and stress-related changes in

intestinal permeability mediate systemic and urinary concentra-

tions. (Altern Ther Health Med. 2008;14(2):40-50.)

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 41Discerning the Mauve Factor, Part 1

for clarity may be substituted for erroneous use of “kryptopyrrole”

in older documents. “High-Mauve” denotes subjects or groups

with elevated HPL or with a tendency to excrete excess HPL.

“Pyrroluria” lacks specifi city, as many pyrroles appear in urine.

HPL is unstable outside the body, readily interconverting

with other structures.19,39,42-45 Exposure to light or to seemingly

mild chemical treatments reduces detectable HPL,8,19,39 which also

is acid labile44 (a study that unadvisedly used hydrochloric acid to

preserve urine failed to detect HPL in schizophrenia,46 a condi-

tion well known for HPL elevation). Graham reported the half-

life of HPL in urine at room temperature to be 10 to 12 hours,

although the extent of light exposure was unspecifi ed.39

Addition of ascorbate preservative and protection from

light and heat maximize detection of HPL. Besides light-shield-

ing transport tubes, one laboratory (Vitamin Diagnostics,

Cliffwood Beach, New Jersey) recommends urine collection

under dim light and employs darkroom assay conditions. If

assay for HPL cannot be performed immediately, overnight

shipment and/or freezing of the urine sample are required by all

North American laboratories surveyed for this review. Gorchein

found that freezing to -8º C stabilized HPL in urine for up to 4

months.47 Re-freezing of thawed specimens diminishes detect-

able HPL (Ellen Hanson, Laboratory Superviser, Direct Health

Care Access II Laboratory, Inc, Mount Prospect, Illinois; oral

communication, September 2006).

KP is readily oxidized,39,48 so laboratories take special pre-

cautions to maintain purity of KP used for colorimetric HPL

assay. Occasionally, the colorimetric assay is invalidated by the

presence of other Ehrlich-reactive compounds which produce

spectrophotometric interference at 540 nm. Urobilinogen is the

most common offender.18,49 Others reportedly include hemoglo-

bin, bilirubin, and mendelamine (oral communication,

September 2006, from Irwin Sommerfeld, Laboratory Director

of Direct Health Care Access II Laboratory).

VALIDATION OF THE COLORIMETRIC ASSAY FOR

URINARY HPL

HPL assay utilizing high-pressure liquid chromatography/

mass spectroscopy (HPLC/MS) and synthetic HPL standard is

highly sensitive and specifi c. In a comparison of split-urine samples

by Vitamin Diagnostics Laboratory, the simpler colorimetric assay

for HPL correlated very highly with HPLC/MS (r=0.98; P<.0001)

(Figure 2). It should be noted that absolute HPL values varied on

the 2 assays. The normal range for colorimetric assay was <15 μg/

dL, but for MS/HPLC, normal was <25 μg/dL. The latter compares

favorably with Graham’s normal range of <26 μg/dL utilizing gas-

liquid chromatography and synthetic HPL standard.39

EFFECTS OF VARIABLE HYDRATION ON HPL

CONCENTRATION

Normalization of values to urinary specifi c gravity (SG)50 or

creatinine corrects for variable hydration. Pfeiffer encouraged

normalization of the colorimetric assay to SG in his later years,

according to Tapan Audhya, PhD (oral communication, June

2006). Examination of results from 600 colorimetric assays from

the BioCenter Laboratory in Wichita, Kansas, revealed that 20%

of HPL values moved into or out of the normal range after adjust-

ment to SG by refractometry. Examination of data from the

Biocenter Laboratory and from the Direct Health Care Access II

Laboratory revealed that normalization affects reported HPL val-

ues up to 4-fold.

Normalization was found to improve correlation with other

laboratory parameters. Before normalization to SG, HPL in

single-void specimens from subjects with mixed diagnoses failed

to correlate significantly with plasma zinc (N=87; r=–0.15;

P=.18). In written communication from July 2006, William

Walsh, PhD, reported that signifi cant correlations were achieved

after normalization of colorimetric HPL to SG (r=–0.28, P=.009)

and to creatinine (r=–0.30, P=.004). Graham’s peer-reviewed

publications adjusted HPL to creatinine.51,52

Addition of ascorbate to urine collections protects HPL from

OHO

3C2H5

C2H5

H

CH

3CH

3CH

3CH

Mauve (HPL) Kryptopyrrole

NH

NH

FIGURE 1 Mauve Factor (HPL) Is Distinct From Kryptopyrrole (KP)

Structural similarity of the compounds affords the use of KP as standard in the colorimetric assay for HPL.

0

20

40

60

80

100

120

0 50 100 150 200

HP

L C

olor

met

ric

Eq

uiv

alen

ts (μ

g/d

L)

HPL by HPLC/MC (μg/dL)

FIGURE 2 HPL by HPLC/MS and Colorimetric Assay

Validation of colorimetric assay for urinary HPL. Same as Figure 1 cohort, but excludes extremely high (>100 μg/dL on colorimetric) values. N=44; r=0.98; P<.0001.

42 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Discerning the Mauve Factor, Part 1

degradation. However, typical quantities of ascorbate employed

(250-500 mg) alter SG of urine in the usual 10 mL transport tube.

Laboratories have found ways to overcome this diffi culty. Vitamin

Diagnostics Laboratory divides the urine at time of collection,

yielding a second, unpreserved specimen for determination of SG.

Vitamin Diagnostics Laboratory director Tapan Audhya, PhD,

reports that for 24-hour urine collection, conservation of HPL

with negligible effects on SG are achieved by addition of 500 mg

of ascorbate to the large, refrigerated container, from which a

small aliquot is examined for HPL and SG.

MAUVE IN BIOLOGICAL FLUIDS

All humans apparently excrete small quantities of HPL in

urine. As assayed by HPLC/MS under strict darkroom conditions,

Vitamin Diagnostics Laboratory fi nds that the normal concentra-

tion of HPL in urine is 2 to 25 μg/dL. In our survey of labs in

North America, Europe, and Australia, the upper limit of normal

for HPL by colorimetric assay varies between 8 and 20 μg/dL.

As an approximate yardstick, clinicians consider urinary HPL

levels over twice the upper limit of normal as highly elevated. Very

high HPL measurements—hundreds of micrograms per decili-

ter—are reported and not strictly limited by primary diagnosis.

HPL is detectable in human blood3,39,45,53,54 and cerebrospinal fl uid.45

In schizophrenics with elevated urinary HPL, Durko report-

ed that whole blood levels for HPL (2-dimensional thin-layer

chromatography, synthetic HPL standard) ranged between 4 and

10 μg/dL. Dialysis cleared HPL from both blood and urine.54

Interfering substances have frustrated efforts to develop a practi-

cal blood test for HPL.

Mauve Excretion Patterns

In most cases, day-to-day deviations around a baseline mean

do not preclude identifi cation of subjects prone to HPL elevation.

Sporadic spikes in HPL well above baseline associate with stress,

as will be discussed later. There is evidence that HPL excretion

can increase very rapidly. In 1992, a study for the US Navy mea-

sured urinary HPL (colorimetric, normalized to SG) after male

volunteers were subjected to brief cold-water immersion stress.

In an oral summary of the study, Tapan Audhya, PhD, reported

in 2002 the observation of signifi cant increases in HPL excretion

at 30 minutes, with peaks (as high as 80 μg/dL) at 1 hour and

reversion to baseline at 24 hours.

HPL excretion appears to be greater during waking hours

than during sleep. According to William Walsh, PhD, Pfeiffer

suggested second-void spot urine specimens for HPL because he

considered fi rst-void measurement misleading (oral communica-

tion, July 2006). At Vitamin Diagnostics Laboratory, HPL in

urine collected from subjects over 24 hours was higher from

noon until midnight than from midnight until noon. It is noted

that specifi c biomarkers for oxidative stress—8 hydroxydeoxy-

guanosine (8-OHdG), malondialdehyde (MDA), and 8-isopros-

tane—peak in early evening.55

While 24-hour urine collection circumvents intra-day varia-

tions in HPL excretion, as a practical matter, most laboratories

accept single-void urines, randomly timed. Hoffer favored same-

time collection of specimens to improve comparability (written

communication, August 2006).

HPL IN NEUROBEHAVIORAL DISORDERS

The discovery of HPL grew out of Hoffer’s interest in the

possible biochemical etiology of schizophrenia. In 1961 he

reported for the fi rst time that certain urinary “unknown sub-

stances” on chromatograms were detectable in most schizo-

phrenics hospitalized for active symptoms or relapses but not

detectable after symptoms improved or abated (P<.001).7,8,56,57 It

is now understood that these substances were HPL and its inter-

converting isomers. Hoffer applied the qualitative urinary test as

an indicator for treatment with vitamin B3, which reduced

schizophrenic symptoms and excretion of HPL.4

In an article that accompanied Hoffer’s initial report, Irvine

fi rst used the term Mauve factor.1 The compound associated sig-

nificantly with psychometric scores for abnormal perception,

paranoia, depression, and other symptoms in schizophrenics.6,45,58

Electroencephalographic (EEG) abnormality associated with the

compound in psychiatric patients.5

It became clear that Mauve is not confi ned to schizophre-

nia. In 1965, O’Reilly reported Mauve elevations in affective psy-

chosis, alcoholism, psychoneurosis, and “disturbed children.”59

According to Joan Mathews Larson, executive director of the

Health Recovery Center, Minneapolis, Minnesota, Mauve is ele-

vated in approximately 75% of subjects seeking treatment for

substance abuse (oral communication, July 2002). Mauve eleva-

tion is documented in many cognitive, affective, and neurobe-

havioral disorders (Table 1).4,8,22,23,30,32,52,58-69

HPL AND STRESS

O’Reilly hypothesized that Mauve excretion increases during

TABLE 1 Neurobehavioral Disorders Associated With Elevated HPL*

Diagnosis Percentage High-Mauve

AIP22,32 100

Latent AIP52 70

Down syndrome60 71

Schizophrenia, acute8,58,61,62 59-80

Schizophrenia, chronic23,30,63,64 40-50

Criminal behavior

Adults, sudden deviance65 71

Youths, violent offenders66 33

Manic depression30,59 47-50

Depression, non-schizophrenic8,64,67 12-46

Autism67,68 46-48

Epilepsy67 44

Learning disability/ADHD64,67 40-47

Neuroses69 20

Alcoholism4,8,59,63,64,69 20-84

*AIP indicates acute intermittent porphyria; ADHD, attention defi cit hyper-activity disorder.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 43Discerning the Mauve Factor, Part 1

physical or psychosocial (“emotional”) stress.59 Over decades, cli-

nicians formed the strong opinion that, irrespective of behavioral

diagnosis, stress increases associated symptoms and excretion of

Mauve.11,16,30 Pfeiffer came to state unequivocally that Mauve is

“a stress-induced factor.”14(p775) Sohler reportedly induced HPL

with experimental stress.45 The effect of cold-water stress in the

unpublished US Navy study was described earlier.

McCabe advocated short-term increases in B6 dosing to

blunt symptomatic deterioration in high-Mauve subjects during

physical or emotional stress.49 Clinicians give higher short-term

“stress doses” of both B6 and zinc.16,70

VITAMIN B6 AND ZINC

Pfeiffer discovered the clinical response of high-Mauve sub-

jects to B6 and zinc in 1971 and saw remarkable improvements in

a series of 1000 high-Mauve patients.16,71

Treatment with B6 and zinc reportedly reduced mean uri-

nary HPL in 99 patients from 60 g/dL to 30 g/dL in 1

month.30 Although randomized trials have not been performed,

combined B6 and zinc are now entrenched as core treatment for

high-Mauve subjects. According to William Walsh, PhD, neu-

robehavioral symptoms associated with elevated HPL may

improve after only a few days of therapy with B6 and zinc (oral

communication, 2006). Discontinuation may result in severe

deterioration within 48 hours.11

Clinicians report proportionality between Mauve excretion

and symptom severity30 and according to the late Hugh Riordan,

MD, former director of the Center for the Improvement of

Human Functioning International, Wichita, Kansas (oral com-

munication, 2000), higher Mauve excretion usually requires

higher dosages of B6 and zinc for suppression. HPL in urine

decreased progressively with higher B6 dosing,16 and progressive

B6 dosing associates with normalization of erythrocyte glutamate

oxaloacetate transaminase (EGOT).72

Initially, Pfeiffer tended to use high doses of vitamin B6

(400-3000 mg daily) and relatively modest (“dietary”) doses of

zinc. Later, some patients were noted to respond optimally to B6

and as much as 160 mg daily of elemental zinc.11 In the collective

experience of the authors, long-term treatment with B6 and zinc

usually is needed for ongoing HPL suppression and symptom

management. Optimal initial dosages may be higher than main-

tenance dosages. Zinc requirements in high-Mauve subjects are

noted to increase during growth spurts then decline abruptly.

Pfeiffer reported that on occasion, previously high-Mauve sub-

jects no longer may require high doses of B6 and zinc16; the phe-

nomenon was confi rmed in oral communication in 2003 with

Mark Vonnegut, MD, a former high-Mauve Pfeiffer patient and

now a practicing pediatrician in Quincy, Massachusetts.

Pfeiffer’s claims of a “double defi ciency” of B6 and zinc in

association with abnormal Mauve excretion10 were based on the

clinical response to supplementation and a pattern of lower blood

levels of zinc and functional B6 status (pyridoxal-5-phosphate

[P5P] and EGOT) among his high-Mauve patients.11,73,74

Numerical data were not published.

Pfeiffer and Sohler proposed that functional B6 defi ciency and

zinc defi ciency in high-Mauve subjects results from increased uri-

nary loss of P5P and zinc due to complexation with Mauve, and

they cited 20 μg/dL higher zinc content in spot urines of Mauve-

postive subjects.11 The finding would extrapolate to relatively

insubstantial total zinc loss, unless the effect extended to other

routes of excretion. Pfeiffer published evidence of binding between

P5P and KP11 and between zinc and KP18 but did not study HPL.

Validation of HPL as a Marker for B6 Status

The original data presented in this review were retrieved

retroactively and anonymously from laboratory records, without

regard to primary diagnosis or other criteria. In samples collect-

ed at the Biolab Medical Unit, London, colorimetric urinary HPL

(single-void, unadjusted to SG or creatinine), correlated moder-

ately with EGOT (n=58; r=–0.42; P=.001). In samples collected at

the Vitamin Diagnostic Laboratory, HPL by HPLC/MS in

24-hour urines, normalized to SG, correlated strongly with

EGOT (n=32; r=–0.77; P<.0001); all 24 subjects with abnormal

HPL had below-normal or borderline-low EGOT (Figure 3).

The data affi rm HPL as biomarker for functional B6 defi -

ciency and rationalize treatment with B6. Clinical response of

high-Mauve subjects to B6 may relate to known mechanisms by

which B6 subserves neuronal function. Numerous signs, symp-

toms, and traits have been observed in association with Mauve

(Table 2). Poor dream recall and mild morning nausea/break-

fast anorexia may relate especially to B6 defi ciency.13,16,73,75 Pfeiffer

suggested that stretch marks result from a combined defi ciency

of B6 and zinc.13

EG

OT

act

ivit

y ra

tio

0.84

0.82

0.8

0.78

0.76

0.74

0.720 50 100 150 200

HPL (μg/dL)

FIGURE 3 HPL and B6 Activity*

HPL by high-pressure liquid chromatography/mass spectroscopy in 24-hour urine correlates strongly with EGOT in mixed cohort. EGOT indicates erythrocyte glutamate oxaloacetate transaminase. Normal ranges: urinary HPL <25 μg/dL; EGOT activity ratio >0.8. N=32; r=–0.77; P<.0001.

44 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2

Validation of HPL as a Marker for Zinc Status

White fl ecks in the nails (Figure 4) are responsive to zinc16,71,76

and reportedly detectable in 60% of high-Mauve subjects.64 HPL

was examined in relationship to 3 different measurements for

zinc. As discussed earlier, Walsh reported that plasma zinc and

single-void colorimetric HPL correlated signifi cantly once normal-

ized to SG (r=–0.28; P=.009) or to creatinine (r=–0.30; P=.004).

Cellular zinc levels correlated more strongly with urinary

HPL. In samples at the BioLab Medical Unit, single-void colori-

metric HPL (unadjusted to SG) from a mixed cohort correlated

substantially with white-cell zinc (N=58; r=–0.60; P<.0001).

Abnormal HPL corresponded to below-normal white-cell zinc in

42 of 58 patients (Figure 5). In samples at Vitamin Diagnostic

Laboratory, stronger association existed between red-cell zinc

and 24-hour urinary HPL (HPLC/MS, adjusted to SG) in a mixed

cohort (N=37; r=–0.88; P<.0001). Twenty-four of 24 subjects

with elevated HPL had below-normal red-cell zinc (Figure 6).

HPL AND OTHER NUTRITIONAL PARAMETERS

Oscar Kruesi, MD, former academic dean for Integrative

Medicine, Capitol University, Washington, District of Columbia,

reported a pattern of low plasma biotin levels in high-Mauve

patients (oral communication, 2005). At the Vitamin Diagnostics

Laboratory, 24-hour urinary HPL (HPLC/MS, adjusted to SG) and

plasma biotin concentrations from a small, mixed cohort strongly

correlated (N=24; r=–0.88, P<.0001). Elevated HPL predicted

below-normal plasma biotin in 16 of 16 subjects (Figure 7). These

data are the fi rst to suggest biotin defi ciency in association with

HPL. Biotin defi ciency causes neurological disease in animals and

humans77,78 and is more common than thought.79

Examination of laboratory records found no association between

HPL and markers for vitamin B3 (urinary n-methyl nicotinamide),

vitamin B12 (urinary methylmalonic acid), folate (urinary formimino-

glutamic acid, FIGLU), or thiamine (red-cell transketolase).

POSSIBLE NEUROTOXICITY OF HPL

Several fi ndings suggest that HPL is neurotoxic in humans:

(1) structural homology to known neurotoxin; (2) acute behav-

ioral effects in animals; (3) porphyrinogenicity in animals; (4)

TABLE 2 Signs, Symptoms, and Traits Clinicians Report as More

Prevalent in High-Mauve Patients*4,10,11,13,16,30,49,64,71,73

Poor dream recall

Nail spots

Stretch marks (striae)

Pale skin/poor tanning

Coarse eyebrows

Knee and joint pain

Acne

Allergy

Cold hands or feet

Abdominal tenderness

Stitch in side

Constipation

Morning nausea

Light/sound/odor intolerance

Tremor/shaking/spasms

Hypoglycemia/glucose intolerance

Obesity

Migraine

Delayed puberty

Amenorrhea/irregular periods

Impotence

Eosinophilia

B6-responsive anemia

Attention defi cit/hyperactivity

Crime and delinquency

Substance abuse

Alcoholism

Stress intolerance

Emotional lability

Explosive anger

Anxiety

Pessimism

Dyslexia

Familial or social withdrawal

Depression

Paranoia

Hallucinations

Disordered perception

Bipolar disorder

Autism

*The frequency of these features and their relationship to biochemical abnor-malities associated with HPL are not well-studied.

Discerning the Mauve Factor, Part 1

Zin

c in

ng/

mill

ion

wh

ite-

cells

7

6.5

6

5.5

5

4.5

4

3.50 10 20 30 40 50 60 70

Colorimetric HPL equivalents (μg/dL)

FIGURE 4 Leukodynia Implies Zinc Defi cit

In this high-Mauve subject, white fl ecks in nails resolved after institution of 100 mg of elemental zinc daily, reoccurred after dosage was lowered to 40 mg, and again abated on higher dosage.

FIGURE 5 Single-void HPL and White-cell Zinc

Colorimetric HPL equivalents in single-void urines, unadjusted to specifi c gravity, correlates with white-cell zinc in mixed cohort. Normal values: HPL <8 μg/dL; white-cell zinc > 5.4 ng/106 leukocytes. N=58; r=–0.60; P<.0001.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 45Discerning the Mauve Factor, Part 1

association in humans with porphobilinogen (PBG) and amin-

olevulinic acid (ALA), potential neurotoxins; (5) acute depres-

sion of non-erythroid heme in animals.

As a class, pyrroles have been called “nerve poisons.”80 HPL is

from the subclass of monopyrroles, well known for biotoxicity. 3,45

Batrachotoxin (poison-dart frog)81 and PBG82 are monopyrroles

which exert potent effects on the nervous system. KP3,10,22,24,25,29,31-33,45,83

and the hydroxylactam of kryptopyrrole (KPL),84,85 highly homolo-

gous to HPL, cause acute neurobehavioral effects in animals.

Structural similarity of HPL to pyroglutamate and kainic acid 41 sug-

gests possible direct effects on neurotransmission.

Irvine produced ptosis, locomotor abnormalities, and hypo-

thermia in rats with unspecifi ed doses of HPL.86 Cutler found that

intraperitoneal injection of HPL 0.65 μmol/kg produced relative-

ly mild acute effects: decreased gross activity, increased prefer-

ence for light areas of the cage, and a trend toward more

aggressive behavior. A higher dose of 1.95 μmol/kg increased

head-twitch and backward locomotion,41 behaviors seen in rats

treated with hallucinogens.87

Strictly by estimation, Cutler discounted signifi cant behav-

ioral effects in humans from HPL, because the plasma concentra-

tion of 0.3 μmol/kg (equivalent to 4.6 μg/dL) achieved in rats

with the higher dose of HPL was adjudged “many-fold” greater

than plausible HPL blood levels in humans.41 The estimation

overlooked published data from Semmelweiss Medical

University, which reported a whole-blood range for HPL of 4 to

10 μg/dL in schizophrenics.54 Cutler’s higher dose of HPL mar-

ginally achieved this range.

HPL defi nitely is porphyrinogenic in animals. Cutler’s lower

dose of HPL significantly increased total urinary porphyrin

excretion in rats.52,85,88 Graham documented peak urinary HPL

immediately prior to a severe attack of acute intermittent por-

phyria (AIP),39 but alteration of porphyrin metabolism by HPL

has not been proven in humans. Nevertheless, elevation of HPL

in the porphyrias is well documented.22,32,89-93 In AIP, HPL is ele-

vated consistently22,32 and during AIP neurovisceral crisis may

reach urinary concentration as high as 946 μg/dL.90 In AIP—

including the latent state—HPL consistently associates with uri-

nary PBG and ALA.52,93

The association of HPL with ALA is not limited to AIP. In a

mixed group of psychiatric patients (N=128), urinary HPL and

ALA correlated positively.94 ALA is a potent oxidant and neuro-

toxin95 with known effects on neuronal energy production96 and

neurotransmission.97,98 ALA binds P5P and produces free radicals

by autooxidation.99 Animal studies that failed to increase ALA

after injection with HPL88 used the Cutler doses.

Ex vivo, guinea-pig ileal contractions were inhibited by HPL at

seemingly high concentrations of 8.5 μmol/kg (132 μg/dL),100 but

HPL in human bowel or stool has not been quantifi ed for reference.

HPL DEPRESSES HEME

Heme is tightly coupled to neuronal metabolic activity.101

Depression of heme leads to metabolic crisis, with mitochondrial102

and neuronal103 decay. Injection of rats with Cutler’s lower dose

(0.65 μmol/kg) of HPL at 0 and 24 hours reduced hepatic

microsomal heme (by 42%) and heme-containing cytochrome

P-450 (by 55%) at 48 hours.88 Equivalent reduction of heme in cul-

tured neurons with N-methylprotoporphyrin IX (NMP) reduces

mitochondrial complex IV, upregulates nitric oxide synthase

(NOS), and reduces intracellular zinc by half.101 NMP inhibits

heme synthesis, the proposed mechanism for HPL.52,88 It is possible

that HPL directly binds heme, as does KPL in vitro.104

Red

-cel

l zin

c (m

g/L

)

18

16

14

12

10

8

6

4

2

00 50 100 150

HPL (μg/dL)

Pla

sma

bio

tin

(n

g/L

)

450

400

350

300

250

200

150

100

50

00 50 100 150

HPL (μg/dL)

FIGURE 6 HPL and Red-cell Zinc

HPL by mass spectroscopy/high-pressure liquid chromatography in 24-hour urine correlates with red-cell zinc in mixed cohort. Normal values: HPL <25 μg/dL; red-cell zinc >9 mg/L. N=37; r=–0.88; P<.0001.

FIGURE 7 HPL and Plamsa Biotin

HPL by high-pressure liquid chromatography/mass spectroscopy in 24-hour urine correlates with plasma biotin in mixed cohort. Normal range: urinary HPL <25 μg/dL; biotin >200 ng/L. N=24; r=–0.88 ; P<.0001.

46 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Discerning the Mauve Factor, Part 1

Non-erythroid heme in high-Mauve subjects has not been

measured, but depressed levels are predictable. Besides potential

depression by HPL, defi ciencies of zinc, B6, and biotin (all cofac-

tors for heme synthesis) independently decrease non-erythroid

heme.99,102 And heme is degraded by stress.102 It should be men-

tioned as well that heavy metals, which have not been examined

in relation to Mauve, are renowned dysregulators of porphyrin

metabolism and increase heme degradation.102

Heme plays a central role in energy production and is

required by a family of biomolecules needed for detoxifi cation

and antioxidant defense: catalase, cystathionine synthase, cyto-

chrome, guanylate cyclase, heme-hemopexin (for production of

metallothionein), NOS, pyrrolase, sulfi te reductase. Ultimately,

heme depression increases oxidant leak from mitochondria and

oxidative damage to cells.99,102

HPL AND OXIDATIVE STRESS

Oxidative stress clearly results from defi ciency of zinc or B6,

as reviewed by McGinnis.105 For example, even marginal B6 defi -

ciency is associated with lower glutathione peroxidase (GSHPx),

lower glutathione (GSH) reductase, lower reduced/oxidized glu-

tathione ratios, higher lipid peroxide levels, and mitochondrial

decay.106-108 The B6 vitamers are themselves highly vulnerable to

damage by oxidative species.109-111 P5P protects neurons from oxi-

dative stress, apparently by increasing energy production and

lowering excitotoxicity,112,113 and zinc supplementation decreases

oxidized biomolecules.114,115 Since HPL is a marker for B6 and zinc

defi ciency, HPL is a potential biomarker for oxidative stress.

Biomarkers for oxidative stress are known to be higher in

high-Mauve disorders such as schizophrenia,116,117 autism,118-120

ADHD,121,122 Down syndrome,123-125 and alcoholism.126-128 In schizo-

phrenia, lower blood levels of glutathione and response to intra-

venous glutathione were reported nearly 50 years ago.129

Plasma levels of reduced GSH, the ubiquitous intracellular

antioxidant, are decreased in diseases associated with greater

oxidative stress,130 including Down syndrome.131 In Alzheimer’s

disease, in which oxidative modification of brain precedes

appearance of neurofibrillary tangles and plaque,132,133 plasma

GSH correlates inversely with brain levels of oxidatively-modifi ed

biomolecules.134 It is reasonable to view plasma GSH as a bio-

marker for pathological effects of oxidative stress.

Initial data from a small cohort of Austrian patients with

mixed diagnoses suggested an association between urinary HPL

and plasma GSH. Peter Lauda, MD, reported that single-void

colorimetric HPL, adjusted to creatinine, correlated modestly

with red-cell GSH (r=–0.41) in a group of patients in whom HPL

was elevated only in 1 of 13 subjects (written communication,

2005). In samples from the Vitamin Diagnostics Laboratory,

24-hour urinary HPL (HPLC/MS, normalized to SG) from a

mixed cohort strongly correlated with plasma GSH (N=30;

r=–0.85; P≤.0001), and abnormal HPL associated with below-

normal plasma GSH in 17 of 17 subjects (Figure 8). Very strong

correlation with plasma GSH substantiates urinary HPL as bio-

marker for oxidative stress.

HPL AND CATALASE

Catalase is an endogenous antioxidant that prevents excess

cellular hydrogen peroxide (H2O2), a freely-diffusible and potent

oxidant. Catalase consists of 4 protein subunits, each requiring a

heme group. Since catalase requires heme and HPL suppresses

heme, it follows that HPL may associate with lower catalase. Lower

catalase in blood is reported in schizophrenia116,135 and autism.136

In samples collected at the Vitamin Diagnostics Laboratory,

red-cell catalase activity in a mixed cohort was found to correlate

inversely with 24-hour urinary HPL by HPLC/MS, normalized to

SG (N=30; r=–0.92, P<.0001). Abnormal HPL corresponded to

subnormal catalase in 15 of 17 subjects (Figure 9). In addition to

proposed direct effects of HPL on heme synthesis, depression of

catalase may result from greater oxidative stress in high-Mauve

subjects, because catalase is sensitive to oxidative degradation137

(as is GSHPx,138 which also can remove H2O2 in a reaction using

GSH as substrate).139

Depressed catalase hypothetically predisposes high-Mauve

subjects to excess H2O2 and presents a possible explanation for

hypopigmentation of skin associated with Mauve—including, in

the extreme, classic “china-doll” complexion.10,11 The pathogene-

sis of vitiligo illuminates the effect of abnormal catalase and

H2O2 on pigmentation. A genetic polymorphism for catalase

apparently predisposes patients to vitiligo.140 All patients with

vitiligo exhibit decreased catalase and increased H2O2 in epider-

mis.141 In the presence of excess H2O2, melanocytes142 and mela-

nin (which normally functions to bind redox-active metals and

thereby reduce oxidative stress) are damaged, resulting in lesser

pigment production.130 If destruction of melanocytes by excess

H2O2 is not complete, treatment with pseudo-catalase restores

skin pigmentation by reducing H2O2.143,144

Pla

sma

GSH

(μ

mo/

L)

6

5

4

3

2

1

00 50 100 150 200 250

HPL (μg/dL)

FIGURE 8 HPL and Plasma-reduced Glutathione

Urinary HPL by high-pressure liquid chromatography/mass spectroscopy in 24-hour urine correlates with plasma GSH in mixed cohort. Normal values: urinary HPL <25 μg/dl; plasma GSH >3.8 μmol/L. N=30; r=–0.88; P<.0001.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 47Discerning the Mauve Factor, Part 1

As stress classically associates with Mauve, so do stressful life

events associate with the onset of vitiligo.145,146 Catecholamines,

which increase as a consequence of stress, are increased in vitiligo

patients, particularly during the active phase.147 Both the synthesis

of catecholamines and their auto-oxidation produce H2O2.139,148,149

Catecholamine excess is cytotoxic in diverse tissues, and the

toxicity is oxidatively mediated by H2O2. Excess is implicated

clearly in human heart disease, and cardiomyocyte apoptosis

produced by catecholamine infusion is prevented by antioxidant

vitamins.150 In cultured neurons, toxicity of epinephrine and nor-

epinephrine is reproduced by addition of equimolar H2O2 or

blocked completely by addition of catalase.151 Catecholamine

excess in neurobehavior was anticipated by Abram Hoffer in the

Adrenochrome Hypothesis of Schizophrenia in 1954.152,153

Besides lighter skin, lighter hair coloration than siblings

and earlier gray is reported in high-Mauve subjects. Excess H2O2

is known to increase proportions of oxymelanin in hair, with

lightening analogous to the effect achieved by topical application

of bleach for cosmetic purposes.154 Excess H2O2 remains hypo-

thetical until levels are measured in the high-Mauve population.

Zinc defi ciency alone may explain hypopigmentation associated

with Mauve. Melanin is rich in zinc and requires zinc for synthe-

sis and maintenance.150,155 Zinc protects melanocytes from oxida-

tion,154,156 and zinc-defi ciency grays the coats of rats.157 Oxidants,

including H2O2,158 displace zinc from binding proteins, and it

has been suggested that clinical zinc depletion results inherently

from greater oxidative stress.105

HPL AND NITRIC OXIDE

Heme depression results in excess nitric oxide (NO),101

which is injurious to the brain159,160 and is suspected to play a role

in such high-Mauve disorders as schizophrenia,161 autism,162 and

Down syndrome.163 In schizophrenia and autism, stable metabo-

lites of NO are elevated in conjunction with greater thiobarbitu-

ric acid-reactive substances in plasma.162

In samples from a mixed cohort at Vitamin Diagnostics

Laboratory, plasma NO, measured directly, and 24-hour urinary

HPL by HPLC/MS, normalized to SG, correlated positively (N=30;

r=0.60; P<.0001). The statistical relationship strengthens substan-

tially (r=0.96) if an extreme outlier is excluded on the presumption

of poor sample preservation (Figure 10). The strong association

with NO enhances Mauve as a biomarker for oxidative stress.

It should be noted that while altered functional B6, zinc,

biotin, GSH, catalase, and NO all point toward increased oxida-

tive stress in association with urinary HPL, the data presented

are from non-congruent cohorts. Proof that these parameters

move together would require same-subject measurement of each.

AcknowledgmentsThe authors wish to acknowledge Nina A. Mikirova, PhD, Bio-Communications Research

Institute, Wichita, Kansas, for statistical analysis of data presented in this report and Jackson

County Library Services, Jackson County, Oregon, for documentary support.

REFERENCES1. Irvine DG. Apparently non-indolic Erhlich-positive substances related to mental ill-

ness. J Neuropsychiatr.1961 Aug;2:292-305. 2. Hoffer A. The presence of malvaria in some mentally retarded children. Am J Ment Def.

1963;67:730-732. 3. Irvine DG. Kryptopyrrole in molecular psychiatry. In: Hawkins D, Pauling L, eds.

Orthomolecular Psychiatry: Treatment of Schizophrenia. San Francisco: WH Freeman and Company; 1973:146-178.

4. Hoffer A. The discovery of kryptopyrrole and its importance in diagnosis of biochemi-cal imbalances in schizophrenia and in criminal behavior. J Orthomolec Med. 1995 First Quarter;10:3-7.

Cat

alas

e u

nit

s/m

in/m

g of

hem

oglo

bin

400

350

300

250

200

150

100

50

00 50 100 150 200 250

HPL (μg/dL)

Nit

ric

Oxi

de

(μm

ol/L

)

200

180

160

140

120

100

80

60

40

20

00 50 100 150 200 250

HPL (μg/dL)

FIGURE 9 HPL and Red-cell Catalase

HPL by high-pressure liquid chromatography/mass spectroscopy in 24-hour urine correlates with red-cell catalase in mixed cohort. Normal values: HPL < 25 μg/dL; red-cell catalase >130 units/min/mg of hemoglobin. N=30, r=–0.92; P<.0001.

FIGURE 10 HPL and Plasma Nitric Oxide

HPL by mass spectroscopy/high-pressure liquid chromatography in 24-hour urine correlates with plasma nitric oxide in mixed cohort. Normal values: HPL<25 μg/dL; plasma nitric oxide 18-36 μmol/L. N=30; r=0.60; with exclusion of an extreme outlier (6.4, 186), r=0.97, P<.0001.

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52 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Research Training at the New England School of Acupuncture

Peter M. Wayne, PhD, was director of research at the New

England School of Acupuncture (NESA), Watertown,

Massachusetts, when this article was written; he is now

instructor of medicine at the Harvard Medical School Osher

Institute, Boston. Julie E. Buring, ScD, is director of clinical

research and Roger B. Davis, ScD, is director of biostatistics at

the Osher Institute. Sally M. Andrews, MBA, is executive direc-

tor of the Osher Institute. Meredith St John, LicAc, is an asso-

ciate professor at NESA. Lisa Conboy, ScD, is an instructor in

medicine at the Osher Institute and current co-director of

research at NESA. Catherine E. Kerr, PhD, is an instructor in

medicine at the Osher Institute. Ted J. Kaptchuk, OMD, is

associate director, and Steven C. Schachter, MD, is associate

director of clinical research at the Osher Institute.

Editor’s note: This article is a follow-up to an article that appeared in

our Jan/Feb 2008 issue, “Increasing Research Capacity at the New

England School of Acupuncture: Building Grants Management

Infrastructure” (Altern Ther Health Med. 2008;14(1):56-64).

Acupuncture schools and other complementary and

alternative medicine (CAM) institutions have the

potential to make signifi cant contributions to CAM

research.1-3 To date, however, few CAM institutions

have developed research programs that have

enabled them to play leading roles in clinical and mechanistic

research. In a companion article, we discussed how limitations in

grants management infrastructure at small CAM institutions can

be a significant barrier to the development of independent

research programs capable of submitting and managing federal

research grants.4 We also discussed how the New England School

of Acupuncture (NESA), in collaboration with the Harvard

Medical School (HMS) Osher Institute and with the support of a

Developmental Center for Research on Complementary and

Alternative Medicine (DCRC) grant awarded by the National

Center for Complementary and Alternative Medicine (NCCAM)

of the National Institutes of Health, developed its grants manage-

ment infrastructure and increased its research capacity.

In the present article, we discuss another DCRC-supported

set of initiatives designed and implemented to increase research

original article

INCREASING RESEARCH CAPACITY AT THE NEW ENGLAND SCHOOL OF ACUPUNCTURE

THROUGH FACULTY AND STUDENT RESEARCH TRAINING INITIATIVES

Peter M. Wayne, PhD; Julie E. Buring, ScD; Roger B. Davis, ScD; Sally M. Andrews, MBA; Meredith St John, LicAc; Lisa Conboy, ScD;

Catherine E. Kerr, PhD; Ted J. Kaptchuk, OMD; Steven C. Schachter, MD

Few complementary and alternative medicine (CAM) institutions

require their students to undergo substantive training in research

literacy and conduct, and well-developed programs to train CAM

institution faculty in research are virtually non-existent. As part

of a National Center for Complementary and Alternative

Medicine (NCCAM) initiative to increase research capacity at

CAM institutions, the New England School of Acupuncture

(NESA), in collaboration with the Harvard Medical School

(HMS) Osher Institute, was awarded a Developmental Center

for Research on Complementary and Alternative Medicine

(DCRC) grant. This article discusses a number of initiatives that

we designed and implemented to train NESA students, faculty

members, and alumni in the foundations of clinical research and

to stimulate interest in both participating in research and receiv-

ing additional research training. Specifi c initiatives included a

30-hour faculty “Foundations of Research” course; a year-long

course entitled, “How to Write a Publishable Case Report”; insti-

tution of a monthly research seminar series; revision of an

already required student research course; and the addition of 2

new student-mentored independent research electives. We dis-

cuss successes and challenges encountered in developing and

administering these initiatives and the overall impact they have

had on research culture and productivity at NESA. (Altern Ther

Health Med. 2008;14(2):52-58.)

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 53Research Training at the New England School of Acupuncture

capacity at NESA––namely, research education and training pro-

grams for faculty members, students, and alumni. We begin by

reviewing the status of research training available at Oriental

medicine (OM) institutions like NESA in the United States and

then describe a number of interrelated initiatives aimed at

improving research knowledge and research capacity within the

NESA community. We discuss initiatives that have been success-

ful, challenges we have encountered, and lessons we learned that

might be relevant to other CAM institutions that wish to develop

a research program. A more complete discussion of the scope of

NESA’s research program and the aims and structure of its DCRC

program within which these educational initiatives were devel-

oped can be found elsewhere.4

RESEARCH TRAINING AT NESA AND OTHER ORIENTAL

MEDICINE COLLEGES AND INSTITUTIONS

Even in OM schools with advanced master’s and doctoral

degree programs, training in research literacy and research con-

duct for students is very limited, as curricula generally focus on

the development of practical clinical skills. The Accreditation

Commission for Colleges of Acupuncture and Oriental Medicine

(ACCAOM) does not have any formal requirements for research

training. Some OM schools in the United States currently offer 1

basic course in research; however, the content of these courses

varies considerably across institutions. Only a few offer advanced

electives in research and/or provide students with opportunities

for practical research experience or training. Well developed pro-

grams to train OM faculty in research are virtually nonexistent.

Like most other OM colleges, before the establishment of

NESA’s research program, NESA was primarily a “vocational,”

clinically-focused program. An aim of both NESA’s overall

research program and the DCRC was to increase faculty, student,

and alumni literacy, knowledge, and skills related to clinical

research so that members of the NESA community could become

effective clinical researchers. To address this aim within the

DCRC, an education sub-committee was established that helped

develop and oversee 5 initiatives related to faculty, student, and

alumni training in research. The committee was composed of

NESA’s research director, HMS Osher Institute’s director of edu-

cation, NESA’s student research coordinator, and faculty mem-

bers representing all research-related courses. The 5 initiatives

were (1) a new course for NESA faculty and alumni entitled,

“Clinical Research Methods and Evaluation”; (2) a second new

faculty and alumni course entitled, “How to Write a Publishable

Case Report”; (3) initiation of a community-wide, monthly OM

research seminar series; (4) curriculum revisions of an already

existing and mandatory student research course; and (5) devel-

opment of 2 new student electives in mentored research. Each

initiative has involved both NESA and HMS faculty members.

Table 1 summarizes these initiatives.

Faculty Clinical Research Methods and Evaluation

This introductory course represents the fi rst research-related

training initiative created for NESA faculty and alumni. The aims

of the course are to (1) introduce the fundamental principles and

methods of clinical, epidemiological, and basic mechanistic sci-

ence research design, conduct, analysis, and interpretation; (2)

develop the skills and literacy required to locate, retrieve, and

evaluate the published OM literature critically; and (3) under-

stand the special issues related to the conduct of CAM or OM

research. The course is taught in 3 discrete units over 3 week-

ends. The goal of the fi rst unit, which covers the fundamentals, is

to introduce participants to the scientifi c method and to specifi c

types of scientifi c inquiry, focusing especially on the randomized

controlled trial (RCT). The unit describes the rationale for the

RCT and the methods used to conduct trials (especially acupunc-

ture trials), including theory and hypothesis generation, blind-

ing, randomization, statistical analysis, and procedures used to

reduce bias. This unit concludes by introducing students to some

of the challenges of conducting ecologically valid RCTs of acu-

puncture and the unique challenges related to acupuncture con-

trol interventions.

TABLE 1 Summary of NESA DCRC Faculty and Student Research Training Initiatives*

Initiative Target population

Hours; frequency

offered Key goals Comments

Clinical Research Methods

and Evaluation

Faculty, alumni 30; annually Fundamentals of research design; research literacy;

key topics in OM research

Continuing

education credits

How to Write a

Publishable Case Report

Faculty 24; bi-annually Contribution of case studies to evidence; greater

familiarity with primary literature and writing skills

Continuing

education credits

Research Seminar Series Faculty, students,

alumni, staff, public

1; monthly Exposure to acupuncture researchers presenting results of

recently completed or ongoing clinical or basic research

Continuing

education credits

Foundations of Research Students 30; annually Fundamentals of research design; literacy; key topics in

OM research

Required Course

Research Electives I & II Students 90 each; annually Mentored independent research; clinical experience or

secondary analysis of literature

Onsite or offsite

*NESA indicates New England School of Acupuncture; DRCR, Developmental Center for Research on Complementary and Alternative Medicine; OM, Oriental medicine.

54 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Research Training at the New England School of Acupuncture

The second unit introduces participants to (1) different

methods for critically reviewing and evaluating research and (2)

purported mechanisms of action (eg, neuroimaging studies, con-

nective tissue signaling research).5,6 Participants take on mini-

projects and learn how to do literature searches. Working in

teams, they become familiar with databases, learn how to con-

duct a literature search on a specifi c OM topic, and then collec-

tively work to evaluate a select group of published RCTs

according to both established criteria (Jadad’s scale) and newer

standards used to evaluate acupuncture (eg, STRICTA7).

In the fi nal unit, participants present short literature reviews

on topics of interest. This fi nal unit also covers new innovative

methods for studying OM (including qualitative research, devel-

opment of valid OM measures). In this unit, participants also

return to the question of what method should serve as the appro-

priate control for studies of acupuncture. At this point in the

course, participants have reviewed and evaluated a wide range of

studies including functional magnetic resonance imaging and

basic science studies. They also have discussed studies that

report to validate different methods for controlling for the non-

specifi c effects of acupuncture. By returning to the issue of acu-

puncture controls that they initially considered in the first

session, participants come to appreciate the growth they have

experienced in their knowledge base and sophistication.

The course content is similar to that of an already existing

and required student research course that is discussed later,

although the format and some of the content is varied when

taught to faculty and alumni. Both this and the student course

were developed and are taught by 2 active OM researchers (Drs

Conboy and Kerr) who hold faculty appointments at both NESA

and HMS. A more detailed outline of the curricula for these

courses is presented in Table 2.

Because NESA faculty members tend to have busy teaching

and clinical schedules and because research is not always viewed

as clinically relevant to OM practitioners, a number of strategies

were developed to recruit faculty to this course. First, faculty

members were surveyed to ascertain the most convenient timing

and format for the course. The results of this survey indicated that

conducting the course over 3 sequential weekends (30 contact

hours in total) was most practical. Second, the research director

sent a personal letter to all faculty members announcing and

describing the course and highlighting how important and unique

an opportunity this was for the OM community, NESA, and the

faculty memebers’ personal professional development. This cam-

paign was supplemented by announcements in faculty meetings

and newsletters and personal phone calls. Finally, the course has

been offered at no cost to active faculty members, and faculty

members and participating alumni have been awarded continuing

education (CE) credits. The course was also open to the larger

community for a fee and was advertised as such through the NESA

Continuing Education Program, which advertises nationally.

The course has now been offered twice and was well attend-

ed. The fi rst time the course was offered, 8 of 70 faculty members

attended. In the second offering, there were 13 participants (12

actively practicing alumni and 1 new faculty member). In both

years, the program received excellent reviews. Representative

qualitative evaluations of this course included the following com-

ments: “this kind of course is something every acupuncturist

needs to take”; “the creative exchange of ideas between the scien-

tists and acupuncturists was fascinating”; “far more interesting

TABLE 2 Outline for Foundations of Clinical Research Methods and Evaluation Course Offered to NESA Faculty, Students, and Alumni*†

Modules Examples of topics and questions considered

Introduction to theory and research What is science? What is research? What are special problems facing investigators studying OM?

Basics of designing a scientifi c study What is a hypothesis? What is a causal relationship?

Finding and evaluating primary research

literature

What tools are available to locate and retrieve OM research articles? What are the key issues to consider in

critiquing a research study?

Research ethics What is an institutional review board and what are its functions?

Basics of measurement and outcomes How do you evaluate your measure? What do reliability and validity mean?

Sampling When should you sample and why? What are your sampling options?

RCTs What is random assignment? Why is it employed? History and prominence of the RCTs. Challenges RCTs

pose to OM research.

Introduction to quantitative analysis What are descriptive statistics (eg, pie chart, bar graph, frequency distribution)?

Introduction to qualitative analysis What is fi eld research? Conducting fi eld research: interviews, analysis of qualitative data.

Grant-writing skills; public presentations Students work alone or in groups to formulate a research project, either a grant proposal or research paper in

grant-draft form. Projects are presented to the larger class.

*Format and emphases of some content vary between faculty/alumni vs student course (eg, grant not part of faculty offering).†NESA indicates New England School of Acupuncture; RCT, randomized controlled trial; OM, Oriental medicine.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 55Research Training at the New England School of Acupuncture

and enjoyable than I expected”; “reading clinical research in this

group really improved my skills and confi dence in critically evalu-

ating primary literature on my own”; and “one of the best CE

classes I’ve ever taken.” Quantitative evaluations of course content

and delivery received an average score of 4.9 of a maximum score

of 5.0. We plan to continue offering this course annually. It is now

administered through NESA’s continuing education program and

is open to alumni and other OM and CAM professionals.

“How to Write a Publishable Case Report or Case Series”

Based on the positive experiences with the first faculty/

alumni research course and a desire expressed by faculty and

alumni to become further engaged in research and academic

training, a second course on writing a publishable case report or

case series was developed. Because nearly all of our OM faculty

members are clinicians, we thought that developing a course that

focused on acquiring the competencies necessary to complete all

the steps involved in publishing a peer-reviewed case study or

case series based on their own patients was a practical and logical

next step in research training. Specific goals for this course

included (1) learning about types of case reports, including retro-

spective, prospective, and case series, and their contribution to

scientifi c inquiry; (2) learning about the history and function of

institutional review boards in the protection of human subjects

in research and developing practical experience with them; (3)

developing skills in OM information literacy; (4) developing sci-

entifi c writing skills; and (5) learning the skills related to identi-

fying and submitting manuscripts to appropriate peer-reviewed

journals. The course was co-developed and administered by 2

NESA faculty members and the director of education at the HMS

Osher Institute and includes didactic lectures, interactive and

independent exercises, and one-on-one mentoring. A more

detailed outline of the course curriculum is presented in Table 3.

As with the fi rst faculty course, a number of initiatives were

undertaken to recruit faculty to this course. The course was ini-

tially designed to span a 9-month period, with one 2-hour meet-

ing per month. Due to slower than expected progress in meeting

our course goals, particularly with respect to facilitating faculty

members in developing their cases, the course has been extended

to a full year. The course was fi rst offered in fall 2005; at the time

this paper was written, it was more than 75% complete. Eleven

faculty members have enrolled in the course; only 2 had partici-

pated in the Foundations of Research course. Group meetings

have been lively and productive. To date 9 faculty members have

identified cases to develop and submitted protocols for IRB

approval or exemption. Example protocol titles include

“Acupuncture regulates atrial fi brillation: a case report”; “A pro-

fi le of users of Chinese herbal medicine at an inner-city Oriental

medicine clinic”; and “Acupuncture for generalized anxiety disor-

der: a case series.” An evaluation for the course assessed at 7

months included the following comments: “This course has

taught me that excellence as a practitioner is only part of my job

the other part is contributing to the public discourse on acu-

puncture by publishing”; ”My skills in the library were outdated.

TABLE 3 Curriculum Outline for Faculty/Alumni Course, “How to Write a Publishable Case Report”

Modules Examples of topics and questions considered

Case Reports: Overview What is a case report and what is it used for? What are the differences between observational and clini-

cal investigations? What is the place of case reports in evidence-based research?

Types of Case Reports What are the differences between retrospective and prospective reports? What are the differences

between case reports and case series and cohort studies?

Identifying and Retrieving Peer-reviewed

Research Literature

What is the process of conducting an electronic literature search? What are the basics skills needed to

use PubMed, Medline, and related search engines? How does one retrieve full-text articles?

Critically Evaluating Primary Literature How do we critically evaluate an already published case study? What are the key features to consider?

What makes a case worthy of publishing?

IRBs* What is the history and purpose of IRBs in protection of human subjects in research? What kinds of case

studies require IRB approval? How does one complete an IRB protocol application?

Outcome Measures Why are outcome measures important for case reports? What are the categories of outcome measures?

How does one choose the most appropriate outcome measure(s)?

Writing What is the structure/format of a case report or case series? What is the function of the background,

results, and discussion sections?

Publishing a Case Report Why is publishing case reports of potential value to both researchers and clinicians? How is authorship

of papers determined? How does one determine the most appropriate journal for submission? How

does one fi nd out about the instructions/guidelines for authors regarding formatting and submission

of manuscripts for review? How does one evaluate and respond to reviewers’ comments?

*IRB indicates institutional review board.

56 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Research Training at the New England School of Acupuncture

This course helped bring me up-to-date”; “Very little of the

research on acupuncture is helpful in my clinical work. Learning

about observational studies in this course showed me a way for

clinicians to help change that.” We will continue to offer this

course to faculty and alumni every other year. Future offerings

will be administered through NESA’s CE program.

Research Seminar Series

Taking advantage of the large quantity and diversity of

research taking place in the greater Boston area, a monthly

research seminar series was established to expose the NESA com-

munity to cutting-edge OM research and researchers. This initia-

tive has been successful in many ways. First, we have had little

diffi culty attracting high-caliber speakers who are either located

in the Boston area or willing to present during visits to the area.

Since March 2004, we have hosted 22 speakers. Fourteen have

presented work supported by NIH grants, and 13 are faculty

members who are associated with HMS-affi liated institutions.

Six NESA faculty members involved in research have also pre-

sented their work. A representative list of the topics addressed by

seminar speakers is presented in Table 4. Most seminars, which

generally take place during lunch, have been well attended, with

an average of 20 to 25 participants consisting of approximately

equal numbers of faculty members, students, and members of

the general public. These monthly seminars have had a signifi -

cant impact on NESA’s culture. They have exposed the NESA

community to cutting-edge work, and researchers from other

institutions have showcased their own faculty members as con-

tributors to this research and fostered greater appreciation for

the value of academic research to clinical practice and to the

credibility of the OM profession as a whole. As of March 2006,

faculty and alumni receive CE credit for attending research semi-

nars. This seminar series will continue to meet on a monthly

basis throughout the academic year.

Foundations of Research and Elective Courses for Students

Since 1998 all students at NESA have been required to par-

ticipate in a 30-hour course introducing the basics of clinical and

epidemiological research. Upon establishing our DCRC, the

broad aims and content of this course were revised (Table 2). For

students who complete this course and are interested in pursuing

further research experience, a new pair of mentored research

electives was developed in 2004. Students who enroll in these

electives are partnered with a research mentor based either at

NESA or in another Boston-area research institute. Projects can

involve conducting literature reviews, serving as a research assis-

tant in an ongoing study, or developing and/or conducting a

small pilot study of their own, alone or with other students.

Working with the mentor, each student is required to write an

elective proposal with clearly defined learning objectives and

fi nal products. The proposals are then reviewed, and if deemed

qualifi ed, approved by NESA’s student research coordinator—a

faculty member in charge of student research. Full academic

credit for this elective requires a minimum of 90 hours of project-

related activity. Students can take this elective up to 2 times for

academic credit. These electives do not necessarily add addition-

al credit hours to the program, as they are taken instead of other

clinically-based electives. To date, 10 students have formally reg-

istered for this elective. Representative projects include an audit

evaluating the quality of NESA’s student clinic medical records; a

systematic literature review of clinical trials employing tradition-

al Chinese medicine diagnoses as a design or outcome variable; a

literature review of the different types of controls employed in

RCTs evaluating acupuncture effi cacy; and development of a tai

chi research literature database.

Research Training Through Hands-on Participation in

Clinical Trials

In addition to the initiatives described above, another

important mechanism for research education and training has

been the active engagement/participation of NESA faculty, stu-

dents, and alumni in ongoing studies. For example, our DCRC

supports 2 pilot clinical trials of acupuncture that have engaged

faculty members and students in a variety of ways, including hav-

ing them serve as project co-leaders (n=2); project coordinators

and/or research assistants (n=5); and acupuncture protocol

developers and providers (n=10). A third DCRC-supported meth-

odological study is focused on evaluating the reliability of the

OM diagnostic process and developing a validated diagnostic

instrument. This study alone has engaged more than 50 acu-

puncturists (the majority of whom are NESA faculty or alumni)

as expert consultants or diagnosticians. In addition to providing

an opportunity for direct participation in a state-of-the-art NIH-

funded clinical trial, each of these studies provides a substantive

orientation session for acupuncturists during which the rationale

and design of the study is described and discussed. Participation

in these and other non-DCRC NESA trials continues to provide

invaluable practical research experience that complements and

informs the more didactic learning that takes place in courses

and seminars.

DISCUSSION

Although many of the education and training initiatives

described above are still in their early phases of implementation,

there are a number of indications that they are positively impact-

ing the general research knowledge/literacy of faculty members,

students, and alumni within the NESA community and also pro-

viding a pool from which more interested and motivated individ-

uals can be trained to become part- or full-time researchers.

First, our faculty, students, and alumni have become more

interested and engaged in research. During the period of support

for our DCRC, more than 75 faculty members and alumni have

been involved in some aspect of an externally funded research

study; some of these studies were not related to the DCRC.

During this time, our faculty members have published more than

25 peer-reviewed articles related to CAM. A number of these are

the fi rst peer-reviewed papers to be published by certain faculty

members. Additionally, more than 30 NESA students have

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 57

participated in some form of research through serving as research

assistants or undertaking independent studies. Perhaps more

signifi cantly, to date, NESA has graduated at least 10 students

who now include research as a signifi cant component of their

OM career (eg, project co-investigators, coordinators, research

assistants, intervention providers); most were students during

our period of DCRC support.

In addition to these tangible and practical accomplish-

ments, the DCRC has been a signifi cant catalyst in helping NESA

achieve its more conceptual goal to transform from a primarily

“vocational” institution to an academic institution. The training

initiatives described above have provided a vehicle for faculty and

staff development and a forum for collegial interactions. One of

the most common responses we have received from faculty mem-

bers who have participated in our research courses and seminars

is that the opportunity to engage in scholarly discussion with

Research Training at the New England School of Acupuncture

TABLE 4 Examples of Invited Speakers and Topics Addressed in the NESA Research Seminar Series*

Speaker Presentation title Institutional affi liation

2004

Vitaly Napadow, PhD, LicAc What Can Functional MRI Tell Us About Acupuncture and the “Sea of Marrow” That

We Don’t Already Know?

HMS, MGH

Richard Hammerschlag, PhD Strengthening the Evidence Base for Acupuncture: Quality Assessment of

Randomized Controlled Trials, 1997-2002

Oregon College of OM

Rosa Schnyer, LicAc Acupuncture in the Treatment of Depression NESA, HMS

Weidong Lu, MB, LicAc Acupuncture in the Treatment of Neutropenia NESA

Jongbae Park, PhD, LicAc Evaluating the Effectiveness of Acupuncture: A Personal Experience HMS

Helene Langevin, MD, LicAc Acupuncture: The Connective Tissue Connection University of Vermont

Andrew Ahn, MD, MPH Biophysics of Acupuncture: Electrical Properties of Connective Tissue HMS

Peter Wayne, PhD Acupuncture for Chronic Stroke Symptoms: A Randomized, Sham-Controlled Trial NESA

2005

Cathy Kerr, PhD Somatosensory Cortical Maps as Neural Correlates of Qigong, Acupuncture, and

Insight Meditation

HMS

Peter Valaskatgis, LicAc/Eric

Macklin, PhD

Results of the “Stop Hypertension with the Acupuncture Research Program”

(SHARP): A Pilot Randomized Controlled Clinical Trial

NESA and New England

Research Institute

Randy Gollub, MD, PhD Functional MRI Investigation of Acupuncture Analgesia HMS

Eric Jacobson, PhD Healing in Tibetan Buddhist Medicine and Religion HMS

Beth Sommers, MPH, LicAc Acupuncture and Side-Effect Management of HIV Medications: Results of a Pilot

Clinical Trial

Boston University

Ji-sheng Han, MD Strengthening of Homeostasis: The Essence of Acupuncture Treatment Peking University

Ary Goldberger, MD Fractals, Chaos, and Complexity in Biology and Medicine HMS

Margaret Naeser, PhD, LicAc Laser Acupuncture: Brief Introduction and Summary of Research to Treat Paralysis

in Stroke and Pain in Carpal Tunnel Syndrome

Boston University

2006

Julie Buring, ScD Evaluating the Role of Vitamin E in the Prevention of Heart Disease: the Women’s

Health Study

HMS

Peter Wayne, PhD Tai Chi Improves Dynamic Postural Stability in Patients with Vestibular Disease:

Results of a Randomized Clinical Trial

NESA

Judith D. Schaechter, PhD Effects of an Acupuncture Protocol on Sensorimotor Function and Brain Activation

in Chronic Stroke Patients

MGH, MIT, HMS

Ted Kaptchuk, OMD Experience, Experiments, and Bias HMS, NESA

Rosa Schnyer, LicAc Acupuncture in the Treatment of Post-menopausal Hot Flashes NESA, HMS

Charles Shang, MD Biology of Acupuncture: From Observation to Prediction HMS

*NESA indicates New England School of Acupuncture; MRI, magnetic resonance imaging; HMS, Harvard Medical School; MGH, Massachusetts General Hospital; OM, Oriental medicine; MIT, Massachusetts Institute of Technology.

58 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Research Training at the New England School of Acupuncture

their peers was the most enjoyable part of the experience. It is

our expectation that over time, our training initiatives will not

only continue to positively impact faculty knowledge and culture

but will also positively impact how and what students are taught

in didactic and practical classes. There is some indication that

this is beginning to happen. For example, one faculty member

who graduated from our basic research course has already begun

to integrate practical evidence-based exercises into her OM

pathology course and is beginning to explore how to expand

such modules throughout the entire NESA curriculum.

The DCRC education and faculty development activities

described above have also catalyzed and dovetailed with broader

initiatives led by NESA’s governance and administration to fur-

ther cultivate and promote scholarly activities. For example, dur-

ing the DCRC program, NESA’s faculty ranking scheme was

altered to more closely resemble that of an academic institution;

participation in scholarly activities such as research and publish-

ing now plays a more prominent position in faculty ranking and

promotion criteria. Since beginning our research program at

NESA, we have added 5 new faculty members with doctoral-level

degrees—all are directly involved in research. Additionally, 6

newly formed half-time faculty positions now explicitly include

up to 30% supported time for participation in research, writing,

or other academic pursuits. The approval of 2 new research elec-

tives also refl ects a commitment to foster more academic oppor-

tunities for students. The value of these programmatic and

cultural shifts is supported by a survey conducted in 2005 among

incoming NESA students that indicated that 41% of them were

attracted to NESA because of its involvement in research. It is

expected that over time, the presence of a stable, well-integrated

research program will continue to catalyze NESA’s evolution

toward a more academic, university-type environment.

The growing presence and impact that research training and

our research program in general has had on the culture of NESA

has not been without some resistance and questioning. One bar-

rier we encountered to the more widespread integration of

research at NESA is concern that scientifi c research and OM may

not be compatible. Many faculty members and students at NESA

were initially attracted to OM explicitly because it represents an

alternative and more holistic philosophy and approach to health

than scientifi c, evidence-based conventional medicine. For some,

the current reductionist research paradigm is believed to be inad-

equate (too limiting) for studying complex, holistic, energy-

based interventions such as acupuncture. According to this

perspective, current approaches to research will inevitably result

in biased conclusions that are unlikely to be of benefi t to the OM

community. This perspective is not unique to NESA and has

been well articulated in a number of recent debates regarding the

benefi ts and limitations of the current evidence-based models for

evaluating CAM practices.2,8,9 Acknowledging, honoring, and

sometimes sharing this concern, NESA’s research department

has been careful to emphasize that one of the motivations for our

program is to engage our faculty in research so as to challenge

this paradigm and help develop alternative research models and

methodologies. Indeed, the majority of studies initiated at NESA

have included unique design components (eg, individualized

treatments, minimally invasive controls) that honor and inte-

grate clinically relevant practices. As more of our community

learns about research and participates in it fi rst-hand, this barri-

er to the more widespread integration of research into our com-

munity is declining.

A primary motivation underlying NCCAM’s DCRC program

is the belief that sound CAM research requires the meaningful

participation of CAM practitioners in all aspects of research––

from study conception and identifi cation of specifi c hypotheses to

development of treatment interventions, choosing outcomes

measures, and interpreting results. Without signifi cant training

to improve research competency, however, the participation of

CAM institutions in research is highly unlikely. The initiatives

described in this article represent our attempt to provide educa-

tion and training to improve basic research knowledge and com-

petency among NESA faculty members, students, and alumni.

Our curriculum and initiatives can be modifi ed to suit other CAM

institutions wishing to develop a research program. Research edu-

cation/training is an important element in NESA’s strategy for

building a sustainable, productive OM research program. Other

elements of this strategy include initiatives at NESA to build

grants management infrastructure, to establish an independent

institutional review board to oversee the ethical conduct of trials,

to develop an OM research library, and to establish a fund-raising

development program to help fi nd alternative sources of income

to supplement federal grant support for research.4

AcknowledgmentsThis study was supported by Grant #5 U19 AT002022 from the National Center for

Complementary and Alternative Medicine (NCCAM). We thank Drs Heather Miller and

Barbara Sorkin for their input into this project and Dr Sorkin for her comments on an earlier

draft of this manuscript.

REFERENCES 1. Lao L, Sherman K, Bovey M. The role of acupuncture schools and individual practitio-

ners in acupuncture research. Clinical Acupuncture and Oriental Medicine. 2002;3:32-38.2. Shea JL. Applying evidence-based medicine to traditional Chinese medicine: debate

and strategy. J Altern Complement Med. 2006;12(3):255-263.3. Zick SM, Benn R. Bridging CAM practice and research: teaching CAM practitioners

about research methodology. Altern Ther Health Med. 2004;10(3):50-56.4. Wayne PM, Pensack LM, Connors EM, et al. Increasing research capacity at the New

England School of Acupuncture: building grants management infrastructure. Altern Ther Health Med. 2008;14(1):56-64.

5. Pariente J, White P, Frackowiak RS, Lewith G. Expectancy and belief modulate the neu-ronal substrates of pain treated by acupuncture. Neuroimage. 2005;25(4):1161-1167.

6. Langevin HM, Churchill DL, Cipolla M. Mechanism signaling through connective tis-sue: a mechanism for the therapeutic effect of acupuncture. FASEB J. 2001;15(12):2275-2282.

7. MacPherson H, White A, Cummings M, Jobst K, Rose K, Niemtzow R. Standards for reporting interventions in controlled trials of acupuncture: the STRICTA recommenda-tions. Complement Ther Med. 2001;9(4):246-249.

8. Verhoef MJ, Casebeer AL, Hilsden RJ. Assessing effi cacy of complementary medicine: adding qualitative research methods to the “Gold Standard.” J Altern Complement Med. 2002;8(3):275-281.

9. Wilson K, Mills E. Closing comment: Evidence-based complementary and alternative medicine: is it a viable concept? J Altern Complement Med. 2002;8(6):875-876.

www.douglaslabs.comCall today 1-888-DOUGLAB (1-888-368-4522) or 1-800-245-4440

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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60 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2

Ian D. Coulter, PhD, is a full professor at the University of

California, Los Angeles; senior health policy researcher at The

RAND Corporation, Santa Monica, California, where he holds

the RAND/Samueli Chair in Integrative Medicine; and research

scientist at the Southern California University of Health

Sciences, Whittier, California. John Walsh, LLM, is a senior lec-

turer in Business Law in the College of Business and Economics,

University of Canterbury, Christchurch, New Zealand. (Altern

Ther Health Med. 2008;14(2):60-64.)

In The Log from the Sea of Cortez, John Steinbeck relates

how his friend Ed Ricketts, after the destruction by fi re of

his Cannery Row laboratory, testified at a trial in the

Superior Court in Salinas. His company, Pacifi c Biological

Laboratories, Inc, was one of the plaintiffs in a suit against

the electric company, unsuccessfully alleging that the fi re was

caused by error or negligence by the company. “Now you take the

case of this fi re,” he went on. “Both sides wanted to win, and nei-

ther had any interest in, indeed both sides seem to have a kind of

abhorrence for, the truth.”1(p233)

In this article we examine an exemplar (dietary supple-

ments) of the clash between science and law and the dangers

inherent in judges wandering in the murky fi eld of scientifi c con-

troversy and using it as the basis of a judgment.

THE CASE

In Commerce Commission v Zenith Corporation Limited

(Auckland, New Zealand), the defendant ultimately faced 23

pairs of alternative charges, all concerning representations in

promotional materials for “Body Enhancer” or its successor,

“Neo Nutrients Body Enhancer.”2 Twenty-three charges alleged

representations liable to mislead the public as to the suitability

for a purpose of goods, in terms of sections 40(1) and 10 New

Zealand Fair Trading Act 1986 (FTA); 23 alternative charges

alleged false or misleading representations as to the benefi ts of

goods, in terms of sections 40 (1) and 13 FTA. Two of the original

informations (ie, legal fi lings) were withdrawn. The defendant

also faced 3 charges relating to representations made on labels of

“Neo Nutrients Body Enhancer,” which are not relevant to this

article. All of the alleged offenses pre-dated the 2003 amend-

ments to the FTA. Section 13 FTA was amended in 2000 and took

effect November 15, 2000. By that date, the events that were the

subject of some of the charges outlined above had already

occurred, but others giving rise to the remaining charges had

not. The effect of the amendment was to replace “false” in the

section heading with “false or misleading” and to replace “falsely

represent” as the opening words of each of paragraphs 13(a)-(f )

with “make a false or misleading representation.” The charges

alleging a contravention of section 13(e) refl ected that amend-

ment. The charges were based on representations in pamphlets

and radio and magazine advertisements and on a website saying

that the product “will assist with” a variety of conditions, includ-

ing weight loss; liver detoxification; preventing the effects of

body collagen depletion; healing of cartilage and strengthening

of joints, tendons, and heart muscles; and others.

Witnesses called by both the prosecution and the defense

gave expert evidence. Judge Moore was critical of some evidence

given by expert witnesses called by the defendant. He described

Professor Vitetta, for example, as a witness “whose approach

seemed founded on a sense that his task was to produce additional

or contradictory evidence rather than to form an overview which

took into account all relevant material.”2 Dr Cortizo was said to be

“quick to fi nd opportunities to allege bias on the part of witnesses

for the informant but, despite his skills at diversionary tactics, that

approach, or rather the justifi cation for it, did not survive cross-

examination.”2 Generally, expert witnesses called by the

Commission found favor with Judge Moore. He found that

Professor Swinburn “adopted apt strategies and limitations, and

that the work and study which lay behind his evidence was carried

out skilfully, painstakingly, logically and with integrity.”2 Professor

Mann was said, like Professor Swinburn, to be “calm, measured,

analytical and detached.”2 Dr Barling “presented as a very relaxed

man, entirely comfortable with who he was and where he was at.”2

Before convicting the defendant on 26 charges, Judge Moore

summarized the expert evidence. When asked, “How simple

Randomized Controlled Trials and the Law

original article

RANDOMIZED CONTROLLED TRIALS AS EVIDENCE IN LEGAL DISPUTES ABOUT THE BENEFITS OF

COMPLEMENTARY AND ALTERNATIVE MEDICINEIan D. Coulter, PhD; John Walsh, LLM

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 61Randomized Controlled Trials and the Law

would it be to conduct a randomised control [sic] trial of a weight

loss product such as Body Enhancer?” Professor Swinburn

replied, “It would be extremely simple actually.”2 In his evidence,

Professor Mann stated that the randomized controlled trial

(RCT) is “an integral part of evidence based medicine and should

wherever possible inform medical opinion and practice” and that

“several RCTs reviewed by a panel of appropriately experienced

professionals or reanalysed statistically in a meta-analysis is

regarded as the highest level of evidence.”2

He noted that RCTs on the effect of vitamin E on humans had

reversed earlier research on animals that had indicated that

vitamin E could favorably improve several risk factors for

coronary heart disease and stated that “there is no reason

evidence [sic] why the reported ingredients of Body Enhancer or

indeed the product itself could not or should not be assessed

using strict RCT procedures.”2 He saw such a trial as “conceptually

simple, it would probably be moderately costly.”2

Professor Mann went on to note that even after a compound

has been tested in several RCTs, several factors, such as form of

delivery, route of delivery, matrix, form of the compound, purity

of the compound, quantity/dose, and physiological state of the

recipient should be considered when assessing claims about

effi cacy.2 Although Judge Moore emphasized with respect to all

of the charges that “a conviction can be entered only if the

informant proves the guilt of the defendant beyond reasonable

doubt”2 and that “there is no obligation on the defendant to

prove its innocence or to prove anything else,”2 he included the

following in his judgment:

One of the noteworthy features of the evidence before the

Court is that, other than the references to dexfenflu-

ramine and orlistat (Zenical [sic]) it does not include

even a reference to any properly conducted clinical stud-

ies as to the efficacy of extensively marketed weight loss

products, whether patented or not. Yet on the evidence

before this Court, sales of Colorad long ago exceeded

$US200 million. If success had been achieved in the

commercial exploitation of any one of the many patents

before the Court, it would be surprising if that had not

given rise to properly conducted double blind clinical

trials to provide a foundation, not only for the advertis-

ing of therapeutic claims, but the re-launch of the prod-

uct as a recognized medicine, able to be prescribed by

doctors. There is, of course, nothing of the sort.2

He noted that it was only when faced with prosecution that

Zenith took any steps to obtain a controlled trial of the product,

and had then contacted a person he described as an “entrepreneur-

ial doctor”2 rather than a reputable organization with the skills nec-

essary for the proper design, conduct, and analysis of such a trial.

Noting that there is more than 1 accepted scale of classifi cation of

clinical studies and similar research, he nevertheless saw “double

blind randomised controlled trials in which neither the study par-

ticipants nor those directly involved in the conduct of the trial

know whether any particular participant is receiving a placebo or

the substance being tested”2 as the “gold standard.”

THE LAW AND RANDOMIZED CONTROLLED TRIALS

Was the judge on good grounds adopting such a stance? To

answer this we need to examine the nature of science itself and in

particular the RCT. Although the Cochrane Collaboration lists

more than 4000 CAM-related RCTs in its database,3 many manu-

facturers and distributors of complementary and alternative

treatments cannot afford to conduct such a trial. RCTs are gener-

ally conducted by manufacturers of conventional medicines,

most often to satisfy the US Food and Drug Administration,

which decides whether a manufacturer has provided “substantial

evidence” from “adequate and well-controlled investigations”

that a drug is effective for its intended use.4 This decision has

usually been based on more than 1 RCT.

This procedure has not escaped criticism. Research can be

falsifi ed but because of the possible criminal and civil penalties,

harm to reputation, and a possible continuing absence of trust

by the regulating authorities, such falsifi cation is generally avoid-

ed, if only because “there may be ways short of fraud to control

the outcome of research.”5(p123) Those ways include biases in the

design of a research study and in the reporting of such a study,

either or both of which may be related to the so-called “funding

effect”—the name for the fact that “strong and consistent evi-

dence shows that industry sponsored research draws pro-industry

conclusions.”6(p59) In addition to these objections, there are other,

more philosophical objections to the primacy of the RCT.

EVIDENCE-BASED PRACTICE: RANDOMIZED

CONTROLLED TRIALS AND THEIR LIMITATIONS

In opting for the RCT as the gold standard, Judge Moore wan-

dered into the field of evidence-based practice, at the heart of

which is the RCT. The defi nition formulated for evidence-based

medicine is that it is “the conscientious, explicit and judicious use

of the current best evidence in making decisions about the care of

individual patients. The practice of evidence-based medicine

means integrating individual clinical expertise with the best avail-

able external clinical evidence from systematic research.”7(p1085)

The dominant focus of evidence-based practice has been the

RCT. However, it is not the single RCT that is the gold standard;

rather it is the systematic review of trials that is the most signifi -

cant, particularly those that result in a meta-analysis.8 In fact, the

results of even a double-blinded trial can be misleading, particu-

larly if the number of subjects is insuffi cient to power the study

(ie, give it statistical legitimacy). Meta-analysis overcomes that

problem by combining studies that are homogeneous so that the

subject pool is larger.

Although other forms of study design may be included in a

systematic literature review (non-random trials, cohort studies,

and simple pre/post case series) the RCT is given most weight

since it is the design that most clearly establishes efficacy.

Unfortunately, such studies generally test a therapy under ideal

conditions and often with homogeneous populations to ensure

62 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Randomized Controlled Trials and the Law

comparability of the groups when comparing outcomes. But

evidence-based practice ultimately requires therapies that can be

applied in normal practice, that is, effectiveness studies.9 Just as a

therapy without any effi cacy will not be effective, a therapy that

demonstrates efficacy in a study may not be effective when

applied to heterogeneous populations under normal practice

conditions. Furthermore, therapies with equal or comparable

effi cacy may differ considerably in terms of effectiveness.

In contrast, however, RCTs test therapies under ideal condi-

tions10 and therefore do not often help with determining effective-

ness in everyday practice as opposed to effi cacy in a controlled,

and usually perfect, setting. There are some very strict ethical lim-

itations to conducting clinical trials that prevent certain popula-

tions from participating. If there is a very high risk but low benefi t

for a sub-group of patients, this might mitigate against them

being included (such as patients with high co-morbidities).

Conversely, some low-risk patients may not be included because

too large a number would need to be enrolled to make the study

feasible.11 The end result, therefore, is that clinically it is not pos-

sible to know if the therapy can be applied to groups that were

not included in the trial.

Although providers do treat populations, they treat them

one at a time. RCTs seldom contain the “soft data” about individ-

ual variations, particularly in response to therapy. The type of

clinical detail essential for a provider to decide whether a given

patient is a candidate for a drug, procedure, or therapy is seldom

provided in an RCT.12 RCTs provide the results of average patients

and even then it is an average of those who meet the inclusion cri-

teria. This problem can be solved through observational studies.

There is a dilemma, however, about the role of observational

studies. On the one hand, they may seem more clinically relevant

and include the populations and sub-populations of interest to

the health provider, but on the other they do not provide the type

of defi nitive evidence that might persuade the provider to recom-

mend the procedure to the patient. Despite this ambivalence,

observational studies continue to be widely published. Ray, in a

2-month survey in 1998 of 3 leading medical journals, found that

observational studies comprised 68% to 87% of their featured

articles and communications, and only 32%, 13%, and 26% of

their publications were RCTs.13 He notes that although we do not

know how observational studies impact practice or policy, given

their propensity to publish them, these journals must feel that

observational studies are important to their readers.

One solution to the dilemma in evidence-based practice has

been to create a hierarchy of evidence. A standard hierarchy is

the following (from the highest to the lowest): evidence provided

by at least 1 appropriately designed RCT; evidence provided by a

controlled trial that is not randomized; evidence provided by a

well-designed cohort or case-control study; evidence provided by

a multiple time series, descriptive studies, case reports, and opin-

ions of experts or respected authorities.14

There is an expanding body of literature on studies examin-

ing RCTs and observational studies for the same disease and

intervention. As Iaonnidis et al note, earlier studies concluded

that nonrandomized studies overestimated treatment benefi ts.15

More recently, the studies show that both randomized and non-

randomized studies yield very similar results. Their own study

found a very good correlation between the 2 but that the nonran-

domized studies did show larger treatment effects. Interestingly,

they found that heterogeneity was frequent between studies in

both groups. Benson and Hartz found little evidence of a differ-

ence in the treatment effects between RCTs and observational

studies when the comparison was made for the same treatment.16

Concato, Shah, and Horwitz found in their study that in the

5 topics they examined where there were bodies of both RCTs

and observation studies, the results of well-designed observation

studies did not systematically exaggerate the magnitude of the

effects of treatment compared to the RCTs for the same topic.17

They concluded that their results challenge the hierarchy of evi-

dence being used in clinical research (and systematic reviews).

Those studies with either a cohort or case control design did not

overestimate the outcomes and the results of the RCTs and these

studies were very similar. In fact, the observational studies have

less variability in point estimates than did the RCTs. This also

meant their results were less heterogeneous.

Discrepancies in RCTs and between RCTs and meta-analyses

have been noted previously.18 This makes using a single RCT as

the gold standard for care a questionable approach. As Concato,

Shah, and Horwitz note, because of the inclusion and exclusion

criterion used in RCTs, an observational study is more likely to

include a broader representation of the population.17 They also

note that earlier studies comparing observation studies and RCTs

had included all types of observation studies in the comparison.

If, however, the comparison is made with cohort and case control

studies, the superiority of RCTs is not so clear. Of course, such a

conclusion raises the question of whether there is a hierarchy of

observational evidence. Stroup et al have put forward a proposal

for improving the reporting of meta-analyses of observational

studies in an attempt to answer the question of the quality of

observation studies.19

According to LeLorier et al, the recent research has begun to

assert that quality observation studies are no more misleading

than RCTs.17 The popular belief that only RCTs produce trustwor-

thy results and that all observational studies are misleading does

a disservice to patient care, clinical investigations, and the educa-

tion of healthcare professionals.

MEDICINE AND EVIDENCED-BASED PRACTICE

There is considerable debate about how much of clinical

practice is evidenced-based. The initial estimates by the Offi ce of

Technology Assessment in 197820 and 198321 were that only about

10% to 20% of medicine could claim to be evidenced-based. As

noted by Imrie and Ramey,22 this fi gure was simply an estimate.23

They further note that other commentators have given fi gures as

low as 15% for practices based on any evidence. The problem of

establishing any figure is you first need to define what will

constitute the evidence. How you do that has a great impact on

the result. If, for example, you demand only 1 good single RCT,

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 63Randomized Controlled Trials and the Law

the figure will be much higher than if you required repeated

RCTs. The use of a single RCT, no matter how good the study,

does pose methodological problems. Single studies can be

contradicted by later studies. To overcome the problem of a

single study, studies are pooled if they are homogeneous enough

to permit a meta-analysis. This also greatly increases the sample

sizes on which analyses can be done.24,25 Examples of misleading

meta-analysis have been documented in the literature.26

Furthermore, studies with negative results are less likely to be

published. This has a tremendous impact on the “evidence.”27,28

THE JUDGE AND THE SCIENCE

When a judge opts to accept the opinion of some scientifi c

experts, he is in fact opting for the lowest ranked of all scientifi c

knowledge in evidence-based practice. He is also supporting 1

scientific paradigm over others—in this case, evidence-based

practice—and elevating 1 form of research design, the RCT, over

all other forms.29 The problem with all this is there is good evi-

dence that expert opinion is shaky at best and frequently down-

right wrong; there is an increasing body of research that

questions whether the RCT is the gold standard the experts claim

it to be. There is considerable evidence to suggest that medicine

itself (or at least about 80% of it) could not meet the standard of

evidence supported by RCTs and, last but not least, there is no

evidence that evidence-based practice, where it does exist, results

in better patient outcomes. In the face of this, how has the law

dealt with expert opinion?

EXPERT SCIENTIFIC EVIDENCE

In common law, the general rule is that witnesses cannot

offer opinion as evidence; one exception to that rule is that suffi -

ciently qualifi ed expert witnesses may give opinion evidence on

matters within their area of expertise. That exception is in turn

circumscribed by a series of subsidiary rules: the “common knowl-

edge” rule, that such an expert cannot give evidence on a matter

within the knowledge of the fi nder of fact; the “ultimate issue”

rule, that such an opinion is inadmissible if it is an issue the fi nder

of fact must determine; the “factual basis” rule, that the facts

upon which the opinion of the expert is based must be proved by

admissible evidence. There is considerable consensus internation-

ally about the circumstances in which such evidence, particularly

when it includes novel or controversial ingredients, can be intro-

duced and considered in court. In R v Calder,30 introducing the

topic of expert evidence of new scientifi c techniques or theories

by quoting an Australian text that stated that “the issue of how to

deal with areas that have not yet fully emerged from their devel-

opmental stages remains unsolved,”31 Judge Tipping examined

authorities from England,32,33 Canada, Australia, and the United

States. In Canada, in R v Johnstone,34 14 points were seen as rele-

vant to whether scientific evidence, if challenged, should be

admitted or excluded; in R v Melarangi,35 9 points, some of which

were the same as or similar to those in Johnstone were deemed rel-

evant. In Australia, in R v Lucas,36 Judge Hampel urged caution

with respect to the introduction of challenged scientifi c evidence,

referring to United States v Baller,37 in which it was noted that

“because of its apparent objectivity, an opinion which claims a sci-

entifi c basis is apt to carry undue weight with the trier of fact.” In

the United States, the leading authority for many years had been

Frye v United States,38 in which “general acceptance” of a scientifi c

technique or theory was required.

That test had been the subject of considerable criticism, and

the Supreme Court of the United States revisited the topic in

light of the Federal Rules of Evidence in Daubert v Merill Dow

Pharmaceuticals,39 in which it was decided that the “general

acceptance” test in Frye was not a necessary pre-condition to

admissibility. Among the factors the court recognized as relevant

to whether expert scientifi c testimony should be considered was

general acceptance, but other factors, such as peer review and

publication, whether the theory or technique can be or had been

tested, and potential or known rate of error, were also regarded

as relevant to the question. The court saw the judge as playing a

“gate keeping” role and believed that vigorous cross-examination,

presentation of contrary evidence, and careful instruction on the

burden of proof were appropriate methods to attack shaky but

admissible evidence.

Judge Tipping also received assistance from a New Zealand

Law Commission discussion paper40 that—although recom-

mending that scientifi c evidence should be assessed for reliabili-

ty, including the reliability of the underlying theory and the

reliability of the procedures and techniques used in a particular

case—nevertheless contended that a theory need not be accepted

by all or even most scientists in an area to be admissible, and

that theories that were new or represented the views of a minori-

ty could be reliable and helpful. The discussion paper contended

that procedures ought to conform to acceptable scientifi c stan-

dards, but that an opinion need not be conclusive in order to be

admitted into evidence. In Calder, Judge Tipping ultimately

decided that, to be admitted, such expert evidence should be rel-

evant, helpful, and more probative than prejudicial; relevant, as

in tending to show that a fact in issue is more or less likely; help-

ful, as in passing a “minimum threshold of reliability” test in that

the proponent of the evidence demonstrates that it has suffi cient

claim to reliability to be admitted. Once the threshold has been

crossed, the weight of the evidence and its probative force can be

tested in cross-examination and counter evidence. Judge Tipping

acknowledged that the “suffi cient claim to reliability” test could

be too general to be of much assistance, but saw fl exibility as a

desirable ingredient; the points set out in the Canadian cases

Johnstone34 and Melarangi35 could be useful in deciding whether

the threshold had been crossed. Whether the judge, as gatekeep-

er, opened the door or kept it shut in any individual case would

depend on a wide variety of subsidiary issues.

CONCLUSION

Imagine that a corporation, instead of selling a weight-loss

product, sold “retroactive prayer” and claimed that such prayer,

offered from 4 to 10 years after an event, can affect outcomes. A

randomized, controlled, double-blind, parallel group study41

64 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Randomized Controlled Trials and the Law

including 3393 patients considered the hypothesis that such ret-

roactive prayer affects outcomes. The study concluded that,

although mortality was similar in both groups, length of stay in

hospital and duration of fever were shorter with such prayer.

Although there may be all kinds of other evidence, should that

RCT evidence be conclusive were the corporation to be charged

with a contravention of the Fair Trading Act 1986, or should the

judge consider all of the evidence tendered? In deciding what evi-

dence should be considered, it is fi tting to conclude with another

quotation from John Steinbeck, this time referring to one of Ed

Ricketts’ fi ctional alter egos, “Doc,” in the novel Sweet Thursday, in

which the local inhabitants decide to bid Doc farewell with a gift,

knowing that he wants a new microscope for his laboratory.

Doc looked at the gift—a telescope strong enough to bring

the moon to his lap. His mouth fell open. Then he smothered the

laughter that rose in him.

“Like it?” said Mack.

“It’s beautiful.”

“Biggest one in the whole goddam catalogue,” said Mack.

Doc’s voice was choked.

“Thanks,” he said. “After all, I guess it doesn’t matter

whether you look down or up—as long as you look.”42(p263-264)

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trials and systematic reviews to individual patients. ACP J Club. 1998;129(3):A15-A16.11. Radford MJ, Foody JM. How do observational studies expand the evidence base for

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in randomized and nonrandomized studies. JAMA. 2001;286(7):821-830.16. Benson K, Hartz A. A comparison of observational and randomized, controlled trials.

N Engl J Med. 2000;342(25):1878-1886.17. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies,

and the hierarchy of research designs. N Engl J Med. 2000;342(25):1887-1892.18. LeLorier J, Gregoire G, Benhaddad, Lapierre J, Derderian F. Discrepancies between

meta-analyses and subsequent large randomized, controlled trials. N Engl J Med. 1997;337(8):536-542.

19. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epide-miology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-2012.

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Technology Assessment, OTA-BP-H-22; August 1983.22. Imrie R, Ramey DW. The evidence for evidence-based medicine. Complement Ther Med.

2000;8(2):123-126.23. Michaud G, McGowan JL, van der Jagt R, Wells G, Tugwell P. Are therapeutic decisions

supported by evidence from health care research? Arch Intern Med . 1998;158(15):1665-1668.

24. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127(9):820-826.

25. Bland CJ, Meurer LN, Maldonado G. A systematic approach to conducting a non-sta-tistical meta-analysis of research literature. Acad Med. 1995;70(7):642-653.

26. Egger M, Smith G D. Misleading meta-analysis. Br Med J. 1995;311:(7007)753-754.27. Eskinazi D, Muehsam D. Is the scientifi c publishing of complementary and alternative

medicine objective? J Altern Complement Med. 1999;5(6):587-594.28. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical

research. Lancet. 1991;337(8746):867-872.29. Kramer MS, Shapiro SH. Scientifi c challenges in the application of randomized trials.

JAMA. 1984;252(19):2739-2745.30. R v Calder (unrep). Tipping J. High Court, Christchurch, New Zealand. T154/94. April

12, 1995. 31. Freckleton I, Selby H, eds. Expert Evidence. North Ryde, Australia: The Law Book

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Review. 1992 Oct:687-698.33. R v Robb, 93 Crim App Rep 161 (1991).34. R v Johnstone, 69 C.C.C. 395 (1992).35. R v Melerangi, 73 C.C.C. (3d) 348 (1992).36. R v Lucas, 2 V.R. 109 (1992).37. US v Baller, 519 F2d 463 (1975).38. Frye v United States, 293 F 1013 (1923).39. Daubert v Merill Dow Pharmaceuticals, 509 United States Supreme Court Reports 469,

1993.40. Evidence Law: Expert Evidence and Opinion Evidence. New Zealand Law Commission

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w i t h b l o o d s t r e a m i n f e c t i o n : r a n d o m i s e d c o n t r o l l e d t r i a l . B M J . 2001;323(7327):1450-1451.

42. Steinbeck J. Sweet Thursday. Heineman, London; 1954:263-264.

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66 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Conversations: Jacob Liberman, OD, PhD

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 67 Conversations: Jacob Liberman, OD, PhD

focusing my attention on reading and schoolwork. I had great

diffi culties in going through school. Because of that, I always had

the feeling something was wrong with me.

I was very tuned in. I could read people very well, but to

concentrate on a 2-dimensional task like looking at a book all

day was hard for me. I would start reading, and I’d feel very dis-

tracted or I would fall asleep. However, I had excellent eyesight.

Whenever my parents took me to the eye doctor, the doctor

would say, “His eyes are perfect.” No one ever put it together that

the diffi culties that I was having in the classroom were in any

way related to my vision because vision was defi ned as eyesight,

and I had 20/20.

When I got out of high school and I entered college, about 10

days into the fi rst semester the teacher gave us a pop quiz. I was

sitting in the back of the class because my eyesight had always

been excellent. In the middle of the test, I looked up at the black-

board, and the blackboard all of a sudden was fuzzy. And it stayed

fuzzy. I got very frightened; I didn’t know what was wrong. I fi n-

ished the test and then went to the eye doctor at the infi rmary.

The doctor examined me and said, “Oh, you’re just near-

sighted.” He didn’t tell me that my near-sightedness was just a

minute amount, and he never mentioned that I had had a spasm

in my accommodative or focusing system from doing so much

close work, which is, of course, what happens when you’re in col-

lege. He gave me glasses. I was just grateful I didn’t have some

pathology. So I started wearing glasses, and I could see the black-

board, but I still couldn’t read for longer than I’d been able to

before. In fact, reading became ever more uncomfortable.

Every 6 months or so, I would notice that I couldn’t see the

blackboard anymore, so I had to keep getting stronger and stron-

ger glasses. But nothing was changing in terms of my ability to

read and learn with greater ease. When I got into optometry

school, the reading demand increased significantly, and I was

barely getting by between working to pay my way through school

and having a full school load—optometry school is basically the

same pre-med as you get in a medical school. It’s very intense. The

fi rst 2 years, I was so close to not getting by that I actually thought

they would not allow me to go into my third year. But they did.

When I entered my third year, which is when you start your

clinical training, they sent me down to the clinic, and they asked

one of the fourth-year doctors to examine me. They gave me a

Jacob Liberman, OD, PhD, received a doctorate of optometry in

1973 from Southern College of Optometry, Memphis, Tennessee; a PhD

in Vision Science in 1986 from The College of Syntonic Optometry,

Leadville, Colorado; and an honorary doctorate of science in 1996 from

The Open International University for Complementary Medicines. He

is a fellow emeritus of The American Academy of Optometry, The

College of Optometrists in Vision Development, The College of Syntonic

Optometry, and The International Academy of Color Sciences. He is

also the recipient of the H.R. Spitler Award for his pioneering contribu-

tions to the fi eld of phototherapy.

For the past 35 years, Dr Liberman has worked with thousands

of individuals, ranging from children with learning difficulties to

Olympic and professional athletes. He has been interviewed on hun-

dreds of radio and television shows, addressing audiences worldwide.

Luminaries in the fi elds of science, medicine, consciousness, and pro-

fessional sports have endorsed his work.

Dr Liberman is founder of Exercise Your Eyes, Inc, and has

authored 3 books: Light: Medicine of the Future (Rochester,

Vermont: Bear & Company; 1990) Take Off Your Glasses and See

(New York: Three Rivers Press; 1995), and Wisdom From an Empty

Mind (Sedona, Arizona: Empty Mind Publications; 2001), all of

which have received international acclaim and have been published

in multiple languages.

Alternative Therapies in Health and Medicine (ATHM): How did

you become interested in natural and holistic approaches to vision?

Jacob Liberman, OD, PhD: I was born in Havana, Cuba, and

when I came to the United States in 1955, I didn’t speak any

English. In fact, English was my third language. It was diffi cult

coming to Miami, Florida, in 1955 and having no one other than

my family that I could speak to.

I found myself having diffi culties in school, initially because

of the language and then I realized I also had some diffi culties

JACOB LIBERMAN, OD, PHD: CHANGE YOUR VISION, CHANGE YOUR LIFE

Interview by Marc David and Suzanne Snyder • Photography by Greg Hoxsie

Opposite: Dr Liberman, photographed near his home in upcountry

Maui, says that the epidemic of deteriorating eyesight is caused

primarily by the stress created by visual confi nement—the cultural

demand to sit and look at a book or a computer all day.

CONVERSATIONS

68 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Conversations: Jacob Liberman, OD, PhD

vision exam, and the young man told me the same thing every-

one before him had told me: “You need a stronger pair of glass-

es.” But he also said, “You know you’re having some problems

using your eyes together and that could be in some way affecting

your comfort during reading.” He suggested that I do some

vision exercises. He gave me a little device and I took it home, but

I never used it. I just stuck it in the corner of my room.

One day I was doing an assignment and after a few minutes

of reading, the same thing happened that always happened: I fell

asleep. When I opened my eyes, the first thing I saw was the

device at the other end of the room. I had a revelation. Something

said, “Pick it up.” I picked it up. I did 1 exercise on it for no more

than 4 or 5 minutes and then I

read for an hour, non-stop, with

the most perfect attention and

comprehension I had ever experi-

enced in my life.

It hit me so hard that I start-

ed crying because my whole life, I

thought I was stupid. I did the rec-

ommended protocol for about 2

months and then made the dean’s

list every quarter until I graduated.

I went from a 2.0 average to end-

ing up in the top 10% of my class.

That was my fi rst profound

experience with the fact that

vision is much more than eye-

sight, and that just because we

have 2 eyes open doesn’t mean

that they’re both being used. You

have 2 legs, but if you had use of

only 1 of them, it would create a

huge imbalance in your life. The

same is true with your vision. If

both eyes are not working together effi ciently, it will affect your

comfort and performance in a very signifi cant way.

Additionally, if one’s vision is functioning excellently, his

response to life will be perfectly timed, so if he’s playing base-

ball, the bat will be swung at the right moment, will hit the ball

on the sweet spot and even if he doesn’t hit the ball hard, it’ll go

a great distance. That’s great vision. So vision is not so much

what you see, it’s what you do with what you see. It’s your

response to life. That fi rst experience, which happened in 1971,

changed my life.

ATHM: What was your next step in getting to where you are

today?

Dr Liberman: In my fi rst several years of practicing optometry, I

was very involved in working with young children and teenagers

who had diffi culties with learning because that was something

that I knew by heart—that was my own story. I worked with

thousands of kids. And in late 1975, the thought came to me: “I

wonder if there’s anything that I can do that could in some way

improve my eyesight.” Because when I went to school, I wasn’t

taught that vision could affect everything; it was just an optical

system, a camera inside the head. We were taught that eyes got

worse because they were too long or too short or oddly shaped.

The idea that vision could be improved was never discussed.

One of the fi rst things that is taught in medical school is that the

body is always seeking homeostasis, always seeking balance.

We know health means balance. You could say that the

heartbeat of life, of the universe, of the human body is a continu-

al movement toward equilibrium. I call it homeodynamics. It’s

not really homeostasis; it’s just a continual movement, a search

for balance.

This is probably why in science we

say, “The only constant is change.” That

change is the continual adjustment of

the inside of the body to the environ-

ment. We know the body has the ability

to self-heal, but for some reason or

other, this is an unknown concept in the

area of vision. Vision specialists know

that very few people enter this world

needing glasses or seeing poorly—prob-

ably less than 1%. Yet by the end of fi fth

grade, more than 80% of kids have mea-

surable vision diffi culties.

In many places where education is

stressed, like Israel, Asia, and the

United States, by the time kids are 16

or 17, well over 80% are near-sighted.

The biggest health epidemic in the

world right now is deteriorating eye-

sight, and yet all we do is give glasses or

contacts. If you look at the records of

any vision specialist in the world, you’ll

notice that the moment a patient begins to wear glasses, his eyes

continue to deteriorate. What I’ve always said is, if the problem

gets worse, the solution can’t possibly be the solution.

And yet we’re not looking for the causative factor. We’re

looking at using glasses or contacts or doing surgical interven-

tion like LASIK as a way of neutralizing the problem, but we’re

still not looking for the cause, and we’re still not broadening our

idea of what vision is beyond the concept of eyesight. So in 1976,

I started doing vision training on myself a few minutes a day

and rather than continually increasing the prescription of my

glasses, which is what my history for 10 years had been, I began

reducing my prescription very subtly every 6 to 8 weeks, gradu-

ally allowing myself to adjust to a weaker prescription as my

vision skills improved.

I also spent time without my glasses on, just to notice how it

felt internally when I wasn’t wearing them. I wasn’t primarily

concerned with whether I could see or couldn’t see, but rather

how I felt emotionally. I noticed that I started feeling out of con-

trol and edgy without my glasses on and noticed that wearing the

ONE OF THE FIRST THINGS

THAT IS TAUGHT IN MEDICAL SCHOOL IS THAT THE BODY IS ALWAYS SEEKING BALANCE.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 69 Conversations: Jacob Liberman, OD, PhD

glasses masked a lot of these symptoms. After a while I noticed

that when I was able to take the glasses off for longer and longer

periods of time, I got more and more comfortable with a lot of

these feelings and as my comfort increased, my eyesight started

to change.

Within 8 or 9 months of doing this, my eyesight improved

about 200% to 300%. I also had a revelation during a meditative

experience that led me to recognize that vision was something

way beyond eyesight. The combination of those experiences

allowed me to see clearly without my glasses on. That happened

in 1976 when I was 29. I just turned 60 in November and have

never worn a pair of glasses for any purpose since that day. I don’t

wear glasses for distance or for read-

ing and personally don’t fi nd a need

for sunglasses.

I uncovered something through

my own personal process that has

allowed me to see vision in a whole

new way and to recognize that if you

can optimize your vision, it can have

life-transforming effects. Vision

accounts for about 90% of the infor-

mation human beings take in during

their lifetime. Vision is not so much

what we see, it’s what we do with

what we see; it’s the body’s naviga-

tional system. So when we optimize

vision, we’re not talking about opti-

mizing eyesight only, we’re talking

about optimizing the ability of the

eyes to aim, focus, track, and work

together as a team.

ATHM: Can you explain those functions in detail?

Dr Liberman: These 4 functions—aiming, focusing, tracking,

and teaming—occur simultaneously and are inseparably con-

nected to one’s consciousness. To give you an example, when you

are speaking with someone and they’re paying attention to you,

how do you know they’re paying attention to you? You know

because they’re looking at you. In order to attend, to be present,

the eyes must converge upon that which is of interest.

When the eyes aim or converge, they simultaneously focus.

This process is inseparably connected with our ability to selective-

ly attend and be present. In other words, aiming and focusing the

eyes is required for us to both suppress external noise and quiet

the mind. This is extremely important because being present and

attentive is the most fundamental function involved in learning.

This is also why most meditative practices have you focus on

something. Even though the eyes are closed, they say, “Focus on a

mantra. Focus on the third eye. Focus on something.”

When we think of the word focus, we think of an optical sys-

tem. But to say something is in focus is to say it is clear. That’s

why people say “I see” to indicate that they understand some-

thing. Seeing is inseparably connected with understanding.

Aiming lays the foundation for presence and effortless attention,

while focusing provides a sense of clarity and knowing.

Next comes tracking, which occurs at the same time as aim-

ing and focusing. We say the only constant is change. So as things

in the environment enter our fi eld of awareness, the eyes are auto-

matically moved toward them. It’s an effortless process because

light and the eye are married. When light strikes the eye, the eye

automatically moves toward it in the same way as a fl ower turns

its face toward the sun. Tracking is the process of continually

moving the eyes from one moment to the next as things in the

environment call our attention.

So the eyes simultaneously

aim, focus, track, and work togeth-

er as a team. The teaming aspect

of vision is very important because

having 2 eyes gives us the ability to

have stereoscopic or 3-dimensional

vision. Dr Arnold Gesell, who at

one time was the leading child-

development expert in the world

and who founded the Gesell

Institute of Child Development at

Yale, said that stereoscopic vision

was the crown jewel of organic

evolution. He said it was the most

highly developed aspect of our

neurological system.

Having 2 eyes not only gives

us the ability to see depth, it also

allows us to determine what’s

foreground and what’s back-

ground, what’s most important

and what’s less important at that moment. It lets us know where

we are in space in relation to other things. Good eyesight is the

ability, for instance, of a baseball player to see the pitcher clearly.

Good vision is the ability of that player to track the baseball at 95

or 100 miles per hour from the pitcher’s hand to the plate and be

so integrated that his arms and body move at the exact moment

necessary for the bat to hit the ball.

In the classroom, that level of vision provides a child the abil-

ity to effortlessly attend, allows the eyes to move smoothly across

a line of print, so that reading and comprehension and attention

become something that’s fun and easy. If a child is having any dif-

fi culty with these functions, learning becomes very diffi cult.

ATHM: Given your explanation of how big the definition of

vision can be, what is creating this epidemic of young people not

being able to see clearly?

Dr Liberman: I’ll tell you exactly what it is. You live in Boulder,

Colorado, a place where there’s a lot of expanse, a lot of space.

When people step outside, most will breathe a sigh of relief

because their eyes can escape all the way out to infi nity. You know

Vision is not so much

what we see, it’s what we do with what we see; it’s the body’s navi-gational system.

70 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Conversations: Jacob Liberman, OD, PhD

how sometimes it’s a little more diffi cult to breathe deeply when

you enter a small space such as an elevator? Well, we have 2 eyes

in order to be able to see all the way out to infi nity. However, if

your visual space is confi ned, your body begins to show signs of

stress. If you, for instance, put an animal in a visually confi ning

environment, so that its eyes can look only as far away as 18 or 20

inches, that animal will become myopic. A high percentage of sail-

ors that are in a submarine for a month or 6 weeks are near-sighted

when they come out. Their near-sightedness may reverse, but

visual confi nement creates a constriction in vision.

Most of the epidemic of near-sightedness that we have today

is because the demand on the eyes is for reading and learning.

Most people spend a good part of their day either looking at a

book 16 to 20 inches away or, even more commonly today, look-

ing at a computer monitor. Many school children sit in window-

less classrooms. Many people work in cubicles or in offices

without windows.

The major problem is that our eyes are very often confi ned to

a close distance, so they adjust to that distance because that is

what society says is important for us to succeed. If our neurologi-

cal system were designed for a 2-dimensional world, we would

only require 1 eye in the center of our head. The reason we have 2

eyes is to give us 3-dimensionality. In other words, our entire neu-

rophysiology is designed for a 3-dimensional world. When you

read or work on a computer, you are restricted to 2 dimensions.

If you take a system that is designed for 3-dimensionality

and primarily use it for 2-dimensional tasks, it creates stress.

Studies that were done many years ago found that when chil-

dren read a book, their pulse rate, respiration rate, etc—all the

markers of stress—signifi cantly increase. If you go into cultures

around the world where people don’t go to school and don’t do

a lot of reading, you see that near-sightedness is unheard of.

Look at Eskimos, for instance: before Alaska institutionalized

education, myopia was unheard of. However, as soon as Eskimos

were required to go to school and read, there was a signifi cant

onset of myopia.

So the epidemic of deteriorating eyesight is caused primarily

by the stress created by visual confinement. And the major

source of visual confi nement responsible for that stress is the cul-

tural demand to sit and look at a book or a computer all day.

ATHM: What do you see as the remedy?

“Our entire neurophysiology is designed for a 3-dimensional

world. When you read or work on a computer, you are restricted to

2 dimensions. ”

“If you go into cultures around the world where people don’t go to

school and don’t do a lot of reading, you see that near-sightedness

is unheard of.”

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 71 Conversations: Jacob Liberman, OD, PhD

Dr Liberman: There are 3 remedies that I immediately see. First

we need to redefi ne what it means to see. People need to become

aware that vision is much more than just eyesight.

Next, I see 2 very practical remedies. In 1928, a group of

visionary optometrists developed the science of functional

optometry and vision training. They realized that vision is seam-

lessly connected with behavior and performance. And since

vision affects every human function, they developed a behavioral

science called behavioral optometry.

Today there are thousands of doctors who practice this type

of care, and one of the major things they do, aside from vision

training, is to prescribe stress-reducing glasses for kids to use in

school for learning. These are not glasses that are prescribed

because of poor eyesight. These are glasses that magnify very

slightly and have a measurable stress-reducing effect. They func-

tion like a wedge. Let’s say you’re cutting a tree down and want

the tree to move in a certain direction. Strategically placing a

wedge of wood on one side helps the tree to fall in the desired

direction. When we want the vision system to begin to normalize

or move in a direction opposite of the way it’s moving, we fre-

quently use what we call a wedge prescription. It’s a very small-

powered magnifying lens that reduces visual stress and is used

primarily for classroom work and reading. That by itself is a

wonderful preventive tool. It’s a practical application that very

often prevents the onset of myopia.

The most important recommendation is vision training.

Consider the value of doing something like yoga, Pilates, or gyro-

tonics, some sort of exercise that maintains the body’s fl exibility.

If we began doing yoga as children, a little bit each day, not as an

exercise but as just a part of our life, as we got older a lot of that

fl exibility would be maintained. The difference between youth

and older age often is a loss of fl exibility. If fl exibility can be

maintained in the body, then I think that it has a direct effect on

not only our physical comfort but on our longevity and our well-

being. The same is true with vision.

Another very effective tool is a little bookmark that I devel-

oped in 1976. It has a stop sign on top and says, “Stop. Look up.

Look away. Breathe. Put me 2 pages ahead.” So that every time

you get to that bookmark, you take a little break, just enough

time to look up, look away, let the eyes escape, and relax the

focusing system. If we merely gave each child in school one of

these bookmarks, that in itself would make a very signifi cant

change in terms of the onset and progression of myopia.

If we just did a few simple vision-training exercises each day,

along with using stress-reducing glasses for close work, I believe

we would probably prevent most myopia. Beyond the prevention

of vision deterioration, this approach would also optimize and

expand our ability to see and learn.

We would attend better with less effort. We could read lon-

ger and more comfortably. Learning would be easier, sports per-

formance would soar, and working at the computer would be

more comfortable.

ATHM: How do you envision making these vision-training prac-

tices more widespread?

Dr Liberman: For years my dream has been to bring this awareness

to the public. If I share these suggestions and skills with athletes, for

instance, it signifi cantly improves their game. Whether it’s baseball,

golf, or tennis, athletes know that the key to peak performance,

aside from physical conditioning, is their vision. And the same is

true in the classroom. Our eyes guide everything we do.

We are now introducing this work to school systems, sports

teams, computer users, pilots, and police recruit training pro-

grams. It’s a whole new paradigm, and the timing couldn’t be

any better. It’s not only because we’re losing our eyesight as a

species, but also one of the biggest epidemics today is attention

defi cit disorder (ADD) and attention defi cit hyperactivity disor-

der (ADHD). Millions of children and adults are being medicat-

ed because they have great diffi culty attending comfortably. I

cannot tell you the huge difference someone can experience in

their ability to attend, read, and learn by doing some very simple

vision exercises.

To make that available to people, I developed a clinically

proven device that can signifi cantly improve those skills. And it’s

“If we just did a few simple vision-training exercises each day,

along with using stress-reducing glasses for close work, I believe we

would probably prevent most myopia.”

72 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Conversations: Jacob Liberman, OD, PhD

backed up by peer-reviewed published research. What’s really

interesting is that someone can spend less than 10 minutes a day

doing these exercises and experience very broad effects—every-

thing from improving visual attention and reading effi ciency and

comprehension to how comfortably they work at the computer

and play their favorite sport.

Vision training has far-reaching effects, and very soon this

information will permeate every area of life because as someone

once said, “Next to life itself, God’s most precious gift is sight.”

When we think about vision, what it means to see, it’s not just an

optical process. Our vision is deeply rooted in our humanity.

A large part of my last 35 years of work has dealt with the

effect of light on the mind, body, and spirit. Now I’m focusing on

light, vision, consciousness, and performance and how all these

things are connected. What I’ve discovered is that they are insep-

arable. Changing one’s vision can truly change one’s life.

One of the most powerful movements today is a drive

toward personal growth and development. We read self-help

books in an attempt to see and understand our lives more clearly.

We try to be more conscious about our diet, exercising regularly

and taking supplements in hopes of fulfi lling our vision of better

health. We meditate as a way of fi nding inner peace and new

vision. In our own way, we are all trying to improve the quality of

our lives by seeing life more clearly. Yet very few of us have con-

sidered the role of vision training in expanding our ability to see.

That’s what my interest is, and I’ve developed a technology that I

feel can really support people in that process.

ATHM: Where can readers go to learn more about resources in

this area?

Dr Liberman: There is a lot of information available through the

Optometric Extension Program Foundation, OEP.org, and the

College of Optometrists in Vision Development, COVD.org. OEP

is the organization that started the science of behavioral optome-

try and vision training in 1928. This is a science that’s been incor-

porated into the optometric profession for more than 80 years.

COVD is the certifying body for doctors of optometry who spe-

cialize in the art and science of vision training.

ATHM: Can you tell us more about the device you created and

how it works?

Dr Liberman: The device is called the EYEPORT Vision Training

System, and people can fi nd out about it at our website, www.

exerciseyoureyes.com. The EYEPORT has been cleared by the

FDA and is the fi rst clinically proven device available to the pub-

lic that improves overall visual performance.

The EYEPORT has a series of alternating red and blue LEDs

that the user tracks horizontally, vertically, diagonally, and from

far to near and back. Our patent deals with a very specifi c effect

that occurs when the eye looks at red vs when it looks at blue.

These colors have opposing effects on the autonomic nervous

system as well as the aiming and focusing mechanism of the eyes.

Red causes the eyes to refl exively over-focus, while blue causes

them to refl exively under-focus.

When you alternately look at red and blue lights, you create

rocking action—a rhythmic expansion and contraction, simulat-

ing the body’s natural state of flow. There’s a reason we rock

babies. It puts them into a state of ease. If you close your eyes and

tune into your body, you will notice that the most fundamental

rhythm is that the body continually expands and contracts—the

breathing cycle.

If you go a little deeper into the body, you will notice that

same continual expansion and contraction in the heart. That

rhythm is then transmitted to the vascular system, the organs,

the glands, and the cells. The whole body is continually expand-

ing and contracting. We say the only constant is change—that’s

called fl ow. When that’s going on, the body is in a state of physio-

logical coherence.

Every time we think, try hard, or put effort into something,

the breath is momentarily held and restricted. When that occurs,

the muscles get tight, mind-body integration is broken, and one’s

visual fi eld begins to collapse. We see less, experience less, and

become less effi cient because the fl ow is gone. What is the fl ow?

The fl ow is what’s described and defi ned by the statement, “The

only constant is change.” It’s the homeodynamic heartbeat of the

human energy system.

By viewing the alternating red and blue lights on the

EYEPORT, you create an involuntary expansion and contraction

within the eye and the nervous system, reminding the body of its

most primal rhythm and natural state of fl ow.

And while the system is expanding and contracting, the eyes

are simultaneously aiming, focusing, tracking, and teaming,

which means these skills are being trained and reinforced with-

out effort. It’s occurring within a state of fl ow. When this occurs

for an athlete, they’re “in the zone.” And when they’re in the

zone, something special happens.

The most important aspect of our technology is that it

encourages and allows the mind-body system to re-experience its

natural state of fl ow, while visual function is enhanced. This is

extremely important because when the mind/body is in a state of

fl ow, it’s at its maximum potential and re-experiences its ability

to function and perform without effort.

ATHM: How successful has the system been?

Dr Liberman: So far, we have 3 published studies in peer-

reviewed journals, all of which demonstrate that using the device

for less than 10 minutes a day—fi ve 90-second exercises—signifi -

cantly improves visual attention; reading effi ciency and compre-

hension; aiming, focusing, tracking, and teaming of the eyes;

speed and span of perception; dynamic depth perception; marks-

manship; and sports performance.

That’s what the studies have demonstrated, whether the

subjects are medical school students, Little League baseball play-

ers, or police recruits. We’ve also completed a pilot study at a

university dealing with using the EYEPORT on kids who have

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 73 Conversations: Jacob Liberman, OD, PhD

been diagnosed with ADHD. Even though it was only a pilot

study, we found statistically signifi cant improvement in visual

attention and focusing ability after using the device less than 10

minutes a day over 3 weeks—which means that these children

used the EYEPORT for less than 3 hours total.

The other thing that’s really interesting is that most of the

change remains even after you stop using the device. If you go to

the gym and exercise your muscles, if you don’t continue to exer-

cise them, they become fl accid after awhile. In vision training, it is

important to recognize that the eyes are direct frontal extensions

of the brain. When you train the

eyes, you’re directly training the

central nervous system. So you

don’t have to do this for the rest of

your life. That’s extremely impor-

tant to me because if you have to

do something for the rest of your

life, there’s a good chance you

won’t do it. You see, if it takes

effort to create change, it will take

effort to maintain it. And if it

takes effort to maintain it, you can

pretty much be assured it will not

be maintained because the body,

just like the universe, functions by

the law of parsimony—it uses the

least amount of energy to get the

job done.

When the subjects who took

part in our studies were reevalu-

ated 3 weeks afterwards, the level

of performance was frequently

just as high as and, in some cases,

higher than it had been immedi-

ately after the study. In other words, if the treatment is really

working, one’s vision and performance should continue to

improve, not decline again. I don’t want people to have to do

something for the rest of their lives to get the benefi t. I haven’t

done vision training in 31 years. I did it in 1976 and something

changed about the way my vision worked and the way my brain

was responding, and it has continued to improve. I do not see my

vision getting worse; I actually see it getting better. That’s inter-

esting at 60. You don’t expect that.

ATHM: How do you explain that?

Dr Liberman: When you create greater balance between the

eyes, you create greater balance in the brain and in the person’s

ability to fi nd balance in his or her life. Because you’re training

the brain, you’re basically creating new, neuronal connections

within the brain, and once people start using these skills the

mere act of looking, reading, paying attention as they’re driving,

sitting in the classroom, or playing golf—whatever they’re

doing—continually reinforces the skills that they have learned.

The device comes with a 3-month protocol that gives you

the exact exercises to do every day. However, all of our studies

were based on using the product less than 10 minutes a day, 6

days a week for 3 weeks. Recently, we started a large-scale study

with the Washington State Criminal Justice Training Commission

where we are incorporating the EYEPORT into police recruit

training because we fi nd that the recruits respond much faster,

much more accurately, and much more appropriately. We’re talk-

ing about enhancing performance in everyday life, but when

someone is in a stressful situation, like police offi cers are, they

can’t afford to respond inappro-

priately. It could mean their lives

or the life of someone else.

Eventually, we want to

introduce this into the armed

forces, so that people who are

under high levels of stress can

rely on their vision to respond

quickly, accurately, and effort-

lessly, allowing them to respond

more appropriately regardless of

the situation they’re in. We’re

trying to introduce not only this

device but the concept of spend-

ing a couple minutes each day

optimizing visual function so

that your eyes can guide you in

the best possible way. So much

of our success in the world is

related to how we see and

respond to life. When we opti-

mize vision, we optimize our

ability to perform. And when we

optimize our ability to perform

with minimal effort, we experience greater self-respect.

This is especially true with children. One of our published

studies was with a group of 12-year-old boys on a Little League team

that was in the lowest division in their group of baseball teams.

These kids used the device exactly as I mentioned, less than 10 min-

utes a day for 3 weeks. They didn’t practice individually, or as a

group, and they had no games over this 3-week period.

At the end of the study, the average player had a 90%

improvement in batting performance. Not only that, but the

team went from the lowest division to winning the champion-

ship. Several of these children started doing better in school as

well. Some people think, “A kid can hit the ball better. How big

a deal could that be?” But when you don’t experience success

early in your life, as I didn’t in my schoolwork, it can really dam-

age your sense of self. In my personal experience, it wasn’t until

sometime in my 40s that I began to recognize that I was actually

gifted in certain areas. I no longer have the reading problem that

I had as a child, but at the time it really affected me.

Over the past 35 years of doing this work, I have had the

pleasure of working with thousands of people. Many of them

So much of our success in the world is

related to how we see and respond to life. When we optimize vision, we optimize our ability to perform.

74 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Conversations: Jacob Liberman, OD, PhD

notice a change after a single session. They can literally feel their

eyes working in a different way. One of the greatest values of

vision training is that it allows you to discover that eyesight is

only a small aspect of how we see. It also allows you to see that

you’re not always looking where you think you’re looking.

For instance, let’s say that you’re playing golf, and you want

to putt the ball into the hole. Most people assume that they’re

looking at the spot on the ball that they want to hit. However,

most of the time, that’s not the case.

I started doing research on this in 1976 and discovered that

about 70% of the population is

not looking where they think

they’re looking. Most people are

actually looking a little closer to

or further away from where the

ball really is. And that’s why most

people don’t sink the putt or hit

the home run more often. The

unfortunate thing is that none of

us can see how we’re seeing, so

we have no idea why our perfor-

mance is less than expected.

Another example of this

same phenomenon is a group of

people at an archery range. They

all want to hit the bull’s eye.

They’re sure that they are looking

at the bull’s eye, and they try hard

to aim for its center. Yet very few

of them actually hit the bull’s eye.

Isn’t this the experience many of

us have? We not only miss the

bull’s eye on the archery range,

but often also in our lives.

One of the beauties of vision

training is that it creates a high

level of congruity and alignment,

so that your physical eye and

your mind’s eye are both focus-

ing at the same point at the same

time. When this occurs you experience a greater sense of timing

and accuracy in everything you do. You start hitting the ball on

the sweet spot more consistently and experience greater success

at whatever you’re doing because there’s greater focus and clarity

in your life.

ATHM: You’ve elevated the whole conversation of vision from a

visual organ system to a psycho-emotional experience and even

to a spiritual organ.

Dr Liberman: There is no question about that. When we talk

about enhanced awareness or expanding consciousness, what are

we talking about? We’re talking about seeing things more clearly.

Now, for some reason or other, we do not recognize that that

level of seeing is inseparably connected with the seeing we’re

doing every day. But they are connected. They are absolutely con-

nected because the thing that is seeing is not the eye; it’s some-

thing much deeper. The eye is just one part of the process.

Vision and seeing are right at the heart of every spiritual tra-

dition. Meditation is all about focusing on something. People do

not connect that practice with the eyes, but whether the eyes are

open or the eyes are closed, when you focus on something, your

eyes also focus on the same thing. There’s no way to separate

these functions.

We must begin to look at

vision in a broader way because

our eyes guide every move we

make. The way we see, where

we perceive things to be, how

accurately we judge distance

and the speed at which things

are moving—all of those fac-

tors are reflected in our

moment-by-moment response

to life. Real vision is the ability

to response automatically,

without thought or effort.

When that happens, our

potential is expanded in ways

that I cannot even describe.

Improving visual performance

directly affects performance on

every level, but if you can sig-

nificantly improve attention,

reading, learning, and comfort

of everyday use of the eyes, all

of that together has a far great-

er effect on how we feel about

ourselves in the world. We can

trust our vision to allow us to

see situations in life more clear-

ly. And when we see more

clearly, we respond more accu-

rately. We begin to trust our

vision and ourselves, and that makes huge changes in our lives. If

we begin training our vision as children, the effects stay with us

through adulthood and permeate our lives.

By doing a few simple vision exercises, you can begin to expe-

riences your potential in a whole new way. I know this not only

from my own experience but because I’ve had the pleasure of work-

ing with thousands of adults and children over the past 35 years.

And I’m not the only one. There are probably 6 thousand to 8

thousand behavioral optometrists around the country who also

specialize in this work and have similar experiences.

We are beginning to recognize the importance of this work

because there’s such an epidemic of vision deterioration.

Additionally, children are experiencing more visual problems in

the classroom in terms of reading and learning, and almost 90% of

One of the beauties of vision

training is that it creates a high level of congruity and alignment, so that your physical eye and your mind’s eye are both focusing at the same point at the same time.

ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 75 Conversations: Jacob Liberman, OD, PhD

computer users complain about their eyes. It’s time to redefi ne

what it means to see and to incorporate techniques into our every-

day life that can preserve our vision and also expand its potential.

ATHM: You’ve taken us into a visionary journey that’s both

extremely practical and, I believe, powerfully sacred. Do you

have other recommendations you would like to share?

Dr Liberman: It’s very important, for instance, for children to

have comprehensive vision examinations. I recommend they see

a behavioral optometrist because a behavioral optometrist spe-

cializes in preventive vision care and looks at vision not in terms

of eyesight but in terms of performance. It’s also important to

check the health of the eyes, and optometrists are licensed to do

that. But pathology is not very common in children. What is

important to a child’s vision is that it’s working properly, that it’s

developing properly, and that the child is able to use it effectively.

It is imperative that we think preventatively because hardly any-

one escapes this epidemic. In Asia approximately 87% of kids

aged 16 years and older are near-sighted. That’s huge. There isn’t

a disease process in the world that effects so many people.

Vision training and the preventive use of stress-reducing

lenses must be used with all children, starting at an early age. It

isn’t a question anymore of, “If my child needs glasses, there’s

something wrong with his eyes.” No.

Children need special kinds of glasses

because we don’t want anything to go

wrong with their eyes. We recommend

nutritional supplements and good eat-

ing habits in order to prevent disease,

not just remediate it once you have it.

Vision training is used in the same way.

However, since you are working with the

body’s navigational system, the effects

can be profound.

ATHM: It sounds like there is a spiritu-

al tie-in to all of this. Do you feel that is

the case?

Dr Liberman: Yes. The thought that

keeps coming through is that in our own

way we are all trying to “see through the

eyes of God.” Whether we are religious or

think of ourselves as spiritual seekers, we

are trying to see things more clearly and

be more in alignment with the source—

whatever the source is for each of us.

ATHM: It seems as though you’re

pointing to the next paradigm of how

we view the body. For a while we saw

the body exclusively as a biologic

machine. More recently, we’ve been

looking through the mind-body lens. Now you’re pointing to

seeing the body as part of the sacred domain.

Dr Liberman: For many years scientists and clinicians working

in the fi eld of mind-body medicine have spoken about the effect

of the mind on the body. It’s the foundation of the fi eld of psy-

choneuroimmunoendocrinology. I can understand how the mind

can effect the body if you identify yourself as the thinker of the

thoughts you are experiencing. However, what happens if you do

not identify yourself as the thinker but merely the observer of

those thoughts as they enter your fi eld of awareness? From my

experience, the only reason we are aware that thinking is occur-

ring is because we are observing that process. We are not the

thinker; we are that which is aware of the thinking. The signifi -

cance of this is the realization that our essence is a fi eld of aware-

ness. We are the seeing mechanism I have been discussing. When

we discover this, we truly discover what it means to see.

Marc David is an associate editor of Alternative Therapies in Health

and Medicine. Suzanne Snyder is managing editor of ATHM.

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78 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Conference Calendar/Advertisers Index

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Metabolic Maintenance Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

Metametrix Clinical Laboratory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

Pedone & Partners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14, 15

Pfl uegerUSA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .65

Program for Integrative Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76

Researched Nutritionals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

Sedona Labs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39

Standard Process. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

Synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76

The Teleosis Institute . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76

Vital Nutrients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .IBC

Washington Homeopathic Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79

advertisers index

Food As Medicine Professional Nutrition Training ProgramJune 12-15, 2008—Marriott Waterfront Hotel, Baltimore, MarylandThis program provides the latest in science-based nutrition education and is designed to give graduates the knowledge, confi dence, compassion, and skills required to integrate food as medicine in their clinical practice. This is the nutrition class that healthcare professionals tell us they’ve been looking for. Topics include The Science of Nutrition, the Art of Nourishment; Sustainable Nutrition: Origins, Evolution & Agriculture; Nutrigenomics; Stress, Nutrition & Hormones; GI Healing & the Science of Detoxifi cation; Obesity & Weight Management; Mindful Eating; Children’s Nutrition; Patient-Centered Counseling; Condition Specifi c Nutrition Therapy; The Science of Supplementation; and Cutting Edge Laboratory Assessment. For more information visit http://www.cmbm.org/ or call (202) 966-7338.

Homeopathic Excellence Since 1873

Washington Homeopathic Products

Receive 15% off your first order!When you mention code sr30c

Washington Homeopathic Products 33 Fairfax Street, Berkeley Springs, WV 25411

W hi t H thi P d tWashington Homeopathic Products

80 ALTERNATIVE THERAPIES, Mar/apr 2008, VOL. 14, NO. 2 Resources

To Advertise in RESOURCES, please visit www.alternative-therapies.com or call 303.565.2034.

The Guide To New Products, Services, and Education Forums

ResourcesI N H E A L T H A N D M E D I C I N E

NeuroCoat™ Trehalose is an all-natural carbohydrate that has a clean, sweet taste and may promote brain health. NeuroCoat is ONLY available at neurocoat.com or by calling 866.61.SMART.

RibosEnergy™— clinically proven to increase energy:• Athletes – 88% increase in muscle strength plus 67%

increase in muscular endurance vs. placebo.• Fibromyalgia/CFS – 42% improvement in

energy; 2/3 of subjects improved in 12 days.• Cardiovascular Function – improved diastolic

heart function, increased physical function score, enhanced quality of life score.

Pure, patented ribose plus magnesium and malic acid.Call 800 755 3402 or visit ResearchedNutritionals.com—available only through health care professionals.

BODYBIO Balance: 4:1 Oil, a mix ofOrganic Sunfl ower and Organic Flaxblended to provide Omega 6 and Omega 3 Essential Fatty Acids to a 4:1 Ratio.

There is more research (Yehuda et al) on the 4:1 ratio of n-6 and n-3s than on any other Essential Fatty Acid blend.

For more information call BodyBio at 1-888-320-8338 or visit www.bodybio.com.

Metabolic Maintenance Products68994 N Pine St Sisters, OR 97759800-772-7873/ 541-549-7800 F ax 541-549-3299www.metabolicmaintenance.comFor 20 years Metabolic Maintenance Products has manufactured preservative and excipient-free nutritional supplements based on scientifi c research and opinions of our physician advisory board. Our pure encapsulation, highest quality, and superior value provided you and your patient with the highest quality fi nished product.

New, Great Tasting, Organic NanoGreens10: Fruit and Vegetable Power of 10-A-Day!NanoGreens10 provides an ORAC of 7,000 per serving. Our patented NanoSorbTM liposomal delivery is proven to enhance bioavailability. Available through health professionals only. Order a FREE WEEK’S SUPPLY and information package at 1-877-772-4362. www.biopharmasci.com

Sedona Labs’ iFlora™ Multi-Probiotic™ Formula contains 16 natural probiotic cultures with a potent 20 billion cells per capsule. The iFlora™ formula is dairy free and does not need to be refrigerated, making it handy to take while traveling, as well as every day at home. www.sedonalabspro.com

New Product Vital Nutrients Sleepaide

SLEEP AIDE provides safe, natural support to calm the central nervous system and encour-age restful sleep. A blend of Valerian and Lemon Balm, two most studied herbs, sup-ports restful sleep. California Poppy, L-Theanine, Lavender Essential Oil and Melatonin act synergistically to enhance the effects of our Sleep Aide formula. Please visit our website: www.vitalnutrients.net or call 1.888.328.9992

The Right Whey—Whey Pro CompleteWhey Pro Complete contains whole food sources to augment weight management; support muscle tissue; enhance immune func-tion; and improve gastrointestinal health. Unique ingredients, such as colostrum and inulin, work in tandem providing immune support, especially in the gastrointestinal tract.* Visit www.standardprocess.com for more information.

*These statements have not been evaluated by the Food and Drug Administration.

These products are not intended to diagnose, treat, cure, or prevent any disease.

Because good health is

N U T R I E N T S

*This statement has not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Douglas Laboratories® Presents...

www.douglaslabs.comCall today 1-888-DOUGLAB (1-888-368-4522) or 1-800-245-4440

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Gly-Sea-Max™

In a world of oversized servings, it’s essential

to feel satisfied after eating a healthy portion

of food. Douglas Laboratories® exclusively

distributes a product that responds above

and beyond this need with Gly-Sea-Max™.

Gly-Sea-Max is a proprietary blend of unique

standardized extracts from two different species

of Brown Seaweed together with Slendesta™,

a novel potato protein extract to support satiety,

fullness, and a decrease in the normal blood

glucose response to a meal, which is critical

to weight management. Gly-Sea-Max does not

contain stimulants.†

Over 64% of adults in

the U.S. are overweight.

—American

Obesity Association

raising the standard for supporting a normal glycemic response, satiety, and fullness.