Blood, Sweat & TearsUsing Biomarkers to Become

Superhuman

Justin Mager, MD

Part 1The Big Picture

becoming superhuman

• Set The Intention & Expectation!

• Hypothesize & Experiment

• Manifest Our Reality

• Biomarkers are a Tool to Measure and Track

Who really intends to become superhuman here?

how?

what are the barriers?

No matter how you plan to get there, BIOMARKERS can play a key role, Why???

Who really intends to become superhuman here?

how?

what are the barriers?

No matter how you plan to get there, BIOMARKERS can play a key role, Why???

Beware of ExpertsZen Mind is Beginner’s

Mind

biomarker |ˈbīōˌmärkər|nouna measurable substance in an organism whose presence is indicative of some phenomenon such as disease, infection, or environmental exposure.

need to switch out phenomenon to “process”

this definition is one fundamental problems!

we measure, make an aboslute judgement, and then try to “manage the marker”

if the marker marks a process, we need to ask why this process is taking place that makes sense the marker is what it is.......

need to switch out phenomenon to “process”

this definition is one fundamental problems!

we measure, make an aboslute judgement, and then try to “manage the marker”

if the marker marks a process, we need to ask why this process is taking place that makes sense the marker is what it is.......

biomarker |ˈbīōˌmärkər|nouna measurable aspect of an organism indicative of some biologic processes occuring at the time of measurement and can be used to track changes over time.

Dynamic Process

Occurring Across Scales of Time

Collective Process

The monkey business of Measuring process

Timing/context Matters

Measurement and Interpretation

the Trees and the forest

Processes are flowing tides of Interconnectedness

• Are Statins Diabetogenic?

• Meta-Analysis, Including JUPITER Trial

• Statin use Assoc. 9-13% increase in diabetes.

• Summary: T2DM is Risk Equivalent for CVD, Statin use creates paradox of decreased and increased risk of CVD.

Sampson UK, Linton MF, Fazio S. Are Statins Diabetogenic? Curr Opin Cardiol. 2011 Jul;26(4):342-7.

Quick Recap

• Biomarkers Indicate Process

• Look at Whole Picture

• Must be Taken into Context of Your Situation

• Must Integrate Markers

Hypercholesterolemia

• Total Cholesterol: 390 (mg/dl)

• LDL: 269

• Triglycerides: 329

• HDL: 36

hyperglycemia/Diabetes

• Glucose: 199 (mg/dl)

• HbA1c: 8.5%

• Insulin: 32 (ul U/ML)

Hyperthyroidism/Graves?

• TSH: 8.1 (uIU/ml)

• Total T3: 300 (ng/dl)

• Free T4: 3.2 (ng/dl)

Hypersomatotropism/Acromegaly

• IGF-1: 641 ng/ml

so, What IF....• Hypercholesterolemia

• Hyperthyroidism

• Hyperglycemia

• Hyperinsulinemia

• Hypersomatotropism

Puberty !

Part IIA Closer Look at a Few Markers

Survival of the Fittest?

System Biomarkers

JAMA

• Conclusion: Low fitness AS important as T2DM and other CVD risk factors as a predictor of CVD mortality and all cause mortality. Clinicians should evaluate fitness in their patients just as they now obtain a medical history and measure blood pressure and cholesterol and plasma glucose levels.

Journal of Obscure and Questionable Medicine (JOQM)

• Wei et al, Relationship between low cardiovascular fitness and mortality in normal-weight, overwieght, and obese men. JAMA, October 27, 1999—Vol 282, No. 16, 1547-1553.

NEJM

• Each 1 Met INCREASE in exercise capacity conferred a 12% IMPROVEMENT in Survival

• CONCLUSION: Exercise Capacity is a more powerful predictor of mortality among men than other established risk factors of cardiovascular disease.

• Exercise Capacity and Mortality among Men Referred for Exercise Testing. Jonathan Myers, Ph.D., Manish Prakash, M.D., Victor Froelicher, M.D., Dat Do, M.D., Sara Partington, B.Sc., and J. Edwin Atwood, M.D.N Engl J Med 2002; 346:793-80

Meta-Analysis33 Studies; 102,000

Women and Men

• Every 1 MET VO2max Increase

• 13% All-Cause Mortality Decrease

• 15% CVD Mortality Decrease

• “Substantial” Risk Reduction >50y.o.

• VO2 > 6 Mets Women

• VO2 > 8 Mets Men

Kodama et al. Cardiorespiratory fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Helathy Men and Women. JAMA, May 20, 2009—Vol 301, No. 19

HR Index Predicts VO2: 6*HRindex(HRmax/HRrest) -5 = VO2 (MET’s)

Telomeres:Health, Aging & Disease

• Unique DN-Protein complexes that “cap and Protect DNA

• May Indicate “Biologic Age”

• Non-specific Marker

Impacting telomeres

• Nutrient Levels

• Omega-3, D, B-Vitamins

• Stress

• Weight Gain/Loss

• Biomarkers

• Homocysteine

Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women, Am. J. Clin. Nutr. 86 (5) (2007) 1420–1425. J.B Richards, A.M. Valdes, et al.

Increased telomerase activity and vitamin D supplementation in overweight African Americans, International Journal of Obesity (2011), 1 – 5 H Zhu1,

Homocysteine levels and leukocyte telomere length, Atherosclerosis 200 (2) (2008) 271–277. J.B. Richards, A.M. Valdes, et al.

Telomere length in peripheral blood mononuclear cells is associated with folate status in men, J. Nutr. 139 (7) (2009) 1273–1278. L. Paul, M. Cattaneo, et al.

Multivitamin use and telomere length in women, Am. J. Clin. Nutr. 89 (6) (2009) 1857–1865. Q. Xu, C.G. Parks, et al.

Diet, nutrition and telomere length, J. Nutr. Biochem. (2011). L. Paul

functional Biomarkers

HBA1c : Fuel Efficiency

• HgbA1c for Optimal Health

• 5% = 90mg/dl, 6% = 135mg/dl

• AGE’s (Advanced Glycation End-Products)

• Ketogenic Diets and Performance?

• 50% fat, 45% Pro, 5% CHO INCREASED VO2 max and Lactate Threshold, Lowers Respiratory Exchange Ratios

Lanfort et al. Effect of low carbohydrates-ketogenic diets on metabolic and hormonal responses to graded exercise tests. J Physiol Pharmacol. 1996 Jun;47(2):361-71.

Mitochondria Biogenesis

T3 thyroid hormone

CR caloric restriction. Turns energy acquisition to fats, see below.

ATP:AMP, 10:1. Energy consumption decreases ratio, turns on PGC-1α, increasing mitochondria

production and efficiency

FFA Rich energy yield, but less efficient rate of production. Paleo Diet promotes “fat adaption” for fueling. Result; your cells will be swimming

in mitochondria in no time!

mTOR/CREP Exercise, specifically overload, turns this on. mTor expression correlates to

muscle building. mTor STRONGEST STIMULATOR OF PGC-1α

Glucose: Notable Inhibitor of PGC-1α. HbA1c a reliable indicator of average BG

HbA1c & Fuel Efficiency

InsulinIGF-IT3

CR

ATP:AMP

FFA

mTORCREP

Glucose

PGC-1α

HbA1c

fuel efficiency

methylation: Metabolic Efficiency

Hormones OS of us

• Metabolic

• Thyroid

• Pregnenolone

• Catabolic

• Adrenaline

• Cortisol

• Anabolic

• Testosterone

• IGF-1

hormone physiology 100m Olympic Swimmer

6’0”, 163 lb., 8% BF

Elite Crossfit Athlete

5’9”, 210 lb., 9% BF

summary: Becoming superhuman

• Remember Your Roots

• Look at the Whole Picture

• System’s Bio Analysis

• Enhancement vs. Compensation

• Human Potential Movement

Age of engagement

• Measurements Matter

• Adapt & Innovate

• It’s Your Life; Don’t Take My Word For It.

• Unique & Incomplete

Medimorphisys

• Self Experimentation

• Crowd Sourcing Solutions

• Outcomes Analysis

• Big Data Analytics

Blood, Sweat & TearsUsing Biomarkers to Become

Superhuman

Justin Mager, MD