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6" Wine, fish, or genes? Volume 12 • June 200 I • inform Health & Nutrition News A Danish study has found dietary iurake of n-J polyunsaturated fatty acids (PUFA) in fish to be correlated with heart rare variability (HRV), a pre- dictor of arrhythmia and sudden car- diac death. Wine intake was also corte- hated to HRV, bur patients with the highest wine intake also had the highest intake of fish. After controlling for n-3 PUFA, the correlation between wine and HRV was no longer significant. The research, published in the Feb. 6, 200 I, Issue of Circulation (103:651-657), verified the patients' dietary intake of n-3 PUFA (through consumption of fish) by measuring the n-3 PUFA composition of the patients' blood granulocyte membranes and adi- pose tissue. Researchers found the level of docosahexaenoic acid in granulo- cytes had the highest correlation with HRV. "Our findings of an association between n-3 PUFA, wine intake, and HRV may have implications for inter- pretation of previous reports on the relation herween alcoholic beverage intake and cardiovascular mortality, especially reports that do not control for fish intake," said Jeppe Hagstrup Christensen of the Aalborg Hospital Department of Nephrology in Aalborg, Denmark. Although some view the antioxi- dants in wine as providing a protective effect against cardiovascular death, other studies have suggested that wine drinkers may simply eat a healthier diet than those who abstain or drink other alcoholic beverages, Christensen said. He admitted that wine intake did have a positive correlation with HRV, "but a more likely explanation may be that fish and wine intake are associated." In a related editorial, J. Thomas Bigger Jr. and Terek El-Sherif said the evidence that HRV can be correlated with arrhythmia is indirect but support- ed by a large body of experimental and clinical evidence. The evidence of the antiarrhythmic effect of n-j PUFA is more direct, in that dietary intake of n-S PUFA does not decrease the risk of cardiovascular events, bur decreases the risk of the events becoming fatal, the authors said. "The details of the antiarrhythmic action for n-S PUFA remain to be eluci- dated ...bur the overall body of evidence from epidemiological studies and two clinical trials suggests that n-3 PUFA have an important antiarrhythmic effect in patients with coronary heart dis- ease," the authors said. "Unfortunately, coronary heart disease IS often announced by sudden cardiac death. Given the safety and low cost of imple- menting a recommendation for a mod- est amount of fish in the diet, adequate dietary fish intake has a significant role to play in the primary and secondary prevention of out-of-hospital sudden cardiac death." RELATIVE RISK OF WINE AND FISH Regarding fish and wine and their influ- ences on cardiovascular disease, the American Heart Association (AHA), publisher of the journal Circulation, has taken strong stands on both issues. In the Jan. 23, 2001, issue of Circulation (103:472-475), the AHA released its position paper on wine intake and cardiovascular disease. Although admitting that "population surveys and ill vitro experiments show that wine may have limited beneficial effects," the AHA was hesitant to endorse a "nonessential dietary compo- nent with significant health hazards" for the purpose of reducing the risk of heart disease ... More compelling data exist for other less hazardous approach- es to cardiovascular risk reduction."

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6"

Wine,fish,

or genes?

Volume 12 • June 200 I • inform

Health & Nutrition News

A Danish study has found dietaryiurake of n-J polyunsaturated fattyacids (PUFA) in fish to be correlatedwith heart rare variability (HRV), a pre-dictor of arrhythmia and sudden car-diac death. Wine intake was also corte-hated to HRV, bur patients with thehighest wine intake also had the highestintake of fish. After controlling for n-3PUFA, the correlation between wineand HRV was no longer significant.

The research, published in the Feb. 6,200 I, Issue of Circulation(103:651-657), verified the patients'dietary intake of n-3 PUFA (throughconsumption of fish) by measuring then-3 PUFA composition of the patients'blood granulocyte membranes and adi-pose tissue. Researchers found the levelof docosahexaenoic acid in granulo-cytes had the highest correlation withHRV.

"Our findings of an associationbetween n-3 PUFA, wine intake, andHRV may have implications for inter-pretation of previous reports on therelation herween alcoholic beverageintake and cardiovascular mortality,especially reports that do not controlfor fish intake," said Jeppe HagstrupChristensen of the Aalborg HospitalDepartment of Nephrology in Aalborg,Denmark.

Although some view the antioxi-dants in wine as providing a protectiveeffect against cardiovascular death,other studies have suggested that winedrinkers may simply eat a healthier dietthan those who abstain or drink otheralcoholic beverages, Christensen said.He admitted that wine intake did have apositive correlation with HRV, "but amore likely explanation may be that fishand wine intake are associated."

In a related editorial, J. ThomasBigger Jr. and Terek El-Sherif said theevidence that HRV can be correlated

with arrhythmia is indirect but support-ed by a large body of experimental andclinical evidence. The evidence of theantiarrhythmic effect of n-j PUFA ismore direct, in that dietary intake ofn-S PUFA does not decrease the risk ofcardiovascular events, bur decreases therisk of the events becoming fatal, theauthors said.

"The details of the antiarrhythmicaction for n-S PUFA remain to be eluci-dated ...bur the overall body of evidencefrom epidemiological studies and twoclinical trials suggests that n-3 PUFAhave an important antiarrhythmic effectin patients with coronary heart dis-ease," the authors said. "Unfortunately,coronary heart disease IS oftenannounced by sudden cardiac death.Given the safety and low cost of imple-menting a recommendation for a mod-est amount of fish in the diet, adequatedietary fish intake has a significant roleto play in the primary and secondaryprevention of out-of-hospital suddencardiac death."

RELATIVE RISK OF WINE AND FISH

Regarding fish and wine and their influ-ences on cardiovascular disease, theAmerican Heart Association (AHA),publisher of the journal Circulation, hastaken strong stands on both issues.

In the Jan. 23, 2001, issue ofCirculation (103:472-475), the AHAreleased its position paper on wineintake and cardiovascular disease.Although admitting that "populationsurveys and ill vitro experiments showthat wine may have limited beneficialeffects," the AHA was hesitant toendorse a "nonessential dietary compo-nent with significant health hazards"for the purpose of reducing the risk ofheart disease ... More compelling dataexist for other less hazardous approach-es to cardiovascular risk reduction."

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The studies that support an associationbetween wine intake and lower heartdisease risk are confounded by lifestyle,diet, and other cultural factors, accord-ing to the AHA.

"Without a large-scale, randomized,clinical end-point trial of wine intake,there is little current justification to rec-ommend alcohol (or wine specifically)as a cardioprotective strategy," theauthors of the position paper said. "Insummary, wine consumption as a meansof cardiovascular prorecnon because ofits antioxidant content is an unprovenstrategy. H

With regard to fish, however, theAHA has issued a recommendation toincrease fish consumption.

"Because of increased evidence forthe cardiovascular benefits of fish (par-ticularly fatry fish), consumption of atleast 2 fish servings per week is now rec-ommended, H according to the AHAdietary guidelines, published in the Oct.31, 2000, issue of Circulation(102:2284-2299). A growing body ofevidence indicates that foods rich in n-3polyunsaturated fatty acids, specificallyEPA and DHA, confer cardioprorecriveeffects beyond those that can beascribed to improvements in bloodlipoprotein profiles. Because of the ben-eficial effects of n-S fatty acids on riskof coronary artery disease as well asother diseases such as inflammarory andautoimmune diseases, the currentintake, which is generally low, shouldbe increased."

ALCOHOL BENEFIT IS GENETIc?

If the benefits of fish intake are certain,perhaps the potential benefits of alcoholintake are less clear because not every-one is genetically predisposed to benefitfrom its consumption.

in the Feb. 22, 2001, issue of theNew England [ournal of Medicille

(344:549-555), researchers at HarvardUniversity, Boston, Massachusettsfocused on the risk of myocardialinfarction with respect to the level ofalcohol consumption and the knownpolymorphism (various alleles or genet-ic forms) for alcohol dehydrogenasetype 3(ADH3).

Men and postmenopausal womenwho are homozygous (having the sameallele) for the slow-oxidizing ADH3allele and are moderate alcohol drinkerswere found to have higher high densitylipoprotein (HDL) levels and a substan-tially decreased risk of myocardialinfarction than those possessing theADH3 allele associated with faster oxi-dation of alcohol.

Two articles questiondietary fat reductionA review of 27 intervention trials hasshown that reduction of dietary fatintake had no effect on total mortality.Even so, decreased fat consumptionreduced cardiovascular mortality andcardiovascular evems .. intervention tri-als lasting over two years showed largerreductions in combined cardiovascularevents than did trials of less than twoyears' duration.

The research, published in the March31, 2001, issue of the British Medical[ovma! (322:757-763), examined ran-domized controlled trials where thestated intention was to reduce or modi-fy fat or cholesterol intake in healthyadult participants over a period of atleast six months. lnrervenrions focusingexclusively on n-3 fany acids were notincluded in the meta-analysis.

The researchers also tried to separateout whether changes in individual fattyacid fractions are responsible for anybenefits to health.

"The answers are not definitive, the

.19

data being tOOsparse to be convincing, H

the authors said. "Despite decades ofeffort and many thousands of peoplerandomized, there is still only limitedand inconclusive evidence of the effectsof modification of total, saturated,monounsaturated, or polyunsaturatedfats on cardiovascular morbidity andmortality. H

In an article published in the March30,2001, issue of the journal Science(291:2536-2545), author Gary Taubescriticizes dietary fat reduction as scien-tifically unfounded.

"Mainstream nutritional science hasdemonized dietary fat, yet 50 years andhundreds of millions of dollars ofresearch have failed to prove that eat-ing a low-fat diet will help you livelonger ."

Taubes covers a lot of ground in hisarticle, from the rise in coronary heartdisease following World War 11 to the1998 attempt by the U.S. SurgeonGeneral's Office to publish the defini-tive report on the dangers of dietary fat.Although Taubes accepts that modifica-tions in dietary fat intake can alterserum cholesterol levels, he questionsthe efficacy of dietary changes com-pared to proven cholesterol-loweringdrugs.

"Diet rarely drops LDL (low densitylipoprotein) by more than 10%, whichis effectively trivial for healthy individu-als, although it may be worth the effortfor those at high risk of heart diseasewhose cholesterol levels respond well toit," Taubes said.

The author also challenges the sci-ence linking dietary fat with weightmanagement, dietary fat with cancer,and dietary fat with heart disease.

"While low-fat diets might help pre-vent heart disease, they might also raisesusceptibility to other conditions,"Taubes said.

Volume 12 • June 200 I • Inform

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Health & Nutrition News

620

IARC: overweightcan cause cancerUp to one-third of tumors of thecolon, breast, and kidney can be artrib-ured to overweight and insufficientphysical activity, according to theInternational Agency for Research onCancer (tARC), a branch of the WorldHealth Organization.

IARC published its estimates in thepreliminary report of a panel of expertsit convened in Lyon, France, Feb.13-20,2001.

Scienrisrs have estimated that in theEuropean Union approximately 21,000cases of colon cancer and 13,000 cases ofbreast cancer could be avoided annuallyif all Europeans maintained a normal

Cancer Prevention, The IARC's officesare at 150 COUTSAlben Thomas, F-69372 Lyon Cedex 08, France.

body weight, IARC said in a preparednews release. Maintaining a healthybody weight, defined by IARC as a bodymass index (a person's weight in kilo-grams divided by the square of that per-son's height in meters) of 25 or less,would reduce the risk of postmenopausalbreast cancer and cancer of the colon,endometrium of the uterus, and kidney,as well as adenocarcinoma of the esoph-agus. Regular physical activity reducesthe risk of breast and colon cancer, andpossibly that of endometrial cancer andprostate cancer, IARC said.

The expert panel's full review andevaluation of relevant scientific infor-mation will be published later in 200 Ias Volume 6 of the (ARC Handbooks of

NETLINK:

International Agency for Researchon Cancer

www.iarc.fr

Body fat may becomesource for stem cellsFat removed from patients by liposuc-rion has been found by rwo reams ofresearchers ar the University ofCalifornia School of Medicine in LosAngeles and at the University ofPittsburgh School of Medicine in

The Resource:Reference SamplesOver 50 different peer-evaluated reference materials now avail-able! AOeS provides fats- and oils-related reference samplematerials that have been analyzed by participants in the AOeSlaboratory Proficiency Program. Samples are shipped withreports that include the mean value and standard deviationderived for various constituent components.

The reference samples include oilseeds and meals, fats and oils,marine oils, specialty oils suitable for the determination of transfatty acids, aflatoxins, cholesterol, and trace metals, as well asformulations for feed microscopy and nutritional labeling.

For ordering information, contact AOeS Technical Services.

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Volume 12 • June 200 I • Inform

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Pittsburgh to be a novel source for mul-tipurpose stem cells that could be usedin making muscle, bone, and cartilage.

The availability of stem cells in farmay bypass the controversy that existswith the usc of fetal tissue or embryonictissue and with the logistical problemsassociated with their isolation from othersources such as bone marrow and brain.Stem cells are not differentiated (special-ized), but can undergo unlimited divisionunder proper conditions to form othercells that either remain as stem cells orchange to form specialized cells associat-ed with organs or tissues, such as muscleand cartilage. The production of replace-ment tissues for diseased or damaged tis-sue from an individual's own stem cellswould avoid the possibility of rejectionof transplanted tissue.

Further development of this tech-nology is limited by the availability ofstem cells, with fat now being consid-ered as a possible alternative. Mostpeople have plenty 10 spare and it isrelatively easy to recover by liposuc-tion. The problem, however, may notbe so easily solved according to some.A definite need exists to identify thestem cells in fat and especially to

develop procedures for specific direc-tion in the production of specializedcells. There arc expectations that labo-ratory-grown tissue will be availablefor medical applications within fiveyears. Ideally the removal of damagedtissue and its replacement with thefresh tissue could be accomplishedwithin a single operation. (Source:Tissue Engineering 7:211-228, 200 I).

Mediterranean-style dietgiven nod by heart groupA statement titled "Lyon Diet HeartStudy. Benefits of a Mediterranean-Style, National Cholesterol Education

Program/American Heart AssociationStep I Dietary Pattern on Cardio-vascular Disease" was approved by theAmerican Heart ASSOCiation ScienceAdvisory and Coordinating Committeein July 2000. The report was written byPenny Kris-Etherton of Penn StateUniversity, University Park,Pennsylvania, and several colleaguesand has now been published(Circufati011 103:1823-1825,2001).

The American Heart Association(AHA) had commissioned the LyonDiet Heart Study to test the effective-ness of a Medirerannean-style diet onthe composite measures of the coronaryrecurrence rate after a first myocardialinfarction. Although there are manysimilarities between the AHA Step I andII diets and the Lyon diet, theMediterranean-style diet was more spe-cific regarding the form and types offat-containing foods and oils. (Key com-ponents of the Step I and II diets arereductions in the proportion of dietarycalories derived from fat and, in partie-ular; a decrease in saturated fats andcholesterol to levels substantially belowthe average American diet. There arealso specific recommendations toincrease the dietary intake of fruits, veg-etables, and whole grain producrs.]

Results of rhe study, conducted over46 months on 204 control and 219intervention patients with similar riskfactor profiles, showed that those in theintervention group had a 50 to 70%reduction of cardiac end points, whichis highly significant. Further research,however, is considered to be necessaryto determine the specific components ofthe Mediterranean-style diet that pro-vide the cardic-protecrive effect. Anindependent role is assigned to theactivity of a-linolenic acid in loweringcardiovascular disease (CVD) risk, andthe effect of its inclusion in the AHA

621

Step I and II diets should be examinedfurther.

The advisory recommends, however,that a modified AHA Step I diet beintroduced to take advantage of theopportunity of lowering the risk ofCVD in the population at large. Thecomponents of the modified Step I dietshould include fruit, rOOI and leafygreen vegetables, breads and cereals,fish, and foods high in a-linolenic acidsuch as flaxseed oil, canola oil and non-hydrogenated vegetable oil salad dress-ing, nuts, and seeds. The provision ofthe desirable monounsaturated fattyacid can be achieved through the use ofolive oil and/or canola oil.

Israeli white wine reportedto lower cholesterol levelsMichael Aviram of the RambamMedical Center, Haifa, Israel, was toannounce to the New York Academy ofSciences Alcohol and WineInternational Meeting in Palo Alto,California, in April 2001 that a kosherwhite wine with potential health benefi-cial properties has been developed at theTechnion-Israel Institute of Technologyin Haifa.

The wine is characterized by a five-fold higher content of flavonoids.

"Processing white wine by puttinggrape skins of chardone or muscatgrapes (which are white or yellow incolor) in contact with alcohol for ashort period helped extract the skin'sflavonoids, and produced white winerich in potent antioxidants similar tothose found in red wine" Aviram said.The beneficial effects of the antioxidantcontent of red wine have been linkedpreviously to reductions in both choles-terol oxidation and possible blockage ofthe arteries.

Flavonols, a group of very potent

Volume t 2 • June 200 I • Inform

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622

flavonoids, appear to be present to agreater extent in Israeli grapes com-pared to most French grapes, whichmay explain some of the differencesfound in studies of the effects of winesfrom the rwc countries on cholesteroloxidation in the body.

Further details 3TC expected to bepublished in the August 2001 issue ofthe [curnai of Agricultural and FoodOJemistry.

Wrinkles may be linkedto elders' dietResearchers at Monash University,Melbourne, Australia; the University ofJakarta, Indonesia; and at Goreborg

Health & Nutrition News

University, Sweden, have found thatskin wrinkling in a sun-exposed site inolder people of various ethnic hack-grounds may be influenced by the diet.Although age and smoking 3TC linked to

premature skin aging, the types of foodsconsumed were found to be of signifi-cance.

The smallest incidence of skin wrin-kling occurred in elderly nativeSwedes followed by Greek-born sub-jects living in Melbourne, Greeks liv-ing in rural Greece, and Anglo-CelticAustralians living in Melbourne. Lessactinic skin damage appeared to beassociated with a higher intake of veg-etables, olive oil, fish (of lower signif-icance), and legumes as well as with

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Volume t 2 - June 200 t • inform

lower intakes of butter and margarine,milk products and sugar goods-gen-erally regarded as the diet for goodhealth. In particular, a high intake ofvegetables, legumes, and olive oilappeared to be protective against cuta-neous actinic damage, whereas highintake of meat, dairy, and butterseemed to have an opposite effect.

Dietary factors offering skin protec-tion are believed to be associated withhigh levels of antioxidants such as vita-mins A, C, and E. The protective actionof olive oil probably reflects the incor-poration in the skin of monounsaturat-ed fatty acid, which is more likely 10resist oxidative damage than polyunsat-urated acid.

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(Source: journal of the America"College of Nutrition 20:71-80, 200 I)

Canadian firm marketingcheese enriched with n-3PurNutra Inc., a Omenee, Ontario,Canada, dairy products company, isproducing cheese enriched in n-3polyunsaturated fatty acids (PUFA) forsale in the United States. Sold under theOmegaSmarr brand name, the cheesecontains higher levels of docosa-hexaenoic acid (DHA) and eicosepen-raenoic acid (EPA) than found in typicalcheese products.

The DHA is not added to the cheesenor the milk used to make the cheese,but instead comes from a patented feedwith higher than normal n-3 sourcesrhur is fed to dairy cattle and is designedto bypass the cow's rumen, or secondstomach. The rumen breaks down feedand normally does not allow DHA inanimal feeds to be absorbed and incor-porated into the cow's milk. Cow's milktypically contains negligible quantitiesof n-j PUFA.

A one-ounce serving (30 grams) ofPurNurm's cheese contains 8.4 gT3mstotal fat, of which 5.1 grams arc satu-rated fat and 176 milligrams arcPUFA. Of the PUFA, 112 milligramsarc n-3 fatty acids, including 35 mgDHA and 12 mg EPA. The remaining65 grams of PUFA is mostly a-linolenic acid (ALA), the n-J precursorof DHA and EPA, according to JimStewart, business manager forPurNutra. Humans convert approxi-mately 4-10% of ALA to DHAIEPA inthe body, Stewart said.

"I salute anyone who wants to pur-sue a product in this direction," saidGeorge Haenlein, professor emeritusin the University of Delaware's animaland food sciences department.

"Decades of research have shown ushow to alter animal feed and achieve aspecialty food product. It is long over-due."

In addition to touting the cheese'sDHA and EPA content on the packag-ing label, the company also lists theconjugated linoleic acid (ClA) content.One serving of OmegaSmart contains44 mg of CU.

"Ours is one of the first food prod-UCtS to spell Out the level of CLA on thelabel," Stewart said.

The product has been cleared by theU.S. Food and Drug Administration(FDA) for sale in the United States. FDAapproval was required for food safetyand inspection purposes and becausePur Nurra lists the amounts of total n-3PUFA, DHA, EPA, and CLA on thelabel, Stewart said.

"The FDA was very helpful to workwith, because they basically said, 'If youcan prove what you say on the label,then it's okay with us.' The approvalprocess is a little more difficult in othercountries," Stewart said.

PurNutra does not make healthclaims about DHA or EPA on theproduct label, because such healthclaims are not allowed for food prod-ucts in the United States. The FDAallows a "qualified dietary supplementclaim" for dietary supplements con-taining DHA and EPA, however(inform 12:65-66).

The OmegaSmart cheese productsare now on sale in the northeasternUnited States and will be marketed inCanada, Japan, and Europe in 2001,Stewart said. The company currentlyproduces 20,000 pounds of cheese permonth but plans to expand productionto 40,000 pounds per month by the endof 2001, primarily by placing addition-al dairy herds under contract to pro-duce DHA-enriched milk. In addition,

62J

the company plans to offer an expand-ed line of DHA-enriched dairy productssuch as ice cream, yogurts, and dairyspreads by early 2002.

Studies have shown that peopleaged 25-49 should consume 1.5 gramsof n-3 fatty acids per day, the companysaid in a prepared news release. Oneserving of OmegaSmart provides 112mg of n-J PUFA, or approximately7.5% of that total, while also providing25% of the U.S. federally suggestedmaximum daily intake of saturated fat.

Martek oils offeredin U.K. infant formulasMartek Biosciences Corporation,Columbia, Maryland, announced inmid-April that the company's nutrition-al oils containing docosahexaenoic acid(DHA) and arachidonic acid (ARA) arenow available in term infant formula inthe United Kingdom.

The infant formula is being manufac-tured by Wyeth NurritionalsInternational, an affiliate of Wyeth-Ayerst Pharmaceuticals, lnc., Radnor,Pennsylvania. Addition of DHAIARAoils is being made to Wyeth's SMA Goldterm infant formula which presently hasa 20% share of the United Kingdominfant formula market.

More recently, DHAIARA oils interm infant formula have becomeavailable in several countries inCentral and South America,Singapore, and South Africa. In total.Manek's licensees are now sellingterm infant formula supplementedwith the DHAIARA oils in nearly 20countries, and supplemented preterminfant formulas in over 60 countriesworldwide, the firm said.

Infant formula fortified with DHAhas been available in Europen nationsusing material from other firms.D

Volume 12 • June 2001 • Inform