During 1995-97, the primary medical and scientific literature has had a steady stream of well-

designed, carefully controlled studies demonstrating a new risk factor for heart disease. Just as

high cholesterol levels, smoking, lack of exercise, and family history are significant factors in

predicting whether an individual will develop heart disease, the level of homocysteine in the

blood is a risk factor. " [E]levated plasma levels of homocyst(e)ine are associated with increased

risk of coronary atherosclerosis, cerebrovascular disease, peripheral vascular disease, and

thrombosis"(20). Homocysteine is an amino acid, produced from the required amino acid

methionine. Homocysteine is not used in making proteins, and is normally metabolized back to

(cobalamin) for the metabolism. One theory is that the modern American diet is so rich in

protein that the methionine content overwhelms our ability to metabolize it, and those with low

intakes of those three vitamins are unable to regulate the homocysteine level adequately.

"Plausible mechanisms by which homocyst(e)ine might contribute to atherogenesis include

promotion of platelet activation and enhanced coagulability, increased smooth muscle cell

proliferation, cytotoxicity, induction of endothelial dysfunction, and stimulation of LDL

oxidation" (20). As an example of the importance of vitamins, in one major study of 14,916 men

(19), those with the lowest 20% of folate levels had a relative risk of 1.4 for heart attack or death.

Those with the lowest 20% of vitamin B6 levels had a relative risk of 1.5. Supplementation of

the diet with those vitamins leads to a corresponding decrease in risk. Thus, many authors have

proposed supplementing foods or giving vitamin supplements to people to reduce the level of

homocysteine in the blood, and thus the risk of heart disease.

QUOTATIONS FROM PUBLISHED HOMOCYSTEINE STUDIES

1. "Serum folate and risk for ischemic stroke. First National Health and Nutrition Examination

Survey epidemiologic follow-up study", Giles WH; Kittner SJ; Anda RF; Croft JB; Casper ML

Cardiovascular Health Studies Branch, Centers for Disease Control and Prevention, Atlanta

30341-3724, USA. , Stroke, 1995 Jul, 26:7, 1166-70

"A serum folate concentration < or = 9.2 nmol/L has been associated with elevated levels of

plasma homocyst(e)ine. Elevated homocyst(e)ine levels have been associated with ischemic

stroke in case-control studies...We used data from the First National Health and Nutrition

Examination Survey Epidemiologic Follow-up Study (n = 2006). ... CONCLUSIONS: These

findings suggest that a folate concentration < or = 9.2 nmol/L may be a risk factor for ischemic

stroke"

2. "Homocysteine and risk of premature coronary heart disease. Evidence for a common gene

mutation," Gallagher PM; Meleady R; Shields DC; Tan KS; McMaster D; Rozen R; Evans A;

Graham IM; Whitehead AS , Department of Genetics, Trinity College, Dublin 2, Ireland.

Circulation, 1996 Nov 1, 94:9, 2154-8

"Plasma homocysteine levels are modulated by nutritional and genetic factors, among which is

the enzyme methylenetetrahydrofolate reductase (MTHFR)... MTHFR, which modulates basal

plasma homocysteine concentration, is folate dependent, and dietary supplementation or

fortification with folic acid may reduce plasma homocysteine levels and consequent coronary risk

in a significant proportion of the general population. "

3. "Serum total homocysteine and coronary heart disease," Arnesen E; Refsum H; B naa KH;

Ueland PM; F rde OH; Nordrehaug JE , Institute of Community Medicine, University of

Troms , Norway. , Int J Epidemiol, 1995 Aug, 24:4, 704-9

"Several studies have observed high plasma levels of homocysteine among patients with

coronary heart disease (CHD). The only prospective study was based on US physicians, and

concluded that homocysteine was associated with subsequent myocardial infarction (MI)... We

conducted a nested case-control study among the 21,826 subjects, aged 12-61 years..

CONCLUSIONS. In the general population serum total homocysteine is an independent risk

factor for CHD... "

4. "New directions in dietary studies of coronary heart disease," Ascherio A; Willett WC

Department of Epidemiology, Harvard School of Public Health Boston, MA. , J Nutr, 1995 Mar,

125:3 Suppl, 647S-655S

"For several decades the debate on diet and coronary heart disease has been dominated by the

classic diet-heart hypothesis, which predicts an adverse effect of dietary saturated fat and

cholesterol and a beneficial effect of polyunsaturated fat intake. However, recent research

suggests that the diet-heart relationship is much more complex than previously recognized.

Antioxidants, and in particular vitamin E, are emerging as potentially useful protective factors,

and there is increasing evidence that hyperhomocysteinemia is a risk factor that may be modified

by dietary changes"

5. "Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine

Study," NygÜrd O; Vollset SE; Refsum H; Stensvold I; Tverdal A; Nordrehaug JE; Ueland M;

KvÜle G , Section for Medical Informatics and Statistics, University of Bergen, Norway.

JAMA, 1995 Nov 15, 274:19, 1526-33

"A total of 7591 men and 8585 women, 40 to 67 years of age, with no history of hypertension,

diabetes, coronary heart disease, or cerebrovascular disease were included...

CONCLUSIONS--Elevated plasma tHcy level was associated with major components of the

cardiovascular risk profile, ie, male sex, old age, smoking, high blood pressure, elevated

cholesterol level, and lack of exercise. These findings should influence future studies on the

etiology and pathogenesis of cardiovascular disease. "

6. "Plasma homocyst(e)ine levels and graded risk for myocardial infarction: findings in two

populations at contrasting risk for coronary heart disease," Malinow MR; Ducimetiere P; Luc G;

Evans AE; Arveiler D; Cambien F; Upson BM , Oregon Regional Primate Research Center,

Beaverton 97006, USA. malinowr@ohsu.edu , Atherosclerosis, 1996 Sep 27, 126:1, 27-34

"Standardized mortality rates for coronary heart disease (CHD) in men are about 3-fold higher in

Northern Ireland than in France. The differences could not be explained by the presence of

conventional risk factors for atherosclerosis. We studied in subjects from these two countries, an

additional risk factor, namely, concentration of plasma homocyst(e)ine which is frequently

elevated in patients with CHD... Results were compatible with global excess of risk for MI being

graded across the distribution of plasma homocyst(e)ine concentrations.... The higher plasma

homocyst(e)ine concentrations we observed in the Irish population could be the reason for the

different CHD mortality rates. This epidemiological observation could prompt dietary and

vitamin supplementation studies aimed at decreasing homocyst(e)ine levels as well as the

incidence of arterial occlusive disease, under controlled conditions in high risk populations."

7. "Prevention of myocardial infarction by vitamin B6," Ellis JM; McCully KS

Titus County Memorial Hospital, Mt. Pleasant, Texas 75455, USA. , Res Commun Mol Pathol

Pharmacol, 1995 Aug, 89:2, 208-20

"Vitamin B6 is effective in the treatment of carpal tunnel syndrome and related disorders in

patients with vitamin B6 deficiency. Hyperhomocysteinemia, a risk factor for atherosclerosis, is

associated with deficiencies of vitamin B6, folate, and cobalamin. Patients who were given

vitamin B6 for carpal tunnel syndrome and other degenerative diseases were found to have 27%

of the risk of developing acute cardiac chest pain or myocardial infarction, compared with

patients who had not taken vitamin B6. Among elderly patients of the author (JE) expiring at

home, the average age at death from myocardial infarction was 8 years later in those who had

taken vitamin B6, compared with those who had not taken vitamin B6. The preventive effect of

vitamin B6 on progression of coronary heart disease may be related to increased formation of

pyridoxal phosphate, the coenzyme that is required for catabolism of the atherogenic amino acid,

homocysteine. "

8."Plasma homocysteine levels and mortality in patients with coronary artery disease," Nyg rd

O; Nordrehaug JE; Refsum H; Ueland PM; Farstad M; Vollset SE , Department of Public Health

and Primary Health Care, University of Bergen, Haukeland University Hospital, Norway.

N Engl J Med, 1997 Jul 24, 337:4, 230-6

"Elevated plasma homocysteine levels are a risk factor for coronary heart disease, but the

prognostic value of homocysteine levels in patients with established coronary artery disease has

not been defined. METHODS: We prospectively investigated the relation between plasma total

homocysteine levels and mortality among 587 patients...: Plasma total homocysteine levels are a

strong predictor of mortality in patients with angiographically confirmed coronary artery

disease."

9. "The role of folic acid in deficiency states and prevention of disease," Swain RA; St Clair L

Department of Family and Sports Medicine, West Virginia University-Charleston Division

25301, USA. , J Fam Pract, 1997 Feb, 44:2, 138-44

"Folic acid, a water-soluble vitamin, has been used since the 1940s to treat some cases of

macrocytic anemia without neurologic disease... the vitamin may reduce the incidence of neural

tube defects by 45% in women who receive 400 micrograms per day. It is recommended that all

women of childbearing age take 400 micrograms of folate per day. Elevations in homocysteine

levels, a metabolite intimately associated with folate, are also being found with increasing

regularity in those with cardiovascular diseases. Homocysteine levels are reduced by folic acid

administration. Therefore, there is some biologic plausibility... for the assumption that folate

supplements may prevent heart disease, stroke, and peripheral arterial disease.

10. "Folic acid fortification of the food supply. Potential benefits and risks for the elderly

population," Tucker KL; Mahnken B; Wilson PW; Jacques P; Selhub J , Jean Mayer US

Department of Agriculture Human Nutrition Research Center on Aging at Tufts University,

Boston, Mass 02111, USA. , JAMA, 1996 Dec 18, 276:23, 1879-85

"To estimate the potential benefits and risks of food folic acid fortification for an elderly

population. Benefits are expected through the improvement of folate and homocysteine status,

but there is also a risk of masking or precipitating clinical manifestations related to vitamin B12

deficiency with increasing exposure to folic acid.... A total of 747 subjects aged 67 to 96 years

who both completed usable food frequency questionnaires and had blood concentrations of B

vitamins and homocysteine measured. .. Percentages of this elderly population with folate intake

below 400 microg/d are projected to drop from 66% at baseline to 49% with 140 microg of folate

per 100 g of cereal-grain product, to 32% with 280 microg, to 26% with 350 microg, and to 11%

with 700 microg. Percentages with elevated homocysteine concentrations (>14 micromol/L) are

projected to drop from 26% at baseline to 21% with 140 microg of folate per 100 g, to 17% with

280 microg, to 16% with 350 microg, and to 12% with 700 microg. "

11. "Relationship between plasma homocysteine, vitamin status and extracranial carotid-artery

stenosis in the Framingham Study population," Selhub J; Jacques PF; Bostom AG; D'Agostino

RB; Wilson PW; Belanger AJ; O'Leary DH; Wolf PA; Rush D; Schaefer EJ; Rosenberg; IH

Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts

University, Boston, MA 02111, USA. , J Nutr, 1996 Apr, 126:4 Suppl, 1258S-65S

"Recent studies demonstrated associations between occlusive vascular disease and

hyperhomocysteinemia of both genetic and nutritional origin. In the present study we analyzed

plasma samples from the 20th biannual examination of the Framingham Heart Study cohort to

determine distribution of plasma homocysteine concentrations with emphasis on relationships to

B vitamins and prevalence of carotid artery stenosis. Results showed that homocysteine exhibited

strong inverse association with plasma folate and weaker associations with plasma vitamin B-12

and pyridoxal-5'-phosphate (PLP). Homocysteine was also inversely associated with intakes of

folate and vitamin B-6, but not vitamin B-12. Prevalence of high homocysteine (>14 micromol/l)

was 29.3% in this cohort, and inadequate plasma concentrations of one or more B vitamins

appear to contribute to 67% of the cases of high homocysteine. Prevalence of stenosis > or =

25% was 43% in men and 34% in women with an odds ratio of 2.0 for individuals in the highest

homocysteine quartile (> or = 14.4 micromol/l) compared with those in the lowest quartile (< or

= 9.1 micromol/l), after adjustment for sex, age, high density lipoprotein cholesterol, systolic

blood pressure and cigarette smoking (Ptrend < 0.001). Plasma concentrations of folate and

pyridoxal-5'-phosphate and folate intake were inversely associated with extracranial carotid

stenosis after adjustment for age, sex and other risk factors."

12. "Relationship among homocyst(e)ine, vitamin B-12 and cardiac disease in the elderly:

association between vitamin B-12 deficiency and decreased left ventricular ejection fraction,"

Herzlich BC; Lichstein E; Schulhoff N; Weinstock M; Pagala M; Ravindran K; Namba T; Nieto

FJ; Stabler SP; Allen RH; Malinow; MR , Department of Medicine, Maimonides Medical

Center, Brooklyn, NY 11219, USA. , J Nutr, 1996 Apr, 126:4 Suppl, 1249S-53S

"We evaluated the association of moderate hyperhomocyst(e)inemia and vitamin B-12 status

with coronary artery disease (CAD) and left ventricular ejection fraction in 367 elderly patients...

The trend among these vitamin B-12-deficient patients and low left ventricular ejection fraction

was significant (P = 0.028).... In conclusion, vitamin B-12-deficient patients had significantly

lower left ventricular ejection fractions than nonvitamin B-12-deficient patients."

13. "Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged

adults,"

Shimakawa T; Nieto FJ; Malinow MR; Chambless LE; Schreiner PJ; Szklo M

Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute,

Bethesda, MD, USA, Ann Epidemiol, 1997 May, 7:4, 285-93

"Many epidemiologic studies have identified elevated plasma homocyst(e)ine as a risk factor for

atherosclerosis and thromboembolic disease. To examined the relationship between vitamin

intakes and plasma homocyst(e)ine, we analyzed dietary intake data from a case-control study of

322 middle-aged individuals with atherosclerosis in the carotid artery and 318 control subjects

without evidence of this disease... from a probability sample of 15,800 men and women who

participated in the Atherosclerosis Risk in Communities (ARIC) Study. .. Plasma homocyst(e)ine

among users of vitamin supplement products was 1.5 mumol/L lower than that among nonusers."

QUOTATIONS FROM VITAMIN B12 STUDIES

14. "Vitamin supplementation and other variables affecting serum homocysteine and

methylmalonic acid concentrations in elderly men and women," Koehler KM; Romero LJ;

Stauber PM; Pareo-Tubbeh SL; Liang HC; Baumgartner RN; Garry PJ; Allen RH; Stabler SP

Clinical Nutrition Program, University of New Mexico School of Medicine, Albuquerque

87131-5666, USA, J Am Coll Nutr, 1996 Aug, 15:4, 364-76

"An elevated serum concentration of the metabolite, homocysteine (Hcys): 1) can indicate folate

or vitamin B12 deficiency, 2) is an independent risk factor for vascular disease. .. to determine

the effect of self-selected vitamin supplementation and other variables ... for elderly volunteers,

age 68-96 years, and compared for those consuming (26 men, 25 women) and not consuming (24

men, 25 women) self-selected vitamin supplements. RESULTS: Compared with the

nonsupplemented group, the supplemented group had lower mean serum MMA (208 +/- 162 vs.

241 +/- 98 nmol/L [+/- SD]) and Hcys (9.5 +/- 2.6 vs. 11.2 +/- 2.7 mumol/L); and higher serum

vitamin B12 (391 +/- 174 vs 292 +/- 107 pmol/L), and serum folate (46 +/- 15 vs. 24 +/- 10

nmol/L) p < 0.05. ..Results showed potential usefulness of serum MMA and Hcys in identifying

subclinical or tissue deficiency of vitamin B12. Clinicians should be aware of the risk of vitamin

B12 deficiency in older people... These elderly volunteers had generally good folate status;

nevertheless, some subjects seemed likely to benefit from an improvement in folate status that

would reduce their serum Hcys within the normal range."

15. "Cigarette smoking, intracellular vitamin deficiency, and occurrence of micronuclei in

epithelial cells of the buccal mucosa," Piyathilake CJ; Macaluso M; Hine RJ; Vinter DW;

Richards EW; Krumdieck CL , Department of Nutrition Sciences, University of Alabama at

Birmingham 35294, USA, Cancer Epidemiol Biomarkers Prev, 1995 Oct-Nov, 4:7, 751-8

"The study focuses on the assessment of chromosomal damage associated with folate and

vitamin B12 deficiency.... The presence of vitamin B12 in the immediate environment (saliva)

and vitamin C and E in the plasma, however, appear to be marginally protective against

chromosomal damage in buccal mucosal cells."

16. "Impaired antibody responses to pneumococcal polysaccharide in elderly patients with low

serum vitamin B12 levels," Fata FT; Herzlich BC; Schiffman G; Ast AL, Maimonides Medical

Center, Department of Medicine, Brooklyn, NY 11219, USA. , Ann Intern Med, 1996 Feb 1,

124:3, 299-304

"To determine whether immunocompetent elderly patients with low serum vitamin B12 levels

have impaired serum antibody responses to the 23-polyvalent pneumococcal polysaccharide

vaccine. ..: Patients with low vitamin B12 levels had impaired antibody responses to

pneumococcal vaccine."

17. "Effects of vitamin B12 on performance and circadian rhythm in normal subjects," Mayer G;

Krîger M; Meier-Ewert K , Sleep Disorder Unit, Hephata Klinik, Schwatmstadt-Treysa,

Germany. , Neuropsychopharmacology, 1996 Nov, 15:5, 456-64

"This preliminary study investigates effects of methyl- and cyanocobalamin on circadian

rhythms, well-being, alertness, and concentration in healthy subjects... the change in the visual

analogue scales items "sleep quality," "concentration," and "feeling refreshed" between

pretreatment and the first week of treatment showed significant correlations with vitamin B12

plasma levels."

18. "Folate and vitamin B12 status of the elderly," Quinn K; Basu TK , Department of

Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada, Eur J Clin

Nutr, 1996 Jun, 50:6, 340-2

" The present study was undertaken to investigate the relationship between estimated folate and

vitamin B12 intakes and their biochemical status in elderly persons. SUBJECTS: Twenty-eight

males and 30 females ( > 65 years)...CONCLUSIONS: The folate status appears to be a greater

concern than the vitamin B12 status for the elderly population. It seems that although mean

values of dietary intake and plasma concentrations of folate may indicate nutritional adequacy, a

proportion of the older population may still be at nutritional risks."

QUOTATIONS FROM VITAMIN B6 STUDIES

19. "A prospective study of folate and vitamin B6 and risk of myocardial infarction in US

physicians," Chasan-Taber L; Selhub J; Rosenberg IH; Malinow MR; Terry P; Tishler PV;

Willett W; Hennekens CH; Stampfer MJ , Department of Epidemiology, Harvard School of

Public Health, Boston, Massachusetts, USA. , J Am Coll Nutr, 1996 Apr, 15:2, 136-43

"To assess prospectively the risk of myocardial infarction (MI) associated with decreased plasma

levels of folate and pyridoxal phosphate (PLP, a form of vitamin B6) in relation to elevated

levels of total homocysteine (tHcy)... SETTING: Participants in the Physicians' Health Study.

SUBJECTS: 14,916 male physicians, aged 40-84 years, with no prior MI or stroke provided

plasma samples at baseline and were followed for 7.5 years. ... RESULTS:...men with the lowest

20% of folate levels ... had a relative risk of 1.4...compared with those in the top 80%. For the

lowest 20% of vitamin B6 values, the relative risk was 1.5 ... these prospective data are

compatible with the hypothesis that low dietary intake of folate and/or vitamin B6 contribute to

risk of MI. "

20. "Homocyst(e)ine: an important risk factor for atherosclerotic vascular disease," Duell PB;

Malinow MR, Department of Medicine, Oregon Health Sciences University, Portland

97201-3098, USA. duellb@ohsu.edu , Curr Opin Lipidol, 1997 Feb, 8:1, 28-34

"Homocysteine is an intermediate compound formed during metabolism of methionine. The

results of many recent studies have indicated that elevated plasma levels of homocyst(e)ine are

associated with increased risk of coronary atherosclerosis, cerebrovascular disease, peripheral

vascular disease, and thrombosis. The plasma level of homocyst(e)ine is dependent on

genetically regulated levels of essential enzymes and the intake of folic acid, vitamin B6

(pyridoxine), and vitamin B12 (cobalamin). Impaired renal function, increased age, and

pharmacologic agents (e.g. nitrous oxide, methotrexate) can contribute to increased levels of

homocyst(e)ine. Plausible mechanisms by which homocyst(e)ine might contribute to

atherogenesis include promotion of platelet activation and enhanced coagulability, increased

smooth muscle cell proliferation, cytotoxicity, induction of endothelial dysfunction, and

stimulation of LDL oxidation. Levels of homocysteine can be reduced with pharmacologic doses

of folic acid, pyridoxine, vitamin B12..."

21. "Association between plasma homocysteine concentrations and extracranial carotid-artery

stenosis," Selhub J; Jacques PF; Bostom AG; D'Agostino RB; Wilson PW; Belanger AJ; O'Leary

DH; Wolf PA; Schaefer EJ; Rosenberg IH , Department of Agriculture Human Nutrition

Research Center on Aging, Tufts University, Boston, MA 02111. , N Engl J Med, 1995 Feb 2,

332:5, 286-91

"BACKGROUND. Epidemiologic studies have identified hyperhomocysteinemia as a possible

risk factor for atherosclerosis... a cross-sectional study of 1041 elderly subjects (418 men and 623

women; age range, 67 to 96 years) from the Framingham Heart Study... CONCLUSIONS. High

plasma homocysteine concentrations and low concentrations of folate and vitamin B6, through

their role in homocysteine metabolism, are associated with an increased risk of extracranial

carotid-artery stenosis in the elderly."

22. "Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6,

B12, and folate," Verhoef P; Stampfer MJ; Buring JE; Gaziano JM; Allen RH; Stabler SP;

Reynolds RD; Kok FJ; Hennekens CH; Willett WC , Department of Epidemiology and Public

Health, Agricultural University, Wageningen, Netherlands. , Am J Epidemiol, 1996 May 1,

143:9, 845-59

"Elevated plasma homocyst(e)ine levels are an independent risk factor for vascular disease. ..

Dietary and plasma levels of vitamin B6 and folate were lower in cases than in controls, and

these vitamins were inversely associated with the risk of myocardial infarction, independently of

other potential risk factors... the authors found that impairment of remethylation of

homocyst(e)ine (dependent of folate and vitamin B12 rather than on vitamin B6-dependent

transsulfuration) was the predominant cause of high homocyst(e)ine levels in cases. Accordingly,

plasma folate and, to a lesser extent, plasma vitamin B12, but not vitamin B6, correlated

inversely with plasma homocyst(e)ine, even for concentrations at the high end of normal values.

These data provide further evidence that plasma homocyst(e)ine is an independent risk factor for

myocardial infarction. In this population, folate was the most important determinant of plasma

homocyst(e)ine, even in subjects with apparently adequate nutritional status of this vitamin."

23. "Vitamin supplementation in the elderly: a critical evaluation," Buchman AL , Nutrition

Support Services, Baylor Institute for Inflammatory Bowel Diseases, Baylor College of

Medicine, Houston, TX 77030, USA. , Gastroenterologist, 1996 Dec, 4:4, 262-75

"Routine vitamin supplementation for the elderly has been advocated by many. Specific vitamin

deficiencies are rare in free-living elderly"

24. "Do antioxidant micronutrients protect against the development and progression of knee

osteoarthritis?," McAlindon TE; Jacques P; Zhang Y; Hannan MT; Aliabadi P; Weissman B;

Rush D; Levy D; Felson DT , Arthritis Center, Boston University Medical Center,

Massachusetts, 02118, USA. , Arthritis Rheum, 1996 Apr, 39:4, 648-56

"Cumulative damage to tissues, mediated by reactive oxygen species, has been implicated as a

pathway that leads to many of the degenerative changes associated with aging. We hypothesized

that increased intake of antioxidant micronutrients might be associated with decreased rates of

osteoarthritis (OA) in the knees... CONCLUSION: High intake of antioxidant micronutrients,

especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with

OA. "

25. "Age-associated problems in nutrition.," Sone Y , Department of Food and Nutrition, Faculty

of Human Life Science, Osaka City University. , Appl Human Sci, 1995 Sep, 14:5, 201-10

"The balanced diet; especially the diet enhanced by vitamins E and B6 and trace mineral zinc is

helpful for the elderly to prevent the declines in the immune system. The foods rich in vitamin D

and calcium; they may help to prevent the elderly from osteoporosis. "

26. "Free radicals, oxidative stress, oxidized low density lipoprotein (LDL), and the heart:

antioxidants and other strategies to limit cardiovascular damage," Sinatra ST; DeMarco J ,

Manchester Memorial Hospital, USA. , Conn Med, 1995 Oct, 59:10, 579-88

"The heart is the most susceptible of all the organs to premature aging and free radical oxidative

stress. Clinical research has clearly documented the role of free radical damage and the

progression of numerous degenerative diseases, particularly cardiovascular disease. This may be

the result of acute ischemia-reperfusion injury, endothelial damage of hyperhomocysteinemia, as

well as chronic oxidative damage secondary to lipid peroxidation. Fortunately, although highly

responsive, and therefore vulnerable to the effects of oxidative stress, the heart is also receptive

to the benefits of targeted phytonutrients, antioxidants, and nutritionals. The effects of

antioxidant nutrients have been extensively evaluated in epidemiological, population, and clinical

studies... The B complex, particularly folic acid, B12, and B6 are also essential in the prevention

of hyperhomocysteinemia, another major risk factor for the circulatory system. Measures to

minimize accumulation of heavy metals in the body, especially iron and copper, which are

capable of initiating adverse free radical reactions, will also help to assuage oxidative stress.

Thus, the combination of a healthy diet supplemented with antioxidants ...may be useful in the

prevention and promotion of optimum cardiovascular health. "

27. "Homocysteine and coronary atherosclerosis," Mayer EL; Jacobsen DW; Robinson K

Department of Cardiology, The Research Institute, The Cleveland Clinic Foundation, Ohio

44195, USA. , J Am Coll Cardiol, 1996 Mar 1, 27:3, 517-27

"Homocysteine is increasingly recognized as a risk factor for coronary artery disease. An

understanding of its metabolism and of the importance of vitamins B6 and B12 and folate as well

as enzyme levels in its regulation will aid the development of therapeutic strategies that, by

lowering circulating concentrations, may also lower risk. Possible mechanisms by which elevated

homocysteine levels lead to the development and progression of vascular disease include effects

on platelets, clotting factors and endothelium. This review presents the clinical and basic

scientific evidence supporting the risk and mechanisms of vascular disease associated with

elevated homocysteine concentrations as well as the results of preliminary therapeutic trials. "

END OF DOCUMENT - THE HOMOCYSTEINE INDCATION FOR HEART DISEASE:

NUTRITIONAL FACTORS IN MAINTAINING GOOD HEALTH