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Life Extension Magazine

LEF Magazine May 1998

Vitamins Prevent Heart Attacks
Information in a prestigious medical journal could have been published years ago

The February 4, 1998, issue of the Journal of the American Medical Association (JAMA) provides the most persuasive evidence to date that folic acid and vitamin B6 significantly reduce the risk of heart disease in humans. JAMA included in the issue an editorial commenting on the study by Kilmer S. McCully, M.D., the pioneer who discovered the role of homocysteine and vascular disease in 1969. imageMcCully's work was the first to show that vitamin B6 and folic acid, among other substances, help reduce homocysteine levels in the blood, thus protecting against heart disease.

As readers of Life Extension magazine know, McCully was persecuted by and ostracized from the medical establishment for his politically unpopular theory that homocysteine is a primary culprit in the development of arteriosclerosis (see our interview with Dr. McCully in the November 1997 issue of Life Extension).

The 14-year-long study published in JAMA revealed that women with the highest intake of folic acid had 47 percent less coronary heart disease than those who consumed the lowest amount of folic acid. In addition, for every 200-microgram increase in folic acid intake, there was an 11 percent decrease in coronary heart disease risk.

The link between vitamin B6 and heart disease also was compelling. Women with the highest intake of vitamin B6 had a 51 percent lower incidence of coronary heart disease than those who consumed the lowest amount of vitamin B6. For each 2 mg increase in B6 intake, there was a 10 percent decrease in coronary heart disease risk

An intriguing aspect of the study showed a link between alcoholic beverage consumption and reduced heart disease. Women who consumed up to one alcoholic beverage a day and who had a high folate intake had a 45 percent reduction in coronary heart disease. Women who consumed more than one alcoholic beverage a day and who had a high folate level had a 78 percent reduction in coronary heart disease. Since alcohol can inactivate folate, those who drink alcohol need a higher folate intake.

These findings were obtained from 80,082 women who participated in the on-going Nurses' Health Study. Other findings about disease prevention have been gleaned from this study. On May 23, 1993, for example, The New England Journal of Medicine published a report from this study showing that women who took vitamin E supplements had a 44 percent reduction in their risk of coronary heart disease.

In 1981, the Life Extension Foundation published several articles on McCully's work showing that homocysteine plays a significant role in the development of heart disease and stroke. In the years that followed, the Food and Drug Administration spent millions of taxpayer dollars pursuing criminal indictments against the leaders of the Foundation for promoting the use of vitamins to prevent heart disease (among other things). The FDA claimed that the Foundation was defrauding consumers by encouraging them to take vitamins to prevent heart disease.

The facts now show that it was the FDA (and others in the medical establishment) who were defrauding the public out of their health and money by denying Americans access to scientific information that could have helped to prevent tens of millions of heart attacks and strokes.

McCully's editorial and the supporting study published in JAMA is the ultimate vindication for a career that was nearly ruined by establishment forces who had too much invested in the cholesterol theory of heart disease to pay attention to scientific reality.

Currently, health freedom activists in England are fighting to keep high-potency vitamin B6 supplements from being designated as prescription drugs, thus limiting their availability. Considering the epidemic of cardiovascular disease throughout Britain, a conspiratorially minded person might think that the British government wants to murder its own citizens by denying them easy and affordable access to a vitamin that has been proven to reduce the incidence of coronary artery disease by 51 percent.

The Life Extension Foundation has been evaluating the role nutrients play in the prevention of heart disease for 18 years. Cardiologists who now know about folic acid often are recommending less-than-optimal doses to their patients with coronary artery occlusion.

Further, most doctors think that if your homocysteine levels are below a measurement of 9 or 10 micromoles per liter of blood serum, you are "normal," since those whose blood levels are above 10 have the greatest incidence of heart attacks and strokes. There is, however, no established safe level of homocysteine. That means that if you have coronary artery disease, or if your homocysteine levels are high, you should be on homocysteine-lowering therapy. The Foundation suggests that homocysteine levels be reduced to below 5 or 6.

Those with coronary artery disease should have their blood tested for homocysteine under the care of a physician, who should then put them on a heavy duty anti-homocysteine program. Those at risk for vascular disease should take homocysteine-lowering nutrients as part of their daily supplement program.

The Foundation's current recommendations are that a person with existing coronary heart disease should take several thousand micrograms of folic acid, at least 500 micrograms of vitamin B12, around 200 mg of vitamin B6, 1,000 to 2,000 milligrams of trimethylglycine (TMG), 400 to 800 IU of vitamin E, and 1,000 mg of magnesium every day. Lower doses should be taken for prevention.


The doctors who conducted the study on folate and vitamin B6, as published in JAMA, made the following comments:

  • The results corroborate and extend recent studies showing a lower risk of coronary artery disease in individuals with higher blood levels of folate and vitamin B6.
  • The high intake of both folic acid and vitamin B6 reduced the risk of coronary heart disease better than either nutrient alone.
  • The strongest apparent benefit was in women who consumed high folate and alcohol.
  • The findings are consistent with evidence linking higher intake of folic acid and vitamin B6 with lower homocysteine levels.
  • The magnitude of the decrease in coronary heart disease in this study is consistent with a parallel study on male health professionals.
  • Vitamin B6 is more effective in lowering homocysteine in response to methionine loading, whereas folic acid is more effective in reducing fasting homocysteine levels.
  • The women in this study had far higher levels of folate and vitamin B6 intake than the average population, but they still benefitted further from even higher intake of these nutrients.
  • The lowest risks for coronary artery disease were in women whose daily intake exceeded 400 micrograms per day of folate and 3 mg a day of vitamin B6. Therefore, the current RDA for folate (180 micrograms per day) and vitamin B6 (1.6 mg per day) may not be sufficient to minimize risks of coronary disease.
  • These results suggest that any widespread increase in folate intake will have a favorable impact on coronary heart disease rates, but that maximum benefit will be achieved at folate intake of at least 400 micrograms a day.

Direct From JAMA

Here is the abstract summarizing the study on the impact of vitamin B6 and folic acid on heart disease, as published in the Feb. 4, 1998, Journal of the American Medical Association. It is accompanied by a note from JAMA.

"Folate and Vitamin B6 From Diet and Supplements in Relation to Risk of Coronary Heart Disease Among Women." Eric B. Rimm, Sc.D.; Walter C. Willett, M.D., Dr.PH.; Frank B. Hu, M.D., Ph.D.; Laura Sampson, M.S.; Graham A. Colditz, M.B., B.S., Dr.PH.; JoAnn E. Manson, M.D., Dr.PH.; Charles Hennekens, M.D., Dr.PH.; Meir J. Stampfer, M.D., Dr. PH., JAMA. 1998;279:359-364

Context. Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available. Objective. To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD. Design. Prospective cohort study.

Setting and Patients. In 1980, a total of 80,082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6. Main Outcome Measure. Nonfatal MI and fatal CHD confirmed by World Health Organization criteria.

Results. During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension, and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95 percent confidence interval [CI]), 0.55-0.87 for folate (median intake, 696 µg/d vs. 158 µg/d) and 0.67 (95 percent CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs. 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95 percent CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake, compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95 percent CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6.

In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR=0.69; 95 percent CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95 percent CI, 0.13-0.58).

Conclusion. These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

Editor's note. Although the separate pieces of the pathway that connect folate and vitamin B6 to coronary artery disease via homocysteine metabolism have been well studied in both laboratory and epidemiologic investigations, this article is the first to examine the entire pathway in an epidemiologic study. Using data from the Nurses' Health Study, the authors appear to confirm the hypothesis that increased intake of these nutrients may prevent coronary artery disease. However, as is the usual limitation of epidemiologic studies, the association needs further research to define the interactions that further delineate patients in whom the association is particularly strong. The interaction with alcohol intake is particularly intriguing, and if confirmed, may complicate the issue of establishing recommended daily nutrient intakes.

-David H. Mark, M.D., M.P.H.,
Contributing Editor