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Life Extension Magazine

LE Magazine August 2001

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Battling Heart Disease with B Vitamins

by Angela Pirisi

Page 1 of 2

Heart disease is the number one killer in North America. Scientists are aggressively seeking to pinpoint the most important risk factors so as to better design a comprehensive preventive strategy against this insidious disease. As it is, heart disease affects 60.8 million Americans and was related to nearly one million deaths in 1998, according to the American Heart Association.

Scientists long ago warned us about the cardiovascular dangers of a high-fat diet, sedentary lifestyle, smoking, high cholesterol-triglycerides and diabetes. In recent years, research has uncovered yet another important culprit in the development of heart disease, namely homocysteine. Study after study over the past decade has shown that, regardless of being clear of other risk factors, even mildly elevated levels of homocysteine in one’s bloodstream can single out victims by making them susceptible to heart disease. Homocysteine is a naturally occurring amino acid in the body which, in excessive amounts, tends to build up in the blood and is believed to be at the root of arterial inflammation and damage. What recent research has also turned up is the discovery that folic acid, vitamin B12 and vitamin B6 supplementation can be used successfully to lower homocysteine levels.

Besides reducing homocysteine concentrations, increasing folic acid, vitamin B6 and B12 intake also works against heart disease by improving vascular endothelial function and related flow-mediated vasodilation.(1-2) A Polish study showed that an eight-week treatment with folic acid (5 milligrams daily), vitamin B6 (300 milligrams daily) and B12 (1000 micrograms weekly) not only cut in half homocysteine levels (from 20 to 10 micromoles/liter). It also diminished the production of a blood-clotting enzyme, thrombin, which plays a proliferative role in heart disease and stroke.(3)

Nutrient status

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Low circulating levels of folate were linked to a 50% greater risk of vascular disease in men. The same study also found that low levels of vitamin B6 increased the risk two to threefold in both sexes.

As scientists attempted to measure homocysteine levels, they began to look for other markers of high homocysteine levels and their associated cardiovascular (and cerebrovascular) risks. One large focus has been the vital role that certain nutritional deficiencies might play in affecting homocysteine levels and precipitating the arterial damage that leads to cardiovascular disease. So, as much as scientists have devoted time to studying the merits of folic acid and vitamin B12 in reducing the risk of heart disease and stroke, demonstrating the harmful impact of nutritional deficiencies has taught researchers even more about certain vitamins as a preventative means.

For instance, recent studies have noted that suboptimal serum levels of folic acid, vitamin B12and vitamin B6 may underlie the development of atherosclerosis and coronary heart disease. Why? It’s believed that such deficiencies lead to inadequate production of S-adenosyl-methionine, creating a state of turmoil called hypomethylation. And this, in turn, may damage the DNA in arterial cells, leading to the mutation and proliferation of smooth-muscle cells, thus paving the way for atherosclerosis. Many experts believe, however, that vitamin supplementation can not only correct the nutritional deficiencies but also help to reverse the atherosclerotic process in people with existing heart disease.(4)

More specifically, low folate status has been seen as one culprit that precipitates the development of cardiovascular disease. The most recent findings suggest that people with the lowest folate status had more than twice the risk of dying from cardiovascular disease as those with the highest levels of the nutrient. The National Heart, Lung and Blood Institute, Bethseda, MD reported such findings after examining the serum folate concentrations of 689 adults, ages 30 to 75, without cardiovascular disease or diabetes.(5)

Similarly, a 15-year Canadian study involving over 5000 men and women with no history of heart disease, aged 35 to 79, showed that the lower the folate levels, the higher was the risk of heart disease-related death. It reported that people with low blood folate levels (below 6.8 nanomoles per liter) have a 69% increase in the risk of fatal coronary heart disease than individuals with higher levels (above 13.6 nanomoles per liter).(6) These study findings are very significant, for one, because the sample included both young and old, male and female. As well, the results point to a correlation between lower blood folate values and mortality, as opposed to just a risk of heart disease, or arterial blockage and damage. What’s even more interesting is that the researchers found an inflated risk of death even in people with so-called normal folate status, which calls into question whether we should be boosting our recommended daily allowance. Meanwhile, one multicenter European study, which compared 750 male and female patients with vascular disease to 800 healthy controls, found that low circulating levels of folate were linked to a 50% greater risk of vascular disease in men. The same study also found that low levels of vitamin B6 increased the risk two to threefold in both sexes.(7)

How Folic Acid and B12
Reduce Homocysteine

Folic acid and B12 are cofactors of methionine synthase, a key enzyme in homocysteine metabolism.(1) As such, they help to break down the amino acid and convert it into another compound, methionine (which is necessary for proper DNA methylation), indeed pointing to an important pivotal role for these nutrients in heart disease prevention.(2-4) Studies to date have shown that folic acid alone may reduce heart disease risk by as much as 30% to 40%, primarily through its ability to lower homocysteine. In fact, folic acid has been deemed the mainstay of treatment for hyperhomocysteinaemia (elevated homocysteine).(5) However, folic acid works best when teamed up with vitamin B12, which enhances the benefits of folic acid supplementation.(6) Generally speaking, doctors recom-mend that vitamin B12 be added to supplements containing folic acid, so as to prevent masking of a B12 deficiency.(7)

1. Auer J, Wien Med Wochenschr 2001;151(1-2):25-28.
2. Saw SM, et al. Am J Clin Nutr 2001 Feb;73(2):232-239.
3. Conri C, et al. Presse Med 2000 Apr 8;29(13):737-741.
4. Osganian SK, et al. JAMA 1999 Apr 7;281(13):1189-1196.
5. Cattaneo, M. Ann Med 2000 Dec;32 Suppl 1:46-52.
6. Bronstrup, A, et al. Am J Clin Nutr 1998 Nov;68:1104-1110.
7. Boushey, CJ, et al. JAMA 1995 Oct 4;274(13):1049-1057.

One study by researchers at the University of Chile even found that, in contrast to other findings, folate levels—and not vitamin B12—were notably low in people with atherosclerosis. The team of scientists had compared serum homocysteine, folate and vitamin B12 measurements among 32 patients with peripheral vascular disease versus 24 healthy controls, and 52 patients with coronary artery disease versus 42 matched controls. Results showed that homocysteine and vitamin B12 levels didn’t vary greatly among patients and controls, but that folate levels were 37% lower in vascular patients and 22% lower in coronary patients compared to controls.(8)

A vitamin B12 deficiency has also been noted as contributing to cardiovascular disease. Consider, for instance, evidence from one study conducted in the Slovak Republic that showed that the frequency of high homocysteine levels is higher in vegans (53%) and vegetarians (28%) compared to omnivores (5%).(9) It’s believed that the reasons for the huge discrepancies lies in vitamin intake, particularly vitamin B12, as vegans consume none from dietary sources, and vegetarians only consume about one third the amount that omnivores do (124% versus 383% of the RDA). In fact, this study, which examined 62 vegetarians, 32 vegans and 59 omnivores, found that 78% of the vegans studied were vitamin B12-deficient, as were 24% of vegetarians, but 0% of the omnivores showed a deficiency. Folate levels, however, were comparable among the three groups. The authors concluded that vitamin B12 deficiency was chiefly responsible for mildly elevated homocysteine levels in vegans and vegetarians.

Similarly, in many developing countries, studies have found diets low in folate and vitamin B12 are what may account for the increased risk of both cardiovascular disease and neural tube defects. In fact, when US researchers measured the folate and vitamin B12 status of adolescent girls in northern Nigeria of marrying and childbearing age (12 to 16 years), 9% of the subjects had serum vitamin B12 concentrations that fell below the lower limit of the reference range for their age group. This was consistent, said the authors, with the fact that their diet lacks vitamin B12.(10)

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Individuals with malabsorption problems, be it from a genetic glitch, gastrointestinal diseases, age or existing cardiovascular disease, may need to step up their daily intake through supplementation just to meet the recommended daily allowance.

Meanwhile, according to a 1998 report by the American Heart Association,(11) about one fifth of the US population may stand a heightened risk of heart attack and stroke because their diet lacks a sufficient amount of vitamin B6 and folic acid. While previous research has suggested that elevated homocysteine levels were the result of too little vitamin B6 or folic acid, the authors of this report were surprised to find that vitamin B6 deficiency was linked to heart disease and stroke risk independently of where homocysteine levels stood. A B6 deficiency was found among 20% of subjects, and levels of these nutrients were generally lower in individuals with heart disease or stroke than in healthy controls. More importantly, those demonstrating a deficiency had twice the risk of heart disease and stroke. Some research suggests that dietary deficiencies of folic acid, vitamin B12 and vitamin B6 seem common among elderly people in North America, which might represent “one pathogenic factor related to the incidence of hyperhomocys-teinaemia.”(12) Such deficiencies might also offer a reason why high homocysteine levels seem to prevail among 30% to 40% of the elderly population compared to only 5% to 10% of the general population.(13)


Continued on Page 2 of 2


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