3 B's Block Cardiovascular Disease This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to: Frankp@chiro.org
From The July 2000 Issue of Nutrition Science News
by Raymond Lombardi, N.D., D.C., C.C.N.How folic acid, B6 and B12 help the heart
Stress, smoking and high cholesterol are the three most commonly recognized risk factors for cardiovascular disease (CVD). This group of diseases includes hardening of the arteries (arteriosclerosis), cholesterol and lipid deposits in arterial linings (atherosclerosis), narrowing of the arteries that cuts blood flow to the myocardium in the heart (coronary artery disease), high blood pressure (hypertension), heart attack (myocardial infarction), and stroke, among others.
More than 58 million Americans have one or more types of CVD, according to current estimates by the Washington, D.C.-based American Heart Association. CVD claimed 959,227 lives in the United States in 1996 and is still America's No. 1 killer today. [1] In 1999, the cost of cardiovascular diseases in the United States was estimated at $286.5 billion. [2] The physical, emotional and financial devastation caused by cardiovascular diseases is undeniable.
Yet the three most commonly recognized risk factors account for only about half of all CVD cases. Thus, other factors must also contribute.
Enter a 30-year-old theory, developed by then-Harvard University researcher Kilmer S. McCully, M.D. In 1969, McCully presented his theory that hardening of the arteries was directly related to the amino acid homocysteine. He found that children with certain rare genetic diseases caused by the absence of critical enzymes led to defects in the body's ability to metabolize the amino acids methionine and homocysteine. This processing defect in turn led to high blood levels of homocysteine and an extremely high risk of premature cardiovascular disease. [3]
McCully said that cholesterol and clogged arteries were not the causes but, rather, the symptoms of heart disease. A critical aspect to his theory was that a buildup of homocysteine in the bloodstream is caused by insufficiencies of important B vitamins, specifically folic acid, B6 and B12. [4] (Other factors—aging, hormones, kidney failure, genetics and toxins—also can contribute to elevated homocysteine levels.)
McCully's homocysteine theory was rejected by mainstream medicine and languished for years. But now, his continuing efforts as well as new research compiled by others during the past 10 years have, indeed, demonstrated a significant relationship between elevated homocysteine levels in the blood and cardiovascular disease. More importantly, it appears that elevated homocysteine levels can be reduced by supplementing with inexpensive folic acid and vitamins B6 and B12, which in turn can prevent, slow and even stop the progression of many CVD conditions.
Homocysteine Dangers
Homocysteine is an amino acid produced in the process of protein metabolism. Protein, particularly its component the amino acid methionine, breaks down into homocysteine. With the help of folic acid and vitamin B12, it recycles back to methionine. Vitamin B6 helps metabolize homocysteine into the harmless amino acid cysteine. The normal role of homocysteine in the body is to control growth and support bone and tissue formation. When homocysteine levels rise, they quickly begin to damage the cells and tissues of arteries and stimulate arteriosclerotic plaque growth, which leads to heart disease. [5]
Homocysteine's existence is intended to be short-lived, but circumstances can cause levels to linger and increase in the bloodstream. For example, inadequate supplies of folic acid or vitamins B6 and B12, which catalyze the conversion of homocysteine to other byproducts, allows abnormal levels of homocysteine to build up in the system. [5]
Studies show at least four proposed mechanisms in which homocysteine causes arterial damage.
First, a dietary im-balance between too much methionine from protein and too little folic acid and vitamins B6 and B12 reduces the body's ability to met-abolize homocysteine. Therefore, people on a high-protein diet especially need adequate B vitamins to control homocysteine levels. [4]
Second, because homocysteine is a growth promoter, too much of it can increase the size of smooth muscle cells in artery linings. This vascular growth can partially or completely obstruct blood vessels and narrow arteries. In a sample of more than 15,000 asymptomatic men and women between 45 and 54 years old, elevated plasma homocysteine was associated with a significant thickening of the inner layer of carotid artery walls. [6]
Third, homocysteine promotes blood clotting. In a recent blinded, randomized, crossover study, Italian researchers illustrated this effect. Using 20 healthy hospital staff volunteers, ages 25 to 45, researchers at the Second University of Naples provided 100 mg/kg methionine in fruit juice to increase homocysteine blood levels from 10.5 micromoles per liter to 27.1. Within four hours, this caused a significant increase in coagulation and adhesion of circulating blood cells in arteries. [7] Interestingly, 10 participants who also supplemented with 800 IU vitamin E and 1,000 mg vitamin C had no increase, suggesting that an oxidative mechanism harms the arteries.
Fourth, homocysteine in the blood damages cells lining the arteries, stripping away areas of the blood vessel walls. This process accelerates with elevated homocysteine levels. These injured bare patches fill with low-density lipoprotein (LDL) cholesterol and other fatty substances that create waxy deposits in the arteries—arteriosclerosis. [8,9]
Once LDL deposits occur, LDL oxidation and endothelial injury are correlated with elevated plasma homocysteine levels. This was shown in a recent study at the Research Institute of Public Health in Finland involving 256 male participants. Lipid peroxidation was 47.5 percent greater among those with homocysteine levels in the highest quintile than among those in the lowest one-fifth. [10] The reason for this may be that homocysteine causes LDL molecules to aggregate and be taken up by inflammatory cells in the arterial lining. Once inside the vascular wall, homocysteine is released, possibly permitting it to cause further damage and more coagulation. The key is whether the adequate presence of B vitamins is there to reduce homocysteine's effects.
The B Vitamin Solution
Current research suggests that the three B's—folic acid, B6 and B12—can control and reduce homocysteine levels. Folic acid seems to be the most important single nutrient in providing protection.
The Hordaland Homocysteine Study, conducted in 199293 at the University of Bergen in Norway, verified this single-nutrient approach. Homocysteine levels of 6 micromol/L of blood is ideal, 10 micromoles is considered normal, and 13 is considered dangerous. Researchers screened 18,043 subjects, ages 40 to 67, and found 67 cases with total plasma homocysteine levels greater than 40 micromol/L. Two years later, 58 subjects were reinvestigated; 41 had homocysteine levels exceeding 20 micromol/L, 37 of whom were given 200 mcg/day folic acid supplements. Within seven weeks, plasma homocysteine levels became normal in 21 of the 37. Most of the remaining subjects obtained normal homocysteine levels with a much larger 5,000 mcg/day folic acid dose for seven months. [11]
Another study, The Nurses' Health Study, conducted at the Harvard School of Public Health in Boston, screened more than 80,000 adult women for their intake of both folic acid and vitamin B6 in relationship to fatal coronary heart disease (CHD) and nonfatal heart attacks. Based on dietary questionnaires, results suggest that dietary or supplemental intake of 400 mcg/day folic acid and 3 mg/day vitamin B6—both above the current recommended dietary allow-ance—may be as important in the primary prevention of CHD among women as is stopping smoking, lowering blood pressure or lowering blood cholesterol. [12]
A meta-analysis of 12 randomized, controlled trials involving 1,114 people indicated daily supplementation with both folic acid and vitamin B12 reduces blood homocysteine concentrations. Researchers found the effects were greater among those with higher initial homocysteine levels or lower folate levels. Folic acid in the range of 5005,000 mcg/day reduced blood homocysteine concentration by 25 percent. Adding a mean 0.5 mg/day vitamin B12 produced an extra 3 to 10 percent drop, while adding 16.5 mg/day vitamin B6 did not have a significant additional effect. Researchers concluded that this amount of folic acid and vitamin B12 could reduce blood homocysteine concentrations by about a quarter to a third. They also noted that large-scale trials are needed to conclude whether lowering homocysteine levels reduces the risk of vascular disease. [13]
Protective Doses
Evidence emphasizes the importance of folic acid, vitamin B6 and vitamin B12 in lowering homocysteine levels. Recom-mended doses are as follows.Folic Acid: Although 200 mcg/day folic acid lowered homocysteine levels in the Hordaland Homocysteine Study, it is recommended to take at least 400 mcg/day. Currently, the RDA for folic acid—180 mcg/day for women, 200 mcg/day for men—is well below the 400 mcg/day that provides maximum protection to reduce the risk of heart disease as well as neural-tube birth defects.
Vitamin B6: The Nurses' Health Study found that most heart protection occurred with 3 mg/day vitamin B6. The current RDA is 2 mg for men and 1.6 mg for women.
Vitamin B12: As with folic acid and vitamin B6, this vitamin is an essential component for reducing homocysteine levels. Extra folic acid could mask a vitamin B12 deficiency, but this risk can be nullified by supplementing 400 mcg/day folic acid with 1 mg/day vitamin B12.Given the traditional American diet typically insufficient in the B vitamins, supplementation with the three B's becomes critical for those individuals susceptible to elevated homocysteine levels. Pointing customers at risk for cardiovascular disease toward these crucial B vitamins is a service they will thank you for.
Sidebars:
SAMe Needs The B's
Raymond M. Lombardi, N.D., D.C., C.C.N., is a certified herbalist with an alternative care holistic practice in Redding, Calif. He is author of Aspirin Alternatives—The Top Natural Pain-Relieving Analgesics (BL Publications, 1999).
References
1. CDC/HCNC and the American Heart Association. National Health and Nutrition Examination Survey II-III (NHANES II-III). The American Heart Association, 1976-94.
2. Hodgson TA. Economic costs of cardiovascular diseases. Division of Health and Utilization Analysis, OAEHP, CDC/NCHS; 1999.
3. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969 Jul;56(1):111-28.
4. McCully KS. The Homocysteine Revolution. New Canaan (CT): Keats Publishing Inc.; 1997.
5.Devlin TM, et al. Textbook of Biochemistry with Clinical Correlations. New York: John Wiley-Liss Inc. 4th edition; 1997. p 470-4.
6. Malinow M, et al. Carotid artery intimal-medial wall thickening and plasma homocysteine in asymptomatic adults. The Atherosclerosis Risk in Communities Study. Circulation 1993;87:1107-13.
7. Nappo F, et al. Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 1999;281(22):2113-8.
8. McCully K, Wilson RB. Homocysteine theory of arteriosclerosis. Atherosclerosis 1975;22:215-27.
9. Dudman NP, et al. Human homocysteine metabolism: three major pathways and their relevance to development of arterial occlusive disease. J Nutr 1996;126:1295-1305.
10. Voutilainen S, et al. Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels. Arterioscler Thromb Vasc Biol 1999;19(5):1263-6.
11. Guttormsen AB, et al. Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (>or=40 micromol/liter). The Hordaland Homocysteine Study. J Clin Invest 1996 Nov;98(9):2174-83.
12. Rimm EB, et al. Folate and vitamin B6 from diet and supplementation in relation to risk of coronary heart disease among women. JAMA 1998;279(5):359-64.
13. Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. Brit Med J 1998;316(7135):894-8
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