Homocysteine, folic acid, and B vitamins
Homocysteine is an amino acid that plays a role in coronary artery disease. It is metabolized (chemically transformed) into methionine and cysteine with the help of the B vitamins; folic acid (B9), B12, and B6 (pyridoxine). Therefore, insufficient amounts of these B vitamins in the body can theoretically hamper the metabolic breakdown of homocysteine, and hence increase its blood levels. High levels of homocysteine in the blood (hyperhomocysteinemia) can damage the inner surface of blood vessels, promote blood clotting, and accelerate atherosclerosis.
The current state of knowledge regarding folic acid, homocysteine, and heart attacks is as follows:
- The level of blood folate is an important determinant of the blood homocysteine level. Low blood folate levels are associated with high blood levels of homocysteine.
- Low blood folate is common among individuals who do not take multivitamins, but unusual among those who do.
- The consumption of folic acid supplements or folic acid fortified cereals can increase blood folate levels and decrease blood homocysteine levels.
- In a large population study involving women, those who had the highest consumption of folic acid (usually in the form of multivitamins) had fewer heart attacks than those who consumed the least amount of folic acid.
Even though current scientific evidence suggests that taking folic acid and vitamin B supplements to lower homocysteine levels should help prevent atherosclerosis and heart attacks, conclusive proof is still lacking because:
- There are no conclusive controlled studies demonstrating that increasing folic acid intake actually prevents atherosclerosis and heart attacks.
- There is no clinical study demonstrating that lowering blood levels of homocysteine actually prevents atherosclerosis and heart attacks.
There is also no official recommendation as to who should be tested for hyperhomocysteinemia. The optimal doses of the B vitamins, folic acid, B12, and B6, required to prevent and treat hyperhomocysteinemia are also uncertain. For folic acid, a daily dose of 0.8-1.0 mg is probably adequate.
What about antioxidants for heart attack prevention?
Antioxidants are food supplements that have been promoted as preventing heart disease and stroke. An important early event in the development of a cholesterol plaque in atherosclerosis is the oxidative modification of LDL cholesterol (low density lipoprotein) particles in the blood and the subsequent interaction of this modified LDL with the wall of the coronary artery. This process initiates the formation of the cholesterol plaque.
Antioxidants that block the oxidative modification of LDL have been shown to slow the progression of atherosclerosis in animal experiments. Examples of antioxidants include vitamin E and beta carotene. In humans, observational studies (studies that observe the frequency of related conditions) have found a relationship between the dietary intake of vitamin E and lower rates of heart attacks.
Observational studies provide only circumstantial evidence, however, and credible evidence is obtained only by way of controlled trials (discussed at the beginning of this article). Several controlled trials performed to date have yielded conflicting results on the benefits of antioxidant therapy. These results may possibly be due to the low doses of vitamin E used, the small number of patients in the study, or the limited duration of treatment.
The Heart Outcomes Prevention Evaluation study used a high dose (400 IU per day) of vitamin E over a span of five years in patients with significant risk factors for heart disease or stroke. This study found no difference in the occurrence of heart attack or stroke in the group treated with vitamin E versus those given the placebo. This study demonstrated that antioxidant therapy does not have any benefit in persons who have or are at high risk for having atherosclerosis.

QUESTION
In the U.S., 1 in every 4 deaths is caused by heart disease. See AnswerHow about exercise for heart attack prevention?
Studies of the effects of exercise in preventing heart attacks have yielded conflicting results. This is likely due to the fact that people who exercise regularly generally have healthier lifestyles and that many risk factors for heart disease can be influenced by exercise. Therefore, the specific role of exercise itself in heart attack prevention is difficult to isolate. For example, regular exercise has direct effects on weight control, blood pressure, diabetes, blood cholesterol, and smoking.
What about smoking cessation for heart attack prevention?
Smoking cessation, by whatever means, has been clearly demonstrated to reduce future heart attacks and death in patients with known coronary artery disease or who have other risk factors for the development of coronary artery disease. While many methods, both chemical and behavioral, have been used to aid smoking cessation, the initial success rate is often low, and the relapse rate is high. Certain medications that affect neurotransmitters in the brain, which are similar to agents often used to treat depression (for example, bupropion [Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban]), have recently been demonstrated to be helpful in many patients trying to stop smoking. While effective, these agents may produce significant side effects and should only be used under the close supervision of a doctor.
Recommendations to prevent heart attacks
- Eat whole, natural, and fresh foods.
- Eat five to ten servings of fruits and vegetables daily and eat more peas, beans, and nuts.
- Increase intake of omega-3 fatty acids by eating more fish, walnuts, flaxseed oil, and green leafy vegetables. An example of meeting the recommended intake of omega-3 fats is to eat 2 salmon portions a week or 1 gram of omega-3-fatty acid supplement daily.
- Drink water, tea, non-fat dairy and red wine (two drinks or less daily for men, one drink or less daily for women).
- Eat lean protein such as skinless poultry, fish, and lean cuts of red meat.
- Avoid trans-fats and limit intake of saturated fats. This means avoiding fried foods, hard margarine, commercial baked goods, and most packaged and processed snack foods, high fat dairy and processed meats such as bacon, sausage, and deli meats.
- Limit glycemic foods. Glycemic foods are those made with sugar and white flour, which increase blood sugar levels. Increased blood sugar levels stimulate the pancreas to release insulin. Chronically high insulin levels are believed to cause weight gain as well as atherosclerosis of the arteries.
- Exercise daily.
- Understand your risk factors and research in this area. For example, the Framingham Heart Study recruited residents of Framingham, Massachusetts, beginning around 1948 and followed the group in an attempt to identify the common factors or characteristics that contribute to heart attack or stroke.
REFERENCES:
The HOPE and HOPE-TOO Trial Investigators. Effects of Long-term vitamin E supplementation on cardiovascular events and cancer: A randomized controlled trial. JAMA 293:1138-1347, 2005.
Guessous I, Bochud M, Bonny O, Burnier M PMID:21677437; Calcium, vitamin D and cardiovascular disease. Kidney Blood Press Res. 2011;34(6):404-17. doi: 10.1159/000328332. Epub 2011 Jun 11.
Hartley L, et al, Cochrane Database Syst Rev. 2013 Jun 4;6:CD009874. Increased consumption of fruit and vegetables for the primary prevention of cardiovascular diseases. PMID:23736950
Hruby A et al, “Magnesium Intake Is Inversely Associated With Coronary Artery Calcification: The Framingham Heart Study'” JACC Cardiovasc Imaging. 2013 Nov 20. pii: S1936-878X(13)00778-X. doi: 10.1016/j.jcmg.2013.10.006. [Epub ahead of print]
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