Homocysteine and heart disease

What is homocysteine?

Homocysteine is an amino acid formed in the body from another amino acid called methionine; these amino acids are formed from the breakdown of protein during the digestion process. For these amino acids to be metabolized by the body, certain B vitamins are required, including vitamin B6, vitamin B12, and folate. A deficiency of any one of these vitamins, most particularly folate, can lead to an elevation in blood levels of homocysteine, which can lead to damage in the arteries of the heart (see below). Deficiency of folate, B6 or B12 can be what is called "sub-clinical," meaning that the measurable amount in the blood is normal but there is a relative, whole body deficiency.

How does homocysteine increase risk of heart attack?

Elevated homocysteine causes problems in cardiac and other blood vessels by directly damaging the vessel wall and also by promoting clot formation in vessels. Damage to the wall of a cardiac blood vessel can ultimately lead to the development of atherosclerosis or "plaque," which blocks blood flow to the heart and increases risk for heart attack. Plaque accumulation may lead to blockage gradually over time, whereas a blood clot may lead to a more sudden blockage and heart attack.

It is estimated that 5-20% of the population has elevated homocysteine levels. Levels of homocysteine increase with age and elevation is more common in men and postmenopausal women.

What can be done about elevated homocysteine?

Very high levels of homocysteine were first found to be a problem in the 1960s, when people with an inheritable defect of an enzyme responsible for the metabolism of homocysteine were suffering from heart attacks and strokes before the age of 30. In the 1970s, researchers began to study the effects of lifestyle factors, such as dietary folate and smoking, in people who developed elevated homocysteine levels. During the last two decades, a connection between even mild to moderate elevations of homocysteine and heart disease has been well established. In addition, studies have found that dietary folate can reduce homocysteine levels in the blood by 25%.

What has not been firmly established is whether taking folate ultimately leads to reduction in heart attacks and other cardiac events. My feeling, though, is that it is safe to supplement your diet with folate (which is called folic acid when taken as a supplement) and it is certainly worth taking if your homocysteine levels are elevated.

A good analogy is cholesterol. For a long time it was well established that blood cholesterol was linked to heart disease, which led to development of medications to reduce cholesterol. These medications (which have more potential problems and side effects than folate) were prescribed for many years before it was scientifically proven that reducing blood cholesterol levels with medication actually reduced heart attacks and other cardiac events.

Please don't misunderstand me—I am not saying that folate can substitute for cholesterol-lowering medication. Cholesterol and homocysteine are two separate and independent risk factors that share an ability to damage cardiac blood vessels and increase risk for heart attack. In addition, there is some suggestion from recent research that they may work synergistically, since homocysteine seems to cause more damage in the presence of elevated cholesterol levels and vice versa. This synergistic relationship is even more clear between homocysteine and high blood pressure as well as homocysteine and cigarette smoking.

Folate and other B vitamins

The current recommended dietary allowance (RDA) for folate for the general adult population is 400 micrograms per day. However, most of the studies of folate and homocysteine seem to show that higher levels (at least 800-1000 micrograms per day) are more effective in lowering homocysteine levels. Folate should be taken in combination with other B vitamins, particularly B12, because a deficiency of B12 (common in the elderly, people with alcoholism, and people who consume a vegan diet) may be masked by taking a folate supplement. Therefore, my general recommendation is a multivitamin containing a B complex and 400 micrograms of folate together with an additional 400 micrograms of folate. Another option is to talk to your doctor about a prescription for 1.0 milligram folate and take a multivitamin with 50 milligrams or more of B complex along with that.

The goal is to bring homocysteine levels to under 10 micromol/liter; this may take some individual adjustment of the amount of folate with guidance and supervision from your doctor. People without heart disease should be treated with folate if their levels are over 13, whereas those with heart disease should be treated if their level is over 10.

But don't be surprised if your doctor is somewhat reluctant to measure your homocysteine level. There is some degree of controversy over whether we as a medical community should regard homocysteine as an independent risk factor for heart disease. That reluctance and controversy is reflected in the fact that many insurance companies will not pay for the cost of the blood test. Some say that if you have heart disease or you are at high risk for heart disease, you should simply take folate together with a vitamin B complex without knowing your homocysteine level. While I agree that folate and a B complex are protective for your heart regardless of your homocysteine level, I feel that it is a more exact art to know your baseline level and, if it is elevated, follow how it responds to folate. Plus, in cases similar to Wayne's, when there is no other clear indicator for why a person develops heart disease, homocysteine can be a good factor to examine.

Since his first measurement of homocysteine four years ago, Wayne has been taking 1.0 milligram folate per day and his homocysteine levels have normalized. Although Wayne has had other health problems, he has not had another distinct cardiac event since his heart attack. This may be attributable to not only the folate, but all his other healthful lifestyle behaviors.