Homocysteine and Heart Disease
Wayne (not his real name) first came to see me when he was 72, shortly after having a heart attack. A seemingly healthy person, he was wondering why this had happened to him, since he did not have any of the "usual" risk factors—he exercised regularly, ate a healthy, well-balanced diet, was not overweight, and never smoked. His blood cholesterol levels, measured annually, were always much better than average.
After his heart attack, Wayne did a lot of research and reading on his own. Wayne asked me two main questions at our initial meeting: Why did this happen in the first place? Is there anything else he could do to prevent future heart attacks?
One of the first things we did was check Wayne's homocysteine level; it was moderately elevated.
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. Deficiency of folate, B6, or B12 can be called "subclinical," meaning that the measurable amount in the blood is normal but there is a relative, whole body deficiency.
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 to 20% of the population has elevated homocysteine levels. Levels of homocysteine increase with age, and elevation is more common in men and postmenopausal women. Whether or not homocysteine is a risk factor for heart disease, however, remains controversial.
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 mild to moderate elevations of homocysteine and heart disease has shown up in some, but not all studies.
What Can Be Done About Elevated Homocysteine?
Homocysteine levels are reduced when intake of folate and vitamin B6 is increased. (Adequate intake of vitamin B12 is also essential). However, there is no evidence yet whether taking these vitamins ultimately leads to reduction in heart attacks and other cardiac events.
The current recommended dietary allowance (RDA) for folate for the general adult population is 400 micrograms per day. However, some 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. (Note that before taking folate at a dose above 400 mcg daily, it is important to be tested for B12 deficiency, because high-dose folate can mask dangerous symptoms of B12 deficiency.)
Vitamin B6 should be taken at a dose of 3-20 mg daily. Vitamin B12 supplements may be necessary for the elderly, people taking medications that reduce stomach acid, or those who consume a vegan diet).
The goal is to bring homocysteine levels to under 10 micromol/liter; with guidance and supervision from your doctor, this may mean individual adjustment of the amount of folate that you take. 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 considerable 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.
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 only not the folate, but all his other healthy lifestyle behaviors.
American Heart Association
National Heart, Lung, and Blood Institute
Heart and Stroke Foundation of Canada
Eikelboom JW, Lonn E, Genest J Jr, et al. Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med.1999 Sep 7;131:363-75.
Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet. 1999 Jul 31;354:407-13.
Moustapha A, Robinson K. Homocysteine: an emerging age-related cardiovascular risk factor. Geriatrics.1999 Apr; 41:49-51.
Last reviewed January 2008 by Michael J. Fucci, DO
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