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?
Amino acids are formed from the breakdown of proteins that we eat. Homocysteine is an amino acid formed in the body from another amino acid called methionine. Certain B vitamins are needed to breakdown these amino acids. The vitamins include ]]>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. The high levels 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 heart and other blood vessels. The high levels directly damage the blood vessel wall and promote clot formation in vessels. Damage to the wall of a cardiac blood vessel can ultimately lead to the development of ]]>atherosclerosis]]> or plaque. The plaque 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 its own 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.
One interventional study did show benefits for patients with current coronary artery disease (CAD). The patients were given folate in combination with vitamins B6 and B12. Although the results were positive this study provide does not have definitive evidence for treatment of general population. The study results are very limited to patients with CAD that have already had a procedure called PTCA. It may not even apply to all CAD patients. This study does indicate folate supplements should be taken in combination with B6 and B12.
As an example of the conflicting evidence a second randomized study examined the effects of folate supplements for people with known, stable CAD. After 24 months there was no significance difference in CAD findings.
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.
Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, Jukema JW, van Veldhuisen DJ. Secondary prevention with folic acid: Effects on clinical outcomes. J Am Coll Cardiol. 2003;41:2105–2113.
Moustapha A, Robinson K. Homocysteine: an emerging age-related cardiovascular risk factor. Geriatrics .1999 Apr; 41:49-51.
Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA. 2002;288:973–979.
Last reviewed January 2009 by ]]>Igor Puzanov, MD]]>
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
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