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High Levels of Homocysteine Increase the Risk of Cardiovascular Disease

In 1969, Dr. Kilmer McCully published in the American Journal of Pathology a report that high-normal serum levels of homocysteine  constituted a risk factor for cardiovascular disease. A study published in 1976 by Wilcken and Wilcken supported this premise, who reported that, following an oral dose of methionine, serum homocysteine levels tended to be higher in patients with premature coronary disease than in healthy controls. Nonetheless, the thesis that homocysteine is an important determinant of vascular disease in the general population attracted little interest until Dr. Meir Stampfer and his colleagues at Harvard, using data from the large Physicians' Health Study, provided striking confirmation: the risk of myocardial infarction was threefold higher in subjects with homocysteine levels in the top 5% of values, compared to subjects with homocysteine in the bottom 90%.

Subsequently, a number of other studies have concluded that high homocysteine levels represent an important independent risk factor for coronary heart disease, heart attack, stroke, peripheral atherosclerosis, and venous thromboembolism (the blockage of a blood vessel by a migrating clot). Furthermore, the risk associated with homocysteine appears to increase throughout the normal range of concentrations; each 1 micromolar rise in the concentration of homocysteine in the blood corresponds to an increase of about 10% in cardiovascular risk. This homocysteine-associated risk is strongly enhanced by smoking and hypertension. For reasons not yet clear, homocysteine levels tend to be higher in males, the elderly, smokers, and caffeine users. In light of evidence that homocysteine can be directly toxic to blood vessels—in particular, much like oxidized LDL cholesterol, it disrupts the healthful function of the cells lining the blood vessels—it seems likely that homocysteine is not merely a marker for some other pathogenic (disease causing) factor. It is therefore highly desirable to develop and implement safe measures for minimizing serum homocysteine levels.1

What is Homocysteine?

Homocysteine is an amino acid in the blood. It is acquired from eating meat. Epidemiological studies have shown that too much homocysteine in the blood (plasma) is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease. Plasma homocysteine levels are strongly influenced by diet, as well as by genetic factors. The dietary components with the greatest effects are folic acid and vitamins B6 and B12. Folic acid and other B vitamins help break down homocysteine in the body. Several studies have found that higher blood levels of B vitamins are related, at least partly, to lower concentrations of homocysteine. Other recent evidence shows that low blood levels of folic acid are linked with a higher risk of fatal coronary heart disease and stroke.2/3

According to the Mayo Clinic, excessive levels of homocysteine in your blood may increase your risk of stroke, certain types of heart disease, and disease of the blood vessels of the arms, legs and feet (peripheral artery disease).4

The Homocysteine Debate

Kilmer McCully determined that inflammation, not cholesterol, was the cause of atherosclerosis and increased cardiovascular risk and that homocysteine was the direct cause of this vascular inflammatory process in at least 40% of cases.

McCully, through a lifetime of medical detective work, had single-handedly and methodically not only discredited the role of cholesterol and the entire low fat / low cholesterol diet debacle but introduced the inflammatory concept of atherosclerosis, now accepted by many, and placed homocysteine firmly in the center of it.5

But this concept has not been widely accepted by the medical business. The AMA and the Heart Association do not endorse having a blood test for homocysteine levels. Instead, the established medical business acknowledges there might be a relationship to homocysteine levels and coronary issues but the real problem are cholesterol levels. Dr. Ladd McNamara says the reason for this is there is are drugs that affects cholesterol levels regardless if this is a actual health issue. But there are no drugs that impact homocysteine levels. Folic acid, and the B vitamins do lower homocysteine levels. So until the drug companies can come up with a drug that lowers homocysteine levels, you have to request your own test and probably at your own expense since insurance companies do not recognize it as an acceptable test.

Get your blood tested for your Homocysteine levels - your MD will not order the test you have to request it.

The clear message from recent scientific findings is that there is no safe “normal range” for homocysteine. Commercial laboratories state that normal homocysteine can range from 5 to 15 micro moles (units of molecular weight) per liter of blood. Research data reveals that homocysteine levels above 6.3 can cause a steep progressive risk of heart attack. One study found each 3-unit increase in homocysteine caused a 35% increase in heart attack.6

bulletElevated homocysteine levels may contribute to cognitive decline and Alzheimer’s disease
bullet Homocysteine may increase the risk for cervical cancer
bulletHigher homocysteine levels had a higher risk of colorectal cancer in women. Women with the highest homocysteine levels had a more than 70% higher colorectal cancer risk than those with the lowest levels.6

A homocysteine increment of 5 mmol/L has been associated with a 49% increase in all-cause mortality, a 50% increase in cardiovascular mortality, a 26% increase in cancer mortality, and a 104% increase in non-cancer, non-cardiovascular mortality.7

C-reactive protein

C-reactive protein (CRP) is a protein produced by your liver as part of an immune system response to injury or infection. CRP is also produced by the muscle cells in the coronary arteries.

It is a marker for inflammation somewhere in the body. However, the CRP tests do not pinpoint exactly where in the body inflammation is occurring. Inflammation plays a major role in atherosclerosis, in which fatty deposits clog your arteries. While measuring CRP alone won't tell your risk of heart disease, factoring in CRP test results with other blood tests results and risk factors for heart disease helps create an overall picture of your heart health.

High levels of CRP in your blood may be associated with an increased risk of heart attack and sudden cardiac death. High levels of CRP appear to be less useful in predicting your risk of a stroke.4


  1. Linus Pauling Institute - The Vascular Toxicity of Homocysteine and How to Control It
  2. American Heart Association - What is Homocysteine? October 16, 2008
  3. WebMD  - Heart Disease: Homocysteine: A New Heart Disease Risk Factor - December 01, 2006
  4. - Blood tests for heart disease -
  5. - The Homocysteine Debate by Duane Graveline MD MPH Former USAF Flight Surgeon
    Former NASA Astronaut Retired Family Doctor
  6. - Homocysteine: Health Concerns and Hearing Loss

  7. - What Is A Safe Homocysteine Level?


Homocysteine: Health Concerns and Hearing Loss by Barry Keate - excellent article that includes a good summary of Dr. McCully's findings.



The Homocysteine Revolution by Dr. Kilmer McCully


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