heartThirty years ago, Kilmer McCully, MD, discovered that cholesterol and clogged arteries are not the culprits, but rather the symptoms, of heart disease. McCully's pioneering 1969 theory that linked homocysteine—an amino acid that accumulates in the blood—and heart disease was not embraced by the medical community. In fact, he was banished from Harvard University and Massachusetts General Hospital and denied a new position for more than two years because of his research. His observations went head-to-head with the accepted medical theory of the day—that cholesterol and lipids cause heart disease.

Times have changed for McCully. The cum laude graduate of Harvard Medical School has received numerous awards for his research, including the 1998 Linus Pauling Functional Medicine Award and the 1999 Burton Kallman Science Award from the National Nutritional Foods Association, Newport Beach, Calif. He is currently a clinical associate professor of pathology at Brown University and a pathologist at the Veterans Affairs Medical Center, both in Providence, RI. His most recent book, The Heart Revolution (HarperCollins), outlines how vitamin B6, B12 and folic acid deficiencies can elevate homocysteine levels and lead to arteriosclerosis, the hardening of the arteries.

McCully first made the connection between homocysteine and heart disease while studying cases of children afflicted with arteriosclerosis, a rare childhood condition, which led him to question the underlying cause.

Bucco: What happened when you discovered the connection between homocysteine and arteriosclerosis?

McCully: At that point, I recalled a series of studies published by a pathologist in the late 1940s, showing that severe deficiency of vitamin B6 in the diet causes arteriosclerosis in monkeys. I realized the monkeys must have had elevated homocysteine. I also found another classic animal model of rats deprived of the compound choline. These rats also developed arteriosclerosis and cancer. I concluded the rats must have had elevated homocysteine levels because of failure to convert homocysteine to methionine by folic acid and vitamin B12. This has also proven to be true. With this observation I was able to explain two of the most interesting and important animal models in the medical literature.

Bucco: So you discovered the correlation between heart disease and a deficiency of B vitamins and published these finding in the American Journal of Pathology in 1969?

McCully: Yes, in that first paper I described these findings and suggested that elevated homocysteine was likely important for people even without genetic defects but who might have dietary deficiencies of the B vitamins. I still remember mailing the manuscript and thinking something will probably come of this. I wasn't sure what, but I thought this was a very significant observation. I had no idea I would spend the rest of my career working on this problem.

After publication I was astounded to find that research scientists around the world who had read the paper were asking me for reprints because they were looking for another explanation for the cause of arteriosclerosis.

Bucco: What led to you being denied tenure at Harvard?

McCully: For about six or seven years I continued work on this project. I made a number of observations and discoveries in homocysteine metabolism. In the early and mid-1970s I published quite a number of papers presenting evidence that supported the observation that homocysteine had something to do with vascular disease.

Then in 1976, the chairman of my department at Harvard retired and the new chairman told me the elders at Harvard felt I had not proved my theory, and unless I could support my salary from grant money I would be cut off and have no position. They moved my lab into the basement where I had no contact with other people. They made the situation so unpleasant I decided I couldn't work there.

I left in January 1979 and tried to find another position. For the next 27 months I was unable to find a position anywhere in North America that would allow me to continue this work.

Bucco: Why is it the medical community became so resistant to your work nearly 10 years after you published that first paper?

McCully: During the first two or three years, my work was presented to the scientific advisory board of Massachusetts General Hospital as a great example of a new observation made by someone who had the correct background. The board knew exactly what I was doing.

They told me later they didn't want to have Harvard or Massachusetts General Hospital associated with my theory because it appeared to contradict the conventional wisdom that cholesterol and fats were the causes of heart disease.

I knew what I was proposing was significantly different from what was accepted in the [conventional medical] literature. My suggestion was that the cause of arteriosclerosis in the general population was an underlying deficiency of certain B vitamins—B6, B12 and folic acid. The role of cholesterol and fats was secondary. This was too much for the establishment to take.

Bucco: Do you think the initial skepticism about your theory has changed in light of all the supporting evidence collected in the last 30 years?

McCully: Yes. I think the climate has totally changed, and now there is wide acceptance of this concept. Every day a new article about homocysteine is published. Many of these articles cite my original data from 1969. People have really given me the credit for pioneering this concept.

Bucco: Let's talk a little about homocysteine. What is its normal function in the body?

McCully: Homocysteine is an amino acid that's normally produced in the body in small amounts from the amino acid methionine. We know now that the normal role of homocysteine in the body is to control growth and support bone and tissue formation. When I began to study this question, homocysteine's medical and nutritional implications were almost totally unknown. My colleagues and I showed that homocysteine is also involved in the normal human growth process.

Bucco: What elevates homocysteine levels?

McCully: Homocysteine becomes elevated in the blood when there is a deficiency of the B vitamins—B6, B12 and folic acid. Other factors also play a role. For example, homocystine levels may rise due to normal aging, menopause, thyroid conditions, kidney failure, cigarette smoking, a number of different drugs and certain industrial toxins.

Genetics also play a role in the development of high homocysteine levels. There's a fascinating genetic defect called thermolabile reductase deficiency. About 12 percent of the population have this hidden defect.

Bucco: How are elevated homocysteine levels related to heart disease?

McCully: When homocysteine levels rise, they begin to damage the cells and tissues of arteries and stimulate growth of arteriosclerotic plaques, which lead to heart disease.

Bucco: So how can we prevent homocysteine from reaching these dangerous levels?

McCully: I'm a strong believer in dietary improvement because I believe the high incidence of arteriosclerosis and heart disease in our population can be traced to diet.

Both folic acid and vitamin B6 are chemically unstable vitamins that are often lost during food processing. It's been shown that the population is not getting enough of these vitamins and this, in turn, leads to elevated homocysteine levels.

The way to get these vitamins is to eat fresh whole foods—fresh vegetables, fruits, meat, fish and dairy products. We should also eliminate foods that contain highly processed ingredients, such as white flour, sugar and oils. If we do this, we can vastly improve the quality of our diet and increase the intake of these important vitamins.

If a person has been eating a nutritionally depleted diet their whole life, it may be difficult to correct this abnormality just by improving diet. Supplemental vitamins may also be needed. Anyone who has a high risk for heart disease, either from family history or poor nutritional background, or who has early signs of heart disease, probably should take vitamin supplements to control their homocysteine levels and stop the arteriosclerotic process.

Bucco: Are homocysteine levels being routinely tested today?

McCully: Oh yes. You can request a homocysteine test from a simple blood sample. Recently, several new tests were introduced that bring the cost of homocysteine testing down and make it available at any hospital. Many people in the field believe it's going to be at least as important, if not more, than cholesterol testing.

Gloria Bucco is an independent journalist and editorial consultant who specializes in alternative medicine and natural health.

Illustration by: Alicia Buelow