The Protein–Heart Connection

Too much of a good thing can be a bad thing. That seems to apply to foods as much as to other pleasures. By now most everyone seems to be convinced that too much fat is bad for cholesterol and heart attacks; and we've heard for years that excess sugar can cause a variety of problems, ranging from dental caries to diabetes and related diseases. Now we have convincing new evidence that too much protein can be even more devastating than fats and sugars!

When methionine, which is an essential amino acid gives up a methyl group (carbon and 3 hydrogens) it becomes homocysteine, a toxic by-product. Normally homocysteine persists for just a brief instant before enzymes controlled by vitamin B6 transform it into cystathionine, an essential substance for brain cells. If that reaction is impaired, then with the help of B12 and folic acid, which provide a fresh methyl group, homocysteine is recycled back to methionine. This way the body conserves methionine and thus requires less meat, fish, egg, dairy or broccoli, cauliflower and wheat, the major dietary sources.

The protein-coronary heart disease connection was first proposed by Russian physician I. A. Ignatovski in 1908, after he produced atherosclerosis in rabbits by feeding them animal proteins. Then in 1962, Dr. Nina Carson found an excess of the amino acid, homocystine, oxidized homocysteine, in a chemical survey of retarded children in Ireland. The full-blown genetic syndrome was soon recognized to include skeletal deformity, e.g. pigeon chest, scoliosis, knock-knees and thinning of bone, osteoporosis. Eye damage, dislocation of the lens and glaucoma also occur. Excessive skin flushing after exertion or in hot weather is characteristic and the skin is often paper thin, atrophic and scarred. Half the patients are retarded but others have epilepsy, chronic nervousness or schizophrenia.

Blood vessel damage with thrombosis and emboli, migration of clots through the blood stream, is a major complication of homocysteine and heart attack and stroke occur in almost half the cases, especially after anesthesia or surgery. Atherosclerosis occurs in some of these children as early as two months of age and many die before puberty. Based on these findings and his own research, in 1969 Dr. Kilmer McCully proposed that as many as a quarter of our cases of heart attack are due to excess dietary protein, not fat and cholesterol.

A flurry of research in the 1970s showed that injections of homocysteine did cause atherosclerosis. In one study, an increase in circulating cells released from the lining of blood vessels was seen within 30 minutes of homocysteine injections in rats. The mechanism behind this is binding of homocysteine to the amino acid, lysine, a component of collagen, the major structural protein of the body. This is particularly likely to occur in areas already damaged but it initiates platelet clumping, clotting and growth of cells in the blood vessel wall that cause plaque and narrowing.

Since vitamin B6 is a major agent for removal of homocysteine, McCully also proposed that B6 deficient diets would permit a build up of homocysteine. This was confirmed by research at the University of Wisconsin: 3 weeks on a low vitamin B6 diet caused human subjects to produce excess homocysteine.

It was also found that human patients with atherosclerosis tend to have low vitamin B6 levels and excess homocysteine. However the studies failed to show the expected increase in number of heart attacks in relatives of homocystinuric children. I think this was because heart attacks in the 1960-1980 period were so frequent due to other causes that the less frequent homocystinuric cases were lost in the epidemic of those due to deficiencies of magnesium, vitamin E, vitamin C, and omega-3 essential fatty acids.

Recently a new study By Dr. Robert Clarke and his colleagues at Trinity College, London, convincingly demonstrates increased risk of vascular disease in patients who produce homocysteine when given a test dose of methionine. Using the methionine load test in 123 patients they found almost 30 times more risk of vascular disease when excess homocysteine was present! This compares to an increased risk only two-fold due to high cholesterol, 3.5-fold due to smoking and 12.4-fold due to high blood pressure. Their findings indicate that high blood homocysteine is the strongest risk factor for vascular disease.

In case of vascular disease before the age of 55 years homocysteine is detected in almost 30 percent! In fact it was found in 42 percent of Clarke's patients with stroke, 28 percent with peripheral vascular disease (leg cramps, claudication, etc) and 30 percent of heart attack cases. Population surveys for homocysteine indicate that, while homozygous homocystinuria, with a gene from each parent, occurs in only 1 birth per 80,000, about 1 person in 80 is heterozygous and carries a single homocysteine gene for the disease. Dr. Jon Pangborn, a leading amino acid chemist, reports that in his experience homocysteine is at least 3 times more frequent in urine samples, i.e. about 1 in 25 patients evaluated at his laboratory. It would seem that homocysteine is one of the most frequently undiagnosed risk factors.

It turns out that deficiencies of vitamins B6, B12 and folic acid can induce homocysteine. This explains the increased frequency of occurrence in Dr. Pangborn's laboratory. Dr. L. Brattstrom has proved that in case of vitamin B12 deficiency normal people, without a gene for homocysteine, can have blood levels even higher than carriers of the gene for homocystinuria.

Meanwhile we are told by the NIH, FDA and the Surgeon General that fat is the villain in heart disease, that it raises cholesterol and thus causes arterial plaque, blockage and heart attacks. Most of you are probably convinced that if you eat no fat you will be safe. I think the high rate of atherosclerosis in concentration camp inmates, who had a low fat, low calorie diet says otherwise. Furthermore research has not demonstrated an over-all health advantage to the low fat, low cholesterol diet as public policy. In fact, cardiac mortality does decline but other causes of death, such as accident, homicide and suicide, increase. This is possibly due to irritability and mental torpor induced by insufficient calories, intestinal malabsorption and low blood sugar, i.e. hypoglycemia.

Our knowledge of the metabolic fate of homocysteine shows that it can be controlled by diet and vitamins. Homocysteine is produced from methionine, by reducing methionine intake less homocysteine is produced. Methionine is one of the 8 essential amino acids for humans. It is the major source of sulfur and therefore critical for the structure of skin, hair and nails, which contain keratins, sulfur proteins. In addition it is the key constituent of antibodies, and many enzymes. Methionine is also involved in providing methyl groups, single carbon fragments, which expedite many of the chemical reactions of the nervous system. Low methionine levels slow down the chemistry of the brain and result in depression. One reason for the popularity of B12 injections is that they restore and recycle methionine, thus assisting in the production of adrenalin in the nerves and adrenal gland.

In its major chemical path methionine undergoes enzymatic transformation into homocysteine and then cystathionine, which is essential for nerve function. Extra cystathionine is converted to useful end-products, including the anti-oxidants cysteine and taurine. No problem--but if vitamins folic acid and B12 are deficient, then homocysteine is likely to accumulate, particularly if B6 is low also. Since zinc is required to activate B6 in cells, the possibility of B6 deficiency is that much greater if zinc is low.

Birth control pills deplete both B6 and folic acid; they also cause blood clots and emboli in some women. This may be due to the production of homocysteine. High dietary intake of protein and fat increase the need for vitamin B6 up to ten-fold. Vitamin B6 supplementation at a dose of 25 to 100 mg per day is sufficient to reverse homocysteine accumulation in half the cases. In resistant cases the use of up to 6 grams of betaine, which donates extra methyl groups to convert homocysteine to methione, has proved effective according to Dr. David Wilcken; however a few people have adverse reactions, including headache, dyspepsia and nervousness so I recommend it be used only under doctor's supervision.

To prevent dietary provocation of homocysteine, we must learn to moderate our food intake, particularly animal protein. It is also important to get enough of vitamins B6, B12, folic acid, betaine and zinc. For many people a vegetarian diet is the simplest and best method of treatment because it is low in methionine and high in vitamin B6 and folic acid. Dr. Dean Ornish has recently demonstrated that low fat, vegetarian diets actually reverse coronary atherosclerosis. However low methionine intake by itself does not prevent homocysteine and many people don't feel well on low protein intake. For these people the use of vitamin supplements plus zinc should make it safe to eat a normal amount of animal protein containing methionine.

Homocysteine is so common and so powerful a risk factor for vascular, nervous, ocular, pulmonary and skin disease conditions that it should be diagnosed by methionine loading and measurement in blood or urine as part of a thorough health evaluation. The information so gained permits you to put nutrition first—before medical disaster can strike!

©2007 Richard A. Kunin, M.D.