Homocysteine and Heart Disease

Homocysteine is an amino acid normally used to build many proteins in the body. It has been over 30 years now since Kilmer McCully, a Harvard pathologist, discovered a connection between high blood levels of homocysteine and cardiovascular disease.

At the time, McCully noted that children suffering from a rare metabolic disorder called homocystinuria had a severe build-up of plaque resembling atherosclerosis in their arteries. He theorized a link between the diseased arteries and the high levels of homocysteine but was met with a great deal of opposition by the proponents of the cholesterol causation of heart disease.

Since that time, the cholesterol cult has been all but silenced by a growing body of scientific evidence confirming the relationship between elevated homocysteine levels and cardiovascular disease. These studies include the Physicians' Health Study, the Tromso Study from Norway, the Framingham Heart Study, and a meta-analysis of nearly 40 other studies. In fact, it is now believed by some scientists that one’s homocysteine level is about 40 times more predictive than cholesterol in determining the risk for cardiovascular disease.

As the following list indicates, high homocysteine levels have been associated in the medical literature with many more adverse health conditions than just heart disease.

High homocysteine levels may cause:

• Abnormal blood clotting
• Angina pectoris
• Arterial muscle wall damage
• Atherosclerosis
• Circulation problems (e.g., intermittent claudication, brain damage)
• Cirrhosis of the liver
• Coronary artery disease
• Depression
• Fibromyalgia
• Heart attack
• High blood pressure
• Impotence
• Memory loss secondary to poor circulation
• Osteoarthritis
• Oxidation of blood fats
• Rheumatoid arthritis
• Stroke

Mildly elevated levels of homocysteine have been documented in 21% of people with coronary artery disease, 24% of those who have suffered a stroke, and 32% of those with peripheral vascular disease like intermittent claudication.

Mechanism of destruction

In the healthy human, homocysteine is made from another amino acid called methionine. Once homocysteine is no longer needed by the body for protein synthesis, it converts to several beneficial compounds required for energy including ATP, cysteine, and S-adenosylmethionine (SAM-e), an amino acid derivative used therapeutically to treat depression and osteoarthritis.

If homocysteine is not completely broken down, it begins to cause oxidative damage to the walls of the arteries, oxidation of blood fats, and abnormal blood clotting by making platelets stick together. Homocysteine also enhances the binding of lipoprotein-a to fibrin, initiating a series of biochemical reactions eventually leading to blockages. Blockages may be followed by heart attacks, strokes, and other circulation calamities.

There are several possible reasons why homocysteine is not broken down:

• A mutated or defective gene may be responsible for an ineffective enzyme needed to break down homocysteine.
• More commonly, deficiencies in enzyme cofactors, especially vitamin B6, B12, and folic acid (a.k.a. folate) are the cause of the failure of optimal enzyme function, poor DNA methylation, and homocysteine clearance from the circulation. In other words, deficiencies of vitamins B6, B12, and folic acid can lead to heart disease and all the adverse health conditions associated with high blood levels of homocysteine.

Smoking and birth controls pills elevate homocysteine levels, possibly because both destroy B complex vitamins. Smokers generally have lower levels of folic acid and vitamin B12. Homocysteine levels also naturally rise with age, regardless of smoking.

A 1993 study at Tufts University analyzed blood samples drawn from elderly participants in the Framingham Heart Study and found that one in three participants had homocysteine levels that were too high. About two-thirds of these cases could be traced to a diet low in vitamin B6, vitamin B12, or folic acid. In 1996, Canadian researchers reported that people who had the least amount of folic acid in their diet were 69% more likely to die of a heart problem than those whose diet was richest in this vitamin.

In my next blog, I will discuss specific ways to normalize elevated homocysteine.

Dr. Zoltan Rona