THE RISK OF VASCULAR ILLNESS: CONVERGENCE OF NUTRITIONAL AND MENTAL FACTORS
by John W. Crayton, MD, Professor of Psychiatry at Loyola University Medical School, Maywood, Illinois, and Chief, Section of Biological Psychiatry, Hines Veterans Administration Hospital, Hines, Illinois.
Today, the vast majority of funding for medical research is tightly controlled by an intricate (some would say labyrinthine) system, which presumes that scientific progress proceeds from fact A to fact B an so on until "the answer" is made obvious by the last in this highly logical sequence of research studies. But, contrary to the views of those who are proponents of this tightly programmed approach to developing new treatments and cures for what ails us, progress in science does not follow this neat, logical pattern. New knowledge comes in bumps and lurches. Promising paths pursued for decades are suddenly found to be dead ends and are unceremoniously dropped. Old findings, forgotten and shunned because of our focus on the "true, logical path" are suddenly resurrected and seemingly overnight become "common knowledge."
The recent excitement about the role of homocysteine (a metabolite of an amino acid in our diet) in the development of cardiovascular illness and strokes is an example of the tendency for science to advance in bumps and lurches. While this story will be familiar to many readers of NOHA NEWS, I would like to emphasize three points that the homocysteine story illustrates: first, the illogical way in which scientific advances really occur; second, the failures of "compartmentalized research"; and third, the necessity for individual assessment of our personal biochemistry and nutritional requirements.
Homocysteine is an amino acid that is normally present in the body. It is a metabolic product of metabolism, which depends on the activity of certain specific enzymes as well as at least two, and probably three vitamins, Vitamin B6, folic acid, and Vitamin B12. Over 20 years ago, K.S. McCully, MD, then at Harvard Medical School, found that children who lacked the appropriate enzymes for metabolism of homocysteine and thus had increased amounts of homocysteine in their blood stream, also had remarkably "old-looking" blood vessels, with signs of widespread arteriosclerosis, even though many of the children were under ten years of age. He suggested that there was a link between the high levels of homocysteine in these children and the presence of arteriosclerosis, and speculated that homocysteine might play a role in the development of heart attacks and strokes in older people.
The scientific community dismissed this idea, and Dr. McCully was dismissed from his position.
Over the past ten years, however, several studies point to a significant role for homocysteine in the development of arteriosclerosis, just as Dr. McCully suggested. These studies have largely confirmed Dr. McCully's idea that elevated homocysteine, which can be caused not only by genetically-determined absence of the necessary enzymes for homocysteine metabolism, but also can be caused by micronutrient deficiencies, ingested toxins, drugs, hormones, and several other factors, may be a "final common pathway" whereby these various factors could lead to heart attacks and strokes.
In 1995 Boushey and colleagues found that very small increments in the blood levels of homocysteine produced significant increases in the risk of cardiovascular illness. After reviewing 27 studies, they found that an increase of just five micromoles of homocysteine (five times its molecular weight in micrograms) per liter increased the risk of coronary artery disease by 60 percent. A similar increase in risk was seen for the development of strokes. The authors also reported that in 11 studies, in which the role of folic acid supplementation was examined, a normalization of the homocysteine levels was found when supplemental folic acid was consumed. They estimated that if individuals added just 200 micrograms of folate to their diets or if grains were fortified with folate, deaths from coronary artery disease could be reduced by 13,500 to 50,000 per year!
In another study, Robinson and colleagues (1995) found similar relationships between homocysteine levels and pyridoxal phosphate (related to vitamin B6) levels. Higher homocysteine levels were associated with lower pyridoxal phosphate levels and vice versa. The conclusion of these findings suggests the obvious: that bringing pyridoxal phosphate levels up with B6 supplementation or with better choice of foods will drop homocysteine blood levels and reduce the risk of heart attacks and strokes.
Recently, our laboratory has been studying the reasons why people with depression are more likely to have heart attacks or strokes. In an important study, Dr. Frasure-Smith found that, in a population of patients who had experienced a heart attack, the risk of a second, fatal heart attack in patients who are depressed was six times higher than if they were not depressed. We now believe that part of the answer to why this should be is that patients with depression are significantly more likely to form blood clots because of a dysregulation of their clotting mechanisms. We have found that blood platelets--critical elements in the development of blood clots--are abnormally active in depressed patients, thus placing them at increased risk of heart attacks and strokes.
What does this finding have to do with the homocysteine story? It turns out that depressed patients also have elevations of homocysteine (a very new finding) and are more likely to be nutritionally deficient in those vitamins necessary for the reduction in homocysteine blood levels. In addition, it is now known that elevated homocysteine levels also increase the probabiliby of blood platelets becoming activated and forming blood clots in heart and brain.
These results stress the importance of simple, inexpensive interventions in the prevention of some of our major medical problems. Being sure that we obtain adequate amounts of folate and B6 through proper diet or supplements could have a major impact on our probability of having heart attacks and strokes. Depressed people, who are at even higher risk of having strokes or heart attacks, would need to pay even more attention to assuring that they were taking adequate amounts of these vitamins.
Boushey C.J., S.A. Beresford, G.S. Omenn, A.G. Motulsky "A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes," Journal of the American Medical Association, 274 (13):1049-57, 1995.
Delisi, S.M., L.M. Konopka, F.L. O'Connor, K. Russell, J.W. Crayton, "Hyperresponsivity to serotonin of platelet cytosolic calcium concentrations in depressed, hypertensive patients," Biological Psychiatry, in press,1997.
McCully, K.S., "Atherosclerosis, serum cholesterol and the homocysteine theory: a study of 194 consecutive autopsies," American Journal of Medical Science, 299 (4): 217-21, 1990.
Robinson, K., E.L. Mayer, D.P. Miller, R. Green, F. van Lente, A. Gupta, K. Kottke-Marchant, S.R. Savon, J. Selhub, S.E. Nissen, et al, "Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease," Circulation, 92 (10): 2825-30, 1995.
Article from NOHA NEWS, Vol. XXIII, No. 1, Winter 1998, pages 4-5.