Folic Acid

Paul Smaglik's article entitled "Folic Acid Deficiency's Role Expands Beyond Birth Defects" (The Scientist, Oct. 13, 1997, page 10) cites several recent epidemiology studies that link folate deficiency with increased plasma levels of homocysteine and heart disease without reviewing the older scientific literature. Such a review would have provided an answer or insight to the question posed in the article as to how a folate deficiency or homocysteinemia is related to heart disease or stroke. Mor

Dec 8, 1997
Laurence Pilgeram

Paul Smaglik's article entitled "Folic Acid Deficiency's Role Expands Beyond Birth Defects" (The Scientist, Oct. 13, 1997, page 10) cites several recent epidemiology studies that link folate deficiency with increased plasma levels of homocysteine and heart disease without reviewing the older scientific literature. Such a review would have provided an answer or insight to the question posed in the article as to how a folate deficiency or homocysteinemia is related to heart disease or stroke.

More than four decades ago, research at the University of California, Berkeley was published in the journal Science on the role of biosynthesis of one-carbon methyl groups and transmethylation in susceptibility to experimentally induced vascular disease (L.O. Pilgeram, D.M. Greenberg, Science, 120:760-1, 1954). This research was presented later in a national symposium sponsored by the Federation of American Societies for Experimental Biology (L.O. Pilgeram, Federation Proceedings, 14:728-32, 1955). Concurrently and independent of my research, Fredrick Stare at Harvard University published his study that found that a dietary deficiency of methionine induced atherosclerosis (G.V. Mann et al., Journal of Experimental Medicine, 98:195-218, 1953).

These two independent studies, more than four decades ago, demonstrated that a deficiency in the formation and availability of one-carbon methyl groups would induce a deficiency of methionine and atherosclerosis. The student of intermediary metabolism will recognize that folic acid is essential for the formation of one-carbon methyl groups and that this deficiency results in deficient conversion of homocysteine to methionine.

The mechanism by which deficient methyl groups leads to lipemia, thrombosis, and occlusive vascular disease is outlined in a recent review for the European Max Planck Society (L.O. Pilgeram, Naturwissenschaften, 80:547-55, 1993), in English. Or see L.O. Pilgeram, Circulation, 94:2990, 1996.

Laurence Pilgeram
P.O. Box 1583
Goleta Station
Santa Barbara, Calif. 93116