Submitted to: Food and Nutrition Bulletin
Publication Type: Proceedings
Publication Acceptance Date: 10/18/2005
Publication Date: 6/1/2008
Citation: Selhub, J. 2008. Public health significance of elevated homocysteine. Food and Nutrition Bulletin. 29(2)(Suppl):S116-S125.
Interpretive Summary: Homocysteine is an amino acid which plays important functions in the body. In the past years there have been many studies including ours which show that many illnesses that afflict the elderly including heart disease, stroke, mortality, dementia as well preeclampsia in pregnant women are associated with higher than normal homocysteine blood concentrations. Because there are so many diseases that are related to high homocysteine, we propose that there is a common denominator which links these diseases to result in high blood homocysteine levels.
Technical Abstract: Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies, we have shown that plasma homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid-artery stenosis > or = 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects (NTD). This multitude of relationships between elevated plasma homocysteine and diseases that afflict the elderly, pregnant women, and the embryo points to the existence of a common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined.