Determinants of Plasma Homocysteine

Homocysteine is a sulphur containing amino acid formed from the metabolism of the essential amino acid methionine. High levels of homocysteine in the plasma have been identified as an independent risk factor for cardiovascular disease. Homocysteine metabolism depends on a number of vitamin co-factors, and without these vitamins enzyme activity falls and homocysteine accumulates in cells and plasma. Raised plasma levels of homocysteine can be lowered by administration of vitamin B12, vitamin B6 and folic acid, because these vitamins are needed for the metabolism of homocysteine to cystathione (B6) or methionine (B12 and folate). Because homocysteine is an independent risk factor for cardiovascular disease, researchers are interested in the lifestyle and dietary factors that might raise plasma levels. Researchers1 in the US have used data from the NHANES survey to assess the determinants of homocysteine plasma levels in 3329 men and 7925 women.

Plasma homocysteine was 9.7% higher in men than women and 5.3% higher in whites than blacks, showing that plasma levels vary between genders and races. Plasma homocysteine was 64.5%, 38.5% and 22.9% higher in individuals aged 20 to 40y, 40 to 60 y and >60y, respectively, compared to individuals < 20 y. Supplement users also had a 5% lower level of homocysteine that non-supplement users, although the types of supplements were not recorded. As would be expected, plasma homocysteine was inversely associated with red blood cell folate levels, serum cobalamin and serum folate levels, as has been shown in previous studies. Those individuals with the highest systolic blood pressure, creatinine levels and cotinine levels (a marker of nicotine intake) had 5.6%, 36.1% and 11.2% higher plasma homocysteine, than those with the lowest levels.

These results are interesting because they show that men have higher homocysteine levels than women. The authors suggested this was because renal cystathione β synthase activity is significantly lower in men than women, because the enzyme is affected by testosterone levels. The higher homocysteine levels in older subject was not caused by folate status, because the eldest subjects generally had the highest folate red blood cell levels. Instead it is likely due to age related decline in enzyme efficiency and an age related decrease in cobalamin absorption. Genetically lower serum cobalamin levels can also explain the difference in homocysteine levels between whites and blacks, which supports data from previous studies. Smoking, as recorded by the plasma cotinine levels, might raise homocysteine plasma levels because it decreases plasma levels of vitamin B6, vitamin B12 and folate and thus reduces metabolism of homocysteine.

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1Ganji, V. and Kafai, M. R. 2009. Demographic, lifestyle, and health characteristics and serum B vitamin status are determinants of plasma total homocysteine concentration in the post-folic acid fortification period. 199-2004. Journal of Nutrition. 139: 345-352

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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