Biological and Environmental Determinants of Plasma Homocysteine

Abstract

This article gives an overview over common physiological, lifestyle, and pathological conditions that may modulate the homocysteine status. The interplay of several environmental factors, including age, gender, nutrition, smoking, and coffee consumption and physical activity with commonly used drugs and prevalent diseases are described. In most cases, an abnormal homocysteine status is not caused by a single factor alone but often is the result of combined effects. We address these frequently found "clusters" of homocysteine-modulating factors. Finally, we give an overview of likely causes of hyperhomocysteinemia found in an authentic material. This material is based on 2462 routine measurements of plasma total homocysteine carried out at the Haukeland University Hospital. The data represent the total number of combined homocysteine and methylmalonic acid determinations, requested by general practitioners in Norway during February 1998.

Dietary methyl-consuming compounds and metabolic syndrome

“…Although guanidinoacetate and phosphatidylethanolamine are known to be two major endogenous methyl consumers used to synthesize creatine and phosphatidylcholine, respectively, 28 there is no evidence of increase in the level of guanidinoacetate or phosphatidylethanolamine in metabolic syndrome or its related diseases. In contrast, increased exogenous methyl consumers, such as niacin, 26,29,30 levodopa 31 and arsenic, 32 may contribute to elevated plasma homocysteine levels. Given that diet is a major risk factor for hyperhomocysteinemia 33 and that there has been a significant increase in dietary methyl consumers in the past few decades due to pollution, food additives, food fortification and high meat intake, 34,35 it seems very likely that increased dietary methyl consumers may be a significant factor in the prevalence of hyperhomocysteinemia and its related diseases.…”

“…postmethionine loading plasma homocysteine, this mutation has little effect on the fasting homocysteine levels. 26 Supplementation of vitamin B 6 , an essential cofactor for cystathionine b-synthase, also has no effect on cardiovascular events. 25 Therefore, the frequency of carriers of cystathionine b-synthase deficiency alone cannot explain the high incidence of hyperhomocysteinemia, neither in healthy nor in vascular populations.…”

“…25 Therefore, the frequency of carriers of cystathionine b-synthase deficiency alone cannot explain the high incidence of hyperhomocysteinemia, neither in healthy nor in vascular populations. 26 One unexplored cause for the increasing prevalence of metabolic syndrome, T2D and CVD are changes in dietary content of methyl consumers. It is known that almost all of the homocysteine is derived as an intermediate in the methionine-homocysteine cycle, because the amount of homocysteine from dietary sources is very limited.…”

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

“…Increased plasma total homocysteine, a risk factor for cardiovascular disease, is related to genetic, environmental, and nutritional factors (43). Evidence is accumulating that elevated levels of homocysteine are correlated with higher risk for cancer (44)(45)(46)(47). Furthermore, a recent report has suggested that by keeping homocysteine levels low, folic acid can protect cerebral vessels and prevent the accumulation of DNA damage in neurons caused by oxidative stress and facilitated by homocysteine (48).…”

Evidence for sex differences in the determinants of homocysteine concentrations

“…The variables known to be significantly associated with homocysteine levels include: vitamin status, in particular folate, riboflavin and vitamin B 12 ; age; sex; lifestyle, in particular smoking status; prescription drugs; renal function; and genetics, in particular the well-established influence of the 677C>T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene [11].…”