Several studies have highlighted that elevated total homocysteine (tHcy) concentrations are linked to an increased risk for coronary, cerebral and peripheral vascular disease. Homocysteine is a sulfur containing amino acid that can be metabolized (re-methylated to methionine) using three different pathways, Vitamin B12-dependant methionine synthase, Betaine-homocysteine methyltranserase or trans-sulfuration. The first pathway uses methyltetrahydrofolate, an active folate derivative (active source), methyltetrahydrofolate is formed by 5,10-methyltetrahydrofolate reductase (MTHFR).
Factors that have been associated with elevated homocysteine, in adults and children, include:
- Lower blood concentrations of Folate
- Lower blood concentrations of Vitamin B12
- Lower blood concentrations of Vitamin B6
More recently, however, it has also been found that a common genetic mutation in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) can also influence total homocysteine levels. Polymorphism of the MTHFR locus (the location of a gene on a chromosome) accounts for approximately 6 percent of elevated homocysteine concentrations. Of the MTHFR polymorphisms, the most extensively studied single nucleotide polymorphism is MTHFR C677T. Individuals presenting as homozygous (presenting with 2 copies) for the polymorphism MTHFR C677T have increased homocysteine levels, especially those individuals who also present with a low folate status. It is important to appreciate that the effect of the MTHFR genotype on plasma homocysteine changes with age and is most significant in young people.
Interestingly, men have been found to have higher homocysteine concentrations, most likely due to larger muscle mass and sex hormones. Homocysteine concentration also increases with age, which can be linked to changes in:
- Renal Function
- Excess Intake of Pharmaceuticals
The lifestyle factors that most influence homocysteine concentrations include:
- High Caffeine Consumption
- Excess Alcohol Consumption
In a recent review, a very high correlation between diet composition (dietary intake) and homocysteine concentrations has been observed. For example, in the Hordaland Homocysteine Study, researchers found that a diet rich in fruits, whole grains, non-processed meats, chicken and eggs lowered total homocysteine concentration. Conversely, high intake of cakes, pies, cookies and sweets was shown to increase total homocysteine concentrations. Moreover, it was also suggested that an intake (dietary) of folate, Vitamin B6, Vitamin B12 and Complex Carbohydrates had a positive effect on reducing total homocysteine concentrations.
Given that an increased homocysteine concentration can be destructive to cardiovascular health, a number of homocysteine lowering therapies have been suggested, based on B Vitamin supplementation or food fortification. For example, some recent studies have reported that a daily dose of folate, of at least 400 mcg, can decrease homocysteine levels. Whereas, other studies have concluded little to no effect. However, what is agreed upon, is that homocysteine concentrations will be positively influenced with administration of methyl-folate for individuals homozygous for MTHFR C677T. This being so, folate supplementation should be discussed with a qualified health care provider.
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