Homocysteine is a product of methionine metabolism in humans. Under conditions of adequate nutrition, this homocysteine is rapidly converted back to methionine or to cysteine through a number of pathways. For this conversion to take place, optimal intakes of folic acid, vitamin B12 and vitamin B6 must be present. These B vitamins act as cofactors in the converting enzymes and their absence causes decrease flux through the pathways, resulting in a buildup of homocysteine. As homocysteine accumulates in cells, it spills over into the plasma where it can cause inflammation. This inflammation and its subsequent oxidative stress is now thought to cause endothelial dysfunction in arteries through depletion nitric oxide synthase. This mechanism explains the association between high plasma homocysteine concentrations and an elevated risk of cardiovascular disease. In addition, the systemic inflammation caused by high homocysteine concentrations may also cause of other health problems.
High homocysteine levels are therefore damaging to the health because the associated chronic inflammation and oxidative stress can cause a number of health problems. Increasingly such inflammation is being implicated as a possible contributory factor in the aetiology of inflammatory bowel disease (IBD) and the subsequent development of colorectal cancer. The association between high homocysteine plasma concentrations and the prevalence of colorectal cancer has been investigated in epidemiological studies. For example, in one study, data from the Women’s Health Initiative cohort of 988 individual was used to assess the odds ratio of developing colorectal cancer at different levels of plasma homocysteine concentrations1. The results showed that there was an odds ratio of 1.46 for colorectal cancer in the highest quartile of plasma homocysteine levels compared to the lowest quartile. However, the odds ratio was 0.57 for colorectal cancer in the highest quartile of cysteine, compared to the lowest quartile.
These results suggest that high concentrations of homocysteine are significantly associated with colorectal cancer. This supports the contention that high plasma concentrations of homocysteine causes systemic inflammation and this is able to increase the risk of IBD which is associated with an increased risk of developing colorectal cancer. The fact that high cysteine levels are associated with a decreased risk of colorectal cancer suggests that conversion of homocysteine to cysteine through the vitamin B6 dependent enzyme cystathionine beta synthase reduces the accumulation of homocysteine in tissues and this reduces the inflammatory burden to the body. The net effect of the reduction of homocysteine and the increase in cysteine is a reduction in the risk of colorectal cancer. This study highlights the importance of adequate B vitamin status in lowering homocysteine plasma concentrations in protecting from disease of inflammation. That large numbers of people are deficient in B vitamins is therefore concerning.
RdB
