Homocysteine is a metabolite of the amino acid methionine and elevated plasma levels are an independent risk factor for cardiovascular disease. Homocysteine levels become elevated due to low intakes of vitamin B6, B12 or folate, which are required as co-factors by enzymes in the pathways that metabolise homocysteine to less harmful substances. The links between homocysteine and cardiovascular disease are well established, and clinical trials have successfully reduced elevated homocysteine levels through supplementation with B vitamins. Elevated plasma homocysteine is accompanied by increased levels of oxidation, presumably because homocysteine is able to create an environment where oxidation is more likely. Researchers1 have shown that homocysteine and oxidative stress are higher in older versus younger subjects, but that young subjects with hypertension and diabetes have similar levels of homocysteine and oxidative stress when compared to older subjects with diabetes and hypertension.
Therefore, elevated levels of homocysteine may occur with increasing age, irrespective of the presence of hypertension or diabetes. However, if diabetes or hypertension are present, homocysteine levels do not rise further with increasing age, suggesting a natural ceiling for homocysteine levels. In addition, because elevated levels of homocysteine are present in subjects with diabetes and hypertension irrespective of age, homocysteine may be implicated in the development of these conditions. Because homocysteine is able to cause systemic oxidative stress, antioxidants may provide some protection against the elevated homocysteine levels. This is supported by data from epidemiology that shows foods high in antioxidants, such as tea, onions, apples, chocolate and wine, are inversely associated with cardiovascular disease. However, studies show that the most effective way to protect from elevated homocysteine levels is to supplement with vitamin B6, vitamin B12 and folate.
The findings from in vitro studies that show low density lipoprotein must become oxidised to induce endothelial damage may provide further evidence that homocysteine is involved in the aetiology of cardiovascular disease. The fact that homocysteine may be involved in lipoprotein oxidisation has been largely ignored by the scientific community, and the lipoprotein theory of cardiovascular disease is still viewed largely in isolation as a pure lipid disorder. Although progress has been made moving away from the role of dietary saturated fat and cholesterol in this theory, ad hoc hypothesis are still created routinely in studies in order to maintain the dogma, despite a large body of evidence that shows that saturated fat and cholesterol in the diet have little impact of blood lipid levels. Further, the fact that homocysteine also is known to cause coagulation, accelerate proliferation of vascular cells and induce inflammation also suggests a pivotal role in cardiovascular disease.
Homocysteine was first postulated to be involved in cardiovascular disease in the 1960’s by Kilmer McCully, and his work was largely ignored or ridiculed for the best part of 3 decades. McCully theorised the involvement of homocysteine in the aetiology of cardiovascular disease after studying patients with homocysteinaemia, a congenital disorder that results in elevated levels of homocysteine in the plasma. Such individuals tend to die prematurely from cardiovascular disease and McCully was able to use his experience with these patients to identify elevated homocysteine as a risk factor for cardiovascular disease in otherwise healthy individuals. The ease and safety with which homocysteine levels can be controlled by B vitamin supplementation, in combination with the almost total ignorance of the matter from the mainstream medical community, can be explained by either ineptitude or deliberate conspiracy to maintain the current market in relatively expensive cholesterol lowering drugs.
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