Raised plasma levels of the amino acid homocysteine are known to damage tissues and are a risk factor for dementia, cardiovascular disease and bone fractures. Homocysteine is synthesised in humans from the essential amino acid methionine and under normal physiological conditions is quickly metabolised to cystathionine, or converted back to methionine in the salvage pathway. The salvage pathway can involve two routes, the first occurring via the enzyme methionine synthase which required cobalamin (B12) and folate as a methyl donor, or alternatively via the enzyme betaine methyltransferase, which requires betaine as a methyl donor. Betaine can be synthesised from choline, or can be derived from the diet from such foods as wheat germ, wheat bran or spinach. Choline is synthesised from phosphatidylcholine (lecithin) or can be derived from the diet from such foods as eggs, beef, pork, liver, soyabean and wheat germ.
Betaine is therefore important in the metabolism of homocysteine, and is reliant of adequate choline plasma levels if dietary sources are limited. In fact, betaine supplementation has been shown to lower plasma levels of homocysteine, and individuals with the highest betaine and choline intakes have been shown to have lower levels of homocysteine, when compared to those with the lowest intakes (here). Betaine is formed by choline oxidation in the mitochondria of the liver and kidney via the enzyme choline dehydrogenase. Researchers1 have investigated the associations between plasma levels of choline and betaine with a number of cardiovascular risk factors in 7074 mean and women aged 47-49 and 71-74 years, respectively. Choline and betaine were lower in women compared to men and lower in younger, compared to older subjects. Mean plasma levels of choline were 9.9 µmol/L and for betaine were 39.5 µmol/L.
Multivariate analysis was carried out, and this showed that choline plasma concentrations were positively associated with serum triglycerides, glucose, BMI, percentage body fat, waist circumference and physical activity, but inversely associated with HDL cholesterol and smoking. Betaine was inversely associated with serum non-HDL cholesterol, triglycerides, BMI, percentage body fat, waist circumference, systolic and diastolic blood pressure and smoking, but positively associated with HDL cholesterol, and physical activity. This suggests that high levels of choline and low levels of betaine are associated with an unfavourable cardiovascular risk profile. Metabolic syndrome is known to be associated with mitochondrial dysfunction, and rat studies suggest that insulin decreases mitochondrial choline dehydrogenase. Thus insulin resistance may cause a decrease in the conversion of choline to betaine, and as a result higher homocysteine levels may then increase cardiovascular disease risk.
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