A large cross-sectional study of a Norwegian population showed a highly significant negative association between Ro 67-4853 plasma betaine concentrations and both plasma lipids and markers of obesity. Consistent with the results reported here, higher plasma betaine was associated with plasma triglyceride and non-HDL cholesterol, with the CID44216842 effect more pronounced in men than in women; there was a trend for HDL cholesterol to be weakly positively associated with plasma betaine but this was only statistically significant in younger males. These results are consistent with the suggestion that betaine can be deficient in patients with symptoms of the metabolic syndrome, and because of the tight regulation of plasma betaine this may not always be detected as plasma concentrations do not reliably reflect tissue levels. Here, we have shown that the association of betaine with BMI and lipid components of the metabolic syndrome are clearly independent of each other and of potential confounders such as gender, age and diabetes. Other animal studies suggest that betaine affects the partitioning of lipid in the body, and in particular increases the export of tissue triglycerides. In normal rats, betaine supplementation leads to increased hepatic production of apolipoprotein B and increased plasma LDL and triglycerides, and these changes are associated with a large decrease in tissue lipid, which has been confirmed in other studies. The overall effect of increased betaine intake probably depends on other dietary components, the presence of disease, and tissue lipids. Two contrasting studies in pigs illustrate this point: betaine supplementation increased plasma lipids in castrated pigs of a genetically obese strain, whereas a lower level of betaine supplementation decreased plasma lipids in non-obese female pigs. A possible dose dependence of the effect of plasma betaine on lipids was suggested by Konstantinova et al., and it is also plausible that the effect of betaine on plasma lipids depends on tissue lipid stores. This is consistent with cross-sectional human data which suggests that those subjects with the combination of elevated triglyceride and non-HDL cholesterol with low plasma betaine are likely to show features of the metabolic syndrome.