Short and long-term variation of plasma glycine betaine concentrations in humans

Background: Glycine betaine is important in cell volume regulation and in remethylating homocysteine, a vascular risk factor. Objective: We investigated changes in circulating glycine betaine concentrations in human volunteers both under acute osmotic stress and over longer time scales. Design: Plasma glycine betaine concentrations were measured in normal human volunteers in three studies: (1) during acute diuresis and antidiuresis; (2) during prolonged diuresis for 5 days, and antidiuresis for 5 days followed by further diuresis for the final 5 days; (3) repeated samples taken 3 years apart. Results: Circulating glycine betaine concentrations remained almost unchanged for several hours after acute diuretic or antidiuretic stresses. There was more (3–10-fold) interindividual variation than intraindividual variation. A similar pattern was found on day 15 of the study. In a 3-year follow-up, plasma glycine betaine concentrations on the two occasions were highly correlated with no systematic change, showing that individual set points remain stable for years. In contrast, there was no relationship among plasma proline betaine concentrations at these times. Urinary glycine betaine excretions measured 3 years apart were also found to correlate once the perturbing effect of dietary proline betaine excretion was allowed for. Conclusions: Human circulating glycine betaine is homeostatically controlled with a distinct control value for each individual. In contrast, peripheral blood concentrations of proline betaine, which is present in the diet (and has no known metabolic or physiological role in mammals), is not controlled.