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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Orally Administered Betaine Has an Acute and Dose-Dependent Effect on Serum Betaine and Plasma Homocysteine Concentrations in Healthy Humans¹

Ursula Schwab^*,,2, Anneli Törrönen^**, Esa Meririnne, Markku Saarinen^**, Georg Alfthan, Antti Aro and Matti Uusitupa^*

^* Department of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Kuopio; ^** Danisco Innovation, Enteromix Research, Kantvik, Finland; and Drug Research Unit, and Biomarker Laboratory, the National Public Health Institute, Helsinki, Finland

² To whom correspondence should be addressed. E-mail: Ursula.Schwab{at}uku.fi

ABSTRACT

Betaine, i.e., trimethylglycine, is linked to homocysteine metabolism. A 3-mo daily betaine supplementation decreased even normal plasma total homocysteine (tHcy) concentrations in humans. The pharmacokinetic characteristics and metabolism of betaine in humans have not been investigated in detail. The aim of this study was to assess the pharmacokinetics of orally administered betaine and its acute effect on plasma tHcy concentrations. Healthy volunteers (n = 10; 3 men, 7 women) with normal body weight (mean ± SD, 69.5 ± 17.0 kg), 40.8 ± 12.4 y old, participated in the study. The betaine doses were 1, 3, and 6 g. The doses were mixed with 150 mL of orange juice and ingested after a 12-h overnight fast by each volunteer according to a randomized double-blind crossover design. Blood samples were drawn for 24 h and a 24-h urine collection was performed. Orally administered betaine had an immediate and dose-dependent effect on serum betaine concentration. Single doses of 3 and 6 g lowered plasma tHcy concentrations (P = 0.019 and P < 0.001, respectively), unlike the 1-g dose. After the highest dose, the concentrations remained low during the 24 h of monitoring. The change in plasma tHcy concentration was linearly associated with betaine dose (P = 0.006) and serum betaine concentration (R² = 0.17, P = 0.025). The absorption and elimination of betaine were dose dependent. The urinary excretion of betaine seemed to increase with an increasing betaine dose, although a very small proportion of ingested betaine was excreted via urine. In conclusion, a single dose of orally administered betaine had an acute and dose-dependent effect on serum betaine concentration and resulted in lowered plasma tHcy concentrations within 2 h in healthy subjects.

KEY WORDS: • Betaine • cysteine • dimethylglycine • homocysteine • human

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