Betaine supplementation modulates betaine concentration by methylenetetrahydrofolate reductase genotype, but has no effect on amino acid profile in healthy active males: A randomized placebo-controlled cross-over study

Betaine supplementation is used by athletes, but its mechanism of action is still not fully understood. We hypothesized that betaine supplementation would increase betaine concentration and alter amino acid profiles in relation to MTHFR genotype and dose in physically active males. The study followed a randomized placebo-controlled cross-over design. Blood samples were collected before and after each supplementation period. Serum was analyzed for amino acid profile, homocysteine, betaine, choline, and trimethylamine N-oxide (TMAO) concentrations. For the washout analysis, only participants starting with betaine were included (n = 20). Statistical analysis revealed no differences in the amino acid profile after betaine supplementation. However, betaine concentration significantly increased after betaine supplementation (from 4.89 ± 1.59 µg/mL to 17.31 ± 9.21 µg/mL, P < .001), with a greater increase observed in MTHFR (C677T, rs180113) T-allele carriers compared to CC (P = .027). Betaine supplementation caused a decrease in homocysteine concentration (from 17.04 ± 4.13 µmol/L to 15.44 ± 3.48 µmol/L, P = .00005) and a non-significant increase in TMAO concentrations (from 0.27 ± 0.20 µg/ml to 0.44 ± 0.70 µg/ml, P = .053), but had no effect on choline concentrations. Serum betaine concentrations were not significantly different after the 21-day washout from the baseline values (baseline: 4.93 ± 1.87 µg/mL and after washout: 4.70 ± 1.70 µg/mL, P = 1.000). In conclusion, betaine supplementation increased betaine and decreased homocysteine concentrations, but did not affect the amino acid profile or choline concentrations in healthy active males. Betaine concentrations may be dependent on MTHFR genotype.