Betaine (trimethylglycine) is an organic osmolyte found in many foods, including spinach, beets, and whole grains . Administration of supplemental betaine for 10–15 days has enhanced performance in several studies but with varying results: Lee et al. Reported increased power output and force production, whereas others reported improvements in muscular endurance but not power. On the other hand, Del Favero et al. reported no improvements in power output, strength, or body composition with 10 days of betaine treatment; however, subjects were instructed to avoid training and supplementation was ceased 5 days prior to performance testing.

To the knowledge, only two studies have examined the effects of betaine on body composition and hypertrophy in humans. Betaine did not improve body composition in obese, sedentary subjects on a 500 kcal/day caloric deficit following 12 weeks of supplementation . Similarly, 10 days of betaine supplementation did not improve body composition in sedentary young male subjects . Though research is limited in humans, chronic betaine supplementation has been shown to reduce adipose mass and increase muscle mass in animals . Greater improvements in body composition with betaine supplementation were observed when pigs were given extra pen space to move and exercise , suggesting that betaine may exert the most influential effects on growth under conditions of metabolic or nutritional stress. Because the subjects in Schwab et al. and Del Favero et al. were instructed not to exercise, the absence of a metabolic stressor may have compromised the effects of betaine. Given the enhanced effects of movement in pigs and the ineffectiveness reported in sedentary, non-exercising humans, we hypothesize that the effects of betaine on body composition, strength and power may be most apparent when supplementation occurs over several weeks accompanied by a resistance training program.

By donating a methyl group to transmethylate Hcy back to methionine (Met), betaine increases Hcy metabolism and the availability of the universal methyl donor, S-adenosylmethionine (SAM) . We hypothesize betaine supplementation may enhance protein synthesis and thus improve body composition by reducing Hcy and homocysteine thiolactone (HCTL). Hcy directly impairs insulin signaling by reducing insulin receptor stubstrate-1 (IRS-1) activation and thus inhibiting Akt-phosphorylation . Moreover, excess dietary Met is metabolized to form Hcy and both high dietary Met consumption and the resultant increase in plasma Hcy contributes to elevated HCTL . A short (10 min) HCTL treatment inhibits insulin signaling, including insulin-mediated mRNA expression and protein synthesis . This suggests that HCTL is more effective than Hcy in promoting insulin resistance. Additionally, HCTL has been shown to modify protein lysine residues, which causes protein aggregation, and inactivates enzymes associated with protein synthesis .

Concentrations of plasma Hcy or HCTL levels in strength athletes have yet to be reported. Given that transmethylation capacity is dependent upon plasma folate and betaine and because weight trainers regularly consume excess Met and inadequate folate and betaine , Hcy transmethylation may be impaired resulting in excess HCTL generation. Thus, by decreasing insulin receptor signaling , elevated HCTL in weight lifters may compromise body composition directly by inhibiting mRNA expression and protein synthesis.

In healthy adults the ingestion of 500 mg of betaine decreased fasting plasma Hcy and attenuated Hcy rise for 24 hr following a Met load , and betaine treatment lowers HCTL in patients with genetically compromised transmethylation capacities ; however, to date there are no published reports investigating the effects of betaine ingestion on HCTL in healthy subjects. We hypothesize that by increasing transmethylation capacity betaine supplementation reduces plasma Hcy and may thus decrease HCTL generation, resulting in improved insulin signaling and myofibril protein synthesis, and ultimately enhancing muscle and strength gains. Therefore, the purpose of this study was to investigate the sub-chronic effects of betaine on strength, power, and body composition during resistance training in experienced strength trained males. Additionally, urine HCTL was measured to determine if betaine affects performance by reducing plasma HCTL. We hypothesized that betaine supplementation would improve strength, vertical jump, limb CSA, and body composition between the 1st week and 6th week over placebo. We also hypothesized that betaine supplementation would reduce urinary HCTL over the course of 6 weeks.