2.5 g/day (performance); up to 6 g/day for homocysteine.
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Betaine, also known as trimethylglycine (TMG) or N,N,N-trimethylglycine, is a quaternary amino acid compound derived from the amino acid glycine to which three methyl groups have been added; it is present in significant amounts in foods such as beetroot (from which it takes its name, since it was originally identified in Beta vulgaris), spinach, shellfish, wheat bran, and quinoa, with typical dietary intakes of 100-300 mg/day in Western diets; its two main biological functions are to act as a cellular osmolyte (a regulator of volume and osmotic stress) and as a metabolic methyl-group donor, contributing to the conversion of homocysteine into methionine through the enzyme betaine-homocysteine methyltransferase (BHMT), a pathway parallel to the one dependent on folate and vitamin B12.
This dual biological function explains the profile of clinical applications of betaine as a supplement: on the one hand, metabolic indications (homocystinuria, hepatic steatosis, modulation of plasma homocysteine) and on the other hand, ergogenic and physical performance indications where the osmolytic activity supports muscle performance under the osmotic and thermal stress characteristic of intense training.
The original clinical indication is homocystinuria, a group of inborn errors of homocysteine metabolism that produces extremely high plasma levels with serious cardiovascular, ophthalmological, skeletal, and neurological risk; in these conditions, betaine at high doses (6-9 grams per day) is a recognized treatment of choice, marketed as a medication (Cystadane), with solid clinical data showing reduced homocysteine and reduced associated clinical complications.
In people with moderate hyperhomocysteinemia (the most common, non-genetic cause), betaine supplementation at moderate doses (1.5-3 g/day) significantly reduces plasma levels; however, the large cardiovascular intervention trials with pharmacological homocysteine lowering (HOPE-2, NORVIT, VISP, SEARCH) have not demonstrated benefit on cardiovascular events, which limits the practical clinical usefulness of lowering homocysteine for cardiovascular prevention, one of the best-known disappointments of interventional clinical nutrition.
In non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), several small trials have documented improvements in transaminases, liver fat, and inflammatory markers with supplementation at 6-20 grams per day for 6-12 months; the data are interesting, but the trials are still small and the indication has not entered conventional clinical guidelines for hepatic steatosis.
In athletic performance, several trials have shown modest but replicable improvements in force production, muscle power, number of repetitions at submaximal intensity, and recovery with supplementation at 2.5 g/day for 1-6 weeks; the effects are small but significant and have been documented in strength and endurance sports, attributed to the osmolytic function that improves cellular hydration and tolerance to the mechanical and thermal stress of intense exercise.
The doses studied vary by indication: for pharmacological homocystinuria, 6-9 g/day divided; for hepatic steatosis, 6-20 g/day divided into 2-3 doses; for athletic performance, 2.5 g/day as a single or divided dose; for modest homocysteine reduction, 1.5-3 g/day; typical commercial products are powder (betaine has a slightly sweet taste and dissolves well in water) or capsules with 500-1,000 mg each; simultaneous use with folate and vitamin B12 is logically more effective than betaine alone for reducing homocysteine.
Generally well tolerated at moderate doses; the adverse effects described are rare and mild (mild digestive discomfort, a persistent unpleasant taste in some products); at very high doses (more than 6 g/day), nausea, diarrhea, and, occasionally, modest increases in plasma LDL cholesterol documented in some studies may appear; people with serious kidney disease should exercise caution because betaine is osmotically active and can alter fluid and electrolyte balance; those who take drugs whose absorption can be altered should separate doses; in people prone to high cholesterol, monitor the lipid profile with sustained high doses; in pregnancy and breastfeeding the specific data as a supplement are limited, although the usual dietary intake is safe; betaine should not be confused with betaine HCl (betaine hydrochloride, used as a digestive aid in hypochlorhydria), which has different clinical applications and a different pharmacological profile.
Information, not medical advice. Scientific evidence reflects the quality of the studies.