Overview
Betaine (N-trimethylglycine) is a naturally occurring compound that functions as a methyl donor and osmolyte, playing key roles in homocysteine metabolism, cellular hydration, and antioxidant defense. It remethylates homocysteine to methionine via the betaine-homocysteine methyltransferase (BHMT) pathway, independent of folate and vitamin B12, making it particularly relevant in managing elevated homocysteine levels [5][6]. Supplementation has been shown to significantly lower fasting and post-methionine-load plasma homocysteine in individuals with mildly elevated levels, suggesting a potential role in cardiovascular risk reduction. Additionally, betaine supports metabolic health by improving insulin sensitivity and hepatic metabolism in prediabetic individuals [7], and exhibits anti-inflammatory and antioxidant effects, particularly in chronic kidney disease models [4]. It also enhances anabolic signaling, increasing growth hormone and insulin-like growth factor-1 responses to acute exercise, indicating potential ergogenic benefits [2].
Dosage Guide
Therapeutic Doses
For treatment of specific conditions
Upper Intake Limit
Maximum safe daily intake
6000 mg— Up to 6 g/day well-tolerated in clinical trials; higher doses may cause GI upset or fishy body odor due to TMA accumulation
Special Forms
Alternative forms for specific needs
Used for gastric acid support; distinct from anhydrous betaine used in metabolic studies
Primary form used in cardiovascular, metabolic, and exercise performance research
Clinical Notes
- High-dose betaine may cause gastrointestinal discomfort or a fishy body odor due to trimethylamine (TMA) production, especially in individuals with trimethylaminuria.
- Betaine hydrochloride should be used cautiously in individuals with peptic ulcer disease or on NSAIDs due to potential gastric irritation.
- Therapeutic use for homocystinuria or chronic disease should be monitored with plasma homocysteine, liver, and kidney function tests.
- Differentiate between betaine HCl (gastric acid support) and anhydrous betaine (metabolic use) — they are not interchangeable for the same indications.
Research
Discusses betaine's role as a methyl donor in homocystinuria and neural tube defect prevention via one-carbon metabolism.
Betaine supplementation (1.25 g BID) enhanced GH response and Akt signaling after acute exercise in trained men.
Betaine acts as an osmolyte improving growth and thermoregulation in heat-stressed pigs.
Review highlights betaine's osmoregulatory, anti-inflammatory, and antioxidant roles, with declining plasma levels in CKD.
6 g/day betaine for 6 weeks significantly reduced fasting plasma homocysteine by 1.8 μmol/L in healthy adults.
Plasma betaine levels correlate with reduced post-methionine-load homocysteine, especially after B-vitamin supplementation.
High-dose betaine (4950 mg twice daily) increased dimethylglycine and modestly improved metabolic markers in prediabetic obese adults.
Narrative review questions clinical efficacy of betaine supplements despite mechanistic plausibility, citing inconsistent RCT results.
