Betaine (Trimethylglycine)

Betaine, also known as trimethylglycine (TMG), is a naturally occurring zwitterionic amino‑acid derivative that functions primarily as a methyl‑group donor and an osmolyte. In humans it is derived from dietary choline and is widely present in plant and animal tissues where it helps maintain cellular hydration and supports methyl-group metabolism.

• IUPAC name: (2‑Bromo‑2‑hydroxy‑N,N,N‑trimethyl‑ethanaminium) (but commonly referred to as N,N,N‑trimethylglycine).
• Molecular formula: C₅H₁₁NO₂.
• Molecular weight: 117.15 g/mol.
• Structure: A quaternary ammonium (–N⁺(CH₃)₃) attached to a glycine backbone where the carboxylate is deprotonated, giving a zwitterionic molecule (positive N, negative carboxylate). This neutral overall charge confers high water solubility (≈1 g/mL) and stability across pH 2–10.
• Physical properties: White crystalline powder, melting point 300 °C (decomposes), pKa of the carboxyl group ~2.3, pKa of the ammonium ~10.6.
• Stability: Stable under normal storage; sensitive to strong acids or bases that may convert it to betaine aldehyde; storage in a dry, cool environment preserves purity.

• Extraction: Betaine is extracted primarily from sugar beet (Beta vulgaris) molasses, where it occurs as the natural osmoprotectant betaine (≈1‑2 % w/w).
• Synthetic routes: Commercial production also utilizes synthetic routes: methylation of glycine with excess methyl iodide or dimethyl sulfate under controlled conditions, yielding high‑purity betaine suitable for pharmaceutical use.
• Natural food sources: Natural food sources include beets, spinach, quinoa, and shellfish; dietary intake averages 0.5–1 g/day in Western diets.
• Supplement quality: For supplements, USP‑grade or GMP‑certified betaine is preferred; analytical testing (HPLC, NMR) confirms ≥98 % purity and absence of heavy metals or residual solvents. Look for products that list “betaine anhydrous” or “betaine HCl” (the latter is a salt form with comparable bioavailability).