Betaine Anhydrous
Also known as: Trimethylglycine, TMG, Betaine, Glycine Betaine
A quaternary ammonium compound functioning as an intracellular osmolyte and primary methyl donor in the methionine-homocysteine cycle, supporting cellular hydration, creatine endogenous synthesis, and exercise performance.
Last reviewed: 2024-08-01 · 3 indexed studies
Set your location for accurate regulatory status
Saved on this device — no sign-in needed.
Overview
Betaine Anhydrous (trimethylglycine) is a naturally occurring osmolyte and methyl donor with dual roles in performance and metabolic health. As an osmolyte, it protects cells from dehydration stress. As a methyl donor, it supports creatine synthesis and homocysteine recycling. Clinical trials show improvements in power output, work capacity, and body composition.
Mechanism & Function
White crystalline trimethylglycine powder. Mildly sweet, fully water-soluble.
- Powder
- Capsule
- RTD
Powder is generally preferred for bioavailability or efficacy.
Mechanism of Action
1) Osmolyte: Accumulates intracellularly to maintain cell volume and protein stability under osmotic, thermal, and exercise-induced stress. 2) Methyl Donor: Donates a methyl group to homocysteine via betaine-homocysteine methyltransferase (BHMT), regenerating methionine and supporting downstream SAMe-dependent methylation reactions including endogenous creatine synthesis. 3) May upregulate IGF-1 signaling and protein synthesis pathways (Akt/mTOR).
Physiological Role
Primary methyl donor in the liver, critical for homocysteine clearance and methionine recycling. Major intracellular osmolyte in kidneys and liver. Supports endogenous creatine biosynthesis by providing methyl groups for the GAMT reaction.
Primary Pathways
Performance / Health Relevance
Improves repetitions to failure, total work capacity, and peak power in resistance training. Supports lean mass gains and fat loss over training cycles (6+ weeks). Enhances cellular hydration — particularly beneficial in heat or dehydration scenarios.
Evidence Review
Practical Use & Dosage
- Minimum Effective Dose
- 1.5g/day
- Optimal Range
- 2.5g/day (most studied dose)
- Upper / Caution Level
- 6g/day
- Timing
- Pre-workout or split AM/PM; timing is less critical than consistency
- Best Format
- Powder (mixes easily; slightly sweet taste)
- Bioavailability
- Well absorbed orally. Natural betaine from beet-derived sources is bioequivalent to synthetic. Plasma betaine peaks within 1–2 hours.
- Absorption Considerations
- Take with or without food. Highly water soluble. No significant interactions affecting absorption.
Safety & Interactions
Side Effects
- •GI discomfort at high doses (>6g)
- •Fishy body odor (rare, related to TMA metabolism)
- •Nausea if taken on empty stomach at high doses
Contraindications
- Trimethylaminuria (TMAU — genetic condition)
Drug Interactions
- •May potentiate effects of medications metabolized via methylation pathways
- •Theoretically synergistic with folate/B12 in homocysteine metabolism
Who Should Avoid
- •Those with TMAU (fish odor syndrome)
- •Individuals with kidney disease at high doses
Monitoring
Monitor homocysteine levels if using for cardiovascular health purposes. Generally very well tolerated.
Frequently Asked Questions
Auto-generated from indexed evidence — dosage, safety, interactions, and more.
When is Betaine Anhydrous typically used or indicated?
Betaine Anhydrous is most commonly used for: Power output, Body composition, Osmolyte cell hydration, Homocysteine metabolism. Primary methyl donor in the liver, critical for homocysteine clearance and methionine recycling. Major intracellular osmolyte in kidneys and liver. Supports endogenous creatine biosynthesis by providing methyl groups for the GAMT reaction.
How does Betaine Anhydrous work?
1) Osmolyte: Accumulates intracellularly to maintain cell volume and protein stability under osmotic, thermal, and exercise-induced stress. 2) Methyl Donor: Donates a methyl group to homocysteine via betaine-homocysteine methyltransferase (BHMT), regenerating methionine and supporting downstream SAMe-dependent methylation reactions including endogenous creatine synthesis. 3) May upregulate IGF-1 signaling and protein synthesis pathways (Akt/mTOR).
What is the recommended dose of Betaine Anhydrous?
The optimal range is 2.5g/day (most studied dose). with a minimum effective dose of 1.5g/day. Best taken: Pre-workout or split AM/PM; timing is less critical than consistency. Upper / caution level: 6g/day.
What are the side effects of Betaine Anhydrous?
Reported side effects include: GI discomfort at high doses (>6g); Fishy body odor (rare, related to TMA metabolism); and Nausea if taken on empty stomach at high doses. Monitoring: Monitor homocysteine levels if using for cardiovascular health purposes. Generally very well tolerated.
Does Betaine Anhydrous interact with medications?
Known or theoretical interactions: May potentiate effects of medications metabolized via methylation pathways; and Theoretically synergistic with folate/B12 in homocysteine metabolism. Always check with a clinician before combining with prescription medication.
Who should avoid Betaine Anhydrous?
Betaine Anhydrous is generally not recommended for: Those with TMAU (fish odor syndrome); Individuals with kidney disease at high doses; and Trimethylaminuria (TMAU — genetic condition).
How strong is the evidence for Betaine Anhydrous?
Evidence level: Moderate (overall score 74/100), based on 3 indexed studies on SuppIndex.
Research & References (3)
Effects of betaine supplementation on power and strength: a systematic review
Systematic review of 7 studies concluding 2.5g/day betaine consistently improved isometric force, power output, and total work capacity in resistance-trained athletes.
Betaine supplementation enhances body composition in trained athletes
6-week RCT in resistance-trained men showing 2.5g/day betaine significantly increased lean mass (+2.4 lbs), reduced fat mass (-3.3 lbs), and improved body composition vs placebo.
Ergogenic effects of betaine supplementation on strength and power performance
14-day betaine supplementation (2.5g/day) significantly increased bench press work capacity, squat repetitions, and peak power output in college-aged men.
Trademark Ingredients
Related Ingredients
Other top-rated ingredients in Pump and Performance Ingredients.
Nitrosigine®
82/100Inositol-stabilized arginine silicate complex that provides sustained elevation of plasma arginine (up to 6 hours) and silicon, enhancing eNOS-mediated nitric oxide production, vascular compliance, and cognitive flexibility during physical exertion.
Beetroot Extract
80/100Concentrated source of dietary inorganic nitrate that undergoes serial reduction via oral microbiome (NO₃⁻ → NO₂⁻) and tissue-level reduction (NO₂⁻ → NO) through the oxygen-independent nitrate-nitrite-NO pathway, enhancing blood flow and exercise efficiency.
Citrulline Malate
78/100Salt of L-citrulline and DL-malic acid (commonly 2:1); citrulline raises plasma arginine and NO; malate enters the Krebs cycle and may buffer fatigue.
Research Overview
Moderate EvidenceCite this ingredient
One-click citation export in APA, MLA, Chicago, BibTeX, or HTML. The URL below is stable and safe to link.
Stable URL
https://thesuppindex.com/ingredients/betaine-anhydrous
SuppIndex. (2026). Betaine Anhydrous: Evidence summary, dosage and clinical studies. Retrieved October 23, 2026, from https://thesuppindex.com/ingredients/betaine-anhydrous
Based on 3 indexed studies · Evidence level: Moderate.
Goal Ratings
Stack Compatibility
Exceptional synergy with creatine (betaine supports endogenous creatine synthesis via methyl donation). Pairs well with citrulline for pump + power stacks. Compatible with all standard pre-workout ingredients.
Products (3)
Transparent Labs
BULK Pre-Workout
Jacked Factory
Nitrosurge
Nutrabio
PRE Extreme