Betaine Anhydrous
Also known as: Trimethylglycine, TMG, Betaine, Anhydrous betaine
This ingredient is classified as unclassified risk (GIRI score: 2.0/10).
Safety Profile
Information not yet available for this ingredient profile.
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Betaine anhydrous (trimethylglycine) is a methyl donor used for homocysteine reduction and sports performance. It is generally well tolerated. GI discomfort and body odour from TMAO production are common adverse effects at high doses (>3 g/day). It may increase LDL cholesterol at high doses. No significant drug interactions are documented at standard doses.
Biological and Chemical Classification
Information not yet available for this ingredient profile.
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 9 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Amino Acids
- Evidence consistency: High consistency across studies (100%)
- No significant safety signals identified in the reviewed literature.
The available scientific evidence for Betaine Anhydrous indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 9/40 |
| Evidence consistency | 20/20 |
| Safety signals | 2/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 9 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 9 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 26 მარ 2026, 14:06
Evidence Distribution
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Observational / other LOW evidence YELLOWAssessment of the feed additives betaine anhydrous (3a920) and betaine hydrochloride (3a925) for all animal species for the renewal of their authorisations… ↗Villa RE et al.. Assessment of the feed additives betaine anhydrous (3a920) and betaine hydrochloride (3a925) for all animal species for the renewal of their authorisations (Orffa Additives B.V.).. EFSA J. 2025. PMID:40276164.PMID 40276164 ↗Journal EFSA JYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40276164/
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Observational / other LOW evidence YELLOWThe Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers,… ↗Machek SB et al.. The Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers, and Hypoxia-Inducible Factor-1u03b1 Gene Expression.. Nutrients. 2022. PMID:36501070.PMID 36501070 ↗Journal NutrientsYear 2022Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/36501070/
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Observational / other LOW evidence YELLOWPostauthorization safety study of betaine anhydrous. ↗Mu00fctze U et al.. Postauthorization safety study of betaine anhydrous.. J Inherit Metab Dis. 2022. PMID:35358327.PMID 35358327 ↗Journal J Inherit Metab DisYear 2022Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/35358327/
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Observational / other LOW evidence YELLOWHuman Serum Betaine and Associated Biomarker Concentrations Following a 14 Day Supplemental Betaine Loading Protocol and during a 28 Day Washout Period:… ↗Machek SB et al.. Human Serum Betaine and Associated Biomarker Concentrations Following a 14 Day Supplemental Betaine Loading Protocol and during a 28 Day Washout Period: A Pilot Investigation.. Nutrients. 2022. PMID:35276860.PMID 35276860 ↗Journal NutrientsYear 2022Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/35276860/
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Observational / other LOW evidence YELLOWBetaine anhydrous in homocystinuria: results from the RoCH registry. ↗Valayannopoulos V et al.. Betaine anhydrous in homocystinuria: results from the RoCH registry.. Orphanet J Rare Dis. 2019. PMID:30871635.PMID 30871635 ↗Journal Orphanet J Rare DisYear 2019Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/30871635/
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Observational / other LOW evidence YELLOWAccumulation of Liver Lipids Induced by Vitamin B(6) Deficiency Was Effectively Ameliorated by Choline and, to a Lesser Extent, Betaine. ↗Kitagawa E et al.. Accumulation of Liver Lipids Induced by Vitamin B(6) Deficiency Was Effectively Ameliorated by Choline and, to a Lesser Extent, Betaine.. J Nutr Sci Vitaminol (Tokyo). 2019. PMID:30814419.PMID 30814419 ↗Journal J Nutr Sci Vitaminol (Tokyo)Year 2019Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/30814419/
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Observational / other LOW evidence YELLOWSafety and efficacy of betaine anhydrous for food-producing animal species based on a dossier submitted by AB Vista. ↗Rychen G et al.. Safety and efficacy of betaine anhydrous for food-producing animal species based on a dossier submitted by AB Vista.. EFSA J. 2018. PMID:32625971.PMID 32625971 ↗Journal EFSA JYear 2018Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/32625971/
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Observational / other LOW evidence YELLOWISMP Medication Error Report Analysis: Betaine Anhydrous Versus Betaine Hydrochloride Look-Alike Generic Names Don't Give Zurampic Without Allopurinol Lantus Overdose Tied to… ↗Cohen MR et al.. ISMP Medication Error Report Analysis: Betaine Anhydrous Versus Betaine Hydrochloride Look-Alike Generic Names Don't Give Zurampic Without Allopurinol Lantus Overdose Tied to Confusing Vial Label More on Lipid Rescue.. Hosp Pharm. 2017. PMID:28439129.PMID 28439129 ↗Journal Hosp PharmYear 2017Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/28439129/
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Observational / other LOW evidence YELLOWCholine and betaine ameliorate liver lipid accumulation induced by vitamin B(6) deficiency in rats. ↗Kitagawa E et al.. Choline and betaine ameliorate liver lipid accumulation induced by vitamin B(6) deficiency in rats.. Biosci Biotechnol Biochem. 2017. PMID:27696964.PMID 27696964 ↗Journal Biosci Biotechnol BiochemYear 2017Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/27696964/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Betaine Anhydrous. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a low safety concern under normal conditions of use.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Low classification for Betaine Anhydrous
A score of 2.0 places this ingredient in the Low band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.