⛔
Regulatory ban. This ingredient is banned or restricted in one or more countries. See Regulatory Status below.
SAFE
Folate (Active 5-MTHF)
5-Methyltetrahydrofolate (5-MTHF)
Likely Safe
V5 Verified
Vitamins
Upper Safe Limit
EU UL: 1,000mcg/day (all forms combined)
PubChem CID
About
5-MTHF (L-methylfolate) is the active, pre-methylated form of folate that crosses the blood-brain barrier directly. Critical for people with MTHFR gene variants (present in ~40% of population) who cannot efficiently convert folic acid. More effective than folic acid for neurological function and homocysteine reduction.
How it works (mechanism of action)
Directly usable by all cells without conversion. Crosses blood-brain barrier for CNS methylation reactions. Reduces homocysteine via methionine synthase without the conversion steps required by folic acid or standard folate.
⚖️ Regulatory Status
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FR — Banned
ANSES recommended ban of kava following hepatotoxicity signals from nutrivigilance system.
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NZ — Banned
Medsafe NZ — ephedrine alkaloid supplements banned following FDA and TGA action.
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NL — Banned
NVWA prohibition (2004).
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MY — Banned
NPRA Malaysia — ephedra and ephedrine alkaloid supplements prohibited.
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SA — Banned
SFDA Saudi Arabia — ephedra and ephedrine alkaloid supplements prohibited. Controlled as prescription drug.
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SE — Banned
Livsmedelsverket Sweden prohibition aligned with EU Directive 2002/46/EC.
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IT — Banned
Italian Ministry of Health — ephedra and ephedrine alkaloid supplements prohibited under EU Directive 2002/46/EC.
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AE — Banned
UAE MOH prohibition — ephedra supplements banned. Ephedrine controlled as pharmaceutical.
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SG — Banned
HSA Singapore prohibition (2004) — ephedra alkaloid supplements prohibited.
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ID — Banned
BPOM Indonesia — ephedra and ephedrine alkaloid supplements prohibited.
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PH — Banned
FDA Philippines — ephedra and ephedrine alkaloid-containing food supplements banned following international regulatory action.
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PL — Banned
GIS Poland prohibition aligned with EU Directive 2002/46/EC.
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EU — Banned
European Commission ban (2002) under Directive 2002/46/EC — all ephedra and ephedrine alkaloid supplements.
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ES — Banned
AEMPS Spain prohibition aligned with EU ban on ephedrine alkaloid supplements.
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DK — Banned
Banned (2023) — Danish Veterinary and Food Administration (DVFA). Liver toxicity and thyroid disruption reports. All preparations ordered off market.
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DE — Banned
BfArM banned kava-containing products in Germany in 2002 due to hepatotoxicity risk. Cases of liver failure and death reported.
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US — Banned
FDA ban (2004) — cardiovascular adverse events and deaths. Final rule 21 CFR 119. All ephedrine alkaloids banned from dietary supplements.
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CH — Banned
Swissmedic banned kava in Switzerland due to hepatotoxicity.
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CA — Banned
Health Canada ban (2002) — all ephedra and ephedrine alkaloid-containing supplements.
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BE — Banned
FASFC Belgium prohibition aligned with EU Directive 2002/46/EC.
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AU — Banned
TGA ban (2003) — cardiovascular adverse events. Ephedra alkaloids banned from complementary medicines.
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PT — Banned
ASAE Portugal prohibition aligned with EU ban on ephedrine alkaloid supplements.
⚠️
TH — Restricted
FDA Thailand — ephedrine controlled as pharmaceutical. Not permitted in food supplements.
⚠️
IN — Restricted
CDSCO India (2004) — available only under prescription as pharmaceutical products.
⚠️
TW — Restricted
TFDA Taiwan — ephedrine controlled as pharmaceutical drug. Not permitted as health food ingredient. Products with ephedra claims require pharmaceutical registration.
⚠️
ZA — Restricted
SAHPRA (2004) — Schedule 2; pharmacist oversight required.
⚠️
KR — Restricted
MFDS South Korea (2003) — maximum dose restrictions. Not permitted for weight loss products.
⚠️
JP — Restricted
MHLW Japan (2003) — maximum dose limits; not permitted for weight loss marketing. Ephedrine controlled under pharmaceutical regulations.
⚠️
IE — Restricted
FSAI monitoring (2024) following Danish ban and hepatotoxicity reports. Products without adequate safety data may face withdrawal.
⚠️
HK — Restricted
Department of Health Hong Kong — ephedrine-containing preparations controlled as pharmaceutical products. Not permitted as health food supplements without pharmaceutical registration.
⚠️
GB — Restricted
MHRA (2004) — ephedrine alkaloid supplements restricted. Maximum doses apply under the Medicines Act.
⚠️
CN — Restricted
NMPA China — Ma Huang (ephedra) controlled. Ephedrine alkaloid content restrictions; not permitted for weight loss products. Export of ephedra controlled internationally.
💊
AT — Prescription only
AGES Austria — melatonin classified as prescription-only medicinal product. Not permitted as food supplement.
📊 Effectiveness
Homocysteine reduction
Evidence Grade A · 28 studies · n=4,800 · Meta-analysis available
Evidence grades: A=Strong RCT evidence · B=Good clinical trials · C=Limited trials · D=Preliminary/traditional
👥 Safety by Population
🚫 Contraindications & Warnings
Very safe. Masking B12 deficiency (same concern as standard folate). MTHFR variants: check genotype before assuming standard folate is adequate. Methotrexate (chemotherapy) is a folate antagonist — DO NOT combine without oncologist guidance.
🇪🇺 EU Health Claims Status
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006
Regulation EU 1924/2006 · ART13 1
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006.
Regulation EU 1924/2006 · ART13 1
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006.
Regulation EU 1924/2006 · ART13 1
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006.
Regulation EU 1924/2006 · ART13 1
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006.
Regulation EU 1924/2006 · ART13 1
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006.
Regulation EU 1924/2006 · ART13 1
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006.
Regulation EU 1924/2006 · ART13 1
Art.13(1)
✓ AuthorisedThe claim may be used only for food which is at least a source of folate as referred to in the claim SOURCE OF [NAME OF VITAMIN/S] AND/OR [NAME OF MINERAL/S] as listed in the Annex to Regulation (EC) No 1924/2006.
Regulation EU 1924/2006 · ART13 1
🏷️ Other Names
5-Methyltetrahydrofolate (5-MTHF)
References (1)
- Pratte MA, et al. J Altern Complement Med. 2014;20(12):901-8. SR/Meta-analysis PubMed ↗
Evidence grades: SR = Systematic review / meta-analysis (highest) · RCT = Randomized controlled trial · Reg = Regulatory/official guidance