Essential trace element cofactor for ~30 enzymes including manganese superoxide dismutase (MnSOD / SOD2), the primary mitochondrial antioxidant enzyme detoxifying superoxide
Cofactor for arginase converting arginine to ornithine and urea in the urea cycle
Cofactor for pyruvate carboxylase, a key gluconeogenesis and TCA cycle anaplerotic enzyme
Cofactor for glycosyltransferases involved in proteoglycan synthesis for cartilage and connective tissue
Activates many hydrolases, kinases, and decarboxylases including glutamine synthetase
Molecular + tissue targets
Mitochondrial antioxidant defense (MnSOD)
Bone and connective tissue (proteoglycan biosynthesis)
Gluconeogenesis and TCA cycle (pyruvate carboxylase)
Urea cycle (arginase)
Energy metabolism (multiple enzyme cofactor)
Dosage range
US IOM AI: 2.3 mg/day adult men, 1.8 mg/day adult women (2.0 mg/day pregnancy, 2.6 mg/day lactation). EFSA NDA AI: 3.0 mg/day adults. EFSA NRV (labelling): 2 mg. Common supplemental doses: 2-5 mg/day. US IOM Tolerable Upper Intake Level (UL): 11 mg/day adults. EFSA UL: not formally set (recommends moderate intake; concern about cumulative neurotoxicity at chronic high doses). Most adults obtain adequate manganese from dietary sources (whole grains, nuts, tea, leafy vegetables).
Safety notes
Manganese has a narrower therapeutic window than most trace minerals due to neurotoxicity concerns. Chronic occupational inhalation exposure causes manganism, a Parkinsonian-like neurological syndrome (Aschner 2007 Toxicol Appl Pharmacol). Oral high-dose chronic supplementation is less well-characterized for neurotoxicity but caution is warranted. Patients with chronic liver disease have reduced biliary manganese excretion and may accumulate manganese with supplementation — avoid in cholestasis. Iron deficiency increases intestinal manganese absorption — IDA patients may benefit from reduced supplemental manganese. Pregnancy/lactation: stay within AI; do not exceed UL. Drug interactions: tetracyclines and quinolones reduce manganese absorption; antacids may also impair absorption. Avoid combining high-dose Mn with high-dose iron in single supplement (competition for DMT1 transporter).
Cross-market regulatory status
🇺🇸 FDA
United States (FDA): NO 21 CFR Part 101 Subpart E Significant Scientific Agreement (SSA) authorized health claim exists for manganese. Manganese is not on the SSA list (limited to 12 specific nutrient-disease pairs). In US commerce, manganese in dietary supplements may carry only DSHEA structure/function statements (e.g., "supports bone health", "supports antioxidant defenses") accompanied by the mandatory FDA disclaimer "This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.". No FDA-authorized Qualified Health Claim (QHC) for manganese has been issued.
🇪🇺 EFSA
European Union (EFSA / Reg 432/2012): Four authorized Article 13(1) general-function health claims for manganese in the Annex to Commission Regulation (EU) No 432/2012 (CELEX:32012R0432) — normal energy-yielding metabolism, maintenance of normal bones, normal formation of connective tissue, protection of cells from oxidative stress. All four share the standard condition: claim may be used only for food which is at least a source of manganese per the SOURCE OF reference in the Annex to Regulation (EC) No 1924/2006 (>=15% NRV per 100 g/100 mL or per portion; NRV = 2 mg per Regulation (EU) No 1169/2011 Annex XIII). Character-level second-pass A/B framing confirmed Row 1 (energy-yielding metabolism) uses NO article "the"; Rows 2/3/4 use "the maintenance of" / "the normal formation of" / "the protection of cells". No Article 14 reduction-of-disease-risk claim authorized for manganese.
🇧🇷 ANVISA
Brasil (ANVISA): Manganês é constituinte autorizado para suplementos alimentares conforme Instrução Normativa IN nº 28/2018 (Anexos I/II/III/IV), com uso restrito a faixas etárias acima de 19 anos conforme Anexo III/IV. As alegações funcionais autorizadas (Anexo V) cobrem famílias consistentes com o escopo EFSA: metabolismo energético, manutenção de ossos, formação de tecido conjuntivo, proteção das células contra os radicais livres, todas iniciando com "O manganês auxilia ...". Verbatim character-for-character requer consulta direta ao PDF oficial do BVSMS (bvsms.saude.gov.br/bvs/saudelegis/anvisa/2018/int0028_26_07_2018.pdf) — authorized_claims ANVISA deste card intencionalmente ausentes até confirmação manual via leitura do PDF oficial.
Claro da Silva T et al.(2016)J Steroid Biochem Mol Biol
Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor
T1 verified · WEAK Mn relevance · cell culture + human duodenal tissue · Vit D3 induces SLC30A10 Mn/Zn efflux transporter expression (regulatory mechanism · not direct Mn supplementation outcome)
Authorized claims · verbatim (4)
Direct quotes from each jurisdiction's framework · never paraphrased · with framework reference and conditions of use.
🇪🇺 EFSA · 4 claims
Reg 432/2012
Manganese contributes to normal energy-yielding metabolism
Conditions: The claim may be used only for food which is at least a source of manganese 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.
Reg 432/2012
Manganese contributes to the maintenance of normal bones
Conditions: The claim may be used only for food which is at least a source of manganese 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.
Reg 432/2012
Manganese contributes to the normal formation of connective tissue
Conditions: The claim may be used only for food which is at least a source of manganese 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.
Reg 432/2012
Manganese contributes to the protection of cells from oxidative stress
Conditions: The claim may be used only for food which is at least a source of manganese 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.
Common use cases
Daily nutritional support for bone and connective tissue maintenance
Antioxidant cofactor support
Cofactor in multinutrient longevity / joint-bone blends
