Mineral

Manganese

Manganese (Mn, element 25)

Evidence TierDWADA NOT PROHIBITED

tuneTypical Dose

2–5 mg per day

watchEffect Window

Not applicable. Manganese supplementation has no acute or chronic performance/cognitive effects in replete individuals.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Manganese is a trace mineral required for bone formation and antioxidant enzymes such as MnSOD. It is used mainly to correct rare deficiency rather than for routine performance benefits.

Adequate manganese supports connective tissue formation, cartilage metabolism, and antioxidant defense. Benefits are most relevant when deficiency occurs due to malabsorption or severe dietary inadequacy. Minority evidence links manganese status to wound healing and oxidative stress resilience biomarkers. Excess intake can accumulate and cause neurologic toxicity, so any use should be conservative and deficiency focused.

Essential cofactor for manganese-dependent enzymes including SOD2 (antioxidant defense), arginase (urea cycle), and pyruvate carboxylase (gluconeogenesis).

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Essential cofactor for mitochondrial SOD2 antioxidant defense
  • Required for bone formation and glucose metabolism
  • Clinical deficiency virtually unknown from varied diets

Secondary Outcomes

  • Cofactor for arginase and pyruvate carboxylase
  • Part of bone health mineral complex with calcium, magnesium, zinc

Safety

Contraindications and Interactions

Contraindications

  • Liver disease (impaired hepatic clearance leads to accumulation)
  • Iron deficiency (increases manganese absorption)

Side effects

  • Neurological toxicity at chronic high doses (manganism, an irreversible Parkinson's-like syndrome)

Interactions

  • Antacids and PPIs may reduce manganese absorption

Avoid if

  • Liver disease or biliary dysfunction
  • Occupational manganese exposure (welders, miners)

Evidence

Study-level References

manganese-SRC-001Narrative review
Sourceopen_in_new

Li L, Yang X. The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid Med Cell Longev. 2018;2018:7580707. doi:10.1155/2018/7580707. PMID:29849912.

Population: Review of human and animal studies on manganese and metabolic disease

Dose protocol: Narrative review of manganese biochemistry, MnSOD role, and metabolic disease links

Key findings: Manganese is essential for MnSOD-mediated mitochondrial antioxidant defense. Both deficiency and excess are associated with adverse metabolic and neuropsychiatric effects, with overexposure increasing ROS and oxidative stress.

Notes: Supports essentiality and safety-risk framing. Not evidence for isolated ergogenic/nootropic supplementation benefits.

Paper content

This review examines the role of manganese in metabolic diseases including type 2 diabetes, obesity, insulin resistance, and nonalcoholic fatty liver disease. Manganese is essential for the synthesis and activation of many enzymes and is a required component of MnSOD, which scavenges reactive oxygen species in mitochondria. Both manganese deficiency and excess exposure can increase ROS generation, exacerbate oxidative stress, and contribute to the pathogenesis of metabolic diseases.

manganese-SRC-002Narrative review
Sourceopen_in_new

Finley JW, Davis CD. Manganese deficiency and toxicity: are high or low dietary amounts of manganese cause for concern? BioFactors. 1999;10(1). doi:10.1002/biof.5520100102. PMID:10475586.

Population: General population, with focus on North American dietary intake patterns

Dose protocol: Review of dietary manganese adequacy and deficiency case reports

Key findings: Only a few vaguely described cases of manganese deficiency exist in the medical literature. Deficiency is not a public health concern in free-living populations eating varied diets.

Notes: Foundational evidence for manganese essentiality. Highlights that deficiency must be experimentally induced.

Paper content

Manganese is essential for several enzyme activities but toxic in large amounts. Isolated cases of deficiency are rare in North America, though low Mn-dependent superoxide dismutase activity may relate to cancer susceptibility. Vegetarian diets and iron deficiency may increase Mn body burden, warranting further study of chronic Mn toxicity under these conditions.

manganese-SRC-003Narrative review
Sourceopen_in_new

Martins AC, Oliveira-Paula GH, Tinkov AA, et al. Role of manganese in brain health and disease: Focus on oxidative stress. Free Radic Biol Med. 2025;232. doi:10.1016/j.freeradbiomed.2025.03.013. PMID:40086492.

Population: Review of preclinical and clinical literature on manganese neurotoxicity

Dose protocol: Narrative review of manganese in brain health focusing on oxidative stress pathways and MnSOD function

Key findings: Manganese is essential for MnSOD-mediated mitochondrial antioxidant defense. Excess manganese promotes neurotoxicity through ROS generation, mitochondrial dysfunction, ER stress, inflammasome activation, and epigenetic modifications.

Notes: Reinforces essentiality of manganese for oxidative stress defense while detailing neurotoxic mechanisms from overexposure. Does not provide evidence for supplementation benefits in replete individuals.

Paper content

This review synthesizes knowledge on manganese-induced oxidative stress and its role in neurotoxicity. It discusses how manganese promotes toxicity through ROS generation, mitochondrial dysfunction, ER stress, and epigenetic modifications, while identifying therapeutic compounds with protective effects.

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