Manganese

Manganese (Mn) is an essential trace mineral that functions primarily as a co‑factor for several enzymes involved in carbohydrate, protein, and lipid metabolism. In humans it is most notable for supporting antioxidant defenses, bone formation, and the synthesis of neurotransmitters.

• Bone health: Mn is a critical component of the enzyme glycosyltransferase, which facilitates the formation of proteoglycans in cartilage and bone matrix, improving bone density and reducing fracture risk (Berglund et al., 2022).
• Antioxidant protection: As a core element of mitochondrial super‑oxide dismutase (Mn‑SOD), it neutralizes super‑oxide radicals, lowering oxidative stress and supporting cardiovascular health (Zhang & Liu, 2021).
• Metabolic support: Mn‑dependent enzymes (e.g., pyruvate carboxylase, arginase) enable gluconeogenesis and amino‑acid metabolism, aiding glucose regulation and muscle recovery (Miller et al., 2020).
• Neuro‑cognitive function: Adequate Mn supports dopamine synthesis and neuronal membrane stability, contributing to normal cognitive development and executive function (Kaur et al., 2023).
• Wound healing: Mn‑dependent collagen cross‑linking accelerates tissue repair, making it useful for post‑injury recovery (Roh et al., 2022).

• Catalytic co‑factor: Manganese acts mainly as a catalytic co‑factor for >20 enzymes.
• Antioxidant activity: The most studied is mitochondrial Mn‑SOD, which converts the super‑oxide anion (O₂⁻) into hydrogen peroxide (H₂O₂) and water, thereby limiting oxidative damage.
• Collagen synthesis and wound repair: Mn also serves as a co‑factor for 2‑oxoglutarate‑dependent dioxygenases (e.g., prolyl‑hydroxylase) that regulate collagen synthesis and hypoxia‑inducible factor (HIF) stability, influencing angiogenesis and wound repair.
• Urea cycle and gluconeogenesis: In the liver, Mn‑dependent arginase converts arginine to ornithine, a key step in the urea cycle, while pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate, supporting gluconeogenesis.
• Cartilage and bone matrix: Additionally, Mn‑dependent glycosyltransferases synthesize glycosaminoglycans essential for cartilage and bone matrix.

• Transition metal: Manganese is a transition metal (atomic number 25) with an electron configuration of [Ar] 3d⁵ 4s².
• Supplement forms: In supplements it appears as the divalent cation Mn²⁺, commonly complexed as manganese sulfate (MnSO₄·H₂O), manganese gluconate (C₁₂H₂₂MnO₁₄), or manganese chelate (e.g., Mn‑bisglycinate).
• Physical properties: The element’s metallic form is grey‑white, with a melting point of 1244 °C and a density of 7.21 g cm⁻³.
• Enzyme binding: Mn²⁺ exhibits high affinity for oxygen‑ and nitrogen‑donor ligands, forming octahedral complexes that facilitate enzyme binding.
• Oxidation states: The oxidation state can range from +2 to +7 (e.g., MnO₄⁻), though only +2 is biologically relevant.

• Dietary sources: Dietary sources include whole grains (brown rice, oats), legumes (soybeans, lentils), nuts (hazelnuts, almonds), leafy greens (spinach, kale), and seafood (mussels, oysters).
• Extraction: Commercially, Mn is extracted from the ore pyrolusite (MnO₂) or rhodochrosite (MnCO₃) via acid leaching and precipitation as sulfate or chloride salts.
• Chelated forms: Synthetic chelated forms (e.g., manganese‑glycinate) are produced by reacting Mn²⁺ salts with amino‑acid ligands under controlled pH, improving bioavailability.
• Supplement quality: High‑quality supplements adhere to USP/NF or USP monographs, undergo heavy-metal testing, and are manufactured under GMP.
• Pharmaceutical grade: For clinical use, pharmaceutical‑grade manganese sulfate‑monohydrate (≥99% purity) is preferred to ensure consistent elemental manganese content.