IngredientsChemical name and symbol: Manganese is an important transition metal of the periodic table, with the atomic number 25 and symbol Mn. It is the first element of the Group VIIB elements, followed by technetium and rhenium, with an atomic weight of 54.94 g, a melting point of 1,246 °C, and a boiling point of 2,061 °C.
Occurrence in nature: Manganese is the third most abundant transition element, present in a number of industrial, biological, and environmental systems. It is a relatively common element in the earth's crust; the average concentration reaches nearly 0.1%, making it the twelfth most abundant element and fourth most abundant of the metals in commercial use. Manganese occurs in nature mainly in the form of oxide, carbonate, and silicate minerals. It is one of the most common elements in nature, which may be found in a free state in pyrolusite and rhodochrosite ores, although despite this relative abundance it is rarely found in its pure state and is usually combined with other minerals.
Oxidation states: Manganese is a first-row transition element found in nature as the stable isotope 55Mn. It exists in the oxidation states +2, +3, +4, +6, and +7, but the +2 (Mn(II)) oxidation state is most prevalent in biological systems.
Classification as a nutrient: Manganese is a trace mineral that is essential to the human body in small amounts; because the body cannot make it, it must be obtained in food or supplements. It is an essential trace element vital for diverse biological processes, including enzymatic catalysis, antioxidant defense, and neurotransmission.
Whole grains, legumes, avocados, grape juice, chocolate, seaweed, egg yolks, nuts, seeds, boysenberries, blueberries, pineapples, spinach, collard greens, peas, and green vegetables are among the best dietary sources of manganese. Common manganese-rich food servings include hazelnuts (1.6 mg/oz), brown rice (1.1 mg/½ cup), chickpeas (0.9 mg/½ cup), spinach (0.8 mg/½ cup), and black tea (0.5 mg/cup).
Processing techniques such as soaking, sprouting, or fermentation can significantly reduce phytate levels and enhance manganese bioavailability, while high heat or refining can strip bran layers, reducing mineral density. Although teas are rich sources of manganese, the tannins present in tea may moderately reduce the absorption of manganese.
Infants are exposed to varying amounts of manganese depending on their source of nutrition. Manganese concentrations in breast milk, cow-based formula, and soy-based formula range from 3 to 10 micrograms/liter (μg/L), 30 to 50 μg/L, and 200 to 300 μg/L, respectively. However, the bioavailability of manganese from breast milk is higher than from infant formulas, and manganese deficiencies in breastfed infants or toxicities in formula-fed infants have not been reported.
In dietary supplements, manganese is present in many different forms, including amino acid chelates such as manganese bisglycinate chelate, manganese glycinate chelate, and manganese aspartate, as well as manganese gluconate, manganese picolinate, manganese sulfate, manganese citrate, and manganese chloride.
No data are available on the relative bioavailability of different forms of supplemental manganese. Not all multivitamin/mineral supplements contain manganese, but those that do typically provide 1.0 to 4.5 mg manganese. Supplements containing only manganese, or manganese with a few other nutrients, are also available, and most contain 5 to 20 mg manganese.
The European Food Safety Authority (EFSA) has evaluated the safety and bioavailability of manganese aspartate, manganese ascorbate, manganese bisglycinate, and manganese pidolate as sources of manganese added for nutritional purposes to food supplements. Although no specific studies on bioavailability were available, it was considered that the bioavailability of these forms would be at least similar to that from other dissociable sources of manganese in the gastrointestinal tract.
Prehistoric and ancient use: The first utilization of manganese can be dated back to the Stone Age; humans were already using manganese dioxide as a pigment for their cave paintings during the upper Paleolithic period, approximately 17,000 years ago. Later in Ancient Greece, the presence of manganese in the iron ore used by the Spartans is a likely explanation as to why their steel weapons were superior to those of their enemies.
Ancient glassmaking: Manganese has also long been used in glassmaking. Egyptian and Roman glassmakers used manganese compounds to either add color to glass or remove color from it. The use as "glassmakers' soap" continued through the Middle Ages until modern times and is evident in 14th-century glass from Venice.
Early chemistry and medicine: In the middle of the 17th century, the German chemist Glauber obtained permanganate, the first usable manganese salt. By the mid-18th century, the Swedish chemist Carl Wilhelm Scheele used manganese dioxide to produce chlorine. After several failed attempts to isolate the metallic component of the mineral in the 1700s, Gahn successfully produced manganese metal in 1774 by heating pyrolusite in the presence of charcoal.
19th-century medicinal use: By the mid-19th century, manganese had entered formal medical practice. Since the publication of a first memoir in 1849, ferro-manganic medicines were extensively used in the south of France and in foreign countries. These preparations included pills of carbonate of iron and manganese (or of iodide), lozenges of lactate of iron and manganese, syrups of lactate or iodide of iron and manganese, ferro-manganic chocolate, and effervescing solutions of iron and manganese.
Recognition of neurotoxicity: Manganism, manganese poisoning, was first identified in 1837 by James Couper. Manganese toxicity was first described in a report of five manganese ore crushers presenting with muscular weakness, paraplegia, tremor, whispering speech, and a tendency to lean forward while walking; in two of the workers, symptoms progressed even after removal from the manganese ore-crushing operations.
Unlike plant-derived supplements, manganese is a single elemental mineral that functions primarily as a metalloenzyme cofactor and as a direct structural component of specific metalloenzymes. Its biological activity derives from its chemical properties as a transition metal capable of multiple oxidation states.
Manganese is an essential trace mineral that plays a number of roles in cellular systems, as cofactors for metalloenzymes, including oxidases and dehydrogenases, DNA and RNA polymerases, kinases, decarboxylases, and sugar transferases. It is a coenzyme that assists many enzymes involved in breaking down carbohydrates, proteins, and cholesterol; it also assists enzymes in building bones and keeping the immune and reproductive systems running smoothly; and it works with vitamin K to assist in wound healing by clotting the blood.
Manganese is known to play a critical role in the body's antioxidant defense system, particularly as a component of the enzyme superoxide dismutase (SOD), which combats oxidative stress. Of the SOD isoforms, manganese-dependent SOD (MnSOD) plays a major role due to its mitochondrial location — the main site of superoxide (O₂•⁻) production — and extensive research has focused on its capacity to modulate oxidative stress.
Manganese is the preferred cofactor of enzymes called glycosyltransferases; these enzymes are required for the synthesis of proteoglycans that are needed for the formation of healthy cartilage and bone.
Wound healing is a complex process that requires increased production of collagen. Manganese is required for the activation of prolidase, an enzyme that functions to provide the amino acid proline for collagen formation in human skin cells. A genetic disorder known as prolidase deficiency results in abnormal wound healing and is characterized by abnormal manganese metabolism.
Arginase is depressed in the livers of manganese-deficient rats, and manganese-deficient rats also show depressed plasma urea and elevated plasma ammonia concentrations. Arginase is a manganese-dependent enzyme essential for the urea cycle, which is the primary route for metabolic disposal of ammonia in mammals.
Manganese serves as a cofactor of several enzymes, including glutamine synthetase and manganese superoxide dismutase (MnSOD). Glutamine synthetase is particularly concentrated in astrocytes of the brain, where it is responsible for detoxifying ammonia and recycling glutamate — a process with important implications for neurological function and susceptibility to excitotoxicity at elevated manganese concentrations.
Manganese is absorbed in the small intestine. Most of the mineral is stored in bone, with smaller amounts in the liver, brain, kidneys, and pancreas. Manganese is excreted primarily in feces, and urinary excretion of manganese is low and has not been found to be sensitive to dietary manganese intake.
Low ferritin concentrations are associated with increased manganese absorption, creating a gender effect on manganese bioavailability. Men generally absorb less manganese than women, which may be related to the fact that men usually have higher iron stores than women.
Manganese competes with iron for absorption, and its absorption can be decreased by fiber, phytates, oxalic acid, calcium, and phosphorus. Phytic acid, present in high levels in soy and cereal-based foods, can inhibit trace element and mineral absorption; in adults, phytic acid has been reported to inhibit the absorption of iron, zinc, calcium, and manganese.
Supplemental magnesium (200 mg/day) has been shown to slightly decrease manganese bioavailability in healthy adults, either by decreasing manganese absorption or by increasing its excretion. In one set of studies, supplemental calcium (500 mg/day) slightly decreased manganese bioavailability in healthy adults.
Manganese levels are difficult to measure in the body as dietary intakes do not always correlate with blood levels.
Given the essential yet potentially toxic nature of this metal, body manganese levels are carefully regulated, largely by hepatobiliary excretion. Manganese may affect liver function, but the threshold of acute toxicity is very high. More than 95 percent of manganese is eliminated by biliary excretion, and any existing liver damage may slow this process, increasing its concentration in blood plasma.
The transporter SLC30A10 plays a pivotal role in Mn²⁺ homeostasis by exporting Mn²⁺ from cells, preventing toxic effects. Mutations in the SLC30A10 gene result in Mn²⁺ accumulation and lead to disorders such as hypermanganesemia with dystonia 1 (HMNDYT1). Endoderm-specific knockouts lacking SLC30A10 in the liver and gastrointestinal tract have markedly elevated manganese levels in the brain, blood, and liver. Thus, under basal physiological conditions, brain manganese is regulated by activity of SLC30A10 in the liver and gastrointestinal tract, and not the brain or just the liver.
Mutations in the SLC39A14 gene have been linked to manganese accumulation in the brain and childhood-onset parkinsonism dystonia, as SLC39A14 deficiency impairs hepatic manganese uptake and biliary excretion, resulting in the accumulation of manganese in the circulation and brain.
The official U.S. recommendations for daily manganese intake are as follows: 0.003 mg for infants up to six months of age; 0.6 mg for infants seven to twelve months; 1.2 mg for children one to three years; 1.5 mg for children four to eight years; 1.9 mg for males nine to thirteen years; 2.2 mg for males fourteen to eighteen years; 1.6 mg for females nine to eighteen years; 2.3 mg for males nineteen years of age and older; and 1.8 mg for females nineteen years of age and older. The recommendation for pregnant women is 2 mg, and for nursing women, 2.6 mg.
These Adequate Intakes (AIs) are based on observed dietary intakes in healthy populations, not on dose-response trials, which means they represent a floor rather than an optimized target.
Tolerable Upper Intake Level (UL): The Tolerable Upper Intake Level (UL) for adults is set at 11 mg/day. The Food and Nutrition Board (FNB) established manganese ULs for healthy individuals based on levels associated with whole-blood manganese concentrations above the normal range of 4 to 15 mcg/L and risk of neurotoxicity.
Supplemental dosing in clinical studies: Davis and Greger (1992) demonstrated that lymphocyte MnSOD activity was elevated in 47 women supplemented with 15 mg/day of manganese for more than 90 days. In a controlled study, five young men were fed a diet of ordinary foods (1.21 mg/day of manganese) supplemented with manganese sulfate or placebo at the evening meal to create five different levels of manganese intake; total manganese intakes ranged from 1.21 to 3.79 mg/day across different study phases.
Current research data show that manganese is actively involved in the processes of bone remodeling by modulating the activity of osteoblasts and osteoclasts — the main cells that regulate bone formation and resorption. Manganese is the preferred cofactor of enzymes called glycosyltransferases, which are required for the synthesis of proteoglycans needed for the formation of healthy cartilage and bone.
Observational evidence: A narrative review that included 4 eligible human studies found that all the literature published is in agreement in showing that osteoporotic women have lower serum manganese levels than women with normal bone mineral density, thus confirming the essential role of manganese in the synthesis of cartilage and bone collagen, as well as in bone mineralization.
Cross-sectional data: A study aimed to evaluate the relationship between blood manganese and bone mineral density/bone mineral content (BMD/BMC) using a representative sample from the National Health and Nutrition Examination Survey (NHANES); a total of 9,732 subjects over the age of 18 with available data were enrolled, and the relationship between blood manganese and BMD/BMC of the total body, spine, and femoral regions was evaluated using multivariate linear regression models. The results observed a negative association between blood manganese and BMD/BMC in the femoral neck and total body in the fully adjusted model, especially femoral neck BMD in women aged 50–70 years. The authors note this was a cross-sectional design with inherent limitations for causal inference.
Intervention trials: Considering human studies that evaluated the effectiveness of oral manganese supplementation for a long period (2 years) on the bone mineral density of menopausal women, both clinical trials showed that bone loss was significantly greater in the placebo group than in the group taking supplementation. However, these trials used manganese in combination with other micronutrients, making it difficult to isolate the specific contribution of manganese alone.
Assessment of evidence strength: Syntheses of experimental models, epidemiological studies, and clinical trials consistently demonstrate manganese's profound impact on bone mineralization and density, particularly through the regulation of key signaling pathways and enzymatic reactions. Maintaining adequate manganese levels is crucial for optimal bone health, as deficiency is linked to impaired bone growth and an increased risk of bone diseases. Conversely, excessive manganese exposure and accumulation can negatively impact bone metabolism. Overall, evidence supports an essential biological role; however, the number of high-quality clinical trials is limited, and evidence specifically for isolated manganese supplementation improving bone outcomes in humans remains preliminary.
Manganese-dependent SOD (MnSOD) plays a major role due to its mitochondrial location, the main site of superoxide production, and extensive research has focused on its capacity to modulate oxidative stress. Manganese-deficient animals have low manganese-superoxide dismutase (MnSOD) activity. Davis and Greger (1992) demonstrated that lymphocyte MnSOD activity was elevated in 47 women supplemented with 15 mg/day of manganese for more than 90 days.
Evidence for antioxidant activity in humans is largely biochemical; direct clinical endpoints (e.g., reduced disease incidence attributable to improved MnSOD activity from supplementation) have not been established in well-powered clinical trials.
Manganese, as the key component of the mitochondrial antioxidant MnSOD, plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in the inhibition of glucose-stimulated insulin secretion (GSIS). People with epilepsy or diabetes have lower-than-normal levels of manganese in their blood, which suggests — but definitely does not prove — that manganese supplements might be useful for these conditions; however, studies that could prove or disprove this idea have not been performed.
Animal evidence: Overexpression of MnSOD in high-fat-diet animals ameliorated the reduction in muscle glucose uptake by 50% (P <0.05), and decreased protein carbonylation was seen in MnSOD-overexpressing muscle, suggesting that interventions causing elevation of mitochondrial antioxidant activity may offer protection against diet-induced insulin resistance in skeletal muscle. This evidence is animal/preclinical only.
Human observational data: In a study of fifty established type 2 diabetics and 30 non-diabetic controls matched for age and sex (with similar dietary intakes of micronutrients assessed by 24-hour dietary recall), fasting plasma glucose and manganese levels were significantly higher in diabetes than in controls; manganese levels in diabetics were greater than twice the levels in controls. This suggests a complex, non-linear relationship between manganese status and diabetes rather than simple deficiency.
Evidence strength: The relationship between manganese and diabetes is characterized by observational associations and mechanistic animal data; dedicated human interventional trials of manganese supplementation for blood glucose outcomes are lacking. Other proposed therapeutic uses of manganese include regulating blood glucose levels to improve glucose tolerance and insulin sensitivity, which may be beneficial for patients with diabetes.
Wound healing is a complex process that requires increased production of collagen. Manganese is required for the activation of prolidase, an enzyme that functions to provide the amino acid proline for collagen formation in human skin cells. Glycosaminoglycan synthesis, which requires manganese-activated glycosyltransferases, may also play an important role in wound healing. Because manganese is involved in the production of collagen, it may help promote wound healing.
Manganese has been examined as a treatment for wound healing; however, manganese is often used in combination with other vitamins and/or minerals, and therefore the effects of manganese alone are difficult to determine. Evidence for wound healing applications remains at the mechanistic and in vitro level; no large-scale, adequately powered human clinical trials of isolated manganese supplementation for wound healing have been published.
One small but rigorous study suggests that getting enough manganese may help control symptoms of dysmenorrhea (menstrual pain). Other symptoms associated with low manganese status may include altered mood and increased premenstrual pain in women. The evidence base for this application consists of a single small study; independent replication and larger trials are needed before this can be considered an established use.
Manganese is an essential trace element for the development and function of the central nervous system. Alterations in manganese concentrations, whether excessive or deficient, can be accompanied by convulsions. Apparently, the first article explicitly relating manganese and epilepsy was published in 1938. Since then, there have been several reports relevant to a possible association between manganese and the occurrence and treatment of epilepsy; a systematic review of available quantitative evidence found that a search of The Cochrane Library included no systematic review or meta-analysis of an association between epilepsy and manganese.
Alterations in manganese concentrations, whether excessive or deficient, can be accompanied by convulsions; the effects of manganese intoxication, or manganism, are clinically similar to Parkinson's, due to alterations in dopamine, glutamate, and GABA regulatory systems. Evidence for manganese supplementation as a treatment for epilepsy is currently absent from clinical literature; the association is observational and correlational only.
The body also needs manganese for strong bones, reproduction, blood clotting, and a healthy immune system. Manganese is an essential trace element vital for diverse biological processes including enzymatic catalysis, antioxidant defense, and neurotransmission. Emerging research highlights its role beyond individual organ systems, revealing coordinated interactions between the liver, intestines, and brain. Specific human clinical evidence for manganese supplementation improving immune outcomes is currently limited.
Symptoms of manganese deficiency are rare and hard to spot. They may include slowed growth in children, abnormal glucose levels, changes in glucose tolerance, and abnormal cholesterol levels. Other symptoms may include a change in hair or beard color, altered mood, and increased premenstrual pain in women.
The evidence regarding deficiency of manganese in humans is scarce. Clinical deficiency is very rare, and blood measurement is usually performed to investigate possible toxicity rather than deficiency.
The Tolerable Upper Intake Level (UL) established by the Food and Nutrition Board is 11 mg/day from all sources combined for adults. The FNB established manganese ULs for healthy individuals based on levels associated with whole-blood manganese concentrations above the normal range of 4 to 15 mcg/L and risk of neurotoxicity; the ULs do not apply to individuals who are taking supplemental manganese under medical supervision.
Chronic exposure to elevated levels of manganese via occupational or environmental settings causes a neurological disorder known as manganism, resembling the symptoms of Parkinson's disease, such as motor deficits and cognitive impairment. Overexposure disrupts dopamine metabolism and mitochondrial function, leading to oxidative stress and inflammatory responses that contribute to neurological disorders such as manganism — a syndrome with Parkinson-like motor symptoms.
Manganism is associated with high exposures to manganese or metabolic disorders that induce hypermanganesemia, resulting in manganese deposition in the basal ganglia and other brain regions. Lower exposures would not be expected to produce the same clinical syndrome; however, exposure to lower manganese levels could produce a more subtle neurotoxic response that may lead to manganism or manganese toxicity under continued exposure.
The exact neurotoxic mechanism of manganese is uncertain, but there are clues pointing at the interaction of manganese with iron, zinc, aluminum, and copper. Based on a number of studies, disturbed iron metabolism could underlie the neurotoxic action of manganese.
Chelating agents such as ethylenediaminetetraacetic acid (EDTA) and para-aminosalicylic acid (PAS) have been shown to reduce acute manganese toxicity by promoting manganese excretion from the body. Intravenous EDTA chelation therapy has been clinically the primary treatment for manganism patients; however, several reports on its effectiveness have been controversial.
Iron deficiency increases manganese absorption and can therefore exacerbate symptoms of manganese toxicity. People with chronic liver disease have impaired manganese elimination in bile and are more susceptible to manganese neurotoxicity and other adverse effects of excess manganese intakes.
In addition to exposure in high-manganese-containing environments, patients with dysfunctional biliary systems (e.g., those requiring parenteral nutrition) are also more susceptible to manganese-induced toxicity, as optimal liver function is required for manganese secretion. Infants and children that receive manganese-containing supplements may also be at risk to manganese toxicity, as younger individuals tend to absorb and maintain higher manganese levels compared to adults. Iron-deficient individuals are also at a greater risk for manganese poisoning, as the two metals compete for shared transporters.
The potential risk for manganese toxicity is highest when bile excretion is low, such as in the neonate or in liver disease. Plasma manganese concentrations can become elevated in infants with cholestatic liver disease given supplemental manganese in total parenteral nutrition solutions.
Systematic reviews of human and animal data conducted to assess evidence regarding excess manganese intake and manganese-induced neurotoxicity found that available human and animal studies support neurotoxicity as a critical effect; however, data are not sufficient and suitable to characterize a dose-response relationship and identify a reference point for manganese-induced neurotoxicity. Given the findings on neurotoxicity and the potentially higher susceptibility of some subgroups in the general population, oral exposure to manganese beyond the amounts normally present in food and beverages could represent a risk of adverse health effects without evidence of any health benefit.
The absorption of manganese may be impaired by simultaneous intake of antacids or calcium or iron supplements. Iron deficiency has also been shown to increase the risk of manganese accumulation in the brain. Prior intakes of manganese and of other elements, such as calcium, iron, and phosphorus, have been found by some investigators to affect manganese retention. Adding calcium to human milk significantly reduced the absorption of manganese from 4.9 to 3.0 percent.
If excessive manganese is taken as supplements, side effects can include loss of appetite, slowed growth, and reproductive issues. It may also cause anemia because manganese competes with iron for absorption.
People who receive total parenteral nutrition (intravenous feeding) can have serious side effects from oral manganese supplements, as can people with liver problems.
Manganese toxicity can occur due to environmental exposures, especially from contaminated air or drinking water in communities near mining, welding, or alloy production. Populations at risk include welders and individuals with impaired liver function, who exhibit reduced biliary manganese clearance. Manganism was described in a group of Moroccan miners and in a group of Chilean miners; of approximately 4,000 miners working in three mines in Morocco, 150 cases of manganism were observed, all in workers who spent considerable time underground, presumably with limited ventilation and a high degree of inhalation exposure. In these workers, onset of symptoms occurred after months to years of work.
Health conditions that Manganese may help support.
Manganese is the catalytic metal center of mitochondrial MnSOD, the primary enzyme neutralizing superoxide radicals in energy-producing cells. This is among the most well-documented roles of manganese in human biology, confirmed by multiple peer-reviewed reviews and institutional sources.
Manganese is required for the synthesis of proteoglycans and glycosaminoglycans in cartilage, structures degraded in osteoarthritis. MnSOD activity is reduced in arthritic joints, and oxidative stress contributes to cartilage degradation. Evidence for therapeutic supplementation benefit is limited.
Multiple population-based studies associate lower blood manganese with higher rates of diabetes and impaired glucose regulation. Manganese acts as a cofactor for pyruvate carboxylase and phosphoenolpyruvate carboxykinase, enzymes critical for gluconeogenesis, and may potentiate insulin action. Evidence is observational and sex-specific; intervention trials in humans are sparse.
Manganese is a required cofactor for glycosyltransferases involved in proteoglycan synthesis in bone matrix and for superoxide dismutase protecting osteoblasts. The NIH ODS and National Academy of Sciences recognize it as an essential trace element for bone health, with deficiency causing skeletal abnormalities in animal models.
Manganese is an essential trace mineral and obligate cofactor for glycosyltransferases required for glycosaminoglycan biosynthesis in cartilage proteoglycans and for MnSOD protecting chondrocytes from oxidative damage. Manganese deficiency impairs proteoglycan synthesis and cartilage integrity in animal models. It is a standard component of evidence-based combination cartilage supplements (e.g., Cosamin-DS with glucosamine, chondroitin, and manganese) validated in clinical trials.
Manganese is required for pyruvate carboxylase—a key enzyme in the TCA cycle and gluconeogenesis—and MnSOD protects the mitochondria where ATP is generated. Manganese's role in cellular energy metabolism is well-established biochemically.
Manganese is required for the activity of glycosyltransferases involved in proteoglycan synthesis in bone matrix and for IGF-1 signaling in bone formation. Deficiency causes skeletal abnormalities. A randomized controlled trial found a calcium supplement combined with manganese, copper, and zinc was more effective than calcium alone for preventing bone loss.
Manganese is an essential trace element serving as a cofactor for antioxidant enzyme manganese superoxide dismutase and enzymes in bone formation and carbohydrate metabolism. IOM-established AIs exist for all pediatric age groups. NIH ODS-funded label surveys confirm manganese in children's MVMs, and it is present in all major branded pediatric formulas.
Manganese is essential to mitochondrial manganese superoxide dismutase (MnSOD), which scavenges superoxide radicals that drive inflammatory signaling. Reduced MnSOD expression is observed in multiple inflammatory diseases, and MnSOD mimetics suppress inflammatory responses in preclinical models. The direct anti-inflammatory benefit of dietary manganese supplementation in humans has not yet been established in controlled trials.
Manganese is a required cofactor for glycosyltransferases involved in glycosaminoglycan and glycoprotein synthesis, making it essential for cartilage and connective tissue ECM formation. It also inhibits elastin-degrading elastases and participates in cross-linking of collagen fibrils. In vitro studies show manganese cofactors are required for glucosamine conversion to hyaluronic acid and chondroitin sulfate.
Human and animal studies document lower blood manganese levels in people with epilepsy, and manganese is a cofactor for glutamine synthetase—critical to regulating excitatory glutamate in the brain. MnSOD activity in mitochondria also modulates seizure susceptibility. Direct therapeutic evidence from human supplementation trials is absent.
Manganese is listed by the NIH ODS as involved in reproduction, and peer-reviewed mineral-fertility reviews identify it as contributing to hormonal regulation, ovarian function, and protection against oxidative-stress-driven infertility. Direct clinical trial evidence for supplementation improving fertility outcomes is lacking.
Manganese is essential for skeletal development through glycosyltransferase-mediated proteoglycan synthesis, collagen formation, and bone mineralization. Deficiency in animals causes skeletal abnormalities, reproductive failure, and impaired growth; the 2018 review confirms development as a primary role.
Manganese co-factors pyruvate carboxylase and PEPCK in hepatic gluconeogenesis, and preclinical data indicate it directly activates hepatic Akt in insulin signaling. Population studies show sex-specific associations between manganese status and insulin resistance markers.
One controlled metabolic study found that lower dietary manganese intake was associated with increased pain symptoms during the menstrual phase, independent of calcium intake. Evidence is limited to a single small trial and requires replication.
Manganese serves as a cofactor for arginase, pyruvate carboxylase, glutamine synthetase, and MnSOD—enzymes that are central to carbohydrate, amino acid, cholesterol, and energy metabolism. These are well-established biochemical roles confirmed by the NIH ODS and multiple peer-reviewed sources.
Manganese is required for glutamine synthetase activity in astrocytes, which regulates glutamate-glutamine cycling and neurotransmitter homeostasis in the brain. MnSOD protects neurons from mitochondrial oxidative stress. Both deficiency and excess manganese disrupt normal nervous system function.
Manganese is a trace mineral that serves as a cofactor for enzymes required in glycosaminoglycan and proteoglycan synthesis in bone matrix. Inadequate manganese intake impairs bone formation, and it is listed among essential bone health minerals by major nutritional authorities. Low manganese is associated with increased bone resorption and reduced bone density.
A controlled metabolic trial found that low dietary manganese was associated with increased mood and pain symptoms during the premenstrual phase. A PMC review identifies manganese among minerals potentially involved in PMS pathophysiology, though only one study with combined manganese/calcium exposure exists.
Altered manganese metabolism is documented in rheumatoid arthritis, with elevated granulocyte manganese correlating with disease activity markers. MnSOD activity is reduced in RA joint tissue. No completed RCT has demonstrated therapeutic benefit of manganese supplementation in RA.
Manganese activates prolidase, the enzyme that recycles proline for collagen synthesis in human skin cells. Deficiency of this pathway impairs dermal integrity, and manganese-containing topical preparations have been studied for chronic wound management.
Manganese participates in the synthesis of thyroxine and is required for normal thyroid function; deficiency may contribute to hypothyroid conditions. Excess manganese intake may conversely interfere with thyroid hormone production.
Manganese activates prolidase to supply proline for collagen synthesis and activates glycosyltransferases for glycosaminoglycan production—both required in wound repair. Early clinical studies of topical manganese-containing formulations show promising results for chronic wound healing.
Manganese is traditionally recommended in integrative MG protocols based on its proposed role in facilitating choline assimilation and supporting muscular contraction. Traditional sources state that muscular coordination and strength are diminished without adequate manganese, and that it is essential for the assimilation of choline needed for neuromuscular function in MG.
Body systems that Manganese may help support.
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