Manganese is an essential trace mineral vital for antioxidant defense, bone formation, and carbohydrate metabolism. It’s found in foods like whole grains, nuts, and leafy greens, with most adults needing just 1.8-2.3 mg daily. Manganese works as a cofactor for enzymes involved in antioxidant protection, cartilage formation, and energy production. While deficiency is rare in humans consuming varied diets, inadequate intake may affect bone health, glucose metabolism, and antioxidant defense. Manganese has a moderate safety profile, with excess potentially affecting neurological health, particularly with long-term exposure. Manganese gluconate and citrate are well-absorbed forms, while manganese glycinate offers superior absorption for those with digestive sensitivities. Maintaining proper manganese-iron balance is important, as high-dose iron can reduce manganese absorption.
Alternative Names: Manganese Sulfate, Manganese Gluconate, Manganese Citrate, Manganese Glycinate
Categories: Mineral, Essential Mineral, Trace Element
Primary Longevity Benefits
- Antioxidant Function
- Bone Health
- Metabolic Support
Secondary Benefits
- Joint Health
- Glucose Metabolism
- Connective Tissue Formation
- Nervous System Function
- Immune Support
Mechanism of Action
Primary Mechanisms
| Mechanism | Description |
|---|---|
| Antioxidant Defense via Manganese Superoxide Dismutase | Manganese serves as a critical component of manganese superoxide dismutase (MnSOD), a primary antioxidant enzyme located in mitochondria. MnSOD catalyzes the conversion of superoxide radicals (O2•-) to hydrogen peroxide (H2O2), which can then be neutralized by other antioxidant enzymes like catalase and glutathione peroxidase. This antioxidant function is particularly important in mitochondria, where energy production generates significant oxidative byproducts. MnSOD protects mitochondrial DNA, proteins, and lipids from oxidative damage, potentially influencing cellular aging, cancer development, and neurodegenerative processes. Unlike cytosolic copper-zinc superoxide dismutase (Cu-Zn SOD), MnSOD is essential for life, as demonstrated by the lethality of MnSOD knockout in animal models. |
| Carbohydrate Metabolism via Pyruvate Carboxylase and Glycosyltransferases | Manganese activates several enzymes involved in carbohydrate metabolism, most notably pyruvate carboxylase, which catalyzes the conversion of pyruvate to oxaloacetate in the first step of gluconeogenesis (glucose production). This process is essential for maintaining blood glucose levels during fasting or intense exercise. Manganese also activates glycosyltransferases, enzymes that transfer sugar moieties to form glycoproteins, glycolipids, and glycosaminoglycans. These enzymes are crucial for the synthesis of proteoglycans in cartilage and bone, as well as for proper glycosylation of proteins involved in cell recognition, signaling, and immune function. Through these roles, manganese influences both energy metabolism and the structural integrity of tissues. |
| Bone and Connective Tissue Formation via Glycosyltransferases and Prolidase | Manganese is essential for the formation and maintenance of healthy bone and connective tissue through multiple pathways. It activates glycosyltransferases required for the synthesis of proteoglycans and glycosaminoglycans, which form the ground substance of cartilage and bone matrix in which mineralization occurs. Manganese also activates prolidase, an enzyme involved in the final step of collagen recycling and formation, which breaks down dipeptides containing proline or hydroxyproline, making these amino acids available for collagen synthesis. Additionally, manganese influences bone mineralization through effects on osteoblast and osteoclast activity, potentially affecting the balance between bone formation and resorption. These combined actions make manganese important for bone development, growth, and repair. |
| Urea Cycle Function via Arginase | Manganese serves as a cofactor for arginase, an enzyme in the urea cycle that catalyzes the hydrolysis of arginine to ornithine and urea. This reaction is the final step in the urea cycle, which is essential for the elimination of excess nitrogen from the body, primarily as a byproduct of protein metabolism. Arginase activity is particularly important in the liver, where most of the urea cycle occurs. By supporting arginase function, manganese contributes to ammonia detoxification and nitrogen balance. Impaired arginase activity can lead to elevated ammonia levels, which can be neurotoxic. Additionally, arginase plays roles in nitric oxide regulation, wound healing, and immune function through its effects on arginine availability. |
| Neurotransmitter Synthesis and Metabolism | Manganese influences neurotransmitter function through several mechanisms. It activates enzymes involved in the synthesis and metabolism of neurotransmitters, including glutamine synthetase, which converts glutamate to glutamine in astrocytes, helping to regulate glutamate levels in the brain. Manganese also affects the activity of monoamine oxidase (MAO), which metabolizes monoamine neurotransmitters like dopamine, serotonin, and norepinephrine. Additionally, manganese influences the function of neurotransmitter receptors and transporters, potentially affecting synaptic transmission and neuronal excitability. These roles make manganese important for normal brain function, with both deficiency and excess potentially causing neurological symptoms. |
Secondary Mechanisms
| Mechanism | Description |
|---|---|
| Immune System Regulation | Manganese influences immune function through multiple pathways. It affects the production and function of immune cells, including macrophages and lymphocytes. Manganese-dependent superoxide dismutase protects immune cells from oxidative damage during inflammatory responses. Manganese also influences the production of cytokines and other signaling molecules involved in immune regulation. Additionally, manganese-dependent glycosyltransferases are important for the proper glycosylation of immune proteins, affecting their function in cell recognition and signaling. These combined effects make manganese important for balanced immune responses, with both deficiency and excess potentially disrupting immune function. |
| Thyroid Hormone Metabolism | Manganese plays a role in thyroid hormone metabolism and function. It influences the activity of deiodinase enzymes that convert thyroxine (T4) to the more active triiodothyronine (T3). Manganese also affects thyroid hormone receptor function and may influence the synthesis and secretion of thyroid hormones. Additionally, manganese-dependent superoxide dismutase protects the thyroid gland from oxidative damage. Interestingly, thyroid function can also influence manganese metabolism, creating a bidirectional relationship. Both manganese deficiency and excess may affect thyroid function, highlighting the importance of balanced manganese status for optimal thyroid health. |
| Lipid and Cholesterol Metabolism | Manganese influences lipid metabolism through several mechanisms. It affects the activity of enzymes involved in fatty acid synthesis and oxidation. Manganese also plays a role in cholesterol metabolism, potentially affecting cholesterol synthesis, transport, and excretion. Additionally, manganese-dependent superoxide dismutase protects lipids from oxidative damage, which is important for maintaining cell membrane integrity and preventing lipid peroxidation. These roles make manganese relevant to cardiovascular health and metabolic function, with some research suggesting associations between manganese status and lipid profiles. |
| Vitamin Metabolism | Manganese interacts with various vitamins and affects their metabolism. It works synergistically with B vitamins in various metabolic processes, including energy production and neurotransmitter synthesis. Manganese also influences vitamin E function through its antioxidant effects, potentially complementing vitamin E’s role in protecting cell membranes from oxidative damage. Additionally, manganese affects vitamin K metabolism and function, which is relevant to both blood clotting and bone health. These interactions highlight the importance of balanced nutrition, as multiple nutrients often work together in metabolic pathways. |
| Reproductive Function | Manganese plays roles in reproductive health and fertility. In males, manganese is important for testicular function and sperm production, potentially affecting sperm motility and viability. In females, manganese influences ovarian function and hormone production. Manganese is also important during pregnancy for fetal development, particularly for skeletal formation and neurological development. These reproductive roles are likely mediated through manganese’s functions in hormone metabolism, antioxidant protection, and enzyme activation. Both deficiency and excess of manganese may affect reproductive function, emphasizing the importance of balanced manganese status. |
Tissue Specific Actions
| Tissue | Actions |
|---|---|
| Brain and Nervous System | In the brain, manganese is essential for several functions but must be tightly regulated as both deficiency and excess can cause neurological problems. Manganese activates glutamine synthetase in astrocytes, which converts the excitatory neurotransmitter glutamate to glutamine, helping to regulate glutamate levels and prevent excitotoxicity. Manganese also influences the metabolism of other neurotransmitters, including dopamine, serotonin, and GABA, affecting mood, cognition, and motor function. Manganese-dependent superoxide dismutase provides antioxidant protection to neurons and glial cells, potentially reducing oxidative stress associated with neurodegenerative diseases. However, excess manganese can accumulate in the brain, particularly in the basal ganglia, potentially causing manganism, a Parkinson’s-like condition characterized by movement disorders and cognitive impairment. |
| Skeletal System | In bone and cartilage, manganese plays crucial roles in development, growth, and maintenance. Manganese activates glycosyltransferases required for the synthesis of proteoglycans and glycosaminoglycans, which form the ground substance of cartilage and bone matrix. These compounds provide structural support and create the environment for proper mineralization. Manganese also activates prolidase, supporting collagen formation, which provides tensile strength to bone. Additionally, manganese influences bone cell function, potentially affecting the balance between bone formation by osteoblasts and bone resorption by osteoclasts. Manganese-dependent superoxide dismutase protects bone cells from oxidative damage, which may be relevant to age-related bone loss. Manganese deficiency in animals causes skeletal abnormalities, reduced bone mineral density, and impaired growth, highlighting its importance for skeletal health. |
| Liver | The liver is a major site of manganese metabolism and function. Manganese activates arginase in the urea cycle, supporting ammonia detoxification and nitrogen elimination. Manganese also influences carbohydrate metabolism in the liver through its role in pyruvate carboxylase activation, affecting gluconeogenesis and glucose homeostasis. Additionally, manganese plays roles in lipid metabolism in the liver, potentially affecting cholesterol synthesis and fatty acid metabolism. Manganese-dependent superoxide dismutase provides antioxidant protection to liver cells, which may be relevant to liver diseases associated with oxidative stress. The liver also plays a key role in manganese homeostasis, as excess manganese is primarily eliminated through biliary excretion. Liver disease can affect manganese metabolism, potentially leading to manganese accumulation and neurological symptoms. |
| Pancreas | In the pancreas, manganese influences both exocrine and endocrine functions. Manganese activates enzymes involved in carbohydrate metabolism, potentially affecting insulin synthesis and secretion from pancreatic beta cells. Manganese-dependent superoxide dismutase protects pancreatic cells from oxidative damage, which is implicated in the development of diabetes. Some research suggests that manganese status may influence glucose tolerance and insulin sensitivity, with potential implications for diabetes risk. Manganese also supports the function of digestive enzymes produced by the exocrine pancreas, contributing to proper nutrient digestion and absorption. |
| Reproductive Organs | In reproductive tissues, manganese supports various functions related to fertility and reproduction. In the testes, manganese influences testosterone production and sperm development, potentially affecting sperm count, motility, and viability. In the ovaries, manganese plays roles in hormone production and ovulation. Manganese-dependent superoxide dismutase provides antioxidant protection to reproductive cells, which may be relevant to fertility issues associated with oxidative stress. During pregnancy, manganese is important for placental function and fetal development, particularly for skeletal formation and neurological development. Both deficiency and excess of manganese may affect reproductive function, highlighting the importance of balanced manganese status for reproductive health. |
Molecular Pathways
| Pathway | Description |
|---|---|
| Manganese Superoxide Dismutase (MnSOD) Antioxidant Pathway | Manganese superoxide dismutase (MnSOD or SOD2) is a homotetramer containing one manganese atom per subunit, located primarily in mitochondria. The pathway begins with the production of superoxide radicals (O2•-) as byproducts of mitochondrial electron transport during cellular respiration. MnSOD catalyzes the dismutation of these superoxide radicals to hydrogen peroxide (H2O2) and oxygen (O2) through a two-step process involving the cycling of manganese between Mn3+ and Mn2+ oxidation states. The resulting H2O2 is then neutralized by other antioxidant enzymes, including catalase and glutathione peroxidase, completing the detoxification process. MnSOD expression is regulated by various factors, including oxidative stress, inflammatory cytokines, and transcription factors like NF-κB and FOXO3a. This pathway is essential for protecting mitochondria from oxidative damage, maintaining mitochondrial function, and preventing cell death. Impaired MnSOD function has been implicated in aging, cancer, neurodegenerative diseases, and other conditions associated with oxidative stress. |
| Pyruvate Carboxylase in Gluconeogenesis | Pyruvate carboxylase is a manganese-dependent enzyme that catalyzes the first committed step of gluconeogenesis, the conversion of pyruvate to oxaloacetate. This biotin-containing enzyme requires manganese (or magnesium) as a cofactor for optimal activity. The pathway begins with pyruvate, a product of glycolysis, entering mitochondria. Pyruvate carboxylase, activated by acetyl-CoA and manganese, adds a carboxyl group to pyruvate using bicarbonate as a substrate, forming oxaloacetate. This reaction requires ATP and involves the transfer of CO2 via a biotin prosthetic group. Oxaloacetate can then be converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase, continuing the gluconeogenesis pathway to eventually form glucose. This process is crucial for maintaining blood glucose levels during fasting, intense exercise, or low-carbohydrate diets. Pyruvate carboxylase also plays roles in lipogenesis and amino acid metabolism by providing oxaloacetate for the citric acid cycle. Manganese deficiency can reduce pyruvate carboxylase activity, potentially affecting glucose homeostasis and energy metabolism. |
| Glycosyltransferases in Proteoglycan Synthesis | Glycosyltransferases are a family of manganese-dependent enzymes that catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. In proteoglycan synthesis, this pathway begins with the production of a core protein. Glycosyltransferases, activated by manganese, then sequentially add specific sugar residues to form the glycosaminoglycan chains attached to the core protein. For example, in chondroitin sulfate synthesis, xylosyltransferase first adds xylose to specific serine residues in the core protein. Subsequent glycosyltransferases add galactose, galactose, and glucuronic acid to form the linkage region, followed by alternating additions of N-acetylgalactosamine and glucuronic acid to extend the chain. Similar processes occur for other glycosaminoglycans like heparan sulfate and keratan sulfate. These proteoglycans are essential components of cartilage, bone matrix, and other connective tissues, providing structural support, hydration, and resistance to compression. Manganese deficiency can impair glycosyltransferase activity, potentially affecting connective tissue formation and maintenance. |
| Arginase in the Urea Cycle | Arginase is a manganese-dependent enzyme that catalyzes the final step of the urea cycle, the hydrolysis of arginine to ornithine and urea. This pathway begins with ammonia, a toxic byproduct of protein metabolism, entering the urea cycle in the liver. Through a series of reactions involving carbamoyl phosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase, and argininosuccinate lyase, nitrogen is incorporated into arginine. Arginase, activated by manganese, then cleaves arginine to produce ornithine (which reenters the cycle) and urea (which is excreted in urine). This process is essential for ammonia detoxification and nitrogen elimination. Arginase exists in two isoforms: Arginase I, primarily in the liver as part of the urea cycle, and Arginase II, found in various tissues and involved in arginine and ornithine metabolism outside the urea cycle. Manganese deficiency can reduce arginase activity, potentially affecting ammonia detoxification and nitrogen balance. Additionally, arginase competes with nitric oxide synthase for arginine, influencing nitric oxide production and vascular function. |
| Prolidase in Collagen Metabolism | Prolidase (peptidase D) is a manganese-dependent enzyme that catalyzes the final step in collagen degradation, the hydrolysis of dipeptides containing proline or hydroxyproline at the C-terminal position. This pathway begins with the breakdown of collagen by various proteases, producing smaller peptides. Prolidase, activated by manganese, specifically cleaves dipeptides with C-terminal proline or hydroxyproline, releasing these amino acids for reuse in collagen synthesis. This recycling is particularly important because proline and hydroxyproline constitute about 25% of collagen amino acids and are essential for collagen’s triple helical structure and stability. Prolidase activity is crucial for collagen turnover, wound healing, and tissue remodeling. The enzyme requires two manganese ions per subunit for optimal activity, with manganese playing both structural and catalytic roles. Prolidase deficiency, a rare genetic disorder, causes impaired collagen metabolism, wound healing problems, skin lesions, and skeletal abnormalities, highlighting the importance of this pathway. Manganese supplementation has been investigated as a potential therapeutic approach for enhancing prolidase activity in certain conditions. |
Metabolic Interactions
| Interaction | Description |
|---|---|
| Manganese-Iron Balance | Manganese and iron have a complex antagonistic relationship in metabolism. They compete for absorption in the intestine, with high iron intake potentially reducing manganese absorption and vice versa. Both minerals are transported by transferrin in the bloodstream and can compete for binding. They also share transport mechanisms across the blood-brain barrier, including divalent metal transporter 1 (DMT1). This competition is particularly significant in the brain, where excess manganese can displace iron, potentially affecting dopamine metabolism and contributing to neurotoxicity. Conversely, iron deficiency can enhance manganese absorption and accumulation, potentially increasing susceptibility to manganese toxicity. Maintaining appropriate balance between these minerals is important for optimal function of iron-dependent and manganese-dependent enzymes. This interaction has clinical relevance in conditions like iron-deficiency anemia, which may alter manganese metabolism, and in occupational manganese exposure, which may affect iron status. |
| Manganese and Glucose Metabolism | Manganese influences glucose metabolism through multiple mechanisms. It activates pyruvate carboxylase, supporting gluconeogenesis and glucose production. Manganese also affects insulin synthesis, secretion, and action, potentially influencing glucose uptake and utilization in peripheral tissues. Additionally, manganese-dependent superoxide dismutase protects pancreatic beta cells from oxidative damage, which is implicated in diabetes development. Some research suggests associations between manganese status and diabetes risk, with both deficiency and excess potentially affecting glucose tolerance and insulin sensitivity. This interaction has clinical relevance in diabetes management, as manganese status may influence glycemic control. However, the relationship is complex, with factors like oxidative stress, inflammation, and other mineral imbalances potentially confounding the association between manganese and glucose metabolism. |
| Manganese and Calcium Metabolism | Manganese interacts with calcium metabolism in several ways. Both minerals play roles in bone formation and maintenance, with manganese supporting the synthesis of bone matrix components and calcium providing the primary mineral component of bone. Manganese and calcium can compete for absorption in the intestine, particularly when taken in high doses as supplements. Manganese may also influence calcium signaling in cells, potentially affecting processes like neurotransmission, muscle contraction, and hormone secretion. Additionally, manganese and calcium interact in enzyme function, with some enzymes requiring specific ratios of these minerals for optimal activity. This interaction has relevance for bone health, neurological function, and cardiovascular health, highlighting the importance of balanced mineral intake for optimal health. |
| Manganese and Antioxidant Network | Manganese is integrated into the broader antioxidant defense network through manganese superoxide dismutase (MnSOD). MnSOD works in concert with other antioxidant enzymes, including copper-zinc superoxide dismutase (Cu-Zn SOD), catalase, and glutathione peroxidase, to neutralize reactive oxygen species. MnSOD converts superoxide radicals to hydrogen peroxide in mitochondria, which is then neutralized by catalase or glutathione peroxidase. This coordinated action prevents oxidative damage to cellular components. Manganese also interacts with non-enzymatic antioxidants like vitamin C, vitamin E, and glutathione, which can regenerate oxidized antioxidants and provide complementary protection against different types of oxidative stress. This interaction has relevance for aging, cancer, neurodegenerative diseases, and other conditions associated with oxidative stress, highlighting the importance of comprehensive antioxidant support rather than single nutrient approaches. |
| Manganese and Neurotransmitter Balance | Manganese influences neurotransmitter balance through multiple mechanisms. It activates glutamine synthetase, which converts glutamate to glutamine in astrocytes, helping to regulate levels of glutamate, the primary excitatory neurotransmitter in the brain. Manganese also affects the metabolism of dopamine, a neurotransmitter involved in movement, motivation, and reward. Excess manganese can inhibit dopamine release and alter dopamine receptor function, potentially contributing to the Parkinson’s-like symptoms of manganism. Additionally, manganese influences the function of other neurotransmitters, including serotonin, norepinephrine, and GABA, affecting mood, cognition, and neurological function. This interaction has relevance for neurological and psychiatric disorders, highlighting the importance of balanced manganese status for optimal brain function. |
Manganese Speciation And Bioactivity
Oxidation States: Manganese exists primarily in two oxidation states in biological systems: Mn2+ (manganous) and Mn3+ (manganic). Mn2+ is the predominant form in most biological contexts and serves as the active form in most manganese-dependent enzymes. Mn3+ is found in certain enzymes, particularly in the catalytic cycle of manganese superoxide dismutase. The ability to cycle between these oxidation states enables manganese’s role in redox reactions.
Binding Forms: In the bloodstream, manganese is primarily bound to transferrin (80%), with smaller amounts bound to albumin and other proteins. Within cells, manganese is bound to various proteins including enzymes, transporters, and storage proteins. Manganese in enzymes is typically coordinated by amino acid residues like histidine, aspartate, glutamate, and cysteine, forming specific binding sites that determine enzyme specificity and activity.
Bioactive Species: The bioactive forms of manganese are primarily the protein-bound forms in enzymes and other functional proteins. Free manganese ions are essentially non-existent in healthy cells due to their potential toxicity, with intracellular free manganese concentrations maintained at extremely low levels through tight regulation of uptake, distribution, and efflux.
Labile Manganese Pool: A small pool of loosely bound, exchangeable manganese exists within cells, serving as an intermediate between manganese uptake and incorporation into manganese-requiring proteins. This labile manganese pool is tightly regulated and may serve as a sensing mechanism for manganese-responsive transcription factors.
Manganese Sensing: Cells monitor manganese status through manganese-sensing transcription factors and other regulatory proteins that modulate the expression of genes involved in manganese uptake, distribution, utilization, and export. These sensing mechanisms ensure appropriate responses to changes in manganese availability and protect against both deficiency and toxicity.
Bioavailability
Absorption Mechanisms
Primary Pathway: Manganese absorption occurs primarily in the small intestine, with the duodenum being the major site. The process involves both passive diffusion and active transport mechanisms, with regulation occurring primarily at the level of absorption based on body manganese status.
Active Transport: Divalent metal transporter 1 (DMT1), also known as natural resistance-associated macrophage protein 2 (NRAMP2), is the primary transporter involved in manganese uptake into enterocytes. DMT1 also transports iron and other divalent metals, creating potential for competitive interactions. Other transporters that may play roles in manganese absorption include ZIP8, ZIP14, and transferrin receptor.
Passive Diffusion: Some manganese absorption occurs through passive diffusion, particularly at higher luminal concentrations, though this represents a smaller component of overall manganese absorption compared to active transport.
Absorption Rates
Overall Range: Approximately 1-5% of dietary manganese is absorbed under normal conditions, with absorption efficiency inversely related to manganese status (higher absorption when status is low, lower absorption when status is high).
By Form:
| Form | Rate | Notes |
|---|---|---|
| Manganese from Food Sources | Approximately 1-5% | Varies widely depending on food matrix, processing methods, and presence of absorption enhancers or inhibitors |
| Manganese Sulfate | Approximately 1-3.5% | Standard bioavailability; absorption regulated based on body stores |
| Manganese Gluconate | Approximately 1.5-4% | Slightly better absorption than inorganic forms due to organic acid binding |
| Manganese Citrate | Approximately 2-4.5% | Good bioavailability with citrate potentially enhancing absorption |
| Manganese Glycinate | Approximately 2.5-5% | Enhanced absorption due to amino acid chelation, which protects manganese from binding to absorption inhibitors |
| Manganese Amino Acid Chelate | Approximately 2-5% | Variable depending on specific amino acid chelate; generally better absorption than inorganic forms |
| Manganese Picolinate | Approximately 2-5% | Enhanced absorption with picolinic acid facilitating transport |
Metabolism And Distribution
Enterocyte Processing: After absorption into enterocytes, manganese can be bound to various proteins or transported across the basolateral membrane into the bloodstream. Unlike iron, manganese does not appear to be significantly regulated at the level of enterocyte storage or efflux.
Transport In Bloodstream: In the bloodstream, manganese is primarily bound to transferrin (approximately 80%), with smaller amounts bound to albumin, alpha-2-macroglobulin, and other plasma proteins. A small fraction exists as free Mn2+ ions. Manganese in plasma is primarily in the Mn3+ oxidation state when bound to transferrin, while Mn2+ is the predominant form within cells.
Hepatic Processing: The liver plays a central role in manganese homeostasis. Hepatocytes take up manganese from the blood, incorporate it into manganese-dependent enzymes, or excrete excess manganese into bile. Biliary excretion is the primary route of manganese elimination and the main mechanism for preventing manganese accumulation.
Tissue Distribution: Manganese is distributed throughout the body, with highest concentrations in the liver, pancreas, bone, kidney, and brain. The adult human body contains approximately 10-20 mg of manganese total. Manganese can cross the blood-brain barrier through several mechanisms, including transferrin receptor-mediated transport and divalent metal transporter 1 (DMT1).
Cellular Uptake And Utilization: Cells take up manganese through various transporters including DMT1, ZIP8, ZIP14, transferrin receptor, and calcium channels. Within cells, manganese is distributed to various compartments including mitochondria (for MnSOD), the Golgi apparatus (for glycosyltransferases), and the cytosol (for other manganese-dependent enzymes).
Enhancement Methods
| Method | Description | Evidence Level |
|---|---|---|
| Using chelated forms | Manganese glycinate and other amino acid chelates provide better absorption by protecting manganese from binding to absorption inhibitors and potentially utilizing amino acid transport systems. | Moderate – Based on established mineral absorption principles and limited studies |
| Vitamin C co-supplementation | Vitamin C may enhance manganese absorption through its reducing properties and effects on mineral solubility and transport. | Low – Limited specific studies on manganese-vitamin C interaction |
| Maintaining adequate thyroid function | Thyroid hormones influence manganese absorption and metabolism; hypothyroidism may reduce manganese absorption and utilization. | Low to Moderate – Based on clinical observations and limited studies |
| Avoiding simultaneous intake with competing minerals | Taking manganese supplements separate from high-dose iron, calcium, or zinc supplements can reduce competitive inhibition of absorption. | Moderate – Well-established mineral interactions |
| Consuming with a balanced meal | Taking manganese with a balanced meal containing protein and carbohydrates may enhance absorption while minimizing potential gastrointestinal side effects. | Low – Based on general principles of mineral supplementation |
| Organic acid complexes | Manganese bound to organic acids like citrate or gluconate generally has better bioavailability than inorganic forms like manganese sulfate. | Low to Moderate – Limited comparative studies |
| Avoiding high-phytate meals | Taking manganese supplements apart from high-phytate foods (whole grains, legumes) can prevent formation of insoluble manganese-phytate complexes that reduce absorption. | Moderate – Based on established mineral-phytate interactions |
Factors Affecting Bioavailability
| Factor | Impact | Recommendation |
|---|---|---|
| Manganese status | Absorption efficiency increases during manganese deficiency and decreases during manganese adequacy or excess, representing a key homeostatic mechanism. | Supplementation is most effective in those with suboptimal manganese status; may have limited benefit in manganese-replete individuals. |
| Iron intake | High iron intake can significantly reduce manganese absorption due to competition for shared transport mechanisms, particularly DMT1. | Separate high-dose iron and manganese supplements by at least 2 hours; consider manganese supplementation with long-term high-dose iron therapy. |
| Calcium intake | High calcium intake may moderately reduce manganese absorption through competition for absorption pathways or non-specific binding in the intestine. | Separate high-dose calcium supplements from manganese supplements by at least 2 hours. |
| Dietary phytates | Phytic acid in whole grains, legumes, and nuts can bind to manganese, forming insoluble complexes that reduce absorption. | Take manganese supplements apart from high-phytate meals or use food preparation methods that reduce phytate content (soaking, sprouting, fermenting). |
| Dietary fiber | High fiber intake, particularly from cereal fibers, may moderately reduce manganese absorption through binding and increased intestinal transit time. | Consider timing manganese intake away from high-fiber meals for optimal absorption. |
| Tannins | Tannins found in tea, coffee, wine, and some fruits may bind to manganese and reduce its absorption from the digestive tract. | Consider taking manganese supplements at least 1 hour before or 2 hours after consuming tannin-rich beverages like tea or coffee. |
| Thyroid function | Hypothyroidism may reduce manganese absorption and metabolism, while hyperthyroidism may increase manganese turnover. | Individuals with thyroid disorders should monitor manganese status and may require adjusted intake. |
| Age | Manganese absorption may decline with age due to reduced gastric acid production and age-related changes in intestinal function. | Older adults may require more bioavailable forms or slightly higher intake to maintain adequate status. |
| Gastrointestinal disorders | Malabsorptive conditions (celiac disease, inflammatory bowel disease, short bowel syndrome) can reduce manganese absorption. | Those with malabsorptive conditions may require more bioavailable forms or monitoring of manganese status. |
Timing Recommendations
General Timing: Manganese supplements can be taken at any time of day, though absorption and tolerability may be optimized with specific timing strategies.
With Or Without Food: Taking manganese with food generally enhances tolerability by reducing gastrointestinal irritation. A balanced meal containing moderate protein may enhance absorption.
Meal Composition: A meal containing moderate protein may enhance manganese absorption, while very high fiber or phytate content may reduce absorption.
Supplement Interactions: Separate manganese supplements from high-dose iron supplements (>25 mg) by at least 2 hours to prevent competitive inhibition of absorption. Similarly, separate from high-dose calcium supplements and zinc supplements.
Medication Timing: Take manganese supplements at least 2 hours before or 4-6 hours after taking medications that reduce stomach acid (antacids, H2 blockers, proton pump inhibitors) for optimal absorption.
Consistency: Regular, consistent supplementation is more important than specific timing for maintaining optimal manganese status, particularly for addressing deficiency.
Excretion And Retention
Primary Excretion Routes: Biliary excretion into the feces is the primary route of manganese elimination, accounting for approximately 90% of manganese excretion. Smaller amounts are excreted in urine (3-8%) and through pancreatic secretions, sweat, and hair.
Homeostatic Regulation: Manganese balance is maintained primarily through regulation of biliary excretion rather than absorption. When manganese status is high, biliary excretion increases; when manganese status is low, biliary excretion decreases to conserve manganese.
Half Life: The biological half-life of manganese in the body is approximately 13-37 days, though this varies by tissue and manganese status.
Tissue Retention: Manganese is retained differently across tissues, with bone, liver, pancreas, and brain maintaining relatively high concentrations. The brain particularly tends to accumulate manganese with chronic exposure, which can be relevant to manganese toxicity.
Factors Increasing Excretion: High manganese intake, certain medications, and some disease states can increase manganese excretion.
Bioavailability Testing
Direct Methods: Direct measurement of manganese absorption using stable isotope techniques or pharmacokinetic analyses of blood and urine levels following supplementation.
Indirect Methods: Measuring changes in whole blood manganese, serum manganese, or functional markers like manganese-dependent enzyme activity following supplementation as indicators of bioavailability.
Research Challenges: Tight homeostatic regulation of manganese makes assessment of absorption from different forms challenging, as the body adjusts absorption and excretion based on status.
Individual Variability: Significant inter-individual differences in manganese absorption and metabolism contribute to variable responses to supplementation in clinical studies.
Safety Profile
Safety Rating
Safety Overview
Manganese has a moderate safety profile with a relatively narrow therapeutic window compared to some other essential minerals.
While manganese supplementation is generally safe
when used within recommended doses (1-5 mg daily), higher doses or long-term excessive intake may lead to manganese accumulation and neurotoxicity. The margin between therapeutic doses and potentially harmful doses is smaller than for many other nutrients, requiring appropriate caution, particularly in certain populations or clinical situations. The brain is especially vulnerable to manganese toxicity, with excess manganese accumulating in the basal ganglia and potentially causing a Parkinson’s-like condition called manganism.
Side Effects
- [“None typically reported at AI levels (1.8-2.3 mg/day)”,”Occasional mild gastrointestinal discomfort”]
- [“Gastrointestinal discomfort”,”Headache”,”Mild lethargy”,”Muscle pain”,”Irritability”]
- [“Severe gastrointestinal irritation”,”Headache”,”Dizziness”,”Fatigue”,”Muscle weakness”,”Irritability and mood changes”]
- [“Neurological symptoms (tremor, difficulty walking, facial muscle spasms)”,”Psychiatric symptoms (irritability, aggression, hallucinations)”,”Cognitive impairment (memory problems, reduced concentration)”,”Parkinson’s-like symptoms (bradykinesia, rigidity, postural instability)”,”Reduced response to levodopa therapy in Parkinson’s disease patients”]
Contraindications
| Condition | Recommendation |
|---|---|
| Liver disease | Use with extreme caution and medical supervision; impaired hepatic function may reduce manganese excretion, increasing risk of accumulation |
| Iron-deficiency anemia | Use with caution; iron deficiency enhances manganese absorption and may increase risk of toxicity |
| Parkinson’s disease or related movement disorders | Avoid supplementation unless specifically prescribed; manganese may worsen symptoms or interfere with treatment |
| Occupational exposure to manganese | Avoid supplementation; occupational exposure (welding, mining, steel production) already increases manganese burden |
| Known hypersensitivity to manganese compounds | Avoid supplementation |
| Chronic kidney disease | Use with caution and medical supervision; altered mineral metabolism may affect manganese handling |
Drug Interactions
| Drug Class | Examples | Interaction | Severity | Recommendation |
|---|---|---|---|---|
| Antacids | Aluminum hydroxide, calcium carbonate, magnesium hydroxide | May reduce manganese absorption by increasing gastric pH and through direct binding | Mild | Separate manganese supplement administration from antacids by at least 2 hours |
| Tetracycline antibiotics | Tetracycline, doxycycline, minocycline | Manganese may form complexes with tetracyclines, reducing absorption of both | Moderate | Separate manganese supplements from tetracycline antibiotics by at least 2-3 hours |
| Quinolone antibiotics | Ciprofloxacin, levofloxacin, moxifloxacin | Manganese may form complexes with quinolones, reducing their absorption | Moderate | Separate manganese supplements from quinolone antibiotics by at least 2-3 hours |
| Levodopa | Sinemet, Madopar | Manganese may reduce the effectiveness of levodopa in Parkinson’s disease treatment, possibly by affecting dopamine metabolism or receptor function | Moderate to significant | Avoid manganese supplements unless specifically prescribed; monitor for reduced response to levodopa therapy |
| Iron supplements | Ferrous sulfate, ferrous gluconate, ferrous fumarate | Competitive inhibition of absorption; high iron intake can reduce manganese absorption and vice versa | Mild to moderate | Separate high-dose iron and manganese supplements by at least 2 hours |
| Calcium supplements | Calcium carbonate, calcium citrate | May reduce manganese absorption when taken simultaneously in large amounts | Mild | Separate high-dose calcium supplements from manganese supplements by at least 2 hours |
| Proton Pump Inhibitors | Omeprazole, esomeprazole, pantoprazole | May reduce manganese absorption by decreasing stomach acidity | Mild | Monitor manganese status with long-term PPI use; consider more bioavailable manganese forms |
| Oral contraceptives | Combined estrogen-progestin contraceptives | May alter manganese metabolism and distribution | Mild (generally not clinically significant) | No specific action needed; be aware that manganese status may be affected |
Upper Limits
Adults: 11 mg/day (from all sources including food and supplements)
Pregnant Women: 11 mg/day
Lactating Women: 11 mg/day
Adolescents 14 18: 9 mg/day
Children 9 13: 6 mg/day
Children 4 8: 3 mg/day
Children 1 3: 2 mg/day
Infants 7 12 Months: Not established
Infants 0 6 Months: Not established
Toxicity Information
Acute Toxicity: Acute manganese toxicity from oral supplementation is rare due to limited absorption and effective homeostatic regulation. However, ingestion of very high doses may cause gastrointestinal irritation, headache, dizziness, and fatigue. The risk of acute toxicity is greater with intravenous administration, which bypasses normal absorption regulation.
Chronic Toxicity: Chronic manganese toxicity, or manganism, typically occurs from long-term excessive exposure, particularly through inhalation in occupational settings (welding, mining) or from contaminated drinking water. It can also occur with long-term parenteral nutrition without proper monitoring or in individuals with impaired manganese excretion (liver disease). Manganism is characterized by neurological symptoms resembling Parkinson’s disease, including tremor, difficulty walking, facial muscle spasms, and cognitive changes. Unlike Parkinson’s disease, manganism typically causes less resting tremor and more dystonia, and responds poorly to levodopa therapy.
Susceptible Populations: Individuals with liver disease, iron deficiency, chronic kidney disease, or impaired biliary excretion are at significantly higher risk for manganese toxicity even with normal intake. Infants and young children may also be more susceptible due to greater absorption, developing blood-brain barrier, and immature excretion mechanisms.
Environmental Exposure: Environmental sources of manganese include drinking water (particularly from groundwater sources), air pollution near industrial emissions, and certain occupational settings. These exposures should be considered when evaluating total manganese intake and risk of toxicity.
Safety During Pregnancy Lactation
Pregnancy: Manganese requirements may increase slightly during pregnancy (AI increases to 2.0 mg/day) to support fetal development. Supplementation within recommended levels is considered safe, but high-dose supplementation (>5 mg/day) should be avoided without medical supervision. Manganese is essential for fetal development, particularly for skeletal formation and neurological development, but excessive exposure during pregnancy may potentially affect fetal neurodevelopment.
Lactation: Manganese requirements increase during lactation (AI is 2.6 mg/day) to support milk production. Supplementation within recommended levels is considered safe. Manganese is secreted in breast milk, and maternal intake influences milk manganese content, though homeostatic mechanisms help maintain relatively stable milk manganese levels.
Safety In Special Populations
Children: Children require manganese for growth and development, but in smaller amounts than adults. Upper limits are lower for children (see upper limits section). Supplementation should only be used when dietary intake is inadequate or in specific clinical situations. Infants and young children may be more susceptible to manganese toxicity due to greater absorption, developing blood-brain barrier, and immature excretion mechanisms.
Elderly: Older adults may have altered manganese metabolism due to age-related changes in liver function, kidney function, and neurological vulnerability. They may be more susceptible to both deficiency (due to dietary factors) and toxicity (due to reduced excretion). Monitoring may be advisable with long-term supplementation.
Kidney Disease: Individuals with kidney disease may have altered mineral metabolism, potentially affecting manganese handling. While biliary excretion is the primary route for manganese elimination, renal function can affect overall mineral homeostasis. Use supplements cautiously and with medical supervision.
Liver Disease: The liver plays a central role in manganese metabolism and excretion. Those with liver disease should use manganese supplements only under close medical supervision, as impaired hepatic function may reduce manganese excretion, increasing the risk of accumulation and toxicity.
Long Term Safety
Carcinogenicity: No evidence suggests that manganese at physiological or moderate supplemental doses is carcinogenic. Some research suggests that maintaining appropriate manganese status may be protective against certain cancers through antioxidant functions, while both deficiency and excess may potentially increase cancer risk through different mechanisms.
Genotoxicity: Manganese at physiological levels is not genotoxic and is essential for enzymes involved in DNA repair. However, excessive manganese exposure may potentially cause oxidative DNA damage through production of reactive oxygen species.
Reproductive Effects: Manganese is essential for normal reproduction and development. Deficiency can impair fertility and fetal development, while excessive intake during pregnancy should be avoided due to potential developmental concerns.
Organ System Effects: Long-term manganese supplementation within recommended doses has not been associated with adverse effects on major organ systems in individuals with normal manganese metabolism. The nervous system is the primary site of concern for long-term excessive intake, with the liver also being potentially affected.
Monitoring Recommendations: For long-term supplementation above AI levels, consider periodic assessment of manganese status (whole blood manganese) and neurological function, particularly in higher-risk individuals.
Overdose Information
Symptoms: Acute overdose symptoms include gastrointestinal irritation, headache, dizziness, fatigue, and muscle weakness. Severe or chronic overdose may lead to neurological symptoms including tremor, difficulty walking, facial muscle spasms, irritability, hallucinations, and cognitive impairment.
Management: Treatment includes discontinuation of manganese exposure, supportive care, and in severe cases, chelation therapy with agents like calcium EDTA. Consult poison control center immediately for guidance.
Antidote: No specific antidote exists for manganese toxicity. Chelation therapy may be used in severe cases to enhance manganese excretion.
Prognosis: With prompt discontinuation of exposure, mild to moderate manganese toxicity may gradually improve, though neurological symptoms may persist in severe cases. The prognosis depends on the duration and severity of exposure, with early intervention generally resulting in better outcomes.
Regulatory Status
United States
Fda Status: Generally Recognized as Safe (GRAS) when used within established limits. Approved as a dietary supplement and food additive.
Dietary Reference Values: 2.3 mg/day for adult men, 1.8 mg/day for adult women, 11 mg/day from all sources, 2.0 mg/day, 2.6 mg/day
Approved Forms: Manganese sulfate, Manganese chloride, Manganese gluconate, Manganese glycerophosphate, Manganese citrate, Manganese amino acid chelates (various), Manganese oxide
Health Claims: No FDA-approved qualified health claims specific to manganese, May make claims related to bone health, antioxidant function, energy metabolism, and connective tissue formation without pre-approval, provided they include the standard FDA disclaimer.
Labeling Requirements: Must include a Supplement Facts panel listing manganese content and the standard FDA disclaimer for structure-function claims.
European Union
Regulatory Framework: Regulated under Directive 2002/46/EC for food supplements and Regulation (EC) No 1925/2006 for fortified foods.
Dietary Reference Values: 3.0 mg/day for adult men, 3.0 mg/day for adult women (EFSA, 2013), 11 mg/day from all sources
Approved Forms: Manganese ascorbate, Manganese carbonate, Manganese chloride, Manganese citrate, Manganese gluconate, Manganese glycerophosphate, Manganese pidolate, Manganese sulfate, Manganese bisglycinate
Approved Health Claims:
| Claim | Regulation |
|---|---|
| Manganese contributes to normal energy-yielding metabolism | Commission Regulation (EU) 432/2012 |
| Manganese contributes to the maintenance of normal bones | Commission Regulation (EU) 432/2012 |
| Manganese contributes to the normal formation of connective tissue | Commission Regulation (EU) 432/2012 |
| Manganese contributes to the protection of cells from oxidative stress | Commission Regulation (EU) 432/2012 |
Country Specific Regulations: Some EU member states have established national recommendations that may differ slightly from EU-wide regulations.
Canada
Regulatory Framework: Regulated as a Natural Health Product (NHP) under the Natural Health Products Regulations.
Dietary Reference Values: 2.3 mg/day for adult men, 1.8 mg/day for adult women, 11 mg/day from all sources
Approved Forms: Manganese (manganous) gluconate, Manganese (manganous) sulfate, Manganese (manganous) citrate, Manganese (manganous) chloride, Manganese amino acid chelate, Manganese (manganous) glycerophosphate, Manganese (manganous) ascorbate
Authorized Claims: Source of manganese for the maintenance of good health, Helps in the formation and maintenance of bones and teeth, Helps in connective tissue formation, Helps the body to metabolize carbohydrates, fats and proteins, An antioxidant for the maintenance of good health
Monograph: Health Canada has published a Manganese Monograph outlining specific requirements for manganese-containing products.
Australia And New Zealand
Regulatory Framework: Regulated by the Therapeutic Goods Administration (TGA) in Australia and Medsafe in New Zealand under a joint regulatory scheme.
Dietary Reference Values: 5.5 mg/day for men, 5.0 mg/day for women, 11 mg/day from all sources
Approved Forms: Manganese sulfate, Manganese gluconate, Manganese citrate, Manganese amino acid chelates, Manganese glycerophosphate
Permitted Claims: Necessary for normal bone formation, Necessary for connective tissue health, Supports energy metabolism, Contributes to antioxidant activity, Supports normal carbohydrate metabolism
Listing Requirements: Manganese-containing supplements must be listed on the Australian Register of Therapeutic Goods (ARTG) as complementary medicines.
Japan
Regulatory Framework: Regulated under the Food with Nutrient Function Claims (FNFC) system and the Foods for Specified Health Uses (FOSHU) system.
Dietary Reference Values: 4.0 mg/day for adult men, 3.5 mg/day for adult women, 11 mg/day from all sources
Approved Forms: Manganese gluconate, Manganese sulfate, Manganese chloride
Permitted Claims: Under the FNFC system, manganese products may claim ‘Manganese is a nutrient which is necessary to maintain the health of the body.’
China
Regulatory Framework: Regulated by the National Medical Products Administration (NMPA) and the State Administration for Market Regulation (SAMR).
Dietary Reference Values: 4.5 mg/day for adult men, 4.0 mg/day for adult women, 11 mg/day from all sources
Approved Forms: Manganese sulfate, Manganese gluconate, Manganese citrate, Manganese chloride
Special Considerations: China has specific regulations for manganese in infant formula and foods for special medical purposes.
India
Regulatory Framework: Regulated by the Food Safety and Standards Authority of India (FSSAI).
Dietary Reference Values: 2.5-5.0 mg/day for adults, Not officially established
Approved Forms: Manganese sulfate, Manganese gluconate, Manganese chloride
Regulatory Status: Manganese is permitted in health supplements under the Food Safety and Standards (Health Supplements, Nutraceuticals, Food for Special Dietary Use, Food for Special Medical Purpose, Functional Food and Novel Food) Regulations, 2016.
International Organizations
Who Fao
- Not established; WHO acknowledges manganese as an essential nutrient but has not set specific intake recommendations
- Recognizes manganese as an essential nutrient with important roles in human health, while also acknowledging concerns about excessive exposure.
Codex Alimentarius
- Has established guidelines for manganese content in infant formula and dietary supplements.
- Provides international food standards that include manganese considerations.
Regulatory Trends
Harmonization Efforts: There are ongoing efforts to harmonize manganese regulations and dietary reference values internationally, though significant differences remain.
Safety Reassessment: Regulatory bodies periodically reassess the safety of manganese compounds, particularly as new research emerges on potential neurotoxicity with chronic excessive exposure.
Form-specific Regulations: Increasing differentiation in regulations based on specific manganese forms, with some forms receiving more scrutiny than others.
Therapeutic Claims: Generally conservative approach to permitted health claims, with most jurisdictions limiting claims to basic physiological functions rather than therapeutic applications.
Water Regulations
Drinking Water Standards: Secondary standard (non-enforceable guideline) of 0.05 mg/L, Guideline value of 0.4 mg/L, No specific parametric value; falls under general requirement for water to be wholesome
Monitoring Requirements: Public water systems are required to monitor manganese levels in many jurisdictions, particularly where geological conditions suggest potential for elevated levels.
Treatment Techniques: Various treatment methods including oxidation-filtration, ion exchange, and adsorption are used to remove excess manganese from drinking water.
Special Population Regulations
Infants: Specific regulations exist for manganese content in infant formula, with requirements for minimum and maximum levels to ensure adequate intake without risk of excess.
Pregnancy: Most regulatory frameworks include specific recommendations for manganese intake during pregnancy, typically similar to or slightly higher than non-pregnant adult recommendations.
Occupational Exposure: Occupational safety regulations in many countries set limits for manganese exposure in workplace air, typically ranging from 0.02 to 0.2 mg/m³ depending on the jurisdiction and specific manganese compound.
Synergistic Compounds
Antagonistic Compounds
Cost Efficiency
Relative Cost Rating
Low
Cost By Form
| Form | Cost Range | Bioavailability | Value Assessment |
|---|---|---|---|
| Manganese Sulfate | $0.01-$0.05 per day (2-5 mg) | 1-3.5% | Good value with standard bioavailability; widely available and very cost-effective |
| Manganese Gluconate | $0.02-$0.08 per day (2-5 mg) | 1.5-4% | Good value with slightly improved bioavailability compared to sulfate; well-tolerated |
| Manganese Citrate | $0.03-$0.10 per day (2-5 mg) | 2-4.5% | Slightly higher cost with improved bioavailability; good option for those with sensitive digestion |
| Manganese Glycinate | $0.05-$0.15 per day (2-5 mg) | 2.5-5% | Higher cost justified by superior absorption and gentler digestive profile; best for those with absorption issues |
| Manganese Picolinate | $0.05-$0.15 per day (2-5 mg) | 2-5% | Higher cost with claims of enhanced absorption; limited independent research on superiority over other chelated forms |
Food Sources Cost Comparison
| Food | Cost Per Serving | Notes |
|---|---|---|
| Oatmeal | $0.20-$0.50 per cup cooked (1.9 mg manganese) | Excellent value considering high manganese content and additional nutrients; commonly consumed food |
| Brown Rice | $0.15-$0.40 per cup cooked (2.1 mg manganese) | Very cost-effective source of manganese; provides other nutrients and fiber as well |
| Pineapple | $1.00-$3.00 per cup (1.5 mg manganese) | Moderate cost for good manganese content; provides vitamin C and other beneficial compounds |
| Spinach | $0.50-$1.50 per cup cooked (0.9 mg manganese) | Good value as a vegetable source; provides numerous other nutrients |
| Pumpkin Seeds | $0.50-$1.00 per ounce (0.6 mg manganese) | Moderate cost for good manganese content; provides other minerals and healthy fats |
| Black Tea | $0.10-$0.30 per cup (0.5-1.0 mg manganese) | Very cost-effective source, though absorption may be limited by tannins; provides antioxidants as well |
Cost Effectiveness By Health Goal
| Health Goal | Most Cost Effective Approach | Notes |
|---|---|---|
| Bone Health Support | Dietary approach focusing on whole grains, nuts, and leafy greens; if supplementing, manganese gluconate (2-5 mg/day) as part of a comprehensive bone support formula with calcium, vitamin D, and other minerals | Most cost-effective when combined with other bone-supporting nutrients; food sources provide additional beneficial compounds |
| Antioxidant Support | Dietary approach emphasizing manganese-rich whole foods; if supplementing, manganese sulfate or gluconate (1-2 mg/day) as part of a comprehensive antioxidant formula | Limited evidence for benefits of manganese supplementation alone for antioxidant purposes; most effective as part of a broader antioxidant strategy |
| Joint Health | Manganese gluconate (2-5 mg/day) combined with glucosamine and chondroitin in a joint support formula | More cost-effective in combination products than as a standalone supplement for this purpose; synergistic effects with other joint-supporting compounds |
| Glucose Metabolism Support | Dietary approach focusing on whole grains, nuts, and legumes; if supplementing, manganese gluconate (1-2 mg/day) | Limited evidence for manganese supplementation alone for glucose metabolism; most cost-effective when combined with lifestyle modifications |
| General Health Maintenance | Dietary approach focusing on manganese-rich whole foods; if supplementing, manganese sulfate or gluconate (1-2 mg/day) as part of a multivitamin/mineral formula | For those without deficiency, obtaining manganese from food is generally more cost-effective than supplementation |
Value Optimization Strategies
| Strategy | Description | Potential Savings |
|---|---|---|
| Dietary optimization | Focus on incorporating manganese-rich foods into regular diet before turning to supplements | 50-100% of supplement cost while providing additional nutrients |
| Form selection based on need | Choose appropriate form based on specific health goals and individual factors rather than defaulting to most expensive option | 30-60% depending on form selected |
| Bulk purchasing | Buying larger quantities of manganese supplements can significantly reduce per-dose cost | 20-40% compared to smaller packages |
| Combination products | For those needing multiple minerals, combination products may offer better value than purchasing supplements separately | 10-30% compared to purchasing supplements separately |
| Subscription services | Many supplement companies offer discounts for subscription purchases | 10-25% compared to one-time purchases |
Cost Trends
Historical Trends: Manganese supplement costs have remained relatively stable over the past decade, with slight decreases in basic forms due to manufacturing efficiencies and increased competition.
Geographical Variations: Manganese supplement costs vary by region, with generally higher prices in Europe and Australia compared to North America and Asia.
Future Projections: Costs are expected to remain stable for conventional forms, with potential premium pricing for newer specialized formulations.
Hidden Costs And Benefits
Potential Hidden Costs
- Healthcare costs from improper dosing (particularly excessive intake)
- Environmental costs of manganese mining and processing
- Potential interactions with medications or other supplements
Potential Hidden Benefits
- Reduced healthcare costs from preventing manganese-related health issues
- Improved utilization of other nutrients through manganese-dependent enzymes
- Enhanced effectiveness of other supplements (e.g., glucosamine/chondroitin for joint health)
Special Populations Considerations
| Population | Cost Efficiency Notes |
|---|---|
| Vegetarians and vegans | Generally have adequate or high manganese intake from plant foods; supplementation rarely necessary and not cost-effective |
| Pregnant women | Moderate cost-effectiveness; typically covered by prenatal vitamins without need for separate supplementation |
| Elderly individuals | Variable cost-effectiveness; those with poor dietary intake may benefit from supplementation, particularly for bone health |
| Individuals with iron deficiency | Should be cautious with manganese supplementation; iron deficiency enhances manganese absorption, potentially increasing risk of toxicity |
Comparative Value
Vs Other Minerals: Manganese supplements are generally less expensive than many other mineral supplements like zinc, selenium, or copper on a per-dose basis
Vs Medical Treatments: For joint health, manganese in combination with glucosamine and chondroitin may be cost-effective compared to some medical interventions, though evidence is limited
Vs Functional Foods: Standard manganese supplements are typically more cost-effective than manganese-fortified functional foods, though the latter may provide additional benefits
Vs Iv Therapy: Oral manganese supplementation is substantially more cost-effective than IV mineral therapies that include manganese
Stability Information
Shelf Life
General Shelf Life: 2-3 years for most manganese supplements when properly stored in original containers.
By Form:
| Form | Shelf Life | Notes |
|---|---|---|
| Manganese Sulfate | 3-5 years | Very stable in dry form; may gradually absorb moisture if exposed to humidity |
| Manganese Gluconate | 2-3 years | Generally stable under proper storage conditions; may gradually absorb moisture if exposed to humidity |
| Manganese Citrate | 2-3 years | Good stability when properly stored; organic acid binding provides reasonable stability |
| Manganese Glycinate | 2-3 years | Amino acid chelation provides good stability under proper storage conditions |
| Manganese Picolinate | 2-3 years | Generally stable under proper storage conditions |
| Liquid Manganese Supplements | 1-2 years unopened; 3-6 months after opening | Requires preservatives to prevent microbial growth; stability decreases after opening |
Storage Recommendations
Temperature: Store between 15-25°C (59-77°F). Avoid temperature extremes and fluctuations.
Humidity: Keep in a dry environment with relative humidity below 60%. Avoid bathroom storage.
Light: Protect from direct sunlight and UV light. Amber or opaque containers provide best protection.
Container: Keep in original container with desiccant if provided. Ensure container is tightly closed after each use.
Special Forms: Liquid manganese supplements may require refrigeration after opening. Check product-specific instructions.
Bulk Storage: For bulk manganese ingredients, sealed containers with desiccants are recommended to prevent moisture absorption.
Degradation Factors
| Factor | Impact | Prevention |
|---|---|---|
| Moisture | Can cause degradation of tablet integrity, potential microbial growth, and accelerated chemical degradation. Some manganese salts (particularly manganese sulfate) are hygroscopic and can absorb moisture from the air. | Use desiccants, maintain proper container closure, store in low-humidity environments. |
| Oxidation | Manganese can undergo oxidation state changes, potentially affecting stability and bioavailability. Mn2+ (the form in most supplements) can oxidize to higher oxidation states under certain conditions. | Proper packaging, protection from strong oxidizing agents, use of antioxidants in formulations when necessary. |
| Heat | Temperatures above 30°C/86°F may accelerate degradation of some organic manganese forms and affect tablet integrity. | Store in temperature-controlled environments, avoid exposure to direct heat sources. |
| Light exposure | UV and strong visible light can potentially affect stability of certain manganese compounds, particularly in liquid formulations. | Use amber or opaque containers, store away from direct light sources. |
| pH extremes | In liquid formulations, pH extremes can affect the stability and solubility of manganese compounds. Different manganese forms have different optimal pH ranges for stability. | Maintain appropriate pH in liquid formulations, use buffering agents when necessary. |
| Interactions with other ingredients | Certain minerals, vitamins, or excipients may interact with manganese compounds, affecting stability and bioavailability. | Formulate with compatible ingredients, use appropriate separating agents in multi-ingredient supplements. |
| Microbial contamination | Primarily a concern for liquid formulations or supplements exposed to moisture. | Use appropriate preservatives in liquid formulations, maintain proper storage conditions. |
Stability During Processing
Heat Stability: Most manganese compounds used in supplements are relatively stable during brief exposure to moderate heat (below 100°C/212°F). Manganese sulfate may lose water of crystallization at higher temperatures but remains effective. Organic manganese forms may be more sensitive to prolonged heating.
PH Stability: Manganese compounds have varying pH stability profiles. Manganese sulfate is most stable at slightly acidic pH (4-6). Manganese gluconate and citrate have good stability across a wider pH range (3-8). Manganese glycinate is generally stable at physiological pH.
Processing Considerations: Avoid excessive heat during tablet compression or encapsulation, Minimize exposure to moisture during processing, Consider coating technologies for sensitive forms, Use appropriate excipients to enhance stability, Validate stability through accelerated and real-time stability testing
Stability In Food Matrix
Cooking Effects: Manganese in foods is generally stable during cooking, with minimal losses. Water-based cooking methods (boiling, steaming) may result in some leaching of manganese into cooking water, particularly with acidic ingredients.
Food Processing: Most food processing methods have limited effects on manganese content, though refining grains removes significant manganese along with other minerals. Manganese can catalyze oxidation reactions in foods, particularly in fats and oils.
Food Storage: Manganese content in foods is generally stable during proper storage. Freezing has minimal impact on manganese content.
Stability Testing Methods
Inductively Coupled Plasma Mass Spectrometry (ICP-MS) or Atomic Absorption Spectroscopy (AAS) for quantification of total manganese content, High-Performance Liquid Chromatography (HPLC) for analysis of specific manganese compounds in some formulations, Accelerated stability testing under controlled temperature and humidity conditions, Real-time stability testing under recommended storage conditions, Dissolution testing to ensure consistent release characteristics over shelf life, Microbial testing for liquid formulations
Packaging Considerations
Recommended Materials: Amber or opaque HDPE (High-Density Polyethylene) bottles provide good protection from light and moisture. Glass bottles with tight-fitting lids are also suitable. Blister packs with aluminum backing provide excellent protection for individual doses.
Packaging Innovations: Desiccant-integrated bottle caps, moisture-resistant coatings for tablets, and nitrogen-flushed containers can enhance stability for sensitive manganese formulations.
Labeling Recommendations: Clear storage instructions, expiration dating, and lot numbers should be prominently displayed. Consider including indicators for exposure to excessive moisture or heat.
Interactions Affecting Stability
Vitamin C: High concentrations of vitamin C (ascorbic acid) in the same formulation may affect the stability of certain manganese compounds through redox reactions. This is primarily a concern in liquid or effervescent formulations.
Reducing Agents: Strong reducing agents may alter the oxidation state of manganese in some formulations, potentially affecting stability and bioavailability.
Chelating Agents: EDTA and other strong chelating agents can bind manganese, potentially affecting its stability and release characteristics in supplement formulations.
Metal Ions: Other metal ions, particularly iron and calcium in high concentrations, may compete with manganese for binding to certain excipients or carriers, potentially affecting stability in multi-mineral formulations.
Stability During Transport
Temperature Excursions: Brief exposure to temperatures outside recommended range during shipping is generally not problematic for manganese stability, but repeated or prolonged temperature cycling should be avoided.
Shipping Recommendations: Use insulated shipping materials during extreme weather conditions. Consider temperature indicators for shipments to regions with extreme climates.
International Considerations: Products shipped internationally may experience more variable conditions and longer transit times, potentially affecting stability. More robust packaging may be warranted.
Testing Methods
Debug Information:
Section: testing_methods
Data type: array
Array keys: testing_methods
testing_methods key exists with type: array
spp_render_generic_fields function exists: Yes
Clinical Assessment
Supplement Quality Testing
Food Testing
Environmental Testing
Emerging Testing Methods
| Method | Description | Potential Applications | Development Status |
|---|---|---|---|
| Metallomics Approaches | Comprehensive analysis of manganese-containing proteins and metabolites using mass spectrometry and other advanced techniques. | Detailed assessment of manganese metabolism and utilization; identification of novel biomarkers | Research tool; emerging clinical applications |
| Single-Cell ICP-MS | Analysis of manganese content in individual cells using specialized ICP-MS techniques. | Cellular distribution of manganese; heterogeneity in manganese metabolism | Advanced research tool; limited to specialized laboratories |
| Manganese Sensors and Probes | Fluorescent or colorimetric probes that selectively bind manganese for visualization and quantification. | Cellular and subcellular manganese localization; real-time monitoring of manganese dynamics | Active research area; some probes commercially available for research use |
| Portable XRF Analyzers | Handheld devices using X-ray fluorescence for rapid, non-destructive manganese analysis. | Field testing of foods, supplements, and environmental samples | Commercially available; continuing improvements in sensitivity and specificity |
Sourcing
Synthesis Methods
| Method | Process | Applications |
|---|---|---|
| Manganese sulfate production | Produced by reacting manganese oxide or manganese carbonate with sulfuric acid, followed by crystallization and purification steps. The monohydrate form (MnSO4·H2O) is commonly used in supplements. | Widely used in supplements due to good solubility and relatively low cost; also used in agriculture as a fertilizer and in animal feed. |
| Manganese gluconate production | Typically produced by reacting manganese carbonate or manganese oxide with gluconic acid, followed by filtration, crystallization, and drying. | Common in supplements and fortified foods; generally well-tolerated with good bioavailability. |
| Manganese citrate production | Produced by reacting manganese carbonate or manganese oxide with citric acid, followed by purification steps. | Used in premium supplements; good bioavailability and stability. |
| Manganese glycinate production | Created by chelating manganese with glycine molecules through a reaction between manganese salts and glycine under controlled conditions. | Used in higher-end supplements; claimed to have superior absorption and gentler digestive profile. |
| Manganese chloride production | Typically produced by dissolving manganese oxide or manganese carbonate in hydrochloric acid, followed by crystallization and purification. | Less commonly used in supplements; more often used in research and industrial applications. |
| Manganese picolinate production | Created by reacting manganese with picolinic acid under controlled conditions to form a chelate. | Used in some specialty supplements; claimed to have enhanced bioavailability. |
Natural Sources
| Source | Manganese Content | Notes |
|---|---|---|
| Whole Grains | 0.5-3.0 mg per 100g | Particularly high in oats (4.9 mg/100g), brown rice (3.7 mg/100g), and whole wheat (3.0 mg/100g); refined grains contain significantly less |
| Nuts and Seeds | 1.0-8.0 mg per 100g | Particularly high in pine nuts (8.8 mg/100g), hazelnuts (6.2 mg/100g), and pecans (4.5 mg/100g) |
| Legumes | 0.5-2.0 mg per 100g (cooked) | Particularly high in soybeans (1.4 mg/100g cooked), lima beans (1.0 mg/100g cooked), and chickpeas (1.0 mg/100g cooked) |
| Leafy Green Vegetables | 0.3-1.5 mg per 100g | Particularly high in spinach (0.9 mg/100g), kale (0.8 mg/100g), and Swiss chard (0.7 mg/100g) |
| Tea | 0.5-1.0 mg per cup (brewed) | Black tea typically contains more manganese than green tea; actual absorption may be limited due to tannin content |
| Spices | 2.0-30.0 mg per 100g | Particularly high in cloves (30.0 mg/100g), cinnamon (17.5 mg/100g), and turmeric (10.0 mg/100g); consumed in small amounts but can contribute to intake |
| Fruits | 0.1-1.5 mg per 100g | Particularly high in pineapple (1.5 mg/100g), blueberries (0.3 mg/100g), and bananas (0.3 mg/100g) |
| Shellfish | 0.1-1.0 mg per 100g | Particularly high in mussels (0.7 mg/100g), clams (0.5 mg/100g), and oysters (0.3 mg/100g) |
| Dark Chocolate | 1.0-2.0 mg per 100g | Higher cocoa content generally correlates with higher manganese content |
| Pumpkin Seeds | 4.5 mg per 100g | One of the richest food sources; provides other minerals as well |
| Sesame Seeds | 2.5 mg per 100g | Rich source; tahini (sesame paste) is also high in manganese |
| Tofu | 1.5 mg per 100g | Good plant-based source; content varies by processing method |
| Maple Syrup | 2.0-3.0 mg per 100g | Surprisingly high in manganese; used in smaller amounts but can contribute to intake |
| Sweet Potato | 0.5 mg per 100g | Moderate source that’s commonly consumed; provides manganese along with other nutrients |
| Acai Berries | 1.0-1.5 mg per 100g | Rich source among fruits; often consumed as powder or in smoothies |
Geographical Variations
- Areas with manganese-rich soils (parts of Brazil, South Africa, Australia)
- Regions with manganese mining activity (may include environmental contamination)
- Areas with high manganese in groundwater (parts of Bangladesh, Cambodia, China)
- Areas with highly leached soils (parts of Scandinavia, New Zealand)
- Regions with sandy soils low in organic matter
- Areas with intensive agriculture and soil depletion
Soil manganese content directly affects manganese levels in crops, which in turn affects manganese content in livestock fed those crops. This creates regional variations in population manganese status. Agricultural practices, including fertilizer use and soil management, can influence manganese content in foods. Water sources can also contribute significantly to manganese intake in some regions, particularly with high manganese in groundwater.
Quality Considerations
Organic forms (gluconate, citrate, glycinate) generally have better bioavailability than inorganic forms. Manganese sulfate has reasonable bioavailability and is commonly used due to its cost-effectiveness.
Item 1
- Specified manganese form
- High – Look for supplements that clearly specify the exact form of manganese (gluconate, citrate, etc.).
- Appropriate dosage
- Critical – Choose supplements with dosages appropriate for your specific needs (typically 1-5 mg for general supplementation).
- Third-party testing
- High – Verify that supplements have been tested by independent laboratories for purity, potency, and contaminants.
- Manufacturing standards
- High – Look for supplements produced in facilities that follow Good Manufacturing Practices (GMP).
- Balanced formulation
- High – For multi-mineral supplements, ensure appropriate ratios with other minerals (particularly iron) to prevent imbalances.
- Additives and fillers
- Moderate – Minimize unnecessary additives, especially for those with sensitivities or allergies.
Those with sensitive digestion may benefit from amino acid chelates like manganese glycinate, which tend to cause less irritation.
Item 1
Sustainability And Ethical Considerations
Manganese is typically obtained from manganese ore mining, which can have environmental impacts including habitat destruction, water pollution, energy consumption, and greenhouse gas emissions.
Manganese mining in some regions may involve poor labor conditions, inadequate safety measures, or exploitation. Responsible companies implement supply chain monitoring.
Research is ongoing into more environmentally friendly production methods, including bioleaching (using microorganisms to extract manganese from low-grade ores) and improved recycling technologies.
Water Sources
- Groundwater can be a significant source of manganese in some regions, with concentrations varying widely based on geological factors. High manganese in drinking water (>0.5 mg/L) can contribute substantially to total manganese intake.
- Manganese content in drinking water varies widely by region, water source, treatment methods, and distribution systems. Some areas have naturally high manganese in groundwater.
- Generally contains minimal manganese unless specifically mineral-enhanced. Manganese content should be listed in mineral analysis.
- Many water filtration systems reduce manganese content, which may be beneficial in areas with excessive manganese but could potentially contribute to inadequate intake in some cases.
Contamination Concerns
- Manganese supplements should be tested for contamination with other heavy metals like lead, arsenic, cadmium, and mercury, which may be present in raw materials.
- Some regions have environmental contamination with manganese and other metals from industrial processes, which could potentially affect locally sourced materials.
- Third-party testing should verify the absence of harmful contaminants. Look for supplements with certificates of analysis or third-party certification seals.
Historical Usage
Discovery And Early History
Discovery: Manganese was first isolated and recognized as an element in 1774 by Swedish chemist Johan Gottlieb Gahn, who extracted it from pyrolusite (manganese dioxide). It had been used in various forms for thousands of years before its formal identification, primarily as manganese dioxide in glassmaking to remove the greenish tint caused by iron impurities.
Early Industrial Use: Manganese has been used in steelmaking since ancient times, with the Spartans using manganese-containing ores to create their exceptional steel weapons. By the 19th century, manganese became essential to modern steel production, where it remains crucial today for improving hardness, strength, and resistance to wear.
Early Medicinal Use: Various manganese compounds have been used medicinally throughout history. In ancient Egypt and Greece, manganese dioxide was used as a pigment and possibly for treating skin conditions. In the 18th and 19th centuries, potassium permanganate was used as an antiseptic, disinfectant, and treatment for various skin diseases.
Recognition As Essential Nutrient
Animal Studies: The essential nature of manganese in nutrition was first demonstrated in 1931 by D.A. McCollum and colleagues, who showed that rats fed manganese-deficient diets developed poor growth, abnormal reproduction, and skeletal abnormalities. Subsequent studies in various animal species confirmed manganese’s essential role in growth, reproduction, and metabolism.
Human Essentiality: Manganese was recognized as essential for humans by the mid-20th century, though clear human deficiency syndromes are rare due to the widespread presence of manganese in foods. The first documented case of human manganese deficiency was reported in 1972 in a man on a purified diet for vitamin K research.
Biochemical Role: The identification of manganese as a component of various enzymes, particularly manganese superoxide dismutase (discovered in 1970), provided biochemical evidence for its essential role in human metabolism. Subsequent discoveries of other manganese-dependent enzymes further established its importance in various physiological processes.
Traditional Medicine Usage
Ayurvedic Medicine: In Ayurvedic medicine, manganese-containing herbs and minerals have been used for centuries to treat various conditions including nervous disorders, diabetes, and bone diseases. Specific formulations like ‘Mandur Bhasma’ contain manganese along with iron and are used for anemia and liver disorders.
Traditional Chinese Medicine: In Traditional Chinese Medicine, manganese-containing minerals and herbs have been used to treat conditions related to bone health, menstrual disorders, and diabetes. Certain herbs known to be high in manganese, such as mulberry leaves, have been used for blood sugar regulation.
Folk Remedies: Various folk remedies worldwide have incorporated manganese-rich plants and minerals for treating conditions like epilepsy, diabetes, and bone disorders, though often without explicit knowledge of the manganese content.
Indigenous Practices: Indigenous cultures in various regions have used manganese-rich clays and minerals for medicinal purposes, including wound healing and treatment of skin conditions.
Modern Research Milestones
Enzyme Discoveries: The identification of manganese as an essential component of various enzymes has been a key area of research. The discovery of manganese superoxide dismutase in 1970 by Irwin Fridovich and Joe M. McCord was particularly significant, revealing manganese’s role in antioxidant defense. Subsequent discoveries of manganese’s role in glycosyltransferases, arginase, and pyruvate carboxylase further expanded understanding of its biological functions.
Neurotoxicity Research: Research in the 1960s and 1970s established that excessive manganese exposure, particularly in occupational settings like mining and welding, could cause a Parkinson’s-like neurological condition called manganism. This led to important occupational safety regulations and improved understanding of manganese’s dual nature as both essential and potentially toxic.
Nutritional Studies: In the 1980s and 1990s, controlled human studies helped establish manganese requirements and the consequences of inadequate intake. These studies led to the establishment of dietary reference intakes for manganese.
Biochemical Pathways: Research in the 1990s and 2000s elucidated the complex pathways of manganese transport, distribution, and utilization in the body, including the roles of transporters like DMT1 and transferrin in manganese homeostasis.
Supplementation History
Early Supplements: Manganese supplements first became commercially available in the mid-20th century, primarily as manganese sulfate or manganese chloride.
Form Evolution: In the 1970s and 1980s, more bioavailable forms like manganese gluconate and amino acid chelates were introduced as understanding of mineral absorption improved.
Dosage Trends: Early supplements often contained relatively high doses (5-10 mg), but dosage recommendations have generally decreased over time as research has refined understanding of requirements and potential toxicity.
Combination Products: Manganese became a standard component in multivitamin/mineral formulations, typically at doses of 1-2.5 mg, and in specialized formulations for specific health concerns like bone health and joint support.
Regulatory History
Dietary Reference Intakes: The first Adequate Intake (AI) for manganese was established in the United States in 2001 at 2.3 mg/day for adult men and 1.8 mg/day for adult women, reflecting the challenges in determining precise requirements due to the rarity of clear deficiency.
Upper Limit: The Tolerable Upper Intake Level (UL) for manganese was set at 11 mg/day in 2001, based on evidence of potential neurotoxicity at higher intakes.
Water Regulations: Regulations for manganese in drinking water have evolved over time. The current US EPA secondary standard (non-enforceable guideline) is 0.05 mg/L, while the WHO guideline value is 0.4 mg/L.
Supplement Regulations: Manganese supplements are regulated as dietary supplements in most countries, with varying requirements for quality, labeling, and claims.
Notable Manganese Researchers
| Name | Contribution |
|---|---|
| D.A. McCollum | Demonstrated the essential nature of manganese in animal nutrition in 1931 |
| Irwin Fridovich and Joe M. McCord | Discovered manganese superoxide dismutase in 1970, revealing manganese’s role in antioxidant defense |
| Carl L. Keen | Conducted extensive research on manganese’s roles in development, reproduction, and metabolism |
| Michael Aschner | Made significant contributions to understanding manganese neurotoxicity and transport across the blood-brain barrier |
| Jeanne H. Freeland-Graves | Conducted pioneering research on manganese requirements, metabolism, and status assessment in humans |
| John L. Beard | Investigated interactions between manganese and iron, particularly in brain development and function |
Changing Perceptions
From Industrial To Nutritional: Manganese’s perception evolved from primarily an industrial metal to an essential nutrient over the course of the 20th century, with increasing recognition of its diverse biological roles.
Toxicity Concerns: Historical concerns about manganese toxicity, particularly for neurological health, have been refined with better understanding of dose-response relationships and mechanisms of manganese homeostasis.
Therapeutic Applications: Interest in manganese’s therapeutic potential has waxed and waned over time, with recent research exploring applications in bone health, diabetes management, and joint health.
Environmental Perspectives: Perceptions of manganese in the environment have evolved from viewing it primarily as an industrial metal to recognizing its dual nature as both an essential nutrient and potential environmental toxicant, depending on concentration and form.
Cultural Impact
Industrial Significance: Manganese has played a crucial role in industrial development, particularly in steelmaking, which has indirectly affected human health through technological advancement and economic development.
Water Quality: Manganese in drinking water has been a significant public health concern in various regions, influencing water treatment practices and public perception of water quality.
Occupational Health: Manganese exposure in occupational settings like mining, welding, and steel production has been an important area of occupational health research and regulation, influencing workplace safety standards.
Modern Applications: Contemporary applications of manganese in batteries, electronics, and medical imaging continue to shape its cultural and health significance in the modern era.
Scientific Evidence
Evidence Rating
Evidence Summary
Manganese has strong evidence supporting its essential role in human health, with well-established biochemical functions in numerous physiological processes including antioxidant defense, carbohydrate metabolism, and connective tissue formation. However, clinical research on manganese supplementation for specific health conditions is limited compared to more extensively studied minerals. The strongest evidence supports manganese’s role in bone health, particularly when combined with other bone-supporting nutrients. Some research suggests potential benefits for glucose metabolism, joint health, and premenstrual syndrome, but results are mixed and often preliminary.
The relationship between manganese status and various health conditions is complex, with both deficiency and excess potentially contributing to adverse outcomes. True manganese deficiency is rare in humans consuming varied diets, making it difficult to study the effects of supplementation in addressing deficiency states.
Key Studies
Meta Analyses
Ongoing Trials
Evidence By Health Condition
| Condition | Evidence Strength | Key Findings | Clinical Relevance |
|---|---|---|---|
| Bone Health and Osteoporosis | Moderate | Animal studies consistently show that manganese deficiency impairs bone formation and reduces bone mineral density. Limited human studies suggest that manganese supplementation, particularly when combined with calcium and other bone-supporting nutrients, may support bone health through effects on bone formation and mineralization. Manganese activates enzymes involved in the synthesis of bone matrix components and may influence the balance between bone formation and resorption. | Manganese may be beneficial as part of a comprehensive approach to bone health, particularly in combination with calcium, vitamin D, and other bone-supporting nutrients. Most effective for prevention rather than treatment of established osteoporosis. |
| Glucose Metabolism and Diabetes | Low to Moderate | Animal studies show that manganese deficiency can impair insulin synthesis and secretion, potentially contributing to glucose intolerance. Observational studies in humans suggest associations between manganese status and diabetes risk, with some evidence that adequate manganese intake may be protective. Limited intervention studies have examined the effects of manganese supplementation on glucose metabolism in humans. | Current evidence does not support routine manganese supplementation for diabetes prevention or management, but ensuring adequate manganese intake through diet may be important for optimal glucose metabolism. May be most relevant for individuals with suboptimal manganese status. |
| Joint Health and Osteoarthritis | Low | Manganese is essential for the formation of cartilage components through its role in glycosyltransferases. Some clinical studies have examined combination products containing glucosamine, chondroitin, and manganese for osteoarthritis, with mixed results. Limited evidence specifically for manganese’s independent effects on joint health in humans. | Manganese may be beneficial as part of a comprehensive approach to joint health, particularly in combination with glucosamine and chondroitin. Most commonly used for mild to moderate osteoarthritis rather than severe joint damage. |
| Premenstrual Syndrome | Low | Limited studies suggest that manganese, particularly when combined with calcium, may help alleviate symptoms of premenstrual syndrome. Manganese’s roles in neurotransmitter function and hormone metabolism may contribute to these effects. Evidence is primarily from small studies with methodological limitations. | Manganese may be considered as part of a comprehensive approach to managing PMS symptoms, particularly in combination with calcium and magnesium. Individual response varies significantly. |
| Antioxidant Protection | Moderate (mechanistic) to Low (clinical) | Strong mechanistic evidence supports manganese’s role in antioxidant defense through manganese superoxide dismutase (MnSOD). Limited clinical studies have examined the effects of manganese supplementation on oxidative stress markers in humans, with mixed results. Most benefits observed in conditions of manganese deficiency rather than supplementation above adequate levels. | Ensuring adequate manganese status is important for optimal antioxidant defense, but supplementation beyond adequate levels may not provide additional antioxidant benefits in individuals with normal manganese status. |
| Wound Healing | Low | Manganese supports wound healing through its roles in collagen formation, antioxidant protection, and immune function. Limited clinical evidence specifically for manganese’s effects on wound healing in humans, with most evidence from mechanistic and animal studies. | Manganese may be beneficial as part of a comprehensive approach to supporting wound healing, particularly in combination with other nutrients important for tissue repair like vitamin C, zinc, and protein. |
| Epilepsy | Very Low | Some case reports and animal studies suggest a potential relationship between manganese status and seizure susceptibility, with both deficiency and excess potentially influencing neurological function. Very limited clinical evidence for manganese supplementation in epilepsy management. | Current evidence does not support manganese supplementation for epilepsy management. Both deficiency and excess of manganese can have neurological effects, making proper dosing critical if considered. |
Research Limitations
Methodological Issues
- Limited number of high-quality randomized controlled trials examining manganese supplementation
- Small sample sizes in many studies
- Variable dosing protocols and manganese forms across studies
- Inconsistent assessment of baseline manganese status
- Limited long-term studies examining effects of manganese supplementation
- Challenges in accurately assessing manganese status due to tight homeostatic regulation
- Many studies examine combination products rather than manganese alone, making it difficult to isolate manganese’s specific effects
Knowledge Gaps
- Optimal manganese intake for different populations and health conditions
- Long-term effects of moderate manganese supplementation
- Interactions between manganese and other nutrients in different clinical contexts
- Genetic factors affecting manganese metabolism and requirements
- Role of manganese in specific disease processes
- Biomarkers that accurately reflect manganese status and function
- Threshold between beneficial and potentially harmful manganese exposure
Future Research Needs
- Larger, longer-term randomized controlled trials of manganese supplementation
- Studies examining manganese requirements in specific populations (elderly, pregnant women, individuals with certain health conditions)
- Research on manganese metabolism in various disease states
- Development of more accurate and functional biomarkers of manganese status
- Studies examining the effects of different manganese forms on bioavailability and clinical outcomes
- Research on manganese’s role in emerging areas like microbiome interactions and epigenetic regulation
- Studies to better define the therapeutic window between deficiency and toxicity
Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.