Manganese

1. Introduction

Manganese (Mn) is an essential trace element naturally present in many foods and available as a dietary supplement. It is a vital component of several enzyme systems and plays a fundamental role in numerous physiological processes within the human body.

Chemical/Botanical Basics

Manganese is a chemical element with the symbol Mn and atomic number 25. In the context of nutrition, it is typically ingested as the divalent cation, $text{Mn}^{2+}$. It is not a botanical product but a mineral micronutrient. In supplements, it is often found in various forms to enhance bioavailability, such as amino acid chelates, manganese bisglycinate chelate, manganese glycinate chelate, manganese picolinate, manganese sulfate, manganese citrate, and manganese aspartate [1].

Mechanism of Action

Manganese acts primarily as a cofactor for a variety of metalloenzymes, which are critical for metabolic function. Key manganese-dependent enzymes include:

• Manganese Superoxide Dismutase (MnSOD): The primary mechanism of action involves its role in MnSOD, the main antioxidant enzyme in the mitochondria. MnSOD catalyzes the dismutation of superoxide radicals ($text{O}{2}^{bullet-}$) into oxygen ($text{O}{2}$) and hydrogen peroxide ($text{H}{2}text{O}{2}$), thereby protecting cells from oxidative damage [1, 3].
• Arginase: Essential for the urea cycle, which detoxifies ammonia.
• Pyruvate Carboxylase: Critical for gluconeogenesis (glucose production) and the metabolism of carbohydrates.

Through these enzymatic roles, manganese is involved in amino acid, cholesterol, glucose, and carbohydrate metabolism, as well as reactive oxygen species scavenging, bone formation, reproduction, and immune response [1].

2. Chemical Composition/Key Bioactive Roles

The key bioactive role of manganese is its function as a cofactor for the following enzymes:

Bioactive Role	Enzyme Name	Physiological Function
Primary Antioxidant Defense	Manganese Superoxide Dismutase (MnSOD)	Catalyzes the conversion of highly reactive superoxide radicals to less harmful compounds, protecting mitochondria from oxidative stress.
Gluconeogenesis	Pyruvate Carboxylase	Converts pyruvate to oxaloacetate, a crucial step in glucose synthesis and energy production.
Urea Cycle	Arginase	Converts L-Arginine to ornithine and urea, essential for ammonia detoxification.
Bone & Connective Tissue	Glycosyltransferases	Required for the synthesis of proteoglycans, which are vital for cartilage and bone formation.

3. Health Benefits

Manganese is essential for health, and its supplementation is primarily studied in the context of bone health and metabolic disorders.

Bone Health

Manganese is a cofactor for several enzymes involved in bone formation, and manganese deficiency can impair bone formation and reduce bone mineral density [1].

• Evidence: A small clinical trial found that supplementation with calcium (1,000 mg) plus trace minerals, including 5 mg of manganese, 15 mg of zinc, and 2.5 mg of copper, for two years improved spinal bone density compared with placebo in 59 healthy postmenopausal women [1]. However, other studies examining the association between circulating manganese levels and bone mineral density have been limited and inconsistent, suggesting that while manganese is necessary, the benefit of supplementation may be most pronounced in cases of deficiency or when combined with other bone-supporting minerals [1].

Metabolic Health and Diabetes

Manganese is involved in glucose, carbohydrate, and lipid metabolism, and manganese deficiency might affect carbohydrate metabolism and cause abnormalities in glucose tolerance [1, 3].

• Evidence: Several studies have found associations between both increased and decreased blood levels of manganese and the prevalence of type 2 diabetes.
  • A case-control study in China found that those in the highest tertile of plasma manganese (>2.42 mcg/L) were 7.88 times more likely to have diabetes than those in the lowest tertile (<1.67 mcg/L) [1].
  • Conversely, a separate large case-control study in China suggested a U-shaped association, where those in the lowest tertile of plasma manganese concentration ($le$4.21 mcg/L) were also 1.89 times more likely to have type 2 diabetes [1].
  • Research in animals suggests that manganese supplementation might improve glucose tolerance, reduce oxidative stress, and improve endothelial dysfunction [1]. The inconsistent human data suggests a complex relationship, possibly where both deficiency and excessive exposure are detrimental to glucose homeostasis [3].

4. Dosage and Usage

The recommended intake for manganese varies by age and sex, and is generally based on Adequate Intake (AI) levels, as insufficient data exists to establish a Recommended Dietary Allowance (RDA) for all age groups [1].

Recommended Dosages (Adequate Intake – AI)

Age Group	Male (mg/day)	Female (mg/day)	Pregnancy (mg/day)	Lactation (mg/day)
19–50 years	2.3 mg	1.8 mg	2.0 mg	2.6 mg
51+ years	2.3 mg	1.8 mg	–	–
14–18 years	2.2 mg	1.6 mg	2.0 mg	2.6 mg
9–13 years	1.9 mg	1.6 mg	–	–
4–8 years	1.5 mg	1.5 mg	–	–
1–3 years	1.2 mg	1.2 mg	–	–

Note: The AI is the daily intake level assumed to ensure nutritional adequacy when evidence is insufficient to develop an RDA [1].

Food Sources

Manganese is present in a wide variety of foods. The best sources include whole grains, nuts, legumes, and certain beverages.

Food Source	Milligrams (mg) per serving
Mussels, blue, cooked, 3 ounces	5.8 mg
Hazelnuts, dry roasted, 1 ounce	1.6 mg
Pecans, dry roasted, 1 ounce	1.1 mg
Brown rice, medium grain, cooked, ½ cup	1.1 mg
Oysters, Pacific, cooked, 3 ounces	1.0 mg
Black pepper, 1 gram (about ½ tsp)	0.2 mg

5. Safety and Precautions

Manganese is considered safe when consumed at levels below the Tolerable Upper Intake Level (UL). Excessive intake, especially from non-dietary sources, can lead to serious health issues.

Safety Warnings (Tolerable Upper Intake Levels – UL)

The UL is the maximum daily intake unlikely to cause adverse health effects. For adults, the UL is 11 mg/day [1].

Age Group	UL (mg/day)
19+ years	11 mg
14–18 years	9 mg
9–13 years	6 mg
4–8 years	3 mg
1–3 years	2 mg

Side Effects and Contraindications

Serious Side Effects (Manganism): Chronic exposure to high levels of manganese, typically from occupational inhalation (e.g., welding, mining) or contaminated drinking water, can lead to manganese toxicity, also known as manganism [1].

• Symptoms: Manganism primarily affects the central nervous system and can cause tremors, muscle spasms, tinnitus, hearing loss, and a feeling of being unsteady. These signs can progress to neuromotor impairments similar to those associated with Parkinson’s disease, including changes in gait and balance, tremor, and rigidity [1].
• Contraindications: Individuals with chronic liver disease have impaired manganese elimination and are more susceptible to manganese neurotoxicity and other adverse effects of excess manganese intakes [1]. They should exercise extreme caution with manganese supplements.

Drug Interactions

Manganese is not known to have any clinically relevant interactions with medications [1].

6. References

[1] Buchman AR. Manganese. In: A. Catharine Ross BC, Robert J. Cousins, Katherine L. Tucker, Thomas R. Ziegler ed. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:238-44.
Source: National Institutes of Health, Office of Dietary Supplements, Manganese Fact Sheet for Health Professionals.[2] Nielsen FH. Manganese, Molybdenum, Boron, Chromium, and Other Trace Elements. In: John W. Erdman Jr. IAM, Steven H. Zeisel, ed. Present Knowledge in Nutrition. 10th ed: Wiley-Blackwell; 2012:586-607.
Source: National Institutes of Health, Office of Dietary Supplements, Manganese Fact Sheet for Health Professionals.[3] Li L, Yang X. The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid Med Cell Longev 2018: 7580707.
Full Text URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907490/
DOI: 10.1155/2018/7580707