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Sources and physiological effects

Dietary sources
The trace element manganese is contained in both animal and plant tissues - but the latter are considered to be a richer source. The reproductive organs of plants are a particularly good source of manganese. The following foods contain manganese in descending quantities: whole grains, legumes, green leafy vegetables, fruits, roots and tubers. Animal products, such as meat or milk, contain rather small quantities of manganese, as do highly purified cereal products and sugar.
Physiological effects
Antioxidant	Cofactor of superoxide dismutase Reduction of oxygen free-radicals
Bone and joint metabolism	Preservation and formation of cartilage tissue as a cofactor of proteoglycan synthesis (chondroitin sulfate, glucosamine sulfate)
Blood	Maintains healthy blood coagulation as a co-factor in the formation of prothrombin
Urea metabolisme	Ammonia detoxification as a cofactor of the enzyme arginase
Fat and carbohydrate metabolism	Cofactor in cholesterol metabolism Influence on cholesterol levels, blood glucose levels and steroid hormone synthesis
Histamine metabolism	Cofactor in histamine degradation
Nerve metabolism	Regulation of neurotransmitter activity in the CNS

EFSA Health Claims

Health Claims		EFSA Opinion
Manganese	Contributes to a normal metabolism Contributes to the preservation of bone Helps protect cells from oxidative stress Contributes to normal connective tissue formation

Recommended intake

D-A-CH Recommended nutrient intake (Reference values EFSA and NHI )
	Age	Manganese (mg/d)
Infants (months)
	0-4	N/A
	4-12	0,6 - 1,0
Children (years)
	1-4	1,0 - 1,5
	4-7	1,5 - 2,0
	7-10	2,0 - 3,0
	10-13	2,0 - 5,0
	13-15	2,0 - 5,0
Teenagers/adults (years)		Women	Men
	15-19	2,0 - 5,0	2,0 - 5,0
	19-25	2,0 - 5,0	2,0 - 5,0
	25-51	2,0 - 5,0	2,0 - 5,0
	51-65	2,0 - 5,0	2,0 - 5,0
	> 65	2,0 - 5,0	2,0 - 5,0
Pregnant women	N/A
Breast-feeding women	N/A
Increased need	Alcohol abuse, diet high in white flour products, long-term medication with psychotropic drugs (manganese complex formation)

Recommended intake according to food labelling regulations
(=100 % TB marking on label)		2 mg
Safety
UL	Long-term daily intake, at which no negative health effects are to be expected	11 mg/d (according to NIH)
NOAEL	Maximum intake, with no observed adverse effect	N/A
Safety	EFSA has been working on the safety of manganese.

Detailed information

Manganese – an important factor in antioxidative defense mechanisms

Manganese is an important cofactor of mitochondrial superoxide dismutase (SOD), which protects the mitochondria from superoxide radicals and thus ensures cellular energy supply (1). In addition, manganese is involved in numerous metabolic processes of carbohydrate, fat and protein metabolism (2).

Manganese – a trace element for cartilage and bones

Manganese is required for normal bone mineralization and is therefore important for osteoporosis patients (3). In one study, supplementation with manganese had a positive effect on bone mineral density and bone formation of lumbar vertebrae (4). Manganese therapy is also indicated for degenerative and/or rheumatoid inflammatory cartilage diseases. Studies have shown that magnesium significantly increases cartilage matrix synthesis during cartilage growth (5)(6). Manganese is a cofactor of glycosyltransferase, which is involved in the biosynthesis of proteoglycans in cartilage and connective tissue and thus directly in the synthesis of cartilage tissue. Manganese as an antioxidant component can also positively influence inflammatory process via superoxide dismutase (7). In arthrosis and joint complaints, especially in younger patients, manganese levels should always be monitored and, if necessary, appropriately supplemented.

Reference values

Parameter	Substrate	Reference value	Description
Manganese in blood	Serum	0.4 - 1.0 µg/l	Manganese determination in serum only of limited significance, since manganese is predominantly intracellular.
	full blood	5 - 15 µg/l	Manganese is predominantly erythrocytically bound. Hematocrit-correlated whole blood analysis allows the correct interpretation of status.
Interpretation
Reduced values		Manganese deficiency is extremely rare and is usually the result of general under- or malnutrition.
Increased values		Acute or chronic manganese poisoning (steel and dye industry)
Note on the measurement results
Incorrect results due to sample contamination, introduction of manganese from cannula material during sampling.

Deficiency symptoms

Impact on	Symptoms
General health	Loss of appetite, growth disorders
Blood	Coagulation disorders hypercholesterolemia, hyperglycemia
Fertility	Disorders of spermatogenesis through reduced production of sex hormones
Bones and cartilage	Disorders in tissue formation, cartilage deformations

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	For the treatment of manganese deficiency determined by laboratory diagnosis	4 mg/d
	Preventive and concomitant therapeutic for osteoporosis	4 mg/d
	Preventive and concomitant therapy in degenerative and/or inflammatory cartilage diseases	4 mg/d

Administration

General mode of administration
When	Manganese should be taken between meals as other micronutrients and food components can interfere with absorption.
Side effects
No side effects are known at low-dose supplementation levels. Occupational chronic manganese poisoning occurs in the metal industry and is associated with severe neurological disorders (sleep disorders, headaches, dementia, parkinson-like tremor). During therapy, micronutrients can be used for the elimination of heavy metals in chronic manganese poisoning (alpha-lipoic acid, L-glutathione, chlorella vulgaris).
Contraindications
High occupational exposure to manganese (metalworking industry), liver and gallbladder diseases (reduced manganese excretion)

Interactions

Drug interactions
Antihypertensive drugs (reserpine)	Can lower manganese levels in the body.
Neuroleptics (e.g. haloperidol, flupentixol, prothipendyl)	Possible increase of cerebral toxicity.
Nutrient interactions
Trace elements (e.g. iron, calcium, magnesium, zinc)	Trace elements can reduce the absorption of manganese.

Description and related substances

Description

Trace element
Formula: Mn
Ion: Mn²⁺

Related substances

Manganese scorbate, manganese bisglycinate, manganese carbonate, manganese chloride, manganese citrate, manganese gluconate, manganese glycerophosphate, manganese pidolate, manganese sulphate

Organic compounds (e.g. gluconate) and chelated manganese compounds are considered to be more bioavailable.

References

1) Aguirre, J.D., Culotta, V.C. 2012. Battles with iron. Manganese in oxidative stress protection. J Biol Chem. 287(17):13541-8.
2) Gröber, U. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte. 2008.
3) Palacios, C. 2006. The role of nutrients in bone health, from A to Z. Crit Rev Food Sci Nutr. 46(8):621-8.
4) Bae, Y. J, Kim, M. H. 2008. Manganese supplementation improves mineral density of the spine and femur and serum osteocalcin in rats. Biol Trace Elem Res. 124(1):28-34.
5) Shimaya, M. et al. 2010. Magnesium enhances adherence and cartilage formation of synovial mesenchymal stem cells through integrins. Osteoarthritis Cartilage. 18 (10):1300-9.
6) Hapeta, B. et al. 2012. Metabolism and protein transformations in synovial membrane of a knee joint in the course of rheumatoid arthritis and degenerative arthritis. Pol Orthop Traumatol. 77:53-8.
7) Fernandez-Moreno, M. et al. 2011. Mitochondrial DNA (mtDNA) haplogroups and serum levels of anti-oxidant enzymes in patients with osteoarthritis. BMC Musculoskelet Disord. 12:264.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.