Drug Monograph

Manganese
Drug Information Provided By Gold Standard
NOTE: In the US, nutraceuticals are marketed under the Dietary Supplement and Health
Education Act of 1994 (DSHEA). Consequently, scientific data supporting claimed benefit(s) are
not always available for nutraceuticals as they are for traditional pharmaceuticals since
nutraceuticals are not regulated as drugs. Consumers should also note that rigid quality control
standards are not required for nutraceuticals and substantial variability can occur in both the
potency and the purity of these products. Monographs on nutraceuticals are included in CP when
reliable clinical data are available. The information presented below is condensed from the best
clinical data we could find.
Description: Manganese is an essential trace element. In the body, manganese is stored in
mitochondria-rich tissues such as the brain, kidney, pancreas, liver, and skeletal muscle
parenchyma. Rich dietary sources include whole grains, cereal products, some vegetables,
legumes and nuts (IOM 2001). There is no established recommended daily allowance (RDA) for
manganese. Instead, adequate intakes (AIs) are representative of the needs of various age groups;
in healthy infants the AIs describe the mean intake obtainable via breastmilk (IOM 2001).
Manganese requirements in humans are low and are easily met with normal dietary sources,
deficiency is rare.
Actions: Manganese is an activator for enzymes such as polysaccharide polymerase, liver
arginase, cholinesterase, and pyruvate carboxylase. Manganese may also serve as a cofactor in
lipid, protein, and carbohydrate metabolism, and is important in bone formation. In animals,
manganese deficiency may lead to poor reproductive performance, growth retardation,
congenital malformations in offspring, abnormal formation of bone and cartilage, dermatitis, and
impaired glucose tolerance.
Uses/Documentation: Manganese is known to be an important nutrient, but manganese
deficiency has not been documented in humans, as dietary intakes often exceed dietary
requirements. The element may be added to TPN solutions in patients who receive chronic
parenteral nutrition.
Contraindications/Precautions: NOTE: Manganese supplements should be used cautiously in
young children and pregnant or lactating females. Do not supplement manganese in these
populations without medical supervision.
Biliary tract or hepatic dysfunction: increased blood concentrations may result because
manganese is excreted in bile. Manganese supplementation to patients on long-term TPN should
be cautious; if patients develop cholestatic liver disease associated with TPN, manganeses may
need to be reduced or discontinued.
Renal impairment or renal failure: Manganese chloride injection contains aluminum; aluminum
may reach toxic levels with prolonged administration if patients with renal impairment. Research
indicates that patients with renal impairment, who receive parenteral aluminum at rates greater
than 45 mcg/kg/day, may accumulate aluminum at levels associated with CNS and bone
toxicity. Tissue loading may occur at lower administration rates.

Neonates: Benzyl alcohol is contained in some manganese injection products as a preservative

and has been associated with a fatal 'gasping syndrome' in neonates. In addition, premature
neonates are at risk for aluminum toxicity following parenteral manganese chloride
administration. Since these neonates have immature kidneys, they may require large amounts of
calcium and phosphate solutions, which also contain aluminum. Research indicates that patients
with impaired kidney function, including premature neonates, who receive parenteral aluminum
at rates greater than 45 mcg/kg/day, may accumulate aluminum at levels associated with CNS
and bone toxicity. Tissue loading may occur at lower administration rates.
Drug Interactions: No drug interactions of clinical significance are expected.
Adverse Reactions: In patients with cholestasis, manganese toxicity may result.Toxicity from
manganese primarily occurs during inhalational exposure in industrial settings; however, case
reports exist of manganese toxicity from overuse of supplementation in TPN (Reynolds N et al.,
1998). In the brain, manganese is concentrated in the basal ganglia, which partially accounts for
the regional specificity of toxicity and the resultant symptoms (IOM 2001). Neuropsychiatric
symptoms such as excitement, irritability, compulsive behavior with parkinsonian-like tremors,
mask-face and impaired gait and muscle control may occur. The risk of serious ADRs occurring
from excess oral intake from dietary or supplement sources appears low in otherwise healthy
individuals, as long as the recommended upper intake levels are not exceeded (see Maximum
Dosage Limits) (IOM 2001).
Available As:
Manganese is found as a single ingredient in oral dietary supplements or oral vitamin-mineral
combinations. Parenteral manganese is found in some combination trace element solutions, and
is also available as single-ingredient injections.
Manganese chloride Injection
various manufacturers
Available as 0.1 mg/ml injection. For IV use after dilution in large volume fluids only.
Manganese sulfate Injection
various manufacturers
Available as 0.1 mg/ml injection. For IV use after dilution in large volume fluids only.
Bioequivalence Issues: Do not confuse the mineral Manganese (Mn) with the mineral
magnesium (Mg). The bioavailability of manganese from oral dietary supplements may be higher
than that from food, and may lead to excessive intakes (IOM 2001).
Dosage:
For nutritional supplementation:
for the prophylaxis of manganese deficiency in patients receiving total parenteral nutrition
(TPN):
NOTE: Manganese is available as part of some intravenous multi trace-element preparations.
Intravenous dosage:
Adults: 200 mcg of elemental manganese IV per day in TPN.
Children: 210 mcg of elemental manganese IV per day in TPN.
for providing recommended adequate intake (No RDA is established) of elemental
manganese via the diet:
Oral dosage:
Adult and adolescent pregnant females: 2 mg PO per day.
Adult and adolescent lactating females: 2.6 mg PO per day.

Adult males: 2.3 mg PO per day.

Adult females: 1.8 mg PO per day.
Adolescent males >= 14 years: 2.2 mg PO per day.
Male children 913 years: 1.9 mg PO per day.
Female adolescents and children >= 9 years: 1.6 mg PO per day.
Children 48 years: 1.5 mg PO per day.
Children 13 years: 1.2 mg PO per day.
Infants 712 months: 0.6 mg PO per day.
Infants birth to 6 months: 0.003 mg PO per day.
Maximum Dosage Limits:
The following are recommended tolerable intake upper limits.
Adults: 11 mg/day PO.
Elderly: 11 mg/day PO.
Adolescents >= 14 years: 9 mg/day PO.
Children 913 years: 6 mg/day PO.
Children 48 years: 3 mg/day PO.
Children 13 years: 2 mg/day PO.
Infants: Upper tolerable intake level is not determinable due to a lack of data.
Patients with hepatic impairment:
Manganese may accumulate if biliary obstruction or hepatic disease is present; manganese is
eliminated primarily via the bile. Premature neonates with immature liver function may also be
at risk (Zlotkin SH et al., 1995). Reduce or discontinue manganese supplementation in TPN
patients with cholestatic liver disease.
Patients with renal impairment:
Manganese undergoes little excretion by the kidney.
References:
clinical overview: Food and Nutrition Board of the Institute of Medicine (IOM). Dietary
Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,
Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. A report of the panel on
Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation
and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation
of Dietary Reference Intakes. National Academy Press, Washington DC, 2001:pp. 311332.
reports (adverse reactions): Reynolds N, Blumsohn A, Baxter JP, et al. Manganese requirement
and toxicity in patients on home parenteral nutrition. Clin Nutr 1998;17:22730.
reports: Ono J, Harada K, Kodaka R, et al: Manganese deposition in the brain during long-term
total parenteral nutrition. JPEN 1995;19:3102.
review (nutritional requirements, neonatal): Zlotkin SH, Atkinson S, Lockitch G. Trace
elements in nutrition for premature neonates. Clin Perinatol 1995;22:22340.
Last revised: January 19, 2011

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