Manganese

Usage

• Manganese is an essential trace mineral crucial for various physiological processes, including bone formation, wound healing, metabolism of carbohydrates, amino acids, and cholesterol, and as a cofactor for numerous enzymes. It is primarily used to treat or prevent manganese deficiency.
• Pharmacological Classification: Mineral Supplement. It functions as a cofactor, specifically for enzymes like superoxide dismutase (MnSOD).

Alternate Names

• Manganese citrate, manganese gluconate, manganese sulfate, MnCl2

How It Works

• Pharmacodynamics: Manganese acts as a cofactor for several enzymes, including glycosyltransferases (involved in cartilage formation), arginase (urea cycle), pyruvate carboxylase (gluconeogenesis), and MnSOD. MnSOD is a crucial antioxidant enzyme that protects mitochondria and cell membranes by scavenging superoxide radicals. Manganese contributes to bone health, wound healing, and carbohydrate and protein metabolism.
• Pharmacokinetics: Manganese absorption is regulated based on the body’s needs; lower levels lead to higher absorption rates. It primarily accumulates in mitochondria-rich tissues like bone, liver, pancreas, and kidneys. It is bound to the transport protein transmanganin (a beta-1-globulin). Excretion mainly occurs through bile and, to a lesser extent, through the kidneys.
• Mode of Action: Manganese’s primary mode of action is its role as an enzyme cofactor. MnSOD catalyzes the conversion of superoxide radicals to hydrogen peroxide, providing antioxidant protection. In bone formation, manganese-dependent enzymes facilitate glycosaminoglycan synthesis.
• Elimination pathways: Primarily biliary excretion with minor renal excretion.

Dosage

Standard Dosage

Adults:

• Recommended Adequate Intake (AI):
  • Men: 2.3 mg/day
  • Women: 1.8 mg/day
• Tolerable Upper Intake Level (UL): 11 mg/day

Children:

• AI varies with age:
  • 0-6 months: 0.003 mg/day
  • 7-12 months: 0.6 mg/day
  • 1-3 years: 1.2 mg/day
  • 4-8 years: 1.5 mg/day
  • 9-13 years: 1.9 mg/day (males), 1.6 mg/day (females)
  • 14-18 years: 2.2 mg/day (males), 1.6 mg/day (females)

Special Cases:

• Elderly Patients: No specific adjustments mentioned, but start at the lower end of the dosage range due to potential age-related organ dysfunction.
• Patients with Renal Impairment: Use with caution; dose reduction or withholding may be necessary.
• Patients with Hepatic Dysfunction: Use with caution; dose reduction or withholding may be necessary due to impaired biliary excretion.
• Patients with Comorbid Conditions: Patients with liver disease should be cautious due to potential manganese accumulation. Patients with iron deficiency anemia may absorb more manganese.

Clinical Use Cases

Manganese supplementation is not routinely recommended for the following, however research is ongoing into effectiveness:

• Intubation: Not applicable.
• Surgical Procedures: Not applicable.
• Mechanical Ventilation: Not applicable.
• Intensive Care Unit (ICU) Use: May be included in parenteral nutrition (PN) formulations for long-term critically ill patients to prevent deficiency. Monitor manganese levels, especially in those with liver dysfunction.
• Emergency Situations: Not applicable.

Dosage Adjustments:

• Adjust dosage based on renal and hepatic function and monitor manganese levels.

Side Effects

Common Side Effects:

Generally well-tolerated at recommended doses.

Rare but Serious Side Effects:

• Manganese toxicity (at high doses, chronic inhalation, or in patients with liver disease): Symptoms include neurological effects resembling Parkinson’s disease (tremors, muscle rigidity, gait disturbances), neuropsychiatric changes (mood alterations, hallucinations), and other systemic issues (pancreatitis).

Long-Term Effects:

• Chronic high-dose manganese exposure can lead to irreversible neurological damage.

Contraindications

• Known hypersensitivity to manganese.
• Severe liver disease.
• Premature infants (due to aluminum content in some injectable forms).

Drug Interactions

• Antacids (magnesium-containing): May reduce manganese absorption.
• Laxatives (magnesium-containing): May reduce manganese absorption.
• Iron supplements: May be affected by manganese intake.
• Some antipsychotic medications: May worsen manganese-related side effects.

Pregnancy and Breastfeeding

• Pregnancy: Adequate intake crucial. Pregnant women have a slightly higher AI (2.0 mg/day). Avoid exceeding the UL (11 mg/day). Inhaled manganese is potentially unsafe during pregnancy.
• Breastfeeding: Higher AI (2.6 mg/day) during lactation. Avoid exceeding the UL (11 mg/day). Inhaled manganese is potentially unsafe while breastfeeding.

Drug Profile Summary

• Mechanism of Action: Cofactor for enzymes, particularly MnSOD, contributing to antioxidant defense, bone health, and metabolic processes.
• Side Effects: Generally well-tolerated; toxicity at high doses can cause neurological, neuropsychiatric, and systemic effects.
• Contraindications: Hypersensitivity, severe liver disease, prematurity (for injectable forms).
• Drug Interactions: Magnesium-containing antacids and laxatives, iron supplements, certain antipsychotics.
• Pregnancy & Breastfeeding: Safe at recommended intake levels.
• Dosage: Adults: 2.3 mg/day (men), 1.8 mg/day (women); pediatric doses vary with age.
• Monitoring Parameters: For patients on PN or with suspected toxicity, monitor blood manganese levels, liver function tests, and neurological status.

Popular Combinations:

Often combined with calcium, zinc, and copper for bone health.

Precautions

• Caution in patients with liver or biliary tract impairment.
• Monitor aluminum content in injectable forms for renal impairment and premature infants.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Manganese?

A: The recommended AI for adults is 2.3 mg/day for men and 1.8 mg/day for women. Pediatric doses vary depending on age.

Q2: What are the signs and symptoms of manganese deficiency?

A: Manganese deficiency is rare. Symptoms can include impaired growth, skeletal abnormalities, impaired glucose tolerance, and altered lipid metabolism.

Q3: How is manganese toxicity treated?

A: Treatment focuses on removing the source of exposure and supportive care. Chelation therapy may be considered in severe cases.

Q4: What is the role of manganese in bone health?

A: Manganese is essential for the formation of glycosaminoglycans, components of cartilage and bone matrix.

Q5: Can manganese supplementation prevent osteoporosis?

A: While manganese is important for bone health, more research is needed to determine if supplementation prevents osteoporosis.

Q6: What are the food sources of manganese?

A: Good food sources include nuts, whole grains, leafy green vegetables, legumes, tea, and some spices.

Q7: How does manganese interact with other minerals?

A: High doses of manganese can interfere with iron and copper absorption. Conversely, iron deficiency can increase manganese absorption.

Q8: What is the role of manganese in diabetes?

A: Manganese is involved in insulin production and glucose metabolism, however more research is needed to determine if manganese plays a role in preventing or treating diabetes.

Q9: Can manganese be given intravenously?

A: Yes, intravenous manganese is used for patients with severe deficiency or those unable to take oral supplements. It is usually given diluted and slowly.