What is the daily recommended dose of 5-Methyltetrahydrofolate (5-MTHF) for peripheral neuropathy?

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Last updated: March 23, 2025View editorial policy

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From the Research

The recommended daily dose of 5-MTHF for peripheral neuropathy is 3 mg, as it has been shown to improve cutaneous sensitivity in diabetic peripheral neuropathy when combined with methylcobalamin and pyridoxal 5'-phosphate 1.

Key Considerations

  • 5-MTHF is the active form of folate, which plays a crucial role in methylation processes and nerve function.
  • Individuals with MTHFR gene mutations may benefit from 5-MTHF supplementation, as they cannot efficiently convert folic acid to its active form.
  • When taking 5-MTHF, it is best absorbed when taken with vitamin B12 (methylcobalamin form, 1000-5000 mcg daily), as these nutrients work synergistically.
  • The bioavailability of 5-MTHF is higher compared to folic acid, with peak concentrations almost seven times higher after administration of 5-MTHF 2.
  • A study on Malaysian women found that l-5-MTHF supplementation increased blood folate concentrations to a greater extent than folic acid supplementation 3.

Monitoring and Adjustments

  • Start with a lower dose (1-3 mg) and increase gradually if needed, monitoring for improvement in neuropathic pain, tingling, or numbness.
  • Some people may experience side effects like sleep disturbances or irritability at higher doses.
  • 5-MTHF supplementation works best as part of a comprehensive approach that addresses underlying causes of nerve damage, and should be discussed with a healthcare provider before starting, especially if taking medications that affect folate metabolism.

Supporting Evidence

  • A study on diabetic peripheral neuropathy found that combination therapy with L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate improved cutaneous sensitivity and reduced symptoms 1.
  • A real-world patient experience trial found that patients with diabetic peripheral neuropathy treated with L-methylfolate-methylcobalamin-pyridoxal-5-phosphate achieved significant improvements in total symptom score and quality of life 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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