Vitamin B1 (Thiamine)

  • Class: water-soluble В-complex vitamin.
  • Use: diabetic neuropathy.
  • Dosing:

о Diabetic neuropathy: 100 mg orally three times daily for 3 months.132

  • Adverse effects: generally well-tolerated.
  • Drug interactions:

° Diuretic drugs: diuretic drugs increase urinary thiamine excretion and evidence of this vitamin deficiency may occur. Depletion of this supplement can worsen heart failure.

  • Contraindications: hypersensitivity to thiamine products.
  • Cautions: none known.

Vitamin B12

  • Class: essential, water-soluble vitamin.
  • Use: diabetic neuropathy, postherpetic neuralgia, peripheral neuropathy.
  • Dosing:

о Diabetic neuropathy:

- Cyanocobalamin 0.25 mg three times daily for 9 weeks, methylcobalamin 1500 meg daily for 3-4 months.133

=> Postherpetic neuralgia: methylcobalamin 100 meg SC six times weekly for 4 weeks.134

=> Peripheral neuropathy: preliminary clinical research shows that taking a specific product containing 3 meg vitamin B12, folic acid 400 meg, and uridine monophosphate 50 mg (Keltican) daily for 60 days reduced pain by 44% and decreased concomitant analgesic requirements by over 75% compared to baseline in patients with peripheral neuropathy, including those with lumbar/lumbosacral radiculopathy, sciatic pain, and cervical radiculopathy.135

  • Adverse effects: none noted, generally well-tolerated.
  • Contraindications: hypersensitivity to cobalt, B12 products, or any component of the supplement product.
  • Drug interactions:

о Chloramphenicol: limited case reports suggest that chloramphenicol can delay or interrupt the reticulocyte response to supplemental vitamin B12 in some patients. Monitor blood counts closely if this combination is needed and cannot be avoided.130

Cautions: not recommended in those with Leber’s disease as it may increase the risk of sudden and severe optic atrophy; patients with severe megaloblastic anemia may have increased risk of hypokalemia, thrombocytosis, and sudden death with administration of В12.


  • Class: water-soluble В vitamin also known as B7.
  • Mechanism of action: biotin modulates gene expression and alters pro-astrocyte glucose utilization that can improve symptoms associated with diabetic neuropathy by activating the Krebs cycle in demyelinating nerve cells and activating fatty acid synthesis that is required for myelin synthesis.136
  • Use: diabetic neuropathy.
  • Dosing:

° Diabetic neuropathy: 5 mg orally for 130 weeks preceded by 12 weeks of IM injections.137

  • Adverse effects: gastrointestinal upset.
  • Contraindications: hypersensitivity to biotin or any of its constituents.
  • Drug interactions:

о CYP1BI inducer: interaction with CYP1B1 substrates can decrease levels of these drugs metabolized by this enzyme.138 ° Anticonvulsants: can impair biotin absorption.

Lab interactions:

° High-dose biotin has been shown to interfere with many lab tests and yield false positive or negative results. Most of the published research on biotin interference covers hormone tests, such as parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), and T4 and T3 tests, as well as tests for troponin. However, because biotin is used in so many immunoassays, scientists say it could interfere with many others.

Evening Primrose

  • Class: biennial plant.
  • Mechanism of action: rich in omega 6 fatty acids and has direct action on immune cells.
  • Use: diabetic neuropathy, relapsing-remitting MS, rheumatoid arthritis.
  • Dosing:

° Relapsing-remitting MS: 0.6-0.7 g three times daily in combination with hemp seed oil for a period of 6 months.139

° Diabetic neuropathy: 360-480 mg daily for 6 months to a year.140

  • Adverse effects: gastrointestinal pain, distention and fullness, diarrhea, vomiting, flatulence, and dyspepsia.
  • Contraindications: hypersensitivity to evening primrose or any of its components.
  • Drug interactions:

о Anesthetic medications: reports of seizures. Unclear in studies if due to evening primrose.

=> Anticoagulant and antiplatelet drugs: reduces platelet aggregation and prolongs bleeding time.

=> Protease inhibitor drugs: may increase the levels of lopinavir and ritonavir when used in combination.

=> Phenothiazines: may lower seizure threshold. Unclear whether primrose has epileptogenic effects with the drug as there is no evidence that evening primrose alone causes seizures.

Cautions: N/A.

Milk Thistle (Silymarin)

  • Class: silybin or silibinin is thought to be the most active component of silymarin.
  • Mechanism of Action: there is interest in using silymarin for complications of diabetes, such as diabetic nephropathy, which is thought to be caused by oxidative stress and inflammation.141 Silymarin also possesses anti-fibrotic properties via downregulation of transforming growth factor-beta (TGF-beta). TGF-beta plays a role in diabetic nephropathy as it causes hardening of the glomerulus in the kidney as well as interstitial fibrosis.
  • Use: multiple sclerosis, diabetic neuropathy.
  • Dosing:

° Diabetic neuropathy: 140 mg orally three times daily for 3 months, in combination with conventional treatment.142

  • Adverse effects: nausea, vomiting, abdominal pain, sweating, and weakness.
  • Contraindications: hypersensitivity to milk thistle or any of its components.
  • Drug interactions:

° Anti-diabetic drugs: can have additive effects of lowering blood glucose, HbA lc levels, and insulin resistance.

° CYP 2C9, 2D6, and 3A4: silymarin is a CYP inhibitor and can increase the levels of CYP substrates of these enzymes.

=> Glucuronidated drugs: may affect the clearance of drugs undergoing glucuronidation and can inhibit uridine diphospho-glucuronosyl transferase, which is necessary for the glucuronidation process.

° Raloxifene: milk thistle contains silibinin constituents and silymarin.

° that, when in combination with raloxifene, inhibit the glucuronidation of raloxifene.

=> Sirolimus: silymarin also interacts with sirolimus. The combination decreases siroli- mus clearance and is found in hepatically and renally impaired patients.

=> P-glycoprotein substrates: Milk thistle inhibits P-glycoprotein substrates and increases drug levels of these medications.

° Tamoxifen: The constituent silibinin in milk thistle may increase plasma levels of tamoxifen, and later conversion into the active metabolite.

Cautions: insufficient reliable information available for use in pregnancy and lactation; avoid use.

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