What impairs the conversion of Vitamin B6 (Pyridoxine) to its active form?

From the Guidelines

Isoniazid is the most significant medication that impairs the conversion of vitamin B6 to its active form, pyridoxal 5'-phosphate (PLP), and its use requires supplementation with pyridoxine to prevent deficiency 1. The conversion of vitamin B6 to its active form can be impaired by several factors, including:

• Medications: isoniazid, penicillamine, and certain anticonvulsants like phenytoin and carbamazepine, which either compete with PLP at binding sites or form complexes that inactivate vitamin B6 1
• Chronic alcoholism: liver damage and acetaldehyde interference with conversion enzymes 1
• Genetic factors: mutations in the PNPO gene or PDXK gene can reduce the body's ability to convert B6 to its active form
• Medical conditions: kidney disease, celiac disease, and inflammatory bowel diseases can impair B6 activation through various mechanisms including malabsorption and increased excretion
• Aging: naturally reduces the efficiency of B6 conversion enzymes, making older adults more susceptible to deficiency It is essential to address these underlying factors when treating vitamin B6 deficiency, as simply supplementing with standard B6 may not be effective if the conversion pathway is compromised. Some key points to consider:
• Isoniazid therapy requires pyridoxine supplementation to prevent deficiency, with a recommended dose of 25-50 mg/day 1
• The optimal dose of pyridoxine for other conditions, such as ethylene glycol poisoning, is 50 mg IV every 6 hours 1
• PLP levels respond to intake and reflect liver stores, plateauing in 6-10 days 1

From the FDA Drug Label

Pyridoxine (vitamin B6) deficiency is sometimes observed in adults with high doses of isoniazid and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.

Isoniazid impairs the conversion of vitamin B6 to its active form by competing with pyridoxal phosphate for the enzyme apotryptophanase 2.

From the Research

Impairment of Vitamin B6 Conversion

The conversion of vitamin B6 to its active form can be impaired by several factors, including:

• Isoniazid (INH) therapy, which can competitively inhibit the action of pyridoxine in metabolic functions, as reported in 3
• High concentrations of pyridoxine, which can lead to decreased vitamin B6 function, as pyridoxine competitively inhibits the active pyridoxal-5'-phosphate, as shown in 4
• Inadequate quality of pyridoxal-5'-phosphate (PLP) supplements, which can result in insufficient effectiveness and safety, as illustrated in 5

Mechanisms of Impairment

The mechanisms of impairment can be attributed to:

• Competitive inhibition of pyridoxine by INH, as discussed in 3 and 6
• Competitive inhibition of pyridoxal-5'-phosphate by pyridoxine, as reported in 4
• Insufficient quality of PLP supplements, which can lead to complications such as seizures and intoxication, as described in 5