Why is folic acid (Vitamin B9) given in cases of toxic alcohol poisoning, specifically methanol poisoning?

Role of Folic Acid in Toxic Alcohol Poisoning

Folic acid is administered in methanol poisoning to enhance the metabolism of formic acid (the toxic metabolite of methanol) to carbon dioxide and water, thereby reducing toxicity and improving outcomes.1, 2

Mechanism of Action

• Methanol itself is relatively non-toxic, but it is metabolized by alcohol dehydrogenase to formaldehyde and then to formic acid, which is the primary toxic compound responsible for metabolic acidosis and ocular toxicity 3
• Formic acid is converted to carbon dioxide and water through a folate-dependent pathway involving 10-formyl tetrahydrofolate synthetase 3
• Folic acid and its derivatives enhance this conversion process, accelerating the elimination of formic acid and reducing its toxic effects 4

Evidence Supporting Folic Acid Use

• Animal studies have demonstrated that administration of folate compounds (including folic acid and 5-formyl tetrahydrofolic acid) significantly decreases blood formate levels and prevents metabolic acidosis following methanol exposure 4
• In primate models, folate administration has been shown to both prevent and reverse methanol toxicity by stimulating formate oxidation 4
• Experimental data suggests that folic acid administration can decrease morbidity and mortality associated with methanol poisoning 1

Clinical Application in Toxic Alcohol Poisoning

• Folic acid is used as an adjunctive therapy alongside the primary treatments for methanol poisoning 2
• The main treatments for methanol poisoning include:
  • Alcohol dehydrogenase inhibition (with fomepizole or ethanol) to prevent formation of toxic metabolites 3
  • Correction of metabolic acidosis with sodium bicarbonate 3
  • Hemodialysis to remove methanol and formic acid 3
  • Folic acid to enhance formic acid metabolism 1, 2

Dosing Considerations

• While specific dosing guidelines for folic acid in methanol poisoning vary, it is typically administered intravenously 3
• In research settings, repetitive doses have shown efficacy in reducing formate accumulation 4

Current Practice Trends

• There has been a decline in folic acid recommendation for methanol poisoning in recent years (from 48% to 12% between 2002-2006 and 2007-2012) 5
• This decline may be related to the approval of fomepizole for methanol poisoning in 2002, which provides more reliable alcohol dehydrogenase inhibition than ethanol infusions 5
• Despite this trend, the biochemical rationale for folic acid use remains valid based on its role in formic acid metabolism 2

Important Considerations

• Folic acid should be considered as part of a comprehensive treatment approach that includes alcohol dehydrogenase inhibition and hemodialysis when indicated 3
• The efficacy of folic acid may be most significant in cases where there is delayed presentation or established formic acid accumulation 4
• While folic acid is generally considered safe, the primary focus should remain on preventing formic acid formation through prompt administration of alcohol dehydrogenase inhibitors 3