Best Evidence Topics
  • Send this BET as an Email
  • Make a Comment on this BET

Leucovorin (calcium folinate) in "antifreeze" poisoning

Three Part Question

In [an adult with methanol/ethylene glycol poisoning] is [the addition of IV Calcium folinate better than ethanol alone] at [reducing the incidence of reduced acuity and retinal oedema)]?

Clinical Scenario

A man attends the emergency department having deliberately taken 150 ml of "antifreeze". The can of antifreeze has conveniently been brought along and you find it consists of a mixture of methanol and ethylene glycol. The Poisons Centre is contacted. In addition to treatment with ethanol it is suggested that intravenous Leucovorin (calcium folinate) is given. You wonder if there is any evidence to support this recommendation.

Search Strategy

Medline 1996-06/03 using the OVID interface.
[exp leucovorin OR folinic OR Calcium] AND [exp methanol OR OR exp ethylene glycol OR ethylene OR] LIMIT to English.

Search Outcome

Altogether 12 papers were found, none of which were relevant to humans. One paper published in two different journals described studies on monkeys and suggested that the results could be extrapolated to humans.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Noker PE & Telphy TR,
Cynomolgus monkeys Effects of 5-fTHF or sodium folate following methanol poisoning are assessedExperimental studyMetabolic acidosisDid not develop in treated monkeys
Serum formate levelLower than untreated monkeys: (p<0.05)


In humans methanol toxicity is characterised by a metabolic acidosis and an ocular toxicity that occur coincident with an accumulation of formate in blood. After experimental studies on monkeys, Noker and Tephly hypothesised that folate compounds could decrease formate accumulation after methanol by stimulating formate oxidation or utilisation and suggested a possible use for folates in the treatment of certain cases of human methanol poisoning.

Clinical Bottom Line

There is no direct evidence of the usefulness of folates in methanol poisoning in humans. Local policy should be followed.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.


  1. Noker PE, Tephly TR. The role of folates in methanol toxicity. Adv Exp Med Biol 1980;132:305-15.