Fallacies of clinical studies on folic acid hazards in subjects with a low vitamin B12 status. (7th February 2020)

• Record Type: Journal Article
• Authors: van Gool, Jan D.; Hirche, Herbert; Lax, Hildegard; Schaepdrijver, Luc De
• Is Part Of: Critical reviews in toxicology. Volume 50:Number 2(2020)
• Page Start: 177
• Page End: 187
• Publication Date: 2020-02-07
• Subjects: Neural tube defects -- spina bifida -- folic acid fortification -- vitamin B12 deficiency -- pernicious anemia -- subclinical cobalamine deficiency -- cognitive impairment -- upper level of intake for folic acid; Toxicology -- Periodicals; Poisons -- Physiological effect -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1080/10408444.2020.1727842
• Languages: English
• ISSNs: 1040-8444

Abstract

Abstract: A 2016 plea for revision of the 1 mg/day upper level of folic acid intake prompted us to comprehensively review the 1945–2017 literature on folic acid hazards in subjects with low cyanocobalamin. The concept of folic acid treatment 'masking' the anemia in undiagnosed cyanocobalamin deficiency, thereby delaying the diagnosis of neuropathy, does not account for the dissociation between the deficiency's hematologic and neurologic manifestations. Possible risks of this concept were addressed by 1963–1971 FDA rulings, classifying all folic acid preparations as prescription-only drugs, delivering ≤1 mg daily. The neuropathy in folic acid trials for 'pernicious anemia' is due to the singular use of folic acid–neuropathy improved or disappeared with replacement of folic acid by liver extract or cyanocobalamin. The hypothesis that cognitive impairment in 'subclinical' cyanocobalamin deficiency is folate-mediated is untenable. Of 6 papers specifically investigating this, none could prove that increased cognitive impairment was related to high folate intake. This review fully supports the safety of the 1 mg/day upper level for folic acid intake.