Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen-Duisburg University, Essen, Germany.
Department of Nonclinical Safety, Janssen Research and Development, Beerse, Belgium.
Crit Rev Toxicol. 2020 Feb;50(2):177-187. doi: 10.1080/10408444.2020.1727842. Epub 2020 Mar 31.
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.
2016 年有人呼吁修订每日 1 毫克的叶酸摄入上限，这促使我们全面回顾了 1945 年至 2017 年间关于低钴胺素人群叶酸危害的文献。叶酸治疗“掩盖”未确诊钴胺素缺乏症引起的贫血，从而延迟神经病诊断的这一概念，并不能解释这种缺乏症在血液学和神经病学表现上的分离。1963 年至 1971 年，美国食品和药物管理局的裁决考虑到了这一概念的潜在风险，将所有叶酸制剂都列为处方药，每日剂量不超过 1 毫克。在用于“恶性贫血”的叶酸试验中出现的神经病是由于单独使用叶酸引起的，而用肝提取物或钴胺素替代叶酸可改善或消除神经病。关于“亚临床”钴胺素缺乏症认知障碍是由叶酸介导的假设是站不住脚的。在专门对此进行调查的 6 篇论文中，没有一篇能证明认知障碍的增加与高叶酸摄入有关。这篇综述完全支持每日 1 毫克的叶酸摄入上限是安全的。
