National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.
Texas A&M University College of Agriculture and Life Sciences, Texas A&M University AgriLife, College Station, TX, USA.
Am J Clin Nutr. 2020 Nov 11;112(5):1390-1403. doi: 10.1093/ajcn/nqaa259.
Folate, an essential nutrient found naturally in foods in a reduced form, is present in dietary supplements and fortified foods in an oxidized synthetic form (folic acid). There is widespread agreement that maintaining adequate folate status is critical to prevent diseases due to folate inadequacy (e.g., anemia, birth defects, and cancer). However, there are concerns of potential adverse effects of excess folic acid intake and/or elevated folate status, with the original concern focused on exacerbation of clinical effects of vitamin B-12 deficiency and its role in neurocognitive health. More recently, animal and observational studies have suggested potential adverse effects on cancer risk, birth outcomes, and other diseases. Observations indicating adverse effects from excess folic acid intake, elevated folate status, and unmetabolized folic acid (UMFA) remain inconclusive; the data do not provide the evidence needed to affect public health recommendations. Moreover, strong biological and mechanistic premises connecting elevated folic acid intake, UMFA, and/or high folate status to adverse health outcomes are lacking. However, the body of evidence on potential adverse health outcomes indicates the need for comprehensive research to clarify these issues and bridge knowledge gaps. Three key research questions encompass the additional research needed to establish whether high folic acid or total folate intake contributes to disease risk. 1) Does UMFA affect biological pathways leading to adverse health effects? 2) Does elevated folate status resulting from any form of folate intake affect vitamin B-12 function and its roles in sustaining health? 3) Does elevated folate intake, regardless of form, affect biological pathways leading to adverse health effects other than those linked to vitamin B-12 function? This article summarizes the proceedings of an August 2019 NIH expert workshop focused on addressing these research areas.
叶酸是一种必需的营养物质，天然存在于食物中，呈还原形式，在膳食补充剂和强化食品中以氧化合成形式（叶酸）存在。人们普遍认为，保持足够的叶酸状态对于预防因叶酸不足而导致的疾病（如贫血、出生缺陷和癌症）至关重要。然而，人们担心过量摄入叶酸和/或提高叶酸水平可能会产生不良反应，最初的关注点是加剧维生素 B-12 缺乏的临床影响及其在神经认知健康中的作用。最近，动物和观察性研究表明，叶酸摄入过量、叶酸水平升高和未代谢的叶酸（UMFA）可能对癌症风险、出生结局和其他疾病产生潜在影响。表明过量摄入叶酸、提高叶酸水平和未代谢的叶酸（UMFA）会产生不良反应的观察结果仍不确定；这些数据没有提供影响公共卫生建议所需的证据。此外，将叶酸摄入增加、UMFA 和/或高叶酸状态与不良健康结果联系起来的强有力的生物学和机制前提尚缺乏。然而，关于潜在不良健康结果的证据表明，需要进行全面的研究来澄清这些问题并弥补知识空白。三个关键的研究问题涵盖了为确定高叶酸或总叶酸摄入是否会导致疾病风险而需要进行的额外研究。1）UMFA 是否会影响导致不良健康后果的生物学途径？2）任何形式的叶酸摄入导致的叶酸水平升高是否会影响维生素 B-12 的功能及其在维持健康方面的作用？3）无论形式如何，提高叶酸摄入是否会影响除与维生素 B-12 功能相关的不良健康后果之外的生物学途径？本文总结了 2019 年 8 月 NIH 专家研讨会的会议记录，该研讨会的重点是解决这些研究领域的问题。
