Smith A David, Kim Young-In, Refsum Helga
Oxford Project to Investigate Memory and Ageing, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom.
Am J Clin Nutr. 2008 Mar;87(3):517-33. doi: 10.1093/ajcn/87.3.517.
Fortification of food with folic acid to reduce the number of neural tube defects was introduced 10 y ago in North America. Many countries are considering whether to adopt this policy. When fortification is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect pregnancy that is prevented. Are the benefits to the few outweighed by possible harm to some of the many exposed? In animals, a folic acid-rich diet can influence DNA and histone methylation, which leads to phenotypic changes in subsequent generations. In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people. Nations considering fortification should be cautious and stimulate further research to identify the effects, good and bad, caused by a high intake of folic acid from fortified food or dietary supplements. Only then can authorities develop the right strategies for the population as a whole.
10年前，北美开始在食品中添加叶酸以减少神经管缺陷的数量。许多国家正在考虑是否采用这一政策。实施强化措施后，每预防一例神经管缺陷妊娠，就有数十万人叶酸摄入量增加。少数人的受益是否会被众多摄入者中部分人可能受到的伤害所抵消？在动物身上，富含叶酸的饮食会影响DNA和组蛋白甲基化，进而导致后代出现表型变化。在人类中，叶酸摄入量增加会导致血液中天然叶酸和未代谢叶酸的浓度升高。高血液叶酸浓度可能与自然杀伤细胞细胞毒性降低有关，而高叶酸水平可能会降低对用于治疗疟疾、类风湿性关节炎、牛皮癣和癌症的抗叶酸药物的反应。在老年人中，高叶酸水平和低维生素B-12状态的组合可能与认知障碍和贫血风险增加有关，而在孕妇中，则与子女患胰岛素抵抗和肥胖症的风险增加有关。叶酸对癌症有双重作用，可预防癌症发生，但会促进癌前细胞和亚临床癌症（在人群中很常见）的进展和生长。因此，高叶酸摄入量可能对某些人有害。考虑实施强化措施的国家应谨慎行事，并鼓励进一步研究，以确定强化食品或膳食补充剂中高叶酸摄入量所产生的利弊。只有这样，当局才能为全体民众制定正确的策略。
