Golding Paul Henry
Unit 5, 18 Webster Road, Nambour, QLD 4560 Australia.
Springerplus. 2014 Sep 23;3:442. doi: 10.1186/2193-1801-3-442. eCollection 2014.
The currently accepted theory, that the human liver store of folate is limited to about four months, is based on the findings of Victor Herbert and others of the era before folate fortification of food. A recent model, developed by Lin et al., predicts far greater liver folate storage capacity than reported by Herbert. The conflict between Herbert's and Lin's models needs to be resolved experimentally, however current research is restricted because ethical considerations prevent such risky experimentation on patients or healthy human volunteers. The objective was to provide a detailed record of the biochemical and haematological responses to the development of severe experimental folate deficiency in an initially replete human subject.
This 58 year old male severely depleted himself of folate, using a folate-deficient diet, until overt megaloblastic anaemia developed. The biochemical and haematological responses were monitored by routine blood tests. Daily intake of dietary supplements prevented deficiencies of other relevant nutrients.
The rate of change of all analytes was significantly slower, and the delay before any change for several analytes was significantly longer, than reported for previous experiments. The time before reporting of abnormal biochemical and haematological results was therefore very significantly longer than reported by Herbert, but was consistent with the recent model of Lin et al. Serum folate and red-cell folate became abnormally low after 219 and 413 days respectively. Macrocytic anaemia was produced after 469 days, and megaloblastic anaemia was confirmed by bone marrow biopsy on day 575. Folate starvation ceased on day 586, and recovery was complete on day 772.
The currently accepted four month time scale for development of megaloblastic anaemia from folate deficiency, based on the early work of Herbert and others, is not consistent with the results from this study. The > 300 day liver folate storage time, predicted by the model of Lin et al., is supported by this experiment. Self-experimentation has produced a detailed record of the biochemical and haematological responses to severe experimental folate deficiency, whereas using patients or healthy volunteers as subjects would be unethical.
目前被广泛接受的理论认为，人体肝脏中叶酸的储存量仅够维持约四个月，这一理论是基于维克托·赫伯特等人在食品叶酸强化之前的研究结果。林等人最近开发的一个模型预测，肝脏叶酸的储存能力比赫伯特报告的要大得多。然而，赫伯特模型和林模型之间的冲突需要通过实验来解决，但目前的研究受到限制，因为伦理考虑因素禁止在患者或健康人类志愿者身上进行这种有风险的实验。目的是详细记录一名初始叶酸充足的人类受试者在实验性严重叶酸缺乏发展过程中的生化和血液学反应。
这名58岁男性通过食用叶酸缺乏的饮食使自己严重缺乏叶酸，直到出现明显的巨幼细胞贫血。通过常规血液检查监测生化和血液学反应。每日摄入膳食补充剂可防止其他相关营养素缺乏。
与之前的实验相比，所有分析物的变化速率明显较慢，几种分析物出现任何变化之前的延迟时间明显更长。因此，报告异常生化和血液学结果之前的时间比赫伯特报告的要长得多，但与林等人最近的模型一致。血清叶酸和红细胞叶酸分别在219天和413天后变得异常低。469天后出现大细胞贫血，第575天通过骨髓活检确诊为巨幼细胞贫血。叶酸饥饿在第586天停止，第772天完全恢复。
基于赫伯特等人早期工作得出的目前被广泛接受的叶酸缺乏导致巨幼细胞贫血发展的四个月时间尺度与本研究结果不一致。林等人模型预测的肝脏叶酸储存时间超过300天得到了本实验的支持。自我实验详细记录了对实验性严重叶酸缺乏的生化和血液学反应，而以患者或健康志愿者为受试者则不符合伦理。
