The second study of experimental human folate deficiency.

Abstract

Dear Editor We believed for over a half century that the landmark study by Herbert (1962) of experimental human folate deficiency is the one and only of its kind. However, there is a recent study by Golding (2014) published in SpringerPlus (2014, 3:442) reporting follow-up of haematological and biochemical changes secondary to a longterm intake of a low-folate diet. In both audacious studies, each author courageously subjected himself as an experimental subject and consumed foods thriceboiled in a large quantity of water. The principal difference between the two studies was that it took only 18 weeks for Herbert (1962) to observed megaloblastic changes in the bone marrow, whereas it was not until 82 weeks for Golding (2014) to detect this most advanced haematological sign of folate deficiency. Herein, to explain this startling difference, we propose two possible mechanisms. First, the difference may be explained by markedly higher baseline serum and erythrocyte folate concentrations (about 7 – 8 times higher than the cutoff for deficiency) in the study by Golding (2014) than those close to the cutoff points reported by Herbert (1962). These values are presented in Table 1, assuming that values by one of the assays in the recent study are believable. These suggest that the baseline total body folate stores must have been markedly different. If we simply calculate based on the duration until the end point of observing megaloblastic changes, the difference is about 4.6 fold (82/18). A vegetarian diet was consumed before the initiation of the experiment, which undoubtedly lead to above normal folate stores (Golding 2014). Such high body stores may be common in the countries where the fortification of staple foods with folic acid is practiced, and Lin et al. (2004) reported that the total body folate store of adults in the US is 225 μmol which is considerably higher than previously believed.