Experimental folate deficiency in human subjects: what is the influence of vitamin C status on time taken to develop megaloblastic anaemia?
https://bmchematol.biomedcentral.com/articles/10.1186/s12878-018-0107-2

Abstract

Background

In 1962 Victor Herbert developed megaloblastic anaemia four months after commencing a severely
folate-deficient diet whereas, in his self-experiment 50 years later, this author took 19 months to fully deplete his
liver folate store. This author proposed that his own larger initial liver folate store, due to his vegetarian diet and
consumption of fortified foods, was the cause of the time difference.

Main text

This author now proposes that Herbert was also likely to have been deficient in vitamin C, thus shortening
the time taken to develop folate deficiency. Several human experiments have confirmed the role of vitamin C in
protecting reduced forms of folate from oxidation. Although there has historically been no consensus on the required
intake of vitamin C, and official recommendations set a level below that required to ensure plasma saturation, recent
research supports an intake that would ensure saturation. There have been no longitudinal experiments on human
subjects since the introduction of voluntary or mandatory folic acid fortification of food, and the few published models
differ significantly in their estimates of human liver folate storage capacity.

Conclusion

Because of the importance of folate in one-carbon metabolism, the potential influence of vitamin C intake
on the time taken to deplete the liver folate store should be experimentally investigated.

Keywords

Experimental folate deficiency, Megaloblastic anaemia, Liver folate, Folate kinetics and metabolism,
Self-experimentation, Vitamin C deficiency