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American Journal of Clinical Nutrition, Vol. 88, No. 2, 480, August 2008
© 2008 American Society for Nutrition

LETTER TO THE EDITOR

Reply to E Baggott and SL Morgan

A David Smith and Helga Refsum

OPTIMA
Department of Physiology
Anatomy & Genetics
University of Oxford
Oxford
United Kingdom
david.smith{at}pharm.ox.ac.uk

Dear Sir:

We agree with Baggott and Morgan that folic acid or its derivatives are valuable in reducing the toxic side effects of methotrexate in patients with rheumatoid arthritis (RA) and, indeed, we (1) pointed this out (page 523). However, we do not think we made a conceptual error in our "thought experiment": what we wrote was that studies need to be done to determine whether the incidence or severity of RA and psoriasis have changed in countries that have introduced folic acid fortification. We also asked whether treatment choice or drug efficacy has changed in these countries. The report by Arabelovic et al (2) that appeared after our Commentary was submitted shows that the average dose of methotrexate used has increased in the United States since 1996; the explanation offered by Baggott and Morgan is just as speculative as the suggestion that this change is a consequence of fortification. A key question is whether Baggott and Morgan consider it ethical to give additional folic acid to untreated RA patients to see whether it changes their symptoms, even if such a trial were to take place in a country without fortification. We think not. Finally, to say that there is no evidence that fortification has increased the incidence of RA simply reflects the fact that no such study has been conducted. We believe that such studies should be conducted, in the same way as they have been to determine the incidence of cancer (3). What we need is more evidence.

ACKNOWLEDGMENTS

No conflicts of interest were declared.

REFERENCES

  1. Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr 2008;87:517–33.[Abstract/Free Full Text]
  2. Arabelovic S, Sam G, Dallal GE, et al. Preliminary evidence shows that folic acid fortification of the food supply is associated with higher methotrexate dosing in patients with rheumatoid arthritis. J Am Coll Nutr 2007;26:453–5.[Abstract/Free Full Text]
  3. Mason JB, Dickstein A, Jacques PF, et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev 2007;16:1325–9.[Abstract/Free Full Text]




This Article
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