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Reply to E Robberecht and S Vandewalle

Toronto Adult Cystic Fibrosis Centre
St Michael's Hospital
30 Bond Street, 6th Floor
Toronto, Ontario M5B 1W8
Canada
E-mail: stephensona{at}smh.toronto.on.ca

Dear Sir:

We are grateful for Robberecht et al's interest and comments on our article (1) and appreciate the opportunity to respond to their letter. We agree with the authors that vitamin D deficiency is an international problem and that normalizing serum 25-hydroxyvitamin D concentrations in patients with cystic fibrosis (CF) has been challenging. Boyle et al (2) showed that, even with high doses of ergocalciferol (vitamin D₂, plant form), serum 25-hydroxyvitamin D [25(OH)] concentrations do not increase as expected. Although our findings need to be confirmed in a randomized control trial, the results suggest that cholecalciferol (vitamin D₃, animal form), at appropriate doses, can increase serum concentrations. Studies have shown that ergocalciferol does not increase serum 25(OH)D concentrations as efficiently as does cholecalciferol, which may explain these divergent results (3, 4). That is not to say that vitamin D₂ is completely ineffective, and supplementation of milk with ergocalciferol in the United States has successfully eradicated rickets. However, the dose of vitamin D needed to prevent rickets is 100 IU/d in infants with little sun exposure. The dose of vitamin D needed to maintain nutritional adequacy on the basis of serum 25(OH)D concentrations is much higher. Robberecht et al raise an excellent point that sunlight may be the most effective and efficient way to normalize serum 25(OH)D concentrations in general and in CF patients in particular. This is undoubtedly the most "natural" way to make vitamin D. As stated in our article, Gronowitz et al (5) showed that 10 min of ultraviolet B exposure 3 times/wk increased serum 25(OH)D to concentrations as high as 124 nmol/L after 24 wk, which is much higher than that attained by supplementation with either cholecalciferol or ergocalciferol. It may be that such serum 25(OH)D concentrations can be achieved with higher doses of oral cholecalciferol, but this is not evident in the CF literature published to date. Natural exposure to sunlight for vitamin D synthesis is affected by season and latitude, which perhaps makes it less reliable. Also, the focus on sunscreen use and skin protection at a very early age has most certainly decreased vitamin D synthesis over one's lifetime. The use of controlled sun exposure as a therapeutic option for vitamin D deficiency in CF patients should be explored in future trials. Furthermore, well-designed randomized clinical trials of vitamin D supplementation with cholecalciferol in CF patients are badly needed to answer the question of whether this therapy is effective in maintaining serum 25(OH)D concentrations above 75 nmol/L.

ACKNOWLEDGMENTS

There were no conflicts of interest.

REFERENCES

1. Stephenson A, Brotherwood M, Robert R, Atenafu E, Corey M, Tullis E. Cholecalciferol significantly increases 25-hydroxyvitamin D concentrations in adults with cystic fibrosis. Am J Clin Nutr 2007;85:1307–11.[Abstract/Free Full Text]
2. Boyle MP, Noschese, ML, Watts SL, Davis ME, Stenner SE, Lechtzin N. Failure of high-dose ergocalciferol to correct vitamin D deficiency in adults with cystic fibrosis. Am J Respir Crit Care Med 2005;172:212–7.[Abstract/Free Full Text]
3. Armas L, Hollis B, Heaney R. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004;89:5387–91.[Abstract/Free Full Text]
4. Trang H, Cole D, Rubin L, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998;68:854–8.[Abstract]
5. Gronowitz E, Larko O, Gilljam M, et al. Ultraviolet B radiation improves serum levels of vitamin D in patients with cystic fibrosis. Acta Paediatr 2005;94:547–52.[Medline]

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