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Providing perspectives on recent research into vitamins and nutritionals

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Do Your Genes Affect Whether Your Circulating Vitamin D Levels Will Increase With Supplementation?

By Julia Bird

Eight years ago, fifteen vitamin D experts headed by Vieth put together a call-to-action on increasing vitamin D intake recommendations. They state that increasing vitamin D intakes by the recommended amount at the time would have only a modest effect on circulating levels of vitamin D. Even when the recommendations increased a few years later, the expected effect would still be relatively small. New evidence by Shab-Bidar and co-workers has found that genes can affect whether we respond to a vitamin D supplement.

Within an intervention study that found that vitamin D supplementation in the form of a yoghurt drink (doogh) had beneficial effects on body fat distribution and insulin sensitivity in subjects with type 2 diabetes when compared to a placebo drink, subjects’ Cdx-2 genotype was determined. This gene, which codes for a transcription protein that is involved particularly in the embryonic development of intestines, has been  linked to risk of osteoporosis (Unterlinden et al.). A common variant of the gene involves an A to G base substitution. The protein produced by the G-variant reduces the transcriptional activity of the vitamin D receptor by 70%, while there is an increase in calcium absorption and bone mineral density with the A-variant.

The researchers divided the 60 subjects in the study according to their genotype.  52% had the AA genotype, 32% had the AG genotype and 16% had the GG genotype.  Unexpectedly, only the AA genotype group showed an increase in circulating vitamin D levels at the end of the study. There was no significant change in vitamin D blood concentrations in the AG and GG groups, although the authors do not mention in the publication how many subjects were supplemented in each of the genotype groups. The AA-genotype group also showed favorable improvements in metabolic health compared to the other groups.

The incidence of each genotype frequencies in different populations was also reported. Although around half of subjects in this study (based in Iran) had the beneficial AA genotype, frequencies were much lower in Chinese (26%), South Asian (18%) and European (4% - Austrian) populations. This means potentially that genetics can have a large impact on whether an individual will respond to a vitamin D supplement, and in particular European populations may have a poor response to supplementation.

While it is too early to be able to tell whether we should be tested for Cdx gene-variants to predict the effect of vitamin D supplementation, this piece of research may in part explain why supplementation studies have not achieved the expected results. If a large proportion of the study group does not show an increase in vitamin D levels due to genetics, then the effect of the supplement is likely to be lower than predicted. Perhaps part of the vitamin D controversy stems from the difficulties in predicting increases in vitamin D levels from intakes?  

Main citation:

Sakineh Shab-Bidar, Tirang R. Neyestani and Abolghassem Djazayery. Vitamin D receptor Cdx-2-dependent response of central obesity to vitamin D intake in the subjects with type 2 diabetes: a randomised clinical trial. British Journal of Nutrition, published online 8th September 2015. doi:10.1017/S0007114515003049.

Supporting citations:

Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2014;810:500-25.

Uitterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Reeve J, Reid DM, Amedei A, Bassiti A, Bustamante M, Husted LB, Diez-Perez A, Dobnig H, Dunning AM, Enjuanes A, Fahrleitner-Pammer A, Fang Y, Karczmarewicz E, Kruk M, van Leeuwen JP, Mavilia C, van Meurs JB, Mangion J, McGuigan FE, Pols HA, Renner W, Rivadeneira F, van Schoor NM, Scollen S, Sherlock RE, Ioannidis JP; APOSS Investigators; EPOS Investigators; EPOLOS Investigators; FAMOS Investigators; LASA Investigators; Rotterdam Study Investigators; GENOMOS Study. The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Intern Med. 2006 Aug 15;145(4):255-64.

Reinhold Vieth, Heike Bischoff-Ferrari, Barbara J Boucher, Bess Dawson-Hughes, Cedric F Garland, Robert P Heaney, Michael F Holick, Bruce W Hollis, Christel Lamberg-Allardt, John J McGrath, Anthony W Norman, Robert Scragg, Susan J Whiting, Walter C Willett, and Armin Zittermann. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr March 2007 85: 3 649-650.