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Monday, April 15, 2013

Vitamin D ~ Down but not out

Vitamin D remains a vitamin of great interest at present with opinions favouring and opposing its role in obesity and the associated morbidity of obesity, the metabolic syndrome, specifically, the glycaemic side of the metabolic syndrome. One recent paper has used a rather clever approach to ascertain the role of vitamin D in obesity[1]. They used data from 21 adult cohorts amounting to over 42,000 subjects for whom data was available on body weight (body mass index) and for whom detailed data on various aspects of gene sequence was also available.  The authors selected 12 genetic variations (single nucleotide polymorphisms) linked to obesity. Based on a previous meta-analysis of the observed effect of each genetic variation on BMI, the authors assigned a score of 0, 1 or 2 to each BMI related gene variant where 2 was a high degree of association with 0 at the lower end of the gene-BMI association. Each subject was thus assigned a score with a maximum of 24 and a minimum of zero. As the BMI gene score increased, so too did BMI. And as it did, the levels of plasma vitamin D fell. Thus for each unit rise in BMI, there was a 1.2% fall in plasma vitamin D. This tells us that as BMI rises, plasma vitamin D falls, a trend that has been observed before. But is it that low levels of vitamin D in blood lead to obesity or is it that high levels of obesity lead to lower plasma vitamin D levels. The latter is of course an attractive hypothesis since vitamin D is a fat-soluble vitamin and it remains possible that this vitamin moves out of plasma into the fatty environment of adipose tissue. To answer that question, the researchers also looked at two forms of genetic variation in vitamin D metabolism – an assortment of genetic variants, which drive vitamin D synthesis and another group, which drive vitamin D breakdown. Based on the mix of inherited genes, vitamin D levels varied but this variation showed absolutely no association with obesity. Together, these data show that the lower levels of vitamin D found in obesity are due solely to the dilution of plasma vitamin D with the migration of significant quantities from blood to adipose tissue.

Obesity is however, a very crude measure of phenotype and it is associated with many metabolic abnormalities, one of which is insulin sensitivity. Inadequate blood levels of vitamin D have been linked to disorders of glucose metabolism including impaired insulin sensitivity. Thus a recent study investigated the effects of supplementing the diets of adolescents with plasma vitamin D on a wide variety of glucose metabolic aspects of metabolism[2].  A group of 18 obese adolescents were given vitamin d for 6 months while a second group of 17 subjects received a placebo. Plasma vitamin D levels {25(OH)} doubled in the treatment group and remained unchanged in the placebo group. No effects were observed on BMI although the group as a whole was severely obese (39kg/m2). A highly significant improvement in insulin sensitivity was found for the vitamin D group but not the placebo group using two reliable methods of measuring (HOMA-IR and QUICKI). Fasting plasma glucose was not altered by vitamin D supplementation although fasting plasma insulin levels showed a significant reduction with vitamin D treatment. Thus a lower level of insulin managed to maintain comparable levels of blood glucose indicating an enhanced efficiency of the function of plasma insulin. Two key hormones associated with energy metabolism leptin and adiponectin did show a change in their ratio (leptin to adiponectin) and the greater the response observed to vitamin D supplementation, the greater was the change in in this ratio.

Clearly, vitamin D is not directly linked to obesity but it continues to display a role in the area of enhanced insulin secretion, enhanced insulin function and improved overall glucose metabolism. The present study would suggest that vitamin D supplementation might be a useful adjunct to standard metabolic management of severe obesity but the results of the present study would need to be replicated and with a larger sample size.

[1] Vimaleswaran KS et al (2013) PLoS Medicine, 10(2), e1001383
[2] Belenchia MA et al (2013) Am J Clin Nutr 97, 774-781