Obesity Can Cause Vitamin D Deficiency, Genetic Study Shows

Laurie Barclay, MD

February 08, 2013

Obesity is a causal factor in vitamin D deficiency, but vitamin D deficiency does not lead to any significant weight gain, according to a multicenter, genetic study published online February 5 in PLoS Medicine.

"While many health messages have focused on a lack of sun exposure or excessive use of suncreams, we should not forget that vitamin D deficiency is also caused by obesity," lead author Elina Hypponen, PhD, from the Institute of Child Health at University College London, United Kingdom, said in a news release.

"Our study highlights the importance of monitoring and treating vitamin D deficiency in people who are overweight or obese, in order to alleviate adverse health effects caused by a lack of vitamin D."

To evaluate the association between body mass index (BMI) and genes linked to vitamin D synthesis and metabolism, the researchers used genetic markers identified by analyzing 21 cohort groups that enrolled up to 42,024 participants for the D-CarDia Collaboration. The researchers confirmed associations between vitamin D and BMI using data from the Genetic Investigation of Anthropometric Traits (GIANT) consortium, which enrolled up to 123,865 participants.

"The researchers used bidirectional Mendelian randomization to examine the direction and causality of the relationship between BMI and 25(OH)D," Valeria Hirschler, MD, researcher in pediatrics, nutrition, and diabetes at the University of Buenos Aires in Argentina, told Medscape Medical News when asked for independent comment. "With this method, causality is inferred from associations between genetic variants that mimic the influence of a modifiable environmental exposure and the outcome of interest."

Across age and sex subgroups, every 10% increase in BMI was associated with a 4.2% reduction in 25(OH)D concentrations, suggesting that higher BMI results in lower vitamin D levels, with a negligible effect of vitamin D deficiency on BMI.

"This study suggests that obesity could cause vitamin D deficiency," Dr. Hirschler said. "However, low vitamin D levels did not [appear to be] a causal factor in the development of obesity."

Proof of Causation Difficult

Without longitudinal studies from childhood to adulthood, and because of confounding inherent in such studies, it is difficult to prove that vitamin D deficiency causes obesity or vice versa. Observational studies cannot determine whether the larger vitamin D storage capacity in obesity lowers 25(OH)D levels or whether 25(OH)D levels affect fat accumulation.

According to Dr. Hirschler, study limitations include potential variability among cohorts and laboratories used to measure vitamin D. Study strengths were large sample size, use of 12 BMI-related gene variants and two 25(OH)D allele scores, and bidirectional genetic approach.

"Plausible mechanisms by which vitamin D status may affect fasting glucose include a direct effect of vitamin D on insulin resistance through parathyroid hormone concentrations or insulin receptor expression, or effects on non-insulin-dependent pathways, such as insulin-independent glucose clearance or glucose uptake in the fasting state," Dr. Hirschler said.

"Given the prevalence and potentially deadly consequences of obesity, and consequently vitamin D deficiency, it is imperative for physicians to recognize the presence of these risk factors in their patients and to familiarize themselves with the recommended treatment strategies," she concluded. "Further research is needed on the prospective association between obesity and vitamin D in order to confirm these findings."

The British Heart Foundation and the UK Medical Research Council funded this study, with support from the Institute of Child Health and Great Ormond Street Hospital for Children National Health Service Trust. The study authors disclosed various financial relationships involving the Canada Institute of Research, Amgen, Eli Lilly, Medtronic, Merck, Novartis, Servier, synlab laboratory services GmbH, Diasorin Inc, and/or GlaxoSmithKline. Dr. Hirschler has disclosed no relevant financial relationships.

PLoS Med. Published online February 5, 2013. Abstract