Vitamin D and human energy expenditure: are we there yet?

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Vitamin D has been implicated in prevention of many chronic non-communicable diseases including, CVD, T2DM, mental health, and cancer. Consistent evidence to date for the many extra-skeletal functions have mostly stemmed from animal and cellular models of investigation and evidence from  humans trials is still equivocal. We have been interested in the vitamin's role in the regulation of body weight, and whether it could play a part in the prevention or treatment of obesity. Resting energy expenditure (REE) makes up ~60% of total energy expenditure; the other two components being physical activity (30%) and the energetic cost of daily food ingestion (10%). Traditionally measured as the whole body oxygen consumption rate at rest, REE makes a major contribution to energy balance while representing the minimal daily energy intake necessary to stay alive!  Some years ago, we discovered that after accounting for several key variables that contribute to REE, vitamin D status and insulin sensitivity (IS) were independent contributors to the residual variation in REE. While vitamin D status (measured as circulating 25OHD) was positively related to REE, IS had a negative association with REE. Given the viewpoint that an improvement in vitamin D status would also improve IS (or reduce insulin resistance), these observations posed a conundrum. So what would be the net effect of vitamin D supplementation on REE? It was important to reconcile these observations as they would be acting in concert. So, in a hypothesis driven, cross sectional mediation analysis, we modelled the direct effect of 25OHD on REE in conjunction with an indirect mediation pathway, through IS.

The results confirmed a direct positive association of 25OHD on REE for all models studied. Importantly, we also noted a strong negative mediation through IS, that impacted on REE. The magnitude of this negative mediation varied with the surrogate index used to quantify IS or IR. However they were sizeable enough for us to conclude that any projected increase in REE, following an improvement in vitamin D status, would be dampened by a concomitant improvement in IS or by a reduction in IR. This has never been shown before, and so represents a new pathway to visualize the potential beneficial effects of vitamin D on energy metabolism, and hence energy balance. We have acknowledged that our cross sectional design does not offer causation. However these data present an imminently testable hypothesis through completed or planned future trials.  Vitamin D is expected to have beneficial effects on a variety of disease endpoints. Our view is the model(s) of vitamin D presented, could also apply to other endpoints of chronic disease that have insulin sensitivity as a key intermediate in their etiopathology. Confirmation of an impact of vitamin D on human energy expenditure would be ground breaking from a scientific viewpoint, and would constitute a cost effective strategy for body weight regulation.  


Assoc Prof, Curtin University