Vitamin D and Its Relationship with Obesity and Muscle


The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function.

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Alex’s Notes: Over the last decade, the research into vitamin D has exploded. For instance, it is now known that there are at least 40 metabolites of vitamin D whose role is only partially known. As many of you may or may not be aware, vitamin D3 is formed in the skin when exposed to ultraviolet radiation. From here it travels to the liver and is converted into 25(OH)D, and then to the kidneys to become 1,25(OH)2D – vitamin D’s most potent physiologically active form. This circulating compound then travels throughout the body to bind to vitamin D receptors (VDR), which exists on most bodily tissues, to perform a number of non-classical actions (things not related to bone metabolism and calcium homeostasis) such as cell proliferation and differentiation, as well as immunomodulatory, anti-inflammatory, and antifibrotic functions.

So how does this hidden elephant relate to obesity? Numerous studies have shown correlations between obesity (BMI greater than 30) and low serum 25(OH)D. But this doesn’t tell us that one or the other causes the other. Several hypotheses have been proposed to explain the correlation:

Personally, I would believe the first hypothesis to be the most probable. As the authors state,

“In obese subjects, not only fat mass is increased but also lean body mass, as an adaptative response to greater body weight. In animal studies it has been shown that 25(OH)D was stored 33% in fat and 20% in muscle [37], suggesting that muscle could be also another reservoir of vitamin D in humans.”

This would certainly explain the correlation between BMI, which is composed of both fat mass and muscle mass, and low serum vitamin D. Not to mention that it has been clearly shown that adipose tissue may both regulate and be regulated by vitamin D.

Continuing onwards to skeletal muscle, vitamin D has been shown to maintain the function of fast-twitch muscle fibers through the VDR by inducing genetic effects that lead to muscle protein synthesis and regulation of calcium transport (important for the muscle to contract). Moreover, 1,25(OH)2D can affect myogenic differentiation of skeletal muscle cell lines through an upregulation of IGF-II and follistatin and a downregulation of IGF-I and myostatin expression. At least in vitro it can.

This begs the question of how this may translate into real world results. Well,

“Short- and long-term studies collectively demonstrate a relationship between vitamin D status and fall prevention and improvement in muscle strength in community-dwelling older individuals receiving a long-term supplementation with calcium and vitamin D.”

On meta-analysis showed that doses of 700 IU to 1000 IU supplemental vitamin D3 a day could reduce falls by 19% or by up to 26% in the elderly.On the contrary, a double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, concluded that an annual oral administration of high dose of vitamin D (500,000 IU) resulted in an increased risk of falls and fractures. Other authors found no significant effect of vitamin D supplementation on muscle strength.

To be honest, all the conflicting evidence is probably a simple result of n=1. All these studies are performed on people of differing ethnicities, age, lifestyles, and the list goes on for miles. The bottom line is that the optimal serum levels of vitamin D are not yet known, and the optimal dosage to achieve those levels varies considerably depending on the person in question. We have a ton of data and very few answers. As the author concludes,

“Notwithstanding the whole amount of data on the field, no consensus currently exists on definition and treatment regimen of hypovitaminosis D, mostly as far as particular conditions (such as obesity) and targeting functions (as muscle strength) are concerned.”

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