Caroline Apovian, MD
December 27, 2022
Caroline Apovian, MD
A recent study found that people with obesity have lower blood levels of vitamin D than people of healthy weight. This association of obesity with low vitamin D levels has led to much speculation on whether low vitamin D levels cause obesity or whether obesity causes low vitamin D levels. The interest in this topic is piqued by the possibility that if vitamin D deficiency causes obesity, perhaps treatment could be as simple as providing vitamin D supplementation to enhance weight loss.
What Is Known About Vitamin D’s Role in the Body?
It’s well known that vitamin D is essential for bone health as well as balancing the minerals calcium and phosphorus, but what is its role in weight management? Approximately 80%-90% of vitamin D in the body is from the skin synthesis of cholecalciferol through ultraviolet B (UBV) radiation from sun exposure. The normal range of 25-hydroxy vitamin D is measured as nanograms per milliliter (ng/mL). Most experts recommend a level between 20 and 40 ng/mL, but this has been a controversial topic of never-ending debate in the medical literature.
Vitamin D Levels and Obesity
A strong link exists between low vitamin D levels (serum 25(OH) vitamin D) and obesity. This has been noted for many years without identifying the underlying reasons beyond the sequestering of vitamin D in adipose tissue, although I’ll discuss other possibilities.
The inverse correlation between vitamin D and obesity has been seen in other diseases, such as cardiovascular disease, hypertension, prediabetes, and insulin resistance, as well as in sarcopenia and aging. Most studies emphasized the correlation between increasing adiposity with vitamin D deficiency in all ethnic and age groups. The causes and potential direct consequences of the vitamin D deficiency state in obesity are not well understood.
Vitamin D and Adipose Tissue
It’s been proposed that low vitamin D status in obesity might be due to increased vitamin D clearance from serum and enhanced storage of vitamin D by adipose tissue.
In adipose tissue, vitamin D exerts a variety of effects on inflammation, innate immunity, metabolism, and differentiation and apoptosis in many cell types. There is a stronger association between 25(OH)D and visceral fat as compared to subcutaneous adipose tissue, which suggests an influence of inflammation and components of the metabolic syndrome on vitamin D metabolism.
Because vitamin D has anti-inflammatory properties, it’s possible that low vitamin D status contributes to adipose tissue inflammation, a key link between obesity and its associated metabolic complications in obesity. A higher storage of vitamin D in adipose tissue, if accompanied by a parallel increase in the local synthesis of 1,25(OH)2D3 and action, may conceivably modulate adipocyte function as well as the activity of adipose tissue macrophages and hence the level of adipose tissue inflammation. In addition, it seems likely that 1,25(OH)2D3 also regulates the function of macrophages and other immune cell populations within adipose tissue.
It’s well known that vitamin D is stored in body fat, leading to the assumption that this was important in the evolution of vertebrates, including humans, who lived at latitudes where vitamin D could not be made in the winter and vitamin D stores had to be mobilized to maintain vitamin D sufficiency.
What Is Vitamin D’s Role in Obesity?
The main question that has eluded an answer so far is this one: Is vitamin D deficiency only a coincidental finding in obesity due to sequestration of the vitamin in fat, or does it have a role in the development of obesity and its complications, such as cardiovascular disease, type 2 diabetes, and hypertension?
Low vitamin D usually leads to impaired calcium absorption in the intestine and a lower calcium level, and eventually enhanced bone turnover and impaired bone mineral density (BMD).
However, it is known that in obesity there is greater BMD than in those who are lean. This leads to the conclusion that because there is a lack of vitamin D deficiency effects on bone in those with obesity, there is not really a vitamin D deficiency, and it may be that the sequestration in adipose tissue leads to a permanent supply that can maintain bone health.
An alternative explanation is that there is greater skeletal loading in obesity, and elevations in hormones such as estrogen and leptin could compensate for the vitamin D deficiency, leading to greater BMD in obesity.
Several other potential mechanisms besides sequestration of vitamin D in adipose tissue have been identified for low vitamin D and obesity. These include impaired hepatic 25-hydroxylation in nonalcoholic fatty liver disease, less sunlight exposure due to lower mobility and different clothing habits in people with obesity vs their lean counterparts, and adverse dietary habits. For example, people with higher BMIs spend less time exercising outdoors and are more sedentary in general than their lean counterparts. Therefore, they are less likely to get sun exposure due to a decrease in time spent outdoors. Those with higher BMIs also tend to cover their bodies, showing less skin when outdoors than their leaner counterparts, and thus there is likely to be less conversion to vitamin D via skin and sun exposure in people with obesity.
Some studies suggest that an increased level of parathyroid hormone due to vitamin D deficiency promotes lipogenesis due to greater calcium influx in adipocytes. Another hypothesis is that the active form of vitamin D, 1,25(OH) D inhibits adipogenesis through actions modulated by vitamin D receptors. These studies are promising, but prospective randomized trials are needed to determine whether vitamin D supplementation is a treatment option in preventing obesity. So far, vitamin D supplementation shows inconsistent results.
To conclude, there is a high prevalence of vitamin D deficiency in obesity, most likely due to dilution and sequestration in greater volumes of fat, blood muscle, and liver in obesity. Low vitamin D levels can’t be ruled out as a cause of obesity because of the research showing some interesting findings in vitamin D receptors in adipose tissue. Vitamin D deficiency in obesity doesn’t seem to affect bone mass but could have deleterious effects on other organ systems.
Weight loss improves obesity and complications, including the risk for cardiovascular disease and type 2 diabetes as well as vitamin D deficiency.
What Do the Guidelines Say?
Treatment of vitamin D deficiency requires higher doses in obesity to achieve the same serum concentration compared with lean persons. Maintenance doses should not differ between those with obesity and lean persons.
The association of vitamin D and obesity remains elusive. Studies need to focus on vitamin D, vitamin D receptors, and actions of vitamin D in adipose tissue to investigate this relationship further.
In the meantime, media attention remains focused on the potential treatment and prevention of obesity with the mighty, all-purpose vitamin D, even though there is scant evidence.
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