Doubts and truths about the extra-skeletal effects of vitamin D

Vitamin D has a long and interesting history. Phytoplankton and zooplankton have been producing vitamin D for more than 500 million years.
Since they had no skeleton, the original function of vitamin D was probably not related to bone metabolism. The dawn of the 20th century saw the rickets epidemic in Northern Europe and the United States, accompanied by an increase in respiratory infections among rickets-affected children.

From cod liver oil

In popular tradition, cod liver oil was widely used as a protective agent, and even after cod liver oil was marketed on a large scale as a medical remedy, the health benefits highlighted in the "package insert" were "the prevention and treatment of coughs and influenza in both children and the elderly".
In 1920, Adolf Windaus identified vitamin D by analyzing the antirachitic effects of cod liver oil. The extra-skeletal effects of vitamin D were only rediscovered in 1941.

Extra-skeletal effects

Today vitamin D (increasingly a hormone and less a vitamin) is receiving growing attention precisely because of its extra-skeletal effects, given that vitamin D receptors are present in almost all tissues and that the hydroxylases that activate vitamin D (enzymes) are likewise widely distributed throughout the various body tissues.

As regards, specifically, the use of vitamin D in the prevention and treatment of obesity, vitamin D would act by promoting the apoptosis of adipocytes through an increase in the intracellular concentration of calcium associated with the activation of proteases capable of producing morphological and biochemical effects that lead to apoptosis. In other words, the calcium concentration combined with the enzymatic processes that break down protein chains would favor the "natural" death (apoptosis, that is, and not necrosis) of those cells responsible for accumulating lipids as a source of energy for the body.
Naturally, further studies will be needed to assess this approach from a safety standpoint and to identify the optimal levels of calcium and vitamin D to take for the prevention and treatment of obesity.

Real requirements, risks and excesses

Although vitamin D toxicity is considered extremely rare and a very sporadic cause of hypercalcemia, the need to reach, for extra-skeletal effects, blood concentrations of vitamin D higher than those effective for bone disease may expose patients to the risk of hypervitaminosis.
The guidelines on food and nutrition indicate 2000 IU per day as the highest dose that can be taken without the risk of hypercalcemia. The use of high doses of vitamin D supplements, often based on emotional information found online and sometimes self-prescribed, can produce blood levels of vitamin D consistent with toxicity (> 100 ng/ml), all the more so because vitamin D, being fat-soluble, tends to accumulate in body fat (even more so in obese individuals).
It is no coincidence that reports of vitamin D toxicity, especially in the elderly, appear ever more frequently in the literature.

In 2011 the North American IOM (Institute of Medicine) published its report on calcium and vitamin D requirements, including a review of the scientific evidence on both skeletal and extra-skeletal effects, titled “The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know”.
Well, the conclusions of this vast and exhaustive —and indeed recent— review are that the available scientific evidence supports the key role of calcium and vitamin D in skeletal system health, demonstrating cause-and-effect relationships and providing a solid basis for defining requirements.
For the extra-skeletal effects, however, the evidence is inconsistent and not conclusive from a cause-and-effect standpoint and —above all— insufficient to define the requirements for obtaining extra-skeletal effects. Vitamin D requirements are identified as 600 IU/day for ages 1 to 70 and 800 IU/day for ages over 70.
In this way, 97.5% of the population shows vitamin D levels above 20 ng/ml under conditions of minimal sun exposure. Higher values have not been consistently associated with greater benefit and, for some outcomes, a U-shaped curve has been observed, with risks at both high and low levels. On the basis of these considerations, the prevalence of vitamin D deficiency in America is overestimated and, given the importance of the issue, urgent research is clearly needed, including a reassessment of the blood ranges of vitamin D, in order to avoid both over- and under-treatment.

What has been described only reaffirms, once again, how research data must be validated by clinical data before being communicated to the public.

The Scientific Committee of Nutricity