Vitamin D is a fat-soluble vitamin derived from cholesterol that has been the subject of many studies recently, confirming that its organic functions extend far beyond its participation in classic phospho-calcium metabolism.

Its classification as a vitamin has even been questioned, given that it can be synthesized by the action of the sun's UVB rays on the skin; therefore, it is proposed that it be considered a prohormone. Its role as a hormone has been proven in various enzymatic, metabolic, physiological, and pathophysiological processes related to many organs and systems in the body. The presence and expression of vitamin D receptors (VDR) have been confirmed in almost all human tissues.

The wide distribution of these receptors allows it, in addition to regulating phospho-calcium metabolism, to participate in a much more complex system that intervenes in processes of hormone synthesis and release, regulation of immune system functionality, cell proliferation and differentiation processes, and regulation of the expression of multiple genes, among others.

90% of this vitamin is obtained through the sun, since very few foods contain vitamin D, and the foods that do contain it are not consumed regularly or frequently enough to reach the recommended daily intake. Unprotected sun exposure in summer, for about 15 minutes a day, between 10 a.m. and 3 p.m., with the face and part of the arms exposed, would be enough to guarantee vitamin D synthesis.

• Vitamin D3 (cholecalciferol), the basic physiological substrate in humans and animals, recommended by scientific societies and formed in the skin from the absorption of ultraviolet (UV) radiation by 7-dehydrocholesterol.
• Vitamin D2 (ergocalciferol), of plant origin, obtained from fungi and plants after being exposed to sunlight. This form of vitamin is not usually marketed as a medication.

The activation of 7-dehydrocholesterol present in the skin by sunlight gives rise to vitamin D3 or cholecalciferol, which is transported through the blood to the liver, where it is converted into calcidiol or calcifediol or 25(OH)D (a metabolite that is used as an indicator and is measured in the blood); subsequently, in the kidney, it is converted by hydroxylation into calcitriol or 1,25-(OH)₂D, which is the final metabolite that binds to different vitamin D receptors located in numerous tissues (Table 1), and it is in these tissues where its hormonal activity occurs.

There are studies showing that vitamin D3 can be 1.7 to 3 times more potent than vitamin D2 in the ability to raise 25(OH)D levels, which is why vitamin D3 supplements are especially recommended.

Calcitriol is credited with functions in stimulating insulin production, modulating the function of activated B and T lymphocytes, effects on myocardial contractility, prevention of inflammatory bowel disease, and promotion of TSH secretion, among others. Therefore, vitamin D deficiency has lately been linked to multiple diseases.

Conditions such as obesity, intestinal malabsorption, renal or hepatic insufficiency, and others such as excessive use of sunscreens, or situations such as housing that does not allow access to sunlight, as well as lifestyle habits that do not include outdoor activities, drastically reduce the physiological bioavailability or access to vitamin D3.

• Promotes the integrity of the respiratory epithelium.
• Stimulates innate immunity by participating in the differentiation of monocytes to macrophages, which facilitate the interaction of vitamin D and cellular DNA to regulate genes that destroy infectious agents, block viral invasion, and prevent cell death of the respiratory epithelium, neutralizing endotoxins.
• Promotes cellular oxidation and reduction (redox) homeostasis, maintains normal mitochondrial function, inhibits the oxidative stress pathway, and modulates free radicals.
• Promotes antiviral response, reduces inflammatory processes by suppressing inflammatory cytokines.
• Promotes autophagy mechanisms in damaged proteins, protecting against viral infections.
• Modulates adaptive immunity activity, acting as an intermediary between innate and adaptive immunity through antigen presentation.
• Participates in the regulation of the Renin-Angiotensin-Aldosterone system, related to the regulation of blood pressure and water and sodium metabolism.

Cases have been published warning about the resurgence of rickets due to insufficient sun exposure combined with insufficient vitamin D intake in the population. Smaller infants are not exposed to the sun, and many breastfed children do not get adequate levels of vitamin D through either breast milk or sun exposure. When D3 is low, the hormone Leptin, a regulator of satiety, is produced in smaller quantities, which increases the accumulation of adipose tissue. Furthermore, since obesity is an inflammatory state and vitamin D3 is anti-inflammatory, being in low amounts promotes obesity.

Studies from the last two decades suggest that vitamin D plays an essential role in maintaining natural immunity, in the prevention of infections, in autoimmune diseases (multiple sclerosis, rheumatoid arthritis), at least 15 types of cancer, osteoporosis, cardiovascular diseases, type 1 and 2 diabetes mellitus, and psychiatric diseases, among others, in ecological epidemiological studies that link these pathologies to populations living in countries where there is less vitamin D synthesis due to solar radiation and that do not receive vitamin D supplements.

One microgram of vitamin D is equivalent to 40 IU.

Various researchers and related organizations suggest a plasma concentration of vitamin D between 40 and 60 ng/ml; other groups indicate 60 to 100 ng/ml in healthy people.

Supplementation ranges from 400 IU daily in children to doses ranging from 800 IU to ranges between 2,000 IU and 5,000 IU daily as a maintenance dose, depending on individual conditions.

The doses to treat COVID-19 are higher.

Bibliography

• Alonso López C., Ureta Velasco N., Pallás Alonso C.R., Pallás Alonso C.R.. Prophylactic vitamin D. Rev Pediatr Aten Primaria [Internet]. 2010 Sep [cited 2021 Feb 13] ; 12( 47 ): 495-510. Available at: http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1139-76322010000400012&lng=es.
• Mariana Seijo, Beatriz Oliveri, Importance of Vitamin D in the time of COVID 19, http://osteologia.org.ar/files/pdf/rid64_2020-11-covid-final.pdf,
• José Manuel Cucalón Arenal*, María Guadalupe Blay Cortés, Jesús Zumeta Fustero, Vicente Blay Cortés Update on treatment with cholecalciferol in hypovitaminosis D from primary care. SEMG Endocrinology, Metabolism and Nutrition Working Group. http://mgyf.org/actualizacion-en-el-tratamiento-con-colecalciferol-en-la-hipovitaminosis-d-desde-atencion-primaria/