Vitamin D is known as sunshine vitamin. Vitamin D exists as two forms - Vitamin D3 and Vitamin D2. Vitamin D3 or cholecalciferol is an inactive form which is synthesized from the skin on exposure to UVB radiation. Vitamin D2 or ergocalciferol is synthesized from plants. Fatty fishes, such as salmon, tuna, and mackerel, as well as beef, liver, and eggs comprise the primary dietary sources of Vitamin D3. The previous literature shows that Vitamin D is indeed a hormone not a nutrient. The body synthesizes Vitamin D after sun exposure, and it is activated by liver and kidneys. During exposure to sunlight, 7-dehydrocholesterol in the epidermis and dermis absorb ultraviolet B radiation resulting in the production of pro vitamin D3.
Pro vitamin D3 is rapidly converted by thermally induced rearrangement of the double bonds to form vitamin D3. Vitamin D3 enters the circulation and is bound to the vitamin D binding protein. It enters the liver where it is converted to 25-hydroxyvitamin D3 [25(OH) D3] Both vitamin D2 and vitamin D3 are converted to their respective 25-hydroxymetabolites, and are known collectively as total 25-hydroxyvitamin D [25(OH) D]. 25(OH) D is the major circulating form of vitamin D that is measured by clinical laboratories to determine a patient’s vitamin D status. 25(OH)D is biologically inactive and is transported on the vitamin D binding protein to the kidneys where it is converted to 1,25-dihydroxyvitamin D [1,25(OH)2D] which is considered to be the biologically active form of vitamin D. It is responsible for regulating serum calcium and phosphorous and is essential for bone metabolism by enhancing intestinal calcium absorption and mobilizing calcium from the skeleton . Researchers consider 1_,25(OH)2D3 to be steroid hormone and believe that it functions the same way as other steroid hormones by interacting with its cognate vitamin D receptor (VDR) .
Vitamin D receptor (VDR) is present in most tissues and cells in the body.1,25(OH)2D has a wide range of biological actions, such as inhibition of cellular proliferation and inducing terminal differentiation, inhibiting angiogenesis, stimulating insulin pro
duction, and inhibiting renin production . Dermal synthesis of vitamin D3 decreases with increasing latitude, increasing age, use of sunscreen, and darker skin pigmentation. Dark skinned populations in temperate climates have been found to demonstrate low levels of vitamin D3. Fair-skinned individuals need approximately 6 to 7 minutes of direct sunlight daily to the face, arms, and hands during summer months and up to 30 minutes in the winter. Darker-skinned individuals require 3-6 times longer exposure than white skinned individuals. This is because of melanin pigment in dark skinned individual doesn’t absorb as much UV radiation .
Vitamin D is widely used in dermatology for various skin disorders like psoriasis, urticaria, vitiligo and alopecia. The skin is the unique organ that is able to synthesize Vitamin D by exposure to UV rays. Vitamin D receptors present in the skin also help in prevention of skin cancer. Vitamin D also improves the immunity of skin and act as a physical barrier. The keratinocytes are the cells expressed in vitamin D receptor (VDR). The biologically active form of vitaminD3 or calcitriol plays a role in keratinocyte regulation by inducing differentiation and limiting keratinocyte proliferation. In psoriasis, keratinocyte proliferation occurs in a very high rate. The current therapy of vitamin D3 aims in controlling keratinocyte proliferation .
VDR is found in almost every cell in the immune system, including monocyte, macrophage lymphocyte, mast cell, natural killer cell, and dendritic cell. Aside from having VDR, those cells also have CYP27B1 enzyme activity and therefore are able to synthesize and secrete calcitriol. In natural immunity, Calcitriol stimulates antigen presenting cell (APC) to produce anti-microbial peptides cathelicidin and defensin and increases phagocytic capacity of APC. Calcitriol maintains mast cell stability and reduces histamine production. This action is helpful in treatment of urticaria. In adaptive immunity, CYP27B1 enzyme activity increases when T and B lymphocytes are activated. Calcitriol inhibits adaptive immune system by limiting proliferation and differentiation of B lymphocyte to plasma cell. Calcitriol inhibits proliferation and function of T helper-1 and T helper-17.
Calcitriol’s effect in suppressing adaptive immune system is
beneficial for several conditions such as autoimmune diseases
. In 2013, Danilo et al. conducted an open-label study in sixteen
vitiligo patients aged 18 years old and above in Sao Paulo
Brazil. In this study, 35,000 IU oral vitamin D3 was administered
daily for six months and demonstrated satisfactory result. This
study found 32% patients had up to 75% repigmentation, 32%
had 50% repigmentation, and the remaining number had up to
25% repigmentation  The studies have shown that mutation
occurring in VDR both in human and in mice resulted in alopecia
. Alopecia aerata is an autoimmune disorder where the vitamin
D3 has a role in etio-pathogenesis and oral supplementation
of vitamin D3 had shown an improvement of outcome .
As VDRs in pancreatic β-cells play an important role in the
progression of type 2 DM Vitamin D deficiency is related to insulin
secretion, insulin resistance, and β-cell dysfunction in the
pancreas. The secretion of pancreatic insulin is inhibited by vitamin
D deficiency in the diabetic animal model. Insulin sensitivity
is also associated with vitamin D. By stimulating the expression
of insulin receptors, vitamin D regulates insulin sensitivity .
Low serum levels of 25(OH)D have been linked through observational
studies to the patho-physiology of Obesity, Diabetes
Mellitus, and Metabolic Syndrome. A number of mechanisms are
explained. First, the VDR is highly expressed in adipocytes and
is responsive to activation by 1,25-(OH)2D Second, vitamin D is
fat soluble and can be stored in adipose tissues, Third, large cohort
studies have shown that an increased percentage of body
fat and high body mass index (BMI) are strongly and inversely
correlated with serum 25(OH)D concentrations, particularly in
Caucasians. Fourth, in rodent models, vitamin D modulates insulin
synthesis and secretion. Importantly, 1,25-(OH)2D regulates
calcium trafficking in _-cells in vitro and in mouse models. (3) In
a randomized controlled trial Vitamin D was supplemented the
diets of non-diabetic overweight South Asian women with 4000
IU/d for 6 months and found a significant improvement in insulin
sensitivity compared with a placebo group .
Vitamin D deficiency has been linked with the renin-angiotensin
system and inflammation, which may be associated with
the cause and progression of CKD. According to the Kidney Disease
Improving Global Outcomes guidelines, 25(OH)D levels
should be determined in patients with CKD stage 3-5, and if levels
are low, physicians should consider vitamin D supplementation.
Low 25(OH)D levels are associated with all-cause mortality
and cardiovascular disease in patients with CKD as well as in patients
undergoing dialysis .
Accumulating evidence suggests that altered vitamin D homeostasis
may also contribute to an increased cardiovascular
disease risk in obese subjects. The major observation involves
the association between low 25-hydroxyvitamin D [25(OH)D;,43
nmol/L] and obesity ; 25(OH)D concentrations ,33–37.5
nmol/L are independently related to a higher risk of myocardial
infarction, cardiovascular mortality, and all-cause mortality than
are 25(OH)D concentrations of 71–75 nmol [13,14]. In addition,
low 25(OH)D concentrations are predictive of elevated concentrations
of parathyroid hormone (PTH) (another biochemical
variable that is related to cardiovascular disease . The previous
RCT shows that vitamin D supplement of 83 mg/d does not
adversely affect weight loss and is able to significantly improve
several cardiovascular disease risk markers in overweight subjects.
In recent years it has been recognized that calcitriol exerts
anti-proliferative and prodifferentiating effects in many malignant
cells and retards the development and growth of tumours
in animal models raising the possibility of its use as an anticancer
agent . Epidemiological studies that identified beneficial
associations of serum 25(0H) D with incidence and case-fatality
rates of breast and colon cancer are supported by confirmatory
laboratory results from studies that have investigated the biological
mechanisms accounting for the action of vitamin D and
its metabolites in prevention of malignancy. For example, oral
administration of Vitamin D3 substantially reduced incidence of
colon cancer in rats fed with high-fat diets . Another study
found that administration of either UVB irradiance or the raising
of vitamin D metabolites with oral supplementation blocked
growth of mammary cancer in mice inoculated with cancer
xenografts that express vitamin D receptor (VDR) .
Recent systematic reviews and meta-analyses from cross-sectional
analyses suggest that low serum vitamin D concentrations
may be associated with Alzheimer’s disease and other forms of
dementia and cognitive impairment [19,20] However, other systematic
reviews could not find an association between cognitive
function and 25(OH)D concentration . A Norwegian trial of
overweight subjects showed that those receiving a high dose of
vitamin D (20,000 or 40,000 IU weekly) had a significant improvement
in depressive symptom scale scores after 1 year versus
those receiving placebo . The result determines a correlation
between vitamin D and the risk of depression.
To conclude, there is increasing evidence to show that there
is an increase in indications of Vitamin D therapy. Vitamin D
is the ‘talk’ of today and the drug of the future. Vitamin D is a
wonder hormone which will increase human healing and also
Holick M (2010) Vitamin D and health: evolution, biologic functions, and recommended dietary intakes for vitamin D. In: Vitamin D: physiology, molecular biology, and clinical applications. Holick M, editor. 2nd ed. Boston: Humana Press,US: p.3-33.
Danilo C Finamor, Rita S, Luiz C, Neves, et al. (2017) A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of J Gen Proced Dermatol Venereol Indones 2(1): 18-23.