Review Article |
Corresponding author: Mohd Alaraj ( ibrahim_naseem@yahoo.com ) Academic editor: Georgi Momekov
© 2022 Mohd Alaraj, Fahaad S. Alenazi, Dania Hassan, Ashfaque Hossain.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Alaraj M, Alenazi FS, Hassan D, Hossain A (2022) Vitamin D as a drug: new therapeutic approaches. Pharmacia 69(3): 765-770. https://doi.org/10.3897/pharmacia.69.e85057
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Vitamin D is one of the essential vitamins and has recently been demonstrated to be much more important for the appropriate functioning of the human body and well-being than initially believed. Although vitamin D is mainly known for its link with bone fractures and bone diseases, recent studies revealed that vitamin D and its analogues have revealed many pharmacological actions covering the regulation of cell growth, inhibition of inflammation, and improvement of neuromuscular function and immune function. Moreover, vitamin D and its analogues are reported to have role in different types of cancers, skin diseases, diabetes mellitus and infections caused by different bacterial and viral pathogens including SARS-CoV-2. The goal of this study is to evaluate the scientific literature on therapeutic uses of vitamin D and its analogues against different diseases and health condition. Special attention has been given to COVID-19 infection, cancer, skin diseases, and diabetes. The molecular mechanisms involved are also explored.
calcidiol, calcitriol, vitamin D3, SARS-CoV-2
Vitamin D comprises a collection of fat-soluble secosteroid organic compounds that have anti-rickets properties. The key D vitamins are vitamin D2 (ergocalciferol) and D3 (cholecalciferol) (
It is estimated that 90–95% of the vitamin D required is generated through skin synthesis, while diet is the secondary source of this vitamin in the human body (
Several years ago, it was found that actual vitamin D3 is calcitriol, while cholecalciferol is a provitamin that is converted to calcitriol in the kidneys (Whiting et al. 2021). Alfacalcide is derived from vitamin D3 as a very strong metabolite that is used in conditions when the body is unable to convert cholecalciferol into calcifediol due to kidney dysfunction. Thus, it is used for patients with liver and kidney injury who have symptoms of hypovitaminosis D (
Absorption; vitamin D3 is a lipid-soluble molecule that is absorbed into the lacteals in the gastrointestinal tract through chylomicrons. It is then transported via the lymphatic system and subsequently into the blood stream (
Vitamin D receptor (VDR) mediates the hormonal function of calcitriol in several physiological processes in the human body (Uberti 2016;
Calcitriol interacts with the receptors via two pathways: the classical genomic associated pathway, where calcitriol interacts with the nuclear VDR, and the non-genomic pathway, where this vitamin interacts with the membrane VDR (
Vitamin D is vital for the appropriate functioning of the whole body, particularly through its effects on metabolic processes (
Vitamin D3 has been suggested as a possible adjunct therapy for COVID-19 due to the in vitro observations of antiviral and protective effects against respiratory tract infections (including rhinovirus and respiratory syncytial virus infections), as well as its immunomodulation effects (
A number of clinical studies have examined or are currently exploring the relationship of vitamin D3 with SARS-CoV-2 infection. A retrospective cohort study showed that people infected with the SARS-CoV-2 virus had more than two-times lower serum concentrations of calcidiol on average than those in the control group (11.1 ng/ml and 24.6 ng/ml, respectively, P = 0.004) (
Vitamin D is reported to have a protective effect against SARS-CoV-2 infection, which prompted its inclusion in both preventive and treatment regimens for COVID-19. Serum vitamin D concentration is reported to serve as predictor of SARS-CoV-2 infection, which is independent of age, sex, race and attitude (
Although some progresses have been made in understanding the molecular basis of action of vitamin D, the total picture is not clear. However, enhanced expression of antimicrobial proteins, defensin and cathelicidin which are reported to play important role in the infection outcome process of various bacterial and viral agent(
SARS-CoV-2 infection is often leads to neurological symptoms such as loss of smell and taste, dizziness and confusion as a result of damages to the neurons caused by the virus. Vitamin D exerts neuroprotective effect by regulating the production of neurophilins, which are key factors modulating survival, differentiation and proliferation of neurons. Studies have shown that vitamin D promotes the migration and proliferation of oligodendrocytes, enhancing the remyelination of damaged neurons in animal models (
Increasing evidence suggests that vitamin D and its derivatives exhibit antitumor effects in mice (
Nonetheless, the key adverse effects of vitamin D – hypercalcemia and hypercalciuria – restrict its utilization in cancer therapy (
Vitamin D can increase the production of several antimicrobial peptides as well as the effects of cytokine and T helper type 2 cells. Thus, using this vitamin could decrease the risk of skin infection (
Although the mechanism of action of vitamin D and its analogues is not fully understood, it is known that this vitamin can augment keratinocyte differentiation and either activate or inhibit keratinocyte growth depending on the dose (
Both type 1 and type 2 diabetes can be prevented or treated with vitamin D and its analogues. This results from normalizing the function of the immune system, promoting B-cell survival and function, facilitating insulin secretion and glucose uptake, and controlling insulin-receptor gene expression (Sintov et al. 2014;
A growing body of clinical, experimental, and epidemiological studies suggests that vitamin D and its analogues may have therapeutic potential, particularly for the prevention and treatment of COVID-19 infection, various cancers, diabetes, and some skin diseases. Nevertheless, further long-term randomized controlled trials on vitamin D and its analogues are required to better understand their efficiency in the prevention and therapy for diseases, their adverse effects, and their molecular mechanisms of actions.
The authors are grateful to the Middle East University, Amman, Jordan, for the financial support to cover the publication fee of this research article.