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Vitamin D

With the novel coronavirus sweeping around the world, everyone is finding ways to protect themselves and their loved ones. A higher consumer demand on vitamins, minerals and nutrients has been reported worldwide. But with a variety of supplements available in the market, which one should we choose? “If you are deficient in vitamin D, that does have an impact on your susceptibility to infection. So I would not mind recommending, and I do it myself taking vitamin D supplements,” mentioned by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. [1] No doubt Vitamin D is important and could play a role in preventing COVID-19.

Our body naturally makes vitamin D when our skin is exposed to sunlight. However, with the factors of pollution, sunscreen and us working and spending lots of time indoors, we do not manage to get as much of vitamin D from the sun as possible [2]. There are also foods that contain Vitamin D, including fish, some dairy products and certain plants. However, foods naturally contain little vitamin D, and it’s challenging if one has certain food allergies or intolerances [3]. Thus, taking supplementation for vitamin D can help ensure we reach the recommended intake everyday. Different groups of people need different amount of vitamin D, for infants under one, 400IU of vitamin D is needed per day, whilst for individuals with the age over 70, 800IU of vitamin D is needed per day [4]. Deficiency of vitamin D can lead to loss of bone density, which can lead to osteoporosis and fractures. In children, it can cause the bones to become soft and bend, a disease known as rickets [5].

There are two major forms of Vitamin D, Vitamin D2 and Vitamin D3. Both Vitamin D2 and Vitamin D3 differ only in their side chain structure. When activated, both D2 and D3 forms exhibit identical responses in the body, having similar capabilities to treat vitamin D-deficiency rickets. Although experimental animal studies have reported that vitamin D2 is less toxic than vitamin D3, but none of the adverse effects have been reported in humans. Both Vitamin D2 and Vitamin D3 forms are considered biologically inactive until it undergoes two enzymatic hydroxylation reactions- liver and kidney. After hydroxylation, Vitamin D is in its physiologically active form, known as calcitriol. Most of vitamin D effect arises when calcitriol entered the nuclear vitamin D receptor. The classical actions of vitamin D due to the active metabolite, calcitriol, is the regulation of serum calcium and phosphate homeostasis that helps in development and maintenance of bone health [6]. Calcitriol has been reported to exert immunomodulatory properties in both innate and adaptive immune system [7].

The importance of Vitamin D in innate immunity came from a study about tuberculosis treatment with cod liver oil [8]. More studies came up later reporting the actions of calcitriol in enhancing the antimicrobial effects of macrophages and monocytes, which play an important role in fighting against pathogens such as Mycobacterium tuberculosis [7]. Monocytes and macrophages are crucial members of the innate immune compartment that exhibit the great ability to sense pathogen-associated molecular patterns (PAMPs) of various infectious agents, providing the first-line defence against dangerous microbial invaders . Apart from that, Vitamin D regulates the expression of an endogenous antimicrobial protein, LL-37, against Mycobacterium tuberculosis in cultured macrophages. Vitamin D also enhances cellular immunity by reducing the cytokine storm stimulated by the innate immune system. Administration of vitamin D was reported to reduce inflammatory cytokines and increases expression of anti-inflammatory cytokines by macrophages [9].

Vitamin D is also a modulator of adaptive immunity. Antigen-presenting dendritic cells interact with T cells to modulate the actions of adaptive immunity. Additionally, the proper action of vitamin D on cells of adaptive immune system is important to prevent autoimmune diseases. The ability of Vitamin D to act as an immunomodulator targeting a plethora of immune cells, including monocytes, macrophages, dendritic cells, T lymphocytes and B lymphocytes, indicating its’ role in maintenance of immune homeostasis [10]. Intriguingly, these are relates dated from ancient Greece describing sunlight’s therapeutic properties. Hippocrates used mostly sunlight for disease treatment. Other examples including Finsen in 1893 cured systemic lupus erythematosus (SLE) using direct light after filtering out the heat rays and Rollier in 1903 utilized sunlight treatment of surgical tuberculosis in Switzerland [9]. Epidemiological studies have linked inadequate vitamin D levels to a higher susceptibility of immune-mediated disorders, which brings a worrying trend. Vitamin D deficiency has been correlated with the incidence of autoimmune diseases, such as T1D (Type 1 Diabetes mellitus), SLE, multiple sclerosis, inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), where a lower serum Vitamin D levels were reported compared to healthy individuals. An interesting fact that a percentage of population in northern hemisphere (less UV radiation) is vitamin D deficient and this is positively correlated with higher percentages of autoimmune diseases [11].

With the world in the grip of COVID-19 pandemic, plenty of posts on social media have been highlighting the use of vitamin D to bolster their immune system and help them fight off COVID-19. Apart from Dr. Fauci, Dr. Tom Frieden, a former director of the center for Disease Control and Prevention has also proposed using vitamin D to combat COVID-19 [12]. Consumption of Vitamin D are highly recommended to older or elderly people as they have lower levels of vitamin D which might due to lessened mobility, increased adiposity, reduced rates of vitamin D synthesis in the skin and absorption of vitamin D in the gut [13].

A recent review has showed that using vitamin D with the loading doses of 200,000 – 300,000 IU in 50,000 IU capsules can reduce the risk and severity of COVID-19 [14]. Studies have reported that a serum level of 40-60 ng/mL calcitriol is necessary to prevent respiratory infection. Evidence of vitamin D’s impact on the ACE2 receptor (the specific receptor where viral envelope of coronavirus binds) is conflicting- Several suggest that vitamin D may downregulate the ACE2 receptor and thus decreasing the risk of COVID-19 infection [15]. Whilst others reported that vitamin D upregulates ACE2 that may mitigate the later effects of COVID-19 [16]. More studies are needed to investigate the relationship between vitamin D and ACE2 receptor. Although contradictory studies have been reported on the correlation of vitamin D with COVID-19, several studies have demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections, by direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. Vitamin D supplementation has also been shown to be safe and effective against acute respiratory tract infections. Thus, people who are at risk of vitamin D deficiency are encouraged to take vitamin D supplements during this global pandemic to maintain the calcitriol optimal levels [17].

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