As the Covid-19 pandemic continues to decimate lives and economies across the globe, medical experts have suggested a number of things that people should do to limit their exposure to the infection.
One of the messages is that people should boost their immune system by consuming food fortified with sufficient Vitamin D, among other nutrients. This is particularly so as South Africa is right in the middle of the winter season where the risk of immune-compromising infections is heightened.
Professor XG Mbhenyane, I Labuschagne and J Vissser
NRF: Please explain the important role played by vitamin D in boosting the immune system?
SARChI team:The immune system relies on adequate nutrients to function properly. It is well-documented that nutritional status is closely associated with immunity and host resistance to infection. There is little argument that deficiency in both macronutrients and micronutrients causes immune function impairment, which can be reversed by replenishing nutrients[i].
Vitamin D is an essential nutrient, and its supplementation is recommended in a number of countries for various ages during their lifecycle and in patients with chronic conditions. People with higher vitamin D levels also tend to be healthier in general. This fact, demonstrated in observational studies, has led to the idea that poor vitamin D status might be a cause and consequence of several diseases.
Vitamin D is unique compared to other vitamins in that it can be found in foods and dietary supplements. In addition, the human body can manufacture it using the chemical compound found in the skin called 7-Dehydrocholesterol (7-DHC) when exposed to sunlight. Both sunlight-induced and diet-derived vitamin D first gets activated through a two-protein enzyme hydroxylation in the liver to 25-hydroxyvitamin D [25(OH)D], and in the kidney to the active form 1,25-dihydroxyvitamin D [1,25(OH)2D].
Several studies have highlighted that there is a link between lower vitamin D status and a wide range of human diseases. For example, chronic inflammatory diseases, such as atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, non-alcoholic fatty liver disease, and others, tend to have lower vitamin D status, which may play a role in the development of diseases[ii].
NRF: What is the role of Vitamin D in the fight against Covid-19?
SARChI team:Vitamin D is strongly linked to a range of COVID-19 risk factors. Vitamin D deficiency is linked with advanced age, obesity, hypertension, reduced concentration in northern climates, and coagulopathy (bleeding disorder), all of which are associated with poorer outcomes. With increased age, concentrations of active vitamin D decrease due to less sunlight exposure and reduced production of 7-dehydrocholesterol (7-DHC) in the skin.
COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. Vitamin D has roles in a wide range of body systems, including in both innate and adaptive immune responses. Vitamin D enhances the innate cellular immunity by activating antimicrobial peptides, such as cathelicidin and defensins, which are the first line of defence against foreign attacks.
Viruses such as influenza are known to significantly damage the integrity of epithelial cells of the respiratory system, increasing the risk of infection and pulmonary oedema (a condition caused by excess fluid in the lungs). Vitamin D is known to maintain the integrity of these epithelial cells and may regulate epithelial function through its capacity to suppress the development of inflammation. In addition, there is emerging evidence that vitamin D is essential for maintaining epithelial integrity and impairing the development of inflammation in the lungs during disease.
Deficiency in vitamin D has been suggested to increase incidence and severity of COVID-19 infection. COVID-19 patients have been repeatedly shown to have lower levels of vitamin D. Using the 25-hydroxy vitamin D-25(OH)D test to monitor vitamin D levels in patients who had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a study in Switzerland found that Covid-19 positive patients had lower levels of vitamin D in their blood compared with negative patients. Moreover, a recent study in Israel found that low vitamin D levels appeared to be an independent risk factor for COVID-19 infection and hospitalisation.
Several studies also highlight the role of Vitamin D in functions such as promoting anti- inflammatory cytokines, bacterial destruction and phagocytosis (a process by which certain living cells ingest or engulf other cells in an effort to destroy something, such as a virus or an infected cell).
NRF: Is there evidence to suggest that Vitamin D plays a role in mitigating the severity of COVID-19 infection?
SARChI team: There is currently no published data on the effects of vitamin D supplementation in SARS-CoV-2 infection. However, human clinical trials have been registered to determine the effect of vitamin D supplementation in COVID-19 patients.
However, considering the studies on the role of vitamin D in the prevention of acute respiratory infections, supplementation of vitamin D may be reasonable also for the prevention of SARS-CoV-2 infections and reducing morbidity and mortality in COVID-19 high-risk patients.
A study which reported the effects of vitamin D supplementation to prevent acute respiratory infections, found that vitamin D supplementation decreased the risk of respiratory tract infections by 12%. A stronger protective effect was observed in those with vitamin D baseline levels greater than 10ng/mL (25nmol/L) compared with those with a baseline levels less than 10ng/mL. This protective effect was much more evident in those receiving daily or weekly doses of vitamin D in contrast to those receiving bolus doses. This meta-analysis included 25 randomised, double-blind, placebo-controlled trials with individual data from 10 933 patients across the lifespan[iii].
Other reviews of note include one whose authors recommended that adults in Ireland take 20-50 micrograms of vitamin D per day to improve resistance to respiratory infections, such as COVID-19, or to improve the course of the disease [iv]. Another review suggests that “…people at risk of influenza and/or COVID-19 take 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25-hydroxy-vitamin D [25(OH)D] concentrations, followed by 5000 IU/d” to reduce the risk of infection[v].
In conclusion, the high-risk groups that have more complications and higher mortality in COVID-19 coincide with groups that have a high incidence of vitamin D deficiency. vitamin D deficiency might be one of the important risk factors for COVID-19 complications and higher mortality.
Future studies should involve experimental models to assess whether vitamin D can impair viral replication, block pro-inflammatory cytokines or have other effects related to SARS‐CoV‐2 pathogenesis.
NRF: What is the recommended daily intake of Vitamin D?
SARChI team:The Institute of Medicine advises that serum 25(OH)D concentrations greater than 20ng/mL (50nmol/L) can be considered sufficient, while values between 12 and 20ng/mL (30–50nmol/L) are insufficient, and lower than 12 ng/mL (30 nmol/L) are deficient.
Doses up to 10 000 IU per day are safe, although well above what is needed. In fact, only 1000–2000 IU may be needed to obtain optimal effects in relation to bone health and immunity. There is no need for people to take mega‐doses as these may only lead to increased risk for adverse events. Small and daily doses are enough to boost immunity.
In persons with confirmed vitamin D deficiency and high-risk individuals, higher dosages of vitamin D will be required to normalise levels, after which maintenance dosages will be required to maintain levels in the long term. In these cases, a medical professional should be consulted for treatment.
| Recommended Dietary Allowances (RDAs) for Vitamin D | ||||
| Age | Male | Female | Pregnancy | Lactation |
| 0-12 months* | 10 mcg (400 IU) | 10 mcg (400 IU) | ||
| 1–13 years | 15 mcg (600 IU) | 15 mcg (600 IU) | ||
| 14–18 years | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) |
| 19–50 years | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) |
| 51–70 years | 15 mcg (600 IU) | 15 mcg (600 IU) |
NRF: What is the difference between vitamin D2 and D3 and which of the two is highly recommended?
SARChI team:Vitamin D has two main forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), that differ chemically only in their side-chain structures.
Vitamin D2 is present in products of plant origin and in mushrooms, is inexpensive to produce, and is often added to foods such as milk to boost their vitamin D content.
Vitamin D3 is synthesised in the skin and found in diet sources which include oily sea fish and fish oil, and to a lesser extent egg yolks and dairy products.
The relative amount of pro-vitamin D3 and inert compounds produced depends on the intensity of ultraviolet (UV) radiation, which diminishes with increasing latitude. Other factors influencing pro-vitamin D3 synthesis are pigmentation, use of sunscreen and length of time of exposure to sunlight.
Vitamin D2 and D3 from the diet, as well as that formed in the skin, is inactive until it is chemically altered in the liver and in the kidney. Once vitamin D3 is activated in the liver, it becomes five times more potent than the pro-vitamin D3. Levels of active vitamin D3 in the blood are dependent on both intake and exposure to sunlight.
Both vitamin D2 and D3 are available as supplements and most steps in the metabolism and actions of vitamins D2 and D3 are identical. However, evidence indicates that vitamin D3 increases serum 25(OH)D levels to a greater extent and maintains these higher levels longer than vitamin D2, even though both forms are well absorbed in the stomach. Other studies indicate that vitamin D3 may be almost twice more effective at raising levels of vitamin D in the blood than vitamin D2.
This article is based on the interview the NRF Research Communications team conducted with the DSI-NRF Research Chair in Food, Environments, Nutrition and Health about the importance of Vitamin D to the immune system and role it can play in fighting against Covid-19. The writers are all from the Division of Human Nutrition at Stellenbosch University. The views expressed in the article are those of the writers and not Torque Media.
