Vitamin D as an Immune Booster: Roles in Enhancing Immunity and Proper Dosage

If we look back just a decade, vitamin D was almost exclusively viewed as a preventive measure against rickets in infants during the first year of life and as a dietary supplement for the prevention and supportive therapy of osteopenia and osteoporosis. Only a few considered vitamin D deficiency, and it was measured sporadically in just a few laboratories in Croatia, usually upon the recommendation of endocrinologists monitoring patients with osteoporosis.

Today, the situation is completely different, and it is difficult to find a field or population group that does not benefit from vitamin D supplementation. A molecule that has beneficial effects on multiple processes in the body is called pleiotropic, and vitamin D is a prime example of a pleiotropic molecule.

The most well-known role of this vitamin is the regulation of calcium and phosphate metabolism and the maintenance of adequate bone mineral density, thus protecting against rickets, osteopenia, and osteoporosis. However, vitamin D also protects the cardiovascular system, plays a key role in blood glucose regulation, affects the gut barrier and microbiota composition, protects against neurological and skin diseases, and is particularly notable for its effects on the immune system. Interest in foods and supplements recommended for immune support has absolutely exploded due to the COVID-19 pandemic. Vitamin D, in particular, is recognized as a powerful protector of immunity, especially in protecting against viral respiratory infections. The global population has learned a great deal about the importance of vitamin D for the immune system, the insufficiency of dietary sources, fortified foods, the role of sunlight, and supplementation with vitamin D.

Vitamin D is not a classical vitamin. It is simultaneously a hormone, an immunomodulator, and an essential micronutrient produced in the skin upon UV exposure. Since dietary intake accounts for only a small portion of daily requirements, we rely on sun exposure. Therefore, during the colder part of the year, most of the population in our region experiences deficiency or hypovitaminosis D. This particularly affects older adults who often stay indoors, patients with chronic illnesses, as well as the rest of the population who have limited sun exposure and live in urban areas with high pollution. The list of at-risk groups for vitamin D deficiency is quite long and is shown in Table 1.

Table 1. Risk factors for vitamin D deficiency

• Individuals rarely exposed to sunlight, wearing protective clothing or using sunscreen

• People with darker skin

• Obese individuals

• People taking medications that interfere with vitamin D metabolism (anticonvulsants, glucocorticoids, antifungals)

• Hospitalized patients and institutionalized individuals

• Older adults

• Patients with osteoporosis

• Patients with malabsorption syndromes (diseases or surgical interventions in the digestive system)

• Patients with kidney and liver diseases

• Patients with autoimmune, malignant, endocrine, neurological, cardiovascular, or psychiatric conditions

Experimental studies have shown that the active form of vitamin D exerts immunological effects on multiple components of both the innate and adaptive immune system. Low concentrations of 25-OH vitamin D have been associated with an increased risk of numerous infectious and autoimmune diseases such as type 1 diabetes, psoriasis, rheumatoid arthritis, tuberculosis, sepsis, respiratory infections, and COVID-19. Vitamin D deficiency is also linked with higher rates of type 2 diabetes and is observed in individuals with hypertension and various digestive system disorders, including celiac disease, inflammatory bowel disease, and liver diseases. Numerous interventional studies are ongoing in which vitamin D3 or its metabolites are used for prevention, therapy, or supportive therapy of these conditions.

Optimal Vitamin D Dosage

Although the appropriate blood concentration of vitamin D that can protect against immune-mediated diseases is still debated, it is generally recommended to maintain 25-OH vitamin D levels above 75 nmol/L, with optimal immune system function possibly requiring levels between 100 and 150 nmol/L. Such concentrations cannot be achieved without regular supplementation in higher doses.

The European Food Safety Authority (EFSA) recommends an intake of 600 IU per day for healthy individuals, with a maximum safe daily intake of 4000 IU. The UK Scientific Advisory Committee on Nutrition previously recommended a daily intake of 400 IU for all individuals. Guidelines for optimal vitamin D dosing are summarized in Table 2, divided for preventive supplementation or therapeutic use in confirmed deficiency.

Table 2. Vitamin D Dosage for Prevention and Therapy of Vitamin D Deficiency

*See Table 1. Recommended dosing should be guided by laboratory determination of vitamin D blood levels. High doses exceeding 4,000 IU/day should be limited to a defined period with periodic monitoring of laboratory parameters under medical supervision.

Role of Vitamin D in Protection Against Respiratory Infections

Before the antibiotic era, tuberculosis therapy relied on sun exposure in sanatoria, and the same strategy was noted during the 1918–1919 influenza pandemic. It is believed that the increased incidence of colds and pneumonia during winter is partly related to reduced sunlight exposure and consequently lower levels of active vitamin D in the blood. Influenza incidence is seasonal in higher latitudes, occurring mainly in winter, while in tropical regions, it occurs sporadically year-round. One proposed explanation for seasonal flu is that it reflects seasonal variations in 25-OH vitamin D blood levels, which reach their lowest during winter. Several studies have supported this hypothesis, demonstrating a connection between low 25-OH vitamin D levels and the incidence and severity of respiratory infections in children and adults.

A recent large study by Jolliffe et al., published in 2021, showed that vitamin D supplementation reduces the risk of respiratory tract infections compared with placebo. Notably, daily supplementation was found to be superior to weekly, monthly, or quarterly dosing. Protective effects were observed in studies using doses of 400–1,000 IU/day, whereas lower (<400 IU) or higher (>1,000 IU) daily doses did not show the same benefit.

References

1. Vranešić Bender D, Giljević Z, Kušec V, et al. Guidelines for Prevention, Recognition, and Treatment of Vitamin D Deficiency in Adults. Liječ Vjesn 2016;138:121–132.

2. Vranešić Bender D, et al. Review of Recommendations for Supplementation of Vitamin D in Children and Adolescents. Central European Journal of Paediatrics, 2018;14(2):123–129.

3. Jolliffe DA, Camargo CA Jr, Sluyter JD, et al. Vitamin D Supplementation to Prevent Acute Respiratory Infections: A Systematic Review and Meta-Analysis. Lancet Diabetes Endocrinol, 2021;9(5):276–292.

4. Cannell JJ, Vieth R, Umhau JC, et al. Epidemic Influenza and Vitamin D. Epidemiol Infect, 2006;134:1129–1140.

5. Gunville CF, Mourani PM, Ginde AA. The Role of Vitamin D in Prevention and Treatment of Infection. Inflamm Allergy Drug Targets, 2013;12:239–245.

6. Vitamin D and Health: Scientific Advisory Committee on Nutrition, 2016. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/537616/SACN_Vitamin_D_and_Health_report.pdf