Vitamin D supplementation in the post-pandemic period

The importance of vitamin D is one of the most discussed topics today. To a large extent, the COVID-19 pandemic also contributed to this. At the same time, the optimal status of vitamin D is the basis of health. In addition to its main importance, maintaining a normal calcium level and bone development by regulating calcium and phosphate homeostasis, it also has significant extraskeletal effects on several target organs (Mosca et al., 2023). Vitamin D has a huge impact on the proper functioning of several systems such as movement, immune, cardiovascular and nervous systems. A low level of vitamin D is related to reduced calcium values, which results in insufficient bone mineralization, which also results in the development of rickets in children or osteoporosis in adults. The result of a low level of vitamin D is both bone deformation and a high susceptibility to bone fractures due to falls (Zmijewski, 2019). Extraskeletal consequences of vitamin D deficiency can be muscle weakness or acute respiratory tract infections. It also proved its importance during the ongoing COVID-19 pandemic, where it was used prophylactically as well as a supplement to treatment, which is also evidenced by its increased prescription during the pandemic. Its benefits in reducing the severity of the course of the disease of COVID-19 have been demonstrated in many studies (Bopape et al., 2023).

Vitamin D

Vitamin D is a fat-soluble secosteroid. We know two forms: D2, which is produced by plants and fungi from ergosterol, and D3 is synthesized in human skin from 7-dehydrocholesterol (7-DHC) by exposure to ultraviolet B radiation (UVB) from sunlight. UV photons subsequently initiate a photochemical reaction in which 7-DHC is converted to provitamin D3; it is subsequently converted into vitamin D3 through a series of thermal isomerization processes. Vitamin D2 and D3 remain inactive until they are activated by enzymatic hydroxylation in the liver and kidneys (Bouilon et al., 2019; Delure et al., 2023).

In the liver, vitamin D is converted by hydroxylation into 25-hydroxyvitamin D [25(OH)D], known as calcifediol, which is the main circulating metabolite of vitamin D and serves as an indicator of its level in the body. Further hydroxylation takes place in the kidneys, where a biologically active form is produced – 1,25-dihydroxyvitamin D [1,25(OH)₂D], called calcitriol. It acts in an endocrine manner on peripheral tissues and after binding to the vitamin D binding receptor (Vitamin D Binding Receptor - VDR) behaves like a steroid hormone (Bouillon et al., 2019).

Intensive research on vitamin D has led to significant insights into its molecular mechanisms of action, which have confirmed that it acts as a hormone. Hormonal activity is mediated by the vitamin D receptor (VDR), which participates in several physiological processes and is expressed in most organs of the human body. Vitamin D acts through the genomic pathway – through the nuclear VDR, as well as through the non-genomic pathway – through the membrane VDR. Two main isoforms are collectively referred to as vitamin D: ergocalciferol (D2) and cholecalciferol (D3), the latter of which is produced by a non-enzymatic UVB-induced heat-sensitive reaction (Bopape et al., 2023).

Sources of Vitamin D

Naturally, vitamin D is contained in only a small amount of food. The most important sources are fatty fish (e.g. salmon, tuna, mackerel, trout) and fish liver oils, egg yolk, cheese, dairy products, liver (Institute of Medicine, 2011). In plant food, the occurrence of vitamin D is minimal, therefore there are recommendations for artificial enrichment of some foods, such as dairy products or cereals. We can get 5-18% of the required dose from the normal diet, which is 50-150 IU per day (Bačová et al., 2019). Some countries, in order to meet the needs of vitamin D intake, enrich food with it. For example, in Canada, vitamin D fortification is mandatory for milk and margarine. In the United States, vitamin D fortification is optional for either milk, fruit juices or cereals (Bendik et al., 2014). The recommended daily intake is 400-800 IU. The serum concentration of vitamin D in the body to ensure the correct application of the biological effects of vitamin D is at least 30 ng/ml. Another main and important source is exposure to sunlight (Bouillon, 2017; Bačová et al., 2019).

UVB radiation with a wavelength of approximately 290-320 nm penetrates unprotected skin and converts 7-dehydrocholesterol into provitamin D3. The amount of synthesized vitamin D is affected by several factors - especially the season, length of day, geographical location, smog and cloudiness, melanin content in the skin or the use of sunscreens. In addition, UVB radiation does not penetrate through glass, so people with darker skin or the elderly produce vitamin D in the skin less efficiently (Institute of Medicine, 2011). Due to the variability of the mentioned factors, there are no exact recommendations determining the length of sun exposure necessary for adequate synthesis of vitamin D. However, several expert authorities believe that exposure of uncovered skin (especially the face, hands or feet) to sunlight without the use of sunscreen for 5-30 minutes, especially between 10:00 a.m. and 4:00 p.m., daily or at least twice a week, can provide sufficient the production of vitamin D (Institute of Medicine, 2011; Bouillon, 2017). Staying in the sun for about 10 minutes without a protective cream, followed by the application of a sunscreen with SPF 15 and higher, is considered a safe procedure (Bendik et al., 2014).

Dietary supplements

Due to the widespread occurrence of vitamin D hypovitaminosis and the existence of risk groups – such as infants, small children under 3 years of age, pregnant women or seniors – the worldwide need and popularity of nutritional supplements containing vitamin D is growing (Lips et al., 2019). These supplements contain either vitamin D2 or D3: vitamin D2 is produced by UV irradiation of ergosterol in yeast, while vitamin D3 is produced by irradiation of 7-dehydrocholesterol derived from sheep wool lanolin; a vegan form of D3 from lichens is also available (Institute of Medicine, 2011). For the vitamin D-sufficient population, a daily intake of 800 IU is recommended, while in deficiency, supplementation usually begins with a dose of 1000 IU of cholecalciferol, which can increase serum 25(OH)D by approximately 10 ng/mL. Vitamin D preparations are available on the market in the form of natural vitamin or cholecalciferol, both in liquid and solid application form (Bačová et al., 2019).

Vitamin D intoxication

For vitamin D intoxication, the so-called hypervitaminosis D, can occur with its excessive intake. After synthetic vitamin D became available at the end of the 20s of the last century, the first cases of poisoning were already described in 1928 and 1932. Hypervitaminosis of vitamin D leads to hypercalcemia (serum calcium > 11.1 mg/dl), hypercalciuria and subsequent calcification of soft tissues. Hypercalcemia is manifested by various symptoms - nausea, vomiting, pain, neuropsychiatric disorders, muscle weakness, loss of appetite, dehydration, polyuria, thirst, or the formation of kidney stones - and in severe cases can cause damage to the kidneys or the cardiovascular system.

Hypervitaminosis occurs mainly with excessive, inappropriate use of vitamin D supplements; excessive exposure to sunlight does not pose this risk. The Food and Nutrition Board (FNB) has set the upper acceptable limit of serum 25(OH)D concentrations at approximately 125–150 nmol/L (50–60 ng/mL) (Institute of Medicine, 2011; NIH, 2025).

Consequences of vitamin D deficiency and risk factors for its occurrence

Vitamin D deficiency can arise for several reasons: low intake below the recommended values, limited exposure to sunlight, reduced ability of the kidneys to convert 25(OH)D into an active form or insufficient absorption of vitamin D in the digestive tract. The risk of a dietary deficiency is higher in persons with a milk allergy, lactose intolerance, as well as in ovo-vegetarians or vegans (NIH, 2025).

Various studies indicate that especially children and adolescents are at risk of hypovitaminosis D, mainly due to a sedentary lifestyle spent mostly indoors, associated with an increased interest in computers, television or smartphones. The measures taken during the COVID-19 pandemic have compounded this problem by restricting the movement of the population for a longer period. Reducing the time spent outdoors reduced exposure to sunlight, thereby limiting the synthesis of cholecalciferol in the lower layers of the epidermis, the main source of vitamin D. There are unconfirmed assumptions that lower levels of vitamin D during the pandemic may have contributed to the worsening of various diseases. Individuals with chronic conditions such as obesity, pancreatic diseases, pharmacologically treated epilepsy or cancer were exposed to an even higher risk of vitamin D deficiency (Mosca et al., 2023).

An analysis of 120 patients from a general practitioner's clinic for adults shows that the level of vitamin D was monitored for various reasons - fatigue syndrome, menopause in women, andropause in men, X-ray findings of osteopenia or osteoporosis, rheumatic diseases, hyperlipoproteinemia, vertebrobialgic syndromes, recent history of fractures or repeated respiratory infections. Patients with cardiovascular diseases were also examined. The results showed that in terms of hypovitaminosis, the group of people aged 50 and over is most at risk, in which there is also a high risk of increased cardiovascular morbidity and mortality (Bačová et al., 2019).

Prevalence of vitamin D deficiency

Vitamin D deficiency is described by several authors as a pandemic. The prevalence of deficiency varies in different parts of the world, with estimates suggesting that up to one billion people have low serum vitamin D levels (Cashman, 2016; Bačová et al., 2019).

The exact threshold for determining vitamin D deficiency has not yet been clearly defined. After reviewing the available data on the need for vitamin D for the proper functioning of various body systems, the Food and Nutrition Board (FNB) and the National Academies of Sciences, Engineering, and Medicine (NASEM) set a serum concentration of 25(OH)D <30 nmol/l (<12 ng/ml) as the limit of a low level of vitamin D. The concentrations recommended for maintaining health are shown in Tab. 1.

Tab. 1 Serum levels of 25-hydroxyvitamin D [25(OH)D].

Data on vitamin D deficiency in the European Union show considerable variability. According to The European Calcified Tissue Society, vitamin D deficiency (serum 25(OH)D <50 nmol/l or 20 ng/ml) is common in Europe, with incidence varying between regions. Hypovitaminosis D occurs in less than 20% of the population in Northern Europe and in 30-60% of the population in Western, Southern and Eastern Europe. Severe vitamin D deficiency (serum 25(OH)D <30 nmol/L or 12 ng/mL) affects more than 10% of Europeans, and the prevalence of deficiency can be as high as 75% in the elderly (Cashman, 2016; Jackuliak et al., 2012). In Middle Eastern countries, vitamin D deficiency is present in up to 80% of the population (Lips, 2019). In the United States, approximately 9–18% of the population suffers from vitamin D deficiency, with up to 75% of the population having vitamin D insufficiency (<30 ng/mL or <75 nmol/L) (Jackuliak et al., 2012). A 2022 study in South Africa showed that 7.6% of school children from a socioeconomically disadvantaged area in Cape Town were vitamin D deficient. A systematic review and meta-analysis including 1,693 studies, including 130 studies with 21,676 participants from 23 African countries, showed that the prevalence of vitamin D deficiency in the African population is significantly high, while on average one in five people has a serum concentration of calcifediol lower than 30 nmol/l (Bopape et al., 2023)

Effect of vitamin D on infectious diseases of the respiratory tract

The potential of vitamin D in the prevention and treatment of acute respiratory diseases and its immunomodulating effects are the subject of international research. It is known that the incidence of respiratory infections is influenced by the seasonal variability of serum vitamin D levels (Smaha et al., 2020). Studies over the past decade have suggested a link between vitamin D deficiency and a higher risk of infections. Vitamin D supports immunity by increasing the secretion of antiviral peptides and acts on the physical barrier, cellular and adaptive immunity. Low serum levels of vitamin D are associated with a higher incidence of acute respiratory infections, including influenza. A meta-analysis of eight observational studies reported that individuals with vitamin D levels below 50 nmol/L (20 ng/mL) had up to a 64% higher risk of community-acquired pneumonia (Nurshad, 2020).

Mosca et al. (2023) investigated the impact of the COVID-19 pandemic on serum 25(OH)D levels in children with chronic diseases at the Santobono-Pausilipon Pediatric Hospital in Naples, analyzing data by age, sex, and season. Patients between the ages of 1 month and 17 years who had routine vitamin D measurement during hospitalization were retrospectively enrolled in the study. Respondents were divided into "pre-COVID" (March 11, 2019 - March 11, 2020) and "post-COVID" (March 2020 - March 2021) groups. The results showed that the lockdown led to a decrease in vitamin D levels, with hypovitaminosis more common in schoolchildren and preschoolers. The "post COVID" group showed a higher proportion of children with severe vitamin D deficiency, especially in children with obesity and respiratory diseases. An interesting finding was that infants maintained normal levels of vitamin D with recommended supplementation, which likely protected this age group and accounted for the low percentage of respiratory distress (Mosca et al., 2023).

Several observational studies in the past have shown a connection between a low serum concentration of 25(OH)D and a higher risk of acute respiratory infections, their increased morbidity and mortality, as well as more frequent development of sepsis in critically ill patients. These studies were based on the observation that the incidence of respiratory diseases is higher in the winter months, when 25(OH)D levels are also lower. However, the causal relationship has not been unequivocally proven, because the increased incidence of respiratory diseases in winter can be influenced by several other factors, such as a deficiency of other trace elements or vitamins (selenium, zinc, vitamin C), limited time outdoors or colder and wetter weather (Smaha et al., 2020).

At present, it is not possible to recommend or reject the use of vitamins, minerals or other dietary supplements as prevention or as an adjunct to treatment for COVID-19 or other acute respiratory infections. However, for the proper function of the immune system, the body needs several vitamins and minerals, including vitamin D, vitamin C or zinc, and their clinical deficiency can increase susceptibility to infections. The COVID-19 pandemic has led to the implementation of several studies investigating the potential impact of vitamin D on supporting immune function and possibly reducing the risk of a severe course of COVID-19 or other respiratory diseases such as colds or flu.

Several studies have confirmed the immunomodulating effects of vitamin D and its importance for maintaining immune homeostasis. Nevertheless, further controlled randomized studies are needed to clarify more precisely its role in the immune response in respiratory diseases and in the prevention of various acute respiratory tract infections (Nurshad, 2020).

Suggested measures

Due to severe vitamin D deficiency in less than 10% of the European population, the European Calcified Tissue Society (ECTS) has issued a recommendation for regular monitoring of serum 25(OH)D levels through standardized programs in at-risk groups, including young children, adolescents, pregnant women, the elderly, and non-Western immigrants. To improve vitamin D status, ECTS recommends food fortification – for example, by adding vitamin D to dairy products, bread or cereals – with supervision and quality control to prevent intoxication, as well as the use of vitamin D supplements, especially in risk groups of the population (Lips et al., 2019).

Conclusion

Vitamin D is essential for bone health, immune function and overall body homeostasis. Vitamin D deficiency is widespread worldwide and affects different age and risk groups, especially children, the elderly, pregnant women and people with chronic diseases. Deficiency can lead to osteoporosis, muscle weakness, increased risk of infections and other health complications. Current evidence suggests that vitamin D has immunomodulatory effects and may influence the course of respiratory diseases, although a causal relationship has not yet been clearly established. The recommendations of professional societies emphasize regular monitoring of 25(OH)D levels in risk groups, food fortification and additional supplementation in cases of deficiency. Maintaining optimal levels of vitamin D is key to supporting bone health, the immune system and preventing complications associated with its deficiency.

Authors: Mgr. Klaudia Šulc, MPH Department of Epidemiology, Penta Hospitals SK, a.s., Bratislava prof. Mgr. MUDr. Erik Dorko, PhD., MPH, MBA Institute of Public Health and Hygiene, UPJŠ LF, Košice

Work supported by KEGA grant projects of the Ministry of Education, Research, Development and Youth of the Slovak Republic no. 001UPJŠ-4/2024 and no. 003UPJŠ-4/2024.

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