VITAMIN D AND THE IMMUNE SYSTEM
It is now well known and confirmed that vitamin D plays a much more important role besides the classic well-known effects on calcium homeostasis and bone structure. Vitamin D metabolizing enzymes as well as vitamin D receptors are present in many cell types (B-cells, T-cells, monocytes and antigen presenting cells), and all these immune cells are capable of synthesizing the active metabolite of vitamin D. Vitamin D can modulate innate and adaptive immune responses. Data from in vivo animal studies and studies on supplementation of vitamin D in humans have shown beneficial effects of vitamin D on immune function.
Over the last decade, perspective on the impact of vitamin D on human health has changed dramatically, with the finding that the vitamin D receptor (VDR) and the enzyme 1-α-hydroxylase have pronounced effects in many cell types not involved in bone and mineral metabolism, such as the gut , pancreas, prostate, and immune system cells [1,2]. This data points to an important impact of vitamin D on a much broader aspect of human health than previously known.
The immune system defends the body against foreign, pathogenic organisms, promoting protective immunity while maintaining tolerance to native cells. The effects of vitamin D deficiency on immune function have become clearer in recent years, and in the context of vitamin D deficiency, there seems to be an increased susceptibility to infections.
Sources of Vitamin D and dependence of organism status on the season
In humans, vitamin D is obtained from the diet or synthesized in the skin (reviewed in ). Vitamin D can come from three potential sources: dietary sources, endogenous production and nutritional supplements. In humans, vitamin D is mainly synthesized in the skin after exposure to UVB sun light, while minority comes from dietary sources. Very few natural, non-enriched products, such as fatty fish (salmon, mackerel, sardines, cod liver oil) or some types of mushrooms, especially dried (Shiitake), contain adequate amounts of one of the two main forms of this vitamin, cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) [1,3,4]. Countries such as the United States and Canada enrich some of the basic products such as dairy products with vitamin D. Thus, individual intake of vitamin D in a diet depends largely on the diet habits and strategy of a particular country. However, a review from a global perspective found that 6 to 47% of vitamin D intake came from dietary supplements [5,6]. Therefore, without vitamin D supplementation, status is strongly dependent on the endogenous production of this vitamin, which is also influenced by genetic determinants, geographical location, season, skin pigmentation and lifestyle, eg. sunblock and clothing use [1,7].
As vitamin D levels have been shown to depend on the season [8,9,10,11], this factor should be considered when interpreting vitamin D status in an individual. Individual vitamin D levels reach their lowest levels after winter, and their maximums at the end of summer. Interestingly, this seasonal variation is similar to the described seasonal variation of some infectious diseases, and even sepsis [12,13]. Get to know our product for the actiel here
Formation and role of vitamin D in human body
Classic actions of Vitamin D are to promote calcium homeostasis and promote bone health, hence Vitamin D enhances intestinal absorption of calcium and phosphate, promotes osteoclast differentiation, calcium reabsorption and bone matrix mineralization. Vitamin D further promotes bone collagen mineralization. As vitamin D is produced skin after exposure to UV radiation, its synthesis is also affected by geographical latitude, season, sunblock use and skin pigmentation. Melanin absorbs UVB radiation by inhibiting the synthesis of vitamin D from 7-dihydrochterol. This initial vitamin D compound is inactive and is followed by hydroxylation in the liver and formation of 25-OH-vitamin D3 (25 D). 25 D is also inactive compound, but it is the most reliable measurement of vitamin D status in the body. In kidneys, it is converted to the active compound 1,25-dihydroxy-vitamin D (1.25 D).
Many tissues other than bone tissue and the GI tract express the presence of VDR (Vitamin D receptor), including cells in the bone marrow, brain, colon, breast, malignant cells and immune cells, which definitely suggests that vitamin D has functions other than calcium homeostasis and bones formation [1,2,14]. In addition, tissues other than kidneys express (display the presence) of the enzyme 1-α-hydroxylase and are capable of converting the inactive 25 D form to the active 1.25 D form of this vitamin in non-renal compartments [1, 15-16].
Some of recently recognized non-classical actions of vitamin D include effects on cell proliferation and differentiation, as well as on immune health, resulting in the ability to maintain tolerance and promote the protective function of immunity. As antigen presenting cells, T-cells and B-cells have the necessary mechanisms to synthesize and respond to 1.25 D, the active form of vitamin D. Furthermore, the local level of 1.25 D may differ from the systemic, circulating level because local regulation of enzymes which synthesize and activate vitamin D differs from the control that originates in the kidney. The enzyme 1-αhydroxylase in macrophages differs from renal hydroxylase . Status is dependent on the circulating level of the inactive 25 D form and can be induced by some cytokines .
Vitamin D has been used in the past (unwittingly) to treat infections such as tuberculosis, before the appearance of effective antibiotics. Patients infected with tuberculosis were placed in sanatoriums, where treatment included sun exposure because sun radiation was thought to directly kill tuberculosis. Cod liver oil, a rich source of vitamin D, has also been used to treat tuberculosis, as well as for general increased protection against infections .
Many scientific researches have been known to associate lower levels of vitamin D with an increased probability of infection. One study examined almost 19,000 subjects between 1988 and 1994. Individuals with lower levels of vitamin D (<30 µg/ml) reported more frequently a recent upper respiratory tract infection compared with subjects with sufficient, higher levels of vitamin D, even after adjusting variables including season, age, gender, body weight and race . Vitamin D levels fluctuate throughout the year. Although the rate of seasonal infections varied (the lowest was in summer and highest in winter), the association between lower serum vitamin D and infection rates was maintained during each season.
Another comparative study on 800 soldiers in Finland examined serum vitamin D levels . Those soldiers with lower vitamin D levels lost significantly more days in service due to active secondary or respiratory infection of upper respiratory tract compared to soldiers with higher vitamin D levels (above 40 µmol). There is a number of other cross-sectional studies that have examined vitamin D levels and rates of influenza  as well as other infections, including bacterial vaginosis  and HIV [24-25]. All studies reported an association between lower vitamin D levels and an increase in infection rates. A 2010 study that used an objective outcome – nasopharyngeal swab culture and vitamin D therapeutic dose – showed that vitamin D administration resulted in a statistically significant (42%) reduction in the incidence of influenza infection .
Vitamin D has important functions beyond those of calcium and bone homeostasis that involve modulation of innate and adaptive immune responses. The cells of the immune system are able to respond to the presence of vitamin D (27). In recent decades, vitamin D-related studies have confirmed the important interaction between vitamin D presence and cells of the innate and adaptive immune systems function. The data showed that a wide range of tissue cells, including immune cells, express the presence of vitamin D metabolizing enzymes, providing a biologically plausible mechanism for the conversion of native circulating forms into the active 1.25 D form of the vitamin. This process appears to be crucial for the normal functioning of the immune system, and therefore a low or insufficient level of vitamin D may lead to impaired regulation of immune responses (28).
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