Vitamins are essential to life. These organic compounds, usually acquired as part of a balanced diet, are required for biological and metabolic processes. Vitamins can act as hormones and antioxidants promoting differentiation, proliferation and signaling. Interestingly, vitamins may also be essential to the function of the immune system, helping to balance inflammatory and suppressive responses.

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The biologically active form of dietary vitamin A, retinoic acid (RA), can have a profound effect on the immune system. So much so, that RA is being tested as a potential therapeutic for treatment of certain autoimmune diseases such as arthritis, psoriasis or multiple sclerosis. The primary role of RA appears to be the induction of the Th2-lineage and inhibition of Th1 cell differentiation. RA also induces expression of Foxp3 and will divert CD4+ T cells towards the Treg lineage at the expense of Th17 development. However, at low concentration, RA appears to be crucial for Th17 cell differentiation and survival. Furthermore, certain cancers have been linked to an altered conversion of metabolic intermediates to RA and, in some cases, administration of RA has ameliorated outcomes of acute promyelocytic leukemia, skin tumours and breast cancer.

Vitamin D has garnered media attention for years as a promoter of calcium homeostatis and thus bone health. However, vitamin D3 (VD3) has also been used in the past to “treat” tuberculosis and has recently been shown to be effective against influenza and Streptococcus A infections. Like RA, VD3 can have a diverse impact on the immune system. In some cases it has been shown to be immunostimulatory and increase proliferation of monocytes and their production of IL-1. On the other hand, VD3 can also promote the differentiation of Th2 and Treg cells while inhibiting Th1 and Th17 differentiation by regulating cytokine expression. Similar to RA, VD3 has also been suggested in treatments of autoimmune diseases.

Much less is known about the immunomodulatory effects of vitamins B, C and E. Bacteria-derived metabolites of B2 (riboflavin) and B9 (folic acid) have recently been shown to activate innate-like mucosal-associated invariant T (MAIT) cells. In response to commensal microbiota and yeast, these MAIT cells appear to be activated by B2 and B9 presented on MHC class I-like molecules. In this way, MAIT cells can survey for the presence of certain bacteria and dampen microbial infections. Furthermore, vitamin B3 (nicotinamide) and its derivative have been shown to induce neutrophil differentiation from hematopoietic precursors.

The effects of vitamin C, or ascorbic acid (AA), on the induction of immune and anti-viral responses have been largely anecdotal. Some in vitro studies have shown that AA has Th1-promoting properties largely by activating DCs and promoting a specific cytokine milieu. However, most studies have focused on its anti-cancer effects with some claiming that AA deficiency has profound effects on tumour recognition and function of NK cells. Others claim that these anti-cancer effects are purely due to the ability of AA to quench free radicals and induce formation of reactive oxygen species, which, in turn, kill cancerous cells.

Finally, vitamin E, while known mostly for its potent antioxidant ability, has also been shown to have anti-inflammatory properties mainly acting to dampen cytokine production by monocytes. It can also stimulate production of cAMP, a known immunomodulator, inhibiting NK cell activity while promoting Th2 cell function. Similar to vitamin C, most of the work on vitamin E has focused on its anti-tumour/cancer effects. Vitamin E can induce apoptosis of tumour cells via induction of cytochrome C and caspase activation. In addition, it can stimulate tumour cells to undergo autophagy and enhance cross-presentation of antigens to CD8+ T cells thus preventing tumour cell survival.

Vitamins not only provide us with much needed nutrients for survival and mental health, but they are also crucial for the proper functioning of the immune system. Of course, the optimal concentrations required to achieve these immunomodulatory effects are still debated and, in high concentrations, some vitamins can be deleterious to your health. Keeping in mind that everything should be consumed in moderation, grab a carrot, soak in some sun, and keep your immune system happy!

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Patrycja Thompson

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