Immunonutrition therapy application is varied, ranging from severely ill patients, perioperative immunonutrition, athletic enhancement, and more recently in the COVID- 19 patients. However, the underlying factor of immunonutrition effectiveness is its capacity to downregulate inflammatory responses and improve immune reactions using pharmaconutrients. Furthermore, immunonutrition seeks to counteract, reverse and repair barrier function, reduce inflammation, improve immune response related to COVID-19, and promote protein synthesis. A large number of bioactive compounds used in Functional Medicine are applied in immunonutrition. In COVID-19 pathogenesis, functional foods, vitamins, essential fatty acids, and immunomodulatory compounds can improve outcomes. Also, a better nutritional status supported by these nutritional compounds can reduce the proinflammatory storm and ameliorate respiratory disturbances present in the obese patient diagnosed with COVID-19.

Vitamin A:

Vitamin A functions as a precursor to immune cells, as well as the differentiation of epithelial tissue. Therefore, functions as an intestinal barrier protectant and immune imprinting factor. Furthermore, its carotenoids have a beneficial influence on the membranes as they improve gap-junction communication. In addition, carotenoids are ROS scavengers, which translates to reduced toxic effects due to the immunoregulatory actions.

Vitamin A deficiency has a pivotal impact on immune function. Not only does its deficiency affects barrier permeability, but it impairs the innate immune system. 

NK cells:  Vitamin A modulates the phagocytic and oxidative activity of the macrophage burst. In addition, this vitamin contributes to the maturation and deficiency of macrophages.

Vitamin A also has multiple effects on acquired immunity as it is involved in Th1 and Th2 cell development and differentiation. Vitamin A modulates the balance between Th2 and Th1 cells, reducing Th2 cells response and increasing the latter. This translates to a modulated Th2 response and suppression of the production of Il-12, TNF-a, and IFN-y by Th1 cells. Furthermore, normal ranges of vitamin A suppress the differentiation of Th17, which ensures better control of adverse immune reactions.

Vitamin C:

Vitamin C is a powerful antioxidant that works together with other bioactive compounds to restore epithelial function. For example, collagen interacts with vitamin C to maintain epithelial integrity, which reduces pathogen translocation.

Also, as part of its scavenger functions, vitamin C protects the cell membrane from reactive oxygen species, protecting epithelial barriers. Additionally, this vitamin is crucial for the proliferation, function, and movement of neutrophils, monocytes, and phagocytes. As for leukocytes, vitamin C promotes its migration to the infection site, phagocytosis, and bacterial killing.

Vitamin D:

Most immune cells have vitamin D receptors. Moreover, some of these cells can synthesize the active form of Vitamin D. Indeed, and this suggests that vitamin D has a substantial immunomodulatory impact. 

As well as the previously mentioned vitamins, vitamin D can improve host defense by enhancing the epithelial barrier integrity. Indeed, calcitriol enhances the production of antimicrobial proteins like cathelicidin and β-defensin that favor the growth of healthy intestinal microbiota and supporting gut barrier function. 

 Vitamin D induces the synthesis of an antimicrobial peptide in epithelial cells and macrophages regarding its immune effects. 

Vitamin D potentiates the differentiation of monocytes from macrophages, enhances superoxide production, and facilitates antigen presentation by dendritic cells. In addition, the functional form of vitamin D, calcitriol, promotes pathogenic death by regulating the expression of antimicrobial proteins: cathelicidin and defensin.

The anti-inflammatory effects of vitamin D rely on its capacity to suppress IFN-y. In addition, this compound counteracts inflammation by promoting the synthesis of anti-inflammatory cytokines by macrophages.

Vitamin E:

This vitamin exists in two different forms:

Tocopherols: mainly found in nuts and vegetable oils. 

Tocotrienols: present in high amounts in some seeds and grains.

Not too long ago, it was believed that there was no vitamin E deficiency, or at least no signs and symptoms were linked to it. However, today we know that high levels of vitamin E in serum associate with positive cell-mediated immune responses. The mechanism behind this is vitamin E’s capacity to repair the integrity of epithelial barriers by reversing the damage caused by free radicals.

Vitamin E immune mechanisms are:

• Vitamin E improves the cytotoxic activity of NK cells.
• Inhibits the activity of cyclooxygenase-2 (COX-2) by mediating the production of nitric oxide (NO).
• Increases the percentage of antigen memory, which enhances the immune synapse formation in naïve T cells.
• Modulates the balance between Th1/Th2 cells 
• Reduces the chain reaction of free radicals by breaking this process with its antioxidant effects.

Micronutrient testing:

Vitamins are essential co-factors that support metabolic pathways in our body. Despite this critical role, they also support the immune system by modulating its response, promoting immune cell differentiation, synthesizing antimicrobial proteins, and protecting the epithelial barrier against ROS. Also, these effects support the gut’s microbiota diversity and growth which results in a better immune response. Nevertheless, in case of an infection, vitamin depletion is expected due to their endless immune benefits. Therefore, micronutrient deficiency should be assessed and supplemented as part of the COVID-19 treatment. – Ana Paola Rodríguez Arciniega, MS

References:

Di Renzo, Laura et al. “COVID-19: Is there a role for immunonutrition in obese patient?.” Journal of translational medicine vol. 18,1 415. 7 Nov. 2020, doi:10.1186/s12967-020-02594-4

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