Immune-Boosting Natural Health Products
Ascorbic acid, more commonly known as vitamin C, has been shown to exhibit potent immunomodulatory, antioxidant, and antimicrobial effects (221). Vitamin C has been shown to restore NK cell cytotoxicity in individuals exposed to toxic chemicals through protein kinase C expression, a critical component in lymphocyte metabolism (222). Additional reports have shown that vitamin C also enhances the expression of NKp46, CD69, CD25 and IFN-γ production by NK cells (223) and can increase the expression of IRF3 in lung tissues of influenza infected, pneumonia-induced mice (224). Vitamin C also harbors potent antioxidant attributes which can scavenge reactive oxygen species (ROS) and prevent lung injury (225, 226). Although ROS production is an important component in the host defense response to viruses, they can be harmful to cells and lead to the pathogenesis of viral-induced host injury (227).
The underlying rationale to investigate the therapeutic potential of vitamin C has been based on two key observations: (i) critically ill patients have lower levels of vitamin C (228–230) and (ii) vitamin C has pleiotropic immunomodulatory, antioxidant, and antiviral effects (221). It is important to underscore that reports on the clinical outcomes of vitamin C treatment in humans are mixed and context dependent. A thorough meta-analysis on vitamin C supplementation for the common cold has been reported by Hemilä and Chalker (231). Briefly, they concluded that while the incidence of colds was not reduced, the duration and severity of colds was reduced when assessing studies of regular vitamin C intake (231). Interestingly, a separate meta-analysis on vitamin C and cardiac surgery showed a reduction in the length of ICU stay and shortened the need for mechanical ventilation (232). This is an important correlation as clinical trials are currently investigating the efficacy of vitamin C to reduce mortality and hospital burden in COVID-19 patients (Table 1). A Phase II clinical trial (NCT04264533) was initiated in Wuhan where COVID-19 patients will be given a high dose intravenous infusion of vitamin C. Lastly, whether oral dosing of vitamin C can achieve therapeutically relevant concentrations, as described in the above studies, is currently unknown, thus caution should be taken as exceeding the recommended dietary allowance of 100–200 mg/day may lead to mild toxicities including abdominal discomfort and diarrhea (231, 233).