**4.4 Cancer**

Vitamin C at a dose of 500 mg/day showed no beneficial effect after 8 years of supplementation among 1943 male patients with several cancers, including 1008 patients with prostate cancer in a randomized controlled trial [37]. More recently, vitamin C at 500 mg/day caused some epigenetic changes in patients suffering from myeloid leukemia [51]. This implies the ability of vitamin C to augment the efficacy of cancer chemotherapy even at such a low dose. The study also demonstrated restoration of the depleted plasma concentration of vitamin C in the supplemented group compared to the placebo group.

In an experimental study, high-dose vitamin C showed great efficacy in inhibiting proliferation and inducing apoptosis of various cell lines of breast cancer, and in combination with anti-cancer agents, the vitamin C administration showed an added advantage [52]. This was probably due to the ability of vitamin C to augment the cellular catalase level and boost the cells defense response against oxidative damage [52]. Interestingly, the normal breast epithelial cells were spared from these effects. These effects are due to the epigenetic modulatory role that vitamin C plays in cancer and other disease conditions [53]. However, the effect of high-dose vitamin C on cancer is highly controversial as many trials fail to show any anti-cancer effect of high-dose vitamin C supplementation in a review by Nowak [54].

## **4.5 Neurodegenerative diseases**

Vitamin C intake has proven effective against neuro-degeneration at different doses in several studies, as reviewed by Harrison [55]. Nevertheless, this is also controversial as shown in a case-control study involving patients with Parkinson's disease [56]. In a countywide study involving 3000 participants over a 7.2-year follow-up period, a positive correlation was observed between high intake of vitamin C and cognition even though dosages above 500 mg/day did not give any added benefit [57, 58]. Again, a cohort study over the same period of 7 years, involving elderly people (61–87 years) on different combinations of vitamins (including vitamin C) and minerals, showed no significant correlation with cognition [59]. However, baseline cognitive assessment was not done as such might have shown a positive correlation.

In mice, vitamin C administration at 250 mg/kg was shown to protect the brain of mice against reserpine-induced motor [60] and cognitive [61] impairments after 4 weeks of administration. In addition, vitamin C preserved, to some extent, the level of dopamine in the mouse brain exposed to auto-oxidation by reserpine [62]. Converted into human equivalent dose, 40.5 mg/kg was obtained [63]. Whether this dosage can be translated in human research or not, the bottom line is that vitamin C showed great potential in halting the progression of some of these neurodegenerative diseases.

## **4.6 Viral diseases including COVID-19**

Biancatelli et al. [64] had reported the efficacy of vitamin C at different dosages against several viral diseases in their review. For example, 50 mg/kg of intravenous vitamin C were given to about 41 herpes zoster patients on days 1, 3, and 5 in a

*Vitamin C Dosage in Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.109657*

double-blind randomized controlled trial [65]. There was a marked reduction in the pain scale scores of those patients compared to the placebo group. In a similar randomized controlled trial, involving 87 patients who received a much higher dose (5 g/day on days 1, 3, and 5), lower pain scale scores and post herpetic neuralgia were recorded [66]. In a review by Hemila [67], trials that utilized high doses (6–8 g/day) of vitamin C were associated with significant reduction in duration and severity of common cold and pneumonia compared to those that used lower doses (3–4 g/day).

In COVID-19, high-dose vitamin C infusion (50 mg/kg 6 hourly for 4–7 days) could act as a pro-oxidant to the over-reactive, hyper-excited immune cells participating in the cytokine storm but as an antioxidant to the normal lung parenchymal cells as well as some of the innate cells, thereby protecting them [68]. This therapy is often combined with a glucocorticoid to prevent treatment-induced inflammation. High-dose vitamin C infusion showed significant improvement in the primary outcomes with reduced mortality and better prognosis among patients with sepsis and adult respiratory distress syndrome [69]. In a similar but multicenter, prospective randomized, placebo-controlled trial involving 308 patients with COVID-19, highdose vitamin C infusion (24 g/day for 7 days) was initiated and expected to improve pulmonary functions and other parameters and reduce mortality [70]. Therefore, extremely high doses of vitamin C should be considered in severe disease conditions.
