Intravenous vitamin C, a potential treatment for COVID-19, was found to have limited efficacy in increasing days free of organ support in adult patients, according to two harmonized clinical trials known as LOVIT-COVID and REMAP-CAP. Contrary to earlier expectations and smaller studies, the results of these trials suggest that vitamin C may not significantly improve outcomes for hospitalized COVID-19 patients. This article provides an analysis of the trials’ findings and their implications for clinical practice.
The study, led by Neill K. J. Adhikari, MDCM, MSc, and his team at Sunnybrook Health Sciences Centre in Toronto, revealed that among critically ill patients who received intravenous vitamin C, the median number of organ support-free days was 7, compared to 10 in the control group. The adjusted odds ratio (OR) for the intervention group was 0.88 (95% CI 0.73-1.06), indicating little to no improvement. The survival rate to hospital discharge was also similar between the vitamin C group (61.9%) and the control group (64.6%).
For patients who were not critically ill, the median number of organ support-free days was the same in both the intervention and control arms, with a median of 22 days. The adjusted OR for this group was 0.80 (95% CI 0.60-1.01). Survival to hospital discharge was also comparable between the vitamin C group (85.1%) and the control group (86.6%).
The posterior probabilities calculated for critically ill and non-critically ill patients indicate that the potential efficacy of vitamin C therapy is minimal. For critically ill patients, the posterior probability for effectiveness was only 8.6%, while the probability for harm was 91.4%, and the probability for futility was 99.9%. Similarly, the posterior probabilities for non-critically ill patients were 17.8% for efficacy, 82.2% for harm, and 98.1% for futility. These probabilities further strengthen the case against the use of vitamin C in COVID-19 treatment.
Before the COVID-19 pandemic, interest in vitamin C as a potential treatment for sepsis arose due to a single-center study in 2017. However, subsequent larger clinical trials found no benefit in using vitamin C for sepsis patients. Despite this, the low levels of vitamin C observed in COVID-19 patients sparked renewed interest in its potential efficacy. A meta-analysis of smaller trials suggested that vitamin C might reduce hospital COVID-19 mortality. To obtain more definitive results, researchers conducted the LOVIT-COVID and REMAP-CAP trials, ensuring a unified intervention, outcome measure set, and statistical analysis plan across 90 ICUs and 40 non-ICU hospital sites in four continents.
The results of the harmonized trials offer a clear message to clinicians: vitamin C should not be used as a treatment for hospitalized COVID-19 patients. The disappointing outcomes and limited efficacy reported in the trials should discourage the use of vitamin C in favor of treatments that have shown proven benefits. Any remaining allure towards vitamin C should be set aside in light of the evidence that it is likely ineffective and potentially harmful.
It is important to note some limitations of the trials. The trials combined data from two distinct study designs, and the placebo-controlled LOVIT-COVID trial had fewer participants. Additionally, the open-label REMAP-CAP study introduced the possibility of differential care. Certain data, such as individual vaccination status, details about the vitamin C product used, and baseline vitamin C levels, were unavailable, potentially impacting the outcomes.
The combined findings of the LOVIT-COVID and REMAP-CAP trials indicate that intravenous vitamin C has limited benefits in terms of increasing days free of organ support in adult patients hospitalized with COVID-19. The trials underscore the necessity of relying on treatments with proven efficacy for COVID-19 patients and caution against the use of vitamin C as a primary treatment option. Future research should continue to explore alternative strategies for improving outcomes in hospitalized COVID-19 patients.