High dose zinc and vitamin C have long been touted as popular cures for the "common cold." As such, they've been flying off the shelves during the covid-19 pandemic, despite a lack of compelling evidence. Some of this is explained by the usual justification: what's the harm? But just how useful are these remedies, truly, in the fight against SARS-CoV-2? Published recently in JAMA Network Open, the "COVID A to Z trial," sought to investigate.
This trial was a multi-center, single health system study which was completed in Ohio and Florida. The patients, who were 45 years old on average, were randomized 1:1:1:1 into groups that either received zinc (50 milligrams), ascorbic acid (also known as vitamin C, 8000 milligrams), both agents, or standard of care for 10 days. The primary outcome of interest was a 50 percent reduction in peak symptoms on a 4-point scale.
Just 214 patients, a small number of subjects, were enrolled. That relatively small number of subjects reflects the fact that—spoiler alert—the study being stopped after an early data analysis showed no benefit. In fact, the statistics were so disappointing, that the statisticians determined that the chances of the study turning out favorably for either zinc, vitamin C, or both was so improbable, that they had to throw in the towel and call it off.
The "standard care" group reported a reduction in symptoms after an average of 6.7 days compared with 5.5 for the vitamin C group, 5.9 in the zinc group and 5.5 days in the dual supplement group. These differences were not statistically significant and the overlap between the likely ranges was seen as destined to overlap (meaning that any difference would remain meaningless) even if they enrolled many more participants. Additionally, there was no difference in other outcomes, such as death or hospitalizations. Also unsettling was that in a secondary outcome (i.e. an outcome that was not the main purpose of the study but was included for the sake of curiosity and hypothesis building for future studies), those who received vitamin C alone had longer recovery times overall. While that finding was also not meaningful, it appeared to the naked eye to be the data point that was by far the most impressive. That does not mean that vitamin C would necessarily have been shown to have caused or even be associated with longer recovery times, but it certainly implies that it's unlikely to ever show a benefit.
Even "negative" trials like these are helpful. After all, zinc and vitamin C frequently show up in remedies and gain attention in the press and internet traffic from sources claiming that these inorganic compounds somehow possess magical powers. This leads to false hope and wasted money. Nevertheless, the unfortunate truth is that despite the lack of clinical evidence supporting the use of these remedies, many in both the medical and health world are likely to continue recommending them.