Ascorbic Acid and Zinc Gluconate Do Not Improve COVID-19 Symptoms

Shot of a young woman wearing a mask and suffering from throat pain in a doctor’s office
Study authors examined the effect of high-dose zinc and/or ascorbic acid on the severity or reduction of SARS-CoV-2 duration compared with the standard of care.

Treatment with high-dose zinc gluconate, ascorbic acid, or both, did not reduce the duration or symptoms of disease caused by SARS-CoV-2, according to a new prospective, randomized clinical trial recently detailed in JAMA Network Open.

Study authors examined 214 patients hospitalized in Florida and Ohio within a single health system between April and October, 2020. Patients were randomly assigned in a 1:1:1:1 ratio to receive 8000 mg ascorbic acid divided over 2 to 3 times daily (n=48), 50 mg zinc gluconate at bedtime (n=58), both ascorbic acid and zinc gluconate (n=58), or usual care (n=50). The primary endpoint was the number of days required reach 50% reduction of symptoms, as defined on both a 4-symptom and a 12-symptom score.

The mean patient age was 45.2 years (standard deviation [SD], 14.6), 61.7% of the cohort were women, and the average symptom composite score of 4.3 point (SD, 1.9).

The study authors found a 50% reduction in symptom score after 6.7 days (SD, 4.4) among the usual care recipients. Statistically insignificant symptom reductions were seen in patients who received ascorbic acid (days, 5.5 days; SD, 3.7), zinc gluconate (days, 5.9; SD, 4.9), and ascorbic acid and zinc gluconate combination therapy (days, 5.5; SD, 3.4; overall P =.45).

Compared with the control group, those who received ascorbic acid required 2.2 more days (95% CI, -0.58 to 5.02) and those who received zinc gluconate required 0.85 (95% CI, -1.91 to 3.62) until symptom score returned to 0. Comparatively, patients receiving combination therapy returned to a symptom score to zero 0.24 days shorter (95% CI, -2.67 to 2.19) compared with the control group.

On day 25, 6.0%, 4.2%, 8.6%, and 12.1% of patients remained hospitalized (P =.50) and 0%, 2.1%, 0%, and 3.4% had died (P =.40) among the usual care, ascorbic acid, zinc gluconate, and combinatorial cohorts, respectively.

Researchers found no adverse events associated with the experimental therapies.

This study may have been limited by the dosing of the drugs; it’s unclear whether higher doses would have an effect on reducing COVID-19 symptoms.

The data indicated there was no therapeutic benefit from zinc gluconate, ascorbic acid, or the combination of the two therapies for the treatment of SARS-CoV-2.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Thomas S, Patel D, Bittel B, et al. Effect of high-dose zinc and ascorbic acid supplementation vs usual care on symptom length and reduction among ambulatory patients with SARS-CoV-2 infection. The COVID a to z randomized clinical trial. JAMA Netw Open. 2021;4(2):e210369. doi:10.1001/jamanetworkopen.2021.0369.