Nicotinamide for COVID-19 Recovery: Restoring Metabolic Balance

Nicotinamide for COVID-19 Recovery: Restoring Metabolic Balance

As COVID-19 continues to leave patients with lingering symptoms long after the acute phase, interest is shifting toward therapies that support recovery rather than prevent infection.

One such candidate is nicotinamide, a form of vitamin B3 that’s being explored for its effects on cellular metabolism. The COVit-2 trial—which was detailed in a report published in Nature Metabolism in May of 2025—takes a closer look at this approach. It focuses on whether boosting nicotinamide adenine dinucleotide (NAD+), a key molecule involved in energy production and immune regulation, can help speed recovery and reduce post-COVID symptoms. Here's a brief look at the study and its findings.

Study Design and Purpose

COVit-2 was a randomized, placebo-controlled trial that enrolled 900 non-vaccinated adults with mild-to-moderate COVID-19. All participants had symptoms but were managed as outpatients. They were randomly assigned to receive either nicotinamide or placebo for 28 days.

The nicotinamide was given in two forms: one designed for rapid absorption, the other targeted to the gut. Researchers aimed to see which delivery strategy could support NAD+ levels, improve recovery, and reduce longer-term symptoms. Stool samples were collected from a small, optional subcohort to track changes in the gut microbiome and identify potential metabolic effects.

Efficacy Findings

By the end of the two-week treatment period, more than half of the nicotinamide group—57.6 percent—reported recovery from a decline in physical performance, compared to 42.6 percent in the placebo group. That difference translates to a number needed to treat of seven, with a statistically significant P value of 0.004 (odds ratio 1.33).

While overall fatigue scores didn’t improve significantly (P = 0.423), participants taking nicotinamide reported greater improvement in their ability to perform normal daily activities (P = 0.009). Resolution of shortness of breath showed a favorable trend (P = 0.012, exploratory), though it was not adjusted for multiple comparisons.

At six months, among participants at risk for post-COVID syndrome (PCS) who had responded to treatment during the acute phase, those in the nicotinamide group reported significantly lower PCS scores in a predefined exploratory subgroup analysis—mean PCS 8.33 versus 11.82  in placebo (P = 0.010).

Microbiome data paralleled clinical findings and may help explain the observed effects. While overall diversity stayed the same, the placebo group showed increased microbial activity related to amino acid production—likely reflecting a compensatory response to deficiency in NAD+ de novo and systemic tryptophan. In contrast, the nicotinamide group maintained baseline activity in these pathways and showed signs of restored metabolic balance. These profiles were more similar to those seen in people who never had COVID-19.

Safety Findings

In terms of safety, nicotinamide was generally well tolerated. Some participants in the treatment group reported mild gastrointestinal side effects, with a higher incidence compared to placebo (25.2% vs. 17.7%, P = 0.007), but these did not differ meaningfully in severity or clinical consequence. There were no increases in hospital visits or serious adverse events, and no substantial change in adverse events among the delivery options. Given the trial’s remote design and minimal monitoring, the safety data are especially reassuring.

Therapeutic Potential and Next Steps

This study doesn’t suggest nicotinamide is a cure for COVID-19, but it does support its use as a recovery aid—particularly for patients at risk of prolonged symptoms. The low risk, low cost, and oral delivery make it a practical option for outpatient care.

That said, the trial excluded vaccinated individuals and mostly captured cases from the Alpha and Delta waves, limiting generalizability to more recent variants or to hospitalized populations. Still, COVit-2 offers a promising model for metabolic support in viral illness—one that may apply beyond COVID-19.