Can fasting and a no-sugar diet alleviate long COVID symptoms?

In a crossover trial evaluating the effect of two intermittent fasting (IF) regimens on long COVID (LC) symptoms, a daily 16-h fast with water-only fast and a no-sugar diet fared better than a daily 14-h time-restricted eating (TRE) regimen for mitigating long COVID symptoms.

“[Our findings] demonstrate that a more intense fasting regimen and once-per-week ~1.5-day water-only fasting, combined with a no-added-sugar diet, reduces LC symptoms more than a less intense TRE,” said the researchers.

Fasting was superior to TRE alone in reducing LC symptom severity scores (LC scores; mean, -10.2 vs -2.8; p=0.008) and number of LC symptoms (-5 vs -1.4; p=0.002). “The two arms [diverged] … during the first 4 treatment weeks and [converged] during the last 4 weeks, reflecting greater improvements from fasting,” the researchers said.

The 28 common LC symptoms saw a reduction in mean severity of -80.6 percent in a subgroup of good responders. ‘Light sensitivity’ and headache had the largest average reductions in severity (-96.4 percent and -93.1 percent, respectively), while ‘nerve pain’ and tinnitus had the smallest (-64 percent and -53.1 percent, respectively).

None had mild symptoms at the beginning of the trial, but by study end, 13 participants had only mild symptoms, while two had none. Ninety percent of participants reported at least one symptom flare-up during the trial; the mean number of flare-ups was 4.4.

Age-stratified analyses showed that the mean change in LC score at 10 weeks was greater in younger (<47.5 years) vs older participants (-70.2 percent vs -44.3 percent; p=0.004). The researchers noted that younger age may be a positive factor due to stronger immune responses and fewer senescent cells. [Sci Rep 2025;doi:10.1038/s41598-025-07461-0]

Two severe adverse events (AEs) were reported (hospitalizations for acute appendicitis before attempting to fast and for left-side pleurisy, inflammation, and bicep tendonitis after a 38-h fast). Of the 47 AEs reported, eight were deemed ‘probably related’ and six ‘possibly related’ to fasting. “In general, AEs were tolerable, and none elected to stop their study participation or were disenrolled due to them,” the investigators noted.

No proven Tx for long COVID

There are no clinically proven treatments for long COVID, and current studies have either yielded negative results or failed to validate potential pharmaceutical interventions, the researchers noted.

“Fasting is known to activate autophagy, enhance antigen presentation, assist viral clearance, decrease autoimmunity by enhancing Treg cells, and decrease inflammation,” they said. “[F]asting may counteract multiple pathways adversely affected by SARS-CoV-2 infection and stimulate antiviral immune responses.”

“[W]hile it is clear that fasting and ketogenic diets affect autophagy in people, there is little data on the optimal fasting and diet regimen to realize the positive effects of autophagy,” the researchers pointed out.

After a 2-week run-in, 58 participants (mean age 49.5 years, 72.4 percent women) were randomized to TRE or fasting for 4 weeks, then crossed over to the other treatment for another 4 weeks. TRE was a no-sugar, optionally no wheat diet, with a 10–12 h daily eating window and water-only fast for the next 12–14 consecutive hours. Fasting included the same no-sugar diet with a more restrictive 8-h daily TRE eating window and 16 consecutive hours of daily fasting, plus a once weekly 23–60 h water-only fast.

Although overall, there were improvements with both regimens throughout the trial, the more stringent fasting regimen had the edge over the less restrictive one in the primary outcome analysis as reflected by the greater reductions in LC scores and the number of LC symptoms.

The researchers called for more trials to verify the findings and ascertain whether IF regimens could complement pharmacologic treatment options for LC that might be validated in the future.