A small dose of the nutritional supplement lithium aspartate may not ease the fatigue and brain fog of long COVID, a small, new trial involving 52 patients has found.

Still, it's possible that a larger dose of the mood-enhancing supplement might work, researchers said.

Importantly, the supplement contains much lower amounts of lithium than prescription lithium, typically 10 milligrams (mg) per pill instead of 300 mg or 450 mg.

“This is a very small number of patients, so these findings can only be seen as preliminary,” said study lead author Dr. Thomas Guttuso, of the University of Buffalo. “Perhaps achieving higher blood levels of lithium may provide improvements to fatigue and brain fog in long COVID.”

Experts estimate that over 17 millions Americans could have long COVID, with many experiencing the sluggishness and brain fog that can accompany the condition.

As Guttuso explained, he recommended lithium aspartate at 5 to 15 milligram (mg) daily doses to 10 patients, and nine claimed to see their fatigue and brain fog ease.

That prompted him to consider a clinical trial. So, Guttuso and his colleagues recruited 52 people with "new, bothersome fatigue or cognitive dysfunction persisting for more than 4 weeks after a self-reported positive test for COVID-19."

Patients were randomly assigned to receive either 10 to 15 mgs per day of lithium aspartate, or a placebo pill that looked identical, for five weeks.

Unfortunately, no benefit in terms of any lowering of fatigue or brain fog was seen, Guttuso's team reported Oct. 2 in the journal JAMA Network Open.

Based on his anecdotal experience with patients, that was disappointing, he said in a university news release.

"I had high hopes that we would see an effect from this randomized controlled trial,” he said. “But that’s the nature of research. Sometimes you are unpleasantly surprised.”

But all may not be lost: Three of the patients went on to complete an extended "dose-finding" study, and they did achieve reductions in fatigue and brain fog if they took lithium aspartate at a daily dose of 40 to 45 mgs. Two patients with especially high blood levels of lithium fared best.

“This is a very small number of patients, so these findings can only be seen as preliminary,” Guttuso cautioned. “Perhaps achieving higher blood levels of lithium may provide improvements to fatigue and brain fog in long COVID.”

It's possible that another trial is needed, Guttoso said.

“The take-home message is that very low-dose lithium aspartate, 10-15 milligrams a day, is ineffective in treating the fatigue and brain fog of long COVID,” he said. “Perhaps we need to do another randomized controlled trial that uses higher lithium aspartate dosages.”