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Study Explores Lithium Aspartate for Long COVID Symptoms

A recent clinical trial conducted by researchers at the University at Buffalo has found that low doses of lithium aspartate do not effectively alleviate the fatigue and cognitive issues commonly associated with long COVID. However, a supplemental dose-finding study indicated that higher doses may yield positive outcomes.

Published in JAMA Network Open on October 2, the research was led by Dr. Thomas J. Guttuso, Jr., a professor of neurology at the Jacobs School of Medicine and Biomedical Sciences at UB, alongside his role at UBMD Neurology.

“While the results of this study leaned towards the negative, there is a silver lining,” Guttuso remarked.

The rationale behind testing lithium was its known anti-inflammatory properties, which have potential relevance for long COVID thought to arise from chronic inflammation. Guttuso had initially suggested low-dose lithium aspartate treatment to a patient who subsequently reported significant relief from fatigue and cognitive fog within days of starting the medication at 5 milligrams daily.

Potential Benefits Observed

This individual case piqued Guttuso’s interest, leading him to recommend lithium aspartate to other long COVID patients. Remarkably, he noted that 9 out of the 10 patients treated with doses between 5-15 mg daily reported substantial improvements in their symptoms of fatigue and brain fog.

“Despite the encouraging results from these nine patients, the randomized controlled trial did not replicate this success,” Guttuso explained. “Such is the nature of scientific inquiry; unexpected results can happen.” The controlled trial found no significant differences in outcomes between patients administered 10-15 mg of lithium aspartate and those receiving a placebo.

A pivotal moment in the study occurred when one participant who increased their lithium dosage to 40 mg daily reported significant symptom improvements. This prompted Guttuso to conduct a focused dose-finding study to investigate higher dosages further.

Among the three participants who completed this phase, notable declines in fatigue and cognitive fog were observed at doses of 40-45 mg per day. Particularly, two participants exhibited blood lithium levels of 0.18 and 0.49 millimoles per liter (mmol/L), showing marked benefits, while another with a level of 0.10 mmol/L experienced only partial improvements.

“With such a small sample size, these findings are preliminary,” Guttuso cautioned. “It appears that achieving higher blood lithium concentrations might be key to improving symptoms in long COVID patients.”

Examining Dosage Efficacy

Guttuso suggested that the lack of efficacy in the randomized controlled trial might have been due to the low dosages tested.

“The main takeaway is that low-dose lithium aspartate at 10-15 mg daily does not offer relief from the fatigue and cognitive fog of long COVID,” he stated. “Further research with higher dosages that reach blood lithium levels of 0.18-0.50 mmol/L is necessary to assess potential effectiveness.”

The prevalence of long COVID is concerning, with around 17 million individuals affected in the U.S. alone, and approximately 65 million globally.

“At present, there are no established therapies supported by evidence for long COVID,” Guttuso noted. He expressed hope that the National Institutes of Health (NIH) would consider lithium aspartate a candidate for more extensive studies, especially as the NIH has allocated an additional $500 million for researching promising long COVID therapies.

He emphasized that if further trials confirm the efficacy of higher lithium doses, patients will need to consult with their healthcare providers before starting treatment and that their blood lithium levels should be regularly monitored.

Collaborating with Guttuso on this research were Gregory E. Wilding, PhD, and Jingtao Zhu, research assistant, both from the Department of Biostatistics at the UB School of Public Health and Health Professions.

The clinical trial was funded as a pilot project by UB’s Clinical and Translational Science Institute.

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