A recent small clinical trial from the University at Buffalo has determined that lithium aspartate at low doses is not effective for alleviating the fatigue and cognitive issues typically associated with long COVID. However, a follow-up study focusing on dosage discovered that higher amounts might show some effectiveness.
Published in JAMA Network Open on October 2, the research was conducted under the guidance of Thomas J. Guttuso, Jr., MD, who is a neurology professor at the Jacobs School of Medicine and Biomedical Sciences at UB and a physician with UBMD Neurology.
“It’s a negative study with a positive twist,” Guttuso summarizes.
Considering that long COVID is thought to arise from chronic inflammation and that lithium exhibits anti-inflammatory properties, Guttuso suggested that one of his patients try low-dose lithium to manage persistent long COVID symptoms. He was astonished when this patient experienced nearly complete relief from fatigue and brain fog just days after starting lithium aspartate at a dosage of 5 milligrams daily.
Symptom Relief
Encouraged by this individual’s experience, Guttuso became interested in lithium aspartate and recommended it to other patients dealing with long COVID.
According to Guttuso, out of 10 long COVID patients he treated with doses ranging from 5 to 15 milligrams of lithium aspartate per day, 9 reported significant improvements in their fatigue and cognitive challenges.
“From the observations with those nine patients, I was optimistic that this randomized controlled trial would show effectiveness,” Guttuso explains. “However, research can sometimes lead to unexpected results.”
The randomized controlled trial revealed no significant improvement with 10-15 milligrams of lithium aspartate compared to a placebo group.
After one participant in the study increased their lithium aspartate intake to 40 milligrams daily and noted substantial relief from fatigue and brain fog, Guttuso decided to conduct a dose-finding study to investigate whether higher doses could offer benefits.
In this follow-up study, the three participants who completed it showed greater reductions in fatigue and cognitive issues when taking higher doses of 40-45 milligrams daily. This effect was particularly notable in two individuals whose blood lithium levels measured 0.18 and 0.49 millimoles per liter (mmol/L), while another with a level of 0.10 mmol/L experienced only partial improvements.
“This is a very small sample size, so these results are preliminary,” Guttuso cautions. “It’s possible that higher lithium blood concentrations may lead to better outcomes for fatigue and brain fog in those with long COVID.”
Possible Low Dosage
Guttuso mentions that the initial randomized controlled trial may not have been successful due to using too low a dose of lithium aspartate.
“The key takeaway is that very low doses of lithium aspartate, specifically 10-15 milligrams per day, do not work for managing fatigue and cognitive issues related to long COVID,” Guttuso states. “We might need to plan another randomized controlled trial utilizing higher doses of lithium aspartate to achieve blood lithium concentrations between 0.18-0.50 mmol/L to assess their effectiveness.”
In the U.S., approximately 17 million people are estimated to be living with long COVID, while globally, this figure rises to around 65 million.
“Currently, there are no therapies with proven effectiveness for long COVID,” Guttuso notes. He is optimistic that the National Institutes of Health will consider further investigating lithium at higher doses, especially as they are allocating an additional $500 million towards promising long COVID treatment studies.
Guttuso emphasizes that if a subsequent randomized controlled trial reveals that higher doses of lithium aspartate are beneficial, long COVID patients should consult their healthcare providers before starting treatment and have their lithium levels monitored if they do proceed with higher doses.
Co-authors of the study include 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 UB trial received funding from UB’s Clinical and Translational Science Institute for its pilot project.
