Initial trials of low-dose lithium failed to improve Long Covid symptoms, but new findings suggest higher doses could offer hope for patients suffering from fatigue and cognitive impairment.
By Tarun Sai Lomte
Extracts
A recent study published in the journal JAMA Network Open investigated the effects of lithium aspartate on cognitive dysfunction and fatigue in post-coronavirus disease 2019 (COVID-19) condition (PCC). Long COVID or PCC is the persistence of symptoms for ≥ four weeks after COVID-19 recovery. PCC symptoms can linger for over six months in 10% of patients; cognitive dysfunction, fatigue, and post-exertional malaise are the most common symptoms. PCC remains a major cause of disability, impacting the quality of life of around 65 million individuals worldwide.
Neuroimaging and autopsy data support chronic brain inflammation as a contributor to neurologic symptoms of PCC – cognitive dysfunction and fatigue. Specifically, increased activation in the ventral striatum, dorsal putamen, and thalamus has been linked to these symptoms. Increased astrocyte and microglia activation has been observed in patients with neurologic PCC symptoms, suggesting elevated neuroinflammation. Therapies that suppress glial activation and neuroinflammation could be promising for neurologic PCC.
About the study
In the present study, researchers investigated the effects of lithium aspartate treatment on cognitive dysfunction and fatigue in PCC. This double-blind, randomized, placebo-controlled trial enrolled patients at a neurologic clinic between November 28, 2022, and June 29, 2023. Eligible patients had a positive COVID-19 test with new/worsened symptoms of cognitive dysfunction and fatigue lingering for at least four weeks post-COVID-19 recovery.
After the trial, a dose-finding study was performed to examine whether lithium aspartate doses up to 45 mg/d were associated with improved BFSS or FSS-7 scores compared to 15 mg/d during the trial. They were instructed to start with two capsules a day (10 mg/d) for the first week and increase one capsule daily every week to a maximum dose of 45 mg/d. The study used an intention-to-treat analysis, adding robustness to the trial’s findings.
Conclusion
Taken together, the study showed that 10 – 15 mg/d of lithium aspartate was ineffective for PCC cognitive dysfunction and fatigue. Only five patients from the trial participated in the dose-finding study, and results from three patients suggested that serum lithium levels of 0.18 – 0.49 mEq/L might offer meaningful improvements in fatigue or cognitive dysfunction.
However, the study has notable limitations, including a small sample size and the lack of biomarker assessments, which could have helped identify patients more likely to benefit from lithium therapy. As such, another trial will be required to examine the benefits of higher lithium doses to treat neurologic PCC.
MEA Comment
Results from another very small study with only small improvements and involving a lithium based supplement that has the potential to cause side effects at higher doses. So, all very speculative at the moment
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE Guideline Committee,
Member of the 2002 Independent Working Group on ME/CFS
Further Media Coverage
- Medical Xpress: Long COVID: Study finds lithium aspartate at low doses is ineffective, but higher doses may be promising | 2nd October
- Medpage Today: Low-dose lithium tested in Long Covid | 2nd October
- University of Minnesota: Lithium aspartate didn't relieve long-COVID fatigue, brain fog in trial participants | 2nd October
- Technology Networks: High-Dose Lithium May Help Alleviate Long COVID Fatigue and Brain Fog | 2nd October