The effectiveness of nonsteroidal anti-inflammatory drugs and acetaminophen in reduce the risk of amyotrophic lateral sclerosis? A meta-analysis

Abstract

To test the hypothesis that aspirin, non-aspirin nonsteroidal anti-infammatory drugs (NA-NSAIDs), or acetaminophen can reduce the risk of ALS, we conducted a systematic review and meta-analysis of related previous studies. A comprehensive search was conducted on the PubMed, Embase, Cochrane Library and SCOPUS databases. It included studies published up to 29 February 2020 that fulfilled our inclusion criteria. Aspirin, acetaminophen and NA-NSAIDs use information, between the ALS and control groups, was collected for the meta-analysis. Rates of aspirin, NA-NSAID, and acetaminophen use in ALS group, compared with control group were investigated. In the results, only three studies that relate the risk of ALS to aspirin, NA-NSAIDs and acetaminophen use satisfied the inclusion criteria for the meta-analysis. Regarding aspirin, the studies did not show any statistically significant difference in aspirin use between the ALS and control groups (Odds ratio, 1.04 [95% confidence interval, 0.90–1.21]). NA-NSAIDs and acetaminophen use, however, did show up statistically significant differences in between the ALS and control groups. (Odds ratio, 0.82 [95% confidence interval, 0.73–0.91]) and (Odds ratio, 0.80 [95% confidence interval, 0.69–0.93]). However, our study has some limitations. Firstly, we only included a small number of studies. Secondly, the included studies did not control for past medical history, which may have confounded their results, and in turn, could have caused bias in our study. Thirdly, in this meta-analysis, the ALS patients were not subdivided into sporadic or familial type. Lastly, the studies also did not consider the types of NSAIDs and dosages used of each drug. For more convincing evidence regarding the effectiveness of aspirin, NA-NSAIDs and acetaminophen to reduce the risk of ALS occurrence, more qualified prospective studies are required. In conclusion, the use of NA-NSAIDs and acetaminophen is associated with a decreased risk for the development of ALS. In contrast, aspirin did not have any effect on the reduction of the risk of ALS occurrence.

Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy

“…Furthermore, our results have shown different pro-inflammatory cytokine profiles for sporadic and SOD1-ALS subtype which agrees with recent data that also shown a negative association with the survival rate [23]. Besides, the use of non-aspirin-NSAIDs and acetaminophen, which decrease the risk for the development of ALS [50], would be especially useful for sALS where high levels of cytokines have been found. On the other hand, decreased levels of NRF2 in SOD1-ALS points to dimethyl fumarate (DMF) [51,52], an inducer of this pathway, as a good therapy for this sub-group of patients.…”

Novel Therapeutic Target for Prevention of Neurodegenerative Diseases: Modulation of Neuroinflammation with Sig-1R Ligands

“…An FDA-approved anti-inflammatory drug (cromolyn sodium) can delay the symptoms of ALS development in a mouse model of the disease [80]. Another meta-analysis resulted in conflicting results: non-aspirin-NSAIDs and acetaminophen were associated with an increased risk of ALS progression; however, aspirin did not affect the development of disease [81].…”

Novel Applications of NSAIDs: Insight and Future Perspectives in Cardiovascular, Neurodegenerative, Diabetes and Cancer Disease Therapy

“…The weak effectiveness of NSAIDs in neurodegenerative disease management could be explained by pharmacokinetic and pharmacodynamics data. In general, NSAIDs cross the blood-brain barrier (BBB) efficiently, but the effective dose reaching the brain can be different under different neuropathological conditions, depending on BBB integrity [ 104 ] and amphiphilic nature of NSAID which allows NSAID interaction with lipid membranes, on the modulation of membrane biomechanical properties and cell signaling events [ 105 ]. NSAID doses required for PPAR-γ agonist activity are in the high micromolar range, largely exceeding those required for in vivo inhibition of COXs.…”