Melatonin Might Benefit ALS Patients, But More Research Needed

People with amyotrophic lateral sclerosis (ALS) who use melatonin have better survival outcomes and experience slower disease progression, a new analysis indicates.

The findings suggest that melatonin may be beneficial for people with ALS. However, because the analysis was not designed to find cause-and-effect relationships, further studies are needed, researchers said.

Results of the study, “Melatonin may slow disease progression in amyotrophic lateral sclerosis: Findings from the Pooled Resource Open‐Access ALS Clinic Trials database,” were published in Muscle & Nerve.

Melatonin is a hormone that is produced naturally by the brain in response to darkness; it helps to regulate sleep cycles. Treatment with melatonin supplements, which are available over-the-counter, is sometimes used to help people fall asleep.

Melatonin has biological effects apart from its effect on sleep, though many of these are poorly understood. Among its effects, melatonin is an antioxidant, which means it can help lessen a type of cellular damage called oxidative stress — an excessive production of toxic oxidative molecules — that has been implicated in the development and progression of ALS.

“Because oxidative stress is a contributing factor in the pathogenesis [development] of ALS, it is reasonable to hypothesize that melatonin may also prove to be beneficial for patients with this disease,” the researchers wrote. “The aim of this study was to investigate if melatonin use among patients with ALS was associated with slower disease progression and longer survival.”

The researchers analyzed data from the PRO-ACT database, which contains data from 23 ALS clinical trials. A total of 1,622 ALS patients were included; of these, 18 were consistently on melatonin in the respective clinical trial.

Melatonin users were significantly younger on average than non-users (52.2 vs. 58.3 years). They also had significantly higher forced vital capacity (FVC), a measurement of lung function, and were less likely to require ventilation. Other demographic and pre-treatment clinical factors were similar between users and non-users.

Of the 18 melatonin users, four (22.2%) died during the studies. Of the non-users, 1,360 (75.1%) died. Statistical analyses showed that the risk of death was significantly lower — by 76% — among the melatonin users.

Disease progression, as measured by a standardized ALS functional rating scale, was significantly slower among melatonin users than non-users. The decline in FVC also was significantly slower in users.

“This small retrospective large-database study suggests that melatonin may be beneficial for patients with ALS,” the researchers wrote.

Importantly, the design of this study makes it impossible to determine whether there is a cause-and-effect relationship between melatonin use and these improved outcomes.

“These findings do not imply causation [cause-and-effect] and simply represent associations between melatonin use and these selected positive outcomes of ALS,” the researchers wrote.

They added: “These results are solely intended to be hypothesis generating and no strong associations can be made between melatonin and ALS disease progression.”

The researchers noted the study has significant limitations, including the small number of melatonin users and the differences between users and non-users prior to treatment.

Additionally, due to the database used, the researchers were unable to account for some factors that are known to affect disease progression and survival in ALS patients (e.g., caregiver support and comorbid conditions).

“Regardless, given its low cost and favorable safety profile, further research of melatonin is warranted to investigate possible efficacy [in ALS],” the researchers concluded.