In this exploratory pilot study, a within-group reduction in nocturnal motor activity was observed among M-5HTP completers, but given the small sample size, high attrition rate, and limited statistical power, these findings should be interpreted cautiously and considered hypothesis-generating.
Key Findings
Results
No statistically significant between-group differences in change scores were observed when comparing melatonin combined with 5HTP (M-5HTP) versus melatonin combined with L-tryptophan (M-LT).
The trial was a single-center, randomized pilot comparative design.
Children were under five years of age with neurodevelopmental disorders (NDDs) and free of sleep-inducing drugs.
M-5HTP dose was 1 mg melatonin + 10 mg 5HTP; M-LT dose was 1 mg melatonin + 20 mg LT, administered at 8 p.m. for at least four weeks.
Of 51 screened children, 26 were enrolled and only 13 completed the study (M-5HTP: 9, M-LT: 4).
Results
Within the M-5HTP group, there was a statistically significant reduction in the Sleep Movement Index (SMI) from baseline to follow-up.
SMI at baseline (T0): 6.55; SMI at follow-up (T1): 1.25; p=0.006.
The SMI reflects nocturnal motor activity as measured by actigraphy.
No significant changes in SMI were observed in the M-LT group.
Actigraphy monitoring was performed both at baseline and post-treatment to assess sleep parameters.
Results
The study experienced a high attrition rate, with only 13 of 26 enrolled children completing the trial.
51 children were screened, 26 were enrolled, and 13 completed the study.
Completion rate was approximately 50% of enrolled participants.
The M-LT group had particularly low completion, with only 4 completers compared to 9 in the M-5HTP group.
The authors note that the small sample size, high attrition rate, and limited statistical power require cautious interpretation of findings.
Background
Combining melatonin with its precursors L-tryptophan and 5-Hydroxytryptophan was hypothesized to influence sleep-related outcomes in children with neurodevelopmental disorders, but evidence prior to this study was limited.
Melatonin plays a key role in sleep regulation.
LT and 5HTP are biosynthetic precursors to melatonin.
The study population targeted children under five years of age with NDDs.
Baseline evaluations and actigraphy monitoring were performed before treatment assignment.
Conclusions
The authors characterize the findings as hypothesis-generating due to the exploratory and pilot nature of the study design.
The study is described as a 'single-center, randomized pilot comparative trial.'
Authors explicitly state findings 'should be interpreted cautiously and considered hypothesis-generating.'
The observed within-group SMI reduction in M-5HTP completers is noted but not considered confirmatory evidence.
The limited sample size and high attrition rate are cited as primary constraints on interpretation.
What This Means
This research suggests that a supplement combining melatonin with 5-Hydroxytryptophan (5HTP) may reduce nighttime movement in young children with neurodevelopmental disorders (NDDs) such as autism or developmental delays. In a small pilot study, children under five who took 1 mg of melatonin plus 10 mg of 5HTP each evening showed a meaningful decrease in their Sleep Movement Index — a measure of how much they moved during sleep — after at least four weeks of treatment. Children who took melatonin combined with L-tryptophan (LT) did not show the same improvement, though the two groups were not statistically different from each other.
However, the study had significant limitations that make it difficult to draw firm conclusions. Only 13 out of 26 enrolled children completed the study, and the very small group sizes — especially just 4 completers in the melatonin-plus-LT group — mean the results could easily be influenced by chance. No statistically significant differences were found when directly comparing the two treatment groups, and the authors themselves emphasize that the findings are 'hypothesis-generating' rather than definitive.
This research matters because sleep problems are very common in children with neurodevelopmental disorders and can significantly affect the whole family. While melatonin alone is already widely used, this study raises the possibility that adding melatonin precursors like 5HTP could provide additional benefit for nighttime restlessness. Larger, well-controlled studies are needed to confirm whether this combination is genuinely effective and safe before any clinical recommendations could be made.
Cruz-Sanabria F, Cenerini G, Bruno S, Ferri R, Fiori S, Faraguna U. (2026). Effect of melatonin enriched with L-Tryptophan and 5-Hydroxytryptophan on sleep parameters in children with neurodevelopmental disorders.. Sleep medicine. https://doi.org/10.1016/j.sleep.2026.108818