Written by Tabish Mehraj, PhD. This study showed that 5-HTP supplementation led to modest cognitive improvements, showing a significant rise in total MoCA scores over 12 weeks. The supplement demonstrated a potential antidepressant effect, as participants showed a significant reduction in depressive symptoms by the eighth week. Since no changes were observed in neurodegeneration biomarkers, the observed benefits are likely attributable to enhanced serotonergic activity rather than structural brain changes.

The population in Singapore is aging, as is that of many developed countries worldwide. Depression and anxiety are quite prevalent and have been associated with a decline in cognitive function. Lifestyle-based strategies, such as diet interventions and increased physical activity, have been emphasized because there are currently limited to pharmaceutical therapies. Numerous studies suggest that regulation of the serotonin system plays a role in controlling cognition, mood, and brain development. Age-related decline in serotonin has been associated with reduced cognitive function. 5-Hydroxytryptophan (5-HTP) is an amino acid and an immediate precursor to the neurotransmitter serotonin. It crosses the blood-brain barrier, bypassing the rate-limiting enzyme tryptophan hydroxylase, allowing the body to rapidly produce serotonin to support cognitive functions, mood, and sleep.

This randomized controlled 12-week, single-blinded trial assessed whether 5-Hydroxytryptophan (5-HTP) could enhance cognitive function and mood. This study enrolled 33 older healthy Singaporean individuals aged 60-85 years and 30 who completed the intervention. Participants were randomly assigned to receive 100 mg of 5-HTP daily before bedtime (n = 15) or to a control group without supplementation (n = 15). Cognition was assessed using the Montreal Cognitive Assessment (MoCA), and mood was assessed using the Geriatric Depression Scale (GDS) and the Geriatric Anxiety Inventory (GAI). Several blood markers were also measured.

Key Findings/ Results

• 5-HTP supplement showed modest improvements in cognitive performance. Individuals receiving the supplement showed a significant increase in total MoCA scores from baseline to week 12, rising from 26.6 ± 1.4 to 27.6 ± 1.4 points.. (P=0.0007) The control group showed a non-significant increase in total MoCA scores. There was no difference in MOCA scores between the 5-HT and the control group.
• Improvements were mainly noted in cognitive functions related to language and naming functions that are dependent on temporal and frontal regions of the brain. there was also a significant difference in naming score vs. baseline in the placebo group.
• Serum serotonin levels increased from 173.7 ± 81.2 ng/mL to 219.6 ± 73.1 ng/mL, whereas serotonin levels declined slightly in the control group.
• Reduction in depressive symptoms was observed with GDS scores, which decreased significantly at week 8. The results showed a potential antidepressant effect on mood of 5-HTP supplementation.
• No significant changes were observed in the biological markers that are associated with neurodegeneration; the changes that were absent in these biomarkers suggest that the cognitive improvements observed were more likely attributable to enhanced serotonergic activity.

A major strength of this study is that it represented an under-researched Asian older population. It is one of the first randomized controlled trials assessing the cognitive effects of 5-HTP supplementation. The randomized controlled design reduces selection bias. Validated tools were used to assess cognitive and physiological health, including MoCA, GDS, and GAI. Both clinical and subjective biochemical measurements enhanced the study’s rigor. Serum serotonin level measurement may provide mechanistic support for the observed cognitive and potential mood improvements. Despite its promising results, the study has several important limitations. Firstly, the small sample size (n = 30) reduces statistical power. The absence of placebo in the control group undermines the possible intergroup comparison since patients knew in what group they were and that fact may influence their answer to MoCA, GDS, and GAI. The 12-week intervention was relatively short. Cognitive decline and neurodegenerative disease progress over many years, which makes it difficult to determine benefits and long-term clinical findings.

This study provides preliminary evidence that daily supplementation with 100 mg of 5-HTP may enhance cognitive performance and improve mood in healthy older adults, potentially by increasing serotonin production. While the findings are encouraging, the modest effect size, small sample size, and short intervention period warrant cautious interpretation. Larger, longer-term studies are needed before firm conclusions can be drawn about the role of 5-HTP as a strategy for maintaining cognitive health and emotional well-being in aging populations.

Reference:

1. Li, S., Sutanto, C. N., Xia, X., & Kim, J. E. (2025). The Impact of 5-Hydroxytryptophan Supplementation on Cognitive Function and Mood in Singapore Older Adults: A Randomized Controlled Trial. Nutrients, 17(17), 2773.