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The aim of this study is to assess the impact of 5-hydroxytryptophan (5-HTP) supplementation on sleep quality and gut microbiome composition in older adults with normal cognition vs. mild cognitive impairment (MCI) using a randomized controlled trial.
This is a 12-wk parallel, single-bind (investigator), prospective study design with subjects randomly assigned to consume 100 mg of 5-HTP or does not consume 5-HTP. Fifty older men and women (aged 60-85y, approximately half men and half women, approximately half subjects with MCI) will be recruited with the expectation that ≥ 40 subjects (≥ 10 subjects per group) will complete the study. Body size, blood pressure, urinary melatonin, sleep quality, cognitive function and mood (including depression and anxiety), gut microbiome, and short chain fatty acids will be assessed. Blood amino acid concentration will be measured as an indicator of compliance to the 5-HTP consumption from the collected blood samples.
Relevance to Singapore: The results from the proposed research will assist a practical guidance of nutritional behavior changes providing gut and brain health promoting effects to Singapore older individuals with or without MCI and may result in reducing cost and manpower for cognitive decline care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal subject without 5-HTP | Active Comparator | Subjects with normal cognition will be randomly assigned to not consuming 5-HTP. |
|
| Normal subject with 5-HTP | Experimental | Subjects with normal cognition will be randomly assigned to consuming 100 mg of 5-HTP. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-HTP | Dietary Supplement | 5-HTP that have Good Manufacturing Practice certification will be used and participants will be suggested to be take the 5-HTP supplementation at bedtime. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in sleep quality assessed by validated sleep questionnaires | Pittsburgh Sleep Quality Index Questionnaire (PSQI) will be used to assess the sleep quality. Overall score ranging from 0 to 21 points, where lower scores denote a healthier sleep quality. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Change in sleep quality assessed by electronic equipment | An electronic equipment, actigraphy, will be used to assess the sleep quality, including sleep timing and wake up timing. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Change in fecal short chain fatty acid (SCFA) concentration as assessed by micromoles per gram (μmol/g) | Fecal SCFA concentration will be measured using gas chromatograph (GC) and assessed by μmol/g. There is no recognized range. Normally the higher level is better. | Pre- and post-intervention (week 0 and week 12) |
| Change in fecal microbiome composition | High-throughput sequencing method (using Illumina MiSeq platforms) will be used to assess the changes in gut microbiome composition. | Pre- and post-intervention (week 0 and week 12) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Quality of Life: WHOQOL | The World Health Organization Quality of Life Assessment (WHOQOL) will be used to assess the quality of life. Score ranging from 0 to 100 points, where higher scores denote higher quality of life. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Change in Cognitive function |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kim J Eun, PhD | National University of Singapore | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National University of Singapore | Singapore | 117546 | Singapore | |||
| Hannah Seniors Activity Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25572038 | Background | Mohajeri MH, Wittwer J, Vargas K, Hogan E, Holmes A, Rogers PJ, Goralczyk R, Gibson EL. Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women. Br J Nutr. 2015 Jan 28;113(2):350-65. doi: 10.1017/S0007114514003754. Epub 2015 Jan 9. | |
| 29031742 |
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Electronic copies of the data with identifiable participant information will be kept on a secure website with access limited to Dr. Kim and her research staff. All data will be de-identified prior to statistical analyses
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| ID | Term |
|---|---|
| D007319 | Sleep Initiation and Maintenance Disorders |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D006916 | 5-Hydroxytryptophan |
| ID | Term |
|---|---|
| D014364 | Tryptophan |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
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| Without 5-HTP | Other | Subject will not take 5-HTP |
|
Montreal Cognitive Assessment (MOCA) will be used to assess the cognitive function. Score ranging from 0 to 30 points. A final total score of 26 and above is considered normal. |
| Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Change in mood (depression) | Geriatric Depression Scale (GDS) Assessment will be used to assess the depression situation. Score ranging from 0 to 15 points. Although differing sensitivities and specificities have been obtained across studies, for clinical purposes a score > 5 points is suggestive of depression and should warrant a follow-up interview. Scores > 10 are almost always depression. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Change in mood (anxiety) | Geriatric Anxiety Inventory (GAI) Assessment will be used to assess the anxiety situation. Score ranging from 0 to 20 points, where higher scores denote higher level of anxiety. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Change in urinary melatonin levels as assessed by nanogram per milliliter (ng/mL) | Change in urinary melatonin levels will be assessed by using enzyme linked immunosorbent assay (ELISA) kits. There is no recognized range. Normally the higher level is better. | Pre- and post-intervention (week 0 and week 12) |
| Change in blood amino acids assessed by nanomole per milliliter (ng/mL) | Amino Acid Analysis System will be used to assess the blood amino acid levels. There is no recognized range. | Pre- and post-intervention (week 0 and week 12) |
| Change in weight and height | Weight (in kilograms) and height (in meters) will be combined to report BMI in kg/m^2. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Change in waist circumference as assessed by centimeter (cm) | Recommended cutoffs for increased health risk are a waist circumference >102 cm for men and >88 cm for women. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Dietary assessment | Dietary assessment will be assessed by 3-day dietary food record. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Blood pressure as assessed by millimeter of mercury (mmHg) | Systolic and diastolic blood pressure will be measured by a blood pressure monitor. For a normal reading, systolic pressure is between 90 and 120 and diastolic pressure is between 60 and 80. | Every 4 weeks (week 0, week 4, week 8 and week 12) |
| Singapore |
| 59002 |
| Singapore |
| Anderson JR, Carroll I, Azcarate-Peril MA, Rochette AD, Heinberg LJ, Peat C, Steffen K, Manderino LM, Mitchell J, Gunstad J. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults. Sleep Med. 2017 Oct;38:104-107. doi: 10.1016/j.sleep.2017.07.018. Epub 2017 Aug 2. |
| 38309227 | Derived | Sutanto CN, Xia X, Heng CW, Tan YS, Lee DPS, Fam J, Kim JE. The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial. Clin Nutr. 2024 Mar;43(3):593-602. doi: 10.1016/j.clnu.2024.01.010. Epub 2024 Jan 17. |
| D001523 |
| Mental Disorders |
| D000602 |
| Amino Acids, Peptides, and Proteins |