Impact of Nutritional Supplementation on Sleep Quality and Gut Microbiome Composition in Older Adults

Impact of Nutritional Supplementation on Gut-brain Axis in Older Adults With Normal Cognition vs. Mild Cognitive Impairment

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.

Study Overview

• Status: Completed
• Conditions: Sleep; Gut Microbiome
• Intervention / Treatment: Other: Without 5-HTP; Dietary supplement: 5-HTP

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 117546
    • National University of Singapore
  • Singapore, Singapore, 59002
    • Hannah Seniors Activity Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to give an informed consent
2. Age 60 ≤years ≤ 85 years old
3. Weight change < 3kg in the past 3 months
4. Not exercising vigorously over the past 3 months
5. Not taking protein (e.g. Whey isolate, Ensure), tryptophan, serotonin and/or 5-HTP supplements for the past one month
6. Not taking sleep medication and/or dietary supplements for sleep (e.g. melatonin, GABA) for the past one month
7. Not taking prebiotic, probiotic and/or dietary fiber supplementations for the past one month
8. Not taking cognitive/brain supplementations (e.g. gingko biloba, acetylcholine) for the past one month
9. Not taking prescription anti-depressant or pain medication (e.g. Zoloft, Tramadol etc.)
10. No acute illness
11. If taking antihypertensive/cholesterol-lowering/ type 2 diabetic medication, he/she has been taking the medication for more than 5 years prior to the study participation
12. Not smoking
13. Not drinking more than 2 alcoholic drinks per day

Exclusion Criteria:

1. Unable to give an informed consent
2. Age < 60 years and >85 years old
3. Weight change >3kg in the past 3 months
4. Exercises vigorously over the past 3 months
5. Taking protein (e.g. Whey isolate, Ensure), tryptophan, serotonin and/or 5-HTP supplements for the past one month
6. Taking sleep medication and/or dietary supplements for sleep (e.g. melatonin, GABA) for the past one month
7. Taking prebiotic, probiotic and/or dietary fiber supplementations for the past one month
8. Taking cognitive/brain supplementation (e.g. gingko biloba, acetylcholine) for the past one month
9. Taking prescription anti-depressant or pain medication (e.g. Zoloft, Tramadol etc.)
10. Having acute illness
11. If taking antihypertensive/cholesterol-lowering/ type 2 diabetic medication, he/she has NOT been taking the medication for less than 5 years prior to the study participation
12. Smoking
13. Drinking more than 2 alcoholic drinks/day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Normal subject without 5-HTP; Subjects with normal cognition will be randomly assigned to not consuming 5-HTP.	Other: Without 5-HTP; Subject will not take 5-HTP
EXPERIMENTAL: Normal subject with 5-HTP; Subjects with normal cognition will be randomly assigned to consuming 100 mg of 5-HTP.	Dietary supplement: 5-HTP; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: National University, Singapore
• Investigators: Principal Investigator: Kim J Eun, PhD, National University, Singapore

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 4, 2020
• Primary Completion (ACTUAL): June 30, 2021
• Study Completion (ACTUAL): June 30, 2021

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (ACTUAL): September 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 8, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Cognitive function; Sleep quality; Gut microbiome; Nutritional supplementation
• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Second-Generation; 5-Hydroxytryptophan
• Other Study ID Numbers: S8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No