Effect of Monosodium Glutamate on Microbiome-Derived Imidazole Propionate Production in Healthy Volunteers

NCT07700368 | Not Yet Recruiting

• 1 other identifier: IRB25-1212
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn whether dietary monosodium glutamate (MSG), a common food flavor enhancer, increases the blood level of a gut-microbiome-derived compound called imidazole propionate (ImP) in healthy adult volunteers. ImP is a compound made by gut bacteria from the amino acid histidine, and higher blood levels have been linked to problems with blood-sugar control. The main questions this trial aims to answer are: Does taking MSG together with L-histidine increase blood ImP levels compared with taking a salt (sodium chloride) placebo together with L-histidine? How do blood ImP levels change over time in response to MSG and L-histidine taken together? Researchers will compare a 7-day period of L-histidine plus MSG against a 7-day period of L-histidine plus sodium chloride (a salt placebo with matching sodium content) to see whether MSG changes blood ImP levels. Each participant completes both periods in random order and serves as their own comparison. Participants will: Take L-histidine capsules twice daily (morning and evening with meals) during two separate 7-day periods. Dissolve either MSG powder or salt powder in water and drink it twice daily during each period, with the two periods separated by a 7-day break (washout). Give a fasting blood sample at the start of the study and on day 7 of each period. Optionally provide a stool sample at the end of each period. Complete a daily treatment diary and a follow-up phone call after the final sample.

Conditions

Healthy Adult

Keywords

Monosodium glutamate

Outcome Measures

Primary Outcomes (1)

• Difference in blood imidazole propionate concentration between the monosodium glutamate and sodium chloride treatment periods

  Blood imidazole propionate concentration measured by liquid chromatography-mass spectrometry (LC-MS) from the blood sample collected on day 7 of each 7-day treatment period. The outcome is the within-participant difference between the day-7 concentration following the L-histidine + MSG period and the day-7 concentration following the L-histidine + NaCl period.

  Day 7 of each treatment period

Study Arms (2)

Sequence 1: L-histidine + MSG, then L-histidine + NaCl

EXPERIMENTAL

Participants receive L-histidine (4 g/day) plus monosodium glutamate (MSG; 3 g/day) during the first 7-day treatment period, followed by a 7-day washout, then L-histidine (4 g/day) plus sodium chloride (NaCl; 940 mg/day) during the second 7-day treatment period. L-histidine is taken as capsules (2 g morning, 2 g evening with meals); MSG and NaCl are dissolved in approximately 240 mL of water and taken twice daily (morning and evening with meals).

Dietary Supplement: L-histidine; Dietary Supplement: Monosodium glutamate (MSG); Dietary Supplement: Sodium chloride (NaCl)

Sequence 2: L-histidine + NaCl, then L-histidine + MSG

EXPERIMENTAL

Participants receive L-histidine (4 g/day) plus sodium chloride (NaCl; 940 mg/day) during the first 7-day treatment period, followed by a 7-day washout, then L-histidine (4 g/day) plus monosodium glutamate (MSG; 3 g/day) during the second 7-day treatment period. L-histidine is taken as capsules (2 g morning, 2 g evening with meals); MSG and NaCl are dissolved in approximately 240 mL of water and taken twice daily (morning and evening with meals).

Dietary Supplement: L-histidine; Dietary Supplement: Monosodium glutamate (MSG); Dietary Supplement: Sodium chloride (NaCl)

Interventions

L-histidine DIETARY_SUPPLEMENT

USP-grade L-histidine, 4 g/day, taken as capsules divided into 2 g in the morning and 2 g in the evening with meals, during each 7-day treatment period. Administered in both treatment periods for all participants.

Sequence 1: L-histidine + MSG, then L-histidine + NaCl; Sequence 2: L-histidine + NaCl, then L-histidine + MSG

Monosodium glutamate (MSG) DIETARY_SUPPLEMENT

Food-grade monosodium glutamate, 3 g/day, provided as identical-appearing single-dose powder sachets divided into 1.5 g in the morning and 1.5 g in the evening, each dissolved in approximately 240 mL

Sequence 1: L-histidine + MSG, then L-histidine + NaCl; Sequence 2: L-histidine + NaCl, then L-histidine + MSG

Sodium chloride (NaCl) DIETARY_SUPPLEMENT

USP-grade sodium chloride, 940 mg/day, provided as identical-appearing single-dose powder sachets divided into 470 mg in the morning and 470 mg in the evening, each dissolved in approximately 240 mL of water and taken with meals during the placebo treatment period. The sodium content is matched to that of the 3 g/day MSG dose to isolate the effect of glutamate.

Sequence 1: L-histidine + MSG, then L-histidine + NaCl; Sequence 2: L-histidine + NaCl, then L-histidine + MSG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• No antibiotic use in the previous 3 months

You may not qualify if:

• Diagnosis of diabetes or prediabetes (any type)
• Inflammatory bowel disease or other gastrointestinal disorder
• Known allergy or intolerance to monosodium glutamate (MSG)
• Pregnancy or breastfeeding
• Current participation in another clinical trial
• High habitual dietary intake of MSG or histidine

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

Duchossois Family Institute, Knapp Center for Biomedical Discovery (KCBD), Room 4214

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Interventions

Histidine; Sodium Glutamate; Sodium Chloride

Intervention Hierarchy (Ancestors)

Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Glutamic Acid; Glutamates; Amino Acids, Acidic; Amino Acids, Dicarboxylic; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Sam Light, PhD

CONTACT

773-702-3435; samlight@uchicago.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 14, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

US (1)