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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adult
• Intervention / Treatment: Dietary supplement: L-histidine; Dietary supplement: Monosodium glutamate (MSG); Dietary supplement: Sodium chloride (NaCl)

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sam Light, PhD; Phone Number: 773-702-3435; Email: samlight@uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Duchossois Family Institute, Knapp Center for Biomedical Discovery (KCBD), Room 4214
      • Contact: Sam Light; Phone Number: 773-702-3435; Email: samlight@uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1: L-histidine + MSG, then L-histidine + NaCl; 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; 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.; Dietary supplement: Monosodium glutamate (MSG); 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; Dietary supplement: Sodium chloride (NaCl); 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.
Experimental: Sequence 2: L-histidine + NaCl, then L-histidine + MSG; 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; 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.; Dietary supplement: Monosodium glutamate (MSG); 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; Dietary supplement: Sodium chloride (NaCl); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Monosodium glutamate
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Inorganic Chemicals; Chlorine Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Amino Acids, Essential; Amino Acids, Cyclic; Sodium Compounds; Chlorides; Hydrochloric Acid; Glutamic Acid; Sodium Chloride; Sodium Glutamate; Histidine
• Other Study ID Numbers: IRB25-1212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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