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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Difference in blood imidazole propionate concentration between the monosodium glutamate and sodium chloride treatment periods [Time frame: Day 7 of each treatment period]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Basic science

Study locations

United States · 1 center

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

Identifiers

NCT: NCT07700368 · IRB25-1212

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗