Metabolic Effects of Short-Chain Fatty Acids in Healthy Individuals

Not Applicable

Not yet recruiting

• Conditions: Healhty; Other: Short-Chain Fatty Acid (SCFA); Other: Butyrate (C4); Other: Propionate (C3)

• Registration Number: NCT07183488
• Lead Sponsor: University of Copenhagen

Brief Summary

The primary objective of this study is to investigate the acute physiological and metabolic effects of ingesting the short-chain fatty acids (SCFA)s propionate (three carbon atoms long; C3:0) and butyrate (C4:0) in healthy men and women. This aim will be addressed through a block-randomized cross-over study including two visits with acute intake of propionate and butyrate, respectively.

The hypothesis is that plasma ketone body levels will increase during the first three hours after intake of butyrate, but not propionate, in healthy individuals in the overnight fasted state.

Detailed Description

The study will be conducted as a block-randomized cross-over study in healty participants (n=10). The participants will undergo two experimental days of three hours separated by a two to four weeks wash-out period. At the test days, participants will consume 3 grams of either propionate or butyrate in the form of sodium-propionate or sodium-butyrate together with 250 ml of water. The order of ingestion is determined by randomization.

The day prior to the experimental days, participants will consume a standardized control dinner and evening snack and abstain from alcohol and vigorous physical activity to ensure similar conditions on the experimental days. The standardized meal will be provided to the participants. On the test days, participants will be instructed to arrive by passive transport in an overnight fasted state (10 hours). Upon arrival, a DXA scan will be performed, after which a catheter will be inserted into an antecubital vein. Following 30 minutes of supine rest, baseline measurements will be performed, including indirect calorimetry, blood pressure measurement, flow-mediated vasodilation (FMD), and a fasting venous blood sample. Participants will then ingest 3 grams of propionate or butyrate within 5 minutes, together with 250 ml of water. After ingestion, participants will remain resting in bed for 3 hours, during which blood samples (15 ml each) will be collected continuously throughout the test day. Indirect calorimetry, blood pressure measurements, and FMD will be repeated at various time points post-ingestion. The test day will end with an ad libitum meal. The entire procedure will be repeated on the second test day.

Study Timeline

• Study First Submitted: 2025-08-27
• Status Verified: 2025-09
• Study Start: 2025-09-10
• Study First Submitted QC: 2025-09-16
• Last Update Submitted: 2025-09-16
• Study First Posted: 2025-09-19
• Last Update Posted: 2025-09-19
• Primary Completion: 2026-01-05
• Study Completion: 2030-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Male or female.
• Age between 18-40 years old
• BMI between 18.5-29

Exclusion Criteria

• Diabetes
• Kidney- or liver disease
• Pregnant, lactating or planning to become pregnant within the study period
• Supplementation with SCFAs
• Supplementation with B12 vitamin
• Special dietary habits (e.g. vegan/ketogenic diet)
• Ongoing cancer treatment
• Metabolic or absorptive disorders, gastric bypass operation, or use of medication affecting metabolism or food absorption
• Crohn's disease, ulcerative colitis or short bowel syndrome
• Inability, physically or mentally, to comply with the procedure required by the study protocol as evaluated by the primary investigator, study manager or clinical responsible

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Ketone Bodies	On day 1 (test day 1) and day 2 (test day 2) at baseline (-30 min and 0 min) and post intake (10 min, 15 min, 22.5 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 180 min).	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on circulating ketone body concentrations.

Secondary Outcome Measures

Name	Time	Method
Glucose	On day 1 (test day 1) and day 2 (test day 2) at baseline (-30 min and 0 min) and post intake (10 min, 15 min, 22.5 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 180 min).	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on circulating glucose.
Fatty acids	On day 1 (test day 1) and day 2 (test day 2) at baseline (-30 min and 0 min) and post intake (10 min, 15 min, 22.5 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 180 min).	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on circulating Short-Chain Fatty Acids.
Flow mediated dilation measurement	On day 1 (test day 1) and day 2 (test day 2) at baseline (min -15) and post intake (min 90).	To measure the vasodilatory effects of the short-chain fatty acids butyrate (SCFA-BUT) and propionate (SCFA-PRO) during flow-mediated dilation measurement.
Resting metabolic rate	On day 1 (test day 1) and day 2 (test day 2) at baseline (min -15) and post intake (30 min, 60 min, 120 min)	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on resting metabolic rate.
Respiratory exchange ratio	On day 1 (test day 1) and day 2 (test day 2) at baseline (min -15) and post intake (30 min, 60 min, 120 min)	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on respiratory exchange ratio.
Fatty Acid Composition	On day 1 (test day 1) and day 2 (test day 2) at baseline (-30 min and 0 min) and post intake (10 min, 15 min, 22.5 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 180 min).	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on fatty acid composition.
Satiety	On day 1 (test day 1) and day 2 (test day 2) at baseline (-15 min) and post intake (30 min, 60 min, 90 min and 120 min).	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on satiety using the Visual Analog Scale (VAS), going from 0 (none) to 10 (worst possible) at a 10cm scale.
Metabolites	On day 1 (test day 1) and day 2 (test day 2) at baseline (-30 min and 0 min) and post intake (10 min, 15 min, 22.5 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 180 min).	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on circulating ketone body concentrations.
Hepatokines	On day 1 (test day 1) and day 2 (test day 2) at baseline (-30 min and 0 min) and post intake (10 min, 15 min, 22.5 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 180 min).	To measure the effect Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on circulating hepatokine concentrations.
HOMA-Index	On day 1 (test day 1) and day 2 (test day 2) at baseline (-30 min and 0 min) and post intake (10 min, 15 min, 22.5 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 180 min).	To measure the effect of Short-Chain Fatty Acid Butyrate (SCFA-BUT) and Short-Chain Fatty Acid Propionate (SCFA-PRO) on HOMO-index.

Trial Locations

Locations (1)

University of Copenhagen; 🇩🇰 Copenhagen, Copenhagen N, Denmark