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NCT Number: NCT07183488

Metabolic Effects of Short-Chain Fatty Acids in Healthy Individuals

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.

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Key information

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Copenhagen

Copenhagen, Copenhagen N, 2200, Denmark

Location status: Recruiting

Location contact

Amalie S Frederiksen, PhD Student

CONTACT

[email protected]

+4528899561

Andreas M Fritzen, Associate Professor

CONTACT

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Propionate followed by Butyrate

Other

The participants will consume Short-chain fatty acid propionate (SCFA-PRO) followed by Short-Chain Fatty Acid Butyrate (SCFA-BUT).

Butyrate followed by Propionate

Other
  • The participants will consume Short-chain fatty acid Butyrate (SCFA-BUT) followed by Short-Chain Fatty Acid Propionate (SCFA-PRO).

Primary outcomes

  1. Ketone Bodies

    Time frame: 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 outcomes

  1. Glucose

    Time frame: 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.

  2. Fatty acids

    Time frame: 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.

  3. Flow mediated dilation measurement

    Time frame: 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.

  4. Resting metabolic rate

    Time frame: 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.

  5. Respiratory exchange ratio

    Time frame: 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.

  6. Fatty Acid Composition

    Time frame: 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.

  7. Metabolites

    Time frame: 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.

  8. Hepatokines

    Time frame: 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.

  9. HOMA-Index

    Time frame: 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.

  10. Satiety

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Amalie S Frederiksen, PhD student

CONTACT

[email protected]

+4528899561

Andreas M Fritzen, Associate Professor

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University of Copenhagen

Other

Registry information

Acronym: SCFA

Important dates

Study start
2025
Primary completion
2026
Study completion
2030
First posted
Sep 19, 2025
Registry last updated
Mar 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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