Current in vitro testing of bioactive peptides is not valuable

Area of Science:

• Biochemistry
• Pharmacology
• Nutritional Science

Background:

• Dietary peptides are investigated for in vivo biological activity, particularly cardiovascular effects, based on in vitro findings.
• Current research often overlooks the poor absorption, distribution, metabolism, and excretion (ADME) properties of peptides, leading to low bioavailability.
• Peptides undergo significant hydrolysis in the gastrointestinal tract, hindering their absorption and systemic availability.

Purpose of the Study:

• To highlight the critical need to assess peptide stability and ADME properties alongside in vitro activity.
• To advocate for a research approach that validates peptide stability and bioavailability before in vivo testing.
• To emphasize the importance of using physiologically relevant concentrations and timeframes in in vitro peptide studies.

Main Methods:

• Review of existing literature on peptide ADME and bioavailability.
• Analysis of studies reporting in vivo peptide concentrations and kinetics.
• Identification of limitations in current research methodologies for dietary peptides.

Main Results:

• Peptides exhibit poor oral bioavailability due to extensive gastrointestinal hydrolysis.
• Few studies quantify peptide concentrations and kinetics in vivo, revealing pico- and nanomolar levels with rapid elimination.
• In vitro findings do not always translate to in vivo efficacy due to ADME limitations.

Conclusions:

• A valid research approach requires demonstrating peptide stability against peptidases and evaluating ADME properties.
• Researchers must consider human bioavailability and ADME data for accurate interpretation of peptide bioactivity.
• Future in vitro studies should utilize physiologically relevant concentrations and durations to better predict in vivo effects.