Absorption and Digestion Kinetics of Human Metabolites

NCT05017428 | Completed

• 1 other identifier: 1725738
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to evaluate the effects oral supplementation with four human metabolites (spermidine, nicotinamide, palmitoylethanolamide (PEA), and oleoylethanolamide(OEA)) at varying doses on the circulating blood levels of these metabolites as well as their immediate effects on plasma functionality and postprandial inflammation. 5 young healthy subjects will participate in a four armed study consisting of a Placebo arm and a Low, Medium, and High Dose arm. Subjects will be given a standardized breakfast along with supplementation with either an escalating dose (Low: 1x, Medium: 2x, High: 3x) of a combination of spermidine, nicotinamide, PEA and OEA or a placebo control and a time course of their blood plasma will be collected after supplementation. Plasma samples will be assessed for their concentration of spermidine, nicotinamide, PEA, and OEA as well as their experimental and clinical functionalities including their anti-inflammatory, antioxidant, and cholesterol efflux abilities on primary human macrophage.

Conditions

Postprandial Inflammation

Outcome Measures

Primary Outcomes (1)

• Circulating Plasma Levels of Metabolites

  Quantitative plasma concentrations of spermidine, nicotinamide, pamitoylethanolamide, and oleoylethanolamide (in nmol/L).

  1, 2, and 4 hours after ingestion

Secondary Outcomes (1)

• Anti-inflammatory capacity of plasma

  1, 2, and 4 hours after ingestion

Study Arms (4)

Low Dose

EXPERIMENTAL

The Low Dose arm provides subjects with supplementation with 5mg of spermidine (in the form of 5g of a 0.1% spermidine wheat germ extract), 500mg of nicotinamide, 400mg of palmitoylethanolamide, and 200mg of oleoylethanolamide.

Dietary Supplement: Spermidine; Dietary Supplement: Nicotinamide; Dietary Supplement: PEA; Dietary Supplement: OEA

Medium Dose

EXPERIMENTAL

The Medium Dose arm provides subjects with supplementation with 10mg of spermidine (in the form of 10g of a 0.1% spermidine wheat germ extract), 750mg of nicotinamide, 800mg of palmitoylethanolamide, and 400mg of oleoylethanolamide.

Dietary Supplement: Spermidine; Dietary Supplement: Nicotinamide; Dietary Supplement: PEA; Dietary Supplement: OEA

High Dose

EXPERIMENTAL

The Low Dose arm provides subjects with supplementation with 15mg of spermidine (in the form of 15g of a 0.1% spermidine wheat germ extract), 1000mg of nicotinamide, 1200mg of palmitoylethanolamide, and 600mg of oleoylethanolamide.

Dietary Supplement: Spermidine; Dietary Supplement: Nicotinamide; Dietary Supplement: PEA; Dietary Supplement: OEA

Placebo

PLACEBO COMPARATOR

In this arm the participants are given supplementation with a placebo control consisting of 15g of wheat flour.

Dietary Supplement: Wheat Flour

Interventions

Spermidine DIETARY_SUPPLEMENT

Spermidine in the form of a 0.1% spermidine wheat germ extract

Also known as: Primeadine

High Dose; Low Dose; Medium Dose

Nicotinamide DIETARY_SUPPLEMENT

Nicotinamide given as niacinamide

Also known as: Jarrow Niacinamide

High Dose; Low Dose; Medium Dose

PEA DIETARY_SUPPLEMENT

Palmitoylethanolamide given at 98% purity

Also known as: Nootropics Depot PEA

High Dose; Low Dose; Medium Dose

OEA DIETARY_SUPPLEMENT

Oleoylehtanolamide given at 90% purity

Also known as: Riduzone

High Dose; Low Dose; Medium Dose

Wheat Flour DIETARY_SUPPLEMENT

Wheat flour given as a placebo control

Placebo

Eligibility Criteria

• Age: 20 Years - 40 Years
• Gender Eligibility Details: Participation in the study will be restricted to males. Women will be excluded from the study as the study protocol includes multiple study arms to be completed within a 1 month timeframe. Biological variations caused by the menstrual cycle throughout a single month may cause week to week variability in the absorption, digestion, and metabolism of our metabolites of interest that cannot be controlled for in this small pilot study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 20-40 years old to constitute a young study population
• BMI: 19-27 kg/m2 to constitute a normal/healthy weight population
• Weight: 133lbs or more
• Subjects must be willing and able to consume a standardized breakfast bar containing cashews and dates (Larabar).
• Subjects must be willing to consume oral dietary supplement versions of spermidine, 1-methlynicotinamide, palmitoylethanolamide, and oleoylethanolamide.
• Subjects must be willing and able to undergo blood draws at the UC Davis Ragle Nutrition Center at 0, 1, 2, and 4 hours after supplementation with spermidine, niacinamide, palmitoylethanolamide, and oleoylethanolamide.

You may not qualify if:

• Smoker
• Anemia
• Documented chronic diseases including diabetes, thyroid disease, metabolic syndrome, cancer, autoimmune diseases, or previous cardiovascular events
• Any inflammatory bowel disease including IBS, Crohn's Disease, Celiac Disease
• Any allergy or sensitivity to wheat, gluten, or soy products
• Consumption of \>1 alcoholic drink/day
• Current consumption of any probiotic, prebiotic, or dietary supplements
• Extreme dietary or exercise patterns
• Recent weight fluctuations (greater than 10% in the last six months)
• Regular use of over-the-counter allergy or pain medications (\>1/week)
• Taking prescription lipid medications (e.g. statins) or other supplements known to alter lipoprotein metabolism such as isoflavones.
• Use of any form of hormonal birth control including oral contraception pills, hormonal IUDs or rings, or hormonal birth control patches
• Illness such as flu or cold of any kind within the last two weeks
• Allergy to components of standardized breakfast bar (cashew/dates)
• Changes to any of the above during the study period.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

University of California Davis

Davis, California, 95616, United States

Location

Related Publications (1)

• Rhodes CH, Hong BV, Tang X, Weng CY, Kang JW, Agus JK, Lebrilla CB, Zivkovic AM. Absorption, anti-inflammatory, antioxidant, and cardioprotective impacts of a novel fasting mimetic containing spermidine, nicotinamide, palmitoylethanolamide, and oleoylethanolamide: A pilot dose-escalation study in healthy young adult men. Nutr Res. 2024 Dec;132:125-135. doi: 10.1016/j.nutres.2024.10.006. Epub 2024 Oct 23.

  PMID: 39549554 DERIVED

MeSH Terms

Interventions

Spermidine; Niacinamide; Flour

Intervention Hierarchy (Ancestors)

Putrescine; Biogenic Polyamines; Biogenic Amines; Amines; Organic Chemicals; Polyamines; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Participants will take a supplement containing 4 metabolites at escalating doses compared with placebo after a standardized meal and their blood will be drawn at mutliple points throughout a postprandial time course to evaluate markers of inflammation, circulating levels of each metabolite, and plasma functionalities.

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 23, 2021
• Study Start: April 8, 2021
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: August 23, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)