Absorption and Digestion Kinetics of Human Metabolites

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.

Study Overview

• Status: Completed
• Conditions: Postprandial Inflammation
• Intervention / Treatment: Dietary supplement: Spermidine; Dietary supplement: Nicotinamide; Dietary supplement: PEA; Dietary supplement: OEA; Dietary supplement: Wheat Flour

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Davis, California, United States, 95616
      • University of California Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose; 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; Spermidine in the form of a 0.1% spermidine wheat germ extract; Other Names: Primeadine; Dietary supplement: Nicotinamide; Nicotinamide given as niacinamide; Other Names: Jarrow Niacinamide; Dietary supplement: PEA; Palmitoylethanolamide given at 98% purity; Other Names: Nootropics Depot PEA; Dietary supplement: OEA; Oleoylehtanolamide given at 90% purity; Other Names: Riduzone
Experimental: Medium Dose; 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; Spermidine in the form of a 0.1% spermidine wheat germ extract; Other Names: Primeadine; Dietary supplement: Nicotinamide; Nicotinamide given as niacinamide; Other Names: Jarrow Niacinamide; Dietary supplement: PEA; Palmitoylethanolamide given at 98% purity; Other Names: Nootropics Depot PEA; Dietary supplement: OEA; Oleoylehtanolamide given at 90% purity; Other Names: Riduzone
Experimental: High Dose; 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; Spermidine in the form of a 0.1% spermidine wheat germ extract; Other Names: Primeadine; Dietary supplement: Nicotinamide; Nicotinamide given as niacinamide; Other Names: Jarrow Niacinamide; Dietary supplement: PEA; Palmitoylethanolamide given at 98% purity; Other Names: Nootropics Depot PEA; Dietary supplement: OEA; Oleoylehtanolamide given at 90% purity; Other Names: Riduzone
Placebo Comparator: Placebo; In this arm the participants are given supplementation with a placebo control consisting of 15g of wheat flour.	Dietary supplement: Wheat Flour; Wheat flour given as a placebo control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-inflammatory capacity of plasma	Ex vivo assessment of the effects of subject plasma on the secretion of pro-inflammatory cytokine TNF-alpha (pg/mL) by primary human macrophage	1, 2, and 4 hours after ingestion

Collaborators and Investigators

• Sponsor: University of California, Davis

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 1725738

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No