Effect of Palmitoleic Acid on C-reactive Protein

Effects of Palmitoleic Acid on Circulating C-reactive Protein Levels in Humans

This clinical trial will test the effects of an n-7 monounsaturated fatty acid known as palmitoleic acid (POA) on a chronic inflammation marker in overweight subjects. The study will enroll male and female subjects from healthy populations with high levels of the inflammatory marker c-reactive protein (CRP). Investigators will then determine over time if palmitoleic acid supplementation can lower circulating levels of c-reactive protein. Investigators will administer palmitoleic acid at two doses in addition to a placebo and conduct a double-blind parallel arm study. Circulating CRP will be the primary endpoint and secondary endpoints are Interleukin 6 (IL-6), Tumor necrosis factor (TNF) alpha, ghrelin, peptide tyrosine tyrosine (peptide YY), cardio lipid markers, glucose, insulin, leptin, adiponectin, and red blood cell (RBC) and serum fatty acids.

Study Overview

• Status: Completed
• Conditions: Overweight; Chronic Inflammation
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Palmitoleic acid, 500 mg (Dose 1); Dietary supplement: Palmitoleic acid, 1,000 mg (Dose 2)

Detailed Description

Palmitoleic acid (POA) is a monounsaturated fatty acid that has recently been shown to function as a lipokine and is present in the human diet and in blood serum. While there is emerging evidence that POA can positively impact beta cell proliferation, reduce lipogenesis, support endothelial function, and suppress cytokine production, POA remains to be poorly studied for its beneficial anti-inflammatory potential. The latest studies suggest that POA could attenuate inflammation in metabolically active tissues. Therefore, the objective of this study is to determine if administration of POA in 2 varying doses to overweight participants with biomarkers of chronic inflammation will lower circulating c-reactive protein (CRP) and cytokine levels, as well as improve metabolism by lowering levels of circulating leptin and raising expression of adiponectin. The rationale for focusing on overweight individuals is that they routinely have elevated c-reactive protein levels and are highly prone to have chronic inflammation.

Investigators propose a 12-week randomized, double blinded study to assess changes in select inflammatory markers, ghrelin, peptide YY, cardiovascular lipids, fatty acid levels, and glucose sensitivity markers in volunteers consuming either the test agent, 500 mg or 1,000 mg POA per day, or an olive oil containing fatty acid (placebo). There are three arms to study and 41 individuals per arm, thus, a total of 123 subjects. Approximately 30% loss of subjects is expected. Administration of the POA supplements and placebo (olive oil capsules) will be double blinded. The study sponsor will hold the code for the subjects and will randomize the capsules. Only the study sponsor will have the code. The identity of the capsules will be revealed after the completion of the study. Subjects will bring back their bottles at each of the concurrent visits and the end of the study to assess compliance and to account for any missed doses of POA. The rationale for selecting olive oil as a placebo is that olive oil is routinely consumed by the public. Additionally, oleic acid (the active ingredient of olive oil) is the most prevalent fatty acid in human circulation, and olive oil is a routine placebo for fatty acid intervention studies. The olive oil will not be extra virgin olive oil that has several bioactive components. POA is virtually tasteless, thus participants should not be able to self-identify their regimen of either placebo or active test agent. The rationale for the experimental dose follows what is commercially available in POA products, which average 700 mg per day and generally range from 450 - 1000 mg per day regimens. The rationale for the 12-week time frame is to ensure uptake of POA into the target cells.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Kannapolis, North Carolina, United States, 28081
      • University of North Carolina Nutrition Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject will be free-living, middle-aged to older men and women between ages 18-80 years with BMIs between 20.0-40.0, and CRP greater than or equal to 2.0 mg/L
2. Generally healthy adults
3. Understand protocol and comply to take supplements during the trial
4. Ability to understand English
5. Be able to report to clinical research center, fasting, at least 3 times
6. Women who are of childbearing potential should be on birth control (one method is acceptable)

Exclusion Criteria:

1. BMI higher than 40.0
2. Taking anti-hyperlipidemia medications (including statins)
3. Taking anti-diabetic medications
4. Auto-immune disease
5. Documented cognitive impairment
6. Unable to draw blood from veins
7. Alcohol or other drug dependency
8. Are currently breastfeeding, or pregnant, or plan to become pregnant
9. Have experienced a significant weight change of 10%, or more, of body weight in previous 3 months
10. If on hormone therapy, no change during study
11. Chronic use of NSAIDs
12. Decreased QOL due to pathology, such as cancer, genetic diseases, Rx side effects, or injury
13. Taking fish oil, within 8 weeks of enrollment
14. Taking Seabuckthorn supplements
15. Taking sterols or fat blockers
16. Fish allergies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; The placebo is olive oil, stripped of polyphenols, 70% oleic acid, and will be administered at two 1 gram capsules per day for twelve weeks. The doses will be administered in single serve packets containing two capsules for each daily dose to be taken at breakfast.	Dietary supplement: Placebo; The placebo is olive oil, stripped of polyphenols, 70% oleic acid, administered as two 1-gram capsules per day. Packaged as single-serve packets containing 2 capsules for each daily dose.; Other Names: Olive oil
Experimental: Palmitoleic acid, 500 mg (Dose 1); POA Dose 1 is a 1 gram capsule containing 500 mg POA and one placebo capsule containing 500 mg olive oil per day for twelve weeks. The doses will be administered in single serve packets containing two capsules for each daily dose to be taken at breakfast.	Dietary supplement: Palmitoleic acid, 500 mg (Dose 1); Palmitoleic acid (POA) 1 gram capsules containing 500 mg POA; Other Names: POA
Experimental: Palmitoleic acid, 1,000 mg (Dose 2); POA Dose 2 is two, 1 gram capsules containing 500 mg POA, totaling 1,000 mg POA per day for twelve weeks.The doses will be administered in single serve packets containing two capsules for each daily dose to be taken at breakfast.	Dietary supplement: Palmitoleic acid, 1,000 mg (Dose 2); Palmitoleic acid (POA) taken as two 1 gram capsules each containing 500 mg POA; Other Names: POA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean c-reactive protein circulating level	Fasting blood draws will be used to evaluate circulating CRP level by high-sensitivity c-reactive protein laboratory blood analysis.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean circulating cytokine IL-6 level	Fasting blood draws will be used to evaluate circulating cytokine IL-6 level by ELISA (enzyme-linked immunosorbent assay).	Week 12
Mean circulating cytokine TNF alpha level	Fasting blood draws will be used to evaluate circulating cytokine TNF alpha level by ELISA (enzyme-linked immunosorbent assay).	Week 12
Mean circulating ghrelin level	Fasting blood draws will be used to evaluate circulating ghrelin level by ELISA (enzyme-linked immunosorbent assay).	Week 12
Mean circulating peptide YY level	Fasting blood draws will be used to evaluate circulating peptide YY level by ELISA (enzyme-linked immunosorbent assay).	Week 12
Mean circulating leptin level	Fasting blood draws will be used to evaluate circulating leptin level by ELISA (enzyme-linked immunosorbent assay).	Week 12
Mean circulating adiponectin level	Fasting blood draws will be used to evaluate circulating adiponectin level by ELISA (enzyme-linked immunosorbent assay).	Week 12
Mean glucose/insulin ratio level	Fasting blood draws will be used to evaluate glucose/insulin ratio level.	Week 12
Mean HbA1c level	Fasting blood draws will be used to evaluate HbA1c level.	Week 12

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Organic Technologies
• Investigators: Principal Investigator: Saame R Shaikh, PhD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Frigolet ME, Gutierrez-Aguilar R. The Role of the Novel Lipokine Palmitoleic Acid in Health and Disease. Adv Nutr. 2017 Jan 17;8(1):173S-181S. doi: 10.3945/an.115.011130. Print 2017 Jan.
• Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013 Feb 18;417:80-4. doi: 10.1016/j.cca.2012.12.007. Epub 2012 Dec 22.
• Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, Ter Horst R, Jansen T, Jacobs L, Bonder MJ, Kurilshikov A, Fu J, Joosten LAB, Zhernakova A, Huttenhower C, Wijmenga C, Netea MG, Xavier RJ. Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. Cell. 2016 Nov 3;167(4):1125-1136.e8. doi: 10.1016/j.cell.2016.10.020. Erratum In: Cell. 2016 Dec 15;167(7):1897. Cell. 2016 Dec 15;167(7):1897.
• de Souza CO, Vannice GK, Rosa Neto JC, Calder PC. Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders? Mol Nutr Food Res. 2018 Jan;62(1). doi: 10.1002/mnfr.201700504. Epub 2017 Dec 11.
• Bernstein AM, Roizen MF, Martinez L. WITHDRWAN: Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: a double-blinded, randomized, placebo controlled study. J Clin Lipidol. 2014 Nov-Dec;8(6):612-617. doi: 10.1016/j.jacl.2014.08.001. Epub 2014 Aug 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Actual): November 29, 2022
• Study Completion (Actual): November 29, 2022

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: chronic inflammation; palmitoleic acid; monounsaturated fatty acid
• Additional Relevant MeSH Terms: Pathologic Processes; Body Weight; Inflammation; Overweight
• Other Study ID Numbers: 17-2316

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with the University of North Carolina at Chapel Hill.
• IPD Sharing Time Frame: 9 to 36 months following publication.
• IPD Sharing Access Criteria: A Data Use Agreement (DUA) specifying the uses of such data to be shared must be in place before any data is shared. The requestor should contact the Principal Investigator for further instruction.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No