The Effect of Omega -3 Supplements on the Serum Levels of ACE/ACE2 Ratio as a Potential Key in Cardiovascular Disease and COVID-19; A Randomized Clinical Trial in the Covid-19 Uninfected Jordanian People

The Effect of Omega -3 Supplements on the Serum Levels of ACE/ACE2 Ratio as a Potential Key in Cardiovascular Disease and COVID-19; A Randomized Clinical Trial in the COVID-19 Uninfected Jordanian People

The Renin-Angiotensin-Aldosterone System (RAAS) is involved in blood pressure regulation and electrolyte balance. Angiotensin-converting enzyme (ACE) is a critical regulator of RAAS by cleaving angiotensin (Ang1) to Angiotensin2 (Ang2), which is the most powerful biologically active product of RAAS [1]. In the same context, angiotensin-converting enzyme 2 (ACE2) converts Ang2 to Ang (1-7), which is a vasodilator, antithrombotic, and antihypertrophic peptide [2]. ACE2 which is found in many tissues [3] has opposite effects to ACE on the heart, kidneys, and lungs [4]. Many pathological conditions, in particular cardiovascular disease (CVD), have shown a link between a disturbance in ACE/ACE2 ratio and the downregulation of ACE2 levels [5]. Also, ACE/ACE2 has been reported to be higher in moderate to severe chronic heart failure [6] as well as systolic blood pressure [7]. Recently, an elevated ACE/ACE2 ratio is linked to Coronavirus disease 2019 (COVID-19). SARS-COV2 enters target cells by binding of the spike protein to ACE2 and a specific transmembrane serine protease 2 (TMPRSS2) for the spike (S) protein priming, which also leads to downregulation of ACE2 [8]. Down-regulation of ACE2 caused by Coronavirus may have a potential role in the pathogenesis of COVID-19 infection. Accordingly, people with a higher ACE/ACE2 ratio may be more at increased risk of worse Covid-19 consequences [9].

On the other hand, omega-3 fatty acids could decrease CVD risk by their anti-inflammatory anti-thrombotic function [10]. A meta-analysis comprising 15,806 patients, showed that omega-3 fatty acids associated with a 30% reduction in fatal myocardial infarction and sudden death, in addition to a 20% reduction in overall mortality [11]. To the best of our knowledge, no clinical trials have evaluated the effect of omega-3 supplementation on serum ACE/ACE2 ratio which is recently ascribed as a potential key in 2019 Covid-19 as well as CVD [5,9].

Study Overview

• Status: Completed
• Conditions: Covid19; Cardiovascular Risk Factor
• Intervention / Treatment: Dietary supplement: 300 mg of omega3-FA

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Jordan
  • Amman, Jordan
    • Mahmoud S Abu-Samak

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 33 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inclusion criteria included males and females in the age range of 35-65 years without a medical diagnosis of COVID-19 infection.

Exclusion Criteria:

• Any subject with any chronic disease such as CVD, diabetes, or immune problems, including autoimmune diseases, chronic or severe infections was excluded.
• Pregnant, breastfeeding, and females using hormonal contraceptives were excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group
Experimental: n-3FA group; Dietary Supplement: 1,000 mg of wild salmon and fish oil complex once daily, which contains 300 mg of omega3-FA for 8 weeks.	Dietary supplement: 300 mg of omega3-FA; The participant will receive 1,000 mg of wild salmon and fish oil complex once daily, which contains 300 mg of omega3-FA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum ACE levels	Angiotensin converting enzyme levels pg/mL	10 weeks
serum ACE2 levels	Angiotensin converting enzyme-2 levels	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid profile mg/dL	TC,LDL,HDL,TG	10 weeks

Collaborators and Investigators

• Sponsor: Applied Science Private University
• Investigators: Study Chair: Mahmoud S Abu-Samak, PhD, Department of Clinical Pharmacy and Therapeutics , Applied Science Private University, Amman -Jordan; Principal Investigator: Sara M Daboul, MSC, Department of Clinical Pharmacy and Therapeutics , Applied Science Private University, Amman -Jordan

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): February 10, 2022

Study Registration Dates

• First Submitted: December 5, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Cardiovascular Diseases
• Other Study ID Numbers: 2020-PHA-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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