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

Study Overview
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Brief Summary
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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].

Official Title
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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

Conditions
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Cardiovascular Risk Factor, Covid19

Intervention / Treatment
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* Dietary Supplement: 300 mg of omega3-FA


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: n-3FA group<br>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<br>* The participant will receive 1,000 mg of wild salmon and fish oil complex once daily, which contains 300 mg of omega3-FA.<br>|
| No Intervention: Control group<br> | |

What is the study measuring?
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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 |