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 \[5,9\].