The COVID-19 pandemic medically, economically, and socially disrupted the world. The virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), swept across the globe affecting people from all walks of life. At the time of writing, the World Health Organization reported over 624 million confirmed cases of COVID-19 infection and over 6.5 million deaths due to the virus.
Since its initiation, researchers and medical professionals have worked tirelessly to better understand and treat the disease’s cause and progression. From the very beginning, nutrients have been examined as a potential answer due to their ability to regulate inflammation, a sign of worsening COVID-19 infection. Years later, the evidence continues to pile up supporting omega-3 fatty acids’ potential in COVID-19 prevention and treatment.
Building a Solid Care in Support of Omega-3s
Omega-3s emerged as a possible solution after several studies noted that one of the markers of worsening COVID-19 was the increased production of inflammatory mediators, particularly interleukin-6 (IL-6). The potentially life-threatening hyper-inflammatory response in severe COVID-19 patients became known as the “cytokine storm”.
In 2020 Panigrahy et al. theorized that omega-3 fatty acids, EPA and DHA, could potentially be used in regulating COVID-19 inflammation through omega-3-derived mediators – resolvins, protectins, maresins, eicosanoids, and lipoxins. Also known as specialized pro-resolving mediators (SPMs), it was hypothesized that these derivatives of EPA and DHA would regulate COVID-19 inflammation by increasing the phagocytosis of viruses and debris by macrophages, suppressing the production of pro-inflammatory cytokines and eicosanoids, and increasing the production of anti-SARS-CoV-2 antibodies.
Since then, this theory has been put to the test. A review published in April 2022 aimed to identify the various studies that had been done on the effects of omega-3 supplementation in COVID-19. The authors searched for articles published from Jan 31, 2020, to Sep 1, 2021, and found four studies that included a randomized controlled trial (Doaei et a., 2021), a case report (Berger et al., 2020), a cross-sectional study (Zapata et al. 2021) and an app-based community survey (Louca et al., 2021).
The results of these studies revealed a clear relationship between omega-3 fatty acids and COVID-19 – reducing the risk of positive SARS-CoV-2 infection, speeding up the duration of symptoms, decreasing the risk of renal and respiratory dysfunction, and increasing patient survival rate.
A second review published in June 2022, which included 18 articles, supported this conclusion. They determined that omega-3 fatty acids could reduce infection and severity of COVID-19 and could be considered a preventative method for public health purposes.
New Evidence Confirms a Relationship between COVID-19 and Omega-3 Index
Most recently, a group of researchers, including OmegaQuant founder, Dr. Bill Harris, used UK Biobank data to study the relationship between plasma DHA% at baseline with three COVID-19-related outcomes: (1) testing positive, (2) hospitalization, and (3) death. The study was published in the Feb. 28th edition of the American Journal of Clinical Nutrition.
The researchers found that omega-3 blood levels were protective against both testing positive for the virus (8% lower risk) and having severe enough symptoms to require hospitalization (11% lower risk). The relationship with risk for death was also lower (6% lower risk), but it was not statistically significant. Therefore, a high omega-3 level emerged to offer protection against both getting infected with the virus and having an infection severe enough to require hospitalization.
The authors went further and translated the DHA% outcomes into the more familiar Omega-3 Index. They found that the highest risk related to COVID-19 was associated with an Omega-3 Index around 3.5%, whereas the lowest risk was an Omega-3 Index around 8%. Interestingly, we have seen these Omega-3 Index values before. These values have been previously recommended as Omega-3 Index risk cut points related to death from cardiovascular disease, established in 2004. Therefore, with the target Omega-3 Index levels for COVID-19 outcomes and cardiovascular outcomes seeming to match, the case continues to build for established Omega-3 Index reference points.
This study reports similar findings to two other studies published utilizing the UK Biobank in the last two years. Julkunen et al. reported increases in DHA% were associated with a 23% reduction in risk for a COVID-19 infection severe enough that it required hospitalization in an age- and sex-adjusted model. Sun et al. concluded that higher circulating polyunsaturated fatty acids, particularly DHA, were associated with reducing COVID-19 susceptibility and were protective against severe COVID-19 infection.
Omega-3’s Mechanisms of Action
Several mechanisms of action have been identified to help explain omega-3s’ role in reducing the risk of a positive COVID-19 infection, both directly and indirectly. SARS-COV-2 virus infects host cells by binding the spike glycoproteins with surface ACE2 receptors. DHA and EPA bind to the spike glycoprotein, holding it in a closed and locked formation, resulting in a reduced binding with ACE2 receptors and directly disabling cellular entry.
EPA has also been found to inhibit the enzymatic activity of transmembrane proteases that normally cleave spike proteins and allow cellular entry, further inhibiting the virus from entering the cell. Finally, omega-3s are intracellular inhibitors of the viral replication pathway. Therefore, EPA and DHA can reduce viral binding, entry, and replication, leading to a potentially lower risk of viral infection.
If infected, omega-3s can reduce the risk of severe illness by blunting the signaling cascade that produces inflammatory cytokines and adhesion molecules, and serving as substrates for several inflammation-resolving mediators that work in harmony to suppress and resolve inflammation providing protection from COVID-19’s severe downstream effects. In SARS-CoV-2 infection, the excessive and uncontrolled production of inflammatory cytokines, the “cytokine storm,” contributes to permeability and vascular leaking, leading to pulmonary dysfunction, acute respiratory syndrome (ARDS), and ultimately systemic inflammation, and multiple organ failure.
As hypothesized early in the pandemic by several scientists, polyunsaturated fatty acids, such as DHA and EPA, play an essential role in modulating immune pathways and inflammatory responses. First, EPA and DHA reduce the activation of NF-kB pro-inflammatory transcription factor, which regulates multiple aspects of innate and adaptive immunity and induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines. Next, studies have found that EPA and DHA can reduce inflammation by acting directly on inflammatory cells and decreasing the production of inflammatory cytokines. Finally, omega-3 fatty acids give rise to SPMs, which activate the resolution of inflammation and calm the “cytokine storm.”
Are You Omega-3 Levels up to Par during this Cold/Flu Season?
How can you be sure to get enough omega-3s to protect yourself during cold/flu season? The answer is simple: test your Omega-3 Index. The Omega-3 Index measures the amount of EPA and DHA in red blood cell membranes and is expressed as a percentage of total fatty acids.
According to the new evidence from Harris et al., an Omega-3 Index around 8% was associated with the lowest risk of infection and severe outcomes of COVID-19, while an Omega-3 Index around 3.5% was associated with the highest risk of infection and severe COVID -19 outcomes. If low, you can raise your Omega-3 Index by increasing your intake of EPA and DHA in your diet, either through food sources or supplementation. The Omega-3 Index may be a modifiable risk factor for severe complications of COVID-19 and may provide a cost-effective, preventative approach to moderate the consequences of this global disease.