At the current moment, we are still struggling with the COVID-19 pandemic. Even today, we are bombarded with medical information on how to prevent complications secondary to this condition. However, the inflammatory cytokine storm derived from the SARS-CoV-2 virus is the main complication that needs to be addressed. Recently, the risk of developing an inflammatory cytokine storm has been associated with an omega-6/omega-3 ratio disbalance. Therefore, it is believed that this complication can be prevented if the anti-inflammatory metabolites derived from omega-3 fatty acids are increased.
Omega-6/omega-3 Ratio and Immunology
Tissue healing and a controlled immune response against pathogens are triggered by the inflammatory metabolites from omega 6 fatty acids. Indeed, arachidonic acid (AA) and linoleic acid can trigger the inflammatory response, including pain, redness, elevated temperature on the injured area, swelling, or loss of function. Regardless of the pain-associated sensation and the deleterious feeling of an injury, these signals are needed to activate our defense and repair mechanisms.
Following this inflammatory response, a quick suppression must take place. Here is where the resolvins come in handy: metabolites from omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Therefore, the presence of inflammatory agents from n-6 and its suppression by EPA and DHA depends on the balance of the omega-6/omega-3 ratio.
However, this ratio’s disbalance (elevated omega 6) results in an excessive and prolonged inflammatory response that cannot be easily suppressed. Consequently, this results in tissue damage and can potentially lead to an autoimmune condition.
Currently, in western civilization, the omega-6/omega-3 ratio is approximately 20:1. This ratio is tightly associated with the population’s pro-thrombotic state and a supraphysiologic inflammatory state that promotes chronic conditions. Indeed, the high amount of omega-6 in our diet is linked to the intake of seed oils such as soybean, corn, cottonseed, and canola oil. On the other hand, the low intake of marine fish in our population is the main cause of low omega-3 fatty acid consumption, perpetuating the chronic low-grade inflammation state.
Omega-3 and immunomodulation.
Lipids can be found on the phospholipidic immune cell membranes. Therefore, the composition of such membrane will predict the inflammatory signals. When Arachidonic acid is the main component of the immune cellular membrane, and this cell becomes activated by constant exposure to dietary or environmental allergens, the result will be an inflammatory 2,4-series eicosanoids overproduction. Furthermore, an exaggerated or prolonged activation of such a condition will lead to an immune system self-attack. On the other hand, incorporating EPA/DHA into the immune cell membrane will increase an anti-inflammatory metabolites production known as 3/5- series eicosanoids, docosanoids, resolving, and protectins. Therefore, by promoting a balance of our essential fatty acids intake, this will translate to a balance cell membrane, ultimately resulting in a modulated and controlled immune response.
The overall consumption of omega 6 fatty acids in the westernized civilization results in a composition of approximately 20% of AA’s immune cellular membrane. Meanwhile, EPA and DHA constitute approximately 1% and 2.0-2.5% of the cellular membrane, respectively. In fact, recent animal model studies have found that a 3.2g of EPA/DHA supplementation can improve the omega-6/omega-3 ratio and increase the omega-3 phospholipid content up to 3.5%.
Human studies have demonstrated that a balance omega-6/omega-3 ratio results in improvements in inflammatory conditions. Furthermore, this is mainly due to omega-3’s modulatory effects on nuclear factor kappa-beta (NF-kB). Also, this particular effect seems to be useful in reducing the cytokine storm caused by SARS-CoV.
Omega-3 PUFAs mechanisms for reducing cytokine storm
|Inhibits NF-kB translocation.|
|Increases the 3/5-series eicosanoids while competing/decreasing AA-derived inflammatory eicosanoids (leukotrienes, interleukins, and cytokines).|
|Competes for immune cell membrane phospholipid component.|
|Suppresses and resolves inflammation, potentially improving survival to sepsis.|
|Increases neutrophils and monocyte phagocytic activity.|
Indeed, NF-kB can translocate to the nucleus and upregulate inflammatory cytokine production. Consequently, the cytokine storm associated with SARS-CoV and SARS- CoV2 is initiated by an NF-kB activation. Animal models infected with coronaviruses have shown that increasing omega-3 intake can inhibit NF-kB nuclear translocation and prevent the inflammatory cytokine storm in the respiratory system, specifically in the lungs.
Also, investigators have concluded that this same omega-3- 3 anti-inflammatory effects can be applied to influenza’s treatment and may improve sepsis and acute respiratory distress syndrome (ARDS).
The underlying anti-inflammatory effects of omega-3 rely on competition of metabolite production against AA. Also, omega-3 PUFAs can inhibit cyclooxygenase and lipoxygenase enzyme activity.
Lastly, the overall conclusion is that we must improve our omega-3 dietary intake and find omega-6/omega-3 balance. Indeed, striving for a 4:1 ratio is recommended by DiNicolantonio and O’Keeffe.
The balance of the immune system and inflammation creates a modulated response to outsiders, pathogens, infections, injuries, and food allergens. All of the environmental factors play a vital role in our reaction to multiple situations. Nevertheless, the balance between what we eat has become part of our immune function. Indeed, the intake of omega-3 fatty acids interacts with our cellular membrane composition that translates to inflammation suppression and immune modulation.
Our immune response is linked with our nutritional intake and inflammatory responses. Nowadays, what we eat initiates a chain reaction that needs to be modulated, and a balanced diet plays a vital function in this regard. The dietary intake of omega-3 fatty acids can be improved by integrating marine fish into our diet more than 2 times a week. Also, fish oil or omega-3 PUFA supplementation is a great way to improve our omega-6/omega-3 ratio. – Ana Paola Rodríguez Arciniega, MS
DiNicolantonio, James J, and James O’Keefe. “The Importance of Maintaining a Low Omega-6/Omega-3 Ratio for Reducing the Risk of Inflammatory Cytokine Storms.” Missouri medicine vol. 117,6 (2020): 539-542. Additional Online Links & Resources (Available 24/7)
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Dr. Alex Jimenez DC, MSACP, CCST, IFMCP*, CIFM*, CTG*
Licensed in Texas & New Mexico