Are there any benefits from Omega-3 supplements during the “Corona Crisis”?

Most people infected by the Corona Virus show typical flu or respiratory disease symptoms, including fever, cough, chest pain, and general tiredness. However, elderly patients over 60 years, with pre-existing conditions (including the chronic heart- or lung disease, or patients in an immunosuppressed state), may show a sudden and very difficult to control excessive release of inflammatory cytokines ("cytokine storm"), often ending in a fatal "covid-19 pneumonia", with symptoms similar to what is known as Acute Respiratory Distress Syndrome (ARDS).

We know that Omega-3 fatty acids (EPA and DHA) have cardioprotective properties [1], such as reducing the blood triglyceride levels and reducing blood pressure.

But is there any benefit from an Omega-3 (DHA & EPA) during the "Corona Crisis"?

To make one thing very clear from the beginning: Omega-3 supplementation will not prevent a Covid-19 infection. However, it may be a supportive tool to reduce the intensity of the inflammation and help reduce the symptoms caused by the disease. Here is why.

the general biochemical pathways involved in the inflammatory response are well known and described elsewhere [2,3]. These biochemical reactions will most likely be the same for every inflammation process, including Covid-19 infection. It is also well described where exactly and how the omega-3 fatty acids EPA and DHA interfere within the inflammatory response pathway and how they may help down-regulate the inflammation cascade. We will discuss here in a simplified way 4 of the main effects, in particular:

• Down-regulation of NFk-beta, IL-6 and other inflammation markers [2,4,7,8,11] Competitive displacement of pro-inflammatory AA (Arachidonic Acid, omega-6) by anti-inflammatory EPA (Omega-3) from COX- and LOX- systems [2,9,10,11]
• Reduction of oxidative stress and cell damage by down-regulating nitric oxide release [2,11,12]
• Inflammation stopping signal and activation of tissue/cell repair mechanism by Resolvins, Protectins, and Maresins.[13,14,15]

 Down-regulation of NFk-beta, IL-6, and other inflammation markers

One very effective way to control any inflammatory process is downregulating the activity of NFk-beta – a highly pro-inflammatory compound in our cells which is produced as soon as our cells note that something is wrong (attack from a bacteria or virus, mechanical damage of the cell or tissue, oxidative stress by increased NO concentration). NFk-beta instructs our cell nucleus to release highly inflammatory substances, for example, IL-6 and TNF. The more NFk-beta is present, the more IL-6 (and other inflammation markers) are removed, and the more severe is the inflammatory reaction. The omega-3 fatty acid EPA, together with Vitamin D3, are essential for IKK-beta Complex activity, which can down-regulate the NFk-beta action before it enters the nucleus and, in this way, prevents excessive production of pro-inflammatory IL-6.

Competitive displacement of pro-inflammatory AA (Arachidonic Acid, omega-6) by anti-inflammatory EPA (Omega-3) from COX- and LOX- systems 

Once the nucleus secretes IL-6 (and others), the enzyme Phospholipase-A2 (PLA-2) releases randomly long-chain fatty acids stored in our cell membranes. These get converted by unique enzyme systems called COX and LOX to highly inflammatory or anti-inflammatory eicosanoids (e.g., Prostaglandins E2 or -E3). To simplify the process, imagine only two types of fatty acids stored in the membranes: pro-inflammatory Arachidonic Acid (AA, omega-6) and anti-inflammatory Eicosapentaenoic Acid (EPA, omega-3). The fatty acid composition of the membrane depends strongly on our daily diet. If our diet is rich in omega-6 (AA) sources like red meat, meat- and milk products, eggs, and omega-6 rich vegetable oils like sunflower oil, we will find a lot of AA in our cell membranes. Thus, the probability that the PLA-2 will release a pro-inflammatory AA from the cell membrane is much higher than the release of an anti-inflammatory EPA.

On the other hand, if we reduce the Omega-6 sources in our diet and include more omega-3, especially EPA and DHA sources like fatty fish (sardine, anchovy, mackerel, tuna, salmon) and use a neutral cooking oil like Olive oil (neither Omega-6 nor Omega-3, but Omega-9), then we can shift the probability that an anti-inflammatory EPA is released from the cell membrane instead of the AA. Due to our modern, often pre-manufactured diet, we ingest daily over 20-times more pro-inflammatory AA than anti-inflammatory EPA. This unhealthy ratio of omega-6 to omega-3 is reflected in our cell membranes. Thus, it is no wonder that our body often overreacts when affronted with an inflammatory response. The good news is that we can influence our cell membranes' fatty acid composition simply by choosing our diet or by supplementing our diet with omega-3 fatty acids (EPA and DHA). It takes approximately 4-6 weeks to ingest 1000 – 2000 mg EPA or DHA per day to reach a certain desirable saturation level of omega-3 fatty acids in your cell membranes. This is a ratio of omega-6: omega-3 anywhere between 4:1 to 1:1.

 Reduction of oxidative stress and cell damage by down-regulating nitric oxide (NO) release

When the nucleus receives the message that the cell has been attacked through the increased NFk-beta concentration, it releases not only the pro-inflammatory IL-6 but also the very aggressive nitric oxide (NO). NO causes oxidative stress, cell- and tissue damage, and accelerates the NFk-beta production, which stimulates the nucleus to produce even more IL-6 and NO. It is a vicious circle that can play an essential role in developing a fatal "cytokine storm."

 

Inflammation stopping signals and activation of tissue/cell repair mechanisms by Resolvins, Protectins, and Maresins.

Finally, every inflammation should come to a stop. The substances signaling the irritated cell to stop the inflammation are called "Resolvins." Then in the next step, the healing process needs to be initiated. This second step is triggered by compounds called Maresins and Protectins. Resolvins, Maresins, and Protectins are all directly derived from the two Omega-3 fatty acids EPA and DHA. This shows once more how important a regular supply of EPA and DHA is for our body and wellbeing. 

Thus, daily supplementation of 1000mg to 2000mg Omega-3 (DHA and EPA) may be an efficient way to prevent an excessive inflammatory response when suffering from a Covid-19 or any other inflammatory condition. To enable its entire range of protective activities, both EPA and or DHA supplementation should be ongoing for at least 4 -6 weeks before the first symptoms show up.

 Disclaimer: There are no FDA-approved treatments for COVID-19; supportive care is the standard of care. Limited treatment data are available & clinical judgment is warranted.

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