Friday Hope: Omega-3, 6 Fatty Acids: Inhibiting the Spike Protein and Restoring Gut Barrier Integrity

Omega-3 fatty acids are also associated with reduced risk of COVID infection, severity and sudden cardiac death.

Anti-inflammatory diet restores gut barrier integrity in NOD mice. (A) RT-qPCR analysis of claudin 1 (Cldn1), tight junction protein 1 (Tjp1) and Occludin (Ocln) on tissue homogenates from the intestine of NOD mice fed with anti-inflammatory (AID) or standard (STD) diet at 14 weeks of age (n=8 per group). (B) RT-qPCR analysis of Muc1, Muc2, Muc3, and Muc4 mucin genes in the intestine of NOD mice fed with AID or STD diet (n=8 per group). (C) Alcian Blue staining of colon sections (20X) of NOD mice fed with AID or STD diet. The arrows on the apical side of the intestine (long arrow) indicate the thickness of the mucus layer while the smaller arrows along the crypts point to GC (stained in Blue). The percentage of GC in the two groups (right panel) was calculated within the total number of epithelial cells on randomly selected sections (n=5 per group, 6 sections/mouse). All data are presented as mean ± SEM. *p < 0.05; **p < 0.01; ****p < 0.0001.

Omega-3 fatty acids have long been celebrated for their multi-faceted health benefits. Colloquially they are known as being “good for the heart.” There is much evidence to support this, and other benefits.

Omega-3 fatty acids have many potential benefits for your cardiovascular health. One key benefit is that they help lower your triglyceride levels. Too many triglycerides in your blood (hypertriglyceridemia) raises your risk of atherosclerosis, and through this, can increase your risk of heart disease and stroke. So, it’s important to keep triglyceride levels under control. In addition, omega-3s may help you by raising your HDL (good) cholesterol and lowering your blood pressure.

Some studies show omega-3s may lower your risk for:

• Cardiovascular disease (CVD).

• Death, if you have CVD.

• Sudden death caused by an abnormal heart rhythm (arrhythmia).

• Blood clots.

Beyond heart health, omega-3s may help lower your risk of developing:

• Some forms of cancer, including breast cancer.

• Alzheimer’s disease and dementia.

• Age-related macular degeneration (AMD).

Research continues to investigate these and other possible benefits.

Omega-3 Fatty Acids
https://my.clevelandclinic.org/health/articles/17290-omega-3-fatty-acids

Today, with the presence of SARS-CoV-2 and its Spike Protein amongst us, Omega-3s and 6s offer additional COVID-specific benefits. First, they are yet another natural therapeutic that can bind Spike Protein and prevent its interaction with our bodies.

Linoleic Acid, derived from Omega-6, locks the Spike Protein in its closed conformation. This prevents it from binding to ACE2 (or other receptors) and entering our cells. For the record, I am not supportive of the Rundeathisnear plug in the quoted paper.

SARS-CoV-2 spike (S) glycoprotein cryoelectron microscopy structure indicates that receptor binding domains firmly bind the crucial free fatty acid linoleic acid (LA) in three composite binding pockets (SARS-CoV-2 spike (S) glycoprotein). SARS-CoV and MERS-CoV have similar pockets (Fig. 1a,b). The LA binding pocket of the human coronavirus receptor binding domain is conserved in other strains. The LA binding pocket comprises key residues like Arg408, Gln409, Ty365, Tyr369, Leu387 and Phe374. The first two, Arg408 and Gln409, perform the gating function, and the rest of the residues from the greasy tube where LA is bound. Remdesivir is a drug approved for treating SAR-CoV-2; its active form works as a nucleoside analogue, mimicking a nucleotide and getting incorporated into the growing RNA chain. This incorporation inhibits the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and other coronaviruses [[9], [10], [11]]. Remdesivir allows adding three more nucleotides before RNA synthesis stops. Linoleic acid binding to the spike protein locks the SARS-CoV-2 spike (S) glycoprotein in the closed conformation and stabilizes, reducing the interaction with angiotensin-converting enzyme 2 (ACE2). Thus, the linoleic acid supplementation with Remdesivir provides a synergistic suppressing effect on SARS-CoV-2 replication. SARS-CoV-2 binding to LA is directly linked to the structure, paving the way for intervention tactics targeting LA binding [12,13].

SARS-CoV-2 inhibitory potential of fish oil-derived 2-pyrone compounds by acquiring linoleic acid binding site on the spike protein
https://www.sciencedirect.com/science/article/abs/pii/S0141813024044398

In complementary fashion, Omega-3s are associated with a reduced risk of COVID infection as well as reduced COVID severity.

In summary, using the large UK BioBank dataset, Harris et al. [1] report that higher DHA status is associated with lower risk of testing positive for infection with SARS-CoV-2 and of being hospitalized with COVID-19. There is also an indication that higher DHA status is associated with reduced risk of mortality for COVID-19, although this effect was attenuated at the very highest status level. These findings suggest that consuming more long-chain omega-3 fatty acids (EPA and DHA) should be encouraged as a strategy to reduce the impact of the ongoing SARS-CoV-2 pandemic and of future respiratory virus infection outbreaks. Increased intake of EPA and DHA can be achieved through consumption of fatty fish or use of supplements containing EPA and DHA.

Bioactive omega-3 fatty acids are associated with reduced risk and severity of SARS-CoV-2 infection
https://ajcn.nutrition.org/article/S0002-9165(22)10558-7/fulltext

The benefits of Omega-3s in relation to SARS-CoV-2 and its Spike Protein do not stop there. The Spike Protein impairs gut barrier integrity (see previous post). Omega-3s can restore gut barrier integrity, almost certainly mitigating the damage done by the Spike Protein.

AID restored GB integrity by promoting expression of tight junction proteins and mucins

The GB alterations in the NOD mice are detectable at 10-12 weeks of age concomitantly with onset of beta cell autoimmunity and thus suggesting that they may have a triggering effect on T1D pathogenesis (10). In order to assess whether prevention of T1D in AID-fed NOD mice is linked to restoration of GB integrity, we performed a gut permeability test (FITC-dextran) and measured by RT-qPCR the expression of mRNA transcripts of tight junction proteins and analyzed different biomarkers of mucus layer integrity (mucus layer thickness, percentage of GC, mRNA expression levels of mucins) in the intestine of AID vs STD diet-fed NOD mice. Our FITC-dextran test confirmed previous findings of increased gut permeability in NOD mice compared to non-autoimmune mice (Supplementary Figure 2) and a decrease of gut permeability in AID-fed NOD mice compared to STD diet-fed counterparts at 24 weeks of age but not earlier in the pre-diabetic phase (14 weeks of age) (Supplementary Figure 2). Importantly, we observed that AID-fed NOD mice had increased mRNA expression levels of claudin 1 (CLDN1), one structural protein of the intestinal epithelial barrier (IEB) (Figure 2A; p<0.0001). Importantly, mRNA transcripts relatives to several mucins including the mucus structural mucin Muc2 (p<0.0001) and immune-regulatory mucins Muc1 (p<0.0001) and Muc3 (p<0.01) were also up-regulated in the intestinal tissue of AID-fed NOD mice (Figure 2B), while Muc4, a pro-inflammatory mucin (40), is decreased in AID-fed NOD mice (Figure 2B; p<0.01). Restoration of the mucus layer integrity in AID-fed NOD mice was confirmed at the histological level with an almost complete absence of mucus layer in STD-fed NOD mice that was corrected by administration of AID (Figure 2C). In line with this observation, we measured a significantly higher percentage of GC in the large intestine of AID-fed NOD mice compared to their STD diet-fed counterparts (Figure 2C; p<0.05).

A diet enriched in omega-3 PUFA and inulin prevents type 1 diabetes by restoring gut barrier integrity and immune homeostasis in NOD mice
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1089987/full

There is yet one more anti-Spike benefit from Omega-3s to discuss. Omega-3s are shown to prevent sudden cardiac death. This is important in the context of the surge of sudden cardiac deaths being observed post Spike Protein exposure.

Sudden cardiac death (SCD) is an unresolved health issue, and responsible for 15% of all deaths in Western countries. Epidemiologic evidence, as well as evidence from clinical trials, indicates that increasing intake and high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect from SCD and other major adverse cardiac events. Levels of EPA+DHA are best assessed by the Omega-3 Index, representing the red cell fatty acid content of EPA+DHA. Work is in progress that will further define the value of the Omega-3 Index as a risk factor for SCD, other cardiac events, and as target for treatment with EPA+DHA.

Omega-3 Index and Sudden Cardiac Death
https://pmc.ncbi.nlm.nih.gov/articles/PMC3257645/

The abilities of Omega-3s and 6s to ameliorate the effects of SARS-CoV-2 and its Spike Protein are most impressive. Along with Vitamin D and Quercetin it may be among the top players. And what wonders Nature has to heal us with. I am inspired and will continue to search further.

Of course, this is a work of medical research and not medical advice. Always consult your Primary Care Provider before using any medication or supplement. That being said, I am extremely looking forward to having Salmon Coulibiac in the upcoming weeks!

Thank you, as always, for your readership, dialog and support. It is full-on, glorious Spring this morning in northern Vermont. Wall to wall sunshine and warmth to usher in Easter Weekend. Wherever you are, please have a blessed and hopeful Easter Weekend and Week.