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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.
WALTER M CHESNUT
APR 18

https://open.substack.com/pub/wmcresearch/p/friday-hope-omega-3-6-fatty-acids

周五希望：欧米茄-3，6脂肪酸：抑制尖峰蛋白并恢复肠道屏障完整性

欧米茄-3脂肪酸还与降低新冠肺炎感染、严重程度和心脏猝死的风险有关。

沃尔特·M·栗子

4月18日

READ IN APP

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. 星期五希望：Omega-3,6脂肪酸：抑制尖刺蛋白和恢复肠道屏障完整性ω-3脂肪酸也与Covid感染，严重程度和突发性心脏死亡的风险降低有关。 沃尔特M Chesnut APR 18在APP抗炎饮食中阅读恢复NOD小鼠的肠道屏障完整性。 （a）克劳丁1（CLDN1），紧密结蛋白1（TJP1）和occludin（OCLN）的RT-QPCR分析来自抗炎小鼠的肠道组织匀浆（ST （b）NOD小鼠肠道中MUC1，MUC2，MUC3和MUC4粘膜基因的RT-QPCR分析（N =每组N = 8）。 （c）NOD小鼠的结肠部分（20x）的ALCIAN蓝染料喂食助剂或STD饮食。 肠道的顶端侧（长箭头）上的箭头表示粘液层的厚度，而沿着隐窝点的较小箭头点（以蓝色染色）。 两组（右侧面板）中的GC的百分比计算在随机选择的切片上的上皮细胞总数内（每组n = 5，6个部分/小鼠）。 所有数据都显示为平均值±SEM。 P <0.05; p <0.01; * p <0.0001。 长期以来一直庆祝欧米茄-3脂肪酸，以便他们的多方面的健康益处。 他们称之为“对心脏有益” 有很多证据支持这一点和其他好处。 Omega-3脂肪酸对您的心血管健康有许多潜在的益处。 一个主要好处是它们有助于降低甘油三酯水平。 血液中的甘油三酯太多（高甘油脂血症）引发了动脉粥样硬化的风险，通过这可以提高您的心脏病和中风的风险。 因此，重要的是要在控制下保持甘油三酯水平。 此外，Omega-3S可以通过培养HDL（好的）胆固醇并降低血压来帮助您。 一些研究显示Omega-3s可能降低您的风险：心血管疾病（CVD）。 死亡，如果你有CVD。 心律失常（心律失常）引起的猝死。 血栓。 超越心脏健康，Omega-3S可能有助于降低开发的风险：某种形式的癌症，包括乳腺癌。 阿尔茨海默病的疾病和痴呆症。 年龄相关的黄斑变性（AMD）。 研究继续调查这些和其他可能的效益。 Omega-3脂肪酸https://my.clevelandclinic.org/health/articles/17290-7290-7290- acga-3-fatty- acids，在SARS-COV-2的存在和其尖峰蛋白 首先，它们是另一个可以染色穗蛋白并防止其与我们的身体相互作用的自然治疗方法。 衍生自Omega-6的亚油酸将尖峰蛋白锁定在其闭合的构象中。 这可以防止其与ACE2（或其他受体）结合并进入我们的细胞。 对于记录，我并不支持引用纸张中的rundeathisnear插头。 SARS-COV-2穗状花序冷冻电子显微镜显微镜结构表明受体结合结构域在三个复合粘结袋中牢固地将关键的游离脂肪酸亚油酸（LA）粘合（SARS-COV-2 SP SARS-COV和MERS-COV具有类似的口袋（图1A，B）。 人冠状病毒受体结合结构域的La结合口袋在其他菌株中保守。 La绑定口袋包括arg408，gln409，ty365，tyr369，Leu387和Phe374等钥匙残留物。 前两个，ARG408和GLN409，执行门控功能，以及来自LA的油腻管的其余残余物。 Remdesivir是一种批准用于治疗SAR-COV-2的药物; 其活性形式作为核苷类似物，模拟核苷酸并掺入生长的RNA链中。 该掺入抑制SARS-COV-2和其他冠状病毒的RNA依赖性RNA聚合酶（RDRP）[[9]，[10]，[11]]。 Remdesivir允许在RNA合成止槽之前添加三种核苷酸。 亚油酸与尖刺蛋白结合锁定SARS-COV-2穗状花序在闭合构象并稳定，降低与血管紧张素转换酶2（ACE2）的相互作用。 因此，用Remdesivir补充的亚油酸补充剂对SARS-COV-2复制提供了协同抑制作用。 与La的SARS-COV-2结合直接连接到结构，铺平靶向La结合的干预策略[12,13]。 SARS-COV-2通过在穗蛋白… …总之，使用大英国Biobank DataSet，Harris等。 [1]报告称，较高的DHA状态与使用SARS-COV-2感染的阳性的风险较低，并与Covid-19住院。 还有表明，较高的DHA状态与Covid-19的死亡风险降低相关，尽管这种效果在最高的地位水平上衰减。 这些研究结果表明，应鼓励消耗更多的长链ω-3脂肪酸（EPA和DHA）作为减少持续的SARS-COV-2大流行和未来呼吸道病毒感染爆发的影响的策略。 通过消耗脂肪鱼或使用含有EPA和DHA的补充剂，可以实现EPA和DHA的摄入增加。 生物活性ω-3脂肪酸与SARS-COV-2感染的风险和严重程度降低有关，https://ajcn.nutrition.org/article/s0002-9165（22 )10558-7/ful 穗蛋白损害肠道屏障完整性（见前一篇文章）。 Omega-3S可以恢复肠道屏障完整性，几乎肯定会减轻尖刺蛋白所做的损伤。 通过促进紧密结蛋白和粘液的表达，递回GB的完整性通过β细胞自身免疫发作，在10-12周龄，在10-12周内可检测到Nod小鼠的GB改变，从而表明他们可能有触发 为了评估辅助NOD小鼠中T1D的预防是否与GB完整性的恢复相关联，我们进行了肠道渗透性试验（FITC-DEXTRAN）并通过RT-QPCR测量了紧密结来的mRNA转录物的表达 与非自身免疫小鼠（补充图2）相比，我们的FITC-DEXTRAN测试证实了NOD小鼠中的肠道渗透率增加的发现和助剂NOD小鼠中的肠道渗透率降低了与STD饮食供给柜台相比 重要的是，我们观察到辅助Nod小鼠具有增加的克劳德1（CLDN1）的mRNA表达水平，肠上皮屏障（IEB）的一个结构蛋白（图2A; P <0.0001）。 重要的是，MRNA转录物对包括粘液结构粘蛋白MUC2（P <0.0001）和免疫调节粘液MUC1（P <0.0001）和MUC3（P <0.01）的几种粘液（P <0.01）的亲属也在上调 在组织学水平的组织学水平证实了粘液层完整性的粘液层完整性，几乎完全没有通过助给施用的STD喂食NOD小鼠的粘液层（图2C）。 符合该观察，与STD饮食喂养对应物相比，我们测量了辅助喂食Nod小鼠的大肠中的显着较高的GC百分比（图2C; P <0.05）。 富含ω-3的葡萄糖和菊粉的饮食通过在NOD小鼠…，中恢复肠道屏障完整性和免疫稳定性，通过恢复肠道屏障完整性和免疫稳定性 显示ω-3s，以防止突然的心脏死亡。 这在被观察到穗蛋白暴露后的突然心脏病死亡的背景下很重要。 突然的心脏死亡（SCD）是一个未解决的健康问题，并负责西方国家所有死亡的15％。 流行病学证据以及来自临床试验的证据表明，增加的摄入量和高水平的己二辛烯酸（EPA）和二乙二醇六烯酸（DHA）保护免受SCD和其他主要不良心脏事件的保护。 EPA + DHA的水平最佳地评估OMEGA-3指数，代表EPA + DHA的红细胞脂肪酸含量。 正在进行中的工作，进一步将ω-3指数的价值定义为SCD，其他心脏事件的危险因素，以及用EPA + DHA治疗的靶标。 Omega-3指数和突发的心死HTTPS:/…改善效果的能力 与维生素D和槲皮素一起，它可能是顶级球员之一。 而且奇迹的自然必须治愈我们。 我受到启发，并将继续进一步搜索。 当然，这是医学研究的工作，而不是医学建议。 在使用任何药物或补充之前，请始终咨询您的初级保健提供者。 据说，我非常期待在即将到来的几周内患有鲑鱼库才能！ 衷心感谢您的读者，对话框和支持。 今天早上在佛蒙特北部，这是全面的辉煌春天。 墙壁到墙壁阳光和温暖，以迎来复活节周末。 无论您身在何处，请在周末和一周内有一个幸福和有希望的复活节。