Dissolution of Spike Protein by Nattokinase
Holy Grail of COVID-19 Vaccine Detoxification
Peter A. McCullough, MD, MPH™
Feb 21, 2023
By Peter A. McCullough, MD, MPH
Far and away the most common question I get from those who took one of the COVID-19 vaccines is: “how do I get this out of my body.” The mRNA and adenoviral DNA products were rolled out with no idea on how or when the body would ever breakdown the genetic code. The synthetic mRNA carried on lipid nanoparticles appears to be resistant to breakdown by human ribonucleases by design so the product would be long-lasting and produce the protein product of interest for a considerable time period. This would be an advantage for a normal human protein being replaced in a rare genetic deficiency state (e.g. alpha galactosidase in Fabry’s disease). However, it is a big problem when the protein is the pathogenic SARS-CoV-2 Spike. The adenoviral DNA (Janssen) should broken down by deoxyribonuclease, however this has not be exhaustively studied.
This leaves dissolution of Spike protein as a therapeutic goal for the vaccine injured. With the respiratory infection, Spike is processed and activated by cellular proteases including transmembrane serine protein 2 (TMPRSS2), cathepsin, and furin. With vaccination, these systems may be avoided by systemic administration and production of Spike protein within cells. As a result, the pathogenesis of vaccine injury syndromes is believed to be driven by accumulation of Spike protein in cells, tissues, and organs.
Nattokinase is an enzyme is produced by fermenting soybeans with bacteria Bacillus subtilis var. natto and has been available as an oral supplement. It degrades fibrinogen, factor VII, cytokines, and factor VIII and has been studied for its cardiovascular benefits. Out of all the available therapies I have used in my practice and among all the proposed detoxification agents, I believe nattokinase and related peptides hold the greatest promise for patients at this time.
Tanikawa et al examined the effect of nattokinase on the Spike protein of SARS-CoV-2. In the first experiment they demonstrated that Spike was degraded in a time and dose dependent manner in a cell lysate preparation that could be analogous to a vaccine recipient. The second experiment demonstrated that nattokinase degraded the Spike protein in SARS-CoV-2 infected cells. This reproduced a similar study done by Oba and colleagues in 2021.
https://substackcdn.com/image/fetch/w_14...0x2200.png
Tanikawa T, Kiba Y, Yu J, Hsu K, Chen S, Ishii A, Yokogawa T, Suzuki R, Inoue Y, Kitamura M. Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2. Molecules. 2022 Aug 24;27(17):5405. doi: 10.3390/molecules27175405. PMID: 36080170; PMCID: PMC9458005.
Nattokinase is dosed in fibrinolytic units (FU) per gram and can vary according to purity. Kurosawa and colleagues have shown in humans that after a single oral dose of 2000 FU D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after administration elevated significantly (p < 0.05, respectively). Thus an empiric starting dose could be 2000 FU twice a day. Full pharmacokinetic and pharmacodynamic studies have not been completed, but several years of market use as an over-the-counter supplement suggests nattokinase is safe with the main caveat being excessive bleeding and cautions with concurrent antiplatelet and anticoagulant drugs.
Based on these findings, nattokinase and similar products such as serrapeptase should undergo well-funded, accelerated preclinical and clinical development programs. The issue at hand is the urgency of time, similar to that with SARS-CoV-2 infection and empiric early therapy. It will take up to 20 years to have a fully developed pharmaceutical profile to characterize the safety and efficacy of nattokinase in the treatment of vaccine injury and post-COVID syndromes. Large number of people are sick now and many believe empiric treatment is justified given sufficiently low risk of side effects and potentially high reward. My recommendation is to discuss this with your doctor or seek a specialist in holistic or naturopathic medicine who is experienced with the safety profile of nattokinase in a range of applications.
If you find “Courageous Discourse” enjoyable and useful to your endeavors, please subscribe as a paying or founder member to support our efforts in helping you engage in these discussions with family, friends, and your extended circles.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458005/
https://www.sciencedirect.com/science/ar...via%3Dihub
https://www.ncbi.nlm.nih.gov/pmc/article...p11601.pdf
Dr. Colleen Huber
Writes The Defeat Of COVID
Feb 21
I have asked my covid-vaccinated patients to take nattokinase 2000 units per day, while running these labs every 3 months: D-dimer, CBC/platelets, fibrinogen, PT/INR. Naturopathic physicians have recommended nattokinase and similar for decades for our cardiovascular patients, and I have never known it to cause new problems. It seems to be generally well-tolerated.
https://petermcculloughmd.substack.com/p...attokinase
Ivermectin's Mechanism of Action Against SARS-CoV-2 Described
SHAME on the hospital systems that systematically denied patients (and their begging families) this FDA-approved, Nobel prize winning, wonder drug.
Peter A. McCullough, MD, MPH™
Jan 2, 2023
By JOHN LEAKE
Satoshi Ōmura, discoverer of Streptomyces avermectinius, winner of the Nobel Prize in Medicine 2015.
Researching our book—The Courage to Face COVID-19: Preventing Hospitalization and Death While Battling the Bio-Pharmaceutical Complex—was often a distressing and maddening experience. The systematic lying about hydroxychloroquine to suppress its use in the outpatient setting was infuriating. However, for me, the most upsetting stories were about people who died in hospital after being systematically denied ivermectin. The sheer brutality of hospital chiefs and their attorneys, who fought tooth and nail against the administration of ivermectin to dying patients, must surely be the most morally repugnant story in modern medical history.
As we document in our book, Drs. Pierre Kory, Paul Marik, and Tess Lawrie were on the front line of fighting for ivermectin in the hospital setting. Drs. Jean-Jacques and Juliana Cepelowicz Rajter published their seminal (ICON) study in the October 12, 2020 edition of the CHEST journal of pulmonary medicine. The investigative journalists, Michael Capuzzo and Mary Beth Pfeiffer, did a splendid job of covering this story in real time. All of the above are heroic figures of great intellectual and moral discernment to whom we should all be grateful.
Many patients who were fortunate enough to prevail in court and receive ivermectin enjoyed an astonishing improvement of their condition within 24 hours of receiving their first dose—a recovery that struck family members as miraculous.
In listening to their stories, I often asked myself: “How on earth could this substance (macrocyclic lactone)—derived from a bacteria (Streptomyces avermectinius) found in a soil sample on a golf course in Japan—possibly work such miracles?” Truly these testimonies struck me as the most wondrous stories I’d ever heard, and I occasionally asked myself if the recoveries observed were a fluke or the result of some other unknown factors.
To be sure, we already knew from in vitro and from prior studies that ivermectin had demonstrated potent anti-viral activity, but the precise cause of action was unknown. Now, thanks to a study recently published by a research team at MEPHI, Aix-Marseille Université, we have a highly plausible description of ivermectin’s mechanism of action against the SARS-CoV-2 spike protein.
In order to understand this mechanism, the reader must first understand that the SARS-CoV-2 Spike Protein Induces Hemagglutination—i.e., a reaction that causes clumping of red blood cells. A glycoprotein on the viral surface, namely hemagglutinin, interacts with red blood cells, leading to the clumping of red blood cells and the formation of a lattice.
As the Aix-Marseille team documents in their study: IVERMECTIN blocked HEMAGGLUTINATION when added to RED BLOOD CELLS prior to spike protein and reversed HEMAGGLUTINATION when added afterward.
By reversing the clumping of red blood cells, ivermectin enabled the dying patient’s proper respiratory function to return, thereby generating his or her astonishing recovery.
If the Aix-Marsaille team’s findings are correct—and we have no reason to doubt that they are—they provide the final validation and vindication of the dying patients and their families who literally begged for the wonder drug.
SHAME on the hospital administrators and their thuggish attorneys who denied the countless dying wishes. SHAME on the federal health officials who propagated the LIE that Ivermectin was merely a “horse de-wormer.” SHAME on the useful idiot media pundits such as CNN broadcasters and Late-Night Comedy hosts who flooded the zone with this foul lie.
https://petermcculloughmd.substack.com/p...on-against
Antiviral Effects of Nattokinase
Inhibition of SARS-CoV-2 and Bovine Herpes Virus-1 Demonstrated in Vitro
Peter A. McCullough, MD, MPH™
May 3, 2023
https://substackcdn.com/video_upload/pos...scoded.mp3
Recently there has been intense focus on “natto” derived from the fermentation of steamed soy by bacillus subtilis. Nattokinase is a proteolytic enzyme used as an oral supplement by the Japanese for the chronic treatment of atherothrombotic cardiovascular disease. Now a recent study in the COVID-19 era by the Japanese demonstrated preventive antiviral effects against SARS-CoV-2 mutant strains and bovine herpes virus type 1. The mechanism appears to be proteolytic cleavage of viral proteins.
Oba and colleagues performed a series of experiments with various concentrations of nattokinase in preclinical models. They found: 1) nattokinase effectively stopped infection of human cells in culture from SARS-CoV-2 and bovine herpes virus type 1, 2) the proteolytic effect of nattokinase was heat sensitive.
https://substackcdn.com/image/fetch/w_14...4x1328.png
Oba M, Rongduo W, Saito A, Okabayashi T, Yokota T, Yasuoka J, Sato Y, Nishifuji K, Wake H, Nibu Y, Mizutani T. Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS-CoV-2 in vitro. Biochem Biophys Res Commun. 2021 Sep 17;570:21-25. doi: 10.1016/j.bbrc.2021.07.034. Epub 2021 Jul 13. PMID: 34271432; PMCID: PMC8276596.
While many around the world feel they cannot wait for large-scale randomized trials of nattokinase in the treatment of vaccine injury syndromes, they may not realize there may be an additional salutary effect—prevention of subsequent COVID-19 infections.
While it is too early to make therapeutic claims, there is no doubt that data on nattokinase is the most promising we have seen among all solutions reviewed to end the final stages of the pandemic crisis—long COVID, vaccine injury syndromes, and recurrent Omicron infections.
If you find “Courageous Discourse” enjoyable and useful to your endeavors, please subscribe as a paying or founder member to support our efforts in helping you engage in these discussions with family, friends, and your extended circles.
https://pubmed.ncbi.nlm.nih.gov/34271432/
Dr. McCullough - Roles of Bromelain and Curcumin in Battling Recurrent SARS-CoV-2 Spike Protein Exposures
Natural Products have Strong Rationale for Use Post-COVID-19 and Vaccine Syndromes
Peter A. McCullough, MD, MPH™
Jun 16, 2023
https://substackcdn.com/video_upload/pos...scoded.mp3
I find it interesting that a large group of post-COVID-19 acute sequalae are occurring in those who have taken failed COVID-19 vaccines. We are a long way off from definitive clinical trials of multidrug strategies for patients who have had multiple exposures to the SARS-CoV-2 Spike protein via vaccination or recurrent COVID-19.
https://substackcdn.com/image/fetch/w_14...8x1328.png
Kritis et al point out: “ Curcumin (diferuloylmethane) is a natural phenol found in turmeric (Curcuma longa), a member of the ginger family of plants [4]. Curcumin modulates inflammation preventing the subsequent cytokine storm by inhibiting multiple transcription factors such as nuclear factor kappa B (NF-kB) and signal transducer and activator of transcription 3 (STAT-3), and downregulating the proinflammatory cytokines, as this has been demonstrated in human macrophages after influenza virus infection [4,6]. Additionally, curcumin inhibits ACE modulating angiotensin II synthesis and downregulating inflammation, while it also promotes fibrinolysis and the anticoagulation process [4,6,7] (Fig. 1). The antiviral actions of curcumin against multiple viruses (influenza and hepatitis viruses, herpes viruses, human papilloma virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus and other coronaviruses), bacteria and fungi have been established by experimental evidence [8]. Remarkably, recent evidence from in silico studies has demonstrated that curcumin prevents SARS-CoV-2 entry into cells by blocking the viral binding sites and the cell ligands (spike protein, ACE-2 receptors and basigin), downregulating trans-membrane serine protease 2 (TMPRSS-2), and by interfering with viral replication through the interaction with various viral proteins [4]. However, the minimal absorption of curcumin following oral administration presents a major limitation in its bioavailability [6].
Bromelain is a cysteine protease, isolated from the pineapple stem (Ananas comosus) [9]. Traditionally, it has been used for its anti-inflammatory and healing effects in cases of arthritis and injury, while it has been approved in Europe for the debridement of burn wounds. Experimental studies have demonstrated that bromelain presents unique immunomodulatory actions: 1) downregulation of the pro-inflammatory prostaglandin E2 (PGE-2) through inhibition of NF-kB and cyclooxygenase 2 (COX-2); 2)upregulation of the anti-inflammatory PGE-1; 3) activation of inflammatory mediators (interleukin 1b, interleukin-6, tumor necrosis factor-a and interferon-g) as an acute response to cellular stress, but also inhibition of inflammatory mediators in states of overt cytokine production; 4) modulation of T cell responses in vitro and in vivo; and 5) enhancement of T-cell dependent antigenspecific B cell antibody responses [5,10e14]. Importantly, bromelain exerts dose-dependent anticoagulant effects: 1) downregulation of PGE-2 and thromboxane A2 (TXA2), thus leading to relative excess of prostacyclin; 2) promotion of fibrinolysis by stimulating the conversion of plasminogen to plasmin and prevention of platelet aggregation. Bromelain also hydrolyzes bradykinin and reduces kininogen and bradykinin levels in serum and tissues, improving inflammation and edema as shown in animal studies [15]. Notably, the latter action supports a potential role of bromelain in alleviating COVID-19 symptoms such as cough, fever and pain, and the more serious implications of inflammation, thrombosis and edema. The effect of bromelain on PGE-2 inhibition exceeds that of prednisone and aspirin, presenting very low toxicity and no major side effects. Interestingly, a recent experimental study demonstrated that bromelain inhibits infection of VeroE6 cells by SARS-CoV-2 through blocking the virus binding and entry into cells via downregulation of ACE-2 and TMPRSS2 expression, and cleavage of the SARS-CoV-2 spike protein, presenting a novel promising therapeutic option that warrants further investigation.
In summary, the combination of curcumin and bromelain are well positioned as supplements in people who are getting repetitive COVID-19/Spike protein exposure. Future randomized trials will elucidate the clinical benefits in specific applications.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661945/
Nattokinase in the Prevention and Treatment of Atherosclerotic Cardiovascular Disease
Human Data Promising as Supplement Widely Used in Post COVID-19 and Vaccine Injury Syndromes
By Peter A. McCullough, MD, MPH
Approximately 15% of Americans who took a COVID-19 vaccine have some new medical illness and regret the shot. Many are looking to nattokinase in formulations of Spike protein support supplements asking is it safe, and what is the track record for this Asian discovery?
Chen et al reviewed human studies before the pandemic on the use of nattokinase with this introduction: “Natto, a cheese-like food made of soybeans fermented with Bacillus subtilis, has been consumed as a traditional food in Asian countries for more than 2000 years. Natto consumption is believed to be a significant contributor to the longevity of the Japanese population. Recent studies demonstrated that a high natto intake was associated with decreased risk of total CVD mortality and, in particular, a decreased risk of mortality from ischaemic heart diseases. Before the 1980s, very little was known about the mechanism by which natto consumption led to overall cardiovascular health. In 1987, Sumi et al discovered that natto contained a potent fibrinolytic enzyme called nattokinase (NK). Since then, a considerable amount of NK research has been performed on NK in Japan, Korea, China, and the United States, and these studies confirmed that NK, an alkaline protease of 275 amino acid residues with a molecular weight of approximately 28 kDa, is the most active ingredient of natto and is responsible for many favourable effects on cardiovascular health. First, NK has potent fibrinolytic/antithrombotic activity. In addition, in both animal and human studies, NK also has an antihypertensive, anti-atherosclerotic, lipid-lowering, antiplatelet/anticoagulant, and neuroprotective actions…The most unique feature of NK is that, as a single compound, it possesses multiple CVD preventative and alleviating pharmacologic effects (namely, antithrombotic, antihypertensive, anticoagulant, anti-atherosclerotic, and neuroprotective effects). There are no other drugs or drug candidates with multiple pharmacologic properties similar to NK. In addition, NK is a natural product that can be administered orally, has a proven safety profile, is economical to use, and provides distinct advantages over other pharmaceutical products.”
In drug development, the most important early observations are on safety. There are two units used in nattokinase dosing, e.g. 100 mg=2000 fibrinolytic units (FU). In the table, Lampe et al in 2016 tested nattokinase up to 10 mg/kg/day (~160,000 FU for an 80 kg person). That means in doses of 100 mg or 2000 FU twice a day are well within a safety range to avoid significant toxicities.
https://substackcdn.com/image/fetch/w_14...3x2234.png
In summary this review is reassuring that the ever increasing use of nattokinase in post-COVID-19 and after COVID-19 vaccine injuries is safe and reasonably well tolerated. There may be additional benefits on the cardiovascular system. There is a pressing need for continued clinical development for the COVID-19 and cardiovascular indications. Patients wanting to use the supplement ahead of the emerging science should discuss with a knowledgeable healthcare professional and be on alert for intolerances, allergic reactions, or bleeding complications.
If you find “Courageous Discourse” enjoyable and useful to your endeavors, please subscribe as a paying or founder member to support our efforts in helping you engage in these discussions with family, friends, and your extended circles.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043915/
https://www.twc.health/collections/covid...ul-formula
https://petermcculloughmd.substack.com/p...ention-and
Prescription and Over-the-Counter Treatments for Post-COVID Syndrome
Long List of Possibilities with Early Data Published
Over three years into the pandemic with nearly the entire country having become sick with SARS-CoV-2, a virus engineered to invade the body, there are millions suffering with long-hauler syndrome. Approximately half of patients admitted to the ICU with COVID-19 will have post-COVID syndrome which is now understood to be due to persistence of the SARS-CoV-2 Spike protein within cells, tissues, and organs. Those vaccinated have been additionally loaded with Spike, so may have even a worse course with prolonged symptoms including fatigue, lethargy, brain fog, muscle loss, skin and hair changes, sleeplessness, and effort intolerance. The magnitude of the problem has driven an all-encompassing search for management strategies to resolve the syndrome(s).
Hope is on the horizon with a preprint paper published by Halma et al summarizing the prescription drug and over-the-counter candidates for therapy. In my practice, I stylize the approach based on the patient and how recent the COVID-19 infection was in their history. If there are lingering signs of infection, then a course of full dose ivermectin can be considered. Aspirin is reasonable given increased rates of heart attack and stroke after the illness. I have found the colchicine appears to have an important role in pleurodynia or chest wall discomfort. Additionally it is used with corticosteroids in vaccine-induced myopericarditis. Low-dose naltrexone has been reported to ameliorate fatigue and inanition. Metformin has supportive data and would be appropriate in pre-diabetes and those with diabetes mellitus.
https://substackcdn.com/image/fetch/w_14...4x2206.png
From the OTC list, I have found nattokinase, the Japanese product derived from natto (a traditional Japanese food made from whole soybeans that have been fermented with Bacillus subtilis var. natto.) to be the most compelling and scientifically supported approach to clear Spike protein out of the body via proteolytic degradation. A host of cellular protective, anti-oxidant approaches are listed with vitamin C and NAC being readily available and widely used.
https://substackcdn.com/image/fetch/w_14...0x1473.png
Halma, M.T.; Plothe, C.; Lawrie, T. Strategies for the Management of Spike Protein-Related Pathology. Preprints 2023, 2023030344. https://doi.org/10.20944/preprints202303.0344.v1.
Patients should push their doctors to refer them to clinical trials, and when that is not feasible, then empiric therapy can be pursued. It is important to realize that in the absence of completed large randomized placebo controlled randomized trials, which are easily 5 or more years away in the future, no therapeutic claims can be made. In the meantime we must be perceptive as patients and open-minded as clinicians to come up with reasonable approaches that can be used to help those sick now with post-COVID syndromes.
If you find “Courageous Discourse” enjoyable and useful to your endeavors, please subscribe as a paying or founder member to support our efforts in helping you engage in these discussions with family, friends, and your extended circles.
https://www.preprints.org/manuscript/202303.0344/v1
https://petermcculloughmd.substack.com/p...he-counter
Which Virus Will Cause the Next Pandemic?
Experts Predict Virus Will Be Airborne--Narrows Field Considerably
We are constantly being barraged by fear-mongering messages about a “next pandemic” as if new global catastrophes have been put on a schedule. I have remarked that it would be quite difficult to anticipate an organism arriving from nature and afflicting the entire world’s population of any mammal, let alone man.
Neumann and Kawaoka published a review of past pandemics, a broad list of viral threats, and then indicated that the likely winner would be a zoonosis (virus that jumped from a bat or rodent) to a human. Additionally, for human to human spread it would need to be airborne and highly contagious. We learned with the fizzled Monkeypox scare that homo- bi-sexual transmission from man to man was not enough the scare the world into mass vaccination or hold the public captive very long in the news cycle. President Biden dropped the US Monkeypox Emergency in January 31, 2023 with no press release.
The list of possibilities for future pandemics is listed in the table. Most have no antiviral therapy that is specific, however, the authors fail to mention viricidal nasal sprays/gargles, vitamin D, curcumin, hydroxychloroquine, ivermectin, favipiravir, famotidine, or other agents to mitigate viral specific inflammation such as maraviroc and nonspecific agents including corticosteroids and colchicine.
https://substackcdn.com/image/fetch/w_14...8x1328.png
The authors outline these steps to get ready: “To prepare for future pandemics, the international research community needs to continue and further strengthen research efforts in various areas, including the following: (i) cataloging the landscape and animal reservoirs of (human-infecting) viruses through surveillance and metagenomics; (ii) development of animal models for viruses that may cause pandemics; (iii) basic research to better understand the molecular virology of such viruses; (iv) early stage vaccine development and testing in animal models; and (v) development of broad antivirals as a first line of defense. The US National Institute of Allergy and Infectious Diseases has suggested that prototype pathogens (selected from virus families that may cause pandemics) be selected for basic research and early stage development of countermeasures. With reasonable resources and advanced technologies, the global community could be much better prepared for future pandemics.
I am cautious about the terms “animal models” “prototype pathogens” “vaccine” or “countermeasure” as these were the words used by the NIH, HHS, and the Cares Act disastrous COVID-19 pandemic response. I suggest we focus on readiness with an arsenal of nasal viricidal washes and gargles to PREVENT the upper respiratory illness as the main measure of contagion control. Solutions of dilute iodine, hydrogen peroxide, xylitol, colloidal silver, and other compounds alone or in combination should serve well for any of the viral threats listed.
https://substackcdn.com/image/fetch/w_14...94x700.png
From the authors (v) “broad antivirals” with adjunctive treatment will be the next line of defense since they will be readily available, scalable, and far more important to large numbers of sick patients instead of vaccines for well persons.
If you find “Courageous Discourse” enjoyable and useful to your endeavors, please subscribe as a paying or founder member to support our efforts in helping you engage in these discussions with family, friends, and your extended circles.
https://petermcculloughmd.substack.com/p...t-pandemic
Holy Grail of COVID-19 Vaccine Detoxification
Peter A. McCullough, MD, MPH™
Feb 21, 2023
By Peter A. McCullough, MD, MPH
Far and away the most common question I get from those who took one of the COVID-19 vaccines is: “how do I get this out of my body.” The mRNA and adenoviral DNA products were rolled out with no idea on how or when the body would ever breakdown the genetic code. The synthetic mRNA carried on lipid nanoparticles appears to be resistant to breakdown by human ribonucleases by design so the product would be long-lasting and produce the protein product of interest for a considerable time period. This would be an advantage for a normal human protein being replaced in a rare genetic deficiency state (e.g. alpha galactosidase in Fabry’s disease). However, it is a big problem when the protein is the pathogenic SARS-CoV-2 Spike. The adenoviral DNA (Janssen) should broken down by deoxyribonuclease, however this has not be exhaustively studied.
This leaves dissolution of Spike protein as a therapeutic goal for the vaccine injured. With the respiratory infection, Spike is processed and activated by cellular proteases including transmembrane serine protein 2 (TMPRSS2), cathepsin, and furin. With vaccination, these systems may be avoided by systemic administration and production of Spike protein within cells. As a result, the pathogenesis of vaccine injury syndromes is believed to be driven by accumulation of Spike protein in cells, tissues, and organs.
Nattokinase is an enzyme is produced by fermenting soybeans with bacteria Bacillus subtilis var. natto and has been available as an oral supplement. It degrades fibrinogen, factor VII, cytokines, and factor VIII and has been studied for its cardiovascular benefits. Out of all the available therapies I have used in my practice and among all the proposed detoxification agents, I believe nattokinase and related peptides hold the greatest promise for patients at this time.
Tanikawa et al examined the effect of nattokinase on the Spike protein of SARS-CoV-2. In the first experiment they demonstrated that Spike was degraded in a time and dose dependent manner in a cell lysate preparation that could be analogous to a vaccine recipient. The second experiment demonstrated that nattokinase degraded the Spike protein in SARS-CoV-2 infected cells. This reproduced a similar study done by Oba and colleagues in 2021.
https://substackcdn.com/image/fetch/w_14...0x2200.png
Tanikawa T, Kiba Y, Yu J, Hsu K, Chen S, Ishii A, Yokogawa T, Suzuki R, Inoue Y, Kitamura M. Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2. Molecules. 2022 Aug 24;27(17):5405. doi: 10.3390/molecules27175405. PMID: 36080170; PMCID: PMC9458005.
Nattokinase is dosed in fibrinolytic units (FU) per gram and can vary according to purity. Kurosawa and colleagues have shown in humans that after a single oral dose of 2000 FU D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after administration elevated significantly (p < 0.05, respectively). Thus an empiric starting dose could be 2000 FU twice a day. Full pharmacokinetic and pharmacodynamic studies have not been completed, but several years of market use as an over-the-counter supplement suggests nattokinase is safe with the main caveat being excessive bleeding and cautions with concurrent antiplatelet and anticoagulant drugs.
Based on these findings, nattokinase and similar products such as serrapeptase should undergo well-funded, accelerated preclinical and clinical development programs. The issue at hand is the urgency of time, similar to that with SARS-CoV-2 infection and empiric early therapy. It will take up to 20 years to have a fully developed pharmaceutical profile to characterize the safety and efficacy of nattokinase in the treatment of vaccine injury and post-COVID syndromes. Large number of people are sick now and many believe empiric treatment is justified given sufficiently low risk of side effects and potentially high reward. My recommendation is to discuss this with your doctor or seek a specialist in holistic or naturopathic medicine who is experienced with the safety profile of nattokinase in a range of applications.
If you find “Courageous Discourse” enjoyable and useful to your endeavors, please subscribe as a paying or founder member to support our efforts in helping you engage in these discussions with family, friends, and your extended circles.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458005/
https://www.sciencedirect.com/science/ar...via%3Dihub
https://www.ncbi.nlm.nih.gov/pmc/article...p11601.pdf
Dr. Colleen Huber
Writes The Defeat Of COVID
Feb 21
I have asked my covid-vaccinated patients to take nattokinase 2000 units per day, while running these labs every 3 months: D-dimer, CBC/platelets, fibrinogen, PT/INR. Naturopathic physicians have recommended nattokinase and similar for decades for our cardiovascular patients, and I have never known it to cause new problems. It seems to be generally well-tolerated.
https://petermcculloughmd.substack.com/p...attokinase
Ivermectin's Mechanism of Action Against SARS-CoV-2 Described
SHAME on the hospital systems that systematically denied patients (and their begging families) this FDA-approved, Nobel prize winning, wonder drug.
Peter A. McCullough, MD, MPH™
Jan 2, 2023
By JOHN LEAKE
Satoshi Ōmura, discoverer of Streptomyces avermectinius, winner of the Nobel Prize in Medicine 2015.
Researching our book—The Courage to Face COVID-19: Preventing Hospitalization and Death While Battling the Bio-Pharmaceutical Complex—was often a distressing and maddening experience. The systematic lying about hydroxychloroquine to suppress its use in the outpatient setting was infuriating. However, for me, the most upsetting stories were about people who died in hospital after being systematically denied ivermectin. The sheer brutality of hospital chiefs and their attorneys, who fought tooth and nail against the administration of ivermectin to dying patients, must surely be the most morally repugnant story in modern medical history.
As we document in our book, Drs. Pierre Kory, Paul Marik, and Tess Lawrie were on the front line of fighting for ivermectin in the hospital setting. Drs. Jean-Jacques and Juliana Cepelowicz Rajter published their seminal (ICON) study in the October 12, 2020 edition of the CHEST journal of pulmonary medicine. The investigative journalists, Michael Capuzzo and Mary Beth Pfeiffer, did a splendid job of covering this story in real time. All of the above are heroic figures of great intellectual and moral discernment to whom we should all be grateful.
Many patients who were fortunate enough to prevail in court and receive ivermectin enjoyed an astonishing improvement of their condition within 24 hours of receiving their first dose—a recovery that struck family members as miraculous.
In listening to their stories, I often asked myself: “How on earth could this substance (macrocyclic lactone)—derived from a bacteria (Streptomyces avermectinius) found in a soil sample on a golf course in Japan—possibly work such miracles?” Truly these testimonies struck me as the most wondrous stories I’d ever heard, and I occasionally asked myself if the recoveries observed were a fluke or the result of some other unknown factors.
To be sure, we already knew from in vitro and from prior studies that ivermectin had demonstrated potent anti-viral activity, but the precise cause of action was unknown. Now, thanks to a study recently published by a research team at MEPHI, Aix-Marseille Université, we have a highly plausible description of ivermectin’s mechanism of action against the SARS-CoV-2 spike protein.
In order to understand this mechanism, the reader must first understand that the SARS-CoV-2 Spike Protein Induces Hemagglutination—i.e., a reaction that causes clumping of red blood cells. A glycoprotein on the viral surface, namely hemagglutinin, interacts with red blood cells, leading to the clumping of red blood cells and the formation of a lattice.
As the Aix-Marseille team documents in their study: IVERMECTIN blocked HEMAGGLUTINATION when added to RED BLOOD CELLS prior to spike protein and reversed HEMAGGLUTINATION when added afterward.
By reversing the clumping of red blood cells, ivermectin enabled the dying patient’s proper respiratory function to return, thereby generating his or her astonishing recovery.
If the Aix-Marsaille team’s findings are correct—and we have no reason to doubt that they are—they provide the final validation and vindication of the dying patients and their families who literally begged for the wonder drug.
SHAME on the hospital administrators and their thuggish attorneys who denied the countless dying wishes. SHAME on the federal health officials who propagated the LIE that Ivermectin was merely a “horse de-wormer.” SHAME on the useful idiot media pundits such as CNN broadcasters and Late-Night Comedy hosts who flooded the zone with this foul lie.
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Antiviral Effects of Nattokinase
Inhibition of SARS-CoV-2 and Bovine Herpes Virus-1 Demonstrated in Vitro
Peter A. McCullough, MD, MPH™
May 3, 2023
https://substackcdn.com/video_upload/pos...scoded.mp3
Recently there has been intense focus on “natto” derived from the fermentation of steamed soy by bacillus subtilis. Nattokinase is a proteolytic enzyme used as an oral supplement by the Japanese for the chronic treatment of atherothrombotic cardiovascular disease. Now a recent study in the COVID-19 era by the Japanese demonstrated preventive antiviral effects against SARS-CoV-2 mutant strains and bovine herpes virus type 1. The mechanism appears to be proteolytic cleavage of viral proteins.
Oba and colleagues performed a series of experiments with various concentrations of nattokinase in preclinical models. They found: 1) nattokinase effectively stopped infection of human cells in culture from SARS-CoV-2 and bovine herpes virus type 1, 2) the proteolytic effect of nattokinase was heat sensitive.
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Oba M, Rongduo W, Saito A, Okabayashi T, Yokota T, Yasuoka J, Sato Y, Nishifuji K, Wake H, Nibu Y, Mizutani T. Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS-CoV-2 in vitro. Biochem Biophys Res Commun. 2021 Sep 17;570:21-25. doi: 10.1016/j.bbrc.2021.07.034. Epub 2021 Jul 13. PMID: 34271432; PMCID: PMC8276596.
While many around the world feel they cannot wait for large-scale randomized trials of nattokinase in the treatment of vaccine injury syndromes, they may not realize there may be an additional salutary effect—prevention of subsequent COVID-19 infections.
While it is too early to make therapeutic claims, there is no doubt that data on nattokinase is the most promising we have seen among all solutions reviewed to end the final stages of the pandemic crisis—long COVID, vaccine injury syndromes, and recurrent Omicron infections.
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https://pubmed.ncbi.nlm.nih.gov/34271432/
Dr. McCullough - Roles of Bromelain and Curcumin in Battling Recurrent SARS-CoV-2 Spike Protein Exposures
Natural Products have Strong Rationale for Use Post-COVID-19 and Vaccine Syndromes
Peter A. McCullough, MD, MPH™
Jun 16, 2023
https://substackcdn.com/video_upload/pos...scoded.mp3
I find it interesting that a large group of post-COVID-19 acute sequalae are occurring in those who have taken failed COVID-19 vaccines. We are a long way off from definitive clinical trials of multidrug strategies for patients who have had multiple exposures to the SARS-CoV-2 Spike protein via vaccination or recurrent COVID-19.
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Kritis et al point out: “ Curcumin (diferuloylmethane) is a natural phenol found in turmeric (Curcuma longa), a member of the ginger family of plants [4]. Curcumin modulates inflammation preventing the subsequent cytokine storm by inhibiting multiple transcription factors such as nuclear factor kappa B (NF-kB) and signal transducer and activator of transcription 3 (STAT-3), and downregulating the proinflammatory cytokines, as this has been demonstrated in human macrophages after influenza virus infection [4,6]. Additionally, curcumin inhibits ACE modulating angiotensin II synthesis and downregulating inflammation, while it also promotes fibrinolysis and the anticoagulation process [4,6,7] (Fig. 1). The antiviral actions of curcumin against multiple viruses (influenza and hepatitis viruses, herpes viruses, human papilloma virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus and other coronaviruses), bacteria and fungi have been established by experimental evidence [8]. Remarkably, recent evidence from in silico studies has demonstrated that curcumin prevents SARS-CoV-2 entry into cells by blocking the viral binding sites and the cell ligands (spike protein, ACE-2 receptors and basigin), downregulating trans-membrane serine protease 2 (TMPRSS-2), and by interfering with viral replication through the interaction with various viral proteins [4]. However, the minimal absorption of curcumin following oral administration presents a major limitation in its bioavailability [6].
Bromelain is a cysteine protease, isolated from the pineapple stem (Ananas comosus) [9]. Traditionally, it has been used for its anti-inflammatory and healing effects in cases of arthritis and injury, while it has been approved in Europe for the debridement of burn wounds. Experimental studies have demonstrated that bromelain presents unique immunomodulatory actions: 1) downregulation of the pro-inflammatory prostaglandin E2 (PGE-2) through inhibition of NF-kB and cyclooxygenase 2 (COX-2); 2)upregulation of the anti-inflammatory PGE-1; 3) activation of inflammatory mediators (interleukin 1b, interleukin-6, tumor necrosis factor-a and interferon-g) as an acute response to cellular stress, but also inhibition of inflammatory mediators in states of overt cytokine production; 4) modulation of T cell responses in vitro and in vivo; and 5) enhancement of T-cell dependent antigenspecific B cell antibody responses [5,10e14]. Importantly, bromelain exerts dose-dependent anticoagulant effects: 1) downregulation of PGE-2 and thromboxane A2 (TXA2), thus leading to relative excess of prostacyclin; 2) promotion of fibrinolysis by stimulating the conversion of plasminogen to plasmin and prevention of platelet aggregation. Bromelain also hydrolyzes bradykinin and reduces kininogen and bradykinin levels in serum and tissues, improving inflammation and edema as shown in animal studies [15]. Notably, the latter action supports a potential role of bromelain in alleviating COVID-19 symptoms such as cough, fever and pain, and the more serious implications of inflammation, thrombosis and edema. The effect of bromelain on PGE-2 inhibition exceeds that of prednisone and aspirin, presenting very low toxicity and no major side effects. Interestingly, a recent experimental study demonstrated that bromelain inhibits infection of VeroE6 cells by SARS-CoV-2 through blocking the virus binding and entry into cells via downregulation of ACE-2 and TMPRSS2 expression, and cleavage of the SARS-CoV-2 spike protein, presenting a novel promising therapeutic option that warrants further investigation.
In summary, the combination of curcumin and bromelain are well positioned as supplements in people who are getting repetitive COVID-19/Spike protein exposure. Future randomized trials will elucidate the clinical benefits in specific applications.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661945/
Nattokinase in the Prevention and Treatment of Atherosclerotic Cardiovascular Disease
Human Data Promising as Supplement Widely Used in Post COVID-19 and Vaccine Injury Syndromes
By Peter A. McCullough, MD, MPH
Approximately 15% of Americans who took a COVID-19 vaccine have some new medical illness and regret the shot. Many are looking to nattokinase in formulations of Spike protein support supplements asking is it safe, and what is the track record for this Asian discovery?
Chen et al reviewed human studies before the pandemic on the use of nattokinase with this introduction: “Natto, a cheese-like food made of soybeans fermented with Bacillus subtilis, has been consumed as a traditional food in Asian countries for more than 2000 years. Natto consumption is believed to be a significant contributor to the longevity of the Japanese population. Recent studies demonstrated that a high natto intake was associated with decreased risk of total CVD mortality and, in particular, a decreased risk of mortality from ischaemic heart diseases. Before the 1980s, very little was known about the mechanism by which natto consumption led to overall cardiovascular health. In 1987, Sumi et al discovered that natto contained a potent fibrinolytic enzyme called nattokinase (NK). Since then, a considerable amount of NK research has been performed on NK in Japan, Korea, China, and the United States, and these studies confirmed that NK, an alkaline protease of 275 amino acid residues with a molecular weight of approximately 28 kDa, is the most active ingredient of natto and is responsible for many favourable effects on cardiovascular health. First, NK has potent fibrinolytic/antithrombotic activity. In addition, in both animal and human studies, NK also has an antihypertensive, anti-atherosclerotic, lipid-lowering, antiplatelet/anticoagulant, and neuroprotective actions…The most unique feature of NK is that, as a single compound, it possesses multiple CVD preventative and alleviating pharmacologic effects (namely, antithrombotic, antihypertensive, anticoagulant, anti-atherosclerotic, and neuroprotective effects). There are no other drugs or drug candidates with multiple pharmacologic properties similar to NK. In addition, NK is a natural product that can be administered orally, has a proven safety profile, is economical to use, and provides distinct advantages over other pharmaceutical products.”
In drug development, the most important early observations are on safety. There are two units used in nattokinase dosing, e.g. 100 mg=2000 fibrinolytic units (FU). In the table, Lampe et al in 2016 tested nattokinase up to 10 mg/kg/day (~160,000 FU for an 80 kg person). That means in doses of 100 mg or 2000 FU twice a day are well within a safety range to avoid significant toxicities.
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In summary this review is reassuring that the ever increasing use of nattokinase in post-COVID-19 and after COVID-19 vaccine injuries is safe and reasonably well tolerated. There may be additional benefits on the cardiovascular system. There is a pressing need for continued clinical development for the COVID-19 and cardiovascular indications. Patients wanting to use the supplement ahead of the emerging science should discuss with a knowledgeable healthcare professional and be on alert for intolerances, allergic reactions, or bleeding complications.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043915/
https://www.twc.health/collections/covid...ul-formula
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Prescription and Over-the-Counter Treatments for Post-COVID Syndrome
Long List of Possibilities with Early Data Published
Over three years into the pandemic with nearly the entire country having become sick with SARS-CoV-2, a virus engineered to invade the body, there are millions suffering with long-hauler syndrome. Approximately half of patients admitted to the ICU with COVID-19 will have post-COVID syndrome which is now understood to be due to persistence of the SARS-CoV-2 Spike protein within cells, tissues, and organs. Those vaccinated have been additionally loaded with Spike, so may have even a worse course with prolonged symptoms including fatigue, lethargy, brain fog, muscle loss, skin and hair changes, sleeplessness, and effort intolerance. The magnitude of the problem has driven an all-encompassing search for management strategies to resolve the syndrome(s).
Hope is on the horizon with a preprint paper published by Halma et al summarizing the prescription drug and over-the-counter candidates for therapy. In my practice, I stylize the approach based on the patient and how recent the COVID-19 infection was in their history. If there are lingering signs of infection, then a course of full dose ivermectin can be considered. Aspirin is reasonable given increased rates of heart attack and stroke after the illness. I have found the colchicine appears to have an important role in pleurodynia or chest wall discomfort. Additionally it is used with corticosteroids in vaccine-induced myopericarditis. Low-dose naltrexone has been reported to ameliorate fatigue and inanition. Metformin has supportive data and would be appropriate in pre-diabetes and those with diabetes mellitus.
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From the OTC list, I have found nattokinase, the Japanese product derived from natto (a traditional Japanese food made from whole soybeans that have been fermented with Bacillus subtilis var. natto.) to be the most compelling and scientifically supported approach to clear Spike protein out of the body via proteolytic degradation. A host of cellular protective, anti-oxidant approaches are listed with vitamin C and NAC being readily available and widely used.
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Halma, M.T.; Plothe, C.; Lawrie, T. Strategies for the Management of Spike Protein-Related Pathology. Preprints 2023, 2023030344. https://doi.org/10.20944/preprints202303.0344.v1.
Patients should push their doctors to refer them to clinical trials, and when that is not feasible, then empiric therapy can be pursued. It is important to realize that in the absence of completed large randomized placebo controlled randomized trials, which are easily 5 or more years away in the future, no therapeutic claims can be made. In the meantime we must be perceptive as patients and open-minded as clinicians to come up with reasonable approaches that can be used to help those sick now with post-COVID syndromes.
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https://www.preprints.org/manuscript/202303.0344/v1
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Which Virus Will Cause the Next Pandemic?
Experts Predict Virus Will Be Airborne--Narrows Field Considerably
We are constantly being barraged by fear-mongering messages about a “next pandemic” as if new global catastrophes have been put on a schedule. I have remarked that it would be quite difficult to anticipate an organism arriving from nature and afflicting the entire world’s population of any mammal, let alone man.
Neumann and Kawaoka published a review of past pandemics, a broad list of viral threats, and then indicated that the likely winner would be a zoonosis (virus that jumped from a bat or rodent) to a human. Additionally, for human to human spread it would need to be airborne and highly contagious. We learned with the fizzled Monkeypox scare that homo- bi-sexual transmission from man to man was not enough the scare the world into mass vaccination or hold the public captive very long in the news cycle. President Biden dropped the US Monkeypox Emergency in January 31, 2023 with no press release.
The list of possibilities for future pandemics is listed in the table. Most have no antiviral therapy that is specific, however, the authors fail to mention viricidal nasal sprays/gargles, vitamin D, curcumin, hydroxychloroquine, ivermectin, favipiravir, famotidine, or other agents to mitigate viral specific inflammation such as maraviroc and nonspecific agents including corticosteroids and colchicine.
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The authors outline these steps to get ready: “To prepare for future pandemics, the international research community needs to continue and further strengthen research efforts in various areas, including the following: (i) cataloging the landscape and animal reservoirs of (human-infecting) viruses through surveillance and metagenomics; (ii) development of animal models for viruses that may cause pandemics; (iii) basic research to better understand the molecular virology of such viruses; (iv) early stage vaccine development and testing in animal models; and (v) development of broad antivirals as a first line of defense. The US National Institute of Allergy and Infectious Diseases has suggested that prototype pathogens (selected from virus families that may cause pandemics) be selected for basic research and early stage development of countermeasures. With reasonable resources and advanced technologies, the global community could be much better prepared for future pandemics.
I am cautious about the terms “animal models” “prototype pathogens” “vaccine” or “countermeasure” as these were the words used by the NIH, HHS, and the Cares Act disastrous COVID-19 pandemic response. I suggest we focus on readiness with an arsenal of nasal viricidal washes and gargles to PREVENT the upper respiratory illness as the main measure of contagion control. Solutions of dilute iodine, hydrogen peroxide, xylitol, colloidal silver, and other compounds alone or in combination should serve well for any of the viral threats listed.
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From the authors (v) “broad antivirals” with adjunctive treatment will be the next line of defense since they will be readily available, scalable, and far more important to large numbers of sick patients instead of vaccines for well persons.
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