Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246018/

Since the outbreak of COVID-19 caused by SARS-CoV-2, we tested 5 different blood specimens that were confirmed positive for SARS-CoV-2 IgG and IgM antibodies [1]. The measurements were for anti-nuclear antibody (ANA), anti-extractable nuclear antigen (ENA), anti-double-stranded DNA (dsDNA), actin antibody, mitochondrial antibody, rheumatoid factor (RF), and C1q immune complexes. We were surprised to find out that 3 of the 5 specimens had significant elevations in ANA, ENA, actin and mitochondrial antibodies, but not against dsDNA or RF. This prompted us to investigate patterns of cross-reactivity between SARS-CoV-2 and autoimmune target proteins.

Vaccine-induced autoimmunity from autoimmune cross-reactivity is associated with narcolepsy, Guillain-Barré syndrome, multiple sclerosis, demyelinating neuropathies, systemic lupus erythematosus, and postural orthostatic tachycardia syndrome in susceptible subgroups as reported by Segal and Shoenfeld [2]. Due to the significant red flags for the potential cross-reactive interactions with the current COVID-19 pandemic, we studied the relationships between spike and nuclear proteins of SARS-CoV-2 and autoimmune target proteins.

Commercially available mouse monoclonal antibody made against recombinant SARS coronavirus spike protein and rabbit monoclonal antibody made against SARS coronavirus nucleoprotein were applied at optimal dilution to the SARS-CoV-2 proteins and to 50 different tissue antigens using enzyme-linked immunosorbent assay (ELISA). Recombinant SARS-CoV-2 spike protein S1 and recombinant SARS-CoV-2 nucleocapsid protein were purchased from RayBiotech. ELISA wells were coated with nuclear antigens, dsDNA, F-actin, and mitochondria (M2) antigen purchased from different companies. An additional 45 tissue antigens used in this study have been previously described [9]. Each SARS-CoV-2 antibody was applied to quadruplicate wells. After the completion of all ELISA steps, the developed color was measured at 405 nm.

Looking at the reaction between SARS-CoV-2 spike protein antibody and tissue proteins (Fig. 1A), we found that the strongest reactions were with transglutaminase 3 (tTG3), transglutaminase 2 (tTG2), ENA, myelin basic protein (MBP), mitochondria, nuclear antigen (NA), α-myosin, thyroid peroxidase (TPO), collagen, claudin 5+6, and S100B. The reaction of this antibody was not as strong with several other antigens (Fig. 1A).

Fig. 1

Fig. 1

(A) Reaction of anti-SARS-CoV-2 spike protein monoclonal antibody with human tissue antigens. (B) Reaction of anti-SARS-CoV-2 nucleoprotein monoclonal antibody with human tissue antigens.

The nucleoprotein antibody showed some overlap in immune cross-reactivity with anti-spike protein antibody. As shown in Fig. 1B, nucleoprotein antibody reacted strongly with mitochondria, tTG6, NA, TPO, ENA, TG, actin, and MBP. Similar to spike protein, the nucleoprotein antibody reaction was not as strong with several other antigens as shown in Fig. 1A and B.

As the number of SARS-CoV-2 infections increase from day to day, scientists are learning that the damage caused by this virus can extend well beyond the lungs, where infection can lead to pneumonia and the often fatal condition called acute respiratory distress syndrome [3]. The virus can in fact affect the body from head to toe, including the nervous [4], cardiovascular [5], immune [6], and digestive systems [7].

Is it possible that some of the extensive organ, tissue, and cellular damage done by SARS-CoV-2 is due to viral antigenic mimicry with human tissue?

If the answer is yes, then we may face an increase in the rates of autoimmune disease in the future, because any factor that causes chronic inflammation in the body can potentially induce autoimmune disease.

Because SARS-CoV-2 attacks the respiratory system first, in a very interesting letter [8] Kanduc and Shoenfeld suggested that because the SARS-CoV-2 spike glycoprotein and lung surfactant proteins shared 13 out of 24 pentapeptides, the immune response following infection with SARS-CoV-2 may lead to cross-reactions with pulmonary surfactant proteins, followed by SARS-CoV-2-associated lung disease [8]. Based on their findings, they warned against the use of the entire SARS-CoV-2 antigens in the vaccines and cautioned that perhaps the use of only unique peptides would be the most effective way to fight the SARS-CoV-2 infection. Very similar suggestions were made by Razim et al., in designing a vaccine against Clostridium difficile [9]. Two sequences, peptide 9 and peptide 10, of C. difficile were recognized not only by the sera of patients with C. difficile infections but also by the sera of patients with autoimmune disease. Razim et al. concluded that before considering a protein as a vaccine antigen, special care should be taken in analyzing the sequence of tissue cross-reactive epitopes in order to avoid possible future side effects [9].

We agree with Razim et al., and we feel that our own findings that 21 out of 50 tissue antigens had moderate to strong reactions with the SARS-CoV-2 antibodies are a sufficiently strong indication of cross-reaction between SARS-CoV-2 proteins and a variety of tissue antigens beyond just pulmonary tissue, which could lead to autoimmunity against connective tissue and the cardiovascular, gastrointestinal, and nervous systems.

We live in critical times when the world may be veering towards the very real possibility of requiring immunity certification “passports” earned by prior infection with SARS-CoV-2 or vaccination before being allowed to travel, or perhaps even to work [10].

At the moment, scientists are frantically trying to develop either a definitive cure, neutralizing antibodies, or a vaccine to protect us from contracting the disease in the first place, and they want it right now. We must consider that finding a vaccine for a disease may normally take years. There are reasons for all the precautions involved in developing a vaccine, not the least of which are unwanted side-effects. In light of the information discussed above about the cross-reactivity of the SARS-CoV-2 proteins with human tissues and the possibility of either inducing autoimmunity, exacerbating already unhealthy conditions, or otherwise resulting in unforeseen consequences, it would only be prudent to do more extensive research regarding the autoimmune-inducing capacity of the SARS-CoV-2 antigens. The promotion and implementation of such an aggressive “immune passport” program worldwide in the absence of thorough and meticulous safety studies may exact a monumental cost on humanity in the form of another epidemic, this time a rising tide of increased autoimmune diseases and the years of suffering that come with them.Go to:

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Go to:

Declaration of Competing Interest

None.Go to:

References

1. Whitman J.D., Hiatt J., Mowery C.T., Shy B.R., Yu R., Yamamoto T.N. Test performance evaluation of SARS-CoV-2 serological assay. MedRxiv. 2020 doi: 10.1101/2020.04.25.20074856. (preprint) [CrossRef] [Google Scholar]2. Segal Y., Shoenfeld Y. Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction. Cell Mol. Immunol. 2018;15(6):586–594. doi: 10.1038/cmi.2017.151. [PMC free article][PubMed] [CrossRef] [Google Scholar]3. Zhou P., Yang X.-L., Wang X.-G., Hu B., Zhang L., Zhang W. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi: 10.1038/s41586-020-2012-7. [PMC free article] [PubMed] [CrossRef] [Google Scholar]4. Nath A. Neurologic complications of coronavirus infections. Neurology. 2020;94(19):809–810. doi: 10.1212/WNL.0000000000009455. [PubMed] [CrossRef] [Google Scholar]5. Zheng Y.-Y., Ma Y.-T., Zhang J.-Y., Xie X. COVID-19 and the cardiovascular system. Nat. Rev. Cardiol. 2020;17(5):259–260. doi: 10.1038/s41569-020-0360-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]6. Shi Y., Wang Y., Shao C., Huang J., Gan J., Huang X. COVID-19 infection: the perspectives on immune responses. Cell Death Different. 2020;27:1451–1454. doi: 10.1038/s41418-020-0530-3. [PMC free article][PubMed] [CrossRef] [Google Scholar]7. Lin L., Jiang X., Zhang Z., Huang S., Zhang Z., Fang Z. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69(6):997–1001. doi: 10.1136/gutjnl-2020-321013. [PMC free article][PubMed] [CrossRef] [Google Scholar]8. Kanduc D., Shoenfeld Y. On the molecular determinants of the SARS-CoV-2 attack. Clin. Immunol. 2020;215:108426. doi: 10.1016/j.clim.2020.108426. [PMC free article] [PubMed] [CrossRef] [Google Scholar]9. Razim A., Pacyga K., Aptekorz M., Martirosian G., Szuba A., Pawlak-Adamska E. Epitopes identified in GADPH from Clostridium difficile recognized as common antigens with potential autoimmunizing properties. Sci. Rep. 2018;8(1):13946. doi: 10.1038/s41598-018-32193-9. [PMC free article] [PubMed] [CrossRef] [Google Scholar]10. Hall M.A., Studdert D.M. Privileges and immunity certification during the COVID-19 pandemic. JAMA. 2020 May 6 doi: 10.1001/jama.2020.7712. [PubMed] [CrossRef] [Google Scholar]

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Effects on the immune system of a three-month consumption of an extremely diverse probiotic: decrease of serum alpha-N-acetylgalactosaminidase activity, detoxification and gut microbiota normalization

Jerry Blythe1 and Marco Ruggiero2

1Retired Medical Doctor, Indianapolis, IN, USA
2National Coalition of Independent Scholars, San Antonio, TX, USA

Corresponding author Marco Ruggiero, MD, PhD. National Coalition of Independent Scholars, San Antonio, TX, USA

E-mail: marco.ruggiero@ncis.org

Abstract

In this study, we describe the changes associated with the consumption of an extremely biodiverse probiotic yogurt in a 55-year-old female from South Vietnam. In August 2019, the subject voluntarily embarked on a three-month nutritional experience and decided to share her experience with the goal of advancing scientific knowledge in the field of nutritional health. Consumption of this biodiverse probiotic yogurt was associated with a decrease in serum alpha- N-acetylgalactosaminidase (nagalase) activity, increased elimination of toxic metals and non- metal toxicants, a trend toward normalization of the lipid profile, and a trend toward a rebalance of the gut microbiota.

Key words: probiotic yogurt; nagalase; detoxification; toxic metals; microbiome

Introduction

We have previously observed and reported in two recent articles (1,2) that the consumption of an extremely biodiverse probiotic yogurt with a unique microbial composition is associated with detoxification of non-metal toxicants (3), decrease of serum alpha-N- acetylgalactosaminidase (nagalase) activity (3,4), decrease of serum C-reactive protein (CRP) (4), decrease of markers specific for multiple myeloma (5), and a dramatic decrease of viral load in Hepatitis B (6).

In this report, we describe the changes associated with consumption of an extremely biodiverse probiotic yogurt in a 55-year-old female from South Vietnam who presented in August 2019 feeling sometimes feverish at night with morning fatigue for several months.

Subject Information

The subject grew up in South Vietnam during the Agent Orange era and left Vietnam at age 17 as part of the “Boat Migration” in the 1970s. Settling in the United States, she earned a college degree in mathematics and computer sciences, and has worked in the Chicago area the past 35 years. The subject is a Buddhist minister, active in her Temple with several outside business interests. She described hour-long commutes for years to and from downtown Chicago to her alternative medical clinic.

She is not a runner but ran the 2019 Peachtree 10 Km road race in Atlanta on July 4 in 90 degree fahrenheit weather without incident. She is married and raised three children. As a teenager she suffered from severe nutritional anemia with delayed menses until 17 (hemoglobin reported 6 g/dL requiring hospitalization and units of blood). The subject returned to South Vietnam in 2016 and again in 2018. Upon returning from her last trip, she described vague abdominal symptoms and not feeling well.

She reported mold exposure, a common finding living in the midwestern part of the United States. She also reported a persistent mild dry cough, sneezing, and sinus congestion, along with fatigue and a poor sleep cycle.

In 2017 the subject had the flu and was bedridden for 6 weeks. It is worth mentioning that 2017 was a record year for the flu in the United States with a significant number of deaths (7). The subject reported few other lifetime illnesses or problems. In August 2019, the subject voluntarily embarked on a three-month nutritional experience that included consumption of an extremely biodiverse probiotic yogurt, as described in references 3-6.

Study Design and Methodology

The subject provided one of the authors Dr. JB selected laboratory studies from 2016 through 2019 to go along with her current studies with the goal of advancing scientific knowledge in the field of nutritional approaches to health. In addition to using the biodiverse probiotic yogurt

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during her three-month experience, the subject reported taking several supplements including a multi-vitamin, 2000 to 5000 IU vitamin D3 daily, Omega-3, glucosamine and recently a non- prescription thyroid supplement containing vitamins and minerals to assist her morning fatigue. It is worth noting that the supplements were consumed both before and during the experience with the regular consumption of the probiotic yogurt. It is therefore plausible that the observed changes are attributed mainly to the consumption of the probiotic yogurt.

Blood and urine analyses were performed at different times before this study and after the three-month experience. Determination of serum alpha-N-acetylgalactosaminidase (nagalase) activity was performed at the Health Diagnostics and Research Institute (South Amboy, NJ, USA), a consociate of European Laboratory of Nutrients, (Bunnik, The Netherlands); the results are expressed as nMol/mL/min. Blood analyses were performed at Lab Corp (Laboratory Corporation of America) and Quest Diagnostics. Analyses of metal and non-metal toxicants in early morning urine samples were performed at The Great Plains Laboratory Inc. (Lenexa, KS, USA) and were normalized per grams of creatinine. Copies of the original records are conserved at the office of Dr. JB. In this article we describe and discuss only the values that changed during the three-month experience and, for the sake of brevity, we omit discussing the values that did not change.

Consent

Since this is a single case report that does not produce generalizable knowledge, nor is it an investigation of an FDA regulated product, it is accepted that Institutional Review Board (IRB) review is not required for this activity (see, for example, ref. 8). Written informed consent for publication of clinical details and laboratory data was obtained from the subject and it is conserved at the office of Dr. JB.

Results

Serum lipid profile

Comprehensive Metabolic Profile Studies by Lab Corp were performed prior to this experience in 2018 and 2019. A lipid profile in July 2018 showed high triglycerides (375 mg/dL; reference range: 30-150 mg/dL), mildly elevated total cholesterol (231 mg/dL: reference range: <199 mg/dL), and normal blood sugar. Triglyceride values improved to 232 mg/dL over the three- month experience with the probiotic yogurt, and cholesterol fell to 209 mg/dL, only slightly elevated. These results seem to indicate that consumption of the probiotic yogurt was associated with a trend toward normalization of the lipid profile and are consistent with previous observation concerning probiotic yogurts and serum lipids (9).

Serum vitamin D3

Vitamin D3 was quite low in 2017 at 15 ng/ml (reference range: 30-100 ng/ml). Levels improved in 2018 to 37 ng/ml and to 43.5 ng/ml in August 2019, and to 100 ng/ml in December 2019

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following the three-month experience with the biodiverse probiotic yogurt. It is worth mentioning, however, that, since beginning the experience in 2019, the subject began walking outdoors in the sun 30 to 45 min two to three days per week and consumed a 2000 to 5000 IU vitamin D3 supplement. It is plausible, therefore, that the normalization of vitamin D3 values has to be ascribed primarily to consumption of the vitamin supplement and exposure to sunlight with possible contribution from the probiotic yogurt (10).

Serum nagalase activity

Serum nagalase activity was elevated prior to the three-month experience at 1.94 nMol/mL/min (reference range: 0.32 – 0.95 nMol/mL/min). Nagalase activity fell 27.8% after the three-month experience. Nagalase is a marker for inflammation often found elevated in viral infections, cancer and other chronic conditions (4,11,12). These results are consistent with previous observations (3,4) and can be interpreted as consequence of high levels of naturally formed Gc protein-derived Macrophage Activating Factor in the probiotic yogurt as hypothesized since 2011 (13) and elegantly demonstrated in 2020 (4).

Toxic metals in urine

Studies of toxic metals in urine, before and after intravenous (IV) chelation, demonstrated significant improvement associated with consumption of the probiotic yogurt.

Cadmium

Cadmium is a ubiquitous metal toxicant that can have adverse effects on the kidneys. The International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) considers cadmium a Group 1 human carcinogen with prolonged exposure usually through the oral route (food or water). Cadmium is typically found in mining, paints, dyes, metallurgy, soils, and foods, but specifically mentioned is that it can enter rice through the soil and water. It is noted in the subject’s history that she consumes rice on a daily basis and has managed a garment factory for a number of years where she was exposed to dyes.

We previously demonstrated that cadmium may be responsible for the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and for abnormalities of breast cancer cell-induced angiogenesis (14, 15). In the subject, cadmium in the urine exceeded twice the maximum expected value at baseline in August. Pre-provocative (i.e., before IV chelation) baseline levels were high at 2.1 ug/g creatinine (reference interval high: <1 ug/g creatinine). Post-provocative cadmium remained high at 1.7 ug/g creatinine, using the IV chelating agent EDTA, as cadmium was being removed and is suggestive of a fair amount of the metal present in the body of the subject. In December, after completing the three-month experience with the probiotic yogurt, pre-provocative cadmium was 1.8 ug/g creatinine, still high and little changed from August; however, post-provocative cadmium was 2.4 ug/g creatinine, suggesting increased removal of cadmium. Such a removal could be explained

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considering that probiotics, such as those present in the product consumed by the subject, inhibit absorption of cadmium by protecting the intestinal barrier (16).

Lead

Lead levels pre-provocative in August were within a reference interval considered low risk at 0.5 ug/g creatinine. Post-provocative lead was high at 7.5 ug/g creatinine (reference range: < 2 ug/g creatinine), over 3 times the upper limit of the reference interval, suggesting the presence of substantial amounts of lead in the subject’s body that chelation was helping remove. In December, after the three-month experience with the probiotic yogurt, pre-provocative lead was again low risk at 0.7 ug/g creatinine, but post-provocation using a chelating agent, urine lead excretion significantly increased to 17 ug/g creatinine, which is 8.5 times the upper limit, considerably higher than in August and suggesting substantial elimination using both the probiotic yogurt and chelation. These results can be interpreted considering that probiotics, such as those present in the product consumed by the subject, are known to protect against lead toxicity (17) and may enhance lead elimination (18).

Barium

Barium is another toxic metal whose elimination was enhanced concomitant with consumption of the probiotic yogurt. This metal can interfere with calcium and potassium metabolism leading to hypokalemia with tingling of the extremities, loss of tendon reflexes and cardiac stimulation. Baseline pre-provocative barium in August was normal at 1.8 ug/g creatinine (reference range: <7 ug/g creatinine); post-provocative barium was 5.5 ug/g creatinine, suggesting some elimination of barium from the body with chelation. In December, after the three-month experience with the probiotic yogurt, pre-provocative barium remained normal at 3 ug/g creatinine. Post-provocative barium however was slightly elevated at 9.3 ug/g creatinine, suggesting further elimination. The subject remembered swallowing some material before an X-ray a number of years ago, presumably containing barium as a contrast agent, but could not fill in further details. Barium is also found in Brazil nuts, peanuts and peanut butter and certain fast foods, and is also found in seaweed and fish, all foods the subject eats. The working hypothesis is that, after the three-month nutritional program with the probiotic yogurt, barium was being eliminated. These results can be interpreted considering that removal of toxic metals is a common feature of probiotics, such as those present in the product consumed by the subject (19).

Non-metal toxicants in urine

Studies of non-metal toxicants in urine, before and after the three-month experience with the biodiverse probiotic yogurt, demonstrated significant changes for a number of toxicants as described in detail below.

Glyphosate

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Glyphosate is the world’s most widely produced herbicide and is found in runoff waters in agricultural areas. The WHO IARC considers glyphosate a probable Group 1 human carcinogen implicated in diseases as non-Hodgkin lymphoma, renal tubule carcinoma and other pathologies. Glyphosate disrupts the microbiome in the intestine, decreasing the ratio of beneficial to harmful microbes. Consistent with these effects of glyphosate, the subject’s stool sample showed a dysbiotic pattern with the absence of the usually present Lactobacilli strains.

Glyphosate in the subject’s urine showed a moderate presence at 1.35 ug/g creatinine in August. However, glyphosate fell to 0.8 ug/g creatinine, a 40% decline in three months, following the three-month experience with the probiotic yogurt. Beneficial Lactobacilli strains were believed added by the probiotic yogurt with the ratio of expected/beneficial flora registering a two-fold increase for Lactobacillus. These results can be interpreted considering that removal of non-metal toxicants is a well-established feature of probiotics, such as those present in the product consumed by the subject (3,20).

2-hydroxyisobutyric acid

2-hydroxyisobutyric acid (2HIB) in urine was within the reference values at 4,082 ug/g creatinine. 2HIB is an additive to improve vehicle octane ratings and is found in exhaust fumes. 2HIB has been shown to cause liver and kidney toxicity, and cancer in animals. After completing the three-month experience with the probiotic yogurt, urinary excretion of 2HIB rose 94% to 7,912 ug/g creatinine, thus suggesting elimination 2HIB from the body at an increased rate, consistent with well-established features of probiotics.

Perchlorate

Perchlorate (PERC) in urine in August was non-detectable; this result may be interpreted in two ways: a) the subject had not been exposed to PERC and no PERC had accumulated in her body; b) the subject was unable to excrete PERC. The first hypothesis seems less plausible because PERC is a ubiquitous pollutant. In addition to being used in rocket fuel and explosives, it is used in fertilizers and ordinary bleach, and often found contaminating food and water supplies. The second hypothesis was confirmed by the observation that, after completing the three-month experience with the probiotic yogurt, PERC was being excreted in December at 2.7 ug/g creatinine. Therefore, these results may be interpreted as increased excretion of PERC in association with consumption of the probiotic yogurt.

N-acetyl-S-(2-carbamoylethyl)cysteine

N-acetyl-S-(2-carbamoylethyl)cysteine (NAE) in urine was 22 ug/g creatinine in August. Acrylamide is the parent polymer used in industrial processes as plastics, food packaging, cosmetics and dyes. Foods like potato chips and French fries, and cigarette smoke exposure, are major sources. The toxicity occurs because asparagine, an amino acid important for central nervous system function, can produce acrylamide when cooked at high temperatures in the presence of sugars. High levels of acrylamide can elevate a patient’s risk of cancer and cause

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neurological damage. Foods rich in asparagine include asparagus, potatoes, legumes, nuts, seeds, beef, eggs and fish. After completing her three-month experience with the probiotic yogurt, NAE excretion levels increased substantially to 115 ug/g creatinine, well above the 75th percentile, indicating increased removal of this toxicant.

N-acetyl(propyl)cysteine

N-acetyl(propyl)cysteine (NAPR) in urine was moderately elevated in August at 19 ug/g creatinine, well above the 75th percentile. NAPR is an organic solvent and metabolite of 1- bromopropane used in dry cleaning, foam gluing and metal cleaning. It is a neurotoxin associated with sensory and motor deficits, decreased cognitive function, and with acute exposures, headaches. After completing the three-month experience with the probiotic yogurt in December, NAPR was no longer detectable, suggesting that substantial removal of the toxicant through urinary excretion had occurred.

2-hydroxyethyl mercapturic

A similar situation occurred with 2-hydroxyethyl mercapturic acid (HEMA), a toxicant that was detectable in the subject’s urine in August at 0.55 ug/g creatinine. HEMA comes from exposure to ethylene oxide used in agrochemicals, detergents, pharmaceuticals and personal care products. Ethylene oxide is also a sterilizer on rubber, plastics and electronics. Chronic exposure is mutagenic, and ethylene oxide is considered a carcinogen with increased incidence of breast cancer and leukemia. HEMA may also develop from exposure to vinyl chloride, an intermediate in the synthesis of these chemicals. These exposures have been associated with autism, headache, dizziness, liver damage and cancer. After completing the three-month experience with the probiotic yogurt in December, HEMA was no longer detectable, suggesting that substantial removal of the toxicant through urinary excretion had occurred.

Diethylphosphate

Diethylphosphate (DEP) in urine was moderately elevated in August at 3.7 ug/g creatinine. Organophosphates such as DEP are among the most toxic groups of substances in the world, and are primarily found in pesticide formulations. 85% of households in United States store at least one pesticide. These cholinesterase inhibitors cause sweating, salivation, diarrhea, and both depression and aggressive behavior. Autism spectrum disorder is associated with organophosphate exposure (21). It may be worth noting that the subject’s house was sprayed with pesticides in 2019. After completing the three-month experience with the probiotic yogurt in December, DEP was no longer detectable, suggesting that substantial removal of the toxicant through urinary excretion had occurred.

3-Phenoxybenzoic acid

3-Phenoxybenzoic acid (3BPA) in urine was moderately elevated in August at 2.1 ug/g creatinine, well above the 75th percentile. 3BPA is a metabolite of six different pyrethroid

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insecticides. They affect neurological development, disrupt hormones, induce cancers, and suppress the immune system. After completing the three-month experience with the probiotic yogurt in December, 3BPA was no longer detectable, suggesting that substantial removal of the toxicant through urinary excretion had occurred.

Stool analysis and microbiota status

Comprehensive stool analysis showed the absence of beneficial Lactobacillus strains at baseline in August. There were no parasites. Bacteria that are indicators of dysbiosis were present including Klebsiella oxytoca. As described above, toxicology testing found toxicants (Glyphosate) which disrupt the balance of the intestinal microbiota and may have contributed to the observed alterations. After completing the three-month experience with the probiotic yogurt in December, marked improvements were seen with the presence of Lactobacillus strains significantly repopulating the colon in high numbers with positive consequences for immune and other biological functions. Consistent with this observation, Klebsiella oxytoca, an indicator of dysbiosis, significantly decreased after completing the three-month experience.

As far as Short Chain Fatty Acids (SCFA) are concerned, significant results were observed for butyrate that increased 1.78 times (from 3.7% to 6.6% of total SCFA) after completing the three-month experience. It is worth noting that butyrate is produced by microbial fermentation in the colon of humans and animals. It is utilized as not only a primary nutrient that is the source of energy for epithelial cells of the colon, but also as a signaling molecule that regulates multiple functions of cells in the colon and other organs by optimizing gene expression, cell differentiation and tissue development, modulation of the immune system, and reduction of oxidative stress (22).

Discussion

Since this is an open-label, non-controlled, retrospective analysis, caution must be used when ascribing cause and effect to any nutritional approach outcome. However, the response associated with consumption of the probiotic yogurt was robust with regard to nagalase activity reduction, as well as to detoxification and microbiota reconstitution. Despite the short observational time period, the results were substantial and confirm and expand previous observations (3-6).

Reduction of serum nagalase activity is consistent with the observation that the extremely biodiverse probiotic yogurt described in this article has high Gc protein-derived Macrophage Activating Factor activity as demonstrated in recent studies (2,4). In addition to the effects on modulation of macrophage activity, it is worth noting that the probiotic yogurt used in this experience is highly fermented. It is known that the acidity associated with fermentation as well as the proteolytic activity of fermenting probiotics lead to formation of molecules, mainly derived from the hydrolysis of caseins, that have immune-modulatory and anti-oxidant properties (23). These may play an additional role in decreasing the subclinical inflammation associated with the presence of toxicants that in turn might have been responsible for the

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elevated nagalase activity observed prior to the experience described here. Also, the probiotic yogurt used in this study has the unique peculiarity of fermenting bovine colostrum; colostrum is endowed with intrinsic immune-modulating properties (24), and has high levels of vitamin D- binding protein that is the precursor of Gc protein-derived Macrophage Activating Factor (25).

Since nagalase is considered an indicator of cancer cell proliferation, viral infections as well as a marker of systemic inflammation (4,11, 12, 26), and since many of the toxicants described in this article are associated with increased cancer risk, immune dysfunction and chronic inflammation, it is tempting to speculate that decrease of nagalase activity represented a reduction of the risks associated with exposure to those toxicants. In other words, we hypothesize that there are two factors involved in the observed decrease of serum nagalase activity: on one side, the of Gc protein-derived Macrophage Activating Factor activity of the probiotic yogurt, a mechanism thoroughly described in previous studies (4,26); on the other side, the removal of toxicants that might have been responsible for elevated nagalase activity (3).

As far as the observed increased urinary excretion of toxic metals and other toxicants is concerned, the present observations extend and expand the results we first described in 2017 (3). In that article, we described increased urinary excretion of lipophilic toxicants associated with intermittent fasting, weight loss and consumption of the probiotic yogurt; in the present article, we are able to add that consumption of this peculiar probiotic yogurt is associated also with increased excretion of toxic metals and non-lipophilic toxicants such as Glyphosate. It is therefore plausible that the detoxifying effect of the probiotic yogurt is a general one and is not limited to a particular class of toxicants.

It is well assessed that probiotic strains help against metal toxicity by reducing the amount of toxicants in the liver and kidney, and by counteracting alterations in the levels of glutathione peroxidase and superoxide dismutase (27). In addition, probiotic strains may help eliminate toxicants by physical binding (28) as it is the case for lactic acid bacteria in the removal of Aflatoxin B1 (29). Furthermore, the present observations support the hypothesis that detoxification associated with probiotic yogurt consumption may be independent of mobilization of lipophilic toxicants from fat cells as a consequence of intermittent fasting or other weight loss protocols. In our previous article, we had postulated that mobilization of lipophilic toxicants from fat cells as a consequence of weight loss protocols was pre-requisite for their urinary excretion and, in that context, the probiotic yogurt helped by increasing the rate of urinary excretion (3). However, the subject described in this article did not lose any weight. Her body weight remained constant during the three-month experience. Therefore, we can deduce that consumption of the probiotic yogurt mentioned in this study helps with detoxification of all types of toxicants without the need of any further nutritional intervention.

The observed trend toward normalization of the gut microbiota and correction of dysbiosis is a well-known phenomenon associated with consumption of probiotics (30). In the case reported in this article, it may be argued that elimination of Glyphosate, a known disruptor of the healthy gut microbiota, contributed to the trend toward normalization.

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Conclusions

The experience of the subject suggests that the consumption of an extremely biodiverse probiotic yogurt described in references 1 and 2 is associated increased urinary excretion of toxicants, modulation of the immune system, and rebalance of the gut microbiota with overall positive effects on health. The authors wish to emphasize that the data in this case report are from one individual, and not part of a larger study even though they confirm and expand the results observed in other, unrelated, articles (3-6).

Without doubt, the observations described here can be classified as anecdotes. Anecdotes, or informal stories, once were the primary instrument for the advancement of medical knowledge; however, in recent times, anecdotes have less standing. According to this interpretation of the process of knowledge in medicine, controlled experiments such as randomized controlled trials provide medical knowledge while anecdotes do not (31). However, the authors share the convincing argument of the philosopher of science, Robert Nunn, when he challenged the deprecation of anecdotes in medicine since they contribute to the advancement of knowledge in medicine with the same significance of randomized controlled trials with impressive statistics or systematic reviews because “All of these stories become evidence of what works in medicine” (31).

Authors’ Contributions

Jerry Blythe, MD: observed the experience described in this article, provided critical input and assisted in revising and improving the article.

Marco Ruggiero, MD, PhD: wrote the first draft of this article, provided critical input and assisted in revising and improving the article.

Disclosures

Jerry Blythe discloses no conflict of interest. The subject described in this study bought all the foods and supplements used during her experience and paid for the analyses reported in this article.

Marco Ruggiero is the founder of Silver Spring Sagl, the company producing the probiotic yogurt used in this experience and has served as CEO of the company until his retirement in 2020. However, he had no prior knowledge of the nutritional plan followed by the subject of this article nor of the results of the analyses that were communicated by Dr. JB only after completion of the experience.

Ethics

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This article is original and contains material that has not been submitted or published in any other scientific journal.

References

1. Pacini S, Ruggiero M. Natural Plasmids in a Swiss Fermented Milk and Colostrum Product assessed by Microbiome Array. Madridge J Immunol. 2019; 3(2): 100-108. DOI: 10.18689/mjim- 1000123

2. Pacini S, Ruggiero M. Phage composition of a fermented milk and colostrum product assessed by microbiome array; putative role of open reading frames in reference to cell signaling and neurological development. J Neurol Stroke. 2020;10(2):80‒90. DOI: 10.15406/jnsk.2020.10.00416

3. Blythe J, Ruggiero M, Pacini S. Intermittent fasting and probiotic yogurt consumption are associated with reduction of serum alpha- N-acetylgalactosaminidase and increased urinary excretion of lipophilic toxicants. Madridge J Immunol. 2017; 1(1): 23-27. doi: 10.18689/mjim- 1000107

4. Carter M, Pacini S, Ruggiero M. Consumption of an Extremely Biodiverse Probiotic and a Supplement based on Microbial Chondroitin Sulfate is Associated with Very Low Serum Alpha- N- acetylgalactosaminidase (Nagalase) Activity and Decrease of C-reactive Protein Values. Am J Immunol 2020; 16: 8-18. DOI: 10.3844/ajisp.2020.8.18

5. Antonucci N, Pacini S, Ruggiero M. Use of an Extremely Biodiverse Probiotic and a Supplement Based on Microbial Chondroitin Sulfate is Associated with a Significant Decrease of Serum Free Kappa Light Chains as well as a Trend Toward Normalization of Kappa/Lambda Ratio and of Plasma Cell Bone Marrow Infiltration in a Case of Multiple Myeloma. Am J Immunol 2019; 15: 5-9. DOI: 10.3844/ajisp.2019.5.9

6. Zunaid IR, Pacini S, Ruggiero M. Significance of hydrophobic and charged sequence similarities in sodium-bile acid cotransporter and vitamin D-binding protein macrophage activating factor. bioRxiv 2020. DOI: https://doi.org/10.1101/2020.03.03.975524

7. Harben K, Schuchat A., Jenrnigan D et al. Transcript for CDC Update on Flu Activity. 2020. https://www.cdc.gov/media/releases/2018/t0202-flu-update-activity.html

8. John Hopkins Medicine. 102.3 Organization Policy on Single Case Reports and Case Series. “It is the policy of the Organization that a “single” case report (three or fewer cases) does not require review by the JHM IRB.“. https://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/organization _policies/102_3.html (accessed July 9, 2020)

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9. Cho YA, Kim J. Effect of Probiotics on Blood Lipid Concentrations: A Meta-Analysis of Randomized Controlled Trials. Medicine (Baltimore). 2015;94(43):e1714. doi:10.1097/MD.0000000000001714

10. Rizzoli, R., Biver, E. Are Probiotics the New Calcium and Vitamin D for Bone Health?. Curr Osteoporos Rep 18, 273–284 (2020). https://doi.org/10.1007/s11914-020-00591-6

11. Yamamoto, N, M. Urade, 2005. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus. Microbes Infect. Apr;7(4):674-81. DOI: 10.1016/j.micinf.2005.01.015

12. Yamamoto, N., 2006. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the envelope glycoprotein gp160 of human immunodeficiency virus Type 1. AIDS Res Hum Retroviruses. Mar;22(3):262-71. DOI: 10.1089/aid.2006.22.262

13. Pacini S, Punzi T, Morucci G, Ruggiero M. Macrophages of the mucosa- associated lymphoid tissue (MALT) as key elements of the immune response to vitamin d binding protein- macrophage activating factor. It J Anat Embryol. 2011; 116(1): 136. doi: 10.13128/IJAE-10160 https://www.torrossa.com/en/catalog/preview/2490419

14. Pacini S, Fiore MG, Magherini S, et al. Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Med Hypotheses. 2012;79(3):403-407. doi:10.1016/j.mehy.2012.06.007

15. Pacini S, Punzi T, Morucci G, Gulisano M, Ruggiero M. A paradox of cadmium: a carcinogen that impairs the capability of human breast cancer cells to induce angiogenesis. J Environ Pathol Toxicol Oncol. 2009;28(1):85-88.

16. Zhai Q, Tian F, Zhao J, Zhang H, Narbad A, Chen W. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier. Appl Environ Microbiol. 2016;82(14):4429-4440. Published 2016 Jun 30. doi:10.1128/AEM.00695-16

17. Zhai Q, Yang L, Zhao J, Zhang H, Tian F, Chen W. Protective Effects of Dietary Supplements Containing Probiotics, Micronutrients, and Plant Extracts Against Lead Toxicity in Mice. Front Microbiol. 2018;9:2134. Published 2018 Sep 11. doi:10.3389/fmicb.2018.02134page12image37490816

18.

J Microbiol

Yi YJ, Lim JM, Gu S, et al. Potential use of lactic acid bacteria Leuconostoc mesenteroides aspage12image37502336page12image37486592

a probiotic for the removal of Pb(II) toxicity.

19. Monachese M, Burton JP, Reid G. Bioremediation and tolerance of humans to heavy metals through microbial processes: a potential role for probiotics? Appl Environ Microbiol. 2012;78(18):6397-6404. doi:10.1128/AEM.01665-12

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. 2017;55(4):296-303.page12image37491200

doi:10.1007/s12275-017-6642-x

20. He, F., Zuo, L., Ward, E., and Arciero, P.J. Serum polychlorinated biphenyls increase and oxidative stress decreases with a protein-pacing caloric restriction diet in obese men and women. Int. J. Environ. Res. Public Health; 2017 14: 59. doi:10.3390/ijerph14010059

21. Sagiv SK, Harris MH, Gunier RB, et al. Prenatal Organophosphate Pesticide Exposure and Traits Related to Autism Spectrum Disorders in a Population Living in Proximity to Agriculture [published correction appears in Environ Health Perspect. 2018 Jul 05;126(7):079001]. Environ Health Perspect. 2018;126(4):047012. Published 2018 Apr 25. doi:10.1289/EHP2580

22. Bedford A, Gong J. Implications of butyrate and its derivatives for gut health and animal production. Anim Nutr. 2018;4(2):151-159. doi:10.1016/j.aninu.2017.08.010

23. Ebner, J., Aşçı Arslan, A., Fedorova, M., Hoffmann, R., Küçükçetin, A. and Pischetsrieder, M. Peptide profiling of bovine kefir reveals 236 unique peptides released from caseins during its production by starter culture or kefir grains. J. Proteomics. 2015; 117:41-57. doi: 10.1016/j.jprot.2015.01.005

24. Shing, C.M., Hunter, D.C. and Stevenson, L.M. Bovine colostrum supplementation and exercise performance: potential mechanisms. Sports Med. 2009; 39:1033-1054. doi:10.2165/11317860-000000000-00000

25. Senda, A., Fukuda, K., Ishii, T. and Urashima, T. Changes in the bovine whey proteome during the early lactation period. Anim. Sci J. 2011; 82:698-706. doi:10.1111/j.1740-0929.2011.00886.x

26. Thyer, L., Ward, E., Smith, R., et al. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients. Oncoimmunology. 2013. 2:e25769. doi: 10.4161/onci.25769

27. Majlesi, M., Shekarforoush, S.S., Ghaisari, H.R., Nazifi, S., Sajedianfard, J. and Eskandari, M.H. Effect of probiotic Bacillus coagulans and Lactobacillus plantarum on alleviation of mercury toxicity in rat. Probiotics Antimicrob. Proteins. 2017; Jan 13. doi:10.1007/s12602-016- 9250-x

28. Zoghi, A., Khosravi-Darani, K. and Sohrabvandi, S. Surface binding of toxins and heavy metals by probiotics. Mini Reviews in Med. Chem. 2014; 14:84-98. doi:10.2174/1389557513666131211105554

29. Haskard, C.A., El Nezami, H. S., Kankaanpää, P. E., Salminen, S. and Ahokas, J.T.
Surface binding of Aflatoxin B1 by lactic acid bacteria. Appl. Environ. Microbiol. 2001; 67:3086– 3091. doi: 10.1128/AEM.67.7.3086–3091.2001

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30. Bull MJ, Plummer NT. Part 2: Treatments for Chronic Gastrointestinal Disease and Gut Dysbiosis. Integr Med (Encinitas). 2015 Feb;14(1):25-33. PMID: 26770128; PMCID: PMC4566455.

31. Nunn R. Mere anecdote: evidence and stories in medicine. J Eval Clin Pract. 2011;17(5):920- 926. doi:10.1111/j.1365-2753.2011.01727.x

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Cafe Castellanos Quarentini 2020

Richard and I are doing very well. It helps so much to not have a mortgage!  That was the trade off of coming to Florida.

We bought our house after the shuttle program ended and all the engineers had to move.

it was down to half price and now with Space x & Blue Origin 

there is construction at the Kennedy Space Center and Tesla’s at our post office.  Yeah!

Otherwise, it is small town, big warm oceans, and lots & lots of nature.

It can really rain here.

We are part of the fabric now and zoom has helped so much 

to stay connected with everyone.

If nothing else comes of this, we know we can be together.

We should indulge ourselves to zoom socially as well.

The kids are doing well.

Ben, My oldest just turned 30.  He is a commercial pilot and flight instructor in San Diego.

He is back to work and very busy again.

Tiffany is a hair stylist in the Gas Lamp district and together they started a mail box

business for custom hair treatment.  Ko just turned 4. 

unknown.tiff

Michael and Sydney, aka “The Tall Beauties” are 28 yrs old. “Corona in the City” shut down fine dining where Michael is a 3 Michelin Star chef at La Bernadine.

Michael’s restaurant asked him if he wanted to handle a private party in the Hampton’s as he has done in the past. But this time, he did so under his own name as a chef and is actualizing his value as the community welcomed them and their work with open arms. I think they had a private bidding war. 😉

They packed for the weekend and haven’t been back except to get some more clothes. They have a suite in the multi-million dollar mansion with acres of private beach, golf, pool and chauffeur. Good, eh? 

unknown_1.tiff

In NYC, Michael’s wife Sydney is a manager at Made Nice, a store front and catering arm of Eleven Madison Park (named best restaurant in the world in 2017).

unknown_2.tiff

Currently, Michael and Sydney are exploring how to balance family and career. This summer offers some interesting alternatives including a pastry shop in town in the Hamptons.

Pasted Graphic.tiff

Life is rich for us in our casa and our hearts. 

We have just done parts of our yard over.  The organic veggie gardens and hydroponics for micro greens and quick herbs like parsley & cilantro are in place.

I am busy at work as a national distributor for health products from Switzerland that are outstanding in action and quality. There is a nano sized fatty acid, vitamin D, vegan chondroitin sulfate product that cleans out and turn up the body function of the imune system, detox system and digestion with “off the chart” action. We need professional help getting the word out and growing our company.

We are also building a patio and summer kitchen. Which is lots of fun.

Richard is immersed in the space program, playing the piano, and his meditation and routine of course. He is working as a tour guide at the space center visitor’s complex and we want you all to come visit. He is the commentator to the crowd at the launches and is the assistant to the astronauts when they come and do special lunch engagements with the crowd. He has found his nerd herd.

unknown_3.tiff

We love being grandparents!

🙂
Richard & Mimi

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Edestiny: Autism One 2020 with Dr. Marco Ruggiero, MD, Ph. D

Autism One 2020  with Dr. Ruggiero

It is not simple to introduce such a diverse and brilliant man as Dr. Marco Ruggiero MD, Ph.D.  He is a molecular biologist, researcher specializing in immunity.  He and his lovely wife Dr. Stefania Pucini came to live in the United States from Florence, Italy.  

Dr. Ruggiero is the inventor of Bravo Yogurt, imuno The Solution, and Edestiny.  Here we get our education on this fascinating subject of creating more immunity with molecular level augmentations to the immune environment.  He explains the use of probiotics and fermented proteins together to increase a new potential of immunity.  

I know that I spend a lot of time holding the energy and peace around these doctors, their products and the movement of immunity that Dr. Marco & Dr. Stefania has been creating. I have been hearing about the excitement of this paring between probiotics and highly energetic proteins and the search for the right combination from the customers whispering for five years now. I look forward to learning the deepest intricacy of the culmination of this project. 

Please join me in holding the energy for these lovely doctors, celebrating their efforts to create great and very new ideas for our health, and for doing the work with authorities to give us the opportunity to use them ourselves.

Thank you doctors.  🙏🏻

Due to the Coronavirus emergency, the conference was held virtually. Purchase of the entire series is available at: https://go.autismonevirtualsummit.org

The Title of the Presentation: A Novel Strategy Combining the Benefits of an Original Vegetal GcMAF with the Benefits of Hemp Fermentation and the Presence of a Unique Array of Probiotics and Phages. A talk by Marco Ruggiero MD PhD


Article 1

Front. Hum. Neurosci., 15 January 2014 | https://doi.org/10.3389/fnhum.2013.00934

A new methodology of viewing extra-axial fluid and cortical abnormalities in children with autism via transcranial ultrasonography

James Jeffrey Bradstreet1,2,3*, Stefania Pacini4 and Marco Ruggiero5,6

https://www.frontiersin.org/articles/10.3389/fnhum.2013.00934/full

Article 2

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The Bravo Microbiome

mimi@bravocoop.com

Our bodies contain 30 trillion human cells and even more microbial cells.  A ratio of 1 to 1.3!  The  microbiome is half of the volume of us and includes 39 trillion (non-human) cells.  By the time we are 21, we have a unique microbiome to support each organ.  We also have a collection of slow growing viruses which have not been sufficiently cleaned out by going back to school or work too early.  With a healthy lifestyle of the basics, food, sleep exercise, sunshine, and love; disease microbes only occur in small numbers.  We are finding that the microbiome is highly beneficial and without it we couldn’t exist.

I heard about the microbiome and how we were supposed to take probiotics after antibiotics but I couldn’t feel the differences.  I did feel a bit of a brightening by probiotics and dutifully kept after them.  I even cultured my own for a while.  Eventually, I just thought I was wasting my time,  money, and I didn’t feel much better.  That changed for me when I started taking Bravo Yogurt.   I felt a big change.  It wasn’t just a structural change, but a functional one and emotional one as well.  I sent the beings love and they loved me back.  It was pretty easy “puppy love” and I learned to give myself and my microbiome the attention and help that I assumed was needed.  I assumed right.

I feel things before others like the canary in the coal mine.  If you don’t feel what I feel, find a way that works for you to understand.  The first thing that I felt was the Bravo Yogurt spread out in my gut after swallowing it and it was attaching itself to the gut wall in a very small layer.  I was super surprised by the level of action it had.  It felt like a queasiness when the yogurt connected into my mucosa wall because it was 10 AM and I was bouncing around doing lots of active things at work.  It felt like a very active shimmering material that cleans.  Like a large cleaning crew.  And it also has the quality of a hand lotion where it can be excessive and if it spreads out, it’s going to detox and clog the drain.   Therefore, the instructions say to start slowly for this reason.  Clear the drains first of toxins and inflammation so that it’s easier to clean and remove the debris.

Now I understand much more about that first moment.  I now realize that the gut has many moods.  When we are in the resting state, or the parasympathetic state, the gut is open and receptive.  This queasiness would have never happened if I was sleepy when I took it.  It happened because it was trying to attach to moving target.  I now understood the openness of the gut when it is in the parasympathetic state.  So I ask people take it when they are sleepy for the first few days.

As I am taking the Bravo yogurt over the next few months and even years, it began to repair me.  It seems to know where my physical gut weaknesses are and has a sense of priority. Over the first six months, viruses would get burned up in a specific area when I sat down to use my computer at the end of the afternoon.  Always in random areas, and always it felt like a 10% response to the virus.  I believe that virus was being removed.   Next, so many new behaviors came in.  Not being sleepy, much more confidence, getting through lots of work and being ready for more.  It was impressive.

I definitely remembering muttering to myself that this or that behavior was new.  It was a change in my capacity!  I did this amazing amount of work without seemingly putting out that much effort. I remember realizing I could think better, as in how I could think 40 years ago. Other people would tell me that they felt this for themselves too.  That reinforced that what was happening to me was coming from the yogurt and not some random good luck or other factors.  And the flip side was true as well.  I learned it isn’t a good idea to take antibiotics because it kills ALL of it.  It took me months to get back up after that.  And while I didn’t have a microbiome?  Ouch.  All my super powers were out the window.  I vowed to tell the world about how important it is to NOT take antibiotics.

Scientists are just beginning to understand that humans couldn’t exist without our symbiotic partners.   This newly accepted discovery is opening the eyes of the medical researchers specifically about the gut as a source of goodness but they also say that it is the epicenter of most of many diseases.  I like the idea of setting a trend to balance the microbes of the body.   I believe that the energy we use to build our lives and take care of ourselves is the energy that we live in ultimately.  Like a big energetic fish tank.  If the fish are sick, you don’t give medicine to the fish you change and care for the water, the environment, thus remaining healthy, well and vibrant.

What is important to me is that Bravo Yogurt is a natural, organic, &  additive-free product. (provided you have a good quality milk that isn’t ultra-pasteurized)  The Bravo Microbiome supports my immune functions, gut health, and brain health by insulating & giving it nutrition.  When I give my body what it need, it feels wealthy & loved.  In Dr. Ruggiero’s research to learn about immunity, he learned how it is first establishes itself in the human baby.  He realized the significance of breast milk and went about recreating the “original conditions”  of having a healthy immunity  installed in increments over months and years of breast feeding.  Bravo Yogurt which feeds and constantly reseeds the microbiome garden inside us.

The Bravo Microbiome is not like other microbiomes.  All forms of microbiomes  will reconstitute a healthy human microbiome provided you are using healthy strains.  What is unique about the Bravo Microbiome, is that Dr. Ruggiero created it with a specific intention to balance and turn on the function of starting up the immune system.  I am sure that over time, it restores and renovates the gut back to full function and is responsive enough to adapt to the highest priority.

The ratios of ingredients in the Bravo Yogurt are natural yet they are also tweaked.  Not only does it include ingredients like kefir and colostrum and pre-biotics to house & feed a healthy microbiome, but Bravo yogurt has a diverse culture of over 100 different types of beneficial microbes.  The Bravo Microbiome is refreshing to the body.   The ratio of ingredients nurtures the body specifically to optimize the immune system which exists independently in may places of the body and can also be tampered with by viruses who incrementally interfere in these areas creating an environment more advantageous to the predatory microbes of disease.  This recovery is ongoing and Bravo is a good long term strategy.

As an immunologist and pioneer, Dr. Ruggiero’s intention was specifically to create a microbiome which provides a microbiome to create GcMAF (scientifically known as Gc protein-derived macrophage activating factor). GcMAF is a protein which specifically turns on the immune system.  After years of study and research on immunity with diseases such as HIV+, Dr. Ruggiero realized the ability to assist in the relationship between the immune system, its occasional lack of vigor, and the action of predatory viral microbes, their biofilms and communication interferences.  This is not an easy accomplishment and requires many layers of analysis at the same time!     He created Bravo Yogurt to encourage a natural and alternative alignment that the body can use to restore a healthy balance in the gut and supply the needed bridge for the creation of GcMAF.

In addition to the Bravo Microbiome making GcMAF, the healthy human microbiome competes for territory with the pathogenic microbes.   The Bravo Microbiome is routinely strengthened  by taking Bravo Yogurt and by protecting its balance by eating foods such as lots of dark green leafy vegetables, not flooding yourself with other yogurts, kefir, etc. and learning to live a life style that stays well without antibiotics.  We can consistently decrease the issues in our body and establish a healthy, vital and joyful balance by maintaining an ongoing Bravo Microbiome.

Get started on your Bravo Microbiome here

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The Big Cycles Over The Last 500 Years

by Ray Dalio 
NEWSLETTER ON LINKEDIN Principled Perspectives  By Ray DalioThe Big Cycles Over The Last 500 YearsNote: To make this an easier and shorter article to read, I tried to convey the most important points in simple language and bolded them, so you can get the gist of the whole thing in just a few minutes by focusing on what’s in bold. Past chapters from the series can be found here: IntroductionChapter 1 and Chapter 2. Additionally, if you want a simple and entertaining 30-minute explanation of how what a lot of what I’m talking about here works, see “How the Economic Machine Works,” which is available on YouTube.In Chapter 1 (“The Big Picture in a Tiny Nutshell”), I looked at the archetypical rises and declines of empires and their reserve currencies and the various types of powers that they gained and lost, and in Chapter 2 (“The Big Cycle of Money, Credit, Debt, and Economic Activity”) and its appendix (“The Changing Value of Money”) I reviewed the big money, credit, and debt cycles.  In this chapter, I will review the rises and declines of the Dutch, British, and American empires and their reserve currencies and will touch on the rise of the Chinese empire. While the evolution of empires and currencies is one continuous story that started before there was recorded history, in this chapter I am going to pick up the story around the year 1600.  My objective is simply to put where we are in perspective of history and bring us up to date.  I will begin by very briefly reviewing what the Big Cycle looks like and then scan through the last 500 years to show these Big Cycles playing out before examining more closely the declines of the Dutch and British empires and their reserve currencies.  Then I will show how the decline of the British empire and the pound evolved into the rise of the US empire and US dollar and I will take a glimpse at the emergence of the Chinese empire and the Chinese renminbi.That will bring us up to the present and prepare us to try to think about what will come next.  The Big Cycle of the Life of an EmpireJust as there is a human life cycle that typically lasts about 80 years (give or take) and no two are exactly the same but most are similar, there is an analogous empire life cycle that has its own typical patterns.  For example, for most of us, during the first phase of life we are under our parents’ guidance and learn in school until we are about 18-24, at which point we enter the second phase.  In this phase we work, become parents, and take care of others who are trying to be successful.  We do this until we are about 55-65, at which time we enter the third phase when we become free of obligations and eventually die.  It is pretty easy to tell what phases people are in because of obvious markers, and it is sensible for them to know what stages they are in and to behave appropriately in dealing with themselves and with others based on that.  The same thing is true for countries.  The major phases are shown on this chart.  It’s the ultra-simplified archetypical Big Cycle that I shared in the last chapter. No alt text provided for this imageIn brief, after the creation of a new set of rules establishes the new world order, there is typically a peaceful and prosperous period.  As people get used to this they increasingly bet on the prosperity continuing, and they increasingly borrow money to do that, which eventually leads to a bubble.  As the prosperity increases the wealth gap grows.  Eventually the debt bubble bursts, which leads to the printing of money and credit and increased internal conflict, which leads to some sort of wealth redistribution revolution that can be peaceful or violent.  Typically at that time late in the cycle the leading empire that won the last economic and geopolitical war is less powerful relative to rival powers that prospered during the prosperous period, and with the bad economic conditions and the disagreements between powers there is typically some kind of war.  Out of these debt, economic, domestic, and world-order breakdowns that take the forms of revolutions and wars come new winners and losers.  Then the winners get together to create the new domestic and world orders.  That is what has repeatedly happened through time.  The lines in the chart signify the relative powers of the 11 most powerful empires over the last 500 years.  In the chart below you can see where the US and China are currently in their cycles.  As you can see the United States is now the most powerful empire by not much, it is in relative decline, Chinese power is rapidly rising, and no other powers come close.  No alt text provided for this imageBecause that chart is a bit confusing, for simplicity the next chart shows the same lines as in that chart except for just the most powerful reserve currency empires (which are based on an average of eight different measures of power that we explained in Chapter 1 and will explore more carefully in this chapter).No alt text provided for this imageThe next chart offers an even more simplified view.  As shown, the United States and China are the only two major powers, you can see where each of their Big Cycles is, and you can see that they are approaching comparability, which is when the risks of wars of one type or another are greater than when the leading powers are earlier in the cycle.  To be clear, I didn’t start out trying to make an argument and then go looking for stats to support it; doing that doesn’t work in my profession as only accuracy pays.  I simply gathered stats that reflected these different measures of strength and put them in these indices, which led to these results.  I suspect that if you did that exercise yourself picking whatever stats you’d like you’d see a similar picture, and I suspect that what I’m showing you here rings true to you if you’re paying attention to such things. For those reasons I suspect that all I am doing is helping you put where we are in perspective.  To reiterate, I am not saying anything about the future.  I will do that in the concluding chapter of this book.  All I want to do is bring you up to date and, in the process, make clear how these cycles have worked in the past, which will also alert you to the markers to watch out for and help you see where in the cycles the major countries are and what is likely to come next.No alt text provided for this imageThe chart below from Chapter 1 shows this play out via the eight measures of strength—education, innovation and technology, competitiveness, military, trade, output, financial center, and reserve status—that we capture in the aggregate charts.  It shows the average of each of these measures of strength, with most of the weight on the most recent three reserve countries (the US, the UK, and the Dutch).[1]  No alt text provided for this imageAs explained in Chapter 1, in brief these strengths and weaknesses are mutually reinforcing—i.e., strengths and weaknesses in education, competitiveness, economic output, share of world trade, etc., contribute to the others being strong or weak, for logical reasons—and their order is broadly indicative of the processes that lead to the rising and declining of empires.  For example, quality of education has been the long-leading strength of rises and declines in these measures of power, and the long-lagging strength has been the reserve currency.  That is because strong education leads to strengths in most areas, including the creation of the world’s most common currency.  That common currency, just like the world’s common language, tends to stay around because the habit of usage lasts longer than the strengths that made it so commonly used.     We will now look at the specifics more closely, starting with how these Big Cycles have played out over the last 500 years and then looking at the declines of the Dutch and British empires so you can see how these things go.1)    The Last 500 Years in About 4,000 Words The Rise & Decline of the Dutch Empire and the Dutch Guilder In the 1500-1600 period the Spanish empire was the pre-eminent economic empire in the “Western” world while the Chinese empire under the Ming Dynasty was the most powerful empire in the “Eastern” world, even more powerful than the Spanish empire (see the green dashed line and the red solid line in chart 2).  The Spanish got rich by taking their ships and military power around the world, seizing control of vast areas (13% of the landmass of the earth!) and extracting valuable things from them, most importantly gold and silver which were the money of the time.  As shown by the orange line in the chart of the relative standing of the great empires, the Dutch gained power as Spanish power was waning.  At the time Spain controlled the small area we now call Holland.  When the Dutch became powerful enough in 1581, they overthrew the Spanish and went on to eclipse both the Spanish and the Chinese as the world’s richest empire from around 1625 to their collapse in 1780.  The Dutch empire reached its peak around 1650 in what was called the Dutch Golden Age.  This period was one of great globalization as ships that could travel around the world to gain the riches that were out there flourished, and the Dutch, with their great shipbuilding and their economic system, were ahead of others in using ships, economic rewards, and military power to build their empire.  Holland (as we now call it) remained the richest power for about 100 years.  How did that happen?The Dutch were superbly educated people who were very inventive—in fact they came up with 25% of all major inventions in the world at their peak in the 17th century.  The two most important inventions they came up with were 1) ships that were uniquely good that could take them all around the world, which, with the military skills that they acquired from all the fighting they did in Europe, allowed them to collect great riches around the world, and 2) the capitalism that fueled these endeavors.  Not only did the Dutch follow a capitalist approach to resource allocation, they invented capitalism.  By capitalism I mean public debt and equity markets.  Of course production existed before, but that is not capitalism, and of course trade existed before, but that is not capitalism, and of course private ownership existed before, but that is not capitalism.  By capitalism I mean the ability of large numbers of people to collectively lend money and buy ownership in money-making endeavors.  The Dutch created that when they invented the first listed public company (the Dutch East India Company) and the first stock exchange in 1602 and when they built the first well-developed lending system in which debt could more easily be created.  They also created the world’s first reserve currency.  The Dutch guilder was the first “world reserve currency” other than gold and silver because it was the first empire to extend around much of the world and to have its currency so broadly accepted.  Fueled by these qualities and strengths, the Dutch empire continued to rise on a relative basis until around 1700 when the British started to grow strongly.  The numerous investment market innovations of the Dutch and their successes in producing profits attracted investors, which led to Amsterdam becoming the world’s leading financial center; the Dutch government channeled money into debt and some equity investments in various businesses, the most important of which was the Dutch East India Company.At this time of prosperity, other countries grew in power too.  As other countries became more competitive, the Dutch empire became more costly and less competitive, and it found maintaining its empire less profitable and more challenging.  Most importantly the British got stronger economically and militarily in the classic ways laid out in Chapter 1.  Before they had become clear competitors they had military partnerships during most of the 80+ years leading up to the Fourth Anglo-Dutch War.  That changed over time as they bumped into each other in the same markets.  The Dutch and British had lots of conflicts over economic issues.  For example, the English made a law that only English ships could be used to import goods into England, which hurt Dutch shipping companies that had a big business of shipping others’ goods to England, which led to the English seizing Dutch ships and expanding the British East India Company.  Typically before all-out war is declared there is about a decade of these sorts of economic, technological, geopolitical, and capital wars when the conflicting powers approach comparability and test and try to intimidate each other’s powers.  At the time the British came up with military inventions and built more naval strength, and they continued to gain relative economic strength.   As shown in the chart of relative standing of empires shown above, around 1750 the British became a stronger power than the Dutch, particularly economically and militarily, both because the British (and French) became stronger and because the Dutch became weaker.  As is classic the Dutch a) became more indebted, b) had a lot of internal fighting over wealth (between its states/provinces, between the rich and the poor, and between political factions)[2], and c) had a weakened military—so the Dutch were weak and divided, which made them vulnerable to attack.As is typical, the rising great power challenged the existing leading power in a war to test them both economically and militarily.  The English hurt the Dutch economically by hurting their shipping business with other countries.  The British attacked the Dutch.  Other competing countries, most importantly France, took this as an opportunity to grab shipping business from the Dutch.  That war, known as the Fourth Anglo-Dutch War, lasted from 1780 to 1784.  The British won it handily both financially and militarily.  That bankrupted the Dutch and caused Dutch debt and equities, the Dutch guilder, and the Dutch empire to collapse.  In the next section we will look at that collapse up close.  At that time, in the late 18th century, there was a lot of fighting between countries with various shifting alliances within Europe.  While similar fights existed around the world as they nearly always do, the only reason I’m focusing on these fights is because I’m focusing just on the leading powers and these were the leading two.  After the British defeated the Dutch, Great Britain and its allies (Austria, Prussia, and Russia) continued to fight the French led by Napoleon in the Napoleonic Wars.  Finally, after around a quarter-century of frequent fighting since the start of the French Revolution, the British and its allies won in 1815.  The Rise & Decline of the British Empire and the British PoundAs is typical after wars, the winning powers (most notably the UK, Russia, Austria, and Prussia) met to agree on the new world order. That meeting was called the Congress of Vienna.  In it the winning powers re-engineered the debt, monetary, and geopolitical systems and created a new beginning as laid out in the Treaty of Paris.  That set the stage for Great Britain’s 100-year-long “imperial century” during which Great Britain became the unrivaled world power, the British pound became the world’s dominant currency, and the world flourished.  As is typical, following the period of war there was an extended period—in this case 100 years—of peace and prosperity because no country wanted to challenge the dominant world power and overturn the world order that was working so well.  Of course during these 100 years of great prosperity there were bad economic periods along the lines of what we call recessions and which used to be called panics (e.g., the Panic of 1825 in the UK, or the Panics of 1837 and 1873 in the US) and there were military conflicts (e.g., the Crimean War between Russia on one side and the Ottoman empire with a coalition of Western European powers as allies on the other), but they were not significant enough to change the big picture of this being a very prosperous and peaceful period with the British on top.  Like the Dutch before them, the British followed a capitalist system to incentivize and finance people to work collectively, and they combined these commercial operations with military strength to exploit global opportunities in order to become extremely wealthy and powerful.  For example the British East India Company replaced the Dutch East India Company as the world’s most economically dominant company and the company’s military force became about twice the size of the British government’s standing military force.  That approach made the British East India Company extremely powerful and the British people very rich and powerful.  Additionally, at the same time, around 1760, the British created a whole new way of making things and becoming rich while raising people’s living standards.  It was called the Industrial Revolution.  It was through machine production, particularly propelled by the steam engine.  So, this relatively small country of well-educated people became the world’s most powerful country by combining inventiveness, capitalism, great ships and other technologies that allowed them to go global, and a great military to create the British empire that was dominant for the next 100 years.  Naturally London replaced Amsterdam as the world’s capital markets center and continued to innovate financial products. Later in that 100-year peaceful and prosperous period, from 1870 to the early 1900s the inventive and prosperous boom continued as the Second Industrial Revolution.  During it human ingenuity created enormous technological advances that raised living standards and made those who developed them and owned them rich. This period was for Great Britain what “the Dutch Golden Age” was for the Dutch about 200 years earlier because it raised the power in all the eight key ways—via excellent education, new inventions and technologies, stronger competitiveness, higher output and trade, a stronger military and financial center, and a more widely used reserve currency.At this time several other countries used this period of relative peace and prosperity to get richer and stronger by colonizing enormous swaths of the world.  As is typical during this phase, other countries copied Britain’s technologies and techniques and flourished themselves, producing prosperity and, with it, great wealth gaps.  For example, during this period there was the invention of steel production, the development of the automobile, and the development of electricity and its applications such as for communications including Alexander Graham Bell’s telephone and Thomas Edison’s incandescent light bulb and phonograph.  This is when the United States grew strongly to become a leading world power.  These countries became very rich and their wealth gaps increased.  That period was called “the Gilded Age” in the US, “la Belle Époque” in France, and “the Victorian Era” in England.  As is typical at such times the leading power, Great Britain, became more indulgent while its relative power declined, and it started to borrow excessively.As other countries became more competitive, the British empire became more costly and less profitable to maintain.  Most importantly other European countries and the US got stronger economically and militarily in the classic ways laid out in Chapter 1.  As shown in the chart of the standing of empires above, the US became a comparable power economically and militarily around 1900 though the UK retained stronger military power, trade, and reserve currency status, and the US continued to gain relative strength from there.From 1900 until 1914, as a consequence of the large wealth gaps, there became 1) greater arguments about how wealth should be divided within countries and 2) greater conflicts and comparabilities in economic and military powers that existed between European countries.  As is typical at such times the international conflicts led to alliances being formed and eventually led to war.  Before the war the conflicts and the alliances were built around money and power considerations.  For example, typical of conflicting powers that seek to cut off their enemies’ access to money and credit, Germany under Bismarck refused to let Russia sell its bonds in Berlin, which led them to be sold in Paris, which reinforced the French-Russian alliance.  The wealth gap in Russia led it to tumble into revolution in 1917 and out of the war, which is a whole other dramatic story about fighting over wealth and power that is examined in Part 2 of this book.  Similar to the economically motivated shipping conflict between the British and the Dutch, Germany sank five merchant ships that were going to England in the first years of the war.  That brought the United States into the war.  Frankly, the complexities of the situations leading up to World War I are mind-boggling, widely debated among historians, and way beyond me. That war, which was really the first world war because it involved countries all around the world because the world had become global, lasted from 1914 until 1918 and cost the lives of an estimated 8.5 million soldiers and 13 million civilians.  As it ended, the Spanish flu arrived, killing an estimated 20-50 million people over two years.  So 1914-20 was a terrible time. The Rise of the American Empire and the US Dollar After World War I[3]As is typical after wars, the winning powers—in this case the US, Britain, France, Japan, and Italy—met to set out the new world order. That meeting, called the Paris Peace Conference, took place in early 1919, lasted for six months, and concluded with the Treaty of Versailles.  In that treaty the territories of the losing powers (Germany, Austria-Hungary, the Ottoman empire, and Bulgaria) were carved up and put under the controls of the winning empires and the losing powers were put deeply into debt to the winning powers to pay back the winning countries’ war costs with these debts payable in gold.  The United States was then clearly recognized as a leading power so it played a role in shaping the new world order.  In fact the term “new world order” came about in reference to US President Woodrow Wilson’s vision for how countries would operate in pursuit of their collective interest through a global governance system (the League of Nations) which was a vision that quickly failed.  After World War I the US chose to remain more isolationist while Britain continued to expand and oversee its global colonial empire.  The monetary system in the immediate post-war period was in flux.  While most countries endeavored to restore gold convertibility, currency stability against gold only came after a period of sharp devaluations and inflation.The large foreign debt burdens placed on Germany set the stage for 1) Germany’s post-war inflationary depression from 1920 to 1923 that wiped out the debts and was followed by Germany’s strong economic and military recovery, and 2) a decade of peace and prosperity elsewhere, which became the “Roaring ’20s.”  During that time the United States also followed a classic capitalist approach to resource allocation and New York became a rival financial center to London, channeling debt and investments into various businesses. Other countries became more competitive and prosperous and increasingly challenged the leading powers.  Most importantly Germany, Japan, and the US got stronger economically and militarily in the classic ways laid out in Chapter 1.  However, the US was isolationist and didn’t have a big colonial empire past its borders so it was essentially out of the emerging conflict.  As shown in the chart of the standing of empires above, Germany and Japan both gained in power relative to the UK during this interwar period, though the UK remained stronger.  As is typical, the debts and the wealth gaps that were built up in the 1920s led to the debt bubbles that burst in 1929 which led to depressions, which led to the printing of money, which led to devaluations of currencies and greater internal and external conflicts over wealth and power in the 1930s.  For example, in the United States and the UK, while there were redistributions of wealth and political power, capitalism and democracy were maintained, while in Germany, Japan, Italy, and Spain they were not maintained.  Russia played a significant peripheral role in ways I won’t delve into.  China at the time was weak, fragmented, and increasingly controlled by a rising and increasingly militaristic and nationalistic Japan.  To make a long story short, the Japanese and Germans started to make territorial expansions in the early to mid-1930s, which led to wars in Europe and Asia in the late 1930s that ended in 1945.   As is typical, before all-out wars were declared there was about a decade of economic, technological, geopolitical, and capital wars when the conflicting powers approached comparability and tested and tried to intimidate the other powers.  While 1939 and 1941 are known as the official start of the wars in Europe and the Pacific, the wars really started about 10 years before that, as economic conflicts that were at first limited progressively grew into World War II.  As Germany and Japan became more expansionist economic and military powers, they increasingly competed with the UK, US, and France for both resources and influence over territories. That brought about the second world war which, as usual, was won by the winning countries coming up with new technologies (the nuclear bomb, while the most important, was just one of the newly invented weapons).  Over 20 million died directly in the military conflicts, and the total death count was still higher.  So 1930-45, which was a period of depression and war, was a terrible time.  The Rise of the American Empire and the US Dollar After World War IIAs is typical after wars, the winning powers—most importantly the US, Britain, and Russia—met to set out the new world order.  While the Bretton Woods Conference, Yalta Conference, and Potsdam Conference were the most noteworthy, several other meetings occurred that shaped the new world order, which included carving up the world and redefining countries and areas of influence and establishing a new money and credit system.  In this case, the world was divided into the US-controlled capitalist/democratic countries and Russia-controlled communist and autocratically controlled countries, each with their own monetary systems.  Germany was split into pieces, with the United States, Great Britain, and France having control of the West and Russia having control of the East.  Japan was under US control and China returned to a state of civil war, mostly about how to divide the wealth, which was between communists and capitalists (i.e., the Nationalists).  Unlike after World War I when the United States chose to be relatively isolationist, after World War II the United States took the primary leadership role as it had most of the economic, geopolitical, and military responsibility.    The US followed a capitalist system.  The new monetary system of the US-led countries had the dollar linked to gold and had most other countries’ currencies tied to the dollar.  This system was followed by over 40 countries.  Because the US had around two-thirds of the world’s gold then and because the US was much more powerful economically and militarily than any other country, this monetary system has worked best and carried on until now.  As for the other countries that were not part of this system—most importantly Russia and those countries that were brought into the Soviet Union and the satellite countries that the Soviets controlled—they were built on a much weaker foundation that eventually broke down.  Unlike after World War I, when the losing countries were burdened with large debts, countries that were under US control, including the defeated countries, received massive financial aid from the US via the Marshall Plan.  At the same time the currencies and debts of the losing countries were wiped out, with those holding them losing all of their wealth in them.  Great Britain was left heavily indebted from its war borrowings and faced the gradual end of the colonial era which would lead to the unraveling of its empire which was becoming uneconomic to have.During this post-World War II period the United States, its allies, and the countries that were under its influence followed a classic capitalist-democratic approach to resource allocation.  New York flourished as the world’s pre-eminent financial center, and a new big debt and capital markets cycle began.  That produced what has thus far been a relatively peaceful and prosperous 75-year period that has brought us to today.As is typical of this peaceful and prosperous part of the cycle, in the 1950-70 period there was productive debt growth and equity market development that were essential for financing innovation and development early on.  That eventually led to too much debt being required to finance both war and domestic needs—what was called “guns and butter.”  The Vietnam War and the “War on Poverty” occurred in the US.  Other countries also became overly indebted and the British indebtedness became over-leveraged which led to a number of currency devaluations, most importantly the breakdown of the Bretton Woods monetary system (though countries like the UK and Italy had already devalued prior to that time).  Then in 1971, when it was apparent that the US didn’t have enough gold in the bank to meet the claims on gold that it had put out, the US defaulted on its promise to deliver gold for paper dollars which ended the Type 2 gold-backed monetary system, and the world moved to a fiat monetary system.  As is typical, this fiat monetary system initially led to a wave of great dollar money and debt creation that led to a big wave of inflation that carried until 1980-82 and led to the worst economic downturn since the Great Depression.  It was followed by three other waves of debt-financed speculations, bubbles, and busts—1) the 1982 and 2000 money and credit expansion that produced a dot-com bubble that led to the 2000-01 recession, 2) the 2002-07 money and credit expansion that produced a real estate bubble that led to the 2008 Great Recession, and 3) the 2009-19 money and credit expansion that produced the investment bubble that preceded the COVID-19 downturn.  Each of these cycles raised debt and non-debt obligations (e.g., for pensions and healthcare) to progressively higher levels and led the reserve currency central banks of the post-war allies to push interest rates to unprecedented low levels and to print unprecedented amounts of money.  Also classically, the wealth, values, and political gaps widened within countries, which increases internal conflicts during economic downturns.  That is where we now are.  During this prosperous post-war period many countries became more competitive with the leading powers economically and militarily. The Soviet Union/Russia initially followed a communist resource allocation approach as did China and a number of other smaller countries.  None of these countries became competitive following this approach.  However, the Soviet Union did develop nuclear weapons to become militarily threatening and gradually a number of other countries followed in developing nuclear weapons.  These weapons were never used because using them would produce mutually assured destruction.  Because of its economic failures the Soviet Union/Russia could not afford to support a) its empire, b) its economy, and c) its military at the same time in the face of US President Ronald Reagan’s arms race spending.  As a result the Soviet Union broke down in 1991 and abandoned communism.  The breakdown of its money/credit/economic system was disastrous for it economically and geopolitically for most of the 1990s.  In the 1980-95 period most communist countries abandoned classic communism and the world entered a very prosperous period of globalization and free-market capitalism. In China, Mao Zedong’s death in 1976 led Deng Xiaoping to a shift in economic policies to include capitalist elements including private ownership of large businesses, the development of debt and equities markets, great technological and commercial innovations, and even the flourishing of billionaire capitalists—all, however, under the strict control of the Communist Party. As a result of this shift and the simultaneous shift in the world to greater amounts of globalism China grew much stronger in most ways. For example, since I started visiting China in 1984, the education of its population has improved dramatically, the real per capita income has multiplied by 24, and it has become the largest country in the world in trade (exceeding the US share of world trade), a rival technology leader, the holder of the greatest foreign reserves assets in the world by a factor of over two, the largest lender/investor in the emerging world, the second most powerful military power, and a geopolitical rival of the United States.  And it is growing in power at a significantly faster pace than the United States and other “developed countries.”  At the same time, we are in a period of great inventiveness due to advanced information/data management and artificial intelligence supplementing human intelligence with the Americans and Chinese leading the way.  As shown at the outset of Chapter 1, human adaptability and inventiveness has proven to be the greatest force in solving problems and creating advances.  Also, because the world is richer and more skilled than ever before, there is a tremendous capacity to make the world better for more people than ever if people can work together to make the whole pie as big as possible and to divide it well.  That brings us to where we now are.  As you can see, all three of these rises and declines followed the classic script laid out in Chapter 1 and summarized in the charts at the beginning of this chapter, though each had its own particular turns and twists.    Now let’s look at these cases, especially the declines, more closely.A Closer Look at the Rises and Declines of the Leading Empires Over the Last 500 YearsThe Dutch Empire and the Dutch GuilderBefore we get to the collapse of the Dutch empire and the Dutch guilder let’s take a quick look at the whole arc of its rise and decline.  While I previously showed you the aggregated power index for the Dutch empire, the chart below shows the eight powers that make it up from the ascent around 1575 to the decline around 1780.  In it, you can see the story behind the rise and decline. No alt text provided for this imageAfter declaring independence in 1581, the Dutch fought off the Spanish and built a global trading empire that became responsible for over a third of global trade largely via the first mega-corporation, the Dutch East India Company.  As shown in the chart above, with a strong educational background the Dutch innovated in a number of areas.  They produced roughly 25% of global inventions in the early 17th century,[4] most importantly in shipbuilding, which led to a great improvement in Dutch competitiveness and its share of world trade.  Propelled by these ships and the capitalism that provided the money to fuel these expeditions, the Dutch became the largest traders in the world, accounting for about one-third of world trade.[5]  As the ships traveled around the world, the Dutch built a strong military to defend them and their trade routes. As a result of this success they got rich.  Income per capita rose to over twice that of most other major European powers.[6]They invested more in education.  Literacy rates became double the world average.  They created an empire spanning from the New World to Asia, and they formed the first major stock exchange with Amsterdam becoming the world’s most important financial center.  The Dutch guilder became the first global reserve currency, accounting for over a third of all international transactions.[7]  For these reasons over the course of the late 1500s and 1600s, the Dutch became a global economic and cultural power.  They did all of this with a population of only 1-2 million people.  Below is a brief summary of the wars they had to fight to build and hold onto their empire.  As shown, they were all about money and power.Eighty Years’ War (1566-1648): This was a revolt by the Netherlands against Spain (one of the strongest empires of that era), which eventually led to Dutch independence.  The Protestant Dutch wanted to free themselves from the Catholic rule of Spain and eventually managed to become de facto independent.  Between 1609 and 1621, the two nations had a ceasefire.  Eventually, the Dutch were recognized by Spain as independent in the Peace of Munster, which was signed together with the Treaty of Westphalia, ending both the Eighty Years’ War as well as the Thirty Years’ War.[8]  First Anglo-Dutch War (1652-1654): This was a trade war.  More specifically, in order to protect its economic position in North America and damage the Dutch trade that the English were competing with, the English Parliament passed the first of the Navigation Acts in 1651 that mandated that all goods from its American colonies must be carried by English ships, which set off hostilities between the two countries.[9]The Dutch-Swedish War (1657–1660): This war centered around the Dutch wanting to maintain low tolls on the highly profitable Baltic trade routes.  This was threatened when Sweden declared war on Denmark, a Dutch ally.  The Dutch defeated the Swedes and maintained the favorable trade arrangement.[10]The Second Anglo-Dutch War (1665–1667): England and the Netherlands fought again over another trade dispute, which again ended with a Dutch victory.[11]The Franco-Dutch War (1672-1678) and the Third Anglo-Dutch War (1672-1674): This was also a fight over trade.  It was between France and England on one side and the Dutch (called the United Provinces), the Holy Roman Empire, and Spain on the other.[12]  The Dutch largely stopped French plans to conquer the Netherlands and forced France to reduce some of its tariffs against Dutch trade,[13] but the war was more expensive than previous conflicts, which increased their debts and hurt the Dutch financially.The Fourth Anglo-Dutch War (1780-1784): This was fought between the Dutch and the rapidly strengthening British, partially in retaliation for Dutch support of the US in the American Revolution.  The war ended in significant defeat for the Dutch, and the costs of the fighting and eventual peace helped usher in the end of the guilder as a reserve currency.[14]The chart below shows the Dutch power index with the key war periods noted.  No alt text provided for this imageAs shown, the seeds of Dutch decline were sown in the latter part of the 17th century as they started to lose their competitiveness and became overextended globally trying to support an empire that had become more costly than profitable.  Increased debt-service payments squeezed them while their worsening competitiveness hurt their income from trade.  Earnings from business abroad also fell.  Wealthy Dutch savers moved their cash abroad both to get out of Dutch investments and into British investments, which were more attractive due to strong earnings growth and higher yields.[15] While debt burdens had grown through most of the 1700s,[16]the Dutch guilder remained widely accepted around the world as a reserve currency so it held up solely because of the functionality of and faith in it.[17]  (As explained earlier, reserve currency status classically lags the decline of other key drivers of the rise and fall of empires.)  As shown by the black line in the first chart above (designating the extent the currency is used as a reserve currency) the guilder remained widely used as a global reserve currency after the Dutch empire started to decline, up until the Fourth Anglo-Dutch War, which began in 1780 and ended in 1784.[18]The simmering conflict between the rising British and the declining Dutch had escalated after the Dutch traded arms with the colonies during the American Revolution.[19]  In retaliation the English delivered a massive blow to the Dutch in the Caribbean and ended up controlling Dutch territory in the East and West Indies.[20]  The war required heavy expenditure by the Dutch to rebuild their dilapidated navy: the Dutch East India Company lost half its ships[21] and access to its key trade routes while heavily borrowing from the Bank of Amsterdam to stay alive.  And the war forced the Dutch to accumulate large debts beyond these.[22]  The main reason the Dutch lost the war was that they let their navy become much weaker than Britain’s because of disinvestment into military capacity in order to spend on domestic indulgences.[23] In other words, they tried to finance both guns and butter with their reserve currency, didn’t have enough buying power to support the guns despite their great ability to borrow due to their having the leading reserve currency, and became financially and militarily defeated by the British who were stronger in both respects.Most importantly, this war destroyed the profitability and balance sheet of the Dutch East India Company.[24] While it was already in decline due to its reduced competitiveness, it ran into a liquidity crisis after a collapse in trade caused by British blockades on the Dutch coast and in the Dutch East Indies.[25]  As shown below, it suffered heavy losses during the Fourth Anglo-Dutch War and began borrowing aggressively from the Bank of Amsterdam because it was too systemically important for the Dutch government. No alt text provided for this image[26]As shown in the chart below the Dutch East India Company, which was essentially the Dutch economy and military wrapped into a company, started to make losses in 1780, which became enormous during the Fourth Anglo-Dutch War. No alt text provided for this imageAs deposit holders at the Bank of Amsterdam realized the bank was “lending” freshly printed guilders to save the Dutch East India Company, there was a run on the Bank of Amsterdam.[27]  As investors pulled back and borrowing needs increased, gold was preferred to paper money, those with paper money exchanged it for gold at the Bank of Amsterdam, and it became clear that there wouldn’t be enough gold.  The run on the bank and the run on the guilder accelerated throughout the war, as it became increasingly apparent that the Dutch would lose and depositors could anticipate that the bank would print more money and have to devalue the guilder.[28]  Guilders were backed by precious metals, but as the supply of guilders rose and investors could see what was happening they turned their guilders in for gold and silver so the ratio of claims on gold and silver rose, which caused more of the same until the Bank of Amsterdam was wiped out of its precious metal holdings.  The supply of guilders continued to soar while demand for them fell. No alt text provided for this imageThe Bank of Amsterdam had no choice since the company was too important to allow to fail both because of its significance to the economy and its outstanding debt in the Dutch financial system, so the Bank of Amsterdam began “lending” large sums of newly printed guilders to the company. During the war, policy makers also used the bank to lend to the government.[29]  The chart below shows this explosion of loans on the bank’s balance sheet through the Fourth Anglo-Dutch War (note: there was about 20 million bank guilder outstanding at the start of the war).[30]No alt text provided for this image[31]Interest rates rose and the Bank of Amsterdam had to devalue, undermining the credibility of the guilder as a storehold of value.[32] Over the years, and at this moment of crisis, the bank had created many more “paper money” claims on the hard money in the bank than could be met so that led to a classic run on the Bank of Amsterdam, which led to the collapse of the Dutch guilder.[33]  It also led to the British pound clearly replacing the Dutch guilder as the leading reserve currency.  What happened to the Dutch was classic as described in both Chapter 1’s very brief summary of why empires rise and fall and in Chapter 2’s description of how money, credit, and debt work.  As for the money, credit, and debt cycle, the Bank of Amsterdam started with a Type 1 monetary system that morphed into a Type 2 monetary system.  It started with just coins that led to the bank having a 1:1 backing of paper money by metal, so the bank provided a more convenient form of hard money.  The claims on money were then allowed to rise relative to the hard money to increasingly become a Type 2 monetary system, in which paper money seems to acquire a value itself as well as a claim on hard money (coins), though the money wasn’t fully backed.  This transition usually happens at times of financial stress and military conflict.  And it is risky because the transition decreases trust in the currency and adds to the risk of a bank-run-like dynamic.  While we won’t go deeply into the specifics of the war, the steps taken by policy makers during the period led to the loss of Dutch financial power so are worth describing because they are so archetypical when there is a clear shift in power and the losing country has a bad income statement and balance sheet.  This period was like that and ended with the guilder supplanted by the pound as the world’s reserve currency and London succeeding Amsterdam as the world’s financial center.  Deposits (i.e., holdings of short-term debt) of the Bank of Amsterdam, which had been a reliable storehold of wealth for nearly two centuries, began to trade at large discounts to guilder coins (which were made of gold and silver).[34]  The bank used its holdings of other countries’ debt (i.e., its currency reserves) to buy its currency on the open market to support the value of deposits, but it lacked adequate foreign currency reserves to support the guilder.[35]  Accounts backed by coin held at the bank plummeted from 17 million guilder in March 1780 to only 300,000 in January 1783 as owners of these gold and silver coins wanted to get them rather than continue to hold the promises of the Bank of Amsterdam to deliver them.[36]The running out of money by the Bank of Amsterdam marked the end of the Dutch empire and the guilder as a reserve currency.  In 1791 the bank was taken over by the City of Amsterdam,[37] and in 1795 the French revolutionary government overthrew the Dutch Republic, establishing a client state in its place.[38] After being nationalized in 1796, rendering its stock worthless, the Dutch East India Company’s charter expired in 1799.[39]The following charts show the exchange rates between the guilder and the pound/gold; as it became clear that the bank no longer had any credibility and that the currency was no longer a good storehold of wealth, investors fled to other assets and currency.[40]No alt text provided for this image[41]The chart below shows the returns of holding the Dutch East India Company for investors starting in various years.  As with most bubble companies, it originally did great, with great fundamentals, which attracted more investors even as its fundamentals started to weaken, but it increasingly got into debt, until the failed fundamentals and excessive debt burdens broke the company. No alt text provided for this imageAs is typical, with the decline in power of the leading empire and the rise in power of the new empire, the returns of investment assets in the declining empire fell relative to the returns of investing in the rising empire.  For example, as shown below, the returns on investments in the British East India Company far exceeded those in the Dutch East India Company, and the returns of investing in Dutch government bonds were terrible relative to the returns of investing in English government bonds.  This was reflective of virtually all investments in these two countries. No alt text provided for this image[42]The British Empire and the British PoundBefore we get to the collapse of the British empire and the British pound, let’s take a quick look at the whole arc of its rise and decline.  While I previously showed you the aggregated power index for the British empire, the chart below shows the eight powers that make it up.  It shows these from the ascent around 1700 to the decline in the early 1900s.  In it, you can see the story behind the rise and decline.  No alt text provided for this imageThe British empire’s rise began before 1600, with steadily strengthening competitiveness, education, and innovation/technology—the classic leading factors for a power’s rise.  As shown and previously described, in the late 1700s the British military power became pre-eminent and it beat its leading economic competitor and the leading reserve currency empire of its day in the Fourth Anglo-Dutch War.  It also successfully fought other European rivals like France in a number of conflicts that culminated in the Napoleonic Wars in the early 1800s.  Then it became extremely rich by being the dominant economic power.  At its peak in the 19th century, the UK’s 2.5% of the world’s population produced 20% of the world’s income, and the UK controlled over 40% of global exports.  This economic strength grew in tandem with a strong military, which, along with the privately driven conquests of the British East India Company, drove the creation of a global empire upon which “the sun never set,” controlling over 20% of the world’s land mass and 25% of the global population prior to the outbreak of World War I.  With a lag, as is classic, its capital—London—emerged as the global financial center and its currency—the pound—emerged as the leading global reserve currency.  As is typical its reserve status remained well after other measures of power started declining in the late 19th century and as powerful rivals like the US and Germany rose.  As shown in the chart above, almost all of the British empire’s relative powers began to slip as competitors emerged around 1900.  At the same time wealth gaps were large and internal conflicts over wealth were emerging.  As you know, despite winning both World War I and World War II the British were left with large debts, a huge empire that was more costly than profitable, numerous rivals that were more competitive, and a population that had big wealth gaps which led to big political gaps.  As I previously summarized what happened in the 1914 to post-World War II period, I will skip ahead to the end of World War II in 1945 and the start of the new world order that we are now in.  I will be focusing on how the pound lost its reserve currency status.  Although the US had overtaken the UK militarily, economically, politically, and financially long before the end of World War II, it took more than 20 years after the war for the British pound to fully lose its status as an international reserve currency.  Just like the world’s most widely spoken language becomes so deeply woven into the fabric of international dealings that it is difficult to replace, the same is true of the world’s most widely used reserve currency.  In the case of the British pound, other countries’ central banks continued to hold a sizable share of their reserves in pounds through the 1950s, and about half of all international trade was denominated in sterling in 1960.  Still, the pound began to lose its status right at the end of the war because smart folks could see the UK’s increased debt load, its low net reserves, and the great contrast with the United States’ financial condition (which emerged from the war as the world’s pre-eminent creditor and with a very strong balance sheet).  The decline in the British pound was a chronic affair that happened through several significant devaluations over many years.  After efforts at making the pound convertible failed in 1946-47, the pound devalued by 30% against the dollar in 1949.  Though this worked in the short term, over the next two decades the declining competitiveness of the British led to repeated balance of payments strains that culminated with central banks actively selling sterling reserves to accumulate dollar reserves following the devaluation of 1967.  Around this time the deutschmark began to re-emerge and took the pound’s place as the second-most widely held reserve currency.  The charts below paint the picture.  No alt text provided for this imageOn the following pages we will cover in greater detail the specific stages of this decline, firstly with the convertibility crisis of 1947 and the 1949 devaluation, secondly with the gradual evolution of the pound’s status relative to the dollar through the 1950s and early 1960s, and thirdly with the balance of payments crisis of 1967 and subsequent devaluation.  We will focus in on the currency crises.  1)     The Pound’s Suspended Convertibility in 1946 and Its Devaluation in 1949The 1940s are frequently referred to as “crisis years”[43] for sterling.  The war required the UK to borrow immensely from its allies and colonies,[44]and those obligations were required to be held in sterling.  These war debts financed about a third of the war effort.  When the war ended, the UK could not meet its debt obligations without the great pain of raising taxes or cutting government spending, so it necessarily mandated that its debt assets (i.e., its bonds) could not be proactively sold by its former colonies.  As such, the UK emerged from World War II with strict controls on foreign exchange.  The Bank of England’s approval was required to convert pounds into dollars, whether to buy US goods or purchase US financial assets (i.e., current and capital account convertibility was suspended).  To ensure the pound would function as an international reserve currency in the post-war era, and to prepare the global economy for a transition to the Bretton Woods monetary system, convertibility would have to be restored.  However, because the US dollar was now the international currency of choice, the global economy was experiencing a severe shortage of dollars at the time.  Virtually all Sterling Area countries (the UK and the Commonwealth countries) relied on inflows from selling goods and services and from attracting investments in dollars to get the dollars they needed while they were forced to hold their sterling-denominated bonds.  The UK experienced acute balance of payments problems due to its poor external competitiveness, a domestic fuel crisis, and large war debts undermining faith in the pound as a storehold of wealth.  As a result, the first effort to restore convertibility in 1947 failed completely, and it was soon followed by a large devaluation (of 30%) in 1949, to restore some competitiveness.[45]Coming into the period, there were concerns that too quick a return to convertibility would result in a run on the pound, as savers and traders shifted to holding and transacting in dollars all at once.  However, the US was anxious for the UK to restore convertibility as soon as possible as restrictions on convertibility were reducing US export profits and reducing liquidity in the global economy.[46]  The Bank of England was also eager to remove capital controls in order to restore the pound’s role as a global trading currency, increase financial sector revenues in London, and encourage international investors to continue saving in sterling [47] (a number of governments of European creditors, including Sweden, Switzerland, and Belgium, were having increasing conflicts with the UK over the lack of convertibility).[48] An agreement was reached after the war, under which the UK would reintroduce convertibility swiftly, and the US would provide the UK with a loan of $3.75 billion [49] (about 10% of UK GDP).  While the loan offered some buffer against a potential run on the pound, it did not change the underlying imbalances in the global economy. When partial convertibility was introduced in July 1947, the pound came under considerable selling pressure.  As the UK and US governments were against devaluation (as memories of the competitive devaluations in the 1930s were fresh on everyone’s minds), [50] the UK and other Sterling Area countries turned to austerity and reserve sales to maintain the peg to the dollar.  Restrictions were imposed on the import of “luxury goods” from the US, defense expenditure was slashed, dollar and gold reserves were drawn down, and agreements were made between sterling economies not to diversify their reserve holdings to the dollar.[51] Prime Minister Clement Attlee gave a dramatic speech on August 6, 1947, calling for the spirit of wartime sacrifices to be made once again in order to defend the pound:     “In 1940 we were delivered from mortal peril by the courage, skill, and self-sacrifice of a few.  Today we are engaged in another battle for Britain.  This battle cannot be won by the few.  It demands a united effort by the whole nation.  I am confident that this united effort will be forthcoming and that we shall again conquer.”[52]Immediately following the speech, the run on the pound accelerated.  Over the next five days, the UK had to spend down $175 million of reserves to defend the peg.[53] By the end of August, convertibility was suspended, much to the anger of the US and other international investors who had bought up sterling assets in the lead-up to convertibility hoping that they would soon be able to convert those holdings to dollars.  The governor of the National Bank of Belgium even threatened to stop transacting in sterling, requiring a diplomatic intervention.[54]The devaluation came two years later, as policy makers in both the UK and the US realized that the pound couldn’t return to convertibility at the current rate.  UK exports were not competitive enough in global markets to earn the foreign exchange needed to support the pound, reserves were dwindling, and the US was unwilling to continue shoring up the pound with low interest rate loans.  An agreement was reached to devalue the pound versus the dollar in order to boost UK competitiveness, help create a two-way currency market, and speed up a return to convertibility.[55]  In September 1949, the pound was devalued by 30% versus the dollar.  Competitiveness returned, the current account improved, and by the mid-to-late 1950s, full convertibility was restored.[56]  The charts below No alt text provided for this imageThe currency move, which devalued sterling debt, did not lead to a panic out of sterling debt as much as one might have expected especially in light of how bad the fundamentals for sterling debt remained.  That is because a very large share of UK assets was held by the US government, which was willing to take the valuation hit in order to restore convertibility, and by Sterling Area economies, such as India and Australia, whose currencies were pegged to the pound for political reasons.[57]  These Commonwealth economies, for geopolitical reasons, supported the UK’s decision and followed by devaluing their own currencies versus the dollar, which lessened the visibility of the loss of wealth from the devaluation. Still, the immediate post-war experience made it clear to knowledgeable observers that the pound was vulnerable to more weakness and would not be able to enjoy the same international role it had prior to World War II.1) The Failed International Efforts to Support the Pound in the 1950s and 1960s and the Devaluation of 1967Though the devaluation helped in the short term, over the next two decades, the pound would face recurring balance of payments strains. These strains were very concerning to international policy makers who feared that a collapse in the value of sterling or a rapid shift away from the pound to the dollar in reserve holdings could prove highly detrimental to the new Bretton Woods monetary system (particularly given the backdrop of the Cold War and concerns around communism).  As a result, numerous arrangements were made to try to shore up the pound and preserve its role as a source of international liquidity.  These included the Bilateral Concerté (1961-64), in which major developed world central banks gave support to countries via the Bank of International Settlements, including multiple loans to the UK and the BIS Group Arrangement 1 (1966-71), which provided swaps to the UK to offset future pressure from potential falls in sterling reserve holdings.[58]In addition to these wider efforts, the UK’s status as the head of the Sterling Area let it mandate that all trade within the Sterling Area would continue to be denominated in pounds and all their currencies would be pegged to sterling. As these economies had to maintain a peg to the pound, they continued to accumulate FX reserves in sterling well after other economies had stopped doing so (e.g., Australia kept 90% of its reserves in sterling as late as 1965).[59]  Foreign loans issued in the UK during the period were also almost exclusively to the Sterling Area. The result of all this is that for the 1950s and early 1960s, the UK is best understood as a regional economic power and sterling as a regional reserve currency.[60]  Yet all these measures didn’t fix the problem that the UK owed too much money and was uncompetitive, so it didn’t earn enough money to both pay its debts and pay for what it needed to import. Rearrangements were essentially futile stop-gap measures designed to hold back the changing tide. They helped keep the pound stable between 1949 and 1967. Still, sterling needed to be devalued again in 1967. By the mid-1960s, the average share of central bank reserves held in pounds had fallen to around 20%, while international trade was overwhelmingly denominated in dollars (about half). However, many emerging markets and Sterling Area countries continued to hold about 50% of their reserves in pounds and continued to denominate much of their trade with each other and the UK in sterling. This effectively ended following a series of runs on the pound in the 1960s. As in many other balance of payments crises, policy makers used a variety of means to try to maintain the currency peg to the dollar, including spending down reserves, raising rates, and using capital controls. In the end they were unsuccessful, and after the UK devalued by 14% versus the dollar in 1967, even Sterling Area countries were unwilling to hold their reserves in pounds, unless the UK guaranteed their underlying value in dollars.Throughout the 1960s, the UK was forced to defend the peg to the dollar by selling about half of its FX reserve holdings and keeping rates higher than the rest of the developed world—even though the UK economy was underperforming. In both 1961 and 1964, the pound came under intense selling pressure, and the peg was only maintained by a sharp rise in rates, a rapid acceleration in reserve sales, and the extension of short-term credits from the US and the Bank of International Settlements. By 1966, attempts to defend the peg were being described by prominent British policy makers as “a sort of British Dien Bien Phu.”[61]  When the pound came under extreme selling pressure again in 1967 (following rising rates in the developed world, recessions in major UK export markets, and heightened conflict in the Middle East),[62] British policy makers decided to devalue sterling by 14% against the dollar.No alt text provided for this imageAfter the devaluation little faith remained in the pound as the second-best reserve currency after the dollar. For the first time since the end of World War II, international central banks began actively selling their sterling reserves (as opposed to simply accumulating fewer pounds in new reserve holdings) and instead began buying dollars, deutschmarks, and yen. As you can see in the chart below on the left, the average share of sterling in central bank reserve holdings collapsed within two years of the devaluation.  At the same time the UK was still able to convince Sterling Area countries not to diversify away from the pound. In the Sterling Agreement of 1968, Sterling Area members agreed to maintain a floor on their pound reserve holdings, as long as 90% of the dollar value of these holdings was guaranteed by the British government. So although the share of pound reserves in these Sterling Agreement countries like Australia and New Zealand remained high, this was only because these reserves had their value guaranteed by the British in dollars. So all countries that continued to hold a high share of their reserves in pounds after 1968 were holding de facto dollars with the British bearing the risk of a further sterling devaluation.[63]No alt text provided for this image[64]By this time the dollar was having its own set of balance of payments and currency problems, but that is for the next installment of this series when I turn to the United States and China.  [1] We show where key indicators were relative to their history by averaging them across the cases. The chart is shown such that a value of “1” represents the peak in that indicator relative to history and “0” represents the trough.  The timeline is shown in years with “0” representing roughly when the country was at its peak (i.e., when the average across gauges was at its peak).  In the rest of this section, we walk through each of the stages of the archetype in more detail. While the charts show the countries that produced global reserve currencies, we’ll also heavily reference China, which was a dominant empire for centuries, though it never established a reserve currency.[2] A good example of this is the popularity of the Patriot movement in the Netherlands around this time: Encyclopedia Britannica, The Patriot movement,  https://www.britannica.com/place/Netherlands/The-18th-century#ref414139[3] While most people think that the ascent of the US came after World War II, it really started here and went on across both wars—and the seeds of that rise came still earlier from the self-reinforcing upswings in US education, innovation, competitiveness, and economic outcomes over the 19th century.[4] Rough estimate based on internal calculations[5] Rough estimate based on internal calculations[6] Rough estimate based on internal calculations[7] In this piece, when talking about “the guilder,” we generally refer to guilder bank notes, which were used at the Bank of Amsterdam, rather than the physical coin (also called “guilder”).[8] Encyclopedia Britannica, Eighty Years’ War, https://www.britannica.com/event/Eighty-Years-War[9] Encyclopedia Britannica, The Anglo-Dutch Wars, https://www.britannica.com/event/Anglo-Dutch-Wars[10] Israel, Dutch Primacy in World Trade, 1585-1740, 219[11] Encyclopedia Britannica, The Anglo-Dutch Wars, https://www.britannica.com/event/Anglo-Dutch-Wars[12] Encyclopedia Britannica, The Dutch War, https://www.britannica.com/event/Dutch-War[13] Israel, The Dutch Republic: Its Rise, Greatness, and Fall 1477-1806, 824-825[14] Encyclopedia Britannica, The Anglo-Dutch Wars, https://www.britannica.com/event/Anglo-Dutch-Wars[15] There was a general rise in foreign investment by the Dutch during this period. Investments in UK assets offered high real returns. Examples include Dutch purchases of stocks in the British East India Company, and the City of London selling term annuities (bonds) to Dutch investors. For a further description, see Hart, Jonker, and van Zanden, A Financial History of the Netherlands, 56-58.[16] Hart, Jonker, and van Zanden, A Financial History of the Netherlands, 20-21[17] Quinn & Roberds, “Death of a Reserve Currency,” 13  [18] Encyclopedia Britannica, The Anglo-Dutch Wars, https://www.britannica.com/event/Anglo-Dutch-Wars[19] Encyclopedia Britannica, The Anglo-Dutch Wars, https://www.britannica.com/event/Anglo-Dutch-Wars[20] Encyclopedia Britannica, The Anglo-Dutch Wars, https://www.britannica.com/event/Anglo-Dutch-Wars[21] de Vries & van der Woude, The First Modern Economy, 455[22] de Vries & van der Woude, The First Modern Economy, 126[23] de Vries & van der Woude, The First Modern Economy, 685-686[24] de Vries & van der Woude, The First Modern Economy, 455[25] de Vries & van der Woude, The First Modern Economy, 455-456 & https://www.britannica.com/event/Anglo-Dutch-Wars[26] This chart only shows the financial results from the Dutch East India Company reported “in patria,” e.g., the Netherlands. It does not include the part of the revenue and debt from its operations in Asia but does include its revenues from goods it retrieved in Asia and sold in Europe.[27] Quinn & Roberds, “Death of a Reserve Currency,” 17[28] “Guilder” in this case refers to devaluing bank deposits in guilder from the Bank of Amsterdam, not physical coin. For details on the run, see Quinn & Roberds, “Death of a Reserve Currency,” 16.[29] Quinn & Roberds, “Death of a Reserve Currency,” 17-18[30] Quinn & Roberds, “Death of a Reserve Currency,” 16[31] Quinn & Roberds, “Death of a Reserve Currency,” 34[32] Quinn & Roberds, “Death of a Reserve Currency,” 15-16[33] The Bank of Amsterdam was ahead its time and used ledgers instead of real “paper money.” See Quinn & Roberds, “The Bank of Amsterdam Through the Lens of Monetary Competition,” 2[34] Quinn & Roberds, “Death of a Reserve Currency,” 19, 26[35] Quinn & Roberds, “Death of a Reserve Currency,” 19-20[36] Quinn & Roberds, “Death of a Reserve Currency,” 16[37] Quinn & Roberds, “Death of a Reserve Currency,” 24[38] de Vries & van der Woude, The First Modern Economy, 685-686[39] Encyclopedia Britannica, The Dutch East India Company, https://www.britannica.com/topic/Dutch-East-India-Company; also see de Vries & van der Woude, The First Modern Economy, 463-464[40] Historical data suggests that by 1795, bank deposits were trading at a -25% discount to actual coin. Quinn & Roberds, “Death of a Reserve Currency,” 26.[41] Note: To fully represent the likely economics of a deposit holder at the Bank of Amsterdam, we assumed depositors each received their pro-rated share of precious metal still in the bank’s vaults when it was closed (that was roughly 20% of the fully backed amount, thus the approximately 80% total devaluation).[42] Gelderblom & Jonker, “Exporing the Market for Government Bonds in the Dutch Republic (1600-1800),” 16[43] For example, see Catherine Schenk, The Decline of Sterling: Managing the Retreat of an International Currency, 1945–1992, 37 (hereafter referred to as Schenk, Decline of Sterling)[44] See Schenk, Decline of Sterling, 39[45] For an overview of the convertibility crisis and devaluation, see Schenk, Decline of Sterling, 68-80; Alec Cairncross & Barry Eichengreen, Sterling in Decline: The Devaluations of 1931, 1949, and 1967, 102-147 (hereafter referred to as Cairncross & Eichengreen, Sterling in Decline).[46] Schenk, Decline of Sterling, 44[47] Schenk, Decline of Sterling, 31[48] Alex Cairncross, Years of Recovery: British Economic Policy 1945-51, 124-126[49] Schenk, Decline of Sterling, 63[50] Schenk, Decline of Sterling, 48[51] Schenk, Decline of Sterling, 62[52] As quoted in Schenk, Decline of Sterling, 62-63[53] Ibid[54] Schenk, Decline of Sterling, 66-67[55] For more detail, see Cairncross & Eichengreen, Sterling in Decline, 139-155[56] See also Cairncross & Eichengreen, Sterling in Decline, 151-155 for a discussion of other contributing factors[57] Schenk, Decline of Sterling, 39, 46; for further description, see https://eh.net/encyclopedia/the-sterling-area/[58] For further description of these and other coordinated policies, see Catherine Schenk, “The Retirement of Sterling as a Reserve Currency After 1945: Lessons for the US Dollar?”[59] John Singleton & Catherine Schenk, “The Shift from Sterling to the Dollar, 1965–76: Evidence from Australia and New Zealand,” 1162[60] For more detail on the dynamics of the Sterling Area, see Catherine Schenk, Britain and the Sterling Area, 1994[61] As quoted by Schenk, Decline of Sterling, 156[62] Schenk, Decline of Sterling, 174[63] For fuller coverage of this, see Schenk, Decline of Sterling, 273-315[64] Data from Schenk, “The Retirement of Sterling as a Reserve Currency After 1945: Lessons for the US Dollar?,” 25DisclosuresBridgewater Daily Observations is prepared by and is the property of Bridgewater Associates, LP and is circulated for informational and educational purposes only.  There is no consideration given to the specific investment needs, objectives or tolerances of any of the recipients.  Additionally, Bridgewater’s actual investment positions may, and often will, vary from its conclusions discussed herein based on any number of factors, such as client investment restrictions, portfolio rebalancing and transactions costs, among others.  Recipients should consult their own advisors, including tax advisors, before making any investment decision.  This report is not an offer to sell or the solicitation of an offer to buy the securities or other instruments mentioned.Bridgewater research utilizes data and information from public, private and internal sources, including data from actual Bridgewater trades. Sources include the Australian Bureau of Statistics, Bloomberg Finance L.P., Capital Economics, CBRE, Inc., CEIC Data Company Ltd., Consensus Economics Inc., Corelogic, Inc., CoStar Realty Information, Inc., CreditSights, Inc., Dealogic LLC, DTCC Data Repository (U.S.), LLC, Ecoanalitica, EPFR Global, Eurasia Group Ltd., European Money Markets Institute – EMMI, Evercore ISI, Factset Research Systems, Inc., The Financial Times Limited, GaveKal Research Ltd., Global Financial Data, Inc., Haver Analytics, Inc., ICE Data Derivatives, IHSMarkit, The Investment Funds Institute of Canada, International Energy Agency, Lombard Street Research, Mergent, Inc., Metals Focus Ltd, Moody’s Analytics, Inc., MSCI, Inc., National Bureau of Economic Research, Organisation for Economic Cooperation and Development, Pensions & Investments Research Center, Renwood Realtytrac, LLC, Rystad Energy, Inc., S&P Global Market Intelligence Inc., Sentix Gmbh, Spears & Associates, Inc., State Street Bank and Trust Company, Sun Hung Kai Financial (UK), Refinitiv, Totem Macro, United Nations, US Department of Commerce, Wind Information (Shanghai) Co Ltd, Wood Mackenzie Limited, World Bureau of Metal Statistics, and World Economic Forum.  While we consider information from external sources to be reliable, we do not assume responsibility for its accuracy.The views expressed herein are solely those of Bridgewater as of the date of this report and are subject to change without notice.  Bridgewater may have a significant financial interest in one or more of the positions and/or securities or derivatives discussed.  Those responsible for preparing this report receive compensation based upon various factors, including, among other things, the quality of their work and firm revenues.


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How does the “Bravo Microbiome” balance our need for GcMAF without the natural signals which are behind the biofilm?

Dr. Ruggiero answered:

An independent laboratory (R.E.D. Labs, Belgium) demonstrated that Bravo products have 100 fold more GcMAF activity against nagalase than purified GcMAF. These results have been published in a peer-reviewed scientific article where the effects of Bravo on nagalase and on C-Reactive Protein – a marker of systemic inflammation – are described. The article can be downloaded at 

https://thescipub.com/abstract/10.3844/ajisp.2020.8.18

Experimental data obtained in vitro and presented in Figs. 5 and 6 of the article demonstrate the GcMAF activity that is present in Bravo. Since it is well assessed that nagalase specifically binds GcMAF, formation of complexes between nagalase and Bravo is direct demonstration of the presence of active GcMAF in PMF as we described since 2011. Figs. 5 and 6 of the article show the kinetics of in vitro interaction between human nagalase and Bravo with resulting formation of nagalase/Bravo complexes. Bravo at 1:100 dilution had an initial value (at time 0) higher than that observed with PBS alone, thus demonstrating the presence of immediate, intrinsic GcMAF activity. At every time point, Bravo showed significantly higher activity in comparison with purified GcMAF and, at 120 h, the GcMAF activity of Bravo was still well above baseline, whereas purified GcMAF did not show any residual activity (Fig. 7 of the article). Therefore, it may be deduced that the GcMAF activity in Bravo is more than 100 fold higher than that of purified GcMAF and more sustained in time. The 100 fold higher activity of Bravo in comparison with purified GcMAF can be explained taking into consideration two elements. 

1. Naturally formed GcMAF in Bravo is associated with vitamin D3, fatty acids and glycosaminoglycans – such as chondroitin sulfate – that are normal constituents of milk and colostrum. Since 2013, we proposed a molecular model describing how non-covalent association of these constituents in a multi-molecular complex significantly enhanced the biological activity of GcMAF. This model was independently confirmed by a recent study demonstrating that association with vitamin D3 significantly increased the immune stimulating activity of GcMAF (Greilberger and Herwig, 2020).

2.  Phages in Bravo synthesize proteins with activities superimposable to that of GcMAF that complement the effects of the naturally formed GcMAF that is present in Bravo. For example, the protein RAD52 that is the human homolog of the protein Sak encoded by Lactococcus phage ul36, shows significant similarity with the active site of GcMAF. When the sequences of human RAD52 (P43351) and GcMAF (P02774) were obtained and aligned using the Align tool of Uniprot, alignment showed a striking similarity between the active site of GcMAF that is the sequence TPTELAK, and the sequence DPAQTSD of RAD52. Since it is well known that phages stimulate the immune system, and it is also known that such a stimulation is associated with macrophage activation, see our article at

https://www.biorxiv.org/content/10.1101/714154v3

it is may be hypothesized that GcMAF-like proteins encoded by phages contribute to the overall GcMAF activity of Bravo.

As far as biofilms are concerned, GcMAF in Bravo is not affected by biofilms since the probiotic microbes that are part of Bravo have been selected so to break biofilms as demonstrated by the following scientific article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049744/

In other words, at variance with regular GcMAF, whose action can be blocked by biofilms, the GcMAF in Bravo, not only is 100 fold more potent, but it is also unaffected by biofilms since the enzymes released by the probiotics of Bravo break the biofilms.

The composition in microbes, phages and plasmids in Bravo has been described in the following scientific articles

https://www.biorxiv.org/content/10.1101/714154v3

https://madridge.org/journal-of-immunology/mjim-1000123.pdf

Finally, the anti-viral activity of Bravo has been clinically demonstrated; the evidence is in the insert of Fig. 4 of this article

https://www.biorxiv.org/content/10.1101/2020.03.03.975524v1.full.pdf+html

where the viral load goes down by 98% in a few weeks.

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Bravo Edestiny Boot Camp

This is an educational compilation for Dr. Ruggiero’s product called Edestiny. It was introduced on 3/31/2020.

The following items are about Bravo Edestiny:

Mimi requests any information that you may have that is not on this page. Send the information to mimi@bravocoop.com

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Bravo Edestiny: Hemp Seed Protein and Bravo Cultures

From Dr. Marco Ruggiero:

BRAVO EDESTINY (CAPSULES) is a product entirely made in Switzerland and contains exclusively ingredients from certified Swiss and European sources; all the microorganisms, probiotic strains, and ingredients in this product are certified safe for human use. They are manufactured exclusively for our Swiss company by state-of-the-art GMP-certified European facilities that guarantee the highest quality. 

In our Swiss facility we choose the best Swiss quality hemp seed protein powder, we blend it with highly selected food ingredients (such as real lemon juice and apple cider vinegar), we add our proprietary blend of fermenting cultures, our array of probiotics and prebiotics, and we leave the product to fully and naturally ferment following our proprietary process. Then, after full and extensive fermentation, we freeze dry the product and we make it available under the form of gastro-resistant (enteric-coated), vegetable, capsules. 

To purchase Bravo Edestiny click here

THE LATEST BREAKTHROUGH FROM BRAVO RESEARCH

I am pleased to announce BRAVO EDESTINY, a completely new product that joins our Bravo family and, just like the other products, it is absolutely unique.  Bravo Edestiny is based on fermentation of hemp seed proteins by the proprietary array of probiotic microbes that are at the core of all Bravo products.  The two major proteins of hemp are Edestin – hence the name Edestiny – and Albumin.

Edestin has the unique ability to stimulate the body’s immunological responses against invasive agents [1]; fermentation of edestin by Bravo microbes leads to formation of a vegetal analogue of GcMAF and makes Bravo Edestiny the only probiotic with active vegetable based GcMAF. Bravo Edestiny comes in the wake of scientific results demonstrating that it has GcMAF activity 100 fold higher than that of purified GcMAF and lowers nagalase [2 3]. 

Albumin, the other protein in Bravo Edestiny, is known to inhibit viral entry into human cells, boost immune responses and attenuate DNA damage [4 5 6].

Some of the properties of fermented Edestin and Albumin are mentioned in my latest talk for Sophia Health Institute, [see here] from min 45. 

To purchase Bravo Edestiny click here

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Bravo European Instructions



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