Bravo’s milk/colostrum

Cow milk and colostrum used for our Bravo products have certified organic quality – awarded with the Bio Suisse bud seal. It is wholesome and contains all naturally occurring ingredients.

In the pictures, G.C.K, one of our colostrum collectors supervising some herds and colostrum suppliers in Switzerland.

We take care of the wellbeing of the cows who make colostrum

All mammals make colostrum that is the so-called first and second milk secreted by the mammary gland within the first 12 hours after birth. Colostrum is essential for survival of the newborn calf not only because it provides nutrition but, more importantly, because it contributes to the build-up of the immune system. At variance with humans, calves do not receive any prenatal passive immunization through antibodies from the mother, and their immunity is absolutely dependent on colostrum that contains a number of immune-stimulating factors. Because of this, we can use only the surplus of colostrum that is available after the calf has received what it needs; since the wellbeing of the calf is the primary interest of the farmer, only colostrum that is in surplus is sold for further processing. It is a very rare raw material which we value and respect.page1image52543488

Why is there a surplus of colostrum?

Colostrum surplus only arises from breeding. This began thousands of years ago; today’s “high- performance” dairy cows produce a surplus of milk and colostrum, that is a quantity much greater than that needed by the calves. The milk yield of dairy cows has increased over decades – and the amount of colostrum too. The cows from our Swiss suppliers (average herd size of our farmers is 18 cows) give an average surplus of 5 liters of colostrum within the first 12 hours after birth. Every farmer knows that a calf can only survive if it gets its share of colostrum; it needs about 6 liters of colostrum in order to build up its own immune system. That’s why every responsible farmer feeds his calves in the first place before using or selling any surplus of colostrum.

So please rest assured that the calf always gets its share in the first place. We love our animals and we take great care of their wellbeing.

Our milk and colostrum are collected exclusively from certified farms

Thanks to the regulations of Swiss organic agriculture, the highest quality of our cow milk and colostrum is guaranteed. Organic agriculture produces milk and colostrum on the basis of environmentally friendly production methods, taking ecological and environmental issues into consideration: no synthetic pesticides, growth promoters, mineral fertilizers or genetic engineering are used. As a result, organic products are less contaminated.

Milk and colostrum used for Bravo products comes exclusively from farms certified by Bio Suisse and thus subject to the highest standards throughout Europe.

Bio Suisse certification stands for foods of the highest organic quality.page3image52525072

Bio Suisse has very strict agricultural guidelines. Feeding, fertilization, hygiene regulations and the use of drugs are regulated and checked regularly. These standards form the framework for our suppliers and they are approved by annual audits. As a manufacturer, we also demand that each cow must be absolutely free from antibiotic treatments for at least one year. Preventive administration of antibiotics as food additives in conventional farming is a major problem in the food chain. Bio Suisse strictly prohibits this detrimental use of antibiotics.

The entire milk production is strictly regulated and controlled. Milk and colostrum as by- products are totally safe. Organic agriculture in particular produces food on the basis of environmentally friendly production methods taking into consideration ecology and environmental protection.

As a result, these products are less polluted.

The use of hormones is strictly prohibited in Switzerland. Antibiotics may only be used on organic farms if prescribed by a veterinary doctor. The cows of our contractual partners must be free of antibiotics for at least one year. This requirement is a prerequisite for best colostrum quality.

Our cow milk and colostrum are obtained exclusively from certified organic and biodynamic agriculture

These two certificates stand for a sustainable agriculture that cares for our precious resources and takes the wellbeing of the animals seriously. All our suppliers are organic and Demeter-certified farmers who adhere to the guidelines and regulations of Bio Suisse which are the strictest in the world. Demeter-products are produced and processed in a holistic manner, in harmony with nature. This means that conditions are right for people, animals, plants and soils alike and their

life forces can unfold in an ideal way. Moreover, Demeter holdings rely on homoeopathic medication for the treatment of sick animals and in cropping they use their own special preparations. In processing, much emphasis is placed on ensuring that the products retain as many of their natural qualities as possible. The Demeter label is recognized worldwide.

Our colostrum suppliers

We visit our suppliers personally on a regular basis. We are always pleased to see how great their responsibility and seriousness is. It demonstrates an incredible down-to-earth attitude and authenticity of the farmers.

One of the Swiss farmers with his family supplying colostrum for Bravo products

This spirit gives confidence in the best quality of colostrum and a responsible consideration for the welfare of the young animals. They need enough first milk to build up a healthy, strong immune system. The farmer also knows that his cows could supply several calves with fresh colostrum. This is due to our ancestors who have bred dairy animals for centuries. With the increasing milk yield the amount of colostrum increased as well.

Today we can totally rely on our Swiss organic colostrum suppliers to collect a product of the highest quality.page4image52894208page4image52893792page5image52945024

G.C.K., one of our colostrum collectors, with a farmer supplying colostrum for Bravo products

How is our colostrum processed?

Colostrum is a sensitive agricultural product whose production and distribution are strongly regulated and controlled by Swiss law. We preserve colostrum by pasteurization, that is a process used to sterilize it. Low temperature pasteurization (LTP) gently sterilizes colostrum, preserving most of all of its bio-activity. Then, our colostrum is freeze-dried (that is, it is gently dried).

Whole cow milk and colostrum, with no further treatment, are used as main ingredients of our Bravo products.page5image52944816page5image52946480

The colostrum used for Bravo undergoes Thorough Quality Control Procedures

CGMP (certified Good Manufacturing Practices) and HACCP (Hazard Analysis and Critical Control Procedures) procedures are being followed throughout the entire colostrum production process.
The product is examined in a laboratory registered with the United States federal government as a clinical laboratory.

Each colostrum product batch is thoroughly analyzed prior to shipment to assure its quality, efficacy and safety. Analytical chemistry, microbiological and other necessary testing is performed using AOAC or other approved testing methods. Colostrum is tested and certified for the immunoglobulin G (IgG) and proline-rich polypeptides (PRPs) content using one of five in-house High Performance Liquid Chromatography (HPLC) units.

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10 Signs Of Magnesium Deficiency

What if your most irritating conditions could be easily removed because they are a symptom of mineral deficiency?

I have been using a magnesium/zinc lotion for the past month and it has made a really powerful impact on such a wide range of issues that I am declaring this information to be at the status of “a must read by all health enthusiasts”.  I am in love with my magnesium rich protocol.  I have super-hero strength, never ending energy,  my skin issues have disappeared but if I let the Mg get low, they do come right back on the meridian that is working the hardest.  (presumably using the most minerals). 

I don’t think my skin is any different from yours.  It simply drinks in what I put on it like it is having a meal.  On the skin, if your body doesn’t need any more, it won’t take it.  If you need it, it’s there.

There are things that you and your family members are “living through” that they don’t have to!!  Like spasms that cause their limbs to tense up, or hearts that are arrhythmic,  and are slow, or hives or other things that people don’t know how to get rid of.  They have something in common.  They are deficiency.

I am rapidly learning the language and technology of lotions so I can make wonderful choices to feed myself and my skin.   I am learning how to suspend minerals in freshly pressed seed oil that I make myself.  I like pumpkin seeds which are full of natural magnesium.  

Now you can have YOU can have your own delicious meals on your skin with your own choices of freshly pressed oils and even have them turned into a lotion with just the right stuff for you!  This is customization at its finest but with it comes delays to get the ingredients you want if we don’t have them and costing out the ingredients.  Once you begin to understand, I believe you will be as excited as I am. Thank you to Masters of Health, Dr. Jockers & team and the dolphins at dolphinlove.com    Meanwhile, read this very thorough article on magnesium deficiency and sit down with your body and get started with what it needs! 

10 Signs Of Magnesium Deficiency

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Bravo rises to the Occasion

Bravo rises to the Occasion

and offers us more choice

People have asked me if Bravo Yogurt has streptococcus bacteria in it.  It does.  It is used to turn on the immune system.  However, if. you don’t want to use it, you have a choice.

Bravo Edestiny has the same wide array of bacteria of Freeze Dried Bravo but NOT Streptococci.

Bravo Edestiny has been designed on the same concept of Freeze Dried Bravo for what concern the fermentation process. Bravo Edestiny is based on fermentation of hemp seed proteins (rather than milk and colostrum) and the microorganisms responsible of such fermentation are the same of Freeze Dried Bravo except the Streptococcus Thermophilus and Lactobacillus bulgaricus (that are specific for milk fermentation).

Thus, in case of people who wish to avoid Streptococci, Bravo Edestiny is a good choice. Bravo Edestiny is also perfect for people who wish to have a dairy-free nutrition.

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Detoxification of Heavy Metals and Organic Toxicants with Bravo Yogurt

Below, please find the link to our most recent study on the effects of Bravo entitled “Effects on the Immune System of a Three-Month Consumption of an Extremely Diverse Probiotic Yogurt: Decrease of Serum Alpha-N-Acetylgalactosaminidase Activity, Detoxification and Gut Microbiota Normalization.”

This study is published in a prestigious peer-reviewed scientific journal, the

American Journal of Immunology (See below in this document or download here)

In this study, we describe the effects of three months of consumption of Bravo on serum nagalase, detoxification, and restoration of the healthy microbiome.

It is worth noticing that in this study Bravo was used alone, that is without other nutritional or immunological interventions. Therefore, we can conclude that all the changes observed in the present study are due only to Bravo, with no other variables involved.

We believe that, among the important effects on detoxification from heavy metals and organic toxicants, the effects of Bravo on elimination of Glyphosate are of utmost importance and constitute a breakthrough since no other probiotic or supplement has these demonstrated effects.

I am certain that you are aware that Glyphosate is involved in onset and development of several diseases including 

ï      Cancer 

ï      Autism

ï      Neurodegenerative diseases

Therefore, the elimination of Glyphosate associated with consumption of Bravo may represent a key element in the health-supporting properties of our product.

In addition, this article demonstrates that consumption of Bravo is associated with reconstitution of the healthy human microbiome and with endogenous production of butyrate, a short-chain fatty acid that regulates multiple functions of human cells by optimizing gene expression, cell differentiation and tissue development, modulation of the immune system and reduction of oxidative stress.

All these positive changes are accompanied by a trend toward normalization of serum triglycerides and cholesterol.

We feel that this article demonstrating the effectiveness of Bravo against Glyphosate and other dangerous toxicants may represent a breakthrough and further supports and expands the health-promoting activities of Bravo that have been observed in the past 10 years and are summarized in the article.

I remain at your service for any further information I may provide and I take this opportunity to thank you for your support.

Yours truly,

Marco 

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An Interview with Prof. Marco Ruggiero: Understanding the GI and Brain Microbiome and the Role of GcMAF in Harmonizing the Immune System with the Microbiome Populations

From the Townsend Letter
October 2016

Order this issue!
An Interview with Prof. Marco Ruggiero: 
Understanding the GI and Brain Microbiome and the Role of GcMAF in Harmonizing the Immune System with the Microbiome Populations
by Jacques Fernandez de Santos 
Page 1, 2, 34
JFS: Hundred of years ago we did not have the same type of diseases that we have today; for instance, autism affects 1 in 68 children today versus 1 in 10,000 in 1990. Why in the case of autism is this happening: is it vaccines and poor nutrition combined that harm the original microbiome and therefore the immune system? 

      
MR: Although the cause of autism remains unknown to this date, I think that with the publication of our paper in Frontiers in Neuroscience, we have at least elucidated some important aspects of its pathogenesis; that is, the mechanisms that lead to the onset and progression of the symptoms. Changes in the nutritional properties of food, increased exposure to chemicals and other toxicants including electromagnetic radiations or radioactivity, excessive exposure to antibiotics and other drugs – all these factors may contribute to the observed increase in the incidence of autism spectrum disorders. In addition, a different way to diagnose and classify disorders of the development may also contribute to such an observed increase. There is, however, a point that is rarely taken into consideration and may prove rather relevant: the effects of low-intensity electromagnetic fields on the human microbiome and hence on the third and fourth brains. We elaborated on this point in a chapter that we wrote for the prestigious Encyclopedia of Cancer. In fact, even though the low-intensity electromagnetic fields to which we are constantly exposed appear to be fairly safe for our human cells, they appear to be detrimental for our microbial counterpart. In our chapter, we write: The effects of electromagnetic fields on the human microbiome open a new perspective in assessing the risks for health and in preventing them. So far, most of the research was concentrated on assessing the effects of electromagnetic fields on those areas of the body that were exposed to their energies. In other words, all the effects of electromagnetic fields on human health were ascribed to their interaction with the human cells of our bodies. However, since we have learned that electromagnetic fields, even of minimal intensity such as the endogenous electromagnetic fields, modify the human microbiome, their effects might be much more complex and far ranging. In fact, microbes and the microbiome may amplify or mitigate carcinogenesis, responsiveness to cancer therapeutics, and cancer-associated complication (Garrett 2015) and, therefore, electromagnetic fields modifying the microbiome may interfere with all such cancer-related responses. It is foreseeable that the development of functional foods containing probiotics for the prevention and treatment of cancer will have to take into account the effects of endogenous as well as exogenous electromagnetic fields on the human microbiome.Quite obviously, all these considerations apply even more to the development of the brain (or at least of the human first brain inside our head).
    
JFS: It is currently proven that there is no good health without a healthy microbiome, or third brain. You and your team have been able after years of research to create a super food that stimulates strongly the immune system through the stimulation of macrophages and natural killer cells. The key component of this super food, amongst others, is the protein GcMAF (Gc protein-derived macrophage activating factor), which could be described simplistically as carrier for the vitamin D. How would you define the main properties and characteristics of this protein as well as the super food you have created as a whole? 

    
MR: 
We began working on this “super food” that comes in the form of a fermented milk and colostrum product, a sort of a yogurt, about 5 years ago, when we were interested in developing a nutrition-based immunotherapeutic protocol. After hundreds of trials and errors, we eventually found the exact formula that is now in production, under the commercial name “Bravo.” This product shows two features that render it unique: it contains the live microbial strains that reconstitute the healthy human microbiome, and it contains about 200 natural, newly formed molecules that contribute to health maintenance in a wide variety of ways. 
      
The live microbial strains contained in Bravo are known to activate the immune system, stimulate macrophages, fight cancer, and help neurological and psychological processes; all these features contribute to the observed health effects of Bravo that have been published in a number of peer-reviewed papers (see, for example, Anticancer Res. 2014 Jul;34[7]:3569–3578). 
      
The newly formed molecules, naturally occurring during the fermentation of colostrum and milk, exert a number of biological functions that may contribute to health. Such biologically active molecules are not present in milk or colostrum but are formed during the process of fermentation, thanks to the enzymes produced and released by the microbes that we carefully selected for such a purpose. Among these molecules, there are peptides that help control blood pressure, others that stimulate the immune system, others that show antimicrobial properties, others that show antithrombotic properties, others that favor the absorption of minerals, others that have antioxidant activity, and others that influence mood and perception. There is, however, one particular molecule that gained great attention in the recent past and that is naturally produced (in other words, it is not added to the product) in Bravo: GcMAF. This powerful stimulator of the immune system shows a number of interesting healthful properties and has proved effective in a variety of pathologic conditions even independently of its main action of stimulating the immune system. 
    
JFS: This super food and its main component, GcMAF, have shown at the beginning of your studies years ago amazing results in pathologies such as AIDS or cancer proliferation. Can you please expand, before going to other pathologies, on the results observed on those important diseases? 

      
MR: Probiotic yogurts had been known for years as very effective tools in the fight against HIV/AIDS or cancer, thanks to the combined action of the microbes and the products of their metabolism. In 2010, a Canadian research team led by Dr. Reid demonstrated that a probiotic yogurt very similar to Bravo increased CD4 cells in African HIV/AIDS patients and ameliorated their clinical situation in a manner quite comparable to that of conventional antiretroviral drugs without the side effects of the latter (J Clin Gastroenterol. 2010 Oct;44[9]:e201–e205). Two years later, the same research group demonstrated that such an effect on HIV/AIDS patients was not limited to those living in impoverished countries and presumably suffering from malnutrition, but was observed in Canadian patients as well (Gut Microbes. 2012 Sep–Oct;3[5]:414–419). Interestingly, the same research group observed that one African patient in the probiotic group experienced seronegativization; that is, while consuming the probiotics, she tested HIV negative after having been confirmed HIV positive before being assigned to the probiotic group, whereas no patients in the placebo group experienced such an occurrence (Gut Microbes. 2011;2[2]:80–85). 
      
It is interesting to notice that all the papers mentioned above were published at about the same time that we were presenting our results at the Sixth International Aids Society Conference on HIV pathogenesis, treatment, and prevention, in Rome in 2011; at that conference, we observed that consumption of “our” yogurt brought about very similar results in terms of stimulation of the immune system. When almost identical results are independently produced by different research groups that report observations spanning from Africa to Italy and Canada, the probability that such results are not the product of serendipity are very high. 
      
Nowadays it is well accepted that probiotics are one of the pillars of the nutritional immunotherapy of HIV and AIDS, since they not only strengthen the individual’s immunity but also help reduce the systemic inflammation and improve the prognosis of HIV-infected individuals (PLoS One. 2015 Sep 16;10[9]:e0137200). The effects of probiotic yogurts such as Bravo on cancer patients are even more striking. For example, a recent review describes the effects of probiotic yogurt on the immune system and in cancer (Endocr Metab Immune Disord Drug Targets. 2015;15[1]:37–45), while another paper states that probiotic yogurt prevents cancer (J Agric Food Chem. 2015 Nov 4;63[43]:9381). When our Bravo yogurt was administered to advanced cancer patients in the context of a natural, nutrition-based, immunotherapeutic protocol, we observed significant results that were published in peer-reviewed journals, with one notable case wherein we even observed the reversal of a genetic marker of cancer (Anticancer Res. 2014 Jul;34[7]:3569–3578; Anticancer Res. 2015 Oct;35[10):5525–5532). In other words, a cancer-causing gene (also known as oncogene HER2) that was highly represented before the nutrition-based approach was no longer present after the implementation of the protocol. 
    
JFS: Also, later on, you and your team started studying the effects of this super food on autism in children and different neurodegenerative adult diseases, with very encouraging positive results. Why does it work, and to what extent have you observed net improvements in specific cases of autism independently of its etiology? 

      
MR: Although we may have contributed to the understanding of the pathogenesis of autism, I am convinced that the etiology, that is, the cause(s), may be multiple and different in each individual. The results of supplementation with Bravo yogurt in the context of an integrated, nutrition-based immunotherapeutic protocol in autism have been widely described in a number of conferences and congresses, and there is ample scientific consensus that probiotics help heal the symptoms of autism. According to some authors, alterations of the gut microbiome could actually be the cause for autism (Drug Metab Dispos. 2015 Oct;43[10]:1557–1771), and therefore it is logical that restoration of the microbiome helps improve the symptoms. However, I think that the dramatic improvements which we observe in children consuming the Bravo yogurt in the context of an individualized protocol are due to the combination of at least two factors: the reconstitution of the microbiome in the gut and in the brain (the third and fourth brain) and the stimulation of the immune system, notably the macrophages, that is in charge of balancing the two microbial populations between the gut and the brain. Whatever the case, we are witnessing significant improvements that are being independently confirmed by doctors from all over the world.
    
JFS: The lymphatic system of the brain is a new and amazing revolutionary discovery, announced not even a year ago, that explains many of the discoveries made by your team regarding immune therapy in the last few years. What are the implications of this new discovery for your work, and therefore for all of us? 

      
MR: The implications are enormous, particularly if we consider that the newly discovered brain lymphatic system now has to be associated with the very novel concept of the brain microbiome. The presence of commensal microbes inside the brain and their role as cells of the central (and probably also of the peripheral) nervous system calls for a complete reassessment of all the notions of neurobiology and neurology. As we describe in our paper in Frontiers in Neuroscience, the direct connection between the brain and the immune system may explain a number of observations that could not be explained before. For example, in 2002 a Brazilian researcher, Matarrazzo, described two cases of children who at first developed normally, but before age 3 developed autistic symptoms following the reactivation of a chronic otorhinolaryngologic infection; that is, an infection of the nose and throat. He then proceeded to administer adrenocorticotropic hormone as a means to reduce inflammation; and, in one case where the drug was prescribed in the first months of the disease, the child was completely cured. The other patient, who was 2 years old when autistic symptoms appeared and was treated only 6 years later, showed a partial but definitive improvement with the treatment (World J Biol Psychiatry. 2002 Jul;3[3]:162–166). In 2002 no one could explain such wonderful results, but now we can interpret them in light of our publication in Frontiers in Neuroscience
      
Chronic inflammation in the nose and throat clogs the deep cervical nodes, the nodes where the lymph drains from the brain. Therefore, the lymph cannot recirculate and toxins or toxicants accumulate in the brain, an occurrence that can be severely detrimental to the developing brain. In addition, the obstacle to of the lymph flow leads to accumulation of fluid inside the brain, and such an accumulation in a closed cavity (the skull) leads to the disruption of the connections between the neurons. Finally, such an impairment of the lymphatic drainage causes a relative immunodeficiency inside the brain, since the cells of the immune system, mainly the macrophages, cannot recirculate. Such an immunodeficiency may lead to an imbalance of the brain microbial population and to the chronic inflammatory status of the brain and the meninges that has been widely described in autism. As Matarrazzo demonstrated in 2002, if the inflammation in the nodes is fought at the early stages of autism progression, all these events do not occur or are rapidly reversed, and the symptoms of autism disappear. Most likely a similar mechanism is at work in a number of neurological conditions ranging from Alzheimer’s disease to multiple sclerosis, wherein the involvement of the immune system is well assessed.
    
JFS: With your recent discoveries the excellent results observed in patients with autism and neurodegenerative diseases treated with therapeutic nutritional approaches can now be explained. Recirculation of the lymph in the brain through the lymphatic vessels could be the key. Is this observation on its way to be fully proved? 

    
MR: 
The discovery of the brain lymphatic system brings about what is termed a paradigm shift; thus, now that a direct connection between the brain and the immune system has been established, the pathogenesis of many brain-based disorders is being revisited. We played our role in defining the importance of inflammation in the deep cervical nodes in autism, but other authors are proposing that a similar mechanism is at work in other neuropathologies such as Alzheimer’s disease. Just a few months ago, researchers from the US, France, and Sweden described “the clearance systems of the brain as they relate to proteins implicated in Alzheimer disease pathology” with particular reference to the newly discovered lymphatic drainage (Nat Rev Neurol. 2015 Aug;11[8]:457–470). Only a few days ago, in 2016, based on the discovery of the brain lymphatic system, other researchers reevaluated the entire corpus of knowledge concerning brain immunology and went so far to title their academic paper “Get It Through Your Thick Head: Emerging Principles in Neuroimmunology and Neurovirology Redefine Central Nervous System ‘Immune Privilege'” (Nat Rev Neurol. 2015 Aug;11[8]:457–470). However, as odd as it may seem, I and my team have been the only ones so far to merge the two observations of the brain lymphatic system and the presence of microbes in the normal brain into a single unitary concept: the brain microbiome, or the fourth brain. Such a concept is too novel to have been accepted by academia; however, there are some hints that other researchers share this intuition. For example, at the beginning of 2016, Irish researchers wrote a scientific paper with a rather unusual title that is fully consistent with all the notions that I have described so far: “The Brain’s Geppetto-Microbes As Puppeteers of Neural Function and Behaviour?” (J Neurovirol. 2016 Feb;22[1]:14–21). In this paper, they write that “there is a growing literature showing active behavioural manipulation in favour of the microbe,” and they conclude that “novel experimental approaches and theoretical concepts, such as the hologenome theory, are necessary to incorporate transgenerational epigenetic inheritance of the microbiome into evolutionary theories.”
    
JFS: In 
Your Third Brain, you write extensively on the importance of correctly feeding the second brain (the GI tract) and the third brain or the microbiome: the second brain with healthful food, including a diet based on 60% high-quality protein, 20% carbohydrates, and 20% fatty acids, and the third brain with what you call “the dessert cup” – the probiotic product with GcMAF that you and your team have been studying for years. How do both healthful alimentation and your team’s probiotic interact? 
      
MR: The nutritional plan that I describe in the book is known under a plethora of different names: ketogenic diet, Paleo diet, caveman diet and so on. All these names refer to the fact that primitive people, before the age of agriculture, ate very little carbohydrates (carbs) and relatively high proteins and fats. Since this type of diet induces the accumulation of ketone bodies, it is also called ketogenic. Such a nutritional approach is recognized as effective in the complementary treatment of a variety of chronic conditions ranging from cancer to neurological disease including autism (Eur J Clin Invest. 2016 Mar;46[3]:285–298). For example, as far as cancer is concerned, this approach is consistent with the 90-year-old observation of Prof. Otto Warburg, who demonstrated how cancer cells depend solely on carbs, whereas normal cells could use also ketone bodies for their survival. Consistent with this approach, our research group has been working for about 30 years on the role of glycolysis (the metabolism of carbs) in carcinogenesis and other human diseases and we have published 13 peer-reviewed papers on the role of a byproduct of glycolysis (diacylglycerol) in cancer as well as in chronic conditions such as neurodegenerative diseases, chronic kidney disease, and cardiovascular disease. We observed that the low-carb-high fat/protein nutrition improves the response to the natural immunotherapy based on Bravo, as well as to all the specific therapeutic approaches for each individual neoplasia, since it makes cancer cells more susceptible to ionizing radiations, chemotherapy or immunotherapy, as we demonstrated several years ago (Biochem Mol Biol Int. 1995 Sep;37[1]:81–88). We designed our nutritional approach around Bravo yogurt in order to exploit its main features that stimulate the immune system and reconstitute the human microbiome in addition to containing healthful fats and proteins with excellent nutritional value.

JFS: Hundred of years ago we did not have the same type of diseases that we have today; for instance, autism affects 1 in 68 children today versus 1 in 10,000 in 1990. Why in the case of autism is this happening: is it vaccines and poor nutrition combined that harm the original microbiome and therefore the immune system? 
      
MR: Although the cause of autism remains unknown to this date, I think that with the publication of our paper in Frontiers in Neuroscience, we have at least elucidated some important aspects of its pathogenesis; that is, the mechanisms that lead to the onset and progression of the symptoms. Changes in the nutritional properties of food, increased exposure to chemicals and other toxicants including electromagnetic radiations or radioactivity, excessive exposure to antibiotics and other drugs – all these factors may contribute to the observed increase in the incidence of autism spectrum disorders. In addition, a different way to diagnose and classify disorders of the development may also contribute to such an observed increase. There is, however, a point that is rarely taken into consideration and may prove rather relevant: the effects of low-intensity electromagnetic fields on the human microbiome and hence on the third and fourth brains. We elaborated on this point in a chapter that we wrote for the prestigious Encyclopedia of Cancer. In fact, even though the low-intensity electromagnetic fields to which we are constantly exposed appear to be fairly safe for our human cells, they appear to be detrimental for our microbial counterpart. In our chapter, we write: 

The effects of electromagnetic fields on the human microbiome open a new perspective in assessing the risks for health and in preventing them. So far, most of the research was concentrated on assessing the effects of electromagnetic fields on those areas of the body that were exposed to their energies. In other words, all the effects of electromagnetic fields on human health were ascribed to their interaction with the human cells of our bodies. However, since we have learned that electromagnetic fields, even of minimal intensity such as the endogenous electromagnetic fields, modify the human microbiome, their effects might be much more complex and far ranging. In fact, microbes and the microbiome may amplify or mitigate carcinogenesis, responsiveness to cancer therapeutics, and cancer-associated complication (Garrett 2015) and, therefore, electromagnetic fields modifying the microbiome may interfere with all such cancer-related responses. It is foreseeable that the development of functional foods containing probiotics for the prevention and treatment of cancer will have to take into account the effects of endogenous as well as exogenous electromagnetic fields on the human microbiome.

Quite obviously, all these considerations apply even more to the development of the brain (or at least of the human first brain inside our head).
    
JFS: It is currently proven that there is no good health without a healthy microbiome, or third brain. You and your team have been able after years of research to create a super food that stimulates strongly the immune system through the stimulation of macrophages and natural killer cells. The key component of this super food, amongst others, is the protein GcMAF (Gc protein-derived macrophage activating factor), which could be described simplistically as carrier for the vitamin D. How would you define the main properties and characteristics of this protein as well as the super food you have created as a whole? 

    
MR: 
We began working on this “super food” that comes in the form of a fermented milk and colostrum product, a sort of a yogurt, about 5 years ago, when we were interested in developing a nutrition-based immunotherapeutic protocol. After hundreds of trials and errors, we eventually found the exact formula that is now in production, under the commercial name “Bravo.” This product shows two features that render it unique: it contains the live microbial strains that reconstitute the healthy human microbiome, and it contains about 200 natural, newly formed molecules that contribute to health maintenance in a wide variety of ways. 
      
The live microbial strains contained in Bravo are known to activate the immune system, stimulate macrophages, fight cancer, and help neurological and psychological processes; all these features contribute to the observed health effects of Bravo that have been published in a number of peer-reviewed papers (see, for example, Anticancer Res. 2014 Jul;34[7]:3569–3578). 
      
The newly formed molecules, naturally occurring during the fermentation of colostrum and milk, exert a number of biological functions that may contribute to health. Such biologically active molecules are not present in milk or colostrum but are formed during the process of fermentation, thanks to the enzymes produced and released by the microbes that we carefully selected for such a purpose. Among these molecules, there are peptides that help control blood pressure, others that stimulate the immune system, others that show antimicrobial properties, others that show antithrombotic properties, others that favor the absorption of minerals, others that have antioxidant activity, and others that influence mood and perception. There is, however, one particular molecule that gained great attention in the recent past and that is naturally produced (in other words, it is not added to the product) in Bravo: GcMAF. This powerful stimulator of the immune system shows a number of interesting healthful properties and has proved effective in a variety of pathologic conditions even independently of its main action of stimulating the immune system. 
    
JFS: This super food and its main component, GcMAF, have shown at the beginning of your studies years ago amazing results in pathologies such as AIDS or cancer proliferation. Can you please expand, before going to other pathologies, on the results observed on those important diseases? 

      
MR: Probiotic yogurts had been known for years as very effective tools in the fight against HIV/AIDS or cancer, thanks to the combined action of the microbes and the products of their metabolism. In 2010, a Canadian research team led by Dr. Reid demonstrated that a probiotic yogurt very similar to Bravo increased CD4 cells in African HIV/AIDS patients and ameliorated their clinical situation in a manner quite comparable to that of conventional antiretroviral drugs without the side effects of the latter (J Clin Gastroenterol. 2010 Oct;44[9]:e201–e205). Two years later, the same research group demonstrated that such an effect on HIV/AIDS patients was not limited to those living in impoverished countries and presumably suffering from malnutrition, but was observed in Canadian patients as well (Gut Microbes. 2012 Sep–Oct;3[5]:414–419). Interestingly, the same research group observed that one African patient in the probiotic group experienced seronegativization; that is, while consuming the probiotics, she tested HIV negative after having been confirmed HIV positive before being assigned to the probiotic group, whereas no patients in the placebo group experienced such an occurrence (Gut Microbes. 2011;2[2]:80–85). 
      
It is interesting to notice that all the papers mentioned above were published at about the same time that we were presenting our results at the Sixth International Aids Society Conference on HIV pathogenesis, treatment, and prevention, in Rome in 2011; at that conference, we observed that consumption of “our” yogurt brought about very similar results in terms of stimulation of the immune system. When almost identical results are independently produced by different research groups that report observations spanning from Africa to Italy and Canada, the probability that such results are not the product of serendipity are very high. 
      
Nowadays it is well accepted that probiotics are one of the pillars of the nutritional immunotherapy of HIV and AIDS, since they not only strengthen the individual’s immunity but also help reduce the systemic inflammation and improve the prognosis of HIV-infected individuals (PLoS One. 2015 Sep 16;10[9]:e0137200). The effects of probiotic yogurts such as Bravo on cancer patients are even more striking. For example, a recent review describes the effects of probiotic yogurt on the immune system and in cancer (Endocr Metab Immune Disord Drug Targets. 2015;15[1]:37–45), while another paper states that probiotic yogurt prevents cancer (J Agric Food Chem. 2015 Nov 4;63[43]:9381). When our Bravo yogurt was administered to advanced cancer patients in the context of a natural, nutrition-based, immunotherapeutic protocol, we observed significant results that were published in peer-reviewed journals, with one notable case wherein we even observed the reversal of a genetic marker of cancer (Anticancer Res. 2014 Jul;34[7]:3569–3578; Anticancer Res. 2015 Oct;35[10):5525–5532). In other words, a cancer-causing gene (also known as oncogene HER2) that was highly represented before the nutrition-based approach was no longer present after the implementation of the protocol. 
    
JFS: Also, later on, you and your team started studying the effects of this super food on autism in children and different neurodegenerative adult diseases, with very encouraging positive results. Why does it work, and to what extent have you observed net improvements in specific cases of autism independently of its etiology? 

      
MR: Although we may have contributed to the understanding of the pathogenesis of autism, I am convinced that the etiology, that is, the cause(s), may be multiple and different in each individual. The results of supplementation with Bravo yogurt in the context of an integrated, nutrition-based immunotherapeutic protocol in autism have been widely described in a number of conferences and congresses, and there is ample scientific consensus that probiotics help heal the symptoms of autism. According to some authors, alterations of the gut microbiome could actually be the cause for autism (Drug Metab Dispos. 2015 Oct;43[10]:1557–1771), and therefore it is logical that restoration of the microbiome helps improve the symptoms. However, I think that the dramatic improvements which we observe in children consuming the Bravo yogurt in the context of an individualized protocol are due to the combination of at least two factors: the reconstitution of the microbiome in the gut and in the brain (the third and fourth brain) and the stimulation of the immune system, notably the macrophages, that is in charge of balancing the two microbial populations between the gut and the brain. Whatever the case, we are witnessing significant improvements that are being independently confirmed by doctors from all over the world.
    
JFS: The lymphatic system of the brain is a new and amazing revolutionary discovery, announced not even a year ago, that explains many of the discoveries made by your team regarding immune therapy in the last few years. What are the implications of this new discovery for your work, and therefore for all of us? 

      
MR: The implications are enormous, particularly if we consider that the newly discovered brain lymphatic system now has to be associated with the very novel concept of the brain microbiome. The presence of commensal microbes inside the brain and their role as cells of the central (and probably also of the peripheral) nervous system calls for a complete reassessment of all the notions of neurobiology and neurology. As we describe in our paper in Frontiers in Neuroscience, the direct connection between the brain and the immune system may explain a number of observations that could not be explained before. For example, in 2002 a Brazilian researcher, Matarrazzo, described two cases of children who at first developed normally, but before age 3 developed autistic symptoms following the reactivation of a chronic otorhinolaryngologic infection; that is, an infection of the nose and throat. He then proceeded to administer adrenocorticotropic hormone as a means to reduce inflammation; and, in one case where the drug was prescribed in the first months of the disease, the child was completely cured. The other patient, who was 2 years old when autistic symptoms appeared and was treated only 6 years later, showed a partial but definitive improvement with the treatment (World J Biol Psychiatry. 2002 Jul;3[3]:162–166). In 2002 no one could explain such wonderful results, but now we can interpret them in light of our publication in Frontiers in Neuroscience
      
Chronic inflammation in the nose and throat clogs the deep cervical nodes, the nodes where the lymph drains from the brain. Therefore, the lymph cannot recirculate and toxins or toxicants accumulate in the brain, an occurrence that can be severely detrimental to the developing brain. In addition, the obstacle to of the lymph flow leads to accumulation of fluid inside the brain, and such an accumulation in a closed cavity (the skull) leads to the disruption of the connections between the neurons. Finally, such an impairment of the lymphatic drainage causes a relative immunodeficiency inside the brain, since the cells of the immune system, mainly the macrophages, cannot recirculate. Such an immunodeficiency may lead to an imbalance of the brain microbial population and to the chronic inflammatory status of the brain and the meninges that has been widely described in autism. As Matarrazzo demonstrated in 2002, if the inflammation in the nodes is fought at the early stages of autism progression, all these events do not occur or are rapidly reversed, and the symptoms of autism disappear. Most likely a similar mechanism is at work in a number of neurological conditions ranging from Alzheimer’s disease to multiple sclerosis, wherein the involvement of the immune system is well assessed.
    
JFS: With your recent discoveries the excellent results observed in patients with autism and neurodegenerative diseases treated with therapeutic nutritional approaches can now be explained. Recirculation of the lymph in the brain through the lymphatic vessels could be the key. Is this observation on its way to be fully proved? 

    
MR: 
The discovery of the brain lymphatic system brings about what is termed a paradigm shift; thus, now that a direct connection between the brain and the immune system has been established, the pathogenesis of many brain-based disorders is being revisited. We played our role in defining the importance of inflammation in the deep cervical nodes in autism, but other authors are proposing that a similar mechanism is at work in other neuropathologies such as Alzheimer’s disease. Just a few months ago, researchers from the US, France, and Sweden described “the clearance systems of the brain as they relate to proteins implicated in Alzheimer disease pathology” with particular reference to the newly discovered lymphatic drainage (Nat Rev Neurol. 2015 Aug;11[8]:457–470). Only a few days ago, in 2016, based on the discovery of the brain lymphatic system, other researchers reevaluated the entire corpus of knowledge concerning brain immunology and went so far to title their academic paper “Get It Through Your Thick Head: Emerging Principles in Neuroimmunology and Neurovirology Redefine Central Nervous System ‘Immune Privilege'” (Nat Rev Neurol. 2015 Aug;11[8]:457–470). However, as odd as it may seem, I and my team have been the only ones so far to merge the two observations of the brain lymphatic system and the presence of microbes in the normal brain into a single unitary concept: the brain microbiome, or the fourth brain. Such a concept is too novel to have been accepted by academia; however, there are some hints that other researchers share this intuition. For example, at the beginning of 2016, Irish researchers wrote a scientific paper with a rather unusual title that is fully consistent with all the notions that I have described so far: “The Brain’s Geppetto-Microbes As Puppeteers of Neural Function and Behaviour?” (J Neurovirol. 2016 Feb;22[1]:14–21). In this paper, they write that “there is a growing literature showing active behavioural manipulation in favour of the microbe,” and they conclude that “novel experimental approaches and theoretical concepts, such as the hologenome theory, are necessary to incorporate transgenerational epigenetic inheritance of the microbiome into evolutionary theories.”
    
JFS: In Your Third Brain, you write extensively on the importance of correctly feeding the second brain (the GI tract) and the third brain or the microbiome: the second brain with healthful food, including a diet based on 60% high-quality protein, 20% carbohydrates, and 20% fatty acids, and the third brain with what you call “the dessert cup” – the probiotic product with GcMAF that you and your team have been studying for years. How do both healthful alimentation and your team’s probiotic interact? 

      
MR: The nutritional plan that I describe in the book is known under a plethora of different names: ketogenic diet, Paleo diet, caveman diet and so on. All these names refer to the fact that primitive people, before the age of agriculture, ate very little carbohydrates (carbs) and relatively high proteins and fats. Since this type of diet induces the accumulation of ketone bodies, it is also called ketogenic. Such a nutritional approach is recognized as effective in the complementary treatment of a variety of chronic conditions ranging from cancer to neurological disease including autism (Eur J Clin Invest. 2016 Mar;46[3]:285–298). For example, as far as cancer is concerned, this approach is consistent with the 90-year-old observation of Prof. Otto Warburg, who demonstrated how cancer cells depend solely on carbs, whereas normal cells could use also ketone bodies for their survival. Consistent with this approach, our research group has been working for about 30 years on the role of glycolysis (the metabolism of carbs) in carcinogenesis and other human diseases and we have published 13 peer-reviewed papers on the role of a byproduct of glycolysis (diacylglycerol) in cancer as well as in chronic conditions such as neurodegenerative diseases, chronic kidney disease, and cardiovascular disease. We observed that the low-carb-high fat/protein nutrition improves the response to the natural immunotherapy based on Bravo, as well as to all the specific therapeutic approaches for each individual neoplasia, since it makes cancer cells more susceptible to ionizing radiations, chemotherapy or immunotherapy, as we demonstrated several years ago (Biochem Mol Biol Int. 1995 Sep;37[1]:81–88). We designed our nutritional approach around Bravo yogurt in order to exploit its main features that stimulate the immune system and reconstitute the human microbiome in addition to containing healthful fats and proteins with excellent nutritional value.

JFS: Is it possible that, just by consuming “the dessert cup,” certain conditions can be improved in places such as Africa, where access to reliable sources of good protein might be difficult? In this sense, your probiotic product has been distributed for free in Malawi and some Asian countries to children and to people living with HIV/AIDS, with, it seems, very good results. 

MR: Probiotic yogurts proved effective in a variety of conditions, in particular where malnutrition and immunodeficiency are present at the same time. In fact, they provide for an excellent source of protein, healthful fats, vitamins, and micronutrients. In addition, all probiotic yogurts contain live cultures that exert positive effects on human health as well as a wealth of proteins and peptides that modulate the immune system, favor the absorption of minerals, decrease inflammation and, in general terms, improve nutritional status. Our Bravo yogurt is peculiar in that it was designed taking into consideration the natural formation of powerful immune-stimulating molecules such as GcMAF. In addition, Bravo contains fermented colostrum, an excellent source of noble proteins and of proline-rich polypeptides (PRP). These molecules are also known as colostrinin and were independently discovered in colostrum and other sources, such as blood plasma, in the US and Poland. In this respect, they resemble the Gc protein, the precursor of GcMAF that also is present in colostrum and in blood. PRPs function as signal-transducing molecules that have the unique effect of modulating the immune system, turning it up when the body comes under attack from pathogens or other disease agents, and damping it when the danger is eliminated or neutralized. In other words, Bravo, which contains fermented colostrum, does not stimulate the immune system in a nonspecific way; it rebalances the immune system, and because of this it has also proved effective in those conditions wherein the immune system is overstimulated, such as with autoimmune diseases. The ferments to prepare the Bravo yogurt were donated to two refuge facilities for children, one in Malawi and one in Thailand, and the yogurt was prepared in loco using local cow milk. So far we have received very encouraging reports, and we hope to be able to help other communities as well.
    
JFS: Throughout your book, you expound extensively on the importance of proteases in order to assimilate the amino acids that compose the proteins we eat. In parallel, you have worked in the pharmaceutical industry, in the field of proteases. Those inhibitors are widely used to treat HIV infection. The official HIV/AIDS hypothesis states that this is due to the inhibition of proteases of the HIV virus, which once its replication is suppressed, allows the immune system to recover. Within this context, is there another explanation of why this proteases or integrase inhibitors work in immune depressed patients, and could those inhibitors be applied to immune deficiencies not related to HIV in general for short periods of time? 

    
MR:
 I began working on the enzymes called proteases and their inhibitors. I was a postdoctoral fellow at the Burroughs Wellcome Research Laboratories in North Carolina in the 1980s. With my supervisor, Dr. Eduardo Lapetina, I published a seminal paper that was presented to the National Academy of Sciences of the USA by the Nobel laureate Sir John Vane (Proc Natl Acad Sci U S A. 1986 May;83[10]:3456–3459). In this paper, we describe the effects of a protease inhibitor derived from a certain bacterium called Actinomycetes. This natural inhibitor is called leupeptin and has several interesting properties that may be exploited in the field of natural immunotherapy with particular reference to viral infections. In fact, many viruses, from the influenza viruses to HIV, rely on proteases to be activated and, because of this, protease inhibitors are effective antiviral agents. Leupeptin was demonstrated to be effective against the influenza virus (Antiviral Res. 2011 Oct;92[1]:27–36) but I am not aware of studies of its effects on HIV. However, natural inhibitors of proteases can be found in a number of other natural compounds and may have a role in the natural immunotherapy of viral infections. For example, it is well known that milk and milk-derived products such as Bravo contain inhibitors of the protease called angiotensin converting enzyme, and it is also well known that there are a number of peptides with antiviral properties in fermented milk products such as Bravo (J Proteomics. 2015 Mar 18;117:41–57). In addition to peptides with protease inhibitory activity, milk and its derivatives contain glycosaminoglycans, such as chondroitin sulfate, that are similar to protease inhibitors called kunins and are known to inhibit the binding of HIV to its target cells that are the CD4 lymphocytes (J Nutr. 1995 Mar;125[3]:419–424). It is interesting to notice that this molecule, commonly found in milk and its derivatives, has been demonstrated to be extremely efficient against HIV since the 1990s. In PubMed there are reports describing how a combination of natural substances that included chondroitin sulfate reduced viral load to nondetectable levels in 10 days, a result not even imaginable today with the most advanced antiretroviral drugs (Posit Health News. 1998 Fall[17]:7–11). The following year, in 1999, an Italian researcher working at the Centre for Virology of the Institute Spallanzani in Rome demonstrated that chondroitin sulfate was efficient not only against HIV itself, but also the opportunistic pathogens that are known to infect immunodeficient patients (Antivir Chem Chemother. 1999 Jan;10[1]:33–38). Curiously, none of the research involving natural protease inhibitors such as leupeptin or the inhibitors in milk has received much attention, while this could be an inexpensive and fully natural way to block viral infections and strengthen the immune system. However, I would not be surprised if in the future it is demonstrated that anti-HIV (antiretroviral) drugs also show other effects that may be responsible (momentarily) for the recovery of the immune system independently of their antiretroviral effects. This is a frequent occurrence in medicine; the positive effects of a drug on the outcome of the disease are at first ascribed to some mechanism that is later on demonstrated to not be completely correct. The positive effects remain, but it may be discovered that the reason why the drug worked is completely different from the one that had been previously hypothesized. If we assume that a competent immune system can fight the supposed HIV infection, then it is reasonable to hypothesize that drugs, remedies, or supplements that strengthen the immune system will help in such a fight.
    
JFS: The dessert cup with the GcMAF protein is an intrinsic part of the vitamin D axis. Is it important to check vitamin D levels and in case of low levels, supplement before taking Bravo or GcMAF? 


MR: The issue of how much vitamin D we need is a truly complex one. So complex that a few years ago, the famous nephrology journal Kidney International, of the Nature Publishing Group, invited me to write a commentary titled “Chronic Kidney Disease and Vitamin D: How Much Is Adequate?” (2009 Nov;76[9]:931–933). There I put forward the idea that the adequate intake of vitamin D has to be reevaluated. In fact, the current indications refer to the biological effects of vitamin D on bone and calcium metabolism, with particular reference to the prevention of rickets. However, such a limited interpretation of the biological effects of vitamin D is now obsolete, and even the designation of the molecule is erroneous. Today we know that it is not a vitamin but a hormone, and that it regulates practically all the aspects of cell physiology and therefore is involved in almost all types of disease. If you search for “vitamin D and cancer treatment” in PubMed, you will find more than 5000 published articles, and the same happens if you search, for example, for “vitamin D and cardiovascular disease,” where you find more than 4000 articles. However, as of today, no one is able to state with certainty what the adequate amount of vitamin D is in each particular condition and whether the amount to treat a disease is the same as that to prevent the same disease. Things are even more complicated if we consider that each individual has a different response to vitamin D because of variations (polymorphisms) in the gene that codes for the receptor of vitamin D. We published several papers on this issue, and, for example, we demonstrated that women harboring a variation of the gene show a significantly higher risk of metastases and recurrences of breast cancer (Oncol Res. 1998;10[1]:43–46). There are physicians in Germany who inject intravenously very high amounts of vitamin D, in the range of 400,000 International Units (IU), in the course of cancer treatment and, interestingly, do not report adverse effects. Personally, I try to expose myself to the sun as frequently as possible since in 30 minutes of exposure my skin produced more than 10,000 IU of endogenous vitamin D. When I don’t have this opportunity, I take the same amount of vitamin D as a supplement but, as I have written, the response and consequently the dosage vary in each individual. The response to any treatment involving stimulation or rebalancing of the immune system needs adequate amounts of vitamin D; and, in case of doubt, supplementation may be required. (In PubMed, “vitamin D and immune system” yields 3459 papers!)
    
JFS: Speaking of heparin, as it is widely mentioned in Your Third Brain, is your team still studying it in order to find ways to administer it to patients, since it appears to have very important properties and it is a very effective molecule to fight cancer cells by inhibiting their replication? 


MR: I began working on heparin in 1985 when I was a young post-doc at the Laboratory of Molecular Biology of the University of Firenze, Italy; and I published a paper in the Biochemical Journal, which was among the most famous scientific journals in those days (1985 Apr 1;227[1]:57–65). In that paper, we described a rather strange association between endogenous heparin and phosphatidylcholine, a major constituent of the cell membrane. While the use of heparin as an anticoagulant drug is very well assessed, the role of endogenous heparin and in particular in the bloodstream remains a mystery, one of the few mysteries in today’s physiology. Back in the 1980s, we postulated that endogenous heparin might have had roles other than the well-known anticoagulant activity, and, given our interest in the biology of cancer, we begun studying whether heparin was a naturally occurring anticancer agent. We published the first paper demonstrating that it is indeed an anticancer agent in 1991, when we showed that heparin inhibited the proliferation of carcinoma cells (FEBS Lett. 1991 Apr 9;281[1–2]:141–144). Two years later, we demonstrated that such an anticancer effect was not limited to carcinoma cells, but it could be observed in a variety of cells transformed by different oncogenes, which are genes whose mutations are known to cause cancer (Cell Biol Int. 1993 Aug;17[8]:781–786). Therefore, we concluded that the role of the heparin that in the bloodstream is related to the natural control of cancer, the so-called anticancer surveillance, a term which indicates the physiological mechanisms that defend us from the cancer cells that constantly arise in the body. Rather obviously, the heparin that is commercially available cannot be used as an anticancer drug as it is, since it would cause bleeding because of its anticoagulant activity. Because of this, for the following 20 years, we kept on studying its physiological assembly in the human body with the goal of discovering the secret of how endogenous heparin can protect from cancer without causing bleeding. We eventually found out that the key lies in its association with plasma proteins. In other words, when the endogenous heparin associates with certain proteins in the plasma, the properties of the proteins and of heparin change dramatically and novel biological properties, such as the anticancer activity, arise. We also found out that heparin regulated gene expression, another apparent oddity considering that the DNA is negatively charged and heparin is the biological molecule with the highest concentration of negative charges. Therefore, according to the principles of electrostatics, DNA and heparin should repel each other. On the contrary, we demonstrated that heparin, once bound to certain proteins, dramatically changes its overall electrostatic behavior and is transported inside the cells, where it can interact with molecules such as DNA, therefore influencing the functioning of the genes (Biochem Biophys Res Commun. 1986 Oct 15;140[1]:294–301). 
    
JFS: “Miraculous” molecules such as GcMAF apparently have many abilities, although the real one would to be the carrier for the good molecules doing the real job. Actually GcMAF could be replaced somehow, as the important aspect is its carrying ability. Could you please further explain this important aspect to better understand this molecule? 


MR: First of all, we have to understand what GcMAF means: it is a macrophage activating factor (and this describes its function) derived from a protein called Gc (from group component; that is, a component of human plasma). The Gc protein is also known as vitamin D binding protein because one of its functions is to bind vitamin D and carry it to the target cells. The functions of the Gc protein have been known for years, long before the observation that it also could activate macrophages. It was very well known that the Gc protein binds actin, a cellular protein that is released when cells die. Therefore, the Gc protein works as a scavenger that prevents the accumulation of actin coming from dead cells that could be very toxic. In addition, it was known that the Gc protein also binds fatty acids such as oleic acid. We could make an analogy and say that the Gc protein is a big truck that can carry away toxic waste (the actin from dead cells), as well as vitamin D and oleic acid to their cellular targets. The Gc protein also carries another molecule with a rather fancy name: alpha-N-acetylgalactosamine. This is a sugar that is present in milk (hence the name with the suffix –galactose), and it is bound to one of the amino acids of the Gc protein. We observed that the function of activating macrophages is due to a molecular triad that happens to be carried by the Gc protein. This molecular triad is composed of alpha-N-acetylgalactosamine, vitamin D, and oleic acid. 

Continuing analogies with vehicles, now we can say that the Gc protein is like a taxi that carries a three-person surgical team to the hospital so that they can perform their duties. These three people/molecules are the alpha-N-acetylgalactosamine, vitamin D, and oleic acid that need to be carried all together at the same time if they are to activate macrophages. The kind of taxi, or whether it is a limousine or a piece of junk, is rather irrelevant as long as it can carry the team to the hospital. Now, imagine that GcMAF is nothing other than a taxi carrying the three-people team to the hospital; we have found a way to replace the Gc protein that derives from blood with another class of molecules called glycosaminoglycans. It is as if we have replaced the taxi that moves slowly in the traffic with a helicopter; it can carry the three-person team to the hospital much faster and more efficiently. In addition, let’s assume that the team is needed in more than one hospital; here it means that more than one macrophage needs to be activated. With a regular taxicab, once they have finished in the first hospital, the three members board the taxi that, slowly and with the uncertainty of traffic, carries them to the next hospital. With the helicopter, the transfer of the surgical team from a hospital to the next will be much more rapid and efficient and a greater number of patients will benefit. When I invented this “helicopter” that is the next generation of GcMAF, I followed this very reasoning, and I had the advantage of having worked on glycosaminoglycan for the previous 30 years. This is the reason why this next-generation MAF (here the Gc prefix is no longer necessary) is so powerful and versatile.
    
JFS: Besides GcMAF-carrying ability, you mention many others, such as inhibition of breast cancer cells, as well as protection of human cells from damage inflicted by heavy metals. Once the vitamin D axis is reestablished, there is an awakening of macrophages and natural killers. Is that correct? Are there other mechanisms by which GcMAF function?


MR: Molecules such as the old GcMAF or next-generation MAF have multiple actions, for the very simple reason that they operate at the most basic genetic level and influence the working of a number of genes that in turn influence a great number of physiologic functions. This translates in a long list of possible clinical applications. Just to name a few, the next-generation MAF could be used to restore the immune system, which is rather obvious, but also to fight several chronic conditions wherein the use of vitamin D, oleic acid, and glycosaminoglycans has already proved effective. I am referring to neurological disorders such as Parkinson’s and Alzheimer’s diseases, multiple sclerosis, amyotrophic lateral sclerosis, and brain aging, or to dermatological conditions such as psoriasis. Another possible area of intervention is related to cardiovascular conditions, since all three members of this “surgical dream team” have been shown to be effective in the prevention and treatment of cardiovascular conditions – and of course cancer. We do not know as yet the minimum length of treatment with this novel, rather revolutionary MAF, but we can safely assume that once the underlying disorders have been addressed, a minimum maintenance dose should be all that is required.
    
JFS: Stimulation of nitric oxide looks like a significant ability of GcMAF molecule, as it has an important effect on the circulatory system. Could you expand on the importance of this aspect and how it relates to cardiovascular health? 


MR: Nitric oxide (NO) is a very interesting molecule; it was even awarded the title of “Molecule of the Year” by the journal Science in 1992. In those days, its fame was mainly due to its role in the mechanism of action of Viagra. In fact, among many other actions, NO cause vasodilation, and the increase in blood flow in different organs may be exploited for different scopes. For example, it had been known for decades that nitrates that release NO are very useful in increasing the coronary blood flow and can solve an attack of angina pectoris. Increased blood flow in the cavernous bodies of the penis fights erectile dysfunction; Viagra essentially works by blocking the degradation of NO, thus favoring its action. Later on, it was discovered that NO also has other interesting functions that could be exploited in the treatment of proliferative diseases such as cancer. In fact, NO selectively kills cancer cells because it causes a type of damage to cancer cells’ DNA that they cannot repair. In other words, NO has the same effect on the DNA of healthy cells and cancer cells, but the cancer cells are unable to repair the damage inflicted by the NO, whereas the healthy cells do have not such a difficulty. We discovered that macrophages, when they are activated by GcMAF or the next-generation MAF, release NO, and such a release can easily be demonstrated by looking at the blood flow with a common ultrasound system (Anticancer Res. 2014 Jul;34[7]:3569–3578). Thus, we may have found something very close to the long-sought-after “magic bullet.” In oncology, before the advent of the “smart bombs,” magic bullet referred to a molecule that could kill only cancer cells, leaving healthy cells unharmed – at variance with what commonly happens with conventional chemotherapy. The principle is rather simple: we activate the macrophages with the old GcMAF or, even better, the next-generation MAF. The macrophages go on a “search and destroy” mission; that is, they look for cancer cells or cells infected by viruses. Once they have found such an abnormal cell, the macrophages bind to it and release NO that causes irreversible damage to the DNA of the cancer cell. As far as the role of the NO released by the activated macrophages in cardiovascular health is concerned, we must take into consideration that a constant, physiological activation of macrophages can be achieved with probiotic products such as Bravo, which in this way may contribute to the maintenance of health. In fact, Bravo not only contains naturally produced GcMAF, but it also has some live microbes such as Lactobacillus rhamnosus that are known to activate macrophages per se (Microbiol Immunol. 2012 Nov;56[11]:771–781).

JFS: Immune therapy started with Dr. William Coley at the end of the 19th century and the beginning of the 20th century. However, the 20th century has been the century of the pharmacology approach in medicine. Teams and researchers like yourself are now working in the 21st century on immune therapy, and have rescued this fundamental approach to the future of medicine. Bearing all this in mind, how do you forecast the future of medicine in the years to come? 
      
MR: It is interesting that you mention the work of Dr. Coley, the father of immunotherapy, since such an approach is being rediscovered in these very days. In a publication in PubMed, aptly titled “Back to the Future,” the author writes: “Cancer patients infected with various bacteria were reported, for at least two centuries, to have spontaneous remission. W.B. Coley, of what is now the Memorial Sloan-Kettering Cancer Center, pioneered bacterial therapy of cancer in the clinic with considerable success beginning in the late nineteenth century. After Coley died in 1936, bacterial therapy of cancer essentially ended. Currently there is much excitement in developing bacterial therapy for treating cancer using either obligate or facultative anaerobic bacteria.” (Methods Mol Biol. 2015;1317:239–260). It should be noticed that Dr. Coley had spectacular results in very advanced cancer cases, results that we cannot even dream of with our most advanced therapeutic strategies. The problem with Dr. Coley’s approach, however, was the lack of standardization and, because of this, the difficulty of reproducing the results that he consistently obtained on a large scale. Quite obviously, our knowledge of the mechanisms of cancer is now much more refined, at the molecular level, and we also know the role of the microbiome in health and disease; therefore, many researchers think that the time is ripe to rediscover Dr. Coley’s observations and interpret them in light of today’s knowledge, with the hope of finding a reliable way to treat patients otherwise labeled incurable. Such an approach is becoming “mainstream,” up to the point that the journal Science recently wrote: “A new class of cancer treatments that unleash the power of the immune system on tumour may depend on some unlikely allies (the microbes)” (2015 Nov 6;350[6261]:614–615). In my opinion, these words do justice to the work of Dr. Coley, since they clearly state that the microbes “unleash the power of the immune system” that in turn represents “a new class of cancer treatments.” It has to be said that researchers are exploring rather innovative ways to exploit the abilities of microbes to fight cancer, and they are finding allies that are even more “unlikely”: the viruses! In a paper titled “Combined Bacterial and Viral Treatment: a Novel Anticancer Strategy,” the author argues: “An idea for a new combination therapy will be described herein. It is a proposition to combine viral and bacterial anticancer therapies and make them fight cancer in concert” (Cent Eur J Immunol. 2015;40[3]:366–372). It may come as a surprise to learn that a virus that could potentially be exploited to fight cancer is no one less than … HIV! As I write, together with John W. Anderson, in the Encyclopedia of Cancer, ” … there exists a HIV accessory protein termed viral protein R (Vpr) that plays a key role in virus replication and also induces cell cycle arrest and apoptosis in various cell types including T cells, neuronal cells, and tumor cells.” Thus, as odd as it may seem, a protein produced by HIV could be exploited as a beneficial antitumor agent in cancers. … In recent years, several investigators have studied the potential use of Vpr as an antitumor therapeutic. … The antitumor properties of certain HIV proteins might even have been responsible for establishing a symbiotic relationship in humans. … ” (Encyclopedia of Cancer. doi:10.1007/978-3-642-27841-9_562-4). These observations are consistent with a rather odd report from Columbia University describing how women carrying HIV, or at least its antibodies, appear to have a better 5-year survival rate (80%) when compared with the general population (70%) (J Surg Oncol. 2005 Jan 1;89[1]:23–27). All these results and the deriving considerations lead me to speculate that we may be on the verge of a revolution in cancer therapy and ready to rediscover and appreciate the long-neglected work of Dr. Coley.
    
JFS: Could this approach, at least in Western countries, counterbalance and refocus the dominance of pharmacological approach in modern medicine by giving more freedom to doctors in order to be able to use all the tools at their disposal? 

      
MR: I truly think that rock-solid scientific evidence is accumulating and supporting those approaches once labeled “alternative.” The microbial therapies of cancer are just an example of such a rapidly evolving field. Regrettably, laws and regulations follow much more slowly, and it may take years before such approaches are officially recognized by regulatory bodies. However, the use of Internet by patients is rapidly changing the scenario within which therapists are called to operate. In fact, it often happens that patients are more updated and prepared than therapists, and it is not infrequent to notice that patients go to their doctors asking for approaches that have solid scientific evidence although they may not yet be approved by regulatory bodies. Patients are often prepared to travel long distances to have therapies performed when these are not available in their countries. Internet, low-cost flights, and globalization are changing also the way that patients perceive their quest for health, and the world of medicine has to adapt if it wishes to survive. The same reasoning applies to doctors as well. It is now commonplace to find European or American doctors in wealthy countries in Asia or the Middle East, free to practice innovative therapeutic approaches with great benefits for those patients who can afford the expenses. If Western medicine does not adapt itself, this phenomenon will only increase, and, sadly, only the wealthy will be able to benefit from the latest discoveries in medical science.
    
JFS: The lack of development of molecules such as GcMAF or heparin could be interpreted as “laziness” by the pharmaceutical industry. The production of such immune components has shown amazing results, being much less harmful that conventional treatments, and less toxic when those treatments need to be administered. Why? Is there a conflict of interest or simply a lack of interest from allopathic medicine and Big Pharma?

    
MR: 
Having worked in the pharmaceutical industry in the US and in Europe, I can say that, just like any other industry, the pharmaceutical industry is not driven by ideology but by profit. Therefore, so-called Big Pharma is not for or against alternative or complementary medicine; it simply follows the paths that lead to profit, and as of today the research and development of allopathic drugs has proved very effective in this respect. The responsibility for such a situation also lies in part in the alternative-practitioner community, which sometimes has a sort of ideological approach to medicine and health-related issues and is against the industrial approach a priori. It is also true that many natural remedies show little appeal to the pharmaceutical industry because it is difficult to patent them and therefore profit. However, I have the perception that things are changing and I am observing a phenomenon that I have already witnessed in the 1980s. Back then, Big Pharma was not interested in the emerging field of molecular biology and biotechnologies; it was focused on the old-fashioned approach of skilled chemists’ synthesizing thousands of putatively helpful molecules in their labs. The community of molecular biologists, however, was composed mainly of hippie-type biologists, rather than chemists in their white coats, and they focused on the biological processes that lead to the onset of diseases, with the goal of exploiting such a knowledge to develop naturally based molecules aimed at restoring cells’ physiology. Those scientists begun founding their microscopic companies, sometimes in little more than their garages, with the goal of producing one single antibody or one single biologically derived molecule. Thirty years later, such companies evolved into the gigantic biotech industries that we know today and lead the market in the research and development of remedies based on the knowledge of how cells function. I hope that such a transition will occur also for what is now defined as alternative or complementary medicine, and I see many signs that this is already occurring.
    
JFS: The final chapters of 
Your Third Brain raise a fascinating field ultrasonography and ultrasound. To what extent could this “remote control” science revolutionize the field of immune therapy? 
    
MR: 
At variance with common perception, ultrasounds are not generated exclusively by machines such as those that are used in diagnostic ultrasonography, a branch of radiology that I mastered in the past. Ultrasounds are commonly generated in nature and are perceived by animals, as anyone who has a god knows very well. According to some theories, ultrasounds have shaped the universe as we know it, and they may have contributed to shaping the DNA that codes for life on this earth. Therefore, it is not surprising that there are genes in our DNA that are turned on by ultrasounds, and, by a leap of imagination, we could visualize someday having a remote control that lets us turn on or off genes, just as we zip between television channels from our sofas. And such a day may be closer than we think. Since 2013, we have published papers demonstrating that ultrasounds alter mental states and may be useful in the treatment of a number of diseases. Quite recently, we published two papers demonstrating how ultrasounds improve neuronal connectivity and how such an effect may be applied to neurological conditions such as autism (Conf Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:8131–8234; Biomed Signal Process Contr. 22[2015]:44–53). These results of ours are consistent with previous observation by Hameroff and colleagues, who described how ultrasound could be used to address untreatable pain (Brain Stimul. 2013 May;6[3]:409–415), and more recent reports describing the potential use of ultrasounds in a series of neurological diseases (Nat Rev Neurol. 2016 Mar;12[3]:161–174). As far as of cancer immunotherapy is concerned, there are not very many studies demonstrating such an effect of ultrasound, probably because most researchers, including ourselves, were mostly interested in its effects on the brain. However, in some preliminary experiments that have not yet been published, we noticed that ultrasound at certain frequencies can kill cancer cells, leaving the healthy cells unharmed. This selectivity can be explained by taking into account the fact that cancer cells have a metabolism quite different from that of normal cells, and therefore the effects of the ultrasound seem to be detrimental to them. Interestingly, healthy cells not only do not suffer any damage as a consequence of ultrasound treatment, but they also seem to be stimulated in their functional activity. In other words, at least in vitro, ultrasounds seem to have a sort of “magic touch” on cells; they kill the cancer cells while benefiting the healthy cells at the same time. Although the precise mechanism of action still has to be determined, such effects are currently being exploited in the field of cancer immunotherapy. For example, in 2014, our Japanese colleagues and competitors in the field of GcMAF research published a paper demonstrating how the combination of GMAF injections and ultrasound therapy (designated sonodynamic therapy) was very effective in breast cancer treatment (Anticancer Res. 2014 Aug;34[8]:4577–4581). In the past few days, working together with one of the most respected medical doctors in the field of integrative medicine, we noticed that a careful application of ultrasound after specific immunotherapy significantly amplified the effects of the immunotherapy itself. Since ultrasound is inherently safe and harmless, as demonstrated by some 50 years of diagnostic ultrasonography, I think that such an approach will become commonplace in a very short period of time.
    
JFS: What last message could you give to our readers? 

      
MR: I wish to give the same message that I used to give my patients not long ago: every day we are witnessing a new boost in scientific discoveries that, at variance with the past, now can immediately be applied to the individual case. Therefore, diseases that yesterday were deemed incurable today can be successfully fought. We are learning so many things about the immune system, the microbiome, the relationship between our human and nonhuman brains, that yesterday’s knowledge already is obsolete. Cancer, autism, and neurological or cardiovascular diseases can now be approached with a variety of options that offer realistic hopes to cases previously designated incurable. We live in a most exciting time, and it seems that there are no boundaries to what we may achieve in health and medicine if we are open to the progress of knowledge.

Jacques Fernández de Santos is an independent journalist based in Spain who has covered different countries, analyzing their economies, politics, and social issues. He has covered missions in countries such as Ukraine, Brazil, Jordan, Bulgaria, Kurdistan-Iraq, and Turkey. His last mission was in Morocco in 2015 (www.marco-hub.fr). He also occasionally undertakes scientific interviews with researchers such as Dr. Marco Ruggiero. 

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Detoxification takes Energy

This month a customer who was using imuno broke out in hives.  She was very concerned that this reaction was a sign that imuno was incompatible with her.  What we learned was very important. . .

It turns out that no one had an answer to what the hives were from.  Itching and dry skin was common among many, especially the kids.  The answer was found a customer from Master’s of Health.  She told us that the body’s normal levels of magnesium are more than bowel tolerance.  That means that we are not getting enough magnesium unless we are taking it topically as well.  She also told us that some liquid magnesium has contaminants which can be avoided.  Thanks you!  This is really helpful information.

Two other clients in Hawaii were suffering from a fungus as well as some in the states and Canada as well.  It was so bad that it affected the skin and also vision.  In looking into this, it became obvious by the products on the market that a specific zinc was often used for clearing this condition and often used both as soap and shampoo.

Information relayed by a Brittish neurologist and osteopath Dr. Chris Astilbe-Smith, told us that both zinc and magnesium are needed to guide the nervous system.  It is as if the nerves need guardrails to hold the electronic signals racing through the nerves in their right channel.   Zinc can hold the nervous system’s impulses from breaking through the bottom of the channel and going into “Low Excitory” (depression) and without enough zinc, that impulse plumets past it’s ability to  return.

Dr. Astilbe-Smith said that magnesium holds the nervous system’s impulse in place and if there is not enough magnesium, the impulses for “High Excitory” (anxiety) then spiral though the guardrail into levels of over excitement and even mania without having the ability to come back.

When we applied topical magnesium and zinc that were easily absorbed through the skin, we got terrific results.  Babies stopped crying, meridians stopped itching, sleep cycles returned to normal, and brains started to work better.  Healthy Energetics began making “emergency batches” of lotion for individuals who needed urgent relief.  Although they got their relief, when the mineral-rich meal was absorbed into the skin, it apparently went into the meridians.  Because when the detoxification organs were working hard, only those meridians that would start itching because they went through their supply before the other meridians.  

The body was working hard to remove the toxins, to balance itself,  and in order to keep the power on in that area, the detoxification channels needed more minerals.  As many at 6-10 applications of the lotion at first to get it to calm down.

Thank you to our clients for confirming their strong needs.  Thank you for Dr. Astilbe-Smith for giving us such a clear understanding.  Thank you to Dr. Ruggiero for telling us in the 2015 Autism One video that minerals were part of our protocol for Bravo Yogurt and now we understand and see that especially for long repair runs can use lots of minerals before we get well.  

We think everyone is a bit stressed right now and can use an extra helping of Mineral-Rich GcMAF Lotion and Shampoo.  Healthy Energetics is willing to share our new prototypes of our newest products!

Mineral-Rich GcMAF Lotion 

Mineral-Rich GcMAF Shampoo

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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

Blythe and Ruggiero 2020 – Probiotics and detoxification

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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

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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

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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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