Valganciclovir is another antiviral similar to Valacyclovir which I reviewed in an earlier post.

According to PubMed:

• “Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV… statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025)…patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months…Further investigation with longer treatment duration and a larger sample size is warranted” [2013] – The term statistically significant (with P > 0.001) usually mean minor improvement.
• “Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response.” [2012]
• “Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV)…Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites.” [2006] Note: these patients did NOT have a Chronic Fatigue Diagnosis, just long term fatigue.

Only Impacts a small percentage of IBD/IBS patients

• “The prevalence of cytomegalovirus disease in our inflammatory bowel disease  cohort (study group of 1023 people) was 1.37%.” [2016]
• ” the prevalence of CMV infection was 22.7% in ulcerative colitis and 16.0% in Crohn’s disease… Immunuosuppressive therapy and age older than 30 years were identified as the main risk factors for the development of CMV infection in exacerbated IBD. ” [2015] CMV does not cause IBS/CFS, rather IBS/CFS increases the odds of getting a CMV infection.
  • “Most cases of cytomegalovirus (CMV) colitis that develop in patients with inflammatory bowel disease (IBD) are caused by reactivation of a latent virus.” [2010]
• “The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate…Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, [2016]
• [This is from the most recent study]”Multiple previous studies have sought evidence for ongoing, active infection with, or reactivation of, Herpesviruses in patients with chronic fatigue syndrome (CFS), with conflicting results….these did not differ between CFS cases and control patients…. data do not support the hypothesis of ongoing or reactivated EBV, HHV-6, or CMV infection in the pathogenesis of CFS. [2010]
  • Chronic Fatigue Syndrome and Herpesviruses: the Fading Evidence. [2000]

Bottom Line

The theory of ongoing or reactivated EBV, HHV-6, or CMV infection in the pathogenesis of CFS has been abandoned by researchers since 2010. This theory continues to be circulated in many CFS support groups.

If a person with CFS happens to also have re-activation of a virus, that reactivation should be treated because such activation was reported to decreases the effectiveness of treatment with IBD. Reactivation will cause some symptoms to increase.

This drug should only be taken upon confirmation of active EBV, HHV-6, or CMV. 

Rerum is another product that was developed by the same person that created Bravo probiotics, Marco Ruggiero MD. PhD. This is even more expensive

This person has been the subject of inquiries over some of his unorthodox ideas.

“In the video below (which opens in a new tab), Dr Marco first dismantles the Goleic hypothesis one piece at a time, and then he re-assembles the evidence to reveal a whole new picture, culminating in a new product, called Rerum. Perhaps the biggest shock, is that it contains NO GcMAF AT ALL! As you will see, the remarkable results originally attributed to GcMAF turn out to be due to the other ingredients in the Goleic protocol.  Firstly the Goleic contains Oleic Acid, originally discovered in olive oil.  This is a known anti-tumor factor.  Then there is the high dose vitamin D3 and thirdly there it the Bravo Yoghurt, which contains significant levels of Chondroitin Sulphate.” from http://thehealtharchive.com/the-end-of-gcmaf/

I am very much in favor of taking Vitamin D, Oleic acid — just not paying $600 for 3ml!

“Prof Ruggiero has written several papers on the efficacy of gcmaf, alongside his wife Stefania Pacini, and other employees of First Immune including David Noakes.  He was one of the founders of the cancer clinic in Laucerne, Switzerland, that was closed by the authorities for not having the correct permits.  The authorities became aware of this clinic after 5 people with terminal cancer died there.  They did not take any notice of the 85% of terminal cancer cases that showed improvement.  He was with the company as the laboratory and production facility in the UK was raided and closed down. ” http://gcmafblogspot.weebly.com/blog/rerum-the-successor-to-gcmaf

Bottom Line

This has the appearance of all hype with no evidence. He appears to have been forced to leave Italy, Switzerland, England and appears to be based in Arizona at the moment.

It seems that every two years, I get requests to review this probiotic. It is neither worth the money and has the appearance of many false claims. See earlier posts:

• 2013 Post
• 2015 Post
• In 2017, the discoverer has invented a new magic, Rerum, and in videos has trashed this product, see this post.

Current state of knowledge based on PubMed articles. At present there are around 67 articles on GCMAF (which is available separate from the Bravo Probiotic). 41 of these were associated with CANCER. 65 was associated with Vitamin-D (i.e.improve uptake of vitamin D)

• “treatments of GcMAF in a patient with MS have potent therapeutic actions with early beneficial responses, especially improvement of motor dysfunction.” [2016]
• “This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects.” [2016] Note: article did not cite any positive effects.
• “Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity…. colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases.” [2015]
• Retraction note to: immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF [2014]. If appears that more careful study of the data resulted in a difference of conclusions.
• “Inconsistencies and questionable reliability of the publication “immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophages-activating, GcMAF” by Yamamoto et al.” [2014]
  • “After several patients asked our organization, the Anticancer Fund, www.anticancerfund.org, about GcMAF as a cancer treatment, we looked for the evidence supporting its use in cancer. The literature showed us striking issues and inconsistencies…
    • 1. The Nagasaki and the Hyogo Immunotherapy Research Groups, that gave IRB approval for these trials, do not exist except in Yamamoto’s clinical papers. Three purported members of these groups, including one chairman, informed us they are not part of these groups and that they have never been involved in Yamamoto’s activities. Other members of these IRBs could not be found.
      2. Yamamoto’s co-authors in these papers could not be found.
      3. We contacted the sponsors of these trials (US Public Health Service and the Elsa U. Pardee Foundation), and we found that they did not support them.
    • Furthermore, it has been demonstrated that naturally occurring GcMAF in cancer patients has a concentration of approximately 4 mg/L, making the 100 ng proposed by Yamamoto meaningless” – Yamamoto claim is the 0.04% increase would cure cancer.
• “By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy (integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily.) was remarkably effective.” [2013] 3/345 is less than 1% – whether GcMAF or the other items were the cause could not be determined.

Bottom Line on GcMAF

There are NO studies for the microbiome or IBS  or Crohn’s Disease or fibromyalgia, etc. Add to this that many published fake-papers associated with fake institution that have been exposed recently — it raises HUGE ALARM BELLS of con-artists taking money from the desperate sick.

Bravo Probiotics

Checking the promotion sites I see that it is alleged that it’s GcMAC may cures depression, autism [not a single study to support that claim]. Their site claims ” inflammation, from infections, inflammation, virals and immune diseases” with a massive number of alleged presentations and papers… none dealing with GcMAC as a probiotic, and many citing the discredited Yamamoto exposed above. Their publications page stop in 2014 – at the same that the fake organizations cited above were exposed.

Doing some digging around, I found that the current manufacturer is “Silver Spring Sagl”, c/o Fulvia Gianetta Allio via Raimondo Rossi 24, 6864 Arzo – founded in 2015. Owned by Marco Ruggiero MD.

Current pricing is $400 for 13 weeks (or $1600/year). It consists of [source]:

• 25% Bifidbacteria
• 12.5% L. Salivarius
• 12.5% L. Acidophilus
• 12.5% L. Paracasei
• 12.5% L. Rhamnosus
• 12.5% L. Lactis
• Rest is colostrum etc.

The cost for alternative probiotics is likely $500/year of less.

With none of the above claims supported for Bravo exclusively by PubMed. Those claims are supported for certain strains of the families of bacteria cited above —  that evidence cannot be applied to unidentified strains.

The table below shows the results order by the number of reporters (Probable – most, Medium – many, low – a few); percentage of reported that got better; percentage that had problems (risk).

The number below are the raw numbers (May 2018)

Recently I visited my dentist and during the visit, she and me got into an interesting discussion of the microbiome and dentistry. She show me in my x-rays some interesting aspects of bacteria in the mouth.

“There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence.” [2016]

Amalgam Impacts – Allergy

My dentist cited growing concerns about interactions between different metals being used for restorative work (i.e. electrolysis). Concerns included shifts of bacteria populations. Some literature:

• “three subjects with CFS and two with fibromyalgia, all of whom suspected metal exposure as a trigger for their ill health…All patients except one were sensitized to metals present in their dental restorations… The removal of sensitizing metals resulted in long-term health improvement.” [2014]
• “Fifteen female FM patients…Reduction of metal exposure in the FM patients was achieved by replacement of dental metal restorations and by the avoidance of known sources of metal exposure…. Objective examination 5 years later showed that half of the patients no longer fulfilled the FM diagnosis, 20% had improved and the remaining 30% still had FM. All patients reported subjective health improvement. This correlated with the normalization of metal-specific responses in vitro.” [2013]
• ” 15 patients who suffered from clinical metal sensitivity in addition to other health problems. … The removal of incompatible dental material (RID) resulted in long-term health improvement in the majority of patients. We postulate that in vivo, metal ions activate T-cells, initiating systemic inflammation, which, through cytokines, affects the brain and hypothalamus-pituitary-adrenal axis.” [2006]
• “Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögren’s syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study… The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested…The most frequent allergens were nickel, mercury, gold and palladium.” [2015]
• ” Studies have shown that chronic Hg exposure from various sources including dental amalgams is associated with numerous health complaints, including fatigue, anxiety, and depression–and these are among the main symptoms that are associated with CFS and FM…several studies have shown that the removal of amalgams is associated with improvement in these symptoms.” [2014]
• “To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients reported considerably alleviated fatigue and disappearance of many symptoms previously encountered; in parallel, lymphocyte responses to metals decreased as well. We suggest that metal-driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown etiology.” [1999]

Metals and Microbiome

Assuming mercury alone is the problem and not the other base metals cited above, is likely false. Mercury is an easy target loaded with emotion.

• “The role of nickel in the biochemistry of bacterial enzymes is discussed here, covering both the beneficial effects of nickel in the human microbiota as well as the role of nickel-depending bacteria in human pathogenesis. In addition, the hazardous health effects caused by nickel exposure to humans, namely nickel-induced carcinogenesis and allergy, are triggered by non-specific interactions of nickel with macromolecules and formation of reactive compounds that mediate cellular damage. Cellular response to nickel is also related to signal transduction cascades.” [2016]
• 
• “The bacterial count results showed that dietary nickel (NiCl2) in the range of 300 to 900 mg/kg decreased the counts of Bifidobacterium spp. and Lactobacillus, increased Escherichia coli (E. coli) and Enterococcus spp. in the ileum and cecum. …This finding implies that NiCl2 has toxicological effect on the intestinal ecosystem and, possibly functions.” [2014]

Root Canals/Dentures as bacteria reserves

I view the mouth as a reserve for many bacteria that contribute to CFS/FM/IBS — fixing the guts may be temporary because the mouth may repopulate it with the bad bacteria.

• Exploration of bacterial species associated with the salivary microbiome of individuals with a low susceptibility to dental caries[2016]. “These results revealed an association between a greater abundance of Porphyromonas pasteri and lower susceptibility to dental caries.”

• “IMPORTANCE Denture stomatitis is a prevalent inflammatory condition of the mucosal tissue in denture wearers that is triggered by microorganisms. While Candida has been extensively studied for its role in stomatitis etiology, the bacterial component largely remains to be investigated. Our data show that certain types of bacteria are significantly associated with denture health and disease.” [2016]
  
  • As shown above — individuals vary greatly — there is no “normal” pattern.

Species to watch out for in microbiome results

• “evaluated the presence and relative levels of 28 bacterial taxa in treated root canals of teeth with posttreatment apical periodontitis … Taxa detected more frequently included Streptococcus species (47%), Lactobacillus species (35%), Dialister invisus (29%), Eubacterium infirmum (29%), Prevotella intermedia (29%), Selenomonas sputigena (29%), Synergistes oral clone BA121 (29%), and Treponema denticola (29%).” [2008]
• “Enterococcus faecalis was the most prevalent species, detected in 77.8% of the study teeth, followed by Peptostreptococcus micros, detected in 51.1%. Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Prevotella nigrescens were detected in 35.6%, 22.2%, 11.1%, and 11.1% of the sampled teeth, respectively. Moreover, PCR detected Filifactor alocis in 26.7%, Treponema denticola in 24.4%, and Tannerella forsythia in 4.4% of the samples. [2008]
  • T. denticola and P. micros were statistically associated with tenderness to percussion (p < 0.05).
  • P. nigrescens was associated with the presence of spontaneous pain and abscess (p < 0.05).
  • P. endodontalis and P. nigrescens were associated with purulent exudates (p < 0.05).

From Endotontic microbiology  [2010] – longer lists are in this article.

1) Black pigmented Gram negative anaerobic rods include species formerly known as Bacteroides melaninogenicus. These bacteria have been reclassified into two genera: (a) saccharolytic species – Prevotella and (b) asaccharolytic species – Porphyromonas.[7]

Prevotella species detected in endodontic infections include

Porphyromonas species detected in endodontic infections include

2) Tannerella forsythia (previously called Bacteroides forsythus or Tannerella forsythenis) was the first periodontal pathogen to be detected in endodontic infection.[8]

3) Dialister species are asaccharolytic obligately anaerobic Gram negative coccobacilli which have been consistently detected in endodontic infections.

4) Fusobacterium is also a common member of endodontic microbiota.

5) Spirochetes are highly motile, spiral-shaped, Gram negative bacteria with periplasmic flagella. All oral spirochetes fall into the genus Treponema.[9] Prevalent species are

6) Gram positive anaerobic rods have also been found in endodontic microbiota like

7) Gram positive cocci that are present in endodontic infection:

Other bacterial spp. which are present in low to moderate values include

Bottom Line

For some past restorative work may be a significant factor for FM/IBS/CFS, with all ceramic replacement being the best alternatives. Good dental health (i.e. no gum disease) may be essential for remission and maintaining remission.