In this post I look at another antiviral that has been used.

• Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers.[2012] “61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV-6 IgG ≥ 1:320, EBV viral capsid antigen (VCA) IgG ≥ 1:640, and EBV early antigen (EA) IgG ≥ 1:160 …Thirty-two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively.
• Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. [2013] “Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial… MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025).. experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months….monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001)….Viral IgG antibody titers did not differ “
• Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. [2015] ” Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence).”

Bottom Line

About 21% had improvement in both physical and cognitive issues, 48% had no benefits. There was no remissions reported (unlike  Valacyclovir which reported some patients with complete resolution of symptoms). Not recommended while higher probability of improvement approaches have been tried (like getting Vitamin D in to the top 10% of the normal range)

Readers sometime share the list of prescription from their MDs and ask for my comment. My usual comment are notes like this page, citing what we know from PubMed.

Valacyclovir and CFS

Studies have been done only on a subset of CFS that were EBV positive. One for FM and none for IBS.

• Valacyclovir treatment of chronic fatigue in adolescents. (2014)
  “. All patients were treated subsequently with valacyclovir, with 93% having a positive response. At the end of treatment, scores on fatigue self-assessment scales improved significantly (P < .001). Vigor subscale scores also improved significantly (P < .001). Some patients experienced complete resolution of symptoms. Although not every patient was tested, available laboratory testing revealed increased counts of natural killer (NK) cells and decreased human herpesvirus 6 (HHV-6) antibody titers in all patients who responded to valacyclovir. This article discusses the significance of infectious agents in the pathogenesis of psychiatric symptoms. The study’s data support an intriguing hypothesis that a portion of treatment-resistant depression in fact may be undiagnosed CFS or other chronic viral infection.”
• Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset. (2012)
  “There is prolonged elevated antibody level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset of CFS patients, suggesting that this antibody panel could be used to identify these patients,”
• Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up. (2007)
  “Patients were given valacyclovir at 14.3 mg/kg every 6 hours… Sinus tachycardias decreased and abnormal cardiac wall motion improved. Serum antibody titers to EBV VCA IgM decreased. Patients resumed normal activities.”
• A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. (2002)
  ” We concluded that the 16 CFS patients (included in both phases of this study) with EBV-persistent infection (EBV single-virus subset) are improved after 6 months of continuous pharmacokinetic dosing with valacyclovir. Nine CFS patients with EBV/human cytomegalovirus co-infection did not benefit from 6 months of similar treatment. Valacyclovir is not an effective anti-human cytomegalovirus antiviral drug.”
• “No effect of antiviral (valacyclovir) treatment in fibromyalgia: a double blind, randomized study.” [2004]

Diagnostic Line:

EBV testing must be positive, CMV testing must be negative if you expect any benefit. Testing for EBV can result in some tests being negative (see below), so do not rely on a single negative test as being reliable.

EBV and Brain Inflammation

Note: Encephalitis is inflammation of the brain and that the traditional name for CFS is Myalgic Encephalomyelitis.

• [Encephalitis due to the Epstein-Barr virus: a description of a clinical case and review of the literature]. [2013]
  “oral valaciclovir with clinical resolution and improvement of the liquoral parameters. Polymerase chain reaction in the cerebrospinal fluid was positive for EBV and negative for the other neurotropic viruses. In blood, the serology test for EBV with IgG was positive, while IgM and heterophile antibody tests [for EBV] were negative… EBV infection can give rise to acute disseminated encephalomyelitis or affect several locations in the central nervous system, especially the cerebellum.”
• Ataxia and Encephalitis in a Young Adult with EBV Mononucleosis: A Case Report.[2013]
  “The patient was clinically diagnosed with EBV-associated cerebellitis and encephalitis, displaying neurological and psychiatric impairment commonly seen in postconcussion syndrome. MRI showed no acute changes. She was started on valacyclovir and a prednisone taper, recovering by the end of twelve weeks.”
• [Effect of the Epstein-Barr virus on the nervous system]. [2001]
  “it has been shown that this infection can be accompanied by acute and chronic affections of the central and peripheral nervous system. The pathogenesis of chronic EBV-infection involves autoimmune disorders, neurosensitization, a hazard of an injury to the muscular tissue”

Alternative EBV treatment

• Bosewellia “showed potent inhibitory effects on EBV-EA induction” [2006]
• Turmeric
  • The effect of curcumin on human B-cell immortalization by Epstein-Barr virus. [1998] “A strongly promote in vitro B-cell immortalization with EBV … and curcumin, an extract of a common spice is an effective inhibitor of this process;”
  • “Seven rhizomes were found to possess inhibitory activity towards EBV activation, induced by TPA; they are:Curcuma domestica, C. xanthorrhiza, Kaempferia galanga, Zingiber cassumunar, Z. officinale, Z. officinale (red variety), and Z. zerumbet.” [1999]
• White Mugwort (Artemisia lactiflora) ” In addition, AL-1 strongly inhibited tumor promoter-induced Epstein-Barr virus (EBV) activation” [1999]

Bottom Line

This is effective for a subset of CFS patients that are positive for only one Herpes virus, EBV. Multiple virus or no virus are unlikely to benefit according to the studies.

This week there was a new article published in nature “Commensal microbiota affects ischemic stroke outcome by regulating intestinal” [2016]. A news story in Spanish is here. “The possibilities being considered are focused on stroke prevention, which could be achieved with probiotics to strengthen beneficial microorganisms for these diseases, the implementation of appropriate diets or even applying transplants fecal for patients who have suffered a heart attack cerebral.”

I have know CFS suffers who frequently had Transient Ischemic Strokes(TIA) prior to antibiotic treatment. They disappeared afterwards (and have stayed away for 10+ years). Additional studies include:

• Gut microbiota: Gut bacteria affect post-ischaemic inflammation in stroke by modulating intestinal T cells.[ 2016]
• Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. [2016]

In terms of CFS patients we have:

• Hypercoagulation, see this post for links to studies
• SPECT:
  • “Radiological imaging studies (SPECT, Xe-CT, and MRS) revealed decreased blood flow in the frontal and thalamic areas, and accumulation of choline in the frontal lobe.” [2004]
  • ” Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis–in both of which conditions chronic fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in the RAS of the brain stem. ” [1997]
  • ” Patients with chronic fatigue syndrome had significantly more defects throughout the cerebral cortex on SPECT scans than did normal subjects (7.31 vs 0.43 defects per subject, p < .001). SPECT abnormalities were present in 13 (81%) of 16 patients, vs three (21%) of 14 control subjects (p < .01). SPECT scans showed significantly more abnormalities than did MR scans in patients with chronic fatigue syndrome(p < .025).” [1994]
  • “Compared with the Normal Control  group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values. The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced.” [1992]

Bottom Line

The microbiome impact on the brain is being recognized more and more recognized. Many of the autoimmune diseases that has cognitive issues are also ones with significant shifts of the bacteria in the gut. Reversal of those shift may result in reversal of cognitive issues — my own experience is that I had a SPECT that a radiologist read as early Alzheimer’s Disease during the last relapse of CFS, I was having severe memory issues. With remission, the brain returned to normal and memory is fine today — working as a senior information technologist..

A reader forward me CHRONIC FATIGUE SYNDROME (C.F.S.) IN A FAMILY OF DOGS,

DIAGNOSIS AND TREATMENT OF 3 CASES First Published in Vet On-Line August 21 2000.  The probable cause was two vancomycin-resistant strains of Staphylococcus xilosus, The treatment was with thiacetarsamide sodium, an organic trivalent arsenical given intravenously in low dosages (0.1/mlk/Kg/day) for 3 days.

Staphylococcus aureus appears to be maintainer of CFS, see this earlier post. The vaccine against this almost eliminates CFS for a period of time, see a forgotten treatment post and can cause a low SED rate.

Above you see how closely they are related in terms of genomic data, “Their differences mainly exist in genes associated with virulence and pathogenicity, such as adhesins, superantigens, resistance to antibiotics, capsular polysaccharide synthesis enzymes, pathogenicity islands, quorum sensing and biofilm formation. This study can help reveal how commensal S. xylosus strains evolved into invasive strains.”  [2015]

• ” further extend previous observations that SAg genes are present not only in S. aureus but also in coagulase-negative staphylococci, including S. xylosus.” [2014]
• Ferritin, an iron source in meat for Staphylococcus xylosus? [2016] – which may explain low iron in some CFS patients
• Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS). [2003]
• Chronic fatigue and immune dysfunction syndrome associated with Staphylococcus spp. bacteraemia responsive to thiacetarsamide sodium in eight birds of prey. [2001]
• Chronic fatigue syndrome in horses: diagnosis and treatment of 4 cases.[2001]

There are no studies for detecting in CFS/IBS/FM patients, however, there was a study dealing with cat bites and humans…

” Samples were collected from 200 clinically healthy cats and processed by standard bacteriological methods and tested for susceptibility to a panel of 16 antimicrobials. A total of 212 staphylococci isolates were obtained from 141 of the 200 cats (70.5%), and more than one colony was recognized in 53 cases. Coagulase-negative species were most frequently found (89.6%) distributed among Staphylococcus xylosus (50.9%), Staphylococcus felis (27.4%), Staphylococcus simulans (6.1%) and Staphylococcussciuri (5.2%). Coagulase-positive species (10.4%) were distributed among Staphylococcus aureus (4.7%) and Staphylococcus intermedius group (SIG) (5.7%). Regarding to antimicrobial resistance, 178 isolates (83.9%) were resistant to at least one antimicrobial, and rifampicin showed the best results with 100% of sensitive strains. Conversely, high rates of resistance were observed for penicillin and tetracycline (56.1%). The 212 staphylococci isolates and 30 (14.1%) strains were resistant to methicillin (on the disc susceptibility test) and may be preliminarily considered as methicilin-resistant staphylococci. In conclusion, this study reports important rates of antimicrobial resistance among the species of Staphylococcusisolated from clinical specimens of cats, which must be considered for the treating of cats’ bites in humans” [2013]

” Three other species (S epidermidis, S xylosus, and S aureus) comprised 32.2% of the isolates,” [1985]

Note: a cat (or dog) licking a hand or a face could easily transfer these bacteria to humans.

Bottom Line

This present an interesting line of investigation that begs a researcher to do a study of the staphylococci species (and strains) in CFS patients. These bacteria are found in the oral microbiome (mouth bacteria) which may easily transit to the gut. As I have stated before, this family of bacteria is very hard to treat because it easily develop resistance to an antibiotic (which is why rotation of antibiotics is likely the best course).

In 2001, The National Forum indicates studies were on going but their results were never published (or completed???) “The National CFIDS Foundation has funded in-vitro testing of arsenic trioxide.  We hope to be able to report results to you in a future Forum”

A 2007, forum post “.Micrococci bacteria, that cause CFS/ME. Antibiotics have not eradicated this condition, but Arsenic treatment has, both in Dr Tarello and his wife, plus patients at the clinic in Denmark.”

A reader asked me about silymarin AKA milk thistle, while I have made passing references to it, I have not done a drill down on PubMed, so it is time to do so. Search on PubMed found for milk thistle….

• and IBS: no articles
• and CFS: no articles
• and fibromyalgia: no articles
• and coagulation: no relevant articles
• and bacteria: 38 articles.
  • ” Affecting the microenvironment of the gut, including SM-bacteria interactions, awaits future investigations.” [2015]
  • “Gram-positive bacteria were inhibited at concentrations between 60 and 120 μg/mL. Gram-negative bacteria were not inhibited by the silymarin concentrations included in this study.. . We demonstrated that silymarin shows antibacterial and antiadherent/antibiofilm activity against certain standard bacterial strains which may be beneficial when used as a dietary supplement or a drug” [2015] – no significant effect, no information on whether the shift would be for the better or the worst.
    • “The results showed that silybin inhibited RNA and protein synthesis on gram-positive bacteria.” [2003]
• “Potentially toxigenic molds from the Aspergillus sections Flavi and Nigri as well as Eurotium, Penicillium, Fusarium and Alternaria species were isolated from Milk Thistle supplements (sold in the US). The predominant molds were Eurotia (E. repens, E. amstelodami and E. rubrum), A. flavus, A. tubingensis, A. niger and A. candidus. To our knowledge, this is the first study reporting on fungal contamination profiles of MT botanicals.” [2013]
  • “A total of 83 Milk Thistle samples from the US market were analysed. The aflatoxigenic fungus Aspergillus flavus were detected in 19% of the samples with levels ranging from 0.04 to 2.0 µg kg(-1).” [2012]

Bottom Line

No demonstrated benefit for CFS/IBS/FM patients have been reported. There is a 1 in 5 risk of toxigenic molds.

Impacts  gram-positive bacteria at high dosages which may includes: Bacillus (in some probiotics), Clostridium (Miyarisan probiotic),  Steptococcus (Enterococcus) and Straphylococcus. Other uses, per wikipedia,  “Milk thistle has been used for a number of purposes including liver disease, and cancer; however, clinical studies are largely heterogeneous and contradictory”

I cannot put this on a recommended list – no demonstrated benefit, risks