While researching another topic, I came across this from 1998, Effects of  vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome. This is logical (just need the RIGHT vaccine) from observations made in my last post.

” Significant improvement was seen in seven of the 15 CPRS items in the vaccine group when pretreatment values were compared to post-treatment values. In CPRS <<fatiguability>>, there were significant intergroup differences, and in CPRS <<pain>> intergroup differences bordered on significance….  In a follow-up study of 23 patients, thevaccine treatment was continued for 2-6 years. Fifty percent were rehabilitated successfully and resumed half-time or full-time work.”

This was followed up with a 2002 study. ” The treatment was well tolerated. Intention-to-treat analysis showed 32/49 (65%) responders in the SB(vaccine) group compared to 9/49 (18%) in the placebo group (P<0.001). … An increase in CPRS symptoms at withdrawal was noted in the SB group. In conclusion, treatment with staphylococcus toxoid injections over 6 months led to significant improvement in patients with FM and CFS. Maintenance treatment is required to prevent relapse.” [2002]

“One hundred and sixty patients with Fibromyalgia and Chronic Fatigue Syndrome, who were on a continuous treatment with a Staphylococcus vaccine, were followed during one year with repeated consultation visits…. showed improvement from start of treatment and also further improvement during the follow-up year. In view of the natural history for these disorders the result is of interest.”[2006 article in Journal of Chronic Fatigue]

Discussion from 2010 on Phoenix Rising.

BENEFITS OF VACCINE FOR ANTIBIOTIC RESISTANT STAPHYLOCOCCUS AUREUS:

• Polyvalent vaccine targets antibiotic resistant strains of S. aureus
• Provides protection against the most common strains of S. aureus
• Targets toxins secreted from S. aureus
• Mechanism of action targets surface proteins

1937 Paper is here.

The vaccine is available for veterinary use.

Bottom Line

It is worth while for a researcher to explore producing a series of vaccines for overgrowth species/strains in CFS/FM. It may be possible to do this with a similar method as was used in the 1930’s (i.e. not high tech). The 50% success rate seen in multiple studies is in line with a microbiome dysfunction that is multiple species — thus any single item will likely only be partially effective.

Recent literature and reports on the vaccine itself (National Institute of….):

• Where does a Staphylococcus aureus vaccine stand? [2014]
• Overcoming Challenges in Staphylococcus aureus Vaccine Development [June 2013]

Fast Track Clinical Trials (not for CFS):

• Pfizer 2015-2017 Article

POTS co-morbid with CFS. It turns out that several vaccines that have a ‘vaccine syndrome’ which included POTS.

• Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus [2015].
• [Neurologic Complications in HPV Vaccination] [2015].  “delayed manifestation of cognitive dysfunction in the post-vaccinated girls has attracted attention. The symptoms include memory loss and difficulty in reading textbooks and/or calculation.”
• Postural tachycardia syndrome after vaccination with Gardasil.[2010]
• Paroxysmal supraventricular tachycardia precipitated by pertussis vaccine [1983].
• [Associated ventricular tachycardia and auricular fibrillation after anticholera vaccination][1973].
• .[Post-vaccinal encephalopathy syndrome] [1957].
• [POST-VACCINAL SCHOELEIN-HENOCH SYNDROME. PRESENTATION OF 3 CASES, 2 OF WHICH PRESENTED AFTER ANTIPOLIOMYELITIC VACCINATION].[1965]
• [Neurological complications after influenza vaccination (author’s transl)]. [1977]
• Neurological complications of swine influenza vaccination. [1982]

This is not that surprising, because the vaccine promotes an immune response which likely includes alteration of the microbiome.

“..a trend for reduced gamma-interferon in the CFS-vaccine group… Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was evidence of altered immune reactivity and virus clearance.” [1997]

The following illustrates how adverse effects are often deem “not significant” in a population [2011].

“RESULTS:

VAERS received 294 reports of AEs in pregnant women who received 2009-H1N1 vaccine: 288 after inactivated and 6 after the live attenuated vaccines. Two maternal deaths were reported. Fifty-nine women (20.1%) were hospitalized. We verified 131 pregnancy-specific outcomes: 95 spontaneous abortions (<20 weeks); 18 stillbirths (≥20 weeks); 7 preterm deliveries (<37 weeks); 3 threatened abortions; 2 preterm labor; 2 preeclampsia; and 1 each of fetal hydronephrosis, fetal tachycardia, intrauterine growth retardation, and cleft lip.

CONCLUSION:

Review of reports to VAERS following H1N1 vaccination in pregnant women did not identify any concerning patterns of maternal or fetal outcomes.”

“Racing heart” is also called Tachycardia. Cort Johnson did an excellent post of Dr.Visser back in 2013. Checking PubMed, I found a relevant study from 2011 on POTS patients (which often overlaps with CFS) using Ivabradine (only approved in the US in 2015). I have known some CFS patients that have been admitted into hospital because of this.

“Twenty-four ME patients with orthostatic intolerance underwent a conventional 10-min active standing test and echocardiography both on a “good day” and a “bad day”, defined according to the severity of their symptoms. The mean heart rate at rest was significantly higher on the “bad days” than on the “good days”. During the standing test on a “bad day”, 5 patients (21 %) failed to maintain an upright posture for 10 min, whereas on a “good day” all the 24 patients maintained it. Postural orthostatic tachycardia (POT) (increase in heart rate ≥30 beats/min) or severe POT (heart rate ≥120 beats/min) was observed on the “bad days” in 10 patients (43 %) who did not suffer from the severe tachycardia on the “good days”, suggesting the exaggerated sympathetic nervous activation.”[2015]

“Not only may patients be affected by more than one of these pathophysiologies but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos syndrome, vasovagal syncope, and inappropriate sinus tachycardia.”[2015]

A reader was just prescribed this and asked for an opinion… what PubMed find is:

• “Inappropriate sinus tachycardia (IST) often causes palpitations, dyspnea, and exercise intolerance,…Ivabradine is effective and safe in short- and medium-term treatment of IST. [2015]
• “In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients.”[2012]
• “Postural orthostatic tachycardia syndrome (POTS) is associated with tachycardia on orthostasis….  At the time of data analysis, 11 (55%) patients continued to use ivabradine, the median duration of treatment was 25 weeks (range 7–113), median daily dose 5 mg (range 2.5–15) taken in one or two divided doses…All those who continued to take ivabradine (55% of POTS patients) reported fewer episodes of palpitations and tachycardia. Eight (44% of those who tolerated ivabradine) reported a reduction in fatigue….  Ivabradine appears to control POTS-related symptoms with an efficacy similar to conventional treatment.[2011]

Role of Bacteria?

Above we see that in CFS, tachycardia increases with the severity of CFS (good day/bad day) this hints that bacteria may play a role in this condition. This aspect does not appear to have been studied yet. Back in 2013, I posted my own observations of a 30% drop in heart rate after taking prescript-assist. It is also associated with throat infections.

• “Staphylococcus aureus (S. aureus) causes a variety of infections… [symptoms include] tachycardia … the significant predictors of mortality(death) were prior hospitalization and antibiotic intake,” [2015]
• Tachycardia in a newborn with enterovirus infection [2014].

Bottom Line

There is a potential to reduce or eliminate tachycardia by a shift of bacteria. The use of ivabradine is another route. It also appear to have desired side-effects:

• Ivabradine inhibits the production of proinflammatory cytokines and inducible nitric oxide synthase in acute coxsackievirus B3-induced myocarditis [2013].
  • Coxsackievirus is associated with many cases of CFS.

Unfortunately, it has been studied only on it’s impact in a few areas.

“Irritable bowel syndrome (IBS) affects approximately 10.5% of the population (6.6% of men and 14.0% of women).[1]”

This is a continuation of what seem to have become a series of DNA Snps associated with CFS and conditions typically co-morbid.

• GI symptom severity was associated with ADRA1D rs1556832 (P = 0.010). [2015] –
  • rs1042717,  rs174697
  • not in 23AndMe

However this articles does include a table that may be helpful for understand what association means:

If the percentage in the Healthy Controls and the IBS Patients for one particular item are far enough apart, and after doing some mathematics, the researchers will conclude that is a positive or negative association of the SNP with a patient or a symptom. For example rs174697 for G/G we have 65.6% versus 78.8% (thus having it suggests IBS is more likely), while for A/G we have 28.1% versus 18.7% suggesting IBS is less likely (1.5x less likely – sometimes called the Odds Ratio or “OR” i.e. 28.1/18.7).

A meta-analysis of immunogenetic Case-Control Association Studies in irritable bowel syndrome [2015].

• [PMID 21636646] Association of TNFSF15 polymorphism with irritable bowel syndrome “The Crohn’s disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2×10(-5); OR 1.37) and more pronouncedly, IBS-C (p=8.7×10(-7); OR 1.79) in the entire sample.”
• [PMID 21304977] An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians.
• [PMID 25028192] Associations between TNFSF15 polymorphisms and susceptibility to ulcerative colitis and Crohn’s disease: A meta-analysis
• [PMID 25824902] A meta-analysis of immunogenetic Case-Control Association Studies in irritable bowel syndrome

Link: https://www.23andme.com/you/explorer/snp/?snp_name=rs4263839 

• The bad pair is “GG” (I have “AG”)

Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome [2014].

“Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)).”

Only one SNP is available in 23AndMe, the one associated with diarrhoea.

Link: https://www.23andme.com/you/explorer/snp/?snp_name=rs2349775 (was previously associated with neuroticism )

• From the literature that I could find,  “CC” is likely the bad one.

There has been considerable interest in the DNA results for CFS and fibromyalgia is typically co-morbid, so I thought a browse through the research, especially for items that can be checked on 23AndMe.

As before, log on to 23andMe and then click the links below

Low COMT Enzyme higher pain in FM

COMT stands for  catechol-O-methyltransferase (COMT) gene.  Studies [2007] [2012] [2013]

Specific reactions catalyzed by COMT include:

• Dopamine → 3-Methoxytyramine
• DOPAC → HVA (homovanillic acid)
• Norepinephrine → Normetanephrine
• Epinephrine → Metanephrine
• Dihydroxyphenylethylene glycol (DOPEG) → Methoxyhydroxyphenylglycol (MOPEG)
• 3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid (VMA)

Which may partially account for the relationship to pain. Interestingly “influences character traits and not only temperament” [2014] as well as “cognitive stability and cognitive flexibility” [2010]

Link: https://www.23andme.com/you/explorer/gene/?gene_name=COMT

The key SNPs are

• rs6269, Mine is AG
  • Type AA is associated with pain
• rs4633, Mine is CT
  • Type CC is associated with pain
• rs4818 — Not Found
  • Type CC is associated with pain
• rs4680 (Val158Met) — Mine is CT
  • AA is associated with pain
  • GG and AG are lower levels.

Severe Pain associated with the SCN9A Gene

“This association raises the possibility that some patients with severe FM may have a DRG sodium channelopathy.”[2012] found rs6754031 polymorphism to be most significant, unfortunately this is not included in the 23AndMe results for me.

Link: https://www.23andme.com/you/explorer/gene/?gene_name=SCN9A

Some SNP appear to be associated, but not at statistical significant levels (given the small sample) and less than half of the SNPs were listed in the 23andMe results.

• rs7607967 – AA (I’m AG)
• rs12994338  – CC (I’m CC)
• rs13017637 – CC (I’m TT)
• rs6746030 – AA – (I’m AG)

I have no FM pain and have only one of the above SNPs – which is what would be expected by randomness.

There are a number of of studies associating the Gene with pain sensitivity. For example:
” there was a statistically significant correlation between SNP rs6746030 and higher maximum NRS scores during the postoperative follow-up of non-PCA patients (P < 0.05). Furthermore, there was a significant association between the tag SNP rs4286289 and both increased postoperative maximum NRS scores (P < 0.05) and higher incidences of severe postoperativepain (P < 0.05) in non-PCA patients. Meanwhile, in PCA patients, rs4286289 exhibited the strongest association (P = 0.001) with increased requirements for postoperative analgesics, which indirectly strengthened the significant association between this SNP and higher postoperative pain.” [2016]

Predisposition to FM – T102C

T102C is the Rs6313 SNP

Link: https://www.23andme.com/you/explorer/snp/?snp_name=Rs6313

I am reported as AG on 23andMe. The CC variation is the one of concern.  SNPedia reports:

Bottom Line

Having the SNPs does not mean that you will or will not get FM. If you go into a FM state, your symptoms may be worst (and your FM state may actually be the same as someone with a lot less pain lacking these SNPs).

This information can be helpful to explain to a MD that your need for pain relief is higher because of your DNA. It could provide justification to the MD to prescribe a higher dosage based on evidence instead of tears.

As a speculation: There seem to be some evidence that mild and worst cases of FM/CFS is not strongly related to disease state, rather to DNA that is responding to the disease state.

Radical suggestion for treating pain!

One of my readers report that many pains disappeared in less than a month after aggressively trying to correct their microbiome. My model is that the symptoms are the results of the shift of chemicals being produced/released by the microbiome.  How the body responds to an increase or decrease of certain chemicals is influenced by the DNA. Symptoms like pain may be reduced or eliminated by shifting that chemical mixture — exactly how to  shift it is beyond current research literature.