So which theory of ME/CFS?

A reader wrote me asking about the different theories of ME/CFS, and I just read Cort’s The Best, the Most, the Strangest and the Worst of 2019 in ME/CFS and Fibromyalgia. I have used different models over the years (going with the best available usually). Often it seems that both patients and researchers are lost in the forest strictly following a compass bearing and crossing over paths (and ignoring) that may lead them out of the forest.

My academic training is modelling. A model is a hypothesis with some extra criteria:

  • Must be predictive
  • Must be testable
  • Must explain existing observations
  • Should be as simple as possible

A good model is one that explains more observations than other models. A good model is one that is easy to test. A good model predicts possible findings (which if the findings comes in correct, confirms the model).

The most challenging set of observations

The following is known to every ME/CFS patient and treating physician: The huge variation of symptoms. For a list of non-lab symptoms, see MEpedia Page, CDC Page, Review of the Evidence on Other ME/CFS Symptoms and Manifestations, and Review of the Evidence on Major ME/CFS Symptoms and Manifestations.

We know that DNA/SNP plays a role – for example, ME/CFS people have smaller hearts, craniocervical instability and certain DNA mutations are more common. These are not causes (people with the same items do not have ME/CFS) but contributing factors that makes people more disposes to developing ME/CFS. Think of the “Perfect Storm”, you have a sea worthy boat — unfortunately you motor died in the middle of gale when you were close to a reef…. a series of unfortunate events.

My criteria for a hypothesis that has merit to investigate or fund — it must give an explanation for the different symptoms! A common response is there are different subsets and we need to identify each subset first, or ‘we have not had time to investigate that yet’ (and likely will never) or even a truthful, “I don’t know” or perhaps a dismissive “that’s not relevant”.

The Microbiome Model explains Symptoms

A rhetoric question — if all of your ME/CFS symptoms disappear do you have ME/CFS. At one time remission was defined as no longer having the minimum number of symptoms required for the CDC definition.

About a seven months ago, I tossed up an analysis page on symptoms to bacteria expecting weak results. I was shocked, Eureka! Specific bacteria are associated with specific conditions and symptoms. Since then the database have grown and the number of people entering symptoms have increased.

Alcohol Intolerance

This occurs in a very high percentage of M/E CFS patients. Our analysis found that there were specific microbiome shifts (high levels of certain bacteria)

http://microbiomeprescription.azurewebsites.net/Data/SymptomExplorer?includes=221

Neurological: Difficulty reading

We find similar patterns, and can drill down to higher resolution (because of more data) and see a strong clustering with people with the highest 15% of some bacteria.

http://microbiomeprescription.azurewebsites.net/Data/SymptomExplorer?includes=92

Neurocognitive: Difficulty paying attention for a long period of time

As we walk thru them, we notice overlaps of some bacteria. Look at what is below and alcohol intolerance above. We see the following in common

  • Butyricimonas (genus)
  • Deltaproteobacteria (class)
  • Desulfovibrionales (order)

These are the main players for some ME/CFS, the other bacteria likely cooperate with them to produce specific symptoms (which often have a DNA requirement to appear).

http://microbiomeprescription.azurewebsites.net/Data/SymptomExplorer?includes=239

I should point out that a P-value of 0.05 or below is often the criteria for getting a finding published in a medical journal. Some of the values we came up with are 0.000194 and lower. Much much stronger evidence than is usually seen.

Summary

The criteria are below:

  • Must be predictive
  • Must be testable
  • Must explain existing observations
  • Should be as simple as possible

The microbiome model beats everything else (please add detail comments if you disagree of which model is better using these criteria).

This model is predictive, it can take a microbiome sample in and based on the content alone predict probable symptom (key word is probable) which from my own experience and other user feedback seems around 75% accurate.

This mode is testable, from a microbiome sample we can determine a list of items that would probably help. Some people have had outstanding results. Again, the key word is probable.

This model explain existing observations, the observations we used above in symptoms. Recent research studies also find that it explains many lab results seen with ME/CFS.

This model is simple to understand. It is a beast to work with because of the number of bacteria involved.

The last issues for me are treatment-actionable and available. Most of the research hypothesis do not have treatments to address the cause. A few that do are usually not available — often because it is a research protocol and not “standard of medical care” .. i.e. no one can use, especially the ordinary family physician sitting in a community clinic in the Australian Outback!

The microbiome can be manipulated without prescription drugs which removes the stumbling block of “standard of medical care”. It can even be done under quasi-medical supervision if a patient uses available tools and present the suggestions to their physician for review. Getting physicians up to speed on the microbiome is a different issue.

If you believe a different model is better — then please provide the details in the comments. I am open to changing models.

An ideal FMT Donor scenario for ME/CFS

A reader pointed me to this blog, our2ndbrain.com. He did a DYI FMT transplant using a donation from his daughter [post] and obtained remission.

” For many of you visiting this site, you may have wondered why I picked my daughter as the donor for Fecal Microbiota Transplant.   “

Kudos!

I say kudos because this is a very ideal choice of donor! (on the matter of DYI Fmt, I choose, for legal reasons, to keep mute). The whys are simple:

  • As close to the same DNA as possible (50%)
  • Same diet (which means that the bacteria mix has already been tuned to the diet)
  • A son could technically be better (since gender is a factor for the microbiome)
  • Same longitude (which is a factor)
  • Younger microbiome — which usually means stronger and more robust. The microbiome “has not slipped into old age”

Bottom Line

I am not advocating people to volunteer to change diapers of their kids and grandkids to get material for DYI FMT. I am advocating, if you have kids (if you do not have kids, if a sibling has children those are better candidates than a random person IMHO), and have a MD willing to go down the FMT path, to advocate for those people as donors, instead of doing the DYI approach on this site.

The following paper gives some background on FMT. There is still disagreement whether family members give better results ( I suspect those studies were done on siblings and not descendents).

THE POWER OF POOP: FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIUM DIFFICILE INFECTION

Drug induced histamine issues

I came across an interest article on enteral-induced histaminosis (Histaminosis: Studies on Three Prognostic Variables in an Epidemiological Model) which identifies some drugs that inhibit DAO production.

This lead me to this page which gives a fuller list with citations.

Active substanceExamples of products ®CategoriesHistamine effectsReferences
Acemetacin AntirheumaticDAO inhibitor[Sattler 1985, Fritzsche 2009]
Acetyl­cysteineFluimucil, Helvetussin, Muco-Mepha, NeoCitran, SolmucolMucolytic, antidoteDAO inhibitor[Jarisch 2004, Maintz et al. 2006]
Acriflavin AntisepticDAO inhibitor[Fritzsche 2009]
Alcuronium Muscle relaxantDAO inhibitor[Sattler 1985, Maintz et al. 2006, Forth 2008]
Alprenolol Beta blockerDAO inhibitor[Maintz et al. 2006]
AmbroxolAmbrovene, Ambroxol, Broxol, Mucosolvan, MucospasExpectorantDAO inhibitor[Jarisch 2004, Maintz et al. 2006]
Aminocycline  DAO inhibitor[Sattler 1985]
AminophyllinEuphyllin, Mundiphyllin, MyocardonAntiasthmaticDAO inhibitor[Sattler 1985, Jarisch 2004, Maintz et al. 2006]
Amiphenazole  DAO inhibitor[Sattler 1985]
AmitriptylineSaroten, Tryptizol, LimbritolTricyclic antidepressantDAO inhibitor[Jarisch 2004, Maintz et al. 2006]
Carbocromene  DAO inhibitor[Sattler 1985]
Cefotiam AntibioticDAO inhibitor[Maintz et al. 2006]
Cimetidine H2 antihistamineDAO inhibitor[Prof. Ralf Bauer Uni Bonn; found in: Jarisch 2004 S.12, Maintz et al. 2006, Fritzsche 2009]
Clavulanic acidAugmentinAntibioticDAO inhibitor[Sattler 1985, Jarisch 2004, Maintz et al. 2006]
Colistin mesilate  DAO inhibitor[Sattler 1985]
DiazepamValiumTranquilizerDAO inhibitor[Fritzsche 2009]
DihydralazineNepresolAntihypertensive, vasodilatorDAO inhibitor[Wantke et al. 1989, Sattler 1985, Maintz et al. 2006, Fritzsche 2009]
Fenpiverinium  DAO inhibitor[Sattler 1985]
Framycetin AntibioticDAO inhibitor[Sattler 1985, Fritzsche 2009]
FurosemideLasixDiureticDAO inhibitor[Fritzsche 2009]
HaloperidolHaldolNeurolepticDAO inhibitor[Fritzsche 2009]
Metamizole, dipyronesNovalgin, MinalginAnalgesic, antipyreticDAO inhibitor[Jarisch 2004, Maintz et al. 2006]
MetoclopramideMigpriv, Paspertin, PrimperanAntiemetic, gastroenterologic, dopamine antagonistDAO inhibitor[Sattler 1985, Jarisch 2004, Maintz et al. 2006]
Neomycin AntibioticDAO inhibitor[Mathelier-Fusade 2006]
Novamine sulfone(=Metamizol) Novalgin, MinalginAnalgesic, antipyreticDAO inhibitor[Jarisch 2004]
Orciprenaline  DAO inhibitor[Sattler 1985]
Pancuronium Muscle relaxantDAO inhibitor[Sattler 1985, Maintz et al. 2006, Fritzsche 2009]
Pentamidine AntibioticDAO inhibitor[Sattler 1985, Maintz et al. 2006]
Pirenzepine  DAO inhibitor[Sattler 1985]
Prilocaine Local anaestheticDAO inhibitor[Maintz et al. 2006, Nesterenko 2010]
PromethazineAtosil, Closin, Proneurin, ProthazinSedative, antihistamine, antipsychoticDAO inhibitor[Irion 2009]
PropafenoneRytmonormAntiarrhythmicDAO inhibitor[Jarisch 2004, Maintz et al. 2006]
Propanidide AnaestheticDAO inhibitor[Nesterenko 2010]
Quinidine CardiacDAO inhibitor[Fritzsche 2009]
Tetroxoprim  DAO inhibitor[Sattler 1985]
VerapamilFlamon, Isoptin, TarkaCoronaryvasodilatant, antihypertensive, antiarrhythmic, calcium antagonistDAO inhibitor[Jarisch 2004, Maintz et al. 2006]
D-CycloserineSeromycinAntibioticDAO inhibitor (Vitamin B6-Antagonist)[Sattler 1985, Steneberg 2007]
IsoniazideRimifon, RifaterTuberculostaticDAO inhibitor (Vitamin B6-Antagonist)[Jarisch 2004, Maintz et al. 2006]
ChloroquineChlorochin, Nivaquine, ResochinAntimalarials, antirheumaticDAO inhibitor, HNMT-Blocker[Sattler 1985, Jarisch 2004, Donatelli et al. 1994, Maintz et al. 2006]

Bottom Line

The list are items that you should NOT take because they reduce DAO and can result in fatal histamine reactions if you already have histamine issues. Decision to stop any should be done in consultation with your medical professional.

Ajwain (Trachyspermum Ammi)

“No good deed goes unpunished” – as a result of my last post on Sumac, I was asked about another atypical herb. It is a herb that has been used in cooking for a long time: Ajwain, ajowan caraway, bishop’s weed, carom, Ptychotis Oil, Ethiopian Cumin,Omam etc.

I was actually an active user of it some 20 years ago for it’s anticoagulation effects.

Trachyspermum ammi commonly known as ‘Ajwain’ is distributed throughout India and is mostly cultivated in Gujarat and Rajasthan. The fruit possesses stimulant, antispasmodic and carminative properties and is used traditionally as an important remedial agent for flatulence, atonic dyspepsia, diarrhea, abdominal tumors, abdominal pains, piles, and bronchial problems, lack of appetite, galactogogue, asthma and amenorrhoea. Medicinally, has been proven to possess various pharmacological activities like antifungal, antioxidant, antimicrobial, antinociceptive, cytotoxic, hypolipidemic, antihypertensive, antispasmodic, broncho-dilating actions, antilithiasis, diuretic, abortifacient, antitussive, nematicidal, anthelmintic and antifilarial. Further, studies reveal the presence of various phytochemical constituents mainly carbohydrates, glycosides, saponins, phenolic compounds, volatile oil (thymol, γ-terpinene, para-cymene, and α- and β-pinene), protein, fat, fiber and mineral matter containing calcium, phosphorous, iron and nicotinic acid. These studies reveal that T. ammi is a source of medicinally active compounds and have various pharmacological effects; hence, it is encouraging to find its new therapeutic uses.

Trachyspermum ammi [2012] – Full text with links to studies

The major component of this seed is thymol which impacts hundreds of different bacteria. It has a higher concentration than thyme.

Handling non 16s Tests

Today I added another tests to the list on this page. This is the 2nd one from this lab.

Dealing with non 16s tests means that a totally different lab process is used with ranges being different. Ranges for most labs is done by taking a sample of people close to the labs and then computing average and standard deviations. This works fine if you are a match for the people in the sample (DNA, diet, etc.) If you are Hindu vegetarian working in pork-country of Germany — your numbers may be very different. The reality is that their values are the only thing we can work from.

The lab may show values like this, with the ranges covering 65-95% of the population according to statistics. The numbers from our 16s samples do not agree. Instead of 5% being outside of the normal range, we could have 80% outside.

1.5 occurs at the 60%ile. 40% are higher.
The labs’ range is 25%-47%, 80% would be abnormal

Each lab will have different normal ranges. The solution that I used to allow people to use the suggestion engine is pretty simple.

  • Red below – pick two down arrows
  • Yellow below – pick one down arrows
  • Green — no errors
  • Yellow above – pick one up arrows
  • Red above – pick two up arrows
The ( %) can be ignored… we really just use the direction.

Can you use Jason Harwelak reference ranges? In general, likely. The values are below, so just copy your numbers across. I used the results from the above A6 test below. Notice that there can be major disagreement between the two on what the desired range is!!!

TaxonomyRankLowHighYour ValueStatus
Bacteroidetes
A6: 27 – 36
class03539.7Not Ideal
Akkermansia
A6: 0.01-1.5
genus135.2Not Ideal
Bacteroides
A6: 12-15
genus02013.2Not Ideal
Bifidobacterium
A6: 0.6 – 4.5
genus2.550.12Not Ideal
Blautiagenus510MISSING
Desulfovibrio
A6: 0 – 0.1
genus00.250.026Ideal
Eubacterium
A6: 0.3 – 2.3
genus0150.342Ideal
Lactobacillus
A6: 0.01 -0.05
genus0.0110.012Ideal
Methanobrevibacter
A6: 0 – 0.03
genus0.00010.020Ideal
Roseburia
A6: 0.5 – 2.4
genus5100.145Not Ideal
Ruminococcus
A6; 4.9 – 8.1
genus0153.9 Ideal
Proteobacteria
A6: 2-5
phylum049.5Not Ideal
Bilophila wadsworthia
A6: 0 – 1.89
species00.250.450Not Ideal
Escherichia colispecies00.01MISSING
Faecalibacterium prausnitzii
A6: 1.9 – 5.0
species10152.986Not Ideal

Remember, on the data entry — you can pick if you want to deem a value to be normal or abnormal. No one has the perfect answer (unfortunately).

Bottom Line

Try to isolate definite issues.

  • If the lab says “normal” skip that bacteria
  • If it says outside of range a little, you may wish to skip it.
  • If it says outside a lot,
    • Check Jason’s ranges
    • Click on the bacteria link and see if your values are:
      • In the top 5-10% of values
      • In the bottom 5% for bacteria that 99% of people have

Then click Analysis and see what suggestions comes up. If the lab has suggestions, compare them. If both agree — those are your first choices. If one is quiet and the other recommends, those are your second choices.

If the suggestions disagree — discuss with your medical professional before doing.

All of the tests below follow the same pattern: