Under the tongue and Brain Fog

The alternative title would be “Neurological issues and sublingual”. I got an email this morning from a ME/CFS person which reminded me of what I do often and I thought that I should share/remind others.

Reporting back. I tried  B1 benfotiamine again. I was feeling tired for no reason  so gave it a shot. I just wanted a low dose and so I opened the cap and sprinkled a quarter in my mouth. I usually take 1 cap. Huge effect. Felt like my muscle and brain came alive. In the past when I’ve taken b1 for a while it usually wears off or causes issues though so my question is how would I used Dr. AI to see if I have a deficiency of b1 and if need be what items to shift the microbiome. I’ve tried it prior to crashing  / PEM before and it didn’t stop it but I will do it again since it’s been a while.

For other experiences of ME/CFS with benfotiamine (a special form of Vitamin B1), see my earlier post from 2015

I have done many things sublingual, including heparin (much cheaper and appears just as effective than Low-molecular-weight heparin to deal with coagulation issues, and no injections!). My personal favorite is Piracetam which works far far better to get a tired brain working than strong coffee (at least for me).

The logic is simple, the amount that gets to the brain (which is close by) is much more than being processed through stomach acid and slowly working it way to the brain via the blood.

There is considerable literature supporting this, a few examples:

Note that the instructions for Symbioflor-1 probiotics, ” Take the drops, hold them in the mouth for a while and gargle with them before swallowing.” could be described as sublingual. Taking probiotics sublingual is not common practice…

Which ones?

There is no easy answer. Often taste can be a factor for tolerance of this approach. It may be a good exercise to try many of your supplements (one at a time) via this route and seen what has significant impact.

REMINDER: Rotate, rotate, rotate. A common complaint is that “a supplement benefit wears off”. In terms of the microbiome, this is expected from almost everything. The bacteria population adapts.

The importance of a large variation of diet with ME/CFS

For items like antibiotics and probiotics, I have for a long time been a strong advocated for continuous rotation. The original source for this attitude was Cecil Jadin’s treatment protocol for occult rickettsia (which originated with the Pasteur Institute for Tropical Medicine). This was followed by reading studies finding that rotating or even just pulsing (2 weeks on/ 2 weeks off) was more effective in reducing bacteria than continuous. Probiotics often function via the natural antibiotics they produce (a lot of prescription antibiotics originated with bacteria); hence probiotic rotation became part of my preaching.

If you have microbiome related issues, my soapbox has been “your goal is make the stable dysfunctional microbiome, unstable. Today I read a study on Nature that further clarifies what may be needed.

Together, these findings suggest that the human gut microbiome’s metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient. The dynamics of this ecological memory also highlight the potential for intra-individual microbiome variation to affect the design and interpretation of interventions involving the gut microbiome.

Ecological memory of prior nutrient exposure in the human gut microbiome [2022]

If the goal is to make the microbiome unstable, then this gives some clear indication of strategy.

  • Every two weeks change the dominant starch – for example, if pasta is a regular meal item then
    • Made from glucomannan—a starch found in the konjac yam/ Konjac Flour (Source)
    • Made from red lentils and quinoa (Source)
    • Made from white rice flour, organic amaranth flour (Source)
    • Made from chickpea flour, organic yellow lentil flour, organic red lentil flour, organic kale powder, organic spinach powder (source)
  • Every two weeks change dominant proteins source
    • Fish
    • Pork
    • Lamb
    • Duck
    • Chicken
    • Turkey
  • Change vegetables and fruit too…
  • Change main spices used….

The key aspect is that every new addition results in a change of the microbiome. If you have microbiome issues, that is what you want to do. You do NOT want to take the same supplements, herbs, spices, vitamin or comfort food – continuously. You want to shake things up!

Phospholipids, the Microbiome and ME/CFS

For almost a decade I have suspected that there was an interaction between the microbiome and Antiphospholipid syndrome (APS) also known as Hughes Syndrome (after the MD, see below). This is also called  “sticky blood syndrome” [HealthLine]. For some researchers, it is deemed to be a significant contributor to fatigue in Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [1999 D. Berg] and likely also applies to Long COVID. My own singleton experience seems to confirm it for myself.

A reader asked about phospholipids on Facebook today, so I revisited available literature

This article by Graham R.V. Hughes, MD, FRCP (the discoverer) in 2016 is well worth reading.

For me, APS/Hughes syndrome is very much a neurological condition. Brain function does seem to be especially targeted—the more APS patients one sees, the wider and wider the neuropsychiatric ripples spread.

APS: What Rheumatologists Should Know about Hughes Syndrome • By Graham R.V. Hughes, MD, FRCP

Of course, running off the experience of just one, or even a few people, is not the best practice. Testimonials suck because of rose color glasses, fake testimonials, mainly positive responders report, and placebo effects. So what does the literature state. First there is some literature that are general discussions without the type of detail that I would love to see:

Then we come to this article: Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity [2019] which uses one of my favorite information source, the Kyoto Encyclopedia of Genes and Genomes. “We found that PGs were positively associated with microbiomes enriched with endotoxin-synthesis genes and associated with markers of inflammation.”

Digging further we find:

 Bacteroides thetaiotaomicron, Actinomyces massiliensis, Pseudopropionibacterium propionicum, Corynebacterium amycolatum, Ruminococcus gnavus and Roseburia intestinalis[2021] lead to the formation of pathogenic T‑cell and autoantibody responses via the cross-reactivity with autoantigens (Ro60, dsDNA and ß2 glycoprotein I). 

The role of the microbiome in lupus and antiphospholipid syndrome [2020]

M. pneumoniae and Streptococcus spp. infections, which are among the most prevalent bacterial infections in children and young adults, were linked to the occurrence of aPL. …. an anaerobic bacterium Fusobacterium necrophorum, although a variety of other bacteria such as streptococci, staphylococci, and enterococci may be also responsible…. a specific change in the gut microbial composition in APS patients. Particularly, a decrease of bacteria belonging to the genus Bilophila and overgrowth of bacteria of the Slackia genus were shown…  enrichment by Slackia spp. and by the lower abundance of butyrate-producing Butyricimonas 

Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation [2019]

More discussion of mechanism is in The Role of the Gut Microbiota in the Pathogenesis of Antiphospholipid Syndrome [2015]

Bottom Line

APS only requires one of the bacteria above to trigger it. In terms of using Microbiome Prescription, I would look at Bilophila and Butyricimonas – if below 50%ile, hand pick it, then look at Slackia, if above 50%ile then hand pick it. Check the other bacteria cited above, and if any are over 75%ile, hand pick those. “It only takes one rotten apple to spoil the barrel” seems to apply here.

I have added APS to my PubMed reference list:

From https://microbiomeprescription.com/library/PubMedCitation?CondId=88

Personal Observations

I checked my samples from my last ME/CFS flare and found that Bacteroides thetaiotaomicron went from 73%ile on first sample after onset, to 96%ile on second sample, down to 79%ile, then 70%ile then 20%ile a few months later with recovery and returning to work. The key triggering bacteria will likely be different for each person but you at least have a candidate list to work from.

A Series of Special Studies are being released…

The current studies are listed below with more being planned. The studies look at specific symptoms reported with uploads of microbiome to Microbiome Prescription. As new studies are added, they will be listed on the first link

Using the results of the study is easy, go to your sample, click on [Change Microbiome] and then select the appropriate item (this list will be growing)

Pyridostigmine bromide – GWI and ME/CFS

A reader message me with a drug that I was not familar with

Hello, my brother has CFS and I would like to ask you a question. We talked to a doctor at the ‘…..’ hospital in Germany who specializes on CFS. The doctor suggested taking Pyridostigmine bromide. What are your thoughts on that?

This is a drug that I am not familiar with and thus interested in finding out more.

First, what is it’s typical use:

Pyridostigmine bromide (PB) is a drug used during the Gulf War as a pretreatment to protect troops from the harmful effects of nerve agents. It has been used for more than 40 years in the routine treatment of myasthenia gravis and may be used following surgery in the reversal of neuromuscular blockade (Williams, 1984).

Gulf War and Health: Volume 1. Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines. (From NIH)

So, if the brother had been involved in the Gulf War, there seem to be some logic to this suggestion. However, constructive logic usually have risk and is inferior to doing research. What I found sent my air-raid alarms sounding.

Results indicate that more than 21 Pyridostigmine Bromide (PB) pill exposure was associated with consistent reporting of fatigue, pain, and cognitive/mood symptoms as well as the development of six additional symptoms over time. Veterans reporting exposure to more than 21 PB pills were more than 8 times as likely to consistently meet the criteria for Chronic Multisymptom Illness over time.

Health symptom trajectories and neurotoxicant exposures in Gulf War veterans: the Ft. Devens cohort [2022]

Ah, ME/CFS had yet another name: Chronic Multisymptom Illness.

And the bad news went on:

Difference of Opinion?

A reader pointed me to Mestinon on ME-Pedia.org which presents some interesting reads. My ground rules have always been to rely on gold standard sources, that is, peer-reviewed PUBMED articles.

This page does cites issues seen:  gastrointestinal symptoms , Multiple chemical sensitivity (MCS). This page also cites:  there are no clinical trials of Mestinon in ME/CFS. Evidence for it was:

My typical reading of OLD thin results is that there were follow up studies that showed no effect or negative effects, hence never submitted for publication (or not accepted by publishers).

Revisited PubMed

PubMed failed me because it did not find this drug by alternative names…

Bottom Line

I would declined, and actually ask the doctor for published studies that shows it would help. The evidence is that it would make the symptoms worst. A single dose appears to help, the evidence of the cumulative effect of multiple doses are a worsening of the symptoms.

This is one of the few cases that I would consider writing to the licensing authorities if the doctor response to being presented with the above information is arrogance.

For your brother, I would suggest getting an appropriate microbiome test (being in Germany, my choice would be BiomeSight.com from the UK), and using “Dr. Artificial Intelligence” at https://microbiomeprescription.com/ . Dr.A.I. fees are reasonable (free), with immediate availability once you get the test results. So far the feedback from people using him has been very positive.

Social Feedback

From Facebook