“The Holy Grail in this field has been to discover how to turn off neuroinflammation in microglia.” Tanzi
It’s been a bitter couple of years for big pharma and the Alzheimer’s community. Just today, Eisai and Biogen announced they were abandoning Elenbecestat, the last BASE inhibitor drug under trial. The BASE inhibitors, which are designed to stop the production of amyloid plaques, have been the big hope and the huge disappointment in Alzheimer’s.
The BACE drug hypothesis has been an epic failure but it could conceivably lead to treatments that help ME/CFS and FM.
That announcement followed similar decisions earlier this year by Novartis and Amgen, last year by Eli Lily, Merck, Pfizer and Johnson and Johnson, and by Roche in 2013. One wonders if in the history of drug manufacturing so many big pharmaceutical companies have ever gotten it all so wrong.
With 400 mostly failed clinical trials and billions spent over the past decade and a half, Alzheimer’s remains a brutally difficult disease to treat. Despite enormous efforts, no new drug has been approved in over 15 years. It’s perhaps no surprise that AD drug development is believed to have the highest failure rate of any disease.
Despite all the failures, one Harvard neurologist believes the effort has not been wasted. Alzheimer’s researcher and drug companies, he believes, now know where to concentrate their efforts.
“I feel like we’re finally seeing a light at the end of the tunnel. We’ve made mistakes, but those mistakes have taught us where we need to get to next.” Tanzi
If Tanzi is right, the silver lining in the Alzheimer’s drug development fiasco may be the development of a drug or protocol that could help with chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) as well. Tanzi and others believe the logical next step in the fight to stop Alzheimer’s is a drug that fights what may be the key factor in ME/CFS and FM – neuroinflammation.
Over the past five years or so, research has, in fact, been pointing more and more of a finger at the microglia and neuroinflammation instead of amyloid plaques. While amyloid plaques clearly play a role in Alzheimer’s, a 2013 Mayo Clinic autopsy study blew away the idea that they were the be all and end all of that disease. That study found that some people who had never come down with dementia had plaque-filled brains. It reported:
Together, these data suggest that amyloid-β plaques and tangles do not inevitably result in neural system derangement and dementia in all individuals.
Some drug companies are now turning to fighting neuroinflammation in Alzheimer’s.
You clearly need more than amyloid plaques to have Alzheimer’s, and one of the necessary partners appears to be glial activation; i.e. neuroinflammation. While the mechanisms are not understand, mounting evidence has implicated the microglia – the same brain cells Jarred Younger proposes are hyperactive in ME/CFS – in Alzheimer’s. That’s causing some drug companies to shift direction and start focusing on drugs that stop neuroinflammation.
- A Boston company called AZTherapies has reformulated Cromolyn, a mast cell stabilizer, so that it can reach the brain and is testing it in a 600 person trial.
- Cassava Sciences has just begun a phase IIb trial of its PTI 125 drug which is reported to have “powerful anti-neuroinflammatory effects”. (The NIH was excited enough by PTI 125 to give Cassava a $6.7 million grant.) The most recent trial indicated that PTI 125 reduced the levels of neuroinflammatory markers in the cerebrospinal fluid.
- INmune Bio is developing XPro1595, a biologic drug it hopes will stop chronic inflammation by neutralizing the soluble form of the proinflammatory form of TNF (sTNF).
- Early results from a new drug called BPN14770 point to the potential add-on results that an Alzheimer’s drug targeting inflammation might achieve. The drug, which is now in phase II trials and targets an enzyme that increases neuroinflammation, appears to facilitate “multiple biological mechanisms that protect the brain from memory deficits, neuronal damage, and biochemical impairments”. It’s also being tested in Fragile X Syndrome.
- Other anti-neuroinflammatory drugs under trial include resveratrol, etanercept, eflamapimod (VX-745) , minocycline, vorinostat and ORY2001.
Parkinson’s Disease
“Blocking the inflammation cycle is thought to be a promising potential disease-modifying therapeutic strategy for PD.” The Cure Parkinson’s Trust
Parkinson’s is another disease with a neuroinflammatory element. (Like Alzheimer’s, Parkinson’s researchers mistook the trees for the forest when they concentrated on dopamine rather than the neuroinflammatory factors which triggered the dopamine problems.)
Numerous trials of anti-neuroinflammatory drugs are underway in Parkinson’s. The Michael J Fox Foundation had created small molecules which in early trials have stopped neuroinflammation in its tracks – and hopes to use them to create drugs. It’s also testing “a novel series of plant-derived compounds with high “anti-inflammatory activity” that have been structurally modified to reduce neurotoxic inflammatory factors in the brain.
The Cure Parkinson’s Trust in the U.K. is repurposing three cancer drugs that it believes may help halt the neuroinflammation present in Parkinson’s, and an Irish pharmaceutical company recently raised almost $50 million to test inflammasome inhibitors in Parkinson’s.
Chronic Fatigue Syndrome and Fibromyalgia
The cognitive issues in ME/CFS and FM, by themselves, suggest that keeping an eye on what’s happening in Alzheimer’s disease might be a good idea. No studies have been done in ME/CFS, but one fibromyalgia study did suggest the disease may increase the risk of dementia.
In an interview, Dr. Klimas said she was keeping a close eye on neurological diseases like Alzheimer’s and Parkinson’s. Dr. Klimas is testing several drugs in Gulf War Illness (GWI) and two in ME/CFS (etanercept (Enbrel)/mifepristone) to fight the neuroinflammation she believes is happening there. She is also incorporating neuroinflammation into her computational biology models of ME/CFS and GWI.
Her ME/CFS Enbrel study got a bit more interesting recently when the Washington Post reported that Pfizer, the drug’s manufacturer, found in a 2015 insurance claim review that Enbrel, an anti-inflammatory, may be dramatically reducing the risk of Alzheimer’s.
In another study, Klimas will pair either glutathione or CoQ10 with intranasal insulin in an attempt to tamp down the fires in the brain. Intranasal insulin has been successfully trialed in animal studies in Alzheimer’s and in small human trials in Parkinson’s.
Jarred Younger’s study on botanicals that he hopes will fight neuroinflammation has finished, and he’s reportedly now investigating a potentially more effective and less side-effect prone version of low dose naltrexone.
On the neuroinflammation front, a recent study suggested that a non-invasive, very fast and low-cost technology called optical coherence tomography (OCT) may be able to detect the neuroinflammatory changes that occur in the eyes in very early Alzheimer’s. Another study may have identified a key neuroinflammatory switch in the brain.
The Functional Medicine Approach to Neuroinflammation
Finally, there’s Dale Bredesen’s functional medicine approach to neuroinflammation and Alzheimer’s. Bredesen leads the Easton Laboratories for Neurodegenerative Disease Research at UCLA. Bredesen’s ReCode program uses functional medicine to treat dementia and has used Aryuvedic medicine to subtype three different types of Alzheimer’s.
Bredesen’s ReCode Diet
Bredesen believes one type of Alzheimer’s is triggered by inflammation (e.g. leaky gut, gum disease, Lyme, mold), another type by hormonal problems, another by insulin issues, and the last by heavy metals and toxins. He singled out mycotoxins and mold in a 2016 article.
In a very small trial in 2016, Bredesen reported he’d used functional medicine to reverse the cognitive declines in Alzheimer’s. In 2018, he reported on 100 patients using his approach in a journal article, which did not, however, make it into PubMed.
The Brain Health and Research Institute (BHRI), recently launched by genomics pioneer Lee Hood, will use Bredesen’s 36 factors to deep phenotype its patients using gut microbiome checks, sleep and activity monitors, blood tests, etc. to create personalized medicine programs. Patients will follow plant-based ketogenic diets, root out environmental toxins such as mold, and do brain enhancing cognitive exercises, among other approaches.
Tanzi, the Harvard researcher, also emphasizes lifestyle changes (anti-inflammatory diet, meditation, exercise) to reduce the inflammation he believes causes Alzheimer’s. UC Berkeley recently received a $47 million grant from the NIH to study the effects of lifestyle changes (diet, exercise, and social and cognitive stimulation).
The Future
Drug companies may have spent billions on BACE inhibitors and amyloid research but most have not backed away from Alzheimer’s. With the population aging and people living longer than ever, the prevalence of Alzheimer’s is projected to go up and up. Alzheimer’s continues to present a potential market like no other.
Time will tell how effective any of the above approaches are at tamping down neuroinflammation, but it is clear that neuroinflammation is getting more attention and will likely continue to get more attention in the future in Alzheimer’s and other central nervous system disorders – and that’s probably good news for ME/CFS and FM.
Dr. Chheda has asserted that the next ten years are going to see a wave of new treatments that could benefit people with ME/CFS and FM and new anti-neuroinflammatory treatments could certainly fit that bill.
- Coming up – a talk with Jarred Younger on his neuroinflammation Studies
I once believed neuroinflammation was THE key to CFS. I’ve gone off the idea a bit, mainly because in my opinion some other theories are more promising, such as theories around glycolysis.
But I haven’t written it off, either.
Time will tell.
Yeah I agree, I think neuroinflammation is just a down stream of a cascade of problems caused by every cell in the body lacking the energy to function properly. Hence immune modulation / inflammation is a result.
Maybe though reducing brain inflammation will reduce the suffering of Post Exertional Malaise. I doubt it will stop the extreme fatigue of ME/CFS
I know I get some benefit by Ibuprofen and antihistamines and a high plant protein and Omega 3s from flaxseed and DHA from algae (i.e. a plant only diet) for preventing inflammation the that triggers a PEM crash. But I’m still mostly house bound. But that’s still better than bedridden
Agree. I too am thinking neuroinflammation might be a downstream effect
I think the glycolysis idea could fit neuroinflammation if it shows up in the brain but De Jurgen would know more about that.
I think it could be absolutely key though. If neuroinflammation starts off Alzheimer’s and Parkinson’s – it could produce virtually anything – including all the fatigue and pain symptoms in ME/cFS. All you need to do is tweak those neurons and they can create all the symptoms. We know, after all, that most of the flu-like symptoms caused during a cold are produced by the brain…
Put me on the skeptics column for any metabolic disorder theory. I recently completed 6 mile hike and have been horizontal in the PEM prison for the past 2 weeks. Energy generation is not a problem, at least for those progressed to the mild end of the spectrum, but PEM still is. True, there may be a way to explain PEM with metabolic anomaly. But I can’t think of way to explain 6 mile/700ft hike as if I completely recovered, only to keel over the next day.
Nice point TK! I too can generate enough energy to do substantial physical work. Not nearly as much as I used to do but still….It’s the aftermath that is the problem.
Dr. Klimas’s exercise testing has found that exercise unleashes a flood of inflammation – which then results in increased oxidative stress, hormonal problems,etc. which then are probably responsible for the PEM which, for me, is often at its worst a day or so later.
This delayed response is clearly a critical response of ME/CFS that must be understood. Thanks for the reminder.
I believe there are two parts to energy production. There is the easy to notice part of having plenty of ATP to do activities on one hand. On the other hand there is IMO a high percentage of our energy production used for protecting and repairing our bodies.
The first form of energy would be more but not completely represented by ATP and NADH production by things as glycolysis and the Krebbs cycle. The second part would be more but not completely represented by NADPH production by things like the Pentose Phosphate Pathway and the Krebbs cycle.
Production of NADPH could be used for immune functioning and recycling of glutathione. That are mainly defensive functions. Part of the protons produced by NADH but lost as in not making ATP could be used to scavenge oxidative stress in the mitochondria. Plenty of ATP could be used for “reparation work”.
This opens the option for ME to be both hypo metabolic and hyper metabolic. Hypo as in producing very few “usable energy” and hyper as in producing and using massive amounts of energy for protection (against ROS, pathogens and others) and reparation.
The body could be sent mainly in “partial inhibition” as in mainly inhibiting energy available for activities. Energy production could still be high but mainly for protection and reparation. Inhibition of glycolysis could fit in here as it seem that massive oxidative stress seems to shift glucose from glycolysis to the PPP (that produces more NADPH) and turning the Krebbs cycle both down and changing it to produce more NADPH then NADH.
When having this disease, producing enough energy to protect and repair is the main goal. Even when that goal is met, producing paltry amounts of energy for activities makes sense too as with a “damaged” body any normal rate of activity easily becomes damaging and inflammatory by itself.
In this hypothesis the body is largely capable of producing reasonable amounts of energy, but turns it to healing and reduces / inhibits activity even if it might have enough capacity for it as many activities quickly become damaging in their own way. That would demand more future healing so inhibiting it now makes sense.
In this hypothesis I also believe the body (brain) steers this inhibition of energy for activities in function of the current state (damage, ROS, pathogens…) and the “estimated” direction things are going. So when someone has paced for a few weeks the body is getting in a better state and the brain could see the continual improvement as a signal to be less strict on conserving energy and inhibiting activities.
Then, especially under the influence of some adrenaline and or dopamine giving a short lived boost in both feelings of energy and energy production, one could be quite active for some time. One could be even more active if the body partly inhibits protection and healing during the activity. But that would soon end disastrous with massive PEM following soon…
And as the direction of health as perceived by the brain would have gone down quickly, the brain would be in a state of emergency and become very strict on inhibiting any activity at all, “exaggerating” the other way as just before the too strong activity.
While not a cure, pacing is still king IMO.
Interesting. Im in this boat too. I can do a little bit of light exercise up to an 8k walk but just can’t recover from it.
“under the influence of some adrenaline and or dopamine giving a short lived boost”.
In my experience, the PEM mitigation effect of dopamine (traveling) or adrenaline (family emergency) has been more important than boosting. Many times I was sure I’d get knocked out with PEM, and I didn’t. For example, I went on 7 day trip registering 10,000 steps a day on average last year. I got away without paying for PEM. If it was the case of “borrow and spend”, then I should’ve had harder PEM after the boost.
I don’t need a boost to walk farther or faster like a (almost) normal person either. It’s just that I’d get sick if I don’t pace, so I measure my speed and limit the distance to half a mile before taking a break.
Anyway, that’s all just one person’s experience. But I suspect there are other mildly ill patients with similar experience.
Count me in to the “Perplexed with PEM” group. Before CFS I was an athlete and expert on my own body. Even when I felt like I was going to drop dead, I could walk 5 more miles. Uphill. And I could do that every day for two weeks. Now with CFS, I can still walk uphill 5 miles. The next day I am so happy because I proved that nothing wrong with me (it’s all in my head!) Just a little tired. And then… the day after that, I’m flat out, inflamed, depressed, gravity has tripled it’s effect on me. Yay PEM.
“dejurgen on September 17, 2019 at 1:56 pm
I believe there are two parts to energy production.” This makes more sense than anything else I’ve read in a decade. It explains so much. Multiple energy factories, each with separate responsibilities. Maybe the manager is damaged, or there is no manager telling which factory to step it up and when. Or maybe the manager knows that we (or our environment) cannot be trusted, so it keeps us on a short leash. Anyway, it explains why we look healthy when we feel so sick. Because there are separate production schedules for maintainence and activity. It explains how I can work for a month (by pushing past my limits) yet nobody suspects there is anything wrong with me – until a month later, I’m physically sick, dumb as a box of rocks, and too “lazy” to get up in the morning. In the past 10 years, each time I get a job, I last a month, and I get a new chronic illness. It’s almost funny. I take a year off and try again. One job gave me constant diarrhea (I still have it: collaginous colitis) The next job sent me into menopause overnight, literally. The next year, I pushed myself through physical therapy for my painful neck, and ended up in the hospital with appendicitis. PT gave me occipital neuralgia as a bonus. The last job I had gave me chronic migraine. Finally tested positive and treated for Lyme disease. I quit trying to work. Then I was denied disability because I can “work”. LOL
Ever hear of a “Mito Crash? PEM is not “exclusive” to ME CFS. It’s also a hallmark symptom of Mitochondrial Disease. Just recently, I’ve been able to achieve symptomatic improvement (able to do more physical activity while avoiding severe PEM (avoiding an ME CFS crash) by following a mito protocol and making adjustments in my treatment regimen based on the results of a recent urinary organics acid test. As everyone with this disease knows only too well, a steady state of improvement is very difficult to achieve with ME CFS. Even on the rare occasion you feel, dare I say, “well.” you must still pace all of your activities. This is no different than those with Mitochondrial Diseases. I wish people with well defined and diagnosed Mito Diseases could be included in some of the ME CFS research studies. It might be very “revealing.” As it is, underlying inborn errors of metabolism (genetic variants) have been found in a small cohort of ME CFS patients.
Thanks Lori,
We have much to learn from mitochondrial diseases. I’m not at all surprised that PEM is a major feature of them.
We will certainly be hearing more about inborn errors of metabolism in ME/CFS. I know of another researcher who has found them.
Very interesting! Thank you, Cort!
Glad to see you picking up on Lee Hood’s work! He’s been doing some great things with personalized medicine. I wish the ME/CFS researchers would interact more with him.
After spending years around neurologists for my mom’s Parkinson’s and my dad’s stroke, I’ve found neurology to be a depressing profession – the drugs they prescribe can impact symptoms, but do little to improve the root cause. Reducing neuroinflammation makes sense.
I regularly use boswellia and. curcumin to reduce the brain and spinal swelling caused by my IVIG – they’re very effective. And Opus23 recommended his dose resveratrol after analyzing my genes. My brain has been more dependable, with less brain fog over time. Glad to hear this may be a very viable strategy.
Thanks for another great article, Cort!
Although there is continued debate about whether Gulf War Illness and ME/CFS are the same condition, I believe that a lot can be learned from the similarity of symptoms like brain inflammation.
A great deal more money has been allocated to studying Gulf War Illnesses…$20 million a year for the last several years.
This report lists treatment trials and some recommended treatments like bacopa which I am currently trying.
https://www.va.gov/RAC-GWVI/meetings/mar2018/LidieMarch2018508compl.pdf
Thanks Betty. I was not aware of that site. Solve ME is trying to get ME/CFS back into the list of diseases that the Congressionally Mandated Program will fund.
You might find this interesting, Betty:
https://www.mdpi.com/1660-4601/16/1/111/htm
Anthony Mawson suggests here that liver damage and retinoid-toxicity may be factors in the development of Gulf War Syndrome.
Cort, do you know the current status of Japanese study for neuro-inflammation imaging? (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033257)
Also, Younger’s MRSt study seems cheap enough for other to replicate. I wonder why there is no effort on that front..
If neuro-inflammation is a fact, that’s a huge clue that ought to be the starting point of any investigation. As such, I think it is imperative to establish it as a fact, not just a theory.
I think the delay is probably a function of this small field and the new technique used but I imagine that Younger’s study will be replicated. A bigger study is actually underway and I hope to report on that soon. Plus Tompkins at the new OMF funded Harvard Collaborative Center wants to take advantage of their brain imaging facilities.
As to the Japanese study I have heard nothing. Thanks for the link. 🙂
That was the link from your “brain on fire” blog 🙂 https://www.healthrising.org/blog/2018/09/24/brain-fire-neuroinflammation-found-chronic-fatigue-syndrome-me-cfs/
Cort, Is it known what doses/protocol Klimas is using in her trials? Any idea how they are going or when we may find out?
Thanks
She using Enbrel followed by mifepristone in women with ME/CFS (not men) and GWI.
She will also be testing either glutathione or CoQ10 in combination with intransal insulin in GWI and I think a separate Bacopa trial in GWI.
All these trials are the results of computer modeling. They are what her computational biological results suggest could work.
What I really like is that even if the trials don’t work out – she’s going to do extensive testing – and then feed the results back into her models.
Haven’t heard any results yet.
What about men with cfs? In her talk from 2017 I thought she said she would try Enebrel and Mifepristone first in GWI, then in post menapause women and then in men with cfs. Has that changed?
If I got it right and I may not have – the men will have to try something else It’s possible I didn’t get it right though. This was the first time I had heard of that.
Could physical activity in ME/CFS patients cause the Krebbs Cycle to produce oxidative or other destructive radicals such as ONOO (NO3), OH-, H2O2+, maybe one other, which macrophages need to gobble up and rearrange into nondestructive ions? (Part of this I saw in a PowerPoint presentation, but I’m unsure of the source.)
I’m certainly no expert but I would guess that is one of the hypotheses. Thus far Shungu is finding that oxidative stress in the brain is the key factor. He (and others) believe that Martin Pall’s ONOO hypothesis comes into play – in which it’s not the mitochondria going wrong but the antioxidant designed to mop up the inevitable free radicals produced during energy production.
But many anti-oxidants like glutathione and vitamin C require NADPH to be recycled. If not, they become a single (glutathione) or dual use (vitamin C) anti oxidant rather then a use-plenty-of-times anti-oxidant. That would result in, in effect, plenty of less anti-oxidant working in the body.
And so we may come back to the idea that the cells and mitochondria in it produce energy for both activities and defense and repair. Under that hypothesis we (or better said the moderately ill, not me) can push out enough energy for “normal” rates of activities for some time but fail to produce (recycle) enough anti-oxidants to clean up the inevitable damage going with that activity. And that would leave our cells littered with “trash” to be cleaned up after it: PEM?
Also, while I think of it, it seems like inflammation initially gives me energy.
1) I used to be able to tell if I was getting a virus infection because I would get an unexplained burst of energy before any other signs or symptoms.
2) They say a person craves what they are allergic to. I think I do, and I think that it is because I crave that burst of energy.in both cases, of course I crash later.
My work as a scientist (pre-ME when I still had to brain to do it!) was focused on what HIV did in the brain, which was basically, even in very low, inactive numbers, act as a neuroinflammatory agent not associated with its effect as a virus. It hit me hard when I realised that was probably what was going on in my brain albeit with a different pathogen. As part of my research I strove to find a marker for the different types of immune systems cells in the CNS (infiltrating macrophages, resident quiescent and active microglia, astrocytes) and looked at Alzheimer’s brains as a contrast. The neuroinflammation in those brains was huge and I overturned much of my neuroscience training that said it was plaques causing damage, to me, it was more than obvious that there was a huge inflammatory component that was being mostly overlooked.
Great to hear from someone on the ground floor so to speak 🙂 Let’s hope the turn to stopping the inflammation benefits ME/CFS and FM as well.
Thank you for the overview Cort. The below article (and the publication linked in it) may be of interest:
https://m.medicalxpress.com/news/2019-09-scientists-combat-alzheimer-disease.html.
It links mitochondrial dysfunction (due to calcium overload) to neuro inflammation in a mouse model for Alzheimer.
Right! Now they’re at the mitochondria as well – and energy production…It’ll be fascinating to see how it all comes together.
I too am plagued by PEM and if my energy stores are within range, I can do quite well, up to 10,000 steps but it is the crash not the next day, but two days later that befuddles me. I am noticing a very similar pattern in my partner who was treated for prostate cancer with both energy killing radiation and adjuvant (testosterone suppressing) Luperon. Blame the treatments, but I can’t help wondering about different causes for all of our variants of ME/CFS.
I am not someone who consistently suffers from brain fog (losing my thoughts and forgetting words) but it seems to come and go–so I wonder about neuroinflammation. It’s almost like with both physical and mental energy, something is depleted and needs time to reestablish itself rather than a constant bombardment of some sort of inflammatory agent. That takes me down the mitochondrial causal path–but it is so much more complicated than that, so at this point who knows?
Now a few posts ago, you, Cort, talked about Klima’s treatment models and bacopa was on the menu. Of course, I don’t want to wait for the study results and immediately went searching for sources of bacopa to try. One of the other posters wanted to know what I might use and upon further investigation, within your very article is embedded a link to a study which answers that question; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269610/ Go to the materials and methods to see what the researchers did–and the bacopa is readily available for anybody to order and try. For myself, I still haven’t tried it yet as I want to try each additional supplement by itself so I can determine if it has an effect.
My most recent trial has been Pycnogenol and I think it is having a positive effect, but I need to try and deny to find out for sure.
I have also noticed in the past that when my diet comes from the Farmers Market (a variety of fresh vegetables mostly), I do substantially better. Unfortunately, often I don’t have the energy to shop and prepare meals that way.
Thanks again Cort for all your most helpful reporting!
I know inflammation is very disruptive to the body, but isn’t inflammation a symptom as well as a cause? Such as a symptom of a chronic bacterial or viral infection? It seems like just stopping the inflammation is helpful, but what about stopping what is causing the inflammation?
One idea is that a pathogen instituted a pattern of kind of runaway inflammation – and then was vanquished. On other other hand, altho efforts to find pathogens have been unsuccessful, it’s possible a pathogen could be doing as you said.
@Lorre Right now, there’s a small group of individuals testing (rather unscientifically—we are our own test subjects) the idea that an excessive build up of retinol/retinoic acid in the human body is responsible for the explosion of inflammatory diseases in the last several decades.
Here is a paper that explains how this might happen in bronchial asthma: https://www.researchgate.net/profile/Anthony_Mawson/publication/11841467_Could_bronchial_asthma_be_an_endogenous_pulmonary_expression_of_retinoid_intoxication/links/00b7d538baccf2f197000000/Could-bronchial-asthma-be-an-endogenous-pulmonary-expression-of-retinoid-intoxication.pdf?origin=publication_detail
A few of our members have seen significant improvement in their CFS symptoms after adopting a low Vitamin A diet.
It’s far from a theory at this point, but I have seen enough positive changes in my own health from avoiding Vitamin A for 9 months that I am curious and hopeful that there might be something to this idea.
A man named Grant Genereux recovered from severe ezcema, kidney disease, fatigue and foggy-headedness by eating an almost zero Vitamin A diet, and has continued to eat the same way for 5 years now in an effort to demonstrate that vitamin A isn’t a vitamin. Sounds a bit crazy to most people I’m sure, but Grant appears to be a sincere and compassionate person. He has written a few books about his ideas and experiences, which he gives away for free here: https://ggenereux.blog/my-ebooks/
He also hosts a forum (free to join) on his website, which is where we are sharing our findings with eachother.
No idea if this is the “answer” or not, but I think it’s healthy to look at crazy ideas from time to time to challenge our perception of reality and truth. And asking the right questions is at least a start, hopefully!
There must be SOMETHING causing the inflammation in everything from asthma to ezcema to chronic fatigue syndrome to arthritis. “What about stopping what is causing the inflammation?” I want the answer to that, too.
“I am not someone who consistently suffers from brain fog… …but it seems to come and go–so I wonder about neuroinflammation.”
ME patients have reduced blood flow to the brain. Exhaustion creates a strong further reduction in the brains blood flow soon after the thing causing exhaustion, for example thought or exercise. That has been shown by several studies.
If that would create partial hypoxia in the finest capillaries in the brain then there is a risk that the neurons release glutamate as the neuro transporters lose ATP to fuel themselves and therefore glutamate transport reverses. That risks to create such high levels of extracellular glutamate that it becomes exotoxic.
https://en.wikipedia.org/wiki/Excitotoxicity
“Ischemia is followed by accumulation of glutamate and aspartate in the extracellular fluid, causing cell death, which is aggravated by lack of oxygen and glucose. The biochemical cascade resulting from ischemia and involving excitotoxicity is called the ischemic cascade.”
If part of our brain got into partial ischemia that would be sufficient to cause a nasty PEM I think. And it would leave plenty of neuro-inflammation too I guess.
We are prone to glucose imbalances during exhaustion too, strengthening what could be going on.
Neuroinflammation! Look at dejurgen post people! Hypoxia and glutamate. Inflammation of the brain and body. Work on this inflammation, find source of glutamate increase, lower inflammation and not as many issues all around. Brain fog and PEM should improve. Of recent we (dejurgen and I) have been researching this together. I have been saying for years there is a glutamate problem in both POTS and CFS. We are finding connections in already published articles. We also are seeing strong connections to mast cell degranulation as an issue with this. Mast cell degranulation (over histamine response) releases all sorts of inflammatory “chemicals” and causes much inflammation. There is a connection to glutamate excess here. And as dejurgen brought out, glutamate is an excitatory stimulant. Can cause neurotoxicity and cell damage. I’m leaving it to him to get into the technical as he is much better at explaining than me.
Dejurgen, I don’t have the scientific training to follow chemical pathways in the body as well as you, but regarding neuroinflammation and mast cell issues, I don’t know if you are familiar with the research of Dr. Theoharides. Having Ehlers-Danlos myself, EDS people seem to be prone to mast cell activation disorders (MCAS), one symptom, (including cutaneous issues and more), is problems thinking.
Dr. Theoharides has written and researched extensively on mast cell stabilizers (among other things). Some of his research points to using bioflavonoids for this purpose. Some like quercetin, luteolin, and rutin are found in fresh produce and certain diets.
I don’t know if using these compounds might help with brain fog. It might be interesting to self apply to see if your glutamate theory is correct. For myself, I haven’t paid close enough attention to determine exactly what circumstances bring on my fog. Sometimes it doesn’t seem to be connected with over stressing my energy envelope–but maybe, there too, the delayed response (as with PEM) might make it difficult to identify.
Just musing…
I follow Issie’s comments for some time as she combines clear observations with insightful ideas. That is a handy combination to work with. One of the things she kept writing about over the years was how badly glutamate could affect here.
I on the other hand am more thinking on the effects of blood flow issues, blood pooling, partial hypoxia, breathing issues and unrefreshing sleep.
When exchanging ideas between us, I stumbled upon the combination of glutamate being toxic when it is dumped on masse out of neurons under the conditions of hypoxia.
Glutamate is one of many chemicals that can’t cross the cell walls just like that. It requires active transport and that requires ATP or energy. That ATP or energy is used to take glutamate outside the cells and transport it into the neurons. But if ATP is short, for example by lack of sufficient oxygen or glucose in (part of) the brain, then this transport is reversed. Glutamate, that is available in higher concentrations in the neurons then outside of it, start to leak quickly out of the neurons into the extracellular space.
The problem with that is that glutamate in high amounts just outside the cells is very excitatory. It triggers the neurons to “fire” at a very fast rate. That “depolarizes” the neurons and leaves them very vulnerable to damage and destruction.
That creates two things (in this hypothesis). The first is a “hyper” state like in very wired in the “wired and tired” thing (glutamate in high concentrations in the extracellular space excites the brain a lot). That also is causing one to be very anxious and have poor sleep when it is present at night. The second thing is plenty of neuronal damage and sometimes dead around the smallest capillaries. That is a very bad thing and really inflammatory.
There are three things I am aware of that can cause a significant change (decrease) in blood flow to the brain. Note that a “modest” decrease in blood flow to the brain will be felt far more in the tiniest brain capillaries as they “lose” more then their proportional share in case of a reduced blood flow.
The first known and proven by research trigger of decreased blood flow to the brain in ME patients is exercise / exhaustion. Brain scans have demonstrated that clearly. Shortage of ATP and energy is already common in ME patients and having exhaustion on top of it wont make it any better. Regions in the brain closest to the smallest capillaries will very likely see an even greater decrease in ATP production combined with less oxygen and glucose. That makes a perfect combination for the above mentioned “toxic glutamate dump”. Exercise / exhaustion is a very well known cause of PEM.
The second known situation where blood flow to the brain drops is when people with POTS stand up without moving their legs for too long. While I “only” have a undefined form of orthostatic intolerance meaning I do experience problems while standing to long but don’t have “real” POTS, I learned the hard way I can crash and get a nasty PEM by standing too long without moving. This happened multiple times before I learned that standing too long caused it. I used the “technique” of “standing in my bones”. With that I mean I locked my joints so they took most of the effort and not my muscles (it’s bad for artrosis unfortunately…). So these PEMs were not mainly effort / ATP / exhaustion based but had the derailed brain flow element in common.
Then there is the third “known” situation of combined reduced blood flow and breathing: laying to sleep at night. Very few muscle movement occurs (reducing muscle blood pumping needed to reduce blood pooling) and hormonal changes reduce both blood volume IMO and breathing at night (at least in healthy people, we may or may not have hormonal day and night changes to counter this one). And unrefreshing nights are the often overlooked hallmark of ME. An unrefreshing night is having less energy in the morning then when going to bed. It is sort of a strong decline on top of what should be normally an improvement in energy during the night. While different it isn’t that different from exercising and overdoing it causing a following decline in health and energy.
In fact I believe these additional “stressors” like standing / POTS and “the night” may be why plenty of patients can’t pace enough to reverse their disease. What does it help to reduce walking from 20 meters a day to 15 meters a day if the damage caused by unrefreshing sleep is so much greater?
In summary: these three known causes of temporary decreased blood flow to the brain all cause PEM-like problems. And all three have a good chance to cause periodical toxic local glutamate dumps near the smallest capillaries in the brain. It sounds to be at least a potential candidate for a PEM and vicious circle enhancing mechanisms in ME.
Dr. Bredesen moves fast. He may still advise Easton Center but was succeeded as director, possibly in 2015, and isn’t on its web staff list. Based on those 110 patients, I guess, his company is selling ReCode testing for $1400. At least the diet isn’t that costly or unique, and largely prebiotic/pro-butyrate.
Our community sure knows the shortcomings of “top” journals, institutions, and Western meds. But I wish some docs stuck more with moving the needle within conventional medicine, even with alternative modalities. UCLA put themselves on the line by announcing his 10-person result and giving it some respectability. If there’s real promise, I’d have rather seen Bredersen pursue further work under their roof.
‘Spent a crash catching up on August’s NIH conference and was very impressed. NIH=credibility, deserved or not. Even though many are published, to have our docs up there together talking about their treatments, though limited in success, was an important step especially for building our research base–bigger than CFSAC and critical given its abolishment. I hope momentum is not lost due to a funding nosedive or limited results from NIH’s own small trial.
Thanks. I considered trying Bredesen’s approach but a year later when I contacted them the cost had skyrocketed enormously – and that was simply for them to get hooked up with a doctor. Really disappointing.
billons on research for Alzehmers??A disease that only hits after people have had 3/4 of their life..compared to pennies for Me/CFS , an ilness that often can rob someone of their whoe adult life?
Ethics??Ths IS crazy and WRONG.When will the ME/CFS community..learn? Take a lead from ACT UP/Aids and fight for the right to get a cure!!!!!!!!!!!!!!!!!!!!!!!
Lead the way Mike!
Post comment added from my last above, Issie, Dejurgen, did you have a chance to peruse Dr. Theoharides’ research? I’m very interested in any ideas you might have about it.
If you watch any of his videos he might seem like the mad professor, but he has an impressive list of research articles behind him. (He, on the other hand, has a side business marketing some of his ‘helpful flavonoids’ so conflict of interest might lurk in some of his commentary).
I also have EDS and POTS, I didn’t start getting better until I started treating mast cell issues. I’m a Long timer as to research about the trilogy associated with POTS, EDS and MCAS. I’ve read a whole lot and experimented with much also.
There appears to be a connection to the H3 receptor with Mast cell and a connection to glutamate. The H3 receptor is mostly in the brain, whereas H1 and H2 are peripheral. I’m trying some new approach as to this and don’t want to comment on it yet, as it’s still being tweaked. But there does seem to be connections here and I’m noticing some positive results. But also caused myself a set back as I maybe went to fast with my changes.
Maybe dejurgen will give more technical as I intend to leave that part to him.
I’ll have to look into him and his ideas. I’ll put it on my long 🙁 to do list. But thanks for mentioning him and new ideas.
I long thought I didn’t had any mast cell (like) issues, but when Issie started explaining / recognizing the / my symptoms better I had to think it over. I am far from a “usual mast cell affected suspect”.
One thing I learned though is that in my case seemingly mast cell triggering rates go up very fast with sleep deprivation.
What did you mean with “one symptom, (including cutaneous issues and more), is problems thinking.”? That isn’t clear to me.
Sorry you didn’t understand my comment “one symptom (including cutaneous issues and more) is problems thinking.” Translation; MCADs can exhibit in many different ways which include all the body systems, and in my commentary I am specifically pointing out the problem of thinking i.e. brain fog.
The multifaceted collection of possible MCAD symptoms is very long and here is a primer; https://rawlsmd.com/health-articles/how-to-cope-with-mast-cell-activation-syndrome
A down and dirty test to see if you are prone to MCAS is to lightly scratch your arm with a pen cap (no blood please!), wait a moment and see if you experience dermographica (I think I spelled that correctly). People with hyperactive mast cells usually get quite a reaction.
Also sorry you have such a long ‘want to do’ list. So do I, so I totally understand!
@Nancy, thanks for link. That’s one of the better articles I’ve read on MCAS. Gives a real good description and symptom list.
I don’t think inflammation is the cause of ME/CFS, but I think it cause of PEM to be worse. I’ve been on LDN for 2 years and Celebrex for 3 years. If I’m not on anti-inflammatories, I have terrible headaches and my cognition is much worse. I feel like these anti-inflammatories have given me a part of my life back. I still have to PACE myself to keep the inflammatory cytokines at bay. I would love to see what these new anti-inflammation drugs would do.
I missed seeing you at the Stanford OMF Symposium
I have to try LDN again.
The new anti-inflammatories will certainly be targeting different areas than the past ones – which is a good sign as Montoya has said he thinks the inflammation in ME/CFS is different.
Unfortunately I missed all the conferences this year 🙁
I have so many things to say, I don’t know where to start,..
Couldn’t write anything as I’d become so exhausted over the last few weeks that my brain felt like it was full of burnt out exhaust debris.
Was listening to Jarred Younger again and his finding that CFS brains can have high amounts of lactate in them, which shouldn’t be there. I heard him say in one talk that it was due to the brain being low in oxygen and another because of low glucose.
Anyway this certainly resonates with me.
I was doing well until a few weeks ago when a friend came to stay. That doesn’t happen with me normally – seriously survival first. Anyway I was panicking at how messy the house is etc made things ok enough and was sort of managing.
Went for a relaxing walk on the beach, had a nice cuppa, sitting overlooking the bay – felt fine ?
After a few days my friend went home. I was absolutely wrecked! I don’t have a problem with fibromyalgia or muscle tiredness from walking – it’s my brain that becomes exhausted.
More specifically talking to people in an intense way absolutely wipes me out.
My brain runs out of something – glucose, oxygen? Then it does feel like it’s clogged with something – lactate? I don’t know…
So, I’m currently trying to restore myself. Read about The Blue Mind and am trying to calm myself down by spending time near water. Went to the beach yesterday and to the beautiful old bridge to look at the river today.
Could have actually slept on this morning but had to get up for work. I ‘normally’ wake up at 5am, so I felt it was a positive sign that I’m less wired.
Also I became interested in the dementia studies as my food intolerances would result in my brain not working well.
Fructose in fruit, vegetables, sugar and particularly corn products – modified maize starch being the worst – would repeatedly result in my memory not working and an inability to do maths. I would also feel extremely tired, feel nausea, my mood would flatten and depending on how much I’d eaten – I’d usually need to lie down. I wouldn’t necessarily go to sleep but I would lie totally immobile for hours.
If I did go to sleep, I wouldn’t move so I would often be in pain like pressure areas in contact with the bed/sofa.
My breathing would also become extremely slow and I’d have to consciously breath in and out. One night I think I stopped breathing as I suddenly woke up as I sat bolt upright and took the biggest breath I’ve ever taken.
I would also need to pee a lot and may have become dehydrated.
If I avoided my triggers my brain was ok.
However my situation became worse a few years ago when I became intolerant to many more foods, I also developed gynaecological issues, which resulted in me losing a lot of blood, getting an infection and becoming anemic.
Those issues were sort of resolved but I developed a very bad flu, a very high temperature 41/105, I think, which lasted intensely for 3 weeks but I didn’t ‘get over’ it for at least 3 months.
Since then Feb 2017, my brain is very easily inflamed. I didn’t have these symptoms before this.
So now any foods apart from unprocessed meat, liver, eggs, mackerel, salmon, kale, spinach, black coffee, tea, olive oil, sunflower seeds, Tumeric, Ginger, linseed, hemp and chia seeds, small bit of peanut butter and various vitamins and supplements.
Carbohydrates like grains and I think maybe preservatives have a terrible affect on my brain.
When I’ve set my brain off (the microglia I presume) my brain feels like an electric bar heater that’s turned a dark red.
I can’t remember anything. My online banking number goes. It’s not like it’s just beyond reach and it’ll come back to me. No it won’t – there is a void where it should be
My mental health becomes very unstable, I become very agitated, very extreme, very desperate.
Luckily I have a training in mental health and so I hang on to the notion that these feelings are temporary and though they are real now, they will pass as my brain becomes less inflamed. But still it’s truly horrible.
I’ve settled things down by avoiding the food that triggers this reaction. At the time when this was a huge problem I did find taking Ibuprofen and Antihistamines helped. However I can’t take these now as they make my heartbeat irregular.
My food intolerances lessened when I managed to unhook myself from being so wired and got better, more restorative sleep.
Before that I couldn’t eat the olive oil, seeds or peanut butter. I would get multiple ulcers, like 5, on my tongue and down my throat. My throat would swell up if I ate any of the oils, olive etc. Overnight I was then able to eat the fish, olive oil, seeds etc – one ‘good’ night sleep.
That made a huge difference because before that, I couldn’t eat anything that really gave me energy without there being a reaction. I have a very long list of bizarre and some terrifying symptoms…
I went wrong with Brazil nuts. I was breaking out in sweats, flushing etc and then one day I could feel my tongue react to the Brazil’s. Once I stopped eating them, all those symptoms went
I had been surviving by eating chocolate too but that had put my blood pressure up and affecting my eyes and I developed interstitial cystitis.
So with the improved sleep, I could now eat the oil, seeds and a small bit of peanut butter and give up the chocolate. My blood pressure has gone down. Also my fasting blood sugar was always a small bit raised. I’ve never had a problem with blood sugar before the last few years. Having stopped the Brazil’s my fasting blood sugar has gone down too.
So today I thought to myself, you’re just really tired.
I see my immune system like the ancient Roman army – you really wouldn’t want to take them on. They never miss anything – they’re thorough, organised and a formidable fighting force.
I just wish it would relax a bit!
On the glutamate issue – it’s seen as being a factor in motor neurone disease – exciting the neurones to death apparently…
The good news is that my memory comes back – it’s not gone forever – just temporarily unavailable. I do have a hopeless short term memory and just have to write everything down.
But my brain is working ok now. I can’t think of lots of things at the same time but I can generally function for limited periods, which is workable for the moment.
@Tracey Anne, there is hope for cognitive function. I have been having trouble due to mold exposure and also there is dementia in my family. I’ve had quite the scare in the last few years, but something I’m doing new is bringing me back my brain. Still tweaking…..but very excited about it. It’s like a light switch has been flipped.
“I would get multiple ulcers, like 5, on my tongue and down my throat.”
I have ulcers as a bad food reaction or as a result of “some” immune reaction too. I long thought it was a reaction against partly undigested proteins passing trough a leaky gut. But olive oil causing it too with you challenges that thought. That isn’t high in proteins to start with.
https://en.wikipedia.org/wiki/Aphthous_stomatitis
“Mast cells and macrophages are also involved, secreting TNF-α along with the T cells. When early aphthous ulcers are biopsied, the histologic appearance shows a dense inflammatory infiltrate, 80% of which is made up of T cells.”
But https://en.wikipedia.org/wiki/Basophil are very similar to mast cells and also release histamine, serotonin
“It used to be thought that basophils that have migrated from blood into their resident tissues (connective tissue) are known as mast cells, but this is no longer thought to be the case.”
“They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever.”
“Basophils have protein receptors on their cell surface that bind IgE… …It is the bound IgE antibody that confers a selective response of these cells to environmental substances, for example, pollen proteins or helminth antigens. Recent studies in mice suggest that basophils may also regulate the behavior of T cells and mediate the magnitude of the secondary immune response.”
=> A mast cell reaction may be very hard to distinguish from a Basophil immune reaction; if mast cell drugs would not mediate basophils too then a person having the later but taking mast cell stabilizers could get the negatives of the drug and none of the positives.
Also Neutrophils can release histamine. When Neutrophils undergo NETosis, likely a very common reaction in ME IMO, they “pop” and hence release their histamine. While it resembles less the action of mast cells or basophils, it could be mistaken for them too. That again could lead to mast cell drugs to be ineffective in some cases.
“My mental health becomes very unstable, I become very agitated, very extreme, very desperate.”
Would that resemble the symptoms of https://en.wikipedia.org/wiki/Serotonin_syndrome?
When mast cells and basophills are activated they dump serotonine too.
This that dejurgen is talking about, we think, happened to me with a supplement. I was on all the mast cell medicine and had a reaction that seemed like mast cell. But since I’m experimenting with tweaking glutamate to GABA receptors this particular supplement paradox with me. (Did opposite of intended result.) Then, my friend asked me to look at this and it fit. So then I took a closer look to make sure nothing else I was using upped serotonin too much. It’s a work in progress, but making headway and seeing improvement.
I will say, one of the new things I’m using that helps with brain function helps blood flow and repurfusion issues. This happens when there is faulty blood flow. Each time there is a big rush of blood back to an area that had little, it can cause big issues. This has a combination of herbs that helps keep things more steady and level. And my brain function has greatly improved.
Thanks so much Dejurgen, I’ll look through all of those ideas in both posts – I really appreciate your input!
Thanks Issue,
You and Dejurgen are in my zone!
In the beginning, like 12 years ago, I couldn’t work out what was going on. I did realise that sweet things made me worse but it took me years to figure out the fructose and actually do something about it.
I then lost the dairy and then a few years ago suddenly most food.
I was then ricocheting around until earlier this year, when I focussed on getting better quality sleep.
My mum had fibromyalgia and gut issues and now has dementia. She also has macular degeneration.
When I had my last eye examination a couple of years ago, they found the beginning of macular degeneration in my left eye. I have been referred to the Opthalmologist but waiting lists here in Ireland are long and people wait years for appointments. I am taking Macushield, developed here in Ireland, which apparently may help. I suppose I will be examined with an OCT machine.
I have heard that the health of the macular is an indication of the health of the brain.
Anyway I have checked myself out on a website called foodforthebrain. They have a test and I am still in their green zone and above average for my age (58) according to them!
I think my main problem now isI can do more things – so I am doing more things and that is wearing my brain out.
Actually I remember Dejurgen’s comment now about pushing through. I don’t think it is about pushing through – I think it’s the opposite but that’s not what our culture’s believe.
The problem is I can now see all the things I need to do. The house is not a complete tip but there’s a lot of junk around. I try and do what I can do in 5 minutes!
I shouldn’t give myself a hard time – I know that considering what my life has been like for the past 12 years, I’m actually doing really well but it’s only meI know that.
I think it’s great that Liz found she improved with her migraine medication. Any positive or negative changes give us clues where to look. The positive ones are better though.
Gotta go my alarm went off, it’s 6.16am – time to get up!
Thanks for your thoughts ?
Thanks Issie! The autocorrect will drive me demented. I had a big argument over Nansy the other day – no not Mandy – Nansy – It wouldn’t give up! It”s done it again to you, thankfully I looked – I’ll go and change it now!
No worries, it happened alot over the years. I just ignore it.
Issie with issues…. lol
I was in mold exposure when parent caring for my parents before they died. Both parents had dementia. They are connecting mold to a cause of Alzheimer’s calling it “Inhalation Alzheimer’s “. Mold can cause the brain to swell and atrophy in other places. (It happened to me.) I’ve been in treatment for CIRS and Chronic Lyme and another fungus that causes tumors and clogs blood vessels for about 4 years now on first two and about 7 on fungus. But, I also have POTS and issues with blood and oxygen delivery to the head. So fighting with alot going against me. But still fighting and making improvements.
I would suggest making sure you aren’t in mold or chemical exposure, checking on Lyme disease and reading Dr. Bredsens book, if you haven’t already. We are close to same age. If you think you have a problem, you probably do. The faster you figure the source, the better the results.
The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline https://www.amazon.com/dp/0735216207/ref=cm_sw_r_cp_apa_i_pJnHDbVTJJWE5
This can all be reversed. There have been many people reverse, and/or stop progress of Alzheimer’s. In 2 months time, when I was at a complete crash stage and to now……my brain is back on-line again. Still not where I was. But I’m not as fearful of losing all function. I can research again and it makes sense to me.
So finding cause is very important.
The CIRS docs are now starting to realize that with some of us not responding to treatment as desired, there may be another additional cause other than mold. I fall into that category. Lyme could play a huge part. As could the fungus found by Dr. Stephen Fry. We know it can go into organs as it was found in my thyroid biopsy. He knows it can cause tumors. (We wonder if it plays a part in my brain tumor as another person’s brain tumor it was found in.) Sonpossibly this fungus that forms biofilm (like Lyme does) and can clog up veins could be a strong contender. This is cutting edge research and still in its infancy. But some have eliminated it from their veins with enzymes. I’m on those daily. I also have to thin my blood due to coagulation issues. That can be another factor. Lots of things to look into and sort and all can affect cognitive abilities.
Seriously, a sense of humour is kind of invaluable, isn’t it?
When I feel worse the sense of humour goes and things look very bad…
Smile as big as you possibly can and realize we are finding new things daily. Try to find an hour of joy, even if it’s to only watch a butterfly. 🙂
Science is advancing.
There is HOPE on the horizon.
Yes, I agree with you Issie,
In the last few years I celebrated if I managed to achieve one hour, or so, of vague normality.
I believed that if I could just manage to expand this a little bit and not lose it, I was doing well.
The evening a few months ago when my brain was smouldering and I was in pain, terrified, having dark thoughts I thought – I know I’ll sit in bed and watch something on Netflix and surely I won’t die if I do that.
I knew that what I had eaten had set my brain off, so I just had to sit it out until everything calmed down.
I try out different foods to get energy and I admit I had been eating very tasty ginger biscuits – yes I know – a very bad thing to do.
They were producing very strange, chilled waves through my body. So I thought oat ginger biscuits were better – no not a good idea. So I tried cheese oatcakes or just plain oatcakes.
These obviously very dangerous substances stoked up a furnace in my brain!
Anyway as you can see I survived – no ginger biscuits/oat cakes for me!
I was mulling over Dejurgen’s comment again about pushing through. I think he’s right in the sense of not giving up; keeping on pushing for new breakthroughs.
People are so smart and so courageous on this site I am in awe.
I see it like trying to work out different passwords. However much I get frustrated it just doesn’t work. I have to pay attention to the tiniest details and just keep going.
Someone complimented me on my ability to focus and stay grounded last year. I smiled and thanked them politely, whilst thinking to myself – my exemplary mindfulness is because I am actually unable to think of more than one thing at a time! You’ve gotta laugh ?
This year I managed to have a few pots of flowers and a little flower bed outside my washing up window.
About a month ago I was chopping down the nettles which were taking over and I stopped when I spotted a whole group of small black caterpillars methodically munching their way through individual nettle leaves.
A bit of googling and remembering a comment my neighbour made about nettles being good for butterflies, I left the caterpillar nursery well alone. However I visited it and showed my son, who was fascinated too.
A few days later, it seemed, my little back garden was full of butterflies feeding on the flowers.
I am grateful to have been able to enjoy that moment.
???☀️?
Sometimes, what appears to be weeds to some is life for another. And we can look at our illness that way……maybe we have weeds for now…….what may we learn and be able to help others with. Will there be a rich reward in the end. Like a beautiful butterfly comes from those weeds. Perception and modifying how we look at things is key to keeping on and staying positive.
Regarding Mayo 2013 autopsy study.
Results seem to mirror what pathologist Dr. Alan Macdonald found where plaque was not the problem in itself.
He found tiny worms in some human brains.
Decidedly icky.
But what disease is pretty?
(https://www.prohealth.com/library/lyme-bacteria-hides-inside-parasitic-worms-causing-chronic-brain-diseases-8904)
NeuroInflammation is it. Great article, thank you! M1&M2 Microglial inflammation pathways are triggered from infection or inflammation (or toxins or trauma). Once M1&2 pathways are triggered (depending on your genetic predisposition or maybe the type of trauma) they NEVER get turned off, they can go into surveillance mode and be re-triggered.
What if a developing fetus has brain inflammation, is born healthy and has a re-triggered brain inflammation from vaccines (too heavy a schedule or simply immune system overstimulation-IT’S NOT THE VACCINES, or it is the vaccines and we need to let the immune system work a little and give less vaccines…). They develop ASD from mild social issues to profound mental development disabilities… I felt like I developed mild “ASD”, cognitive changes processing information as an adult, after an episode of brain inflammation. IVIG infusions helped tremendously for me (I found out that I have CLL and low immunoglobulins, and low NKC function-viral issues, so I pushed to get IVIG for my brain inflammation).
Researchers are finally catching on to Neuroinflammation as the cause of a spectrum of mild “mental disorders”, anxiety and depression, to profound life ruining neurological conditions, Alzheimer’s & Parkinson’s, etc. The best solution is prevention, but if we can get better testing (at birth!) & medications to spare those of us with repairable inflammation (damage can be irreversible and/or worsen with each episode, re-trigger, or be reversed!), it could save the next generation.
Random: I had very high TGF-beta 1 levels with an episode of major cognitive dysfunction, brain inflammation, it was normal a few months later-no change cognitively. TGF B1 is a brain inflammation marker that some people produce and some don’t (?), it clears beta amyloid plaques. I may have a little brain damage, or develop a different kind of dementia-I hope not, but I am more likely to not develop Alzheimer’s.
I used research articles and HealthRising articles to figure out what was happening to me because I knew it wasn’t “Chronic Fatigue”, or “Chronic Lyme Disease”. I was treated with high dose Doxycycline for two months and it helped the migrating joint pain, I feel that I was treated sufficiently for the Lyme, but the Doxy also helped my cognitive issues… This all makes logical sense now. Crowd sourcing healthcare. Thank you again.