My e-book “Tracing Chronic Fatigue Syndrome to mtDNA” will be free Wednesday and Thursday on Amazon

[aquariusgirl]

Got it. J1c2 here.
14798T/C ..what’s the gene?

 

[wigglethemouse]

Thank you @BeautifulDay for making the book free to download. Took me three days to read, a little bit at a time, and I thoroughly enjoyed it. Fascinating. Need to read a few more times for it to really sink in (brain fog).

It's an interesting theory you present, that J1c's and U5's have reduced OXHPOS capacity resulting in increased susceptibility to getting ME/CFS.

It makes me wonder if genes that result in exercise intolerance, likewise lead to an increased susceptibility to getting ME/CFS. Perhaps this could account for some paternal lines of ME/CFS.....

I also got some clarity of genetic testing from the book. i.e. the quality of the testing is very important, and interpretation is very difficult and prone to errors. You probably need multiple testing from different sources to properly validate findings. I saw this in a very limited way with analysis of my 23andme data which called out false data.

I was secretly hoping to be a J1c and get some "answers", but according to 23andme my maternal Haplogroup is an "I". So long living, northern climate ancestry, like a J1C, but not susceptible to accelerated AIDS progression as they are.

One observation I had. You mention Gulf War a few times. Nancy Klimas has stated in a few videos that clinically she cannot tell GWI and ME apart, but metabolically they are opposite with GWI exhibiting hyper-metabolism. Any idea why if they probably also have mitochondrial dysfunction they exhibit hyper instead of hypo metabolism?

I wish geneticists were more available to rule out, or advise on, mitochondrial disease in our patient population. Most seem to operate in pediatric clinics as that is where mitochondrial disease is most obvious. Adult onset is very difficult to detect.

Thanks again!

 

[wigglethemouse]

14798T/C ..what’s the gene?

I believe it is the CYB gene
https://ghr.nlm.nih.gov/gene/MT-CYB#

 

[nandixon]

There's a poll here which is still active and which could potentially be helpful if people would continue to participate:

https://forums.phoenixrising.me/ind...ossible-indicator-for-me-cfs-phenotype.36870/

I made it a few years ago to try to determine whether one maternal haplogroup versus another was more likely to experience increased energy impairment with ME/CFS.

Although not a scientific poll, it's set up in such a way that if the idea that @BeautifulDay presents in her book is correct regarding there being a genetic component to ME/CFS, then it should eventually show up in that poll. Right now the poll is favoring her idea but too few people have participated so far to draw any conclusions.

 

[wigglethemouse]

There's a poll here which is still active and which could potentially be helpful if people would continue to participate:

Done thanks.

 

[BeautifulDay]

Thank you @BeautifulDay for making the book free to download. Took me three days to read, a little bit at a time, and I thoroughly enjoyed it. Fascinating. Need to read a few more times for it to really sink in (brain fog).
.....
One observation I had. You mention Gulf War a few times. Nancy Klimas has stated in a few videos that clinically she cannot tell GWI and ME apart, but metabolically they are opposite with GWI exhibiting hyper-metabolism. Any idea why if they probably also have mitochondrial dysfunction they exhibit hyper instead of hypo metabolism?

I'm putting "watching Nancy Klimas videos" on my "to do list". Especially, watching for the mention of hyper-metabolism.

Hypometabolism and hypermetabolism can happen in the same person in different organs, body systems, and chemicals with regard to different processes. The hypometabolism mentioned in the book, was the overall hypometabolism often experienced with low overall energy (energy conservation mode). However, our bodies are constantly trying to overcome any perceived extremes and fix them (both over and unders). Overshooting the fix can happen.

I have hypoglycemia whereas my mother eats like a bird and has diabetes type 2. Yet, we have the same mtDNA variants. Both opposing symptoms can be due to mitochondrial dysfunction. Here the UMDF lists both hypoglycemia and diabetes as symptoms of mitochondrial disease. https://www.umdf.org/what-is-mitochondrial-disease/possible-symptoms/
Article: "Hyperglycemia / hypoglycemia-induced mitochondrial dysfunction and cerebral ischemic damage in diabetics". https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199931/

The article "Defining Chemical Injury: A Diagnostic Protocol and Profile of Chemically Injured Civilians, Industrial Workers and Gulf War" can be dowloaded at this link (use safe mode):
http://www.oldbluewater.com/illness/Defining chemical injury - 2 08 06.doc
From that article: "EEG abnormalities may be asymmetrical after chemical exposure, which can cause slowing, dysrhythmia, and also occasionally seizure activity. Long-term effects were first described by Duffy et al. in 1979. If seizure activity is suspected, an EEG together with PET scanning is the optimal approach. The senior author has found hypermetabolism, raising the suggestion of seizure activity, in the deep subcortical (e.g. amygdala) areas of the brain after chemical exposure [Heuser, 1999; Heuser and Wu, 1999, 2000]."

Therefore, until I watch the Nancy Klimas videos, it's hard to tell if she is looking at a specific body part/function/chemical like these above researchers. That could explain the difference in the use of hypometabolism vs hypermetabolism.

The Department of Veterans Affairs has been heavily researching the link of mitochondrial dysfunction and Gulf War Illness. Here is an example from 2015. https://www.research.va.gov/pubs/docs/GulfWar-AnnualSummary2015.pdf
I especially like that they are investing in these projects. The quotes below are from this above linked document. The additional link below each (additional information) is a link to updated information since 2015.

"*DoD-245, “Biomarkers and Brain Mechanisms of Gulf War Illness” will use a multimodal
approach, including advanced brain scanning techniques like MRI (magnetic resonance
imaging), to examine neuroinflammation, oxidative stress, and mitochondrial dysfunction in
the brains of 20 patients with Gulf War illness. Investigators will also compare metabolic
data from cerebral spinal fluid between ill GW patients and controls to elucidate underlying
pathophysiology in GWI."
Additional information: https://apps.dtic.mil/docs/citations/AD1034289 and
https://apps.dtic.mil/dtic/tr/fulltext/u2/1044623.pdf

"*DoD-251, “Muscle Mitochondrial Assessments in Gulf War Illness” will investigate the
character of mitochondrial impairments in symptomatic Gulf War Veterans to better
understand the pathobiology of GWI and to identify objective signatures of GWI that may
aid diagnosis. Muscle biopsies from 27 symptomatic Veterans and the same number of
matched controls will be examined for mitochondrial appearance (density, elongation,
networks, cristae patterning) and function (energy production), plus oxidative stress
measures."
Additional information: https://www.golombresearchgroup.org/participateinourresearch/#musclebx

"*DoD-260, “Extending Benefits of Q10: Mitochondrial Cocktail for Gulf War Illness” aims to secure preliminary information to support that a full trial of this mitochondrial cocktail is justified in GWI and to develop the critical information to ensure a successful large-scale trial, e.g., to select outcomes, duration, and sample size. Thirty-two symptomatic ill GW Veterans will be randomly allocated to either a mitochondrial cocktail with individualized treatment (for impaired bioenergetics) or a sham treatment in identical capsules."
Additional information: https://clinicaltrials.gov/ct2/show/NCT02865460

Other Department of Defense Projects include(d):

DoD-179 Mechanisms of Mitochondrial Defects in Gulf War Syndrome
Additional information: https://clinicaltrials.gov/ct2/show/NCT01264471

DoD-239 Mitochondrial and Nuclear Genetics in Gulf War Illness
Additional information: https://www.golombresearchgroup.org/mitohaplo/

There are many other studies and related projects ongoing under the DOD. They are taking the mitochondrial dysfunction in GWI very seriously. Their findings are likely to impact (further) ME/CFS research, treatments, etc....

 

[BeautifulDay]

It makes me wonder if genes that result in exercise intolerance, likewise lead to an increased susceptibility to getting ME/CFS. Perhaps this could account for some paternal lines of ME/CFS.....

Yes, I agree. It would be very interesting to find out if any of the ME/CFS patients on this board (or elsewhere) have any of the exercise intolerance variants listed in Chapter 24.

 

[BeautifulDay]

I wish geneticists were more available to rule out, or advise on, mitochondrial disease in our patient population. Most seem to operate in pediatric clinics as that is where mitochondrial disease is most obvious. Adult onset is very difficult to detect.

I agree. The more the mitochondrial experts know, the wider spectrum of patients they will need to take on.

Early on, the mitochondrial experts focused on the children who were on life support from day one. It was easiest to identify this population and of course, these children rightly were in need of their immediate attention.

Due to this early focus, Children's Hospitals are more likely to have the mito experts. Some of these experts now see both children and adults (but not many do). Some mito experts only will see patients with a certain disease (such as Leigh's). Thankfully, as the word gets out that a broad spectrum of diseases (not just childhood diseases) are impacted by mitochondrial dysfunction, more medical schools are staffing up for the need in this field.

I've been watching a few University Hospitals exploring and gearing up for the future demand. The one's that invest now will be ahead of the curve.

 

[BeautifulDay]

There's a poll here which is still active and which could potentially be helpful if people would continue to participate:

https://forums.phoenixrising.me/ind...ossible-indicator-for-me-cfs-phenotype.36870/

I made it a few years ago to try to determine whether one maternal haplogroup versus another was more likely to experience increased energy impairment with ME/CFS.

Although not a scientific poll, it's set up in such a way that if the idea that @BeautifulDay presents in her book is correct regarding there being a genetic component to ME/CFS, then it should eventually show up in that poll. Right now the poll is favoring her idea but too few people have participated so far to draw any conclusions.

Thanks @nandixon

Right now your poll has J's with fatigue at 14-16% of the participants. That is more than the frequency of J's in the general population. The most telling portion of the population for having a genetic component will be found in the patients with multiple cases of ME/CFS in family members. Patients with ME/CFS with mtDNA known to cause mitochondrial dysfunction are the easier cases to locate.

From Chapter 46:
"This is just the beginning. In my study, I picked the easy to grab low hanging fruit. It’s easier to identify the mitochondrial link when you are looking at patients with multiple relatives with the disease. For most ME/CFS patients, the cause is significantly more complex and can include mitochondrial DNA variants, nuclear DNA variants, and environmental stressors (such as mononucleosis, Lyme Disease, and chemical exposure).

There is a threshold of mitochondrial dysfunction that must be reached before ME/CFS symptoms appear. While finding the exact combination of culprits behind anyone’s mitochondrial dysfunction is difficult, what is closer at hand is the link between ME/CFS+ and hypometabolism, metabolomics, and the potential ME/CFS diagnostic tests and treatments.

Many health conditions, including Multiple Sclerosis, Fibromyalgia, and Autistic Spectrum Disorder, can be viewed in a similar light to ME/CFS with studies linking them to mitochondrial dysfunction."

 

[wigglethemouse]

I'm putting "watching Nancy Klimas videos" on my "to do list". Especially, watching for the mention of hyper-metabolism.

You may enjoy this Nancy Klimas Powerpoint from Aug 2017 on GWI
https://www.va.gov/RAC-GWVI/meetings/aug2017/KlimasAUG2017.pdf

FYI - she is the one doing the COQ10 study you described

 

[wigglethemouse]

It would be very interesting to find out if any of the ME/CFS patients on this board (or elsewhere) have any of the exercise intolerance variants listed in Chapter 24.

Do you know if there is a list for non-mtDNA variants that cause exercise intolerance? That might be very useful for researchers as well. For example AMPD1 deficiency is very common

People who do have symptoms typically have muscle pain (myalgia), cramping, and weakness after exercise, and often get tired faster than others. Some affected people appear to have more severe symptoms. AMPD1 deficiency is caused by changes (mutations) in the AMPD1 gene and is inherited in an autosomal recessive manner.

Link : https://rarediseases.info.nih.gov/diseases/547/adenosine-monophosphate-deaminase-1-deficiency

Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).

Link : https://www.omim.org/entry/615511

1.8% seems like a rather large number to me.

 

[BeautifulDay]

You may enjoy this Nancy Klimas Powerpoint from Aug 2017 on GWI
https://www.va.gov/RAC-GWVI/meetings/aug2017/KlimasAUG2017.pdf

FYI - she is the one doing the COQ10 study you described

Thank you @wigglethemouse

I found Nancy Klimas’ Powerpoint from Aug 2017 on Gulf War Illness to be excellent. It covers many of my questions regarding the COQ10 study.

Trials with both ubiquinol and ubiquinone. Check mark.
Softgels (avoids compromising the potency). Check mark.
Trials with morning dosing and split dosing. Check mark.
And on and on…… Check, check, check.

I had not known that ubiquinol had a second peak. Fascinating.
“Time to peak, serum: 5-10 hours first peak; 24 hours. Second peak (enterohepatic recirculation)”

Again thank you @wigglethemouse . Outstanding!!!

 

[BeautifulDay]

Do you know if there is a list for non-mtDNA variants that cause exercise intolerance? That might be very useful for researchers as well. For example AMPD1 deficiency is very common

Link : https://rarediseases.info.nih.gov/diseases/547/adenosine-monophosphate-deaminase-1-deficiency

Link : https://www.omim.org/entry/615511

1.8% seems like a rather large number to me.

I do not know of a list for non-mtDNA variants that cause exercise intolerance. There are many variants that should be on the list including:
Cav3: http://discovery.ucl.ac.uk/1496854/
ISCU: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=43115
ETFA, ETFB, and ETFDH: http://n.neurology.org/content/neurology/91/4/187.full.pdf
PYGM: https://www.ncbi.nlm.nih.gov/pubmed/26465709
SLC25A32: https://www.omim.org/entry/616839

Combining the fact that the mito experts at MSeqDr are currently watching 1,570 nuclear genes with the fact that a key symptom of mitochondrial dysfunction is often exercise intolerance, the number of genes that could potentially impact exercise intolerance is likely to be very high.

In this recent article from the Journal of Applied Genetics titled "Nuclear genes involved in mitochondrial diseases caused by instability of mitochondrial DNA", the authors state that:
"nDNA encodes not only respiratory chain subunits but also all the proteins responsible for mtDNA maintenance, especially those involved in replication, as well as other proteins necessary for the transcription and copy number control of this multicopy genome. Mutations in these genes can cause secondary instability of the mitochondrial genome in the form of depletion (decreased number of mtDNA molecules in the cell), vast multiple deletions or accumulation of point mutations which in turn leads to mitochondrial diseases inherited in a Mendelian fashion. The list of genes involved in mitochondrial DNA maintenance is long, and still incomplete."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799321/

 

[wigglethemouse]

Combining the fact that the mito experts at MSeqDr are currently watching 1,570 nuclear genes with the fact that a key symptom of mitochondrial dysfunction is often exercise intolerance, the number of genes that could potentially impact exercise intolerance is likely to be very high.

Ahhhhhhhhh ...... this is where studying families with multiple affected is really powerful to narrow down possible genetic variant influences on disease.

 

[wigglethemouse]

@BeautifulDay This is timely. I wonder if they read your book?

Bateman Horne Center
Please join us for our free live stream event, tomorrow Weds. Dec. 5th 6pm MST. Mutations in Energy and Autoimmune Genes Cooperate to Cause ME/CFS" with Alan Light, PhD. New findings suggest that multiple mitochondrial mutations create susceptibility for ME/CFS. Watch the event from our Facebook page. Q&A to follow.

https://www.facebook.com/search/top/?q=bateman horne center&epa=SEARCH_BOX

 

[BeautifulDay]

Thank you @wigglethemouse

That truly is very timely. “New findings suggest that multiple mitochondrial mutations create susceptibility for ME/CFS.” That is also what I found in the families with a strong history of multiple cases of ME/CFS. Specifically, families with the most cases of ME/CFS in close relatives came from two maternal haplogroup subclades (haplotypes). These two subclades were also mentioned in multiple medical journal studies that found individuals in these subclades had a significantly increased risk of several diseases due to the combination of the mitochondrial variants causing mitochondrial dysfunction.

It will be very interesting if Alan Light, PhD. has proof from a study of the general population of ME/CFS patients (not just those with a family history of ME/CFS) that there is an increased frequency of deleterious mitochondrial mutations in patients with ME/CFS. I look forward to the details.

I’m not sure if others have this, but I have a 2-3 hour window every evening where I have to sleep. If I’m woken up during that period of time, I feel like I’m at death’s door and everything pains (even the sheet) and my mind is nonsensical. That window right now falls during his livestream. It’s highly unlikely that I’ll be able to catch it live.
When I wake, I’ll be excited to read on PR what he had to say and if there is a link to the video.

 

[wigglethemouse]

It will be very interesting if Alan Light, PhD. has proof from a study of the general population of ME/CFS patients (not just those with a family history of ME/CFS) that there is an increased frequency of deleterious mitochondrial mutations in patients with ME/CFS. I look forward to the details.

Yes he did. I created a new thread for the talk
Link : https://forums.phoenixrising.me/ind...te-to-cause-me-cfs-with-alan-light-phd.62439/

 

[BeautifulDay]

I've gotten several notes from people stating that they missed the free days for my book on Amazon. For anyone who missed it, my book will be free this Saturday, December 15, 2018 on Amazon.