Finding my problem with AI - BARD and ChatGPT and CFS/ME

[Pgrovetom]

I was diagnosed with CFS by Stanford's Dr Montoya many years ago. My symptom set was unique as it is with almost anyone. I've been to Stanford many times, Mayo Clinic, UCSF and John Hopkins in trying to track down the cause. It was all a bust. I have never encountered a doctor willing to give more than 45 minutes to my problem. I have never seen a doctor willing to discuss underlying medical causes that I have researched.

I have written here about things I've discovered, some helped a little but most it turns out were chasing secondary problems that flow from my one central problem. I have read 100's of medical research papers along the way trying to understand possibilities while slowly gaining some understanding of human biology. We are essentially a sack of salt water with groups of specialized cells in the trillions mostly floating in it all communicating for the common good via some sort of communication receptor on their outside interface to that salt water. Various messenger chemicals get distributed mostly via the blood and float along until they find their receptor pair.

In this In reading of many medical papers they would never answer my so closely related questions around my symptoms or test results meaning. Of course they wouldn't as the research typically was exploring one biological issue closely related to my questions but I was always left knowing more, getting closer but frustrated I couldn't just speak with the authors. In the mean time I had given up on doctors as "only technicians" and not engineers or scientists that have curiosity. My symptoms worsened while I slept. I discovered by desperation that a little caffeine before bed and around 3AM stopped the horrific symptoms. My CFS was due to a sleep issue. Two Stanford sleep studies showed nothing.

About 6 years ago a cardiologist made an interesting comment to me while investigating heart related issues. Basically my heart was ok but he made the comment that my problem seemed "metabolic" in nature. Well it turns out he was correct in a few ways.

Then UCSF discovered that my leg muscles had about 15% of the mitochondria had a 6kb deletion. That's very bad since the 3rd step in the electron chain was shut off. But alas I had 85% working making ATP and doing other good things. Suspicious! Turns out that mitochondria make ATP and ATP is broken down to cAMP ( cyclic adenosine mono phosphate) which is the substrate for a critical pathway.

Then a UCSF muscle neurologist made a comment that caffeine is a complex molecule that had other profound effects. I then learned that my heart rate was dropping below 40 while sleeping and the low Oxygen while sleeping due to slow heart and saturation in the low 90% range were setting this in motion. So I was able to prove this and I got a cardiac pacemaker and the symptoms stopped. Then after about 4 months they started coming back. The human body biology is quite adaptable. What the pacemaker fixed, it adapted back and it came back but not quite as bad. At first adding O2 while I slept helped.

I studied what caffeine does and followed up on its function as a PED. A PED ( Viagra is a PED) breaks down another molecule called cyclic AMP (cAMP). Cyclic AMP in turns regulates everything from metabolism to the immune system via another molecule called PKA which activates various genes in the nucleus. This varyies from cell type to cell type. . Caffeine is a general as opposed to specific PED and by interfering with cAMP. This about where Google BARD and CHATGPT come in. I now knew enough about the pathway from papers but could ask meaningful questions of the AI tools from Google BARD and OpenAI/MS CHATGP. Very specific questions. I had begun to suspect a chronically low cAMP might be my problem.

So I asked one at a time about my symptoms. I have very high IgE ( allergies), low T and B cells and IgG subclasses and total. So asked BARD how the cAMP pathway could effect the immune system. The answer described all of these and why. Interesting. Low cAMP slows the heart especially at night. I asked it about constipation and blood circulation and it said those are both smooth muscle and it would make them contract - constipation and low blood flow. It also said It causes a parasympathetic dominance - slow intestines. That explained the muscle pain while sleeping and intestinal problems. I asked more but the most important question was why this would happen and are there any drugs to artificially increase cAMP. It gave me the answers. I won't tell you the "why" right now but the drug was Forskolin. It comes from a plant and can be bought on Amazon. So what the hell, the doctors are mostly brain dead, I bought it and took it. It eliminated most of my symptoms like magic. That's not the end since I'm now trying to eliminate the cause which is due to adaption as I thought and will take months. It was a drug causing the problem. Not on doctors questioned. But medical papers combined with my suspicions, the caffeine link and Artificial Intelligence ( both BARD and ChatGPT) combined did the trick.

So I would strongly recommend anyone who is searching the medical papers and looking for answers, once you know the right questions, try Goog BARD and Open AI's ChatGPT to get the last little details. You need to know what to ask but if you do, its the bridge after the medical papers.

Good Luck

 

[ChristianBonanno]

I’ll have a lot to talk about with you after this comment clears moderation. I’ve discovered something almost completely similar in myself.

 

[Pgrovetom]

Love to hear it

 

[ChristianBonanno]

I want to preface this with that it is not really cAMP that is the fundamental issue, but a low ATP:ADP ratio (meaning the mitochondria has more ADP than ATP. This leads to low cAMP.

(I also think that people ME/CFS have high GTP but I am still working on that. So a person with ME/CFS will have high ADP and GTP)

I will be using the norepinepherine receptor as an example.

First a diagram:

You can see how ATP is needed to make cAMP (via Adenylate cyclase) which needs magneisum as a cofactor.

(For simplicty we will forget about soluble Adenylyl Cyclase (sAC) and its role in making cAMP)

So, Adenylyl Cyclase (AC) uses ATP when a receptor is triggered by Norepinepherine (that green squiggly line on the left is the norepinepherine receptor).

The result is we make cAMP, and the cAMP triggers PKA which all go on to increase gene expression that increases our blood pressure. Note that most people with ME/CFS complin of hypotension. So it is obvious that even when there is norepinephrine available, if there is not enough cAMP, then we will not get vasocontriction and they will have POTS.

So what can we do?

Taking SNRI's will only help for a littel while. Nor NorEpi will mean habituation and then you will need to take more SNRI's.

Note that PDE enzymes, like PDE4B (which use zinc as a cofactor) and will metabolize (lower) cAMP. So a specific PDE Inhibitor (4, 7 or 8) might help. But I do not like drugs becasue I do not think they solve the underlying issue and it will also mean lower AMP, so, what else. We can lower our zinc intake, but there are problems with that becasue zinc will also lower cGMP and I will get to why that is a problem another day.

We can take Forskolin which will increase Adenylyl Cyclase activit,y buit if we are low in ATP this will work fro a short while.

So what else can we do??? Let's look at how we recycle AMP back into ATP.

The first step is turning AMP into ADP via Adenylate kinase. Nothing to do there since it only relies on a source of AMP. And this prbably means people with ME./CFS have a lot of ADP.

So the next step is using Creatine kinase. But since this enzyme is bidirectional, to turn ADP into ATP we need Creatine Phospahte (Phosphocreatine) which is creatine with a phosphate added to it. (Taking Creatine will make thins worse by lowering ATP.)

And I think this is the choke point, but the answer is in this next diagram. In order to increase Pcr we need to stimulate glycolosis!

So what stimulates glycolosis?

Magneisum!

Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency

The paramount importance of magnesium in the glycolytic pathway [53] and mitochondrial synthesis of ATP [54] has been known for a long time. Many of the glycolytic enzymes are sensitive to magnesium, whose principal function is to facilitate the transfer of high energy phosphate. Thus, hexokinase, phosphofructokinase, phosphoglycerate kinase, and pyruvate kinase work in this manner, while aldolase and enolase require Mg2+ for their stability and activity [53].

What else? Insulin! Do people with ME/CFS have lower insulin? No, but they do have insulin resistance!

So to me the first thing anyone with ME/CFS should figure out is what is casuing the insulin resistance.

So lets look at "Gene could help explain insulin resistance" They found an enzyme NAT1 that are deficient in NAT1 had insulin resitance. NAT1 participates in the detoxification of a plethora of hydrazine and arylamine drugs. So taking these drugs casues insulin resistance.

Arylamines are Aromatic amines.

What are aromatic amines?

Aromatic amines are byproducts of manufacturing plastics, industrial chemicals and other products. They can be divided into three categories and have been classified as known, probable, and possible human carcinogens by the International Agency for Research on Cancer (IARC).

Aromatic amines are found in industries such as iron, steel, dyes, pharmaceuticals, oil refining, personal household services, textile manufacturing, leather manufacturing, and rubber.[4],[5] They are also found in tobacco smoke, well-cooked meat, hair dye and diesel exhaust and can be produced by burning wood chips.[6],[7]

Wow, so pollution can casue insulin resistance AND ME/CFS! Yes, air pollutuion casues insulin resistance!

But NAT1 also needs acetyl-CoA as a substrate, and this is where we source Acetyl-CoA:

From Fatty Acid Oxidation
From Pyruvate, the end product of Glycolosis, via PDC (needs Thiamine, Lipoic Acid, B2, adn NAD)
From Citrate via ACL (ACLY) which needs Magnesium.
And from Ketones.

So magnesium seems really importnat in ME/CFS as a way to increase ATP, as does limiting your exposure to NAT1 adn NAT2 inhibiting pollutants and medications.

The sugar cravings that ME/CFS patienst experience are only exacerbaitng the problem since this will increase insulin resistance. How each person figues this out will be personal depending on their current weight and genetics, but thsi I feel this at the core of ME/CFS.

 

[Pgrovetom]

"I want to preface this with that it is not really cAMP that is the fundamental issue, but a low ATP:ADP ratio (meaning the mitochondria has more ADP than ATP. This leads to low cAMP."

"We can take Forskolin which will increase Adenylyl Cyclase activit,y buit if we are low in ATP this will work fro a short while."

First, I'll comment that Forskolin almost completely resolved my symptoms for 6 about months or so. When it gradually stopped working I was bummed. I had previously had success with both caffeine and even better with 400mg of extended release Theophylline presumably due to its being a PDEI4 which prevented PDE from breaking cAMP down. So both had artificially help cAMP up.

But its quite true that cAMP must be produced from ATP which is mostly produced by the mitochondria from pyruvate ( derived from - carbohydrates, fats, and protein) and oxygen ( with lots of help) in oxidative phosphorylation (OXPHOS).

Preventing cAMP breakdown with a PDEI4 or activating AC doesn't help if the ATP is very low. ATP is created inside the mitochondria via the KREBs (Citric Acid) cycle which creates NADH which is the main electron donor for the Electron Transport Chain electron pump along with FADH. The KREBs cycle and Electron Transport Chain (ETC) are considered the core of life since they produce all the ATP derived energy used for many purposes. After the ATP ( "T" =3 phosphate groups) is used ( the energy taken from the 3rd phosphate group added by the last complex IV of the ETC via proton gradient flow) it becomes ADP and then is recycled back to ATP.

But recycling and production of ADP to ATP requires the mitochondrial KREBs cycle and ETC to be working smoothly. They have lots of of things that can go wrong. For example: 15% of my thigh muscle mitochondria DNA ( mtDNA) have 11 genes missing also known as a 6.3kb deletion. Obviously that 15% cannot produce ATP. But that was 7 years ago. Whats going on now and in my brain????

I'm working on increasing NADH artificially but its tricky. If you just swallow NADH, NAD+ or most NADH based supplements, they partly are destroyed by your gut and then cannot penetrate the mitochondria. Their electrons can be used via some skinny alternative paths utilized by some NADH produced outside the KREBs cycle. But increasing NADH this way is difficult. Possibly the best way is too help the NAD salvage pathway to reduce mito NAD loss by improving recycling what gets inside the mito.

My thinking is effectively increasing NADH inside the mito eliminates the KREBs cycle and tests the ETC by providing it with plenty of electrons for ATP production. I'm also assisting the ETC with CoQ10, B-Complex, and L-Carnitine. We will see if this helps. Since ATP is used as energy for numerous body functions, low ATP would not only cause fatigue but could result in a wide range of issues as many biochemical reactions required are either inhibited or occur at a reduced rate.

Unfortunately there is no easy way to just measure ATP as each cell of trillions creates its own from its mitochondria and uses it intercellular. So its difficult to know if your mitochondria are producing adequate ATP. Each cell can have from hundreds to hundreds to thousands ( muscle and brain) hundreds of thousand ( mothers egg) mitochondria so ATP production is massively redundant. If only 50% of a cells mitochondria are working properly, you can live.

But if all the biochemical prerequisites of functional mitochondria are not working properly, each cell type in the body will begin to misbehave or fail at a different level. Its easy the understand how an oddball biochemical bottleneck could turn down the ATP production of all mitochondria which is different than just have say 15% bad mitochondria. So where is the bottleneck if there is one? Providing an increase in NADH bypasses a lot of possible bottlenecks by going around the KREBs cycle.

NADH, once inside the mitochondria donates an electron to the complex I which starts the electron (-) pumping or proton (+) gradient buildup. Losing the electron turns it in NAD+. That proton gradient buildup leads to complex IV proton flow ( to equalize (+) proton gradient) that creates ATP. So I hypothesize that finding a successful method of increasing NADH inside the mitochondria via the salvage pathway enhancement plus assisting the ETC with extra CoQ10, Vitamin B's, L-Carnitine ( mito cocktail) and maybe a few other supplements as secondary support, will test the ETC portion of the mitochondria and eliminate most of the other biochemical bottleneck possibilities. If that makes sense.

More later on how to enhance the NAD salvage pathway. Here is a decent overview of how the salvage pathway fits into the NAD picture. This lady has a PhD so does know what she is talking about.

 

[ChristianBonanno]

First, I'll comment that Forskolin almost completely resolved my symptoms for 6 about months or so. When it gradually stopped working I was bummed.

Yes! That is what predicted. So it is clear you are not making enough ATP.

For example: 15% of my thigh muscle mitochondria DNA ( mtDNA) have 11 genes missing also known as a 6.3kb deletion.

How did you find that out? I know I have many polymorphism on Complex I (ND4L, ND1, ND4) and III (MT-CYB) that were not helping me but I thing B2 fixes those issues for me.

I have Sami heritage, they are like the Inuit of Finland, and changing my diet to reflect that helped me sooo much.

If you want to make NAD you need B2 and B6 since they are needed to make it from tryptophan.

B2 helped me so much with my fatigue and brain fog as B6 helps me with other things.

You might also want to look at your FADS SNPs and see if you need long chain PUFAs, especially Omega 3 since it is crucial for the mitochondria.

If you do not mind I would be interested to hear in some of your more odd symptoms.

Also, I wrote this today:

The Genetic Cause of my Chronic Illness

I did not know where else to put this, because it is not really (yet) a recovery story, but kind of is since I am med free but fro an occasional Klonopin but I still have extreme sensitivities. Many of you would have known me here as "Croatoan" back in 2016 when I vanished to just focus on my...

www.healthrising.org

 

[Pgrovetom]

For example: 15% of my thigh muscle mitochondria DNA ( mtDNA) have 11 genes missing also known as a 6.3kb deletion.

How did you find that out?

In 2017 I had a muscle biopsy off my right thigh. The sample was sent to UCSF pathology who used staining techniques and a microscope to describe my anomalies. They did mention a mitochondrial problem may be the cause and nothing more. They then put my sample in the deep freeze at UCSF.

Later I was seeing a UCSF geneticist who did an Exome which looked ok. He went to Kaiser and was replaced by the head of UCSF Genetics. She suggested a blood mitochondrial sequencing. It came back with some small issues but couldn't explain my problems. Since the immune cells they actually sequence from your blood are fairly recently derived from stem cells, they don't really represent older cells like your muscles or brain. If one has an acquired problem, it probably won't show up in a blood mtDNA test. So I told the UCSF doctor about my biopsy of my thigh that might be in their freezer. She was great. She found it and sent it to the same lab. The lab confirmed both the blood and freezer thigh muscle sample were from the same individual - me. Here are some cut outs of the report:

Gene Summary:
Mitochondrial DNA (mtDNA) deletion syndromes are characterized by the presence of single large-scale deletion of the mitochondrial genome with differing levels of heteroplasmy across tissues. These syndromes predominately consist of three
overlapping phenotypes that usually occur in a single individual in a family (Goldstein et al., 2019). The three phenotypes are Pearson syndrome, Kearns-Sayre syndrome (KSS), and progressive external ophthalmoplegia (PEO). Pearson syndrome is characterized by sideroblastic anemia and exocrine pancreas dysfunction and may be fatal in infancy; children who survive the disease typically develop neurological symptoms and KSS. Deletions associated with Pearson syndrome are usually more abundant in blood than in other tissue types; the deletion load gradually decreases in blood and increases in muscle as the phenotype evolves from Pearson syndrome to KSS and PEO. KSS typically presents before 20 years of age and consists of a triad of symptoms: 1) pigmentary retinopathy 2) PEO 3) cardiac conduction abnormality. Deletions associated with KSS can be present in all tissues, but are most abundant in muscle. PEO symptoms include ptosis, ophthalmoplegia, and variably severe proximal limb weakness that may be the early sign of KSS in younger individuals. Deletions associated with PEO are confined to skeletal muscle. The majority of individuals with an mtDNA deletion syndromes have a heteroplasmy level of 15% or greater. However several individuals with heteroplasmy levels lower than 15% have been reported to have a disease phenotype (Grady et al., 2014). Mitochondrial DNA deletion thresholds are not well-defined in skeletal muscle, and skeletal muscle may be mosaic for different levels of heteroplasmy of a mtDNA variant (Schroder et al., 2000; Grady et al., 2014). In most cases, single large-scale mtDNA deletions arise de novo (Chinnery et al., 2004). The presence of multiple large deletions of the mitochondrial genome in muscle can be observed in individuals with a multiple mtDNA deletion syndrome. This group of disorders are caused by pathogenic variant(s) in nuclear genes that are involved in mtDNA biogenesis and maintenance and are commonly associated with autosomal dominant or autosomal recessive PEO.

m.9422_15695del6274 in the mitochondrial genome (NC_012920.1) Heteroplasmic 6.3 kb deletion including m.9422_15695 encompassing the following genes:* MT CO3, MT-TG, MT-ND3, MT-TR, MT-ND4L, MT-ND4, MT-TH, MT-TS2, MT-TL2, MT ND5, MT-ND6, MT-TE and MT-CYB of the mitochondrial genome was identified Majority of individuals with a mitochondrial disorders associated with mtDNA deletions have a heteroplasmy level of 15% or greater (Schroder et al., 2000; Grady et al., 2014). However, several individuals with heteroplasmy levels lower than 15% have been reported to have a disease phenotype (Grady et al., 2014) Mitochondrial DNA variant thresholds are not well-defined in skeletal muscle, and skeletal muscle may be mosaic for different levels of heteroplasmy of a mtDNA variant (Schroder et al., 2000)
We interpret this as a Pathogenic Variant.

This was 2017 but its been 7 years so who knows if the deletion heterplasmy has increased. Hoping to convince someboy to do a needle biopsy and check again. We will see.

 

[ChristianBonanno]

This was 2017 but its been 7 years so who knows if the deletion heterplasmy has increased. Hoping to convince someboy to do a needle biopsy and check again. We will see.

I am still trying to understand heteroplasmy but I think I get it. So are we thinking that the Deletion is responsible for excess oxidative stress which increases Heteroplasmy? If so I have a lot to say about that as well. Oxidative Stress was my first specialty.

 

[Pgrovetom]

I am still trying to understand heteroplasmy but I think I get it. So are we thinking that the Deletion is responsible for excess oxidative stress which increases Heteroplasmy? If so I have a lot to say about that as well. Oxidative Stress was my first specialty.

Every cell type ( muscle, brain, liver, skin etc..) has a different number of mitochondria depending on its intrinsic energy needs. So a muscle or brain cell might have 1000 mitochondria per cell as they both have high energy needs. The female egg is the highest around 100,0000 since it must provide its progeny with many mitochondria to seed all the cell types in a fetus. All one's mitochondria can trace their lineage back to one of these 100,000 mitochondria from the mother's egg. Dad's sperm provides none - sorry dad. This is why they are able to trace maternal lineage all the way back to a single women - Mitochondrial Eve who lived about 150,000 years ago - everyone's great.....great grandmother.

If a muscle cell cell contains 1000 mitochondria, and they sequence all 1000 mitochondria mtDNA and find 15% of them have my deletion, then its - then its heteroplasmic 15%. Heteroplasmy simply means its a mix of normal mtDNA with some number of damaged mtDNA. The damaged mtDNA may be pathogenic that cause problems or non-pathogenic. Since the creation of ATP is their primary role, if 15% are unable but that leaves 85% ok. So heteroplasmy is also a measure of how bad things are. A 15% heteroplasmy isn't terrible because 85% is a lot of good ATP making mitochondria in the cells. But a heteroplasmy of 60% can be a death sentence since only 40% are making ATP which may be inadequate in high demand cells like the brain or muscle. When they sequence a biopsy sample, it has many millions of cells which have 1000's of mtDNA. They just sequence all they can find so you get a heteroplasmy number not for one mitochondria but for the average across many cells with their many mtDNA.

Since both cells and mitochondria do replication, the damaged mtDNA might begin as one but after years of division becomes many in that cell. Those cells also divide and spread the damaged mtDNA to their progeny. The damage can be a single SNP to a major deletion of 11 genes like me. Damage like a single SNP probably was caused by something simple like oxidative damage by ROS, UV light, a toxin, infection, replication error etc.. But a large deletion is believed to be caused by a major mistake during replication. Since nuclear genes are largely in control of mitochondria division ( rather than their own), they are typically involved in the creation of a large deletion error that occurred while they were helping the mitochondria divide due to mistake that stopped before completing with those 11 genes. - A big mistake.

The division somehow left off 11 genes in my case. That got the ball rolling. If there is a problem with one of the nuclear genes that are involved, it could cause systematic identical deletion errors eleswhere. That's why they sent my Exome back to re-examine the specific nuclear genes that are involved, looking for problems in them, that might have caused the deletion during nuclear gene assisted division. They didn't find anything obvious but that science is so new, they just haven't seen many examples to know everything to look for.

If it was a single one time mistake and the mitochondria divided and their parent cells divided, it should stay near its orignal location forever. If it was a systematic error then it could occurr again and again in any cell type and appear in muscles, brain liver, etc... That's why I would like another needle biopsy in my other leg. If its there too, its systematic.

Some of odd problems I've had over the years include:
- Everything revolves around something that happens in my body during sleep
- I use a CPAP and O2 in blood always remains in 92%-97% while sleeping - not blood O2
- My current thinking is during sleep while mitochondria are making ATP for next day, they are unable due to my problem and lowering oxygen aggravates and increasing O2 helps some but its secondary
- I could be fighting the deletion heteroplasmy level in my cells
- During sleep ATP generation just isn't making it. While awake I'm using ATP.
- There does seem to be a brain neurotransmitter problem adding to things because if I take a benzo like 3mg Ativan, before sleep, symptoms the next day are reduced. But I can't take that much Ativan daily or it will create more problems. It was test that seemed to show that the low ATP disturbed neurotransmission which in turn disturbed my Central, Somatic , Autonomic, Sympathetic and
Parasympathetic Nervous Systems- causing my oddbal symptoms and disturbed systems:
- Thick Fluid in lungs - Lots
- Heart conduction, sick sinus syndrome, and slowly lowering rate ( had to get pacemaker)
- Excess IgE ( >1000) with no allergies
- High Muscle CK - last test was over 300
- IgG subclass deficiency and low T cells and B cells but they come back
- GI issues that resemble C-IBS - never ending constipation
- Muscle and joint pain that were triggered during sleep
- Fluctuating Kidney function as creatine has gone from 1.0 to 2.5 to 1.0 to 1.8 to 1.1 etc...
- Extreme loss of thinking, balance, bodywide pain and stiffness upon awkenning at 12AM-3AM
- My body loses ability to move in late afternoon and often my mind barely works
- Loss of smell
- Memory and word recall loss
- Loss of planning skill, anxiety
- Loss of skills like building, software, hardware,
- Numbness in feet and to lesser extent in legs - these come and go

and more I probably forgot

 

[Aidan Walsh]

I am still trying to understand heteroplasmy but I think I get it. So are we thinking that the Deletion is responsible for excess oxidative stress which increases Heteroplasmy? If so I have a lot to say about that as well. Oxidative Stress was my first specialty.

I am showing only one in the tests you mentioned in 23andme results the

Chromosome 14 rs1049564 build 37 variant AorG I have G/G
build 38 variant AorG I have G/G
All others show 'no genotyped'
Can I have PNP with only one mutation or variant? I have low BP/Syncope

 

[Aidan Walsh]

I have some Genes in SCID Severe Combined Immune Deficiency & also PIDD Primary Immune Deficiency Disease & a lot in Common Variable Immune Deficiency I will post all of them here. SCID I have ADA many G/G's JAK3 4G/G's 1A/G.

In PIDD I have CD40 G/G WAS is C which means positive. I also show positive in Chediak Higashi Syndrome an Albino gene, I have LYST gene positive as well.

I also have JAK1, and JAK2 with the JAK3 above.

CVID Genes: Yes to PTEN, CD19 ,CD81, CD20, 7TTC37. No to CD20, CD21,TWEAK,BAFF,TRTN1

I even show some in the ALPHA1 gene SERPINA1 & I have an Emergency room Doctor who suggested my mucus sleeping is Dyspnea also known as Nocturnal Dyspnea or other names, I cannot breathe properly and short of breath he says it is a type of heart failure. Dyspnea can go with ALPHA 1 Antitrypsin Deficiency.

I show numerous genes 5 in HFI ALDOB gene i-5012664, rs190464963, rs10123355, rs76917243 rs1800456 plus MTHFR & COMT genes. I stopped all flour all folic acid even vitamins minerals folic acid fruit/sugar. I have stopped all sugar all fruits. no additives. I cook in Celtic sea salt/little water fat from foods

I eat some vegs on list of Hereditary Fructose Intolerance Meat fish poultry mild white cheese lactose Milk Water no coffee no tea no alcohol garbage

 

[ChristianBonanno]

I am showing only one in the tests you mentioned in 23andme results the

Chromosome 14 rs1049564 build 37 variant AorG I have G/G
build 38 variant AorG I have G/G
All others show 'no genotyped'
Can I have PNP with only one mutation or variant? I have low BP/Syncope

G is the normal or common SNP.

My point of what I wrote was that I have gene changes that give me the opposite of chronic fatigue. It’s highly unlikely anyone with chronic fatigue would have the June changes that I do in PNP.

 

[Aidan Walsh]

G is the normal or common SNP.

My point of what I wrote was that I have gene changes that give me the opposite of chronic fatigue. It’s highly unlikely anyone with chronic fatigue would have the June changes that I do in PNP.

ok thank you

 

[ChristianBonanno]

Some of odd problems I've had over the years include:
- Everything revolves around something that happens in my body during sleep

Have you ever had you magnesium tested and have you tried taking magnesium long term? (You know they inject magnesium into the hart of patients with sick sinus syndrome.)
Do you Vape or Smoke and have you ever?
Have any photo-sensitivity/
What would you say your BMI is?

It makes sense your CK and Creatine is high:

UniProt

www.uniprot.org

If you have high CK it means you are rapidly turning ATP into ADP. This is fascinating to me. The CK the measure is probably all in the cytosol so your mitochondrial CK is probably really low.

Here is the pathway again:

This would make sense if your mitochondria are messed up. You might want to check out your CKMT2 genetics.

 

[Aidan Walsh]

My CK is Normal, but my Creatinine always comes back low my Doctor only says muscle/weight loss is why. I never had magnesium levels checked. A lot of my genes above also show TT's or other answers

 

[Aidan Walsh]

G is the normal or common SNP.

My point of what I wrote was that I have gene changes that give me the opposite of chronic fatigue. It’s highly unlikely anyone with chronic fatigue would have the June changes that I do in PNP.

I did the rhabdomyolysis blood test it was negative but the genes are mixed

results all the way down 23andme from the first one down 37-38 are
rs142913020 G/G with rs117042618 CC, rs109042945 T/T, rs2277034 G/G. Are these ok?

I did only one blood test there are 2 it was Negative for Stiff Person Syndrome a lot of so-called ME/CFS have this all along. I will look today for these genes. thanks, Christian Bonano

 

[Ken Lassesen]

I was diagnosed with CFS by Stanford's Dr Montoya many years ago. My symptom set was unique as it is with almost anyone. I've been to Stanford many times, Mayo Clinic, UCSF and John Hopkins in trying to track down the cause. It was all a bust. I have never encountered a doctor willing to give more than 45 minutes to my problem. I have never seen a doctor willing to discuss underlying medical causes that I have researched.

I have written here about things I'

I was diagnosed with CFS by Stanford's Dr Montoya many years ago. My symptom set was unique as it is with almost anyone. I've been to Stanford many times, Mayo Clinic, UCSF and John Hopkins in trying to track down the cause. It was all a bust. I have never encountered a doctor willing to give more than 45 minutes to my problem. I have never seen a doctor willing to discuss underlying medical causes that I have researched.

I have written here about things I've discovered, some helped a little but most it turns out were chasing secondary problems that flow from my one central problem. I have read 100's of medical research papers along the way trying to understand possibilities while slowly gaining some understanding of human biology. We are essentially a sack of salt water with groups of specialized cells in the trillions mostly floating in it all communicating for the common good via some sort of communication receptor on their outside interface to that salt water. Various messenger chemicals get distributed mostly via the blood and float along until they find their receptor pair.

In this In reading of many medical papers they would never answer my so closely related questions around my symptoms or test results meaning. Of course they wouldn't as the research typically was exploring one biological issue closely related to my questions but I was always left knowing more, getting closer but frustrated I couldn't just speak with the authors. In the mean time I had given up on doctors as "only technicians" and not engineers or scientists that have curiosity. My symptoms worsened while I slept. I discovered by desperation that a little caffeine before bed and around 3AM stopped the horrific symptoms. My CFS was due to a sleep issue. Two Stanford sleep studies showed nothing.

About 6 years ago a cardiologist made an interesting comment to me while investigating heart related issues. Basically my heart was ok but he made the comment that my problem seemed "metabolic" in nature. Well it turns out he was correct in a few ways.

Then UCSF discovered that my leg muscles had about 15% of the mitochondria had a 6kb deletion. That's very bad since the 3rd step in the electron chain was shut off. But alas I had 85% working making ATP and doing other good things. Suspicious! Turns out that mitochondria make ATP and ATP is broken down to cAMP ( cyclic adenosine mono phosphate) which is the substrate for a critical pathway.

Then a UCSF muscle neurologist made a comment that caffeine is a complex molecule that had other profound effects. I then learned that my heart rate was dropping below 40 while sleeping and the low Oxygen while sleeping due to slow heart and saturation in the low 90% range were setting this in motion. So I was able to prove this and I got a cardiac pacemaker and the symptoms stopped. Then after about 4 months they started coming back. The human body biology is quite adaptable. What the pacemaker fixed, it adapted back and it came back but not quite as bad. At first adding O2 while I slept helped.

I studied what caffeine does and followed up on its function as a PED. A PED ( Viagra is a PED) breaks down another molecule called cyclic AMP (cAMP). Cyclic AMP in turns regulates everything from metabolism to the immune system via another molecule called PKA which activates various genes in the nucleus. This varyies from cell type to cell type. . Caffeine is a general as opposed to specific PED and by interfering with cAMP. This about where Google BARD and CHATGPT come in. I now knew enough about the pathway from papers but could ask meaningful questions of the AI tools from Google BARD and OpenAI/MS CHATGP. Very specific questions. I had begun to suspect a chronically low cAMP might be my problem.

So I asked one at a time about my symptoms. I have very high IgE ( allergies), low T and B cells and IgG subclasses and total. So asked BARD how the cAMP pathway could effect the immune system. The answer described all of these and why. Interesting. Low cAMP slows the heart especially at night. I asked it about constipation and blood circulation and it said those are both smooth muscle and it would make them contract - constipation and low blood flow. It also said It causes a parasympathetic dominance - slow intestines. That explained the muscle pain while sleeping and intestinal problems. I asked more but the most important question was why this would happen and are there any drugs to artificially increase cAMP. It gave me the answers. I won't tell you the "why" right now but the drug was Forskolin. It comes from a plant and can be bought on Amazon. So what the hell, the doctors are mostly brain dead, I bought it and took it. It eliminated most of my symptoms like magic. That's not the end since I'm now trying to eliminate the cause which is due to adaption as I thought and will take months. It was a drug causing the problem. Not on doctors questioned. But medical papers combined with my suspicions, the caffeine link and Artificial Intelligence ( both BARD and ChatGPT) combined did the trick.

So I would strongly recommend anyone who is searching the medical papers and looking for answers, once you know the right questions, try Goog BARD and Open AI's ChatGPT to get the last little details. You need to know what to ask but if you do, its the bridge after the medical papers.

Good Luck

ve discovered, some helped a little but most it turns out were chasing secondary problems that flow from my one central problem. I have read 100's of medical research papers along the way trying to understand possibilities while slowly gaining some understanding of human biology. We are essentially a sack of salt water with groups of specialized cells in the trillions mostly floating in it all communicating for the common good via some sort of communication receptor on their outside interface to that salt water. Various messenger chemicals get distributed mostly via the blood and float along until they find their receptor pair.

In this In reading of many medical papers they would never answer my so closely related questions around my symptoms or test results meaning. Of course they wouldn't as the research typically was exploring one biological issue closely related to my questions but I was always left knowing more, getting closer but frustrated I couldn't just speak with the authors. In the mean time I had given up on doctors as "only technicians" and not engineers or scientists that have curiosity. My symptoms worsened while I slept. I discovered by desperation that a little caffeine before bed and around 3AM stopped the horrific symptoms. My CFS was due to a sleep issue. Two Stanford sleep studies showed nothing.

About 6 years ago a cardiologist made an interesting comment to me while investigating heart related issues. Basically my heart was ok but he made the comment that my problem seemed "metabolic" in nature. Well it turns out he was correct in a few ways.

Then UCSF discovered that my leg muscles had about 15% of the mitochondria had a 6kb deletion. That's very bad since the 3rd step in the electron chain was shut off. But alas I had 85% working making ATP and doing other good things. Suspicious! Turns out that mitochondria make ATP and ATP is broken down to cAMP ( cyclic adenosine mono phosphate) which is the substrate for a critical pathway.

Then a UCSF muscle neurologist made a comment that caffeine is a complex molecule that had other profound effects. I then learned that my heart rate was dropping below 40 while sleeping and the low Oxygen while sleeping due to slow heart and saturation in the low 90% range were setting this in motion. So I was able to prove this and I got a cardiac pacemaker and the symptoms stopped. Then after about 4 months they started coming back. The human body biology is quite adaptable. What the pacemaker fixed, it adapted back and it came back but not quite as bad. At first adding O2 while I slept helped.

I studied what caffeine does and followed up on its function as a PED. A PED ( Viagra is a PED) breaks down another molecule called cyclic AMP (cAMP). Cyclic AMP in turns regulates everything from metabolism to the immune system via another molecule called PKA which activates various genes in the nucleus. This varyies from cell type to cell type. . Caffeine is a general as opposed to specific PED and by interfering with cAMP. This about where Google BARD and CHATGPT come in. I now knew enough about the pathway from papers but could ask meaningful questions of the AI tools from Google BARD and OpenAI/MS CHATGP. Very specific questions. I had begun to suspect a chronically low cAMP might be my problem.

So I asked one at a time about my symptoms. I have very high IgE ( allergies), low T and B cells and IgG subclasses and total. So asked BARD how the cAMP pathway could effect the immune system. The answer described all of these and why. Interesting. Low cAMP slows the heart especially at night. I asked it about constipation and blood circulation and it said those are both smooth muscle and it would make them contract - constipation and low blood flow. It also said It causes a parasympathetic dominance - slow intestines. That explained the muscle pain while sleeping and intestinal problems. I asked more but the most important question was why this would happen and are there any drugs to artificially increase cAMP. It gave me the answers. I won't tell you the "why" right now but the drug was Forskolin. It comes from a plant and can be bought on Amazon. So what the hell, the doctors are mostly brain dead, I bought it and took it. It eliminated most of my symptoms like magic. That's not the end since I'm now trying to eliminate the cause which is due to adaption as I thought and will take months. It was a drug causing the problem. Not on doctors questioned. But medical papers combined with my suspicions, the caffeine link and Artificial Intelligence ( both BARD and ChatGPT) combined did the trick.

So I would strongly recommend anyone who is searching the medical papers and looking for answers, once you know the right questions, try Goog BARD and Open AI's ChatGPT to get the last little details. You need to know what to ask but if you do, its the bridge after the medical papers.

Good Luck

Example of NEW AI+PubMed Studies report from MicrobiomePrescription.com​

To use, you need a sample to get the analysis (Biomesight, Thorne, Ombre)​

​

---

 

[ChristianBonanno]

Ken, I’m not saying this to be mean, but I just think that is going to lead nowhere and it’s a waste of money.

We have no idea yet what the balance of the Microbiome looks like. It might even be that an imbalance Microbiome when we’re sick is beneficial.

Plus, I think these people are more interested in making money than helping anyone heal.

 

[Ken Lassesen]

I agree about the TESTING company focus is on making money. MicrobiomePrescription goal is NOT to make money -- all analysis is free and fully documented - it intent has always to help (and occasionally challenge the MONEY-FOCUSED companies for giving lousy advice to SNOW their customers.

Why sites suggestions disagree on the same data – Microbiome Prescription Blog

The taxonomy nightmare before Christmas…

See also: The taxonomy nightmare — Episode II The taxonomy nightmare before Christmas… Episode III There is no normal nor reference microbiome! – Reference ranges ignore critical factors…

cfsremission.com

Recently I got multiple emails from people who reversed long COVID using the site, from a Uni-student, an EU Lawyer and a person who won silver metal at the Olympics.

I do NOT post such stories on my site --- that is what for money folks do. I saw this on Facebook this week (and pretty sure that the AI site is my site -- we have worked closely with biomesight for years)

My mom had hypoglycemias and weight gain that was getting a bit worse, along with some food intolerances. I got her to do a biomesight and then followed the top recommendations from an AI-based recommendations website. Top of the list was Miyarisan, she took it and actually it got rid of her hypoglycemia ! it was impressive with a normal meal she would have much better ability to whistand not eating for long period of time.

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Log into Facebook to start sharing and connecting with your friends, family, and people you know.

www.facebook.com

You are likely tossing the baby out with the dirty money-grubbing bath water.

 

[Aidan Walsh]

I just tried to post some of my results on Facebook group Alpha1in the UK one picked up I have something in my results & this can cause numerous issues with hypoglycemia I now show 4 genes 2 are CC Carriers 2 are TT's. I know Alpha1 Antitrypsin Deficiency can also go with CVID in some. I would need to get some blood tests to see if I am deficient...

On another Facebook group, run by a Boston Doctor on MTHFR Gene Mutation, Dr Carol Savage a few have found immediate relief using a natural product by Life Extension called Lithium Orotate 2 or more of 1,000 mcg to push their vitamin B12 up into their cells they have MTHFR mutations. She has a lot of scientific data on there in their files xx