Discussion in 'General ME/CFS Discussion' started by mariovitali, May 8, 2017.
What's with all the cloak and dagger?
That's because i am currently looking to other problems as well, not associated with CFS/ME. Anything related to CFS/ME i will fully disclose it to OMF and Professor Ron Davis.
I noticed a thread that you posted that mentioned IgA levels. I will be posting shortly about the importance of CYP7B1 and CCing Janet but you may want to see this.
See below yet one more node from Network Analysis where CYP7B1 can be shown :
Then i found this, regarding CYP7B1 and 25-hydroxycholesterol (=an oxysterol which is also shown as a Topic in the Graph and was mentioned in previous posts) :
From the same paper, mentions about porphyrins :
A simple search about "Porphyrins" on PR shows many mentions about elevated Porphyrins.
I tried ferulic acid, half a tablet. It did provide me with extra energy and seemed to improve many symptoms. However, it also gave me a terrible headache and some unpleasant feelings of overstimulation. I've since learned that FA is an AChE inhibitor:
I'm considering trying Tetradecylthioacetic acid (TTA) next. Also Propolis is on my list.
I had no idea about TTA, if it activates PPARa it might work. Out of 62 DNA samples that i have, by far the most common problem is found to the LXR Receptor then it's MYO9B.I don't know if LXR should be activated instead to be honest and/or PPARs as well. However i have ordered a known LXR Inducer , called Jiaogulan and i will report back.
About Ferulic Acid : So something happened there but you got these sides. This is all understandable. If you been following my posts i mentioned several Genes that may have importance and i think this is what happens given the 62 DNA Samples. What i found is combinations of mainly homozygous mutations to LXR, PPARs, MYO9B, FXR,CYP7B1, CYP46A1 a gene called ERN1 (which i haven't discussed so far) and other genes pertinent to autophagy, ER Stress and Bile Acid Metabolism.
My hypothesis is that we have a Liver with suboptimal functioning even before CFS/ME. We are born with this however our Liver compensates and we have a normal life. Now, there are some CFS sufferers that say that "they had some symptoms for all of their life" even before CFS.
So we have a compensatory functioning until a Liver Stressor (=Some Medications / EBV Virus / Hepatitis virus , even prolonged stress and subsequently elevated cortisol levels) brings the final blow to an already fragile Liver functioning.
As discussed, what i have seen in the DNA Data i collected are combinations of problems, there is no SPOF. This is why i believe that the only way to solve this puzzle is a personalised regimen.
After you sent me a message about Xanthine Oxidase i revisited it in wanting to understand more about it. As discussed during our messages, i told you that algorithmically xanthine oxidase was chosen as being important.
@Janet Dafoe (Rose49) I am CCing you here because i would like to give an example to Ron on how this Technology can help us find the solution much faster. Please give this technology a chance.
After @Gondwanaland has messaged me i used the software to identify associations of Xanthine Oxidase that could be of interest.Please look at the following screenshot :
So we see associations of Xanthine Oxidase with :
2) Uric Acid
3) ROS (=Reactive Oxygen Species)
4) Sulfite Oxidase (SUOX)
Several other Topics (not shown) suggested a connection of Xanthine Oxidase (which is a source of ROS and therefore not good to have too much of it circulating in the blood ) with Sulfates.
Then i find the following :
Taken from "Cellular and Molecular Mechanisms of Inflammation - Volume 4 ", pp 107-108
I discussed the importance of Sulfation in one of my posts and had mentions on Glycosaminoglycans (GAGs) and heparan sulfate :
@Gondwanaland : I believe that you must support your Sulfation phase. That will generate GAGs and these will bind Xanthine Oxidase. Please check your Liver with a Fibroscan to rule out any Liver disease. This is the Second best way after taking multiple samples (=biopsy). There is no other way to completely rule out Liver disease.
This makes no sense to me because heparin and coumadin had horrible effects in my joints, uric and oxalic acid homeostasis. Additionally I thought heparin is linked with increasing leaky gut.
Perhaps because exogenous heparin supresses endogenous heparin-sulfate and causes the whole mess?
I definetly have problems with low levels of GAGs and hyaluronic acid...
I can't imagine any dr ordering such a test for me with my "healthy" US + lab results
But I guess it is the only explanation to the pain I get after eating... Endoscopy showed no signs of gastritis...
I don't know about exogenous heparin to be honest and its effects. I did read however that Glycosaminoglycans are necessary for creating the gut lining :
So yet one more reason to make sure that Sulfation phase is working correctly.
I confirm that Bee Propolis is working wonders (at least for me). I have a homozygous mutation on rs1800977 and a heterozygous mutation on rs2230806 (both are ABCA1 - see below) and Bee propolis works by upregulating LXR + PPARγ through ABCA1.
I assume that you found this paper regarding propolis and LXR?
I just received Jiaogulan and will try it tonight.
EDIT : Wikipedia entry for Jiaogulan states :
I am a bit concerned for the fact that increases T Cell activity. In any case i will give it a try, i believe that an increase in macrophage activity is beneficial in our case.
Great find there @adreno, Thanks
Could you make a list of the most important SNPs, and which allelles to look for in 23andme?
For rs1800977 I have A/A. On rs2230806 I am C/C. Is that good or bad?
Will do very soon. I will post detailed gene information so that Dr. Davis can test the hypothesis that i described in their CFS cohorts. The data that i have are 62 DNA data files from patients of CFS/ME, Post-Accutane Syndrome, Post-Finasteride Syndrome and Fibromyalgia.
You are Homozygous at rs1800977 and ok on rs2230806.
If you look below, A is listed as Minor Allele :
But have in mind : We look at combinations of SNPs, not at individual problems. You work through the pathway that cleaves cholesterol then generates Oxysterols, Bile Acids, induces LXR / PPARs and so forth and see where you have issues.
Please let us know if you try Bee Pollen or Jiaogulan. This by no means is a silver bullet and you have to support many other Pathways but you can give it a try. I would say that it appears that Magnesium and Biotin appear to be beneficial (=hypothesis) for the majority of cases.
@adreno - This is @mariovitali's entire basis for recommending treatment as far as I can tell. He seems to believe that any minor allele (the allele with less than 50% prevalence) on certain genes is causing problems.
There are several major problems with his approach. The first is that a great deal of scientific research has shown that most SNPs have no effect. It doesn't matter which genotype someone has for most SNPs. To know if they do have an impact upon gene function, it's necessary to read the research. If there is no research, the assumption should typically be that the SNP has no impact, just like most other SNPs.
The second problem is that most of these minor alleles are extremely common. rs1800977 has a MAF (minor allele frequency) of over 36%. That means that 13% of people are homozygous and another 46% are heterozygous. It is extremely unlikely that such a common allele is causing any problems, because a huge portion of the population would be affected if it was.
Another problem comes in using 23andMe data for this sort of approach. It only tests for a very small percentage of the SNPs on any gene, and is not particularly targeted at known or likely pathogenic mutations. If the entire genome were examined, every person on the planet would have hundreds of minor alleles on every gene. Ergo literally every person should have whatever illness @mariovitali thinks is connected to the particular genes he's interested in. Obviously that is not the case.
And finally, even if an allele were extremely rare, it wouldn't make sense to assume that any potential trouble it causes is either a down-regulation or an up-regulation. Mutations can have either effect, and often either can trouble. So even if playing "every minor allele is dangerous", it can't be assumed that the solution is to either speed up or slow down the gene product. In fact, it might be extremely dangerous to make such an assumption, as someone could end up aggravating the situation if there actually is a problem with that gene.
As discussed, even though i do not like forums because they disperse information, they do keep track of things. And i am really happy that what we all said, answered and not answered , it's all here.
Let's assume for a moment that my theory has a 1 in a million chance to be correct.
-What is the "cost" of considering this solution and this solution to be indeed incorrect?
-What is the "cost" of NOT considering this solution and this solution to BE correct?
Could you answer this simple question please?
Leaving SNPs aside for now, some time ago i suggested to you to take a Fibroscan. Let's remember the dialog :
You said :
while we know for a fact that the following holds :
Since you haven't provided any references back then for the "exceedingly uncommon" part, would you like to give some references now?
According to my understanding this question -and the answer to that question- is far more basic that discussing about SNPs. So let's start with the Basics.
No thanks, I was only discussing the SNPs. You have offered absolutely no response regarding those.
Berberine Is a Potent Agonist of Peroxisome Proliferator Activated Receptor Alpha
Telmisartan also seems interesting as in enhances PPAR alpha/delta, AMPK, decreases TGF-beta, and more. Bunch of studies on this.
And have you considered AICAR?
I came across Berberine but didn't really look at it more closely. I never heard before of Telmisartan and AICAR.
What i usually do when there is a new Topic is to collect Research about it from PubMed and then have these Topics being scored algorithmically for their relevance. I will add them.
I think that Jioagulan also works but need more time as i am upping the dose slowly. Have you tried Jiaogulan/Bee Propolis by any chance?
Ok. Just note that it's aicar, not alcar. There is often some confusion there.
I tried propolis but didn't like it. I suspect it to be strongly cholinergic, which I don't tolerate at all.
Unfortunately, things are not that easy. As discussed, you have to support several pathways at the same time. It's not only about LXR unfortunately. For example consider the following Genes that have to do with Thiamine Metabolism :
SLC19A2 - rs2038024 (MAF= 12% - 'C' / Heterozygous =43.1%, Homozygous = 3.45%)
SLC19A2 - rs6427193 (MAF=14% - 'C' / Heterozygous = 50% / Homozygous = 8.62%)
The percentages shown are the Mutations found in the sample of 62 DNA Files i have.
If you have SNPs there, i believe that you should supplement with Thiamine.
Note that there are cases in PR where Thiamine was important :
and also note mentions about Biotin on the same Thread :
Now look at the associations of SLC19A2 with BTD (That's Biotinidase) And Sulfur Metabolism :
Again, several pathways need to be supported to get out of this Vicious cycle we got ourselves into. Note also the SLC19A3 association.
It's not appropriate to give medical advice, especially on such a flawed basis.
I believe that you should not dismiss theories so easily especially when you state that Liver function is irrelevant, repeatedly dismissing *facts* shown to you that normal Liver enzymes do not imply normal Liver function.
Thiamine is not medication by the way, it is a Vitamin sold even in Super Markets.
You can also try a Google Site Search
Separate names with a comma.