Help Interpreting 23andMe Results

[JPV]

I've never been able to determine whether I do or do not have issues with methylation.

I've tried both Rich and Freddd's methylation protocols, several times over the years, with little measurable success. I don't know if it's an issue with missing cofactors, detox reactions or if it's just something that doesn't apply to me. I find that much of the information for this approach is so convoluted and scattered all over the forum that I basically gave up trying to figure it out.

Currently, I've been following the "Unfolded Protein Response and A Possible Treatment for CFS" thread with great interest. I'd like to try the treatment proposed by @mariovitali but he mentions that methylation may be some sort of limiting factor so I'd like to rule this out before proceeding with his recommendations.

I was wondering if anyone that was knowledgeable about methylation defects would be so kind as to look at my 23andMe results and let me know if it's something I should even bother to concern myself with...

Genetic Genie Methylation Profile

Genetic Genie Detox Profile

Thanks.

 

[mariovitali]

@JPV

Thank you for your interest in Unfolded Protein Response-ER Stress Therapy. Unfortunately i don't understand what you mean by "Methylation being a limiting factor" so please let me explain here again, just to be on the safe side :

There are several reasons for improper Protein Misfolding within the Endoplasmic Reticulum, some of them are the following :

-HHcy (Hyperhomocysteinemia)
-Impaired Calcium Homeostasis
-Impaired Production of BH4 which leads to Phenylketonuria
-Inhibition of N-Linked Glycosylation

Methylation causes elevated Homocysteine, however there can be more causes for problems in Protein Misfolding and therefore this could be the reason for which you haven't seen many benefits with Fredd's/Rich's Protocols.

FYI I also tried both Methylation support regimens and they made me feel better but weren't able to achieve a full remission of my problems as the regimen i propose did.For what its worth i am following Fredd's suggestion to use Adenosylcobalamin. Methylcobalamin would give me Brain Fog for some reason.

 

[JPV]

Perhaps "limiting factor" was the wrong choice of words. I assumed that you meant that methylation defects would need to be addressed either before or while on the protocol that you are proposing...

So at first you have to make sure that you do not have :

a) Methylation problems

Looks like you have since edited the message for clarity.

Either way, I'd love to get an opinion on my test results.

 

[adreno]

I don't see anything exotic in those results. Looking at them, I should think a good quality B complex should suffice to support methylation. Do you have high homocysteine?

 

[JPV]

I don't see anything exotic in those results. Looking at them, I should think a good quality B complex should suffice to support methylation. Do you have high homocysteine?

Thanks for looking at my test results.

I've never taken a test to determine homocysteine levels and I'm not quite sure what the symptoms might be. I guess it's just one of those things that must have slipped past me.

 

[mariovitali]

Perhaps "limiting factor" was the wrong choice of words. I assumed that you meant that methylation defects would need to be addressed either before or while on the protocol that you are proposing...


Looks like you have since edited the message for clarity.

Either way, I'd love to get an opinion on my test results.

You are right and Thank you for pointing this out.

What you want to do is to make sure that you deal with anything that creates ER Stress (Methylation problems, impaired BH4 Production), avoid agents that impair Proper Protein Folding capacity ( Statins, HSP70 inhibitors, DHT Inhibitors, etc) and use Supplements that limit ER Stress and help in Protein Folding (TUDCA, Selenium, Curcumin, HSP70 Induction) and you will have to take all of these actions at the same time.

Interestingly, i searched for TUDCA on the Forum and it was never mentioned previously. However, there is one mention in Customer Reviews regarding CFS :

http://www.amazon.com/review/RNV4VYPXS14PS

 

[adreno]

Thanks for looking at my test results.

I've never taken a test to determine homocysteine levels and I'm not quite sure what the symptoms might be. I guess it's just one of those things that must have slipped past me.

I don't think there are any specific symptoms for high homocysteine. But it could give you a broad idea whether you have methylation problems.

 

[JPV]

Interestingly, i searched for TUDCA on the Forum and it was never mentioned previously.

Yeah, I had mentioned to @adreno that I hadn't seen much mention of Clostridium Butyric/Miyarisan as a potential treatment for ME/CFS anywhere on the internet. He felt that was a good thing because so few other known treatments have really shown that much promise.

 

[Sidereal]

Never seen a methylation panel looking as clean as that, @JPV. One thing less to worry about.

 

[mariovitali]

@JPV

Have you ever used :

-Finasteride/Proscar ?
-Nizoral?
-Any P450 inhibitor in general?
-Statins?

How/When did you first experienced CFS?

 

[JPV]

Never seen a methylation panel looking as clean as that, @JPV. One thing less to worry about.

Thanks, I would have thought with all the hetero results it might have meant something. It's good to hear otherwise.

 

[Sidereal]

Thanks, I would have thought with all the hetero results it might have meant something but it's good to hear otherwise.

You don't have the most important MTHFR C677T mutation so you don't need to worry about being hetero for A1298C. VDR hetero SNPs are just normal variation, blown out of all proportion by Yasko. COMT +/- is actually better than -/- (and of course +/+) in my opinion because it gives you a better balance between working memory (big component of intelligence) and anxiety/physiological arousal. Much of the other stuff on the panel is rubbish of no relevance. Hope this helps you avoid a pointless detour down the online SNP quackery rabbit hole.

 

[JPV]

I will say that I bought some sulfate testing strips and my readings where off the charts. I've cut out some sulfur foods and brought it down in half, but still high. Maybe I don't need to worry about it.

 

[JPV]

Have you ever used :

-Finasteride/Proscar ?
-Nizoral?
-Any P450 inhibitor in general?
-Statins?

I have not.

How/When did you first experienced CFS?

I've had minor fatigue issues throughout my 20's. I had a lot of allergies so I assumed that they contributed to why I felt bad. The more severe symptoms didn't manifest until later in life.

In my early 30's I started occasionally using methamphetamines. One evening, while using meth, I had a sudden onset of what I assumed were some sort of neurological problems. My skin felt as if it was burning all over my whole body. It was so severe that I wasn't sure that I'd have the ability to live with the pain for very long. This went on for about 6 months or so until it finally subsided a bit. This sudden onset seems to correlate to Jay Goldstein's theory that some sort of switch is flipped in the brain that throws the whole body out of balance.

I now have mild and occasional burning, mostly in my legs, when symptoms flare. I also suffer from fatigue, brain fog, mental confusion, disrupted sleep cycle, tinnitus (started after an ear infection I had when I was young), depression, lack of motivation and numerous other health problems.

 

[mariovitali]

@JPV

This might be the culprit (First study made in rats) :

Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells

We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction.

http://paperity.org/p/27549344/meth...lum-stress-related-gene-chop-gadd153-ddit3-in


and also here :

Role of Sigma Receptors in Methamphetamine-Induced Neurotoxicity

Methamphetamine (METH) is a widely abused substance world over. Currently, there is no effective pharma- cotherapy to treat its effects. This necessitates identification of potential novel therapeutic targets. METH interacts with sigma (σ) receptors at physiologically relevant micromolar concentrations. In addition, σ receptors are present in organs like the brain, heart, and lungs at which METH acts. Additionally, σ receptors have been implicated in various acute and subchronic effects like locomotor stimulation, development of sensitization and neurotoxicity, where σ receptor antagonists attenuate these effects. σ Receptors may also have a role in METH-induced psychiatric complications such as depression, psychosis, cognitive and motor deficits. The neurotoxic effects of METH, which are cause for concern, can be prevented by σ receptor antagonists in mice. Mechanistically, METH-induced neurotoxicity involves factors like dopamine release, oxidative stress, endoplasmic reticulum stress, activation of mitochondrial death cascades, glutamate release, apoptosis, microglial activation, and hyperthermia. This review compiles studies from the literature that suggests an important role for σ receptors in many of the mechanisms of METH-induced neurotoxicity.

http://benthamscience.com/journal/abstracts.php?journalID=cn&articleID=73512

 

[JPV]

Thanks for sharing the research. Not sure how to interpret it though. I haven't done any drugs for years now so I wonder why the symptoms still perist. Does your theory of unfolded proteins factor into this in any way? Seems like there might be some overlap here.

 

[mariovitali]

@JPV

Yes, because both papers discuss about induction of ER (Endoplasmic Reticulum) Stress from Methamphetamine. ER Stress is the common factor of our problems (in my theory).

Regarding your permanent effects : It seems that our bodies fall into a vicious loop of ER Stress from which they cannot come out. My problems were triggered when i decided to stop Propecia for hair loss. See here : http://propeciahelp.com/overview

90% of PERMANENT side effects from Propecia use are the same with CFS.

Please Try the regimen i listed and share your results with us.


EDIT : I added 'Methamphetamine' to the list of Substances that induce ER Stress to my original post.

 

[JPV]

Yes, because both papers discuss about induction of ER (Endoplasmic Reticulum) Stress from Methamphetamine. ER Stress is the common factor of our problems (in my theory).

So, I'm assuming you believe that I may have arrived at the same condition via a different trigger mechanism that disrupted much of the same biological processes.

Please Try the regimen i listed and share your results with us.

Will do. I have an ever changing regimen but 'm currently focusing on the probiotic Clostridium Butyric/Miyarisan which I feel is giving good results. I also take Yucca for Ammonia. Magnesium Threonate and L-Ornithine for excitotoxicity symptoms that I suspect stems from excess Glutamate. Low dose (300mcg) melatonin for sleep.

I'd be interested to hear what you think of David Whitlock's theories regarding ME/CFS and Nitric Oxide...

An Engineering Perspective on CFS – by Dave Whitlock

It seem's to correlate to some of Jay Goldstein's experiments with Nitric Oxide...

Dr Jay Goldstein's Instant Remission ME/CFS Treatments

Whitlock has an interesting product called AOBiome that I'm interested in experimenting with. It's a probiotic body spray that is supposed to consume Ammonia while boosting Nitric Oxide...

AO+Mist

I wonder if any of this might relate to your theories of unfolded proteins.

 

[mariovitali]

@JPV

I tried the following :

-P450 induction
-Nitric Oxide Induction through Nitrates Consumption
-Methylation Support by Fredd/ and (late) Rich
-HCG Injections
-Thyroid Medication

If you log in to propeciahelp.com and solvepfs.com and search for user 'mariovitali', all of my attempts are documented through the years. NOTHING worked even close to how i feel now. All of these attempts would have good results but these results wouldn't last.