Summarise further report pros and cons after 23andme?

[sb4]

I have both these SNPs and can take deplin-like doses of methylfolate without problem. In fact too little methylfolate causes insomnia for me.

I don't have any doubt that for some people, methylfolate can cause problems, but it has nothing to do with these SNPs.

I'm not really doubting what you are saying but maybe you just aren't expressing the COMT SNPs or maybe your brain mitochondria are healthy and so the enzymes don't need to be perfect to work, or maybe something in some other SNPs are cancelling it out. Or maybe as you say it isn't COMT.

 

[alicec]

maybe you just aren't expressing the COMT SNPs

That makes no sense. If the gene is expressed then any SNP within it will be expressed.

maybe your brain mitochondria are healthy

Judging by my degree of brain fog and rapid mental fatigue from even mild concentration I don't think so.

or maybe something in some other SNPs are cancelling it out.

Mechanistically I can't imagine how that would work.

Or maybe as you say it isn't COMT.

Well there's no evidence that that COMT +/+ causes sensitivity to methyl groups and plenty of people on PR who are COMT +/+ have reported that they are not sensitive. That suggests we should look elsewhere.

It is really simplistic to attribute sensitivity to a particular supplement to a single SNP. Biochemical pathways are much more complex and interact in much more complex ways. From some of the serious errors she has made in interpreting biochemical studies and misreading pathway diagrams, I think that Yasko doesn't have a strong grasp of biochemistry. There's no reason to place faith in her guesses.

 

[bertiedog]

I don't have any doubt that for some people, methylfolate can cause problems, but it has nothing to do with these SNPs.

So what other reason do you propose for this very widely reported problem with COMT at the very least?

Pam

 

[Valentijn]

So what other reason do you propose for this very widely reported problem with COMT at the very least?

I propose that anecdotal evidence is not reliable, especially when an astronomical number of other possibilities exist to cause symptoms. The COMT variations are extremely common, so it's not unexpected that many or even most people with any given symptom will also have a COMT variant.

 

[bertiedog]

I propose that anecdotal evidence is not reliable, especially when an astronomical number of other possibilities exist to cause symptoms. The COMT variations are extremely common, so it's not unexpected that many or even most people with any given symptom will also have a COMT variant.

They might well have a COMT variant but perhaps if you are homozygous you are more at risk of having certain issues.

Pam

 

[Valentijn]

They might well have a COMT variant but perhaps if you are homozygous you are more at risk of having certain issues.

Extremely unlikely. If it was a significant factor for "certain issues", a huge proportion of the population would have those issues.

 

[alicec]

So what other reason do you propose for this very widely reported problem with COMT at the very least?

The observed problem is sensitivity to methylfolate, or sometimes it is framed as a problem with all methyl donors. The proposition is that this is related to COMT.

I can't find a single report of a study of the proposition, though there are certainly widely repeated claims that a linkage exists. As far as I can see the claims all have their origin in Yasko's hypothesis that there is a causal relationship between the two. For some unknown reason this proposition captured peoples' imagination and spread like wildfire, quickly going from hypothesis to fact without any studies whatsoever.

There is no evidence that the two things are linked and plenty of reports which show that they aren't.

As to why people are sensitive to methyl folate, I don't know and I don't think that anyone else does either. There could be many reasons which vary from person to person.

I can't think of any reason to separate out this sensitivity from the many others which people, especially PWME, experience - ie, I don't know why we have become fixated on this sensitivity being attributable to a single SNP. I can't think of another sensitivity which has been so simplistically explained.

People have many and varied responses to many and varied supplements. It defies logic to think that these are directly linked to particular SNPs. Genetics may make some contribution to some of these responses, but it is only a contribution to a far more complex system.

Here is a recent post which canvases some of the reasons that people think may be behind supplement sensitivity. They are all armchair theories - there is little evidence to support any of them. Still it shows the breadth of possibilities that are envisaged. Possibly there might be something there that you can relate to and might be worth experimenting with.

I would add variations in gut bacteria as an important thing to consider. They can metabolise dietary compounds (including those in supplements) in many different ways. We might lack some that would degrade compounds which our bodies can't handle well or maybe we have too much of others that produce intermediates that again our bodies can't handle. There are many other variations of this theme.

 

[sb4]

Extremely unlikely. If it was a significant factor for "certain issues", a huge proportion of the population would have those issues.

Well, huge percetages of the population have SNPs and have no symptoms. They only become expressed when you get ill, your cell redox drops and enzymes have to work harder for the same effect. I didnt have any problems with methylation until I got ill with gastroparesis.

 

[Valentijn]

They only become expressed when you get ill, your cell redox drops and enzymes have to work harder for the same effect.

Most people get ill at some point. And most people have those variants. Thus you'd expect to see a huge number of people developing these supposed problems on a chronic basis, if "expression" were really an issue.

But in the context of methylation and other fads, talk of "expression" is just the default response to the SNPs themselves haven been repeatedly shown to have little or no negative effect. It's what people say when they're unwilling to admit they were wrong about certain SNPs, and need to invoke a magical explanation for symptoms still being tied to those SNPs. At best it is complete conjecture, and such an application has absolutely nothing to do with science or genetics.

I didnt have any problems with methylation until I got ill with gastroparesis.

There are many alternative possibilities other than a genetic defect with methylation which has somehow opted not to "express" itself until now:
1) There is no problem with methylation, and it's just gastoparesis
2) Gastoparesis impacts methylation due to reduced absorption of B12 and folate, regardless of SNPs
3) Something else causes both gastoparesis and methylation problems

It simply isn't logical to blame very common SNPs, especially when they have been researched thoroughly and no such problem has ever been attributed to them.

 

[bertiedog]

The observed problem is sensitivity to methylfolate, or sometimes it is framed as a problem with all methyl donors. The proposition is that this is related to COMT.

I have been thinking a bit about this. There are lots of studies that show there is a much higher likelihood of a central nervous system problem if you are homozygous for COMT. Following on from that folates can convert to glutamate which in excess is a neurotoxin and I would have thought this was especially likely if one has SNPs in the GAD enzyme like I do. Therefore one might describe this as a "sensitivity" to added folates because of a COMT SNP (plus others too).

I also was doing a bit of thinking over the remarks that Yasko has it wrong about many SNPs and this seems to be felt very strongly by a few people on here. What I would say to this in general is that she is purported to have treated many hundred patients with various SNPs and various symptoms. Surely one can take something from this experience? If she is seeing a certain reaction repeatedly with the various SNPs then this shouldn't just be discounted because there isn't published data?

On the other hand I recall Dr Jill James also making the same type of connections and I believe she has published her research regarding her findings with autistic kids, their sensitivities and also her findings on the type of SNPs they have so it isn't just Yasko that gives out this type of information.

For me if I repeatedly react to a certain substance and I fit the Yasko explanation, then I fail to see why I should discount the theory even though others might disagree.

Pam

 

[Valentijn]

What I would say to this in general is that she is purported to have treated many hundred patients with various SNPs and various symptoms. Surely one can take something from this experience?

That would be anecdotal. It is of much less usefulness due to various types of bias when we rely solely on our observations. Scientific processes are used in research to control for those types of biases. And for the SNPs where there is scientific research, that research often directly contradicts Yasko's claims.

In other cases (CBS C699T) she seems to be referring to research papers regarding some claims. But upon reading those papers, it is apparent that Yasko is very badly misinterpreting them. And in one case, I believe on the SUOX gene, she is talking about a pathogenic SNP, but actually testing and wrongly interpreting its harmless neighbor instead.

 

[sb4]

Most people get ill at some point. And most people have those variants. Thus you'd expect to see a huge number of people developing these supposed problems on a chronic basis, if "expression" were really an issue.

There are many alternative possibilities other than a genetic defect with methylation which has somehow opted not to "express" itself until now:
1) There is no problem with methylation, and it's just gastoparesis
2) Gastoparesis impacts methylation due to reduced absorption of B12 and folate, regardless of SNPs
3) Something else causes both gastoparesis and methylation problems

It simply isn't logical to blame very common SNPs, especially when they have been researched thoroughly and no such problem has ever been attributed to them.

When I say ill, I mean significantly ill. As in your mitochondria stop producing as much energy.

I'm not saying everybody is 100% right about SNPs. I am saying it makes more sense that they are only a problem (expressed) when your significantly ill already. If your mitochondria are working well, then lets say the IR they put off will cause the exclusion zone of water around enzymes to decrease whilst giving them more electric potential. This will mean it is easier for the enzymes to get close to there target and even the shitty ones work well. OR you produce more enzymes with healthy mitochondria. OR the enzymes have higher redox when made with better mito...

I'd say it's probably "3) Something else causes both gastoparesis and methylation problems" but my point is, whatever caused me problems caused me to loose energy to the point where my SNPs became a problem.

With regards to COMT it would depend on, if yasko is right, how ill you are, and how mutated they are.

As for me I have two COMT +/+ and MAO-A +/+ and I'm awful with SSRIs, methylgroups and other things that stimulate neurtransmitters. Could be a coincidence but a bunch of others report the same...

 

[alicec]

I have been thinking a bit about this. There are lots of studies that show there is a much higher likelihood of a central nervous system problem if you are homozygous for COMT. Following on from that folates can convert to glutamate which in excess is a neurotoxin and I would have thought this was especially likely if one has SNPs in the GAD enzyme like I do. Therefore one might describe this as a "sensitivity" to added folates because of a COMT SNP (plus others too).

Sorry to spoil the party but as well as a bunch of COMT+/+ SNPs, I also have a bunch of GAD1 SNPs, some +/+. some +/-. I don't have problems with methyl folate.

Rather than clinging to the notion that methylfolate sensitivity is directly linked to COMT and somehow extending the definition to cover exceptional cases, maybe you should move away from the proposition altogether.

Methylfolate sensitivity has a more complex metabolic basis. Genetics may make a contribution, but it is nothing as crude as a direct consequence of a particular SNP.

What I would say to this in general is that she is purported to have treated many hundred patients with various SNPs and various symptoms.

To really evaluate her contribution, we would need to know how many people have tried her recommendations and had little or no help.

But setting that aside, I think we should separate the treatments from her claims about them.

She says treatments are directed at particular SNPs but where there are independent scientific studies into many of these SNPs, they just don't support her claims for what they supposedly do. Furthermore, a number of the SNPs she says she treats do nothing at all - eg MAO A R297R.

So I am left with the conclusion that when her treatments work, it is probably for reasons other than those she claims. This is hardly surprising since the treatments are very broad and general; giving a bunch of vitamins and minerals to a sick person could well hit on something helpful. The response doesn't have to be for the reasons she claims, it could just as easily be for some other reason.

On the other hand I recall Dr Jill James also making the same type of connections and I believe she has published her research regarding her findings with autistic kids, their sensitivities and also her findings on the type of SNPs they have so it isn't just Yasko that gives out this type of information.

I am not familiar with the work of Dr James. I don't have any problem with the notion that there are common metabolic disturbances leading to common sensitivities in autistic children and that maybe there are some genetic predisposing factors involved. This is a far cry from the direct linkage of symptoms and SNPs which Yasko proposes. It is the latter that I object to.

For me if I repeatedly react to a certain substance and I fit the Yasko explanation, then I fail to see why I should discount the theory even though others might disagree.

That is entirely your prerogative.

 

[alicec]

I am saying it makes more sense that they are only a problem (expressed) when your significantly ill already.

With regards to COMT it would depend on, if yasko is right, how ill you are, and how mutated they are.

So you are saying that all the people on PR, including myself, who are COMT +/+ and say they have no problems with methyl folate, are just not sick enough. If we wait and get sicker, we too will become sensitive to methyl folate.

Get a grip!

 

[Valentijn]

To really evaluate her contribution, we would need to know how many people have tried her recommendations and had little or no help.

It would be difficult to evaluate, since Yasko won't run trials. I signed up for her forum once, because I was curious to see if there was any explanations or debate regarding the science disagreeing with Yasko's claims. When finally approved to join, there was an automatic notification that the forum is only for discussing the implementation of the protocol, and disagreement with it and other negativity is not allowed.

That told me pretty much everything I needed to know about Yasko and her business.

 

[sb4]

So you are saying that all the people on PR, including myself, who are COMT +/+ and say they have no problems with methyl folate, are just not sick enough. If we wait and get sicker, we too will become sensitive to methyl folate.

Get a grip!

Not sure why you are getting so defensive. I'm simply saying that MAYBE environmental factors are more important than SNPs, only when you are ill/in a bad enviroment do they show up. I am not saying you are not ill enough, this is not a competition, I'm saying there could be other factors to why COMT isnot being a problem for you. Maybe your diet is helping, maybe other mutations, maybe you are getting more sun than other people which helps reduce norepinephrine.

I am not saying my position is 100% right and yours is 100% wrong!

 

[Valentijn]

Not sure why you are getting so defensive.

She wasn't being defensive ... she was attempting to explain why COMT almost certainly does not behave in the manner which was being ascribed to it by others. People are welcome to believe what they want, but I think it's important to point out when the science contradicts beliefs which they are attempting to spread to others.

I'm simply saying that MAYBE environmental factors are more important than SNPs, only when you are ill/in a bad enviroment do they show up.

This is quite a random and extremely unlikely thing to suggest, at least in the case of the SNPs under discussion. There is no scientific basis to believe such a thing, so it amounts to nothing more than mere whimsy, and isn't really helpful unless your intent is to start a properly conducted scientific study. But as it stands, it would not be at all applicable to treatment or diagnosis of anything at all.

Maybe your diet is helping, maybe other mutations, maybe you are getting more sun than other people which helps reduce norepinephrine.

In those cases, the SNPs involved would again be extremely irrelevant, if minor differences are capable of completely over-riding then. And again, it's highly implausible that factors are somehow interacting with or compensating for the SNP variants under discussion.

 

[sb4]

She wasn't being defensive ... she was attempting to explain why COMT almost certainly does not behave in the manner which was being ascribed to it by others. People are welcome to believe what they want, but I think it's important to point out when the science contradicts beliefs which they are attempting to spread to others.


This is quite a random and extremely unlikely thing to suggest, at least in the case of the SNPs under discussion. There is no scientific basis to believe such a thing, so it amounts to nothing more than mere whimsy, and isn't really helpful unless your intent is to start a properly conducted scientific study. But as it stands, it would not be at all applicable to treatment or diagnosis of anything at all.


In those cases, the SNPs involved would again be extremely irrelevant, if minor differences are capable of completely over-riding then. And again, it's highly implausible that factors are somehow interacting with or compensating for the SNP variants under discussion.

So your and her position is that SNPs barely matter at all?

Maybe I'm not great at explaining the science behind what I am saying but I know from my and others experience that environmental factors are far more important than SNPs, and my SNP problems only came after I got ill. I have COMT and MAO-A and definitely have problems with neurotransmitters, could be a coincidence, but if I'm right that they are only expressed in certain circumstances then many could have the same as me and be fine.
I have found IR light and SUN light to help significantly re leave symptoms. These 2 things increase mitochondrial efficiency and with that reduce expression of SNPs.

Here is a post from Jack Kruse that might help explain it better
"
Vitamin D is, from evolutionary and biological perspective is an endogenous neuro-hormone rather than a nutrient. It is very likely that ultraviolet light-initiated endogenous synthesis of vitamin D is safer than oral intake from a quantum perspective. SNP's are the most misunderstood thing in healthcare today because eno one has a quantum viewpoint in healthcare. All SNP's are a result of a change in the local zip code to optimize mitochondrial heteroplasmy. During most of human evolution, people spent considerable time outdoors and exposed to sunlight. Ultraviolet (UV) radiation in sunlight initiates the conversion of steroid precursors in the skin to vitamin D from sulfated cholesterol. People who live and work in sunny climates synthesize approximately 10,000-20,000 IU of vitamin D daily, which is approximately 50-100 times more than the recent U.S. gov- ernmental recommendation of 200 IU (5 mcg) daily for children and for adults up to age 50 years. These were recently elevated by the US but are still woefully low. Recommended levels increased modestly to 400 IU daily for people ages 51-70 years and 600 IU daily for people age 70 and older. If you are obese your ability to make is also lowered. No one altered their dosing and if you have dark skin you need even more vitamin D. No altered their dosing regimen. The body’s innate ability has a deep lesson for the quantum clinician. It can safely produce 10,000-20,000 IU of vitamin D daily. In fact, today I produced 411 IU per minute at my current location. When you consider our endogenous ability in conjunction with our evolutionary heritage from the East African rift zone, this data strongly suggests that this high saturation levels in the blood might be biologically optimal for health. Such a high level of vitamin D is capable of saturating the VDR receptor, and VDR polymorphisms remain of little consequence as long as high (historically normal) vitamin D levels are maintained. What happens when humans invent a modern world that disconnects them from the evolutionary history? Over the past 50,000 years, endogenous synthesis of vitamin D has become less reliable than in earlier times, a trend that has continued and even accelerated over the past century. Technology has steepened the slope of the deficit. Around 50,000 years ago, humans migrated away from the equator and became subject to significant seasonal variations in UV ray exposure and vitamin D synthesis. In addition, wearing more clothes, spending little time outside, wearing sun glasses and sun screen when out doors, and spending more time indoors at home, in offices, and in autos has also greatly limited exposure to UV rays and reduced vitamin D synthesis. There is also evidence that a major component of the modern diet–consumption of refined and whole grains–reduces which harbors high levels of bromine alters vitamin D metabolism in the skin by altering the dielectric constant in water in cells in our eyes and skin. As vitamin D synthesis has declined, the health risks related to VDR polymorphisms appear to have become more problematic. Recent research has identified numerous polymorphisms in the VDR associated with low vitamin D blood levels and an increased risk of disease. A high prevalence of VDR gene polymorphisms have been identified in people with osteoporosis, periodontal disease, type 2 diabetes, Addison’s disease, inflammation, psoriasis, and breast, prostate, and colon cancers. Indeed, the relation- ship between low vitamin D and cancer is so well established that there is widespread research on vitamin D analogs as chemo- therapeutic drugs. Low levels of vitamin D also have been found in people with type 1 diabetes, multiple sclerosis, and congestive heart failure, suggesting that VDR gene polymorphisms may be involved in these diseases as well. It is possible that modern increases in longevity, with subsequent increases in random age-related genetic mutations, amplifies the deleterious effects of VDR gene polymorphisms. https://www.jackkruse.com/time-10-can-you-supplement-sunlight/


Let me use an example here: A1298C. Aerose this SNP is an epigenetic modification for the environment your mitochondrial come from. All mitochondrial DNA comes from mom. Where mom comes from is coded for in your % heteroplasmy. Today’s modern humans who think they understand SNP’s will recommend taking supplements for this by itself. I won’t ever tell you that first. You need to move to an equatorial zone and see how you do then consider supplementation. Understanding quantum evolutionary health is the key in my opinion. A variety of genetic polymorphisms reduce the biological activity of folic acid and vitamin D pathways and increase the risk of specific diseases in humans. MTHFR defects are always linked to changes in environmental light exposure to sunlight. If you understand the linkage you might find out you don’t need a supplement. Extreme equatorial sunlight is well known to reduce folate in tissues. Normally this will reduce the amount of RBC’s in equatorial humans because we need folate’s to maintain them. Recall that RBC’s contain both porphyrins and hemoglobin. Both proteins absorb UV light. When you absorb a lot of UV light you also raise venous oxygen saturation so you do not need as much oxygen carrying capacity from hemoglobin. In this way the the homo defect of A1298C is a key "fuse switch" for an environment who has a lot of UV light and a lot of oxygen. This local environment would be close to the equator and at sea level next to a large amount of plants who are excellent photosynthetic yield. This ideal environment was found in human history from the East African rift zone and the exodus out of Africa to the Mediterranean basin. This is likely where you got this SNP. A 23andme test would tell you where your maternal DNA came from to give you a clue to this link to light and a high oxygen tension. People rarely realize that oxygen levels are ideal temperature sensors for a quantum biologist. Look up Harold Urey some day. You might learn something about our quantum ecosystems. Mitochondria use oxygen as its only terminal electron acceptor…….and that determines electron flow on the electron chain transport. There are places on Earth that call for these specific SNP’s to maintain mitochondrial DNA heteroplasmy at low rates. This is Doug Wallace’s basic research."

 

[Valentijn]

So your and her position is that SNPs barely matter at all?

Most SNPs don't matter at all. That is something which has been very well established. Thus it makes it rather silly to guess that a SNP is doing something significant when there is a lack of evidence to that effect, especially if there is research contradicting that guess. It is similarly nonsensical to create an elaborate explanation for a SNP having an effect sometimes, but not others. Either there is scientific evidence supporting such a proposition for that specific SNP, or people are engaged in making wild and baseless suppositions that are no more meaningful than attributing the behavior of a gene to the phase of the moon.

I have COMT and MAO-A and definitely have problems with neurotransmitters, could be a coincidence, but if I'm right that they are only expressed in certain circumstances then many could have the same as me and be fine.

There a lot of assumptions inherent in your statement. First that there actually is a problem with neurotransmitters. Have you had your blood values of those tested? Which ones are specifically out of range? What are the blood values for those neurotransmitters for a cohort of people with the same SNPs? If you're going to blame a common SNP for causing serious problems, these are very basic questions which first must be answered.

Here is a post from Jack Kruse that might help explain it better

"Jack Kruse says" is not a scientific authority any more than "Yasko says". I prefer citations to actual research, not to people with a dubious reputation.

 

[sb4]

There a lot of assumptions inherent in your statement. First that there actually is a problem with neurotransmitters. Have you had your blood values of those tested? Which ones are specifically out of range? What are the blood values for those neurotransmitters for a cohort of people with the same SNPs? If you're going to blame a common SNP for causing serious problems, these are very basic questions which first must be answered.


"Jack Kruse says" is not a scientific authority any more than "Yasko says". I prefer citations to actual research, not to people with a dubious reputation.

I haven't but I have symptoms of neurotransmitter issues. Big Insomnia problems, heart rate going real fast, wired tired. These are worse with even small amounts of SSRIs, methylfolate, CES, etc.

I am no longer concerned with somebody being a scientific authority. I care about does it make sense and does it work. Also there is data to back up UV and IR lights affects but I'm not sure about data on the SNP stuff.