Help me with my 23andme results

[Jonathan Edwards]

Rich's main idea was that the increased oxidative stress often hypothesized in ME (Pall et al) is caused by low intracellular glutathione.

He explained how the pathophysiology of ME could lead to a functional deficiency of (in particular) B12, leading to a hypoactive methylation cycle, in turn causing low glutathione.

I think his hypothesis was sound, but never proven. Please see his paper for a better understanding. It also discusses similarities between ME and autism. At least look at the theory before you dismiss it. Rich's hypothesis is an important part of PR history.

http://phoenixrising.me/research-2/...ue-syndrome-by-richard-a-van-konynenbury-ph-d

I think I have looked at this before. It is a long and rambling account of various suggested analogies and broad concepts but I cannot actually find a clear theory in it. I have tried to follow what van Konynenburg was saying on several occasions but it has always seemed to me that there are no plausible system dynamics to the theory. And the biochemical abnormalities that the theory is supposed to explain do not seem to be recognised as reproducible features of ME by the research community. I get the impression of an enthusiast with a brainstorm but not much more.

The fact that nobody on PR seems to be able to paraphrase what he said seems maybe relevant - maybe nobody quite understood how it hung together?

 

[Helen]

I would add these links to the one that @adreno posted. Rich pointed out that Dr. Neil Nathan and he had taken the clinical study as far as they could as they for different reasons couldn´t do it in a more scientific way that should be needed. He hoped that any ME/CFS researcher would go further.

FWIW Rich had received more than 200 Methylation Pathways Panels from people on PR and all but a few showed low reduced glutathione among other abnormal findings.

Open Medicine Institute announced earlier that they planned a " MTHFR, B12, folate trial". @Mark you posted about this, do you know how it goes?

 

[adreno]

I think I have looked at this before. It is a long and rambling account of various suggested analogies and broad concepts but I cannot actually find a clear theory in it. I have tried to follow what van Konynenburg was saying on several occasions but it has always seemed to me that there are no plausible system dynamics to the theory. And the biochemical abnormalities that the theory is supposed to explain do not seem to be recognised as reproducible features of ME by the research community. I get the impression of an enthusiast with a brainstorm but not much more. Combined with MTR/R and MTHFR defects, along with an unhealthy portion of environmental stressors (which deplete B12) might lead you into trouble.

The fact that nobody on PR seems to be able to paraphrase what he said seems maybe relevant - maybe nobody quite understood how it hung together?

I don't have the biochemical knowledge to discuss it in detail. The basics of Rich's protocol, as I understand it, is trying to optimize intracellular glutathione levels to ameliorate ROS. He tried using exogenous glutathione earlier on, but found it ineffective, and this lead him to the methylation cycle.

I would think that oxidative stress is a feature (rather than a cause) of ME, and trying to optimize antioxidant systems, including intracellular glutathione production, would be helpful, at least in terms of symptoms management. This makes ensuring intake of the basic nutrients necessary for the methylation cycle to run seem like a good idea to me.

Now, can you get these nutrients from foods? Perhaps, but that would depend on several factors, including your diet, genetic makeup and gastrointestinal health. For example, digestive problems could lead to poor uptake of B12. This, combined with mtr/r and mthfr defects, along with an unhealthy portion of environmental stressors might lead you into problems.

I know @alex3619 discussed these things with Rich and Pall, perhaps he has something to add.

 

[Valentijn]

I would think that oxidative stress is a feature (rather than a cause) of ME, and trying to optimize antioxidant systems, including intracellular glutathione production, would be helpful, at least in terms of symptoms management. That makes ensuring intake of the basic nutrients necessary for the methylation cycle to run seem like a good idea to me.

I think that was Rich's conclusion too, eventually, due to patients in his study as well as on the forum who were helped by B12 still being far from recovered. He was trying to figure out what was going on upstream, from what I recall, and how methylation/glutathione/B12 might be fitting into that.

He was very open-minded, even (especially) about his own theories.

 

[Sidereal]

Is there a relation between autism and methylation?

There is some evidence of this from the work of Dr Jill James (which Rich was influenced by).

http://www.ncbi.nlm.nih.gov/pubmed/15585776

Am J Clin Nutr. 2004 Dec;80(6):1611-7.
Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.
James SJ1, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA.
Author information

Abstract
BACKGROUND:
Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism.

OBJECTIVE:
The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism.

DESIGN:
Plasma concentrations of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children.

RESULTS:
Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children.

CONCLUSIONS:
An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.

 

[Helen]

He also began investigating the possible impact from mutations in the GST-genes (glutathione-s-transferase) as an decreased ability to conjugate also would be detrimental. There are some GST SNP´s that are analyzed in a 23andme test.

Quote: "There is a subset of PWMEs who have normal glutathione levels on the methylation pathways panel, but still have a partial methylation cycle block. I've had a small amount of data that suggests that these people may have SNPs in their GST enzymes, so that even though they have enough glutathione, they are not able to use it as well as normal to conjugate heavy metals, such as mercury, because the enzymes that normally do the conjugating have genetic problems.

I'd be interested in hearing more about how you have been able to stimulate your GST enzymes. I think that could be helpful for others who have this situation.

Best regards,

Rich "

 

[Hip]

I think I have looked at this before. It is a long and rambling account of various suggested analogies and broad concepts but I cannot actually find a clear theory in it. I have tried to follow what van Konynenburg was saying on several occasions but it has always seemed to me that there are no plausible system dynamics to the theory. And the biochemical abnormalities that the theory is supposed to explain do not seem to be recognised as reproducible features of ME by the research community. I get the impression of an enthusiast with a brainstorm but not much more.

The fact that nobody on PR seems to be able to paraphrase what he said seems maybe relevant - maybe nobody quite understood how it hung together?

Rich Van Konynenburg gives an overview of his ideas in this pdf document:

Application of the Yasko Protocol to the Treatment of Chronic Fatigue Syndrome, Rich Van Konynenburg

In that document (page 4) he states his hypothesis which he thinks may explain ME/CFS:

A chronic partial block of the methylation cycle, significant draining of folate from the cells, and a chronic depletion of glutathione.

However, my own guess is that Rich's hypothesis probably does not provide an explanatory mechanism for ME/CFS. Nevertheless, a partial block of the methylation cycle may be occurring in a subset of ME/CFS patients (as well as in a subset of the healthy population), and this block may be worsening their ME/CFS symptoms.

For example, if we assume a viral cause of ME/CFS, then a partial methylation block may hamper the antiviral/intracellular immune response, thereby worsening ME/CFS symptoms (and Rich speculated that this may be the case, as depletion of intracellular glutathione inhibits intracellular immunity).

Thus ME/CFS patients with this block may well benefit from taking methylation promoting supplements (ie, vitamin B12 and active forms of folate).

This partial methylation block, where it exists, is probably underpinned by certain SNPs in methylation-related genes, such as the MTHFR C677T.

And this is why I think it would be a good idea conduct a poll on ME/CFS patients who reported major benefits from taking methylation promoting supplements, to see if these patients have SNPs like MTHFR C677T which hinder methylation.

Although in my case, I have MTHFR C677T +/+ but have never found any benefit from the methylation protocol, in any of its variations.


In summary: while Rich's partial methylation block hypothesis may not provide the explanatory mechanism for ME/CFS, boosting methylation with B12 and active folate seems to help a subset of ME/CFS patients, and so this treatment just of itself can be examined empirically and statistically, independent of any theoretical hypotheses.

In other words, we can just give these methylation supplements to ME/CFS patients, and observe what percentage of patients improve on them.

That's not a poll of ME/CFS patients - it's a poll of forum users. And that particular subforum has a HUGE number of non-ME/CFS patients who come to discuss methylation.

It's possible that some non-ME/CFS patients may have voted in the poll. However, Rich's own informal study on 30 ME/CFS patients (see page 43 of the above-linked document) found a similar percentage (27%) of patients getting major improvements after three months on the methylation protocol:

Study Results at 3 months

• All 30 patients completed the study requirements at 3 months.

• 25 out of 30 patients reported improvement (83%).

• Among the group that reported improvement, 8 out of 30 reported marked improvement (27%).

 

[Jonathan Edwards]

It all seems very vague and disconnected to me. A redox shift was proposed as an explanation for rheumatoid arthritis in the 1970s but the idea never got anywhere because it was not specific enough. The same seems to apply here. There is not enough of a theory to make any useful predictions. And maybe it isn't a theory of ME anyway!

Supplements may be worth trying. But if they have the capability to have major effects on health one has to assume that might be both bad and good, so the ethical thing to do is a proper controlled trial with extended follow up. Anything else will not provide a clear answer and may expose people to health risks.

I don't think it would be much good polling people on PR because there will be major systematic bias in the way they respond if they already know their genotypes - it's called human nature.

 

[Hip]

I don't think it would be much good polling people on PR because there will be major systematic bias in the way they respond if they already know their genotypes - it's called human nature.

Yes that could be the case, though there are probably many patients on this forum who like myself tried the methylation protocol before they had their genotype determined; so we could restrict the poll to those people. It was only a couple of years ago that 23andme dropped their price to $99 (before that I believe it was $300), and this is when a lot more people, myself included, seemed to get their genotype determined.

Although many people when they get their genotype results seem to be clueless as to how to interpret them in the context of Yasko's theories (as I was myself when I first saw my SNPs). So that cluelessness may prevent bias.

 

[pogoman]

Although in my case, I have MTHFR C677T +/+ but have never found any benefit from the methylation protocol, in any of its variations.

from my case I believe if mitochondrial processes are weakened by whatever reason, they will not respond to methylation supplements very well.
have you had labs that indicated what body systems are not normal?
I was lucky enough that my labs clearly showed I had no inflammation, that ruled out alot of the more researched diseases like RA or lupus but pointed in a more obscure but smaller list of possibilities.

 

[starlily88]

I think I have looked at this before. It is a long and rambling account of various suggested analogies and broad concepts but I cannot actually find a clear theory in it. I have tried to follow what van Konynenburg was saying on several occasions but it has always seemed to me that there are no plausible system dynamics to the theory. And the biochemical abnormalities that the theory is supposed to explain do not seem to be recognised as reproducible features of ME by the research community. I get the impression of an enthusiast with a brainstorm but not much more.

The fact that nobody on PR seems to be able to paraphrase what he said seems maybe relevant - maybe nobody quite understood how it hung together?

I have tried on multiple occasions to be still my heart when I read your comments. As a Yale University Epidemiologist and Medical Study/Public Health Advocate I disagree with you, and find you truly short change people who have CFS.
First off ,Rich was an engineer, PhD in applied physical sciences, worked in nuclear materials and technology for 30 years, and studied CFS for 15 years.

So how he explained things might be a "biochemical abnormality" to you but not to me. Just because people
on PR don't respond to paraphase Rich - you think we don't "understand" how it hung together??
I suppose this is a polite way of saying that we are not smart enough to understand his chemistry.

This reminds me of the Cancer Doctor at Duke University on 60 minutes last week who was interviewed on
how he came to use Polio vaccine to invade cancer tumors. His lab biologist worked for 25 years to put polio into rats without causing polio. He came up with taking one branch of the polio and replacing it with the cold virus so the polio would not replicate.
The Oncologist at Duke said that he thought that his lab guy was crazy, he literally would not believe it.
So did the many other oncologists who now use HIV, Measles, Cold virus to treat dying cancer patients.

Do you remember years ago when all women with breast cancer had to have a mascectomy?
They removed all the muscles, tendons, everything - it was terrible. Then one little cancer researcher
realized that it was not necessary. It wasn't how much you took off, but where the cancer was and what kind it was, and if it had spread. He was totally ostracized - Not one doctor would talk to him, no one would dare fund him - he was laughed at by all doctors.

Then in 1975 -1985 he was allowed to run a 10 years study comparing women with breast cancer - 2 different treatments. After this doctor been shut out of medicine for years by the doctors who had so much to loose, the 10 year study showed that the total mascectomy did NOT extend life compared to those who had the other
treatment - so that was the end of total mascectomy. I am happy because I was allowed to get a lumpectomy for my breast cancer. Lucky me.

See Mr. Edwards - some of us on here, at least me, are not spring chickens anymore.
I have been sick with this for over 2 decades. Like the dying cancer patients I don't have time for 20 year placebo studies.Taking tiny amounts of B12 or Folinic acid is not the same thing as putting HIV into the brain tumor. You seem to get more bothered by the not so big conclusions of Dr. Amy Yasko and Rich than by
all those horrible oncologists putting HIV into little children's body - and still no double blind!!!
I worked at the National Institutes of Health for years. Many times, we stopped doing the double blind because it was not compassionate to let the people die for no reason.

When you have nothing else to loose, have absolutely no quality of life, can't shop, eat food, leave the house, do bills, do a job, visit parents, or drive it is unfair to hear one guy spouting off at how Rich is not "followable", not "reproducible" "no one can paraphrase him on PR" So what - he is just talking about what all the other guys talked about - B12 and Folinic acid. This is not Rocket science here. Just some supplements. It is just a chance for perhaps one person to feel better.

And he never ever said there was a similarity to autism, if you actually watch his 3 hour video in Sweden. He is quite up front, and quite logical on the biochemical makeup of why he came up with what he did.
I sent his studies to 3 researchers at Yale, Harvard, and Columbia Presbyterian. All three of them knew most of this already, and said it was fine for me to do. Actually they enjoyed Rich's thinking.

After years of trying to get glutathione into our bodies - Rich read Dr. Amy Yasko's study on autism. Coincidentally she had the very same problem. He used her solution for his new protocol in fact.
And of course Dr. Nathan used all of Dr. Amy Yasko's supplements for the 6 month study.

Rich was never ever ""an enthusiast with a brainstorm but not much more" as you say. To disparage an incredible scientist who helped move CFS research into a more scientific realm is disrespectful.
To reduce Rich's life's work to someone who had a "brainstrorm" strikes me as somewhat arrogant.

I say this to do no harm but to allow the members of PR who are so very sick to continue following the brave researchers and scientists who get little reward to help us, who unlike the HIV patients do not have an advocacy group nor funding. I say let us go forward with positive thoughts and much less negativity.

 

[Changexpert]

How is it possible to make a statement that SNP profile has no relationship to ME/CFS when this whole subject has been studied closely only for a short period of time? Remember the time when Dr. Marshall's idea of H. Pylori causing gastritis and eventually ulcer was dismissed by everybody in the medical community initially? To overcome the crowd's disbelief, Dr. Marshall had to ingest H. Pylori to make him infested, and gastritis developed within a week (1). Sometimes, it takes courage and extreme luck to find a solution to the unknown.

Given that there are so many SNP's with unknown effects and lack of consensus on how one SNP interacts with each other, it is a stretch to claim the relationship between methylation and ME/CFS. However, it is just as a big stretch to claim that such relationship does not exist when not all data has been accumulated and analyzed. Only God knows how long it will take for this jumbo mumbo to be truly meaningful (or completely irrelevant) in treating certain medical conditions.

Also, always remember nature vs nurture when it comes to health issues. Even though many members on PR are passionate about studying methylation and "suggesting medical advice" (never provide medical advice without relevant license), nobody knows what exactly happened in your life. Heck, maybe you don't even fully realize or understand what happened in your life and how they connected dots to result in where you are now.

My guess is that a lot of people on this forum are seeking for help because of not only some kind of genetic defect, but also some combination of accidents/trauma/poor habit/malnutrition/lifestyle that have occurred in the past. SNP profile is only half of the puzzle. Do not become blinded by SNP profile, but rather take it as a guideline to predict and analyze what supplements would work better for you. I have yet to see two people with exactly same SNP profile with identical treatment, protocol, and lifestyle on this forum. I doubt that will ever happen in the time we live in unless human genetic replication for lab testing becomes legal and supported. Please take this opportunity to understand the connection between your past, present, and what you were born with rather than waiting for other people to catch a fish for you.

 

[adreno]

I agree that functional tests are more likely to point to effective treatment at this point. Rich relied on functional methylation test to guide him. I don't think he recommended the 23andme test to anyone.

SNP panels are nice theoretically, but trumped by functional panels, which shows how those genes pan out in real life. SNP panels do not account for epigenetics.

 

[Jonathan Edwards]

I am sorry to sound negative, but science is all about putting up a hypothesis and then testing it by trying to knock it down. (Nothing ever gets 'proven' the best is to stand up to challenge.) I am equally critical of mainstream views on immunology or physiology that do not seem to me to hold up.

The SNPs people discuss have been looked at in CFS/ME and there is no obvious over-representation as far as I can establish. They are very common in healthy people so it is unlikely that they have a causal role in ME. That hypothesis does not stand up because we have data that is inconsistent.

It might be that once you have ME that feeling well depends to some extent on optimising your B12 and folate metabolism. If you have a bad knee, feeling well depends to an extent on keeping slim and fit. But my impression is that we do not know enough to know the significance of the SNPs in this context so one might as well do without them.

What worries me here is that people tend to interpret biochemical pathway information in terms of what the homeopaths might call a 'narrow allopathic view'. I am not a fan of hoeopathy. However, I do agree that too often conventional doctors tend to think 'oh, this is too low, we need something to make it higher' (or vice versa). Vaccination showed that sometimes the treatment looks like the disease, not the opposite. Giving insulin to lower blood sugar in an obese diabetic just makes them more obese. Dr van Konynenburg was himself interested in the complexity of the pathways, and proposed a vicious cycle loop. But I don't see his theory addressing the complexity enough. If there is a vicious cycle then one huge dose of B12 and folate should solve the problem - continuous usage does not make much sense.

The reason why good conventional medicine is not in fact 'narrow allopathy' is that it requires that even if you have a theory about what ought to work you have to test that theory in a reliable enough way to publish it. You may find, as was the case for giving protein to nephrotic patients with low protein, that it actually makes them worse. So the approved treatment is to NOT give protein. So far I am not aware of anything based on SNPs in ME that indicates that we know what benefit or otherwise you really get. So advising people on protocols according to SNPs seems to me to be unjustified.

 

[renerdrat]

lol this thread was totally hijacked.... into why 23andme and your mthfr status is important or not, I feel like no one actually helped OP much at all.

 

[Jonathan Edwards]

lol this thread was totally hijacked.... into why 23andme and your mthfr status is important or not, I feel like no one actually helped OP much at all.

I thought Valentijn gave a very clear explanation. Is it not helpful to know that there is no agreement about whether these tests are of any use to cas0620?

 

[Hip]

Hi everyone! New to the forums and excited to get to know all of you and learn more. I uploaded my 23andme results into nutrahacker and livewello today but I'm still pretty confused. Can anyone explain some of the snps and mutations to me in layman's terms? Thank you!

If @cas0620 would like an interpretation of her SNPs for methylation protocol purposes, then the links and documents @caledonia has provided on this page may be helpful.