Bill Walsh Finally Explains Over-Methylation In A Way I Can Understand

[caledonia]

Folks, I haven't really heard of Bill Walsh using acetyl named supplements to balance acetylation in neurotransmitters. I've read his book, Nutrient Power and from what I remember he uses more core/basic supplements like various minerals or B vitamins (or in certain cases, not using folate).

I do suggesting consulting with a Walsh practitioner if these are major issues for you, instead of guessing what supplements to take. They do very specific lab tests to determine what supps are right for each person.

 

[Kimsie]

This applies to people whose main problem is mental health issues.

I've always had trouble with the concept of what Walsh calls over methylation. It's actually something way different than I thought it was.

In his recent Youtube video, Bill Walsh explains that there are two SNPs affecting SAMe - AGAT and GAMT. These are upregulations which cause too much SAMe (the final donor of methyl groups for methylation).

{...}

I have been reading Dr. Walsh's book the last couple of days and I think he has some really good ideas. This is the first time I have felt that anyone said anything about over or undermethylation that made any sense. However, he is talking mainly about the state of methylation of the histones, which I had not heard of before, not methylation in general.

I don't understand why AGAT and GAMT would cause too much SAMe and although I might watch the video, I wonder if anyone can tell me about where in the video he talks about this is so I can go right to it. The synthesis of SAMe is normally regulated (slowed) by inhibiting MTHFR and upregulating CBS and that sort of thing and I don't see how GAMT or AGAT would have any effect.

 

[Kimsie]

I have been reading Dr. Walsh's book the last couple of days and I think he has some really good ideas. This is the first time I have felt that anyone said anything about over or undermethylation that made any sense. However, he is talking mainly about the state of methylation of the histones, which I had not heard of before, not methylation in general.

I don't understand why AGAT and GAMT would cause too much SAMe and although I might watch the video, I wonder if anyone can tell me about where in the video he talks about this is so I can go right to it. The synthesis of SAMe is normally regulated (slowed) by inhibiting MTHFR and upregulating CBS and that sort of thing and I don't see how GAMT or AGAT would have any effect.

Never mind, I found the spot at about minute 38. I still question whether this could be the cause of overmethylation, though, since as far as I can see SAMe is regulated by factors completely unrelated to these enzymes and if the enzymes are not working well, the body will simply make less SAMe. I am still holding to my former idea that overmethylation is simply a lack of niacin or niacinamide in the body, which I can explain in my hypothesis by the need for the body to have a larger NAD pool. This fits in very well with Dr. Walsh's idea that niacinamide helps overcome overmethylation.

However, I really like Dr. Walsh's ideas about the cause of undermethylation and I feel it is very, very relevant for those who are undermethylators, which includes both of my sons. My son with depression, D, had fatigue until he started taking large doses of folate. Then after about 6 weeks on the folate he began to gradually become depressed. If Dr. Walsh is correct, then my other ideas about how the folate made him depressed are wrong and I have to revise parts of my hypothesis to include Dr. Walsh's ideas, which I am in the process of doing and I will be posting on it in a new thread pretty soon but right now I am still studying his materials and book and thinking it all through.

 

[caledonia]

I have been reading Dr. Walsh's book the last couple of days and I think he has some really good ideas. This is the first time I have felt that anyone said anything about over or undermethylation that made any sense. However, he is talking mainly about the state of methylation of the histones, which I had not heard of before, not methylation in general.

I don't understand why AGAT and GAMT would cause too much SAMe and although I might watch the video, I wonder if anyone can tell me about where in the video he talks about this is so I can go right to it. The synthesis of SAMe is normally regulated (slowed) by inhibiting MTHFR and upregulating CBS and that sort of thing and I don't see how GAMT or AGAT would have any effect.

AGAT and GAMT are upregulations. So even if MTHFR is slowing things down, there will still be a speed up at SAMe.

 

[Kimsie]

AGAT and GAMT are upregulations. So even if MTHFR is slowing things down, there will still be a speed up at SAMe.

You are misunderstanding what he was saying. He said that the AGAT and GAMT are downregulations that cause the body to use less SAMe (because GAMT uses SAMe and AGAT makes the substrate for GAMT) and therefore there is "extra SAMe looking around for something to methylate."

This doesn't make any sense because when SAMe levels rise it attaches to MTHFR and stops it from working and there are a couple of other ways high levels of SAMe slows the synthesis of SAMe. In other words, there is a feedback regulation for SAMe that has at least 2 or 3 backup ways to slow SAMe production when it gets high. People who have GAMT deficiency, which is an actual illness, don't have elevated methionine or SAMe levels.

It looks to me as if what is referred to as overmethylation is not a general overmethylation, but overmethylation of the histones, which leads to higher amounts of serotonin, dopamine and norepinephrine in the synapses of the neurons. This is not caused by too much SAMe, but by other factors. I am studying this to try to get a better idea of what these factors might involve.

I think Dr. Walsh's ideas about the state of methylation of the histones is probably correct and his ideas about treatment are very helpful, but not all of his ideas about what is causing it are correct. This is true of my own ideas, too (they are not all correct), and I am having to revise my own ideas again now to include what I have learned from Dr. Walsh's ideas, and I have to revise them pretty often as I learn more and more.

 

[Kimsie]

You are misunderstanding what he was saying. He said that the AGAT and GAMT are downregulations that cause the body to use less SAMe (because GAMT uses SAMe and AGAT makes the substrate for GAMT) and therefore there is "extra SAMe looking around for something to methylate."

This doesn't make any sense because when SAMe levels rise it attaches to MTHFR and stops it from working and there are a couple of other ways high levels of SAMe slows the synthesis of SAMe. In other words, there is a feedback regulation for SAMe that has at least 2 or 3 backup ways to slow SAMe production when it gets high. People who have GAMT deficiency, which is an actual illness, don't have elevated methionine or SAMe levels.

It looks to me as if what is referred to as overmethylation is not a general overmethylation, but overmethylation of the histones, which leads to higher amounts of serotonin, dopamine and norepinephrine in the synapses of the neurons. This is not caused by too much SAMe, but by other factors. I am studying this to try to get a better idea of what these factors might involve.

I think Dr. Walsh's ideas about the state of methylation of the histones is probably correct and his ideas about treatment are very helpful, but not all of his ideas about what is causing it are correct. This is true of my own ideas, too (they are not all correct), and I am having to revise my own ideas again now to include what I have learned from Dr. Walsh's ideas, and I have to revise them pretty often as I learn more and more.

I took a closer look at the article I linked to above, and there is something else that can increase SAMe levels. It's when a person has less GNMT activity. I'm going to check this out more because glycine is something that is heavily involved in my hypothesis about these illnesses.

Edit: It looks like if a person has less function of this enzyme they have high methionine so has anyone here had their methionine levels tested who also feels they are in the overmethylation category? Another possibility is low glycine levels. Does anyone who is overmethylated have low glycine?

 

[caledonia]

You are misunderstanding what he was saying. He said that the AGAT and GAMT are downregulations that cause the body to use less SAMe (because GAMT uses SAMe and AGAT makes the substrate for GAMT) and therefore there is "extra SAMe looking around for something to methylate."

This doesn't make any sense because when SAMe levels rise it attaches to MTHFR and stops it from working and there are a couple of other ways high levels of SAMe slows the synthesis of SAMe. In other words, there is a feedback regulation for SAMe that has at least 2 or 3 backup ways to slow SAMe production when it gets high. People who have GAMT deficiency, which is an actual illness, don't have elevated methionine or SAMe levels.

It looks to me as if what is referred to as overmethylation is not a general overmethylation, but overmethylation of the histones, which leads to higher amounts of serotonin, dopamine and norepinephrine in the synapses of the neurons. This is not caused by too much SAMe, but by other factors. I am studying this to try to get a better idea of what these factors might involve.

I think Dr. Walsh's ideas about the state of methylation of the histones is probably correct and his ideas about treatment are very helpful, but not all of his ideas about what is causing it are correct. This is true of my own ideas, too (they are not all correct), and I am having to revise my own ideas again now to include what I have learned from Dr. Walsh's ideas, and I have to revise them pretty often as I learn more and more.

I'll have to recheck that again to understand it thoroughly. There were also a couple of functional situations he listed (beyond those SNPs) that would cause a problem with SAMe. So you could have the functional issues or the SNPs or both causing overmethylation problems.

 

[ppodhajski]

SAM is used by several methyltransferases, like COMT and HNMT, to degrade catecholamines (serotonin, dopamine, epinphereine). It makes sense that if SAMe si too high or low you can have mood issues. Note the MT on the end of those genes stands for methyltransferase.

https://en.wikipedia.org/wiki/DNA_methyltransferase

There are a lot of ways one can be low in SAM. A low methionine diet is one, or any slow enzymes (SNPs) in the methionine cycle will do it as well.

 

[PeterPositive]

SAM is used by several methyltransferases, like COMT and HNMT, to degrade catecholamines (serotonin, dopamine, epinphereine). It makes sense that if SAMe si too high or low you can have mood issues. Note the MT on the end of those genes stands for methyltransferase.

https://en.wikipedia.org/wiki/DNA_methyltransferase

There are a lot of ways one can be low in SAM. A low methionine diet is one, or any slow enzymes (SNPs) in the methionine cycle will do it as well.

Wouldn't a test for homocysteine level give an indication of methionine insufficiency?

E.g. in my case I have low SAM-e but high Hcy, suggesting methionine is not the limiting factor.

 

[ppodhajski]

Wouldn't a test for homocysteine level give an indication of methionine insufficiency?

E.g. in my case I have low SAM-e but high Hcy, suggesting methionine is not the limiting factor.

HCY test would just measure where in the cycle you are stuck. If you are B2, B12, or Zinc deficient this would stop you from recycling methionine. Add a N6 deficiency and your HCY is higher, Eating more methionine would just make HCY higher.

 

[PeterPositive]

HCY test would just measure where in the cycle you are stuck. If you are B2, B12, or Zinc deficient this would stop you from recycling methionine. Add a N6 deficiency and your HCY is higher, Eating more methionine would just make HCY higher.

What is N6?

 

[ppodhajski]

What is N6?

Sorry, that was supposed to be B6

 

[Johnmac]

@caledonia, wish it was possible to like your original post multiple times! Thank you for posting this!

Money quote for me: "you have to balance methyl groups with acetyl groups in order to balance reuptake of neurotransmitters".

IMO this would explain the oft-discussed mind/body connection, and also explain why so many of us seem to do well physically with a methylation protocol, but we reach a plateau. And in the long run something seems to be lacking. We have better physical health and energy, but overall still seem to be somewhat dragging.

I recently had a really good experience using choline, ALC, and some other things that address neurotransmitter production and function. For several weeks I found myself with mental processes that startlingly matched the physical health and energy I'd found over the last year with @Freddd's methylation protocol. One fine day during those few weeks I did about 7 hours' housework in the same day without getting frustrated, bored, sore, or crashing physically or mentally. It was like I was 20 years younger.

Maybe a missing bit for many of us is targeting our neurotransmitters with supplements in the same way we're targeting snps and physical health.

Just thinking out loud. Thanks again for the original post!

@whodathunkit:
So did you work out how to make the gains continue? I too have had lots of big gains from the FP - which don’t last.

 

[ahmo]

@Johnmac Awhile back, on a thread about supplements, alex speculated that there's some mechanism that keeps pulling us back to some new (unwell) equilibrium. A very rough paraphrase. I wouldn't say that my gains haven't lasted, but there is a distinct ceiling on my cognitive and physical energies, that I've been unable to transcend. I shifted my focus to feeding the mitochondria and avoiding peroxynitrite with antioxidants. And choline is a big ingredient in mitochondrial health.

 

[Dreambirdie]

@Johnmac Awhile back, on a thread about supplements, alex speculated that there's some mechanism that keeps pulling us back to some new (unwell) equilibrium. A very rough paraphrase. I wouldn't say that my gains haven't lasted, but there is a distinct ceiling on my cognitive and physical energies, that I've been unable to transcend. I shifted my focus to feeding the mitochondria and avoiding peroxynitrite with antioxidants. And choline is a big ingredient in mitochondrial health.

Hello @ahmo 2 questions...

What are you using specifically to "feed" the mitochondria? Do you mean like the Wahl's diet?

And what does "avoiding peroxynitrite with antioxidants" mean? Can you spell that out for me, please.

thnx

 

[ahmo]

@Dreambirdie I'm linking to some excellent mito threads. I think the correct fatty acids are pretty central, eg. phos choline. I'm sure the Wahl diet is a good baseline.

Peroxynitrite is from Martin Pall's work on the nitric oxice cycle, NO/ONOO. There are 2 links in my signature. Central to this is antioxidants, listed in the last 20" of his vid.

I've added various antioxidants this year, beginning w/ astaxanthine and resveratrol; olive leaf extract or tea, green tea. Most recently I added bilberry, French Melon, which is supposed to help w/ SOD, and acai. I don't experience any difference from the Fr. melon compared to the others, my body seems to prefer acai. I also eat a lot of carrots, w/ antioxidant properties. My body seems to prefer food-based antioxidants.

http://forums.phoenixrising.me/index.php?threads/reverse-mitochondrial-damage-101.28175/

Mitochondria 101 Part 2
http://forums.phoenixrising.me/index.php?threads/mitochondria-101-part-2.29249/#post-446295

Poisoning the Mitochondria

http://forums.phoenixrising.me/index.php?threads/poisoning-the-mitochondria.27790/

http://phoenixrising.me/archives/19805

Mitochondrial Dysfunction

http://forums.phoenixrising.me/index.php?threads/mitochondrial-dysfunction.12947/

http://forums.phoenixrising.me/index.php?threads/resveratrol-mitochondria.25884/

This is from a press release for Sarah Myhill's book last year:

http://forums.phoenixrising.me/index.php?threads/dr-myhill-publishes-new-book.29377/#post-448553
Diagnosis & Treatment of Chronic Fatigue Syndrome - it’s mitochondria not hypochondria’
by Dr Sarah Myhill
CFS is all in our cells, not in our minds!
Dr Sarah Myhill has treated over 5,000 patients with CFS since qualifying from Middlesex Hospital Medical School in 1981. She is now one of the leading authorities on Chronic Fatigue Syndrome (CFS) in the UK. As she emphasises, CFS is not a diagnosis but a clinical picture that has many causes, and her book, Diagnosis & Treatment of Chronic Fatigue Syndrome, looks at the underlying nutritional, biochemical, immunological, toxic, hormonal, and lifestyle mechanisms that cause the symptoms, collating many years of research and revealing that CFS is a result of mitochondrial failure.

Dr Myhill clearly explains what mitochondria are, the importance of the job they do and how failure can arise. Their key role is to supply energy to every cell in our bodies in the form of a chemical compound called adenosine triphosphate (ATP). ATP is known as the ‘universal currency of energy’; it is essential for all sorts of biochemical jobs, from muscle contraction to hormone production. When mitochondria fail this results in a poor supply of ATP (i.e. energy); consequently, cells go slow, which means that all bodily functions go slow. What is exciting, as the book describes, is the research conducted by Dr Myhill, withDr John McLaren-Howard of Acumen Laboratory and Dr Norman Booth of Mansfield College Oxford, which supports an objective ‘ATP Profile Test’ that correlates with subjective experience of fatigue. This test can now measure the rate at which ATP is made and also looks at where the problem behind poor function lies.
In Diagnosis & Treatment of Chronic Fatigue Syndrome Dr Myhill reviews the clinical picture of CFS and uses a really simple analogy throughout, likening bodily functioning to what a car needs to work properly:
• Engine = Mitochondria * Accelerator pedal = thyroid
• Fuel = Diet and function * Oxygen = lungs
• Gearbox = Adrenals * Service and repairs = Sleep
• Cleaning – oil = Antioxidants * Cooling system = Detoxification
• Driver = The brain
Dr Sarah Myhill says: ‘My book Diagnosis & Treatment of Chronic Fatigue Syndrome is based on years of scientific evidence and clinical experience. Finding a test that can now measure fatigue that is based on solid scientific evidence has allowed me to write this book. My treatment package works and again is based on scientific evidence. For CFS sufferers it’s about re-laying good “foundations” that can actually work for anyone who wants to have good health’.
Dr Myhill’s treatment plan is based on 5 key pillars which she explains in detail in her book:
Rest & pacing: By this Dr Myhill really does mean complete rest - no reading, computers, TV or noise – and she talks about doing things in short bursts and varying activity as energy returns. She advocates simplifying your life, asking others for help and doing things by the clock, as the body likes things to happen (especially sleeping and eating) at certain regular times.
Stone Age diet: Diet is the fuel in the tank and Dr Myhill recommends eating a Stone Age diet, saying: ‘Modern studies of ancient tribes who continue to eat a Stone Age (Paleolithic) diet show that these people do not suffer from diabetes, obesity, heart disease or cancer.’ The book outlines the principles of this diet and how to put it in place, including low ‘glycaemic index’ foods as well as foods that are chemical and allergen free. Her book gives a clear list of what you can eat (e.g. meat, salads, root vegetables, eggs, fishes, green vegetables and all herbs, seeds, certain spices and low carbohydrate fruits such as berries) and when. A suggested menu is also included with daily dietary suggestions.
Nutritional supplements: Dr Myhill confirms that taking nutritional supplements is essential in the 21st century and outlines the rationale for this. She recommends a daily programme that includes the multi-mineral mix (MMM) that she has developed herself, with no bulking agents or preservatives, vitamins D and B12, plus an omega-3 supplement high in the essential fatty acid EPA, such as Igennus’s Vegepa, or Biocare’s MicroCell Essential Fatty Acids for vegetarians, with a high dose of vitamin C in the evening. MMM contains essential minerals such as calcium, zinc, potassium, iron, manganese, iodine boron magnesium, selenium and chromium.
Adequate sleep: This, she says, is essential for life, recuperation and repair and she sets out the key rules that we should pay heed to: we need more sleep in winter than summer and one hour’s sleep before midnight really is worth two after because growth hormone (needed for bodily repair) is produced only during the hours of sleep before midnight. The book is full of tips on how to get the best night’s sleep and explains that many people have disturbed sleep because of hypoglycaemia – a crash in blood sugar during the night that puts the body into stress mode; adopting the Stone Age diet will put a stop to this.
Chemical check up: The book looks at toxins the body produces (especially free radicals) and also toxins that the body is exposed to, such as dental amalgam, air pollution, indoor pollution, silicone implants, smoking, pesticide residue in food, hair dyes and also occupational exposure for people like farmers, firemen, aviation staff and war veterans. It looks at toxic stress and highlights the benefits of antioxidants, chelation therapy and far-infrared sauna-ing as approaches to detox.
Diagnosis & Treatment of Chronic Fatigue Syndromeis an easy to read self-help book based on years of clinical experience and supported by evidence-based research. Written in a clear, logical and concise way, the book is full of practical, comprehensive, step-by-step solutions for patients, and is equally a ‘must read’ for doctors and other health professionals as it provides a detailed treatment solution with an evidence-based approach.
‘Diagnosis & Treatment of Chronic Fatigue Syndrome - - it’s mitochondria not hypochondria’ - £14.99 (print) and £7.50 (ebook) from www.hammersmithbooks.co.uk. Launched 5 April 2014 in print and for Kindle, Nook, Kobo and ipad.
Dr Sarah Myhill’s biog
Dr Myhill has worked in the NHS and private practice since qualifying from the Middlesex Hospital Medical School in 1981 (medicine with Honours). For 17 years she was the Honorary Secretary of the British Society for Ecological Medicine (renamed from the British Society for Allergy, Environmental and Nutritional Medicine), a medical society interested in looking at causes of disease and treating through diet, vitamins and minerals and through avoiding toxic stress. She helps run, and lectures at, the Society’s training courses and lectures regularly on organophosphate poisoning, the problems of silicone, CFS and so on. Dr Myhill is fully media trained and has had many appearances on TV and radio. She is also a founder member of OPUS (organophosphate users support group) – a charity to help sufferers of pesticide poisoning.

 

[Dreambirdie]

Thanks @ahmo That will keep me busy for a while!

 

[South]

Well I'm glad some people understand Walsh's explanations. I'll have to watch this thread or future threads about it until it can be simplified though, none of it makes any sense to me still.

 

[Johnmac]

@Johnmac Awhile back, on a thread about supplements, alex speculated that there's some mechanism that keeps pulling us back to some new (unwell) equilibrium. A very rough paraphrase. I wouldn't say that my gains haven't lasted, but there is a distinct ceiling on my cognitive and physical energies, that I've been unable to transcend. I shifted my focus to feeding the mitochondria and avoiding peroxynitrite with antioxidants. And choline is a big ingredient in mitochondrial health.

Sorry @ahmo - just saw this for some reason.

I've managed to prevent the reversals of gains this time, by simply following the protocol (d'oh). The main thing has been to ramp up doses once gains start to melt away (as Freddd recommends). That's resulted in some great progress. (I was barely functional 3 months ago - now I can work full time.)

I wonder if this could be relevant to the slide back into depression by @Kimsie's son (above). Freddd lists "reappearance of old symptoms" at the top of his list of paradoxical folate deficiency symptoms - i.e. the symptoms you get if you don't keep increasing doses.

I don't know how well this approach works for others, but it does work for me.

 

[Kimsie]

Sorry @ahmo - just saw this for some reason.

I've managed to prevent the reversals of gains this time, by simply following the protocol (d'oh). The main thing has been to ramp up doses once gains start to melt away (as Freddd recommends). That's resulted in some great progress. (I was barely functional 3 months ago - now I can work full time.)

I wonder if this could be relevant to the slide back into depression by @Kimsie's son (above). Freddd lists "reappearance of old symptoms" at the top of his list of paradoxical folate deficiency symptoms - i.e. the symptoms you get if you don't keep increasing doses.

I don't know how well this approach works for others, but it does work for me.

Hi Johnmac,I have finally come to realize that the reason that folate causes depression in my son is because high dose folate can greatly increase the capacity to synthesize glycine through the SHMT enzyme. This would be complicated to explain completely here, but I will probably explain why I believe this happens in another post, but not quite yet. The upshot is that taking large doses of folate creates a black hole for B6 and zinc in my sons because it supplies glycine which feeds the metabolic pathway which is draining the B6 and zinc.

The "reappearance of old symptoms" that you are talking about, in which a person continually needs to increase the dose, or in many cases simply means that when a person takes a supplement or supplements that are helping they often only work for a limited time and the person gets the symptoms back again - I believe that this is because what is actually happening is that the person's body is compensating for something abnormal that is going on by making changes in genetic expression and upping the dose of the supplements pushes enzymatic pathways so that these changes in genetic expression are overcome until the body has time to adjust the enzymes in those pathways back to where it is compensating for the something abnormal . The something abnormal isn't causing perceptible symptoms, it's the compensation that causes distressing symptoms. If the person is very low on whatever is supplemented, then this process can go on for quite a while with small increases in doses of the supplements, but if they are not low, it takes a large dose of the supplement to have an effect and eventually they reach a point where the dose is so high that it doesn't work any more - this has been our experience.

If the something abnormal that the body is compensating for is a deficiency of one of the supplements that the person is taking, then gradually raising the levels of that supplement will eventually have a lasting effect when the person reaches the level of supplementation where that vitamin or other substance is no longer deficient.