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

[caledonia]

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).

Sterling's app pulls up GAMT. AGAT is not available via 23andme (at least not the V chip 3, which is what I have).

There can also be arginine or glycine deficiency, CBS issues, or methyltransferase SNPs. (I'm not sure which or what methyltransferase he's referring to.)

These can all cause overload of SAMe - i.e. overmethylation.

In addition, you have to balance methyl groups with acetyl groups in order to balance reuptake of neurotransmitters. The relative levels of neurotransmitters are not nearly as important as the reuptake functioning.

This is why some of his treatment suggestions seem contradictory. Some people need to avoid folate or it will increase reuptake of serotonin (opposite of what an SSRI does), even though you're producing more serotonin. This will make less serotonin available in the long run, and make you feel worse. The same applies to dopamine and other neurotransmitters.

He is now also acknowledging the existence of methylfolate and recommends it for those with MTHFR (previously he only used or avoided folic acid).

If a person wishes to try out Walsh's treatment, they should find themselves a Walsh practitioner. He is just starting to train practitioners and there are now 200 of them. http://www.walshinstitute.org/

Here's the video:

https://www.youtube.com/watch?v=W14kkO61Ano

 

[NilaJones]

I don't do well with videos, but I know many folks here love them, so I am glad you posted .

Does he say something that is relevant to how folks like you and I, who cannot tolerate larger doses of b12, might alter that?

 

[musicchick581]

Nila, you can take a different form of b12. Generally, folate is avoided with Undermethylators And taken for overmethylation.

 

[beaverfury]

This is very interesting, @caledonia

He has a behavioural profile for undermethylators. Most of these used to fit me quite well.

At 1:29:00 , he is suggesting that some undermethylators may not benefit from methylfolate.
He says ' folates also incease gene expression of SERT transport proteins, resulting in reduced serotonin neurotransmission'.

And ' most undermethylated depressives with low serotonin activity are intolerant to folates'.


On his site he suggests that undermethylators may be deficient in calcium, magnesium, vitamin b 6, methionine.
I found this on pubmed. I wonder what effect straight supplementation of methionine would have in me/cfs.
No doubt thousands have tried it to no effect.

http://www.ncbi.nlm.nih.gov/pubmed/16306417?dopt=Abstract&holding=npg

'Methionine might also be essential to reversing damaging methylation of glucocorticoid receptors caused by repeated stress exposures, with implications for depression.

 

[beaverfury]

There is a thread here where @Adster is posing the same question.

http://forums.phoenixrising.me/inde...6-b12-mfolate-supplimentation-vs-sam-e.11822/

 

[PeterPositive]

Nila, you can take a different form of b12. Generally, folate is avoided with Undermethylators And taken for overmethylation.

It should be the other way around.

 

[caledonia]

@beaverfury I haven't really heard of people trying methionine. I think it's a newer supplement and on the expensive side.

Yasko's Holistic Health All in One Multi has folate, B12, methionine, and SAMe - basically taking you all the way around the cycle with precursors for methyl groups. I'm doing well with it, although I'm only taking a teeny amount.

When I read his book, Nutrient Power, I fit descriptions for over and undermethylators equally well. On the boiled down list in this video, I look much more like an overmethylator.

Now to check my GAMT SNPs and report back....

The ones Sterling's app pulls are
GAMT rs17851582 A = +
GAMT rs55776826 T = +

Hmmmm, I'm +/- for both of those...so perhaps his personality descriptions are at least somewhat accurate after all. (Assuming Dr. Walsh is looking at the same GAMT SNPs.)

I don't have depression though, so I don't think it's anything to worry about.

 

[caledonia]

I don't do well with videos, but I know many folks here love them, so I am glad you posted .

Does he say something that is relevant to how folks like you and I, who cannot tolerate larger doses of b12, might alter that?

Walsh doesn't say anything about not tolerating B12.

You could possibly try Ben Lynch's suggestions for not tolerating methylfolate. There is a shortcut CBS protocol mentioned (although he doesn't call it by that name specifically). His liposomal glutathione might be helpful to get you over the hump of methylation startup where glutathione will drop lower. Potassium deficiency could be another issue.

He does say his suggestions also apply to methylation in general, so that would, by definition, include B12.
http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/

 

[picante]

In addition, you have to balance methyl groups with acetyl groups in order to balance reuptake of neurotransmitters. The relative levels of neurotransmitters are not nearly as important as the reuptake functioning.

Oh my! I did not know this. I found these snps in my 23andme data:

NAT2 G590A (R197Q) rs1799930 AA +/+
NAT2 C282T rs1041983 TT +/+
​

Here is one thing I found about these NAT2 genes:

“We identified an 'ultra-slow' acetylator phenotype based on combined *6A/*6A, *6A/*7B and *7B/*7B genotypes containing the homozygous minor alleles of C282T (rs1041983, *6A, *7B) and G590A (rs1799930, *6A).”
http://www.ncbi.nlm.nih.gov/pubmed/24221535​

Would this indicate a need for acetyl groups, @caledonia? I've been taking both MeB12 and Mefolate. And I've had quite the slowdown in brain function -- I get groggy and bloated every time I eat. It feels like someone drugged me. I was assuming it was an ammonia problem, since my urine smells really strong.

I presume that these snps have been expressed most of my life. The reason: caffeine has never had any effect on me. I hate coffee, but I can drink tea or eat dark chocolate, even before bed, with zero effect.

The rest of the NAT1 and NAT2 snps on my MTHFRsupport report are -/-.

​

 

[caledonia]

Oh my! I did not know this. I found these snps in my 23andme data:

NAT2 G590A (R197Q) rs1799930 AA +/+
NAT2 C282T rs1041983 TT +/+
​

Here is one thing I found about these NAT2 genes:

“We identified an 'ultra-slow' acetylator phenotype based on combined *6A/*6A, *6A/*7B and *7B/*7B genotypes containing the homozygous minor alleles of C282T (rs1041983, *6A, *7B) and G590A (rs1799930, *6A).”
http://www.ncbi.nlm.nih.gov/pubmed/24221535​

Would this indicate a need for acetyl groups, @caledonia? I've been taking both MeB12 and Mefolate. And I've had quite the slowdown in brain function -- I get groggy and bloated every time I eat. It feels like someone drugged me. I was assuming it was an ammonia problem, since my urine smells really strong.

I presume that these snps have been expressed most of my life. The reason: caffeine has never had any effect on me. I hate coffee, but I can drink tea or eat dark chocolate, even before bed, with zero effect.

The rest of the NAT1 and NAT2 snps on my MTHFRsupport report are -/-.

​

As far as I know the NATs are more about detoxing smoke. I have a bunch of them too. Caffeine is CYP1A1 I think. You're probably a fast metabolizer with ok adrenals.

 

[whodathunkit]

@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!

 

[picante]

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.

Thank you! I've been taking various forms of choline, but without anything "acetyl-". My brain's been getting more and more sluggish. I suspect it's because of the homozygous NAT2 snps I mentioned above, but haven't heard yet from anyone who is snp-literate regarding N-acetyl Transferase.
ALC is ordered and on its way.

 

[caledonia]

I've done ALC and liked it for energy (assuming you mean acetyl l carnitine). My Kreb's cycle (via Nutreval) was showing deficient for that. Haven't done much with choline, but that was something Rich Vank had suggested for cell membrane health.

So I guess anything with Acetyl in the name would help with acetylation?

 

[ahmo]

This is really interesting. I've just introduced ALC because it's one of the things Martin Pall recommends for helping with the NO/ONOO- cycle. Amazing if it helps my mental stamina as well!!!

 

[picante]

because it's one of the things Martin Pall recommends for helping with the NO/ONOO- cycle.

Well, that's interesting! Now I'm really eager to try it. I've got three homozygous NOS2 snps, which makes it the worst gene in my methylation profile.

I wonder if starting up acetylation is as dramatic as starting up methylation, hmmm.

 

[picante]

So I guess anything with Acetyl in the name would help with acetylation?

That is what I've asked on 3 different threads now.

 

[whodathunkit]

@picante & @ahmo: IMO the effects of addressing brain chemistry specifically (since I don't understand it well right now I'm hesitant to say "starting acetylation") can be similar to starting methylation. Using supplements that specifically target neurotransmitters and cross the blood-brain barrier can come with a whole set of sides unto themselves. So we should be alert and aware.

I was brief in my post above. But to go a little more in-depth, while I count my overall experience with the nootropics (the term loosely used for non-pharmaceutical substances like ALC and choline that can boost cognitive function) as good, I've had to STOP doing them because of some side effects. There seems to be a connection between stuff that boosts choline (like ALC or even straight choline itself) and dry skin and blurry vision, for example (what I'm currently dealing with). The choline has seemed to aggravate my episodic but long-standing mild blepharitis, which is an inflammatory condition of the eyes and eyelids. I've had it occasionally since I was in my 20's but it hasn't really bothered me since I quit wearing make-up. Now it's back. It feels like I have a film across my eyes that I can't wipe away, and my lids are flaky. Yuck. It will pass, but it's annoying until it does.

Good news is the mental benefits seem in large measure to have stuck around. I'm not as good as when I was actually taking them, but things are still improved. Baby steps. My primary motto about all this we're doing around here at PR is that we can complete a journey of 1000 miles by going three steps forward and two steps back. It's slow, but still the net progress is a step forward.

Anyway...keep in mind if you're using ALC or something similar, you're supposed to cycle it. A week on, week off, or something like that. You find the rhythm that's best for you, but take some time off it to avoid the sides and to prevent yourself from building a tolerance. If you wait to cycle until the sides start (like I did) you may have to be off your stuff for much longer than you want to be (like I am right now).

Finally, I never got anything out of ALC until I paired it with a thiamine analog called "sulbutiamine". Thiamine in general is supposed to be good for cognitive function if a person is deficient, and sulbutiamine is fat soluble and crosses the blood-brain barrier very efficiently. When I paired the it with ALC it seemed like the effect of both really improved. But sulbutiamine is a synthetic and quite powerful, so possibly ALC with higher-dose thiamine may be a better choice, especially for someone whose energy is not quite up to speed in the first place. I plan to try ALC with regular thiamine when I start using again. I would also suppose we still need to cycle both ALC and thiamine, especially since high-dose thiamine can cause dry skin just like lower-dose sulbutiamine, but the effect of thiamine is probably milder than sulbutiamine since it doesn't cross the blood-brain barrier nearly as efficiently.

HTH. I think these nootropics can give us a big boost, and possibly, along with methylation and other health-supporting protocols, get many of us back to normal or very close to it if we learn enough about them and use them properly, but they do come with their own set of side effects to be worked through as our health recovers, just like the stacks of methylation supplements we use.

 

[picante]

Wow, thank you for this description, @whodathunkit! The blurry vision is a symptom I'm already experiencing off and on. Dry skin-- I've had that all my life. I slather myself with grapeseed oil every time I take a shower, LOL.

Thanks for the warning about cycling AlCar. I'll switch off between that and LCF or L-carnitine for my methylation protocol. What sort of dose were you taking? I've ordered Doctor's Best, 500 mg.

 

[whodathunkit]

@picante: dunno what forms of choline you're using, but citicholine (aka CDP choline) in particular can cause blurry vision. I was taking that specifically, along with ALC, AGP choline, and sulbutiamine (also supposed to be able to cause blurry vision and particularly dry skin).

As far as dose of ALC...I was taking about 1500mg/day divided morning and afternoon. But I'd say 1000mg/day is probably okay.

I didn't take any of this stuff late in the day. It can impact your sleep, too. I got a bit wired there at the end, when I cycled off for a week.

 

[Gondwanaland]

acetyl groups in order to balance reuptake of neurotransmitters

Which process are we talking about? Both? Sorry if it has already been clarified.

Pyruvate decarboxylase depends on cofactorsthiamine pyrophosphate (TPP) and magnesium. This enzyme should not be mistaken for the unrelated enzyme pyruvate dehydrogenase, an oxidoreductase (EC1.2.4.1), that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA.

Pyruvate dehydrogenase
E1 has two catalytic sites, each providing thiamine pyrophosphate(TPP) and magnesium ion as cofactors. The α- subunit binds magnesium ion and pyrophosphate fragment while the β-subunit binds pyrimidine fragment of TPP, forming together a catalytic site at the interface of subunits.