Lack Of Methyl Donors, Demethylation, Folic Acid, B12

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Zpol

Zpol

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Thanks Mito. Good info.

I have current blood plasma tests indicating elevated homocysteine so I'm going to give the creatine a go.

Makes sense to supplement the methylfolate every other day instead of everyday, to avoid overdosage.

Hydrolized collagen for extra glycine seems good too. I think where I went wrong with this before is not taking with meals (I was putting it in coffee; not a balanced meal or snack).

Someone posted a link to a page about Walsh and how he treats schizophrenia regulating methylation. Many Mentally Ill Have Histamine-methylation Ratio Imbalance

Undermethylators shouldn't take b9 or b12 but methionine. After reading this I took some methionine I had laying around and my face looked noticeably less tired and worn after a few days. I had looked this tired and run down for months and it was affecting my self esteem, methionine fixed it.

I do have low creatinine. Need to listen to that podcast.

Seems to me Peats advice is mainly geared towards overmethylators (?)

I highly recommend the Methylate Your Way to Mental Health With Dopamine podcast as well.
It's important to get enough glycine with methionine (the podcast explains why too much methionine in one sitting could disrupt proper methylation).
RP does caution against too much methylation because too many methyl donor groups attached to DNA is an indication of cellular aging (not necessarily chronological aging though). One cause of methyl donor groups attaching to DNA is excess estrogen. Basically anything that damages DNA will require methyl donor groups to repair the damage but these get left behind and sort of forgotten.

Bottom line is that one needs adequate methylation but not too much.
B9 and B12 are risky supp's to take for everyone as studies show a correlation to cancer.
This thread explains the risks (apologies if you've already read it)...
DNA Methylation, Aging, And Cancer
Thanks for the link to that study, I will read it more thoroughly soon!
 

managing

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Ok so I finally got the chance to listen to whole podcast... and, wow, I'm blown away! Things are making a lot more sense to me now.
So glad he addressed the issue of supplementing Methyl folate and how it's basically just a band-aid (it doesn't fix the up-stream problem). And the alternate pathway involving creatine!!... I had not come across this anywhere before! The use of creatine instead of taking methyl donor supp's and risking overmethylation is pretty big news to me :)

I do recall him mentioning B12 but I don't remember the context. I also listen to
Methylate Your Way to Mental Health With Dopamine. It might have been on this podcast that he mentioned it.

Also, he addressed my glycine quandary!
"The note regarding Magnesium in a non glycinate or aspartate form is based on the observation that many people who have such "methylation issues" often come with a dysfunctional Glycine Cleavage System (which itself is NAD+ dependent, and thus requires a high NAD+/NADH ratio) -- Glycine cleavage system - Wikipedia . Usually this comes with an unfavourable GAD SNP, which does affect GABA levels in the brain."
From the thread ...
MTHFR Mutations AND Thiamine-Responsive Megaloblastic Anemia

Basically, he said one must have sufficient choline in order for the Glycine Cleavage System to function properly. That is if I understood correctly. I think I'm going to have listen again to these two podcasts to thoroughly understand everything.

Mito, what do you think about using MitoLipin to provide the needed choline if one could not get enough from food?
Per
haidut...
"In theory, it is a precursor to acetylcholine. However, the studies with PC (and especially saturated PC) did not show any cholinergic effects. See the studies in the brain/mood section of the original thread. The primary benefit of saturated PC is to protect the cell from PUFA toxicity and re-saturate the cardiolipin inside the mitochondria. If it has any cholinergic effets, they are probably seen in multi-gram doses. In the doses found in MitoLipin, it is similar to eating 2 eggs, but without the PUFA that they contain. See this:
Dipalmitoylphosphatidylcholine (dppc) Protects From Pufa Cytotoxicity"


He's saying it would not have a cholinergic effect in the recommended dose, but also that it would be similar to eating 2 eggs in terms of choline effect. I'm confused by this. Perhaps he meant that the recommended dose would not provide ALL the choline one would need per day. I'm thinking if I ate 2 eggs, plus took one dose of MitoLipin, I should be getting pretty close to the total recommended amount. (Can't eat liver, gives me GERD symptoms.) I do realize that MitoLipin is not intended as a choline supp but I have been considering taking this for other reasons and so it'd be great if it would have dual effects for me.
The other supp's Masterjohn recommends don't seem too appealing; have you tried any of them?

Can't thank you enough pointing me in the direction of Chris Masterjohn :)
I've been taking Mitolipin with great success. You can read about my experience on the newest pages of that thread.

The two egg thing: there is a small amount of choline. But not enough for "cholinergic effects" is what I think he means.
 
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Zpol

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I've been taking Mitolipin with great success. You can read about my experience on the newest pages of that thread.

The two egg thing: there is a small amount of choline. But not enough for "cholinergic effects" is what I think he means.

Good to know, I will check out your post on that thread.

Thanks for clarifying the above statement. I see the the distinction now.
 

Texon

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Good to know, I will check out your post on that thread.

Thanks for clarifying the above statement. I see the the distinction now.

I believe the cancer threat is from synthetic folic acid not methyl folate etc. Three genetic aspect can be problematic. Haven't heard about b12 being link to cancer. I do take sublingual methyl B12 but not every day. I have to be careful with it. The reason for hydroxocobalamine and adenosyl forms is that they don't overload people with COMT snps with methyl groups. Too much methylation for people like me with homozygous COMT issues will have severe reactions due to dopamine and catecholamine overload. The only way to stop the reaction is to take niacin or niacinamide which act as methyl sinks. I can't go near methyl folate supps. One time my doc gave me a 'medical food' which was a prescription (imagine that) high dose (5 mgs) methyl folate supp. I dumped half the capsule and took the other half....once....I will never forget it. I told my wife, "This must be what dying feels like." It felt like every bit of my energy was draining into the ground. For me, methylation is a tough balancing act for sure. The event that may have triggered all this may have tryptophan poisoning in 1989 known as eosinophilia myalgia syndrome (EMS). A lot of people died from it, and one researcher said people who went through it are now genetically different. Guess that includes me.
 
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I believe the cancer threat is from synthetic folic acid not methyl folate etc. Three genetic aspect can be problematic. Haven't heard about b12 being link to cancer. I do take sublingual methyl B12 but not every day. I have to be careful with it. The reason for hydroxocobalamine and adenosyl forms is that they don't overload people with COMT snps with methyl groups. Too much methylation for people like me with homozygous COMT issues will have severe reactions due to dopamine and catecholamine overload. The only way to stop the reaction is to take niacin or niacinamide which act as methyl sinks. I can't go near methyl folate supps. One time my doc gave me a 'medical food' which was a prescription (imagine that) high dose (5 mgs) methyl folate supp. I dumped half the capsule and took the other half....once....I will never forget it. I told my wife, "This must be what dying feels like." It felt like every bit of my energy was draining into the ground. For me, methylation is a tough balancing act for sure. The event that may have triggered all this may have tryptophan poisoning in 1989 known as eosinophilia myalgia syndrome (EMS). A lot of people died from it, and one researcher said people who went through it are now genetically different. Guess that includes me.

I read the methyl folate is better due to not contributing to cancer as well, but I have an SNP too, the MTHFR one, so can't afford to take anything that will donate methyl groups either. I don't experience any symptoms from the methylated folic acid or b12 but don't want to take chances. The only reason i'm considering them is to reduce elevated homocysteine. If you are taking niacin or niacinamide to act as 'methyl sinks', are you experiencing elevated homocystiene? I'm really trying to get to the bottom of this question. So many people on this forum are taking niacin or niacinamide based on RP's suggestions, and from what I've read by RP, he suggests niacinamide a lot, yet he never mentions the statistically significant issue of it raising homocysteine!? It's like the elephant in the room.
Hope you have improved after that scary situation!

None of his specific recommendations. I supplement 400 mcg methylfolate three days per week but I use Pure Encapsulations. I also use Great Lakes hydrolized collagen for extra glycine. I might try creatine but I want to test homocysteine again first.

@Mito has suggested taking the methyl folate every other day. I might try this but haven't got the guts to yet. Super freaked out about these methyl groups.

Speaking of... @Mito , have you retested your blood plasma homcysteine yet? Have you started with the creatine?

I'm more inclined to try the creatine first, then get retested, then try the methyl folate if needed (my original tests show I'm low in folic acid so gotta do something about this sooner or later). The only thing about creatine that is freaky is the methionine and arginine components, which are not necessarily good, but hopefully the third component, glycine, balances them out. As a person with the MTHFR snp, it is not advisable to take glycine alone either since you could get overload. I know it's best to get all these things from food, but I have a severely impaired digestive system and cannot eat many healthy foods, and cannot eat too much quantity of food either.
 

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have you retested your blood plasma homcysteine yet?
Yes just recently. It droped to 8.5 umol/dL from 10.9 umol/dL on the previous test. So it droped even though I supplement with 250 mg niacinamide most days. Also use methylfolate and methyl-B12 three days per week and Energin almost everyday.

Have you started with the creatine?
Yes started using a Creatine supplement (2 grams) 4 to 5 days a week . I’d prefer homocysteine in the 6-7 range.
 
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Yes just recently. It droped to 8.5 umol/dL from 10.9 umol/dL on the previous test. So it droped even though I supplement with 250 mg niacinamide most days. Also use methylfolate and methyl-B12 three days per week and Energin almost everyday.

Great news! I'll start with the methylfolate and methyl-B12, in combo with Energin, and get retested for Hcy and B-vitamin status. Theoretically, if I take the methylfolate and methyl-B12 and get up to 'normal' range, I won't be contributing too many methyl donors, but just the right amount. Good to know that you are taking niacinamide and were still able to get your Hcy down. I wonder if it has to do with the added benefit of the B6 in the Energin. So thankful to @haidut for creating a supp with B6 that doesn't cause me headaches.
Thanks for the update @Mito !
 

Mito

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Great news! I'll start with the methylfolate and methyl-B12, in combo with Energin, and get retested for Hcy and B-vitamin status. Theoretically, if I take the methylfolate and methyl-B12 and get up to 'normal' range,
I’m going to switch to a liquid B12 supplement so I can take it in lower dosages. There appears to be some evidence that excess B12 that doesn’t get absorbed in the stomach feeds gut bacteria. https://fixyourgut.com/vitamin-b-12-gut-health/
 
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Interesting. This explains why my vegan friends started taking the injections instead of the pills and lozenges. I thought they were crazy but it's making sense now. I did ask them why and they said they just needed more b-12, they didn't know why. I for one do not trust my gut microbiota or my genetic make up to properly handle any vitamin. Smaller amounts 2 or 3 times a day seems like a good idea. If you find one that can be dosed minimally, please do tell! Meanwhile, I'm going to resume my studies of the b-12 patches. I started researching these many years ago when I was vegan but there weren't very good options, things might have changed since then so maybe there's better ones out there. Thanks for the tip @Mito !
 
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Thanks @Mito
I've read the methylcobalamin and the methylcobalamin are more toxic than the hydroxocobalamin but haven't researched the Adenosyl yet. For sure sublingual is the best. I trust my saliva more than my guts!
 

Texon

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Thanks @Mito
I've read the methylcobalamin and the methylcobalamin are more toxic than the hydroxocobalamin but haven't researched the Adenosyl yet. For sure sublingual is the best. I trust my saliva more than my guts!
@Mito
Also consider Trimethylglycine. It's cheap and effective. 1300 mgs/day of it dropped my homocysteine from 15-16 down to 10.6 pretty quickly.
 
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@Mito
Also consider Trimethylglycine. It's cheap and effective. 1300 mgs/day of it dropped my homocysteine from 15-16 down to 10.6 pretty quickly.

Wow, that's a big improvement! TMG is one I've had my eye on. It can be tricky though since it could increase methyl donors too much (I have a lack of them but also don't want too many). I wonder if just taking glycine (additional to the glycine I get in gelatin) would have the same effect, bypassing the need for methyl groups. My plan has formed: 2 Tbls of collagen hydrolysate/day, 1 or 2 caps of glycine at the end of dinner/per day, Creatine 2x per week. Plus I have started taking Energin, Methyl folate and b12 every other day. This should do it, but I'll have to get another NutraEval in a few months to make sure. If it's still high I'll have to add in the TMG.
Thanks!
 

Mito

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@Mito
Also consider Trimethylglycine. It's cheap and effective. 1300 mgs/day of it dropped my homocysteine from 15-16 down to 10.6 pretty quickly.
Thanks for that idea but I eat egg yolks everyday which provides the precursor (choline) to betaine . I don’t want to add any additional betaine (trimethyglicine) because my preference is not to lower homocysteine by metabolizing it to methionine (thereby creating additional methyl groups). I’d prefer more of the homocysteine to metabolize down the transsulfuration pathway to cysteine. Or better yet I’d like to minimize the amount of homocysteine that is generated in the first place. Creatine synthesis is one of the largest demands for methylation so in theory creatine supplementation can lower homocysteine by downregulating endogenous production of creatine. So this should minimize the amount of homocysteine generated because homocysteine is a byproduct of creatine synthesis.
 

Texon

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Thanks for that idea but I eat egg yolks everyday which provides the precursor (choline) to betaine . I don’t want to add any additional betaine (trimethyglicine) because my preference is not to lower homocysteine by metabolizing it to methionine (thereby creating additional methyl groups). I’d prefer more of the homocysteine to metabolize down the transsulfuration pathway to cysteine. Or better yet I’d like to minimize the amount of homocysteine that is generated in the first place. Creatine synthesis is one of the largest demands for methylation so in theory creatine supplementation can lower homocysteine by downregulating endogenous production of creatine. So this should minimize the amount of homocysteine generated because homocysteine is a byproduct of creatine synthesis.

Very interesting. I eat egg yolks every day too, but homocysteine was stubbornly high in the teens. I'll have to try the creatine idea, as I heard somewhere (ergo log.com?) that it can lower homocysteine. Please let us know how it works.
 

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Thanks @Mito
I've read the methylcobalamin and the methylcobalamin are more toxic than the hydroxocobalamin but haven't researched the Adenosyl yet. For sure sublingual is the best. I trust my saliva more than my guts!
Hydroxocobalamin also lowers nitric oxide so possible better than methylcobalamin for several reasons
 

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Ive read through the thread, in the light of all of that would this be a simpler "solution"?

Your "MTHFR" Is Just a Riboflavin Deficiency

"1.6 milligrams of riboflavin per day decreases homocysteine, and this decrease is highly concentrated among people with the C677T MTHFR polymorphisms who also have poor riboflavin status. In them, 1.6 milligrams of riboflavin decreases homocysteine a whopping 40%!"
 

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