[Non Peat] Undermethylators, Ketogenesis

[DaveFoster]

Understanding ketogenesis, mitochondria and ATP production

Just an update; I've received P5P, along with magnesium chloride flakes, but not my ionized magnesium liquid dropper.

One oral magnesium chloride bath flake made me go to the bathroom immediately in a good sort of way, and my temperature went up slightly. I popped a 50 mg P5P capsule, and I can say I'm astounded.

My focus improved, depression lifted, and I can swear that I'm holding on to weight less easily (probably due to lowered estrogen and prolactin). My libido has also improved noticeably. Pyridoxine HCL did not have this effect like the biologically active form of B6, so thank you kineticz. P5P earned itself a permanent place in my stack of supplements.

 

[NathanK]

Understanding ketogenesis, mitochondria and ATP production

cool, thank you. what are the implications here? those with the "mutant" gene are told that it negatively (?) affects methylation, so they get on a bunch of supplements to methylate "better"?....all the while the "mutant" gene shows lower rates of cancer? am i understanding correctly? i don't understand how the "mutant" gene really affects methylation, though. i also don't know if its affects on methylation are what contribute to a lower risk of cancer. I also don't understand who the people are that have the "less active form of that enzyme" and what connection the writer is making about their diet. in other words, i really didn't understand any of this. : )

That is what ive heard. Low methylation has less chance of cancer. I've heard the main benefit of fasting is lowering methylation as well. Ray has mentioned that methylation is correlated with aging. As we age, we methylate more to make up for the lack of CO2 production.

In short, genetics has been a lot of marketing of tests and supplements with no cures. MTFHR refers to "busted" MAO and COMT genes that effect COMT and MAO metabolizing enzymes in methylation causing a backlog. I really haven't put all the pieces together systematically to get into too much detail. As with this or anything out there, weeding through the bull**** is 90% of the battle

 

[Nicholas]

Understanding ketogenesis, mitochondria and ATP production

interesting, i recently had a sudden and identical reaction (every reaction you had) to taking digestive enzymes. It was, as you say "astounding"....like, "oh, this is what a normal person probably feels like." : ) so it's interesting to me that P5P is a coenzyme and is responsible for some amino acid synthesis. still trying to understand this...

i wonder what the real mechanism is behind a person being deficient in enzyme activity in the body....

 

[Nicholas]

Understanding ketogenesis, mitochondria and ATP production

post 114490 Just an update; I've received P5P, along with magnesium chloride flakes, but not my ionized magnesium liquid dropper.

One oral magnesium chloride bath flake made me go to the bathroom immediately in a good sort of way, and my temperature went up slightly. I popped a 50 mg P5P capsule, and I can say I'm astounded.

My focus improved, depression lifted, and I can swear that I'm holding on to weight less easily (probably due to lowered estrogen and prolactin). My libido has also improved noticeably. Pyridoxine HCL did not have this effect like the biologically active form of B6, so thank you kineticz. P5P earned itself a permanent place in my stack of supplements.

interesting, i recently had a sudden and identical reaction (every reaction you had) to taking digestive enzymes. It was, as you say "astounding"....like, "oh, this is what a normal person probably feels like." : ) so it's interesting to me that P5P is a coenzyme and is responsible for some amino acid synthesis. still trying to understand this...

the depression lifting was quite profound.....like not really knowing it was there.

i wonder what the real mechanism is behind a person being deficient in enzyme activity in the body....

 

[Tarmander]

Understanding ketogenesis, mitochondria and ATP production

cool, thank you. what are the implications here? those with the "mutant" gene are told that it negatively (?) affects methylation, so they get on a bunch of supplements to methylate "better"?....all the while the "mutant" gene shows lower rates of cancer? am i understanding correctly? i don't understand how the "mutant" gene really affects methylation, though. i also don't know if its affects on methylation are what contribute to a lower risk of cancer. I also don't understand who the people are that have the "less active form of that enzyme" and what connection the writer is making about their diet. in other words, i really didn't understand any of this. : )

That is what ive heard. Low methylation has less chance of cancer. I've heard the main benefit of fasting is lowering methylation as well. Ray has mentioned that methylation is correlated with aging. As we age, we methylate more to make up for the lack of CO2 production.

In short, genetics has been a lot of marketing of tests and supplements with no cures. MTFHR refers to "busted" MAO and COMT genes that effect COMT and MAO metabolizing enzymes in methylation causing a backlog. I really haven't put all the pieces together systematically to get into too much detail. As with this or anything out there, weeding through the bull**** is 90% of the battle

Before I got into Peat, I was "into" methylation. If anyone wants to read more about it, you can check it out here:

http://www.heartfixer.com/AMRI-Nutrigenomics.htm

I hung out at the phoenix rising forums where a lot of those peeps are experimenting with Methylfolate and b12 in high doses. A lot of them chronically under eat as well, which I think could solve a great deal of their problems, but that is besides the point. I tested my genes and had one defect on the MTHFR gene so I thought my problems MUST come from my inability to detoxify.

What I found when I messed around with methylation was that the window where you feel good is very small, at least it was in my case. There were all these convoluted steps you would have to go through. First you would have to get your sulfur metabolism going if you had a CBS mutation. Then you would have to look at MAO and finally when you got that cleared you could start with the methylfolate. It was more convoluted then that, but to be honest I forgot most of it as useless after awhile.

I would experiment with methylfolate and niacinamide, raising and lowering methylation. If I crashed my methylation with a large dose of Niacinamide, I would feel sluggish and not so great, and so I would take methylfolate. For about a day I would feel pretty good. After that I would start to feel manic and have symptoms of over methylation (too much dopamine, mania, anger etc) Of course this was all "detox." Ehh turned out eating just vegetables and meat all day was my problem and once I started getting more then 2k calories a day all those issues were resolved.

My take away from it all was that methylation was important, but probably not the end all be all that the guys at Phoenix Rising and the Autism forums are giving it. Taking a large dose of B6 like Dave Foster did CAN make you feel amazing, especially if it is high quality and sub-lingual. You will get a nice boost in Dopamine, lowering of cortisol, and a million other things that B6 can do. Just do a search for Haidut and B6 and there is some great reading. But if you take 50mg of P5P per day, I am going to go out on a limb and say there will need to be heavy compensation in some other direction to keep that up and not go insane. Maybe like 5-10mg is sustainable.

 

[NathanK]

Understanding ketogenesis, mitochondria and ATP production

My take away from it all was that methylation was important, but probably not the end all be all that the guys at Phoenix Rising and the Autism forums are giving it. Taking a large dose of B6 like Dave Foster did CAN make you feel amazing, especially if it is high quality and sub-lingual. You will get a nice boost in Dopamine, lowering of cortisol, and a million other things that B6 can do. Just do a search for Haidut and B6 and there is some great reading. But if you take 50mg of P5P per day, I am going to go out on a limb and say there will need to be heavy compensation in some other direction to keep that up and not go insane. Maybe like 5-10mg is sustainable.

Thanks for the input. I'll check out that site. You kind of summed up my feelings on methylation. It would be nice to spend a 6 months go deep into it all, but I've decided to trust Ray on this one. Haidut has some great b vitamin posts too.

I personally just started taking 50mg of p5p a few weeks ago after I noticed my homocysteine at 10 (15 is top of the lab's range). I haven't noticed much difference, tbh. I read that alzheimers and Parkinson's is correlated to high homocysteine and low B12. My B12 has always been in range but low in the 350-450 range (I remember being shocked because I was eating so much animal protein and still being low). My family has a history of Parkinson's so it's something I try to watch.

 

[YuraCZ]

Understanding ketogenesis, mitochondria and ATP production

I'm still so confused about B vitamins and how much we need. I know it's different from person to person. But there are numbers from couple of mg to hundreds of mg.. You can buy B complex where is maybe 5-10mg for each B vit and, B complex where is 50-100mg for each B vit and then you can buy B vits separately, where can be up to 500mg in one capsule for single B vit..

 

[supernature]

Undermethylators, Ketogenesis

post 114497

Before I got into Peat, I was "into" methylation. If anyone wants to read more about it, you can check it out here:

http://www.heartfixer.com/AMRI-Nutrigenomics.htm

I hung out at the phoenix rising forums where a lot of those peeps are experimenting with Methylfolate and b12 in high doses. A lot of them chronically under eat as well, which I think could solve a great deal of their problems, but that is besides the point. I tested my genes and had one defect on the MTHFR gene so I thought my problems MUST come from my inability to detoxify.

What I found when I messed around with methylation was that the window where you feel good is very small, at least it was in my case. There were all these convoluted steps you would have to go through. First you would have to get your sulfur metabolism going if you had a CBS mutation. Then you would have to look at MAO and finally when you got that cleared you could start with the methylfolate. It was more convoluted then that, but to be honest I forgot most of it as useless after awhile.

I would experiment with methylfolate and niacinamide, raising and lowering methylation. If I crashed my methylation with a large dose of Niacinamide, I would feel sluggish and not so great, and so I would take methylfolate. For about a day I would feel pretty good. After that I would start to feel manic and have symptoms of over methylation (too much dopamine, mania, anger etc) Of course this was all "detox." Ehh turned out eating just vegetables and meat all day was my problem and once I started getting more then 2k calories a day all those issues were resolved.

My take away from it all was that methylation was important, but probably not the end all be all that the guys at Phoenix Rising and the Autism forums are giving it. Taking a large dose of B6 like Dave Foster did CAN make you feel amazing, especially if it is high quality and sub-lingual. You will get a nice boost in Dopamine, lowering of cortisol, and a million other things that B6 can do. Just do a search for Haidut and B6 and there is some great reading. But if you take 50mg of P5P per day, I am going to go out on a limb and say there will need to be heavy compensation in some other direction to keep that up and not go insane. Maybe like 5-10mg is sustainable.

Hi "Tarmander", thanks for sharing, i assume as a necessary step is to balance first the Methylation process and Metabolism as general, before one can expect satisfactory output from a particular diet or protocols, as the Metabolism wont be fixed when digestion, assimilation of nutrients etc. are not optimal.
Here is a case study on Overmethylation and Undermethylation in MTHFR gene mutation which shows how sensible is Methylation and how quickly can be disturbed and fixed with the right amount of nutrients.
In this case the patient is on Thyroid suplements and showing how taking too much of particular methyl groups - B9, B12 can lead to Overmethylation and also shows how by taking methyl "sponge" - B3 in high amount can quickly cause Undermethylation if not balanced with enough methyl groups.

http://mthfr.net/overmethylation-and-undermethylation-case-study/2012/06/27/

"...What is going on here?
This is a classic balancing act between how much methylation is ideal.
You can see exactly how fast the balance can shift.
First, the client is obviously undermethylated due to his symptoms so his doctor appropriately addressed it through prescribing methylfolate and methylcobalamin.
The only issue is the doctor did not realize how effective methylation is at supporting neurotransmitters and thyroid hormone production.
So what happened is the gentleman decided to skip his methylfolate and methylcobalamin dose, take a lot of niacin (which is a methyl ‘sponge’) and he immediately tanked his methyl groups which caused symptoms of undermethylation.
Then, upon restarting the methylfolate and methylcobalamin, and maintaining his current dosage of medications, he felt great for a few hours.
Then anxiety hit due to excessive neurotransmitter production and likely thyroid hormone production.
So – in order to quiet those symptoms, I told him about how niacin works and how to take it and his anxiety decreased almost immediately.
...Why Niacin??!
You’re likely wondering why niacin was so effective at reducing this gentleman’s anxiety. I’ll let you in on the secret and wonderful actions of biochemistry.
Niacin restored his mood in two ways – at least the two three ways that I am familiar with:

1. Nicotinic acid (Niacin USP) requires SAMe to be metabolized. SAMe is a major methyl donor. Thus, when one consumes niacin, SAMe gets used up and methyl donors drop. Thereby excessive methylation goes away.

2. Nicotinic acid also supports the elimination of glutamate. Many with elevated levels of glutamate do not do well with methylfolate or any type of folate until the levels of glutamate are balanced.

3. Niacin supports the feedback inhibition of the IDO1 gene which feeds into the kyurenine pathway. This pathway can deplete one’s tryptophan levels which makes them low in serotonin. The niacin slows the loss of tryptophan by pushing it towards serotonin formation. ..."

 

[supernature]

post 114507 I'm still so confused about B vitamins and how much we need. I know it's different from person to person. But there are numbers from couple of mg to hundreds of mg.. You can buy B complex where is maybe 5-10mg for each B vit and, B complex where is 50-100mg for each B vit and then you can buy B vits separately, where can be up to 500mg in one capsule for single B vit..

You are right, there is B complexes that has for example P5P of 30+mg per capsule and the recommended dosage is 3 capsules which is almost 100mg of that particular vit. As was just stated previously one could benefit from a high dose of 50mg per day and feel good, especially if depleted currently, but if try to keep the same dose for too long, probably will roll him over, as that are nutrients needed every day but probably in tiny amounts. I guess its not the same with conditions like those with severe depletion of nutrients where such amount are advisable and sometimes not even enough to compensate.
I dont know but of high doses of P5P im getting nightmares, i might be wrong this is the cause.

 

[YuraCZ]

post 114529

post 114507 I'm still so confused about B vitamins and how much we need. I know it's different from person to person. But there are numbers from couple of mg to hundreds of mg.. You can buy B complex where is maybe 5-10mg for each B vit and, B complex where is 50-100mg for each B vit and then you can buy B vits separately, where can be up to 500mg in one capsule for single B vit..

You are right, there is B complexes that has for example P5P ot 30+mg per capsule and the recommended dosage is 3 capsules which is almost 100mg of that particular vit. As was just stated previously one could benefit from a high dose of 50mg per day and feel good, especially if depleted currently, but if try to keep the same dose for too long, probably will roll him over, as that are nutrients needed every day but in tiny amounts.
I dont know but of high doses of P5P im getting nightmares, i might be wrong.

Hehe since I started taking 2x25mg of p5p. My dreams are definitely more intense. B vits are powerful for sure.. I ordered B1- 100mg tabs. I think I'm deficient. Since I don't eat B1 rich foods at all + I was last couple of years under heavy physical and emotional stress, which probably deplete all B vitamins. So I need higher doses from the start..

 

[YuraCZ]

Hi "Tarmander", thanks for sharing, i assume as a necessary step is to balance first the Methylation process and Metabolism as general, before one can expect satisfactory output from a particular diet or protocols, as the Metabolism wont be fixed when digestion, assimilation of nutrients etc. are not optimal.
Here is a case study on Overmethylation and Undermethylation in MTHFR gene mutation which shows how sensible is Methylation and how quickly can be disturbed and fixed with the right amount of nutrients.
In this case the patient is on Thyroid suplements and showing how taking too much of particular methyl groups - B9, B12 can lead to Overmethylation and also shows how by taking methyl "sponge" - B3 in high amount can quickly cause Undermethylation if not balanced with enough methyl groups.

http://mthfr.net/overmethylation-and-undermethylation-case-study/2012/06/27/

"...What is going on here?
This is a classic balancing act between how much methylation is ideal.
You can see exactly how fast the balance can shift.
First, the client is obviously undermethylated due to his symptoms so his doctor appropriately addressed it through prescribing methylfolate and methylcobalamin.
The only issue is the doctor did not realize how effective methylation is at supporting neurotransmitters and thyroid hormone production.
So what happened is the gentleman decided to skip his methylfolate and methylcobalamin dose, take a lot of niacin (which is a methyl ‘sponge’) and he immediately tanked his methyl groups which caused symptoms of undermethylation.
Then, upon restarting the methylfolate and methylcobalamin, and maintaining his current dosage of medications, he felt great for a few hours.
Then anxiety hit due to excessive neurotransmitter production and likely thyroid hormone production.
So – in order to quiet those symptoms, I told him about how niacin works and how to take it and his anxiety decreased almost immediately.
...Why Niacin??!
You’re likely wondering why niacin was so effective at reducing this gentleman’s anxiety. I’ll let you in on the secret and wonderful actions of biochemistry.
Niacin restored his mood in two ways – at least the two three ways that I am familiar with:

1. Nicotinic acid (Niacin USP) requires SAMe to be metabolized. SAMe is a major methyl donor. Thus, when one consumes niacin, SAMe gets used up and methyl donors drop. Thereby excessive methylation goes away.

2. Nicotinic acid also supports the elimination of glutamate. Many with elevated levels of glutamate do not do well with methylfolate or any type of folate until the levels of glutamate are balanced.

3. Niacin supports the feedback inhibition of the IDO1 gene which feeds into the kyurenine pathway. This pathway can deplete one’s tryptophan levels which makes them low in serotonin. The niacin slows the loss of tryptophan by pushing it towards serotonin formation. ..."

Very interesting.. So I wonder how someone can find, how much of each Bvit he needs for ideal methylation..

 

[YuraCZ]

Does Calcium Suppress Metabolism?

post 112772 Yep. The sodium potassium ATPase pumps keep things operating smoothly.

Increase sodium to minimise aldosterone, which should naturally increase progesterone stores, and increase magnesium to keep calcium extracellular.

I have difficultly thinking that taking calcium is necessary, due to the reaction of the kidneys which reduce vitamin D to ensure that calcium is lowered.

I think that minimising cortisol and taking a good K2 supplement is the best way to limit calcium and osteoporosis.


High cortisol, calcium, glutamate, and oxidized fatty acids are a cells worst enemy.

Keep the myelin sheath happy in the brain and generally makes ATP a whole lot more likely in the heart, kidneys, lungs, muscles and liver. When glutamate signal is high in the brain the whole system switches to angiotensin and cortisol to sustain energy, [highlight=yellow]as opposed to the methylation of creatine, carnitine, and glutathione and taurine detoxification.[/highlight]
I know Peat is anti-fatty acids but I've had really good results from this:

http://www.doctormyhill.co.uk/wiki/Phos ... d_exchange

The myelin sheath is made up mostly of these fats. Healthy membranes means the ion pumps and bundles of nutrients are retained.

I already ordered 1kg of L carnitine. Also I think I will need some coQ10 and what about creatine maybe 5-10g a day? Next nutrient with L carnitine found in beef in good amounts... It's really interesting. I was doing all this things in purpose for bodybuilding and I was relatively ok even with TSH more than 3. But when I drop bodybuilding, started 4-5 hour bicycle rides. My health went to the toilet so fast.. Now I really need to rebuild my body(health) and restore all micronutrients exactly as years ago and no more then 1 hour on the bicycle at the time. 2+ hours of hard aerobic exercise is so devastating for the body, metabolism etc..

 

[CoolTweetPete]

post 114339 Has anyone gave the phospholipid exchange a go yet? I know a few said they were gonna try it.

I did not notice any additional benefit from the phospholipid exchange, as compared to simply using the ionic magnesium (dissolved in OJ) with P5P, which does seem to be a fairly powerful tranquilizer as Kineticz reported.

I am going to continue increasing magnesium intake and lowering calcium because I have noticed my body (legs in particular) feels significantly better and I have lost some weight around my abdomen since beginning P5P / Natural Calm just a week ago. I got a mild stomach ache when I did it with phospholipid exchange so I will probably not do that again.

Thank you for the fresh perspective, Kineticz.

 

[jyb]

I don't see the need for ionic magnesium if you have standard magnesium chloride. It dissolve very easily in water, no need for strong stomach acid.

 

[CoolTweetPete]

I saw Haidut and others discussing a preparation of magnesium bicarbonate that they are having success with. I will probably try that also because Natural Calm is very expensive.

 

[tara]

Have those of you who feel better after 50mg P5P assessed whether you get these benefits from smaller doses too? eg. 5 or 10mg?

 

[Peata]

In the past, some of us tried B5, P5P, magnesium and other things mentioned here with varying results. Maybe these supplements weren't used at the same time, it was a couple years ago so I don't remember. I ran across some of our talk about it during searches.

I personally had good, noticeable results from plain old B6 (doses of 25 - 100 mg per day) and felt nothing from P5P.

In fact I started B6 again today because all this talk of it reminded me about it. The only reason I stopped it before was because some members were having symptoms of nerve damage that spooked me. Even though I had none of those bad symptoms. But I also wondered in the back of my mind why I needed high doses of B6 (if I went too low the good effects went away) when RP seemed to recommend no more than 10 mg per day. So that's another reason I didn't stick with it. I guess I was afraid it would do harm at higher doses. But I read about others online who have success at 100 - 200 mg per day, so I guess it's ymmv. For now I will trust my body and the results I got back then and take higher doses, at least for a while.

 

[CoolTweetPete]

post 114628 Have those of you who feel better after 50mg P5P assessed whether you get these benefits from smaller doses too? eg. 5 or 10mg?

I am going to try this with Haidut's Energin when I receive it. I'll let you know how it goes!

 

[michael94]

post 114490 Just an update; I've received P5P, along with magnesium chloride flakes, but not my ionized magnesium liquid dropper.

One oral magnesium chloride bath flake made me go to the bathroom immediately in a good sort of way, and my temperature went up slightly. I popped a 50 mg P5P capsule, and I can say I'm astounded.

My focus improved, depression lifted, and I can swear that I'm holding on to weight less easily (probably due to lowered estrogen and prolactin). My libido has also improved noticeably. Pyridoxine HCL did not have this effect like the biologically active form of B6, so thank you kineticz. P5P earned itself a permanent place in my stack of supplements.

I had the same experience with that and the ionic magnesium, intracellular magnesium is an important consideration and probably the biggest take away from this thread. I can't speak to the phospholipid exchange because I don't plan on doing it.

 

[kineticz]

intracellular magnesium is an important consideration and probably the biggest take away from this thread.

Indeed. It is not enough to say 'are you getting enough magnesium' without understanding it's effect on liver protein synthesis. Ray never discusses it and so it isn't pushed here. Sodium doesn't solve an intracellular magnesium problem.

The reduction in weight retention is probably due to reduction in edema due to calcified/de-energised cells and a happier heart (not due to estrogen - why does everything have to be related to estrogen on this forum lol.) The heart increases water retention via arginine vasopressin when magnesium and other nutrients are low. The liver is then more likely to resume glutathione and taurine protein synthesis. A better functioning heart will allow sodium retention to increase, increasing blood pressure and fuel delivery to the brain. The heart always supercedes the localised angiotensin of the kidneys and lungs when brain ATP is low and the liver is undermethylating. This is accountable for the toxic effects of arginine and nitric oxide.

Magnesium and glutathione are great for keeping red blood cells clean and ensuring they properly utilise glucose and oxygen delivery for the NADH/P450 enzymes for metabolism. Better intracellular glucose delivery means less chance of zinc/insulin deficiency.

Better magnesium to the brain combined with P5P increases ATP and therefore neurotransmitters. Dopamine probably involved, because magnesium displaces toxic calcium and stimulates the K+/Na- ion pumps. These stimulate all neurotransmitters including inhibitory, whereas calcium/glutamate only stimulate and deplete the excitatory neurotransmitters in order to provide cell energy to dieing cells.

You will not get the reduction in depression from P5P or B6 alone in this way. P5P has been shown to be specifically needed by magnesium to transport it into the intracellular space.

Myhill outlines a highly intelligent overview of magnesium deficiency: http://drmyhill.co.uk/wiki/Magnesium_-_ ... deficiency

"In dairy products the ratio is 10:1. So, consuming a lot of dairy products will induce a magnesium deficiency."

This is where Ray comes in.

It is then your duty to ensure cells are prevented from exposure to free roaming fatty acids and oxidative stress, while you take measures to boost ATP and thyroid activity most importantly to the brain via the liver. Next in line is the heart, then the kidneys. As angiotensin goes down due to an energised brain, it is more likely your DHEA and vit D will go up. Both great for cardiovascular health.

Agreed ionic magnesium can be taxxing on the digestive system. Oral works ok only with P5P in the same swallow.

"Hypochlorhydria – magnesium requires an acid environment for its absorption and hypochlorhydria will result in poor magnesium absorption."