Dietary HDAC Inhibitors

haidut

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Ray wrote recently in one of his newsletters about Histone Deacetylase (HDAC) inhibitors and their role in protecting from cancer. Niacinamide is one well-known HDAC inhibitor. This study lists some other potential HDAC inhibitor some of which have been mentioned by Peat before but not in regards to their HDAC role.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737738/

"...Other dietary agents such as butyrate, biotin, lipoic acid, garlic organosulfur compounds, and metabolites of vitamin E have structural features compatible with HDAC inhibition."

"...Molecular modeling studies with other dietary compounds, such as biotin, α-lipoic acid, and metabolites of vitamin E and conjugated linoleic acids, also provided support for their role as putative HDAC inhibitors."
 

Elephanto

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I can't believe how powerful Niacinamide is. It induces the P53 gene which has many protective aspects but that gene can impair liver function through downregulation of HNF4a. But here's the thing I just found, "P53 down-regulation of hnf4a was partially recovered by inhibition of HDAC activity". It autocorrects its only weakness. It also inhibit tnf-alpha, which downregulates HNF4a too.

You can also add berberine which has the same function as metformin, ampk activity (atp blocks it, and ampk inhibit excess collagen production by tgf beta) but unlike metformin it upregulates hnf4a instead of down-regulating it. If you do a google search you'll find that people complain about hair loss on metformin, makes sense as hnf4a upregulates shbg and there's also some warnings about liver toxicity. Hnf4a is important.
 
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haidut

haidut

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Elephanto said:
I can't believe how powerful Niacinamide is. It induces the P53 gene which has many protective aspects but that gene can impair liver function through downregulation of HNF4a. But here's the thing I just found, "P53 down-regulation of hnf4a was partially recovered by inhibition of HDAC activity". It autocorrects its only weakness. It also inhibit tnf-alpha, which downregulates HNF4a too.

You can also add berberine which has the same function as metformin, ampk activity (atp blocks it, and ampk inhibit excess collagen production by tgf beta) but unlike metformin it upregulates hnf4a instead of down-regulating it. If you do a google search you'll find that people complain about hair loss on metformin, makes sense as hnf4a upregulates shbg and there's also some warnings about liver toxicity. Hnf4a is important.

Yep, I love my niacinamide. Btw, it is also an HDAC inhibitor. So, I assume this is the reason you posted about it in this thread.
 

Drareg

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:crazy::crazy::crazy:Would anyone have insight to the following questions?
The latest newsletter from Peat on nitric oxide mentions this stress response can take generations fix.
HDAC inhibitors are the big thing in epigenetics next to demethylating agents which are more potent like lidocaine and cocaine.

HDAC inhibitors have interested me because of this, when I took phenibut it increases my pulse to spot on 85,I end up warm with a quiet mind, for obvious reasons I don't use it, it's not a tool either as the rebound effects are too full on. Valerian is doing the same,again has side effects. Most what you mention there Haidut works well for a clear quiet mind,high temps and pulse.

Co2 is involved acts on the above as does coenzyme A, what's interesting here is lysine increases co enzyme A? Many people got good effect from lysine on here, k2 also involved in co2 so is it acting as a HDAC inhibitor??
The environment being stimulating helps but Peat mentions this can take a while also. GDNF ,BDNF etc are all influenced by inhibiting HDAC.
Electrophylic ketones are hdac inhibitors and what haidut posted shows more.

Over methylation under stress is causing hibernation,this is generally inhibited metabolism as we know causes most of the diesase ,those of us from a harsh background not just dealing with current environment will be more inclined to get this response from any stress, increasing metabolism in this scenario is not good unless you inhibit HDAC??? Or simply inhibiting HDAC will alleviate Stress and allow metabolism function on its own??

I Understand our main object is to manage stress response and increase metabolism, some us have found metabolism naturally comes up when stress response is alleviated, individual perceptions of stress,CBT therapy all helps people, what about those who have this increased methylation that Peat speaks of ?

Increasing calories and metabolism will fix this system for many but I was guessing that for those who have stressful childhood or from a culture with famines in the past or stress in general will need help lifting excess methylation and stopping such a strong stress response when undertaking stress.
 

CoolTweetPete

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@Drareg Interesting. When I was looking into nutrigenomics it seemed most people I spoke to were working to increase methylation, but you mention demethylating agents to reduce it for some people. I tend to have very aggressive stress responses, and used to suffer from chronic anxiety. It has gotten better but I still notice when I have a strong stress response, particularly from intense exercise, it tends to linger.

Do you have any good resources regarding the information you discussed here? Thanks.
 

Drareg

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Histone deacytlases remove acetyl groups from histone proteins repressing gene expression.
Inhibit these enzymes and you drive up gene expression. This is safer than more potent demethylating agent like lidocaine for regular use, there is a snap back effect when you cease use/abuse ,look at cocaine use as an example.

I don't no where increasing methylation idea comes from but I feel bad for people doing it,you need methylation but not in excess,increased methylation is implicated in many cancers.

Initially by increasing methylation I think people get an amphetamine like response similar to estrogen, modern day this is seen as the persona to have in many circles,it makes them quick on the uptake/respond with little reflecting ability imo.

Nessa Childers has a good book called epigenetics revolution, it's heavy reading and a touch main stream.
Don't go near anything by Tim Spector ,he is like the Richard Dawkins of epigentics.
Ray Peat is the best source for me. His articles are starting contain more info on it as his understanding evolve.

I'm not sure but I think nutrigenomics is going to be the next medical fad, I was interested at the start but looking at invidual snp's and treating with a vitamin makes no sense after reading Peat, just look at what's being achieved with human genome. This is ripe for corruption,like increasing methylation recommendations as example.

Mae Wan Ho shows the we are some sort of crystal with water and nutrients shifting and shaping at crazy speeds,these guys are showing Dna and Rna to be something more than ticker tape.
I'm still trying to understand it.
 

Drareg

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Haidut does make any sense to you? You may have seen it.
It's about SAHA a very strong HDAC inhibitor being created from DMSO I think? It epigentically modified haemoglobin cells to turn them bright red, I'm not 100% is this only a response to leukaemia cells however.

Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. - PubMed - NCBI
http://www.chemistry.illinois.edu/research/organic/seminar_extracts/2003_2004/nickels.pdf

not sure if this was all brought up over in, "DMSO gate thread", this in relation to hdac inhibitors .
 

Parsifal

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Could work in principle, as would taurine and glycine. The latter have been found to increase topical absorption of many vitamins and even steroids. But I am more interested in things that can match DMSO and so far only Azone looks like it is up to the task.

:crazy::crazy::crazy:Would anyone have insight to the following questions?
The latest newsletter from Peat on nitric oxide mentions this stress response can take generations fix.
HDAC inhibitors are the big thing in epigenetics next to demethylating agents which are more potent like lidocaine and cocaine.

HDAC inhibitors have interested me because of this, when I took phenibut it increases my pulse to spot on 85,I end up warm with a quiet mind, for obvious reasons I don't use it, it's not a tool either as the rebound effects are too full on. Valerian is doing the same,again has side effects. Most what you mention there Haidut works well for a clear quiet mind,high temps and pulse.

Co2 is involved acts on the above as does coenzyme A, what's interesting here is lysine increases co enzyme A? Many people got good effect from lysine on here, k2 also involved in co2 so is it acting as a HDAC inhibitor??
The environment being stimulating helps but Peat mentions this can take a while also. GDNF ,BDNF etc are all influenced by inhibiting HDAC.
Electrophylic ketones are hdac inhibitors and what haidut posted shows more.

Over methylation under stress is causing hibernation,this is generally inhibited metabolism as we know causes most of the diesase ,those of us from a harsh background not just dealing with current environment will be more inclined to get this response from any stress, increasing metabolism in this scenario is not good unless you inhibit HDAC??? Or simply inhibiting HDAC will alleviate Stress and allow metabolism function on its own??

I Understand our main object is to manage stress response and increase metabolism, some us have found metabolism naturally comes up when stress response is alleviated, individual perceptions of stress,CBT therapy all helps people, what about those who have this increased methylation that Peat speaks of ?

Increasing calories and metabolism will fix this system for many but I was guessing that for those who have stressful childhood or from a culture with famines in the past or stress in general will need help lifting excess methylation and stopping such a strong stress response when undertaking stress.

Very interesting! Do you think that applying niacinamide on the elbow if you have cubitus valgus or somewhere with varicose veins could help to retrain the genes in this area to make it normal again?
 

Drareg

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@Parsifal
If it's there along time you might need something stronger, Peat spoke about novocaine in Kmud interview as means.
DMSO does help with scars according some reports, niacinamide as we know is great on the skin,it all seems to point in the same direction.
Demthylating agents are more potent ,be very careful I'd say, I would be reluctant to try them, but severe burns/scars it might be worth it.

I think estrogen is more the cause of varicose veins,thread on here about that somewhere.
Anything lowering stress then will help you there it seems.
 

mujuro

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The lot over at PhoenixRising would probably strongly dispute your points Drareg. Similarly to you, I'm one to err on the side of caution first. Going overboard with methylating agents seems a little premature, however vets from the methyl/SNP circles consistently reinforce the claim that overcoming folate SNPs with dietary methyl factors is necessary for the avoidance of malignancies. Advised dosage is always individual, generally as low as possible to begin with.

What would you say about the practice of getting small but necessary quantities of a B complex that covers a methyl cycle deficit?
 

Drareg

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If you have a deficit go for it. It's just b vits , you should notice the effect quick enough. Careful it's not hypervigilant amphetamine effect they perceive as good. Report back if you do.

The cell is a dynamic gel like crystal moving between living and resting states ,everything in between. This is why I look at Ray Peats point of view, he uses Gilbert Lings AI hypotheses ,Mae Wan Ho's work,Gerald pollack, etc. water structure is far more important it seems. Getting back to the rested state mainly with sleep,allow current to flow ,Mother Nature or the ether/implicate order takes care of us at that point.

Mae Wan Ho shows Dna/RNA to have electromagnetic qualities, the environment is signalling to your personal state,your perception/consciousness is relevant to this, enzymes appear to be quantum tunnelling, life is flowing through you and the Dna/rna seem to be providing the information to adapt ,when Dna around histones are too tight it can cause issues. It's stops you adapting and makes you want to hibernate, if don't hibernate and keep pushing forward,health issues start to pop up.
I think then it's a feedback mechanism going on ,metabolism can be considered the flow of life through you by consuming the environment,this flow allows electric current to flow,Peat speculated that LSD might correct this current flow immedietaly, electro shock therapy has evidence of working also, speculating you could say it shakes off the overmethylation. Plugs you back in. It's no surprise that psychedelic mushrooms and regular mushrooms are in season and abundance in the northern hemisphere as winter is approaching, food abundance besides mushrooms is limited.
Peats last 2 newsletters mention nitric oxide as directly and indirectly influencing methylation.

nothing is working without water,that's the key to remember, molecules at a cellular level have different geometry when wet than dry, this geometry is informing us. The DNA is not the start of everything,it's on equal terms with everything else mentioned.

I'm still trying to grasp it all. Im not being dogmatic about Peat but his understanding is the best fulcrum to work from without harming yourself.
Look at the people on Dave aspreys forum, it's mania the amount of stuff they take, some of them will do this for years based off the fact he spent 100k to hack biology anchor, he will die young if keeps it up.
 
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haidut

haidut

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Haidut does make any sense to you? You may have seen it.
It's about SAHA a very strong HDAC inhibitor being created from DMSO I think? It epigentically modified haemoglobin cells to turn them bright red, I'm not 100% is this only a response to leukaemia cells however.

Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. - PubMed - NCBI
http://www.chemistry.illinois.edu/research/organic/seminar_extracts/2003_2004/nickels.pdf

not sure if this was all brought up over in, "DMSO gate thread", this in relation to hdac inhibitors .

That's pretty interesting. If you look at the Wiki for the derivative drug it says that it may eradicate HIV completely in people. DMSO has been shown to do the same in animal models.
Vorinostat - Wikipedia, the free encyclopedia
 

Drareg

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That's pretty interesting. If you look at the Wiki for the derivative drug it says that it may eradicate HIV completely in people. DMSO has been shown to do the same in animal models.
Vorinostat - Wikipedia, the free encyclopedia

Considering the direction it seems to be pointing to it may be possible inhibiting acetylcholinesterase could potentially help the cardiolipin under ideal conditions,speculative of course.
 
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Parsifal

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If you have a deficit go for it. It's just b vits , you should notice the effect quick enough. Careful it's not hypervigilant amphetamine effect they perceive as good. Report back if you do.

The cell is a dynamic gel like crystal moving between living and resting states ,everything in between. This is why I look at Ray Peats point of view, he uses Gilbert Lings AI hypotheses ,Mae Wan Ho's work,Gerald pollack, etc. water structure is far more important it seems. Getting back to the rested state mainly with sleep,allow current to flow ,Mother Nature or the ether/implicate order takes care of us at that point.

Mae Wan Ho shows Dna/RNA to have electromagnetic qualities, the environment is signalling to your personal state,your perception/consciousness is relevant to this, enzymes appear to be quantum tunnelling, life is flowing through you and the Dna/rna seem to be providing the information to adapt ,when Dna around histones are too tight it can cause issues. It's stops you adapting and makes you want to hibernate, if don't hibernate and keep pushing forward,health issues start to pop up.
I think then it's a feedback mechanism going on ,metabolism can be considered the flow of life through you by consuming the environment,this flow allows electric current to flow,Peat speculated that LSD might correct this current flow immedietaly, electro shock therapy has evidence of working also, speculating you could say it shakes off the overmethylation. Plugs you back in. It's no surprise that psychedelic mushrooms and regular mushrooms are in season and abundance in the northern hemisphere as winter is approaching, food abundance besides mushrooms is limited.
Peats last 2 newsletters mention nitric oxide as directly and indirectly influencing methylation.

nothing is working without water,that's the key to remember, molecules at a cellular level have different geometry when wet than dry, this geometry is informing us. The DNA is not the start of everything,it's on equal terms with everything else mentioned.

I'm still trying to grasp it all. Im not being dogmatic about Peat but his understanding is the best fulcrum to work from without harming yourself.
Look at the people on Dave aspreys forum, it's mania the amount of stuff they take, some of them will do this for years based off the fact he spent 100k to hack biology anchor, he will die young if keeps it up.

About LSD, do you know why it could cause bad trips and hallucinogen persisting perception disorder? I've read on the FB group that the psillocybin molecule is really close to serotonin as is DMT while the LSD molecule is quite different?
 

Makrosky

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About LSD, do you know why it could cause bad trips and hallucinogen persisting perception disorder? I've read on the FB group that the psillocybin molecule is really close to serotonin as is DMT while the LSD molecule is quite different?

What do they mean with "really close" ? For example, one molecule can be an agonist for a certain receptor and a single atom change(substract/add/changeposition) can make it an antagonist, ineffective, etc.
 

Drareg

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About LSD, do you know why it could cause bad trips and hallucinogen persisting perception disorder? I've read on the FB group that the psillocybin molecule is really close to serotonin as is DMT while the LSD molecule is quite different?

I agree with Makrosky here.
The receptor theory causes many to believe this, we all still talk about receptors to make a point but we know receptors are not lock and key from reading Peat and others.
Is it not more about what the molecule are doing to water through geometrical shape formed by the water around the molecule,not the molecules shape to be clear,how the water forms around it.
Many in mainstream view still look at lock and key,dry chemistry , they seem to be way off, I'm not in that industry so could be wrong.
 

Drareg

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Interesting article here about how Russia is giving kids a biology text book that supports creationism and epigentics. Seems positive for Russian kids ,only thing is what type of creationism ,ether or Christian styled God etc
When Biology Meets Ideology
 

Motorneuron

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Hdac inibhitors slower methylation or increase?
 

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