HDAC Inhibitors Affect Every Function Of The Cell And May Extend Lifespan

haidut

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The use of HDAC inhibitors such as valproic acid or various butyrate salts for cancer treatment has been studied experimentally for decades. Until now, it was assumed that the process of histone acetylation and deacetylation affected mostly the processes associated with cell division and differentiation. However, this recent study shows that the acetylation/deacetylation process affects virtually every process the cell performs and dietary HDAC inhibitors may be viable candidates for treating virtually all conditions, as well as lifespan extension. In addition to valproic acid and butyrate, a very common, potent and cheap HDAC inhibitor is niacinamide. Niacinamide exerts its HDAC inhibiting effects by acting as a sirtuin (SIRT) antagonist, which is yet another indication that sirtuin activation with substances like resveratrol may be undesirable/dangerous.

From cell division to ageing

"...Previously scientists believed that acetylation was mainly involved in regulation of gene expression. The new study shows that practically all cellular processes are influenced, e.g. cell division, DNA-repair or signal transduction - without acetylation cells could not survive. The significance of this process is highlighted by the example of Cdc28: This protein is necessary for the budding yeast. If the acetyl-switch of Cdc28 is defect, the yeast cell dies. Defective protein regulation plays a role in the development of numerous diseases, therefore acetylation switches are promising target points for the development of new therapies. Especially in the treatment of cancer there are already successful medications based on the inhibition of deacetylases. Two of these drugs are presently in use against certain types of leukemia. "Another process that is influenced substantially by acetylation is ageing", explains Chunaram Choudhary from the University of Copenhagen. Therefore manipulation of these molecular switches might also be a valuable tool for the treatment of age-related neurological diseases like Alzheimer’s or Parkinson’s."
 

haidut

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Hi Haidut,

After reading many good things about HDAC inhibitors the only concern I've got is they seem to Induce reactivation of the HSV virus. Can you make any sense of this?

Histone Deacetylase Inhibitors Induce Reactivation of Herpes Simplex Virus Type 1 in a Latency-Associated Transcript (LAT)-Independent Manner in Neuronal Cells

I doubt it, especially in the case of chemicals like niacinamide since specifically for B3 it was found that it inhibits a large number of viral infections. If viral infections depend mostly on the host's metabolic status, then niacinamide should be OK since it improve that status. Some other HDAC inhibitors may be toxic and permit/enhance viral load but niacinamide is safe IMO.
 

Koveras

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Hi Haidut,

After reading many good things about HDAC inhibitors the only concern I've got is they seem to Induce reactivation of the HSV virus. Can you make any sense of this?

Histone Deacetylase Inhibitors Induce Reactivation of Herpes Simplex Virus Type 1 in a Latency-Associated Transcript (LAT)-Independent Manner in Neuronal Cells

I doubt it, especially in the case of chemicals like niacinamide since specifically for B3 it was found that it inhibits a large number of viral infections. If viral infections depend mostly on the host's metabolic status, then niacinamide should be OK since it improve that status. Some other HDAC inhibitors may be toxic and permit/enhance viral load but niacinamide is safe IMO.

Histone Deacetylase Inhibitors Reduce the Number of Herpes Simplex Virus-1 Genomes Initiating Expression in Individual Cells. - PubMed - NCBI
 

Aleeri

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Bumping this thread, I did a consult with a geneticist awhile back and because of some specific genes that give a higher risk for Alopecia he recommended me looking into valproic acid.

He also recommended me resistant starch for the butyrate but this gave me GI issues. Regular butyrate supplements I find a pain since high dosage is required, they often bound to minerals so I almost overdose on those and in my part of the world (Asia) Butyrate is not on the market.

Anybody know a good source for Valproic acid? I suppose I should be using it as a topical.
 

Teres

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The use of HDAC inhibitors can be benefical, depending on the objectives and the proteins in question that have to be targeted, but also dangerous if one does not know how things should be done. Inhibiting certain HDAC proteins will lead to various results, depending on what kind of issues one wants to adress. Addictions can be aleviated, certain aspects of cognition can be affected, fear extinction can be achieved, traumatic memories can become quite easy to overcome, in some inhibitors there is a potential for HIV treatment and whatnot.


Bumping this thread, I did a consult with a geneticist awhile back and because of some specific genes that give a higher risk for Alopecia he recommended me looking into valproic acid.

He also recommended me resistant starch for the butyrate but this gave me GI issues. Regular butyrate supplements I find a pain since high dosage is required, they often bound to minerals so I almost overdose on those and in my part of the world (Asia) Butyrate is not on the market.

Anybody know a good source for Valproic acid? I suppose I should be using it as a topical.

Butyrate taken directly is completly useless. Even if you find it for sale, buying it will cost you time in waiting for an effect to take place, which will never happen. Prodrugs and raw materials for Butyrate on other hand do work, but in quite higher doses. They are dirt-cheap, so the high dosage isn't a concern from financial point of view.

Valproate is tricky. And I haven't heard of a topical one too. But there's Depakine (Sodium Valproate/Valproic acid) I've heard good things of, as far as potency goes. But it's in pills.
 

DaveFoster

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Many antieplieptic drugs act as HDAC inhibitors:

"Various antiepileptic drugs such as valproic acid, carbamazepine, oxcarbazepine, lamotrigine and levetiracetam are known to exert histone deacetylase inhibitory (HDACi) properties, which can modify aberrantly silenced gene expression by an epigenetic mechanism. This study was initiated to examine a potential beneficial effect of these drugs on prostate cancer (PC) development. The prostate-specific antigen (PSA) levels of 106 patients under long-term treatment with antiepileptic drugs and known HDACi properties were examined. PSA represents a hallmark in the early detection of PC, and its levels may predict an invasive disease in subsequent years. For in-vitro experiments, the PC cell line LNCaP was treated with HDACi drugs; subsequently, PSA and further PC markers were assessed. When men over 50 years of age were treated with HDACi drugs they had lower age-corrected PSA levels compared with control groups, according to the following ranking: valproic acid>levetiracetam>carbamazepine/oxcarbazepine>lamotrigine. Furthermore, there was a correlation between PSA reduction and the number of HDACi drugs within the medication, lending credence to the idea that a synergistic effect might be possible. Moreover, in vitro, HDACi drugs decrease PSA on mRNA and protein levels and exhibit further oncoprotective properties.The fact that HDACi drugs exert antiproliferative effects on neoplastic cells in vitro and in vivo, which are paralleled by expression alterations of aberrantly regulated genes, underlines the potential therapeutic value of HDACi drugs. These data suggest that long-term HDACi treatment can positively influence the characteristically slow transformation of tumour precursor cells in the prostate and may thus reduce a patient's risk of developing PC."

Reference: Long-term antiepileptic treatment with histone deacetylase inhibitors may reduce the risk of prostate cancer. - PubMed - NCBI
 

Aleeri

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The use of HDAC inhibitors can be benefical, depending on the objectives and the proteins in question that have to be targeted, but also dangerous if one does not know how things should be done. Inhibiting certain HDAC proteins will lead to various results, depending on what kind of issues one wants to adress. Addictions can be aleviated, certain aspects of cognition can be affected, fear extinction can be achieved, traumatic memories can become quite easy to overcome, in some inhibitors there is a potential for HIV treatment and whatnot.




Butyrate taken directly is completly useless. Even if you find it for sale, buying it will cost you time in waiting for an effect to take place, which will never happen. Prodrugs and raw materials for Butyrate on other hand do work, but in quite higher doses. They are dirt-cheap, so the high dosage isn't a concern from financial point of view.

Valproate is tricky. And I haven't heard of a topical one too. But there's Depakine (Sodium Valproate/Valproic acid) I've heard good things of, as far as potency goes. But it's in pills.

Thanks for the details, I looked up Depakine and I could probably get it here, the problem is that a common side effect is hair loss, and I would be taking it to prevent hair loss so this does not make a whole lot of sense.

However, this study with sodium valproate suggest that it works topically for hair loss: Topical valproic acid increases the hair count in male patients with androgenetic alopecia: a randomized, comparative, clinical feasibility study u... - PubMed - NCBI

In terms of people trying it, this is the only account I could find and not successful: Hair Loss Forum - Just ordered Valproic Acid, help me make the topical
 

Teres

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Thanks for the details, I looked up Depakine and I could probably get it here, the problem is that a common side effect is hair loss, and I would be taking it to prevent hair loss so this does not make a whole lot of sense.

However, this study with sodium valproate suggest that it works topically for hair loss: Topical valproic acid increases the hair count in male patients with androgenetic alopecia: a randomized, comparative, clinical feasibility study u... - PubMed - NCBI

In terms of people trying it, this is the only account I could find and not successful: Hair Loss Forum - Just ordered Valproic Acid, help me make the topical

So, you want to address a hairloss issue. My knowledge in this direction is non-existent, to be frank. But I do believe there's a lot of content across the forums here, the volume measured in pages. It may be a wise idea to read everything there is, before trying to use Valproate solely for hairloss. As I mentioned, the use of HDAC inhibitors, the more potent ones, has it's dangers, DNA damage being one of them, especially with chronic use. We're not talking about excess vitamin use here, which we can pee away three hours later. That's first.

Second - By saying that Valproate is tricky, I did mean that it is a dirty HDAC inhibitor. In other words, it's not selective by any means and it's spectrum of actions is very broad. Some HDAC proteins are distributed across your whole organism. Their inhibition will take place everywhere, not just in the desired places and tissues. The inhibition will have different outcomes and consequences, because these enzymes do have different roles in the numerous organs and tissues. Others are distrubited in just certain organs and tissues, differently than the rest, and their inhibition will take place in the organs and tissues they are distributed. Depending on which HDAC proteins you want to target, you have to know the areas of ther distribution and the roles they play. With the aid of the available information and knowledge, you can be one step closer in predicting the outcome and the consequences of an inhibition.

There's a lot to be learnt and if you allow me, I'd suggest you to not be in a rush for this.
 

Aleeri

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So, you want to address a hairloss issue. My knowledge in this direction is non-existent, to be frank. But I do believe there's a lot of content across the forums here, the volume measured in pages. It may be a wise idea to read everything there is, before trying to use Valproate solely for hairloss. As I mentioned, the use of HDAC inhibitors, the more potent ones, has it's dangers, DNA damage being one of them, especially with chronic use. We're not talking about excess vitamin use here, which we can pee away three hours later. That's first.

Second - By saying that Valproate is tricky, I did mean that it is a dirty HDAC inhibitor. In other words, it's not selective by any means and it's spectrum of actions is very broad. Some HDAC proteins are distributed across your whole organism. Their inhibition will take place everywhere, not just in the desired places and tissues. The inhibition will have different outcomes and consequences, because these enzymes do have different roles in the numerous organs and tissues. Others are distrubited in just certain organs and tissues, differently than the rest, and their inhibition will take place in the organs and tissues they are distributed. Depending on which HDAC proteins you want to target, you have to know the areas of ther distribution and the roles they play. With the aid of the available information and knowledge, you can be one step closer in predicting the outcome and the consequences of an inhibition.

There's a lot to be learnt and if you allow me, I'd suggest you to not be in a rush for this.

Thanks Teres, you're posts are very helpful.

I agree. I think in terms of hair loss it would be ignorant to think that I am HDAC inhibitor deficient and if I just used one my problems would be gone. Of course, the issues around hair loss go so much deeper than that. What interested me is that this guy pointed out valproic acid for me specifically when looking at my genetic SNPs.

Right now I am doing the SolBan topical (Caffeine, Niacinamide, Aspirin) which I am adding further Taurine and Korean Ginseng Extract to, while micro needling 1-2 times per week. Also taking NDT.

In the last couple months, my hair quality has improved substantially, I also see increased growth in my vellus hairs, almost like a short bed of fur now. Of course, I have little faith in that these hairs will reverse and go back to their default thickness and grow out again into real hairs. But I feel most comfortable with this treatment regiment of all the ones I have tried over the years. No side effects and not very expensive.
 

aarfai

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Oct 16, 2015
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I've used oral doses of 75 mg Lidocaine HCL ~10 times. It's an extremely low dose but helped with GI issues. It would be interesting to get Rays perspective on using Lidocaine HCL for fear extinction and trauma

I believe caffeine and components of the coffee bean like chlorogenic acid are also a HDAC inhibitors. Might aspirin for it's acetyl group also be one?
 

James b

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I've used oral doses of 75 mg Lidocaine HCL ~10 times. It's an extremely low dose but helped with GI issues. It would be interesting to get Rays perspective on using Lidocaine HCL for fear extinction and trauma

I believe caffeine and components of the coffee bean like chlorogenic acid are also a HDAC inhibitors. Might aspirin for it's acetyl group also be one?
Very interesting reference regarding lidocaine and fear extinction/trauma! I can’t find it can you point me in the right direction?
 
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