Histone Deacetylase (HDAC) Inhibitors and the Ketogenic Diet

[Martin aka paused||M.E.]

Every cancer happens at some point and the longer the body doesn't undergo a "regeneration" process like the ketogenic diet, fasting period, Ramadan, etc. the more likely cancer happens. With 30, the chances of cancer therapy are far better than with 80. HDAC inhibitors are actually used for cancer therapy, e.g. in combination with chemotherapy.

I'm aware of the off-label and patent-price issue, so I'm trying to create a protocol that circumvents the need for drugs that can not be acquired easily. I can simulate the ingestion of multiple drugs/supplements/foods at the same time and their accumulative enzyme interactions. But there isn't always sufficient raw data to work with. The typical databases don't list all the parameters. So I need more simulations for the raw data, e.g. when there is no in vitro IC50 available. And for this, I need appropriate molecule models. Not all molecules are available in databases the way I need them, so I might need to remodel them. This is where I'm currently at the moment. I try to find appropriate free HDAC molecule structures and not complexes that need remodeling.

If I had your brain...
As soon as you have something I might help you getting in contact with OMF that you cut thru the noise

 

[perrier]

If I had your brain...
As soon as you have something I might help you getting in contact with OMF that you cut thru the noise

Dr Janet Dafoe is reading the other thread. Maybe Mr. Nerd ought to mention some of this to her. This sounds very gripping.

 

[Boba]

Sounds very interesting. Good brain!! @nerd what do you think about autoimmunity? Where’s the link? Aren’t the Autoantibodies against Gprotein receptors a plausible cause of ME or are they just a product of the Root cause? Would love to get your thoughts on this.

 

[Boba]

Dr Janet Dafoe is reading the other thread. Maybe Mr. Nerd ought to mention some of this to her. This sounds very gripping.

@HTester needs to read this as well and the other thread concerning the inconsistencies:
https://forums.phoenixrising.me/thr...the-ido-trap-theory.84067/page-2#post-2345648

 

[nerd]

As soon as you have something I might help you getting in contact with OMF that you cut thru the noise

Thank you, but It's too soon. Once I have more results to present, I'd appreciate it. Maybe it leads nowhere, who knows. Research needs its time and all of the researchers are busy already while having little to no funds.

Dr Janet Dafoe is reading the other thread. Maybe Mr. Nerd ought to mention some of this to her. This sounds very gripping.

I've done a mistake in the comment on EBV-IDO in that EBV doesn't encode its own IDO. It can only regulate the human one. I'd like to not repeat such mistakes and waste their time.

Sounds very interesting. Good brain!! @nerd what do you think about autoimmunity? Where’s the link? Aren’t the Autoantibodies against Gprotein receptors a plausible cause of ME or are they just a product of the Root cause? Would love to get your thoughts on this.

Autoantibodies are usually the result of too much waste of something that looks like self. When many cells become dysfunctional for pathological reasons, it's waste that has to be processed by other cells and this would show up as autoantibodies, which unfortunately trigger even more destruction and waste by immunological pathology. You'd hope that the immune system eventually finds the real trigger in the waste, the common denominator, and build antibodies against this, but it doesn't always work this way when there are also proteins in the waste that affect the lymphocytes and block antigens from being built or presented.

The other possibility is that viral genes are too similar to the human genes to that the antibodies can not be specific enough to the viral ones, so they attack self all along.

Fortunately, antibodies disappear over time once the trigger disappears completely. Lymphocyte filtration and donation can even boost this process. As long as there is latent or abortive viral/pathogen pathology, the immune system will keep producing antibodies. That's why the causal option is getting rid of these cells by cell cycle therapy in my opinion.

 

[nerd]

Quercetin (QCT)

Even though QCT is a fitting ligand for HDAC inhibitory binding sites, its main problem is the low bioavailability and fast clearance rate. It's almost impossible to achieve sufficient concentrations with QCT, to achieve IC50 of viral activity or IC50 of HDACs. Liposomal delivery might improve this a little bit but yet not sufficient for the use case [1]. QCT has many mechanisms though, all of which can aggregate to provide a combined efficacy on viral activity and cell cycles. There are simply too many of those to estimate precise numbers. Same issue as with Ivermectin.

150mg of oral non-liposomal QCT achieves a Cmax of 431 nmol/l at a Tmax of 5h [3]. 500mg of liposomal QCT achieves a Cmax of 738.16 nmol/l at a Tmax of 202.50m and a half-time of 226.84m [1]. Both studies deliver inconsistent numbers on the oral form though. The liposomal study only found a Cmax of 36.164 nmol/l for 500mg of oral non-liposomal QCT [1].

The antiviral IC50s of QCT are the following.

1. 3.2 micromol/l for CMV [4]
2. 118.12 micromol/l for DENV-2 [5]
3. 58.8 micromol/l for HIV (protease only) [6]
4. 42.79 micromol/l for SARS-CoV [7]
5. 62 micromol/l for EBV-mutagenic cytotoxicity [8]
6. 75-100 micromol/l for the minimum effective concentration on histone acetylation [9, 10]

Clearly, the in vivo concentrations from the recommended oral dosages can not reach substantial effective concentrations. If all the different mechanisms of QCT are aggregated, I gauge that the recommended dosage might be able to achieve EC10. You would need to take so much QCT for IC50s that its safety becomes unclear and the use not cost and risk efficient.

Spoiler: References

1. Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin (2019) [10.1007/s13318-018-0517-3]
2. Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo (2014) [10.1155/2014/580626]
3. Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans (2008) [10.1093/jn/138.9.1615]
4. Human cytomegalovirus-inhibitory flavonoids: Studies on antiviral activity and mechanism of action (2005) [10.1016/j.antiviral.2005.08.002]
5. Antiviral activity of four types of bioflavonoid against dengue virus type-2 (2011) [10.1186/1743-422X-8-560]
6. Inhibitory Activity of Flavonoids and Tannins against HIV-1 Protease (2000) [10.1248/bpb.23.1072]
7. Binding interaction of quercetin-3-β-galactoside and its synthetic derivatives with SARS-CoV 3CLpro: Structure-activity relationship studies reveal salient pharmacophore features (2006) [10.1016/j.bmc.2006.09.014]
8. Quercetin-induced apoptosis prevents EBV infection (2014) [10.18632/oncotarget.3687]
9. Histone hyperacetylation is involved in the quercetin-induced human leukemia cell death (2008) [10.1691/ph.2008.7693]
10. Inhibition of glioblastoma cell proliferation, invasion, and mechanism of action of a novel hydroxamic acid hybrid molecule (2018) [10.1038/s41420-018-0103-0]

 

[GlassCannonLife]

Just bumping this awesome thread! Would love to see this keep going ahead!

Also, anyone taking any of the keto-style supps? Eg sodium butyrate?

I thought I remembered @BrightCandle you mentioned it, is that right.? Are you taking it for this reason?

 

[BrightCandle]

Are you taking it for this reason?

I am taking it due to my biomesight/microbiome study showing a severely low Bifido and Faecalibacterium prausnitzii bacteria in my gut both of which are pretty important for the production of Butyrate. Buytyrate being pretty important for energy production in the body and large amounts being from gut bacteria meant is was something I was looking at. I have been heavily working on my microbiome and getting some benefit (I need to run another biomesight to see where I am at some point this summer) but I wondered if I could just add Butyrate after I saw Sodium Butyrate it on Amazon. Turns out I get a bit of a boost from it. It was a bit of a random idea after a discussion I had here that inspired me to look to see what it would cost, I try a lot of random things like that just to see, stick with them for 2 months then drop them if I notice nothing. Nothing to do with HDAC inhibitors and keto in my case.

Its not done in isolation, there is a whole range of things I do to boost SCFA and butyrate production with every meal and every element of my diet is selected on some basis on what it will do microbiome wise or for driving the energy cycle.

I do use Caffeine too with coffee twice a day, curcumin and Quercetin don't do anything for me. I think the effect from the Caffeine is more to do with its vasoconstriction although it does so much in the body its impossible to know which effect is helping me. Decaf doesn't work the same that much I do know.

 

[GlassCannonLife]

I am taking it due to my biomesight/microbiome study showing a severely low Bifido and Faecalibacterium prausnitzii bacteria in my gut both of which are pretty important for the production of Butyrate. Buytyrate being pretty important for energy production in the body and large amounts being from gut bacteria meant is was something I was looking at. I have been heavily working on my microbiome and getting some benefit (I need to run another biomesight to see where I am at some point this summer) but I wondered if I could just add Butyrate after I saw Sodium Butyrate it on Amazon. Turns out I get a bit of a boost from it. It was a bit of a random idea after a discussion I had here that inspired me to look to see what it would cost, I try a lot of random things like that just to see, stick with them for 2 months then drop them if I notice nothing. Nothing to do with HDAC inhibitors and keto in my case.

Its not done in isolation, there is a whole range of things I do to boost SCFA and butyrate production with every meal and every element of my diet is selected on some basis on what it will do microbiome wise or for driving the energy cycle.

I do use Caffeine too with coffee twice a day, curcumin and Quercetin don't do anything for me. I think the effect from the Caffeine is more to do with its vasoconstriction although it does so much in the body its impossible to know which effect is helping me. Decaf doesn't work the same that much I do know.

Cool, thanks. You just take the recommended 2 pills of the bodybio? It's on sale on iherb atm so I might get some (20 % off)

 

[BrightCandle]

You just take the recommended 2 pills of the bodybio?

Yes just the 2, in the morning.