From brain fog to clarity in 30 minutes

[frozenborderline]

I consider phenibut to be almost as bad as a benzo. On the other hand, sodium butyrate may give you some of what you are looking for:

Histone Deacetylase Inhibitors Protect Against Pyruvate Dehydrogenase Dysfunction in Huntington's Disease

Abstract
Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We showed previously that the histone deacetylase inhibitors (HDACIs) trichostatin A and sodium butyrate (SB) ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work, we investigated the effect of HDACIs on the regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases 1 and 3 (PDK1 and PDK3). Exposure to dichloroacetate, an inhibitor of PDKs, increased mitochondrial respiration and decreased production of reactive oxygen species in mutant cells, emphasizing PDH as an interesting therapeutic target in HD. Treatment with SB and sodium phenylbutyrate, another HDACI, recovered cell viability and overall mitochondrial metabolism in mutant cells. Exposure to SB also suppressed hypoxia-inducible factor-1 (HIF-1α) stabilization and decreased the transcription of the two most abundant PDK isoforms, PDK2 and PDK3, culminating in increased PDH activation in mutant cells. Concordantly, PDK3 knockdown improved mitochondrial function, emphasizing the role of PDK3 inactivation on the positive effects achieved by SB treatment. YAC128 mouse brain presented higher mRNA levels of PDK1-3 and PDH phosphorylation and decreased energy levels that were significantly ameliorated after SB treatment. Furthermore, enhanced motor learning and coordination were observed in SB-treated YAC128 mice. These results suggest that HDACIs, particularly SB, promote the activity of PDH in the HD brain, helping to counteract HD-related deficits in mitochondrial bioenergetics and motor function.SIGNIFICANCE STATEMENT The present work provides a better understanding of mitochondrial dysfunction in Huntington's disease (HD) by showing that the pyruvate dehydrogenase (PDH) complex is a promising therapeutic target. In particular, the histone deacetylase inhibitor sodium butyrate (SB) may indirectly (through reduced hypoxia-inducible factor 1 alpha stabilization) decrease the expression of the most abundant PDH kinase isoforms (e.g., PDK3), ameliorating PDH activity and mitochondrial metabolism and further affecting motor behavior in HD mice, thus constituting a promising agent for HD neuroprotective treatment.

well phenibut is probably as addictive as a benzo, but Ive always been more intrigued by it because it doesnt compromise cognitive function in the same way. is a gabapentinoid but also seems to be more nootropic than gabapentin

 

[NilaJones]

Nicotinamide riboside works topically, too, in case anyone else finds that useful.

It's a very powerful supplement for me! I initially tried 50 mg, which turned out to be way too much. I couldn't stop working .

I'm experimenting with dosage. So far 3 topical doses of about 2mg each, a few hours apart, seems to be pretty good.

Thank you so much, folks for posting your experiences and inspiring me to try it! It looks like it may possibly be life-altering for me.

 

[nanonug]

Quick update: I've been taking 2g/day of DCA since May 10th. As I am feeling good on this dosage, I don't plan further increases. I am now fully focused on the thing that is probably behind SEID in my case, my GI system.

 

[Chris]

Wow--2g!! I started at 333mg a day about two weeks ago--felt improved for 7 days, decided to take a break for a couple of days (seems that is a good idea), OK, restarted, got a bottle of 500mg, yesterday morning took my first 500, felt great all morning--good energy for my little morning beach walk, really enjoyed the sun, cool clear air, sound of waves, did some computer work--still good, decided to take a 333 early afternoon--relapsed into deep fatigue (no pain, mind you--PEM without the M)--slept OK, think I will restart with a 333 this morning and see how I go. It definitely does things, mostly good, but I will have to carefully experiment with what dose works for me. I can now choose 333, 500, 666 (ominous!), 833, 1,000--some experimenting to do! And also time of day...anyone have thoughts on this?

 

[EtherSpin]

Before DCA I was mostly housebound and unable to do any useful work. My small business went down the tube because of this. Physical and mental fatigue were overwhelming.

At the current dosage (1.5g/day), I have no trouble falling asleep and I wake up refreshed with my brain fully engaged - there is no brain fog at all. Physical fatigue is not yet completely gone but I am at a point where I am considering playing table tennis again.

.

this is very intriguing, very much considering trialling parts of your regimen.
Im wondering though, do you have P.O.T.S or OI in general ? if so hows that going ?

 

[perchance dreamer]

With phenibut, you can develop a tolerance, but in my case, 100 MG on occasion is fine and really helps my sleep. When I've googled phenibut side effects or addiction, I've been shocked at what huge and frequent doses some people take. Even with my small dose, I use it no more than twice a week and never on consecutive nights.

 

[leokitten]

@nanonug thanks for all the detailed info. May I ask, realistically how much has this protocol helped you? What percentage of healthy, pre-disease capacity were you before protocol and now after? Are you able to work again and resume a fairly normal life?

 

[vortex]

@nanonug What is your dose of fursultiamine ?

I found 50mg capsules but then see in the reviews that some people take 6-8 capsules (300-400mg)

I also found this
http://www.ergo-log.com/fursultiamine-stamina-strength.html

"For practical applications, we recommend that athletes should consume a daily intake of 40 mg/kg thiamine tetrahydrofurfuryl disulfide (equivalently converted from a mouse 500 mg/kg dose,

For a 70 kilogram athlete, that dose would therefore amount to 2,800 milligram !!!

That would be a whole bottle everyday!

 

[Blasted]

Watching the new tv series Afflicted has encouraged me to retry a supplement regimen for my SEID. Researching PQQ brought me to this thread. Do you see the supplements you list as a good place to start or might supplements like carnitine, ribose, coq10 be a better jumping off point? I'm trying to improve my mitochondrial function.

 

[hmnr asg]

hi @nanonug hope you have been continuing to improve with your 2g of DCA. Could you give us an update please on your progress? im seriously considering starting DCA.

 

[Blasted]

Our friend nanonug doesn't have any activity on PR in over a month which is odd given how frequently he was posting before. I hope all is well with him.

 

[hmnr asg]

@Blasted @nanonug
Maybe that's a good sign that he has gotten much better and isn't staying at home

 

[frozenborderline]

By the way, @debored13, I want to thank you for pointing out that phenylbutyrate is also a PDK inhibitor. The following article, in particular, points to a combination of phenylbutyrate and dichloroacetate as a potential alternative to higher dosage DCA. It might be very useful in case of DCA toxicity.

Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate

Abstract
Pyruvate dehydrogenase complex (PDHC) is a key enzyme in metabolism linking glycolysis to tricarboxylic acid cycle and its activity is tightly regulated by phosphorylation catalyzed by four pyruvate dehydrogenase kinase (PDK) isoforms. PDKs are pharmacological targets for several human diseases including cancer, diabetes, obesity, heart failure, and inherited PDHC deficiency. We investigated the inhibitory activity of phenylbutyrate toward PDKs and found that PDK isoforms 1-to-3 are inhibited whereas PDK4 is unaffected. Moreover, docking studies revealed putative binding sites of phenylbutyrate on PDK2 and 3 that are located on different sites compared to dichloroacetate (DCA), a previously known PDK inhibitor. Based on these findings, we showed both in cells and in mice that phenylbutyrate combined to DCA results in greater increase of PDHC activity compared to each drug alone. These results suggest that therapeutic efficacy can be enhanced by combination of drugs increasing PDHC enzyme activity.

Just responding to this thread to remind myself to investigate this stuff if my thyroid trial doesn't work :/ I don't have a good way of taking easily accessible notes since my macbook crashed

DCA definitely looks promising and even if I got the kind of gains you get but used it short term I could have the energy to research the toxicity of it and research all these metabolic pathways--it would be like buying time even if it doesn't look good long term. I would do almost anything for just two to three weeks of near normalcy levels of energy, I swear I think i could figure out this illness in that time

Someone on the ray peat forum had some weird, possibly dangerous but intriguing-sounding method for making their own acetate to feed the kreb's cycle in the absence of pyruvate oxidation occuring fully ?
It was like vinegar mixed with some kind of sodium bicarbonate or potassium bicarbonate. And also was recommended super high doses of niacinamide... apparently low doses don't necessarily help .

 

[frozenborderline]

Here's the specific quote, this strikes me as an interesting solution to pyruvate dehydrogenase issues:

"I have lactic acid buildup due to advanced prostate cancer. I do apple cider vinegar and potassium bicarbonate ( can use baking soda) to make an acetate which will combine with CoA and form acetyl- CoA and feed the Krebs cycle and start the oxygenation process and form carbon dioxide which will reduce lactic acid made from Pyruvate (fermentation process). 2-3 grams of niacinamide will inhibit FAS and reduce lactic acid further. Aspirin will inhibit COX1 and COX2 and prevent prostaglandins which will prevent inflammation...do not eat fermented foods"

I have had short benefits from very high doses of niacinamide

 

[ljimbo423]

Here's the specific quote, this strikes me as an interesting solution to pyruvate dehydrogenase issues:

"I have lactic acid buildup due to advanced prostate cancer. I do apple cider vinegar and potassium bicarbonate ( can use baking soda) to make an acetate which will combine with CoA and form acetyl- CoA and feed the Krebs cycle and start the oxygenation process and form carbon dioxide which will reduce lactic acid made from Pyruvate (fermentation process). 2-3 grams of niacinamide will inhibit FAS and reduce lactic acid further. Aspirin will inhibit COX1 and COX2 and prevent prostaglandins which will prevent inflammation...do not eat fermented foods"

I have had short benefits from very high doses of niacinamide

I'm having really good success with BCAA's and pantethine. 2 of the 3 BCAA's, isoleucine and leucine are converted to Acetyl CoA and feed the krebs cycle.

The third, Valine, feeds into the krebs cycle directly. Pantethine (co-enzyme B-5) is the precursor to CoA, which is converted to Acetyl CoA and feeds the krebs cycle, like isoleucine and leucine.

Both BCAA's and pantethine feed the krebs cycle after the pyruvate dehydrogenase enzyme.

 

[frozenborderline]

I'm having really good success with BCAA's and pantethine. 2 of the 3 BCAA's, isoleucine and leucine are converted to Acetyl CoA and feed the krebs cycle.

The third, Valine, feeds into the krebs cycle directly. Pantethine (co-enzyme B-5) is the precursor to CoA, which is converted to Acetyl CoA and feeds the krebs cycle, like isoleucine and leucine.

Both BCAA's and pantethine feed the krebs cycle after the pyruvate dehydrogenase enzyme.

I have a supplement that has b5 and succinic acid in it. have BCAAs but always don't take them b/c lack the energy to weigh out like 1 million powders, etc. but it's on my mind. apparently mushrooms are good BCAA source

 

[frozenborderline]

Here's the specific quote, this strikes me as an interesting solution to pyruvate dehydrogenase issues:

"I have lactic acid buildup due to advanced prostate cancer. I do apple cider vinegar and potassium bicarbonate ( can use baking soda) to make an acetate which will combine with CoA and form acetyl- CoA and feed the Krebs cycle and start the oxygenation process and form carbon dioxide which will reduce lactic acid made from Pyruvate (fermentation process). 2-3 grams of niacinamide will inhibit FAS and reduce lactic acid further. Aspirin will inhibit COX1 and COX2 and prevent prostaglandins which will prevent inflammation...do not eat fermented foods"

I have had short benefits from very high doses of niacinamide

Okay so I don't know much chemistry but how could I forget that this is essentially the quintessential middle school chem project, mixing baking soda and vinegar. So it makes sodium acetate, so this fellow is correct that you can make an acetate with this reaction. the other product is carbonic acid which i'm assuming is the bubbles/gas and dissipates mostly???

 

[frozenborderline]

Okay so I don't know much chemistry but how could I forget that this is essentially the quintessential middle school chem project, mixing baking soda and vinegar. So it makes sodium acetate, so this fellow is correct that you can make an acetate with this reaction. the other product is carbonic acid which i'm assuming is the bubbles/gas and dissipates mostly???

this might be promising

 

[frozenborderline]

https://www.scbt.com/scbt/browse/pdk-Inhibitors/_/N-1594us9

This list of pdk inhibitors may be useful to anyone in this thread. DCA is a pdk inhibitor, which is why it helps people with impaired pyruvate dehydrogenase.

I don't think this is a full list, iirc some b vitamins also do this; it looks like a list of pdk inhibitors that are specifically pharmaceuticals or patented or something? Still very interesting

@Hip @nanonug @Learner1 @pattismith @Iritu1021

 

[frozenborderline]

https://www.scbt.com/scbt/browse/pdk-Inhibitors/_/N-1594us9

This list of pdk inhibitors may be useful to anyone in this thread. DCA is a pdk inhibitor, which is why it helps people with impaired pyruvate dehydrogenase.

I don't think this is a full list, iirc some b vitamins also do this; it looks like a list of pdk inhibitors that are specifically pharmaceuticals or patented or something? Still very interesting

@Hip @nanonug @Learner1 @pattismith @Iritu1021

It doesn't look like all of these are commonly used pharmaceuticals