From brain fog to clarity in 30 minutes

[nanonug]

I've been taking DCA for several weeks now, at 333mg BID, without ill effects. For this reason, I decided to increase the dosage to 1g/day. As I still have 333mg capsules available, I'm doing 666mg in the morning plus 333mg at night. New capsules will be 500mg and I'll be doing 500mg BID. I've also increased the amount of Ubiquinol to 200mg BID.

 

[ebethc]

I also find it important to supplement with pyrroloquinoline quinone (PQQ) in a long term basis as this promotes mitochondrial biogenesis. Without a sufficient number of mitochondria, the above four substances wouldn't be able to do much.

PQQ helps your body create MORE mitochondria? I didn't know that was possible..

 

[nanonug]

This past Saturday I ended up in the ER with terrible lower abdominal pain. Had a CT Scan done and after a while the doctor told me I was passing a (previously known) kidney stone. There was also an associated UTI for which I'm still taking antibiotics. Because I didn't want to be forcing my metabolism down through a particular pathway while dealing with an infection, I stopped the DCA. Will resume once I'm done with the antibiotic.

The lack of DCA has been very noticeable as I've been feeling way more tired, both physically and mentally. I'm looking forward to restarting the DCA, at 500mg BID, and see what kind of acute effect, if any, it'll have.

 

[aquariusgirl]

Are you experiencing a lot of urination? Feeling extra tired? Like you’re detoxing?

 

[nanonug]

Are you experiencing a lot of urination? Feeling extra tired? Like you’re detoxing?

Yes to all three. Prior to passing the stone, I wasn't peeing all that much but now things are flowing quite well!

 

[aquariusgirl]

I’m wondering if it’s peetox....
Also if you are reversing the metabolic trap or correcting the mito dysfunction, will other treatments work better like antibiotics??

 

[nanonug]

Also if you are reversing the metabolic trap or correcting the mito dysfunction, will other treatments work better like antibiotics??

I don't know. I'm still taking everything minus DCA. DCA is the only thing that I take that forces a particular metabolic pathway.

 

[aquariusgirl]

Do you feel like your metabolism is cranking along now you are treating the block @ dehydrogenase?

I am not on DCA but I am getting allergy type symptoms...increased excretion .,,gallbladder issues

 

[nanonug]

I've restarted DCA yesterday. I decided to be a bit more aggressive and instead of 500mg BID I went for 1g in the morning plus 500mg at night. It took me several hours to feel a difference. What is surprising, however, is that today I woke up feeling very refreshed and with zero brain fog. I'm going to continue the 1g/500mg dosage for a few weeks and see what happens, paying particular attention to any undesirable side effects.

 

[nanonug]

I just posted this and it is relevant for those seeking both restorative sleep and (hopefully) reduced brain fog: "Sleep and Brain Energy Levels: ATP changes during sleep".

 

[frozenborderline]

Maybe i missed this while reading, but what would you rate your fatigue prior to DCA? bedridden, housebound, mostly housebound, etc??? able to work?

Did the DCA help with fatigue or just brain fog?

 

[nanonug]

Maybe i missed this while reading, but what would you rate your fatigue prior to DCA?

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.

If my DCA trial at 1.5g/day causes no issues with toxicity, I intend to increase my dosage to 2g/day. That will hopefully happen in the second or third week of May.

DCA toxicity is something that I am definitely concerned about. Besides neurotoxicity, which one can "feel", there is also a possibility of hepatotoxicity so I'll be testing for liver enzyme elevations every few months. I do take NAC and TMG and this should hopefully afford some protection. At this point, I feel comfortable with DCA's risk/reward ratio but I am prepared to reduce the dosage, or even stop for a certain amount of time, if necessary.

 

[frozenborderline]

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.

If my DCA trial at 1.5g/day causes no issues with toxicity, I intend to increase my dosage 2g/day. That will hopefully happen in the second or third week of May.

DCA toxicity is something that I am definitely concerned about. Besides neurotoxicity, which one can "feel", there is also a possibility of hepatotoxicity so I'll be testing for liver enzyme elevations every few months. I do take NAC and TMG and this should hopefully afford some protection. At this point, I feel comfortable with DCA's risk/reward ratio but I am prepared to reduce the dosage, or even stop for a certain amount of time, if necessary.

Interesting, so there really has been a dramatic difference. I will look into it and weight the risks/benefits. I am at a similar level as you discussed, although I am getting worse and predict being bedbound if things don't change

 

[nanonug]

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.

 

[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.

I had forgotten about phenylbutyrate for awhile but the thread made me remember about it. You're right that even if PDH isn't the only issue, it makes a pretty promising drug target that could even alleviate a portion of the fatigue. have been suffering so much daily that even a little improvement would be amazing.

I will bring up DCA and phenylbutyrate to my doctor. May be something to try if my thyroid trial does not work. and like most things I might try it even if the doctor doesn't think it promising, I can't be waiting for cures for years, don't have that.

 

[frozenborderline]

where to obtain sodium phenylbutyrate and dca?

 

[nanonug]

where to obtain sodium phenylbutyrate and dca?

The DCA that I use (and the one that was used in the pilot trial) is this one: https://www.dcalab.com/
It is also available on Amazon but it costs a few bucks more.

Sodium phenylbutyrate is a prescription drug not available in the US (as far as I know.) It may be possible to order it from Europe but I haven't looked yet.

 

[frozenborderline]

The DCA that I use (and the one that was used in the pilot trial) is this one: https://www.dcalab.com/
It is also available on Amazon but it costs a few bucks more.

Sodium phenylbutyrate is a prescription drug not available in the US (as far as I know.) It may be possible to order it from Europe but I haven't looked yet.

bummer. I will look into sourcing it

 

[frozenborderline]

um... phenibut is "aminophenylbutyric acid", wonder if it's similar. I've had temporary alleviation from fatigue from phenibut, but the "hangover" always fucked me up. Wonder if there's more than a superficial similarity

 

[nanonug]

phenibut

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.