From brain fog to clarity in 30 minutes

[nanonug]

First of all, let me clarify that I take much more stuff than the things I am about enumerate. They are important in their own right and include support for methylation and glutathione production, for example. Also, the disclaimer applies that these things work for me and there is absolutely no guarantee that they will work for anyone else. That being said, there are good reasons why they might work for others as well.

There is nothing revolutionary here, and there is most likely room for improvement, but the following are the things that appear to have a quick effect on my brain fog:

• Ubiquinol
• Nicotinamide Riboside
• Fursultiamine
• Dichloroacetate

Ubiquinol, nicotinamide riboside and fursultiamine are all involved in mitochondrial oxidative phosphorylation. Nicotinamide riboside is a precursor to NAD+ and fursultiamine is a thiamine analog and precursor to thiamine pyrophosphate (aka, cocarboxylase.) Dichloroacetate inhibits pyruvate dehydrogenase kinase, therefore "forcing" pyruvate (via acetyl-CoA) through the Krebs cycle. Dichloroacetate is potentially toxic so care with dosage of this substance is of utmost importance.

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.

 

[Runner5]

Are those supplements or prescription? I've never heard of them.

 

[nanonug]

Are those supplements or prescription? I've never heard of them.

None of them is prescription, at least not in the US. Dichloroacetate is really not a supplement but to my knowledge doesn't require a prescription anywhere.

 

[rodgergrummidge]

Hi @nanonug, very interesting. Be careful with the DCA. Clinical trials have basically stopped for DCA because of the toxicities, but it is still used in cases of congenital PDH deficiencies where kids can die if left untreated. Probably a good idea to monitor toxicities. For example, clinicians treating with DCA will sometimes measure the accumulation of maleylacetone and delta-aminolevulinate (heme precursor) which are potentially are toxic to the liver and peripheral nerves.

What dosing regimens do you use? And where do you buy Nicotinamide Riboside, Fursultiamine and PQQ?

Do you have mitochondrial defect? PDH? lactic acidosis? If so, how did you diagnose it?

Rodger

 

[nanonug]

Be careful with the DCA.

Yes, I'm aware of the dangers, something I mentioned in my original post. Based on my research, there has been no issues with toxicity when dosages are kept under 5mg/kg BID. I currently take 333mg BID which is below that threshold.

What dosing regimens do you use? And where do you buy Nicotinamide Riboside, Fursultiamine and PQQ?

Nicotiname riboside (250mg BID): https://www.amazon.com/gp/product/B072R2LVLV/
Fursurtiamine (150mg morning / 50mg night): https://www.amazon.com/gp/product/B0058AB268
PQQ (10mg BID): https://www.amazon.com/gp/product/B00GXC9OHE

Do you have mitochondrial defect? PDH? lactic acidosis? If so, how did you diagnose it?

Don't know. Don't know. Don't know. I didn't diagnose it, I'm using the research by Naviau et al and Fluge et al (hypometabolic state/PDH dysfunction) as guide and assuming that it applies in my case as well.

 

[rodgergrummidge]

Yes, I'm aware of the dangers, something I mentioned in my original post. Based on my research, there has been no issues with toxicity when dosages are kept under 5mg/kg BID. I currently take 333mg BID which is below that threshold.



Nicotiname riboside (250mg BID): https://www.amazon.com/gp/product/B072R2LVLV/
Fursurtiamine (150mg morning / 50mg night): https://www.amazon.com/gp/product/B0058AB268
PQQ (10mg BID): https://www.amazon.com/gp/product/B00GXC9OHE



Don't know. Don't know. Don't know. I didn't diagnose it, I'm using the research by Naviau et al and Fluge et al (hypometabolic state/PDH dysfunction) as guide and assuming that it applies in my case as well.

Very interesting @nanonug, the Fursurtiamine (aka TTFD) is a modified version of Thiamine or Vit B1 (Med Sci Monit, 2004; 10(9): RA199-203). It has a disulfile 'linker' that helps with the uptake of the drug into cells. When TTFD comes into contact with cell membranes, the disulfide is fractured and it remains outside the cell. The remainder of the molecule passes through the cell membrane, the thiazolium ring closes and the cell now has an intact molecule of free thiamine in the cytosol.

The disulfide makes TTFD more powerful in its actions compared with the readily available water-soluble thiamine salts, since it does not require the rate limiting transport system required for thiamine (Med Sci Monit, 2004; 10(9): RA199-203). Essentially, there is a rapid buildup of intracellular thiamine and so the effective concentration of B1 is much higher than achieved by conventional B1 supplements.

The pharmacologic activity of the disulfide link in TTFD or its toxicities are not known. After oral administration of TTFD to human subjects, urinary recovery of the labelled disulfide was 90% and so it might be prudent to monitor kidney toxicity.

Rodger

 

[sb4]

I'm pretty interested in dichloroacetate. I have looked at the side effects and it seems that neurophathy is one, presumably from the increased PDH using up B1. So taking B1 should be a remedy, and gastrointestinal. Are there more extreme side effects I'm missing?

How do you think it will interact with those on ketogenic diets? Might it push too of already low levels of sugar, down into Acetyl CoA instead of into oxaloacetate causing blood sugar issues?

 

[nanonug]

I'm pretty interested in dichloroacetate. I have looked at the side effects and it seems that neurophathy is one [...] Are there more extreme side effects I'm missing?

To my knowledge, neuropathy is the only one, at least within the dosages normally used in humans. Also, to my knowledge, all cases of neuropathy have been reversible.

How do you think it will interact with those on ketogenic diets?

That's a good question. I don't know!

 

[CFS_for_19_years]

PQQ (10mg BID): https://www.amazon.com/gp/product/B00GXC9OHE

I agree that PQQ helps a lot with energy and being more alert. It should be taken no later than noon since it is energizing. Several people here on PR said that it was like speed to them, so I recommend starting at 5mg per day, then if no improvement in 3 days, increase to 10mg per day, etc.

This is the brand I use because it is a 20mg TABLET that can be broken into quarters (a 5mg dose) with a pill-splitter:
https://www.amazon.com/SOURCE-NATURALS-Mind-Tablet-Count/dp/B00BQS87D2

 

[dreamydays]

Twenty-two consecutive patients suffering from refractory myalgic encephalitis/chronic fatigue syndrome (ME/CFS) were treated with an innovative nutriceutical containing sodium dichloroacetate in a proof-of-principle, pilot, open-label prospective cohort trial. Ten patients experienced significant improvement of their health condition with reduction to almost half of their score in the fatigue severity scale. In twelve patients treatment failed to exert any beneficial effect. In the latter patients several other diseases have commonly been revealed by extensive biological and imaging investigations. These preliminary findings sustain the hypothetical role of mitochondrial hypo-metabolism due to inhibition of the activity of the pyruvate dehydrogenase in the pathogenesis of primary ME/CFS, and suggest a possible benefit of nutriceutical treatment by sodium dichloroacetate.

http://www.medical-hypotheses.com/article/S0306-9877(18)30105-1/fulltext#s0040

 

[nanonug]

http://www.medical-hypotheses.com/article/S0306-9877(18)30105-1/fulltext

Nice find! Thanks for posting!

 

[RustyJ]

Hi nanonug, could you also provide brand and dosage for your Ubiquinol, and brand for the Dicholoacetate.

 

[rodgergrummidge]

I'm pretty interested in dichloroacetate. I have looked at the side effects and it seems that neurophathy is one, presumably from the increased PDH using up B1. So taking B1 should be a remedy, and gastrointestinal. Are there more extreme side effects I'm missing?

How do you think it will interact with those on ketogenic diets? Might it push too of already low levels of sugar, down into Acetyl CoA instead of into oxaloacetate causing blood sugar issues?

I'm pretty interested in dichloroacetate. I have looked at the side effects and it seems that neurophathy is one, presumably from the increased PDH using up B1. So taking B1 should be a remedy, and gastrointestinal. Are there more extreme side effects I'm missing?

How do you think it will interact with those on ketogenic diets? Might it push too of already low levels of sugar, down into Acetyl CoA instead of into oxaloacetate causing blood sugar issues?

some information on DCA can be found here

some information on DCA toxicity and the risks of self-medication can be found here

In terms of combinnig DCA with a ketogenic diet, it wouldnt really make much biochemical sense unless there was a really serious PDH defect such as sometimes occurs in congenital disorders. The reasoning would be that:

On a carbohydrate diet, the glycolytic pathway converts carbohydrates and sugars into pyruvate which is then converted by PDH into acetyl CoA to fuel the TCA cycle. Thus, on a carbohydrate diet, PDH provides a vital link that funnels the product of glycolysis (pyruvate) into the mitochondrial where the TCA and oxidative phosphorylation (OXPHOS) convert it into energy (ATP). If PDH is only weakly active in an individual (as can occur in congenitial diseases), then there will be insufficient Acetyl CoA to fuel the TCA and OXPHOS and so not enough ATP to fuel tissue functions. In such a situation, DCA might be used therapeutically to activate PDH activity and increase Acetyl CoA production in order to increase aerobic energy production from carbohydrates.

A ketogenic diet provides a 'short-cut' that skirts around PDH to allow the generation of energy from fatty acids and amino acids rather than pyruvate. On a ketogenic diet lacking significant amounts of carbohydrates and sugars, glycolysis is largely inactive and so there is little pyruvate produced. Under these conditions, fatty acids and amino acids enter the TCA cycle at steps 'after' PDH. Thus, activating PDH activity using DCA under conditions where there is little glycolysis and pyruvate production wouldnt make biochemical sense (one exception might be really serious congenital defects in PDH where the patient has gone into lactic acidosis). Thats because the whole purpose of the ketogenic diet is to 'skirt around PDH' and provide alternative fuels (fatty acids and amino acids) to the TCA.

Rodger

 

[researcher]

So you guys think that brainfog is a consequence of a dysfunctional mitochondria?

 

[nanonug]

Hi nanonug, could you also provide brand and dosage for your Ubiquinol, and brand for the Dicholoacetate.

This is what I take:
Ubiquinol (100mg BID): https://www.amazon.com/gp/product/B002CBXR46/
Dicholoacetate (333mg BID): https://www.amazon.com/gp/product/B071S3SRSP

 

[nanonug]

So you guys think that brainfog is a consequence of a dysfunctional mitochondria?

Not necessarily. Most likely cause is inhibition of pyruvate dehydrogenase complex in the mitochondria due to physiological stresses, such as excessive reactive oxygen/nitrogen species (ex: superoxide, peroxynitrite.)

 

[Frenchguy]

@nanonug

Thanks for sharing,
What's your function level ?

 

[nanonug]

@nanonug What's your function level ?

With the amount of stuff that I take, close to normal. But I still need to be careful not to overexert myself. So I guess I'd put myself in the mild SEID category.

 

[Insomniac]

@nanonug Did you ever try DCA alone or only part of the whole protocol you listed in the opening post?

Can you remember how long it took before this whole protocol or DCA alone started helping?

I assume you need to be on these supplements permanently to stay functioning near normal?

 

[nanonug]

@nanonug Did you ever try DCA alone or only part of the whole protocol you listed in the opening post?

Never alone, only part of the complete protocol.

Can you remember how long it took before this whole protocol or DCA alone started helping?

It took me a few days to start feeling a difference. I no longer recall exactly how many but I'd say after 7 days I was "feeling it."

I assume you need to be on these supplements permanently to stay functioning near normal?

At this point, that's my understanding. It's not a permanent fix, it's a band-aid.