Succinic acid studied for mito disease. Fumaric acid also

[robinhood12345]

Hi all. So have to be careful with the way things are worded because apparently can't give medical advice here.

In the dropbox link is a lot of studies on succinic acid

https://www.dropbox.com/sh/kq2p8rwpyu3xu0p/AABtBrxSKbZu3nNVZAns8wYxa?dl=0

There is study showing 6g a day treats MELAS syndrome- a severe mitochdondrial disease caused by a mutation in the electron transport chain. There is another study saying succinic acid can treat all electron transport chain diseases. Because of its role in the electron transport chain it could treat any blockage anywhere in krebs cycle or the pyruvate dehydrogenase complex.

Medical geneticists, pharmacists, and other experts in the field know about it but keep it secret so they can exploit sick people for money. Unpleasant but oh well don't dwell on it.

I am on succinic acid for 3 days now, 20g first day, 15g second day, and only about 3g today, and will continue taking it as I suspect I have an undiagnosed mitochondrial disease. I will find a standard dose, and settle on it, maybe around 5-6 g a day. I will update when I get better on it.

The amino acid threonine has been studied for PKU (it lowers phenylalanine), and MS (loosens muscles/stops spasticity). Studies on that are in the file too.

This was copy pasted from a website in Russian, as they have more info on succinic acid in their country than in English countries. The website is in the public domain.
http://www.prosto-mariya.ru/yantarnaya_kislota_svoistva_i_primenenie_220.html

In Western countries, the coenzyme Q10 is very popular. In some experiments, coenzyme Q10 showed the ability to express prolonged life. But here that is interesting; There is a drug that plays in the body a role similar to coenzyme Q10. It is also, and perhaps more effective, at a price that is about 10 times cheaper. It's succinic acid. Perhaps, it is because of such a low price that amber acid is not promoted to the market.

We should pay special attention to succinic acid (hereinafter YaK)! By the ratio of price / effectiveness, this thing is almost the leader among the means to prolong life. Yak is a natural substance (present in all organisms), has a powerful healing effect, without causing side effects and addictive. There are many reasons for this, but there are basic reasons.
Amber acid:

(more in the succinic acid info text file- not allowed to post too much text).

 

[Hip]

Medical geneticists, pharmacists, and other experts in the field know about it but keep it secret so they can exploit sick people for money.

I am all for trying interesting supplements, but "Secret Cures They Don't Want You To Know About" is the top of the list of alternative medicine marketing cliches.

 

[Learner1]

@whatareyoulookingat OK, I'll bite. I keep having no succinic acid showing up every time I do a NutrEval test. I have adequate amounts of all the other Krebs cycle metabolites. What do you suppose this means?

Thanks for the many docs in your Dropbox link... Can you summarize, please? I do like to read, but its quite a lot to digest. Dont worry, I won't take it as medical advice...

 

[robinhood12345]

The summary is in the text file in the drop box.

 

[Learner1]

The summary is in the text file in the drop box.

Thanks for pointing that out.

My question is where is it all going? Why do I have the other Krebs metabolites, but absolutely no succinic acid?

I suspect its all going to make ATP as fast as I can make it, but am not sure. Supplementing is one answer, but how can we increase production? Or reduce demand?

 

[Jesse2233]

... and to complicate things, why is my succinic acid high?

 

[robinhood12345]

I will write a response, and get back to you.

 

[robinhood12345]

I did an organic acid test with Genova years ago back when they were called Metametrix. After finding info about succinic acid recently, I looked at the test again. Succinic acid was high, a few other things high, and low. It says on the test "not to be used for diagnosis of neonatal inborn errors of metabolism", and "not to be used for diagnostic purposes". A hospital lab runs organic acids tests on people for the exact purpose of diagnosis. On page 135 in this book he will give reasons not to trust private labs

http://gen.lib.rus.ec/book/index.php?md5=51CB2D41FA2EC95C2D2ED7A2D76EF174

I think it is even worse than he says though- in some cases they may not even do the test but just make up random results, and send it to the doctor/patient. By saying not to be used for diagnostic purposes they remove any liability for someone using it for diagnostic purposes.... So I have no reason to believe my results from years ago were accurate, and wouldn't trust other results also.

I did an amino acid test years ago with a private lab, and they all came back low or low normal- none were normal or high. Now years later, and was 50 times sicker (I will be better soon on succinic acid) I did an amino acid blood test at a hospital lab, and every single one was normal...... so don't trust any results from private labs.

A PDF called "mitochondrial disease consensus criteria" in the sub folder "Mitochondrial disease studies" gives the order of tests if someone wants to test for mitochondrial diseases. Someone could print it out, and take it to their doctor. If wanting to do a urine organic acid try do it with a hospital lab though I'm not sure if they run it without prior blood work to indicate possible mitochondrial problems (abnormal blood pyruvate:lactate ratio or abnormal carnitines or some other things) or unless the patient displayed severe muscle/brain symptoms which is indicative of a mitochondrial disease. Better off just buying, and taking succinic acid.

The succinate to fumarate conversion happens on the inner mitochondrial membrane NOT in the cytosol of the mitochondria like the rest of krebs cycle so some pictures of krebs cycle are misleading. Succinic acid is very important to make ATP. It ties a number of the reactions in the several complexes of the electron transport chain together.

This guy has good videos on the 5 complexes of the electron transport chain

Food grade/99% pure succinic acid is sold on Amazon.com, someone from Bulgaria is selling it on ebay, and posting worlwide, and chemical supply company websites sell it so google around to find one in ones own country. Or I got 1kg from Ali Baba for 160 AUD including delivery. If buying 5kg it would likely be 300 AUD inc delivery. The more someone buys the cheaper it gets. 1000s of tonnes of it are made every year because it is widely used in industry. For 1 tonne it is only 2500 USD. Not that someone needs that just an interesting tidbit.

I took 20g the first day, and about 15g for the past 2 days but will likely settle on 5-10g a day.

 

[robinhood12345]

Succinic acid is the best organic acid for ATP production, and for treating most mitochondrial disease however all the other krebs cycle intermediates can be taken also. Fumaric acid, citric acid, calcium pyruvate, malic acid, ornithine AKG. These are for sale cheap on ebay. Amino acids don't do anything (except proline, and threonine they can help some problems like making collagen, sports, PKU, MS). Minerals don't do anything. B vits don't do anything.

 

[Jesse2233]

point taken on Genova, though I shudder to think they just randomly generate results

I just checked my labs and I've also had Succinic tested 3x via UCLA Urine Organic Acids

Succinic: (Ref: <= 25) - 9 (6/15/17), 4 (6/28/17), 8 (9/29/17)

Seems it can bounce around quite a bit. Unfortunately UCLA didn't give a lower cut-off for low values

 

[robinhood12345]

Interesting. Well I would believe the university lab over what looks like a private lab results you posted above. And on the Genova results if something comes back low instead of saying "take citric acid" or "take succinic acid" they say to take things like B vits, minerals, amino acids etc even though presumably they know about oral organic acids. It's just one big scam.

I have only been on the succinate a few days I will update in 1-2 weeks with how it is going.

In order of supplements to think about I would do
1) succinic acid
2) fumaric acid
3) other krebs cycle intermediates.

They should work for 99.9% of people I would estimate.

4) If none of them worked then
NADH,
COQ10,
Riboflavin 5 phosphate aka active b2 which is needed to make FAD which is needed for a number of reactions in the body including the succinate dehydrogenase complex by the looks of some diagrams on it. I have actually ordered 1g of FAD from Ali Baba to take 10mg a day orally if succinate didn't work in case I had a disease where I couldn't make that. It was 270 AUD. Bulk NADH is a lot cheaper.
The mineral boron- apparently all the worlds soils are deficient in it so they have to artificially add it to plants. If the plants don't have enough then we don't have enough from eating them or eating cows that ate them. Borax which is around 10% boron is available from supermarkets. It lowers estrogen, and raises testosterone in men which is something body builders want to do. I took 1g a day for a few days, and might start taking some again.

 

[Learner1]

My family has been doing Genova Diagnostics tests for 9 years, multiple family members once a year. We've had other tests done which corroborate what the Genova tests say, allowing for variability based on diet and envirinmental factors varying.

Just found this on the Feel Good Biochemistry site - how are your B2 and B3 levels, @Jesse2233 ? I don't have high aluminum, but do have a BH4 problem...

Low succinic acid can be due to excess aluminum in your system. Look for other signs of aluminum excess, such as high aluminum on a HMT and UEE, imbalances in other Krebs cycle intermediates on the MAP, or a need for BH4 as evidenced by high phenylalanine, tyrosine, or tryptophan on a UAA. If these indicators suggest that aluminum and BH4 are issues, then consider MetalAway, EDTA soap, or EDTA soak, and BH4 supports, such as BH4 itself and MTHFR A1298C Liver Support capsules. In addition, succinate helps to limit the enzyme urocanase, which plays a role in increasing FIGLU and glutamate. So, low levels of succinate may be a factor in high FIGLU and high glutamate. If succinic acid is too low, consider Vitamin E succinate and Adenosyl B12. Low B2 (riboflavin) and B3 (niacin) generally lead to extremely high levels of succinic acid. If succinic acid is high, consider Riboflavin-5-Phosphate and MTHFR A1298C Liver Support capsules. In addition, consider NADH, Niacinamide or Ultimate B to support vitamin B3. Thallium can cause issues with riboflavin levels, so if thallium is present on the UTM or HMT, consider additional Riboflavin-5-Phosphate to help convert succinate to fumarate. High succinate may combine with excess glycine to increase porphyrins. Check glycine on a UAA, and use AHCY/SHMT compound if needed.

 

[robinhood12345]

If succinic acid is too low, consider Vitamin E succinate and Adenosyl B12

Those vitamins do nothing usually. Consider taking actual succinic acid.

Diet provides all the b vits we need. Unless someone has phenylkeotnuria or another severe genetic disease where they can't process phenylanine then there is pretty much no such thing as a BH 4 problem. Some people just want to sell expensive, ineffective supplements. Yasko is not an honest person.

Succinate chelates all toxic metals better than DMPS, cilantro or DMSA, and it can even chelate them out of the mitochdonria. DMSA is a toxic analog of succinic acid that is a competitive inhibitor of the same enzyme succinate works on- succinate dehydrogenase- which is why someone feels so bad while taking it.

 

[Hip]

Succinic acid is the best organic acid for ATP production, and for treating most mitochondrial disease however all the other krebs cycle intermediates can be taken also.

Although it says in this paper on mitochondrial disease that "succinate may be used as an anaplerotic compound in specific patients," it is not clear to me how succinic acid / succinate would get into the Krebs cycle, as there are only a limited number of inputs and output for this cycle (ie, not all steps in the Krebs cycle have inputs and outputs to the outside world).

Here is a diagram of the Krebs cycle: the red arrows indicate where Krebs cycle intermediates (the compounds used in the steps in the cycle) may be drawn out of the cycle for use elsewhere, and the black arrows indicate where compounds can enter the Krebs cycle, in order to replenish the Krebs cycle intermediates:

The Krebs Cycle, showing inputs (black arrows) and outputs (red arrows)

As you can see, the succinate step itself has no inputs or outputs, although the step just before succinate, the succinyl-CoA step, does have both inputs and outputs.

The inputs to succinyl-CoA include odd-chain fatty acids. One odd-chain fatty acid that enters the Krebs cycle at the succinyl-CoA step is triheptanoin, which we have talked about on this forum. Unfortunately it is very difficult to get hold of.

 

[gregh286]

Hi all. So have to be careful with the way things are worded because apparently can't give medical advice here.

In the dropbox link is a lot of studies on succinic acid

https://www.dropbox.com/sh/kq2p8rwpyu3xu0p/AABtBrxSKbZu3nNVZAns8wYxa?dl=0

There is study showing 6g a day treats MELAS syndrome- a severe mitochdondrial disease caused by a mutation in the electron transport chain. There is another study saying succinic acid can treat all electron transport chain diseases. Because of its role in the electron transport chain it could treat any blockage anywhere in krebs cycle or the pyruvate dehydrogenase complex.

Medical geneticists, pharmacists, and other experts in the field know about it but keep it secret so they can exploit sick people for money. Unpleasant but oh well don't dwell on it.

I am on succinic acid for 3 days now, 20g first day, 15g second day, and only about 3g today, and will continue taking it as I suspect I have an undiagnosed mitochondrial disease. I will find a standard dose, and settle on it, maybe around 5-6 g a day. I will update when I get better on it.

The amino acid threonine has been studied for PKU (it lowers phenylalanine), and MS (loosens muscles/stops spasticity). Studies on that are in the file too.

This was copy pasted from a website in Russian, as they have more info on succinic acid in their country than in English countries. The website is in the public domain.
http://www.prosto-mariya.ru/yantarnaya_kislota_svoistva_i_primenenie_220.html


(more in the succinic acid info text file- not allowed to post too much text).

Did you see any improvement yet more to the point....

 

[Learner1]

Reading below, from Elmhurst College's site, it says succinic acid is the product if the steps that makes ATP.

So, if you take succinic acid, isn't that AFTER when the ATP is made? And best case, useful if you go around the cycle again?

I'm still wondering if I have no succinic acid, does that mean my ATP production was limited too? If so, why? And what can be done? More BCAAs?

Reaction 6: Oxidation, Decarboxylation, Thiol Ester Synthesis

This complex oxidative decarboxylation is guided by three enzymes in much the same fashion as the formation of acetyl CoA from pyruvic acid. This is actually the only non-reversible step in the entire cycle and prevents the cycle from operating in the reverse direction.

This is the second oxidation reaction in which an alcohol is converted to a ketone. Two hydrogens and 2 electrons are transferred to NAD+ to NADH + H+. This another the entry point into the electron transport chain.

This is the second step where a carbon group is lost as carbon dioxide in a decarboxylation reaction. Essentially, although not the exact same carbons, the two carbons from the acetyl CoA have been converted to carbon dioxide at the end this step.

The remaining 4 carbon group is attached to the CoA through a thiol ester high energy bond. Notice that the final product, succinyl CoA, has 4 carbons in the succinate group at one end of the CoA molecule.

This reaction is catalyzed by alpha-ketoglutarate dehydrogenase complex.


Reaction 7: Hydrolysis of Succinyl CoA;
Synthesis of ATP

The hydrolysis of the thioester bond (exothermic) is coupled with the formation of ATP (Actually guanosine triphosphate is formed first but is further coupled with the ADP to make ATP). This is the only "visible" ATP formed in the entire cycle.

Succinic acid, a 4 carbon acid, is the product of this reaction. This is the start of the return to the beginning of the cycle.

This reaction is catalyzed by succinyl CoA.

 

[gregh286]

i had no succinic either.
quite hard to get a hold of, so never supplemented.

 

[Learner1]

i had no succinic either.
quite hard to get a hold of, so never supplemented.

Interesting. Bet you lack energy, too?

As an experiment, my doctor gave me NAD+ in an IV this week. I had "normal" energy for about 36 hours and was able to have a brisk 3 mile walk without ill effects. He said if it worked, I could try a nebulizer with it. It sure seems like I have some sort of limit on making energy.

 

[gregh286]

Interesting. Bet you lack energy, too?

As an experiment, my doctor gave me NAD+ in an IV this week. I had "normal" energy for about 36 hours and was able to have a brisk 3 mile walk without ill effects. He said if it worked, I could try a nebulizer with it. It sure seems like I have some sort of limit on making energy.

Yep for sure i lack energy. Stamina shit too.
Ketogenic Diet seems to boost NAD+
http://alivebynature.com/what-is-nad-why-do-you-need-it-and-how-does-it-work/

 

[robinhood12345]

So, if you take succinic acid, isn't that AFTER when the ATP is made? And best case, useful if you go around the cycle again?

No. Succinate dehydrogenase is complex 2 of the electron transport chain so it feeds directly into that. I can't help but think you already know this.