Succinic acid studied for mito disease. Fumaric acid also

[Learner1]

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.

All right, since all I'm getting is snarky comments from you, I looked into it.

One needs both B2 AND CoQ10 to make complex II work, in addition to your succinic acid. So, looks like those of us short of succinic acid may have sufficient B2 and CoQ10, and those with elevated levels may be short of either CoQ10 or B2 (or both).

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.

Taking organic acids may be beneficial. However, your heart will stop without sufficient amounts of magnesium or potassium, chromium is used in blood sugar regulation, selenium is used for thyroid and glutathione production, zinc is needed in the immune system, iron and B6 are essential for hemoglobin, B vitamins are essential for immune function, neurotransmitter production, DNA replication, detoxification, oh, and ATP production. Amino acids are pretty handy, too. They are definitely not a scam.

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.

Well, yes, everyone needs them. However, our bodies have processes for making them. If we are not, it is important to ask why.

Additionally, it is naive to think that just supplementing these will fix 99.9% of people. Many of have other nutrient needs, which, unmet, will keep us sick.

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.

Yes, these are useful, too.

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.

FAD is not interchangeable with NADH. They both have uses.

Your 10mg a day of FAD is ridiculously low. Based on repeated lab tests, my body needs about 225mg. It is used for many other jobs in the body:

“Riboflavin is also used for the development and function of the skin, lining of the digestive tract, blood cells and other vital organs,” Dr. Sherry Ross, women’s health expert at Providence Saint John’s Health Center in Santa Monica, California, told Live Science.

Vitamin B2 is also important for eye health. According to the University of Michigan, this vitamin is needed to protect glutathione, which is an important antioxidant in the eye. The U.S. National Library of Medicine (NLM) reports that eating a diet rich in riboflavin can lower the risk of developing cataracts. Taking supplements containing riboflavin and niacin may also be helpful in preventing cataracts.

Levels of certain vitamins, chemicals and minerals in the bloodstream seem to be dependent on healthy levels of B2, as well. For example, riboflavin changes vitamin B6 and folate (vitamin B9) into forms that the body can use. According to the American Journal of Clinical Nutrition, riboflavin is important to how the body processes iron. Without it, research shows that the body is more likely to develop anemia. Taking riboflavin can also reduce homocysteine levels in the blood by 26 to 40 percent, according to the NLM.

B2 may be important to pregnancy health, as well. According to a study by the University Women's Hospital, Heidelberg, Germany, riboflavin deficiency may be a factor in causing preeclampsia, a condition that causes high blood pressure in late pregnancy.

Those suffering from migraines may find that taking doses of B2 may help. A study by the department of neurology of Humboldt University of Berlin found that those taking high doses of riboflavin had significantly fewer migraines.

Thank you got bringing succinic acid to our attention. But, it sure seems like there are a few layers of complexity here.

 

[robinhood12345]

Supplementing amino acids do nothing positive. The majority of the population takes in at least twice the RDA of protein it might be more like 2.5-3 times as much. No one in English speaking countries has a protein deficiency.

Same with B vitamins.

Even though textbooks say carbohydrates, and amino acids yield the same amount of energy they don't- amino acids will make less ATP than carbohydrates because they feed into krebs cycle after glycolysis where some ATP, and NADH is made, and the further around into krebs they feed the less NADH is made, and so the less ATP is made. Carbohydrates are mans main fuel source not protein, or fat, or ketones, or anything else.

And if someone eats an apple a day they will get most of the minerals they need including magnesium. But to sell it first a scare has to be created that everyone is deficient in it, which is not true. Potassium on the other hand is something the literature says is at low levels in the diet but I don't see many companies selling potassium supplements.

I didn't sat FAD, and NAD are the same. If you have low levels (well those labs can't be trusted anyway) take active b2, and if that doesn't work try actual FAD from Ali Baba. FAD is incredibly important to make nitric oxide, succinate dehydrogenase looks to use it in some diagrams, AKG dehydrogenase looks to use it in some diagrams, and lots of other things also.

If someone wants to increase nitric oxide which opens all blood vessels in the body, and POTENTLY lowers blood pressure take sodium nitrite. It is so strong so start at 10 milligrams, and work up. Someone on prescription medication should talk to their doctor first or it is dangerous.

If someone has low levels of succinic acid or fumaric acid or any other krebs cycle thing then take that actual thing- not cofactors for the enzyme. In people with normal functioning mitochondria/electron transport chain taking citric acid -which is available at supermarkets -will make a lot of ATP. Or malic acid. Or any of the other ones.

 

[pamojja]

And if someone eats an apple a day they will get most of the minerals they need including magnesium. But to sell it first a scare has to be created that everyone is deficient in it, which is not true. Potassium on the other hand is something the literature says is at low levels in the diet but I don't see many companies selling potassium supplements.

How much I wished not to believe that myth - that everyone get's enough Mg despite biochemical-individuality (or all other essential minerals and vitamins) - my whole life. Only with serious disability did I get my levels actually tested. And in case of Mg my deficiency was so severe, that even 1.5 g of supplemented elemental oral Mg could't correct it during the last 9 years (despite an additional whooping 600 mg from diet). Had to resort to Mg-sulfate IVs instead.

 

[ErdemX]

@whatareyoulookingat How did your experiment with succinic acid go? Could you get any benefits from it?

 

[frozenborderline]

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.

I may ask my doctor about this next

 

[frozenborderline]

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 black 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 red 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)
View attachment 25486​

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.​

I will talk to my pharma-adjacent friend who worked for a non-profit that was doing research on triheptanoin for other disorder. I would love to try it, had a dream about it the other day

 

[robinhood12345]

I took succinic acid for bit but it didn't help. high temperatures destroy nutrients, and raw tastes nicer. i bought a lamb liver last week from the butchers, put it in the fridge, and eat 100g or so a day. Watch sv3ridge, Frank Tufano, Sally Fallon, and Natasha Mcbride on youtube.

 

[frozenborderline]

ppl should b careful about raw liver, esp immunocompromised ppl

 

[Learner1]

This discusses succinate and riboflavin which is a key player in both the ETC and the Krebs cycle:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874626/

 

[renski]

one of my doc's in the past said oxidised glutathione blocks the complex II and that would cause elevated succinic acid

https://m.facebook.com/mthfrsupport/posts/1048091038542466

 

[Learner1]

one of my doc's in the past said oxidised glutathione blocks the complex II and that would cause elevated succinic acid

https://m.facebook.com/mthfrsupport/posts/1048091038542466

Elevated succinic acid can also be caused by riboflavin deficiency and/or heavy metals.

I have greatly benefited from IV and oral NAD+, as in the image you shared, in doses of 50-200mg. But, is it for this reason, or is it also because it may help with the IDO2 metabolic trap problem?

 

[Pondering]

You also could eat more fiber

• The microbiota produces high amounts of succinate in response to dietary fibers

• Succinate activates intestinal gluconeogenesis by serving as a glucose precursor

• Succinate supplementation contributes to improved plasma glucose and body weight

• Succinate is a microbial product with previously unsuspected metabolic benefits

https://www.sciencedirect.com/science/article/pii/S1550413116302996

 

[Learner1]

I eat plenty of fiber. My fasting glucose and HbA1C are low normal. Upping riboflavin is a key for improving succinic acid and FAD, needed in Complex II.

Thanks for the link.

 

[nandixon]

I took succinic acid for bit but it didn't help.

That makes sense because succinic acid is not able to cross cellular membranes and therefore can't be used to increase intracellular levels by taking it orally (or intravenously). Some work is ongoing I think to develop succinate pro-drugs to try to overcome this limitation.