Succinic Acid For Metformin Induced Lactic Acidosis

Jam

Member
Joined
Aug 10, 2018
Messages
2,212
Age
52
Location
Piedmont
Now I understand why supplementing "Peaty" dosages (100-200mg) of succinic acid does absolutely nothing for me... I already get much more than that from my daily glass of red wine... and I like it tart.


SUCCINIC ACID PRODUCTION BY WINE YEASTS​

De Klerk, Jean-Louis (2010-03)
Thesis (MScAgric (Viticulture and Oenology))--University of Stellenbosch, 2010.
THESIS
ENGLISH ABSTRACT: One of the most striking qualities of wine is its tart, sour taste. The sensory perception of sourness is mainly attributed to the presence of hydrogen ions (protons) at high concentrations. Large amounts of weak carboxylic acids (organic acids) are the main sources of these ions within wine. Once wine enters a person's mouth, the dissociable protons of the weak organic acids within wine are partially neutralized or, in other words, titrated by the saliva secreted inside one's mouth. This explains why the duration and intensity of a wine's sourness is related to its titratable acidity content. The sour taste of wine is usually considered refreshing and it helps balance wine flavour. In fact, wines become watery when its titratable acidity content is too low. After alcoholic fermentation, the titratable acidity of wine will usually be less than that of the grape juice from which was made due to ethanol-induced precipitation of potassium bitartrate crystals and partial consumption of malic acid by fermenting wine yeasts. Occasionally however, increases in titratable acidity are observed during alcoholic fermentation. If wine is produced from grape juice with optimum levels of titratable acidity, unforeseen increases in titratable acidity during alcoholic fermentation can be detrimental to the quality of the final product. Although the net production of malic acid by wine yeasts contributes to increases in titratable acidity seen during grape juice fermentations, the production of succinic acid is regarded as the primary contributor. In fact, succinic acid accounts for approximately 90% of the non-volatile acids produced during fermentation of grape juice. Between 0.5 and 1.5 g/L succinic acid is normally found in wine, but higher concentrations thereof (up to 3.0 g/L) have been detected within certain red wines. Acidity adjustments should preferably be carried out before the onset of alcoholic fermentation to allow better integration of the added compound(s) and to ensure that conditions during fermentation favour the quality and microbial stability of the final product. In doing so unfortunately, winemakers run the risk of ending up with wines that may taste too sour if they are unable to accurately predict and take into consideration the amount of succinic acid produced during alcoholic fermentation. Knowledge with regard to the factors involved in succinic acid's production by fermenting wine yeasts is therefore required in order to manage the titratable acidity of wines more accurately. Ever since Louis Pasteur first noticed succinic acid amongst the by-products of alcoholic fermentation, attempts have been made to determine the metabolic pathways and factors involved in its production by fermenting wine yeasts. Up until now however, it remains unclear why wines sometimes end up with exceptionally high levels of succinic acid. For these reasons it was decided to investigate the possible causes of very high succinic acid concentrations within wine. Due to complexity of grape juice's chemical composition and the problems associated with sterilizing grape juice, fermentation experiments were conducted within a chemically defined grape juice-like medium. Succinic acid production by nine different industrial wine yeast strains was studied under various conditions with regard to the nutrient status of the synthetic grape juice, temperature and availability of molecular oxygen during alcoholic fermentation. The amount of succinic acid produced during alcoholic fermentation was found to depend on the yeast strain, fermentation temperature and chemical composition of the synthetic grape juice. Out of the nine commercial yeast strains selected for this study, strain WE372 produced the largest amount of succinic acid in synthetic grape juice at 28°C. Strain WE372 produced significantly smaller amounts of acetic acid than the other yeast strains of this study and very little acetic acid at 28°C, which indicated that strain WE372 may have less acetaldehyde dehydroganase activity than the other yeast strains of this study under the conditions tested. The effect this has on NAD: NADH balance is the probable cause for its ability to form more glycerol, succinic and malic acid than the other strains. Results from our study show that succinic acid production is influenced primarily by the metabolizable fraction of YAN, which we termed metabolically available nitrogen (MAN). Succinic acid production by fermenting yeasts will be favoured by moderate to high fermentation temperatures (20°C to 28°C) in grape juice with a nicotinic acid and/ or nicotinamide deficiency, high sugar content (200 g/L to 240 g/L), moderate amounts of metabolically available nitrogen (300 ± 50 mg/L MAN), the presence of flavonoids and large supplies of unsaturated long-chain fatty acids. Even higher concentrations of succinic acid were produced when oxygen was made available to fermenting yeasts by aerating the fermenting grape juice. Fermentation temperatures below 18°C, too much metabolizable nitrogen (> 450 mg/L MAN), very high concentrations of fermentable sugar (> 240 g/L), lipid deficiencies and a lack of pantothenic acid, thiamine, biotin or pyridoxine will decrease the amount of succinic acid produced fermenting yeasts.
 

Validus

Member
Joined
May 11, 2022
Messages
283
Location
USA
@Hans This is very interesting, thank you for sharing. Ever since I had COVID, I've lost my athletic & lifting performance and I consistently experience lactic acid in my muscles, even when doing simple tasks like brushing my teeth.

Would you then not recommend someone in my position take metformin & aspirin?

What other compounds are you aware of that increase lactic acid production?

Like succinic acid, are you aware of other compounds that would help mitigate lactic acid?

Thanks again for sharing - this is very helpful!
 

Inaut

Member
Joined
Nov 29, 2017
Messages
3,620
@Hans This is very interesting, thank you for sharing. Ever since I had COVID, I've lost my athletic & lifting performance and I consistently experience lactic acid in my muscles, even when doing simple tasks like brushing my teeth.

Would you then not recommend someone in my position take metformin & aspirin?

What other compounds are you aware of that increase lactic acid production?

Like succinic acid, are you aware of other compounds that would help mitigate lactic acid?

Thanks again for sharing - this is very helpful!
Baking soda, hydrogen, taurine, agmatine (i think?) to name a few.
 

Validus

Member
Joined
May 11, 2022
Messages
283
Location
USA
Baking soda, hydrogen, taurine, agmatine (i think?) to name a few.
Thanks! Anything to avoid?

Seems there's so many alleged benefits to both metformin and aspirin.

Think they should be avoided?
 
OP
Hans

Hans

Member
Forum Supporter
Joined
Aug 24, 2017
Messages
5,856
@Hans This is very interesting, thank you for sharing. Ever since I had COVID, I've lost my athletic & lifting performance and I consistently experience lactic acid in my muscles, even when doing simple tasks like brushing my teeth.

Would you then not recommend someone in my position take metformin & aspirin?

What other compounds are you aware of that increase lactic acid production?

Like succinic acid, are you aware of other compounds that would help mitigate lactic acid?

Thanks again for sharing - this is very helpful!
Berberine might have the same effects as metformin, but no common natural compound is likely to be detrimental.
I'd try high dose vitamin B1, B2, niacinamide, magnesium and succinic acid for exercise intolerance. You can also try ginseng as it's been shown to lower exercise-induced serotonin. But I think in your case, complete oxidative phosphorylation is slow, thus glycolysis is upregulated. So even CoQ10 might help.
 

Validus

Member
Joined
May 11, 2022
Messages
283
Location
USA
Berberine might have the same effects as metformin, but no common natural compound is likely to be detrimental.
I'd try high dose vitamin B1, B2, niacinamide, magnesium and succinic acid for exercise intolerance. You can also try ginseng as it's been shown to lower exercise-induced serotonin. But I think in your case, complete oxidative phosphorylation is slow, thus glycolysis is upregulated. So even CoQ10 might help.
Thanks! I've had the same theory; atp production shifted to anaerobic metabolism and away from oxygen and glucose.

I've found relief using cardarine, sr9009, mildronate and pyrucet.

Cardarine is stated to increase fatty acid oxidation and mildronate/pyrucet increases glucose oxidation.

Do you think it's silly to combine cardarine and mildronate/pyrucet and they end up nullifying each other's effects?

I don't really see evidence that cardarine a ppar alpha agonist specifically shifts metabolism away from glucose to fat as much as it just unregulates energy metabolism and mitogenesis.
 

Validus

Member
Joined
May 11, 2022
Messages
283
Location
USA
You used them together or on its own?
Lately, together, but Im looking to stack them for synergy and I'm concerned they may nullify or counter the others positive effects.

My goal is to maximize and restore mitochondrial function and atp output.

Whats your opinion on cardarine and PPARδ receptor agonists?
 
Last edited:
OP
Hans

Hans

Member
Forum Supporter
Joined
Aug 24, 2017
Messages
5,856
Whats your opinion on cardarine and PPARδ receptor agonists?
Animal studies have shown that large doses can contribute to cancer, but humans use much less. Many things, such as caffeine, thyroid, etc., also improve fat oxidation, so I don't think it's bad when used short term.
 

Validus

Member
Joined
May 11, 2022
Messages
283
Location
USA
Animal studies have shown that large doses can contribute to cancer, but humans use much less. Many things, such as caffeine, thyroid, etc., also improve fat oxidation, so I don't think it's bad when used short term.
Thank you! What do you think about it being used in combination with mildronate and pyrucet?
 
OP
Hans

Hans

Member
Forum Supporter
Joined
Aug 24, 2017
Messages
5,856
Thank you! What do you think about it being used in combination with mildronate and pyrucet?
Cardarine will boost fat oxidation, but mildronate will inhibit it. Likely, peroxisomal beta-oxidation will become upregulated and convert long-chain fats into medium chain fats, which will then enter the mitochondria for mitochondrial beta-oxidation, which will not interfere as much with glucose oxidation.

It will probably be an ok experiment.
 

Validus

Member
Joined
May 11, 2022
Messages
283
Location
USA
Cardarine will boost fat oxidation, but mildronate will inhibit it. Likely, peroxisomal beta-oxidation will become upregulated and convert long-chain fats into medium chain fats, which will then enter the mitochondria for mitochondrial beta-oxidation, which will not interfere as much with glucose oxidation.

It will probably be an ok experiment.
Great thanks again!
 

EchoTango

Member
Joined
Jan 25, 2021
Messages
120
I haven't tried that! But I'm curious, although I need to order more....

Have you any experience with topical succinic acid?
No, I hadn't thought of skin application til I saw your post. But it has a logic to it, like how salicylic acid is used in toners. I actually haven't tried succinic acid at all. I'm still researching, but it sounds like a fascinating substance.
 

LadyRae

Member
Joined
Mar 20, 2021
Messages
1,525
No, I hadn't thought of skin application til I saw your post. But it has a logic to it, like how salicylic acid is used in toners. I actually haven't tried succinic acid at all. I'm still researching, but it sounds like a fascinating substance.
I was looking at skin creams on Amazon the other day and noticed that succinic acid is in several targeted for acne
 

EchoTango

Member
Joined
Jan 25, 2021
Messages
120
I was looking at skin creams on Amazon the other day and noticed that succinic acid is in several targeted for acne
Very interesting .. thanks. So it's pretty safe. I think I'll try it on the skin first.
 

ddjd

Member
Joined
Jul 13, 2014
Messages
6,722
Really interesting. Do you feel stronger in a way and more explosive at that dose?
Hans I thought you might find this interesting.

I read that ray thought copper succinate would be a good way to get copper so decided to try and make my own copper succinate. (Although I have no idea if this is right)

a capsule of 2mg copper bisglycinate into hot water. Added around 500mg- 1g of succinic acid.
added sodium bicarbonate to neutralise the acidity.
= Copper succinate(?)

Drank half of the mixture as around 500mg succinic acid is a good dose from what I understand

EXTREMELY dopaminergic. Feels like I've had 3 coffees. But very pleasant. Succinic acid is also a GABA promoter if I remember.

Definitely noticed feeling extremely strong like all my muscles had all woken up.

Can highly recommend 👍

Looking forward to experimenting more with succinic acid
 
OP
Hans

Hans

Member
Forum Supporter
Joined
Aug 24, 2017
Messages
5,856
Hans I thought you might find this interesting.

I read that ray thought copper succinate would be a good way to get copper so decided to try and make my own copper succinate. (Although I have no idea if this is right)

a capsule of 2mg copper bisglycinate into hot water. Added around 500mg- 1g of succinic acid.
added sodium bicarbonate to neutralise the acidity.
= Copper succinate(?)

Drank half of the mixture as around 500mg succinic acid is a good dose from what I understand

EXTREMELY dopaminergic. Feels like I've had 3 coffees. But very pleasant. Succinic acid is also a GABA promoter if I remember.

Definitely noticed feeling extremely strong like all my muscles had all woken up.

Can highly recommend 👍

Looking forward to experimenting more with succinic acid
Nice! I've used succinic acid before but not consistently for 1 month or so. Can't say I noticed much. I think my dopamine is already pretty high. Anything that energizes the brain, like succinic acid, can increase dopamine.
 

ddjd

Member
Joined
Jul 13, 2014
Messages
6,722
Succinate Increases Athletic Performance By Oxidizing NADH - Fire In A Bottle

Succinate Increases Athletic Performance By Oxidizing NADH​


When I first wrote about the benefits of supplementing with succinate, most of the data available was about long term benefits. Oh sure, it can increase metabolic rate by causing beiging of fat cells. This can help you lose weight over time.
And yes, it can have the long term benefit of muscle fiber transition type. A hallmark of obesity and diabetes is a lack of oxidative muscle fibers. Most muscle fibers are the glycolytic type, which quickly tire and then produce lactic acid. In rodent models, succinate caused a much higher proportion of oxidative fibers, which allow you to go stronger longer!

Succinate Increases Strength Acutely and Increases NAD+ and ATP Levels​

The research group that had showed long term benefits in muscle fiber type published another paper this January showing the acute, short term benefits of succinate supplementation. Mice that were injected with succinate showed increased muscle strength within 30 minutes of injection!
Screenshot-2022-10-12-1.13.46-PM.png

The mice also has a massively reduced NADH/NAD+ ratio in skeletal muscle. If you’ve been following my recent posts, The Onion would tell you that lowering the NADH/NAD+ level is the way to cut through the red tape and put the cells straight into catabolic (fuel burning) mode. Lactate levels also drop, a second indicator that the redox balance of the cell has improved.
Screenshot-2022-10-12-12.53.16-PM.png

The drop in NADH levels are presumably caused in part by increased Reactive Oxygen Species
Reactive oxygen species (ROS) are pro-oxidants. They are produced in many places, but this blog is largely focuses on mitochondrial ROS produced during respiration. ROS is generated as superoxide, which is rapidly converted to hydrogen peroxide. Hydrogen peroxide does it job by switching on or off redox-sensitive enzymes. ROS are a signal from the mitochondria that tells the rest of the cell what is happening from a fuel burning perspective. Burning long chain saturated fat quickly generates the most ROS due to the high FADH2/NADH ratio which overloads the mitochondrial bottleneck. Burning unsaturated fats and/or glucose generate minimal ROS.
" style="box-sizing: inherit; background-color: transparent; text-decoration: none !important; color: rgb(0, 0, 0) !important; transition: all 0.2s linear 0s; border-bottom: 1px dotted rgb(0, 0, 0) !important;">ROS production at mitochondrial Complex II. Remember that mitochondrial ROS pushes the cell into catabolic mode. Reactive Oxygen Species
Reactive oxygen species (ROS) are pro-oxidants. They are produced in many places, but this blog is largely focuses on mitochondrial ROS produced during respiration. ROS is generated as superoxide, which is rapidly converted to hydrogen peroxide. Hydrogen peroxide does it job by switching on or off redox-sensitive enzymes. ROS are a signal from the mitochondria that tells the rest of the cell what is happening from a fuel burning perspective. Burning long chain saturated fat quickly generates the most ROS due to the high FADH2/NADH ratio which overloads the mitochondrial bottleneck. Burning unsaturated fats and/or glucose generate minimal ROS.
" style="box-sizing: inherit; background-color: transparent; text-decoration: none !important; color: rgb(0, 0, 0) !important; transition: all 0.2s linear 0s; border-bottom: 1px dotted rgb(0, 0, 0) !important;">ROS are electron acceptors. The electrons from NADH flow to Reactive Oxygen Species
Reactive oxygen species (ROS) are pro-oxidants. They are produced in many places, but this blog is largely focuses on mitochondrial ROS produced during respiration. ROS is generated as superoxide, which is rapidly converted to hydrogen peroxide. Hydrogen peroxide does it job by switching on or off redox-sensitive enzymes. ROS are a signal from the mitochondria that tells the rest of the cell what is happening from a fuel burning perspective. Burning long chain saturated fat quickly generates the most ROS due to the high FADH2/NADH ratio which overloads the mitochondrial bottleneck. Burning unsaturated fats and/or glucose generate minimal ROS.
" style="box-sizing: inherit; background-color: transparent; text-decoration: none !important; color: rgb(0, 0, 0) !important; transition: all 0.2s linear 0s; border-bottom: 1px dotted rgb(0, 0, 0) !important;">ROS via the glutathione reductase/NNT pathway, regenerating NAD+.



Succinate-1024x575.png
Electrons passed into complex II from succinate tend to flow back out of Complex I in a process called Reverse Electron Transport. This generates Reactive Oxygen Species
Reactive oxygen species (ROS) are pro-oxidants. They are produced in many places, but this blog is largely focuses on mitochondrial ROS produced during respiration. ROS is generated as superoxide, which is rapidly converted to hydrogen peroxide. Hydrogen peroxide does it job by switching on or off redox-sensitive enzymes. ROS are a signal from the mitochondria that tells the rest of the cell what is happening from a fuel burning perspective. Burning long chain saturated fat quickly generates the most ROS due to the high FADH2/NADH ratio which overloads the mitochondrial bottleneck. Burning unsaturated fats and/or glucose generate minimal ROS.
" style="box-sizing: inherit; background-color: transparent; text-decoration: none !important; color: rgb(0, 0, 0) !important; transition: all 0.2s linear 0s; border-bottom: 1px dotted rgb(0, 0, 0) !important;">ROS, which Complex VI (aka NNT) uses to regerate NAD+. NAD+ allows the citric acid cycle to keep turning.
The result of all of this NAD+ availability was an immediate increase in mitochondrial complex I and II activity, increased ATP levels (energy, power) and increased weight lifting ability.

Screenshot-2022-10-12-12.53.33-PM.png

Screenshot-2022-10-12-12.54.04-PM.png

Screenshot-2022-10-12-12.53.50-PM.png

Screenshot-2022-10-12-12.52.46-PM.png



This all happened in the first hour. I’m sorry, were you hoping for more? Oh, that’s right. The succinate also decreased oxidative stress, since (say it with me) oxidative stress is caused by reductive stress. Producing some Reactive Oxygen Species

Reactive oxygen species (ROS) are pro-oxidants. They are produced in many places, but this blog is largely focuses on mitochondrial ROS produced during respiration. ROS is generated as superoxide, which is rapidly converted to hydrogen peroxide. Hydrogen peroxide does it job by switching on or off redox-sensitive enzymes. ROS are a signal from the mitochondria that tells the rest of the cell what is happening from a fuel burning perspective. Burning long chain saturated fat quickly generates the most ROS due to the high FADH2/NADH ratio which overloads the mitochondrial bottleneck. Burning unsaturated fats and/or glucose generate minimal ROS.
" style="box-sizing: inherit; background-color: transparent; text-decoration: none !important; color: rgb(0, 0, 0) !important; transition: all 0.2s linear 0s; border-bottom: 1px dotted rgb(0, 0, 0) !important;">ROS from succinate keeps the NAD pool oxidized (NAD+). A reduced NAD pool (NADH) is the source of electrons that causes oxidative stress.


Screenshot-2022-10-12-12.54.14-PM.png
When the authors say Reactive Oxygen Species
Reactive oxygen species (ROS) are pro-oxidants. They are produced in many places, but this blog is largely focuses on mitochondrial ROS produced during respiration. ROS is generated as superoxide, which is rapidly converted to hydrogen peroxide. Hydrogen peroxide does it job by switching on or off redox-sensitive enzymes. ROS are a signal from the mitochondria that tells the rest of the cell what is happening from a fuel burning perspective. Burning long chain saturated fat quickly generates the most ROS due to the high FADH2/NADH ratio which overloads the mitochondrial bottleneck. Burning unsaturated fats and/or glucose generate minimal ROS.
" style="box-sizing: inherit; background-color: transparent; text-decoration: none !important; color: rgb(0, 0, 0) !important; transition: all 0.2s linear 0s; border-bottom: 1px dotted rgb(0, 0, 0) !important;">ROS production, what they really mean is a change in Reactive Oxygen Species
Reactive oxygen species (ROS) are pro-oxidants. They are produced in many places, but this blog is largely focuses on mitochondrial ROS produced during respiration. ROS is generated as superoxide, which is rapidly converted to hydrogen peroxide. Hydrogen peroxide does it job by switching on or off redox-sensitive enzymes. ROS are a signal from the mitochondria that tells the rest of the cell what is happening from a fuel burning perspective. Burning long chain saturated fat quickly generates the most ROS due to the high FADH2/NADH ratio which overloads the mitochondrial bottleneck. Burning unsaturated fats and/or glucose generate minimal ROS.
" style="box-sizing: inherit; background-color: transparent; text-decoration: none !important; color: rgb(0, 0, 0) !important; transition: all 0.2s linear 0s; border-bottom: 1px dotted rgb(0, 0, 0) !important;">ROS concentration, which is a totally different thing.

Running Faster​

Scott Burtis, a customer, is the one who sent that article over. He followed up with this:

I borrowed a scoop of my wife’s Succinade before my run today. Typically on a good run I’ll get down to a 9:30 a mile pace. (Hey, I’m 60 years old!!). I attached my results from today. Holy COW!! I’ll do a few more of these, just an N of 1 so far, but very promising!
Dr. Scott Burtis
Screenshot_20221004-152937-485x1024.jpg

This could be a placebo effect, of course. Or maybe Scott was just having a good day. Still, it’s plausible that something that increases NAD+ and ATP levels would

He followed up and said he’s waiting for the new shipment to retry his n=1. BTW, the Succinade is back in stock and shipping!


Xu, Guli, et al. “Acute Succinate Administration Increases Oxidative Phosphorylation and Skeletal Muscle Explosive Strength via SUCNR1.” Frontiers in Veterinary Science, vol. 8, 2022, Acute Succinate Administration Increases Oxidative Phosphorylation and Skeletal Muscle Explosive Strength via SUCNR1.
 
EMF Mitigation - Flush Niacin - Big 5 Minerals

Similar threads

Back
Top Bottom