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!

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.

The drop in NADH levels are presumably caused in part by increased ROS production at mitochondrial Complex II. Remember that mitochondrial ROS pushes the cell into catabolic mode. ROS are electron acceptors. The electrons from NADH flow to ROS via the glutathione reductase/NNT pathway, regenerating NAD+.

Electrons passed into complex II from succinate tend to flow back out of Complex I in a process called Reverse Electron Transport. This generates 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.

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 ROS from succinate keeps the NAD pool oxidized (NAD+). A reduced NAD pool (NADH) is the source of electrons that causes oxidative stress.

When the authors say ROS production, what they really mean is a change in 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

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, https://doi.org/10.3389/fvets.2021.808863.

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7 thoughts on “Succinate Increases Athletic Performance By Oxidizing NADH”

  1. Just ordered some of the new formulation, hopefully it’ll go down a little easier.
    Anyway, I do resistance training 4-5 days a week. I’ve never used a pre-workout before, but I’ll give this a go and report back.

    1. Update:
      I haven’t been very scientific with this unfortunately. I’ve been mixing the succinade in with some other things (creatine, EAA, L-arginine, citruline, calcium pyruvate, L-carnatine, and a flavored electrolyte mix) as a pre-workout. Never done a pre-workout before, if I had these things it was always after my workout. I’m drinking this mixture about 1hr to 45 min before I go to the gym.

      Anecdotally, I have been doing dumbbell bench presses for the last several months (switched because the dumbbells are more comfortable than the bar), I had just moved up to my last set being 90lb in each hand the week before my succinade order came in. I only move up weight when I can do 8 reps with the weight I use on my last set. Here barely 2 weeks later I’m only 1 rep away from moving up to the 95’s. I’m 46 and I have been resistance training 4-5x’s/week for 2.5 years.

      Note: the unflavored succinade goes down way easier than the old formula. Especially if you use a flavored electrolyte mix.
      I’ve been mixing everything in about 2″ of hot water in a large mason jar when I get up. Then filling my jar to the top with water and sticking it in the fridge to let it get cold. Drink about 11ish before I go to the gym at noon.

  2. Succinate is an interesting topic. I think this supplementation simulates the effect of long-term training by accelerating succinate disposal from the TCA cycle, increasing PHD2 activity, and decreasing HIF-1 levels. As a result, it increases the oxidation of NADH. There are a number of studies investigating the effect of training on HIF-1 and PHD. Succinate as a by-product of PHD activity is likely to be a potent regulator of HIF-1alpha hydroxylation.

    1. And by the way, I wouldn’t be surprised if succinate also affects ACC2 function by modulating PHD3 activity and could thus improve the regulation of fat entry into mitochondria.

      This brings me to the importance of omega oxidation of a certain percentage of fats, since succinate is the end product of beta oxidation of dicarboxylic acids.

  3. Hi Brad,

    I am using succinate / Calcium Pyruvate and Alpha Lipoic Acid at the moment all twice a day an hour before meals.

    Is there any reason why that’s not a good idea?? I am half thinking if taking the ALA 30 mins before I take the other 2 is best.

    Lee

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