# NAD+ and NADH

Category: Metabolism

Nicotinamide adenine dinucleotide, and its reduced form are coenzymes for many oxidation and reduction reactions in cells.

9 passages · 3 authors · 2014–2021 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/nad-and-nadh

## Synthesis

**NAD+ and NADH** form a critical redox couple whose ratio, rather than absolute quantity, defines cellular health. Ray Peat argued that in normal oxidative metabolism, the cell maintains an extreme preponderance of the oxidized form, with **NAD+** outnumbering **NADH** by three to five hundred, or even seven hundred, to one. [Source 1, 2, 8] This highly oxidized state reflects a *rapidly oxidising* environment where electrons from fuel substrates like sugar are efficiently streamed through NAD+ to the mitochondrion and finally to oxygen. [Source 1] Stressors that interfere with oxygen availability or deplete the total pool of these nucleotides cause a failure of this balance, shifting the cell toward a *reduced, NADH-dominant state* that is characteristic of sickness and aging. [Source 1, 3, 9]

The shift toward a low NAD+/NADH ratio is both a consequence and a driver of metabolic dysfunction. Peat identified that a buildup of NADH acts as a signal to turn off **pyruvate dehydrogenase (PDH)**, the enzyme complex that links glycolysis to the Krebs cycle. [Source 2] This blockade forces the cell to reduce pyruvate to lactate as an emergency oxidant to regenerate NAD+, a process that reinforces the reductive stress and leads to a destructive, primitivizing metabolic direction. [Source 2, 8] In the absence of sufficient oxygen to accept electrons, Peat noted that the cell activates an intrinsic alternative: the synthesis of fats, driven by estrogen and other stressors, to consume the excess NADH. [Source 2, 8] Georgi Dinkov has written that this is why using pyruvate to oxidize NADH back to NAD is "really bad," as it essentially mimics a *cancer metabolism*. [Source 7]

A major point of contention in the scientific community, according to Peat, is the interpretation of this ratio. He stated that many researchers, including prominent ketosis advocate Richard Veech, hold a "very confused attitude," believing that a higher proportion of the reduced form, NADH, is optimal. [Source 2, 4, 8] Peat fundamentally disagreed, aligning his view with the bioelectronic perspective of Gilbert Ling, where the cell's healthy state is defined by a scarcity of electrons. [Source 4] He explained that **carbon dioxide** functions as a cardinal adsorbent that pulls electrons out of the system, acidifies proteins, and shifts the entire electronic state of the cell toward the oxidized NAD+ side. [Source 4, 6] This concept is supported by the discovery of trans-plasma membrane oxidases, which demonstrate that cells can remove electrons and oxidize NADH to NAD+ right at the cell surface, without mitochondrial involvement. [Source 4, 6]

The total pool of NAD+ and NADH is vulnerable to catastrophic depletion, particularly during DNA damage. Peat described how the repair of DNA strand breaks by **PARP** enzymes consumes large amounts of the NAD+/NADH pool to build repair chains, and excessive damage can drain this pool so severely that it cripples cellular energy production. [Source 1] He identified **niacinamide** as a very safe PARP inhibitor that can prevent this wasteful depletion, giving the cell a chance to rest or proceed to apoptosis. [Source 1] Dinkov has extended this, noting that niacinamide's primary role in restoring the NAD+/NADH ratio is not simply as a precursor, but through its ability to lower lipolysis, which allows for more glucose metabolism and shifts the ratio back in favor of NAD+. [Source 5] This contrasts with popular but misguided approaches like NAD+ IV drips or the use of NADH pills, which Dinkov criticizes as an expensive and less safe alternative to simple precursors like niacinamide. [Source 7]

## People also ask

### Why did Ray Peat consider a high NADH proportion harmful?

Peat believed a healthy cell maintains an extreme preponderance of oxidized NAD+, and that a shift toward a reduced, NADH-dominant state is characteristic of sickness, aging, and reductive stress.

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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Longevity

Ray Peat · Interview · Apr 12, 2014 · https://www.youtube.com/watch?v=XEgfGJ4BAGk

> **Ray Peat:** Our cells are constantly in a process of oxidising and things like sugar, the electrons go to the oxidizing NAD+ and reduce it so that it becomes NADH and NADH can then pass those electrons on eventually to oxygen. So there's a streaming through NAD+/NADH to the mitochondrion and oxygen and in the normal metabolism you should have three to five hundred times as much NAD+ as NADH because there's then a rapidly oxidising state, and stresses that interfere with oxygen or that subtract the NAD+ and NADH, the lower the supply of the total NAD and NADH is, the more easily a stress causes a failure of the balance, so it shifts more easily through a very reduced NADH-dominant state.
>
> **Andrew Murray:** So stress depletes NAD+?
>
> **Ray Peat:** Well, it depletes both of them, right. One of the things that depletes both of them is damage to the DNA, such as radiation, and in repairing the DNA breaks there are enzymes that build up a chain of repetitive bases, so it's a meaningless chain but it plugs up the hole basically in the DNA and to do that, to repair the chain, the ADP is attached. ADP comes from the supply of NAD and NADH, and so when you get a nick in the DNA you have this huge amount of NAD+/NADH available and you draw it down to repair the damage. But if you draw it down in repairing too many broken DNAs, then that interferes with the energy production of the cell. And if you have ways to block those enzymes and stop the DNA repair, then the cell can make the decision to die and stop wasting energy from the organism and instead it becomes raw materials for the stem cells.

### Source 2 — Generative Energy #35: CO2, Ketosis, and Mitochondria | PUFA, Sugar, Iron, and AGEs | Progesterone and Cell Stability

Ray Peat (with Danny Roddy) · Interview · Aug 29, 2020 · https://open.spotify.com/episode/2Iz99Wy5JmrbohNj4OZCxP

> ## The NAD+/NADH Ratio
>
> **Danny Roddy:** A few years ago, we talked about the NAD+/NADH ratio. I was reading a paper by Veech, and he stated that he thought the NADH should be higher relative to the NAD. Is that a common belief in academia?
>
> **Ray Peat:** It's a very confused attitude towards NADH. It should be 700 NAD+ to each NADH. The oxidized form should be extreme. When you're under stress, it gets down more like 200 or 300 to one.
>
> **Danny Roddy:** Since NAD is so popular now with those NAD drips, are people trying to pretend like they never held those beliefs before?
>
> **Ray Peat:** A lot of them don't know about it, but they think they're raising their NADH. Lots of places are selling the reduced form of NADH as being better because it's reduced.
>
> **Georgi Dinkov:** Higher NADH is one of the signals to turn off pyruvate dehydrogenase (PDH). Some ketosis advocates, like Jeff Volek, talk about how that's a consequence of ketosis. What's the problem if PDH is turned off?
>
> **Ray Peat:** That makes the whole cell shift in that direction. Once it starts with the excess reducing environment, it tends to reinforce it and make it get worse.

### Source 3 — #08: Mitochondria, Low-Carb Advocates, Metabolic Stress, and Gilbert Ling with Kyle Mamounis

Danny Roddy · Interview · Aug 16, 2019 · https://open.spotify.com/episode/6mXcU4jilQVGWrvJr1eJI6

> **Kyle Mamounis:** Right. And I mean it has a lot of – I mean most – so most of the salient points are pretty much the same as the mainstream model. But it's – we were talking about earlier about – NAD plus and NADH and the ratio. And that's, that, that got really popular a couple of years ago because it seems to be a pretty good indicator of health and that the ratio gets, you know, the, the NADH increases in proportion to NAD plus as people get less healthy and old.
>
> **Danny Roddy:** Uh, is that not a, not a fringe idea? I mean, no, okay.
>
> **Kyle Mamounis:** It's not, it's not fringe. Uh, because it's very clear, like all of the date, it's just not discussed because the, um, the big, the big ideas in the space, you know, like things that become really big, like sugar is bad or like saturated fat is bad. Like the big ideas, there isn't a framework to put this in. So like it, it can't be blamed on like a big macronutrient. It can't be, nobody's figured out how to frame it, you know, um, Like you listened to that Matt Blackburn thing, right? That I, that I talked to him. So how like language, like there's a language to science and depending on what people are, the, the things that are popular, the tech, the scientific techniques that are being used the most and that are considered the most valid, they drive what types of questions are interesting and how to frame things. So There really is no way to ask this question in a way that it can become really popular. But it is not controversial to say that a low NAD plus to NADH ratio is a sign of poor health.

### Source 4 — Carbon Dioxide, Redox Balance, and The Ketone Body Ratio with Ray Peat  [Generative Energy #26]

Ray Peat (with Danny Roddy) · Interview · Apr 21, 2016

> ## The NAD+/NADH Ratio and Ketosis
>
> **Danny Roddy:** Normally, protein, fat, and carbohydrate are the substrates for the electron flow. You're saying that because the electrons were in the cell without any substrates, that led Szent-Györgyi to think there was an electric conductivity to the cell that wasn't previously thought?
>
> **Ray Peat:** Yeah, that proteins of the cell might be catching electrons from the environment. In the last 15 years, people are now talking about the trans-plasma membrane oxidases. Many people are experimenting with these indicators of dehydrogenase activity. They turn red or purple when they get reduced. Using chemicals that don't enter cells because they're strongly electrically negatively charged, they show that oxygen is removing electrons from the cell—oxidizing NADH to NAD, taking electrons out and changing color without entering the cell. So they're showing that cells don't need mitochondria for oxidative metabolism. It can happen right at the surface of the cell. Someone designed cells lacking the gene necessary to make mitochondria and still the cell respired.
>
> **Danny Roddy:** In your *Receptors, Fields, and Therapies* 2014 newsletter, I wanted to talk about the ketone body ratio. Some people think that the NADH should be increased relative to NAD+. Is that where the confusion about the ketone body ratio is? For example, Veech says beta-hydroxybutyrate as a substrate increases NADH relative to NAD+.

### Source 5 — #71: SSRIs Increase Estrogen | Keto, Stress, and NAD+/NADH | Bioenergetic Tradition | Alzheimer's with Georgi Dinkov

Georgi Dinkov (with Georgi Dinkov) · Interview · Oct 11, 2021 · https://open.spotify.com/episode/2hlfiw5ub0mYOnB9r80l6U

> **Danny Roddy:** This George Cahill is like a keto god person. People always reference him all the time. And when I read through his paper, Keto Acids as Good Medicine, he himself says that with beta-hydroxybutyrate as a substrate, NADH increases relative to NAD+. But that's so funny because I know we've talked about this before, but a lot of keto people will say, oh yeah, keto increases NAD relative to NADH. But their foremost expert in ketones is saying the opposite is true.
>
> **Georgi Dinkov:** Why does he recommend keto if he says that this is his own words that it causes pseudohypoxia?
>
> **Danny Roddy:** Well, remember, not that many people think NAD relative to NADH is like a good thing. Like Ray was saying, NADH to NAD, having a higher ratio of NADH was optimal. And he said most people believe that and that him and Gilbert Ling are some of the only people. I think more people think NAD is important now, but that's kind of a new belief, I think.
>
> **Georgi Dinkov:** That it's more – I guess because they're linking it to oxidative stress, right, and to increase metabolism. They're saying, oh, if your NAD to the NADH ratio is high, which means – this means you're experiencing oxidative stress and your metabolism is high, so you're going to burn out faster.

### Source 6 — Carbon Dioxide, Redox Balance, and The Ketone Body Ratio with Ray Peat  [Generative Energy #26]

Ray Peat · Interview · Apr 21, 2016

> ## The NAD+/NADH Ratio and Ketosis
>
> **Danny Roddy:** Speaking of carbon dioxide, a lot of people are talking about ketogenesis and ketosis diets. I think I read that carbon dioxide stimulated NADH oxidase. Would that be something, besides supporting mitochondrial respiration in general, that would support the NAD+ to NADH ratio?
>
> **Ray Peat:** Yeah, I think it's the function in Gilbert Ling's sense: an adsorbent that pulls electrons out of the system and makes a protein more actively acidic. I think it has that effect all through the cell. One of the effects of that is to let the cell release any excess water, so it has an anti-swelling effect. The retraction of the electrons by that cardinal adsorbent action on the proteins shifts the whole electronic state of the cell, making electrons scarcer. That ends up shifting the ratio between NAD and NADH towards the oxidized NAD side. After reading Gilbert Ling, I read Ephraim Racker and Albert Szent-Györgyi talking about electrons in cells. Szent-Györgyi's book was called *Bioelectronics*. Ephraim Racker coined the phrase "Nothing Dehydrogenases." Szent-Györgyi, working in England in the 1920s, studied related things—that there seems to be electrons or the equivalent of hydrogen from unidentified sources in living cells. Ephraim Racker removed all of the known fuel sources from cells, but his indicators of reductants kept getting reduced. He said the dehydrogenases were causing these chemicals to be reduced, but without a known source, it seemed to be an endless supply of electrons. So he called them the "nothing dehydrogenases." Szent-Györgyi theorized that these were some of the mobile electrons in the cytoplasmic protein-lipid systems and nucleic acid systems. Some of his associates were showing semi-conductive properties for both nucleic acids and proteins based on this mobility of electrons.

### Source 7 — Georgi Dinkov: more is not better, Russian spies, sanity, orthorexia, NAD, D3 and how to drink vodka

Georgi Dinkov · Interview · Jan 21, 2021 · https://www.youtube.com/watch?v=KSuhf6PS2jk

> **Leo Wik:** Okay, so not a smart way of raising your NAD, but what about doing just a straight NAD plus IVs? What's the difference between NAD? You can do it.
>
> **Georgi Dinkov:** You can do it. So basically, like they said, oh, if you take NAD as a pill, actually they sell NADH as a pill, right? But it's the reduced form. And then they tried taking NAD as a pill, and they found out, they basically, they said, oh, it gets destroyed by the stomach acid. not much of it gets absorbed. I'm like, really? It's not much different than NADH. If you have the NADH as a pill and continue to sell it and don't make any claims that it's getting destroyed and whatnot, the NADH should work as well. Yes, it tends to be unstable, but it's always NADH. There's nothing fundamentally different between these two chemicals. But, of course, they're looking to popularize a type of therapy that looks exclusive, it looks exotic, it looks expensive, and it can only be done by this special doctor. Again, it's like the exclusivity club. They're a member of a club that you are not a member of. So yes, it works. It probably works better, but there's safer ways like taking the precursor niacinamide or nicotinamide riboside or nicotinamide mononucleotide, which is actually the best precursor of the three.

### Source 8 — Generative Energy #35: CO2, Ketosis, and Mitochondria | PUFA, Sugar, Iron, and AGEs | Progesterone and Cell Stability

Ray Peat · Interview · Aug 29, 2020 · https://open.spotify.com/episode/2Iz99Wy5JmrbohNj4OZCxP

> ## The NAD+/NADH Ratio
>
> **Georgi Dinkov:** If you turn off PDH, you're starting to immediately build up lactate because pyruvate will be used as the emergency oxidant.
>
> **Ray Peat:** Yeah, and to keep the production of lactate going, you need something to get rid of the buildup of higher levels of NADH. The intrinsic alternative to oxygen is the synthesis of fats. When the cell gets convinced that it isn't going to get enough oxygen, it starts synthesizing fatty acids like crazy. Estrogen and other stressors will turn on this enzyme system to consume excess NADH in the absence of oxygen. It runs glycolysis and lactic acid production, intrinsically changing the cell over to consuming energy at a high rate but in a destructive, primitivizing direction.

### Source 9 — #08: Mitochondria, Low-Carb Advocates, Metabolic Stress, and Gilbert Ling with Kyle Mamounis

Danny Roddy · Interview · Aug 16, 2019 · https://open.spotify.com/episode/6mXcU4jilQVGWrvJr1eJI6

> **Danny Roddy:** Well, I didn't ask you, but like when that in the mitochondria, when all that, the, when all that, the things that we talked about are happening, where, where's the NAD and the, because the most of the NAD is being produced on the business end of respiration in through the electron transport chain. Any little bit of NAD is produced in glycolysis. And then the NADH is most is produced in the TCA cycle. Is that right?
>
> **Kyle Mamounis:** Well, okay, so NADH and FADH2 are both produced in glycolysis, beta oxidation, the TCA cycle. And they're basically just, so these molecules that go around NAD plus and FAD, they pick up high energy electrons as the glucose or the fatty acid substrate is broken down.
>
> **Danny Roddy:** Mm-hmm.
>
> **Kyle Mamounis:** They're broken down two carbons at a time, and every time that happens, they get put on an acetyl-CoA and sent through the TCA cycle, and it breaks them down into basically carbon dioxide one step at a time, and every step closer. So carbon dioxide is basically maximally oxidized carbon, and glucose and fatty acids and a couple of other energy substrates are maximally reduced. So as they go from maximally reduced to completely oxidized, they give off those reductive electrons to NAD plus and FAD. And that's what makes NADH and FADH2.

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