# Gluconeogenesis

Category: Metabolism

Gluconeogenesis is the creation of new glucose from non-carbohydrate precursors, a process that Ray Peat’s framework views as a stress-driven adaptation rather than a benign, demand-driven feature of metabolism. Peat argued that under stress, when efficient glucose oxidation…

10 passages · 3 authors · 2012–2024 · Most-cited: [Danny Roddy](https://bioenergeticoracle.com/md/voices/danny-roddy/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/gluconeogenesis

## Synthesis

**Gluconeogenesis** is the creation of new glucose from non-carbohydrate precursors, a process that Ray Peat’s framework views as a *stress-driven* adaptation rather than a benign, demand-driven feature of metabolism. [Source 1, 2] Peat argued that under stress, when efficient glucose oxidation fails, the body shifts to burning fat and breaking down tissue protein to produce sugar, a process mediated by the rise of **cortisol** and **ACTH**. [Source 2, 10] He emphasized that this shift is a restrained, *catabolic* reaction because the body has no protein storage; thus, when cortisol rises to drive gluconeogenesis, it means some part of the body is undergoing a loss of function and structural integrity. [Source 2]

The hormonal cascade governing this process is hierarchical and reveals why proponents of low-carbohydrate diets misinterpret its activation. Danny Roddy, drawing on Peat’s work, has detailed that **glucagon** and **catecholamines** are the immediate "emergency hormones" released when blood sugar falls, acting to mobilize stored glycogen. [Source 3, 9] Cortisol is a slower, more sustained *late-stage stress hormone* that becomes necessary when glycogen is depleted, breaking down tissue to supply amino acids for glucose production. [Source 5, 9] Roddy notes that the claim that gluconeogenesis is harmless because it is driven by glucagon rather than cortisol is a false comfort, as glucagon itself is a **stress hormone** rapidly released in response to various stressors, and its elevation is part of a complex biochemical web that includes adrenaline and ultimately requires cortisol to sustain the process. [Source 7, 9]

The context of dietary carbohydrate restriction fundamentally alters the nature of gluconeogenesis. Kyle Mamounis, in discussion with Roddy, distinguished between a normal, demand-driven state—where intense exercise might transiently upregulate the process—and the *supply-driven* state of a low-carb diet, where excess dietary protein beyond what can be used for synthesis is inevitably converted to glucose. [Source 1] This chronic reliance on gluconeogenesis for baseline blood sugar maintenance is seen as inherently stressful, chronically activating the hypothalamic-pituitary-adrenal (HPA) axis. [Source 1, 8] Roddy has pointed out that elevated fasting blood glucose in a low-carb context, often misattributed to dietary carbohydrate, is frequently a direct result of this hormonally-driven glucose production, a phenomenon observed in meticulous self-experimentation by individuals attempting to lower their glucose by manipulating protein intake. [Source 4, 6]

The inefficiency and systemic cost of this pathway are central to its negative characterization. Peat explained that forcing physiology to rely on fat and protein for energy produces less **carbon dioxide**, a protective molecule that prevents glycation and delivers oxygen to tissues, and generates more inflammatory breakdown products. [Source 10] Roddy and Mamounis further note that the process is linked to increased ammonia production and is fundamentally inefficient compared to direct glucose oxidation. [Source 1, 5] The broader bioenergetic view holds that a healthy metabolism should have a robust appetite for carbohydrate, and the absence of this appetite signals a reliance on the *life-subtracting* adaptive substances like glucagon and cortisol that drive gluconeogenesis. [Source 5]

## People also ask

### Why does Ray Peat consider gluconeogenesis a stress-driven process?

Peat argued that when efficient glucose oxidation fails under stress, the body breaks down fat and tissue protein to produce sugar, a catabolic reaction mediated by cortisol and ACTH that indicates a loss of structural integrity.

### How does a low-carb diet change the nature of gluconeogenesis?

The corpus describes a shift from a transient, demand-driven state to a chronic, supply-driven one where excess dietary protein is inevitably converted to glucose, which is seen as inherently stressful and activates the HPA axis.

### What is the relationship between glucagon and cortisol in gluconeogenesis?

Glucagon and catecholamines act as immediate emergency hormones to mobilize glycogen, while cortisol is a slower, sustained stress hormone that breaks down tissue for glucose when glycogen is depleted, sustaining the process.

## Related concepts

- [Glucagon](https://bioenergeticoracle.com/md/concepts/glucagon/index.md)
- [Adrenaline](https://bioenergeticoracle.com/md/concepts/adrenaline/index.md)
- [Albumin](https://bioenergeticoracle.com/md/concepts/albumin/index.md)
- [Amyloid](https://bioenergeticoracle.com/md/concepts/amyloid/index.md)
- [Autophagy](https://bioenergeticoracle.com/md/concepts/autophagy/index.md)
- [Estrone](https://bioenergeticoracle.com/md/concepts/estrone/index.md)

## Cited passages

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

### Source 1 — #02: Zero-Carb and Carnivore Diet Critique with Ex-Carnivore Kyle Mamounis

Danny Roddy · Interview · May 17, 2019 · https://open.spotify.com/episode/5ngFPotpHRqRbU6OmcHpbB

> **Danny Roddy:** OK, so I skipped a little bit ahead, but the gluconeogenesis, this is a huge point of contention, I guess. And so one of the big proponents says like this is what do they say? Demand driven rather than supply driven. And so, again, I think they're talking about this outside the context of the metabolic rate and outside the context of stress or metabolic or counter regulatory hormones, et cetera, and things. So do you think that's why they're viewing it differently? uh, as a, as a, like some rampant increase in gluconeogenesis is, is a negative thing.
>
> **Kyle Mamounis:** Yeah. Um, I think that there are, so it's demand side when you are eating a normal diet. So if you have like an, like you eat a normal amount of carbohydrate and then you do really intense exercise, like anaerobic exercise, like you'll turn on gluconeogenesis because you'll use up your blood glucose and the glucose in your muscles pretty fast. But when you're on a low-carb diet, that also will, I guess, be ramped up to some extent if you exercise and use the very small amount of glucose that you have in reserve. But it's supply-driven in that situation. There's only so much protein that can be used for protein synthesis at any given time. So if you eat more than that no matter what's happening it's going to be used to make glucose or glucose equivalents

### Source 2 — Weight Loss, Macros, Prolactin, Cancer, Cold Therapy & More, Q&A

Ray Peat · Interview · Oct 11, 2020 · https://www.youtube.com/watch?v=EK8qhzo4w9s

> **Ray Peat:** No. Usually, if your adrenals respond by making... cortisol that keeps the adrenaline down and the first reaction when you don't get enough glucose into your system first reaction is to increase your adrenaline to mobilize stored glycogen release it in the form of glucose and if you run out of glycogen then adrenaline can't do that, and that's when ACTH rises. But normally, adequate glucose or carbohydrate will keep down both adrenaline Yeah, so when I read his question, that's what I was wondering too. I was thinking, well, I think it's the other way around. It's the high adrenaline that actually leads to the high ACTH, right? Yeah. It's the body's first reaction, and then if it doesn't produce enough sugar, then the body brings in the deadlier arm. cortisol and the reason that that's a restrained reaction is that the way cortisol and ACTH produce the glucose is by breaking down tissue protein and we don't have any protein storage so when cortisol goes up it means some part of our with loss of function and strength of connective tissue, for example. So a surge of adrenaline is a good warning that you should either improve your efficient sugar metabolism or increase the amount of carbohydrate in your diet.

### Source 3 — Generative Energy #48: Optimal Foods and Supplements | Do Carnivore Diets Increase Cortisol? | Porn and Masturbation

Danny Roddy · Interview · Feb 3, 2021 · https://app.podcastguru.io/podcast/1525148857/episode/48-optimal-foods-and-supplements-do-carnivore-diets-increase-cortisol-porn-and-masturbation-with-danny-roddy-7a0d31b33384ba1630b9ac990facebb3

> **Danny Roddy:** And so, again, I if somebody lives a long time and they have higher levels of cortisol, that is not necessarily super appealing to me, because if you've ever been really sick, you know that like the quality of life, like I wouldn't want to live a long time feeling really cold. Like that is a torturous symptom. And that that's not appealing to me. And so, again, I think you have to plug in other variables. And I'm sure Amber does that besides longevity. And I'm just talking about this question pretty much. I haven't seen what Amber believes about that specifically. But maybe she did say that. Okay, so let's get to that third part. Cortisol isn't necessary for gluconeogenesis because glucagon is activated before cortisol is raised when blood sugar falls under a specific threshold. Okay, so if glucagon is raised, that ameliorates the whole cortisol gluconeogenesis argument that's so prevalent. And so before I answer this question, I did want to talk about one thing. So keto, well, something I've noticed, keto, low carb and carnivore people spend an exorbitant amount of time defending high levels of cholesterol because it's so common on their style of eating. And so and would anybody really argue with that? I mean, say something in the comments, but I think that is a very obvious fact. And so it turns out, what do you think is associated with high levels of cortisol? Let's read on. So Dibsdale in 1982, they say, these studies span a remarkable breadth of stressful situations, such as from viewing disturbing films to taking examinations or participating in military training courses. Free fatty acid levels were almost invariably elevated in the context of a stressful event. Most studies also found that cholesterol increased from 8% to 65% above baseline under stressful conditions. Okay, so stress, even mild stress, increases cholesterol.

### Source 4 — #09: Estrogen, Fluoride, Pregnancy, Children, and Metabolism with Georgi Dinkov and Emma Sgourakis

Georgi Dinkov · Interview · Aug 23, 2019 · https://open.spotify.com/episode/3t0SPCgbBtB77LJdFi2jbP

> **Danny Roddy:** Well, just to step back a little bit, when somebody is getting a high HbA1c back, they're making – they're tending to make an assumption that it is because of the dietary carbohydrate that they're eating. Yes, exactly. When in reality, it could be the gluconeogenesis. Yes, high cortisol. Keeping the glucose level chronically high.

### Source 5 — BV #1: Bryan Johnson’s Longevity Diet, How Stress Affects Our Cells, & Whether Glucagon is Evil

Danny Roddy · Interview · Sep 19, 2024 · https://www.youtube.com/watch?v=5tXXW85Sb4o

> **Jay Feldman:** Hey, Danny, I'm thinking let's skip the do you really want to maximize your energy efficiency one because he doesn't actually make any... He just kind of lays out a basic view of raised views but doesn't have any response to it. So why don't we just do the too much gluconeogenesis can be bad, and then we'll go to the how to balance your blood sugar.
>
> **Danny Roddy:** Got it, got it, got it. In his podcast, Jay Feldman argues that gluconeogenesis raises glucagon and is inefficient and stressful for the body. To some extent, I agree with this, but context is critical. So if your goal is this then very next thing or yeah
>
> **Jay Feldman:** No, there's like a couple of lines in between but they are I don't think they really said anything
>
> **Danny Roddy:** got it So if your goal is to maximize satiety I Mean we should just interject here and say that this is like ridiculous You're probably you're probably don't want to drop your net carbs below 10% of calories But at the same time there's no need to drown yourself in honey and fruit to avoid gluconeogenesis at all costs you'll you'll just overfill your glucose fuel tank and down regulate fat oxidation oh that is the point this is like i mean I know a lot of people have this hypothesis, but I mean, just in light of everything that's going on, it just seems like your main goal is to make sure you're not hungry. Speaking of Hans Selye, he said one of the first signs of being sick was losing your appetite. And I think our buddies at Analyze and Optimize. They talked about a person's appetite. They were interconnecting with serotonin, but basically explaining how alive a person is. Like you should have an appetite for carbohydrate. Like if you didn't, that would mean that you're running on these adaptive kind of life subtracting substances.

### Source 6 — #02: Zero-Carb and Carnivore Diet Critique with Ex-Carnivore Kyle Mamounis

Danny Roddy · Interview · May 17, 2019 · https://open.spotify.com/episode/5ngFPotpHRqRbU6OmcHpbB

> **Danny Roddy:** and you had reminded me in on lex's journal he had he had done some performed some experiment to figure out the amount of gluconeogenesis he was doing i had completely forgotten but do you recall like kind of the details of his experiment
>
> **Kyle Mamounis:** yeah he was he was um Cause he went to the doctor on a very regular basis. I don't know how often, but I wish I had his labs.
>
> **Danny Roddy:** They were, they were, they were very interesting.
>
> **Kyle Mamounis:** And he was trying to get his fasting blood glucose down.
>
> **Danny Roddy:** Cause it was like hovering at like 120 or something, right?
>
> **Kyle Mamounis:** Yeah. And he thought he could do that by, he was slowly, cause you know, he used the scale and everything and he would mix like different percentages of lean and, uh, meats to get like, to get an exact, uh, number or as close as you can without, you know, an isolated synthetic diet, uh, an exact amount of carbs and well, no carbs, but grams of protein and fat per day. And he couldn't, um, get it lower. And I think actually it went up at one point when he lowered protein, uh, like it would just kind of bounce up and down. It didn't really seem to, it wasn't a linear thing where less protein caused less, um, fasting glucose, but One thing that while he was doing that, he was doing literature review, and he found that it seems like half, even in somebody who eats a normal diet, half of the amino acids in most situations go to gluconeogenesis. And it would be more in a low-carb diet.

### Source 7 — Generative Energy #48: Optimal Foods and Supplements | Do Carnivore Diets Increase Cortisol? | Porn and Masturbation

Danny Roddy · Interview · Feb 3, 2021 · https://app.podcastguru.io/podcast/1525148857/episode/48-optimal-foods-and-supplements-do-carnivore-diets-increase-cortisol-porn-and-masturbation-with-danny-roddy-7a0d31b33384ba1630b9ac990facebb3

> **Danny Roddy:** So they say, however, glucagon alone cannot sustain an increased gluconeogenesis since the process is dependent on the availability of gluconeogenic precursors. Thus, concomitant lack of insulin and or increased levels of counter-regulatory hormones acting on peripheral tissues like catecholamines or cortisol are also required. So it doesn't sound super awesome to have like increased functioning of glucagon. And that doesn't even sound, well, I think you can have frequent, I forgot what it's called, like hyperglucogonemia, I think. I had the papers, but I didn't put them in here. Anyways, okay. So let's, again, glucagon is central in this whole stress cascade. And somebody saying, oh, cortisol doesn't raise, glucagon raises. Like that's not better. It's not a better situation. And more or less these, all these hormones are entangled in a big complex biochemical web. And so I don't think any of them act alone, you know? Okay. So again, just to bring this point home, the stress of life behind by Hans Selye in 1984. He says in connection with disturbances in carbohydrate metabolism, it is noteworthy that Dr. S.R. Bloom has recently summarized a good deal of evidence indicating that glucagon, an anti-insulin substance of the pancreas, is a stress hormone. Stress increases energy requirements and creates a demand for an increased supply of energy yielding glucose, which is satisfied with glucagon. In fact, a sudden rise in blood glucagon concentrations have been demonstrated both animals and in man under the influence of many stressors. And in one of those papers, they say when conscious lightly or the paper that Selye specifically mentioned by Bloom, he says when conscious lightly restrained primates were startled by noise, the levels of glucagon in the plasma rose rapidly. And this rise was followed by an elevation of blood glucose, but not a plasma insulin.

### Source 8 — Kyle and Frens Episode 3 - Danny Roddy - Discussing how Nutrition is Discussed

Danny Roddy · Interview · Jan 18, 2021 · https://www.youtube.com/watch?v=CofMJtPkXCc

> **Danny Roddy:** well i'll bounce this off you i so i entertain the idea that i had adrenal fatigue you know for a long time And people said, oh, well, it's from your blood sugar going up and down. And of course, burning fat is the best way to keep your blood sugar stable. And there was one other point I was about to make. But your synthesis of the idea of producing your own sugar through gluconeogenesis is activating the adrenals. I don't recall hearing that a single time in my exhaustive adrenal fatigue research that I had done.
>
> **Nutricrinology:** Yeah. So it's almost like when you go to one place, you can get a certain type of information. Like if you just crack open a medical textbook where you're learning about, oh, what do the adrenals do? And then you look and say, okay, well, they make epinephrine. What does that do? They make norepinephrine. They make cortisol. What do these things do? And you can clearly see how it's like, you know, increasing free fatty acids, lipogenesis, and stimulating gluconeogenesis, and... glycogenolysis and all that stuff, right? All the stuff kind of in the fasted state metabolism milieu and partially also in the stress milieu. And then you go over to these people talking about low carb diets and internal fatigue. And that information is just like, you know, it definitely silent, you know? So I thought it's just one of those things where people are doing the thing. that would just very clearly, like a normal doctor would be like, well, have you tried not making your adrenal gland support your blood sugar 24 hours of the day? Let's start with that. And you know what I mean? And call me in the morning. That never comes up. And it's like the exact opposite.

### Source 9 — Generative Energy #48: Optimal Foods and Supplements | Do Carnivore Diets Increase Cortisol? | Porn and Masturbation

Danny Roddy · Interview · Feb 3, 2021 · https://app.podcastguru.io/podcast/1525148857/episode/48-optimal-foods-and-supplements-do-carnivore-diets-increase-cortisol-porn-and-masturbation-with-danny-roddy-7a0d31b33384ba1630b9ac990facebb3

> **Danny Roddy:** And so we already kind of know that that is, um, We'll get to it, but that already doesn't sound right because of like this paper talking about the study's remarkable breadth of stressful situations from viewing a disturbing film can increase your cortisol and cholesterol and things like that. And so you have to reach vomit inducing exercise to increase cortisol. So again, just an argument. It's something very trivial could increase your cortisol, but somehow on this stress activating diet. Your cortisol is kept in check. Okay, I guess we'll see. So let's just read a little bit from this Ulf, Smith, and Lager paper. They say the autonomic nervous system and the adrenal medulla become activated when the blood glucose concentration falls and hypoglycemia develops. This in turn leads to an increased level of counter-regulatory hormones, glucagon, catecholamines, cortisol, and growth hormone. All these hormones exert potent insulin antagonistic effects and also enhance glucose formation and the release from the liver. However, the time course for both and the release and the onset of action differ between these hormones. Glucagon and catecholamines are true emergency hormones, which in conjunction with hypoglycemia peak at glucose nadir and have an immediate onset of action. Cortisol and in particular growth hormone have a delayed release and are slower in onset but also have prolonged duration of effect. And so the catecholamines like adrenaline and glucagon are like immediate emergency hormones to promote glycogenolysis, release the sugar from the liver to restore blood sugar levels during a stressful event. And cortisol and apparently growth hormone too are like more sustained late stage stress hormones to cortisol in particular to break down the structures, produce more sugar via gluconeogenesis. Okay, so let's scroll down here. And just to run home the point here.

### Source 10 — Ask the Herb Doctor: Dementia and Progesterone

Ray Peat · Interview · Dec 21, 2012 · http://l-i-g-h-t.com/files/herb-octors-dementia-and-progesterone-60-mins.mp4

> ## Metabolic Energy and Stress
>
> **Andrew Murray:** I wanted to talk a little bit more about energy. If there's something we want to get across, it is the need for metabolic energy in our bodies. Every organism ultimately uses energy to convert chemicals into other chemicals, and all the cellular processes require a currency of some kind of energy. Ultimately, ours is oxidatively burning glucose. That's the best way of doing it, isn't it?
>
> **Ray Peat:** Yeah. Under stress, we can force our physiology over to burning fat instead of glucose. That causes several changes. It produces less carbon dioxide and is likely to produce a lot of breakdown products that can cause inflammation.
>
> **Andrew Murray:** And the carbon dioxide is useful. I think most people think of oxygen as being life-giving, but ultimately the oxygen is not particularly good for you, is it?
>
> **Ray Peat:** No. Most people have heard about the glycated proteins that people get in diabetes or aging—they call them AGEs (Advanced Glycation End products). Those stick to certain parts of protein molecules. It happens that carbon dioxide also has a spontaneous ability to attach to those same groups. If carbon dioxide is abundant, you can't get glycation because carbon dioxide is protecting that.

_Generated 2026-07-20 from the Bioenergetic Oracle corpus._