# Free Fatty Acids (FFAs, NEFA)

Category: Metabolism

Also known as: Free Fatty Acids, free fatty acids, NEFA, nefa, ffas

When the body doesn't have enough glucose, free fatty acids are released from the tissues, and their oxidation blocks the oxidation of glucose even when it becomes available from the breakdown of protein caused by cortisol, which is released during glucose deprivation.

10 passages · 3 authors · 2013–2026 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/free-fatty-acids-ffas-nefa

## Synthesis

**Free fatty acids (FFAs, also called non-esterified fatty acids or NEFA)** are a primary vector of stress-induced tissue damage, and their chronic elevation is inseparable from the pathology of diabetes, heart failure, neurodegeneration, and aging. [Source 1, 3, 6] Peat argued that when the body lacks sufficient glucose, FFAs are released from adipose stores, and their oxidation actively blocks the oxidation of glucose even when it becomes available, creating a self-perpetuating energy deficit. [Source 1] He identified this *Randle cycle* interference as the core mechanism by which stress causes harm, noting that "just about everything that goes wrong involves free fatty acid increase." [Source 3] Even saturated FFAs, while less harmful than polyunsaturated ones, still tend to shift mitochondrial metabolism away from glucose and fructose oxidation, lowering **carbon dioxide production** and turning on stress-related pathways. [Source 3]

The toxicity of circulating FFAs is overwhelmingly determined by their degree of unsaturation. Peat explained that when fat stores contain predominantly **polyunsaturated fatty acids (PUFAs)** from dietary sources like corn or safflower oil, the FFAs liberated during stress will be mostly *linoleic acid* and *arachidonic acid*. [Source 5, 7] These unsaturated FFAs are more water-soluble and are preferentially released into the bloodstream, where they stimulate the stress hormones ACTH, cortisol, adrenaline, glucagon, and prolactin, which in turn drive further lipolysis in a vicious, self-amplifying circle. [Source 5] In contrast, the stress reaction is self-limiting in the relative absence of PUFA, because saturated FFAs provide negative feedback that inhibits the production of adrenaline and adrenal steroids. [Source 5] This distinction explains why Peat considered the chronic, spontaneous release of small amounts of arachidonic acid from tissue phospholipids to be a major driver of the *mild chronic inflammation* underlying obesity and metabolic syndrome. [Source 4]

At the cellular level, elevated NEFA causes **mitochondrial respiratory damage**, cell swelling, and a generalized increase in membrane permeability that admits calcium and water, depleting blood volume and leading to a systemic inflammatory state that can culminate in shock. [Source 5, 6] Dinkov has written that one of the main roles of adipose tissue is to sequester dangerous PUFAs in an inert triglyceride form, keeping them away from vital organs, and that rapid weight loss through fasting or exhaustive exercise is harmful precisely because it floods the bloodstream with these stored PUFAs. [Source 9] In nerves, the energy failure caused by FFA-driven suppression of glucose oxidation prevents the production of protective **neurosteroids** from cholesterol and instead upregulates the enzyme *aromatase*, increasing local estrogen synthesis and contributing to diabetic neuropathy and brain degeneration. [Source 2] Dinkov and Roddy have further noted that the lipid peroxidation of released PUFAs is necessary for the formation of **lipofuscin**, a primary structural change of aging that accumulates inside mitochondria and progressively slows metabolism. [Source 10]

Therapeutically, Peat pointed to **niacinamide** and **aspirin** as very good regulators of FFA expression, capable of restoring energy production in failing hearts and protecting nerves by suppressing the lipolytic release of fatty acids. [Source 2] He also emphasized that dietary sugar and protein quickly end the stress-driven liberation of FFAs, whereas high-meat, low-carbohydrate diets chronically elevate both free fatty acids and free amino acids, accelerating degenerative processes. [Source 3, 5] Roddy has summarized this perspective by noting that the liberation of FFAs into the blood interrupts glucose oxidation in both the short and long term, and that the use of fat as fuel supplies less **carbon dioxide** than the complete oxidation of glucose, undermining the anti-stress, pro-respiratory state governed by active thyroid hormone. [Source 8]

## People also ask

### How do free fatty acids block glucose metabolism?

Peat argued that through the Randle cycle, the oxidation of free fatty acids actively inhibits glucose oxidation, creating a self-perpetuating energy deficit even when glucose becomes available.

### Why are polyunsaturated fatty acids more dangerous when released during stress?

The corpus describes how unsaturated FFAs like linoleic acid are preferentially released and stimulate stress hormones, driving further lipolysis in a vicious circle, whereas saturated FFAs provide negative feedback to limit the stress reaction.

### What substances did Peat recommend to suppress harmful free fatty acid release?

Peat pointed to niacinamide and aspirin as effective regulators that suppress lipolytic FFA release, and he noted that dietary sugar and protein can quickly end the stress-driven liberation of fatty acids.

## Related concepts

- [Albumin](https://bioenergeticoracle.com/md/concepts/albumin/index.md)
- [Cholesterol](https://bioenergeticoracle.com/md/concepts/cholesterol/index.md)
- [Cholesterol (HDL, LDL)](https://bioenergeticoracle.com/md/concepts/cholesterol-hdl-ldl/index.md)
- [Saturated Fat](https://bioenergeticoracle.com/md/concepts/saturated-fat/index.md)
- [Uncoupling](https://bioenergeticoracle.com/md/concepts/uncoupling/index.md)
- [Adrenaline](https://bioenergeticoracle.com/md/concepts/adrenaline/index.md)

## Cited passages

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

### Source 1 — Glossary

Ray Peat · Glossary

> Free Fatty Acids (FFAs, NEFA)
>
> When the body doesn't have enough glucose, free fatty acids are released from the tissues, and their oxidation blocks the oxidation of glucose even when it becomes available from the breakdown of protein caused by cortisol, which is released during glucose deprivation.

### Source 2 — Diabetes II and How to Restore and Protect Nerves KMUD 2014

Ray Peat · Interview · 2014 · https://www.youtube.com/watch?v=Lj4ewp2YH1k

> **Herb Doctor:** So Dr Peat, getting back to the topic of tonight, about the treatment with aspirin you mentioned niacinamide as very good regulators of FFAs expression. I want to ask, even in the presence of supplemented insulin per se, for people that are truly insulin diabetic, the nerve damage, neuropathy, these processes that diabetics still get even in the presence of insulin, and those sensation-loss they get, particularly in the feet or the soles of the feet, which are the initial symptoms of the so-called sugar excess syndrome: how is this process at odds with excess sugar, when sugar is a vital energy-producing currency?
>
> **Ray Peat:** I’ve gone through many articles, recently I watched a video by Gershom Zajicek, who’s a very amazing biology medical professor in Israel. He has a very good understanding of physiology, and he has a video on diabetes and explains how the increased blood glucose is called for by the brain to make up for its needs. But after explaining the compensatory effect of high glucose for the brain, he uses the term glycotoxic, for the harmful effects supposedly of glucose. And, basically, he just resorted to a word to explain how glucose affects the other organs. And, looking through the literature, I see that people do that without really explaining what’s happening, why extra glucose would be harmful; if it’s within a moderate osmolarity, the mechanism just isn’t explained, even though they say it’s doing the harm. The changes in the nerves, include everything that is failing because of lack of energy. And when the cells are known to be living on fatty acids, and the fatty acids are intrinsically disturbing the metabolism of phosphate, turning off glucose energy production, slowing it down, even activating nitric oxide, the respiratory inhibitor, you know that the energy of the cell being reduced, is going to slow all kinds of repairing processes. And, incidentally, in the pancreas, glucose stimulates regeneration of new insulin producing cells. And it’s the bad balance (too much FFAs and not enough glucose to defend the cells) that causes them to die. And anywhere else that a cell is deprived of it’s energy and forced to eat fatty acids instead… that’s now well recognized in heart failure: a simple treatment such as niacinamide can restore great amounts of heart energy production and improve the failure. Drugs are being developed to do the same as aspirin and niacinamide.

### Source 3 — Ray Peat Full Interview: Cholesterol, PUFA, Coconut Oil, Thyroid, and the Metabolic Truth

Ray Peat · Interview · Jul 12, 2025 · https://www.youtube.com/watch?v=lQB95tLW7eE

> **Ray Peat:** What was the material in the blood?
>
> **Danny Roddy:** Free fatty acids? Yeah.
>
> **Ray Peat:** Correct.
>
> **Danny Roddy:** Can you explain why somebody would not want that to happen, i.e., like a low-carb diet?
>
> **Ray Peat:** Would not want which to happen?
>
> **Josh Rubin:** He's saying that a group of people that follow the paleo diet out there, which is a high-protein, low-carb diet, and they're saying through their research that having higher levels of free fatty acids in the blood is actually beneficial. And you're saying it's not. So he was asking you to kind of elaborate on that.
>
> **Ray Peat:** Yeah, that's my main argument against eating a high meat diet. That's one of the important functions of sugar, I think, because my next newsletter in four months, I think, will be talking about free fatty acids. But basically, they're one of the means by which stress causes its damage. I've known people who were eating two or three pounds of meat a day and who were getting sicker and sicker as their free fatty acids and free amino acids increased and that started me reading more about the free state of fatty acids in the blood and just about everything that goes wrong involves free fatty acid increase. If they're totally saturated fatty acids, such as from coconut oil and butter, those are less harmful, but they still tend to shift the mitochondrial cellular metabolism away from using glucose and fructose and turning on various stress related things by lowering the carbon dioxide production I think is the main mechanism amazing thank you so much dr. P and thank

### Source 4 — Diabetes II and How to Restore and Protect Nerves KMUD 2014

Ray Peat · Interview · 2014 · https://www.youtube.com/watch?v=Lj4ewp2YH1k

> **Herb Doctor:** So that’s the thing behind what you’re describing now as the component free fatty acids (FFAs); if somebody’s eating a lot of saturated fat like butter, ghee, coconut oil then they’re not going to liberate the same free fatty acids that they would if they were consuming polyunsaturated ones in their diet?
>
> **Ray Peat:** Right
>
> **Herb Doctor:** Getting back to the classic description of diabetes as being a wasting disease, which actually we see very little of, as opposed to what now is generically diabetes, and it’s very largely linked to obesity in the general population, that obesity is probably directly linked to the polyunsaturated thyroid-suppressive diet some people consume?
>
> **Ray Peat:** It’s now increasingly seen as a fat inflammation condition, a mild chronic inflammation. And a major thing that causes that is the continual spontaneous release of small amounts of arachidonic acid, which is a highly unsaturated fatty acid. Even if you don’t eat it, linoleic acid for example will be turned into it by enzymes in the body. So, it becomes one of the most toxic stored fats, both in phospholipids and in the triglyceride storage. And when that’s released, that allows it to be turned into various things, but especially prostaglandins which are probably our biggest inflammatory problem.

### Source 5 — Fats, Functions & Malfunctions

Ray Peat · Article · 2013

> Combining anything with fat makes it more likely to enter cells. Stress (which increases free fatty acids and lowers cell energy) makes cells more permeable, admitting a broader range of substances, including those that are less lipophilic.
>
> Linoleic acid and arachidonic acid, which are said to make the lipid membrane more permeable, in fact make the whole cell more permeable, by binding to the structural proteins throughout the cell, increasing their affinity for water, causing generalized swelling, as well as mitochondrial swelling (leading to reduced oxidative function or disintegration), allowing more calcium to enter the cell, activating excitatory processes, stimulating a redox shift away from oxidation and toward inflammation, leading to either (inappropriate) growth or death of the cell.
>
> When we don't eat for many hours, our glycogen stores decrease, and adrenaline secretion is increased, liberating more glucose as long as glycogen is available, but also liberating fatty acids from the fatty tissues. When the diet has chronically contained more polyunsaturated fats than can be oxidized immediately or detoxified by the liver, the fat stores will contain a disproportionate amount of them, since fat cells preferentially oxidize saturated fats for their own energy, and the greater water solubility of the PUFA causes them to be preferentially released into the bloodstream during stress.
>
> In good health, especially in children, the stress hormones are produced only in the amount needed, because of negative feedback from the free saturated fatty acids, which inhibit the production of adrenalin and adrenal steroids, and eating protein and carbohydrate will quickly end the stress. But when the fat stores contain mainly PUFA, the free fatty acids in the serum will be mostly linoleic acid and arachidonic acid, and smaller amounts of other unsaturated fatty acids. These PUFA stimulate the stress hormones, ACTH, cortisol, adrenaline, glucagon, and prolactin, which increase lipolysis, producing more fatty acids in a vicious circle. In the relative absence of PUFA, the stress reaction is self limiting, but under the influence of PUFA, the stress response becomes self-amplifying.
>
> When stress is very intense, as in trauma or sepsis, the reaction of liberating fatty acids can become dangerously counter-productive, producing the state of shock.

### Source 6 — Denckla's Death Hormone: The Role of The Pituitary in Stress, Aging & Disease

Danny Roddy · Article · May 2, 2013

> The blogosphere has been polluted with the idea that burning fat is beneficial, however, increased levels of free fatty acids causes cell swelling, lipid accumulation in cells, and damages the mitochondrial respiratory complexes, decreasing the ability to produce efficient energy overtime. Diabetes, old age, and chronic illness, tend to be associated with higher levels of NEFA (Frayn KN, et al. 1996).
>
> Menage à Trois: Growth Hormone, Prolactin & Estrogen
>
> One of the best-known metabolic effects of growth hormone is its ability to mobilize free fatty acids (Raben, Hollenberg 1959). Moreover, growth hormone may create a bias towards the oxidation of the unstable, fragile unsaturated fatty acids (Clejan & Shulz, 1999).
>
> Increased levels of NEFA blocks the oxidation of glucose, raising blood sugar levels (insulin resistance), while increasing insulin levels to compensate for the (GH induced) insulin resistance (Krag et al. 2007).
>
> This is interesting considering that people engage in activities like "intermittent fasting" and "cold thermogenesis" in an attempt to increase growth hormone levels for the sake of "longevity" (i.e., the rate of living hypothesis, or The Race to Torpor).
>
> To the agonizing mental distress of many, bovine growth hormone is used to make cows give more milk. Similarly, in humans, growth hormone is closely associated with the hormone responsible for lactation, prolactin. While I've mostly talked about prolactin's "anti-hair" qualities on this weblog, high levels of prolactin (and estrogen) are implicated in breast cancer (Meyer F, et al. 1986), and increase parathyroid hormone (Raymond JP, et al. 1982), which is a large factor in bone loss (Adami S, et al. 2007).
>
> While it may seem paradoxical given that I'm suggesting that growth hormone is an adaptive (stress) hormone, it's highest concentration (along with prolactin) is usually at night. This may be due to the pro-respiratory effect of light (Barrett DW, et al. 2012) and the inherent "stress" of darkness.
>
> Hormones of Adaptation: ACTH, TSH, LH & FSH
>
> [references]
>
> Hans Selye found that increased levels of ACTH invariably led to an elevation in cortisol.

### Source 7 — Diabetes II and How to Restore and Protect Nerves KMUD 2014

Ray Peat · Interview · 2014 · https://www.youtube.com/watch?v=Lj4ewp2YH1k

> **Ray Peat:** A fat such as butter, or lard or corn oil, most of them consist of about 18 carbon atoms in a chain with oxygens on one end (making it acidic) and the rest of it, either just plain carbon and hydrogen, or occasionally, with the hydrogens removed (that’s called an unsaturated fatty acid, with a carbon chain interrupted by pure hydrogens). And those chains are attached to a glycerine molecule (3 carbons), technically an alcohol, that forms an ester with these free fatty acids, blocking the acid group, which makes the free fatty acid water soluble to some extent. And when the glycerine, which is also very water soluble, is combined with free fatty acids, it becomes very water insoluble. And that is the form in which it’s stored in the fat cells. Because you just form a drop of pure fat in the cell, and it’s very reluctant to diffuse away because of its insolubility. So, when you need energy, you have to activate enzymes that break the free fatty acids loose; when that happens from stress, or hunger, or fasting, these free fatty acids get into the bloodstream and enter cells and are available as energy production in the absence of glucose. The trouble is that, that process also tends to keep the stress going if the free fatty acids are unsaturated; those are more water soluble. And when they're polyunsaturated, like from corn oil, safflower and so on, those have further stress inducing action that tends to keep the breakdown of fat going and the stress reproducing itself.

### Source 8 — How to Burn Fat and Why You Shouldn’t

Danny Roddy · Article · Feb 16, 2013 · https://180degreehealth.com/2013/02/how-to-burn-fat-and-why-you-shouldnt

> # How to Burn Fat and Why You Shouldn’t
>
> Traversing through the blogosphere reveals much text, but little art. This is, until you stumble upon the site of low-carb sage Petro Dobromylkyj. Similar to da Vinci’s “David” or Shakespeare’s Hamlet, Petro’s exudes extraordinary vision. One doesn’t have to read past the header for the first glimpse of his contribution to The Great Work:
>
> [references]
>
> If I was forced to interpret Petro’s poem, I would say that he’s trying to tell us that carbohydrates reassure men that they can be masters of their own reality—but then turns around and says that actually, reality is not real.
>
> Another interpretation, which sounds less plausible, could be that one must decide where to obtain their fuel from: carbohydrate or fat.
>
> While the blogosphere has been polluted with the idea that “ using fat as fuel ” is somehow more desirable than glucose, in this article, I intend to describe how lipolysis (i.e., the liberation of free fatty acids into the blood) is a feature of stress, disease and aging.
>
> ## Lazy Reader Summary:
>
> - Glucose and oxygen, which are substrates for efficient energy production, are the two most basic anti-stress substances
>
> - Carbon dioxide (CO2), which is produced under the influence of active thyroid hormone, is needed to use glucose and oxygen efficiently
>
> - Stress liberates free fatty acids (non-esterified fatty acids or NEFA) into the blood for use as fuel The use of free fatty acids as fuel supplies less carbon dioxide than the complete oxidation of glucose The liberation of free fatty acids into the blood interrupts the use of glucose in the short- and long-term Over time, free fatty acids damage the cell’s highly evolved ability to produce oxidative energy (i.e., glucose to carbon dioxide)
>
> - Those with obesity and diabetes have markers suggestive of stress and the production of energy through inefficient glycolysis (i.e.

### Source 9 — Rapid fat loss can cause diabetes and liver disease, likely due to systemic exposure to free fatty acids

Georgi Dinkov · Article · Feb 18, 2026 · https://haidut.me/?p=3007

> When people asked Ray during interviews and in emails about weight loss, he always cautioned that rapid weight loss through fasting and/or exhaustive exercise is likely to be harmful due to increased lipolysis and thus PUFA flooding the bloodstream and literally poisoning the rest of the body. It seems that one of the main roles of adipose tissue is not only to store energy (in the form of fat) for use during emergencies (e.g. prolonged lack of food), but also to keep the evil PUFA away from other organs. Multiple studies have demonstrated that when a meal is consumed, the saturated fats are preferentially oxidized as fuel, while PUFA (and to a lesser degree, MUFA) are preferentially stored in adipose tissue in an inert (triglyceride) form. While in “storage”, PUFA is a lot less dangerous than when floating around the blood and while still subject to peroxidation the negative effects are largely contained to the adipose tissue. Said peroxidation can also be safely inhibited by taking antioxidants such as vitamin E, but that approach only works while PUFA is stored. When PUFA is released into the blood, it is released in the form of free fatty acids (NEFA), and the elevation of NEFA has been shown by countless studies to cause damage to virtually any organ exposed to NEFA. It is now known that the kidney damage seen in virtually all patients with diabetes II is due to chronic exposure to NEFA, and the same has been shown to be true for liver disease, and even neurodegenerative conditions such as Alzheimer’s. As such, keeping PUFA stored rather than floating around is perhaps the best approach while a person works on thyroid and eliminating PUFA from diet so that total PUFA stores are replaced slowly and with as little NEFA elevation as possible. So, it seems that carrying extra weight and working to slowly get rid of it while also changing its composition is preferable to the “shock and awe” approach we keep heating about from every doctor and fitness/exercise commercial on TV and social media.
>
> [references]

### Source 10 — #11: Testosterone, DHEA, PUFA, Libido, Aspirin, Progesterone, and Saturated Fat with Georgi Dinkov

Georgi Dinkov (with Georgi Dinkov) · Interview · Sep 20, 2019 · https://open.spotify.com/episode/12hdzF0qSQrADo1cLDop6C

> **Danny Roddy:** We kind of already went over it, but did you – somebody posted on the Ray Peep Forum something saying like it's not glucose that causes diabetes. It's the free fatty acids. Did you catch that article?
>
> **Georgi Dinkov:** I have that on the blog as well. I mean basically – yeah. So it's called – I think my title is fatty acid buildup and inflammation is not glucose is what drives diabetes.
>
> **Danny Roddy:** Okay. This was from a little while ago, right?
>
> **Georgi Dinkov:** Yeah, it was from August.
>
> **Danny Roddy:** Oh, okay. Okay, that wasn't brand new.
>
> **Georgi Dinkov:** It was a duplicate post or something, but I don't want to go to the thread and say, hey, that's my stuff, right? If they post it and it spurs a good discussion, by all means, I like discussion.
>
> **Danny Roddy:** One last thing before we move on. Do you think the lipid peroxidation is that uncontroversial pro-aging aspect? Because there was a paper that I stole from somebody, but they basically said the lipid peroxidation lights the mitochondria on fire. Like that was the imagery they were saying, but that is the really offensive part of the, I mean, I know there are lots of aspects that are bad about the free fatty acids, but that's one of the worst ones.

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