# Free fatty acid theory of insulin resistance

Category: Theories & Frameworks

Also known as: FFA theory, Randle cycle

Free fatty acid theory of insulin resistance holds that the inability of cells to oxidize glucose—the hallmark of type 2 diabetes—is driven primarily by elevated free fatty acids (FFAs) in the bloodstream, not by excess sugar. Peat explained that this phenomenon was described…

10 passages · 3 authors · 2008–2022 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/free-fatty-acid-theory-of-insulin-resistance

## Synthesis

**Free fatty acid theory of insulin resistance** holds that the inability of cells to oxidize glucose—the hallmark of type 2 diabetes—is driven primarily by elevated **free fatty acids** (FFAs) in the bloodstream, not by excess sugar. [Source 1, 2, 5] Peat explained that this phenomenon was described biochemically in the 1960s by P.J. Randle, who demonstrated that increasing fatty acids directly blocks glucose oxidation. [Source 6] Peat consistently rejected the term “Randle cycle,” insisting there is no true cycle but simply a *competition* for oxidation: when FFAs are high, cells oxidize fats and ignore glucose, causing blood sugar to rise. [Source 1, 3] This was starkly demonstrated in hospitals when patients receiving intravenous soy oil emulsions became hyperglycemic within 15 minutes. [Source 4, 7]

The mechanism is a self-perpetuating stress cascade. When FFAs block glucose oxidation, cells signal for more fuel, prompting the liver to produce additional glucose and worsening hyperglycemia. [Source 2, 4] Peat argued that the resulting high blood sugar is a compensatory adjustment, not the root cause of the pathology. [Source 2] The glucose that does enter cells cannot proceed through mitochondrial respiration and is instead wasted as **lactic acid**, which the liver converts back into glucose, further straining the system. [Source 4, 9] Dinkov has written that this competition means cells can only process one fuel at a time, and that lowering FFAs—through inhibiting lipolysis—allows cells to resume glucose oxidation and reverses insulin resistance, barring other enzymatic defects. [Source 3] Roddy notes that stress hormones like *adrenaline*, *cortisol*, and *estrogen* are all lipolytic, liberating FFAs into the blood and directly inhibiting glucose use to spare it for the brain and muscles. [Source 5]

Peat drew a critical distinction between fat types, arguing that the theory is fundamentally a problem of **polyunsaturated fatty acids** (PUFAs). He stated that PUFAs systematically turn on the very stress hormones that block energy production, creating a vicious cycle. [Source 1] While all FFAs can block glucose oxidation acutely via the Randle effect, PUFAs produce long-range damage by spontaneously oxidizing and forming **advanced glycation end-products** (AGEs), which are more powerfully driven by PUFAs than by glucose itself. [Source 7] In contrast, Peat noted that even when a very high sugar diet forces the body to synthesize new fats, these endogenously produced fats are saturated or monounsaturated, and they lower the toxic effects of free radicals rather than promoting them. [Source 6] He later clarified that coconut oil, rich in saturated fats, increases oxidative metabolism and is protective against diabetes, partly because its shorter fatty acids oxidize like sugar and partly because it displaces the *antimetabolic effects* of stored PUFAs. [Source 10]

The clinical implications reframe diabetes as an endocrine disorder of fat metabolism. Peat recounted a case where a diabetic friend’s gangrenous toes healed completely on thyroid hormone, which lowers stress and FFAs, only to rot again when his doctor withdrew the treatment, repeating this cycle three times. [Source 2] Dinkov has emphasized that insulin resistance is not a fixed cellular defect but a state driven by the environment of elevated FFAs; agents like **niacinamide** and **aspirin** can lower FFAs and restore glucose metabolism. [Source 3, 9] Roddy has highlighted evidence that chronic exposure to FFAs destroys insulin-secreting pancreatic beta cells, while glucose infusion can regenerate beta cell mass by 250 percent in days, further implicating fat rather than sugar as the primary toxin. [Source 5] The theory thus posits that the modern epidemic of diabetes tracks the increased consumption of industrial polyunsaturated oils, which block energy production at the cellular level. [Source 6, 8]

## People also ask

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

Peat explained that free fatty acids compete directly with glucose for oxidation inside cells, so when fatty acid levels are high, cells oxidize fats and ignore glucose, causing blood sugar to rise.

### Why did Peat consider polyunsaturated fats especially harmful in diabetes?

Peat argued that while all free fatty acids can acutely block glucose use, polyunsaturated fats cause lasting damage by spontaneously oxidizing and forming advanced glycation end-products, and by activating stress hormones that further liberate fatty acids.

### What substances did Peat and his colleagues suggest could lower free fatty acids?

The corpus describes that agents like niacinamide, aspirin, and thyroid hormone can lower free fatty acids, allowing cells to resume glucose oxidation and reverse the insulin-resistant state.

## Related concepts

- [The Randle Cycle (Randle Effect)](https://bioenergeticoracle.com/md/concepts/the-randle-cycle-randle-effect/index.md)
- [Hyperammonemia](https://bioenergeticoracle.com/md/concepts/hyperammonemia/index.md)
- [Saturated Fat](https://bioenergeticoracle.com/md/concepts/saturated-fat/index.md)
- [Adrenaline](https://bioenergeticoracle.com/md/concepts/adrenaline/index.md)
- [Benign Prostatic Hyperplasia (BPH)](https://bioenergeticoracle.com/md/concepts/benign-prostatic-hyperplasia-bph/index.md)
- [Bohr effect](https://bioenergeticoracle.com/md/concepts/bohr-effect/index.md)

## Cited passages

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

### Source 1 — Energy Production Diabetes Saturated Fats KMUD 2011

Ray Peat · Interview · 2011 · http://www.l-i-g-h-t.com/files/herb-doctors-energy-production,-diabetes-and-saturated-fats.mp4

> **Ray Peat:** Some people call it the Randle cycle, but there is no cycle involved; it's just a competition. When you raise your free fatty acids, you inhibit the ability to oxidize glucose. Stress increases the free fatty acids. Oxidizing glucose is what you need to overcome the stress. And so, it's sort of a counterproductive reaction. But the reason it’s counterproductive is that our systems are designed not to eat PUFA. And it's the PUFA which very systematically - it's just an amazing black-and-white almost difference- the way the PUFA turn on the very stress hormones that interfere with the energy, making it the body need more stress hormones, blocking the energy. So that if we eat more [PUFA], we are turning on the very things that cause the problem.
>
> **Herb Doctor:** Why does the body want to do that?
>
> **Ray Peat:** The body is designed, apparently from how completely systematic it is, to respond to saturated fat. Saturated fats block the stress reaction. So the properly functioning body would be logical: the stress reaction would provide energy in the absence of food, would provide the saturated fats from the storage, and at the same time it would inhibit the stress hormones and allow the cycle to be broken.

### Source 2 — Herb Doctors: Diabetes I

Ray Peat · Interview · Feb 21, 2014 · http://l-i-g-h-t.com/files/herb-doctors-diabetes-I.mp4

> **Ray Peat:** And in hyperglycemia, what you have is the body’s adjustment to the inability of cells to get enough energy, because they can’t oxidize glucose, because the fats are blocking it. That’s been known since the 60’s, called Randle cycle, in which free fatty acids block the use of glucose. So, the thyroxine, the body tries to overcome that poisonous effect of the free fatty acids by increasing glucose production. And so it kind of get around the block just by stuffing more glucose into the blood. So, to a great extent, the rise in blood sugar shouldn't be thought in itself the cause that interferes with the use of glucose, it shouldn’t be concentrated on. And when cells can’t get enough glucose, that not only turns on the stress hormones it turns off the production of thyroid hormone. And so, in all diabetics (if the cell isn’t able to take up and use glucose) the liver becomes unable to activate the pre thyroid hormone, turning it into the active T3. So, supplementing the active T3 thyroid hormone will cure lots of the so-called effects of diabetes. I had an old friend whose toes were basically rotting (because of what was diagnosed as diabetes degenerative nerve and circulation problems in the legs and feet), and 2 weeks after he had started using Armour thyroid, his feet recovered completely. His toes had been black with ulcerated sores going right into the bones, but they completely healed up on thyroid. But we went through 3 cycles in which his doctor said the Armour thyroid is going to increase his blood sugar and make his diabetes worse, so he would tell him to stop it and his feet would start to rotting again. So, it wasn’t just a coincidence: we did it 3 times.

### Source 3 — A Bioenergetic View of Weight Loss [Generative Energy #9]

Danny Roddy (with Danny Roddy) · Interview · Oct 16, 2015 · https://www.youtube.com/watch?v=3OhCZ5YEou8

> **Danny Roddy:** You mentioned the Randall cycle and myself coming from a low carb background. This was I think I first read about it from Ray and I was just completely oblivious to this idea. And it's not actually a cycle, but it helped me at least understand in the beginning how I had been fooled by the idea that fat oxidation was. preferable over glucose. Can you explain a little bit about the Randall cycle? And I'm still confused why almost no low carb person I've ever read ever mentions it.
>
> **Georgi Dinkov:** The Randall cycle is also known as the glucose fatty acid cycle. And it is a metabolic process which involves the competition of glucose and fatty acids for a substrate of oxidation. In other words, your cells at any given point of time sense the presence of either glucose and fatty acids and they can only process one at a time. I don't know if the exact ratio is known, but let's say if you have a ratio that favors more fatty acids in the bloodstream versus glucose, your cells will oxidize the fatty acids and they will ignore the glucose just because they can't oxidize it. That's what directly leads to hyperglycemia. Your cells just cannot process the glucose as long as there is a sufficient amount of fatty acids in the blood to prevent the oxidation of glucose. And it has been shown that inhibiting lipolysis, which lowers the amount of free fatty acids in the blood, effectively allows the cells to resume the oxidation of glucose, unless you have another problem like a deficiency in one of the enzymes of the Krebs cycle or there's a deficiency in the electron transport chain. But by and large, in most people, lowering the free fatty acids will reverse this insulin resistance, the inability to oxidize glucose. And several drugs on the market that actually try to do that, but niacinamide has been known to do it efficiently very well, and so does aspirin.

### Source 4 — Ask the Herb Doctor: Sugar I

Ray Peat · Interview · Sep 17, 2010 · https://www.youtube.com/watch?v=pgnzAR_a2MI

> ## Diabetes, The Randle Effect, and Polyunsaturated Fats
>
> **Sarah Murray:** So in diabetes, people have high levels of free fatty acids blocking the sugar from getting into the cell. Doesn't that feedback to the system to tell the body to raise the blood sugar higher?
>
> **Ray Peat:** Yes, it's a self-stimulating cycle. When you block the cells from using glucose, they call for more, and the liver obliges by making extra glucose. Diabetics often have very high lactic acid concentrations, showing that the glucose *is* getting into the cell, but it can't be used oxidatively because the fatty acids are blocking the respiratory system. So then lactic acid goes to the liver, which turns it into more glucose.

### Source 5 — Hair Like a Fox: A Bioenergetic View of Pattern Hair Loss

Danny Roddy · Book · 2013

> Later on, when insulin secretion begins to fall off, high blood glucose levels (hyperglycemia) develops, and a diagnosis of type II diabetes is made. Excess carbohydrate consumption is often thought to cause or greatly exacerbate these issues, and some have suggested that limiting our overall intake of carbohydrates, especially of sugar, would greatly ameliorate these problems. Rather than excess carbohydrate, however, the preponderance of evidence suggests that excess fat, by elevating free fatty acids (non-esterified fatty acids or NEFA), causes insulin resistance.16 The accumulation of free fatty acids in the blood can be thought of as a condition brought about by stress (any kind), executed by way of the adaptive “stress” hormones.17 These stress hormones are all “lipolytic”—meaning that they liberate fatty acids into the blood. Adrenaline, cortisol, estrogen, growth hormone, and aldosterone (among others), inhibit the use of glucose in various tissues in order to spare that glucose for certain areas of the brain and the muscles as means to supply energy to power short bursts of explosive activity. While “burning fat” has become synonymous with meaningless diet jargon, Wolfe and his colleagues noted that 57 “the enhanced mobilization and oxidation of fat is a fundamental response to stress,” and that there was “little doubt that there are signals for the increased mobilization of fat [present] in shock, trauma, and sepsis.”18 Free fatty acids interfere with energy metabolism in both the short-term and the long-term. In the short-term fatty acid metabolism inhibits the uptake and oxidation of glucose, as the British biochemist Sir Phillip Randle’s hypothesis states.19 In the long-term, free fatty acids have been referred to as a “toxic candidate” for the insulin-secreting pancreatic beta cells.20 In fact, it was found that chronic exposure to even moderate amounts of fatty acids dysregulates and impairs the functioning of the beta cells, even destroying them in severe cases.21 In contrast to the beta cell destroying effect of fatty acids, glucose has been shown to initiate the regeneration of beta cells, thereby restoring the physiological proportion of insulin secretion to glucagon secretion by the pancreas.

### Source 6 — Cholesterol Is an Important Molecule KMUD 2008

Ray Peat · Interview · 2008

> **Herb Doctor:** Diabetes seems to be exploding. Can you talk a bit about diabetes? What can be done to treat it, and why is it such a prevalent diagnosis today?
>
> **Ray Peat:** The diet of Americans and Europeans has changed over these years in which diabetes has been increasing, with the greatly increased consumption of polyunsaturated vegetable oils. Even eggs now, they feed chickens so much corn and soy that even eggs have less cholesterol and more polyunsaturated fats. In 1963 or '64, a researcher named P.J. Randle observed that he could block the oxidation of glucose just by feeding an increased amount of the fatty acids. And that's now called the Randle cycle. When it became popular to feed hospitalized patients intravenously with a fat emulsion to try to keep them from losing weight, they very quickly discovered that it suppressed their immune system and caused a variety of other symptoms. But it almost immediately would cause an elevation of blood glucose. And that was exactly what P.J. Randle had noticed in his animal studies. So, diabetes was basically explained biochemically in the 1960’s, when if you eat more fat, you block the response to insulin, create insulin insensitivity or resistance. And that's now called type 2 diabetes, or syndrome X.

### Source 7 — Ask the Herb Doctor: Sugar I

Ray Peat · Interview · Sep 17, 2010 · https://www.youtube.com/watch?v=pgnzAR_a2MI

> ## Diabetes, The Randle Effect, and Polyunsaturated Fats
>
> **Andrew Murray:** What is the deal with the link between diabetes and sugar?
>
> **Ray Peat:** The principle in physiology that explains it was proposed a few decades ago called the Randle effect or the Randle cycle. It refers to the fact that free fatty acids block the use of glucose by cells. This was demonstrated in hospitals when giving nutritional support to patients in the form of a soy oil emulsion. About 15 minutes after injecting this emulsified soy oil, people would get hyperglycemic. When the fatty acids involved in blocking the sugar are *polyunsaturated*, they produce long-range damage. A group led by Fu demonstrated that the glycated proteins seen in diabetic people—which are usually blamed on glucose—are actually caused more powerfully by polyunsaturated fatty acids. Spontaneously oxidized polyunsaturated fats stick to the proteins. So, the free fatty acids not only block sugar use instantaneously (Randle effect), but they produce these advanced glycation end-products (AGEs) associated with diabetes and aging. The chronic effect of a high-fat diet, if the fat is predominantly unsaturated, produces diabetes and all the things that result from glycated proteins.

### Source 8 — #86 - The Estrogen Industry, the magic of progesterone and the importance of thyroid with Dr Ray Peat & Kate Deering

Ray Peat · Interview · Jan 31, 2022

> **Kate Deering:** Right, so essentially when the diabetic state is often referred to having hyperglycemia or high blood sugar, that's the association you hear in the medical industry. But what you're saying is it's really an abundance of free fatty acids in the blood, essentially, and they are inhibiting the sugar. And that's why it's staying in the blood and you actually see hyperglycemia?
>
> **Ray Peat:** Yeah. It's called the Randall effect. The fact that fatty acids block the ability to oxidize glucose. The polyunsaturated fatty acids are actually the ones that are doing the most blocking of the glucose oxidation. Here's the food industry going back to the need to dispose of soybean oil because they couldn't sell it for a paint stock. And then the shift 30 years later to fish oil and the N-3 series, that happened to coincide with the intervention of the environmental protection agency that forced the fish industry to stop polluting the bays and surrounding land areas with dumps of fish fat. And right at the time the EFA told them to stop polluting with fish fat, it came on the market as a health food.

### Source 9 — Does sugar cause insulin resistance and make you fat? Ray Peat Criticisms Part 2 with Georgi Dinkov

Georgi Dinkov · Interview · Jun 8, 2021 · https://www.youtube.com/watch?v=yRcXtTjfb-M

> **Strong Sistas:** so I think that that's a really important point that we should cover just briefly. So what does someone do who's insulin resistant and is interested in switching from a low carb to more of a pro metabolic or carbohydrate fueled?
>
> **Georgi Dinkov:** okay so a couple of things uh it is an endocrinological problem typically associated with cortisol and estrogen in both men and women but the direct insulin resistance is driven by elevated levels of free fatty acids in the blood and because the cell can only metabolize either carbohydrates or fats at any single point in time due to the infamous randall cycle If you're oversupplying fatty acids, basically obese people, some obese people tend to have elevated so-called lipolysis and stress raises lipolysis, right? So as long as you're flooding your bloodstream with fat, whether through diet or by being stressed, which causes cortisol and adrenaline to shred your fatty tissue as well. This prevents the cells from metabolizing glucose, which means that if you take something or do something that lowers the supply of fat to the bloodstream, whether through diet or through the fatty tissue, right? Then this should improve the metabolism of glucose because there's nothing damaged inside the cell. Many people have looked for very carefully, I mean, for decades and thought that insulin resistance and diabetes are actually some kind of a defect in the cell, just like cancer is. Turn out there is no such thing. Basically, the cell can only do what environment allows it to do and what has been set up to do naturally. So which means I can only oxidize either carbs or fats. If you're giving me fats all the time, I cannot metabolize those carbs, which means they're going to float around.

### Source 10 — Ray Peat Email Advice Depository — Post 253

Ray Peat · Email · Aug 10, 2016

> ## Thread 4
>
> **Question:** [Coconut Oil and the Randle Cycle] It's known that in the 1940s Bernardo Houssay found that coconut oil protected animals from poison-induced diabetes and in 1963 Randle described the inhibition of glucose oxidation by free fatty acids. I'm trying to reconcile the above two facts; is coconut oil exempt from becoming free fatty acids and competing with glucose in the randle cycle?
>
> **Ray Peat:** Relative to PUFA, yes. When the body contains a lot of PUFA, eating coconut oil increases oxidative metabolism, partly because of the shorter fatty acids that are more quickly oxidized, like sugar, and partly because of the antimetabolic effects of the PUFA that they displace. More recently, several investigators have found that a “deficiency of essential fatty acids” is highly protective against diabetes.

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