Polyunsaturated fatty acids (PUFA) are fats with two or more double bonds. In ordinary diets the main problem load is linoleic acid from seed oils, with long-chain highly unsaturated fats from fish-oil products as a second issue. Stored PUFA clears slowly: by Ray Peat's estimate, a complete change in dietary fat type takes about four years to show in body fat stores.[1] In the Minnesota Coronary Experiment, replacing saturated fat with linoleic-acid-rich corn oil lowered serum cholesterol but did not lower deaths, and the larger the cholesterol drop, the higher the risk of death.[2]

Reactivity

[edit]

Double bonds make these fats chemically reactive. They incorporate into cell membranes and oxidize into toxic fragments. Stress chemistry and aging both interact with that load.

Saturated fatty acids terminate the stress reactions, polyunsaturated fatty acids amplify them.

— Ray Peat[3]

The most highly unsaturated fats accumulate with age; fish-oil style DHA is not automatically protective in this frame.[4]

Diet sources

[edit]
  • Seed oils: soybean, corn, canola, sunflower, safflower, cottonseed, grapeseed
  • Packaged snacks, restaurant fryers, many dressings
  • Nuts and seeds in bulk amounts
  • Industrial fish-oil capsules

Lower-PUFA cooking fats: butter, ghee, beef tallow, coconut oil in modest amounts.

Specific seed oils

[edit]

The common pantry and restaurant seed oils differ mainly in how much linoleic acid they carry and how fast that makes them oxidize once heated or stored. Higher-linoleic oils go rancid faster and pose a bigger membrane-loading problem; a lower-linoleic oil is still a seed oil, not a fix.

Oil Predominant fat Smoke point Notes
Soybean oil Polyunsaturated (linoleic acid) ~230°C (450°F) The largest single PUFA source in the US food supply; fills restaurant fryers, packaged foods, and animal feed
Sunflower oil Polyunsaturated (linoleic acid, ~65%) ~225°C (440°F) Marketed as "light"; among the highest-linoleic common seed oils
Canola oil (rapeseed) Mixed monounsaturated/polyunsaturated (linoleic acid, ~20%) ~204°C (400°F) Lower linoleic acid than sunflower or soybean oil, but still oxidizes with heat and storage and is sold on the same "heart-healthy" marketing[5]
Sesame oil Polyunsaturated ~210°C (410°F) Used mainly as a flavoring rather than a frying-fat base; still a linoleic acid source

Trials that compare two seed oils against each other, rather than against a genuinely low-PUFA diet, can make a lower-linoleic oil like canola look "anti-inflammatory" relative to a higher-linoleic oil like sunflower; see Oil-vs-oil trial design below.

Practical moves

[edit]
  1. Stop buying liquid seed oils for the pantry.
  2. Read labels; "heart healthy" badges commonly mark high-PUFA products.
  3. Ask restaurants what they fry in; prefer grilled or butter-cooked when possible.
  4. Do not replace seed oils with mega fish-oil capsules as a "fix."
  5. Expect membrane change over months to years, not one clean week.

How long depletion takes

[edit]

Stored PUFA doesn't clear on a diet-change timeline; it clears on a fat-tissue-turnover timeline.

If you totally change your diet from saturated to unsaturated, it takes about four years for the complete change to be reflected in your stores. So you can figure that the average fat molecule is four years old.

— Ray Peat[6]

The same logic applies going from unsaturated back to saturated: eliminating dietary PUFA is step one, not the finish line. Stored PUFA keeps circulating for years, released whenever free fatty acids rise from stress, fasting, cold exposure, or illness, so a single "clean" week or month doesn't reflect the underlying tissue ratio.

Supporting clearance

[edit]

The body clears circulating PUFA mainly by conjugating it to glucuronic acid to make it water-soluble for excretion in urine, carried to the liver bound to albumin.

The main way they [PUFA] are detoxified is by attaching glucuronic acid, making them water soluble, so they leave in the urine. Keeping the free fatty acids low in relation to albumin, they will largely be carried bound to the albumin to the liver.

— Ray Peat[7]

ReciPeats tags dishes worth limiting or reworking as diet-red or diet-yellow, often for PUFA content among other flags.

Burr experiments of 1929

[edit]

The studies still cited for PUFA "essentiality" were done in 1929 by George Burr and his wife, who pronounced linoleic acid and linolenic acid essential to prevent "scaly tail disease" in rats. About 17 years later, Roger Williams' lab recognized that same rat disease as a vitamin B6 deficiency, reproducing it on the Burrs' identical diet and curing it with B6 alone, no added fat.[8]

George Burr himself demonstrated that his fatty acid-deficient rats were burning fuel and consuming oxygen at a rate 50% higher than the rats on his "adequate" diet. He didn't understand that the fats were lowering the metabolic rate, drastically suppressing thyroid function so the rats could get along on fewer calories and vitamins.

— Ray Peat[9]

Burr's own "deficient" rats were, by this reading, simply running a faster, thyroid-driven metabolism; the PUFA-fed "adequate" rats were the ones running suppressed. A series of papers in the French Annals of Endocrinology found PUFA blocks the blood transport proteins that carry thyroid hormone, with the degree of blocking rising with the degree of unsaturation, and blocks the cell's response to thyroid hormone even when it arrives.[8]

The Minnesota Coronary Experiment

[edit]

A gold-standard double-blind randomized trial (1968-73) tested substituting vegetable-oil-based PUFA for saturated fat in over 9,000 institutionalized adults. The results went unpublished for decades; when the raw data were finally recovered and analyzed in 2016, the PUFA group had lower serum cholesterol as predicted, but no reduction in cardiovascular death or overall mortality, and each 30 mg/dL drop in serum cholesterol was associated with 22% higher mortality risk, opposite to the diet-heart hypothesis the trial was designed to support.[2]

Oil-vs-oil trial design

[edit]

Some trials framed as evidence that seed oils are anti-inflammatory compare two different seed oils against each other rather than a genuinely low-PUFA diet. A 92-subject randomized trial in adults with type 2 diabetes assigned participants to plain canola oil, gamma-oryzanol-fortified canola oil, or sunflower oil for 12 weeks and reported the canola arms showed "boosted anti-inflammatory effects" relative to sunflower oil.[5] Sunflower oil is roughly 65% linoleic acid, well above canola oil's roughly 20%. A design like this measures a lower-PUFA seed oil against a higher-PUFA seed oil, not seed oils against a genuinely low-PUFA diet.

[edit]

High free fatty acids from stress and fasting worsen the picture when the fats released are PUFA-rich. Vitamin E need rises with PUFA load. Estrogen and PUFA reinforce inflammatory tone in primary essays on fats and hormones.

Lipid peroxidation of linoleic acid produces 4-hydroxynonenal (4-HNE), proposed as a shared mechanistic driver linking diabetes and cancer through oxidative stress, insulin resistance, and inflammation.[10] Circulating linoleic acid is separately elevated in Alzheimer's dementia and negatively correlated with mitochondrial bioenergetic capacity.[11]

A double-blind crossover trial of 18 healthy adults found that a single 40g-fat meal from corn oil or flaxseed oil (both PUFA) raised GlycA, a marker of systemic inflammation, more than the same meal from butter or coconut oil (both saturated); flaxseed oil also raised IL-17C, a signaling protein that drives inflammation in mucosal tissue like the gut lining.[12]

PUFA-rich cell membranes also change how the body handles cold and low energy. Hibernating chipmunks fed a high-PUFA diet went into longer bouts of torpor, with lower body temperature and lower metabolic rate, than chipmunks on a saturated-fat diet.[13] Low temperature and low metabolic rate mark the same low-energy state as hypothyroidism; a PUFA-loaded membrane pushing an animal toward colder, slower physiology fits the broader pattern of PUFA suppressing metabolism.

Free-radical attack on PUFA double bonds yields malondialdehyde and 4-HNE, the two main omega-6 peroxidation products, which at higher levels inhibit gene expression and promote cell death.[14] Whole-body conversion of alpha-linolenic acid to DHA is below 5% in humans; about 60% of a dose is burned to CO₂ within a week.[15] Fish oil inhibits platelet aggregation; in one elderly patient on warfarin and fish oil, the bleeding tendency after a blunt head injury could not be reversed.[16]

Immune suppression

[edit]

Intravenous emulsions of unsaturated "essential fatty acids" suppressed immunity in patients fed this way, and such emulsions were then used in organ-transplant patients to help prevent rejection.[17][18][19] The underlying animal research found that dietary polyunsaturated fat prolonged skin allograft survival in mice and suppressed both primary and secondary cytotoxic immune responses, at a human-equivalent dose in the range of an ordinary Western daily intake of PUFA.[20] Since immune suppression is implicated in cancer risk, Peat-aligned writers have connected this PUFA effect to rising cancer rates independent of PUFA's other proposed mechanisms.[19] A model built on age-related thymic decline in T cell output fit cancer incidence across many cancer types better than a mutation-accumulation model.[21]

In rats, n-6 PUFA changed key enzyme activities in the thymus, spleen, and gut-linked lymph nodes more than saturated fat. N-6 PUFA in the diet are widely reported to suppress immune function.[22] The weight of the thymus is reduced by PUFA in the diet.[23] See Thymus.

In hairless mice fed 20% fat with rising sunflower-oil PUFA (0 to 20%) during UV photocarcinogenesis, tumor incidence, multiplicity, progression to squamous cell carcinoma, and mortality rose with the polyunsaturated fraction. Acute UV suppressed contact hypersensitivity by more than half on 20% polyunsaturated fat, while 20% saturated fat gave almost complete protection from that photoimmunosuppression; unirradiated CHS was unaffected by fat type.[24]

The immunosuppression is proposed to start with membrane incorporation. Polyunsaturated fatty acids, especially of the n-3 class, alter the lateral organization of the T cell membrane, which inhibits T cell receptor signaling and suppresses T cell activation and proliferation. They also alter the expression and conformation of MHC molecules and so antigen presentation, and PUFA acyl chains are sterically incompatible with cholesterol.[25]

Arachidonic acid

[edit]

Arachidonic acid is a 20-carbon omega-6 polyunsaturated fatty acid. Humans make it from dietary linoleic acid. Under stress, enzymes free it from membranes. Free arachidonic acid feeds prostaglandins and other inflammatory products. It blocks glucose oxidation and injures vessels and brain when liberated in bulk.

Public talk tagged arachidonic acid as the toxic "animal fat." Tissue levels track linoleic acid from seed oils.[26]

Along the way, the highly unsaturated arachidonic acid, which we and other animals make out of the linoleic acid in foods, was coming to be identified with the harmful animal fats. But we just didn't hear much about how the amount of arachidonic acid in the tissues depended on the amount of linoleic acid in the diet.

— Ray Peat[27]

Stress release and practice

[edit]

Stress frees arachidonic acid from tissues. Vessels disorder. When body fat is seed-oil heavy, free fat in blood is mostly linoleic and arachidonic acid.[28] Estrogen activates phospholipase that frees arachidonic acid. Progesterone opposes that path.[26] In brain injury, arachidonic acid and DHA both add secondary damage. Saturated fats sit on the calmer side. See Free fatty acids and PUFA.

Lower dietary linoleic acid. Tissue arachidonate falls over time. Skip fish-oil omega-3 megadoses as a clever fix. Those oils bring their own peroxidation and anti-metabolic load. Anti-stress hormones and steady sugar oxidation cut how much arachidonic acid dumps into blood under ordinary stress.

Essential fatty acid deficiency

[edit]

Essential fatty acids are polyunsaturated fats the body cannot make in needed amounts: classically linoleic (omega-6) and alpha-linolenic (omega-3). The size of the actual requirement is debated.

Effects of high intake

[edit]

The essential fatty acids: Suppress metabolism and promote obesity; are immunosuppressive; cause inflammation and shock; are required for alcoholic liver cirrhosis; sensitize to radiation damage; accelerate formation of aging pigment, cataracts, retinal degeneration; promote free radical damage and excitoxicity; cause cancer and accelerate its growth; are toxic to the heart muscle and promote atherosclerosis; can cause brain edema, diabetes, excessive vascular permeability, precocious puberty, progesterone deficiency.

— Ray Peat[29]

Modern intake of linoleic acid from seed oils far exceeds the small historical requirement. A US food-supply analysis found per-capita soybean oil consumption rose more than 1,000-fold between 1909 and 1999, pushing dietary linoleic acid from about 2.2-2.8% of calories up to 7.2% over the century, while alpha-linolenic acid barely moved (0.35-0.39% up to 0.72%); the modeled net effect was a drop in tissue omega-3 status from roughly 8.3 to 3.8 on the omega-3 index scale.[30] The practical move is cutting industrial PUFA, not chasing fish-oil megadoses; tiny essential amounts are a different scale from gram-quantity seed-oil cooking.

Linoleic acid

[edit]

Linoleic acid is an 18-carbon omega-6 polyunsaturated fatty acid (two double bonds). Main fat in soy, corn, safflower, sunflower, and canola oils. Animals stretch it into longer, more unsaturated products including arachidonic acid.

Industry sold it as an "essential fatty acid" and heart protector. It is oxygen-reactive. Excess drives inflammation, immune suppression, lipid peroxidation, and insulin resistance. The essential story never rested on complete diets once vitamins and minerals were known.[31]

Burr experiment and marketing

[edit]

In 1929 George and Mildred Burr said linoleic acid prevented dandruff, skin disease, slow growth, sterility, and fatal kidney failure in rats on a purified diet.

In 1929 George and Mildred Burr published a paper claiming that unsaturated fats, and specifically linoleic acid, were essential to prevent a particular disease involving dandruff, dermatitis, slowed growth, sterility, and fatal kidney degeneration.

— Ray Peat[32]

In 1929 most B vitamins and essential trace minerals were unknown. Those deficiencies cause the same symptoms. The Burr diet never proved a linoleic need on complete food.[33] Amounts labeled "essential" sit near amounts that raise cancer rates in careful work.[34]

Phase one marketing: linoleic acid protects the heart; saturated fat is the enemy. Phase two: linolenic (omega-3) is better still. Arachidonic acid got tagged as the "bad animal fat." Few heard that tissue arachidonate tracks dietary linoleic acid.[35] U.S. marketing owns the media channel. Harm from PUFA for cancer, diabetes, obesity, aging, clots, arthritis, and immunity stays quiet in that channel.[35] The scale of that marketing win shows in the numbers: per capita soybean oil consumption in the US rose more than 1,000-fold from 1909 to 1999, and linoleic acid's share of dietary energy rose from 2.79% to 7.21% over the same period.[36]

In the body

[edit]

Stored linoleic acid becomes free linoleic and arachidonic acid under stress. Those free fats block glucose oxidation (Randle cycle), feed prostaglandins, and keep stress hormones up. See Free fatty acids and PUFA.

During migraine attacks in 10 patients, plasma free fatty acids rose and platelet serotonin fell; linoleic acid showed the largest rise among the measured fatty acids. Oral linoleic acid (20 g) lowered platelet serotonin in non-migrainous controls, and linoleic acid released platelet serotonin in vitro. Linoleic acid acts as a serotonin-releasing factor and a precursor for vasodilating prostaglandin E1 that can aggravate migraine symptoms.[37]

Seed oils in feed turn eggs, pork, and chicken into linoleic delivery. Vitamin E destruction, yellow-fat disease, and tissue breakdown hit livestock decades ago under polyunsaturated and fish-oil feeds.[38] Experimental "essential fatty acid deficiency" raises resistance to diabetes and shock.[39]

Remove seed oils from cooking and packages. Lower body linoleic stores over time. Steady low intake plus good thyroid and sugar oxidation turns fat over. Skip "essential fatty acid" oil bottles. Prefer ruminant fats and coconut. Grain-fed monogastrics run higher linoleic acid.

Lipid peroxidation

[edit]

Lipid peroxidation is the free-radical chain reaction that destroys polyunsaturated fats in cell membranes and tissues, producing toxic aldehydes (malondialdehyde, 4-HNE, acrolein) and isoprostanes. Established biochemistry; Ray Peat places it at the center of how stored PUFA, Estrogen, Iron, and Endotoxin damage metabolism and accelerate Aging.[40][41][42]

Estrogen and age pigment

[edit]

Estrogen, at least when it is not opposed by a very large concentration of progesterone, creates all of the conditions known to be involved in the aging process. These effects of estrogen include interference with oxidative metabolism, formation of lipofuscin (the age-pigment), retention of iron, production of free radicals and lipid peroxides...

— Ray Peat[43]

Estrogen increases lipid peroxidation, and maintains a chronically high circulating level of free fatty acids, mainly PUFA, activates the phospholipases that release arachidonic acid from cells leading to formation of prostaglandins and isoprostanes...

— Ray Peat[44]

Age pigment is the brown material that forms spots on aging skin, and that accumulates in the lens of the eye forming cataracts, and in blood vessels causing hardening of the arteries, and in the heart and brain and other organs, causing their functions to deteriorate with age. It is made up of oxidized unsaturated oils with iron.

— Ray Peat[45]

Animal experimental data

[edit]

Rats depleted of essential (polyunsaturated) fatty acids resist endotoxin-induced vascular leak (rat study): 30 minutes after endotoxin they showed a smaller hematocrit rise than normal rats (47% vs 54%) and a milder change in splanchnic vascular permeability index (1.2 vs 4.9 x 10⁻³/min). Preferential production of leukotriene C3, which raised blood pressure and hematocrit less than LTC4 in normal rats, is the authors' proposed partial explanation.[46][47] Pigs fed fish oil or linoleic acid had worse LPS lung injury than pigs on palmitic acid.[48] Animal models; human extrapolation requires caution.

In ApoE-knockout mice made vitamin E deficient by deleting the alpha-tocopherol transfer protein gene, aortic F2-isoprostanes roughly doubled and total aortic lesion area grew about 36% (mouse study).[49]

Excess PUFA with iron or other oxidants worsens brain lipid peroxidation; vitamin E, Selenium, and saturated fats limit the damage in animal models he cited.[50] NO and lipid peroxidation drive demyelination in MS discussion Peat referenced.[51]

Diet and buffers

[edit]

Lowering dietary PUFA is the structural fix. Partial buffers include Vitamin E, Aspirin, saturated fats, Thyroid, and Progesterone. Saturated fats slow PUFA degradation and act partly as antioxidants in free-radical chemistry Peat cited on the cholesterol-longevity page.[52] See PUFA, Harm reduction.

...the fact that vitamin E could prevent some of their toxic effects led to the idea that vitamin E was essentially an antioxidant. Unfortunately, the protective effect of vitamin E against the PUFA is only partial.

— Ray Peat[53]

Free fatty acids and lipolysis

[edit]

Lipolysis is the release of fatty acids from stored fat. Hormones and energy status control the rate.

Mechanism

[edit]

Nearly all stored fat sits as triglyceride, three fatty acids on a glycerol backbone. Three enzymes strip it in sequence, ATGL, hormone-sensitive lipase (HSL), and monoacylglycerol lipase, releasing free fatty acids and glycerol into blood. HSL drives most of the rate above baseline. Adrenaline, noradrenaline, glucagon, growth hormone, and cortisol turn it up; insulin is the main brake.[54]

Free fatty acids and insulin

[edit]

Chronic exposure of pancreatic beta cells to elevated plasma free fatty acids impairs glucose-induced insulin secretion. Estrogen (probably via growth hormone) increases free fatty acid release, and adrenaline, elevated in hypothyroidism, increases release from storage; free fatty acids impair mitochondrial energy production.[55] The same elevated free fatty acid state shows up in obesity, type 2 diabetes, and insulin resistance; it is one of the few things that is both raised in obese people and produces insulin resistance when raised experimentally, and reduces it when lowered.[54]

Undernutrition by itself raises whole-body lipolysis. In a tracer study, cachectic patients released more glycerol than normal-weight volunteers whether or not they had cancer.[56] Low-carbohydrate dieting, fasting, hard exercise, poor sleep, and psychological stress all raise free fatty acids through the same hormone set, HSL turned up by adrenaline or cortisol, insulin turned down, so the same pattern that marks starvation shows up any time one of those is chronic.

Constant fasting, low-carbohydrate dieting, and stimulant-driven fat release push free fatty acids up the same way undernutrition does, which feeds insulin resistance and slows metabolism. Steady blood sugar and a lower stress load bring FFA back down.

Persistent pollutant release during fat loss

[edit]

Fat tissue is the body's main storage compartment for lipophilic persistent organic pollutants (POPs), industrial chemicals such as PCBs, dioxins, and organochlorine pesticides that resist breakdown and accumulate over a lifetime. Storing them in fat protects other organs from direct exposure, but the store is not inert. Fat continually releases small amounts of accumulated POPs back into blood, and release rises further during active fat loss, making body fat a standing source of internal exposure to these compounds rather than a permanent sink.[57]

Omega-6

[edit]

Omega-6 fats are polyunsaturated fatty acids with the first double bond at the sixth carbon from the methyl end. Linoleic acid and arachidonic acid dominate seed oils (soy, corn, safflower, sunflower) and much poultry fat.

Mainstream diets since the mid-twentieth century shifted toward linoleic acid when seed oils were marketed as heart protective. That campaign reversed the protective role of saturated fat in Peat's account.[58][59]

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... These PUFA stimulate the stress hormones, ACTH, cortisol, adrenaline, glucagon, and prolactin, which increase lipolysis, producing more fatty acids in a vicious circle.

— Ray Peat[60]

Linoleic acid, arachidonic acid, and inflammation

[edit]

Linoleic acid disturbed cytoskeletal filaments in cell experiments Peat cited, more than colchicine did.[61] Arachidonic acid feeds prostaglandins and isoprostanes when phospholipases are activated by Estrogen and Endotoxin in Peat's leakiness article.[62]

Free omega-6 fatty acids reduce sex-hormone-binding globulin's ability to neutralize estrogen, raising effective estrogen activity in Peat's fats writing.[63] A 12-week randomized controlled trial in 52 healthy adults comparing a low-LA diet (2.5% of energy) to a high-LA diet (10.0% of energy) found high LA intake shifted the body's lipid mediator balance toward a more inflammatory, n-6-dominant profile.[64] Tissues progressively accumulate linoleic acid on typical diets, altering mitochondrial cardiolipin and thyroid hormone response in MS and carrageenan articles, part of Ray Peat's broader fat-storage theme.[65][66]

Animal studies

[edit]

Pigs fed linoleic acid or fish oil had worse lung injury with LPS than pigs on palmitic acid.[67] EFA-deficient rats resisted endotoxin-induced vascular permeability.[68] Oxidized linoleic acid in food accelerates arterial cholesterol deposits in animal work Peat cited on cholesterol-longevity.[69]

Prostaglandins

[edit]

Prostaglandins are lipid signaling molecules derived mainly from arachidonic acid. They mediate Inflammation, pain, fever, and vascular tone. NSAIDs block their synthesis.

Ray Peat treats excess prostaglandin activity as part of stress-hormone and estrogen-driven inflammation. Aspirin inhibits prostaglandins pharmacologically and appears often in his metabolic writing.[70][71]

Leakiness

[edit]

Estrogen increases lipid peroxidation... activates the phospholipases that release arachidonic acid from cells leading to formation of prostaglandins and isoprostanes, and increases the enzymes that form the inflammation-promoting platelet activating factor (PAF)...

— Ray Peat[72]

Endotoxin and carrageenan (in animal models) synergize through prostaglandins and nitric oxide.[73]

Vitamin E and PGE2

[edit]

Gamma-tocopherol and gamma-CEHC inhibit cyclooxygenase activity and lower PGE2 in macrophages and epithelial cells at low micromolar concentrations; alpha-tocopherol does not match that effect.[74] In carrageenan inflammation in rats, gamma-tocopherol, but not alpha-tocopherol, significantly reduced PGE2 at the inflammation site.[75]

Human data: aspirin and prostaglandins

[edit]

A human RCT found aspirin (800 mg/day × 3 days) significantly blunted exercise-induced rises in prolactin, ACTH, cortisol, and growth hormone, implicating prostaglandins in pituitary stress responses.[76]

High-dose nicotinic acid (niacin) causes flushing via prostaglandin-mediated vasodilation, why Peat prefers niacinamide for metabolic support.[77]

Niacinamide, progesterone, sugar, carbon dioxide, and red light protect against both free fatty acids and prostaglandins.

— Ray Peat (via FunctionalPS)[78]

Stress mediators

[edit]

Peat groups prostaglandins with Histamine and Serotonin as defensive mediators that become harmful when chronically elevated alongside Estrogen and PUFA.[79] NSAID use has established risks. See Serotonin, Inflammation, Harm reduction.

Seed oils

[edit]

Primary foods to remove from the pantry and fryer. Marketing as heart-healthy conflicts with the membrane-stability view. Butter and animal fats replace them for cooking.

Heart-health marketing history

[edit]

The strange idea that cholesterol causes atherosclerosis was revived in the 1950s when the vegetable oil industry learned that their polyunsaturated oils lowered serum cholesterol.

— Ray Peat[80]

The American Heart Association (AHA) became a national fundraising group in 1948, and accounts differ on who paid for that start. In a 2023 history review, the source was $1.7 million from Procter & Gamble, the maker of Crisco; the review quotes the AHA's own 1964 history calling that money the "bang of big bucks" that launched the group.[81] The AHA disputes this. By its account the money came from listeners of the radio show Truth or Consequences, which Procter & Gamble sponsored and used to advertise its soaps. A contest on the show ran from January 3 to March 6, 1948, and drew more than 2 million letters with donations totaling $1.58 million.[82] Both accounts agree that the AHA's growth began with this 1948 show and that Procter & Gamble paid for the program.

In 1961 the AHA first advised men to cut saturated fat, and to use polyunsaturated vegetable oils in its place where possible; the advice was later extended to women.[83][81] The same review counts this advice among the most influential nutrition policies ever issued, since the US government adopted it in 1980.[81]

Specialty high-PUFA oils

[edit]

Supplement and "health" oils that are still high-PUFA specialty products, not cooking foundations or metabolic fixes: borage oil and evening primrose oil (GLA-rich omega-6), hemp oil, and similar seed extracts. Same structural problem as pantry seed oils: unstable polyunsaturates. Prefer not expanding them into separate doctrine pages.

Adulteration of avocado and olive oil

[edit]

A processed food labeled "avocado oil" can still contain seed oil. A 2026 UC Davis study tested 54 avocado-oil-labeled processed foods (chips, mayonnaise, salad dressing) bought from California stores and online retailers in 2025-2026.[84] 89% of the products were inconsistent with authentic avocado oil: 93% of chips, 71% of mayonnaise (100% of U.S.-made mayonnaise), and 100% of salad dressings tested.[85] Olive oil products in the same study fared much better, 1 of 20 failed.

Genuine avocado and olive oil are mostly oleic acid (monounsaturated), with linoleic acid around 10% or less. The adulterated samples showed a diluted fatty-acid and sterol profile that indicates cutting with cheap seed oils (soybean, sunflower, canola), plus reduced cis-vaccenic acid, a second independent marker for seed-oil adulteration.[85] A "100% avocado oil" label on a processed food, especially chips, mayonnaise, and dressings, is not proof of an oleic-acid-dominant product.

Cooking oil fumes and lung cancer

[edit]

Heating seed oils to frying temperatures creates an airborne exposure as well as an ingested one. A meta-analysis of thirteen Chinese case-control studies (3,596 lung cancer cases, 6,082 controls) found long-term cooking oil fume exposure associated with roughly double the risk of lung cancer in nonsmoking women, with the highest risk in kitchens lacking a fume extractor.[86] The pooled studies were mostly traditional high-heat wok frying in Chinese households, so the size of the effect may not transfer directly to other cooking styles, but heated linoleic acid breaks down into reactive aldehydes and other oxidized fragments, the same class of compounds implicated in PUFA's other harms.

Thromboxane

[edit]

Thromboxane A2 is an eicosanoid that is mainly activated in times of inflammation. Like the prostaglandins and leukotrienes it is made from, it is derived from the polyunsaturated fats linoleic acid and arachidonic acid, fats the body cannot synthesize on its own, which means diet directly influences how much of it is produced.[87]

Dosing

[edit]

Not used as a medication.

History

[edit]

Etymology

[edit]

The name combines Greek thrombo- ("clot") with "oxane," referring to the oxane (tetrahydropyran) ring in its structure, since the compound promotes blood clotting.

Bengt Samuelsson's group discovered thromboxane A2 in 1975 while studying platelet products of arachidonic acid metabolism; Samuelsson shared the 1982 Nobel Prize in Physiology or Medicine for this and related prostaglandin research.

Thromboxane was named for its role in thrombosis, blood clot formation, first identified in platelets in the 1970s alongside the discovery of the related prostacyclin.

Structure/Chemical properties

[edit]

Thromboxane A2 is a 20-carbon eicosanoid built from arachidonic acid via the cyclooxygenase pathway. It is chemically unstable, breaking down within about 30 seconds into the inactive thromboxane B2, which limits its action to the immediate area where it is produced.

Function/Mechanism of Action

[edit]

Thromboxane A2 is released by activated platelets and promotes further platelet aggregation and vasoconstriction, the core steps of clot formation. Because it is made from the same polyunsaturated fatty acids as the inflammatory prostaglandins, its production rises along with the broader unsaturated-fat-driven inflammatory pathway considered central to degenerative disease.[88] Caffeine stabilizes platelets and reduces thromboxane production, one of several mechanisms behind caffeine's anti-clotting, anti-inflammatory effects.[89] Aspirin works largely by the opposite route, irreversibly blocking the cyclooxygenase enzyme that makes thromboxane, which is why low-dose aspirin lowers thromboxane A2 output. In mice, blocking platelet thromboxane A2 with aspirin reduced cancer metastasis by releasing T cells from a thromboxane-triggered brake on their attack.[90]

Medical uses/Effects

[edit]

Thromboxane A2 itself is not used medically, but it is a target of medical intervention: low-dose aspirin is now recommended for pregnant women to lower thromboxane production, since a functional imbalance between vascular prostacyclin and platelet-derived thromboxane A2 is thought to play a central role in preeclampsia and fetal growth retardation, and reversing that balance toward prostacyclin reduces the risk of both.[91] A randomized, placebo-controlled trial of 1,776 high-risk pregnant women found 150 mg/day aspirin cut preterm preeclampsia incidence to 1.6%, versus 4.3% with placebo.[92]

Side/Adverse effects

[edit]

Excess thromboxane A2 activity, from high polyunsaturated fat intake or from conditions that chronically activate platelets, contributes to abnormal clotting, vasoconstriction, and the vascular dysfunction seen in preeclampsia.

See also

[edit]

References

[edit]
  1. ↑ Ray Peat, "Ask the Herb Doctor: Thyroid and Polyunsaturated Fatty Acids", KMUD, 25:04
  2. ↑ 2.0 2.1 Ramsden CE, Zamora D, Majchrzak-Hong S, et al. "Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)," BMJ. 2016;353:i1246. PMID 27071971.
  3. ↑ Fats, functions & malfunctions
  4. ↑ Ray Peat, Fats, functions & malfunctions
  5. ↑ 5.0 5.1 Nikooyeh B, Zargaraan A, Ebrahimof S, Kalayi A, Zahedirad M, Yazdani H, Rismanchi M, Karami T, Khazraei M, Jafarpour A, Neyestani TR. "Added γ-oryzanol boosted anti-inflammatory effects of canola oil in adult subjects with type 2 diabetes: a randomized controlled clinical trial," Eur J Nutr. 2024;63(2):425-433. doi:10.1007/s00394-023-03275-w. PMID 37971692.
  6. ↑ Ray Peat, "Ask the Herb Doctor: Thyroid and Polyunsaturated Fatty Acids", KMUD, 25:04
  7. ↑ Polyunsaturated Fats (PUFAs), Ray Peat email exchange
  8. ↑ 8.0 8.1 Ray Peat, "It's Rainmaking Time: Life Supporting Substances," interview with Kim Greenhouse, 2011-07-04.
  9. ↑ It's Rainmaking Time: Life Supporting Substances, 2011-07-04.
  10. ↑ Jaganjac M, Zarkovic N. "Lipid Peroxidation Linking Diabetes and Cancer: The Importance of 4-Hydroxynonenal," Antioxidants & Redox Signaling. 2022;37(16-18).
  11. ↑ Amick KA, et al. "Plasma glycocholic acid and linoleic acid identified as potential mediators of mitochondrial bioenergetics in Alzheimer's dementia," Frontiers in Aging Neuroscience. 2022.
  12. ↑ Limani N, Henriksen HB, Minge MM, et al. "Effect of different sources of saturated and polyunsaturated fatty acids on postprandial inflammation: A double-blind randomized crossover trial," Clinical Nutrition ESPEN. 2026 Aug (online May 2026). Effect of different sources of saturated and polyunsaturated fatty acids on postprandial inflammation: A double-blind randomized crossover trial
  13. ↑ Geiser F, Kenagy GJ. "Polyunsaturated lipid diet lengthens torpor and reduces body temperature in a hibernator," American Journal of Physiology. 1987;252(5):R897-901.
  14. ↑ Ayala A, Muñoz MF, Argüelles S. "Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal," Oxid Med Cell Longev. 2014;2014:360438. PMID 24999379.
  15. ↑ Brenna JT. "Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man," Curr Opin Clin Nutr Metab Care. 2002;5(2):127-132. PMID 11844977.
  16. ↑ Gross BW, Gillio M, Rinehart CD, Lynch CA, Rogers FB. "Omega-3 fatty acid supplementation and warfarin: a lethal combination in traumatic brain injury," J Trauma Nurs. 2017;24(1):15-18. PMID 28033135.
  17. ↑ Ray Peat, "Coconut oil," raypeat.com.
  18. ↑ Haw MP, Linnebjerg H, Chavali SR, Forse RA. "The effect of dietary polyunsaturated fatty acids (PUFA) on acute rejection and cardiac allograft blood flow in rats," Transplantation. 1995;60(6):570-577. doi:10.1097/00007890-199509270-00009. PMID 7570953.
  19. ↑ 19.0 19.1 "PUFA are immunosuppressive, fasting and protein restriction (possibly) even more so", Georgi Dinkov (Haidut), haidut.me.
  20. ↑ Mertin J. "Effect of polyunsaturated fatty acids on skin allograft survival and primary and secondary cytotoxic response in mice," Transplantation. 1976;21(1):1-4. PMID 1108321.
  21. ↑ Palmer S, Albergante L, Blackburn CC, Newman TJ. "Thymic involution and rising disease incidence with age," Proc Natl Acad Sci U S A. 2018;115(8):1883-1888. doi:10.1073/pnas.1714478115. PMID 29432166.
  22. ↑ Guimarães AR, Sitnik RH, Curi CM, Curi R. "Polyunsaturated and saturated fatty acids-rich diets and immune tissues. 2. Maximal activities of key enzymes of glutaminolysis, glycolysis, pentose-phosphate-pathway and Krebs cycle in thymus, spleen and mesenteric lymph nodes," Biochem Int. 1990;22(6):1015-1023. PMID 2090103.
  23. ↑ Ray Peat, "weight of the thymus is reduced by PUFA," Unsaturated fatty acids: Nutritionally essential, or toxic?
  24. ↑ Reeve VE, Bosnic M, Boehm-Wilcox C. "Dependence of photocarcinogenesis and photoimmunosuppression in the hairless mouse on dietary polyunsaturated fat," Cancer Lett. 1996;108(2):175-182. doi:10.1016/S0304-3835(96)04460-6. PMID 8973605.
  25. ↑ Shaikh SR, Edidin M. "Polyunsaturated fatty acids, membrane organization, T cells, and antigen presentation," Am J Clin Nutr. 2006;84(6):1277-89. doi:10.1093/ajcn/84.6.1277. PMID 17158407.
  26. ↑ 26.0 26.1 Ray Peat, "Fats and degeneration," raypeat.com. Also Library:Fats and degeneration.
  27. ↑ Fats and degeneration, Ray Peat newsletter
  28. ↑ Ray Peat, "Fats, functions & malfunctions," raypeat.com.
  29. ↑ Membranes, plasma membranes, and surfaces, Ray Peat newsletter
  30. ↑ Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. "Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century,"Am J Clin Nutr. 2011;93(5):950-62. doi:10.3945/ajcn.110.006643.
  31. ↑ Ray Peat, "Unsaturated fatty acids: Nutritionally essential, or toxic?," raypeat.com. Also Library:Unsaturated fatty acids: Nutritionally essential, or toxic?.
  32. ↑ Unsaturated fatty acids: Nutritionally essential, or toxic?, Ray Peat newsletter
  33. ↑ Ray Peat, "Unsaturated fatty acids," raypeat.com.
  34. ↑ Ray Peat, "Unsaturated fatty acids," raypeat.com.
  35. ↑ 35.0 35.1 Ray Peat, "Fats and degeneration," raypeat.com. Also Library:Fats and degeneration.
  36. ↑ Blasbalg TL, Hibbeln JR, Ramsden CE, et al. "Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century," Am J Clin Nutr. 2011;93(5):950-962.
  37. ↑ Anthony M. "Individual free fatty acids and migraine," Clin Exp Neurol. 1978;15:190-196. PMID 756014.
  38. ↑ Ray Peat, "Suitable fats, unsuitable fats," raypeat.com.
  39. ↑ Ray Peat, Ray Peat email Q&A - Randle Cycle, raypeatemails.com.
  40. ↑ "Not the "female hormone," but the shock hormone," Ray Peat article
  41. ↑ "Leakiness, aging, and cancer," Ray Peat article
  42. ↑ "Iron's Dangers," Ray Peat article
  43. ↑ "Not the "female hormone," but the shock hormone," Ray Peat article
  44. ↑ "Leakiness, aging, and cancer," Ray Peat article
  45. ↑ "Iron's Dangers," Ray Peat article
  46. ↑ Li EJ et al., "Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability," Circulatory shock, 1990. Hematocrit P<0.01; permeability index P<0.05.
  47. ↑ Ray Peat, "Fats, functions & malfunctions," raypeat.com (lists Li et al. 1990 among its references).
  48. ↑ Wolfe RR et al., "Dietary fat composition alters pulmonary function in pigs," Nutrition (Burbank, Los Angeles County, Calif.), 2002
  49. ↑ Terasawa Y, Ladha Z, Leonard SW, et al. "Increased atherosclerosis in hyperlipidemic mice deficient in alpha-tocopherol transfer protein and vitamin E," Proc Natl Acad Sci U S A. 2000;97(25):13830-13834. doi:10.1073/pnas.240462697. PMID 11095717.
  50. ↑ "BSE - mad cow - scrapie, etc.: Stimulated amyloid degeneration and the toxic fats," Ray Peat article
  51. ↑ "Multiple sclerosis, protein, fats, and progesterone," Ray Peat article
  52. ↑ "Cholesterol, longevity, intelligence, and health.," Ray Peat article
  53. ↑ The Great Fish Oil Experiment, raypeat.com
  54. ↑ 54.0 54.1 Althaher AR. "An overview of hormone-sensitive lipase (HSL)," ScientificWorldJournal. 2022;2022:2314658. PMID 36530555.
  55. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  56. ↑ Klein S et al. 1990, "Whole-body lipolysis" (Klein S, Wolfe RR, Whole-body lipolysis and triglyceride-fatty acid cycling in cachectic patients with esophageal cancer), J Clin Invest. 1990;86(5):1403-1408. PMID 2243120. Glycerol release was 48% higher in cachectic patients, with no difference between the cancer and non-cancer groups.
  57. ↑ La Merrill M, Emond C, Kim MJ, et al. "Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants," Environ Health Perspect. 2013;121(2):162-169. PMID 23221922.
  58. ↑ "Fats, functions and malfunctions.," Ray Peat article
  59. ↑ "Cholesterol, longevity, intelligence, and health.," Ray Peat article
  60. ↑ "Fats, functions and malfunctions.," Ray Peat article
  61. ↑ "Fats, functions and malfunctions.," Ray Peat article
  62. ↑ "Leakiness, aging, and cancer," Ray Peat article
  63. ↑ "Fats, functions and malfunctions.," Ray Peat article
  64. ↑ Johnson GH, Chilton FH, et al. "Effect of Dietary Linoleic Acid Intake on Eicosapentaenoic Acid Status and Lipoxygenase-Mediated Oxylipin Biosynthesis in Healthy Adults: A Randomized Controlled Trial," Nutrients. 2026;18(11):1814. doi:10.3390/nu18111814.
  65. ↑ "Multiple sclerosis, protein, fats, and progesterone," Ray Peat article
  66. ↑ "Food-junk and some mystery ailments: Fatigue, Alzheimer's, Colitis, Immunodeficiency.," Ray Peat article
  67. ↑ Wolfe RR et al., "Dietary fat composition alters pulmonary function in pigs," Nutrition (Burbank, Los Angeles County, Calif.), 2002
  68. ↑ Li EJ et al., "Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability," Circulatory shock, 1990. Hematocrit P<0.01; permeability index P<0.05.
  69. ↑ "Cholesterol, longevity, intelligence, and health.," Ray Peat article
  70. ↑ "Leakiness, aging, and cancer," Ray Peat article
  71. ↑ "Ray Peat, PhD on Endotoxin"
  72. ↑ "Leakiness, aging, and cancer," Ray Peat article
  73. ↑ "Ray Peat, PhD on Endotoxin"
  74. ↑ Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN. "gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells," Proc Natl Acad Sci U S A. 2000;97(21):11494-11499. PMID 11005841.
  75. ↑ Jiang Q, Ames BN. "Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats," FASEB J. 2003;17(8):816-822. PMID 12724340.
  76. ↑ Di Luigi L et al., "Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans," Medicine and science in sports and exercise, 2001
  77. ↑ "Ray Peat, PhD Quotes on Therapeutic Effects of Niacinamide"
  78. ↑ "Ray Peat, PhD Quotes on Therapeutic Effects of Niacinamide"
  79. ↑ "Leakiness, aging, and cancer," Ray Peat article
  80. ↑ Cholesterol, longevity, intelligence, and health, Ray Peat newsletter
  81. ↑ 81.0 81.1 81.2 Teicholz N. "A short history of saturated fat: the making and unmaking of a scientific consensus." Curr Opin Endocrinol Diabetes Obes. 2023;30(1):65-71. doi:10.1097/MED.0000000000000791. PMID 36477384. Narrative history review: "in 1948, it had received $1.7 million, or about $20 million in today's dollars, from Procter & Gamble (P&G), the makers of Crisco oil", citing the AHA's official history (Marvin HM, 1924-1964: The 40 Year War on Heart Disease, 1964).
  82. ↑ American Heart Association, "No, Procter & Gamble Didn't Give $20M to the American Heart Association", heart.org: "Procter & Gamble did not make the $1.5 million donation... The company sponsored the radio show"; "more than 2 million letters with donations, totaling $1.58 million at the time".
  83. ↑ Central Committee for Medical and Community Program of the American Heart Association. "Dietary fat and its relation to heart attacks and strokes. Report by the Central Committee for Medical and Community Program of the American Heart Association." JAMA. 1961;175:389-391. PMID 14447694. Also Circulation 1961;23:133-136. Content as summarized in the Teicholz 2023 review; the original text was not checked.
  84. ↑ Wang, S. et al. "Authenticity of avocado and olive oils used as ingredients in commercially processed foods." Applied Food Research (2026). https://doi.org/10.1016/j.afres.2026.102389
  85. ↑ 85.0 85.1 "That avocado oil chip you're eating may not be made with pure avocado oil." UC Davis, July 15, 2026. https://www.ucdavis.edu/food/news/avocado-oil-chip-youre-eating-may-not-be-made-pure-avocado-oil
  86. ↑ Xue Y, Jiang Y, Jin S, Li Y. "Association between cooking oil fume exposure and lung cancer among Chinese nonsmoking women: a meta-analysis," Onco Targets Ther. 2016;9:2987-92. PMID 27284248.
  87. ↑ Ray Peat, "Regeneration and Degeneration: Types of Inflammation Change with Aging," raypeat.com.
  88. ↑ Ray Peat, "Regeneration and Degeneration: Types of Inflammation Change with Aging," raypeat.com.
  89. ↑ Ray Peat, "Caffeine: A Vitamin-Like Nutrient, or Adaptogen," raypeat.com.
  90. ↑ Yang J, Yamashita-Kanemaru Y, Morris BI, et al. "Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity," Nature. 2025;640(8060):1052-1061. doi:10.1038/s41586-025-08626-7. PMID 40044852. Animal study.
  91. ↑ Haidut, "Aspirin Now Officially Recommended for Preeclampsia Prevention," Ray Peat Forum.
  92. ↑ Rolnik DL, et al. "Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia," N Engl J Med. 2017;377(7):613-622. doi:10.1056/NEJMoa1704559.