Aspirin (acetylsalicylic acid) is an old anti-inflammatory drug with a wider metabolic role than pain relief. It breaks down into acetic acid and salicylic acid. Salicylic acid appears in many fruits and protects tissues that competing anti-inflammatories injure.[1]

Aspirin
Chemical structure of aspirin
Chemical structure of aspirin
Formula C9H8O4
Class Salicylate (NSAID)
Administration Oral; topical (skin, off-label)
Solubility Slightly soluble in water; freely soluble in ethanol
Legal status OTC at low doses in most countries
Brand names Bayer, Ecotrin, Bufferin, Aspegic; sold mostly as plain generic aspirin
Bioavailability Rapidly and almost completely absorbed orally, then hydrolyzed to salicylic acid
Recommended dose A little regularly, with vitamin K; about 500 mg at night in Peat's own use
Upper limit 1000-1500 mg/day (Peat's usual ceiling); several grams/day used short-term in some clinical contexts, with kidney/thyroid monitoring
LD50 200 mg/kg (rat, oral)
Ray's verdict Generally helps
One of the few drugs Ray Peat considered safe for regular use alongside thyroid and progesterone, when taken with food and adequate vitamin K; best used alongside fixing the underlying stress/PUFA problem.

Taken with food and enough vitamin K, it lowers inflammation and stress chemistry and supports energy production.

Dosing

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Dose tracks the problem and the person rather than a single "heart health" tablet. Higher daily totals appear in arthritis and cancer contexts in the primary correspondence, sometimes several grams a day, always with attention to kidney function, age, and thyroid status.[2]

I have known a few people who took 4 to 6 grams per day for several years for arthritis or cancer, but I usually think of 1000 to 1500 mg per day as a maximum safe dose, but it depends on things like age and thyroid function; with low kidney function, even that much could accumulate to a toxic level.

— Ray Peat[3]

I think a little aspirin, regularly if not daily, is good prevention, if you are sure to get enough vitamin K, to prevent excess bleeding. The amount depends on how you react to it, and can change as your metabolism adjusts. Taking some at bedtime can be very helpful for sleeping; sometimes I take about 500 mg at night, but other times just a little.

— Ray Peat[4]

I think the amount is too small for most people. And if you take vitamin K, you don't have to worry about the bleeding thing from chronic aspirin use.

— Ray Peat, on baby aspirin[5]

Chewed aspirin at the first sign of a heart attack is mainstream emergency advice and fits the same anti-clotting action. In 2022 the US Preventive Services Task Force advised against starting low-dose aspirin for heart prevention at 60 or older and left it as an individual choice at 40 to 59 for people with higher heart risk.[6]

Children with viral illness and Reye risk remain a standard caution. Late pregnancy needs medical oversight. Allergy to salicylates is a hard stop.

Structure / Chemical properties

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Aspirin is the acetylated form of salicylic acid. The acetyl group itself does real work: in aspirin, it is the acetyl group that, by a free-radical action, blocks the enzyme involved in prostaglandin synthesis, distinct from salicylic acid's own antioxidant action.[7]

Salicylic acid itself, without the acetyl group, was already widely known in the 19th century for useful antiinflammatory action. Cyclooxygenase block is only one textbook account of aspirin; other actions include antioxidant protection against lipid peroxidation and stimulation of mitochondrial respiration.[8]

Function / Mechanism of action

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Aspirin, like T3, increases mitochondrial uncoupling.[9] At 6 mg/ml, aspirin cut quorum-sensing signals, motility, biofilm, and toxin genes in Pseudomonas aeruginosa without killing the bacteria.[10]

Aspirin blocks cyclooxygenase enzymes that make prostaglandins from polyunsaturated fatty acids. Prostaglandins carry much of the inflammatory and stress signal. When they fall, the body raises less cortisol and prolactin under the same physical load.[11]

If a newly discovered substance had aspirin's anti-infective, anti-cancer, anti-stress, antioxidant, and anti-inflammatory actions, it would be the most researched substance in history.

— Ray Peat[12]

That same shift favors glucose oxidation in mitochondria over free-fat burning. Lactate falls. Potential for useful CO2 rises. In the same framework, PUFA-rich membranes and free fatty acids push the opposite way: less respiration, more inflammatory eicosanoids. Aspirin sits with thyroid, progesterone, and sugar oxidation as anti-stress support rather than as a pure "pain pill."[1][8]

Aspirin is an antioxidant that protects against lipid peroxidation, but it also stimulates mitochondrial respiration.

— Ray Peat[13]

Taking aspirin without an infection present typically raises temperature and pulse rate rather than lowering them, because it activates the respiratory system the same way thyroid does, and even sensitizes cells to thyroid's own action.[14]

Medical uses / Effects

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Cancer and inflammation

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Prostaglandins are so involved in cancers of all sorts that aspirin and other prostaglandin inhibitors belong in basic cancer therapy.[15] A 2025 meta-analysis of observational studies and trials linked aspirin use with lower cancer incidence and mortality, most clearly for colorectal and liver cancers.[16]

Anti-inflammatory drugs such as aspirin, or prostaglandin inhibitors such as indomethacin, have a rational place in cancer therapy; aspirin also has some antihistamine activity and estrogen tends to concentrate in inflamed tissue.[17] In one account, a woman with painful inflammatory breast cancer that doctors would not treat had her redness, swelling, and pain subside within two or three days of taking aspirin for the pain, an anti-inflammatory effect large enough to change what care she could tolerate.[18] Aspirin, along with acetazolamide or anything that raises the body's CO2, can slow the growth of leukemia and lymphoma.[18]

Older medical writers, working before opioid receptor pharmacology existed, still reached for aspirin over morphine as cancer pain relief.

Opiates are still commonly used for pain relief in cancer patients, despite the evidence that has accumulated for several decades indicating that they promote inflammation and cancer growth, while suppressing immunity and causing tissue catabolism, exacerbating the wasting that commonly occurs with cancer. Their use, rather than alternatives such as procaine, aspirin, and progesterone, is nothing but a medical fetish.

— Ray Peat[19]

A 2015 review in the journal Cancer supports the mechanism: activation of the mu-opioid receptor by opioids such as morphine promotes tumor proliferation, invasion, and angiogenesis across several cancer types in preclinical and clinical studies, while blocking the receptor slows tumor growth in animal models.[20] From the receptor-blocking side, naloxone and naltrexone, which block the actions of endorphins and morphine, have been used to inhibit growth of several cancers including breast and prostate cancer.[21]

Aspirin combined with high-dose injected vitamin C has anti-tumor effects in rodents. In rats with chemically induced liver cancer, aspirin by mouth plus vitamin C injected into the abdomen for 90 days brought liver tumor markers, inflammation markers, and liver tissue closer to normal than a standard chemotherapy drug did. In cell culture the combination was about 3.7 times more toxic to liver cancer cells than to normal lung cells, while the chemotherapy drug harmed both alike.[22] In mice with Ehrlich solid tumors, ten days of the same combination shrank tumor volume by about 46%. Each drug alone also shrank tumors, but those smaller drops were not statistically significant.[23]

Sunburn and radiation protection

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Aspirin has a similar protective effect to coconut oil against the harmful effects that develop in skin after sunlight overexposure; it reduces the iron content of blood serum and inhibits the formation of toxic prostaglandins from fatty acids, and both vitamin E and aspirin reduce sunburn damage even when applied after exposure.[24][25][26] A trial in pre-eclamptic pregnancy found aspirin reduced both lipid peroxides and thromboxane in the placenta, an antioxidant and anti-eicosanoid action.[27]

Multiple sclerosis (animal model)

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In mice bred to model multiple sclerosis, low-dose aspirin (1-3 mg/kg daily, comparable to a human "baby aspirin") halved clinical disease scores, reducing limb and tail weakness, paralysis, and death, by reversing the loss of regulatory T-cells that normally happens during the disease.[28] The finding comes from a mouse model, worth tracking as a mechanistic lead until it's tested in people with MS.

Remyelination after white matter injury

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In rats with chronic bilateral carotid occlusion (a model of vascular white matter lesion), aspirin promoted oligodendrocyte precursor cell proliferation and differentiation into mature, myelinating oligodendrocytes, and improved performance on a spatial-memory task four weeks later.[29] The rats had vascular white matter injury rather than multiple sclerosis, and no human trial has followed up, but it fits the general pattern of aspirin supporting nerve-sheath repair.

Autism spectrum disorder (animal model)

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In rats exposed to valproic acid before birth, a standard chemical model of autism, 21 days of oral aspirin (50 mg/kg/day) starting after weaning brought social-interaction scores up to the level of unexposed control rats and restored novel-object recognition memory, while also lowering total oxidant status and the oxidative stress index compared with untreated valproic-acid rats, though glutathione levels stayed abnormal.[30] Scaled to a person by the standard FDA body-surface-area conversion (rat dose × 0.162), the 50 mg/kg rat dose works out to roughly 600 mg for a 70 kg adult, within aspirin's ordinary dose range rather than a specialized megadose. The study used a prenatal chemical rat model; nothing here has been tested in autistic people.

Aromatase and estrogen

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Aspirin lowers estrogen production at the source rather than just blunting its downstream effects. In human breast cancer cells, aspirin and other cyclooxygenase inhibitors suppress both the expression and the activity of aromatase, the enzyme that converts androgens into estrogen.[31]

In human ovarian granulosa cells, 1 µM aspirin cut estradiol production by roughly half over 12–24 hours. It irreversibly and covalently inhibits adenylate cyclase (binding Lys350 and Lys426 on the recombinant enzyme, matching Lys938 and Lys1014 on full-length AC2), lowering cAMP and then aromatase expression through AKT/mTOR and CREB. In a mouse PCOS model the same pathway lowered androgen and insulin and reduced cystic follicles.[32]

Aspirin sits alongside coffee and flavonoids as a practical aromatase inhibitor on Fertility.

Diabetes prevention and glucose metabolism

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In a five-year longitudinal cohort of elderly people with prediabetes, daily low-dose aspirin associated with a 47% reduction in the risk of developing type 2 diabetes.[33] Anything that reduces serotonin's interference with sugar metabolism should improve glucose handling.

A mechanistic trial in nine people with type 2 diabetes tested this directly: two weeks of high-dose aspirin (about 7 g/day) lowered fasting glucose by roughly 25%, cut triglycerides by about 50%, and improved insulin-stimulated glucose uptake by about 20%, tracing the effect to aspirin's inhibition of the inflammatory kinase IKKbeta.[34] That dose is well above aspirin's ordinary range and was used short-term under clinical supervision, not as a standing recommendation.

Fatty liver disease (NAFLD)

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A nine-year prospective cohort of 361 adults with biopsy-confirmed nonalcoholic fatty liver disease found daily aspirin users were roughly 30% less likely to have active NASH and about half as likely to have fibrosis at study entry than non-regular users, and among those who started with early-stage fibrosis, daily aspirin use was associated with a lower, duration-dependent risk of progressing to advanced fibrosis over follow-up; non-aspirin NSAIDs showed no such association.[35]

Metastasis and cancer prevention trials

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In mice, aspirin cut the rate of lung and liver metastasis by blocking platelet thromboxane A2, a signal that switches off the T cells that would otherwise kill cancer cells newly arrived in an organ.[36] A 2026 systematic review of cell, animal, and small clinical studies found aspirin limits spread through lower thromboxane, less of the cell-state switch that lets tumor cells detach and migrate, and restored T-cell attack, while excluding trials that reported only survival or incidence.[37] In a small uncontrolled phase II trial, aspirin lowered circulating tumor cell counts in metastatic colorectal cancer and left them unchanged in metastatic breast cancer.[38] A randomized phase II trial of aspirin plus a second platelet-blocking drug in metastatic breast cancer found no change in circulating tumor cells compared with no treatment.[39] Metastasis is often credited with 90% of cancer deaths; Norwegian registry data put the share at about two thirds for solid tumors.[40]

A pooled analysis of randomized cardiovascular trials found daily aspirin lowered cancer deaths, and in the low-dose primary-prevention trials it lowered new cancers from about three years onward.[41] Taken daily for several years, aspirin lowered deaths from several common cancers in pooled data from the old heart-prevention trials, and the benefit grew the longer people took it (randomized trials, pooled).[42] In the 20-year follow-up of the same kind of trials, at least 75 mg a day for several years cut both new cases of and deaths from colorectal cancer.[43] A large randomized trial in healthy adults aged 70 and over found 100 mg/day aspirin did not lower cancer incidence, and it raised the risk of cancers found already spread or at stage 4.[44] Over about nine years of follow-up in the same trial, aspirin still showed no effect on cancer incidence, including colorectal cancer, and was associated with higher cancer mortality.[45] In a randomized trial in high-risk early breast cancer, daily aspirin did not reduce recurrence and the trial stopped early for futility.[46]

Pensions and lifespan

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After these trials, an insurance-risk modeling firm worked out what wider aspirin use would cost pension funds: if pensioners took up daily aspirin quickly, a typical 65-year-old man could gain about a year of life expectancy, and UK male pension liabilities could rise 0.7% within 20 years, about the same as everyone quitting smoking within a generation. Across North American and European pension liabilities, the firm put the cost at more than $100 billion.[47]

I think a little aspirin, regularly if not daily, is good prevention, if you are sure to get enough vitamin K, to prevent excess bleeding.

— Ray Peat[48]

Colorectal cancer recurrence

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In the ALASCCA trial, a randomized placebo-controlled study across Sweden, Denmark, Finland, and Norway, patients with stage I-III colorectal cancer carrying PI3K-pathway gene mutations (PIK3CA, PIK3R1, or PTEN) who took 160 mg/day aspirin after surgery for 3 years had roughly half the cancer recurrence rate of the placebo group in the subgroup with the strongest-acting mutations (7.7% vs. 14.1% at 3 years).[49] A separate randomized pilot trial found 325 mg/day aspirin for 6 weeks shifted gut microbial composition in healthy adults toward taxa associated with lower colorectal-cancer risk, one candidate mechanism (alongside direct anti-inflammatory action) for aspirin's protective association with colorectal cancer.[50]

Colorectal adenomas and tumor COX-2

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In patients whose colorectal cancer had been removed, 325 mg/day aspirin lowered the number who grew new adenomas, the polyps most colorectal cancers start from.[51] Pooling the four adenoma trials gave a smaller drop in any adenoma and a larger one in advanced adenomas.[52]

In carriers of Lynch syndrome, the inherited form of colorectal cancer, 600 mg/day aspirin for about two years did not change adenoma rates during treatment, but fewer colorectal cancers appeared in the aspirin group over the following years.[53]

Two large trials that gave aspirin only every other day found no effect on colorectal cancer over about ten years.[54][55] In two large cohorts, regular use was linked to fewer colorectal cancers whose tumors made a lot of COX-2, the inducible prostaglandin enzyme, and not to fewer of those that made little.[56]

Brain aneurysm growth

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In 480 patients with unruptured brain aneurysms, daily aspirin users were about 80% less likely to have an aneurysm grow over follow-up.[57]

Vascular erectile dysfunction

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A randomized prospective study assigned 336 men with vascular erectile dysfunction to aspirin (100 mg/day), tadalafil (5 mg/day), both drugs, or placebo. Mean erectile-function scores improved by 7.2 points with aspirin, 7.3 with tadalafil, 7.5 with the combination, and 2.0 with placebo. The similar group averages don't establish formal equivalence between aspirin and tadalafil, but they provide preliminary clinical evidence for aspirin in vascular erectile dysfunction.[58]

Prostate and macular degeneration

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Aspirin and thyroid support together can reduce ordinary inflammation of an enlarged prostate.[59] For dry macular degeneration, aspirin is generally protective against the leaky, deteriorating capillaries involved, alongside good nutrition and other retinal-metabolism support.[59]

Bone

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Aspirin improves calcium retention in bones, and it isn't as profitable as an osteoporosis drug as the bisphosphonate and such things. But it's very safe as long as you take vitamin K along with it.

— Ray Peat[60]

And both aspirin and vitamin K are known practical bone-building supplements.

— Ray Peat[61]

Side / Adverse effects

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Stomach and intestines

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Aspirin alone does not meaningfully increase small-intestinal permeability. In a controlled study, aspirin given by itself had no significant effect on intestinal permeability or gut morphology; injury only appeared when aspirin was combined with a mitochondrial uncoupler (DNP), or with indomethacin alone.[62] Tablet aspirin on an empty stomach still irritates many people in practice; Ray Peat attributed this to any concentrated crystalline substance (vitamins, salt, sugar) being able to injure stomach membranes on its own, a general irritant effect rather than something specific to aspirin, and recommended always taking it with food or milk.[2][63] Dissolved aspirin with food is a gentler option: heat a little water, dissolve the tablet with a pinch of baking soda, let it fizz, discard sediment, and take the clear liquid with a meal or juice.[2]

I don't know anyone who has a stomach reaction when they dissolve the aspirin in hot water, and then take it with food.

— Ray Peat[64]

Bleeding risk

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Aspirin increases the need for vitamin K. Prolonged or multi-gram use without vitamin K raises bleeding risk; food first, with K1 or K2 alongside regular use, is the practical pair.[2] Compared to the newer direct oral anticoagulants (DOACs) often prescribed instead of it, aspirin holds up well: a 2024 meta-analysis found no significant difference in intracranial hemorrhage risk between DOACs and aspirin, but a significantly higher risk of major hemorrhage overall with DOACs.[65]

Reye's syndrome

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Much of the fear around pediatric aspirin use tracks Tylenol marketing in the 1970s and reports of Reye's syndrome; at least one Australian study reported higher rates of so-called Reye's syndrome in children given Tylenol than in those given aspirin.[63] Standard toxicology guidance still treats aspirin as contraindicated in children with viral illness because of the Reye's-syndrome association, and that caution stands regardless of the marketing history. Aspirin largely left children's medicine after studies in the early 1980s tied it to Reye's syndrome, a rare liver and brain illness after flu or chickenpox.

In Australia, a study of Reye syndrome cases found that six times as many of them had been using acetaminophen as had used aspirin.

— Ray Peat[66]

Reported cases fell from a peak of 555 children in 1980 to no more than 36 a year from 1987 on (US surveillance).[67][68]

Acetaminophen (Tylenol) interaction

[edit]

Acetaminophen (Tylenol) relieves pain and fever but has weak anti-inflammatory action. Its central mechanism remains unsettled; proposed mechanisms include central COX and cannabinoid-system activity.

Acetaminophen associates with kidney failure and, in pregnancy or prematurity, with liver failure and autism risk; aspirin acts as an antidote to acetaminophen toxicity.[63]

Aspirin's breakdown product, salicylic acid, has protective effects on the stomach and other tissues that acetaminophen does not share because it is not a salicylate.[69] In cell studies of dopaminergic neurons exposed to glutamate excitotoxicity, acetaminophen was one of three drugs, with aspirin and ibuprofen, that preserved dopamine uptake.[69]

Exercise adaptations

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In young men, the maximum over-the-counter dose of acetaminophen, 4,000 mg per day, and ibuprofen, 1,200 mg per day, both prevented the normal 24-hour rise in muscle protein synthesis after high-intensity eccentric resistance training. Protein synthesis rose 76% in the placebo group and did not rise significantly in either drug group. Neither drug affected whole-body protein breakdown, creatine kinase, or perceived soreness.[70]

In a separate eight-week resistance-training study, low-dose aspirin, 75 mg per day, impaired muscle-volume and strength gains less than high-dose ibuprofen, 1,200 mg per day. On this comparison, the effect may vary with anti-inflammatory dose and potency instead of applying equally to every COX-inhibiting drug.[71]

Prenatal exposure and male development (animal studies)

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Male mammal genitals and the nervous system are masculinized during fetal development by a cascade involving prostaglandins and androgens. Acetaminophen's COX-inhibiting action can interfere with that cascade.[72] In mice, exposure in utero reduced neuron counts in the sexually dimorphic nucleus of the hypothalamus. Exposed males later showed altered urinary marking, less aggressive territorial behavior, and fewer intromissions and ejaculations during mating.[72] The study was conducted in mice and does not establish the same behavioral effect in humans. Separate human and rat work has linked prenatal acetaminophen exposure to anti-androgenic effects on the fetal testis and to cryptorchidism risk.[73] Continuous early-life paracetamol exposure, 5 or 15 mg/kg during pregnancy and the first two postpartum months, lowered testicular testosterone in rat offspring and changed expression of steroid-making genes.[74]

Prenatal exposure and female reproductive development

[edit]

In the COPANA cohort, fetal paracetamol exposure before 17 weeks was associated with smaller ovarian and uterine volumes in infant girls. Mid-to-late fetal exposure was associated with fewer ovarian follicles, and exclusive early exposure was associated with lower AMH. Maternal first-trimester urinary paracetamol was inversely associated with ovarian and uterine volume and breast-tissue diameter. An independent cohort linked fetal exposure to smaller uterine volume at puberty and smaller ovarian volume in adolescence.[75] Animal work also finds impaired primordial follicle formation and later fertility in female offspring; the human associations remain observational.[75]

NAPQI and glutathione

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A fraction of acetaminophen is oxidized to NAPQI. The liver normally conjugates NAPQI to glutathione; when that pool is depleted, NAPQI binds cell proteins and causes liver injury. Classic rodent work found that glutathione loss tracks acetaminophen liver injury and that sustaining GSH protects against necrosis.[76] Therapeutic doses normally undergo safe conjugation, while high or repeated exposure increases glutathione demand and can deplete the available pool. The same chemistry explains why NAC is used as the antidote and why low baseline GSH leaves less margin against repeated or high exposure.[77] See Glutathione and Autism.

Overdose risk

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Acetaminophen has a narrow margin between an effective dose and a liver-damaging dose. It is a leading cause of acute liver failure in overdose, whether accidental or intentional, a risk profile that aspirin does not share at comparable use.

Brands and sources

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Plain, uncoated aspirin without extra additives (talc, coatings) is preferred; some tablets include fillers that Peat considered unnecessary.[63] White willow bark, aspirin's original plant source, is sold as a lower-dose, less concentrated alternative.[63] Aspirin is genericized and inexpensive; branded versions (Bayer, Ecotrin, Bufferin) mostly differ in coating or buffering rather than the core drug.

What it is not

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Aspirin can't stand in for thyroid, food, sleep, or light, and it won't cancel out a high seed-oil diet by itself. It's one lever that lowers prostaglandin and free-fat stress while mitochondrial glucose use recovers.

Bereavement and cardiovascular risk

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In a randomized controlled trial of 85 recently bereaved people (spouses or parents of the deceased), a once-daily low-dose combination of the beta-blocker metoprolol and aspirin (100 mg) reduced spikes in blood pressure and heart rate and improved clotting-risk markers during acute grief, without worsening the psychological experience of bereavement.[78]

Other NSAIDs

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Ibuprofen is a propionic-acid NSAID, among the most commonly used OTC pain relievers and fever reducers worldwide, working like aspirin by blocking cyclooxygenase enzymes to reduce prostaglandin production.

Comparison to aspirin

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In cell studies of dopaminergic neurons exposed to glutamate excitotoxicity, ibuprofen was one of three drugs (with aspirin and acetaminophen) found to attenuate the drop in dopamine uptake, indicating some shared neuroprotective effect across the class.[79]

All three NSAIDs significantly attenuated the decrease in dopamine uptake caused by glutamate, indicating preservation of neuronal integrity.

— Ray Peat[80]

Unlike aspirin, ibuprofen does not release salicylic acid on breakdown, so it lacks the stomach- and tissue-protective effect of that specific metabolite (see NSAIDs).[81] Regular ibuprofen use also carries standard NSAID risks of GI irritation and, at high or chronic doses, kidney stress.

Blunting exercise adaptations

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The maximal OTC dose (1,200 mg/day) prevented the normal 24-hour rise in muscle protein synthesis after high-intensity eccentric resistance training in young men, matching acetaminophen's effect at its own maximal dose; the placebo group's synthesis rate rose 76%, ibuprofen and acetaminophen showed no significant increase.[70] An 8-week trial comparing high-dose ibuprofen (1,200 mg/day) against low-dose aspirin (75 mg/day) during resistance training found ibuprofen produced less muscle-volume and strength gain than the aspirin group, suggesting ibuprofen's blunting effect is stronger than a low-dose salicylate's.[71] Occasional or low-dose use around training looks safer than routine maximal-dose post-workout use for anyone training for muscle gain.

NSAIDs (non-steroidal anti-inflammatory drugs) block cyclooxygenase enzymes to reduce prostaglandin production, lowering inflammation, pain, and fever. Aspirin, ibuprofen, naproxen, indomethacin, and piroxicam are all NSAIDs, differing mainly in potency, duration, and side-effect profile.

Aspirin as the outlier

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In Ray Peat's framework, aspirin is pharmacologically distinct from the rest of this class, not just another NSAID. Its breakdown product, salicylic acid, is itself protective to the stomach and other tissues, an effect the non-salicylate NSAIDs (ibuprofen, indomethacin, piroxicam, etc.) don't share:[82]

Salicylic acid is protective to the stomach and intestine, and other organs. When aspirin was compared with the other common anti-inflammatory drugs, it was found that the salicylic acid it releases protects against the damage done by another drug.

— Ray Peat[83]

In a tumor-regression comparison Peat cited, aspirin performed comparably to indomethacin and piroxicam at far lower relative dosing (30% regression at 1 mg/day for aspirin versus 45% at 90 mg/day for indomethacin), suggesting the class shares real anti-inflammatory efficacy even where mechanisms diverge in detail.[82]

Anabolic effect in the elderly

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In elderly subjects, NSAIDs paired with resistance training have produced greater muscle growth and strength gains than training alone in several studies; among adults around 85, NSAID users had a substantially lower rate of sarcopenia.[84] The effect appears age- and context-dependent rather than universal. Aspirin's salicylate-mediated benefits are described separately.

Practice

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Non-aspirin NSAIDs carry the same GI-irritation and kidney-stress risks associated with the class generally, without aspirin's offsetting salicylate effect, and are not interchangeable with aspirin in Peat's framework even though they act on the same enzyme family.

See also

[edit]

References

[edit]
  1. ↑ 1.0 1.1 Ray Peat, "Aspirin, brain, and cancer," raypeat.com.
  2. ↑ 2.0 2.1 2.2 2.3 Ray Peat, Aspirin email Q&A, raypeatemails.com.
  3. ↑ Maximum Aspirin Dosage, Therapeutic Interventions forum answers
  4. ↑ Ephemera: Emails & Exchanges from the Archives
  5. ↑ Ray Peat, "A Plethora of Wide-Ranging Questions", One Radio Network, 1:29:05
  6. ↑ US Preventive Services Task Force; Davidson KW, Barry MJ, Mangione CM, et al. "Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement," JAMA. 2022;327(16):1577-1584. doi:10.1001/jama.2022.4983. PMID 35471505. Grade D for adults 60 or older; grade C for 40-59 with 10% or higher 10-year risk; updates the 2016 statement.
  7. ↑ Ray Peat, "From PMS to Menopause", p. 100
  8. ↑ 8.0 8.1 Ray Peat, "Aspirin, brain, and cancer," raypeat.com.
  9. ↑ Ray Peat, "Fatigue, aging, and recuperation," raypeat.com.
  10. ↑ El-Mowafy SA, Abd El Galil KH, El-Messery SM, et al. "Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa," Microb Pathog. 2014;74:25-32. doi:10.1016/j.micpath.2014.07.008. PMID 25088031.
  11. ↑ Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans
  12. ↑ Aspirin, brain, and cancer, Ray Peat newsletter
  13. ↑ Ray Peat, "Aspirin, brain, and cancer," raypeat.com.
  14. ↑ Ray Peat, "Your Health Questions Answered", One Radio Network, 38:11
  15. ↑ Ray Peat, "Prostate cancer," raypeat.com.
  16. ↑ Petrelli F, Ghidini A, Antista M, et al. "Effect of aspirin use on cancer incidence and mortality: An updated systematic review and meta-analysis," Public Health. 2025;248:105924. doi:10.1016/j.puhe.2025.105924. PMID 40865396.
  17. ↑ Ray Peat, "From PMS to Menopause", p. 116
  18. ↑ 18.0 18.1 Ray Peat, "Your Health Questions Answered", One Radio Network, 37:05
  19. ↑ Preventing and treating cancer with progesterone, raypeat.com.
  20. ↑ Singleton PA, Moss J, Karp DD, Atkins JT, Janku F. "The mu opioid receptor: A new target for cancer therapy?" Cancer. 2015;121(16):2681-2688. doi:10.1002/cncr.29460. PMID 26043235.
  21. ↑ Ray Peat, "Preventing and treating cancer with progesterone," raypeat.com.
  22. ↑ El Sadda RR, Elshahawy ZR, Saad EA. "Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C," BMC Cancer. 2023;23:175. doi:10.1186/s12885-023-10644-5. PMID 36809998. Rat study, 12 per group (4 killed at day 45 and 8 at day 90 of treatment); thioacetamide-induced HCC; aspirin 60 mg/kg orally plus vitamin C 4 g/kg i.p. every other day vs doxorubicin 0.72 mg/rat weekly; tumors were not measured, only markers (AFP, CA19.9, IL-6, TNF-a, p53), photos and histology; selectivity index 3.663 vs 0.819 for doxorubicin (HepG-2 vs WI-38 cells).
  23. ↑ El Ezaby NM, Saad EA, El Basuni MA. "Acetylsalicylic Acid with Ascorbate: A Promising Combination Therapy for Solid Tumors," Drugs R D. 2024;24(2):303-316. doi:10.1007/s40268-024-00479-1. PMID 39012613. Mouse study, 6 tumor-bearing mice per group at sacrifice; aspirin 60 mg/kg/day orally and ascorbate 4 g/kg/day i.p. for 10 days; tumor volume -46% with the combinationvs untreated), -36% ascorbate alone and -40% aspirin alone (Table 2).
  24. ↑ Ray Peat, "From PMS to Menopause", p. 147
  25. ↑ Ray Peat, "From PMS to Menopause", p. 148
  26. ↑ Ray Peat, "From PMS to Menopause", p. 150
  27. ↑ Ray Peat, "From PMS to Menopause", p. 183(citing Wang VP, Walsh SW, Free Radic Biol Med 18(3):585-591, 1995)
  28. ↑ Mondal S, et al. "Aspirin ameliorates experimental autoimmune encephalomyelitis through interleukin-11-mediated protection of regulatory T cells," Sci Signal. 2018 Nov 27;11(558):eaar8278. PMID 30482850.
  29. ↑ Chen C, et al., "Aspirin promotes oligodendrocyte precursor cell proliferation and differentiation after white matter lesion," PLoS One. 2014;9(1):e89229. PMID 24478700.
  30. ↑ Mana M, Ghotbeddin Z, Khazaeel K, et al. "Aspirin's Role in Reducing Oxidative Stress: Implications for Cognition and Heart Function in Autism Spectrum Disorder," Vet Med Int. 2025;2025:4089667. doi:10.1155/vmi/4089667.
  31. ↑ Díaz-Cruz ES, Shapiro CL, Brueggemeier RW. "Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells," J Clin Endocrinol Metab. 2005;90(5):2563-70. PMID 15687328.
  32. ↑ Shi XK, Sheng YW, Cao DY, Shi N, Zhang GL, Wang F. "Aspirin Suppresses Aromatase-Mediated Estrogen Biosynthesis to Alleviate Polycystic Ovary Syndrome by the Inhibition of Adenylate Cyclase," FASEB J. 2025;39(11):e70688. doi:10.1096/fj.202403152R. PMID 40464588.
  33. ↑ Lembo M, Trimarco V, Pacella D, et al. "Daily low dose aspirin halves incident type 2 diabetes in elderly subjects with prediabetes: a five-year longitudinal cohort study in a real-word population," Cardiovasc Diabetol. 2025;24(1):259. doi:10.1186/s12933-025-02802-9. PMID 40533771.
  34. ↑ Hundal RS, Petersen KF, Mayerson AB, et al. "Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes," J Clin Invest. 2002;109(10):1321-6. PMID 12021247.
  35. ↑ Simon TG, Henson J, Osganian S, et al. "Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease," Clin Gastroenterol Hepatol. 2019. doi:10.1016/j.cgh.2019.04.061. PMID 31077838.
  36. ↑ 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; effect depended on T-cell ARHGEF1 and thromboxane signalling.
  37. ↑ Kanwal R, Jawed B, Zakir SK, et al. "The Anti-Metastatic Role of Aspirin in Cancer: A Systematic Review," Int J Mol Sci. 2026;27(3):1288. doi:10.3390/ijms27031288. PMID 41683716. Systematic review, PROSPERO CRD420251231581.
  38. ↑ Yang L, Lv Z, Xia W, et al. "The effect of aspirin on circulating tumor cells in metastatic colorectal and breast cancer patients: a phase II trial study," Clin Transl Oncol. 2018;20(7):912-921. doi:10.1007/s12094-017-1806-z. PMID 29243075. 21 colorectal and 19 breast patients; colorectal CTC decline p < 0.001; no control arm.
  39. ↑ Roop RP, Naughton MJ, Van Poznak C, et al. "A randomized phase II trial investigating the effect of platelet function inhibition on circulating tumor cells in patients with metastatic breast cancer," Clin Breast Cancer. 2013;13(6):409-415. doi:10.1016/j.clbc.2013.08.006. PMID 24267729. RCT, 42 evaluable;at 4 weeks.
  40. ↑ Dillekås H, Rogers MS, Straume O. "Are 90% of deaths from cancer caused by metastases?," Cancer Med. 2019;8(12):5574-5576. doi:10.1002/cam4.2474. PMID 31397113. Registry study, Cancer Registry of Norway 2005-2015; 66.7% of solid-tumor cancer deaths listed metastases.
  41. ↑ Rothwell PM, Price JF, Fowkes FGR, et al. "Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials," Lancet. 2012;379(9826):1602-1612. doi:10.1016/S0140-6736(11)61720-0. PMID 22440946. Individual-patient meta-analysis; cancer death OR 0.85, 34 trials, 69,224 participants; incidence from 3 years OR 0.76 (0.66-0.88), 6 trials.
  42. ↑ Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. "Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials," Lancet. 2011;377(9759):31-41. doi:10.1016/S0140-6736(10)62110-1. PMID 21144578. Individual patient data from 8 randomized trials of daily aspirin.
  43. ↑ Rothwell PM, Wilson M, Elwin CE, et al. "Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials," Lancet. 2010;376(9754):1741-1750. doi:10.1016/S0140-6736(10)61543-7. PMID 20970847.
  44. ↑ McNeil JJ, Gibbs P, Orchard SG, et al. "Effect of Aspirin on Cancer Incidence and Mortality in Older Adults," J Natl Cancer Inst. 2021;113(3):258-265. doi:10.1093/jnci/djaa114. PMID 32778876. RCT, 19,114 participants, median 4.7 years; all cancers HR 1.04 (0.95-1.14), not significant; metastatic at diagnosis HR 1.19 (1.00-1.43); stage 4 HR 1.22 (1.02-1.45).
  45. ↑ Orchard SG, Polekhina G, Zalcberg J, et al. "Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial," JAMA Oncol. 2026;12(3):285-294. doi:10.1001/jamaoncol.2025.6196. PMID 41609798. RCT plus observational extension, median 8.6 years; incidence HR 0.98 (0.92-1.05); cancer mortality HR 1.15 (1.03-1.29).
  46. ↑ Chen WY, Ballman KV, Partridge AH, et al. "Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial," JAMA. 2024;331(20):1714-1721. doi:10.1001/jama.2024.4840. PMID 38683596. RCT, 3,020 participants, 300 mg/day; invasive disease-free survival HR 1.27 (0.99-1.63),, not significant; overall survival HR 1.19 (0.82-1.72).
  47. ↑ Coburn A, et al. "Longevity Risk: The Impact of Daily Aspirin Intake on Pension Liabilities," RMS LifeRisks Whitepaper 03-2013, Risk Management Solutions Inc., March 2013. Scenario model based on Rothwell 2011/2012; 65-year-old male +12 months life expectancy and 40% higher chance of reaching 100 in the high-uptake scenario.
  48. ↑ Ephemera: Emails & Exchanges from the Archives, Ray Peat
  49. ↑ Martling A, Hed Myrberg I, Nilbert M, Grönberg H, et al. "Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer," N Engl J Med. 2025. doi:10.1056/NEJMoa2504650. PMID 40961426.
  50. ↑ Prizment AE, Staley C, Onyeaghala GC, Vivek S, et al. "Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk," Aliment Pharmacol Ther. 2020;52(6):976-987. doi:10.1111/apt.16013. PMID 32770859.
  51. ↑ Sandler RS et al. 2003. "A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer." N Engl J Med 348(10):883-890. doi:10.1056/NEJMoa021633. PMID 12621132. RCT, 635 randomized, 517 with follow-up colonoscopy at median 12.8 months; adjusted RR for any recurrent adenoma 0.65.
  52. ↑ Cole BF et al. 2009. "Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials." J Natl Cancer Inst 101(4):256-266. doi:10.1093/jnci/djn485. PMID 19211452. 4 RCTs, 2967 participants, 81-325 mg/day; any adenoma RR 0.83 (0.72-0.96), advanced lesions RR 0.72 (0.57-0.90).
  53. ↑ Burn J et al. 2011. "Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial." Lancet 378(9809):2081-2087. doi:10.1016/S0140-6736(11)61049-0. PMID 22036019. 861 randomized, mean follow-up 55.7 months; colorectal cancers 18/427 aspirin vs 30/434 placebo; intention-to-treat HR 0.63 (0.35-1.13,, per-protocol HR 0.41 (0.19-0.86).
  54. ↑ Cook NR et al. 2005. "Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial." JAMA 294(1):47-55. doi:10.1001/jama.294.1.47. PMID 15998890. 39,876 women, 100 mg every other day, mean 10.1 years; colorectal cancer RR 0.97 (0.77-1.24).
  55. ↑ Gann PH et al. 1993. "Low-dose aspirin and incidence of colorectal tumors in a randomized trial." J Natl Cancer Inst 85(15):1220-1224. doi:10.1093/jnci/85.15.1220. PMID 8331682. Physicians' Health Study, 22,071 men, 325 mg every other day.
  56. ↑ Chan AT et al. 2007. "Aspirin and the risk of colorectal cancer in relation to the expression of COX-2." N Engl J Med 356(21):2131-2142. doi:10.1056/NEJMoa067208. PMID 17522398. Nurses' Health Study and Health Professionals Follow-up Study, 636 cancers typed; COX-2 high RR 0.64, COX-2 weak or absent RR 0.96; P for heterogeneity 0.02. Observational.
  57. ↑ Zanaty M, Roa JA, Nakagawa D, et al. "Aspirin associated with decreased rate of intracranial aneurysm growth," J Neurosurg. 2020;133(5):1478-1485. doi:10.3171/2019.6.JNS191273. PMID 31662579. Odds ratio 0.19.
  58. ↑ Bayraktar Z, Albayrak S. "Efficacy and safety of combination of tadalafil and aspirin versus tadalafil or aspirin alone in patients with vascular erectile dysfunction: a comparative randomized prospective study," Int Urol Nephrol. 2019;51(9):1491-1499. doi:10.1007/s11255-019-02211-4. PMID 31230261.
  59. ↑ 59.0 59.1 Ray Peat, "Your Health Questions Answered", One Radio Network, 1:01:35
  60. ↑ Ray Peat, "Hair Loss, Inflammation, Osteoporosis", Ask the Herb Doctor, KMUD, 2011-07-15, 53:02
  61. ↑ Ray Peat, "Hair Loss, Inflammation, Osteoporosis", Ask the Herb Doctor, KMUD, 2011-07-15, 54:05
  62. ↑ Somasundaram S, et al. "Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat," Aliment Pharmacol Ther. 2000;14(5):639-650.
  63. ↑ 63.0 63.1 63.2 63.3 63.4 Ray Peat, "Your Health Questions Answered", One Radio Network, 41:11
  64. ↑ Aspirin email Q&A, raypeatemails.com.
  65. ↑ Coyle M, Lynch A, Higgins M, et al. "Risk of Intracranial Hemorrhage Associated With Direct Oral Anticoagulation vs Antiplatelet Therapy: A Systematic Review and Meta-Analysis," JAMA Netw Open. 2024;7(12):e2449017. doi:10.1001/jamanetworkopen.2024.49017. PMID 39630447.
  66. ↑ “Aspirin, brain, and cancer”
  67. ↑ Belay ED, Bresee JS, Holman RC, Khan AS, Shahriari A, Schonberger LB. "Reye's syndrome in the United States from 1981 through 1997," N Engl J Med. 1999;340(18):1377-1382. doi:10.1056/NEJM199905063401801. PMID 10228187. National surveillance, 1,207 cases under age 18, 1981-1997.
  68. ↑ Hurwitz ES, et al. "Public Health Service study of Reye's syndrome and medications. Report of the main study," JAMA. 1987;257(14):1905-1911. PMID 3820509. Case-control study.
  69. ↑ 69.0 69.1 Ray Peat, "Aspirin, brain, and cancer," raypeat.com.
  70. ↑ 70.0 70.1 Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans WJ. "Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis," Am J Physiol Endocrinol Metab. 2002;282(3):E551-556. PMID 11832356.
  71. ↑ 71.0 71.1 Lilja M, Mandić M, Apró W, et al. "High doses of anti-inflammatory drugs compromise muscle strength and hypertrophic adaptations to resistance training in young adults," Acta Physiol (Oxf). 2018;222(2). PMID 28834248.
  72. ↑ 72.0 72.1 Hay-Schmidt A, Finkielman OTE, Jensen BAH, et al. "Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour," Reproduction. 2017;154(2):145-152. PMID 28559473.
  73. ↑ Kristensen DM, Hass U, Lesné L, et al. "Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat," Hum Reprod. 2011;26(1):235-244. PMID 21059752.
  74. ↑ Blecharz-Klin K, Sznejder-Pacholek A, Wawer A, et al. "Early exposure to paracetamol reduces level of testicular testosterone and changes gonadal expression of genes relevant for steroidogenesis in rats offspring," Drug Chem Toxicol. 2022;45(4):1862-1869. PMID 33657953.
  75. ↑ 75.0 75.1 Fischer MB, et al. "Fetal exposure to paracetamol is associated with altered markers of ovarian development and reduced uterine volume in girls: the COPANA study," Hum Reprod Open. 2026. PMID 42713612.
  76. ↑ Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. "Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione," J Pharmacol Exp Ther. 1973;187(1):211-217. PMID 4746329.
  77. ↑ Hjelle JJ, Grubbs JH. "Therapeutic doses of acetaminophen stimulate the turnover of cysteine and glutathione in man," J Clin Invest. 1986;78(5):1412-1420. PMID 3584929.
  78. ↑ Tofler GH, Morel-Kopp MC, Spinaze M, et al. "The effect of metoprolol and aspirin on cardiovascular risk in bereavement: A randomized controlled trial," Am Heart J. 2020;220:264-272. doi:10.1016/j.ahj.2019.11.003. PMID 31923768.
  79. ↑ Ray Peat, "Aspirin," raypeat.com.
  80. ↑ Aspirin, brain, and cancer, Ray Peat newsletter
  81. ↑ Ray Peat, "Aspirin," raypeat.com.
  82. ↑ 82.0 82.1 Ray Peat, "Aspirin," raypeat.com.
  83. ↑ Aspirin, brain, and cancer, Ray Peat newsletter
  84. ↑ Schoenfeld BJ. "Non-steroidal anti-inflammatory drugs may blunt more than pain," Acta Physiol (Oxf). 2018;222(3):e13007. Review discussing the age-dependent, sometimes anabolic effect of NSAIDs on muscle.