Ray Peat, PhD on Aspirin

Also see:
Aspirin and Exercise
Benefits of Aspirin
PUFA Promote Cancer
Arachidonic Acid’s Role in Stress and Shock
Sunburn, PUFA, Prostaglandins, and Aspirin
Phospholipases, PUFA, and Inflammation
Dietary PUFA Reflected in Human Subcutaneous Fat Tissue
Toxicity of Stored PUFA
PUFA – Accumulation and Aging
Ray Peat, PhD Quotes on Therapeutic Effects of Niacinamide
Altitude Sickness: Therapeutic Effects of Acetazolamide and Carbon Dioxide
Carbonic Anhydrase Inhibitors as Cancer Therapy
Lab study: Daily aspirin could block growth of breast, other cancers

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“When a drug such as caffeine or aspirin turns out to have a great variety of protective effects, it’s important to understand what it’s doing.

Because aspirin has been abused by pharmaceutical companies that have competing products to sell, as well as by the original efforts to promote aspirin itself, people can easily find reasons why they shouldn’t take it.

Early in the 20th century, people were told that fevers were very bad, and that aspirin should be used whenever there is a fever.

In the 1980s, there was a big publicity campaign warning parents that giving aspirin to a child with the flu could cause the potentially deadly Reye syndrome. Aspirin sales declined sharply, as sales of acetaminophen (Tylenol, etc.) increased tremendously. But in Australia, a study of Reye syndrome cases found that six times as many of them had been using acetaminophen as had used aspirin. (Orlowski, et al., 1987)

Until the 1950s and 1960s, when new products were being promoted, little was said about the possibility of stomach ulceration from aspirin. Lately, there has been more publicity about the damage it can do to the stomach and intestine, much of it in connection with the sale of the new “COX-2 inhibitors.” (These new drugs, rather than protecting the circulatory system as aspirin does, damage it.) Aspirin rapidly breaks down into acetic acid and salicylic acid (which is found in many fruits), and salicylic acid is protective to the stomach and intestine, and other organs. When aspirin was compared with the other common antiinflammatory drugs, it was found that the salicylic acid it releases protects against the damage done by another drug. (Takeuchi, et al, 2001; Ligumsky, et al., 1985.) Repeated use of aspirin protects the stomach against very strong irritants. The experiments in which aspirin produces stomach ulcers are designed to produce ulcers, not to realistically model the way aspirin is used.”

“Soon after vitamin E was discovered, tocopherol was defined as a brain-protective, pregnancy protective, male fertility protective, antithrombotic, antiestrogenic agent. But very soon, the estrogen industry made it impossible to present ideas that explained vitamin E, progesterone, vitamin A, or thyroid hormone in terms of the protection they provide against estrogenic substances. Since the polyunsaturated fats caused the same conditions that were caused by unopposed estrogen, vitamin E came to be known as an “antioxidant,” because it reduced their toxicity. (Vitamin E is now known to suppress COX-2, synergizing with aspirin and opposing estrogen.)”

“The competition between fatty acids and glucose, which has been called the “Randle cycle” for about 50 years, can be applied to the treatment of diabetes and other degenerative/stress problems by adjusting the diet, or by using supplements such as niacinamide and aspirin, which improve glucose oxidation by lowering the free fatty acids in the serum.”

“A few years later, aspirin was found to inactivate the enzyme that forms prostaglandins, by the transfer of the acetyl radical to the enzyme. This became the orthodox “explanation” for what aspirin does, though it neglected to explain that salicylic acid (lacking the acetyl radical) had been widely known in the previous century for its very useful antiinflammatory actions. The new theory did explain (at least to the satisfaction of editors of medical magazines) one of aspirin’s effects, but it distracted attention from all the other effects of aspirin and salicylic acid.

Aspirin is an antioxidant that protects against lipid peroxidation, but it also stimulates mitochondrial respiration. It can inhibit abnormal cell division, but promote normal cell division. It can facilitate learning, while preventing excitotoxic nerve injury. It reduces clotting, but it can decrease excessive menstrual bleeding. These, and many other strangely beneficial effects of aspirin, strongly suggest that it is acting on very basic biological processes, in a coherent way.

In explaining aspirin’s effects, as in explaining those of estrogen and progesterone, or polyunsaturated fats and vitamin E, I think we need concepts of a very broad sort, such as “stability and instability.””

“Aspirin activates both glycolysis and mitochondrial respiration, and this means that it shifts the mitochondria away from the oxidation of fats, toward the oxidation of glucose, resulting in the increased production of carbon dioxide. Its action on the glycolytic enzyme, GAPDH, is the opposite of estrogen’s.

The shift away from fat oxidation under the influence of aspirin doesn’t lead to an accumulation of free fatty acids in the circulation, since aspirin inhibits the release of fatty acids from both phospholipids and triglycerides. Estrogen has the opposite effects, increasing fat oxidation while increasing the level of circulating free fatty acids, since it activates lipolysis, as do several other stress-related hormones.

The polyunsaturated fatty acids, such as linolenic, linoleic, arachidonic, EPA, and DHA, have many directly toxic, antirespiratory actions, apart from the production of the prostaglandins or eicosanoids. Just by preventing the release of these fatty acids, aspirin would have broadly antiinflammatory effects.

Since the polyunsaturated fats and prostaglandins stimulate the expression of aromatase, the enzyme that synthesizes estrogen, aspirin decreases the production of estrogen. So many of aspirin’s effects oppose those of estrogen, it would be tempting to suggest that its “basic action” is the suppression of estrogen. But I think it’s more likely that both estrogen and aspirin are acting on some basic processes, in approximately opposite ways.

Bioelectrical functions, and the opposition between carbon dioxide and lactic acid, and the way water is handled in cells, are basic conditions that have a general or global effect on all of the other more specific biochemical and physiological processes. Originally, estrogen and progesterone were each thought to affect only one or a few biochemical events, but it has turned out that each has a multitude of different biochemical actions, which are integrated in globally meaningful ways. The salicylic acid molecule is much smaller and simpler than progesterone, but the range of its beneficial effects is similar. Because of aspirin’s medical antiquity, there has been no inclination to explain its actions in terms of an “aspirin receptor,” as for valium and the opiates, leaving its biochemistry, except for the inadequate idea of COX-inhibition, simply unexplained.”

“The competition between aspirin and salicylic acid, and other antiinflammatories, for the active site on the COX enzyme (Rao, et al., 1982), shows that the structural features of these molecules are in some ways analogous to those of the polyunsaturated fatty acids. Wherever there are phospholipids, free fatty acids, fatty acid esters, ethers, etc. (i.e., in mitochondria, chromosomes, cytoskeleton, collagen networks–essentially everywhere in and around the cell), the regulatory influence of specific fatty acids–or their surrogates–will be felt.

Although it would undoubtedly be best to grow up eating foods with relatively saturated fats, the use of aspirin preventively and therapeutically seems very reasonable under the present circumstances, in which, for example, clean and well ripened fruits are not generally available in abundance. Preventing blindness, degenerative brain diseases, heart and lung diseases, and cancer with aspirin should get as much support as the crazy public health recommendations are now getting from government and foundations and the medical businesses.

When people with cancer ask for my recommendations, they usually think I’m joking when I tell them to use aspirin, and very often they don’t take it, on the basis of what seems to be a very strong cultural prejudice. Several years ago, a woman whose doctors said it would be impossible to operate on her extremely painful “inflammatory breast cancer,” had overnight complete relief of the pain and swelling from taking a few aspirins. The recognized anti-metastatic effect of aspirin, and its ability to inhibit the development of new blood vessels that would support the tumor’s growth, make it an appropriate drug to use for pain control, even if it doesn’t shrink the tumor. In studies of many kinds of tumor, though, it does cause regression, or at least slows tumor growth. And it protects against many of the systemic consequences of cancer, including wasting (cachexia), immunosuppression, and strokes.

Opiates are the standard medical prescription for pain control in cancer, but they are usually prescribed in inadequate quantities, “to prevent addiction.” Biologically, they are the most inappropriate means of pain control, since they increase the release of histamine, which synergizes with the tumor-derived factors to suppress immunity and stimulate tumor growth.

It has recently become standard practice in most places to advise a person who is having a heart attack to immediately chew and swallow an aspirin tablet.

The same better-late-than-never philosophy can be applied to Alzheimer’s disease, Parkinson’s disease, and other degenerative nerve diseases. Aspirin protects against several kinds of toxicity, including excitotoxicity (glutamate), dopamine toxicity, and oxidative free radical toxicity. Since its effects on the mitochondria are similar to those of thyroid (T3), using both of them might improve brain energy production more than just thyroid. (By activating T3, aspirin can sometimes increase the temperature and pulse rate.) Magnesium, niacinamide, and other nerve protective substances work together.

In multiple organ failure, which can be caused by profound shock caused by trauma, infection, or other stress, aspirin is often helpful, but carbon dioxide and hypertonic glucose and sodium are more important.

Aspirin, like progesterone or vitamin E, can improve fertility, by suppressing a prostaglandin, and improving uterine circulation.

Although the animal studies that showed stomach damage from aspirin often used single doses equivalent to 10 or 100 aspirin tablets, the slight irritation produced by a normal dose of aspirin can be minimized by dissolving the aspirin in water. The stomach develops a tolerance for aspirin over a period of a few days, allowing the dose to be increased if necessary. And both aspirin and salicylic acid can be absorbed through the skin, so rheumatic problems have been treated by adding the drug to bath water.

The unsaturated (n-6 and n-3) fats that accumulate in our tissues, instead of being part of the system for reestablishing order and stability, tend to amplify the instability that is triggered by excitation, by estrogen, or by external stresses.

I think it’s important that we don’t allow the drug publicists to obscure the broad importance of substances such as aspirin, vitamin E, progesterone, and thyroid. For 60 years, a myth that was created to sell estrogen has harmed both science and the health of many people.”

“Aspirin protects against iron toxicity, clot formation, and reduces lipid peroxidation while blocking prostaglandin formation. Aspirin and other antiinflammatory drugs, taken for arthritis, have been clearly associated with a reduced incidence of Alzheimer’s disease. Aspirin reduces the formation of prostaglandins from arachidonic acid.”

“When I taught endocrinology, I annoyed my tidy-minded students by urging them to consider the potential hormone-like action of everything in the body, and to think of layers of control, ranging from sugar, salt, and carbon dioxide, through the “official hormones,” to complex nervous system actions such as expectancy, and biorhythms. Certain things that are active in very important processes deserve special attention as “signals,” but they still have to be understood in context. In this sense, we can think of Ca2+ as a signal substance, in its many contexts; it is strongly regulated by the cell’s energy charge. Magnesium and sodium antagonize it in certain situations. Linoleic acid, linolenic acid, arachidonic acid: Their toxicity is potentially prevented by the Mead acids, and their eicosanoid derivatives, which behave very differently from the familiar prostaglandins, as far as they have been compared; can be drastically reduced by dietary changes. Prostaglandins, prostacyclin, thromboxane: Formation is blocked by aspirin and other antiinflammatory drugs.”

“Aspirin’s antiinflammatory actions are generally important when the polyunsaturated fats are producing inflammatory and degenerative changes, and aspirin prevents many of the problems associated with diabetes, reducing vascular leakiness. It improves mitochondrial respiration (DeCristobal, et al., 2002) and helps to regulate blood sugar and lipids (Yuan, et al., 2001). Aspirin’s broad range of beneficial effects is probably analogous to vitamin E’s, being proportional to protection against the broad range of toxic effects of the polyunsaturated “essential” fatty acids.”

“Both preventively and therapeutically, the use of the antiinflammatory and antioxidative substances such as aspirin, caffeine, progesterone, and thyroid hormone would seem appropriate. Aspirin is coming to be widely accepted as an anticancer agent, and at moderate doses can cause cancer cells to die. It, like progesterone and thyroid, has a wide variety of anti-estrogenic effects. Especially when a tumor is painfully inflamed, aspirin’s effects can be quick and dramatic. However, people aren’t likely to be pleased if their cancer doctor tells them to “take aspirin and call me in six months.” Aspirin’s reputation for causing stomach bleeding causes people to avoid it, even when the alternative is something that’s seriously toxic to other organs, and it might just seem too ordinary to be considered as a powerful anticancer drug.”

“Aspirin protects against a variety of inflammatory processes, but it’s most famous for the inhibition of prostaglandins. While aspirin is often used to relieve pain in MS, and another inhibitor of prostaglandin synthesis, indomethacin, has been used therapeutically in MS, it would seem appropriate to investigate more carefully aspirin’s possible role in preventing or relieving MS.”

“Protein deficiency is an important cause of deranged calcium metabolism. Vitamins K, E, and A are important in regulating calcium metabolism, and preventing osteoporosis. Aspirin (with antiestrogenic and vitamin E-like actions) is protective against bone resorption and hypercalcemia.”

“If the physiology of shock has some relevance for eclampsia, so does the physiology of heart failure, since Meerson has shown that it is a consequence of uncompensated stress. The failing heart shifts from mainly glucose oxidation to the inefficient use of fatty acids, which are mobilized during stress, and with its decreased energy supply, it is unable to beat efficiently, since it remains in a partly contracted state. Estrogen (which is increased in men who have had heart attacks) is another factor which decreases the heart’s stroke volume, and estrogen is closely associated with the physiology of the free unsaturated fatty acids. The partly contracted state of the heart is effectively a continuation of the partly contracted state of the blood vessels that causes the hypertension, and reduced tissue perfusion seen in shock and eclampsia. Since shock can be seen as a generalized inflammatory state, and since aspirin has been helpful in protecting against heart disease, it’s reasonable that aspirin has been tried as a treatment in pre-eclampsia. It seems to protect the fetus against intrauterine growth retardation, an effect that I think relates to aspirin’s ability to protect in several ways against excesses of unsaturated fatty acids and of estrogen. But, since aspirin can interfere with blood clotting, its use around the time of childbirth can be risky, and it is best to correct the problem early enough that aspirin isn’t needed.”

“Some types of dementia, such as Alzheimer’s disease, involve a life-long process of degeneration of the brain, with an inflammatory component, that probably makes them comparable to osteoporosis and muscle-wasting. (In the brain, the microglia, which are similar to macrophages, and the astrocytes, can produce TNF.) The importance of the inflammatory process in Alzheimer’s disease was appreciated when it was noticed that people who used aspirin regularly had a low incidence of that dementia. Aspirin inhibits the formation of TNF, and aspirin has been found to retard bone loss. In the case of osteoporosis (A. Murrillo-Uribe, 1999), as in Alzheimer’s disease, the incidence is two or three times as high in women as in men. In both Alzheimer’s disease and osteoporosis, the estrogen industry is arguing that the problems are caused by a suddenly developing estrogen deficiency, rather than by prolonged exposure to estrogen.”

“Vitamin E, like progesterone and aspirin, acts within the cellular regulatory systems, to prevent
inflammation and inappropriate excitation. Since uncontrolled excitation causes destructive oxidations, these substances prevent those forms of oxidation.”

“Later, referring to the decades of hostility of the medical establishment to vitamin E, Dr. Shute said “…an obstetrician was unduly hardy and audacious to try it.” The spectrum of vitamin E’s protective effects (like those of aspirin) has been consistently misrepresented in the medical literature.”

“Abruptio placentae (premature detachment of the placenta) has often been blamed on the use of vitamin E, because of vitamin E’s reputation for preventing abnormal clotting, though the evidence tends to suggest instead that vitamin E (like aspirin) reduces the risk of pregnancy-related hemorrhaging.”

“But many very useful drugs that already existed, including cortisol and aspirin, were found to achieve some of their most important effects by inhibiting the formation of the prostaglandins. It was the body’s load of polyunsaturated fats which made it very susceptible to inflammation, stress, trauma, infection, radiation, hormone imbalance, and other fundamental problems, and drugs like aspirin and cortisone, which limit the activation of the stored “essential fatty acids,” gain their remarkable range of beneficial effects partly by the restraint they impose on those stored toxins.”

“Inflammation activates beta-glucuronidase, and antiinflammatory substances such as aspirin reduce many of estrogen’s effects.”

“Both the excitatory amino acids and a peptide that promotes inflammation, tumor necrosis factor (TNF), activate the enzyme which makes estrogen, aromatase. Estrogen, by activating NF kappaB, increases the formation of TNF, which in itself can promote the growth and metastasis of cancer. Various antiinflammatory agents, including aspirin, progesterone, testosterone, saturated fats, and glycine, can inhibit the production of NF kappaB.”

“The use of aspirin, which reduces inflammation and inhibits the formation of neurotoxic prostaglandins, is known to be associated with a lower incidence of Alzheimer’s disease, and in other contexts, it offers protection against estrogen. Naloxone, the antiendorphin, has been found to reverse some of the cumulative effects of stress, restoring some pituitary and ovarian function, and it promotes recovery after brain injury; in a variety of ways, it corrects some of estrogen’s toxic effects.”

“People who take aspirin, drink coffee, and use tobacco, have a much lower incidence of Alzheimer’s disease than people who don’t use those things. Caffeine inhibits brain phospholipase, making it neuroprotective in a wide spectrum of conditions. In recent tests, aspirin has been found to prevent the misfolding of the prion protein, and even to reverse the misfolded beta sheet conformation, restoring it to the harmless normal conformation. Nicotine might have a similar effect, preventing deposition of amyloid fibrils and disrupting those already formed (Ono, et al., 2002). Vitamin E, aspirin, progesterone, and nicotine also inhibit phospholipase, which contributes to their antiinflammatory action. Each of the amyloid-forming proteins probably has molecules that interfere with its toxic accumulation.”

“Aspirin protects cells in many ways, interrupting excitotoxic processes by blocking nitric oxide and prostaglandins, and consequently it inhibits cell proliferation, and in some cases inhibits glycolysis, but the fact that it can inhibit FAS (Beynen, et al., 1982) is very important in understanding its role in cancer.

There are several specific signals produced by lactate that can promote growth and other features of cancer, and it happens that aspirin antagonizes those: HIF, NF-kappaB, the kinase cascades, cyclin D1, and heme oxygenase.”

“The pituitary hormones, especially prolactin and TSH, are pro-inflammatory, and darkness increases TSH along with prolactin, so to compensate for a light deficiency, the pituitary should be well-suppressed by adequate thyroid. Armour thyroid or Thyrolar or Cynoplus, Cytomel, would probably be helpful. (Eye-drops containing T3 might be a way to restore metabolic activity more quickly.) Limiting water intake (or using salt generously) helps to inhibit prolactin secretion. The saturated fats protect against the body’s stored PUFA, and keeping the blood sugar up keeps the stored fats from being mobilized. Aspirin (or indomethacin) is generally protective to the retina, analogously to its protection against sunburn. Adequate vitamin E is extremely important. There are several prescription drugs that protect against serotonin excess, but thyroid and gelatin (or glycine, as in magnesium glycinate) are protective against the serotonin and melatonin toxicities.”

“In aspirin, it has been found that it is the acetyl group which (by a free radical action) blocks an enzyme involved in prostaglandin synthesis.”

“Carbon dioxide, high altitude, thyroid, progesterone, caffeine, aspirin, and decreased tryptophan consumption protect against excessive serotonin release. When sodium intake is restricted, there is a sharp increase in serotonin secretion. This accounts for some of the antiinflammatory and diuretic effects of increased sodium consumption–increasing sodium lowers both serotonin and adrenalin.”

“Aspirin, by inhibiting prostaglandin synthesis (and maybe other mechanisms) often lowers free radical production.”

“Antiinflammatory and anticoagulant things, especially aspirin and vitamin E, protect against the accelerated turnover of fibrinogen/fibrin caused by estrogen and the various inflammatory states.”

“I have known adults and children who were diagnosed as diabetic, and given insulin (and
indoctrinated with the idea that they had a terminal degenerative disease) on the strength of a single test showing excessive glucose. When I taught at the naturopathic medical school in Portland, I tried to make it clear that “diabetes” (a term referring to excessive urination) is a function, and that a high level of glucose in the blood or urine is also a function, and that the use of insulin should require a greater diagnostic justification than the use of aspirin for a headache does, because insulin use itself constitutes a serious health problem. (And we seldom hear the idea that “diabetes” might have a positive side [Robinson and Johnston], for example that it reduces the symptoms of asthma [Vianna and Garcialeme], which get worse when insulin is given. Normal pregnancy can be considered “diabetic” by some definitions based on blood sugar. I got interested in this when I talked to a healthy “diabetic” woman who had a two year old child whose IQ must have been over 200, judging by his spontaneous precocious hobbies. Old gynecologists told me that it was common knowledge that “diabetic” women had intellectually precocious children.)”

“Despite the nutritional value of those vitamins, fish oils are generally much more immunosuppressive than the seed oils, and the early effects of fish oil on the “immune system” include the suppression of prostaglandin synthesis, because the more highly unsaturated long chain fats interfere with the conversion of linoleic acid into arachidonic acid and prostaglandins. The prostaglandins are so problematic that their suppression is helpful, whether the inhibition is caused by aspirin or vitamin E, or by fish oil.”

“For a long time, gelatin’s therapeutic effect in arthritis was assumed to result from its use in repairing the cartilage or other connective tissues around joints, simply because those tissues contain so much collagen. (Marketers suggest that eating cartilage or gelatin will build cartilage or other collagenous tissue.) Some of the consumed gelatin does get incorporated into the joint cartilage, but that is a slow process, and the relief of pain and inflammation is likely to be almost immediate, resembling the antiinflammatory effect of cortisol or aspirin.”

“In aspirin, it has been found that it is the acetyl group which (by a free radical action) blocks an enzyme involved in prostaglandin synthesis.”

“(Chen, Y, et al., 1999: BRCA represses the actions of estrogen and its receptor, and, like progesterone, activates the p21 promoter, which inhibits cell proliferation. Aspirin and vitamin D also act through p21.)”

“Aspirin, which stimulates bone formation, has other thyroid-like actions, including activation of mitochondrial respiration and energy production, with an increase of cytochrome C oxidase (Cai, et al., 1996), and it lowers serotonin (Shen, et al., 2011). It also apparently protects against calcification of the soft tissues, (Vasudev, et al., 2000), \ though there has been surprisingly little investigation of that. “Aspirin can promote trabecular bone remodeling, improve three-dimensional structure of trabecular bone and increase bone density of cancellous in osteoporotic rats by stimulating bone formation. It may become a new drug for the treatment of osteoporosis,” Chen, et al., 2011.”

“Defensive aggression is probably a response intermediate between fearful giving up and confident achievement. When a rat is restrained, held down on its back, it quickly develops ulcers, but if it has a stick to bite, it is very resistant to the formation of the ulcers. The ability to do something with a defensive meaning prevents the excessive production of serotonin and its consequences, such as increased production of cortisol and other stress hormones, and disturbance of circulation and energy production. Endotoxin and prostaglandins activate these same systems, and progesterone and aspirin are among the protective factors that can oppose those effects.”

“In 1927, Bernstein and Elias found that rats eating a fat free diet had almost no spontaneous cancer, and many studies since then in animals and people have shown a close association between polyunsaturated fatty acids and cancer. The polyunsaturated fatty acids in themselves, and their breakdown products, are excitatory and destabilizing to normal cells, but by modifying the sensitivity and energy production of cells, they limit cells’ ability to respond to stimulation and destabilizing influences. Although they aren’t essential for wound healing (Porras-Reyes, et al., 1992), they and their metabolites, the prostaglandins, are very conspicuous in wounds and tumors, and their proportion generally increases with aging. The prostaglandins are involved in several vicious cycles, including that with HIF mentioned above. This makes the PUFA and prostaglandins important to consider in relation to optimizing wound healing, and decreasing cancerization. Aspirin’s protective and therapeutic effects in cancer are starting to be recognized, but there are several other things that can synergize with aspirin to reduce the circulation of free fatty acids and their conversion to prostaglandins. Niacinamide, progesterone, sugar, carbon dioxide, and red light protect against both free fatty acids and prostaglandins.”

“Increasing carbon dioxide lowers the intracellular pH, as well as inhibiting lactic acid formation, and restoring the oxidation of glucose increases CO2. Inhibiting carbonic anhydrase, to allow more CO2 to stay in the cell, contributes to intracellular acidification, and by systemically increasing carbon dioxide this inhibition has a broad range of protective anti-excitatory effects. The drug industry is now looking for chemicals that will specifically inhibit the carbonic anhydrase enzymes that are active in tumors. Existing carbonic anhydrase inhibitors, such as acetazolamide, will inhibit those enzymes, without harming other tissues. Aspirin has some effect as an inhibitor of carbonic anhydrase (Bayram, et al., 2008). Since histamine, serotonin (Vullo, et al., 2007), and estrogen (Barnett, et al., 2008; Garg, 1975) are carbonic anhydrase activators, their antagonists would help to acidify the hypoxic cells. Testosterone (Suzuki, et al., 1996) and progesterone are estrogen antagonists that inhibit carbonic anhydrase.”

“The foods that nourish the patient well enough to support healing while permitting energy reserves to be built up are also the foods that don’t interfere with the hormones, that don’t cause spurious excitation of the tissues. The polyunsaturated fats directly stimulate the stress hormones, activate the excitatory amino acid signals, and directly excite cells, while the saturated fats have opposite effects, and are anti-inflammatory, and also don’t interfere with mitochondrial function. When we eat more carbohydrate than can be oxidized, some of it will be turned into saturated fats and omega-9 fats, and these will support mitochondrial energy production. Carbohydrates in the diet also help to decrease the mobilization of fatty acids from storage; niacinamide and aspirin support that effect. Sugars are probably more favorable than starches for the immune system (Harris, et al., 1999), and failure of the immune system is a common feature of cancer. Polyunsaturated fats are generally known to suppress the immune system. Foods that provide generous amounts of sodium, calcium, magnesium, and potassium, help to minimize stress. Trace minerals and vitamins are important, but can be harmful if used excessively–iron excess is important to avoid.”

“While lactic acidosis causes bone loss, acidosis caused by increased carbonic acid doesn’t; low bicarbonate in the body fluids seems to remove carbonate from the bone (Bushinsky, et al., 1993), and also mineral phosphates (Bushinsky, et al., 2003). The parathyroid hormone, which removes calcium from bone, causes lactic acid to be formed by bone cells (Nijweide, et al., 1981; Lafeber, et al., 1986). Lactic acid produced by intense exercise causes calcium loss from bone (Ashizawa, et al., 1997), and sodium bicarbonate increases calcium retention by bone. Vitamin K2 (Yamaguchi, et al., 2003) blocks the removal of calcium from bone caused by parathyroid hormone and prostaglandin E2, by completely blocking their stimulation of lactic acid production by bone tissues. Aspirin, which, like vitamin K, supports cell respiration and inhibits lactic acid formation, also favors bone calcification. Vitamin K2 stimulates the formation of two important bone proteins, osteocalcin and osteonectin (Bunyaratavej, et al., 2009), and reduces the activity of estrogen by oxidizing estradiol (Otsuka, et al, 2005).”

“Aspirin, which is antilipolytic, decreasing the release of free fatty acids, as well as inhibiting their conversion to prostaglandins, lowers the production of stressed induced aldosterone, and helps to lower blood pressure, if it’s taken during the night. Aspirin increases insulin sensitivity.”

“Aspirin and vitamin E are protective against toxic radiation, and the consequent inflammatory processes.”

“Antioxidant, antiinflammatory, and antiestrogenic substances are protective against radiation damage. Aspirin, vitamin e, progesterone, saturated fats, and thyroid have these functions.”

“In recent years inflammation’s role in cancer and heart disease has been acknowledged to some extent, and simple antiinflammatory treatments such as aspirin have been more widely accepted in prevention and treatment of both heart disease and cancer. I think the next step is to recognize the importance of preventing all sorts of inflammation during the reproductive years, to protect the brains of the unborn, and the inheritance of future generations.”

“Aspirin and niacin help to prevent fatigue symptoms, and to prevent many of the harmful systemic oxidative after-effects. (Both are antilipolytic; aspirin uncouples mitochondria.)”

“Uncoupling of mitochondrial oxidative metabolism from ATP production helps to consume the sugar which otherwise would be diverted into lactic acid, and converts it into carbon dioxide instead…Aspirin and thyroid (T3) increase uncoupling. A drug that used to be used for weight reduction, DNP, also uncouples mitochondrial metabolism, and, surprisingly, it has some of the beneficial effects of thyroid and aspirin. It stimulates the consumption of lactic acid and the formation of carbon dioxide.”

“The “treatment” for intracellular fatigue consists of normalizing thyroid and steroid metabolism, and eating a diet including fruit juice, milk, some eggs, liver, and gelatin, assuring adequate calcium, potassium, sodium, and magnesium, and using supplements of niacinamide, aspirin, and carbon dioxide when necessary.”

“The excitatory metabolite glutamate, and nitric oxide, are both inhibited by aspirin (Moro, et al., 2000).”

“Aspirin and saturated fats can also be protective when applied topically.”

“Aspirin, increased levels of carbon dioxide (Ni Chonghaile, et aI., 2005), and progesterone (Deroo and Archer, 2002; Kelly, et al., 2001; Allport, et al., 2001; van der Burg and van der Saag, 1996; Caldenhoven, et aI., 1995) inhibit NF kappa-B, and NF kappa-B inhibits the synthesis of both testosterone (Hong, et aI., 2004) and progesterone (Allport, et aI., 2001).”

“Salicylic acid, which occurs naturally in many fruits, as well as in aspirin, is unlike the other antiinflammatory drugs so vaguely classified with it as “nonsteroidal,” in having a broad spectrum of antiinflammatory effects, inhibiting the prostaglandins and NF kappa-B, TNF, and IL-6, besides contributing to the inhibition of estrogen synthesis and actions.”

“Other things that protect against excessive polyamines are procaine and other local anesthetics (Yuspa, et al., 1980), magnesium, niacin, vitamin A, aspirin, and, in some circumstances, caffeine.”

“The amounts needed seem large if niacinamide is thought of as “vitamin B3,” but it should be considered as a factor that compensates for our unphysiological exposure to inappropriate fats. Aspirin and vitamin E are other natural substances that are therapeutic in “unnaturally” large amounts because of our continual exposure to the highly unsaturated plant-derived n-3 and n-6 fats.”

“Aspirin has a very broad spectrum of antiinflammatory actions, and is increasingly being recommended for preventing complications of diabetes. One of the consequences of inflammation is hyperglycemia, and aspirin helps to correct that (Yuan, et al., 2001), while protecting proteins against oxidative damage (Jafarnejad, et al, 2001).”

“The contractile ability of smooth muscle, that’s impaired by swelling and inflammation, can be restored by antiinflammatory agents, for example aspirin (or other inhibitor of prostaglandin synthesis) or antihistamines. This applies to the muscles of lymphatic vessels (Wu, et al., 2005, 2006; Gosling, 2000), that must function to reduce edema, as well as to the bowel muscles that cause peristalsis.”

“Another kind of adaptogen resembles the body’s intrinsic defensive substances, but isn’t produced in significant quantities in our bodies. This type includes caffeine and the anthraquinones (such as emodin) and aspirin and other protective substances from plants. These overlap in functions with some of our intrinsic regulatory substances, and can also complement each other’s effects.”

“This makes the PUFA and prostaglandins important to consider in relation to optimizing wound healing, and decreasing cancerization. Aspirin’s protective and therapeutic effects in cancer are starting to be recognized, but there are several other things that can synergize with aspirin to reduce the circulation of free fatty acids and their conversion to prostaglandins. Niacinamide, progesterone, sugar, carbon dioxide, and red light protect against both free fatty acids and prostaglandins.”

“The drug industry is now looking for chemicals that will specifically inhibit the carbonic anhydrase-enzymes that are active in tumors. Existing carbonic anhydrase inhibitors, such as acetazolamide, will inhibit those enzymes, without harming other tissues. Aspirin has some effect as an inhibitor of carbonic anhydrase (Bayram, et al., 2008).”

“When we eat more carbohydrate than can be oxidized, some of it will be turned into saturated fats and omega-9 fats, and these will support mitochondrial energy production. Carbohydrates in the diet also help to decrease the mobilization of fatty acids from storage; niacinamide and aspirin support that effect.”

“Many of the things that can be achieved by vaccination and treatment with safe antiinflammatories such as aspirin could be done better by long-term changes of diet, and by taking into account the interactions of the hormones, especially progesterone, estrogen, and thyroid, with nutrients and stressors. But much more than that is needed: The nature of the relationships between environmental factors and the body’s reactions has to be clarified, so that the processes of healing and regeneration can more closely resemble the prenatal condition, possibly even continuing in adulthood the “pedomorphic” process, realizing human potentials that haven’t previously been seen.”

“The continuing accumulation of polyunsaturated fats in the tissues is undoubtedly important in the changing relationship between the pancreas and the adrenal glands in aging. Aspirin, which is antilipolytic, decreasing the release of free fatty acids, as well as inhibiting their conversion to prostaglandins, lowers the production of stress induced aldosterone, and helps to lower blood pressure, if it’s taken in the evening, to prevent the increase of free fatty acids during the night. Aspirin increases insulin sensitivity. A low salt diet increases the free fatty acids, leading to insulin resistance, and contributing to atherosclerosis (Prada, et al., 2000; Mroka, et aI., 2000; Catanozi, et al., 2003; Garg, et al., 2011).”

“Recognizing causal connections between premature birth and respiratory distress and retinopathy of prematurity, it would be obvious that the greatest effort should be made to prevent the problems by improving the health of pregnant women. Hospitals, however, are invested in high technology systems for treating these problems, and even though their results are dismal, they can’t make money by getting pregnant women to eat enough protein to prevent preeclampsia, which is a major cause of premature birth, or by treating the problems with salt, magnesium, progesterone, thyroid, and aspirin when the women haven’t had a good diet.”

“The saturated fats protect against the body’s stored PUFA, and keeping the blood sugar up keeps the stored fats from being mobilized. Aspirin (or indomethacin) is generally protective to the retina, analogously to its protection against sunburn.”

“Since polyunsaturated fatty acids become integrated into all types of cell, and cause so many types of damage when they are released, everything which inhibits their release is protective. Niacinamide, Benadryl, aspirin (Yu, et aI., 2003), and procaine help to reduce the release of free fatty acids.”

“Aspirin’s similarity to benzoate and phenylacetate suggests that it might sometimes help to remove ammonia. The safest procedure is to use foods, such as fruit juices, that regulate nitrogen metabolism in varied ways.”

“Aspirin protects against some of the worst stressors, including the polyunsaturated fats, so despite its mild toxicity, long term studies usually show that it decreases sickness and mortality.”

“Aspirin, by inhibiting the production of estrogen, of carbon monoxide, and of several cytokines and toxic lipid products, and by supporting normal respiration, helping to correct hyperglycemia, and suppressing lactate production, is an especially valuable therapy. Sacca et aI., have recently (October, 2004) demonstrated that aspirin’s anticancer effect appears to involve the inhibition of heme oxygenase.”

“Caffeine, by inhibiting FAS and sparing glucose, and inhibiting many of the toxic lipid inflammatory mediators, additive effects when products and other should have at least combined with aspirin.

Vitamin D, by its antiestrogenic and antiinflammatory actions, and by suppressing FAS, parallels the effects of aspirin and caffeine in several ways.”

“The prostaglandins were discovered in prostatic fluid, where they occur in significant concentrations. They are so deeply involved with the development of cancers of all sorts that aspirin and other prostaglandin inhibitors should be considered as a basic part of cancer therapy.”

“The PUFA (especially the omega -3 fatty acids) spontaneously decompose into a variety of toxins, and arachidonate is also enzymically converted into prostaglandins, some of which exacerbate the excitatory damage (Pepicelli, et aI., 2005); aspirin’s neuroprotective effect (Riepe, et aI., 1997) is probably partly caused by inhibiting prostaglandin synthesis. Besides the prostaglandins, other mediators of inflammation including nitric oxide and interleukins are produced by excessive excitation, as cells lose their ability to retain magnesium, and to control excitatory intracellular calcium.”

“Inhibitors of estrogen synthesis are being considered for use in controlling epilepsy (Reddy, 2007), but aspirin and progesterone and thyroid can produce similar results.”

“It’s the stored PUFA, released by stress or hunger, that slow metabolism. Niacinamide helps to lower free fatty acids, and good nutrition will allow the liver to slowly detoxify the PUFA, if it isn’t being flooded with large amounts of them. A small amount of coconut oil with each meal will increase the ability to oxidize fat, by momentarily stopping the antithyroid effect of the PUFA. Aspirin is another thing that reduces the stress-related increase of free fatty acids, stimulating metabolism. Taking a thyroid supplement is reasonable until the ratio of saturated fats to PUFA is about 2 to 1.”

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8 Responses

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  1. Birdie says

    I enjoy reading the info. So sad that I’ve tried so many times to login and can’t. :(

  2. Ms says

    Simply a great overview of the benefits of aspirin ! Additional information on it’s antibacterial action could also be mentioned

  3. ed says

    Hello Rob, did RP make the quote about DNP above in an interview? I have not been able to find that quote in any of his articles on his site. Do you think a dose of 0.75 mg per lb of body weight (or 150mg for a 200lb person) be considered a safe form of ‘mild’ uncoupling ?
    Thanks, ed

  4. Team FPS says

    The quote is from page 8 of the “Fatigue, Aging, and Recuperation” newsletter from November 2006. I am not familiar with the dosing of DNP. You may want to email Dr. Peat directly.

  5. Harry says

    I’m confused. It appears that Aspirin prevents lipolysis

    >Aspirin, which is antilipolytic, decreasing the release of free fatty acids,

    But at the same time it sounds like Aspirin is pro-thryroid which is important for lipolysis

    >Aspirin, which stimulates bone formation, has other thyroid-like actions, including activation of mitochondrial respiration and energy production.

    Moreover, DNP (a known fat burner is bodybuilding circles) is described as having similar effects to Aspirin

    >DNP, also uncouples mitochondrial metabolism, and, surprisingly, it has some of the beneficial effects of thyroid and aspirin.

    So is Aspirin beneficial or harmful for weight loss efforts?

  6. Team FPS says

    It’s beneficial. I suspect that the role aspirin plays depends upon the immediate state of the organism.

    The increased cellular energy effects (bioenergetic), anti-estrogen, and PUFA-protective properties make it ideal for long-term health management and body composition changes. The lipolytic nature of aspirin (or thyroid) occurs during times of stability and low energy demands rather than during the high energy demands of stress.

    Inhibition of lipolysis by aspirin (or niacinamide) during duress is helpful because it’s the release of PUFA from the tissue during the high-energy demands of stress that keep the metabolic rate down by interfering with the thyroid and glucose oxidation, raising estrogen, and increasing inflammation (prostaglandins).

  7. James says

    Thank you for the information!

Continuing the Discussion

  1. What did you Peat today? - Page 82 | Mark's Daily Apple Health and Fitness Forum page 82 linked to this post on November 14, 2013

    […] for taking aspirin, and it's not the "age old" stuff like keeping heart disease at bay. Ray Peat, PhD on Aspirin – Functional Performance Systems (FPS) Huh, I guess my supplementing Vit E is a Peat concept too, though I didn't realize it. […]