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- <html>
- <head><title>Aspirin, brain, and cancer</title></head>
- <body>
- <h1>
- Aspirin, brain, and cancer
- </h1>
-
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- Early in the 20th century, people were told that fevers were very bad, and that aspirin should be used
- whenever there is a fever.
- </p>
- <p>
- 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)
- </p>
- <p>
- 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.
- </p>
-
- <p>
- Recently, the public has been led to believe that drugs are being designed to fit certain cellular
- "receptors." The history of the "COX-2 inhibitors" is instructive, in a perverse way. The structures of DES
- and other synthetic estrogens were said to relate to "the estrogen receptor." Making these estrogenic
- molecules more soluble in water made them somewhat anti-estrogenic, leading to products such as Tamoxifen.
- But some of the molecules in this group were found to be antiinflammatory. The structure of Celecoxib and
- other "COX-2 inhibitors" is remarkably similar to the "designer estrogens." Considering this, it's a little
- odd that so few in the U.S. are openly discussing the possibility that estrogen's function is directly
- related to inflammation, and involves the production of many inflammatory mediators, including COX-2. (See
- Lerner, et al., 1975; Luo, et al., 2001; Cushman, et al, 2001; Wu, et al., 2000; Herrington, et al., 2001.)
- </p>
-
- <p>
- Soot and smoke contain many chemicals that produce inflammation (Brune, et al., 1978). In the 1930s, soot
- was known to be both carcinogenic and estrogenic, and analysis of its components led to the production of
- the early commercial estrogens. Any intelligent person reading the chemical and biological publications of
- that time will see how closely associated cancer, inflammation, and estrogen are.
- </p>
- <p>
- 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.)
- </p>
- <p>
- In 1970, when I was beginning to see the ways in which unopposed estrogen and accumulated polyunsaturated
- fats interacted with a vitamin E deficiency during aging and in infertility, I got some prostaglandins to
- experiment with, since they are products of the oxidation of linoleic acid. The prostaglandins are an
- interesting link between estrogens and inflammation, in normal physiology as well as in disease.
- </p>
- <p>
- I wanted to test their effects on the uterus, especially the sites where the embryos implant. There was a
- theory that the electrical charge of the surface of the uterus was decreased at the implantation sites, to
- reduce the repulsion between two negatively charged things. Although there were regions of lower surface
- charge along the lining of the uterus, the charge changed as waves of muscle contraction moved along the
- uterus, and the prostaglandins affected the contractions.
- </p>
- <p>
- To understand the differences between the different types of prostaglandin, I tested them on my arm, and
- those with the most hydroxyl groups produced regions with an increased negative charge. For comparison, I
- exposed another spot to sunlight for an hour, and found that there was a similar increase in the negative
- charge in that spot. Apparently the prostaglandins were causing an injury or excitation, a mild
- inflammation, in the skin cells.
- </p>
-
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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."
- </p>
- <p>
- The COX (cyclooxygenase) enzymes, that make prostaglandins, are just one system among many that are
- activated by stress. Aromatase, that makes estrogen, enzymes that make histamine, serotonin and nitric
- oxide, the cytokines, and the stress-induced hormones of the pituitary and adrenal glands, are turned on in
- difficult situations, and have to be turned off when the threat has been overcome. The production of energy
- is the basis for overcoming all threats, and it has to be conserved in readiness for future needs.
- </p>
-
- <p>
- The fetus produces saturated fats such as palmitic acid, and the monounsaturated fat, oleic acid, which can
- be turned into the Mead acid, ETrA (5,8,11-eicosatrienoic acid), and its derivatives, which are
- antiinflammatory, and some of which act on the "bliss receptor," or the cannibinoid receptor. In the adult,
- tissues such as cartilage, which are protected by their structure or composition from the entry of exogenous
- fats, contain the Mead acid despite the presence of linoleic acid in the blood.
- </p>
- <p>
- At birth, the baby's mitochondria contain a phospholipid, cardiolipin, containing palmitic acid, but as the
- baby eats foods containing polyunsaturated fatty acids, the palmitic acid in cardiolipin is replaced by the
- unsaturated fats. As the cardiolipin becomes more unsaturated, it becomes less stable, and less able to
- support the activity of the crucial respiratory enzyme, cytochrome oxidase.
- </p>
- <p>
- The respiratory activity of the mitochondria declines as the polyunsaturated oils replace palmitic acid, and
- this change corresponds to the life-long decline of the person's metabolic rate.
- </p>
- <p>
- In old age, a person's life expectancy strongly depends on the amount of oxygen that can be used. When the
- mitochondria can't use oxygen vigorously, cells must depend on inefficient glycolysis for their energy.
- </p>
- <p>
- Estrogen activates the glycolytic pathway, while interfering with mitochondrial respiration. This resembles
- the aged or stressed metabolism, in which lactic acid is produced instead of carbon dioxide.
- </p>
-
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- If we didn't eat linoleic acid and the other so-called "essential fatty acids," we would produce large
- amounts of the "Mead acid," n-9 eicosatrienoic acid, and its derivatives. This acid in itself is
- antiinflammatory, and its derivatives have a variety of antistress actions. The universal toxicity of the
- polyunsaturated fats that suppress the Mead fats as they accumulate, and the remarkable vitality of the
- animals that live on a diet deficient in the essential fatty acids, indicate that the Mead fats are
- important factors in the stability of our mammalian tissues. This protective lipid system probably interacts
- with cellular proteins, modifying the way they bind water and carbon dioxide and ions, affecting their
- electrons and their chemical reactivity.
- </p>
- <p>
- If salicylic acid and the structurally similar antiinflammatories, local anesthetics, muscle relaxants,
- expectorants, and antihistamines, act as surrogates for the absent Mead acid family, and thereby act as
- defenses against all the toxic effects of the unstable fats, it would explain the breadth and apparent
- coherence of their usefulness. And at the same time it explains some of the ways that estrogen goes out of
- control, when it exacerbates the toxicity of the accumulated unstable fats.
- </p>
- <p>
- 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.
- </p>
-
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
-
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- Aspirin, like progesterone or vitamin E, can improve fertility, by suppressing a prostaglandin, and
- improving uterine circulation.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
- <p>
- 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.
- </p>
-
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- glutamate, indicating preservation of neuronal integrity."
- </p>
-
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- </p>
- <p>
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- significantly less in groups B and C than in group A (p < 0.01). Hyperconstriction induced by autacoids 1
- week after injury were significantly less in group B than in group A (p < 0.01) and were significantly
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- </p>
- <p>
- Proc Soc Exp Biol Med 1985 Feb;178(2):250-3. <strong>Salicylic acid blocks indomethacin-induced
- cyclooxygenase inhibition and lesion formation in rat gastric mucosa.</strong> Ligumsky M, Guth PH,
- Elashoff J, Kauffman GL Jr, Hansen D, Paulsen G. "Salicylic acid has been shown to decrease gastric mucosal
- lesions induced by indomethacin in the rat."
- </p>
- <p>
- Z Naturforsch [C] 2001 May-Jun; 56(5-6):455-63. <strong>Constant expression of cyclooxygenase-2 gene in
- prostate and the lower urinary tract of estrogen-treated</strong>
- <strong>male rats.</strong> Luo C, Strauss L, Ristimaki A, Streng T, Santti R.
- </p>
-
- <p>
- Neuropharmacology 2000 Apr 27;39(7):1309-18. <strong>Mechanisms of the neuroprotective effect of aspirin
- after oxygen and glucose deprivation in rat forebrain slices.</strong> Moro MA, De Alba J, Cardenas A,
- De Cristobal J, Leza JC, Lizasoain I, Diaz-Guerra MJ, Bosca L, Lorenzo P "Apart from its preventive actions
- against stroke due to its antithrombotic properties, recent data in the literature suggest that high
- concentrations of ASA also exert direct neuroprotective effects." "We have found that ASA inhibits neuronal
- damage at concentrations lower than those previously reported (0.1-0.5 mM), and that these effects correlate
- with the inhibition of excitatory amino acid release, of NF-kappaB translocation to the nucleus and iNOS
- expression caused by ASA." "Our results also show that the effects of ASA are independent of COX inhibition.
- Taken together, our present findings show that ASA is neuroprotective in an in vitro model of brain
- ischaemia at doses close to those recommended for its antithrombotic effects."
- </p>
- <p>
- Pediatrics 1987 Nov;80(5):638-42. <strong>A catch in the Reye.</strong> Orlowski JP, Gillis J, Kilham HA.
- </p>
-
- <p>
- Prostaglandins Leukot Med 1982 Jul;9(1):109-15. <strong>
- Effect of acetaminophen and salicylate on aspirin-induced inhibition of human platelet
- cyclo-oxygenase.</strong> Rao GH, Reddy KR, White JG. "Recent studies have shown that salicylic acid, a
- metabolite of aspirin, effectively competes for the same site on the platelet cyclo-oxygenase enzyme."
- </p>
- <p>
- Stroke 1997 Oct;28(10):2006-11. <strong>Acetylsalicylic acid increases tolerance against hypoxic and
- chemical hypoxia.</strong> Riepe MW, Kasischke K, Raupach A.
- </p>
- <p>
- Cancer Res 1998 Dec 1;58(23):5354-60. <strong>Prevention of NNK-induced lung tumorigenesis in A/J mice by
- acetylsalicylic acid and NS-398.</strong> Rioux N, Castonguay A
- </p>
-
- <p>
- J Endocrinol 1989 Jun;121(3):513-9. <strong>Indomethacin inhibits the effects of oestrogen</strong>
- <strong>
- in the anterior pituitary gland of the rat.</strong> Rosental DG, Machiavelli GA, Chernavsky AC,
- Speziale NS, Burdman JA.
- </p>
- <p>
- Int J Cancer 2001 Aug 15;93(4):497-506.<strong>
- Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration,
- invasiveness and angiogenesis.</strong> Rozic JG, Chakraborty C, Lala PK.
- </p>
- <p>
- Res Commun Mol Pathol Pharmacol 1998 Sep;101(3):259-68. <strong>Protective ability of acetylsalicylic acid
- (aspirin) to scavenge radiation induced free radicals in J774A.1 macrophage cells.</strong> Saini T,
- Bagchi M, Bagchi D, Jaeger S, Hosoyama S, Stohs SJ.
- </p>
-
- <p>
- Mol Cell Biochem 1999 Sep;199(1-2):93-102. <strong>
- Antioxidant properties of aspirin: characterization of the ability of aspirin to inhibit silica-induced
- lipid peroxidation, DNA damage, NF-kappaB activation, and TNF-alpha production.</strong> Shi X, Ding M,
- Dong Z, Chen F, Ye J, Wang S, Leonard SS, Castranova V, Vallyathan V
- </p>
- <p>
- J Physiol Paris 2001 Jan-Dec;95(1-6):51-7. <strong>Protection by aspirin of indomethacin-induced small
- intestinal damage in rats: mediation by salicylic acid.</strong> Takeuchi K, Hase S, Mizoguchi H,
- Komoike Y, Tanaka A. "Most of non-steroidal anti-inflammatory drugs (NSAIDs) except aspirin (ASA) produce
- intestinal damage in rats." "ASA did not provoke any damage, despite inhibiting (prostaglandin) PG
- production, and prevented the occurrence of intestinal lesions induced by indomethacin, in a dose-related
- manner."
- </p>
-
- <p>
- FASEB J 2001 Oct;15(12):2057-72. <strong>Cyclooxygenase-independent actions of cyclooxygenase</strong>
- <strong>
- inhibitors.</strong> Tegeder I, Pfeilschifter J, Geisslinger G.
- </p>
- <p>
- J Indian Med Assoc 1997 Feb;95(2):43-4, 47. <strong>Role of low dose aspirin in prevention of pregnancy
- induced hypertension.</strong> Tewari S, Kaushish R, Sharma S, Gulati N
- </p>
- <p>
- J Chromatogr B Biomed Appl 1995 Jul 21;669(2):404-7. <strong>Aspirin inhibits collagen-induced platelet
- serotonin release, as measured by microbore high-performance liquid chromatography with electrochemical
- detection.</strong> Tsai TH, Tsai WJ, Chen CF.
- </p>
-
- <p>
- Clin Exp Immunol 1991 Nov;86(2):315-21. <strong>Piroxicam, indomethacin</strong>
- <strong>
- and aspirin action on a murine fibrosarcoma.</strong> Effects on tumour-associated and peritoneal
- macrophages. Valdez JC, Perdigon G. "We also studied the effect on tumour development of three inhibitors of
- prostaglandin synthesis: indomethacin, piroxicam and aspirin. Intraperitoneal administration of these drugs
- during 8 d was followed by the regression of palpable tumours. Indomethacin (90 mg/d) induced 45%
- regression, while with piroxicam (two 400 mg/d doses and six 200 mg/d doses) and aspirin (1 mg/d) 32% and
- 30% regressions, respectively, were observed. The growth rate of nonregressing tumours, which had reached
- different volumes by the end of the treatment, was delayed to a similar extent by the three
- anti-inflammatory non-steroidal drugs (NSAID)."
- </p>
- <p>
- Int J Radiat Biol 1995 May;67(5):587-96. <strong>Amelioration of radiation nephropathy by acetylsalicylic
- acid.</strong> Verheij M, Stewart FA, Oussoren Y, Weening JJ, Dewit L.
- </p>
-
- <p>
- Semin Perinatol 1986 Oct;10(4):334-55. <strong>The role of arachidonic acid metabolites in
- preeclampsia.</strong> Walsh SW, Parisi VM.
- </p>
- <p>
- Proc Natl Acad Sci U S A 1999 Apr 27;96(9):5292-7. <strong>Suppression of inducible cyclooxygenase 2 gene
- transcription by aspirin and sodium salicylate.</strong> Xu XM, Sansores-Garcia L, Chen XM,
- Matijevic-Aleksic N, Du M, Wu KK. "Aspirin and sodium salicylate at therapeutic concentrations equipotently
- blocked COX-2 mRNA and protein levels induced by interleukin-1beta and phorbol 12-myristate 13-acetate."
- </p>
- <p>
- Hum Reprod 1994 Oct;9(10):1954-7. <strong>The benefits of low-dose aspirin therapy in women with impaired
- uterine perfusion during assisted conception.</strong>
-
- Wada I, Hsu CC, Williams G, Macnamee MC, Brinsden PR. "Higher pregnancy rates (47 versus 17%) were achieved
- in those taking aspirin from day 1 of HRT." "The addition of low-dose aspirin to a standard HRT protocol in
- women with impaired uterine perfusion is associated with improved blood flow and satisfactory pregnancy
- rates."
- </p>
- <p>
- J Ethnopharmacol 1991 Sep;34(2-3):215-9. <strong>Radiation-protective and platelet aggregation inhibitory
- effects of five traditional Chinese drugs and acetylsalicylic acid following high-dose
- gamma-irradiation.</strong>
- Wang HF, Li XD, Chen YM, Yuan LB, Foye WO.
- </p>
- <p>
- Fertil Steril 1997 Nov;68(5):927-30. <strong>Low-dose aspirin for oocyte donation recipients with a thin
- endometrium: prospective, randomized study.</strong> Weckstein LN, Jacobson A, Galen D, Hampton K,
- Hammel J. "Low-dose aspirin therapy improves implantation rates in oocyte donation recipients with a thin
- endometrium."
- </p>
-
- <p>
- Dermatologica 1978;156(2):89-96. <strong>Effect of topical salicylic acid on animal epidermopoiesis.</strong
- > Weirich EG, Longauer JK, Kirkwood AH. In contrast to its antihyperplastic effect on pathological
- proliferation of the epidermis, salicylic acid promotes epidermopoiesis in the normal guinea pig skin. After
- the application of 1% w/w salicylic acid in acetone-ethanol for 4 weeks, the thickness of the surface
- epithelium was increased by 40% and that of the deep epithelium by 19%. The mitotic index rose by 17%.
- </p>
- <p>
- Arch Exp Veterinarmed 1981;35(3):465-70. <strong>[Control of implantation in rats and sows by peroral
- administration of prostaglandin synthetase inhibitors. 2. Effects of prostaglandin F2 alpha,
- progesterone/estrone, and acetylsalicylic acid on implantation and various biochemical parameters of
- amniotic fluid in the rat]</strong> Wollenhaupt K, Steger H. "The highest number of normally developed
- (97 per cent) and the lowest number of degenerated foetuses (three per cent) were recorded following
- acetylsalicylic acid treatment, as compared to the control group (91 and nine per cent)."
- </p>
- <p>
- Biomed Pharmacother 1999 Aug;53(7):315-8. <strong>Aspirin induced apoptosis in gastric cancer cells.</strong
- > Wong BC, Zhu GH, Lam SK
- </p>
-
- <p>
- Scand J Immunol 2000 Oct;52(4):393-400. <strong>Tamoxifen decreases renal inflammation and alleviates
- disease severity in autoimmune NZB/W F1 mice.</strong> Wu WM, Lin BF, Su YC, Suen JL, Chiang BL. "It has
- been documented that sex hormone may play a role in the pathogenesis of murine lupus."
- </p>
- <p>
- Science 2001 Aug 31;293(5535):1673-7. <strong>Reversal of obesity- and diet-induced insulin resistance with
- salicylates or targeted disruption of Ikkbeta.</strong> Yuan M, Konstantopoulos N, Lee J, Hansen L, Li
- ZW, Karin M, Shoelson SE.
- </p>
- <p></p>
- <hr />
- <p>
- <strong><em>Since the 1970s, aspirin has been thought of as an inhibitor of prostaglandin synthesis, but
- that is only part of its effect. Sometimes its effect is the opposite of the effects of other
- prostaglandin inhibitors.</em></strong>
- </p>
- <p>
- <strong><em>It protects against the harmful effects of estrogen, prolactin, serotonin, cortisol, histamine,
- and radiation (u.v., x-rays, gamma rays).</em></strong>
- </p>
-
- <p>
- <strong><em>It prevents cancer, and can cause its regression. It inhibits vascular proliferation. It
- inhibits interleukin 6 (and other inflammatory cytokines), which is a factor in heart disease and
- breast and liver cancer.</em></strong>
- </p>
- <p>
- <strong><em>It protects the brain, and can improve learning. It's an antioxidant, prevents cataracts, and
- protects against glycation in diabetes.
- </em></strong>
- </p>
- <p>
- <strong><em>It prevents premature birth and prevents birth defects caused by diabetes, preeclampsia, and
- exposure to alcohol. It prevents recurrence of neural tube defects and protects against many of the
- gestational problems associated with lupus.</em></strong>
- </p>
- <p>
- <strong><em>Although aspirin protects against uncontrolled cell proliferation, as in cancer and psoriasis,
- salicylic acid increases normal cell division in the skin.</em></strong>
- </p>
- <p>
- <strong><em>Aspirin protects against many forms of shock and stess, and corrects imbalances in the nervous
- system.</em></strong>
- </p>
- <p><strong><em>It protects against several kinds of toxins involved in brain degeneration.</em></strong></p>
-
- <p>
- <strong><em>"Aspirin elevated ATP levels not only in intact cortical neurons but also in isolated brain
- mitochondria, an effect concomitant with an increase in NADH-dependent respiration by brain
- submitochondrial particles."</em></strong>
- </p>
- <p>
- <strong><em>
- De Cristobal, et al., 2002</em></strong>
- </p>
- <p>
- <strong><em>"The pharmacological action of salicylate cannot be explained by its inhibition of
- cyclooxygenase (COX) activity." ". . . salicylate exerts its antiinflammatory action in part by
- suppressing COX-2 induction. . . ." XM Xu, et al., 1999</em></strong>
- </p>
-
- <p>© Ray Peat 2006. All Rights Reserved. www.RayPeat.com</p>
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