Acetylsalicylic Acid

Brand Names: Anacin, Arthritis Foundation Safety Coated Aspirin, Asriptin, Bayer Aspirin, Bayer Children's Aspirin, Bufferin, Ecotrin, Excedrin, and many others

Clinical Names: Aspirin, Acetylsalicylic Acid

Summary

generic name: Acetylsalicylic acid

synonym: Aspirin

trade names: Common sources of aspirin include Anacin®, Arthritis Foundation Safety Coated Aspirin, Asriptin®, Bayer® Aspirin, Bayer Children's Aspirin, Bufferin®, Ecotrin®, Excedrin®, and many others.

type of drug: Nonsteroidal anti-inflammatory.

used to treat: Inflammation, pain and fever; long-term use of aspirin in low-doses is also used to reduce the risk of heart disease and stroke.

overview of interactions:
• nutrient affected by drug: Folic Acid

• nutrient affected by drug: Vitamin C

• nutrient affected by drug: Iron

• nutrient affected by drug: Potassium

• substance affected by drug: Alcohol

• herb affecting drug toxicity: Glycyrrhiza glabra (Licorice)

• herb/nutrient affecting drug toxicity: Capsicum (Cayenne)

• herb group affecting drug performance and toxicity: Platelet Interactors



Interactions

nutrient affected by drug: Folic Acid

• mechanism: The use of aspirin is associated with increased urinary excretion and reduced blood levels of folate, particularly in rheumatoid patients and those with arthritis.
(Buist RA. Intl Clin Nutr Rev 1984;4(3):114; Alter HJ, et al. Blood 197138:405-416; Lawrence VA, et al. J Lab Clin Med 1984 Jun;103(6):944-948.)

• nutritional support: Even though the clinical significance of this process remains unclear, individuals who take aspirin regularly would most likely benefit from supplementing with 400 mcg of folic acid per day. This amount of folate is easily available in a multivitamin formula.

nutrient affected by drug: Vitamin C

• mechanism: The use of aspirin is associated with increased excretion of vitamin C through the urine to such a degree that vitamin C depletion can result.
(Coffey G, Wilson CWM. Br Med J. 1975 Jan 25;1(5951):208; Daniels A, Everson GJ. Proc Soc Exp Biol Med. 35:20-24, 1936-1937.)

• nutritional support: Even though the clinical significance of this process remains unclear, individuals who take aspirin regularly would most likely benefit from supplementing with at least a few hundred milligrams of vitamin C per day as a counterbalance. A multivitamin formula may be an adequate source of vitamin C at this level.

nutrient affected by drug: Iron

• mechanism: Gastrointestinal bleeding is a universal and virtually unavoidable side effect of taking aspirin. It can cause ulcerations, abdominal burning, pain, cramping, nausea, gastritis, and even serious gastrointestinal bleeding and liver toxicity. Sometimes, stomach ulceration and bleeding can occur without any abdominal pain. Black tarry stools, weakness, and dizziness upon standing may be the only signs of internal bleeding. Often there are no externally observable symptoms or obvious blood in the stool. Gastrointestinal bleeding caused by aspirin causes iron loss, which can create a state of iron deficiency if aspirin is taken regularly.
(Leonards JR, et al. N Engl J Med. 1973 Nov 8;289(19):1020-1022.)

• nutritional support: Chronic aspirin ingestion is a frequent cause of iron deficiency and anemia. Anyone who is fatigued should consider whether they might be suffering from the side effects of aspirin and if they might be taking an iron supplement. Nevertheless, supplementing with iron may not be necessary or appropriate until iron deficiency has been determined. Laboratory tests can determine if iron deficiency anemia exists. Only when such tests show deficiency should iron be supplemented. At that point the various methods of restoring the body's healthy levels of iron can be considered and an appropriate method of supplementing iron agreed upon with your healthcare provider.

nutrient affected by drug: Potassium

• mechanism: High doses of aspirin can result in hypokalemia.
(Smith MJH, Smith PK, eds. 1966.)

substance affected by drug: Alcohol

• mechanism: Alcohol absorption can be enhanced by taking aspirin before drinking.

• dietary concerns: The combined use of alcohol and aspirin should be avoided.

herb affecting drug toxicity: Glycyrrhiza glabra (Licorice)

• mechanism: DGL (deglycyrrhizinated licorice) is a concentrated extract of licorice root containing flavonoids that are especially effective in countering the irritating effects aspirin has on the stomach and intestines.
Note: The licorice has been "deglycyrrhizinated" because use of the whole root can induce high blood pressure in some individuals with extended use.

• research: One study found that when 350 mg of chewable DGL was taken at the same time as each dose of aspirin gastrointestinal, bleeding caused by the aspirin was significantly reduced.
(Rees WDW, et al. Scand J Gastroenterol 1979;14:605-607.)

DGL also helps to heal mucous membranes and repair ulcers throughout the stomach and intestines, including those due to aspirin or other nonsteroidal anti-inflammatory drugs, such as indomethacin.
(Morgan AG, et al. Gut 1982,23:545-551; Morgan AG, et al. Gut 1985 Jun;26(6):599-602.)

• herbal synergy: According to one animal study, the combined action of DGL and Tagamet together was more effective in preventing harmful effects of aspirin than either medicine alone.
(Bennett A, et al. J Pharm Pharmacol 1980;32:151.)

herb/nutrient affecting drug toxicity: Capsicum (Cayenne)

• mechanism: Capsaicin is a key constituent of cayenne known for its potent effect on special neurons found in the stomach lining.

• research: Studies using rats found that capsaicin stimulated these nerves in the stomach lining in a way that reduced the harmful effects of aspirin in the stomach. After conducting a human trial Yeoh et al concluded that eating 20 grams of Cayenne peppers before taking aspirin could protect against gastroduodenal mucosal injury and ulcer formation.
(Abdel Salam OMB, et al. Pharmacol Res 1995;32:209-215; Holzer P, et al. Gastroenterol 1989;96:1425-1433; Yeoh KG, et al. Dig Dis Sci 1995;40:580-583; Teng CH, et al. J Gastroenterol Hepatol. 1998 Oct;13(10):1007-1014.)

• nutritional support: Despite this supportive evidence it would be wise to consult a healthcare provider trained in herbal medicine before relying on cayenne peppers or extracts to counteract the effects of frequent or excessive use of aspirin.

herb group affecting drug performance and toxicity: Platelet Interactors

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.

References

Abdel Salam OMB, Moszik O, Szolcsanyi J. Studies on the effect of intragastric capsaicin on gastric ulcer and on the prostacyclin-induced cytoprotection in rats. Pharmacol Res 1995 Oct;32(4):209-215.
Abstract: The effect of intragastric (i.g.) capsaicin on experimental gastric ulcer was studied in the 1 h pylorus-ligated rats. Capsaicin applied in 40 ng ml-1 concentration (0.1 microgram kg-1) protected against gastric mucosal injury evoked by i.g. application of acidified aspirin, 96% ethanol or 0.6 M HCl. After a capsaicin concentration of 400 micrograms ml-1 (1 mg kg-1) protection occurred initially, while several hours later mucosal damage evoked by acidified aspirin was enhanced. Capsaicin in 2 and 6 ml kg-1 (10 and 30 mg kg-1) invariably aggravated the aspirin and ethanol-induced gastric mucosal damage. Capsaicin in 0.1 microgram kg-1 did not modify the mucosal protective action of prostacyclin (5 micrograms kg-1) on gastric mucosal injury produced by i.g. application of acidified aspirin, 96% ethanol or 0.6 M HCl. Local capsaicin desensitization induced by application of capsaicin in 2 mg ml-1 (10 mg kg-1) did not interfere with the mucosal cytoprotective effects of prostacyclin against ethanol and aspirin-induced mucosal damage. It is concluded that i.g. capsaicin exerts a dual dose-dependent effect on development of experimental gastric ulcer. Neither i.g. capsaicin in small doses nor local capsaicin desensitization modify the mucosal cytoprotective effects of prostacyclin.

Alter HJ, Zvaifler MJ, Ruth CE. Interrelationship of rheumatoid arthritis, folic acid and aspirin. Blood 1971 Oct;38(4):405-416.

Bennett A, Clark-Wibberley T, Stamford IF, Wright JE. Aspirin-induced gastric mucosal damage in rats: Cimetidine and deglycyrrhizinated liquorice together give greater protection than low doses of either drug alone. J Pharm Pharmacol 1980 Feb;32(2):151.

Buist RA. Drug-nutrient interactions - an overview. Intl Clin Nutr Rev 1984;4(3):114. (Review)

Coffey G, Wilson CWM. Ascorbic acid deficiency and aspirin-induced haematemesis. Br Med J. 1975 Jan 25;1(5951):208. (Letter)

Daniels A, Everson GJ. Influence of acetylsalicylic acid (aspirin) on urinary excretion of ascorbic acid. Proc Soc Exp Biol Med. 35:20-24, 1936-1937.

Lawrence VA, Loewenstein JE, Eichner ER. Aspirin and folate binding: in vivo and in vitro studies of serum binding and urinary excretion of endogenous folate. J Lab Clin Med 1984 Jun;103(6):944-948.
Abstract: To clarify the effect of aspirin on folate balance, we studied serum concentration, protein binding, and urinary excretion of endogenous folate. A healthy woman twice followed an 11-day protocol of constant diet, blood sampling twice daily, collection of all urine, and 650 mg of aspirin by mouth every 4 hours on the middle 3 days. As determined by equilibrium dialysis and Lactobacillus casei assay, aspirin induced a brisk, significant but reversible fall in total and bound serum folate and a small but insignificant rise in urinary folate excretion. Aspirin in vitro also displaced significant amounts of bound serum folate. Thus, aspirin in therapeutic doses can contribute to subnormal serum folate values, and if it increases urinary folate excretion even slightly, may impair folate balance.

Holzer P, Pabst MA, Lippe IT. Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa. Gastroenterol 1989 Jun;96(6):1425-1433.
Abstract: Previous work has indicated that capsaicin-sensitive afferent neurons are involved in gastric mucosal defense mechanisms. The present study investigated whether stimulation of these neurons by intragastric administration of capsaicin would protect against aspirin-induced mucosal damage in the luminally perfused rat stomach. Capsaicin (25-640 microM), administered together with acidified (pH 1.5) aspirin (25 mM), inhibited macroscopically visible lesion formation and gastric bleeding in a concentration-dependent fashion. Capsaicin (160 microM) also attenuated the aspirin-induced fall in the gastric potential difference. An inhibitory effect of capsaicin (160 microM) on aspirin-induced gastric injury was also seen by light and scanning electron microscopy. Aspirin alone caused a vast ablation of the gastric surface epithelium, resulting in exposure of the lamina propria. In the presence of capsaicin, the depth of mucosal injury, the area totally deprived of surface epithelial cells, and the severity of surface desquamation were diminished. As capsaicin is a selective stimulant of thin afferent neurons, it would appear that these neurons participate in mechanisms of gastric defense against aspirin injury. Prevention of hemorrhagic damage seems to be the primary effect of afferent nerve-mediated gastroprotection, although injury to the surface epithelium is also reduced to some degree.

Leonards JR, Levy G, Niemczura R. Gastrointestinal blood loss during prolonged aspirin administration. N Engl J Med. 1973 Nov 8;289(19):1020-1022.

Mazur W, et al. Antiplatelet therapy for treatment of acute coronary syndromes. Cardiol Clin. 1999 May;17(2):345-57, ix. (Review)
Abstract: Acute coronary syndromes and the postpercutaneous coronary intervention state share the common feature of atherosclerotic plaque disruption and subsequent intraluminal thrombus formation. In most cases, vascular patency is maintained but partial occlusion causes myocardial ischemia and can either progress to complete occlusion or result in distal embolization with subsequent small vessel obstruction, the core section of an intraarterial thrombus is platelet-rich and can serve as a nidus for further thrombosis. Aspirin, by virtue of its anticycloxygenase activity inhibits platelet activation and aggregation to a mild degree. Clinically, aspirin has been shown to reduce the rates of myocardial infarction in patients with acute coronary syndromes and to reduce the number of ischemic complications which follow coronary angioplasty. More potent inhibitors of platelet aggregation antagonize the interaction between the platelet surface protein GP IIb-IIIa and fibrinogen. The result is profound inhibition of platelet aggregation. Three intravenous antagonists of platelet GP IIb-IIIa are clinically available and a fourth is under phase III study. When used in addition to aspirin therapy, these agents have been shown to produce further reductions in either peri-interventional infarctions or in recurrent myocardial infarctions in patients with acute coronary syndromes.

Morgan AG, McAdam WAF, Pascoo C, Darnborough A. Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy. Gut 1982 Jun;23(6):545--551.
Abstract: One hundred patients with benign gastric ulceration were treated in a single-blind, endoscopically controlled trial to assess the relative efficacy of cimetidine (1 g daily) and Caved-S (six tablets daily). Ulcer healing was assessed after six weeks' treatment, and, if incomplete, after a further six weeks. There was no significant difference between the two drug regimens (approximately 63% at six weeks and 91% at 12 weeks). If an ulcer remains unhealed after 10 weeks' treatment the patient should undergo surgery. There was no difference in the relief of day pain between the two drug regimens but cimetidine was more effective over the first two weeks of treatment relieving night pain, than was Caved-S (p less than 0 . 02). After ulcer healing, drug dosage was reduced (cimetidine to 400 mg at night and Caved-S to two tablets twice daily). So far, 56 patients, 28 in each group, have completed the first year's maintenance treatment, and there have been four ulcer recurrences in each group (14%).

Morgan AG, Pacsoo C, McAdam WA. Maintenance therapy: a two year comparison between Caved-S and cimetidine treatment in the prevention of symptomatic gastric ulcer recurrence. Gut 1985 Jun;26(6):599-602.
Abstract: Eighty two patients with an endoscopically healed gastric ulcer, were treated for two years with either Caved-S tablets, two twice daily or cimetidine 400 mg at night. During the first year, 12% (four out of 34) of the Caved-S group and 10% (four out of 41) of the cimetidine group had an ulcer recurrence. By the end of the second year, the recurrence rate was 29% (nine out of 31) in the Caved-S group, and 25% (eight out of 32) for the cimetidine group. Ulcer relapse occurred frequently in patients with either a dyspeptic history of over six months (p less than 0.05), or a past history of a gastric ulcer (p less than 0.001). Ulcers recurred rapidly after maintenance therapy; Caved-S two out of 22; cimetidine seven out of 23, within four months (NS). This study shows that long term maintenance therapy is safe and reasonably effective. The high recurrence rate after stopping treatment suggests that therapy in high risk or elderly patients should be for life.

Okumura H, Takayama K, Obayashi K, Ichikawa T, Aramaki T. [Chronic toxic hepatitis caused by aspirin]. Nippon Rinsho. 1965 Aug;23(8):1633-1636. [Article in Japanese]

Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol 1979;14(5):605-607.
Abstract: Gastric mucosal damage induced by giving 60 mg aspirin orally to rats was reduced by simultaneous administration of 100-500 mg deglycyrrhizinated liquorice. Human faecal blood loss induced by 975 mg aspirin orally three times a day was less when 350 mg deglycyrrhizinated liquorice was given with each dose of aspirin.

Smith MJH, Smith PK, eds. The Salicylates: A Critical Bibliographic Review. New York: Interscience, 1966.

Teng CH, Kang JY, Wee A, Lee KO. Protective action of capsaicin and chilli on haemorrhagic shock-induced gastric mucosal injury in the rat. J Gastroenterol Hepatol. 1998 Oct;13(10):1007-1014.
Abstract: Chilli and its pungent ingredient, capsaicin, have been shown to protect against experimental gastric mucosal injury induced by various necrotizing agents such as ethanol and aspirin and stress. We investigated the effect of capsaicin and long-term ingestion of chilli on haemorrhagic shock-induced gastric mucosal injury in the rat. Anaesthetized male Sprague-Dawley rats were subjected to haemorrhagic shock by withdrawing blood to reduce the mean arterial blood pressure to 30-40 mmHg with subsequent reinfusion of shed blood. This resulted in gastric mucosal injury with readily identifiable haemorrhagic lesions. Capsaicin (5 mg) administered prior to, but not after, haemorrhagic shock, significantly reduced the gastric mucosal injury in intact animals. Sensory ablation with capsaicin pretreatment (125 mg/kg bodyweight) abolished the gastroprotective effect afforded by capsaicin. Similarly, 4 week intake of chilli powder (360 mg daily) reduced the gastric mucosal injury in intact, but not in capsaicin-desensitized rats. Capsaicin and long-term chilli intake protected against haemorrhagic shock-induced gastric mucosal injury and the protection may be mediated by capsaicin-sensitive afferent neurons. Our studies are of potential significance in the context of stress ulcer disease in the human.

Yeoh KG, Kang JY, Yap I, Guan R, Tan CC, Wee A, Teng CH. Chili protects against aspirin-induced gastroduodenal mucosal injury in humans. Dig Dis Sci. 1995 Mar;40(3):580-583.
Abstract: Capsaicin, the pungent ingredient of chili, has a gastroprotective effect against experimental gastric mucosal injury in animals. Such an effect has not, however, been documented in humans to date. Eighteen healthy volunteers with normal index endoscopies underwent two studies four weeks apart. Each subject took 20 g chili orally with 200 ml water in one study and 200 ml water in another study. In each case this was followed half an hour later by 600 mg aspirin BP with 200 ml water. Endoscopy was repeated 6 hr later. Gastroduodenal mucosal damage was assessed by a previously validated scoring system. The median gastric injury score after chili was 1.5 compared to 4 in the control group (P < 0.05), demonstrating a gastroprotective effect of chili in human subjects.