In 205 healthy postmenopausal women, caffeine consumption (three cups of coffee per day) was associated with bone loss in women with calcium intake of less than 800 mg per day.1 In a group of 980 postmenopausal women, lifetime caffeine intake equal to two cups of coffee per day was associated with decreased bone density in those who did not drink at least one glass of milk daily during most of their life.2 However, in 138 healthy postmenopausal women, long-term dietary caffeine (coffee) intake was not associated with bone density.3 Until more is known, postmenopausal women should limit caffeine consumption and consume a total of approximately 1,500 mg of calcium per day (from diet and supplements).
Gastrointestinal (GI) bleeding is a common side effect of taking aspirin. A person with aspirin-induced GI bleeding may not always have symptoms (like stomach pain) or obvious signs of blood in their stool. Such bleeding causes loss of iron from the body. Long-term blood loss due to regular use of aspirin can lead to iron-deficiency anemia. Lost iron can be replaced with iron supplements. Iron supplementation should be used only in cases of iron deficiency verified with laboratory tests.
Taking aspirin has been associated with increased loss of vitamin C in urine and has been linked to depletion of vitamin C.4 People who take aspirin regularly should consider supplementing at least a few hundred milligrams of vitamin C per day. Such an amount is often found in a multivitamin.
Intake of 3 grams of aspirin per day has been shown to decrease blood levels of zinc.5 Aspirin appeared to increase loss of zinc in the urine in this study, and the effect was noted beginning three days after starting aspirin.
Increased loss of folic acid in urine has been reported in rheumatoid arthritis patients.6 Reduced blood levels of the vitamin have also been reported in people with arthritis who take aspirin.7 Some doctors recommend for people with arthritis who regularly take aspirin to supplement 400 mcg of folic acid per day—an amount frequently found in multivitamins.
In a study of people hospitalized with heart disease, those who had been taking aspirin were nearly twice as likely as nonusers to have a low or marginally low blood level of vitamin B12.8 That finding by itself does not prove that taking aspirin causes vitamin B12 deficiency. However, aspirin is known to damage the stomach in some cases, and the stomach plays a key role in vitamin B12 absorption (by secreting hydrochloric acid and intrinsic factor).
Silymarin is a collection of complex flavonoids found in milk thistle (Silybum marianum) that has been shown to elevate liver glutathione levels in rats.10 Acetaminophen can cause liver damage, which is believed to involve glutathione depletion.11 In one study involving rats, silymarin protected against acetaminophen-induced glutathione depletion.12 While studies to confirm this action in humans have not been conducted, some doctors recommend silymarin supplementation with 200 mg milk thistle extract, containing 70–80% silymarin, three times per day for people taking acetaminophen in large amounts for more than one year and/or with other risk factors for liver problems.
Cayenne (Capsicum annuum, Capsicum frutescens) contains the potent chemical capsaicin, which acts on special nerves found in the stomach lining. In two rat studies, researchers reported that stimulation of these nerves by capsaicin might protect against the damage aspirin can cause to the stomach.13 , 14 In a study of 18 healthy human volunteers, a single dose of 600 mg aspirin taken after ingestion of 20 grams of chili pepper was found to cause less damage to the lining of the stomach and duodenum (part of the small intestine) than aspirin without chili pepper.15 However, cayenne may cause stomach irritation in some individuals with stomach inflammation (gastritis) or ulcers and should be used with caution.
The flavonoids found in the extract of licorice (Glycyrrhiza glabra) known as DGL (deglycyrrhizinated licorice) are helpful for avoiding the irritating actions aspirin has on the stomach and intestines. One study found that 350 mg of chewable DGL taken together with each dose of aspirin reduced gastrointestinal bleeding caused by the aspirin.16 DGL has been shown in controlled human research to be as effective as drug therapy (cimetidine) in healing stomach ulcers.17 One animal study also showed that DGL and the acid-blocking drug Tagamet® (cimetidine) work together more effectively than either alone for preventing negative actions of aspirin.18
Food, especially foods high in pectin (including jellies), carbohydrates, and many types of cruciferous vegetables (broccoli, Brussels sprouts, cabbage, and others) can interfere with acetaminophen absorption.19 It is unclear how much effect this interaction has on acetaminophen activity.
One small study found that hibiscus could decrease levels of acetaminophen if the drug was taken after the tea was consumed though it was not entirely clear if the decreases were clinically significant.20
Food, especially foods high in pectin (including jellies), carbohydrates, and many types of cruciferous vegetables (broccoli, Brussels sprouts, cabbage, and others) can interfere with acetaminophen absorption.21 It is unclear how much effect this interaction has on acetaminophen activity.
Until 2004, many herbal weight loss and quick energy products combined caffeine or caffeine-containing herbs with ephedra. This combination may lead to dangerously increased heart rate and blood pressure and should be avoided by people with heart conditions, hypertension, diabetes, or thyroid disease.23
Caffeine is found in coffee, tea, soft drinks, and chocolate. To reduce side effects, people taking caffeine-containing drug products should limit their intake of caffeine-containing foods/beverages.
There have been two case reports suggesting a possible interaction between ginkgo Ginkgo biloba and an anticoagulant drug or aspirin leading to increased bleeding.24 , 25 In the first, a 78-year-old woman taking warfarin developed bleeding within the brain following the concomitant use of ginkgo (the amount used is not given in the case report). In the second, a 70-year-old man developed slow bleeding behind the iris of the eye (spontaneous hyphema) following use of ginkgo (80 mg per day) together with aspirin (325 mg per day). While this interaction is unproven, anyone taking anticoagulant medications or aspirin should inform their physician before using ginkgo.
Hospitals use oral and intravenous NAC to treat liver damage induced by acetaminophen overdose poisoning.26 NAC is often administered intravenously by emergency room doctors. Oral NAC appears to be effective for acetaminophen toxicity.
An uncontrolled trial compared intravenous NAC with oral NAC in children with acetaminophen poisoning and found that both methods were equally effective in reversing acetaminophen-induced liver toxicity.27 However, acetaminophen toxicity is a potential medical emergency, and should only be managed by qualified healthcare professionals.
Although vitamin E is thought to act like a blood thinner, very little research has supported this idea. In fact, a double-blind trial found that very high amounts of vitamin E do not increase the effects of the powerful blood-thinning drug warfarin.28 Nonetheless, a double-blind study of smokers found the combination of aspirin plus 50 IU per day of vitamin E led to a statistically significant increase in bleeding gums compared with taking aspirin alone (affecting one person in three versus one in four with just aspirin).29 The authors concluded that vitamin E might, especially if combined with aspirin, increase the risk of bleedings.
There are theoretical grounds to believe that coleus (Coleus forskohlii) could increase the effect of anti-platelet medicines such as aspirin, possibly leading to spontaneous bleeding. However, this has never been documented to occur. Controlled human research is needed to determine whether people taking aspirin should avoid coleus.
Guaraná (Paullinia cupana) is a plant with a high caffeine content. Combining caffeine drug products and guaraná increases caffeine-induced side effects.
Gomisin A is a constituent found in the Chinese herb schisandra (Schisandra chinensis). In a study of rats given liver-damaging amounts of acetaminophen, gomisin A appeared to protect against some liver damage but did not prevent glutathione depletion30 (unlike milk thistle, as reported above). Studies have not yet confirmed this action in humans.
Taking 3 grams vitamin C with acetaminophen has been shown to prolong the amount of time acetaminophen stays in the body.31 This theoretically might allow people to use less acetaminophen, thereby reducing the risk of side effects. Consult with a doctor about this potential before reducing the amount of acetaminophen. However, increasing the time acetaminophen is in the body might also theoretically increase its toxicity. Consult with a doctor before taking vitamin C along with acetaminophen.32
1. Harris SS, Dawson-Hughes B. Caffeine and bone loss in healthy postmenopausal women. Am J Clin Nutr 1994;60:573–8.
2. Barrett-Connor E, Chang JC, Edelstein SL. Coffee-associated osteoporosis offset by daily milk consumption. The Rancho Bernardo Study. JAMA 1994;271:280–3.
3. Lloyd T, Rollings N, Eggli DF, et al. Dietary caffeine intake and bone status of postmenopausal women. Am J Clin Nutr 1997;65:1826–30.
4. Coffey G, Wilson CWM. Ascorbic acid deficiency and aspirin-induced haematemesis. BMJ 1975;I:208.
5. Ambanelli U, Ferraccioli GF, Serventi G, Vaona GL. Changes in serum and urinary zinc induced by ASA and indomethacin. Scand J Rheumatol 1982;11:63–4.
6. Buist RA. Drug-nutrient interactions—an overview. Intl Clin Nutr Rev 1984;4(3):114 [review].
7. Alter HJ, Zvaifler MJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid and aspirin. Blood 1971;38:405–16.
8. Van Oijen MGH, Laheij RJF, Peters WHM, et al. Association of aspirin use with vitamin B12 deficiency (results of the BACH study). Am J Cardiol 2004;94:975–7.
9. Endo H, Higurashi T, Hosono K, et al. Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled study. J Gastroenterol 2011;46:894–905.
10. Valenzuela A, Aspillaga M, Vial S, Guerra R. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 1989;55:420–2.
11. Threlkeld DS, ed. Central Nervous System Drugs, Acetaminophen. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1997, 247–f.
12. Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 1989;55:417–9.
13. Abdel Salam OME, Mószik G, Szolcsányi J. Studies on the effect of intragastric capsaicin on gastric ulcer and on the prostacyclin-induced cytoprotection in rats. Pharmacol Res 1995;32:209–15.
14. Holzer P, Pabst MA, Lippe IT. Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa. Gastroenterology 1989;96:1425–33.
15. Yeoh KG, Kang JY, Yap I, et al. Chili protects against aspirin-induced gastroduodenal mucosal injury in humans. Dig Dis Sci 1995;40:580–3.
16. Rees WDW, Rhodes J, Wright JE, et al. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol 1979;14:605–7.
17. 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;23:545–51.
18. Bennett A, Clark-Wibberley T, et al. 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;32:151.
19. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.
20. Kolawole JA, Maduenyi A. Effect of zobo drink (Hibiscus sabdariffa water extract) on the pharmacokinetics of acetaminophen in human volunteers. Eur J Drug Metab Pharmacokinet 2004;29:25–9.
21. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.
22. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.
23. Tyler VE. Herbs of Choice: The Therapeutic Use of Phytomedicinals. New York, Pharmaceutical Press, 1994, 88–9.
24. Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage [letter]. Neurology 1998;50:1933.
25. Rosenblatt M, Mindell J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract [letter]. N Engl J Med 1997;336:1108.
26. Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet 1995;346:547–52.
27. Perry HE, Shannon MW. J Pediatr 1998;132:149–52.
28. Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol 1996;77:545–6.
29. Liede KE, Haukka JK, Saxén LM, Heinon OP. Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid. Ann Med 1998;30:542–6.
30. Yamada S, Murawaki Y, Kawasaki H. Preventive effect of gomisin A, a lignan component of schizandra fruits, on acetaminophen-induced hepatotoxicity in rats. Biochem Pharmacol 1993;46:1081–5.
31. Houston JB, Levy G. Drug biotransformation interactions in man. VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218–21.
32. FDA Information on Acetaminophen, Jan 13, 2011. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm
Last Review: 05-01-2013
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