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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. 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. 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. Reduced blood levels of the vitamin have also been reported in people with arthritis who take aspirin. 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. 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).

Propoxyphene may cause gastrointestinal (GI) upset. Propoxyphene-containing products may be taken with food to reduce or prevent GI upset. A common side effect of narcotic analgesics is constipation. Increasing dietary fiber (especially vegetables and whole-grain foods) and water intake can ease constipation.

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. 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. 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. DGL has been shown in controlled human research to be as effective as drug therapy (cimetidine) in healing stomach ulcers. 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.

There have been two case reports suggesting a possible interaction between ginkgo Ginkgo biloba and an anticoagulant drug or aspirin leading to increased bleeding. 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.

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. 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). 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.