Aluminum hydroxide may increase urinary and stool loss of calcium.¹ Also, aluminum is a toxic mineral, and a limited amount of aluminum absorption from aluminum-containing antacids does occur.² As a result, most doctors do not recommend routine use of aluminum-containing antacids.³ Other types of antacids containing calcium or magnesium instead of aluminum are available.

Folic acid is needed by the body to utilize vitamin B12 . Antacids, including sodium bicarbonate, inhibit folic acid absorption.⁴ People taking antacids are advised to supplement with folic acid.

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.

Depletion of phosphorus may occur as a result of taking aluminum hydroxide. For those with kidney failure, reducing phosphorus absorption is the purpose of taking the drug, as excessive phosphorus levels can result from kidney failure. However, when people with normal kidney function take aluminum hydroxide for extended periods of time, it is possible to deplete phosphorus to unnaturally low levels.

Taking aspirin has been associated with increased loss of vitamin C in urine and has been linked to depletion of vitamin C.⁶ 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.⁷ Aspirin appeared to increase loss of zinc in the urine in this study, and the effect was noted beginning three days after starting aspirin.

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 B12.¹¹ 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).

A thick gel derived from algae has been used together with aluminum antacids to treat heartburn. Together, alginate gel and antacid were more effective at relieving symptoms¹² and improving healing.¹³ Alginate is believed to work by physically blocking stomach acid from touching the esophagus. According to these studies, two tablets containing 200 mg alginic acid should be chewed before each meal and at bedtime.

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.^{14 , 15} 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.¹⁶ 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.¹⁷ DGL has been shown in controlled human research to be as effective as drug therapy ( cimetidine ) in healing stomach ulcers .¹⁸ 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.¹⁹

Several studies have shown that combination of citrate, either as calcium citrate supplements or from orange and lemon juice, with aluminum-containing antacids increases aluminum levels in the body.^{20 , 21 , 22} Calcium in forms other than calcium citrate has been shown to not increase aluminum absorption.²³ Drinking 7–10 ounces of orange juice provides sufficient citrate to be problematic.^{24 , 25} Intake of 950 mg calcium citrate greatly elevates aluminum absorption.²⁶ People with renal failure may be at particular risk of kidney damage due to elevated aluminum levels if they combine aluminum hydroxide with citrate.²⁷

There have been two case reports suggesting a possible interaction between ginkgo Ginkgo biloba and an anticoagulant drug or aspirin leading to increased bleeding.^{28 , 29} 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 .³⁰ 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).³¹ 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.