Proton Pump Inhibitors
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Proton Pump Inhibitors

These drugs are the most powerful medications for reducing stomach acid levels; in fact, they almost completely shut down the stomach's ability to produce acid. (Their science fiction–sounding name comes from the last stage of the acid-secreting process, called the "proton pump.") Proton pump inhibitors are used for ulcers as well as for the treatment of moderate to severe esophageal reflux, commonly known as heartburn.

Drugs in this family include lansoprazole (Prevacid), omeprazole (Prilosec), and others.

St. John's Wort

Possible Harmful Interactions

The herb St. John's wort is known to interact with numerous drugs. There are two potential harmful interactions between St. John's wort and proton pump inhibitors.

One study found that use of St. John's wort greatly decreases levels of omeprazole in the body. 13 This would be expected to lead to markedly reduced efficacy.

The other potential risk is more theoretical. When taken to excess, the herb St. John's wort can cause an increased risk of sunburn. Some evidence hints that proton pump inhibitors might increase this risk. 12

Vitamin B12

Supplementation Likely Helpful

Vitamin B12 deficiency is a concern with the use of all drugs that reduce stomach acidity.

In food, vitamin B12 is always accompanied by proteins, and it must be separated from them before it can begin to be absorbed. Following separation, B12 is then attached to a substance called intrinsic factor, which allows B12 to be absorbed in the intestines.

Stomach acid plays a role in this separation. If you don't have enough stomach acid, the process of freeing vitamin B12 from protein so that it can be bound to intrinsic factor may be impaired.1,2

Studies suggest that treatment with proton pump inhibitors might significantly reduce the absorption of vitamin B12 . 3,4,5

Interestingly, there is some evidence that cranberry juice might increase B12 absorption in individuals taking proton pump inhibitors, 6 possibly because the juice is somewhat acidic.


Supplementation Possibly Helpful

Research on related medications suggests that proton pump inhibitors may slightly reduce the body's absorption of folate. 7 The decrease in folate absorption should be quite small, but since folate deficiency is quite common and potentially harmful, taking extra folate might make sense as insurance.


Supplementation Possibly Helpful

By reducing stomach acid levels, proton pump inhibitors might interfere with the absorption of iron , zinc , and perhaps other minerals. 8-11 Taking mineral supplements to meet the US Dietary Reference Intake (formerly known as the Recommended Dietary Allowance) levels for these nutrients should help.


1.   Streeter AM, et al. Cimetidine and malabsorption of cobalamin. Dig Dis Sci 1982;27:13-16.

2.   Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H2-receptor antagonists. Med Toxicol Adverse Drug Exp. 1988;3:430-448.

3.   Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr 1994;13:584-591.

4.   Marcuard SP, et al. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med 1994;120:211-215.

5.   Shils M, et al. (eds.). Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams and Wilkins, 1999: 1634.

6.   Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr. 1194;13:584-591.

7.   Russell RM, Golner BB, Krasinski SD, et al. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med. 1988;112:458-463.

8.   D'Arcy PF and McElnay JC. Drug interactions in the gut involving metal ions. Rev Drug Metabol Drug Interact. 1985;83:2-3.

9.   Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc. 1985;44:124.

10.   Sturniolo GC, et al. Inhibition of gastric acid secretion reduces zinc absorption in man. J Am Coll Nutr. 1991;4:372-375.

11.   Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H 2-receptor antagonists. Med Toxicol Adverse Drug Exp. 1988;3:430-448.

12.   Mirossay A, Mirossay L, Tothova J, et al. Potentiation of hypericin and hypocrellin-induced phototoxicity by omeprazole. Phytomedicine. 1999;6:311-317.

13.   Wang LS, Zhou G, Zhu B, et al. St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther. 2004;75:191-197.

Last reviewed October 2007 by EBSCO CAM Review Board

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.