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The Downside of Acid-Blocking Drugs

By Jacob Schor, ND

HEARTBURN DRUGS are among the most widely prescribed medicines in the United States, accounting for more than $13 billion in annual sales.

New research on the side effects say that the money spent on acid-blocking drugs may be the least of the costs of using them.

Pay a few moments of attention to the drugs used to treat reflux disease and you are all but guaranteed your own stomachache. In the past few years, the drug maker AstraZeneca has spent a billion dollars to switch buyers from its old drug, Prilosec, which was about to go off-patent, to its newer version of the same drug, Nexium. While the switch was occurring, scientists were documenting a range of health risks caused by long-term use of these medications. They blame these drugs for increased risk of intestinal infection, pneumonia and hip fractures.

Background of the Purple Pill

Before talking about the medical side of this, we need a little business background. In 2000, Prilosec was the world's largest selling prescription drug, with annual sales of more than $6 billion. Sales of Prilosec accounted for 39 percent of AstraZeneca's income. Patent protection for Prilosec was set to expire in 2001. The loss of patent protection and the expected introduction of inexpensive, but equally effective generic competitors were obvious threats to AstraZeneca.

In anticipation of the patent expiration, AstraZeneca began an advertising campaign to transfer patients from Prilosec to Nexium, which became the most heavily advertised drug in the United States. Surely you remember the ads: "Today's purple pill is Nexium, from the makers of Prilosec." AstraZeneca priced Nexium slightly below Prilosec, gave discounts, stuffed doctors with free samples, and even offered discount coupons in newspapers. Estimates put the cost of this campaign between a quarter and a half billion dollars in 2001. The introduction and promotion of Nexium allowed AstraZeneca to prevent revenue loss. In 2003, although revenues from Prilosec slid to under $1 billion, Nexium sales were up worldwide to $3.9 billion.

Even when Prilosec did go OTC in 2004, they managed to keep up the sale of the prescription version at almost six times the cost by accidental shortages of the identical OTC version. A 2005 article in The New York Times reported, “A study by the University of Arkansas last year suggested that substituting Prilosec OTC for Nexium, Prevacid and other prescription heartburn drugs could cut spending on those medicines by about 50 percent, or almost $7 billion nationally – enough money to pay for health coverage for more than a million uninsured Americans.”1

Advertisements for those purple pills are still so ubiquitous that they crowd out any questions regarding their safety. Cynic that I am, my guess is that advertising revenues dissuade newspapers from reporting on the negative studies as they arise. Yet questions on drug safety are showing up repeatedly in the scientific literature. As much as the manufacturers may be overcharging for these drugs, this financial loss may be only a fraction of the real cost of people using these drugs. Acid-blocking drugs increase the risk for antibiotic-resistant infections, including gastritis, pneumonia, bone fractures and possibly cancer. Just because they are as common as M&Ms does not mean those purple pills are as safe.

Our bodies go to a great deal of trouble to make stomach acid, and they do so for good reason. Acid kills bacteria, viruses and molds before they can enter the body. Acid also converts the minerals in food into chemical forms we can absorb. In addition, acid is essential for digesting food so nutrients can be absorbed. It should come as little surprise that interfering with the process of making acid creates problems.

Although advertising would like to make you think Nexium is in a class of its own, it isn’t. Acid-blocker drugs are divided into two general drug groups. One group is the histamine-receptor antagonists and includes the drugs ranitidine (Zantac), cimetidine (Tagamet) and famotidine (Pepcid AC). The other and more potent group of drugs is called proton-pump inhibitors (PPIs) and includes omeprazole (Prilosec), pantoprazole (Protonix), lansoprazole (Prevacid) and rabeprazole (Aciphex). Nexium is also a proton-pump inhibitor. The important distinction when talking about these drugs is the drug type, not the individual brand name.

Antibiotics and Acid Suppression: A Bad Combination

Taking antibiotics can frequently cause intestinal upset. Taking them in combination with acid blockers compounds the problem. Antibiotics kill off bacteria in the intestines that normally protect the body from invasion by outside pathogenic bacteria. Acid in the stomach has a similar protective effect. Removing both these protective barriers at the same time leaves the body defenseless.

To test this idea, researchers gave mice two kinds of live, antibiotic-resistant bacteria for three days. Then they gave the mice an acid-suppressing drug and/or an antibiotic. Mice that were given both the acid-suppressing drug and the antibiotic were three times as likely to end up with intestinal infections as mice given just the antibiotic.

Acid suppression from an acid-blocking drug in combination with suppression of normal gut bacteria from an antibiotic makes the intestines a warm and welcoming home for antibiotic-resistant microbes. Reducing acid in the stomach gave “free passage through the stomach” for the germs. Normally, stomach acid would kill them. The antibiotic killed bacteria such as Acidophilus and Bifidobacter, allowing the drug- resistant bugs to thrive.2 We already worry that antibiotics disrupt bowel flora. Taking acid-blocking drugs triples the risk of serious bowel infection.

Given this information, it came as no surprise when JAMA published an article in June 2006 linking acid blockers and Clostridium dificile infections. Back in 1994, only one person in 100,000 got what was then a rare infection. By 2004, the occurrence rate had jumped to 22 times higher than what it had been. People who use proton-pump inhibitor acid-blocking drugs, such as Nexium, are three times more likely to get infected by Clostridium dificile than people not taking these drugs.3 Interestingly, this is the same increase in risk predicted by the mice.


Dutch researchers reported in the Oct. 27, 2006 issue of JAMA that acid-blocking drugs increase a person’s chance of getting pneumonia. The researchers consulted the medical records from 1995 and 2002 of more than 360,000 people and found that those using acid blockers were 4.5 times as likely to develop pneumonia as were people who never actually used the drugs.

The scientists then looked at pneumonia rates among 475 people who used acid blockers and matched each of these individuals with 10 people who had stopped taking the drugs at some earlier date. From the records, the researchers calculated that a person taking a proton-pump inhibitor has nearly twice the risk of getting pneumonia as does someone who has stopped taking the drug. The weaker type of acid-blocking drugs, histamine2-receptor antagonists, increased the risk of pneumonia by about two-thirds.4

Without acid in the stomach, bacteria from the intestine may be moving upstream to reach the throat and then the lungs to cause infection. It is logical to assume these drugs also increase the risk of other milder types of lung infection.

Increased Fractures

Back in naturopathic school, our teachers warned that without adequate stomach acid, a person would not absorb enough calcium to keep their bones strong. I confess to thinking, after seeing no research to support this contention, that this might not be so serious a problem. I was wrong. The old guys were right. Recent research tells us this is a big problem, at least with the newer and stronger drugs.

A study published in the Dec. 27, 2006 issue of JAMA says that the strong acid blockers, the proton-pump inhibitors, almost triple the risk of hip fracture. The authors looked at British data, combed medical records and found 13,556 people over age 50 who had suffered a broken hip. They compared these people with approximately 135,000 people of similar ages who had not broken a hip. The researchers checked to see which patients had taken any kind of acid blocker.

Their results are very troubling. People taking high doses of proton-pump inhibitors for longer than a year were 2.6 times as likely to break a hip as were people not taking an acid blocker. Those taking even modest doses of PPIs regularly for one to four years were 1.2 to 1.6 times as likely to break a hip. Fracture risk rose with duration of use. The weaker histamine-agonist medications also increased fracture risk, but not to the extent PPIs did.5

The most common side effect of medications such as Fosamax, used to treat osteoporosis, is reflux. Patients may be prescribed Nexium so they can tolerate their Fosamax. In the end, the contribution Nexium makes to increasing fracture rates may outweigh any reduction provided by the Fosamax.

The old explanation we learned that the body needs acid in the stomach to absorb calcium may not be accurate. Some researchers suggest that the acid blockers weaken the bone through another mechanism. These drugs may prevent the osteoclasts from generating the acid they need to dissolve old bone. This would slow or stop burn turnover. This may be what makes the bones weaker and thus more prone to fracture.

Vitamin B12

Of course, the other thing we learned in naturopathic school is that you need acid in your stomach to absorb vitamin B12 in your intestine. It seems other medical schools did not teach this. Authors of a 2002 paper sound almost surprised when describing a 78-year-old woman who had B12 deficiency resulting from chronic acid-blocker use.6 These good people from the school of pharmacy here in Denver went on to examine their 'discovery' further and reported a clear association between acid suppression and B12 deficiency in the April 2004 issue of the Journal of Clinical Epidemiology.7 They suggest testing B12 levels in anyone taking acid blockers for longer than four years.

Vitamin B12 deficiencies are especially common in older people. Anywhere from 10 percent to 43 percent of the elderly is deficient, depending on the testing method used.8 Acid blockers are a greater threat to this age group; thus, we should probably test older people using acid blockers much more frequently than the suggested every four years.


Blocking stomach acid production also may affect cancer rates – for the worse. In a 2005 paper, researchers studied 20 mice, half of which were genetically engineered to lack gastrin, the hormone that runs stomach-acid production. Six of the mice lacking gastrin developed stomach tumors at 12 months of age, but none of the normal mice did.9 This is not the strongest study; it is only about a few mice and it did not even use any acid- blocking drugs. But it does point out that acid production plays some role in cancer protection. In mouse years, 12 months is about a third of their lifetime. Those purple pills have not been on the market long enough for a person to have taken them a third of their lifetime. Even if they caused cancer in a significant percentage of users, we will not see this effect for years. We should thank the generous people taking those purple pills; they are volunteering as experimental subjects to see if this mouse data can be applied to humans.

Yet with all this, many doctors and people still consider these various acid-blocking pills to be wonderful drugs. Ask anyone who has found relief using them, even with these recent studies that bring their safety into question. They certainly provide many people relief. We have to understand there are risks that come with their use. How serious those risks are is something we are just now starting to discover.

There are certainly naturopathic therapies that can sometimes be substituted for these drugs. The advantage they provide is their low risk of side effects. Given the low risk in employing these therapies over the long term, especially in comparison to these drugs, one should consider trying them first before resorting to chemical acid blockers. If relief is found through these alternative treatments, then one can avoid having to make the decision whether the risks are worth the benefits in using these drugs.

Probably the best review of treating GERD from a naturopathic perspective is the chapter Eric Yarnell, ND, has written in his textbook, Naturopathic Gastroenterology. The many treatments to consider can be boiled down to three basic approaches: First, use demulcent herbs to soothe and heal esophageal irritation. Second, avoid foods and drugs that trigger symptoms. Third, try lowering stomach pH by using supplemental acid, or digestive herbs will tighten the tone of the lower esophageal sphincter. Dr. Yarnell, herbalist though he is, suggests a number of homeopathic remedies to consider using to prevent symptoms. Someday, he will make a fine homeopath.

In the course of writing this article, I contacted Dr. Yarnell and asked him for his current thoughts on treating GERD. This is what he suggested:

  • Always assess for hiatal hernia, as it is a common contributing factor.
  • Don’t forget to elevate the head of the bed (don't prop someone up on pillows; this makes things worse).
  • Eliminating Helicobacter pylori too aggressively may worsen GERD. (Some studies show eradication correlates to elevated acid levels and elevated GERD.)
  • Use demulcent herbs in aqueous extracts (powder in water or cold infusions).
  • Try cholagogue herbs, especially fumaria (fumitory), which he has seen improve lower esophageal function.


  1. Berenson A. “Where Has All the Prilosec Gone?” The New York Times, March 2, 2005.
  2. Stiefel U, Jump RL, Donskey CJ. Suppression of gastric acid production by proton pump inhibitor treatment facilities colonization of the large intestine by vancomycin-resistant Enterococcus and Klebsiella pneumoniae in clindamycin-treated mice (Abstract B-1123). 46th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, Sept. 27-30, 2006.
  3. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA, Dec. 21, 2005;294(23):2989-95.
  4. Laheij RJ, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA, Oct 27, 2004;292:1955-1960.
  5. Yang Y, Metz DC, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA, Dec. 27 2006;296:2947-2953.
  6. Ruscin JM, Page RL, Valuck RJ. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother, May 2002;36(5):812-6.
  7. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol, April 2004;57(4):422-8.
  8. Wolters M, Strohle A, Hahn A. Cobalamin: a critical vitamin in the elderly. Prev Med, Dec. 2004;29(6):1256-66.
  9. Zavros Y, Merchant JL, et al. Chronic gastritis in the hypocholorhydric gastrin-deficient mouse progress to adenocarcinoma. Oncogene, March 31;24:2354-2366.

About the Author: Dr. Jacob Schor graduated with a bachelor of science degree from Cornell University and received his naturopathic training at National College of Naturopathic Medicine. He currently practices at the Denver Naturopathic Clinic. E-mail Dr. Schor at

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Date Last Modified - Friday, 17-Oct-2008 12:10:56 PDT