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Medications for GERD

Of all the medications covered in these pages, I am most concerned about the widespread, enthusiastic, reckless dispensing and consuming of drugs used to treat gastroesophageal reflux disease (GERD).

When I was growing up, GERD did not exist. People had heartburn, which they relieved with simple, safe antacids like Tums—chewable, mint-flavored tablets of calcium carbonate (that is, chalk). Most sufferers understood that heartburn is the stomach’s way of letting you know you mistreated it: by eating too much, eating the wrong foods or combinations of foods, or not paying attention to the disruptive effects of stress and negative emotions on digestion. The goal is to correct those habits, not to suppress the symptom so that you can keep them up.

Now, heartburn has been medicalized, with total focus on overproduction of stomach acid as the primary problem and treatment with acid-blocking drugs as the primary intervention. Acid (and the enzymes it activates) in gastric secretions can irritate the lining of the stomach and lower esophagus, causing the pain and other symptoms of GERD, but except in very rare circumstances, overproduction of acid is not to blame. Moreover, adequate acid in the stomach facilitates digestion of protein and absorption of key vitamins (B₁₂) and minerals (calcium, iron, magnesium). It is also an important defense against infection, because strong acid kills potentially harmful bacteria and viruses. Trying to manage GERD solely by blocking acid production in the stomach without attending to the many other factors involved is not a wise strategy, especially in the long term.

Acid-blocking drugs are now some of the most widely sold medications worldwide. In the United States they have been among the top ten best-selling classes of medications since 2000. The first to come on the market were the H2 blockers—drugs that block histamine receptors, which are part of the acid production pathway in specialized cells in the stomach. Cimetidine (Tagamet) was approved in 1979; ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid) soon followed. These medications mostly affect meal-induced acid production but work poorly in between meals. Both prescription and over-the-counter (OTC) forms are available.

H2 blockers are less expensive, less potent, shorter-acting acid suppressors than the next generation to come along: the proton-pump inhibitors, or PPIs. Proton-pump inhibitors are the most potent acid-blocking drugs available. Omeprazole (Prilosec) was the first one to come on the market, in 1989. Five other PPIs are now sold in the United States: dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix). In 2009, approximately 21 million people filled at least one PPI prescription. About 113 million prescriptions for them are filled globally each year. More recently, these powerful medications have become available over the counter and are vigorously promoted by manufacturers. (Think of television ads for Nexium, the “purple pill.”) Several years ago the total cost expenditure on PPIs was more than $13 billion. I consider a great deal of that cost to be attributed to inappropriate use of these drugs.

Blocking acid is a necessary aspect of treating certain medical conditions. PPIs are used to heal stomach and intestinal ulcers, treat inflammation and erosions in the esophagus from reflux, prevent Barrett’s esophagus (a precancerous condition), prevent ulcers in critically ill patients in intensive care units, and help eradicate Helicobacter pylori, an organism that causes many upper gastrointestinal (GI) problems. PPIs have been shown to be superior to H2 blockers in healing gastric and intestinal ulcers and in the treatment of H. pylori. For most acute medical conditions, therapy with drugs of either class should not exceed 90 days. (Barrett’s esophagus and severe inflammation in the esophagus may require longer treatment.)

For mild cases of GERD and indigestion, the two classes of medication are equally effective, but they should be considered short-term solutions only. When people take them regularly, they can cause real trouble.

Here are the stories of two patients.

Elena, a sixty-five-year-old woman with osteoarthritis, had been prescribed daily naproxen (Aleve) for joint pain. After three months on the drug, she developed dark, black stools and felt light-headed. During an emergency room visit, she was found to have a gastrointestinal bleed from an ulcer in her stomach. She was admitted to the hospital, where the doctors took her off the naproxen, gave her 40 milligrams via IV of the proton-pump inhibitor pantoprazole twice a day, and performed an endoscopy. The bleeding stopped, and she was discharged with a prescription for oral pantoprazole, 40 milligrams twice daily with six refills.

Six months later, an upper respiratory tract infection brought Elena back to the doctor’s office, where she was prescribed the antibiotic amoxicillin. After three days on it, she developed severe diarrhea and was diagnosed with Clostridium difficile (C. diff) colitis. Her doctor told her that the PPI had made her more susceptible to this serious infection, which required more aggressive antibiotic therapy, and that she would be at higher risk for recurrence of C. diff if she continued it.

John, age fifty-two, asked his new primary care provider for a refill of the omeprazole he had been faithfully taking for the past five years following a diagnosis of GERD. Back then, he had experienced gradually worsening heartburn as well as frequent belching. His then primary care doctor referred him to a gastroenterologist, who performed an endoscopy that showed only mild inflammation of the lower esophagus. Neither doctor took a dietary history from John or inquired about other aspects of his lifestyle. He was started on omeprazole, which eliminated the heartburn, although whenever he tried to stop taking the medication, his symptoms returned with a vengeance. He was disappointed to be so dependent on drug therapy, but the gastroenterologist had assured him that omeprazole was safe, and besides, what else could he do?

Then his wife showed him an article about long-term consequences of suppressing stomach acid, including infection and reduced absorption of important nutrients. He decided to stop the omeprazole cold turkey and, just as in the past, his heartburn returned within days, worse than ever. He had recently been switched to a new primary care physician but had yet to meet with her. He telephoned her to request a refill of his prescription, but the doctor insisted that she have the chance to evaluate him first. At their meeting, he described what happened when he stopped taking the medication, expecting that this would indicate the need for continued, possibly lifelong, treatment with a PPI.

The doctor, however, explained the phenomenon of rebound acid hypersecretion—a worsening of heartburn symptoms that commonly occurs after sudden cessation of PPI use. This can last months, she said, but alone did not mean he would need to stay on the drug. In addition, she went over the long list of possible side effects of PPIs, and expressed her opinion that he should stop taking them. She suggested weaning off the medication very slowly, cutting the dose according to a schedule she gave him. She told him also that if he experienced significant discomfort on a lower dose, he should not hesitate to go back up to the previous amount for a week or so, then try again to cut it. And she gave him handouts detailing dietary changes he should strongly consider, such as reducing caffeine and alcohol intake, as well as stress-management techniques, including breath work, that over time could help soothe the irritated lining of his esophagus. She even mentioned natural remedies that might help in a pinch.

John was skeptical of her approach, convinced that without the PPI, his heartburn would never go away. But the doctor assured him that he could successfully discontinue the medicine if he followed the schedule. That was all the motivation he needed to commit to the recommended changes. It wasn’t easy for John; over the next few months, as he gradually decreased the dose of omeprazole, the pain at times made him very uncomfortable. During these episodes he questioned his doctor’s guidance, but she encouraged him to stick with it. After six months, he was completely off the PPI and symptom-free. His whole family adopted the satisfying eating plan he was on, and he continued to practice the stress-management techniques he had learned. At a follow-up appointment, John told his doctor that he had never felt better.

HOW H2 BLOCKERS WORK

H2 blockers inhibit the action of the regulatory substance histamine on the acid-secreting cells in the stomach, decreasing their production of acid. The body develops tolerance to these drugs over time, lessening their effectiveness. H2 blockers work more rapidly than PPIs (within thirty minutes) and have a shorter duration of action (no more than twelve hours). They can be used as needed to control symptoms, not just as maintenance therapy, and work best at blocking surges in stomach acid in response to eating. These drugs are meant to be taken thirty minutes before meals, and no more than twice a day.

HOW PPIS WORK

PPIs block the last stage in gastric acid production—the operation of the “proton pump” in acid-secreting cells. This mechanism takes potassium ions from inside the stomach and exchanges them for acidic hydrogen ions. PPIs are potent agents, decreasing gastric acid secretion by up to 99 percent. And because they bind irreversibly to and deactivate the proton pump, the effect of a single daily dose lasts almost a full twenty-four hours. Intake of food or other antacids at the same time decreases the efficacy of PPIs, as these medications require an acidic environment to be activated. Thus they should be taken on an empty stomach thirty minutes prior to a meal to obtain maximum benefit. Maximal effects occur after five to seven days of regular use; taking them intermittently may not suppress acid sufficiently to produce satisfactory clinical results.

THE PROBLEMS WITH H2 BLOCKERS AND PPIS

In the short term, H2 blockers may cause constipation, diarrhea, nausea, or vomiting. They may also affect the central nervous system, causing confusion, lethargy, headaches, and dizziness, especially in elderly patients and those with kidney or liver dysfunction. Cimetidine appears to cause more central nervous system side effects than the other three H2 blockers.

Headaches, nausea, abdominal pain, diarrhea, skin rashes, dizziness, weakness, and constipation are the most commonly reported short-term side effects of PPIs.

Short-term use of these medications is generally well tolerated. However, with both H2 blockers and PPIs so widely available, many consumers take them casually with little or no awareness of their long-term risks.

Dependence

The most serious risk of long-term PPI therapy is dependence—a striking example of the homeostatic trap that ensnares patients who use suppressive medications over the long term. The body reacts to suppression of acid production in the stomach by trying to make more of it. As soon as the drugs are stopped or the dosage reduced, acid secretion increases, with consequent worsening of symptoms. This common reaction is known as rebound acid hypersecretion and is defined as an increase in gastric acid secretion above levels prior to starting therapy. Symptoms of heartburn, indigestion, and dyspepsia (burping up of gas and stomach juices) develop within two weeks of PPI cessation. Patients (and their doctors) may falsely believe that these symptoms argue for further therapy with PPIs when, in fact, they are a withdrawal reaction associated with dependence on the medication. In one study, healthy individuals without heartburn, reflux, or acid indigestion were given 40 milligrams of esomeprazole daily for eight weeks; upon cessation, most of them experienced acid-related symptoms. In other words, over time, these drugs can cause the very problem they are meant to treat.

Dependence on PPIs is very stubborn. Most people affected by it have great difficulty getting off these drugs. Integrative medicine practitioners recommend weaning off them slowly while instituting the lifestyle measures and other therapies described here.

Disruption of the Microbiome

Altering the acidity of the stomach disrupts the normal gut microbiome—the population of microorganisms living in the lower GI tract that are necessary for normal digestion and GI function and strongly influence all aspects of health. Long-term use of acid-suppressing drugs can inhibit normal, beneficial organisms, while encouraging overgrowth of harmful bacteria.

Pneumonia

Reduced acid diminishes the stomach’s ability to maintain a sterile environment free of bacteria, viruses, and yeast. Some studies suggest there may be a higher rate of pneumonia in those taking H2s and PPIs due to silent reflux and aspiration of gastric contents into the lungs.

GI Infections

Reduced gastric acidity can promote bacterial overgrowth in the small intestine, making patients more vulnerable to colonization and illness caused by pathogens like C. diff. Rates and recurrences of C. diff infection are higher than average in patients on PPI therapy. They are also elevated, but less so, in those on H2 blockers. People with low stomach acid are more susceptible to cholera and certain infections contracted by eating raw shellfish.

Micronutrient Deficiency

Gastric acid is important for breaking down and digesting food and releasing nutrients and vitamins. Problems with iron and B₁₂ absorption are typically mild and easily corrected with oral supplementation, but magnesium deficiency may have more serious consequences, including heart arrhythmias and seizures. In March 2011 the FDA issued a safety warning regarding this risk. It advised doctors to check serum magnesium levels prior to starting on a PPI and monitor them periodically for the duration of the therapy.

Poor Absorption of Calcium and Impaired Bone Health

PPI therapy can block calcium absorption, leading to osteoporosis and fractures. To prevent these problems the FDA recommends using the lowest effective dose for the shortest duration of time as well as supplementing with calcium and vitamin D.

Cardiac Disease

A recent study brought to light the possibility of an increased risk of heart attack in patients using PPIs long term (but no such risk in those on H2 blockers). The risk was shown to be in the general population and not just among patients who were at high risk or had a history of cardiac disease. The reason is not clear but may involve adverse effects on blood vessels.

Kidney Disease

Evidence suggests an association between PPI use, kidney inflammation, and increased risk of chronic kidney disease (CKD). As noted earlier, PPIs reduce absorption of magnesium. They also appear to induce immune-mediated kidney damage. Both may contribute to the development of CKD. The author of one recent study on this risk writes, “The results emphasize the importance of limiting PPI use to only when it is medically necessary, and also limiting the duration of use to the shortest duration possible.”

Dementia

A study examining the use of PPIs in people age seventy-five and older showed that taking the medication was associated with a 44 percent increased risk of dementia. The finding is not definitive, but it raises serious concerns about the use of PPIs in the elderly.

Medication Interactions

H2 blockers have multiple interactions with other medications, including antibiotics, antivirals, and anticoagulants. Before starting on one of them, patients should check with their doctor or pharmacist to make certain there are no interactions of concern.

INTEGRATIVE MEDICINE APPROACHES TO MANAGING GERD

Despite their shortcomings and the many serious consequences of long-term use, PPIs and H2 blockers are commonly given as first-line treatments for acid reflux, dyspepsia, and heartburn. Once started on PPIs or H2 blockers, many people continue to take them indefinitely. Too often doctors prescribe them without inquiring into the dietary habits, stress levels, and other aspects of patients’ lives known to affect GI function. And too often patients take OTC forms of these drugs without giving any thought to managing their symptoms in other, safer ways, such as those described below.

Dietary Modification

Examining and changing dietary habits should be a primary approach to managing GERD.

The lower esophageal sphincter (LES) keeps acidic gastric contents within the stomach and out of the esophagus. It is normal for some amount of stomach acid to reflux into the lower esophagus with transient relaxation of the LES. In people with GERD, periods of relaxation are more prolonged and frequent. A common cause of this is distension of the stomach from overeating. High intra-abdominal pressure associated with obesity also predisposes to reflux, leading to heartburn, GERD, and esophagitis. (Waist size has a direct correlation to the risk of developing reflux esophagitis and to its severity and attendant risk of developing cancer. Weight loss can significantly help with these symptoms and prevent long-term complications.)

These dietary strategies are worth trying: consuming frequent small meals, avoiding high-fat meals, and limiting spicy and acidic foods—such as citrus and tomatoes—as well as coffee (caffeinated and decaffeinated) and other caffeinated drinks, chocolate, alcohol, carbonated beverages, onions, and garlic. An upright position should be maintained for at least three hours after eating to allow food to digest and empty from the stomach. Elevating the head of the bed at night and sleeping on the left side have been shown to benefit patients with nighttime reflux symptoms.

Finally, there is some literature to support that food allergies may be a contributor to GERD symptoms, and even that PPIs may promote the development of food allergies by disrupting the gut microbiome. Cow’s milk allergy in children is a well-known cause of GERD that does not respond to PPI therapy. Following a gluten-free diet improves symptoms of GERD in those with celiac disease.

Other Lifestyle Measures

Smoking is a potent relaxer of the LES. Smoking cessation reduces acid reflux and decreases the risk of gastritis.

Avoiding or limiting nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen, aspirin, and naproxen) is important; used frequently, they strongly irritate the lining of the stomach and increase the risk of bleeding.

Stress is a notorious trigger for heartburn. A prominent symptom of anxiety is the feeling of a knot or “butterflies” in the stomach, a familiar example of the connection between that organ and emotions. A recent study of GERD patients showed that feeling stressed was the most common lifestyle factor correlated with the disorder, present in 45.6 percent of 12,653 patients surveyed. Up to 50 percent of first responders involved in the 9/11 attacks in New York City suffered from post-traumatic stress disorder (PTSD), with 70 percent of them having chronic reflux-related symptoms.

In states of chronic stress and anxiety, the body’s gut-brain hormonal regulation is disrupted. As part of the fight-or-flight response, heightened sympathetic nervous system activity freezes stomach motility and relaxes the LES, increasing the possibility of reflux. Under stress there is also a breakdown of the integrity of cells in the lining of the stomach, making it more vulnerable to irritation by acid and digestive enzymes.

There are many practices to consider for neutralizing the harmful effects of stress on the body and mind: tai chi, yoga, meditation, hypnotherapy, breath work, and more.

Coating Agents

Sucralfate (Carafate) is a prescription medication that protects the gut lining, without any of the long-term adverse effects of H2 blockers and PPIs. It coats ulcers and erosions as well as “cracks,” protecting tissues from the caustic effects of acid and digestive enzymes. It can actually heal erosions and ulcers, something the acid-suppressive drugs cannot do.

Natural products that strengthen the protective mucous lining of the stomach and esophagus include slippery elm (Ulmus fulva) powder or lozenges and deglycyrrhizinated licorice (DGL) powder or chewable tablets to be taken before meals and at bedtime.

Approximately 60 percent of patients who experience GERD have a hiatal hernia—a protrusion of part of the stomach into the chest cavity. This impairs the ability of the LES to prevent acid reflux and also creates a pocket that retains irritating gastric juices; these tend to back up into the esophagus. OTC coating medications, like Gaviscon, are available for the problem. They contain alginate (made from brown algae) and bicarbonate, which together coat the stomach lining and form a barrier against reflux from the pocket. A recent study has shown these agents to be as effective as PPIs for management of GERD associated with hiatal hernia.

Protecting the lining of the stomach and esophagus from acid irritation versus suppressing acid production with powerful drugs illustrates the difference between Eastern and Western medical philosophy. A wise practitioner of modern Chinese medicine once told me that his goal was “to dispel evil and support the good.” Western medicine focuses mostly on dispelling evil, especially by using drugs to oppose or destroy what it sees as causes of disease: antibiotics against harmful bacteria, for example, and suppressive drugs to block acid secretion in the stomach. Eastern medicine directs much more attention to supporting the good—that is, protecting and enhancing the body’s natural defenses. Integrative medicine uses both approaches. In the case of GERD, making the lining of the gut more resistant to the potentially irritating effects of acid may be as important as trying to make acid go away—or even more so.

Antacids

Simple antacids, like calcium carbonate, provide fast and effective short-term relief of heartburn and symptoms of GERD. They also promote esophageal motility to clear acid from that organ. Used frequently, they may cause constipation, which can be mitigated by taking supplemental magnesium. I recommend avoiding aluminum-containing antacids (like Maalox and Mylanta), because of possible harmful effects of that element.

Other Natural Products

Many herbal therapies are available for the treatment of GI disorders. Ginger has been shown in numerous studies to help with nausea, vomiting, and GI upset. When consumed in the form of capsules containing powdered root, ginger promotes gastric motility. Two to three teaspoons of apple cider vinegar mixed in 8 ounces of water may help relieve acid reflux by mechanisms that are not yet fully understood. Chamomile tea can help soothe stomach inflammation. (Avoid peppermint tea, often used for simple indigestion; it worsens GERD by relaxing the LES.) Aloe juice, a popular home remedy to soothe inflamed and irritated skin, can also soothe internal inflammation. A half cup of the juice twice a day is the recommended dose. D-limonene, derived from the rind of lemons, helps promote healthy gastric motility and prevent reflux; dosage is 1000 milligrams once every other day for a total of ten doses, then as needed.

A few studies have shown benefit in 6 milligrams of melatonin taken at bedtime. Melatonin is a safe and effective remedy for insomnia. Poor sleep promotes GERD, and GERD interferes with sleep. Melatonin is also a weak blocker of stomach acid and may increase LES tone; one study showed it to be as effective as a PPI when used in combination with other supplements, such as DGL.

BOTTOM LINE

GERD is a complex problem marked by decreased resilience of the GI tract to deal with external and internal stressors. Heartburn is a warning sign of disturbed GI function that should prompt us to identify and change the habits responsible for it. A pill that blocks stomach acid will make symptoms of GERD disappear as if by magic but cannot address its root causes. Over time, the pill will become less effective, create dependence, and increase risks of more serious problems. It is best to use H2 blockers and PPIs for short-term therapy and for longer-term management only of relatively rare, very severe conditions. Addressing the root causes of GERD with lifestyle changes and safe and effective alternative remedies is a much better approach.