New research suggests that in many people, heartburn may be caused by something other than acid reflux. But gastroenterologists are often stumped as to what it is and how to treat it.
Some 44% of Americans have heartburn at least once a month, and 7% have it daily, according to the International Foundation for Functional Gastrointestinal Disorders. Heartburn that frequent is the most common symptom of gastroesophageal reflux disease, a diagnosis believed to be rising world-wide with obesity and advancing age. One 2004 study cited a 46% increase in GERD-related visits to primary-care physicians over a three-year period alone.
But up to one-half of GERD patients don't get complete relief from even the strongest acid-reducing medications, called proton-pump inhibitors (PPIs), and most don't have any evidence of acid erosion when doctors examine their esophagus with an endoscope. Gastroenterologists have dubbed this condition non-erosive reflux diseases, or NERD.
It has become a hot topic for discussion and research. "It used to be thought that all GERD was the same—you give patients PPIs and they'll all respond," says Prateek Sharma, a gastroenterologist at the University of Kansas School of Medicine. "But we're finding that a subset of these patients don't have acid as a cause of their symptoms."
Gastrointestinal experts now estimate that 50% to 70% of GERD patients actually have NERD, and studies show they are more likely to be female—and younger and thinner—than typical acid-reflux sufferers. They are also about 20% to 30% less likely to get relief from acid-blocking drugs. But their episodes of heartburn are just as frequent, just as severe and just as disruptive of their quality of life, studies show.
Doctors suspect some may be suffering from a reflux of bile, a digestive liquid produced in the liver, rather than stomach acid, or from hypersensitivity to sensations in the esophagus.
Another guess is psychological stress. A 2004 study of 60 patients conducted at the University of California, Los Angeles, found that those with severe, sustained stress in the previous six months were more likely to have heartburn symptoms during the next four months.
"It's probably a bunch of different conditions put together in one basket," says Loren Laine, a professor of medicine at Yale University School of Medicine and president of the American Gastroenterological Association. "The ones we worry about are the ones who don't respond to standard therapy," he says. "Then we have to figure out why they don't respond."
Most people with heartburn take over-the-counter antacids, H2 receptor blockers or PPIs, often on the advice of pharmacists or primary-care physicians. Many H2 blockers and PPIs are available in stronger prescription form as well. More than 113 million prescriptions are filled for PPIs each year, at a cost of $14 billion, making it the third largest-selling drug category in the world.
A Glossary for Your Gut
- Heartburn: A burning pain behind the sternum, or breast bone, that may radiate up into the throat.
- Acid reflux: Occurs when acid secretions in the stomach splash up into the esophagus (food pipe), a frequent cause of heartburn.
- GERD (Gastroesophageal reflux disease): Digestive distress caused by acid reflux, usually diagnosed when heartburn occurs at least weekly.
- NERD (Non-erosive reflux disease): Chronic heartburn with no evidence of acid damage in the esophagus.
- Functional heartburn: A catch-all term for heartburn with no apparent cause.
- Antacids: Over-the-counter medications that neutralize excess stomach acid, e.g Rolaids, Tums, Pepto-Bismol.
- H2 blockers*: Drugs that reduce stomach acid by blocking histamines that produce it, e.g. Pepcid, Tagamet, Zantac.
- Proton-pump inhibitors* (PPIs): The most potent drugs that block the stomach's production of acid, e.g. Nexium, Prevacid, Prilosec, Aciphex. Can take up to several months to work.
Not surprisingly, what you eat can come back to haunt you, heartburn-wise.
Common dietary triggers include:
Patients are typically referred to gastroenterologists only if their heartburn persists, or if they experience so-called alarm symptoms, such as nausea, vomiting blood or extreme discomfort. Gastroenterologists generally only do an endoscopy when the patient doesn't respond to taking a PPI twice a day for 12 weeks.
Doctors seldom see evidence of acid erosion when they use an endoscope—a long tube with a lighted camera that lets them examine the esophagus—but there is debate over what that means. Some patients' heartburn may be caused by micro-erosions only visible with special equipment. Some may have symptoms that haven't produced damage yet, and in some cases, the damage in the esophagus may have been healed by the acid-blocking medication, but still, the heartburn pain persists.
"The patient doesn't care if they have esophageal erosion of not. They are more concerned about the pain," says Dr. Sharma.
To investigate whether acid reflux is involved at all, doctors can do a 24-hour pH test, inserting an acid-sensitive probe through the patient's nose into the esophagus, where it records any episodes of reflux. If acid secretions are normal, or if they don't correlate with the patient's symptoms, it is a strong clue that the heartburn has another cause.
A newer version currently attracting physician interest, called impedance testing, can detect nonacid reflux, including bile.
If reflux is normal and doesn't correlate with patient's symptoms, doctors typically diagnose "functional heartburn," which means they have ruled out known explanations. "That's what you call it when you don't know what else to call it," says David Clarke, a gastroenterologist in Portland, Ore.
By some estimates, functional heartburn accounts for up to 50% of NERD patients. One theory is that sufferers have a hypersensitive esophagus, in which nerve endings interpret even normal digestive sensations as painful, similar to fibromyalgia. Acid-suppressing medication doesn't help, but low-dose tricyclic antidepressants seem to modulate the pain in some patients.
Studies also show that patients diagnosed with functional heartburn exhibit a high percentage of psychological stress. Dr. Clarke says he found that about one-third of his patients with heartburn didn't get better on proton-pump inhibitors, or have evidence of acid reflux, but in virtually every case, they had severe stress in their lives. Once the stress was recognized and resolved, their GI symptoms improved.
"Many people with those conditions aren't as aware of them as you would think," says Dr. Clarke, who is president of the Psychophysiologic Disorders Association, a nonprofit advocacy group for stress-induced medical conditions. And many GI specialists don't have the time or training to help patients understand how stress might cause their symptoms, he says.
There is surprisingly little research on whether certain foods may cause heartburn. "Why not try diet first instead of drugs?" asks Jan Patenaude, director of medical nutrition at Oxford Biomedical Technologies, Inc. The South Florida lab company tests patients' blood to see if it forms an inflammatory reaction to any of hundreds of foods. Patients then stop eating any suspect food, then gradually add them back to see if their heartburn returns.
Mainstream gastroenterologists say there is little evidence that an inflammatory reaction causes heartburn. Then again, doctors have long counseled patients to avoid common "trigger" foods such as chocolate, peppermint, peppers, alcohol and caffeine. "A lot of standard advice that we give hasn't been proven," says Dr. Sharma.
Other standard recommendations are to quit smoking, not lie down within three hours of eating, get sufficient sleep, avoid tight clothes (particularly those that constrict the waist) and lose weight. A recent study in the Journal of Obesity found that when patients who were overweight or obese lost weight, they had a reduction in symptoms.
Many doctors tell patients with NERD or functional heartburn to continue taking proton-pump inhibitors, despite studies showing they are less effective in such cases. The Food and Drug Administration has issued warnings that long-term use and high doses can increase the risk of bone fractures and bacterial infections—and may reduce the absorption of key nutrients, including magnesium, calcium and vitamin B12.
Write to Melinda Beck at HealthJournal@wsj.com