Gastroesophageal reflux disease (GERD) is an extremely prevalent condition in our society as evidenced by the constant television commercials bombarding us with ads for drugs that are supposed to solve all our heartburn problems and lead us to a better life. It has been estimated the prevalence of GERD symptoms in the general population may be up to 30% in the U.S. but other studies show it could be as high as 34% to 40%. Make no mistake about it. These are block-buster drugs that make the pharmaceutical companies billions of dollars annually. Proton-pump inhibitors (PPIs) are the third-highest selling class of drugs in the United States, with $13.9 billion in annual sales. Sales of Nexium (the “purple pill” by Astra Zeneca) topped $6.1 billion in 2013 alone, the second highest prescribed medication in the U.S.
The symptoms of GERD include heartburn, chest pain and sour regurgitation. It is commonly believed to result from excess acid production in the stomach. This is what the drug companies want us to believe because this is the mechanism their drugs target. However, most of the medical literature on GERD indicates otherwise.
“First, excessive gastric acid secretion is not a major factor in GERD pathogenesis. Second, a substantial proportion of symptom-provoking reflux episodes are not caused by acid reflux.” 
Let’s think about this. We know that as we age, gastric acid production decreases, along with pancreatic enzyme secretion. If excess acid production was really the primary mechanism involved in GERD, we would expect to see young children at their peak of digestive function and enzyme secretion popping the purple pills to treat their heartburn! We would expect to see decreased incidence of GERD as people age. As we know, this is far from the reality and in fact, the opposite is the case. GERD is a much more common condition in the elderly, and the incidence of GERD increases, not decreases, as people age. So obviously something else must be going on here that results in GERD. But of course, the drug companies won’t tell you this. And most doctors continue to prescribe PPIs to treat GERD telling their patients that they suffer from a problem of excess acid production. So what’s really going on in GERD?
I will attempt to summarize a somewhat complex condition in the following section. For a more thorough explanation of GERD and the cause of GERD and bacterial overgrowth, please see my article: The Cause of GERD and Bacterial Overgrowth (coming soon)
An important cause of GERD is related to failure of the valve mechanism which exists between the esophagus and the stomach, formed by the lower esophageal sphincter (LES) and the diaphragm, which normally prevents reflux of stomach contents into the esophagus. A decrease in pressure of the LES can allow esophageal reflux of gastric contents. Some patients with GERD have a constantly weak, low-pressure LES, which permits reflux every time the pressure in the stomach exceeds the LES pressure. Periodic relaxation of the LES in normal individuals is called “transient lower esophageal sphincter relaxation” (TLESR). When it becomes more frequent and prolonged, TLESRs are believed to contribute significantly to reflux disease.
In patients with GERD, TLESRs account for the majority of reflux episodes. Gastric distension (also known as “intra-abdominal pressure” or IAP) has been recognized as a major factor inducing TLESRs.[146-148]
“We conclude that gastric distention, by significantly increasing the rate of transient LES relaxations in both normal subjects and patients with gastroesophageal reflux disease, may contribute to the postprandial increase in gastroesophageal reflux.”
But the million-dollar question that few people are asking is: “What causes gastric distension or intra-abdominal pressure (IAP) in the first place?” There are several related conditions that lead to IAP, including hypochlorhydria, protein putrefaction, carbohydrate malabsorption and bacterial overgrowth. Let’s briefly take a look at these related conditions.
It is well-documented in the scientific literature that indigestion of proteins in the intestines leads to a process known as protein putrefaction which can result in dyspepsia (indigestion), gas, bloating and diarrhea.[150,151] Protein putrefaction is caused by bacterial decomposition of undigested protein and results in production of foul-smelling odors. This can also occur in the stomach. Hydrochloric acid production and activity in the stomach is an important part of protein digestion. HCl partially digests protein so that it is more rapidly and efficiently digested by pancreatic enzymes in the small intestine. Decreased production of HCl (hypochlorhydria) or decreased pancreatic enzymes can lead to decreased protein digestion and increased protein putrefaction in the intestinal tract. In addition, when hypochlorhydria is present, there is usually pancreatic enzyme deficiency present as well, since the acidity of the digested food stimulates the release of pancreatic enzymes. This then leads to carbohydrate malabsorption.
“Protein putrefaction is often found alongside that of carbohydrate (malabsorption), though the latter is always the more marked.”
In a book called, “Heartburn Cured: The Low-Carb Miracle”, microbiologist Norm Robillard, Ph.D., postulates that carbohydrate malabsorption leads to an increase in intra-abdominal pressure (IAP) resulting in acid reflux. Dr. Robillard points out that intestinal bacteria primarily feed on carbohydrates and that these bacteria will ferment any carbohydrate that is not absorbed. Bacterial fermentation leads to excess gas production. The resulting gas increases IAP, which is the driving force behind loss of LES function, acid reﬂux and GERD.
When stomach acid is suﬃcient and carbohydrates are consumed in moderation, they are properly broken down into glucose and rapidly absorbed in the small intestine before they can be fermented by small intestinal bacteria. However, if stomach acid is insuﬃcient or carbohydrates are consumed in excess, some of the carbohydrate can escape absorption and become available for fermentation by intestinal bacteria. Carbohydrate malabsorption therefore leads to an increase in bacterial fermentation and increased gas production.
Dr. Robillard cites a study by Suarez and Levitt, showing that 30 grams of carbohydrate that escapes absorption in a day could produce more than 10,000 mL (ten liters) of hydrogen gas! Additionally, increased undigested carbohydrate in the stomach and intestines allows for bacterial overgrowth since these intestinal bacteria will proliferate with large amounts of undigested food. So his solution to GERD and bacterial overgrowth is simple: decrease carbohydrate intake!
Stomach acid (HCl) is primarily involved in protein digestion, however, HCl content can also affect carbohydrate digestion. HCl supports the digestion and absorption of carbohydrates by stimulating the release of pancreatic stimuli such as CCK and secretin, which then stimulate pancreatic secretion of enzymes. If the acidity of the intestinal contents is too low (due to insuﬃcient stomach acid), this can affect the secretion of pancreatic enzymes and can affect carbohydrate digestion. Interestingly, human trials examining the effects of HCl on carbohydrate digestion are unavailable in a thorough search of the literature. However, in vitro studies have shown that carbohydrate digestion of rice, starches and vegetables, is improved in the presence of increased hydrochloric acid (HCl). [167-169] Human studies have also shown improved fat digestion and absorption in the presence of HCl.
It’s really quite shocking how few studies have been done to investigate the benefits of HCl supplementation in the treatment of GERD. Why is this? The most probable explanation is that there is no profit in carrying out this type of study since drug companies cannot patent HCl. There was one small study performed which examined whether the symptoms of gastric distension (IAP) in a group of 9 people were influenced by gastric infusion of HCl. Not surprisingly, the study concluded that sensations of gastric distension were reduced by adding HCl into the stomach in the study group. A more interesting study, much larger in size and involving over 350 people with GERD, divided the participants into 2 groups. The first group (A) received a supplement that contained a combination of betaine HCl, melatonin, l-tryptophan, vitamins B6, B12 and folic acid and methionine. The other group (B) received 20 mg of omeprazole (PPI). Here’s what the study concluded:
“All patients of the group A (100%) reported a complete regression of symptoms after 40 days of treatment. On the other hand, 115 subjects (65.7%) of the omeprazole (PPI) reported regression of symptoms in the same period. There was a statistically significant difference between the groups (P < 0.05). This formulation promotes regression of GERD symptoms with no significant side effects.”
Conventional treatment of GERD relies on acid-suppressing medications, primarily PPIs (proton-pump inhibitors) such as omeprazole. However, as discussed, there are several problems with using PPIs or other acid-suppressing medication to treat GERD. First, PPIs do not address the underlying cause of GERD (LES dysfunction due to increased intra-abdominal pressure secondary to hypochlorhydria and carbohydrate malabsorption) and therefore are not very effective in the management of GERD. Second, there are many adverse effects associated with PPIs. Let’s start by briefly reviewing the research on the efficacy of PPIs in the treatment of GERD. We will then take a close look at the research on the various adverse effects associated with this class of medications.
Proton-pump inhibitors (PPIs) are the strongest class of acid-suppressing medications available. They are very effective in inhibiting the production of acid in the stomach. However, as we have seen, excess acid production is not the cause of GERD. Since we now know the cause of GERD is insufficient production of HCl leading to carbohydrate malabsorption, bacterial fermentation and increased intra-abdominal pressure causing dysfunction of the LES, we can see how acid-suppressing medications, such as PPIs, do nothing to address the underlying cause of GERD or reduce the incidence of GERD. This has been shown to be the case by several large studies.[135,173,174] People continue to have the same underlying problems of GERD while on PPIs. The only difference is there is less acid content available in their refluxate to irritate the esophagus.[135,173,174] And like most drugs, once the medication is stopped, the original condition returns.
“The simultaneous use of intra-esophageal impedance and pH measurement of acid and non-acid gastroesophageal reflux has clearly shown that treatment with PPIs only changes the pH of the refluxate, without stopping reflux through a functionally or mechanically incompetent LES. Vela et al have shown that during treatment with omeprazole, postprandial reflux still occurs but it becomes predominantly non-acid.”
“Emerging data illustrate the potential risks associated with both short-and long-term PPI therapy, including Clostridium difficile–associated diarrhea, community-acquired pneumonia, osteoporotic fracture, vitamin B12 deficiency, and inhibition of antiplatelet therapy. Due to these associations, it is recommended that clinicians assess the continuing need for PPI therapy and use the lowest possible dose to achieve the desired therapeutic goals.”
“…mounting data demonstrate concerns about the long-term use of PPIs…the collective body of information overwhelmingly suggests an increased risk of infectious complications and nutritional deficiencies.”
“The risk of pneumonia was increased 27-39% in short-term use of PPIs in three meta-analyses. C. difficile infections were also associated with the use of PPIs (odds ratio: 2.15; 95% CI: 1.81-2.55; p < 0.00001). This effect appears to be dose related. The U.S. FDA has recently issued a warning regarding fractures and the impaired magnesium absorption associated with the use of PPIs. Thrombocytopenia, iron deficiency, vitamin B12 deficiency, rhabdomyolysis and acute interstitial nephritis have also been reported with the use of PPIs.
There is mounting evidence that PPIs are associated with serious adverse effects. Practitioners should be vigilant and counsel patients accordingly.”
PPIs act by strongly inhibiting the enzyme in parietal cells that allows for acid production in the stomach. They represent the most powerful class of acid-suppressing medications ever developed. Since stomach acid has three primary functions in the stomach (ie: prevent bacterial infection, aid in digestion of protein and aid in nutrient absorption) it’s not surprising that the risks associated with the use of PPIs or other acid-suppressing medications would be related to these critical functions of stomach acid. Studies have shown both short- and long-term use of these medications have been associated with various side effects, such as decreased absorption of vitamins and minerals, such as calcium, vitamin B12, iron and magnesium and increased risk of bone fractures.[179-182]
PPIs are recently being associated with increased risk of bacterial overgrowth in the small intestine (SIBO) due to their acid-suppressing effects, related to the important role that acid plays in preventing bacterial infection and preventing dysbiosis (imbalance of gut bacteria). [183-186] They have also been shown to inhibit digestion of proteins and cause food allergy in an animal model study. PPIs are now routinely used in infants and children who suffer from vomiting attributed to acid reflux but not without adverse effects. One long-term study found that adverse effects have been reported in 34% of children treated with PPIs and include headaches, diarrhea, nausea and constipation. PPIs have also been associated with more severe infections, including hospital-acquired life-threatening infections in immune-suppressed infants and children.
“Acid suppression may place immune deficient infants and children or those with indwelling catheters, at risk for the development of lower respiratory infections and nosocomial sepsis.”
As the current literature makes clear, excess acid production is not the underlying cause of GERD. Recent research has found that GERD results from dysfunction of the lower esophageal sphincter (LES), which allows gastric contents (including stomach acids) to reflux into the esophagus, causing the symptoms associated with acid reflux. The cause of dysfunction of the LES appears to be related to increased intra-abdominal pressure (IAP), which results from incomplete digestion of protein and carbohydrates due to insufficient production of stomach acids. Stomach acid is important in protein digestion and also aids in stimulation of the pancreas to secrete digestive enzymes which are used in carbohydrate digestion and absorption.
Dr. Robillard’s pioneering work supports the concept that incomplete carbohydrate digestion and absorption causes increased bacterial fermentation in the intestines leading to increased gas and IAP. According to his research, this is the cause of GERD, which is supported by the literature on this topic, pointing to IAP as the cause of GERD. Acid-suppressing medications such as PPIs have no impact on the frequency or severity of esophageal reflux. The only impact that PPIs have on the symptoms of GERD is making the contents of the refluxate less acidic, thereby decreasing symptoms associated with stomach acid entering the esophagus. However, there are many adverse effects associated with PPI use, including increased risk of bacterial infection, decreased absorption of various vitamins and minerals leading to nutritional deficiencies and osteoporosis-related bone fractures. Worse than that, by suppressing acid production, PPIs lead to decreased protein and carbohydrate digestion and increased risk of malabsorption, intra-abdominal pressure and GERD. One editorial entitled “Evidence That Proton-Pump Inhibitor Therapy Induces the Symptoms it is Used to Treat” commented on an article published in a British gastroenterology journal which came to this very conclusion:
“Treating gastroesophageal reflux disease with profound acid inhibition will never be ideal because acid secretion is not the primary underlying defect. Acid secretion is normal in most patients with reflux disease and acid inhibitory therapy makes it abnormally low. It is never ideal to treat one abnormality by creating another, as was the case for many years with management of ulcer disease before the disco- very of H. pylori infection. The pathophysiology of acid reflux concerns the dysfunction of the gastroesophageal barrier and research needs to refocus on ways of restoring its competence rather than merely suppressing gastric acid secretion.”
Many functional medicine doctors have found that supplementation with betaine HCl and pepsin has been extremely helpful in managing GERD and its associated symptoms. Some people will experience a “burning” sensation in the stomach when they supplement with HCl. I attribute this to irritation or thinning of the gastric lining that protects the stomach from the acidic HCl. In many cases, when we address the irritated gastric lining, they are able to tolerate HCl supplementation. I believe the evidence is strong enough to warrant the use of HCl and pepsin and the clinical response with minimal side effects further justifies its use in the management of GERD. In addition, zinc carnosine has been shown to be helpful in managing a wide range of gastrointestinal conditions. Zinc has been shown to improve the integrity of gastrointestinal epithelial tight junctions and barrier function and have protective effects of the stomach lining against gastric HCl.[239,240]
In the next segment, we will take a closer look at the adverse effects associated with PPIs according to the most current literature. In the following segment, we will continue to examine the most common disorders that result from dysfunction of the stomach, including gastric (peptic) ulcers and duodenal ulcer disease.
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