Advanced Topic: H. pylori, Hypochlorhydria, Auto-Immune Gastritis

migraine In this Undoctored Advanced Topic, we first consider H. pylori and its consequences, as well as how to identify and eradicate it, a project that you have the option of tackling on your own without the doctor. We then consider hypochlorhydria, the lack of stomach acid that can result from H. pylori infection or from autoimmune gastritis.

Part I: H. pylori: Why it is important, how to confirm its presence, how to eradicate it on your own

Helicobacter pylori—Disrupter of Stomach Health

Into the delicate balance of stomach acid production enters a microorganism that first infected humans around the time that primitive humans first migrated out of Africa, but became common somewhere around the advent of the industrial age: Helicobacter pylori, or H. pylori.

H. pylori has an interesting history in the medical world. For centuries, gastritis, heartburn, and stomach and duodenal ulcers were viewed as the product of stress, consuming acidic foods, and myriad other explanations, often treated with ineffective advice to avoid vinegar, tomato sauce, other acidic foods and drink more milk. Then two Australian researchers, Barry Marshall and Robin Warren, upended the entire gastroenterology world by identifying H. pylori in the base of human ulcers, publishing their observations in 1984. Infection by this organism explained why people treated with only stomach acid-suppressing drugs frequently experienced relapse or inadequate relief from symptoms. Unfortunately, Marshall and Warren were ridiculed and ostracized from medical circles (even prompting Marshall to infect himself with H. pylori, then have biopsy-proven gastritis develop). Subsequent work, however, proved them right, earning them a Nobel Prize for Medicine 20 years later in 2005. It is now clear that stomach and duodenal ulcers that are not caused by aspirin or anti-inflammatory drugs (such as naproxen or ibuprofen) are nearly all caused by H. pylori.

It has since become clear that H. pylori is oddly ubiquitous, a parasite that can be found in about 15-35% of Americans (variation due to age, geography, and other factors), 50% of people around the world, with increasing likelihood of infection as we age. While originally identified as the cause for ulcers, then gastric cancer, it has become clear that H. pylori is responsible for a lot more, including alterations in bowel flora composition further down the gastrointestinal tract from the stomach.

H. pylori: More than ulcers

Among the health conditions that have been associated with H. pylori are:
  • Increased stomach acid (hyperchlorhydria)—Particularly in younger people in which H. pylori infects the antrum of the stomach (towards the duodenum). This explains why acid reflux, reflux esophagitis, and ulcers respond to stomach acid-blocking drugs, the H2 blockers and PPIs, and why 80-95% of people positive for H. pylori develop stomach or duodenal ulcers. In later phases, hypo- or achlorhydria, i.e., low or absent stomach acid, can develop, the situation that sets the stage for stomach cancer. (The World Health Organization has classified H. pylori as a class I carcinogen.) Note that acid-blocking drugs can also provide relief from acid reflux and esophagitis, conditions separate from H. pylori-based issues.

  • Increased gastrin hormone levels—If hypo- or achlorhydria develop from H. pylori, increased gastrin hormone secretion in response to the lack of stomach acid can, over time, lead to stomach cancer, as gastrin provokes proliferation of stomach lining. Stomach cancer is the third most common form of cancer worldwide with H. pylori as the leading cause.

  • Skin rashes—A variety of skin rashes have been associated with H. pylori, but persistent psoriasis and rosacea are among the most common. In the case of rosacea, eradication of H. pylori is more effective in reversing the rash than modern rosacea treatments.

  • Coronary disease—Especially virulent varieties of H. pylori (that express the CagA toxin) are more likely to be found in people who develop heart disease.

  • Idiopathic thrombocytopenic purpura (ITP)—An uncommon condition in which blood platelet counts dip dangerously low and bruising and hemorrhage can occur.

  • Autoimmune conditions—The list of autoimmune conditions that accompany H pylori and recede with its eradication continue to grow and includes ITP, Sjogren’s syndrome, Henoch-Schlonlein purpura, some forms of autoimmune nephropathy (kidney disease) and peripheral neuropathies.

  • A variety of lung diseases–Such as chronic bronchitis and other conditions.

  • Parkinson’s disease—People with Parkinsonism have greater likelihood of having H. pylori with improvement in Parkinson’s symptoms with eradication.

  • Small intestinal bacterial overgrowth (SIBO)—may occur along with H. pylori in as many as 50% of people diagnosed with either.

  • Fatty liver, insulin resistance, inflammation—This combination of abnormalities improve with H. pylori eradication.

  • Deficiencies of vitamin B12, vitamin D, and iron

  • Other cancers that include lung, liver, biliary, and pancreatic.

In other words, H. pylori is not just about stomach and duodenal ulcers, but has wide implications for health across many health conditions.

Oddly, over the tens of thousands of years that this bacteria has coexisted with humans, it may also have developed the ability to provide beneficial effects such as modest reduction in potential for asthma, some forms of allergy, inflammatory bowel disease, and and cancer. On balance, however, the benefits of eradication of the bacteria outweigh the modest potential for benefit.

H pylori is therefore more like E. coli or Staphylococcus aureus, i.e., species that can inhabit the human body without harm but have potential to exert pathological effects when circumstances permit, and less like, say, a Lactobacillus species that provides benefits but poses almost no pathogenic potential. It is therefore helpful to 1) identify whether you harbor this organism, then 2) take steps to suppress or eradicate the organism. It is a hotly-debated question whether people without symptoms or other outward manifestations should pursue such a course, so it is a question to decide on your own. But you will have Undoctored tools to do so on your own, should you choose.

Identifying the presence of H. pylori Unlike some issues in the Undoctored world such as SIBO in which identifying the condition can be a bit tricky, identifying the presence of H. pylori is straightforward. There are several choices. The old way was to perform an endoscopy and examine a stomach biopsy sample for the presence of the organism by culturing it; this is not the best way as, besides involving an invasive procedure, it can often fail to identify the organism even when it is present.

We therefore have access to several other methods that have advantages, including being available directly to consumers, if necessary. Among the methods available to you are:
  1. Blood testing—for presence of the IgG antibody against H. pylori that has been shown to be a fairly reliable, though not infallible, test, identifying around 85% of infections. Downside: It cannot distinguish between active infection or prior infection, a problem if trying to assess response to efforts to eradicate H. pylori. The IgG test is therefore most useful for initial identification, but not for follow-up. Several direct-to-consumer labs make this available, including finger stick test kits, though the number of labs offering it are diminishing as breath testing and stool antigen testing have been proven to be superior and useful for follow-up after treatment. One particularly convenient test is the SELFCheck Stomach Ulcer Test that requires a finger stick and yields results in 10 minutes and does not have to be mailed to a laboratory.

  2. Urea breath test—Is relatively easy to perform, has high reliability (sensitivity, specificity) for detecting the presence of H. pylori, and can be used to both identify initial presence and effects of eradication efforts. Downsides: It involves drinking orange juice in (what we would regard as) an excessive quantity, requires a pre-testing fasting period, and also requires radioactive carbon, though the quantity of radiation is low. Urea breath testing is also available via direct-to-consumer lab services in most states. Note that taking a PPI drug such as Prilosec, Protonix or Aciphex reduces the reliability of test results; for this reason, people are typically advised to hold off taking a PPI for 2 weeks before conducting the test. Also, urea breath test can yield a misleadingly positive result for H. pylori if urease-containing species such as Klebsiella and Streptococcus are present, an issue when hypochlorhydria, autoimmune stomach inflammation, or SIBO are present.

  3. Stool antigen testing—Examining stool for evidence of the presence of H. pylori has emerged as the preferred method of identification, as it is the most accurate, less costly than urea breath testing, involves no radioactivity, and no period of pre-test fasting is required. It is also useful to monitor treatments effects. Note that a sample for stool antigen testing should not be obtained if stool is unformed or watery as the concentration of the H. pylori antigen is diluted; obtain a sample when stool is solid. Several direct-to-consumer testing services are available such as RequestATest and Verisana.

Interestingly, tongue color has been used in traditional Chinese medicine as a means of identifying H. pylori that has proven to be a fairly reliable sign when compared to conventional testing methods. Yellow, red, and purple discoloration and/or a “greasy” texture has proven to be highly suggestive of the presence of H. pylori, though its absence cannot be used to prove that the organism is not present.

Management of H. pylori

Conventional treatment of H. pylori involves so-called triple or quadruple therapy that consist of the antibiotics clarithromycin or amoxicillin, bismuth (e.g., PeptoBismol), a PPI drug such as omeprazole, and the antibiotic metronidazole. The effectiveness of these combinations has been declining in recent years, presumably due to H. pylori’s ability to resist antibiotics with eradication rates between 60 and 80%. This has sparked efforts to find alternative agents, including supplements and nutritional agents. Clarithromycin is also known to have substantial toxic effects,

The science on management of H. pylori has not progressed to the point of allowing us to craft a specific Undoctored approach, but here are some strategies to consider:

Probiotics—Probiotics alone have not been shown to eradicate H. pylori but have been demonstrated to modestly improve treatment efficacy when combined with conventional therapy, though the species responsible for these effects are not clear. Because of this, it is likely worth including a broad spectrum, high-potency probiotic as part of your H. pylori eradication efforts. The L. reuteri strains that we use in our yogurt have also been shown to suppress (though not eradicate by itself) H. pylori via production of antibacterial bacteriocins and hydrogen peroxide. L. reuteri is also resistant to stomach acid and bile and is able to colonize the stomach, effects that protect against H. pylori overpopulation. Lactobacillus rhamnosus GG has also been shown to help suppress H. pylori.

Nigella sativa—The seeds of this plant have been used for thousands of years in southern Europe, the Middle East, and Asia for treatment of a variety of disorders, as well as food, used much like poppy seeds to top baked products. It has come under study most recently as a source for antibacterial compounds. A recent small clinical trial demonstrated that 2 grams (approximately 1 level teaspoon) of the ground seed eradicated H. pylori in 67% of people, nearly as effective as conventional triple therapy. Nigella sativa seeds are available from a number of online retailers.

Mastic gum—The oddly-named mastic gum is a traditional food and folk treatment for stomach upset in Greece and the Mediterranean dating back 2500 years, sourced from an evergreen shrub that grows in that region. There is evidence that even one milligram per day taken over two weeks can eradicate H. pylori and thereby heal peptic ulcers, though higher doses were typically used in the few small clinical trials. In one clinical trial, 350 mg three times per day and 1050 mg three times per day over 14 days eradicated H. pylori in one-third to one-half of participants. (Also see below.)

Proton pump inhibitors (PPIs)—PPIs are widely overprescribed for suppression of stomach acid and esophageal reflux, even when stomach acid is deficient. Nonetheless, PPIs exert suppressive effects on H. pylori by blocking the action of several bacterial enzymes, as well as disrupting the acidic environment that is hospitable to H. pylori. For these reasons, while PPIs alone are ineffective for eradication, conventional triple or quadruple therapy for eradication of H. pylori includes a PPI such as omeprazole (Prilosec) to increase efficacy. Long-term PPI use has been shown to disrupt intestinal flora, so this should be limited to a short-term strategy.

Bismuth subsalicylate/subcitrate—Available over-the-counter as Pepto Bismol, bismuth was the original treatment for H. pylori in combination with H2 blocking agents. This antacid and antidiarrheal was, in the early history of H. pylori eradication efforts, nearly as effective as modern triple or quadruple therapy, but has become less effective in recent years. However, it may still provide advantage when used in combination with other efforts.

Vitamin C—Vitamin C 500 mg twice daily taken orally has, in several studies, demonstrated an H. pylori-reducing or eradicating effect, particularly when used along with other therapies. This may be due to vitamin C’s ability to block the urease enzyme expressed by H. pylori. There is some suspicion that intravenous vitamin C may achieve blood levels that hold greater potential for eradication.

N-acetyl cysteine (NAC)—NAC is a biofilm disrupter, i.e., it disrupts the mucous layer that H. pylori produces for its own protection. Administration of NAC (in a variety of different dosing regimens, e.g., 600 mg once or twice per day) has been shown to substantially improve treatment efficacy in combination with conventional therapies, including in people who have proven resistant to conventional treatment, presumably by making the organism more susceptible to antibiotics.

Given the growing resistance of H. pylori to conventional therapies, there have been increasing efforts to identify additional alternative or additive treatments. There are preliminary data to suggest that key lime, the juice of the bergamot fruit, polyphenols from almonds, the traditional Chinese treatment Chenopodium ambrosioides L, extracts of the Mallotus philippinensis plant from Pakistan, and some traditional yogurts and kefirs containing various Lactobacilli and yeasts may also provide suppressive or eradicative effects.

A combination of natural agents was used in a small study of 39 participants that yielded successful eradication of H. pylori by stool antigen testing in 29 (74.3%), on a par with conventional three- or four-drug treatment. The regimen used was:
  • Mastic gum (Jarrow Formulas, Los Angeles, California ): 500 mg, 1 capsule 3 times daily

  • Emulsified oil of oregano as A.D.P. 50 mg (Biotics Research Corporation): 1 tablet 3 times daily

  • Pepto-Bismol: 4 to 6 tablets daily in divided doses between meals

In addition, a probiotic containing 5 billion CFUs of 10 species taken twice daily (Vital 10, Klaire Laboratories) and a prebiotic fiber supplement were included.

The composition of bowel flora changes with eradication of H. pylori, though it is not clear whether these changes are favorable or not. While bacterial species diversity is unchanged, the relative percent of Firmicutes species increases while Bacterioidetes decreases and (potentially pathogenic) Proteobacteria also increases. The meaning and consequences of these shifts in bacterial populations are of uncertain significance, but suggest that purposeful efforts to restore presumably healthy bacterial species may be in order.

The Undoctored Approach to H. pylori

In the Undoctored experience, 80% of people with symptoms of gastroesophageal reflux respond to the elimination of wheat and grains, freeing them of the need for long-term acid-suppressing medications and the health-complicating issues they introduce. The remainder who have persistent symptoms typically have small intestinal bacterial overgrowth, SIBO, that requires specific efforts to confirm, then correct and manage. (See the Undoctored Protocol for SIBO in this Inner Circle.)

However, this does not address the presence of H. pylori. If there is a history of stomach or duodenal ulcers, persistent acid reflux symptoms despite the above efforts, or SIBO is present, efforts should be made to determine whether H. pylori is part of the picture. On balance, eradication of H. pylori yields advantages in long-term health and strong consideration should be given to confirming with a IgG blood test, stool antigen or urea breath testing. The combination of mastic gum, oil of oregano, Pepto Bismol, with a probiotic and prebiotic fibers, perhaps with efficacy enhanced with the biofilm-disrupting properties of N-acetyl cysteine, would be a reasonable regimen to start, treatment that appears to not hold the same bowel flora-disrupting effects of standard antibiotic treatments.

In addition, because H. pylori can interfere with nutrient absorption, it would also be helpful to assess the status of iron, vitamin B12, and vitamin D. 

Part II: Hypochlorhydria and Autoimmune Gastritis

The production of stomach acid is a basic requirement for human digestion, as well as protection from foreign microorganisms contained in food and water that humans ingest and microorganisms that ascend up from the lower reaches of the bowels. The acidic environment of the human stomach is so powerful that, if you were to insert your finger into stomach contents, you wouldn’t have much left besides bone within a few minutes. The stomach lining therefore maintains a complex protective mechanism that allows it to produce the acidic material that breaks down food yet protects itself from this potentially toxic mix, a fascinating and delicate balance.

Along with production of hydrochloric acid, the stomach maintains a continuous mucous lining, or biofilm, that coats the stomach for its protection. The parietal cells of the stomach lining produce acid, while other cells produce mucous.

Disorders of stomach acid production, despite being common, yield a confusing array of symptoms since, for example, excessive stomach acid causes similar symptoms to inadequate stomach acid.

The two most common causes for low stomach acid, hypochlorhydria, are H. pylori infection of the stomach and autoimmune gastritis.

While H. pylori can cause hyperchlorhydria (increased stomach acid) early in the infectious process, hypochlorhydria (low stomach acid later) is a common late manifestation. Because the symptoms of hyperchlorhydria, hypochlorhydria, and esophageal acid reflux are similar, it is not uncommon to see people taking stomach acid-suppressing medications for years for the wrong reasons.

For instance, if H. pylori leads to hypochlorhydria, taking a proton pump inhibiting drug like Prilosec or Aciphex provides no benefit and may add to complications such as cultivating small intestinal bacterial overgrowth, SIBO. Likewise, if esophageal acid reflux was really SIBO all along—as it often is—it will not respond to acid-suppressing drug, or respond only partially, while SIBO (and all its long-term consequences) is unaddressed.

Stress is also a cause for increased stomach acid and can manifest as symptoms of acid reflux or as ulcers when H. pylori is present. (Ulcers in the absence of H. pylori is uncommon and largely confined to people experiencing extreme physical stress during hospitalization in intensive care units.)

It is, no doubt, a tangle, but a tangle that is most commonly not disentangled by the cursory approach that dominates in most healthcare settings, from the primary care doctor’s office who reflexively prescribes stomach acid-suppressing drugs to the gastroenterologist most interested in scheduling more endoscopies.

A pivotal decision-making issue is to therefore distinguish hyperchlorhydria from hypochlorhydria.

Gastroesophageal reflux vs. ulcer: An important distinction

Gastroesophageal reflux vs. ulcer: An important distinction Even more common than stomach/duodenal ulcers are gastroesophageal reflux and esophagitis, i.e., feelings of heartburn associated with reflux of stomach contents, including stomach acid, up past the gastroesophageal sphincter and into the esophagus. Relief provided by acid-suppressing drugs is felt to be diagnostic of this condition, as is abnormal acid measured with a pH meter or inflammation seen with endoscopy.

Problem: PPIs and H2-blockers are often prescribed to provide relief but no effort is made to determine whether H. pylori is the driver of excess stomach acid. You can imagine that the difficulty is that H. pylori remains unidentified and its long-term consequences unsuppressed, even if symptoms are relieved.

Should gastroesphageal reflux be identified as the cause of symptoms and H. pylori is ruled out, then the question of small intestinal bacterial overgrowth, SIBO, should be pursued, as many, if not most, cases of acid reflux are really just reflections of undesirable bacterial species that have ascended up the gastrointestinal tract.

While the prevalence of H. pylori in the U.S. has been decreasing, the incidence of autoimmune gastritis is increasing Of the two common causes of hypochlorhydria, i.e., lack of stomach acid, H. pylori and autoimmune gastritis, H. pylori has been gradually decreasing due to efforts to eradicate this microoganism, while the incidence of autoimmune gastritis has been increasing.

Autoimmune gastritis involves an autoimmune attack against the stomach lining’s parietal cells. Loss of stomach parietal cells results in hypochlorhydria that, in turn, leads to iron and vitamin B12 deficiencies. Iron deficiency results because stomach acid is required to extract iron from food, while B12 deficiency develops because the parietal cells no longer produce the so-called “intrinsic factor” necessary for B12 absorption when it reaches the ileum further down the intestinal tract. If uncorrected, iron deficiency can lead to a form of anemia, microcytic (meaning small red blood cells), while B12 deficiency can lead to a macrocytic (large red blood cells) anemia. In advanced stages, the stomach lining becomes atrophied (“atrophic gastritis”) and stops producing stomach acid altogether. Identification of vitamin B12 or iron deficiency should therefore prompt an investigation into whether hypochlohydria is to blame.

Atrophy of the stomach lining, whether triggered by H. pylori or autoimmune gastritis, results in reduction in stomach acid that, in turn, causes levels of the hormone gastrin to rise in the bloodstream as a response to try to increase stomach acid. An abnormally high gastrin blood level is therefore a reliable sign that there is insufficient stomach acid present. The high gastrin level also stimulates abnormal growth of the stomach lining, a process that can lead to stomach cancer.

Autoimmune gastritis is closely associated with Hashimoto’s thyroiditis, with over 50% of people carrying anti-thyroperoxidase antibodies. It is also commonly associated with vitiligo, alopecia, myasthenia gravis, autoimmune hepatitis, type 1 diabetes, and celiac disease–conditions that are also all closely associated with wheat/grain consumption. Up to 10% of people with type 1 diabetes, for instance, develop autoimmune gastritis. A direct connection between wheat/grain consumption and autoimmune gastritis has not yet been made, but many arrows point in that direction. Autoimmune gastritis can also occur in tandem with H. pylori infection, though it is not clear whether H. pylori is a causal factor.

The conventional medical “solutions” to autoimmune gastritis, high gastrin levels, and stomach atrophy are—no surprise—generally unsatisfactory, solutions such as removal of the stomach or blocking the action of the hormone gastrin with the drug, netazepide.

Identification of autoimmune gastritis therefore typically involves:
  • Suspecting the presence of autoimmune gastritis if symptoms of acid reflux, esophagitis, heartburn, or unexplained abdominal discomfort are present, or feeling full with a modest quantity of food or the feeling that food remains in the stomach for extended periods

  • If symptoms of acid reflux fail to respond to stomach acid-blocking drugs, PPIs and H2-blockers

  • Identifying increased blood levels of anti-parietal cell antibodies and anti-intrinsic factor antibodies

  • Suspecting the presence of autoimmune gastritis if H. pylori has been ruled out as a cause of hypochlorhydria or if symptoms of esophageal reflux/esophagitis persist despite eradication of H. pylori.

  • If iron deficiency or vitamin B12 deficiency are present and without other explanation

  • If there is poor response to vitamin D supplementation

  • If SIBO is recurrent and without other explanation (e.g., stress, PPI drugs, course of antibiotics, etc.)

Because most autoimmune inflammation recedes with adoption of the Undoctored Wild, Naked, Unwashed strategies, the same efforts should be made to subdue or reverse autoimmune gastritis if identified, namely wheat/grain/sugar elimination, vitamin D, magnesium, EPA + DHA from fish oil, iodine and thyroid optimization, and basic efforts to cultivate healthy bowel flora. As with hypochlorhydria from H. pylori, the status of iron and vitamins B12 and D should be assessed.

Stomach Acidification

Unfortunately, however, once autoimmune gastritis damages the parietal cells of the stomach, the parietal cells do not regenerate and you can be left with persistent hypochlorhydria, nutrient deficiencies, symptoms such as reflux, and increased risk for SIBO. While unproven, acidification of the stomach appears to relieve symptoms of reflux, heartburn, and intolerance to protein digestion. It is not clear, however, whether stomach acidification reduces levels of gastrin, has any impact on risk for stomach cancer, impacts the likelihood of SIBO, or can improve nutrient status.

Among the choices in methods to acidify stomach contents are:

Carbonated beverages—Consumption of a carbonated beverage before or during meals that acidifies the stomach contents may partially replace the functions of stomach acid such as breakdown of dietary proteins. The level of acidity achieved is modest with a pH of 2.5 typically achieved, not the pH of 1-2 of natural stomach acid production. It is not clear how much such a practice will restore effects such as vitamin B12 and iron absorption. However, be aware that repeated contact of highly acidic beverages with teeth may add to dental decay.

Vinegars—Vinegar, e.g., 1-2 tablespoons before or during meals, as with carbonated beverages, helps acidify stomach contents. Apple cider vinegar is the most popular for this purpose, since it also contains probiotic bacterial and fungal species, but other vinegars work, as well. Vinegars suffer the same dental hazards as carbonated beverages.

Betaine HCL—Betaine HCL dissociates in the stomach into betaine (a naturally occurring compound found in food) and hydrochloric acid and is the most effective means of acidifying the stomach contents, recreating the very acidic pH of normal stomach acid production (0.6-2.0). Effective doses range from 750 to 1500 mg prior to or during a meal that yields an acidic pH within 2-12 minutes of ingestion and maintains an acid pH for about 75 minutes after consumption (though can be as brief as 30 minutes or as long as 120 minutes in some individuals). Because of the more effective acidification achieved with betaine HCl, along with the absence of dental issues, betaine HCl is the preferred method of acidifying the stomach when hypochlorhydria is present.

Due to the uncertainties with efforts at stomach acidification, it is worth tracking blood levels of iron and vitamins B12 and D over time, as well as being alert to the signs of SIBO.