The Hype of Hypochlorhydria: A Brief Review of Gastric Acid Analysis
Taylor Seier, BCom
Thara Vayali, BSc, MA, ND
Naturopathic medicine distinguishes itself upon established principles of healing, including Tolle Causam (identify and treat the cause). Diagnostic procedures within our profession vary by provider experience and knowledge; hence, a discrepancy exists between validated and unvalidated approaches to identifying the cause of a condition. These approaches contribute to the understanding of a patient’s adaptive physiological process and assist in providing accurate measures for treatment and prognosis. Reliable and valid diagnostic procedures are essential for proper assessment and care of a patient in clinic practice.
Gastric acid output is one clinical concern that is frequently assessed by unsubstantiated tests, and, as such, may result in misleading interpretations. The purpose of this paper is to review diagnostic approaches for low gastric acid assessment so that physicians can choose their testing from an informed perspective. Throughout this paper, the term conventional tests refers to assessments regularly utilized by the allopathic medical profession, whereas the term functional tests refers to assessments commonly used in naturopathic practice. Included will be a brief review of gastric physiology, with discussion of the signs, symptoms and pathologies that may indicate a state of suppressed gastric function. This paper serves to benefit the naturopathic profession by highlighting strengths and weaknesses of available gastric assessments, to act as a nucleus for further discussion, and to enhance and validate available functional testing through future research. The literature summarized for this topic was obtained through peer-reviewed publications via PubMed and Google Scholar scientific databases, as well as books compiled by respected medical authors.
A Review of Physiology
The production of hydrochloric acid (HCl) in the lumen of the stomach serves important functions, such as breaking down food and aiding in the immune system barrier. HCl converts pepsinogen to pepsin for protein digestion, sterilizes meal contents, prevents bacterial overgrowth, and stimulates pancreas and gallbladder actions. HCl is also required to facilitate the extraction and absorption of vitamin B12, iron, calcium, and trace minerals, the deficiencies of which may be one of the first signs of inadequate stomach acid. Calcium absorption is particularly important in the elderly, where the long-term use of proton pump inhibitors (and acid suppression) is associated with increased risk of hip fractures.1
The production of HCl is already present on the first day of life, and increases as the infant matures, becoming similar in function to that of adults by 2 years of age.2 HCl and intrinsic factor are released from the parietal cells within the oxyntic glands located in the fundus and body of the stomach. The acid is secreted at a concentration of 160 mmol/L, producing a pH of 0.8, with total secretion per day estimated at 2.5 L.3 The epithelium of the stomach is protected by a superficial layer of mucus to protect against acid and pepsin; this mucus layer is composed mostly of water, electrolytes, glycoproteins and bicarbonate. Stimulation of HCl secretion during the cephalic phase of digestion begins with inputs of smell, sight, taste, and chewing of food. These factors are processed by the limbic system and stimulation of the vagus nerve, eventually leading to parietal cell release of HCl and G-cell release of gastrin. The most dominant phase of digestion is the gastric phase, which occurs when secretions are stimulated by gastric distention, peptides, amino acids, and further activity of the vagus nerve. The intestinal phase of digestion occurs when stomach secretions enter the duodenum. Signals, including somatostatin, inhibit gastric secretory function, followed by release of cholecystokinin and activation of pancreatic and gallbladder secretion.
Causes & Effects of Hypochlorhydria
The underlying pathologies of insufficient acid secretion are varied and at times unclear. Achlorhydria is an expression of atrophic gastritis, which is associated with an increased risk of gastric cancer.4 Ruling out gastric carcinoma is important early in assessment, due to its aggressive nature and 5-year survival rate of only 20%.5 Autoimmune atrophic gastritis and pernicious anemia results from autoantibodies against the parietal cell and intrinsic factor, preventing the absorption of B12.6 Acute Helicobacter pylori (H pylori) infection is a cause of transient hypochlorhydria,7 which occurs to facilitate the survival and colonization of H pylori.8
Most chronic infections with H pylori lead to pangastritis and decreased acid production.3 In children with H pylori infection, low stomach acid has been shown to reduce serum iron and transferrin, playing a role in refractory iron deficiency anemia.9 It has been hypothesized that low stomach acid reduces protein absorption and is a risk factor for depression, due to the relatively reduced levels of tryptophan and tyrosine in the brain.10 A low level of pepsin with hypochlorhydria causes incomplete protein digestion, which may lead to improper absorption of macromolecules into the circulation, as well as immune-complex deposition diseases.11 Other causes of hypochlorhydria include chronic overeating, hypoadrenalism, chronic stress, excess intake of processed foods and carbohydrates, caffeine, and alcohol.12
Diagnosis of Low Stomach Acid
The rationale for assessment of gastric acid production is usually considered during the history portion of a patient intake. Reported symptoms often relate to indigestion or functional dyspepsia developing during or after meals.13 Complaints such as gas, bloating, muscle cramps, epigastric heaviness and easy satiety can relate to a hypochlorhydric state, although the condition can also be asymptomatic.13 The symptomatic state is related to several factors, including mucosal integrity, parietal cell concentration, extrinsic inhibition, gastric reserve, and/or lower esophageal sphincter tone, to highlight a few theoretical causes.
Clinical presentation can vary widely, and hypochlorhydria should always be considered in patients with deficient states of depleted micro- and macromolecules, low vitality, and changes in gastrointestinal function. Signs may include deficiencies of vitamins and minerals, muscle cramps and twitches, acne, food allergies, dilated capillaries on cheeks and nose, brittle and peeling nails, and halitosis.11,13 Neurological symptoms due to nerve demyelination, including paresthesias or numbness and gait problems, are related to vitamin B12 deficiency caused by inadequate intrinsic factor from parietal cell loss. If pernicious anemia is suspected, testing for anti-parietal cell and anti-intrinsic factor antibodies is warranted, as the Schilling test is no longer used.14 To evaluate vitamin B12 deficiency, serum homocysteine and methylmalonic acid are most useful in making the diagnosis.14 Although not gastric-specific, a complete digestive stool analysis may be useful in assessing the nature of a gastrointestinal illness and involved organs.
The following is a brief overview of available lab tests for clinical practice, beginning with conventional tests, and followed by functional approaches.
Conventional Tests for Hypochlorhydria
Direct acid aspiration has been the longest-used method of gastric acid analysis, and remains the gold standard compared to other available methods.15 Aspiration of contents may be performed using a nasogastric tube, or suctioned during endoscopy or intubation. This method is used with test meals, histamine augmentation, or the gastrin analogs pentagastrin/tetragastrin, to enhance the analysis of gastric acid output. However accurate these exams are, they are invasive and uncomfortable and require an experienced provider to perform them.15
The Heidelberg test, involving a capsule containing a pH-sensitive radio-transmitting device, has been in use since the 1960s.15 A small pH sensor, with or without a tether, is swallowed, and gastric acid fluctuation is evaluated before and after ingestion of a sodium bicarbonate solution. The presence of a tether allows the pH of gastric contents to be measured and evaluated through challenge; the absence of a tether allows the capsule to flow through, giving information on emptying time and intestinal pH.16 This method only provides a measure of pH, with no information on gastric acid quantity.15 Using the Heidelberg capsule allows categorizing the degree of hypochlorhydria with rate-of-return to baseline pH after a challenge, further narrowing the best treatment options for the observed condition.17
The SmartPill is a validated wireless motility device for monitoring liquid meal-stimulated gastric acid output.18 The device is non-invasive, well-tolerated, and reproducible in the measurement of gastric acid output, providing both quantitative and qualitative measurements. Compared to the Heidelberg capsule, the SmartPill is larger, does not leave the stomach as quickly, there is no need for tethering, and the entire stomach is sampled.18 The patient is able to remain mobile, to replicate physiologic gastric movement, thereby enhancing gastric motility evaluation.18 The SmartPill can also be used for evaluation of regional and whole-gut transit time in patients with motility issues, which allows the ability to assess and further refine diagnosis of small bowel disease.19
The gastric string test can measure basal acid output (with 8 to10-hour period of fasting before test) or peak acid output (protein-rich meal eaten 2 hours before test).12 A capsule, which is attached to an absorbent cotton string, is swallowed and held in the stomach for about 10 minutes; it is then removed and pH paper is applied to the string in various locations to determine the stomach acidity.13 A bicarbonate challenge or stimulation with bitters can also be applied, to further refine assessment of gastric function.12
Functional Tests for Hypochlorhydria
The HCl challenge test consists of taking an escalating dose of HCl capsules during meals until a symptomatic response is perceived (such as burning or dyspepsia) or a dose of 7 capsules is reached, whichever comes first.11 The ability to handle excess stomach acid has the potential to confound results due to a range of factors, including visceral sensitivity, timing of last meal, and gastric-emptying rate.17 HCl capsules are then supplemented at a dose 1 less than the amount that caused the initial symptoms to be experienced with the challenge, until the original sensation of discomfort begins. The dose of HCl is then decreased by 1 capsule every 3 days, or when a symptomatic response occurs, thus allowing the stomach to slowly regain its endogenous ability to produce HCl.11 The lack of symptomatic response once the maximum HCl dose is achieved is considered a sign of hypochlorhydria.17
The baking soda (sodium bicarbonate) challenge test instructions are based on anecdotal evidence, as there are currently no published protocols available at the time of this writing. The test requires drinking ½ tsp of baking soda mixed in a small amount of water, and then measuring time to eructation, which occurs when carbon dioxide (CO2) is released after bicarbonate reacts with HCl. Even though the chemical reaction between HCl and bicarbonate is instantaneous, the resulting gas production is slow and poses little risk of gastric rupture when a recommended dose of ½ tsp sodium bicarbonate is used.20 The deduced hypothesis of this test is that if time to eructation is extended or no eructation occurs at all, there is insufficient HCl present to buffer the bicarbonate, and the volume of CO2 produced will be incapable of release in the form of an eructation.
The functional gastrointestinal exam can reveal specific areas of the body that exhibit signs in relation to a hypochlorhydric state. This includes the use of Ridler reflex points, Chapman’s reflexes, muscle testing, lingual-neuro testing, and tongue reflex markers.13 The application and interpretation of these tests is beyond the scope of this paper. For further information, please refer to Sandberg-Lewis’ 2009 book for a more detailed description.13
Gastric acidity assessment is a valuable tool for naturopathic physicians, keeping in mind that the reliability and efficacy of a diagnostic approach will depend on practitioner experience, patient preference, availability, invasiveness, and cost. Clinicians are responsible for considering confounding variables with the use of all functional and conventional tests, which includes being cognizant of other factors that influence results. When hypochlorhydria is a leading differential diagnosis and an etiological factor for comorbidities, investigating the underlying cause of low gastric acid must be undertaken. Once the cause has been postulated, accurate measurement of gastric acidity will target the most effective treatment, providing the most benefit and resulting in the least harm.
It takes an astute physician to utilize the safest and most useful diagnostic tests, placing the pieces of the puzzle together, and reaching the essence of Tolle Causam. While achlorhydria has well established testing protocols, there is varied evidence for tests assessing hypochlorhydria. The review of current research suggests further inquiry, and discourse is needed for functional gastric acidity assessments. It is these considerations that will lead to high-quality patient care with clinically significant outcomes.
Taylor Seier, BCom, is a new father and 4th-year naturopathic student at Boucher Institute of Naturopathic Medicine (BINM). He received his bachelor’s degree in commerce, with a major in finance, from the University of Alberta. Taylor also worked as an EMT-A from 2006 to 2010, gaining valuable experience in the medical field. He has a passion for pediatrics and cardiology, with plans to pursue further homeopathic and environmental medicine training following graduation.
Thara Vayali, BSc, MA, ND, is a graduate from the University of British Columbia (Nutritional Sciences), Royal Roads University (Environmental Communications) and the Boucher Institute of Naturopathic Medicine. She practices in Vancouver, BC, and is the creator of Change: Natural Medicine. Her clinical focus is on gastrointestinal, immune, and endocrine health. As a speaker, teacher, and researcher, her passion is translating high-quality information into an understandable format.
- Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. 2006;296(24):2947-2953.
- Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Philadelphia, PA: Saunders/Elsevier; 2010.
- Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology. 2008;134(7):1842-1860.
- Svendsen JH, Dahl C, Svendsen LB, Christiansen PM. Gastric cancer risk in achlorhydric patients. A long-term follow-up study. Scand J Gastroenterol. 1986;21(1):16-20.
- Nagini S. Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 2012;4(7):156-169.
- Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis-pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10(9):529-541.
- Smolka AJ, Backert S. How Helicobacter pylori infection controls gastric acid secretion. J Gastroenterol. 2012;47(6):609-618.
- Zaki M, Coudron PE, McCuen RW, et al. H. pylori acutely inhibits gastric secretion by activating CGRP sensory neurons coupled to stimulation of somatostatin and inhibition of histamine secretion. Am J Physiol Gastrointest Liver Physiol. 2013;304(8):G715-G722.
- Harris PR, Serrano CA, Villagrán A, et al. Helicobacter pylori-associated hypochlorhydria in children, and development of iron deficiency. J Clin Pathol. 2013;66(4):343-347.
- Cater RE 2nd. The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes. Med Hypotheses. 1992;39(4):375-383.
- Pizzorno JE, Murray MT, eds. Textbook of Natural Medicine. St Louis, MO: Elsevier/Saunders; 2012.
- Weatherby D. In-Office Lab Testing: Functional Terrain Analysis. Ashland, OR: Bear Mountain Publishing; 2007.
- Sandberg-Lewis S. Functional Gastroenterology: Assessing and Addressing the Causes of Functional Gastrointestinal Disorders. Portland, OR: NCNM Press; 2009.
- Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160.
- Ghosh T, Lewis DI, Axon AT, Everett SM. Review article: methods of measuring gastric acid secretion. Aliment Pharmacol Ther. 2011;33(7):768-781.
- Heidelberg Medical. [Product description] Available at: http://www.phcapsule.com. Accessed August 27, 2013.
- Yarnell E. Natural Approach to Gastroenterology. East Wenatchee, WA: Healing Mountain Publishing, Inc; 2011.
- Weinstein DH, DeRijke S, Chow CC, et al. A new method for determining gastric acid output using a wireless pH-sensing capsule. Aliment Pharmacol Ther. 2013;37(12):1198-1209.
- Tran K, Brun R, Kuo B. Evaluation of regional and whole gut motility using the wireless motility capsule: relevance in clinical practice. Therap Adv Gastroenterol. 2012;5(4):249-260.
- Fordtran JS, Morawski SG, Santa Ana CA, Rector FC Jr. Gas production after reaction of sodium bicarbonate and hydrochloric acid. Gastroenterology. 1984;87(5):1014-1021.