The combination of hydrochloric acid, lipase, and pepsin combine to create the acidic gastric juices found in the stomach. These healthy stomach acid levels serve as a first line of defense for the gastrointestinal system, preventing infectious agents from reaching the intestines. A normal gastric pH is considered to be present with pH values >3, with values below 4 capable of killing bacterial invaders within 15 minutes. Gastric juices with a pH >3 mark the beginning stages of hypochlorhydria. As the pH increases above 4, there is an increased prevalence of bacterial overgrowth. Achlorhydria is defined as a pH >7.

Click here to learn more about the Hedberg Institute Membership.

There are two main categories of hypochlorhydria: iatrogenic and acquired. Iatrogenic hypochlorhydria is the most common, resulting from the use of medications to reduce gastric acid secretions. Proton pump inhibitors (PPIs) are one of the top ten most prescribed drugs in the world, contributing to the rise in iatrogenic hypochlorhydria. Malnutrition is the leading cause of acquired hypochlorhydria.

Individuals taking PPIs generally have a pH between 5-7. Individuals with hypochlorhydria are at an increased risk for infection and disease due to a loss of this protective barrier. Research conducted by Martinsen, Fossmark, and Waldum (2019) demonstrated that individuals with hypochlorhydria were at an increased risk of a variety of infections including bacterial, fungal, and parasitic infections. One study they reviewed reported a significant decrease in Shannon’s diversity of the GI microbiome and changes in 20% of the bacterial taxa in PPI users versus non-users.

The increased use of PPIs makes it necessary to review current medications, both prescribed and over the counter, at each patient encounter. Nutritional status should also be evaluated utilizing blood labs, anthropometrics, diet diaries, food allergies/sensitivities, etc. Other useful factors in screening a patient for gastric hypoacidity include assessing gender, age, stress levels/eating behaviors, geographic origin/nationality, testing of stomach acid levels, and labs to rule out concurrent diseases such as Helicobacter pylori, chronic gastritis, parietal cell autoantibodies, hypothyroidism, etc. Keep in mind that there can be discrepancies between different testing methods and cutoff values depending on the labs used.

Malnutrition can be the cause of or the result of hypochlorhydria. Malnutrition that leads to a deficiency in the nutrients needed to make HCL can cause hypochlorhydria. These include chloride, sodium, potassium, zinc, and iodine. Malnutrition can also develop as a result of hypochlorhydria. Decreased gastric acidity impairs nutrient absorption resulting in possible nutrient deficiencies for most of the essential vitamins and minerals including protein, iron, calcium, magnesium, zinc, vitamins A and E, copper, and all of the B vitamins. The presence of both malnutrition and hypochlorhydria increases the risk of enteric infections. There is also an increased prevalence of food allergies in individuals with reduced gastric acidity as they lose the ability to sufficiently denature proteins. With hypochlorhydria, larger protein peptides remain which can trigger an immune system response, resulting in allergic symptoms. Therefore, screening for hypochlorhydria should be conducted in individuals that suffer from malnutrition and/or food sensitivities/allergies.

There is also an increased prevalence of food allergies in individuals with reduced gastric acidity as they lose the ability to sufficiently denature proteins. With hypochlorhydria, larger protein peptides remain which can trigger an immune system response, resulting in allergic symptoms. Therefore, screening for hypochlorhydria should be conducted in individuals that suffer from malnutrition and/or food sensitivities/allergies.

Stress management is also important in regulating gastric acid secretion. This is due to the digestive inhibition created by the sympathetic nervous system and the splanchnic nerves. Splanchnic nerve activation inhibits digestive activity (suppression of gastric juices and HCL production), pancreas, and gallbladder. It is therefore necessary to evaluate an individual’s eating environment. Recommendations may need to be made that decrease sympathetic stimulation during meal time such as FaceBook, reading/listening to news, controversial discussions, etc.

Reduced gastric acidity can impair the absorption of some prescription medications, in effect reducing the dosage needed for a given condition. The decreased gastric acidity caused by PPI usage can impair the absorption of pH dependent, weakly basic drugs. A study by Yago et al (2013) showed that 1500mg of betaine HCL was able to lower gastric acid pH levels to < 3 within a mean time of 6.3 (+ 4.3) minutes. The healthy gastric pH was short lived with reacidification lasting ~ 75 minutes.

The authors also noted that serum gastrin levels remained unchanged and did not show a correlation with the measured pH changes observed. This lack of correlation between serum gastrin levels and gastric pH decreases the validity of using serum gastrin as a marker for hypochlorhydria.

Yago et al (2014) went on to prove that betaine HCL increased absorption of a drug with pH-dependent solubility. Betaine HCL is well tolerated and easy to administer, offering a viable treatment option for those with hypochlorhydria. The recommended dosage is 1500 mg per meal. This dosage was shown to work nearly as fast as higher dosages (3000 mg and 4500 mg) and with less risk of irritation and with less pills to swallow.

Recommended—Moss Nutrition Betaine HCL

• Please consult your doctor before taking Betaine HCL.
  
• Contains 750 mg per capsule.
  
• Dose is dependent on the size of the meal and how much protein is being consumed. A large steak requires more HCL compared with beans and rice.
  
• Taking niacin or niacinamide (> 500 mg) can have a buffering effect on stomach pH, requiring higher doses of HCL.
  

Bitters

Bitters provide an excellent option for those who cannot take HCL. Bitters promote digestion by stimulating the secretion of stomach acid, digestive enzymes, and bile.

• Cephalic Vagal reflex—Stimulation of oropharyngeal bitter receptors increases saliva and vagal stimulation to the digestive organs.
  
• Local reflex—Stimulation of oropharyngeal and gastrointestinal bitter receptors acts locally to increase digestive secretions.
  
• Alcohol—can improve digestion (rather than the bitter taste)
  
• Hyperemia—the major influence of bitters on digestion is improved blood circulation in the abdominal organs.
  

Proper Bitters Dosing

Recommended—David Winston’s Original Bitters

• Please consult your doctor before taking bitters.
  
• 30 drops—taken straight or in a small amount of water before meals
  
• Ideally take bitters 15-20 minutes before a meal.
  
• Take for at least two months
  
• Use caution with GERD, gastric ulcers, or gastritis
  
• Do not use in hyperchlorhydria
  

Coffee

Boekema et al (1999) found that coffee, caffeinated and decaffeinated, stimulated HCL production. Rubach et al (2014) found that higher caffeine coffees (market blends) had a quicker reacidification time versus lower caffeine coffees (Dark French roast).

Vitamin C

O’Connor et al (1989) found that individuals with hypochlorhydria (pH > 4) had low fasting levels of gastric vitamin C. They noted a significant correlation between gastric juice and plasma concentrations of vitamin C (p=0.002).

Proper Vitamin C

Recommended –Moss Nutrition Buffered C Select

• Please consult your doctor before taking vitamin C.
  
• 1 b.i.d.
  
• Use vitamin C along with HCL. Improves iron absorption, important in the production of HCL
  
• Reduces the conversion of nitrites to carcinogenic nitrosamines at both acidic and neutral pH
  
• Effective against H. pylori
  

Alternative Enzyme Options

Pancreatin Select (Moss Nutrition)—(more global digestive support, including HCL)

• Please consult your doctor before taking this or a similar product.
  
• 1-3 per meal.
  
• This does contain ox bile so do not use with plant-based diets.
  

Digest Select (Moss Nutrition)

• Please consult your doctor before taking this or a similar product.
  
• 1-3 per meal.
  
• Can be used with plant-based diets. Does not contain HCL, ox bile, or bitters.
  
• This can be used with those that have ulcers.
  
• This can be used with those that have increased sensitivities to previous digestive supports mentioned.
  

How to Assess and Manage Hypochlorhydria (Quick Reference Guide)

Assess:

• Review current medications at each patient encounter
  
• Screen for the use of PPIs.
  
• Evaluate diet for imbalances/deficiencies/food allergies
  
• Evaluate for Signs and Symptoms of hypochlorhydria (see below)
  
• Assess stress levels in general and meal-time behaviors/environment.
  
• Assess geographic origin/nationality, gender, and age.
  
• Note: Gastric HCL levels increase during follicular phase and decrease during luteal phase of menstrual cycle.
  
• In general, aging is associated with a decrease in stomach acid production. There is a large variance in fasting hypochlorhydria in the elderly with one study reporting it to be less common in Americans (10%) compared with Japanese (>60%) or Norwegians (80%).
  

Test:

• Radio-telemetric capsules—Heidelberg pH Diagnostic System
  
• pH-sensitive tablets—https://gastro-tests.com/
  
• Anti-parietal cell antibodies
  
• Intrinsic factor antibodies
  
• H. Pylori
  
• Iron/ferritin levels
  
• Thyroid panel
  
• Rule out other anemias
  

Signs and Symptoms

• Belching after meals
  
• Bloating
  
• Gas
  
• Morning diarrhea
  
• Diarrhea after heavy meals
  
• Constipation
  
• Muscle cramping
  
• Oral symptoms-dentures
  
• Rosacea
  
• Dilated capillaries around the maxilla and nose
  
• Early satiety
  
• Weight loss
  
• Anemia
  
• Heartburn
  
• Indigestion
  
• Sensation of food sitting in the stomach
  
• Halitosis
  
• Fatigue
  
• Depression
  
• Poor quality fingernails
  
• Brittle hair
  
• Hair loss
  
• Symptoms tend to be worse with meat
  

Miscellaneous Information

Adverse effects of Proton Pump Inhibitors

• Alteration of gastrointestinal microbiome—SIBO, dysbiosis, candidiasis, etc.
  
• Increased risk of infection—C.difficile infection, other enteric bacterial infections, colitis, pneumonia, etc.
  
• Impaired absorption of nutrients and drugs. Nutrient deficiencies—iron, calcium, magnesium, B vitamins, protein
  
• Gastric cancer
  
• Osteoporosis
  
• Kidney injury/disease
  
• Impaired drug absorption
  
• Overall mortality
  

Causes of Hypochlorhydria

• Atrophic gastritis due to antibodies against parietal cells
  
• Stomach cancer
  
• Stress
  
• H. pylori—eradication of infection restores normal HCL levels
  
• Severe iron deficiency
  
• Antacids, PPIs, histamine blockers
  
• Post gastroenteritis
  
• Hypothyroidism
  
• Pernicious anemia
  
• Radiation therapy involving stomach
  
• Gastric bypass surgery
  
• Vasoactive intestinal peptides and somatostantinomas –both are islet cell tumors of the pancreas
  
• Pellagra, caused by niacin deficiency
  
• Chloride, sodium, potassium, zinc and/or iodine deficiency. These are all elements needed to produce adequate levels of stomach acid
  
• Sjogren’s Syndrome
  
• Menetrier’s disease, characterized by hyperplasia of mucous cells in the stomach also causing excess protein loss leading to hypoalbuminemia. Presents with abdominal pain and edema
  

Pathogens involved with Hypochlorhydria

Bacterial infections:

• Non-typhoid salmonellosis
  
• Cholera
  
• Campylobacter jejuni
  
• Diarrhoeagenic Escherichia coli
  
• Clostridium difficile
  
• Shigellosis
  
• Listeriosis
  
• Brucellosis
  
• H. pylori
  

Parasitic infections:

• Strongyloides
  
• Giardia
  
• Entamoeba histolytica
  

Fungal infections:

• Candida albicans
  

Other Infections:

• Yersinia enterocolitica
  
• Enteroviruses
  
• Prions – Creutzfeld-Jakob
  
• Strep
  
• Staph
  
• Enterococcus
  

Hedberg Institute Members can download my hypochlorhydria protocols by logging in and visiting the Practice Tools page.

Click here to learn more about the Hedberg Institute Membership.

References

1. Martinsen TC, Fossmark R, Waldum HL. The Phylogeny and Biological Function of Gastric Juice—Microbiological Consequences of Removing Gastric Acid. Int J Mol Sci. 2019;20(23):6031. doi:10.3390/ijms20236031
   
2. Guilliams TG, Drake LE. Meal-Time Supplementation with Betaine HCl for Functional Hypochlorhydria: What is the Evidence? Integr Med Clin J. 2020;19(1):32-36.
   
3. Schubert ML. Functional anatomy and physiology of gastric secretion. Curr Opin Gastroenterol. 2015;31(6):479-485. doi:10.1097/MOG.0000000000000213
   
4. Minalyan A, Gabrielyan L, Scott D, Jacobs J, Pisegna JR. The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors. Curr Gastroenterol Rep. 2017;19(8):42. doi:10.1007/s11894-017-0577-6
   
5. Yago MAR, Frymoyer AR, Smelick GS, et al. Gastric Re-acidification with Betaine HCl in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria. Mol Pharm. 2013;10(11):4032-4037. doi:10.1021/mp4003738
   
6. Yago MR, Frymoyer A, Benet LZ, et al. The Use of Betaine HCl to Enhance Dasatinib Absorption in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria. AAPS J. 2014;16(6):1358-1365. doi:10.1208/s12248-014-9673-9
   
7. Surofchy DD, Frassetto LA, Benet LZ. Food, Acid Supplementation and Drug Absorption – A Complicated Gastric Mix: A Randomized Control Trial. Pharm Res. 2019;36(11):155. doi:10.1007/s11095-019-2693-5
   
8. Shay H, Gershon-Cohen J, Fels SS. Gastric anacidity: Its physiologic and clinical significance and its management. Am J Dig Dis. 1941;8(4):115-123. doi:10.1007/BF02998210
   
9. Maron FS. Enamel erosion resulting from hydrochloric acid tablets. J Am Dent Assoc 1939. 1996;127(6):781-784. doi:10.14219/jada.archive.1996.0314
   
10. Boekema PJ, Samsom M, van Berge Henegouwen GP, Smout AJ. Coffee and gastrointestinal function: facts and fiction. A review. Scand J Gastroenterol Suppl. 1999;230:35-39. doi:10.1080/003655299750025525
    
11. Rubach M, Lang R, Bytof G, et al. A dark brown roast coffee blend is less effective at stimulating gastric acid secretion in healthy volunteers compared to a medium roast market blend. Mol Nutr Food Res. 2014;58(6):1370-1373. doi:10.1002/mnfr.201300890
    
12. O’Connor HJ, Schorah CJ, Habibzedah N, Axon AT, Cockel R. Vitamin C in the human stomach: relation to gastric pH, gastroduodenal disease, and possible sources. Gut. 1989;30(4):436-442.
    
13. Elias E, Targownik LE. The Clinician’s Guide to Proton Pump Inhibitor Related Adverse Events. Drugs. 2019;79(7):715-731. doi:10.1007/s40265-019-01110-3