Acid reducers are commonly used medications to treat gastrointestinal conditions such as acid reflux, heartburn, indigestion, and peptic ulcers. The symptoms associated with these conditions are often uncomfortable and painful, driving people to try these medications to find relief. For those 20% of Americans with gastroesophageal reflux disease (GERD), these unpleasant symptoms occur frequently, typically leading to daily and prolonged use of acid reducers.
Even though these medications are highly prescribed, the associated risks of long-term treatment are not as well known as the relief they may bring. In particular, the impact of acid reducers on nutrient absorption is often minimized or overlooked.
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Overview of Acid Reducers
As their name implies, acid reducers decrease the amount of acid produced in the stomach. For conditions such as peptic ulcers, this temporary acid reduction allows the tissue to heal. For conditions such as heartburn or GERD, the contents refluxed from the stomach into the esophagus are less acidic, and therefore less pain or heartburn is experienced. There are different types and mechanisms of acid reducers used to treat gastric acid-related conditions.
Proton Pump Inhibitors (PPIs) are considered first-line therapy and are the most commonly used acid reducers as they are the most potent. They bind irreversibly to the gastric proton pump within the membrane of parietal cells and block the final step in acid secretion. These medications include omeprazole, esomeprazole, pantoprazole, rabeprazole and lansoprazole.
Histamine H2-receptor antagonists, often referred to as H2 blockers, are another option to reduce stomach acid. These medications work by reversibly binding to the histamine receptor on gastric parietal cells. This prevents histamine from binding to its receptor, inhibiting its activity of stimulating acid secretion from the parietal cells. H2 blockers include famotidine and cimetidine.
Liquid or chewable antacids can also be used to reduce acid, though these are more appropriate for mild and occasional indigestion or heartburn and aren’t used as commonly as PPIs or H2 blockers. Active ingredients vary depending on the product but generally contain calcium, magnesium, or aluminum salts in various combinations. These compounds neutralize gastric acid quickly. Popular brand names include Tums, Rolaids, Mylanta, and Pepto-Bismol.
Importance of Stomach Acid in Nutrient Absorption
The role of stomach acid in digestion is one of the primary functions of the stomach. When food is chewed and swallowed, contents travel down the esophagus, through the lower esophageal sphincter (LES), and into the stomach. This triggers a cascading effect of various molecules leading to the secretion of pepsinogen, intrinsic factor, and stomach acid within its gastric juices. The presence of stomach acid is crucial as an acidic environment is required to facilitate optimal digestion. When stomach acid is released, the pH of the stomach is decreased and this in turn activates pepsin from its inactive form pepsinogen, one of the main enzymes involved in breaking down protein into peptides and amino acids. When stomach acid is reduced, the inverse can occur. The pH of the stomach increases and the digestion process is hindered, resulting in the insufficient breakdown of food. This can be problematic as you can’t go on to absorb what you don’t first digest, potentially impacting the absorption of specific nutrients. Stomach acid and nutrient absorption are linked - for optimal digestion and absorption of our food, we need stomach acid.
Nutrients Impacted by Acid Reducers
Long-term use of acid reducers may affect the absorption of key nutrients. In particular, nutrients such as vitamin B12, iron, calcium, and magnesium have all been linked to acid reducers or low stomach acid. These nutrients require an acidic environment to be absorbed. In addition to lowering the pH to create this environment, stomach acid is also responsible for releasing vitamin B12 and iron from their dietary proteins so they can go through the absorption process.
Acid reducers promote unfavorable conditions for these nutrients and resulting low levels are known side effects of these medications. One study evaluated long-term use (defined as two or more years) of PPI or H2 blocker therapy and their effect on vitamin B12 levels. Both PPI and H2 blocker therapy were associated with an increased risk of vitamin B12 deficiency. Prolonged therapy increases the risk of nutrient deficiencies and associated consequences. If these are not identified and addressed, over time new symptoms can present depending on which nutrient is depleted:
- Vitamin B12 deficiency can lead to anemia, neuropathy, cognitive impairment, weakness, fatigue, headaches, dizziness or loss of balance, and glossitis (inflammation of the tongue).
- Poor iron absorption can lead to iron deficiency anemia. Symptoms include headache, fatigue, pale skin, brittle nails, hair loss, weakness, dizziness, rapid heartbeat, and shortness of breath.
- Low levels of magnesium can cause various symptoms depending on the severity of the deficit. Symptoms range from constipation, anxiety, and muscle tension to seizures, cardiac arrhythmias, and tremors.
- Inadequate calcium absorption can increase fracture risk and negatively affect bone turnover balance.
Risks Associated with Long-term Use of Acid Reducers
In addition to nutrient deficiencies, long-term use of acid reducers carries several other health risks. Side effects of prolonged acid reducer use have received more awareness in recent years due to research findings, particularly regarding PPIs. The FDA reviewed seven epidemiological studies evaluating PPI use and fracture risk, prompting the revision of drug labeling to include this warning. Other data have shown increased susceptibility to infections, most notably Clostridium difficile-associated diarrhea, pneumonia, and small intestinal bacterial overgrowth (SIBO), though other enteric infections of Campylobacter and Salmonella species have also been reported. As stomach acid plays an important role in protecting the body from pathogenic microbes, reducing stomach acid leads to changes in gut microbiota and impacts the immune system.
A recent study explored the connection between PPI therapy and the development of autoimmune disease. PPI use can also affect kidney function and has been linked to both acute interstitial nephritis and the risk of chronic kidney disease. Early evidence indicates an association between chronic PPI therapy and the risk of dementia. This is possibly due to vitamin B12 deficiency and increased amyloid plaque formation, though further research is needed. Finally, one study suggests an indirectly increased risk of gastric cancer with continued PPI use post Helicobacter pylori treatment in certain high-risk patients. Chronic PPI use is associated with both acute and chronic health conditions. If PPI therapy is needed, the best way to diminish these side effects is to use the lowest effective dose for the shortest duration possible.
Strategies to Mitigate Nutrient Absorption Issues
There are different strategies to consider in reducing the risk of nutrient malabsorption. One dietary strategy with acid reducers is to increase the intake of vitamin B12, iron, calcium, and magnesium through foods that are rich in these micronutrients. This can help offset the risk of deficiencies. Regular monitoring of nutrient levels identifies instances in which additional supplementation may be appropriate, such as a vitamin B complex or magnesium supplement. Digestive enzymes can be another helpful supplement to support digestion and nutrient absorption. Various formulas are available, some of which contain betaine hydrochloride (HCl), a supplemental source similar to stomach acid. Betaine HCl can be beneficial in some patients who have low stomach acid, or hypochlorhydria, a potential underlying contributor to acid-related conditions. Lastly, consider the timing of acid-reducing medications.
For once daily dosing of H2 blockers, the best time to dose is at bedtime. This provides acid control through the night and doesn’t reduce nutrient absorption to the extent that might occur with daytime dosing. For patients occasionally using liquid or chewable antacids and also requiring iron supplementation, dosing of iron should be separated by 2 hours from antacids to prevent the minerals from binding to the iron and interfering with absorption. A personalized approach based on individual health needs and medication regimens is central to mitigating nutrient absorption issues.
Alternatives to Acid Reducers
The great news is that there are alternative treatments available for managing acid-related conditions without relying solely on acid reducers. Lifestyle modifications and natural remedies for GERD and heartburn can effectively reduce or eliminate symptoms. These include:
- Demulcent herbs such as slippery elm, marshmallow root, or deglycyrrhizinated licorice (DGL). These soothing herbs coat the lining of the esophagus and stomach and promote the healing of irritated or inflamed tissue.
- Melatonin has been shown to improve GERD symptoms through its protective effects on GI mucosal tissue as well as improving the muscle tone of the LES, strengthening the barrier between the stomach and esophagus.
- Probiotics with Lactobacillus and Bifidobacterium strains can be effective for GERD symptoms as reported in this recent systematic review. Evaluated studies included daily doses ranging from 1 - 46 billion colony-forming units (CFU) for up to 12 weeks.
- Lifestyle modifications, particularly dietary changes and stress management. Consider avoiding potential triggers such as spicy foods, coffee, tomatoes, gluten, citrus fruits, chocolate, alcohol, and for some individuals, dairy products. Additional measures include eating smaller meals, ensuring 3 hours between the last meal of the day and bedtime, and elevating the head of the bed. Stress management is an important component as well, as research shows acid reflux is significantly associated with stress, and symptom severity is correlated with stress levels. Mitigating stress through deep breathing and other mindfulness practices can help manage acid-related conditions and improve quality of life.
In some instances, alternative treatments and lifestyle modifications are sufficient, and acid reducers aren’t needed. These approaches are best utilized while also working to identify and address the underlying cause of acid-related conditions with a healthcare provider.
Monitoring and Adjusting Treatment Plans
Regular monitoring and follow-up are important for individuals taking acid reducers. Nutrient levels should be assessed periodically and appropriate supplements used if needed. Treatment plans may warrant adjusting, including evaluating whether an acid reducer is still indicated, as up to 70% of people take them without an appropriate indication. Consider the dose and determine whether reducing the dose and/or frequency can be attempted, or if step-down therapy is an option, such as switching from a PPI to an H2 blocker as these medications tend to be a safer alternative in most cases. If underlying root causes are being addressed and other strategies such as lifestyle modifications or alternatives are being utilized, it may be time to discontinue acid reducer therapy. If acid reducers have been used long-term, it is best to taper therapy slowly to minimize rebound acid hypersecretion. Healthcare providers play a significant role in these ways by tailoring treatment strategies to optimize outcomes. Monitoring overall health with acid reducers is central to the appropriate use of these medications.
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Acid Reducers and Nutrient Absorption: Key Takeaways
An important part of navigating health with acid reducers is awareness of the associated risks, including the impact on nutrient absorption. Without knowing the potential pitfalls, the risk/benefit ratio is incomplete. Vitamin B12, iron, calcium, and magnesium levels should be assessed regularly to avoid deficiencies in these key nutrients. Acid reducers are widely available without a prescription, and many people start taking these medications without knowing the most appropriate way to use them to minimize their risk. Consulting with healthcare providers allows for personalized advice, including possible alternatives and mitigation strategies.
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References
1. Antunes, C., Curtis, S. A., & Aleem, A. (2023, July 3). Gastroesophageal reflux disease. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK441938/
2. Bang, C. S., Yang, Y. J., & Baik, G. H. (2019). Melatonin for the treatment of gastroesophageal reflux disease; protocol for a systematic review and meta-analysis. Medicine, 98(4), e14241. https://doi.org/10.1097/md.0000000000014241
3. Bhardwaj, K., & Kishore, L. (2021). Natural remedies: For gastroesophageal reflux disease. ~ 114 ~ Journal of Medicinal Plants Studies, 9(4), 114–118. https://www.plantsjournal.com/archives/2021/vol9issue4/PartB/9-4-17-566.pdf
4. Carabotti, M., Annibale, B., & Lahner, E. (2021). Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach. Nutrients, 13(1), 208. https://doi.org/10.3390/nu13010208
5. Cheng, J., & Ouwehand, A. C. (2020). Gastroesophageal Reflux Disease and Probiotics: A Systematic Review. Nutrients, 12(1), 132. https://doi.org/10.3390/nu12010132
6. Christie, J. (2022, March 8). Weakness, Pale Skin, And Headache Are Signs Of This Mineral Deficiency. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-iron-deficiency
7. Cloyd, J. (2023, February 21). A Functional Medicine GERD Protocol. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-gerd-protocol
8. Cloyd, J. (2023b, October 18). The Top 6 Essential Health Benefits of Magnesium That You Should Know. Rupa Health. https://www.rupahealth.com/post/the-top-6-therapeutic-uses-of-magnesium-you-need-to-know
9. Cunningham, R., Dale, B., Undy, B., & Gaunt, N. (2003). Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. Journal of Hospital Infection, 54(3), 243–245. https://doi.org/10.1016/s0195-6701(03)00088-4
10. Drugs.com. (2016, December 14). Betaine Hydrochloride Uses, Benefits & Side Effects - Drugs.com Herbal Database. Drugs.com. https://www.drugs.com/npc/betaine-hydrochloride.html
11. El-Serag, H. B., Sweet, S., Winchester, C. C., & Dent, J. (2014). Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut, 63(6), 871–880. https://doi.org/10.1136/gutjnl-2012-304269
12. Ensrud, K. E., Duong, T., Cauley, J. A., Heaney, R. P., Wolf, R. L., Harris, E., & Cummings, S. R. (2000). Low Fractional Calcium Absorption Increases the Risk for Hip Fracture in Women with Low Calcium Intake. Annals of Internal Medicine, 132(5), 345. https://doi.org/10.7326/0003-4819-132-5-200003070-00003
13. Florentin, M. (2012). Proton pump inhibitor-induced hypomagnesemia: A new challenge. World Journal of Nephrology, 1(6), 151. https://doi.org/10.5527/wjn.v1.i6.151
14. Florent, C. (1993). Progress with proton pump inhibitors in acid peptic disease: treatment of duodenal and gastric ulcer. Clinical Therapeutics, 15 Suppl B, 14–21. https://pubmed.ncbi.nlm.nih.gov/7911399/
15. Gomm, W., von Holt, K., Thomé, F., Broich, K., Maier, W., Fink, A., Doblhammer, G., & Haenisch, B. (2016). Association of Proton Pump Inhibitors With Risk of Dementia. JAMA Neurology, 73(4), 410. https://doi.org/10.1001/jamaneurol.2015.4791
16. Gritti, I., Banfi, G., & Giulio Sergio Roi. (2000). PEPSINOGENS: PHYSIOLOGY, PHARMACOLOGY PATHOPHYSIOLOGY AND EXERCISE. Pharmacological Research, 41(3), 265–281. https://doi.org/10.1006/phrs.1999.0586
17. Heda, R., Toro, F., & Tombazzi, C. R. (2023, May 1). Physiology, Pepsin. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK537005/
18. Helgadottir, H., & Bjornsson, E. (2019). Problems Associated with Deprescribing of Proton Pump Inhibitors. International Journal of Molecular Sciences, 20(21), 5469. https://doi.org/10.3390/ijms20215469
19. Jaynes, M., & Kumar, A. B. (2018). The risks of long-term use of proton pump inhibitors: a critical review. Therapeutic Advances in Drug Safety, 10, 204209861880992. https://doi.org/10.1177/2042098618809927
20. Kalaichandran, A. (2023, November 9). Melatonin for GERD: The Sleep Hormone’s Role in Acid Reflux Relief. Rupa Health. https://www.rupahealth.com/post/melatonin-for-gerd-the-sleep-hormones-role-in-acid-reflux-relief
21. Kresge, K. (2022, December 7). How Does Low Stomach Acid Affect Your Body? Rupa Health. https://www.rupahealth.com/post/low-stomach-acid
22. Kuo, C.-J., Lin, C.-Y., Chen, C.-W., Hsu, C.-Y., Hsieh, S.-Y., Chiu, C.-T., & Lin, W.-R. (2021). Risk of Enteric Infection in Patients with Gastric Acid Supressive Drugs: A Population-Based Case-Control Study. Journal of Personalized Medicine, 11(11), 1063. https://doi.org/10.3390/jpm11111063
23. Laheij, R. J. F. (2004). Risk of Community-Acquired Pneumonia and Use of Gastric Acid–Suppressive Drugs. JAMA, 292(16), 1955. https://doi.org/10.1001/jama.292.16.1955
24. Lam, J. R., Schneider, J. L., Quesenberry, C. P., & Corley, D. A. (2017). Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology, 152(4), 821-829.e1. https://doi.org/10.1053/j.gastro.2016.11.023
25. Lam, J. R., Schneider, J. L., Zhao, W., & Corley, D. A. (2013). Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA, 310(22), 2435–2442. https://doi.org/10.1001/jama.2013.280490
26. Lazarus, B., Chen, Y., Wilson, F. P., Sang, Y., Chang, A. R., Coresh, J., & Grams, M. E. (2016). Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Internal Medicine, 176(2), 238. https://doi.org/10.1001/jamainternmed.2015.7193
27. Lehault, W. B., & Hughes, D. M. (2017). Review of the Long-Term Effects of Proton Pump Inhibitors. Federal Practitioner : For the Health Care Professionals of the VA, DoD, and PHS, 34(2), 19–23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372031/#:~:text=These%20include%20calcium%20and%20magnesium
28. Leonard, J., Marshall, J. K., & Moayyedi, P. (2007). Systematic review of the risk of enteric infection in patients taking acid suppression. The American Journal of Gastroenterology, 102(9), 2047–2056; quiz 2057. https://doi.org/10.1111/j.1572-0241.2007.01275.x
29. Lin, S.-H., Chang, Y.-S., Lin, T.-M., Hu, L.-F., Hou, T.-Y., Hsu, H.-C., Shen, Y.-C., Kuo, P.-I., Chen, W.-S., Lin, Y.-C., Chen, J.-H., & Chang, C.-C. (2021). Proton Pump Inhibitors Increase the Risk of Autoimmune Diseases: A Nationwide Cohort Study. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.736036
30. Lo, W., & Chan, W. W. (2013). Proton Pump Inhibitor Use and the Risk of Small Intestinal Bacterial Overgrowth: A Meta-analysis. Clinical Gastroenterology and Hepatology, 11(5), 483–490. https://doi.org/10.1016/j.cgh.2012.12.011
31. Maholy, N. (2023a, April 14). How to reduce stress through mind-body therapies. Rupa Health. https://www.rupahealth.com/post/how-to-reduce-stress-through-mind-body-therapies
32. Maholy, N. (2023, June 29). The Role of Probiotics and Prebiotics in Gut Health: An Integrative Perspective. Rupa Health. https://www.rupahealth.com/post/the-role-of-probiotics-and-prebiotics-in-gut-health-an-integrative-perspective
33. National Library of Medicine. (2021, August 11). Slippery Elm: MedlinePlus Supplements. Medlineplus.gov. https://medlineplus.gov/druginfo/natural/978.html
34. Nugent, C. C., & Terrell, J. M. (2019, May 7). H2 Blockers. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK525994/
35. Oshima, T., & Miwa, H. (2018). Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases. Journal of Neurogastroenterology and Motility, 24(3), 334–344. https://doi.org/10.5056/jnm18029
36. PROTONIX® (pantoprazole sodium) Warnings and Precautions | Pfizer Medical Information - US. (n.d.). Www.pfizermedicalinformation.com. Retrieved February 2, 2024, from https://www.pfizermedicalinformation.com/protonix/warnings
37. Ramsay, P. T., & Carr, A. (2011). Gastric acid and digestive physiology. The Surgical Clinics of North America, 91(5), 977–982. https://doi.org/10.1016/j.suc.2011.06.010
38. Singh, P., & Terrell, J. M. (2019). Antacids. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK526049/
39. Song, E. M., Jung, H.-K., & Jung, J. M. (2012). The Association Between Reflux Esophagitis and Psychosocial Stress. Digestive Diseases and Sciences, 58(2), 471–477. https://doi.org/10.1007/s10620-012-2377-z
40. Sweetnich, J. (2023, March 28). Calcium 101: Testing, top foods, & supplements. Rupa Health. https://www.rupahealth.com/post/calcium-101-testing-top-foods-supplements
41. Sweetnich, J. (2023, April 26). Unlocking the Benefits of Vitamin B12: The Importance of Maintaining Optimal Levels. Rupa Health. https://www.rupahealth.com/post/vitamin-b12-101
42. Tan, M. C., & Graham, D. Y. (2018). Proton pump inhibitor therapy after Helicobacter pylori eradication may increase the risk of gastric cancer. BMJ Evidence-Based Medicine, 23(3), 111–112. https://doi.org/10.1136/bmjebm-2018-110935
43. U.S. Food & Drug Administration. (2019). FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. FDA. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-possible-increased-risk-fractures-hip-wrist-and-spine-use-proton-pump
44. William, J. H., & Danziger, J. (2016). Proton-pump inhibitor-induced hypomagnesemia: Current research and proposed mechanisms. World Journal of Nephrology, 5(2), 152. https://doi.org/10.5527/wjn.v5.i2.152
45. Xue, W., You, J., Su, Y., & Wang, Q. (2019). The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article. Iranian Journal of Public Health, 48(3), 379–387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570791/