Article highlights:
- PPIs and antacids are widely used, but many long-term prescriptions may be unnecessary and prolonged use may carry health risks.
- Potential long-term risks include nutrient deficiencies, kidney disease, infections, bone loss, and dementia and other conditions.
- Support digestive health through diet and lifestyle habits.
Millions of people use proton pump inhibitors (PPIs) or OTC antacids to relieve heartburn and acid reflux. But growing research shows these popular prescription and over-the-counter medications may carry health risks when used long-term. In nearly 40 years of use since their introduction in 1989, a number of concerns have been raised and identified. Are you aware of the risks?
Widespread Use of Antacids Worldwide
According to the Antacid Market report, over 72% of adults in the U.S. and 60% of adults worldwide experience heartburn symptoms at least once per month, prompting PPI or antacid use. North America now accounts for 37% of the global antacid usage with the global market valued at $6.85 billion in 2026. The number of individuals who experience acid reflux and indigestion is expected to increase lending to an increase to $9.47 billion in 2035. An estimated 43% of adults 60 and older have digestive problems.
Common antacid medications include cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), famotidine (Pepcid), omeprazole (Prilosec), rabeprazole (Aciphex), esomeprazole (Nexium), as well as non-PPI acid blockers such as calcium carbonate (Tums or Rolaids), magnesium hydroxide (Milk of Magnesia), and others. Nearly 70% of antacid purchases are over-the-counter products.
PPI medications are the most potent inhibitors of gastric acid secretion. They are prescribed for acute, severe problems such as a bleeding ulcer and severe GERD as well as occasional indigestion and acid reflux. They are also commonly used prophylactically to prevent potential problems. A recent critical review study suggests that PPIs are overused with 25-70% of prescriptions having no appropriate indication of use.
Long-Term Risks of Antacids and PPIs
Across the globe, many have increasingly questioned the risks associated with long-term antacid/PPI use and overutilization. Currently, long-term PPI use has strong associations with Clostridium difficile/C. diff infection, chronic kidney disease and kidney damage, and nutritional deficiencies as the drugs affect vitamin B12, vitamin C, calcium, iron and magnesium metabolism.
Other risks include osteoporosis and bone fractures, major cardiovascular events when combined with certain medications, dementia, gallstones, gallbladder disease, complications with liver disease, increased gastrointestinal cancer risks, gut microbiome disruptions/SIBO, gastrointestinal bleeding and other concerns. Researchers often cite conflicting results and indicate that more studies are needed to verify these associations.
Increased Upper Respiratory Infections, C. Diff and Candida
Increased risk of upper respiratory infections with C. Diff and pneumonia are a significant concern with chronic PPI use. This is due to blocking of stomach acid pumps, changes in the esophageal sphincter tones and pH levels. These changes allow bacteria to migrate and colonize in the stomach, esophagus, lungs, throat, and sinuses changing the flora or microbiome of these tissues and disrupting mucosal barrier integrity.
In addition, fungal overgrowth such as Candida is more common in the gastrointestinal tract of PPI users. Changes in the mouth microbiome occur even with short-term use.
PPIs Increase Risk of Alzheimer’s Disease and Dementia
Several studies suggest that long-term, regular use of PPIs increase the risk of Alzheimer’s disease by 44% and dementia by 38%. It is thought that enzymes that normally break up beta amyloid are inhibited by PPIs.
Another recently published study evaluated the associations between current and cumulative PPI use and risk of dementia. This 30-year long ARIC study analyzed data from nearly 6000 adults with and without PPI use. Results showed “This study provides Class III evidence that the use of prescribed PPIs for >4.4 years by individuals aged 45 years and older is associated with a higher incidence of newly diagnosed dementia.”
Risk of Vitamin B12 Deficiency
Acid blocking drugs interfere with vitamin B12 absorption. B12 requires enzymes and gastric acid to remove it from dietary proteins for absorption which are blocked with PPIs. Other popular medications like Metformin are often taken with PPIs, contributing to more drug-nutrient malabsorption and B12 depletion.
Vitamin B12 is essential for brain function, peripheral nerve functions such as sensation, balance, and movement. It is required for homocysteine metabolism, mitochondrial function, blood sugar metabolism, phosphatidylcholine production, histamine clearance, estrogen metabolism, menstrual cycle and reproductive health, neurotransmitter metabolism, cholesterol and cardiovascular function, and more. B12 insufficiency adds to the long-terms concerns of decreased brain health. Current research shows us that normal levels of vitamin B12 may not be enough.
Calcium and Bone Density
PPI use interferes with calcium absorption in the digestive tract and bones contributing to bone density changes. PPIs change the pH in the stomach which affects calcium absorption in the small intestine. Furthermore, PPIs interfere with proton pumps in bone, which reduces calcium resorption and bone remodeling activities. Decreased bone health and osteoporosis have been associated with long term acid blocking drug use.
All-Cause Mortality
A British Medical Journal observational study published in 2017 evaluated the risk of death with long-term PPI use in U.S. veterans. Their conclusion stated, “The results suggest excess risk of death among PPI users; risk is also increased among those without gastrointestinal conditions and with prolonged duration of use. Limiting PPI use and duration to instances where it is medically indicated may be warranted.”
Expert Review
The American Gastroenterological Association in 2017 provided Expert Review and Best Practice Advice on long-term use of PPIs. Amongst a myriad of recommendations when using PPIs, they recommend not to supplement beyond the RDA and avoid monitoring bone density, kidney function or nutrient levels. Does this have your nutritional needs and health in mind?
Support Risk Reduction Behaviors
PPI/antacid medications are a multi-billion-dollar industry across the globe with use expected to increase over time. It used to be thought that aspirin, Tylenol, ibuprofen, statins, tobacco products, glyphosate/Roundup, BPA, and other chronically used compounds posed no significant threat and were safe for long-term health. Time has shown us otherwise.
If you use PPIs/antacid meds long-term and perhaps indiscriminately, be aware of risks and changes that occur with their use and engage in appropriate risk reduction behaviors. Is it time for you to rethink your approach to these meds? If you are on long-term PPIs or other acid blockers, please work with your prescribing practitioner for proper management. You can also support your digestive system with healthy choices such as:
• Chew food thoroughly.
• Follow the Five Rules of the Leptin Diet to allow your digestive system time to do its work between eating.
• Take a few minutes before meals to de-stress as stress interferes with digestion.
• Choose whole foods at least 80-90 percent of the time as ultra-processed foods create substantial digestive stress.
• Avoid ice-containing beverages and large amounts of fluid immediately before or with meals as this also interferes with digestion.
• Add warming spices like ginger when cooking foods to aid in digestion.
• Optimize your nutrient status
• Monitor bone density, kidney function, cognitive health, etc. with your licensed health-care practitioners.
• Empower yourself with health-oriented resources like our Wellness Resources News, Health Topics and select additional resources listed below. Share with others!
Additional Resources
How Common Medications Change Gut Health and Affect the Brain
Chewing Well and Relaxed Meals Essential for Metabolism, Brain Health, and Healthy Poop
Vitamin B12 Essential for Energy, Mood, and Overall Health
The Truth About Vitamin B12: Why ‘Normal’ Levels May Not Be Enough
Aspirin Riskier Than Previously Thought
How Statins Impair Cognitive Function
Nighttime Eating, Sleep-Wake Cycles, and Stress Management
