Up to 7.8% of the U.S. adult population takes proton pump inhibitors (PPIs), medications that are prescribed for acid-related disorders like heartburn, gastroesophageal reflux (GERD) and chronic indigestion.1 For years, the aggressively advertised medications have been a lucrative Big Pharma venture, but they’re also controversial because they are linked to many health risks.
PPIs have been overprescribed, wrongly prescribed and over-advertised. For example, 46% to 63% of patients seen in ambulatory care settings who were taking PPIs had no gastrointestinal (GI) complaint or "documented indication for anti-secretory therapy," according to an article in Clinical Correlations, the NYU Langone Online Journal of Medicine.2 They are also routinely used in intensive care unit (ICU) settings.3
Though PPIs were designed to be taken for no more than eight weeks when first approved by the FDA, they are often used long-term despite their well-documented risks.4 According to Clinical Correlations, PPIs:5
"… are inappropriately continued long-term, leading to significant overuse of this medication class. PPIs therefore represent an important target for physicians to reduce unnecessary medication use and lower the risks associated with polypharmacy."
Further, PPIs are habit-forming and difficult to quit. Now, scientists writing in the American Journal of Gastroenterology have added another layer to the recognized risks of these drugs: They have found links between taking PPIs and the risk of developing COVID-19.6
Increased Risk of COVID-19 Seen With PPI Use
In the study, of 86,602 eligible survey respondents, 53,130 (61.3%) listed "prior abdominal pain or discomfort, acid reflux, heartburn or regurgitation" on their surveys. They were asked about their use of PPIs and H2 receptor antagonist (H2RA) drugs, which are also prescribed for acid-related disorders.7 Of that group, 3,386 (6.4%) participants reported that they had tested positive for COVID-19.8
Upon analyzing the data, the researchers found that people taking PPIs once a day had more than two times the risk of contracting COVID-19 than those who didn’t.9 For people taking PPIs twice a day, it was even worse: They had more than three times the risk of contracting COVID-19 than those not on the drugs.10 People on H2RAs did not have an elevated risk.11
To rule out confounding data, people who had taken PPIs for less than a month, possibly for COVID-19-like symptoms, were classified as nonusers.12 In their analysis, the study’s authors did not find that taking PPIs increased the odds for reporting such symptoms. Based on the results, the researchers warned:13
"Since meta-analysis reveals that twice daily PPIs do not offer clinically meaningful benefits over once daily dosing for gastroesophageal reflux disease, our findings further emphasize that PPIs should only be used when clinically indicated at the lowest effective dose."
What Explains the Increased Risk of COVID-19?
From their observations in the medical setting, the researchers arrived at the theory that PPIs may increase COVID-19. “We developed this hypothesis at the beginning of the COVID-19 pandemic when we started to see a high incidence of GI symptoms and learned that the virus sheds into saliva, and thus can be swallowed into the stomach," said Dr. Christopher V. Almario, the study's lead author.14
The basis of the findings is likely PPIs' induction of a condition called hypochlorhydria, a low level of stomach acid, say the researchers. Hypochlorhydria impairs the body’s ability to defend against ingested bacteria and viruses. In one study, once-daily PPI use "increased the odds for enteric infection by 33%."
Since it is known that pH ≤3 impairs the infectivity of a virus similar to COVID-19 (SARS-CoV-1), though its effect on COVID-19 is not yet known, the researchers wrote:15
"As SARS-CoV-2 employs the angiotensin-converting enzyme-2 receptor to rapidly invade and replicate within enterocytes, increases in stomach pH >3 from PPI use might allow it to gain entry into the GI tract more easily, leading to enteritis, colitis, and systemic spread to other organs, including the lungs.
… there is biological plausibility for our findings as the similar SARS-CoV-1 is pH-sensitive and remains infective at a pH >3; twice daily PPI use can lead to 24-hour median intragastric pH >6 and sustain pH >4 for more than 20 hours.
We also found evidence of a dose-response relationship as those using PPIs twice daily have higher odds for COVID-19 positivity when compared to those taking lower-dose PPIs or those not using PPIs at all. Moreover, individuals taking the less potent H2RAs are not at increased risk."
The Researchers Discuss the Study
Upon hearing the results of the study, some who are taking PPIs may want to abruptly stop. But Dr. Brennan Spiegel, one of the study authors, cautions against it.16
"This study does not mean that people on PPIs should just stop their medicines … As always, the decision about whether, when, and how to modify PPI dosing should be based on a thoughtful assessment of the risk-benefit ratio for individual patients.
As with any medication, the lowest effective dose should be used when clinically indicated, and, when appropriate and consistent with best-practice guidelines, H2RAs may also be considered as an alternative treatment for acid-related conditions."
H2RAs, medications like Pepcid, Tagamet and Zantac, generally available over the counter, are not linked to contracting COVID-19 in the research. They are considered safer than PPIs and their use is suggested as a way to discontinue PPIs by tapering off treatment.17
However, one H2RA, Zantac, has a red flag of its own. In 2019, the FDA said tests revealed the presence of the carcinogen N-nitrosodimethylamine (NDMA) in Zantac, whose generic name is ranitidine. According to Harvard Health Publishing:18
"NDMA is an environmental contaminant that is found in water and foods, including dairy products, vegetables, and grilled meats. Its classification as a probable carcinogen is based on studies in animals; studies in humans are very limited."
In April 2020, the FDA requested manufacturers to withdraw all prescription and over-the-counter Zantac drugs from the market.19
PPIs Are Dangerous Regardless of COVID-19 Links
PPIs are designed to reduce acid in the stomach, yet hydrochloric acid, along with pepsin, is necessary to break down protein in your intestinal tract. That means a reduction in acid from the use of PPIs changes nutrient absorption and digestion for the worse.
Without adequate breakdown of protein, you increase the risk of experiencing dysbiosis,20 or an imbalance in the gut microbiome between pathogenic bacteria and friendly bacteria. This condition opens the door for a host of other problems like candida, Helicobacter pylori (H. pylori), C. difficile and leaky gut.
Moreover, when people suffer from heartburn, GERD and chronic indigestion, the problem is rarely caused by too much acid. Patients with these ailments are usually suffering from other stomach issues that can be addressed with a healthy diet and natural treatments. Unless an endoscopy has confirmed high levels of stomach acid, it's actually more likely that you don't have enough.
PPIs Have Serious Side Effects and Limited Uses
According to gastroenterologist Dr. Mitchell Katz, PPIs are warranted for only a few conditions, including:21
- Ulcerative esophagitis
- GERD
- Zollinger-Ellison syndrome
- H. pylori
Prescribing PPIs for other conditions is irresponsible because they are linked to many concerning conditions, as I’ve noted. According to The New York Times:22
“Several studies also have shown an increased risk of bone fractures from osteoporosis in patients taking P.P.I.’s, though the results aren’t consistent. Possibly the change in stomach acidity reduces the body’s ability to absorb calcium.”
PPIs are especially problematic for seniors, wrote the Times. Dr. Ian Logan, a Scottish physician, said:23
“When patients were admitted to our geriatric wards, a lot of them didn’t have clear indications for taking these drugs … And they’d remained on them for a lot longer than they should have … They do have significant side effects, especially in older patients.”
Among the side effects often seen are increased risk of pneumonia, gastrointestinal infections and severe diarrhea. Here are more scientifically documented risks of PPIs:
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Increased risk of heart attack24 |
Serious allergic reactions25 |
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Kidney problems26 |
Stevens-Johnson syndrome27 |
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Increased risk of fractures28 |
Increased risk of pneumonia29 |
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Pancreatitis30 |
Increased risk of C. difficile31 |
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Reduced liver function32 |
Iron and B12 deficiencies33 |
How to Wean Off PPIs
If you’re already taking a PPI, you'll want to get on a lower dose than you're on now, if possible, and then gradually decrease your dose even further. Once you get down to the lowest dose of the PPI, you can start substituting with an over-the-counter H2 blocker like Tagamet or Cimetidine, but not Zantac or ranitidine.
Then, gradually wean off the H2 blocker over the next several weeks while implementing the lifestyle strategies addressed below. As always, be sure to check with your doctor before starting any new medications or making changes to the ones you’re currently taking.
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Safe, Natural Alternatives for Heartburn, Acid Reflux and Indigestion |
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Consume Enough Probiotics — This will help balance your bowel flora, which can help eliminate helicobacter bacteria naturally. |
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Eliminate Food Triggers — Food allergies can be a problem, so you'll want to completely eliminate items such as caffeine, alcohol and all nicotine products. |
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Increase Your Body's Natural Production of Stomach Acid — Start with high-quality sea salt (unprocessed salt) such as Himalayan salt. |
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Take a Hydrochloric Acid Supplement — Try a betaine hydrochloric supplement, which is available in health food stores without prescription. |
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Modify Your Diet — Eat a lot of vegetables and high-quality, organic, biodynamic, locally grown foods. |
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Optimize Your Vitamin D levels — Vitamin D helps fight infectious diseases. |
There Are Many Safe Alternatives to PPIs
In summary, PPIs are linked to many serious side effects for which the 7.8% of the U.S. adult population who take them may be at risk. Yet, the painful, acid-based conditions that people take PPIs for can often be relieved by making relatively simple lifestyle changes. These changes are especially important with the reported links between PPIs and COVID-19.
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