February 2017
By Tracy Garfield
In profoundly troubling studies published in 2015-2016, acid reducing drugs called proton pump inhibitors, or PPIs, were associated with an increased risk of dementia.1-3
One of these studies found cognitive impairment in response to short-term use of drugs sold under the names Prevacid®, Nexium®, Protonix®, AcipHex®, and Prilosec®.2
People age 75 and older who use proton pump inhibitors have a 44% greater risk of developing dementia, including Alzheimer’s.1
As many as 70% of people taking proton pump inhibitors don’t require them.4 Thousands of cases of dementia may have been avoided if people weren’t overusing these drugs.
In this article we will examine how proton pump inhibitors pose a hidden long-term threat to our brains. We’ll discuss natural options that can help alleviate heartburn symptoms without increasing dementia and other health risks such as bone fractures, kidney failure, and stroke.5-10
Proton Pump Inhibitors Increase Dementia Risk
The recent studies showing an association between proton pump inhibitors and increased risk of dementia are frightening.1-3 These drugs are some of the most widely used in America,11 and their use among the elderly is on the rise.1,12
Proton pump inhibitors are most often used to fight heartburn, gastroesophageal reflux (GERD), and other painful disorders of the upper digestive tract. They are available over the counter and by prescription.
The most recent of the new studies appeared online in the Journal of the American Medical Association Neurology in February 2016.1 The researchers evaluated data collected over a 7-year period on nearly 74,000 participants age 75 and older who did not have dementia at the beginning of the study.
What they found was a strong statistical relationship between regular use of proton pump inhibitors and the risk of developing dementia. Those taking proton pump inhibitors were 44% more likely to develop dementia compared with those not using the drugs, even after statistical adjustments for age, sex, and the use of multiple medications.
The implications of this finding are enormous. An important editorial that appeared alongside the study’s publication puts these numbers in perspective. Given the size of the population at risk, that 44% increase could expand the overall incidence of dementia from 6% to about 8.4% per year. That would translate to roughly 10,000 new cases annually in this older age-group alone.13
Of course, it did not take long for others in the mainstream medical community to attack these findings as an anomaly, concluding that “you don’t need to change therapies on the basis of concern about dementia.”14 The connection between Big Pharma and physicians is as strong as ever! But this is not the only study to make this unfortunate connection. Two studies published just last year validate the findings in separate ways, and with surprising consistency.
WHAT YOU NEED TO KNOW
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Heartburn Drugs Increase Dementia Risk
- Stomach acid, undigested food and drink, bile, and digestive enzymes that flow into the esophagus produce painful symptoms of heartburn and reflux in millions of Americans.
- This has led to the widespread use of proton pump inhibitor drugs, which are effective at reducing stomach acid production.
- Proton pump inhibitor drugs also reduce acid production in the brain’s cleanup cells, which impairs their ability to clear dangerous and toxic abnormal proteins associated with neurodegenerative diseases and dementia.
- Clinical studies now show a significantly increased risk of dementia in older patients taking proton pump inhibitor drugs.
- Even taking proton pump inhibitor drugs for just one week impairs cognitive function in healthy young adults.
- Given the high rate of overprescription of proton pump inhibitors and their risks, those taking these drugs should consider safer alternatives.
Findings Validated in Second Study
In a second study, researchers examined data from a large, longitudinal study (called the German Study on Aging, Cognition, and Dementia) among older patients in primary care.3
More than 3,300 people age 75 or older were followed up every 18 months for 6 years. Although they began the study with no signs of dementia, by the fourth follow-up, 431 had developed dementia, including 260 specifically with Alzheimer’s disease.
Patients who used proton pump inhibitor drugs during this time were found to have a 38% increased risk of dementia, and a 44% increase in the risk of Alzheimer’s, compared to those with no history of proton pump inhibitor use.3
If this 44% figure looks familiar, it’s because it is the exact same percentage of increase in dementia risk the 2016 study found in proton pump inhibitor users. It seems highly unlikely that these closely-convergent findings are simply the result of coincidence.
Short-Term Proton Pump Inhibitor Impairs Cognition
A study published in 2015 examined the cognitive effects of short-term proton pump inhibitor use in otherwise healthy young adults.2
The rationale for this study was that, if proton pump inhibitors produce long-term mental decline, even short-term use might have a measurable effect on standard cognitive testing.
The study included 60 healthy volunteers ages 20-26 who had no signs of age-related cognitive decline, and who would be expected to perform normally on cognitive tests.2 The subjects were divided into six groups. Each of five groups received a different proton pump inhibitor drug (omeprazole, lansoprazole, pantoprazole, rabeprazole, or esomeprazole) for one week, while the sixth received a placebo.
After just 7 days of exposure to proton pump inhibitors, all of the drug recipients had a statistically and clinically significant impairment in cognitive functions.
They performed more poorly than at baseline on visual memory, attention, executive function (sorting and deciding on strategies), working memory, and planning functions.2 While all of the proton pump inhibitors impaired cognition, some were worse than others. Omeprazole (Prilosec®) was the worst offender, which reduced function on 7 subtests. Lansoprazole and pantoprazole influenced 5 subtests, rabeprazole, 4, and esomeprazole, 3.
These outcomes make it clear not only that proton pump inhibitors can impact brain function, but also that different drugs affect it in different ways.
These changes occurred after just one week of treatment in healthy young adults. What are the likely effects in older adults, who are already more prone to cognitive decline, and who may have been exposed to proton pump inhibitors for years or even decades? And what could be the impact on overall rates of dementia as rates of proton pump inhibitor use continue to skyrocket?
Clearly, it is too soon to have the answers to these questions in human populations. But a number of basic science and animal lab studies have shed some light on why proton pump inhibitors are so closely connected to cognitive decline, as we’ll now see.
Proton Pump Inhibitor-Induced Brain Changes
One of the hallmarks of Alzheimer’s disease (as well as other kinds of dementia) is the accumulation of abnormal proteins in regions of the brain that are important for memory. The best-known of these is called beta-amyloid. One way beta-amyloid contributes to Alzheimer’s disease is by provoking inflammation that ultimately kills brain cells.15-17
Our brains have developed systems for clearing harmful beta-amyloid plaque from the body. Scientists believe that whether a person develops Alzheimer’s or not depends ultimately on whether we can clear out beta-amyloid faster than we produce it.18-20
There is now strong evidence that proton pump inhibitors not only promote beta-amyloid production, but also impair the body’s ability to clear beta-amyloid plaques in the brain.18-21
PROTON PUMP INHIBITORS INCREASE BONE FRACTURE AND STROKE RISKS
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In recent years, concerns about the long-term safety profile of proton pump inhibitors have been raised, including increased risk of bone fractures and stroke.
A 2011 meta-analysis published in The Annals of Family Medicine reported that high doses or long-term use of proton pump inhibitors is associated with an increased risk of bone fractures.33
Researchers confirmed these findings in a more recent and larger meta-analysis that led the authors to conclude that “…PPI [proton pump inhibitor] use modestly increased the risk of hip, spine, and any-site fracture.”34
In a shocking recent study, a group of researchers evaluated the use of proton pump inhibitors and the risk of first-time ischemic stroke. For the study, more than 240,000 adults (mean age 57 years) were included and an approximate 44% of the patients had filled a prescription for a proton pump inhibitor. Overall, the researchers found that those using proton pump inhibitors had a 21% greater risk of ischemic stroke, compared to nonusers.35
Proton Pump Inhibitors Prevent Removal of Beta-Amyloid Plaque
Proton pump inhibitors act by blocking the proton pumps that secrete acid in the stomach, which reduces acid levels. The problem is that the same mechanism of action also impairs acid production in the brain’s “cleanup cells,” which use the acid to break down beta-amyloid plaque so that it can be removed from brain cells.
Much of this cleanup work is shouldered by cells called microglia, which are immune system cells living in the brain.18,20 These cells are rich in lysosomes, which are essentially cellular garbage collectors that accumulate “junk” proteins (like beta-amyloid) and then break them down with intense bursts of acid.22,23
It has now been demonstrated that proton pump inhibitor drugs pass through the blood-brain barrier and reduce the amount of acid contained in the lysosomes.22 Additional studies have shown that the lysosomes in the brains of Alzheimer’s patients are less acidic than those of healthy people, which means they are less able to clear dangerous beta-amyloid.24,25
The bottom line is that proton pump inhibitor drugs interfere with one of the brain’s most fundamental self-cleaning mechanisms: the acidic destruction of toxic beta-amyloid proteins that trigger the cell death, inflammation, and neuronal dysfunction typical of Alzheimer’s disease.
While proton pump inhibitors have only been studied in this capacity in Alzheimer’s disease, it’s quite possible that they could have a negative impact on other neurodegenerative diseases. This is because the accumulation of abnormal proteins is also a main feature of diseases such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and Huntington’s disease. And as with Alzheimer’s, the poor function and acidification of lysosomes has been implicated in these disorders as well.26,27
RISING BURDEN OF DEMENTIA
Raft-like floating foam
creates a soothing barrier
that prevents acid in the
stomach from pushing up
into the esophagus.
creates a soothing barrier
that prevents acid in the
stomach from pushing up
into the esophagus.
Dementia (literally, “loss of mind”) is on the rise throughout the world and currently represents a leading cause of disability, heartbreak, and economic stress for its victims and their families alike.
According to the World Health Organization (WHO), dementia is broadly defined as “…deterioration in cognitive function (i.e. the ability to process thought) beyond what might be expected from normal aging. It affects memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. Consciousness is not affected. The impairment in cognitive function is commonly accompanied, and occasionally preceded, by deterioration in emotional control, social [behavior], or motivation.”36
In other words, dementia today means precisely what the word’s origins imply: loss of the human part of the mind.
Dementia is on the rise both in the United States and globally as populations live longer. Here are some of the troubling facts about the growing epidemic of dementia:36-39
- 47.5 million people worldwide live with dementia today.
- About 7.7 million new cases of dementia occur annually worldwide.
- The worldwide prevalence of dementia is expected to reach 75.6 million by 2030 and to almost triple to 135.5 million by 2050.
- People with mild cognitive impairment are up to 15 times more likely to develop Alzheimer’s disease than those with normal cognition.
- Before death, most people with Alzheimer’s disease become dependent on caregivers, amplifying the number of people directly affected.
Alternatives to Proton Pump Inhibitor Drugs
There’s no question that proton pump inhibitor drugs are effective at reducing stomach acid and at alleviating painful heartburn and reflux symptoms.
The problem is that they also interfere with needed acid production in other parts of the body, specifically in the brain, where insufficient acid may lead to the accumulation of toxic proteins. Does this mean you have to choose between heartburn and Alzheimer’s? No, there are alternatives that can safely alleviate the painful symptoms of heartburn without increasing the risk of Alzheimer’s.
A unique combination of two well-known nutrients, zinc and carnosine, has shown excellent effectiveness in people with stomach ulcers, especially in those cases associated with the bacterium Helicobacter pylori.28-30These ingredients have also been shown to work together to reduce inflammation, which is itself a risk for stomach and esophageal cancers.31,32
Another approach is to use a raft-forming alginate. Alginates are complex carbohydrates that form a foamy gel on contact with stomach acid. They then float, like a raft, atop the stomach contents, preventing acid and other damaging gastric contents from refluxing up into the esophagus. Raft-forming alginates can prevent reflux symptoms such as heartburn.5-10
Raft-forming alginates have advantages over other treatments, including the fact that they do not alter the acid content in the stomach or the brain, and they act only locally in the stomach and are not absorbed into the bloodstream. And in addition to physically blocking stomach acids, they alsoblock other erosive stomach contents such as protein-digesting enzymes, bile from the liver, and acidic foods/drinks from rising into the esophagus.8
THE OVERPRESCRIBING OF PROTON PUMP INHIBITORS
Proton pump inhibitors are currently the mainstay of treatment for conditions related to gastric and esophageal irritation by stomach acid, such as heartburn, gastroesophageal reflux, peptic ulcer disease, and more.2 They are the third top-selling drugs in America, with annual sales approaching $14 billion. Prescription-writing for these drugs increased more than 12% between 2009 and 2013.2
Proton pump inhibitors effectively lower stomach acid and have relatively few short-term side effects.2 But, as more and more people use these drugs for longer periods, we are now discovering the potential damage they might cause.40
That’s especially concerning in light of estimates that there is no appropriate indication for proton pump inhibitor use in 25%-70% of patients taking those drugs.4 Indeed, there has been growing concern about physicians’ readiness to prescribe them, particularly in older adults.2,41-44
People taking proton pump inhibitor drugs should evaluate their real need for relief, discuss their situation with their physicians, and consider, when possible, alternate therapies that pose fewer risks.
Improved Antacid Chewables
For decades, endless commercials were aired on television promoting the heartburn alleviating effects of antacid tablets like TUMS® and Rolaids®.
These kinds of antacids often relied on calcium (and sometimes aluminum) to partially neutralize stomach acid. They are laden with sugar and artificial flavors. These antacids did nothing to improve the protective barrier in the esophagus or reduce the acid-induced inflammation that can lead to serious gastroesophageal health problems.
A new chewable antacid has been developed that contains equal amounts of acid-neutralizing magnesium andcalcium plus a special licorice extract that helps protect the esophageal lining from continuous inflammatory damage.
These new lozenges are sweetened with stevia and natural flavors, so they can safely be used daily without concern about dental enamel erosion and elevated blood glucose.
PROTON PUMP INHIBITORS AND B12
Recent studies show a potential link between the use of proton pump inhibitors and dementia. One way proton pump inhibitors might affect brain function is by interfering with the absorption of vitamin B12.45
B12 is essential for normal cognition, and low B12 levels are not uncommon in older adults even in the absence of acid-reducing therapy.46
Because dietary B12 is tightly bound to proteins, it requires ample stomach acid to release it for absorption. This means that reducing stomach acid through the use of proton pump inhibitors may increase the risk for B12 deficiency. Experts now recommend testing B12 levels regularly for patients taking larger doses of proton pump inhibitors for long periods of time.45
Summary
Acid reflux is a common condition among adults.
Its prevalence has created a multibillion-dollar market for drugs to alleviate the symptoms. Proton pump inhibitors are the most popular drugs based on their effectiveness and ease of dosing.
Unfortunately, proton pump inhibitor drugs work all too well, blocking acid production not only in the stomach, but also in the brain’s “cleanup” cells. These cells require acid for the cleanup of “junk” proteins in brain cells such as beta-amyloid.
Clinical studies show that people on long-term proton pump inhibitor therapy have a significantly increased chance of developing dementia (and other problems like bone fractures).
In addition, taking proton pump inhibitors for as little as one week measurably impairs cognitive performance.
Fortunately, natural approaches like raft-forming alginates and new chewable antacid lozenges offer an alternative to proton pump inhibitors for those suffering from mild-to-moderate heartburn or reflux.
Those with severe heartburn or erosive esophagitis may be able to reduce their dose of proton pump inhibitors by substituting these natural approaches as often as possible.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
