Not Again! Just when we thought the bad news about proton pump inhibitors (PPIs) could not get any worse, an article in the journal JAMA Neurology (online, Feb. 15, 2016) suggests that these acid-suppressing drugs are linked to dementia. This large German epidemiological study found a 44 percent increased risk of dementia among older people taking PPIs compared to those people not on such medications. More about this scary new research in a moment.
Just a week ago it was announced that drugs like dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), rabeprazole (Aciphex) and pantoprazole (Protonix) were associated with chronic kidney disease (JAMA Internal Medicine, Feb. 2016). That comes on top of other serious complications:
Adverse Reactions Linked to Proton Pump Inhibitors:
- Clostridium difficile (C diff) intestinal infections
- Weakened bones (osteopenia, osteoporosis, fractures)
- Kidney disease
- Poor absorption of calcium, iron, magnesium, zinc and vitamin B12
- Thrombocytopenia (a severe blood disorder that can lead to excessive bleeding)
- Heart attacks (myocardial infarction) & other cardiovascular complications
- Adenocarcinoma of the esophagus
PPIs and Dementia:
The new study involved an analysis of German health insurance data collected between 2004 and 2011. The investigators had access to records of 73,679 patients who were over 75 years of age. None had dementia at the beginning of the study.
Roughly 3,000 people took a proton pump inhibitor during the seven-year study period. Occasional users of PPIs were excluded. Regular users were defined as people who filled a prescription for these acid-suppressing drugs at least once in each quarter of an 18-month period of time.
The authors concluded that their analysis of the German insurance data “revealed a significant increased risk of dementia [44%] with the use of PPIs.” This result was similar to prior findings from a different study. The authors concluded:
“Thus, the avoidance of PPI medication may contribute to the prevention of dementia.”
Possible Reasons For a PPI Dementia Link:
Most people have a hard time imagining how heartburn drugs could cause dementia. In fact, it seems illogical that seemingly safe medications to control reflux could cause so many complications, including heart attacks, hip fractures, lung infections and maybe even cancer.
An editorial in JAMA Neurology points out that:
“there is some biological plausibility to the hypothesis that PPIs can cross the blood-brain barrier. They may increase both production and degradation of amyloid, at least in animal models, and bind to tau. There is also evidence of reduced levels of B12 and other nutrients among PPI users that could possibly relate to an increased risk of dementia.”
What that means in less technical jargon is that PPIs may impact brain enzymes that could lead to the formation of plaques and tangles. Lower levels of vitamin B12 might also increase the risk for cognitive decline. In other words, it is conceivable that there is a reason for a PPI dementia link.
Association Not Causation:
The authors of the research are quick to point out that this is an observational study. That means it is not a randomized, double-blind, placebo-controlled trial. Therefore it can only suggest a linkage and not actually prove that PPIs cause dementia.
The likelihood that any drug company would spend a large amount of money to actually conduct such a long-term study is remote. After all, most of these medications are now available in generic formulations. Billions have been made and the horses are out of the barn. Why would a drug company want to determine whether there really is a PPI dementia link?
The editorial article points out, though, that if this association is true, it “could result in an increase of about 10,000 new cases of incident dementia per year just in this age group [75 to 84 years of age]…”
How Big A Problem are PPIs?
When these drugs were introduced over 25 years ago they were perceived as super safe. The FDA still seems to believe that these acid-suppressors are great and without serious complications. That is why you can now buy Prevacid 24HR, Prilosec OTC and Nexium24HR without a prescription.
At last count, 15 millions Americans took a prescription PPI in 2013. The cost was $10 billion. That does not take into account the millions who are now buying OTC proton pump inhibitors and paying out of pocket. Given the potential risks of fractures, infections, heart attacks, cancer and dementia, we are beginning to wonder about the FDA’s judgment.
Getting Off PPIs:
Stopping strong acid-suppressing drugs is not easy. In fact, it can be downright disastrous. That is because the body compensates for acid suppression by over-producing acid-making cells. When the drugs are stopped suddenly, it is not uncommon for people to experience rebound hyperacidity. That leads to unbearable heartburn that can last for weeks or even months.
We have written extensively about this condition and you can find our recommendations about getting off PPIs at this link. One of our favorite recipes for phasing off drugs like omeprazole involves persimmon punch. Here is a link to it and several other intriguing approaches.
Of course we would NEVER recommend that anyone stop a PPI without consulting the prescriber first and finding out whether this is an advisable thing to contemplate.
Our radio show (February 14, 2016) goes into this issue in greater detail. Here is a link should you wish to listen to a free MP3 version or the program. When you visit that page you will also find links to new studies suggesting a relationship between the long-term use of PPIs to cancer.
The People’s Pharmacy Bottom Line:
As worrisome as the latest research on proton pump inhibitors seems to be, the real concern for us is the length of time it has taken to uncover these potential adverse reactions. Although tens of millions of Americans have taken these drugs over the last couple of decades, we have only recently learned about problems such as heart attacks, fracture, kidney disease or dementia.
What does this tell us about the long-term consequences of other drug treatments? Remember, PPIs were considered so safe the FDA granted them OTC status. In many cases it can take decades before we learn about potentially serious complications of medications.
The fluoroquinolone-class of antibiotics includes familiar brands such as Cipro (ciprofloxacin) and Levaquin (levofloxacin). Tens of millions of Americans have taken these drugs over the decades, but it is only in the last few years that the FDA has warned about side effects such as permanent nerve damage. It took the FDA quite a while to alert people about tendon problems (tendonitis, tendon rupture). How many other medications could be causing complications that we do not yet know about?
What Do You Think?
Share your own PPI story below in the comment section. Have you ever experienced a side effect that was not discussed in advance by the prescriber or the pharmacist? What do you think about the latest research on proton pump inhibitors?
Please vote on this article at the top of the page.