THE MICROBIOME SUMMIT : The Established Thinking
The risks and benefits of proton pump inhibitors (PPIs)
Dr. Talia Zenlea, PhD
Proton Pump Inhibitors (PPIs) are one of the most prescribed drugs in North America. Dr. Talia Zenlea, a gastroenterologist at Women’s College Hospital, explains what these medications are and how they work in our body, who would benefit from this therapy, risks & benefits of use, and potential health implications and effects on the microbiome. Anyone who is taking a PPI should watch this video.
- Tracey:
- We’re here at the University of Toronto with Dr. Talia Zenlea, a gastroenterologist. Welcome!
- Talia:
- Thank you. Thanks for having me!
- Tracey:
- There are another class of drugs that are used in gastroenterology called Proton Pump Inhibitors. Can you explain those to us?
- Talia:
- Sure. So, Proton Pump Inhibitors are medications that we use, to decrease acid in the stomach. And we do that for people who have acid-responsive conditions. So, things like acid reflux – for heartburn. The other thing- major development, or the other condition that PPIs have been super-helpful for has been peptic ulcer disease – so these are a great treatment of ulcers that are due to too much acid. And so, we call them Proton Pump Inhibitors because there is a pump in the stomach that pumps the acid in, in response to food. So that’s a normal way that we digest food, is with stomach acid: so, you put food in your mouth and it sends signals to your brain to turn these pumps on, these pumps pump acid into the stomach and that helps break down the food product. Now, in some people who have too much stomach acid or have some other reason to have their stomach lining be compromised, for example, if they use certain medications, like aspirin, or other non-steroidals (NSAIDS), they’re prone to being sensitive to acid, and then these people, they might go on to develop ulcers. Other people, just for a combination of reasons that I’m not going to get into now, might have symptoms from heartburn. So, in any of these groups of people, they often respond to acid-suppressive therapies – and why is that beneficial? Because, well, in the case of ulcers – it’s obvious. We don’t want people to have ulcers because those can go on to bleed and perforate and cause major problems, and people with chronic acid-reflux; they’re predisposed to esophagus cancer. So, there’s a real – other than just controlling one’s symptoms – there is a real reason to want to have that acid be supressed, to prevent some morbidity down the road. So that’s why we recommend those medications, and they work really well for those conditions.
- Tracey:
- Do we know if they have an effect on the microbiome?
- Talia:
- We’ve thought that they might, and part of the reason is because if you’re decreasing the normal acid environment of the stomach, you’re impacting – so, you said that- and this is a really great analogy – we have this garden of organisms, and we are basically a petri dish feeding these organisms. And like any petri dish- the environment is so important. So, the bacteria, the organisms that grow there, grow based on the climate that they’re in, so there’s the bugs that are used to living in Hawaii, and those that are living in Alaska, and if you suddenly switch the environment around, those particular organisms might not thrive. So, there are certain organisms that live in our stomach that thrive in that acidic environment, and if you supress that, they’re not there anymore. And so, people have wondered, “might that be related to certain infections?” – and there were some initial studies to say “could this be related to C. diff (C. Difficile), or could this be related to pneumonia?”. Initially, we thought that the answer might be “yes” because we did show higher rates on people who were on Proton Pump Inhibitors. But as with many studies in medicine, they are just observational: they don’t imply causation. When we delved further we thought, “you know what? It probably isn’t causative, it was probably coincidence, because the sicker people who were probably going to get pneumonia anyway were also more likely to be on Proton Pump Inhibitors” because it is so common to be on them. So, subsequent research hasn’t shown that those risks are clearly tangible, but theoretically, it only makes intuitive sense that they might be related. So again, what I tell people is that you have to balance risk and benefit: if you don’t need to be on the medication, then you shouldn’t be on it. Because then how can I justify the risk, if there is no clear benefit to be on it.
- Now, for someone with Barrett’s Esophagus has pre-cancerous changes because of the chronic acid- reflux that their esophagus has been seeing- in those people, I would rather they get pneumonia, and I treat it, than have them to go on to get esophagus cancer. So, I would rather take a theoretical risk, than a real, known one – so what’s the lesser of two evils? That’s sort of the way I always think of it: you have to balance risk and benefit.
- Tracey:
- Right…. So, they are one of the most prescribed medications, so maybe not everyone who is taking it, needs it. So, if a person made a decision with their doctor to come off of this, what do they need to know?
- Talia:
- So, what I recommend to anybody on a Proton Pump Inhibitors for symptoms, is that they try annually to come off of it. Meaning, a risk, because these are chronic medications, is that people get put on them for some reason and then that reason gets lost. Then they just remain on it forever, and 15 years later no one knows why they were even on it in the first place. Particularly with something like an ulcer, we can treat the ulcer in a couple of weeks, and with advances in endoscopic procedure, I can just do a scope 2 months later and see if the ulcer is gone. And often times I can reverse the cause of that ulcer in the first place, so the Proton Pump Inhibitors is going to help that ulcer to heal, but that ulcer may have been from something called H. Pylori, an organism which I can treat. Or it may have been because they were using a lot of non-steroidals because they had a knee injury that they don’t have anymore, so they aren’t using the non-steroidal anymore so their likelihood of getting an ulcer is very low and they don’t need to be on that Proton Pump Inhibitor forever and ever. So, anytime anyone is on any type of medication – not just a Proton Pump Inhibitors, we should always be asking “do they need to be taking this?”, and with Proton Pump Inhibitors, the vast majority of the time people remain on them because of persistent heartburn symptoms. The Proton Pump Inhibitors most of the time controls their symptoms, so they stay on it, so then I say about once a year “let’s see what happens. Let’s come off of it, and let’s see how you do”. Or, instead of being on it every day forever and ever, let’s say if you have recurrence of your symptoms, let’s just take it for 6 weeks, 8 weeks, get you better and then come off of it. And if you end up being on two, 2 month courses every year, that’s better than being on it for 365 days of the year for the rest of your life.
- Tracey:
- Is there a risk with discontinuation of the Proton Pump Inhibitors with something that’s called a “rebound effect”?
- Talia:
- Yeah, so some people, when their bodies are used to not having any acid around, when we stop the Proton Pump Inhibitors, there’s going to be a normal amount of stomach acid and they might feel symptoms from that right away because their bodies aren’t used to seeing that and they might feel some heartburn symptoms. So, for some people it’s not that big of a deal and they can tough it out for a week or two, and then they feel great. And that’s fine. For people with really bad symptoms I recommend trying over-the- counter antacids. There’s no harm in having heartburn for a couple of days, a couple of weeks, or even a couple of months. Now when I saw there’s no harm, people look at me in my office like, “you must be nuts, because this is making my life miserable!”, so I don’t mean that it’s not uncomfortable, I mean it’s not going to shorten your life or lead to esophagus cancer from a few weeks of heartburn symptoms, so if they are tolerable, that’s ok. Now, if they’re NOT tolerable, that’s a different story, but using an over-the- counter like TUMS, or a different acid-supressing or heartburn medication while we get through some of that rebound is probably fine, as long as it’s tolerable. Now some people just have really bad acid reflux, so it’s not rebound, it’s just recurrence of their normal state, which is what they were before they were on the drug, and those are the people that probably need to go back on it.
- Tracey:
- Any concerns about hypochlorhydria in starting a PPI?
- Talia:
- So, hypochlorhydria is just a description of what happens normally when you’re on a Proton Pump Inhibitor. So, the proton pump, pumps protons into the stomach, and protons are hydrogen, or acid, so it’s just pumping that acid into the stomach. So hypochlorhydria just means that you have low stomach acid, so that’s not a bad thing, it’s the intended effect of the drug – so it’s just a description of that term. So, it doesn’t necessarily look like anything, you know we put people on these medications, we supress their stomach acid and they feel really good. Not that’s where some of these sequelae, or the questions about these sequelae have arisen. So people have said “in the context of hypochlorhydria, or low stomach acid, are you more prone to getting C. diff infection, pneumonia, low absorption of certain nutrients like magnesium and calcium, because the stomach acid is responsible for driving some of the things that prevent those infections or allow for the absorption of those nutrients and that’s where the studies haven’t been very convincingly for or against. SO, just like a said with the pneumonia and the C. diff, they were observational studies that suggested there might be a relationship with stomach acid and those entities, but the subsequent studies didn’t corroborate that. As far as absorption goes, again, it makes intuitive sense that if you need to have an acidic environment in the stomach to absorb calcium, then taking the acid in the stomach away is going to make it problematic to absorb some of those nutrients. But the question is: we only care about the absorbing those nutrients because they prevent certain identifiable conditions. So, one of those examples is osteoporosis and osteopenia, so if you’re not doing a good job of absorbing calcium and magnesium, are you more prone to osteoporosis and osteopenia? So, the initial studies, when they showed that the people with low stomach acid didn’t do a great job of absorbing calcium, the next question was “well, does it matter? Do they have more incidents of hip fractures and osteoporosis?” and the answer was no.
- Tracey:
- Wow!
- Talia:
- So, if they’re not getting more fractures, then why does it really matter? And so, this is where things in medicine things get confusing, because we show the next step, and the next step, but then the next question is ultimately, “does this impact me?” And if the answer is “it doesn’t impact me” then the risk of the medication becomes a lot less. So we always balance, as I said, the risk and the benefit, and so if I have somebody who has a lot of risk factors for osteoporosis, or let’s say they have osteoporosis and they’ve already had pathologic fractures, and they are elderly, and maybe have impaired vision and they’re likely to fall, that’s maybe not the best person to have on a chronic Proton Pump Inhibitor unless there’s a really good reason.
- Tracey:
- Right.
- Talia:
- Where is if I have an otherwise healthy man with no risk factors for osteoporosis, but a lot of risk factors for Barrett’s Esophagus, or esophagus cancer with horrible heartburn symptoms who’s obese and a smoker, to me, it’s worth the risk – the theoretical risk – of osteopenia or osteoporosis if it means I’m doing a better job of preventing his heartburn, and hopefully lessening his risk factors for esophagus cancer.
- Tracey:
- Right. Thank you!
- Talia:
- Thank you! Thanks for having me!
