The link between acid suppressing medication and vitamin B12 deficiency

Monday 24 March 2014 5:30PM (view full episode)

Researchers in California found that the long-term use of commonly prescribed drugs to lower the acid in our stomach, particularly for treating heartburn and acid reflux, may be linked to vitamin B12 deficiency.

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Today, how having an infection may bring on dementia and make cancer worse, but how Spiderman might be able to come to the rescue.

Plus, how one cause of poor memory and thinking ability—low vitamin B12 levels—may be linked to some of the most commonly prescribed medications in Australia. These are drugs to lower the acid in our stomach to treat in particular acid reflux and heartburn. They're called proton pump inhibitors and go by names such as omeprazole, esomeprazole and lansoprazole. Nearly 150 million prescriptions have been written for them by Australian doctors in the last 20 years or so.

The study was led by gastroenterologist Doug Corley who's at Kaiser Permanente in Northern California.

Douglas Corley: As a gastroenterologist one of the main questions that comes up for people who have heartburn and reflux is they take medications and they are wondering whether or not there is any long-term side-effects of taking those. And so in thinking about this and looking at what these medications do, one of the things that it might be changed is that there may be certain nutrients or vitamins that depend upon acid for their absorption. So when we started to look at this we saw that there wasn't a lot of information on these but that vitamin B12 is one of those nutrients that people take in and that they need that might be affected by changing the stomach acid.

Norman Swan: Kaiser Permanente, it has to be said, is a health maintenance organisation where you take, if you like, the holistic care for populations, it's not a fee for service, so you have primary care, what we would call GPs and hospital services as well. So you keep the records for quite a large population.

Douglas Corley: Right, in any given year we have about 3.3 million members, and just as you have said, in addition to seeing physicians at the health plan they also get their hospital care and their medications, their pharmacy prescription from the health plan. So that was really what enabled us to be able to do this study because you know whether or not someone received a medication, then you also know whether or not they developed any health problems further down the line or had abnormal lab tests such as low vitamin B12 levels on their labs.

Norman Swan: So what do you do?

Douglas Corley: What it was for this was looking at whether someone had gotten a prescription and then whether further down the road they develop vitamin B12 deficiency, and whether that was different from people who were otherwise similar, how likely those people were to develop vitamin B12 deficiency and whether there was a difference. And what we found was that people who had taken the acid suppressing medications, mainly the more potent ones which are called proton pump inhibitors, these are ones such as omeprazole.

Norman Swan: The trade names in Australia would be things like Losec and Nexium, there's a whole group of them, there's a whole family of them now. So it's not the Zantac type drugs, the older form of acid suppressing drugs?

Douglas Corley: We did look at both types and found that both types actually…people who took them were more likely to develop vitamin B12 deficiency than people who weren't. But people who were taking the stronger ones, the proton pump inhibitors, they had the higher risk. People who were taking the proton pump inhibitors were about 65% more likely to develop vitamin B12 deficiency. And the ones that were like Zantac, those people who were taking those for at least two years had about a 25% increased chance of developing vitamin B12 deficiency, or they were 25% more likely, I should say.

Norman Swan: Since this wasn't a randomised trial, this could just be a chance association, it might not be anything to do with the acid suppressing drugs at all. In fact we did an interview last year with somebody at Mass General who looked at the whole story of osteoporosis and PPIs and reckoned that it was ephemeral, it wasn't actually a real finding. How do you know this is getting towards cause and effect?

Douglas Corley: That's a great question, and you can never really know without doing a randomised trial whether or not it's cause and effect. What you try to do is you try to look for what are called confounders, you know, other things that might explain the same association between the two, and then you try to adjust or make things similar. So an example would be…let's say people who went to the doctor were more likely to get these medications and were more likely to get their blood drawn to test for vitamin B12…

Norman Swan: Damn it, you've just asked the question I was going to ask you.

Douglas Corley: Right, so it's only because they've gone to the doctor, and so they're more likely to be diagnosed and they are more likely to get the medication. And so what we did to be able to check and see whether that was the case was we said, well, if that's the case then probably a lot of commonly prescribed drugs, like drugs for hypertension or for your cholesterol or for other things like that, probably a lot of those things would probably be more likely to be associated with vitamin B12 deficiency. So we looked at a number of those medications to see if there was a similar kind of association, and there wasn't. And then the next thing we did was we said, well, there are some medications and other things that we know should probably be associated because it's been reported before. And so we looked to see whether or not those medicines had the associations that we would expect.

Norman Swan: Such as?

Douglas Corley: One of them is called metformin, it's a diabetes medication, and those did have the association we expected. So there were a number of these additional analyses you do to look for confounding, and those all suggested that this association was probably causal, although you can never prove that.

Norman Swan: And the more PPIs they took, the higher the dose, the more likely it was that they got B12 deficiency, so that's another reason, and then if they went off their PPIs their B12 tended to go back up. Is that right?

Douglas Corley: Right, those are all other things that tended to support that.

Norman Swan: Now, why did they have B12 tests done in the first place? The average person going to the average general practitioner in Australia would not have a B12 test done. That's an unusual test to be done, at least by Australian medical standards. Why were they having it done in Kaiser? You're not known for wasting money.

Douglas Corley: Another excellent question, and one of the things that we looked at was why people were having the test done, because this would also get to the confounding, that if people were actually just having it done for a screening test, they weren't having any symptoms, just having it done as a screening test, maybe people who are taking these medications are more likely to get screening tests and other things done. But we did a medical record review of a subset of the patients who had the vitamin B12 deficiency, and it seemed like most of them were getting it checked because they were having symptoms.

Norman Swan: Such as?

Douglas Corley: Vitamin B12 deficiency can cause nerve damage, so it can cause numbness or tingling in the hands or the feet. In severe cases it can cause dementia and nerve damage to the brain. And it can also cause anaemia. So most of the people had one of those problems as the reason for why they were getting the vitamin B12 level checked.

Norman Swan: Looking at your paper it shows that 67 people have got to take proton pump inhibitors for two years for one person to develop vitamin B12 deficiency. So two questions arise; is that a lot, a little, is it a high risk, a low risk?

Douglas Corley: The number that you mentioned, which is something which is called the number needed to treat…

Norman Swan: Or the number needed to harm.

Douglas Corley: Yes, in this case it would be the number needed to harm. And there isn't an absolute cut-off in terms of what's a high number or what's a low number, it just gives you somewhat of a feel for it. I would say this is somewhere in the middle. I think that in general the main question comes to whether or not this is a number that people should be concerned about. I think the question for that is as much about how many people have vitamin B12 deficiency as how many people are exposed to proton pump inhibitors.

Norman Swan: Which is vast.

Douglas Corley: I think that's actually the more important number, because if you have a lot of people who are exposed, then one out of 67 ends up being a lot of people.

Norman Swan: Because they are amongst the most commonly prescribed medications in both the United States and Australia.

Douglas Corley: Right.

Norman Swan: So what's a person to do? They've got reflux, they've got acid indigestion, and the one thing that relieves it are these PPIs. But they could go and have an operation to do a little bit of a tuck at the bottom of their oesophagus, or they could take fewer of these medications to see whether the symptoms come back. What are you telling your patients?

Douglas Corley: This is a single study, and so I think it's hard to completely say from a single study how practice should be effected or changed. This does make some biological sense based on what we know from some other studies that have looked at that people taking these medications may have lower absorption. But in a nutshell I don't think these findings recommend against taking acid suppressing medications if you have a clear reason to take them. This is something that can be checked. I think these findings don't recommend against taking medications if you need them, but you should, as with all medications, exercise appropriate vigilance about what medications you take. You know, take them at the lowest effective dose, and consider asking your physician whether or not you should be checked for vitamin B12 deficiency if you are taking these medications for long periods of time.

Norman Swan: And if you're getting odd symptoms which are hard to explain, particularly neurological ones.

Douglas Corley: Particularly if you are having symptoms, but that should probably be worked up whether or not you are taking these medications anyway.

Norman Swan: Doug Corley is a gastroenterologist at Kaiser Permanente in Northern California and he is also an investigator in their research division.



Dr Douglas Corley
San Francisco Medical Center
Research Scientist
Kaiser Permanente Division of Research


Dr Norman Swan
Brigitte Seega

Comments (7)

Add your comment

  • Tin :

    24 Mar 2014 5:52:29pm

    Ever since i've been on the antacid medication i've felt listless and lacking in stamina. maybe a B12 vitamin tablet may compensate. Thanks Doc.

  • Dr Margaret Taylor :

    25 Mar 2014 6:15:04pm


      • alphabeta :

        05 Aug 2014 10:32:28pm

        Heartburn is supposedly not directly due to too much acid in the stomach but too much acid in the eosophagus. This is supposedly due to inappropriate relaxations of the Lower Eosphageal Sphincter allowing acid to refluc into the eosophagus. The ability of acid artificially introduced into the lower eosophagus to trigger symptoms of reflux was established in 1958 by Baker and Bernstein.

        I doubt that the many people (who think more acid is the solution to heartburn) to whom you refer can be sufferers themselves; The discomfort of heartburn is not only a burning sensation as the name implies, but in the form of non-cardiac chest pain can be an intense squeezing or stabbing pain behind the sternum that can spread around the 3rd ribs to the thoracic vertebrae between the shoulder blades. Aggressive suppression of acid in the stomach appears to keep this noxious experience at bay.

  • rooster :

    27 Mar 2014 12:35:39pm

    Many aren't aware or told that early studies identified that proton pump inhibitors caused pancreatic cancer in rats. I also understand that suppressing the gastric acid may reduce the symptoms but doesn't necessarily reduce the risk of cancer. the jury is still out why some people progress to cancer and others don't. managing weight , food quantity and type , may be a better intervention than pharmacopeia .

  • peter :

    27 Mar 2014 4:09:38pm

    What about rabeprazole? I have stopped taking and have lost tingles in hands and feet.

  • Godel :

    28 Mar 2014 10:29:12am

    The program fails to address the obvious question of whether B12 supplementation would help.

  • linda :

    14 Apr 2014 9:47:38am

    I was so pleased to find this podcast in my casts download as I have been using a double daily dose of Pariet for the past 12 months and worryingly, my intraocular pressures have risen and my optic nerve is showing changes over that time after being stable for decades. As well, my blood pressure rose during the same period. You might say that the rises could be due to other causes but coincidences do not fit well with me. Thanks for a terrific program Norman!