
Proton pump inhibitors (heartburn meds) linked with increased risk of dementia - Urgo
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12113
======
patall
From abstract: "Given that accumulating evidence points at cholinergic
dysfunction as a driving force of major dementia disorders, our findings
mechanistically explain how prolonged use of PPIs may increase incidence of
dementia. This call for restrictions for prolonged use of PPIs in elderly, and
in patients with dementia or amyotrophic lateral sclerosis."

This is classical A causes B and B causes C, so A leads to C which is
something we have had before with amyloid plaques. This does not tell us this
is false, but really just a link and nothing more.

Some beautiful day, we will fully understand the cause of dementia. Today is
not that day.

~~~
breischl
Somewhat tangentially, do you have an opinion on whether PPIs cause dementia,
regardless of what the mechanism may be?

Reason I ask is that I've been taking them daily for years to control GERD, so
I'm wondering if I'm frying my brain. But I'm not really qualified to
understand the intricacies of this kind of research.

Even further tangent: seems like they may also cause acute kidney injury.
Yaaaay. I guess everything is a tradeoff.
[https://www.ncbi.nlm.nih.gov/pubmed/30779194](https://www.ncbi.nlm.nih.gov/pubmed/30779194)

~~~
patall
Sorry but no, I do not have an opinion on that.

------
fpgaminer
Somewhat tangential, but I have a story about acid reflux that I think is
worth sharing for anyone who is in a similar boat.

Basically, I was having reflux symptoms minus the heartburn. Lots of throat
issues, digestive issues, coughing, etc. My doctor looked everything over and
concluded that reflux was the most likely cause and we did a treatment of PPIs
for a few weeks.

The PPI didn't help, but by the time the treatment was over we were in the
middle of this pandemic so I couldn't go back into the doc for a next step.

Luckily a few weeks later I randomly stumbled into a fix. One day I noticed
the symptoms were gone and when I thought about it I realized I had started
taking an additional allergy medication a few days prior. So it seems that
instead of reflux I had postnasal drip.

To be fair to the doctor he did mention postnasal drip as a possibility, but
reflux was deemed as more likely because I was already on allergy meds and the
symptoms were very reflux-y.

Obviously if you have reflux like symptoms, see a doc, but I thought my
experience was worth sharing for anyone in a similar boat. It's fairly simple
to try new allergy meds and see if that's the root cause. In my case adding a
steroidal nasal spray into the mix was what helped. And it resolved the issue
in a couple days, whereas trying out PPIs was a two month long experiment of
continued suffering. (Side note: not all steroidal nasal sprays are created
equal. I had previously tried Flonase which did nothing for me.)

~~~
2OEH8eoCRo0
Anedcote from me: I took Omeprazole for years and had to stop when I entered
USMC bootcamp. All stomach issues disappeared when I started exercising and
eating right. That was over 10 years ago and to this day my stomach is fine.
I've kept up the habit of eating well and exercising mildly.

TL;DR change your eating habits and exercise before trying to solve everything
with a drug

~~~
fpgaminer
Yeah obviously lifestyle should be a first course of action. In my case, no
lifestyles changes helped. Which makes sense, since the underlying cause
appears to have been allergies.

------
atian
Stomach is known to kill stuff before they become harmful to us. If PPIs let
more things through... well that makes sense.

Specifically: \- [https://www.statnews.com/2020/05/06/researchers-show-
herpes-...](https://www.statnews.com/2020/05/06/researchers-show-herpes-link-
to-alzheimers/)

There are more relating to opportunistic fungal, bacterial, and so on.
Relating to the mechanism of increased susceptibility to infection may be
related to our stomach's part in naturally being an infection load regulator
through its acid, in combination with our hydration gradient providing for our
saliva in (that tract). Someone please credit me in the future if they win a
nobel prize.

------
Droobfest
This is just anecdotal, but I've had problems with heartburn for years and am
having great succes with betaine hcl + pepsin supplements. This actually
increases stomach acid. That + dietary changes almost completely cleared my
problems. Just throwing it out there. YMMV.

~~~
ambivalents
What dietary changes?

Idk if what I have is heartburn but the past 2 months or so I have been waking
up to horrific stomach aches. Taking a round of Prilosec seems to have helped
it. But I may want to backpedal on it given this news.

~~~
pkaye
Typically people are asked to avoid acidic foods (tomatoes, citrus), raw
onions, chocolate, caffeine, sodas, peppermint and high fat foods.

~~~
wincy
I don't get why high fat foods are lumped in here. I've started avoiding all
the others you mentioned, and my reflux has stopped, but I'm on a ketogenic
diet that's very high in fat.

~~~
pkaye
Some foods loosen the sphincter making it easier to get reflux. Like eating a
slice of pepperoni pizza. My dietitian said each individual is different so
you need to determine what works or doesn't works for you.

~~~
ashtonkem
I think the most effective dietary advice in the world is this:

Change one thing for two weeks, and see if it gets better or worse.

You can fix a surprisingly wide range of problems by changing your diet in a
slow, methodical way.

------
sseagull
While there are some eyebrow-raising studies suggesting the correlation
between PPI use and dementia, it is far from settled science. There are
conflicting studies, and some meta-analyses suggest no association. Of course,
studies saying drugs are safe don't make the news.

"No association between proton pump inhibitor use and risk of dementia:
Evidence from a meta‐analysis" Journal of Gastroenterology and Hepatology (Jan
2020, [https://doi.org/10.1111/jgh.14789](https://doi.org/10.1111/jgh.14789))

"Dementia, cognitive impairment and proton pump inhibitor therapy: A
systematic review" Journal of Gastroenterology and Hepatology (August 2017,
[https://doi.org/10.1111/jgh.13750](https://doi.org/10.1111/jgh.13750))

"Risk factors for dementia diagnosis in German primary care practices"
International Psychogeriatrics (July 2016,
[https://doi.org/10.1017/S1041610215002082](https://doi.org/10.1017/S1041610215002082))

From the last article: "The use of statins (OR: 0.94; 0.90–0.99), proton-pump
inhibitors (PPI) (0.93; 0.90–0.97), and antihypertensive drugs (0.96,
0.94–0.99) were associated with a decreased risk of developing dementia."

~~~
Scipio_Afri
This article is stating a correlation but the reason they did this is that
there is molecular evidence for cholinergic pathways in the body, and drugs
which are anti-cholinergic, causing Alzheimer's because of this system being
integral to the development of Alzheimer's disease.

The whole reason they decided to do this correlational study - and other
studies like it - is because they have evidence that this cholinergic system
plays a part in developing Alzheimers. Then, to back up that molecular theory
and evidence, they're looking at correlations that the drugs that target this
system have in developing Alzheimers. Sure enough things like how much one
uses Diphenhydramine (active ingredient in benadryl and the same can be said
for other allergy medications that are anti-cholinergic) shows that increased
use has a direct correlation with increased risks of developing Alzheimer's
disease.

Many studies on these anti-cholinergic drugs shows this correlation, they also
have an understanding of the molecular basis of why, however in addition they
also show that drugs that target this system in certain ways help reduce the
symptoms of the disease.

Because of this, the evidence points to medications that fall into this "anti-
cholinergic" or "slighly anti-cholinergic" drug category - allergy medications
(diphenhydramine, loratadine) some PPI and others - might also amplify the
chances of getting the disease.

There seems to be a lot of evidence pointing to this, and while its still an
emerging area I'm confused as to how you are stating that this system and
these drugs that interact with it, which has a lot of evidence that it is part
of the disease pathophysiology, are weak on evidence?

What is your background and the experience you have to be able to state what
you just said?

Here is some background on this system and its implications with Alzheimer's :

[https://www.medscape.com/viewarticle/900644](https://www.medscape.com/viewarticle/900644)

"The Cholinergic System in the Pathophysiology and Treatment of Alzheimer's
Disease"

"Cholinergic synapses are ubiquitous in the human central nervous system.
Their high density in the thalamus, striatum, limbic system, and neocortex
suggest that cholinergic transmission is likely to be critically important for
memory, learning, attention and other higher brain functions. Several lines of
research suggest additional roles for cholinergic systems in overall brain
homeostasis and plasticity. As such, the brain's cholinergic system occupies a
central role in ongoing research related to normal cognition and age-related
cognitive decline, including dementias such as Alzheimer's disease. The
cholinergic hypothesis of Alzheimer's disease centres on the progressive loss
of limbic and neocortical cholinergic innervation. Neurofibrillary
degeneration in the basal forebrain is believed to be the primary cause for
the dysfunction and death of forebrain cholinergic neurons, giving rise to a
widespread presynaptic cholinergic denervation. Cholinesterase inhibitors
increase the availability of acetylcholine at synapses in the brain and are
one of the few drug therapies that have been proven clinically useful in the
treatment of Alzheimer's disease dementia, thus validating the cholinergic
system as an important therapeutic target in the disease. "

~~~
sseagull
> There seems to be a lot of evidence pointing to this, and while its still an
> emerging area I'm confused as to how you are stating that this system and
> these drugs that interact with it, which has a lot of evidence that it is
> part of the disease pathophysiology, are weak on evidence?

Because there is evidence to the contrary, which I posted. Some even from a
few months ago.

My goal is to bring balance to the discussion. Too often we see only the
headlines that something might cause ${DREADED_DISEASE}, but ignore studies
saying the opposite. It's a play on fear.

> What is your background and the experience you have to be able to state what
> you just said?

This is needlessly confrontational.

My background: PhD in chemistry. While relatively unrelated, I do know how to
read and find follow-up research. My interest also stems from taking a PPI,
and hearing only the one side from concerned family members.

------
tyingq
And untreated chronic heartburn has a fairly strong link to cancer. And some
of the better non-PPI drugs, like ranitidine were just pulled by the FDA for
impurities. Then, famotidine is in short supply because of some study that it
might treat COVID-19. Yikes.

------
riedel
I remember aluminum and particularly aluminum hydroxide as a heartburn drug
was linked to dementia before. Nothing happened, because proofing causation
seems close too impossible ruling out other confounders. I wonder without
understanding all of the reasoning if this is any different? Can you prove
sth. without an intervention?

~~~
jacobush
I don't know, but where I live, it's basically impossible to buy these
anymore.

------
toastflambe
Interesting study linked from this one: "Cognitive impact after short-term
exposure to different proton pump inhibitors"
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696341/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696341/)

~~~
golemotron
A good next study would to see if the study participants' decline reversed
after being removed from the drugs.

------
wisecoder
I had severe acidity issue and ended up in a condition called Barrett's
esophagus . Doctor advised me to Omeprazole 40mg life long. After taking it
for 6 months, i started following gluten free diet and all my gerd symptoms
gone away. After 3 years, my Barrett's esophagus condition also reversed.

------
buboard
i dont see it mentioned here, but for occasional acid reflux, a tsp of baking
soda in water works great

~~~
ornornor
Came here to say that. It’s dirt cheap and probably has less interactions and
side effects too.

------
Koshkin
Off-topic: Maybe it's just me, and this is not important in the least, but I
have been always slightly irritated by the use of the term "proton" in
chemistry which they use to denote the (positive) hydrogen ion. Two reasons:
unlike "electron", the term "proton" belongs in physics exclusively and not
chemistry which only deals with point-like nuclei carrying mass plus an
electric charge, and the electron cloud; the other reason was that just like
many - if not most - chemical elements, hydrogen has several isotopes, and it
is conceivable that at least some of the ions may have a neutron in its
nucleus.

~~~
JumpCrisscross
> _the use of the term "proton" in chemistry which they use to denote the
> (positive) hydrogen ion_

H+/K+ ATPase is a proton pump, not a hydrogen ion pump. It evolved to pump
protons, and mostly pumps protons.

> _the term "proton" belongs in physics exclusively and not chemistry which
> only deals with point-like nuclei carrying mass plus an electric charge, and
> the electron cloud_

Lots of biological machinery fails with heavy hydrogen isotopes, including
some proton pumps [1]. This is why heavy water is poisonous [2].

[1]
[https://tbiomed.biomedcentral.com/articles/10.1186/1742-4682...](https://tbiomed.biomedcentral.com/articles/10.1186/1742-4682-4-9)

[2]
[https://en.m.wikipedia.org/wiki/Heavy_water](https://en.m.wikipedia.org/wiki/Heavy_water)

~~~
CamperBob2
I agree with the GP. Biology is chemistry, and the hydrogen electron shell is
what's important in chemistry, not the nucleus. If the proton didn't act as a
hydrogen nucleus, we wouldn't use the term PPI at all.

Heavy water being (slightly) toxic doesn't have any bearing on the larger
point.

~~~
Metacelsus
>hydrogen electron shell is what's important in chemistry, not the nucleus

The kinetic isotope effect would like to have a word with you.

~~~
CamperBob2
Yes, there are extremely obscure corner cases in nature. The larger point,
once again, stands.

