Anyone take a PPI?

I have been on PPI originally it was called Prilosec now it is called omeprazole and I’ve been taking it since 1990. I take 40 mg twice daily sometimes three times daily. The neuropathy in my feet is so bad but I’ve been told it’s diabetes which I have type two but it’s always been controlled completely, so I’m not sure what’s caused it . It’d be interesting to know if PPI do cause this.

Related discussions:
- Anyone seen research on long term Proton Pump Inhibitor use and PN?: https://connect.mayoclinic.org/discussion/anyone-seen-research-on-long-term-proton-pump-inhibitor-use-and-pn/
- Neuropathy + Proton-pump Inhibitor use?? Anyone had this experience?
https://connect.mayoclinic.org/discussion/neuropathy-and-ppi-use-has-anyone-had-this-experience/
@bigjohnscho, have you talked with your doctor about alternatives to taking a proton pump inhibitor (PPI) to decrease stomach acid production?

I would never have known there was a connection between PPI use and neuropathy had it not been for those posting about it here. I was on pantoprazole 40 mg per day for 18 months. In December I noticed my feet would burn painfully after a walk and sometimes just sitting around at night my toes would start to burn. All my blood tests, e.g. B12 and diabetes, didn't show anything. I have an appointment with a neurologist tomorrow to see what's up. In the meantime I have been tapering off of the pantoprazole for about 8 weeks. It will probably take another eight weeks to be completely off. This has been a struggle but I'm getting by with all the OTC stuff. And I'm motivated. Yesterday I found another study conducted by Kaiser in 2013 showing a likely connection. Funny how doctors prescribe these and let us stay on them indefinitely. So I'm posting to tell my story and keep the conversation going. Thank you for being here, and thank you for letting me share.

@llmartin Thank you for posting. I did not know of the connection between PPI and neuropathy. I was on a PPI for years, took myself off, a new MD (previous one left the practice) put me back on a PPI. So I've been on and off and on again. During this process, I was diagnosed with idiopathic progressive peripheral neuropathy, and have been under the care of a neurologist, and now under the care of an even more experienced primary care provider. No medical provider has mentioned the possible relationship between PPI and neuropathy. I'll ask at my March appointment. Thank you for your post.

@joanland thank you for replying. I could not find the link and would probably have trouble sharing it if I did, but in several discussions in the neuropathy support group last year, many contained links to relevant studies. It will be interesting to see if your doctor can tell you anything. There is so much research to keep up with nowadays, sometimes sometimes our doctors don't know and we have to be our own advocate. I do hope you find some solutions that work for you in dealing with this terrible disease. Please keep us posted on your progress. Kind regards, L

Hello @llmartin,

I combined your discussion with an existing discussion titled:

"Anyone take a PPI?"
- https://connect.mayoclinic.org/discussion/anyone-take-a-ppi/

@bigjohnscho started this discussion relating some of the same issues. @joanland also shared their experience as well.

I took dexilant 60 mgs twice a day.
I had in 2002 MRSA Bacterial Spinal Meningitis. That’s when mine started I have severe axonal sensorimotor peripheral polyneuropathy, small fiber neuropathy, dysautonomia, CIDP, cardiac autonomic neuropathy aka called CAN. Mine is also caused by my autoimmune immune diseases. Mixed
Connective tissue disease. Lupus, Sojourns and Hashimotos.

@artemis1886 Thank you for sharing. That is quite a story. I have been researching the connection between autoimmune disease and neuropathy, also, since I have inflammatory arthritis. Thanks for your input. Regards, L

Reference:
T. Makunts, Sama Alpatty, Kelly C. Lee, Rabia S. Atayee, and R. Abagyan. “Proton-Pump Inhibitor Use Is Associated with a Broad Spectrum of Neurological Adverse Events Including Impaired Hearing, Vision, and Memory.”
Scientific Reports, 2019.

This single study employed an observational design analyzing voluntary adverse event reports from the FDA FAERS database. The investigators selected monotherapy reports to minimize confounding from concurrent medications and validated cohort comparability through overlapping demographic parameters. The study examined six commonly prescribed PPIs and used H2RA users as a comparison group to control for the underlying indication (acid suppression therapy).

Effects
The study reported a substantial association between PPI use and peripheral neuropathy-related adverse events:

Outcome
Neuropathic/neurological
impairment adverse drug
reactions

Odds Ratio
8.68

95% Confidence Interval
[3.86, 19.49]

Interpretation
Over eight-fold increased reporting of neuropathy in PPI users compared to H2RA users

The odds ratio of 8.68 indicates that reports containing PPIs had substantially higher odds of including peripheral neuropathy adverse events compared to reports containing H2RAs. The confidence interval excludes the null value of 1.0, suggesting statistical significance. However, the study did not report specific dose-response relationships, duration-response relationships, or incidence rates in exposed versus unexposed populations. The number needed to harm was not calculated.

The study did not provide granular details about the neuropathy outcomes themselves, including specific types
of peripheral neuropathy (sensory, motor, sensorimotor, or autonomic), anatomical distribution, severity grading, diagnostic methods, specific symptoms, time to onset after PPI initiation, or reversibility upon discontinuation. The broad category of ”neuropathic/neurological impairment” encompasses cranial and peripheral neuropathies, sciatica, and nerve injury.

Regarding PPI exposure characteristics, the study did not report dosage, frequency, route of administration, indication for use, or timing of exposure relative to neuropathy onset. The authors noted that PPI treatment duration should not exceed two or three weeks according to recommendations, with long-term use beyond eight weeks warranting particular caution.

Methodological considerations
The pharmacovigilance design using FAERS data introduces several important considerations for interpreting these findings. The study did not ascertain a temporal relationship between PPI use and neuropathy onset, nor did it observe reversibility upon discontinuation, as these determinations would require longitudinal clinical data rather than cross-sectional adverse event reports. The absence of follow-up duration data and participant demographic information, including age distribution, gender, comorbidities, concurrent medications, clinical setting, and geographic location, limits assessment of effect modification and generalizability.

The investigators attempted to control confounding by restricting analysis to monotherapy reports, though they acknowledged that concurrent medications and comorbidities may be underreported in FAERS. No statistical adjustment methods for confounding or sensitivity analyses were reported. The authors explicitly characterized their findings as associative rather than causal, noting the inherent limitations of pharmacovigilance data for establishing causality.

The proposed biological mechanism involves vitamin B12 deficiency, which is plausible given that B12 deficiency can cause reversible peripheral neuropathy. However, the authors noted that few case reports in the literature directly link PPI use to peripheral neuropathy, indicating limited consistency with previous evidence. The study did not apply Bradford Hill criteria or other formal causal frameworks.

@stjohnsriverrat Very interesting stuff. It definitely makes a case for short-term use only. Other side effects include dementia. The problem is, when going off it, the rebound effect is terrible. I've been tapering for 2-3 months now and it's still a challenge to quit entirely. Thank you for your reply.