Anyone take a PPI?

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.

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 My primary doctor started giving me an injection of B12, the past 3 or 4 months and I have noticed some improvement. I asked her she could order it for every week and she did. My son-in-law a podistrist has gave me a injection the past 2 week's. I do believe I can tell a big difference. I wonder if anyone else has tried the B12 injections.

@stjohnsriverrat Thank you for this information. It makes me even happier that I dumped PPIs after being on them for four years. They damaged my kidneys and did leave me with B12 deficiency. If I had to do it all over again, I would have used famotidine, which reduces stomach acid much less than a PPI. I also would have changed my diet and lifestyle earlier. Many people can control their GERD on a low-acid, whole food diet (yes pills are easier but eating better has good side effects, not bad ones).

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.

@indyjo i have recently learned that years on ppi medicine omeprazole had likely been blocking my stomach from breaking down food rich in vitamin b12 and caused me to be mildly deficient. B12 deficiency symptoms include neuropathy alongside many other symptoms including memory loss fatigue confussion ect. I feel somewhat lucky as i was able to present my findings to my GP who agreed to start me on b12 injections. Since then i have definitely noticed some improvements in my neuropathy and my cognitive issues. However i belive the nerve take a long time to regenerate something like 1ml a month. Good luck to you!