Case-control studycited by the Tayebat archiveabstract only checked★ key study A-PPI-09 in-depth review
Acid blockers and low vitamin B12
Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency.
Overview
Lam JR et al.. JAMA 2013 · PMID 24327038 · DOI 10.1001/jama.2013.280490
Two or more years of PPI supply was associated with 65% higher odds of B12 deficiency.
Does the study support the specific claim? Yes · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
B12 deficiency association.
- How was the study done?
Case-control in a health system.
- How many people, animals or samples were studied?
210,155 patients.
- What was actually found?
Higher odds with PPI and H2RA.
- How large was the observed effect?
OR 1.65 / 1.25.
- What do the results mean in everyday life?
Long-term users may need B12 checks if symptoms.
- What are the study's limitations?
Detection bias.
- What does it say about Elawady's specific claim?
Supports C-PPI-03.
- Do the results apply to Germany and Europe?
Applicable.
- What can explicitly not be concluded from this study?
Exact causal size.
Scientific in-depth review
1. Full reference
- Authors
- Lam JR, Schneider JL, Zhao W, Corley DA
- Journal
- JAMA
- Year
- 2013
- Identifier
- PMID 24327038 DOI 10.1001/jama.2013.280490
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract
2. Research question
Association between PPI/H2RA use and vitamin B12 deficiency
3. Study design and population
- Study design
- Case-control study – Case-control study within Kaiser Permanente Northern California
- Population
KPNC members
- Country
USA
- Period
1997–2011
- Sample size
25,956 cases; 184,199 controls
- Inclusion and exclusion criteria
Incident B12 deficiency diagnoses vs patients without deficiency
4. Methods and endpoints
- Exposure / intervention
≥2 years' supply of PPI or H2RA; dose
- Comparator
No acid suppressant
- Endpoints
Vitamin B12 deficiency
- Statistical methods
Conditional logistic regression
5. Actual results
- Results
≥2 yr PPI OR 1.65 (1.58–1.73); ≥2 yr H2RA OR 1.25 (1.17–1.34); >1.5 PPI pills/d OR 1.95 (1.77–2.15) vs <0.75 pills/d OR 1.63 (1.48–1.78).
- Absolute risks
12.0% of cases vs 7.2% of controls had ≥2 years of PPI supply.
- Authors' conclusion
Gastric acid inhibitor use was significantly associated with vitamin B12 deficiency; consider in risk–benefit balance.
6. Strengths
- Very large
- Electronic pharmacy and lab data
- Dose-response
7. Weaknesses
- Case-control
- Testing bias (users may be tested more)
- Confounding
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Detection bias plausible; mechanism supports causality.
9. Assessment of the statistical interpretation
Moderate OR with dose-response and plausible mechanism; likely partly causal.
10. Relevance to the specific claim
11. Independent contrary findings
AGA 2017: no routine B12 screening recommended.
12. Transferability to Germany and Europe
High: European (Swedish, UK, Dutch, German) data show similar associations; PPIs are widely used in Germany.
13. Overall methodological judgement
Strong association with plausible mechanism.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | high |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | essentially correct but incomplete |
14. Open questions
Clinical significance (neuropathy, anaemia) frequency.
15. Linked fact checks
- Long-term acid suppression is linked to vitamin B12 deficiency and low magnesium. – Studies supporting the claim
- Acid blockers stop the absorption of all minerals, iron and vitamin B12, so nothing that is eaten benefits the body, the immune system stops working, and hair falls out. – Studies supporting the claim
Use by the Tayebat archive
Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.
- What the archive says about the study
Kaiser case-control: 2+ years of PPI use raises B12 deficiency risk 65%; H2 blockers 25%.
- A. What was actually studied?
Association of acid suppression with B12 deficiency.
- B. What did the authors find?
OR 1.65 for PPI, 1.25 for H2RA, dose-response.
- C. What conclusions do the authors themselves draw?
Significant association.
- D. What does the archive derive from it?
Presented as causal increase in risk.
- E. Is this derivation scientifically justified?
Essentially correct; OR from case-control, not risk increase proven.
- Adequacy of the interpretation (by the archive)
- essentially correct but incomplete