Case-control studyindependent cross-checkabstract checked★ key study I-PPI-116 in-depth review
Long-term acid blockers linked to iron deficiency
Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency.
Overview
Lam JR et al.. Gastroenterology 2017 · PMID 27890768 · DOI 10.1053/j.gastro.2016.11.023
People who took PPIs for 2 years or more had about 2.5 times the odds of iron deficiency, more with higher doses.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Check acid suppression and iron deficiency.
- How was the study done?
Case-control study.
- How many people, animals or samples were studied?
77,046 cases, 389,314 controls.
- What was actually found?
OR 2.49 for >=2 y PPI; dose-response; reversible.
- How large was the observed effect?
2.49 (2.35-2.64).
- What do the results mean in everyday life?
Long-term users may need iron checked if symptomatic.
- What are the study's limitations?
Observational.
- What does it say about Elawady's specific claim?
Supports nutrient-specific effects, not 'nothing is absorbed'.
- Do the results apply to Germany and Europe?
Applicable.
- What can explicitly not be concluded from this study?
Cannot prove causation in every user.
Scientific in-depth review
1. Full reference
- Authors
- Lam JR et al.
- Journal
- Gastroenterology
- Year
- 2017
- Identifier
- PMID 27890768 DOI 10.1053/j.gastro.2016.11.023
- Verification
- verified – PubMed efetch 2026-10-26 + Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Not stated in abstract
2. Research question
Is long-term acid suppression associated with iron deficiency?
3. Study design and population
- Study design
- Case-control study – Community-based case-control study (Kaiser Permanente Northern California)
- Population
Members without pre-existing iron-deficiency risk factors
- Country
USA
- Period
1999-2013
- Sample size
77,046 cases; 389,314 controls
- Inclusion and exclusion criteria
Excluded pre-existing iron-deficiency risk factors
4. Methods and endpoints
- Exposure / intervention
>=2-year supply of PPI or H2RA
- Comparator
No use
- Endpoints
New iron deficiency diagnosis
- Statistical methods
Conditional logistic regression
5. Actual results
- Results
>=2 years PPI aOR 2.49 (2.35-2.64); >=2 years H2RA OR 1.58 (1.46-1.71); stronger for >1.5 pills/day; >1.5 pills/day for >=10 years OR 4.27 (2.53-7.21); associations decreased after discontinuation.
- Absolute risks
3.0% of cases vs 0.9% of controls had >=2-year PPI supply
- Authors' conclusion
Acid inhibitor use for >=2 years was associated with increased iron deficiency risk, rising with potency and falling after discontinuation.
6. Strengths
- Very large
- Dose-response and reversibility
7. Weaknesses
- Observational; residual confounding (occult bleeding)
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
Confounding by occult GI blood loss possible.
9. Assessment of the statistical interpretation
Crude OR from counts 3.61 vs adjusted 2.49; only 3% of iron-deficiency cases had long-term PPI exposure (stats/C-PPI-03_04_micronutrients.py).
10. Relevance to the specific claim
Supports a real, dose-dependent iron effect (C-PPI-03 extension; partial support for C-PPI-04) while showing it concerns a minority.
11. Independent contrary findings
COMPASS found no excess of major adverse outcomes beyond enteric infections (I-PPI-01).
12. Transferability to Germany and Europe
Applicable.
13. Overall methodological judgement
Iron absorption effect plausible and reproducible; not 'all minerals'.
| 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) | not applicable |
14. Open questions
Clinical relevance in well-nourished users.
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 with mixed or unclear results