Randomised controlled trialindependent cross-checkabstract only checked★ key study I-PPI-07 in-depth review
Does ranitidine form NDMA in people?
Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA): A Randomized Clinical Trial.
Overview
Florian J et al.. JAMA 2021 · PMID 34180947 · DOI 10.1001/jama.2021.9199
Ranitidine did not raise NDMA in urine compared with placebo.
Does the study support the specific claim? No · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
In-vivo NDMA.
- How was the study done?
Crossover RCT.
- How many people, animals or samples were studied?
18 healthy adults.
- What was actually found?
No increase.
- How large was the observed effect?
Median difference 0 ng.
- What do the results mean in everyday life?
Lab extremes not seen in people.
- What are the study's limitations?
Small; urinary marker.
- What does it say about Elawady's specific claim?
Contradicts C-PPI-08.
- What can explicitly not be concluded from this study?
Long-term cancer risk.
Scientific in-depth review
1. Full reference
- Authors
- Florian J et al.
- Journal
- JAMA
- Year
- 2021
- Identifier
- PMID 34180947 DOI 10.1001/jama.2021.9199
- Verification
- verified – PubMed efetch 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract
2. Research question
Does oral ranitidine increase 24-h urinary NDMA?
3. Study design and population
- Study design
- Randomised controlled trial – Randomised double-blind placebo-controlled crossover trial (FDA)
- Population
Healthy adults
- Country
USA
- Period
June–July 2020
- Sample size
18 (17 completed)
- Inclusion and exclusion criteria
Healthy participants
4. Methods and endpoints
- Exposure / intervention
Ranitidine 300 mg with non-cured and cured-meat diets
- Comparator
Placebo
- Endpoints
24-h urinary NDMA
- Statistical methods
Paired differences
5. Actual results
- Results
Median NDMA: ranitidine 0.6 ng vs placebo 10.5 ng (non-cured), 11.9 vs 23.4 ng (cured); paired differences 0 (P=.54) and −1.1 ng (P=.71).
- Absolute risks
not applicable
- Authors' conclusion
Findings do not support that ranitidine is converted to NDMA in a general, healthy population.
6. Strengths
- Randomised, blinded, crossover
- Diet with high nitrite tested
7. Weaknesses
- Small
- Urinary NDMA is an indirect marker
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Simplified.
9. Assessment of the statistical interpretation
Small but direct human test.
10. Relevance to the specific claim
11. Independent contrary findings
12. Transferability to Germany and Europe
Ranitidine not marketed in EU.
13. Overall methodological judgement
Direct in-vivo evidence against large NDMA formation.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | low |
| Precision of results | low |
| Directness | direct |
| Reproducibility | unknown |
| Consistency with the overall evidence | unknown |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Gastric NDMA in people with high nitrite.
15. Linked fact checks
- Ranitidine forms the carcinogen NDMA in the human stomach at levels thousands of times above safety limits (up to 320,000 ng per tablet). – Studies contradicting or limiting the claim