Laboratory / cell studycited by the Tayebat archivefull text checked★ key study A-PPI-18 in-depth review
Ranitidine and NDMA in the lab
Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions.
Overview
Braunstein LZ et al.. JAMA Netw Open 2021 · PMID 33512515 · DOI 10.1001/jamanetworkopen.2020.34766
In simulated stomach fluid with very high nitrite, a tablet produced up to 320,000 ng NDMA.
Does the study support the specific claim? Partly · Methodological quality: low
Plain-language summary
Study explained simply
- What did the researchers want to find out?
NDMA formation conditions.
- How was the study done?
Lab experiment.
- How many people, animals or samples were studied?
Tablets in simulated gastric fluid.
- What was actually found?
NDMA rose with nitrite and acidity.
- How large was the observed effect?
947–320,000 ng (150 mg).
- What do the results mean in everyday life?
Chemically possible, human relevance unclear.
- What are the study's limitations?
In vitro; extreme nitrite; COI.
- What does it say about Elawady's specific claim?
Supports recall, not in-vivo levels.
- Do the results apply to Germany and Europe?
Drug not marketed in EU.
- What can explicitly not be concluded from this study?
Human gastric NDMA levels.
Scientific in-depth review
1. Full reference
- Authors
- Braunstein LZ, Kantor ED, O'Connell K, Hudspeth AJ, Wu Q, Zenzola N, Light DY
- Journal
- JAMA Netw Open
- Year
- 2021
- Identifier
- PMID 33512515 DOI 10.1001/jamanetworkopen.2020.34766 · PMC7846938
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
PubMed lists: ErratumIn (JAMA Netw Open. 2022 Mar 1;5(3):e227178. doi: 10.1001/jamanetworkopen.2022.7178.)
- Extent checked
- full text
- Conflicts of interest and funding
not stated in abstract; grants: NCI NIH HHS
2. Research question
Under which simulated gastric conditions does ranitidine yield NDMA?
3. Study design and population
- Study design
- Laboratory / cell study – In-vitro laboratory study (research letter): NDMA formation from ranitidine tablets in simulated gastric fluid
- Population
Commercial ranitidine 150/300 mg tablets
- Country
USA
- Period
June 2019–Aug 2020
- Sample size
Laboratory samples
4. Methods and endpoints
- Exposure / intervention
Varying pH (1.2–5.5) at 50 mmol/L nitrite; varying nitrite (1–50 mmol/L) at pH 2.5; 2 h at 37 °C
- Comparator
Tablets directly diluted (controls)
- Endpoints
NDMA amount by LC-HRMS (FDA method)
- Statistical methods
Descriptive
5. Actual results
- Results
At pH 2.5, 150 mg tablet: 947 ng NDMA at 1 mmol/L nitrite up to 320,000 ng at 50 mmol/L; at 50 mmol/L nitrite: 198,000 ng at pH 1.2 and 3,310 ng at pH 5.5; 300 mg tablet under 'optimally reactive' conditions 612,000 ng (full text).
- Absolute risks
not applicable (in vitro)
- Authors' conclusion
Ranitidine may be a significant source of NDMA under a range of physiologically relevant conditions; authors note that some reactive conditions exceed the usual gastric milieu; data support regulatory actions.
6. Strengths
- Validated FDA analytical method
- Dose-response with nitrite and pH
7. Weaknesses
- In vitro only
- Very high nitrite concentrations
- Four of seven authors affiliated with Valisure LLC (the laboratory that filed the citizen petition)
- Erratum for a figure error (2022)
8. Risk of bias
- Orienting tool
- none applicable
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- not assessable
- Rationale
Laboratory study; relevance to in-vivo exposure is the key limitation; potential commercial interest of co-authors' company.
9. Assessment of the statistical interpretation
Not a human exposure measurement; detection under extreme conditions ≠ harmful exposure in patients.
10. Relevance to the specific claim
11. Independent contrary findings
Florian 2021 RCT (I-PPI-07).
12. Transferability to Germany and Europe
Ranitidine withdrawn in EU; little current relevance.
13. Overall methodological judgement
Lab evidence of chemical possibility; not evidence of human gastric exposure.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | low |
| Risk of bias | not assessable |
| Precision of results | not applicable |
| Directness | very indirect |
| Reproducibility | not replicated |
| Consistency with the overall evidence | inconsistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | partly correct but over-interpreted |
14. Open questions
Long-term cancer epidemiology of ranitidine users.
15. Linked fact checks
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
Under simulated physiologic gastric conditions, a single ranitidine tablet generated NDMA up to 320,000 ng – vastly above the daily intake limit of 96 ng; supported the global recall.
- A. What was actually studied?
NDMA formation in simulated gastric fluid.
- B. What did the authors find?
Up to 320,000 ng at 50 mmol/L nitrite.
- C. What conclusions do the authors themselves draw?
May be a significant source; supports regulatory action.
- D. What does the archive derive from it?
Presented as what happens in the stomach.
- E. Is this derivation scientifically justified?
Partly: the number is reported correctly, but the archive omits that it occurs at the highest nitrite level, which the authors say can exceed usual gastric conditions, and that an RCT in humans found no increase in NDMA excretion.
- Adequacy of the interpretation (by the archive)
- partly correct but over-interpreted