Laboratory / cell studyindependent cross-checkabstract checked★ key study I-PPI-118 in-depth review

Ranitidine does not make NDMA in realistic stomach conditions

In Vitro Analysis of N-Nitrosodimethylamine (NDMA) Formation From Ranitidine Under Simulated Gastrointestinal Conditions.

Overview

Gao Z et al.. JAMA Netw Open 2021 · PMID 34181009 · DOI 10.1001/jamanetworkopen.2021.18253

FDA tests found NDMA formation only at nitrite levels at least 50 times above normal stomach levels.

Does the study support the specific claim? No · Methodological quality: moderate

Study explained simply

What did the researchers want to find out?: Test NDMA formation from ranitidine in simulated stomach fluid.
How was the study done?: Laboratory study.
How many people, animals or samples were studied?: Ranitidine tablets.
What was actually found?: Only background NDMA at physiological nitrite.
How large was the observed effect?: 21-24 ng background vs 11,822 ng at extreme nitrite.
What do the results mean in everyday life?: The huge laboratory numbers do not reflect the real stomach.
What are the study's limitations?: In vitro only.
What does it say about Elawady's specific claim?: Contradicts the claim.
Do the results apply to Germany and Europe?: Universal.
What can explicitly not be concluded from this study?: Does not address contamination already present in tablets.

Authors: Gao Z et al.
Journal: JAMA Netw Open
Year: 2021
Identifier: PMID 34181009 DOI 10.1001/jamanetworkopen.2021.18253
Verification: verified – PubMed efetch 2026-10-26 + Crossref 2026-10-26
Retracted: no
Corrections: ErratumIn: JAMA Netw Open 2021;4(7):e2123189 'Errors in Figure Captions' (PMID 34283234); results unaffected
Extent checked: abstract only
Conflicts of interest and funding: US government (FDA) research

Does ranitidine form NDMA in simulated gastric fluid at physiological nitrite concentrations?

Study design: Laboratory / cell study – In-vitro laboratory study (US FDA) of NDMA formation in simulated gastric fluid
Population: Not applicable (150-mg ranitidine tablets)
Country: USA (FDA)
Period: Published 2021
Sample size: Not applicable
Inclusion and exclusion criteria: Not applicable

Exposure / intervention: Ranitidine in 50 or 250 mL simulated gastric fluid; nitrite 100-10,000 umol/L; pH range
Comparator: No added nitrite
Endpoints: NDMA after 2 hours (LC-MS)
Statistical methods: Descriptive means (SD)

Results: At 100 (upper physiological), 1000 or 5000 umol/L nitrite in 50 mL: only background NDMA (21-24 ng). At 10,000 umol/L: 222 ng at pH 5 to 11,822 ng at pH 1.2. In 250 mL: none at 100-1000 umol/L; 7353 ng at 5000 umol/L.
Absolute risks: Not applicable
Authors' conclusion: Ranitidine is not converted to NDMA in gastric fluid at physiological conditions.

Braunstein's maximum used 500 times the upper physiological nitrite (stats/C-PPI-08_ranitidine.py).

Directly tests the archive's laboratory claim under physiological conditions and finds no conversion.

Braunstein 2021 (A-PPI-18) at supraphysiological nitrite.

Universal.

Refutes in-stomach formation at realistic nitrite.

Multidimensional assessment
Multidimensional assessment
Authenticity of the source	verified
Methodological quality	moderate
Risk of bias	low
Precision of results	not applicable
Directness	indirect
Reproducibility	partly replicated
Consistency with the overall evidence	consistent
Regional transferability	high
Adequacy of the interpretation (by the archive)	not applicable

Product impurity levels over shelf life (a different issue).