NOTE: On 11/5/2020 I published an updated blog post on this topic. You can read it here.

When you’re about to pop a prescription pill into your mouth, do you momentarily wonder if it might contain a tiny amount of something dangerous in addition to the active drug? You probably don’t. You trust the pharmaceutical industry that formulated the drug’s ingredients, the plant where it was packaged, and the drugstore where you picked it up.

Suddenly, there’s some cause for concern about metformin, a common drug used to control diabetes that is also being explored for potentially broader health benefits. In fact, I have previously written about studies suggesting that metformin has the potential to prevent prostate cancer — though a February, 2019 paper questioned that connection. That said, it turns out that the way metformin is manufactured may make it an actual time bomb for causing disease.

NDMA

The culprit is a substance called N-Nitrosodimethylamine (NDMA), part of a class of compounds called nitrosamines. NDMA can cause liver damage, and is known to cause cancer in lab animals. It is fairly easy to ingest in tiny amounts because it is an unintended byproduct formed during chemical processes used to treat drinking water with chlorine, and during other processes used to cure meat, fish and tobacco. Thus, it can be found at very low levels in many (but not all) of these products.

The question is, what is a safe level of NDMA? The Emergency Planning and Community Right-to-Know Act of 1986 has a section on dealing “…with the many hazardous substances that are used throughout our society.”[i] This act classifies NDMA as an extremely dangerous substance subject to strict reporting requirements by facilities that produce, store or use it in significant quantities.[ii] Although it is listed as a priority pollutant by the Environmental Protection Agency, no federal standard has been set for drinking water.[iii] In California, a state that tends to have stringent environmental standards, the allowable drinking water level is 10 ng/L, while in Ontario, Canada it is 9 ng/L.

Metformin red flag, December 2019

It falls to the US Food and Drug Administration (FDA) to investigate and report on contaminants in prescription medications available in the U.S. According to an FDA statement, the agency has set 96 ng/L as the upper safe limit for the presence of NDMA in pharmaceuticals, a number considerably higher than the drinking water standards cited above. Within the past two years the agency evaluated the over-the-counter (OTC) stomach acid reducer Zantac, which did not contain NDMA but it does contain a molecule that may break down during digestive processes and form NDMA in the body. The FDA also investigated certain blood pressure and heart failure medicines call Angiotensin II Receptor Blockers, and recommended numerous recalls for unacceptable nitrosamine levels.[iv]

Prior to December, 2019 the FDA had been alerted by reports of “low-level NDMA contamination of metformin in other countries and of a few regulatory agencies issuing recalls for the drug,”[v] and began its own investigation into the matter. A statement was issued by Dr. Janet Woodcock, Director of the FDA’s Center for Drug Evaluation and Research. It contained the following reassurance:
 

While we are aware that some regulatory agencies outside the U.S. may be recalling some metformin drugs, there are no metformin recalls affecting the U.S. market at this time. The FDA is investigating whether metformin in the U.S. market contains NDMA, and whether it is above the acceptable daily intake limit of 96 nanograms. The agency will also work with companies to test samples of metformin sold in the U.S. and will recommend recalls as appropriate if high levels of NDMA are found. If as part of our investigation, metformin drugs are recalled, the FDA will provide timely updates to patients and health care professionals.[vi]

 
Dr. Woodcock noted that there are many reasons for the presence of NDMA in medications: how the drug is manufactured, its molecular structure, packing/storing conditions, and processing within the body leading to its formation, all of which the FDA continues to research and test for in metformin and other pharmaceuticals. She writes that despite increased cancer risk if a person is exposed to NDMA at high levels for a long period of time, “… a person taking a drug that contains NDMA at-or-below the acceptable daily intake limit every day for 70 years is not expected to have an increased risk of cancer.”

In conclusion, at this time the FDA is continuing to test for NDMA levels in metformin, but has yet to find anything to worry about. Their statements did not identify particular manufacturers, but since there are literally dozens of companies that produce it, it may be wise to seek a U.S. or European source if you are prescribed the drug for diabetes or any off-label use of it. It always pays to be a wise consumer.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you have health concerns or questions of a personal medical nature.

References

[i] Chemicals in Your Community: A Guide to the Emergency Planning and Community Right-to-Know Act. U.S. Government Printing Office: 1988 516-002/80246.
[ii] Chemicals in Your Community: A Guide to the Emergency Planning and Community Right-to-Know Act. U.S. Government Printing Office: 1988 516-002/80246.
[iii] “Technical Fact Sheet – N-Nitroso-dimethylamine (NDMA).” Environmental Protection Agency, Jan. 2014. https://www.epa.gov/sites/production/files/2014-03/documents/ffrrofactsheet_contaminant_ndma_january2014_final.pdf
[iv] Statement issued by Janet Woodcock, MD. Director, Center for Drug Evaluation and Research. Sep. 13, 2019.
[v] Franki, Lucas. “FDA investigates NDMA contamination in metformin.” Clinical Endocrinology News, Dec. 11, 2019. https://www.mdedge.com/endocrinology/article/214062/diabetes/fda-investigates-ndma-contamination-metformin
[vi] Statement issued by Janet Woodcock, MD. Dec. 5, 2019. https://www.fda.gov/news-events/press-announcements/statement-janet-woodcock-md-director-fdas-center-drug-evaluation-and-research-impurities-found