ACE inhibitors aren’t snake venom, no evidence they cause cancer

A Facebook reel that received more than 82,000 views claimed that snake venom has been “published to cause rapid turbo cancers to form in any tissue in the human body”, that ACE inhibitors (a type of medication used to treat high blood pressure) are actually snake venom, and that the U.S. National Cancer Institute knew this in 1956.

The claims were made by chiropractor Bryan Ardis, who spoke on the podcast Conversations With Adrian on 3 November 2024. It’s not the first time Ardis has invoked snake venom in health-related claims that he’s made. In April 2022, Ardis falsely claimed that COVID-19 is caused by snake venom and that COVID-19 vaccines contain snake venom.

Then as now, Ardis’ claims on the podcast aren’t grounded in evidence, as we will explain below.

ACE inhibitors aren’t snake venom, but synthetic molecules mimicking one component in snake venom

Blood pressure is regulated through several mechanisms. One of them is the renin-angiotensin-aldosterone system. A key lever of this system is angiotensin, a hormone that increases blood pressure in various ways. These include vasoconstriction (narrowing of blood vessels through muscular action of vessel walls), increasing sodium reabsorption by the kidneys—in turn increasing water reabsorption and thus blood volume—and stimulating the release of antidiuretic hormone, which also increases water reabsorption.

The active form of angiotensin is produced through the action of an enzyme called angiotensin-converting enzyme (ACE). Understanding angiotensin and ACE’s significant influence on blood pressure made scientists realize that both could be viable targets for treating high blood pressure (hypertension).

Among those scientists was John Vane, who won the Nobel Prize for Physiology or Medicine in 1982 for his study of how aspirin worked. In the 1960s, Vane and colleagues discovered that one component of the venom from the Brazilian viper Bothrops jararaca was a powerful inhibitor of ACE. This work, along with that of other scientists, paved the way for the eventual synthesis of the first ACE inhibitor captopril, based on the component of B. jararaca venom that inhibited ACE^[1].

Captopril was produced through peptide synthesis in the laboratory, and lisinopril, the ACE inhibitor named by Ardis, is a synthetic derivative of captopril.

Neither captopril nor lisinopril are snake venom—both molecules simply mimic the structure and function of a particular component present in the venom of B. jararaca. Therefore Ardis’ claim that lisinopril and other ACE inhibitors are snake venom is inaccurate and misleading.

No evidence that snake venom causes “turbo cancer”

Ardis didn’t provide evidence to back up his claim that snake venom causes “turbo cancer”, or that the NCI “paid scientists to figure that out in 1956”. The term “turbo cancer” is closely linked to the anti-vaccine movement, which has repeatedly pushed the false claim that COVID-19 vaccines are responsible for skyrocketing rates of cancer, particularly in young people.

As past reviews from Science Feedback showed, this claim has been based on a misinterpreted mouse study, a flawed analysis of cancer patients in two Croatian hospitals, and baseless speculations about residual DNA in COVID-19 mRNA vaccines.

We were unable to find a published study showing that the U.S. National Cancer Institute (NCI) discovered in 1956 that snake venom causes cancer. But a Google search^# led us to this study, which may have been what Ardis was referring to.

The study, published in 1956 in the Proceedings of the National Academy of Sciences, reported that a component of snake venom, when tested on mouse sarcoma cells cultured in the laboratory, could stimulate nerve cell growth^[2]. One of the study’s authors is Rita Levi-Montalcini, who won the 1986 Nobel Prize in Physiology or Medicine precisely for her work on nerve growth factor.

But the study was unrelated to studying cancer growth and didn’t show that snake venom causes cancer, let alone “turbo cancer”. Nor did the NCI fund the study. Instead, it was funded in part by the American Cancer Society and the National Institute of Neurological Diseases and Blindness (today the National Institute of Neurological Disorders and Stroke).

We reached out to Ardis for comment and will update this review if new information becomes available.

No clear evidence showing that ACE inhibitors increase cancer risk

When unmanaged, high blood pressure is dangerous as it can damage several organs like the heart, the brain, and the kidneys. Consequently, it raises the risk of a wide variety of complications, including heart failure, stroke, kidney failure, and vision loss, some of which are potentially fatal.

Medications that keep high blood pressure under control help to reduce the risk of such complications and thus save lives. However, some studies have found an association between antihypertensive medication and cancer, raising questions about the safety of ACE inhibitors (ACEI) treatment^[3,4]. That said, it’s important to clarify here that association alone isn’t sufficient evidence of causation.

One 2018 study in the U.K. looking at ACEI treatment found that it was associated with a 14% increased risk of lung cancer. It also found that this risk increased the longer a person received ACEI^[3].

However, the study was criticized by other scientists. Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, told Science Media Centre that while the study performed “a fairly rigorous statistical analysis” with a large dataset, “[i]t has a number of weaknesses, which make it quite likely that the observed association is not a causal one”.

He explained that smoking status wasn’t well-recorded in the database that the researchers had used, and even if recorded, doesn’t differentiate between heavy and light smoking. This meant that the study was unable to fully account for smoking status in its analysis.

This caveat makes it possible that many of those classified as non-smokers in the study were actually smokers. Such errors “could have large effects on the estimates of risk”, since heavy smoking can increase lung cancer risk by 20 times, Evans said.

Adding credence to this consideration is the study’s unusual finding that smoking status didn’t affect lung cancer risk. This finding conflicts with the fact that smoking is well-established as the number one risk factor for lung cancer. But if the study misclassified some smokers as non-smokers, it could have masked smoking-related lung cancer risk when smoking and non-smoking groups were compared. This would explain the finding that lung cancer risk didn’t differ much between smoking and non-smoking groups.

A 2020 analysis by Battistoni and Volpe in the European Cardiology Review discussed several studies examining the association between ACEI and cancer^[5]. The analysis also included the 2018 study from the U.K. and some of its criticism of that study also mirrored that of Evans.

Battistoni and Volpe concluded that overall, the evidence didn’t consistently point to an association between ACEI and increased cancer risk. In fact, some studies either found no association^[6,7] between ACEI and cancer or even lower cancer risk in people receiving ACEIs^[8].

They stated that “At this time, recommendations to interrupt successful antihypertensive therapies with [angiotensin receptor blockers], ACE inhibitors or diuretics to avoid a generic risk of cancer do not appear to be justified”.

A 2021 study in Denmark reported “a modestly increased risk of lung cancer associated with use of high cumulative doses of ACEIs”^[4]. However, this association disappeared with lower doses of ACEIs. The authors also cautioned that “the long-established benefits of ACEI therapy should be considered when interpreting these findings”.

A 2021 meta-analysis by Copland et al. which examined 33 clinical trials reported that it “found no consistent evidence that antihypertensive medication use had any effect on cancer risk”^[9].

In summary, the scientific evidence currently available doesn’t demonstrate a clear association between ACEIs and increased cancer risk. Association alone is also insufficient to demonstrate causality and no studies have yet demonstrated that ACEIs cause cancer in people.

Conclusion

In summary, Ardis’ claim that ACE inhibitors are snake venom is false and misleading. While it was research on one particular component in snake venom that paved the way for the development of ACE inhibitors, the drugs aren’t snake venom themselves. They were synthesized in the laboratory to mimic the function and structure of a component in snake venom.

While a few studies reported an association between ACE inhibitors and increased cancer risk, other studies found no such association or even a lower cancer risk. More research to clarify this question is still needed. It’s also important to keep in mind that association alone isn’t sufficient evidence of causation. ACE inhibitors have well-established benefits for people with hypertension, which can be a dangerous condition when left unmanaged. There’s currently not enough evidence to support the claim that the as-yet hypothetical cancer risk of ACE inhibitors outweighs their benefits.

Footnotes

#: Search terms used were “snake venom” 1956 “national cancer institute”.

REFERENCES

• 1 – Cushman and Ondetti. (1991) History of the Design of Captopril and Related Inhibitors of Angiotensin Converting Enzyme. Hypertension.
• 2 – Hicks et al. (2018) Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study. BMJ.
• 3 – Kristensen et al. (2021) Use of ACE (Angiotensin-Converting Enzyme) Inhibitors and Risk of Lung Cancer: A Nationwide Nested Case-Control Study. Circulation: Cardiovascular Quality and Outcomes.
• 4 – Battistoni and Volpe. Recent Warnings about Antihypertensive Drugs and Cancer Risk: Where Do They Come From? European Cardiology Review.
• 5 – The ARB Trialists Collaboration. (2011) Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138 769 individuals. Journal of Hypertension.
• 6 – Bangalore et al. (2011) Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncology.
• 7 – Rao et al. (2013) Angiotensin receptor blockers: are they related to lung cancer? Journal of Hypertension.
• 8 – Copland et al. (2021) Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis. Lancet Oncology.