Nature Nurtures Nicotine Nonsense

 

The prestigious scientific journal Nature draws considerable attention to its articles from scientists and others worldwide.  That makes it imperative that we point out the many serious flaws in a recent article, misleadingly titled, “Is nicotine bad for long-term health? Scientists aren’t sure yet.”

At this writing, MEDLINE, “the world's leading bibliographic source for biomedical scholarly literature and research,” offers citations to 28,241 articles with the keyword “nicotine”.  While it is true that science always demands additional research, one can reasonably assume that there is sufficient data on nicotine effects to draw meaningful conclusions about its safety.

Apparently, the authors of the Nature article went to great lengths to secure comments from what is surely a minuscule community of “unsure” scientists and from entrenched opponents of recreational nicotine consumption and tobacco harm reduction. 

Aruni Bhatnagar, who runs a tobacco regulation and addiction center sponsored by the American Heart Association, is quoted saying, “We believe that much of the cardiovascular effects of smoking are because of nicotine,” and he postulates that the drug can change the timing of electrical signals in the heart.  This sounds ominous, but the article includes a refutation of these comments by Neal Benowitz, a recognized nicotine authority: “Nicotine is a minor player with respect to smoking-induced cardiovascular disease.”  Benowitz points to “studies of snus – a chewable tobacco product that is popular mainly among men in Sweden and is gaining traction elsewhere – which do not generally show a detectable rise in heart problems among people who use it.”

Maciej Goniewicz of the Roswell Park Cancer Center in Buffalo offers insignificant insights, such as, “[Nicotine] changes lots of functions in our bodies, it’s not a harmless compound.”  That can be said of everything humans consume.  Goniewicz also muses, “Someone chronically exposed to nicotine might have chronic inflammation. There is speculation that it might contribute to increased risk of cancer. [Emphasis added] From animal and cell studies, yes, nicotine is doing something. How this translates into a risk for the [human] user, we don’t know.”  Benowitz counters: “the evidence, for me, is not convincing in tying [nicotine] to cancer in humans.”  The evidence for a nicotine-cancer link is next to nil.

Frequent nicotine critic Laura Crotty-Alexander of the University of California San Diego notes, “We’ve underplayed the role that nicotine has in the health effects of tobacco products.”  Basing her opinion on her own research, in which cells and animals are tortured with nicotine (more info here and here), she offers a weak indictment of the drug, saying, “I’ve been more and more surprised at the changes I’m seeing when I expose cells to nicotine.”

One of the most extreme views in the Nature article comes from Kjersti Aagaard, a maternal-fetal doctor at Houston’s Baylor College of Medicine: “No amount of nicotine is known to be safe in pregnancy. None. If you are exposed to nicotine in the womb, there could be lifelong consequences.”  Aargaard implies that failure to meet that standard could have criminal consequences for the pregnant woman, but the journal contrasts those remarks with the position of the UK National Health Service, which “describes e-cigarettes as safer than smoking for pregnant women, but it notes that there is little research to support the safety of e-cigarettes beyond that. It recommends pregnant women use nicotine patches and gums to stop smoking.”  This is but one example of the startling differences between prohibitionist American and science-based British positions on vaping.

Despite the Nature article’s complaint that “the lack of knowledge about whether nicotine contributes to the damaging health effects of smoking is becoming more worrying,” there is a wealth of knowledge supporting the finding that the effects of nicotine on health are minimal to nonexistent. 

 

   

Cigarette-Nicotine Fadeout Fails; NIH-Funded Researchers Back “Easy Alternative Sources of Nicotine”

Drs. Neal Benowitz and Jack Henningfield were respected tobacco researchers in 1994 when they introduced a flawed smoking cessation prescription: force smokers to quit by reducing the nicotine content of cigarettes (here).  I criticized the idea in my 1995 book, For Smokers Only (now available as an e-book with a bonus chapter on e-cigarettes).

In the 20 years since, the nicotine fadeout strategy has failed to gain traction, while the alternate concept of tobacco harm reduction has attracted substantial support.  When Drs. Benowitz, Henningfield and their anti-tobacco allies attempted five years ago to resurrect nicotine fadeout as an FDA regulatory strategy, I labeled it “the most idiotic idea ever proposed by tobacco control advocates” (here) and described “the disaster that would result from radical reduction (prohibition) of nicotine in cigarettes” (here).

Today we have a fresh clinical trial (abstract here) from Dr. Benowitz that may mark the last gasp for this scheme.

Dr. Benowitz and coworkers enrolled 135 smokers who were “interested in a reduced nicotine cigarette study, and not interested in quitting smoking in the next 6 months.”  Eighty participants “smoked five levels of progressively lower nicotine content cigarettes, the first four levels being smoked for 4 weeks each.  The lowest nicotine content cigarette was smoked for 7 months.  [I call this the fade-out group.]  The control group smoked their usual brand of cigarettes for 12 months.”  Everyone got a year’s worth of free cigarettes, and information was collected for one additional year.

The results were dismal, starting with completion rates.  Smokers were paid to participate, which may have prompted 87% of the control group to complete the first year and 69% to make it through the second; the rates in the fade-out group were 46% and 38%.

The authors reported that “Quit rates were low in both [fade-out] and control groups, and not significantly different between groups at any time.”  That is an understatement.  The quit rate, validated by lab studies, was 2% among controls at one year and at two years.  Among the fade-out group, the rates were 3.8% at one year and 7.5% at two years.

There’s more bad news.  At one year, 43% of fade-out smokers admitted they had violated the study protocol by smoking regular cigarettes.

Dr. Benowitz likely intended the study to provide cover for the FDA to gradually reduce cigarette nicotine levels to near zero.  Instead, as he acknowledged, the fadeout theory was disproven: “Simply reducing the nicotine content of cigarettes alone may be insufficient to extinguish smoking behavior.”

Importantly, Dr. Benowitz concedes that “…easy access to alternative sources of nicotine (such as nicotine medications or electronic cigarettes) may be needed to achieve cessation of

cigarette smoking.”

Dr. Benowitz, welcome to Tobacco Harm Reduction.

A final note: I recently discussed how the National Institutes of Health have influenced the debate about tobacco harm reduction by doling out massive grants to university researchers nationwide (here).  The Benowitz study was supported by four grants from the National Cancer Institute and the National Institute on Drug Abuse; the total taxpayer tab was $29.2 million.

The Tide Is Turning: More Scientific Support for E-Cigarettes

E-cigarettes get a positive health review in the new issue of the journal Addiction (here).  Quoting from the abstract:

[Electronic cigarettes, EC] aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower.  Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders.  EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children.  EC enable some users to reduce or quit smoking.

Conclusions: Allowing EC to compete with cigarettes in the market-place might decrease smoking-related morbidity and mortality.  Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence.  Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use.

The study confirms what I and others (here) have documented about bogus claims regarding toxicants, poison episodes and gateway.  Here are excerpts:

Claim: Chemicals in EC cause excess morbidity and mortality.

Evidence: Long-term use of EC, compared to smoking, is likely to be much less, if at all, harmful to users or bystanders.

Claim: Smokers who would otherwise quit combine EC and cigarettes instead of quitting and maintain a similar smoking rate.

Evidence: EC use is associated with smoking reduction and there is little evidence that it deters smokers interested in stopping smoking tobacco cigarettes from doing so.

Claim: Young people who would not try cigarettes otherwise start using EC and then move on to become smokers.

Evidence: Regular use of EC by non-smokers is rare and no migration from EC to smoking has been documented...The advent of EC has been accompanied by a decrease rather than increase in smoking uptake by children.

Claim: EC use will increase smoking prevalence indirectly, e.g. by making smoking acceptable again in the eyes of people who cannot tell the difference between EC and cigarettes, via machinations of the tobacco industry, or by weakening tobacco control activism.

Evidence: There are no signs that the advance of EC is increasing the popularity of smoking or sales of cigarettes.

In other words, the far-fetched claims by anti-tobacco zealots are derived from thin air, not vapor.

The article is authored by established tobacco harm reduction advocates Peter Hajek, Jean-Francois Etter and Hayden McRobbie; and two Americans – Tom Eissenberg, a member of the FDA advisory panel on tobacco with a moderate record on e-cigarettes and tobacco harm reduction, and Neal Benowitz.  The latter is a surprise, as Benowitz has previously opposed tobacco harm reduction (here and here) and last year endorsed gateway speculation about smokeless tobacco (here).  It is welcome news that he has aligned his view on e-cig vapor with his position on marijuana vapor.

Drs. Benowitz and Eissenberg acknowledge research support from the National Institutes of Health and the FDA and note that the review “…does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.”

But it should.

Federal Judge to FDA: Tobacco Advisory Panel Tainted by Conflicts of Interest

“The presence of conflicted members on [FDA Tobacco Products Scientific Advisory Committee, TPSAC] irrevocably tainted its very composition and its work product” and “the Committee’s findings and recommendations…are, at a minimum, suspect, and, at worst, untrustworthy.”  So ruled federal judge Richard Leon this week (here).

A lawsuit by Lorillard et al. claimed that the FDA appointment of TPSAC members Neal Benowitz, Jack Henningfield and Jonathan Samet was “arbitrary, capricious, an abuse of discretion, and otherwise not in compliance with the law” because they had conflicts of interest.  The evidence was abundant and uncontested.  Here are excerpts from the judge’s opinion:

“Since the 1980s, Dr. Benowitz has consulted for numerous pharmaceutical companies about the design of the NRT and other smoking-cessation drugs.  He consulted for affiliates of Pfizer, Inc. and GlaxoSmithKline (GSK) as to such products, even while serving on the TPSAC…Dr. Benowitz has also served as a paid witness for lawyers suing tobacco-product manufacturers.  He testified as a paid expert witness while serving on the TPSAC, and…he was designated to testify in 585 pending tobacco cases.”

“Before and while serving on the TPSAC, Dr. Henningfield consulted for GSK and other drug companies as to NRT and other smoking-cessation drugs.  He also had ownership interest in a company that was developing a patented NRT drug.  Dr. Henningfield has testified as an expert for GSK and for lawyers suing tobacco-product manufacturers… he was designated to testify in 350 pending tobacco cases.”

“Dr. Samet received grant support from GSK at least six times, including in 2010.  He also led the Institute for Global Tobacco Control, funded by GSK and Pfizer.  Dr. Samet also testified for lawyers suing tobacco-product manufacturers…he was designated to testify in two pending tobacco cases.”

Judge Leon’s ruling notes that the composition of TPSAC is different from other FDA advisory committees, because the enabling legislation bans any expert “who received ‘any salary, grants, or other payment or support’ from any tobacco company in the 18-month period prior to serving on the TPSAC.”  

TPSAC was structured to exclude qualified authorities who have had industry support.  Experts with industry support are not precluded from serving on other FDA advisory committees, in which scientific issues are more important than industry demonization.   

Judge Leon noted that the provision should apply evenly to any conflict of interest: “If Congress deemed that past remuneration from tobacco companies constituted a conflict of interest, it stands to reason that past remuneration from direct competitors of those companies, such as manufacturers of smoking-cessation drugs, would also constitute a conflict of interest.”

Judge Leon’s ruling bars the FDA from using a 2011 TPSAC report on menthol, and it also “enjoins the FDA to reconstitute TPSAC’s membership so that it complies with the applicable ethics laws.”  Dr. Samet is the only conflicted member remaining on TPSAC, as chair (until 2016).  Another member, Claudia Barone, may have a conflict, because she received a Pfizer Educational Grant through 2013 and was appointed to the TPSAC on April 1, 2014 (here).

Although the ruling applies specifically to committee actions on menthol cigarettes and dissolvable products, it is relevant to all TPSAC activities until conflicted members are removed.

It is common for experts to be co-opted by financial support from organizations committed to a tobacco free society, a euphemism for the obliteration of the tobacco industry (an objective that is at odds with the principle of regulation).  Any individual who is funded by organizations such as the American Cancer Society, the American Heart Association, the American Lung Association, the National Cancer Institute, the Centers for Disease Control and Prevention, or the Robert Wood Johnson Foundation should be ineligible for membership on TPSAC.

(Updated July 23)