Vitamin C and Pregnant Women Who Smoke

Improving pulmonary function in newborns.

500 mg of daily vitamin C given to pregnant smoking women “decreased the effects of in-utero nicotine” and “improved measures of pulmonary function” in their newborns, according to a study  by Cindy T. McEvoy and others at the Oregon Health and Science University in Portland, published in a recent issue of the Journal of the American Medical Association (JAMA).

Researchers have long known that smoking during pregnancy can harm the respiratory health of newborns. Maternal smoking during pregnancy can interfere with normal lung development, resulting in lifelong increases in asthma risk and other pulmonary complications. The researchers note that “more than 50% of smokers who become pregnant continue to smoke, corresponding to 12% of all pregnancies.” That adds up to a lot of newborns each year who will start off with more wheezing, respiratory infections, and childhood asthma than their counterparts born to non-smoking mothers.

McEvoy and her colleagues wanted to find out whether a daily dose of vitamin C would improve the results of pulmonary function tests in newborns exposed to tobacco in utero.

It did. In an accompanying editorial, Graham L. Hall calls the randomized, double-blind, placebo-controlled clinical trial “well-conceived and executed…. Lung function during the first week of life was statistically significantly better (by approximately 10%) among infants born to mothers randomized to receive Vitamin C compared with infants born to mothers randomized to received placebo.” Moreover, the prevalence of wheezing in the first year was reduced from 40% in the placebo group to 21% in the Vitamin C group.

The decreases in asthma and wheezing in the Vitamin C newborns were documented through the first year of life. 

A 10% reduction does not sound like a lot, but, as Hall writes, “small population-level changes in lung function may lead to significant public health benefits, and the improvements in lung function reported here could be associated with future benefit.”

In their paper, the researchers conclude: “Vitamin C supplementation in pregnant smokers may be an inexpensive and simple approach (with continued smoking cessation counseling) to decrease some of the effects of smoking in pregnancy on newborn pulmonary function and ultimately infant respiratory morbidities, but further study is required.”

Pregnant women should not smoke, and quitting is by far the healthiest option.  As Hall writes: “By preventing her developing fetus and newborn infant from becoming exposed to tobacco smoke, a pregnant woman can do more for the respiratory health and overall health of her child than any amount of vitamin C may be able to accomplish.”

McEvoy C.T.,  Nakia Clay,  Keith Jackson,  Mitzi D. Go,  Patricia Spitale,  Carol Bunten,  Maria Leiva,  David Gonzales,  Julie Hollister-Smith &  Manuel Durand &  (2014). Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants, JAMA, 311 (20) 2074. DOI: http://dx.doi.org/10.1001/jama.2014.5217

Graphics Credit: http://www.quitguide.com/

Why the CDC Director Hates E-Cigarettes

The pros and cons of getting your vape on.

Last month, the Food and Drug Administration (FDA) began a new era—regulating e-cigarettes. With a non-controversial first step, the FDA banned the sale of e-cigarettes to minors, required health warnings, prohibited health claims, and outlined a plan to register and license all electronic nicotine products at some future date. The FDA’s proposed rules would also give the agency the power to regulate the currently unregulated mixture of chemicals and flavorings that are heated during e-cigarette use.  Whatever regulations the FDA promulgates for electronic cigarettes will also apply to nicotine gels, water pipe tobacco, and hookahs.

Perhaps what rankles e-cigarette activists the most is the FDA’s insistence that companies will have to provide scientific evidence before making any implied claims about risk reduction for their product, compared with cigarettes. The FDA did not restrict advertising or prohibit flavorings (bubble gum, apple-blueberry, gummi bear, and cappuccino are popular).

Within a few days after the FDA’s announcement, Chicago, New York City, and other major cities placed e-cigarettes under the same municipal smoking bans as cigarettes. 

The battle over e-cigarettes is both a public health issue and a private enterprise war for market share. Corporate giants Altria and Lorillard, which dominate the corporate tobacco landscape in the U.S., are fighting for a piece of what has become nearly a $2 billion market in a few short years. (Altria recently boosted  its growth forecast to 6-9% growth for 2014). Lorillard has been making heavy acquisitions of its own, and commands more than half the present market with its Blu brand. Altria has made its own vapor acquisitions, and is launching its own brand, MarkTen.

So far, the moves being contemplated by the FDA do not have these companies shaking in their boots. They anticipated the ban on sales to minors, a system of formal FDA approval, a disclosure of ingredients, and health warnings about the addictive nature of nicotine. And Congress gave the FDA legal authority to draft a set of rules for e-cigarettes five years ago, so the FDA’s reluctance to step in on liquid nicotine delivery systems has been evident.

In an interview with the Los Angeles Times, Tom Frieden, director of the Center for Disease Control and Prevention (CDC), listed the reasons for his opposition to electronic cigarettes:

—E-cigarettes are an additional means of hooking another generation of kids on nicotine, making them more likely to become adult smokers.

—Smokers who might have quit smoking will maintain their nicotine addiction, remaining highly vulnerable to tobacco craving.

—Ex-smokers might make themselves more vulnerable to relapse if they take up vaping.

—Smokers might forego medications that could help them quit, in favor of the unproven promise of tobacco abstention via e-cigarette.

—E-cigarettes might have the cultural effect of “re-glamorizing” smoking.

—E-cigarette users might be exposing children and pregnant women to nicotine via secondhand smoke mechanisms.

—E-cigarette users can refill cartridges with liquid cannabis products and other drugs.

Dr. Michael Siegel, a tobacco expert at the Boston University School of Public Health, worries that smaller players will be squeezed out due to costs associated with the FDA approval process, driving sales toward the traditional cigarette industry leaders. Go-go analysts have predicted market penetration of as much as 50% for e-cigarettes, but Siegel is more pessimistic, and believes the e-cigarette share could top out at 10% if FDA regulations set back efforts by vaping proponents to position their product as a safer and healthier alternative to tobacco cigarettes. And that, says Siegel, would be a shame. He told the Boston Globe: “There simply is no product on the market that’s more dangerous than tobacco cigarettes, and nobody in their right mind would argue that cigarette smoking is less hazardous or even equally hazardous to vaping.”

Frieden at the CDC is sympathetic to the fact that many smokers have indeed quit smoking tobacco with the aid of e-cigarettes. “Stick to stick, they’re almost certainly less toxic than cigarettes.” But like many tobacco experts, he sees the possibility of a new generation of nicotine addicts. Almost two million high school kids have tried e-cigarettes, Frieden told the LA Times, “and a lot of them are using them regularly…. That’s like watching someone harm hundreds of thousands of children.”  The CDC reported that the percentage of high school students who have used an e-cigarette jumped from 4.7% in 2011 to 10% in 2012. Calls to poison control centers involving children and e-cigarettes have increased sharply as well.

Frieden views the Food and Drug Administration as David under siege by Goliath. The FDA, he said, “tried to regulate e-cigarettes earlier, and they lost to the tobacco industry…. So the FDA has to balance moving quickly with moving in a way that’s going to be able to survive the tobacco industry’s highly paid legal challenge.” If E-cigarette makers really want to market to people trying to quit smoking, Frieden told the LA Times, “then do the clinical trials and apply to the FDA. But they don’t want to do that.” (See my post on Big Tobacco’s move into the e-cigarette market).

“It’s really the wild, wild West out there,” a beleaguered FDA commissioner Margaret Hamburg told the press.   “They’re coming in different sizes, shapes and flavors in terms of the nicotine in them.”

On May 4, the New York Times published a report by Matt Richtel, based on an upcoming paper in the journal Nicotine and Tobacco Research. Nicotine researchers discovered that high-end electronic cigarette systems with refillable tanks produce formaldehyde, a known carcinogen, as a component of the exhaled nicotine vapor. Moreover, unlike disposable e-cigarettes, tank systems require users to refill them with liquid nicotine, itself a potent toxin. “Nicotine is a pesticide, fundamentally,” Michael Eriksen, dean of the School of Public Health at Georgia Statue University, told CNN. “We take so many precautions about pesticides for our lawns and how to wear gloves. But what precautions do consumers take when they put the nicotine vials in?”

This was not good news for harm reductionists, who view the advantages of e-cigarettes as self-evident. The New York Times report says that the toxin is formed “when liquid nicotine and other e-cigarette ingredients are subjected to high temperatures,” according to the research. “A second study that is being prepared for submission to the same journal points to similar findings.” In addition, a new study by researchers RTI International documents the release of tiny metal particles, including tin, chromium and nickel, which may worsen asthma and bronchitis.

Eric Moskowitz at the Boston Globe  reported that “thousands of gas stations and convenience stores statewide carry e-cigarettes, usually stocking disposable or cartridge-based versions that resemble traditional cigarettes.”

In U.S. News, Gregory Conley, president of the trade group American Vaping Association, predicted “a huge influx of anti-e-cigarette legislation in the last half of 2014 and especially in 2015 when the legislative sessions get going again.” 

According to Carl Tobias, a law professor at the University of Richmond, “it may be years before  regulations are imposed. The lobbying at FDA and Congress will be intense.”

Effectively regulated, e-cigarettes have the potential to drastically reduce deaths from tobacco-related diseases among cigarette smokers. In an editorial for the journal Addiction, Sara Hitchman, Ann McNeill, and Leonie Brose of King’s College, London, wrote: “E-cigarettes may offer a way out of the smoking epidemic or a way of perpetuating it; robustly designed, implemented and accurately reported scientific evidence will be the best tool we have to help us predict and shape which of these realities transpires.”

Photo credit: http://ecigarettereviewed.com

The Escalating Debate Over E-Cigarettes

Follow the bouncing ping-pong ball.

“E-cigarettes are likely to be gateway devices for nicotine addiction among youth, opening up a whole new market for tobacco.”

—Lauren Dutra, postdoctoral fellow at the UCSF Center for Tobacco Control Research and Education.

“You’ve got two camps here: an abstinence-only camp that thinks anything related to tobacco should be outlawed, and those of us who say abstinence has failed, and that we have to take advantage of every opportunity with a reasonable prospect for harm reduction.”

—Richard Carmona, former U.S. Surgeon General, now board member of e-cigarette maker NJOY. 

“Consumers are led to believe that e-cigarettes are a safe alternative to cigarettes, despite the fact that they are addictive, and there is no regulatory oversight ensuring the safety of the ingredients in e-cigarettes.”

—From a letter to the Food and Drug Administration (FDA) signed by 40 state attorneys general.

“E-cigarettes need more time to develop and to out-compete deadly conventional cigarettes, but they have the potential to end the tobacco epidemic. So if regulators decide to ban them or submit them to stricter regulations than conventional cigarettes, this would be detrimental to public health.”

—Professor Peter Hajek, director of the Tobacco Dependence Research Unit at the Wolfson Institute of Preventive Medicine. 

“There is no scientific evidence that e-cigarettes are a safe substitute for traditional cigarettes or an effective smoking cessation tool. In fact, they may entice young people into trying traditional cigarettes.”

—Russ Sciandra, New York State Director of Advocacy, American Cancer Society.

“I firmly believe that the [New York] City Council’s bill restricting e-cigarettes is a major blow to people who are trying to stop smoking and will end up accomplishing the opposite of advocates’ intended goals of improving people’s health and reducing smoking-related deaths.”

—Tony Newman, director of media relations for the Drug Policy Alliance.

“Once a young person gets acquainted with nicotine, it’s more likely that they’ll try other tobacco products. E-cigarettes are a promising growth area for the tobacco companies, allowing them to diversify their addictive and lethal products with a so-called ‘safe cigarette.’”

—Alexander Prokhorov, head of the Tobacco Outreach Education Program, University of Texas.

“What would constitute a final victory in tobacco control? Must victory entail complete abstinence from e-cigarettes as well as tobacco? To what levels must we reduced the prevalence of smoking? What lessons should be drawn from the histories of alcohol and narcotic-drug prohibition?”

—Amy L. Fairchild, professor of sociomedical sciences, Mailman School of Public Health, Columbia University. 

Photo Credit: St. Paul Pioneer Press (Chris Polydoroff).

Built-In Advantages Give Big Tobacco an Edge in E-Cigs

The Big Three are now in it to win it. 

If there was ever any doubt that major tobacco companies have designs on the emerging electronic cigarette market, a recent roundup in the Wall Street Journal makes the case with ease, something that eager acolytes of e-cigs are anxious to avoid. No doubt about it, Big Tobacco wants in.

Results from intensive test marketing in Colorado have, like a political primary, provided an early indication of where the popularity lies. Reynolds American, the nation’s 2nd largest tobacco company (Camel), led the, uh, pack with its offering, the Vuse e-cigarette, introduced in July. Vuse racked up a 55% market share in that state. Next in line, with 25%, was Blu, owned by the 3rd largest cigarette maker, Lorillard (Newport). NJOY, an independent company, came in third.  The elephant in the room, Altria Group, the largest U.S. tobacco firm (Marlboro), is still in the test marketing stage with its e-cigarette entry, the MarkTen. Altria began testing the MarkTen in Indiana and Arizona in late summer.

It took Reynolds less than 16 weeks to achieve market dominance in Colorado, and the company made sure that investors heard about it. With 1,800 retail outlets in Colorado, and a database of 12 million tobacco consumers, Reynolds is perfectly poised to benefit from the inherent advantages of being Big Tobacco. The Big Three have three major head starts, the Wall Street Journal reported: “extensive distribution networks, existing customer relationships numbering in the millions, and deep pockets.”

The market for electronic cigarettes has broken a billion dollars, say stock watchers. This magic number seems to have energized the Big Three to take a heavy step into a market that has been around in nascent form since 2006, even though it’s still small change compared to the $100 billion U.S. tobacco market. It was not clear, in the beginning, whether Reynolds, Lorillard, and Altria would attempt to, pardon me, snuff out the competition, or dominate it. That decision now appears to have been made, and the game is on.

Stephanie Cordisco, president of R.J. Reynolds Vapor Company, which markets Vuse, said the marketing tagline in Colorado was: “A perfect puff. First time, every time.” 

So far, e-cigarettes, which heat nicotine-based liquid to create a vaporized mist, have benefitted from the fact that they are not, at present, savagely taxed like regular cigarettes. And e-cigs come in flavors, cherry and pina colada being among the favorites.

In April of 2012, Lorillard broke the e-cig barrier when it acquired Blu Ecigs for $135 million. At the Wall Street Journal, Mike Esterl suggested that the move came “as the Food and Drug Administration weighs a possible crackdown on menthol-flavored cigarettes, which represent about 90% of revenue at Greensboro, N.C.-based Lorillard, owner of the popular Newport brand. The FDA already has banned all other cigarette flavors.”

Reynolds followed Lorillard into the market early in 2013 with Vuse. And the giant Altria Group announced in October that it planned to expand sales of the MarkTen after successful “lead market” sales. It’s too early too say how it will go for the MarkTen, but Altria CEO Marty Barrington said in a conference call reported by the Richmond Times-Dispatch that the company is not overly worried about cannibalizing Marlboro sales: “I can tell you that with respect to who is trying the products in e-vapor generally,” he said, “ we do know that there is dual use. As adult smokers try e-vapor products, we know that some of them are satisfied and others are not. Some of them use [e-cigarettes] situationally.”

That does not sound like an executive rolling out a stop-smoking therapy tool.

Graphics Credit: http://seekingalpha.com

Smoking and Surgery Don’t Mix

Even routine operations are riskier for smokers.

Smokers who are scheduling a medical operation might want to think seriously about quitting, once they hear the results of a new review of the impact of smoking on surgical outcomes.

A scheduled operation is the perfect incentive for smokers to quit smoking. The fact that smokers have poorer post-surgical outcomes, with longer healing times and more complications, is not a new finding. But the study by researchers from the University of California in San Francisco, and Yale University School of Medicine, published in the Journal of Neurosurgery, spells out the surgicial risks for smokers in graphic detail.

Cellular Injury

The systematic effects of nicotine and carbon monoxide in the blood of cigarette smokers result in tissue hypoxia, which is a lack of adequate blood supply caused by a shortage of oxygen.  When carbon monoxide floods the bloodstream in high concentrations, as it does in smokers, it is capable of binding with hemoglobin and thus lowering the oxygen-carrying capacity of the blood. A cascade of physiological reactions then lead to the possibility of low coagulation levels, vasoconstriction, spasms, and blood clots. 

Wound Healing and Infection

If the circulatory system is dysfunctional, healing will be impaired. “In addition,” the researchers say, “tobacco may stimulate a stress response mediated by enhanced fibroblast activity, resulting in decreased cell migration and increased cell adhesion. The net consequence is inappropriate connective tissue deposition at the surgical site, delayed wound healing, and increased risks of wound infection.”

Blood Loss

 In their review of the neurosurgical literature, the researchers found higher blood loss for smokers particularly following surgery for certain kinds of tumors and for lumbar spine injuries. Smoking causes “permanent structural changes of vessels such as vessel wall thickening,” and there is evidence that smoking is linked to “larger and more vascularized tumors, which may further contribute to intraoperative blood loss during resection.”

Cardiopulmonary Effects

Even smokers who don’t have any chronic conditions associated with smoking are at increased risk during and after surgery. Oxidative damage from smoke can cause “mucosal damage, goblet cell hyperplasia, ciliary dysfunction, and impaired bronchial function,” all of which impedes the ability to expel mucus, which increases the bacterial load, which alters the respiratory immune response, and which ultimately leads to higher rates of postoperative pneumonia in smokers.

The authors of the review note that the evidence is particularly strong in certain specialties: Cranial surgery, spine surgery, plastic surgery, and orthopedic surgery. One randomized clinical trial showed that a 4-week smoking cessation program lead to a 50 relative risk reduction for postoperative complications. Another study showed significant improvement in wound healing when patients abstained from smoking for 6 to 8 weeks prior to surgery. And a third trial of smokers cited in the study showed a major decrease in complications following surgery for the repair of acute bone fractures in patients who quit before surgery.

The authors close by suggesting that the seriousness of surgery can be used to create a “teachable moment” for patients who smoke. Other studies show consistently that “patients tend to be more likely to quit smoking after hospitalization for serious illness.” All of this makes the act of scheduling surgery a perfect point of contact with smokers in medical settings. Clinicians can neutrally lay out the facts of the matter, in a way that truly brings home the health consequences of tobacco.

Lau D., Berger M.S., Khullar D. & Maa J. (2013). The impact of smoking on neurosurgical outcomes, Journal of Neurosurgery,   1-8. DOI: 10.3171/2013.5.JNS122287

Graphics Credit:  http://www.ontarioanesthesiologists.ca/

A Weak Smoker’s Vaccine Might Be Worse Than None

New PET scans show wide responses to antibodies.

One of the brightest hopes of addiction science has been the idea of a vaccine—an antibody that would scavenge for drug molecules, bind to them, and make it impossible for them to cross the blood-brain barrier and go to work. But there are dozens of good reasons why this seemingly straightforward approach to medical treatment of addiction is devilishly difficult to perform in practice.

Last January, health care company Novartis threw in the towel on NicVax, a nicotine vaccine that failed to beat placebos in Phase III clinical trials for the FDA. And back in 2010, a report in the Archives of General Psychiatry demonstrated that a vaccine intended for cocaine addicts only generated sufficient antibodies to dull the effects of the cocaine in 38 percent of the test subjects. Moreover, it proved possible to overcome immunization by upping the cocaine dose, which sounded like an invitation to overdose.

And now, neuroscientists at the Society of Nuclear Medicine and Molecular Imaging annual meeting have presented a new study, the conclusions of which might help researchers understand why the vaccine results have been so mixed. The research “represents one of the first human studies of its kind using molecular imaging to test an investigational anti-nicotine immunization,” lead author Alexey Mukhin, professor of psychiatry and behavioral science at Duke University Medical Center, said in a prepared statement.


Subjects underwent two PET brain scan as they smoked nicotine labeled with radioactive C-11, one before the vaccine was administered, and one after. Ten subjects who developed “high-affinity antibodies” after vaccination showed a slight decrease in nicotine accumulation in the brain, as judged by the scans. However, another group of ten subjects, who showed “intermediate serum nicotine binding capacity and low affinity of antibodies” actually showed an increase in brain nicotine levels. What the PET scans showed was that “strong nicotine-antibody binding, which means high affinity, was associated with a decrease in brain nicotine accumulation. When binding was not strong, an increase in brain accumulation was observed.”

If the bond that holds the antibodies to the nicotine molecules is weak, the bond can break during passage through the blood-brain barrier, potentially allowing excess nicotine to flood in. This result, said Mukhin, tell us “we should care about not only the amount of antibody, but the quality of the antibody. We don’t want to have low-affinity antibodies because that can negate the anti-nicotine effects of the vaccination.”

Back to the drawing board? Not entirely. Another of the study authors, Yantao Zuo of Duke University Medical Center, said that “with reports of new generations of the vaccines showing potentially much higher potencies in animal studies, we are hopeful that our current findings and methodology in human research will facilitate understanding of how these work in smokers.”

Photo Credit:http://www.medgadget.com

Big Tobacco Hasn't Given Up On Smoking. Have You?

World No Smoking Day.

Six Arguments For the Elimination of Cigarettes

Prohibition and the “tobacco control endgame.”

Despite all our efforts in recent years to reduce the percentage of Americans who smoke cigarettes—currently about one in five—the idea of full-blown cigarette prohibition has not gained much traction. That may be changing, as prominent nicotine researchers and public police officials start thinking about what is widely referred to as the “tobacco control endgame.”

Considering the new regulatory powers given the FDA under the terms of the Tobacco Control Act of 2009, as a commentary in Tobacco Control framed it, “will the government be a facilitator or barrier to the effective implementation of strategies designed to achieve this public health goal?”
Two newer approaches have gained some traction in the research community: Reduce the level of nicotine in cigarette products (the FDA is prohibited by law from reducing nicotine content to zero), and continuing to emphasize the non-combustible forms. Plus, everybody pretty much agrees on higher prices.

Here are the six arguments for going all the way:

1) Death. Six million of them a year, worldwide, a number that will grow before it starts shrinking. A billion deaths this century, compared to 100 million in the 20th Century. Robert Proctor, author of The Golden Holocaust and a professor of history at Stanford, whose six arguments these are, calls the cigarette “the deadliest object in the history of human civilization.” So there’s that.

2) Other product defects. The cigarette is defective, Proctor writes in defense of his six arguments in Tobacco Control, because it is “not just dangerous but unreasonably dangerous, killing half its long-term users.” Indeed, it is hard to imagine the FDA green-lighting a drug product like that today. In addition, Proctor claims cigarettes are defective because the tobacco has been altered by flue curing to make it far more inhalable than would otherwise be the case. “The world’s present epidemic of lung cancer is almost entirely due to the use of low pH flue-cured tobacco in cigarettes, an industry-wide practice that could be reversed at any time.”

3) Financial burdens. These can be reckoned principally in terms of the costs of treating smoking-related illnesses. This, in turn, leads to diminished labor productivity, especially in the developing world, a process that “in many parts of the world makes the poor even poorer,” Proctor observes.

4) Big Tobacco’s impact on science. By sponsoring shoddy and distracting research, by publishing “decoy” findings and by otherwise confusing and corrupting scientific discourse on the cigarette question in the advertising-dependent popular media. The tobacco industry has proved to everyone’s satisfaction that it can put politicians and regulators under intense pressure to see things its way. Not to mention other institutions that have been “bullied, corrupted or exploited,” according to Proctor: The AMA, The American Law Institute, sports organizations, Hollywood, the military, and the U.S. Congress, for starters. (Until 2011, American submarines were not smoke-free.)

5) Environmental harms. More than you might think falls into this category: Deforestation, pesticide use, loss of savannah woodlands for charcoal used in flue curing, fossil fuels for curing and transport, fires caused by burning cigarettes, etc.

6) Smokers want to quit. Smoking is not a recreational drug, as Proctor takes pains to point out. Most smokers hate it and wish they could quit. This makes cigarettes different from alcohol or marijuana, Proctor insists. He quotes a Canadian tobacco executive, who said that smoking isn’t like drinking; it’s more like being an alcoholic. This rings true to for the majority of addicted smokers I know, and was certainly true of me when I was a smoker.


So there it is, the case for tobacco prohibition. But hasn’t all this prohibition business been tried and found wanting? We know the results of drug and alcohol prohibition, whatever their rationales: Smuggling, organized crime, increased law enforcement, more money. This argument, says Proctor, has been central to the cigarette industry since forever: “Bans are ridiculed as impractical or tyrannical. (First they come for your cigarettes…)”

Proctor’s response is that smuggling is already common, and people should be free to grow tobacco for their personal use. He advocates a ban on sales, not possession.

There are at least two major obstacles to cigarette prohibition. First, an enormous amount of tax revenue is generated by the production and sale of cigarettes. And the troubling question of a steep rise in black marketeering goes largely ignored or unaddressed. In the same special issue of Tobacco Control, Peter Reuter has sobering thoughts on that front: “Cigarette black markets are commonplace in high tax jurisdictions. For example, estimates are that contraband cigarettes now account for 20-30% of the Canadian market, which has restrained government enthusiasm for raising taxes further. All the proposed ‘endgame’ proposals for shrinking cigarette prevalence toward zero run the risk of creating black markets.”

In the end, Proctor argues that the cigarette industry itself has repeatedly promised to quit the business if its products where ever found to be profoundly harmful to consumers. As recently as 1997, Philip Morris CEO Geoffrey Bible swore under oath that if cigarettes were found to cause cancer “I’d probably… shut it down instantly to get a better hold on things.” Incredible statements like this by company executives go back to the 1950s. Perhaps it’s time to let them stop lying. “The cigarette, as presently constituted,” writes Proctor, “is simply too dangerous—and destructive and unloved—to be sold.”

Proctor R.N. (2013). Why ban the sale of cigarettes? The case for abolition, Tobacco Control, 22 (Supplement 1) i27-i30. DOI: 10.1136/tobaccocontrol-2012-050811

Photo: AAP/April Fonti

Smokers’ Genes: Evidence From a 4-Decade Study

How adolescent risk becomes adult addiction.

 Pediatricians have often remarked upon it: Give one adolescent his first cigarette, and he will cough and choke and swear never to try another one. Give a cigarette to a different young person, and she is off to the races, becoming a heavily dependent smoker, often for the rest of her life. We have strong evidence that this difference in reaction to nicotine is, at least in part, a genetic phenomenon.

But so what? Is there any practical use to which such knowledge can be put? As it turns out, the answer may be yes. People with the appropriate gene variations on chromosomes 15 and 19 move very quickly from the first cigarette to heavy use of 20 or more cigarettes per day, and have more difficulty quitting, according to a new report published in JAMA Psychiatry. From a public health point of view, these findings add a strong genetic rationale to early smoking prevention efforts— especially programs that attempt to “disrupt the developmental progression of smoking behavior” by means of higher prices and aggressive enforcement of age restrictions on smoking.

What the researchers found were small but identifiable differences that separated people with these genetic variations from other smokers. The gene clusters in question “provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure,” according to authors Daniel W. Belsky, Avshalom Caspi, and colleagues at the University of North Carolina and Duke University.

The group looked at three prominent genome-wide association studies of adult smoking to see if the results could be applied to “the developmental progression of smoking behavior.” They used the data from the genome work to analyze the results of a 38-year prospective study of 1,037 New Zealanders, known as the Dunedin Study. A total of 405 cohort members in this study ended up as daily smokers, and only 20% of the daily smokers ever achieved cessation, defined as a year or more of continual abstinence.

The researchers came up with a multilocus genetic risk score (GRS) based on single-nucleotide polymorphisms associated with smoking behaviors. Previous meta-analyses had identified several suspects, specifically a region of chromosome 15 containing the CHRNA5-CHRNA3-CHRNB4 gene cluster, and a region of chromosome 19 containing the gene CYP2A6. These two clusters were already strong candidate genes for the development of smoking behaviors. For purpose of the study, the GRS was calculated by adding up the alleles associated with higher smoking quantity. The genetic risk score did not pertain to smoking initiation, but rather to the number of cigarette smoked per day.

When the researchers applied these genetic findings to the Dunedin population cohort, representing ages 11 to 38, they found that an unfortunate combination of gene types seemed to be pushing some smokers toward heavy smoking at an early age. Individuals with a high GRS score “progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting,” according to the study. However, these effects took hold only when young smokers “progressed rapidly from smoking initiation to heavy smoking during adolescence.” The variations found on chromosomes 15 and 19 influence adult smoking “through a pathway mediated by adolescent progression from smoking initiation to heavy smoking.”

Curiously, the group of people who had the lowest Genetic Risk Scores were not people who had never smoked, but rather people who smoked casually and occasionally—the legendary “chippers,” who can take or leave cigarettes, sometimes have one late at night, or a couple at parties, without ever falling victim to nicotine addiction. These “light but persistent smokers” were accounted for “with the theory that the genetic risks captured in our score influence response to nicotine, not the propensity to initiate smoking.”

Naturally, the study has limitations. Everyone in the Dunedin Study was of European descent, and the life histories ended at age 38. Nor did the study take smoking bans or different ages into account. The study cries out for replication, and hopefully that won’t be long in coming.

Could information of this sort be used to identify high-risk young people for targeted prevention programs? That is the implied promise of such research, but no, probably not. The gene associations are not so dramatic as to cause youngsters with the “bad” alleles to inevitably become chain smokers, nor do the right set of genes confer protection against smoking. It’s not that simple. However, the study is definitely one more reason to push aggressive smoking prevention efforts aimed at adolescents.


Belsky D.W.  Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine DependenceEvidence From a 4-Decade Longitudinal StudyDevelopmental Progression of Smoking Behavior, JAMA Psychiatry,   1. DOI: 10.1001/jamapsychiatry.2013.736

Graphics Credit: http://cigarettezoom.com/

Big Tobacco Easily Evades “Light” Cigarette Ban

Color coding allows smokers to easily identify their former brands.

The tobacco industry has once again made a mockery of the Food and Drug Administration’s attempts to ban ‘light” cigarettes from the marketplace, by simply eliminated the objectionable wording and substituting an easily-decoded color scheme. In a brochure prepared for cigarette retailers marked “For trade use only: not to be shown or distributed to customers,” tobacco giant Philip Morris wrote that “some cigarettes and smokeless packaging is changing, but the product remains the same.”

Research done at Harvard demonstrates "the continued attempts of the industry to avoid reasonable regulation of tobacco products,” said Hillel Alpert, co-author of a new study on light cigarettes, in a prepared statement. The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 highlights the banning of light cigarettes as a critical mission, since cigarettes marketed in this way are in fact no safer than regular cigarettes. What makes a cigarette Light or Ultra-light is a series of tiny holes drilled through the filter (See earlier post). This “filter ventilation” was calibrated to the descriptors: Ultra-lights had more holes drilled in the filter than Lights. Studies have demonstrated conclusively that such filter schemes do not make smoking safer or cut down on related diseases. A 2001 report from the National Cancer Institute documented how smokers were compensating for the ventilation holes by smoking more cigarettes, smoking them more intensely, or by blocking the filter holes with fingers or lips.

In a study for Tobacco Control, Gregory Connolly and Hillel Alpert of the Harvard School of Public Health documented the process. In 2010, Philip Morris sent manuals to retailers detailing how they were to deal with the new sales situation. Philip Morris made clear that “current pack descriptors such as light, ultra-light and mild will be removed from all packages.” All well and good. However, the Philip Morris material also specified how a series of new package names were to be doled out. Marlboro Light became Marlboro Gold. Marlboro Mild morphed into Marlboro Blue. And Marlboro Ultra-light reemerged as Marlboro Silver.

When the researchers commissioned a large public survey to document the state of affairs one year after the official “light” ban, they found that “88%-91% of smokers found it either ‘somewhat easy’ or ‘very easy’ to identify their usual brand of cigarettes by the banned descriptor names, Lights, Mediums or Ultra-Lights.” Sales figures for these brands in the first two quarters of 2010 were essentially unchanged, the authors report. They conclude that “the majority of smokers of brands in all categories correctly identified their brands’ pack color.”

The lesson here may well be that countries like Australia and the UK are on the right track: Plain packaging may be best. If lawmakers allow “misleading numbers, the use of colors, imagery, brand extensions, and other devices that contribute to deception” in place of words, nothing has really changed. “The findings of the present research strongly suggest that tobacco manufacturers have evaded one of the most important provisions of the FSPTCA for protecting the public health from the leading cause of preventable death and disease,” the authors conclude.

In a press release, co-author Gregory Connolly, director of the Center for Global Tobacco Control at Harvard, explained that the industry “was found guilty by a federal court in 2006 for deceptively promoting ‘light’ cigarettes as safer after countless smokers who switched to lights died prematurely, thinking they had reduced their health risks.”

Connolly G.N. & Alpert H.R. (2013). Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?, Tobacco Control, PMID: 23485704

Photo Credit:http://www.mydiscountcigarette.net

Novartis Gives Up On Nicotine Vaccine

Another one bites the dust.

Novartis, a leading health care products company, called it quits on its NIC002 nicotine vaccine project, which failed badly three years ago in Phase II studies undertaken with an eye toward government approval. Novartis said it would terminate the license it has for the NIC002 vaccine with Cytos Biotechnology, for which it paid $38 million in 2007. The Phase II study “showed formation of nicotine-specific antibodies in patients but did not meet its primary endpoint of increased smoking cessation,” according to Genetic Engineering and Biotechnology News

Much the same arc was followed by Nabi Biopharmaceuticals, which announced in 2011 that its vaccine, NicVax, had failed to outdo placebos in Phase III clinical trials—the only addiction vaccine to advance that far in the approval process. The company’s own studies had shown happier results in 2007. In regulatory filings, the company claimed that the NicVax vaccine triggered a reliable antibody response, thus preventing nicotine molecules from reaching the brain. The antibodies bind with the nicotine molecules, making nicotine too large to cross the exceedingly fine blood-brain barrier of the brain. Roughly 15 per cent of smokers who received injections of NicVax were nicotine-free after one year in company-funded studies. For comparison, early studies of Chantix as an anti-smoking medication show a quit response rate in the range of 20 per cent for heavy smokers.

As I have previously written, the idea of vaccinating for addictions is not new. If you want the body to recognize a nicotine molecule as a foe rather than a friend, one strategy is to attach nicotine molecules to a foreign body--commonly a protein that the body ordinarily rejects--in order to switch on the body’s immune responses against the invader. A strong advantage to this approach, say researchers, is that the vaccinated compound does not enter the brain and therefore is free of neurological side effects.

There remain a wealth of questions related to the effects of long-lasting antibodies. And it is sometimes possible to “swamp” the vaccine by ingesting four or five times as much cocaine or nicotine as usual.

Drugs that substantially reduce a smoker’s craving for nicotine, like Chantix, may yet prove to be a more fruitful avenue of investigation. While several anti-craving medications have been approved for use by the Food and Drug Administration (FDA), no vaccines have made it onto the approved list. However, as the Genetic Engineering article reminds us, “all is not lost for the vaccine yet: in November of 2010, Duke University, in collaboration with Wake Forest University, commenced a Phase II clinical study with NIC002 performed with 65 smokers that aims to assess how nicotine antibodies, induced by vaccination, affect the pharmacokinetics of nicotine during cigarette smoking. The study is being conducted in the United States with funding from the NIH.”

Photo: Creative Commons / juliealicea1947

Big Tobacco Makes a Move Into E-Cigarettes

“A battery-operated, addiction-based market.”

While the FDA dithered, and health advocates argued, Big Tobacco began placing its bets on the e-cigarette market last year. Tobacco firm Lorillard Inc., the third largest tobacco company in America, bought privately held Blue Ecigs of Charlotte, N.C., for $135 million, driven by what the company says is a market that’s been doubling ever year since e-cigs first arrived from China in 2008.

According to the Wall Street Journal, Blue Ecigs had $30 million in revenues last year, selling through retail outlets like Walgreens, where it competes with e-brands such as NJOY and 21s Century. The FDA has announced vague plans to regulate, and state lawmakers have threatened to ban them outright, or at least place them under the same public smoking bans as cigarettes—bans that some e-smokers love to flout. (E-cigarette manufacturers, based primarily in Asia, quickly changed the electric orange glow at the end of the e-cigarette to a cool shade of blue, to help make clear to bartenders and bouncers that the thing wasn’t a lit cigarette.)

Meanwhile, Reynolds, an industry leader in smokeless products, is developing its own line of e-cigs, and is test-marketing its Vuse and Zonnic brands. “We will be in this category in 2013,” an RJ Reynolds representative said in a CNBC article by Jane Wells. “We have very big plans.”

Altria, the industry giant, is now generating $1.6 billion from smokeless tobacco products, and is expected to make a move into what is viewed as a billion-dollar industry with unlimited growth potential. Last year, the company began testing a new “nicotine-extract product” called Verve, a lozenge that can be sucked or chewed and contains about 1.5 milligrams of nicotine. Late last year, the company reportedly engaged in acquisition talks with e-cig maker Eonsmoke.

Meanwhile, the company that invented the electronic cigarette, Dragonite/Ruyan, is suing practically everybody. And the Argentinean and Venezuelan governments have attempted to ban the use and marketing of electronic cigarettes altogether.

In December, astute American TV viewers may have noticed what looked for all the world like a television commercial for cigarettes—the first since 1971, when Congress banned cigarette ads on TV. It was a commercial for NJOY Kings electronic cigarettes, a brand that currently owns about one-third of the U.S. e-cig market. Patent lawyer Mark Weiss, who founded NJOY, told Time that the company was only competing for the 45 million Americans who are current smokers, not attempting to make new recruits. In the article, Weiss noted three advantages for e-cigarettes: They’re odor free, they don’t burn tobacco, and, at about $8 per e-cigarette, Weiss claims, they’ll last you as long as two regular packs of cigarettes.

When major tobacco companies make moves like this, people notice. “I think they see this as an opportunity to get a seat at the table with opportunities to talk to the FDA about regulation over this growing category,” according to Bonnie Herzog, senior analyst and managing director of tobacco, beverage and consumer research for Wells Fargo Securities. “Lorillard wants to help steer that conversation in the right direction.”

While still a relatively modest market—no more than $500 million, compared to the $100 billion tobacco market in the U.S.—electronic cigarettes have the potential of becoming the most contentious entry in the market for nicotine delivery systems since the advent of the machine-rolled cigarette. “We think e-cigs are to tobacco what energy drinks are to beverages,” Herzog told the media.

Lorillard chairman and CEO Murray Kessler said in an earnings conference call late last year that with e-cigarettes, “you get all of the benefits of not having combustion, but on the other hand you are maintaining the behavior that cigarette smokers enjoyed.” That’s one way of putting it. And according to critics, that’s part of the problem. Anti-smoking activists often view e-cigarettes as gateway products for young adults.

They are cheaper, primarily because of heavy taxes on traditional cigarettes, and produce no second-hand smoke, only steam-like vapor that quickly dissipates. But they have had a rocky start in the U.S. An article in the Winston-Salem Journal in prime tobacco country stated that consumers have “shied away out of safety concerns since most e-cigs are made in China.” Even North Carolina health officials have expressed concerns about “limited regulatory oversight of their contents.” But according to Wells Fargo’s Herzog, Lorillard’s purchase of Blu Ecigs had the effect of “lending credibility and legitimacy to the entire category.”

Brad Rodu, professor of medicine at the University of Louisville, insisted that “tobacco manufacturers have an obligation to smokers to develop, manufacture and sell these vastly safer cigarette substitutes.” In this view, smokers smoke for the nicotine, but it’s the tar that kills them. 

In the same Winston-Salem Journal article, a professor of family and community medicine at Wake Forest School of Medicine said that “many of the carcinogens in tobacco are volatile and would vaporize, and thus be inhaled when heated. I would not recommend that product.”

It seems safe to predict that this “battery-operated, addiction-based market,” as Forbes dubbed it, will be one to watch.

Image by 55Laney69/hansel5569 via Flickr, under Creative Commons License

Have We Killed Half of our Soldiers with Cigarettes?

Two long-term studies yield grim stats, and women are no exception.

We know that smoking kills. But until the results of 50 years’ worth of observations on British male smokers was published by Richard Doll and coworkers in the British Journal of Medicine in 2004, we didn’t know how many.  Cigarettes will kill at least half of those who smoke them past the age of 30—possibly more. In older, specific populations, possibly as many as 2/3.

It took a prospective study of more than 34,000 British doctors, starting in 1951 and ending in 2001, to establish the grim parameters with some degree of precision. As the study authors of the 2004 summary paper put it: “A substantial progressive decrease in the mortality rates among non-smokers over the past half century… has been wholly outweighed, among cigarette smokers, by a progressive increase in the smoker v non-smoker death rate ratio due to earlier and more intensive use of cigarettes.” In other words, the great reduction in disease mortality rates achieved in the 20th Century, courtesy of better prevention and treatment, effectively never happened for long-term male smokers. Smoking in Britain and America took off in a major way between the two world wars, and sufficient time has now passed to conclude that “men born in 1900-1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers.”

As for women, it took a few decades longer to nail down the truth, because women did not begin smoking in peak numbers until the 1960s. While men born between 1900 and 1930 took to cigarettes in a big way, women born around 1940 were the first cohort of female smokers to consume a substantial number of cigarettes throughout their adult lives. This 20-year lag is crucial, because it means that solid numbers for female mortality rates require solid figures on mortality rates in the 21st Century. And now we have them, courtesy of the Million Women Study in the UK. The results were recently published in The Lancet by Kirstin Pirie and others. They are just as bad as you might have guessed, putting women on a firm equal footing with their male counterparts when it comes to smoking deaths.

The Million Women Study, a database originally used for the UK’s National Health Service Breast Screening Program, recruited female volunteers between the ages of 50 and 69. The figures were eerily similar to those from the earlier study of male British doctors: “If combined with 2010 UK national death rates, tripled mortality rates among [female] smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference…. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater.” In this study, the researchers found little difference between female smokers and nonsmokers when it came to confounding variables like weight, blood pressure, or lipid profile. A four-year head start—beginning to smoke at the age of 15 rather than 19, say—can put women at a measurably greater risk for lung cancer deaths.  And a little goes a long way: “Even those smoking fewer than ten cigarettes per day at baseline had double the overall mortality rate of never-smokers.” Low-tar won’t save them, either. “Low-tar cigarettes are not low-risk cigarettes,” the investigators write, “and the Million Women Study shows that more than half of those who smoke them will eventually be killed by them, unless they stop smoking in time to avoid this.”

There it is again: Half of all smokers are going to die from smoking.  As the authors of the Lancet study wrote: “If women smoke like men, they die like men.”

In summary, those who stop smoking at age 50 gain about six years of life expectancy. Quit at 40, and you get an extra nine years. A non-smoker’s chances of living from 70 to 90 are three times higher than a smoker’s. The researchers found that the doctors who stopped smoking by age 30 managed to avoid almost all of the lifespan penalties associated with smoking—primarily lung cancer, COPD, and heart disease. (Only about 3% of smoking deaths are due to fires, accidents, poisonings, etc.). And even lifelong smokers who do not quit until the age of 60 are still rewarded with an extra three years of life span, on average.

Perhaps the saddest thing about the findings is the ways in which they suggest that British and American military commanders may have been sentencing countless numbers of soldiers to death for decades, through the simple act of giving away cigarettes in K-rations, and selling them cheaply in other circumstances. As the report in the British Medical Journal states, “widespread military conscription of 18 year old men, which began again in 1939 and continued for decades, routinely involved provision of low cost cigarettes to the conscripts. This established in many 18 year olds a persistent habit of smoking substantial numbers of manufactured cigarettes, which could well cause the death of more than half of those who continued.” In a perverse reminder of the Agent Orange scandal in Vietnam, American and British military command may have exposed their soldiers to a much greater threat, for a much longer period, with worse odds for survival.

One obvious confounding variable in such studies is alcohol. It requires a sensitive statistical analysis to work through correlations between drinking, smoking, and, say, liver disease.  But “the large majority of the excess overall mortality among smokers is actually caused by smoking,” the Lancet researchers maintain with confidence.  The overall point seems clear: These long-term results show that the risks from continual cigarette smoking are even greater than we thought.

The dismal bottom line of the two smoking studies is that we appear to be right on schedule for meeting the UN’s prediction of one billion tobacco deaths in this brave new century.

Pirie, K., Peto, R., Reeves, G., Green, J., & Beral, V. (2012). The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK The Lancet DOI: 10.1016/S0140-6736(12)61720-6

Photo Credit: Ianier67 via Creative Commons.

States Quietly Defunding Anti-Smoking Programs For Kids

Only 2 cents of each tobacco settlement dollar goes to smoking prevention plans.

If there’s one thing we know about smoking, it’s that for every smoker who quits, we gain a net financial benefit. These health cost savings can be huge for states, which is why all of them have put in place smoking cessation plans and programs for their citizens. And they are able to run this programs because of the monies that come to them under the 1998 master tobacco settlement.

Perhaps it doesn’t come as a huge surprise, but it’s depressing, all the same: The Campaign for Tobacco-Free Kids estimates that states will spend less than 2 per cent of these court-mandated funds on actual programs to prevent kids from smoking. The report accuses the states of failing to reverse budget cuts to “programs that have set back the nation’s efforts to reduce tobacco use.”

The report was undertaken to access whether states have been using the estimated $246 billion over 25 years—plus cigarette taxes—to reduce tobacco use. What they found was that “states have failed to reverse deep budget cuts that reduced funding for tobacco prevention by 36 percent” from 2008 to 2012. Only North Dakota and Alaska are currently funding smoking cessation programs at the level recommended by the Centers for Disease Control and Prevention (CDC). Four states—New Hampshire, New Jersey, North Carolina, and Ohio—have allocated ZERO funds for tobacco prevention programs in FY 2013.

“Given such a strong return on investment,” the report concludes, “states are truly penny-wise and pound-foolish in shortchanging tobacco prevention and cessation programs.” The report declined to speculate on where the money actually goes, but noted that this was the “second lowest amount states have spent on tobacco prevention programs since 1999, when they first received tobacco settlement funds.”

The cries of outrage came thick and fast:

“The states have an obligation to use more of their billions in tobacco revenues to fight the tobacco problem. Their failure to do so makes no sense given the evidence that tobacco prevention programs save lives and save money by helping reduce health care costs."—Matthew L. Myers, President of the Campaign for Tobacco-Free Kids

"States with comprehensive tobacco control programs experience faster declines in cigarette sales, smoking prevalence and lung cancer incidence and mortality than states that do not invest in these programs."—John R. Seffrin, CEO of the American Cancer Society Cancer Action Network

"The paltry amount of money that states spend on tobacco prevention and cessation programs is extremely disappointing…. These programs work and it’s time for states to put more skin in the game."—Nancy Brown, CEO of the American Heart Association

"Too many states are failing their citizens by abandoning their responsibility to invest in proven programs that prevent people from smoking and help smokers quit…. Supporting these programs at recommended levels is not only the right thing to do, it's the smart thing to do — quitting smoking or never starting saves lives and saves money."—Paul G. Billings, senior vice president of Advocacy & Education at the American Lung Association

In 2007, the CDC concluded: “We know how to end the epidemic. Evidence-based, statewide tobacco control programs that are comprehensive, sustained, and accountable have been shown to reduce smoking rates, tobacco-related deaths, and diseases caused by smoking.”

Two cents on every dollar. About 20 percent of Americans smoke. “Tobacco companies spend more than $18 to market tobacco products for every one dollar the states spend to reduce tobacco use.” What’s wrong with this picture?

Photo Credit: http://www.tobaccofreekids.org

Cigarettes: Should the FDA Mandate a National Taper?

Addiction expert calls for reduced-nicotine tobacco.

For years now, nicotine researcher Neal Benowitz has been a man on a mission. Dr. Benowitz, a professor of medicine at the University of California in San Francisco, has been pushing a Big Idea about how to eliminate cigarette smoking in America: Reduce the amount of nicotine in cigarettes.

In essence, Benowitz is calling for a national nicotine taper. Whether the FDA is interested remains an open question. But the result, several years down the road, would be a nation of teenagers confronted with only weakly addictive tobacco products.

It is an old idea, often viewed with great suspicion because of the failure of “light” and “low-tar” cigarettes to reduce nicotine intake, and in fact causing smokers to smoke harder. But Benowitz, one of the nation’s premier tobacco scientists, believes that when it comes to the roughly one out of five Americans who still smoke, a new generation of so-called “low-nicotine delivery” cigarettes is the answer. 

In a controlled study of 135 smokers of various ages, participants smoked cigarettes with progressively lower nicotine over a two-year period, and did so “without evidence of compensation”—meaning that they did not smoke more cigarettes or smoke differently when using the low-nicotine offerings. This varies dramatically from the behavior associated with light cigarettes and special filters—innovations that were marketed as “safer” cigarettes—that simply increase ventilation. The light cigarettes themselves contain the same amount of nicotine as a “regular” cigarette. And smokers quickly learn to puff harder, or cover small holes in the filter paper with their fingers, in order to extract more nicotine from each cigarette.

But with low-nicotine delivery cigarettes, you can’t get more nicotine, no matter what kind of smoker’s gyrations you perform. And the result, according to a paper by Benowitz and coworkers in Cancer, Epidemiology, Biomarkers and Prevention, is that “when the nicotine content of cigarettes is progressively decreased at monthly intervals over 6 months there is a progressive decline in nicotine intake by smokers, with only a small degree of compensation at the lowest nicotine content levels.”

The two-year study was randomized but unblinded, in order to simulate situations in which smokers are fully aware of using cigarettes with progressively less nicotine. A control group smoked their usual brands of cigarettes throughout the study. Benowitz, who led the studied, said in prepared remarks that the U.S. Food and Drug Administration (FDA) now has the authority to regulate the nicotine content of cigarettes sold in the U.S. (Benowitz is a member of the FDA’s Tobacco Products Scientific Advisory Committee.) “The idea is to reduce people’s nicotine intake, so that they get used to the lower levels, and eventually get to the point where smoking is no longer satisfying.”

The study was small, and there were dropouts. As always, further long-term study will be needed to track smokers during this kind of long-term nicotine taper. Traditionally, tapering has not been an effective method of breaking a nicotine addiction. But the reason for that may have to do with the easy availability of full-strength cigarettes in every store and gas station. The obvious goal for Benowitz is the reduction of nicotine in cigarettes to the point where they are no longer addictive. But would a robust black market in strong cigarettes leap up if nicotine reduction were a federally mandated program?

“Progressive reduction of the nicotine content of cigarettes as a national regulatory policy might have important potential benefits for the population,” the authors write, adding that “some people who had no intention of quitting upon entry into the study had… either quit spontaneously or were thinking about quitting in the near future after smoking reduced-nicotine content cigarettes.” Low-nicotine cigarettes could be produced by extracting nicotine from existing tobacco, or by genetically engineering tobacco with a lower nicotine content.

“Adolescents initiate smoking for social reasons, with friends, and later begin to smoke for pharmacologic reasons related to dependence,” the authors conclude. “Presumably a cigarette with very low nicotine content would be less likely to support the transition from social to dependent smoking, although the threshold level of nicotine to prevent this transition is not yet known.”

Benowitz NL, Dains KM, Hall SM, Stewart S, Wilson M, Dempsey D, & Jacob P 3rd (2012). Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 21 (5), 761-9 PMID: 22354905

Photo Credit: http://chronicle.uchicago.edu

The Hidden Story of How Big Tobacco Invented Freebasing

Review of The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition.

Part I

It’s easy to think of cigarettes, and the machinations of the tobacco industry, as “old news.” But in his revealing 737-page book, The Golden Holocaust, based on 70 million pages of documents from the tobacco industry, Stanford professor Robert N. Proctor demonstrates otherwise. He demonstrates how Big Tobacco invented freebasing. He shows how they colluded in misleading the public about “safe” alternatives like filters, “low-tar,” and “ultra-lights.” We discover in Lorillard’s archives an explanation of menthol’s appeal to African Americans: It is all part of a desire by “negroes” to mask a “genetic body odor.” Radioactive isotopes were isolated in cigarette smoke, and evidence of the find was published, as early as 1953. He reveals that the secret ingredient in Kent’s “micronite filter” was asbestos. And he charges that the “corruption of science” lies behind the industry’s drive to continue its deadly trade. “Collaboration with the tobacco industry,” writes Proctor, “is one of the most deadly abuses of scholarly integrity in modern history.”

Half of all cigarette smokers will die from smoking—about a billion people this century, if present trends continue. In the U.S., this translates into roughly two jumbo jets crashing, killing everyone onboard, once daily. Cigarettes kill more people than bullets. The world smokes 6 trillion of them each year. (The Chinese alone account for about 2 trillion). Some people believe that tobacco represents a problem (more or less) solved, at least in the developed West.

All of this represents a continuing triumph for the tobacco industry. The aiders and abettors of tobacco love to portray the tobacco story as “old news.” But as Stanford Professor Robert M. Proctor writes in The Golden Holocaust, his exhaustive history of tobacco science and industry: “Global warming denialists cut their teeth on tobacco tactics, fighting science with science, creating doubt, fostering ignorance.”

Checking in at 737 pages, The Golden Holocaust is nobody’s idea of a light read, and at times its organization seems clear only to the author. But what a treasure trove of buried facts and misleading science Proctor has uncovered, thanks to more than 70 million pages of industry documents now online (http://legacy.library.ucsf.edu) as part of the Master Settlement Agreement of 1998. Once the material was finally digitized and available online, scholars like Proctor could employ full-text optical character recognition for detailed searchability. Ironically, this surreal blizzard of documentation was meant to obscure meaningful facts, not make them readily available, but tobacco executives seem not to have factored in digital technology when they turned over the material.

The single most important technological breakthrough in the history of the modern cigarette was flue-curing, which lowers the pH of tobacco smoke enough to make it inhalable. The reason few people inhale cigars, and very few used to inhale cigarettes, is that without some help, burning tobacco has a pH too high for comfortable inhalation. It makes you cough. But flue-curing lowered pH levels, allowing for a “milder,” less alkaline smoke that even women and children could tolerate.

World War I legitimized cigarettes in a major way. Per capita consumption in the U.S. almost tripled from 1914 to 1919, which Proctor considers “one of the most rapid increases in smoking ever recorded.” After World War II, the Marshall Plan shipped a staggering $1 billion worth of tobacco and other “food-related items.” (The U.S. Senator who blustered the loudest for big postwar tobacco shipments to Europe was A. Willis Robertson of Virginia, the father of televangelist Pat Robertson.)

The military, as we know, has historically been gung-ho on cigarettes. And Proctor claims that “the front shirt pocket that now adorns the dress of virtually every American male, for example, was born from an effort to make a place to park your cigarette pack.” In addition, cigarette makers spent a great deal of time and effort convincing automakers and airline manufacturers to put ashtrays into the cars and planes they sold. Ashtrays were built into seats in movie theaters, barbershops, and lecture halls. There was even an ashtray built into the U.S. military’s anti-Soviet SAGE computer in the 50s.

In the early 50s, research by Ernest Wynder in the U.S. and Angel Roffo in Argentina produced the first strong evidence that tobacco tars caused cancer in mice. Roffo in particular seemed convinced that tobacco caused lung cancer, that it was the tar rather than the nicotine, and that the main culprits were the aromatic hydrocarbons such as benzpyrene. Curiously enough, it was influential members of Germany’s Third Reich in the 40s who first took the possibility of a link seriously. Hans Reiter, a powerful figure in public health in Germany, said in a 1941 speech that smoking had been linked to human lung cancers through “painstaking observations of individual cases.”

In the December 1953 issue of Cancer Research, Wynder, et al. published a paper demonstrating that “tars extracted from tobacco smoke could induce cancers when painted on the skins of mice.” As it turns out, the tobacco industry already knew it. Executives had funded their own research, while keeping a close eye on outside academic studies, and had been doing so since at least the 30s. In fact, French doctors had been referring to cancers des fumeurs, or smokers’ cancers, since the mid-1800s. All of which knocks the first leg out from under the tobacco industry’s classic position: We didn’t know any stuff about cancer hazards until well into the 1950s.

Only weeks after the Wynder paper was published, tobacco execs went into full conspiracy mode during a series of meetings at the Plaza Hotel in New York, “where the denialist campaign was set in motion.” American Tobacco Company President Paul Hahn issued a press release that came to be known as the “Frank Statement” of 1954. Proctor calls it the “magna carta of the American’s industry’s conspiracy to deny any evidence of tobacco harms.” How, Proctor asks, did science get shackled to the odious enterprise of exonerating cigarettes? The secret was not so much in outright suppression of science, though there was plenty of that: In one memorable action known as the “Mouse House Massacre,” R.J. Reynolds abruptly shut down their internal animal research lab and laid off 26 scientists overnight, after the researchers began obtaining unwelcome results about tobacco smoke. But the true genius of the industry “was rather in using even ‘good’ science, narrowly defined, as a distraction, something to hold up to say, in effect: See how responsible we are?”

Entities like the Council for Tobacco Research engaged in decoy research of this kind. As one tobacco company admitted, “Research must go on and on.”

A good deal of the industry’s research in the 50s and 60s was in fact geared toward reverse engineering competitors’ successes. Consider Marlboro. Every cigarette manufacturer want to know: How did they do it? What was the secret to Marlboro’s success?

As it turns out, they did it by increasing nicotine’s kick. And they accomplished that, in essence, by means of freebasing, a process invented by the cigarette industry. Adding ammonia or some other alkaline compound transforms a molecule of nicotine from its bound salt version to its “free” base, which volatilizes much more easily, providing low-pH smoke easily absorbed by body tissue. And there you have the secret: “The freebasing of cocaine hydrochloride into ‘crack’ is based on a similar chemistry: the cocaine alkaloid is far more potent in its free base form than as a salt, so bicarbonate is used to transform cocaine hydrochloride into chemically pure crack cocaine.” Once other cigarette makers figured out the formula, they too began experimenting with the advantages of an “enhanced alkaline environment.”
  
(End of Part I)

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