Quit-Smoking Medicines and Episodes of Violence

A new study published in Public Library of Science One (available here) reports that two drugs widely prescribed to help smokers quit -- varenicline (brand name Chantix) and bupropion (brand names Wellbutrin and Zyban) - are associated with thoughts or acts of violence towards others.

The study was conducted by Thomas Moore at the Institute for Safe Medication Practices, and colleagues from Harvard and Wake Forest Universities. Moore et. al. analyzed data from the FDA Adverse Event Reporting System, extracting all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. The researchers focused on homicide, homicidal ideation, physical assault, physical abuse and violence related symptoms. They reported the number of events, as well as proportional reporting ratios (PRRs), which allows for comparison of the proportion of violence events for each medicine with the proportion from all other evaluable drugs (those in wide clinical use with adequate post-marketing surveillance).

Moore found that “among 484 evaluable drugs, 31 drugs met the study criteria for
a disproportionate association with violence, and accounted for 1527/1937 (79%) of the violence cases…Varenicline has the largest number of reported violence cases (n = 408), [and] the highest proportion of violence cases (PRR= 18.0).”

The PRR for varenicline was so high that it was in a class all by itself. As Moore and colleagues noted, “We have previously examined varenicline’s association with serious psychiatric symptoms including aggression/violence [references omitted]. The aggression/violence case series for varenicline was consistent with these data but revealed other features that may or may not occur in cases attributed to other drugs. These features include early onset of psychiatric symptoms (usually within a few days), a senseless act of aggression/violence directed at anyone who happened to be near by, and resolution of the symptoms upon discontinuation.”

Moore also found that bupropion, an antidepressant prescribed to aid smoking cessation, was also associated with violence, although at a much lower rate (35 episodes, PRR = 3.9). As he and his associates note, “bupropion is indicated for both depression and as an aid to smoking cessation, so those results are not limited to the smoking cessation population.”

Moore also studied pharmaceutical nicotine, which was associated much less frequently with violent episodes (11 cases, PRR = 1.9).

Tobacco prohibitionists like the American Cancer Society often claim that tobacco harm reduction is unnecessary, since medicines represent the gold standard for smoking cessation. This study demonstrates that the gold standard is substantially tarnished. At a minimum, the Cancer Society should update its website discussion of smoking cessation (here). The current version promotes varenicline and bupropion, but fails to mention the drugs’ possible side effect of violent behavior.

POTUS Puffing?

On December 10, White House press secretary Robert Gibbs was asked pointed questions about whether President Obama had quit smoking. Gibbs responded by saying, “I've not seen or witnessed evidence of any smoking in probably nine months,” which prompted an optimistic headline in the Washington Post: “Obama Kicks His Smoking Habit.” But after watching the video of Gibbs’ actual comments (available here), one is left with the impression that the press secretary was practicing plausible deniability; he never actually said President Obama had quit smoking.

Two and a half years ago, in June 2008, I wrote to then-Senator and presidential candidate Obama, encouraging him to consider practicing tobacco harm reduction. I also submitted my letter to the Chicago Tribune, which published it on June 22. The text of that letter (also available here) is as relevant to millions of Americans, and very likely the President, as we move into 2011 as it was two years ago:

An Open Letter To Barack Obama

Dear Senator Obama:

I viewed with great interest your recent comments about your struggle to quit smoking. As a professor of medicine at the University of Louisville with a long-term research program focused on tobacco use and its consequences, I strongly believe that your discomfort is entirely unnecessary; your dependency on cigarettes can readily be resolved.

First, understand that you are not alone. Some 25 million adult Americans are inveterate smokers – that’s about 50% of all who smoke. They are unable or unwilling to stop using tobacco and nicotine. For them, conventional quit-smoking tactics, which require abstinence, simply don’t work.

A growing number of public health experts – including Britain’s Royal College of Physicians, one of the world’s oldest and most prestigious medical societies – believe that inveterate smokers could benefit from alternative tobacco products that are effective quit-smoking aids and vastly safer substitutes for cigarettes.

The Royal College has observed that “smokers smoke predominantly for nicotine” and “nicotine itself is not especially hazardous.” You probably appreciate that nicotine is among the most powerful of addictive substances. But nicotine doesn’t cause any smoking-related disease. In fact, nicotine itself is about as safe as caffeine, another addictive drug consumed safely by millions of Americans.

Research and consumer experience show that smokers can obtain satisfying doses of nicotine from smoke-free (and spit-free) tobacco products. Available as small packets or pellets of tobacco that are placed inside the upper lip, modern smokeless tobacco products can be used invisibly in all social settings, including stressful press conferences.

Most importantly, smokeless tobacco products are 98% safer than smoking. While no tobacco product is completely safe, the majority of cigarette smokers are routinely misinformed – by government agencies and by anti-tobacco extremists – about the relative safety of smokeless products. Unlike cigarettes, smokeless does not cause lung cancer, heart disease or emphysema. Smokers rightfully worry about mouth cancer, but they should take comfort in the fact that the risk for mouth cancer with smokeless is far lower than it is with cigarettes. Statistically, smokeless users have about the same risk of dying from mouth cancer as automobile users have of dying in a car wreck.

In fact, switching from cigarettes to smokeless provides almost all of the health benefits of complete tobacco abstinence.

Substituting satisfying and vastly safer sources of nicotine for cigarettes is called “tobacco harm reduction”. Tobacco harm reduction has worked in Sweden, where men have smoked less and used more smokeless tobacco over the past century than in any other Western country. The result: Swedish men have the lowest rates of lung cancer – indeed, of all tobacco-related deaths – in the developed world.

A colleague and I recently published research, based on an analysis of the federal government’s National Health Interview Survey, documenting that tobacco harm reduction has also worked for American smokers.

The Royal College characterized harm reduction as “a fundamental component of many aspects of medicine and, indeed, everyday life, yet for some reason effective harm reduction principles have not been applied to tobacco smoking.” It concluded, “If nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved.”

Senator, your genuine desire to quit tobacco altogether is commendable. But if you find this goal unachievable, like millions of inveterate smokers, I urge you to switch to smokeless tobacco for your physical and emotional wellbeing. In doing so, you can provide inspiration for American smokers, and you can effect a profound positive change in the nation’s public health. Yes, you can.

Sincerely,

Brad Rodu
Professor of Medicine
Endowed Chair, Tobacco Harm Reduction Research
University of Louisville

Snus Not Linked to Colorectal Cancer

Researchers from the Swedish Karolinska Institute have published a study in the International Journal of Cancer showing that snus use is not a risk factor for cancers of the colon, rectum and anus among Swedish men (abstract here).

Caroline Nordenvall, from the Department of Medical Epidemiology and Biostatistics, and colleagues studied over 300,000 male Swedish construction workers who enrolled in a health program from 1971 to 1992. The workers were followed for up to 37 years, and Nordenvall calculated the relative risks (RRs) for cancer of the colon, rectum and anus among smokers and snus users.

Compared with non-users of tobacco, smokers had RRs of 1.08 (95% Confidence Interval = 0.99 – 1.19) for colon cancer and 1.16 (CI = 1.04 – 1.30) for rectal cancer. These are very small increases, and only the latter is statistically significant. The RR for anal cancer among smokers was 2.41 (CI = 1.06 – 5.48). Although smoking has been implicated for many years as a risk factor for anal cancer, the sexually transmitted human papillomaviruses are known causes of this malignancy. Information on sexual behavior or venereal infections, not found in this study, might affect Nordenvall’s risk estimate for smoking.

Snus users did not have significantly elevated risks for any of these cancers. The RRs were 1.08 (CI = 0.91 – 1.29) for colon cancer, 1.05 (CI = 0.85 – 1.31) for rectal cancer and 0.61 (CI = 0.07 – 5.07) for anal cancer.

Nordenvall concluded her study with the following: “Our results from a large and homogenous cohort of Swedish male construction workers with up to 37 years of
follow-up do not convincingly support an important role of tobacco use in the etiology of colorectal cancer. As expected, an increased risk of anal cancer was associated with smoking.”

Distorting Tobacco Facts to Sway Major League Baseball

Tobacco prohibitionists have for many years pressed Major League Baseball (MLB) to ban player use of smokeless tobacco. Despite decades of misinformation from advocates like Joe Garagiola (example here), many ballplayers still use smokeless products. The U.S. Congress entered the fray in April, when House Health Subcommittee Chairman Henry Waxman convened a hearing to browbeat baseball executives for failing to implement a ban. Witnesses pitched a barrage of misinformation. I responded in this blog (here and here).

More misinformation flowed on November 19, when the presidents of ten organizations dedicated to tobacco prohibition called on the commissioner and the director of the MLB players’ association to ban smokeless tobacco use. Their rationale for a ban was wholly unscientific; earlier this week I wrote the commissioner and the MLB association to set the record straight. The text of my letter follows:

December 6, 2010

Mr. Allen H. (Bud) Selig
Commissioner
Major League Baseball
245 Park Avenue, 31st Floor
New York, NY 10167

Mr. Michael Weiner
Executive Director
Major League Baseball Players Association
12 East 49th Street, 24th Floor
New York, NY 10017

Dear Commissioner Selig and Mr. Weiner:

On November 19, 2010, the presidents of ten organizations dedicated to tobacco prohibition wrote you “…to urge Major League Baseball and the Major League Baseball Players Association to prohibit the use of all tobacco products, including smokeless tobacco, by players, coaches, managers, and other team personnel, at all Major League Baseball venues.” The letter (available here, hereafter referred to as Myers et al.) contains distorted and inaccurate statements about the health risks of smokeless tobacco.

I am a professor of medicine, and I hold an endowed chair in tobacco harm reduction research at the University of Louisville. I have conducted research for two decades on the health effects of smokeless tobacco use, and I believe you are entitled to know what tobacco research and policy experts consider an indisputable scientific fact: the health risks from smokeless tobacco use are so low that they are difficult or impossible to measure with modern epidemiologic methods.

Myers et al. make unsupported allegations that smokeless tobacco causes a litany of cancers. They cite no scientific evidence for their claims, because the risks are either barely measurable or completely nonexistent. In 2009, a comprehensive analysis (Reference 1) of all available epidemiologic studies documented that smokeless tobacco users do not have significantly elevated risks for ANY of the cancers listed by Myers et al.

Myers et al. also claim that “Tobacco use is the number one preventable cause of death in the United States.” This is grossly misleading, as it combines smoking’s dramatic fatality figures with the far more benign use of smokeless tobacco (2). For example, the U.S. Centers for Disease Control and Prevention estimate that over 400,000 Americans die every year from smoking-attributable diseases (3), but the comparable number attributed to smokeless tobacco use is so low that the CDC has never attempted to provide an estimate. American Cancer Society Vice President Emeritus Michael J. Thun participated in a 2004 study concluding that “…smokeless tobacco products pose a substantially lower risk to the user than do conventional cigarettes. This finding raises ethical questions concerning whether it is inappropriate and misleading for government officials or public health experts to characterize smokeless tobacco products as comparably dangerous with cigarette smoking.” (4)

The use of smokeless tobacco may be a legitimate topic of discussion between Major League Baseball and the Major League Baseball Players Association. However, the facts about smokeless tobacco vs. cigarettes should not be twisted to satisfy an anti-tobacco agenda or to influence public health policy.

Please do not hesitate to contact me if you would like more factual information on this important subject.

Sincerely,

Brad Rodu
Professor of Medicine
Endowed Chair, Tobacco Harm Reduction Research

References

1. Lee PN, Hamling JS. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Medicine 7: 36, 2009. Available here.

2. Rodu B, Godshall WT, 2006. Tobacco harm reduction: an alternative cessation strategy for inveterate smokers. Harm Reduction Journal 3:37. Available here.

3. Centers for Disease Control and Prevention. Smoking-attributable mortality, morbidity, and economic costs (SAMMEC). Available here.

4. Levy DT, Mumford EA, Cummings KM, Gilpin EA, Giovino G, Hyland A, Sweanor D, Warner KE. The relative risks of a low-nitrosamine smokeless tobacco product compared with smoking cigarettes: estimates of a panel of experts. Cancer Epidemiology Biomarkers and Prevention 13: 2035-2042, 2004.

A Medical Association in Denial on Smokeless Tobacco

A few weeks ago I highlighted misinformation about smokeless tobacco from the Mayo Clinic (here). The foolishness continues, this time from the American Academy of Otolaryngology - Head and Neck Surgery (here). Commonly called Ear, Nose and Throat specialists, or ENTs, these physicians are often involved in the treatment of oral and throat cancers. Regrettably, the Academy and spokesman Dr. Daniel Deschler are perpetuating myths about smokeless tobacco and harm reduction.

“Using smokeless tobacco products, like chew, is not a safe way to quit or a healthier alternative to smoking,” says Dr. Deschler in an Academy press release. He asserts that smokeless tobacco users run the same risks of gum disease, heart disease, high blood pressure, and addiction as cigarette users, but an even greater risk of oral cancer. Only one of these claims is true: Smokeless users are just as addicted to nicotine as smokers, and that is exactly why smokeless is an excellent alternative to cigarettes.

The reality is that smokeless users have almost no risks for gum disease, heart disease or high blood pressure. They certainly don’t have “an even greater risk for oral cancer” than smokers. This gross misstatement should not be made by a physician-spokesman for a professional medical society. As I have documented many times, the oral cancer risk for smokeless use is barely measurable in most epidemiologic studies, and negligible when compared with smoking.

Is the American Academy of Otolaryngology - Head and Neck Surgery deliberately misleading the public? In an effort to correct websites that had false and misleading information about smokeless tobacco, tobacco harm reduction colleagues at the University of Alberta sent a detailed letter to the Academy describing misinformation on its site and explaining why it was potentially harmful to inveterate smokers (read about it here). The organization never responded.

Patients believe their doctors make decisions based on sound science, not on moral judgments. Physicians and organizations that mischaracterize medical facts violate the sacred trust upon which our health care system is based. The American Academy of Otolaryngology - Head and Neck Surgery should correct its message.

The Consequences of Tobacco Prohibition and Misinformation in the U.S. Air Force

A new study about tobacco use among Air Force recruits, before and one year after basic training, has been published in the American Journal of Public Health (abstract here). The authors include two vocal tobacco opponents, Dr. Robert C. Klesges of the University of Tennessee (Memphis) and Dr. Jon O. Ebbert of the Mayo Clinic.

Dr. Klesges looked at tobacco use among airmen (an Air Force term used for both men and women) who made up a control group in a large study combining universal forced tobacco abstinence during 6 weeks of basic training and an “intervention” consisting of tobacco prevention or cessation. The results from the large study were published in 2006 (I refer to it as Klesges I, the abstract is here; I refer to the current study as Klesges II).

Klesges classified recruits based on their tobacco habits prior to basic training (baseline): nonusers of tobacco, smokers, smokeless users and dual users. In addition, he described tobacco prohibition:

“During basic military training, there is a total tobacco ban…and the prohibition is strictly enforced. At the beginning of basic military training, airmen are searched and all tobacco products are confiscated. Tobacco products are considered ‘‘contraband’’ along with alcohol, drugs, weapons, and chewing gum. The airmen recruits are required to maintain a ‘money list’ (i.e., a list of all serial numbers for all their money), which is checked regularly by basic military training instructors. Airmen are under constant supervision, and there are no tobacco products accessible even during those rare occasions when airmen are not supervised. An honor code is established early in basic training so that if a recruit breaks the rules, fellow airmen are duty bound to report the infraction. Finally, the punishment for tobacco use during basic military training is severe. In virtually all cases, the airman is ‘recycled’ (forced to repeat some or all of basic training), a possible sanction that few airmen dare risk.”

That is serious tobacco prohibition, and perhaps Klesges et al. hoped that none of the 5,225 Air Force recruits would be using tobacco 12 months later. That didn’t happen.

Klesges reported that 11% of recruits who were nonusers at baseline were smoking 12 months afterwards. As he admitted in Klesges I, “the smoking prevention program had no impact on smoking initiation.” So airmen started smoking in large numbers despite boot-camp tobacco prohibition and prevention programs.

In Klesges II, the main focus was on the 6% of smokers at baseline who were dual users afterwards. He classified this transition as harm escalation, which is an appalling misrepresentation of reality. It is scientifically established that smokers who switch to dual use smoke fewer cigarettes and have lower health risks (described here).

Other data in Klesges II were informative. Fewer than 1% of baseline smokers were smokeless users at follow-up, but 15% of baseline smokeless users were dual users and 14% were smokers at follow-up. In addition, 42% of dual users at baseline were smokers at follow-up. Thus, the transition from smokeless to cigarettes was more common than from cigarettes to smokeless. How did this happen? This is strong evidence that tobacco users in the Air Force are not properly informed about the risks of smoking and smokeless use. Unfortunately, they are making very bad decisions based on misinformation.

A big concern with this study is that the numbers don’t add up, compared with Klesges I. That study started with 7,974 airmen, compared with only 5,225 airmen in this study. In Kleges I, there were 312 smokeless users at baseline, but in Klesges II, there were only 193 (38% fewer). In Klesges I dual use was not a tobacco category, so we have no idea how it classified those 249 airmen from Klesges II. In short, reconciliation of different numbers between Klesges I and II is impossible, which is an indicator of low quality and inconsistency.

Klesges concludes that “[harm] escalation is a possible unintended consequence of promoting smokeless tobacco as a harm reduction strategy for smokers.” He is wrong. Harm escalation is the unintended consequence of not telling smokers and smokeless users the truth about the health risks.

American Evidence that Snus Is An Effective Substitute

Scientists from the University of Minnesota Tobacco Use Research Center have just published the results of a clinical trial from 2006-7 showing that RJ Reynolds’ Camel Snus and Philip Morris’ Taboka (a precursor of Marlboro Snus) were viable substitutes for cigarettes. The trial was conducted by Michael Kotlyar and colleagues; the results are published in Cancer Epidemiology and Biomarkers (abstract here).

Kotlyar recruited smokers who were interested in quitting, and assigned them to use one of three products: 4 milligram nicotine gum or lozenge, Camel Snus or Taboka (participants had a choice of various flavors for each product). Participants used only 1 or two products per day during a one-week sampling period; for the next four weeks, they used the product at least 6 to 8 times daily. During week 5, participants were required to reduce consumption of the substitute; by the end of that week they had to be completely tobacco- and nicotine-free.

There were several interesting results. First, all participants in all groups had a reduction in exhaled carbon monoxide, clearly demonstrating that they smoked less than before the study. Participants in all groups had a reduction in the urine concentration of two chemicals that are considered carcinogens, abbreviated here as NNN and NNAL. The reductions were statistically significant except for NNN in Camel Snus users (p = 0.07).

Overall craving and withdrawal scores decreased over the 4 weeks in all groups, with no differences between the groups.

Continuous abstinence rates over the 4 treatment weeks varied from 33% (Taboka) to 43% (Camel Snus). Two weeks after the treatment ended, 39% of the Taboka group, 47% of the Camel Snus group and 56% of the nicotine group were not smoking, but these percentages dropped to 23%, 31% and 33% respectively after ten weeks of complete abstinence.

One possible reason for the precipitous drop in the smoke-free percentages was the insistence on abstinence after 4 weeks. If this philosophy prevails, it will guarantee that smokeless products are no more effective than pharmaceutical nicotine, which has a documented failure rate of 93% (evidence here).

There is evidence that the FDA is starting to think about offering smokers “long-term” nicotine substitution (review a symposium on the topic was held on October 26-27 here), which is a strategy I called “nicotine maintenance” in 1999 (here). I recommend that readers look at the FDA presentations, especially the one by Neal Benowitz (here). He indicates that the best information about the long-term risks of nicotine come from the epidemiologic studies of Swedish snus use.

There were other interesting aspects of the Minnesota study. The Taboka group smoked significantly more than those using nicotine or Camel Snus. It is possible that Taboka, which had very low nicotine levels, simply didn’t satisfy smokers.

A total of 1,159 smokers responded to advertisements for the study. According to the researchers, 800 “were able to be reached and were screened over the telephone,” and 429 qualified and were interested in participating. Another 212 did not show up for the orientation. The attrition didn’t stop there: 211 smokers were enrolled in the study but only 130 were randomized to one of the three groups. Just 80 participants completed the 4-week treatment period and the one-week transition to abstinence.

These numbers represent one of the biggest challenges of clinical trials, especially in the field of risky behaviors like smoking. The 80 participants who completed the study represent only 6.9% of the smokers who originally responded, so they are an especially motivated group. That has been one of the problems with quit-smoking trials: It is impossible to generalize their results because they are from a highly selected population that is not representative of smokers in general.

In the past, I have criticized the Minnesota group for publishing biased and distorted studies about smokeless tobacco (here and here). But this is a fair and balanced report of the potential for smokeless tobacco as a substitute for cigarettes.

The CDC: Your Online Source for Incredible Tobacco Information

The U.S. government is battling tobacco and tobacco users, based to a great extent on misinformation promulgated by the Centers for Disease Control and Prevention (CDC). The CDC bills itself as “Your Online Source for Credible Health Information,” but two recent reports clearly demonstrate that the agency is deliberately deceiving Americans about fundamental facts concerning tobacco use.

Last week, the CDC published an article in the Morbidity and Mortality Weekly Report (MMWR) about the dual use of smokeless tobacco and cigarettes among men and women in the U.S. (available here). The data was from the 2009 Behavioral Risk Factor Surveillance System (BRFSS), an on-going telephone health survey tracking U.S. health conditions and risk behaviors yearly since 1984.

The information in the CDC report was routine: Smokeless tobacco use was highest in Wyoming and West Virginia (9 percent), and lowest in California (1 percent). Smoking rates were highest in Kentucky, West Virginia and Oklahoma (about 26 percent), and lowest in Utah (10 percent), California (13 percent) and Washington (15 percent).

Still, CDC director Dr. Tom Frieden used the results to rejoin the attack, with a special focus on smokeless products: “Tobacco use is the leading preventable cause of death in this country and unfortunately smokers are also using smokeless tobacco. If you smoke, quitting is the single most important thing you can do to improve your health. Use of smokeless tobacco may keep some people from quitting tobacco altogether. We need to intensify our anti-tobacco efforts to help people quit using all forms of tobacco.”

This week, with the help of the Wall Street Journal (here), the CDC turned its attention back to cigarettes, with the claim that smoking rates stopped declining several years ago. Here’s the lead:

“Many cash-strapped U.S. states are slashing budgets for tobacco-prevention programs, raising alarms among public-health groups as the nation's progress toward getting adult smokers to quit has stalled. The adult smoking rate was 20.6% in 2009, the same as a year earlier and largely unchanged since 2004, according to the Centers for Disease Control and Prevention.”

The basis for these numbers was the 2009 National Health Interview Survey (NHIS)(available here), which reported that the prevalence of smoking has been “largely unchanged” for the past several years, at just above 20%. But what about the BRFSS (discussed above)? What does that survey say about smoking rates?

For 2004, BRFSS reported the prevalence of current smoking as 20.9%, about the same as the NHIS. But for 2009, according to BRFSS, smoking prevalence had dropped to 17.9%. That’s a whopping decline of 14% in just 5 years!

One year ago I discussed in this blog how different federal surveys report contrasting data on smoking in the U.S. (here). We now have a brilliant example of how the CDC creates a consistent anti-tobacco narrative by cherry-picking data from what are essentially conflicting datasets. The public, and government budgeting officials, would be better served by a CDC that focused on reporting and explaining the unvarnished facts, free of any social behavioral bias.

Mayo Clinic Misinformation About Smokeless Tobacco

For many years, tobacco “experts” at the Mayo Clinic have tarnished the institution’s name by fabricating misinformation about smokeless tobacco. In a 2004 article about such tactics (available here), I noted that the Mayo website contained this irresponsible, unprofessional and demonstrably false statement: “…smokeless tobacco, also called spit tobacco, has health risks just as severe or even more severe as those associated with cigarette smoking.”

Last week, Jennifer A. Kern, a Mayo Clinic behavioral counselor and former smoker, published a quit-smoking blog entry for the official Mayo Clinic web site, in which she invented new health risks related to smokeless tobacco use (here).

Ms. Kern begins with an explicit acknowledgment that smokeless tobacco is an effective substitute for cigarettes: “Those of us who live in the north are moving into the cooler seasons…it's not uncommon to see people switching tobacco products in order to stay indoors while still getting their nicotine fix. Some folks put down cigarettes and pick up smokeless tobacco products such as chewing tobacco and snuff instead.”

Ms. Kern doesn’t like smokers switching to vastly safer smokeless products, so she tries to convince them not to do so by invoking a “just-as-harmful” theme: “Smokeless tobacco products carry carcinogens, or cancer-causing chemicals, just like cigarettes do.”

Next, Ms. Kern turns to outright fabrication: “In fact, a variety of cancers that can be caused by smokeless tobacco use include: mouth and gum, larynx (voice box), esophagus, and salivary gland, as well as non-oral cancers like pancreas, kidney and penile cancer.”

My readers know that a comprehensive meta-analysis published in 2009 found that smokeless tobacco use is not associated with cancers of the mouth and gum, larynx, esophagus, pancreas or kidney (for a full discussion, click here). But what about salivary gland and penile cancer?

For salivary gland cancer, Ms. Kern may have misread a story involving Tony Gwynn, a former major league baseball player. In early October, Gwynn was diagnosed with cancer of the parotid salivary gland (described here), and he commented that “I haven't discussed that with the doctors yet, but I'm thinking it's related to dipping.” Apparently Gwynn and Ms. Kern are unaware that no epidemiologic studies have linked smokeless tobacco use and salivary gland cancer.

Ms. Kern’s most bizarre claim is that smokeless tobacco use causes penile cancer. According to the National Cancer Institute, penile cancer is extremely rare, occurring in only 1,250 American men each year (here). Penile cancer is strongly related to human papillomavirus infections and lack of circumcision (here). Maybe Ms. Kern was referring to a 1995 report linking penile cancer and smokeless use in India (here), but Swedish and American products have not been implicated in numerous epidemiologic studies.

Someone should counsel Ms. Kern and her employer about the public health imperative of sticking to the facts.

Good News You Never Knew About Life Expectancy in the U.S.

The National Center for Health Statistics in May released final data on life expectancy and deaths in the U.S. for the year 2007 (read it here). It is an extraordinary report, because it further documents that Americans continue to live longer and healthier lives, year after year.

Compared with 2006, the age-adjusted death rate from all causes declined 2.1% in 2007. This is an extraordinary single-year decline, and it was driven by impressive reductions in five of the top 10 causes of death, as noted in the table.







Top Ten Causes of Death, and Percentage Change from 2006 to 2007

Cause of Death	Percent Change From 2006
1. Heart Diseases	- 4.6
2. Cancer	- 1.3
3. Stroke	- 3.2
4. Respiratory Diseases	+ 0.7
5. Accidents	+ 0.5
6. Alzheimer’s Disease	+ 0.4
7. Diabetes	- 3.4
8. Influenza/pneumonia	- 9.0
9. Kidney Diseases	None
10. Blood Infection	None

Heart disease, accounting for about one-quarter of all American deaths, declined almost 5% in 2007, and stroke deaths dropped by over 3%. Deaths from cancer were down over 1%, and there were impressive declines for diabetes (-3.4%) and influenza/pneumonia (-9%). These aren’t just one-year wonders; declines have been occurring for 20 to 30 years.

Chances are that you knew nothing about these incredible statistics. That’s because the federal government and most health organizations cast every health issue as a crisis. They argue that Americans are in poor health and are being killed by obesity, as well as chemicals in our food and in our environment. They portray our health care system as ineffective. They don’t want you to know the truth: death rates for most major diseases continue to plummet.

The long-term decline in smoking is playing a role, especially in the impressive reductions in heart disease, cancer and stroke rates. But many Americans are also eating healthier foods, and using preventive medications like aspirin and statins (that lower cholesterol levels) to reduce risks. And the health care system is providing ever-improved treatments.

I offer the following example to illustrate that the decline in American death rates over the past couple decades is truly astounding: let’s compare 2007 with 1987. In 2007, the nation’s age-adjusted death rate for all causes was 760 deaths per 100,000, and a total of 2,423,712 Americans died. Just twenty years earlier, the age-adjusted death rate was 970, about 28% higher than 2007 but still far lower than in previous decades. If the 1987 rate had been effective in 2007, there would have been 669,000 more deaths!

The average life expectancy at birth for the U.S. population in 2007 was the highest in history at 77.9 years, an increase of 0.2 year over the 2006 number. In other words, every American gained almost 2½ months of life expectancy in just one year! This is irrefutable evidence that our health and social system, despite its limitations, has sustained remarkable advances in the prevention and treatment of most life-threatening diseases, extending and improving the lives of millions of Americans.

Snus Users and Smokers in Stockholm

A new study published in Biomed Central Public Health (available here) describes the socioeconomic and lifestyle characteristics of snus users and smokers in Stockholm County, Sweden. Based on a 2006 survey of 35,000 residents, it was authored by Karin Engström and colleagues at the Department of Public Health Sciences at the Karolinska Institute. In addition to providing interesting information about snus users, this study has important implications for Karolinska Institute claims about the link between snus use and cancer.

Among men, 17% were exclusive snus users, 11% smoked and 2.4% were dual users. Among women, cigarette smoking was dominant (15%), while snus use and dual use were only 3.1% and 0.5% respectively. Given this, I will focus on the findings for men.

It is noteworthy that the prevalence of snus use was highest among men less than 35 years old. This means that young men in Stockholm strongly prefer snus, a lifestyle choice that will have little or no effect on their health as they age.

Snus users were somewhat more likely to have lower education levels than nonusers of tobacco, a trend that was even stronger among smokers. Smokers were also more likely to be unskilled and skilled workers in the very low income group, while snus users were more evenly distributed among all occupational classes and across all income levels.

One of the more interesting results concerned alcohol consumption. Risky alcohol consumption was defined as 14 standard drinks per week; the survey also asked about weekly or monthly binge drinking. Snus users and smokers were more likely to practice risky consumption than nonusers (odds ratios = 1.8 – 1.9), and they were more likely to have weekly binge-drinking episodes (ORs around 3.1).

This information on alcohol abuse among snus users is important, because a Karolinska epidemiology group, led by Olof Nyrén, published studies suggesting that snus use is associated with a small risk of pancreatic, stomach and esophageal cancer (abstracts here and here) among workers in the Swedish construction industry. Alcohol abuse is a strong risk factor for esophageal cancer and may be linked to stomach and pancreas cancer; this makes it a confounder with respect to snus use. In other words, if snus users are more likely to be alcohol abusers, then some of the cancers attributed to snus might instead be caused by alcohol. In many modern epidemiologic studies, standard procedures are used to account for confounders. In this case, to accurately separate the risks due to snus use from those due to alcohol abuse.

But the construction worker studies had no information on alcohol consumption, so alcohol abuse could not be ruled out as a competing risk factor. The lack of information about alcohol in these studies is a serious deficiency that raises questions about the validity of Nyrén’s claims.

In summary, men in Stockholm from all income levels and all occupations prefer snus over cigarettes. The impact of this preference on their health is so small that it is barely measurable by modern epidemiologic methods. Furthermore, snus users, like smokers, are more likely to abuse alcohol, which may be a distinct risk factor for some cancers that has not been evaluated in previous Karolinska Institute reports on snus use.

Noteworthy News From Norway: Snus is Superior Cigarette Substitute

In 2008, the European Commission released a report entitled “Health Effects of Smokeless Tobacco Products.” (available here). Except for one small part discussing tobacco harm reduction (Section 3.8, pages 111-118), most of the report was very negative, even denying that snus use has had any effect on smoking in Sweden and Norway.

The report concluded: “It is difficult to envision any significant impact of snus use on smoking cessation in Norway…” This was especially baffling, as Figures 19-22 (pages 42-43) show clearly that increased snus use over the last 20 years was concomitant with decreased smoking.

The Commission report also surprised Dr. Karl Erik Lund, a respected tobacco researcher with SIRUS, the Norwegian Institute for Alcohol and Drug Research. Lund has 20 years experience in tobacco research and has authored more than 85 journal articles in the fields of tobacco epidemiology, evaluation and prevention. This year, he published landmark studies showing unequivocally that snus use has had a profound impact on smoking in Norway.

Lund’s current study was published in Addiction (abstract here). He compared quit rates, defined as the percentage of ever smokers who are now former smokers, among snus users and never users in seven previously published Norwegian surveys.

Lund Survey No.	Quit Rate- Snus Users (%)	Quit Rate- Never Snus Users (%)
1	80	52
2	55	23
3	81	63
4	62	53
5	75	45
6	90	50
7	73	43

As seen in the table, the quit rates for snus users were always higher than for those who had never used snus; the results are statistically significant for all surveys except number 4. This is compelling evidence that snus has played a powerful role in smoking cessation among Norwegians. As Lund notes, it is consistent with the Swedish evidence. Equally important, it is consistent with evidence I have published from federal surveys in the U.S. (discussed in this March blog post).

Earlier this year, Lund published evidence in Nicotine & Tobacco Research that Norwegian men preferred snus over ALL other methods to quit smoking (abstract here).

The SIRUS survey asked 3,583 former or current smokers age 20-50 years what method they used when they last tried successfully (former) or unsuccessfully (current) to quit. Snus was used by 32% of all respondents, making it the most popular method by far. Other methods that enjoyed modest popularity were nicotine gum (18%), self-help material (12%), and the nicotine patch (10%). Nicotine inhaler, Zyban, Champix, telephone quit line, and help from health care professionals were also included in the survey, but they had negligible usage rates.

Lund reported an adjusted odds ratio (AOR) to indicate effectiveness of products compared with nicotine gum, the reference product. For quitting completely, the AOR for snus was 2.7, meaning that it was nearly three times more effective than gum. Snus was also three times more effective than nicotine gum in “greatly reducing cigarette consumption” among continuing smokers (AOR = 3).

Lund observed: “Of those smokers who reported that they had tried to quit by using snus, 62.4% reported that they still used snus at the time of the survey, either daily (43.8%) or occasionally (18.6%)…In comparison, only 9.5% who had used nicotine chewing gum or nicotine patches at the last attempt to quit were still using these medicinal nicotine products at the time of the survey.” In other words, snus was effective precisely because it was a satisfying and enjoyable substitute, rather than an unsatisfying and distasteful temporary medication. This represents the fundamental advantage of a recreational approach to smoking cessation, compared to treating smokers’ nicotine addiction with medications. Smokers aren’t sick; they just want to have safer alternatives.

There is no question that snus is an effective and PERMANENT nicotine substitute for many former smokers. This is important, because a dominant theme in the U.S. is that quit-smoking methods must all eventually lead to permanent nicotine and tobacco abstinence. Given that the outcome measure for all smoking cessation trials in the U.S. is complete abstinence, it is no wonder that most cessation methods are deemed failures. For successful tobacco regulation, the FDA must break the public health community’s addiction to abstinence promotion. Unfortunately, the FDA is still focused on abstinence (here).

Norwegian authorities have a more realistic and rational strategy. Lund and colleagues noted that in 2009, the Norwegian Health Directorate “agreed that health care personnel can recommend snus in individual cases of inveterate smokers.” It is refreshing that the directorate recognizes that saving smokers’ lives is more worthy and achievable than simply breaking the chain of tobacco addiction.

Imagining Tobacco Without Nicotine

In June, I called attention to the unscientific proposal by two FDA tobacco advisory committee members, Drs. Jack Henningfield and Neal Benowitz, to radically reduce nicotine in cigarettes in order to force smokers to quit and prevent children from starting to smoke (read my post here). They are now the co-authors of another thinly veiled call for reducing nicotine to “non-addictive levels” in cigarettes, just published in the journal Tobacco Control (abstract here).

Henningfield and Benowitz are joined by fellow committee member Dr. Dorothy Hatsukami, the National Cancer Institute’s Dr. Cathy Backinger (read about her previous pronouncements here), FDA staffer Dr. David Ashley, and Mitch Zeller, a lawyer. Zeller works for a consulting firm employed by GlaxoSmithKline, the pharmaceutical manufacturer that last week called on the FDA to ban dissolvable tobacco products (read about it here). According to Dr. Elizabeth Whelan of the American Council on Science and Health, “GSK is clearly trying to protect its own market…” by eliminating tobacco products that it perceives as competition with its medicinal nicotine products.” (For insights on medicinal nicotine’s dismal track record, see my previous blog post).

The Tobacco Control article is an urgent call for research that would inform policy decisions regarding reduced nicotine cigarettes. Here are the questions these “six leading tobacco research and policy experts” (as they describe themselves in their press release) want answered about reducing cigarette nicotine content:

"What is the nicotine threshold dose(s) for addiction…? What are the effects of reduced nicotine cigarettes on the brain in adult smokers and in adolescents…? What is the extent of compensatory smoking…and what interventions can be used to minimize compensatory smoking, such as making nicotine available through less hazardous delivery systems (e.g. nicotine replacement therapy)…? What are the effects of reduced nicotine cigarettes in subpopulations (consumers who smoke for self-medication purposes such as those with comorbidity or who are severely addicted)…and how can negative consequences be mitigated? What would be the public’s reaction…? How could we frame the message and educate the public…? What are the potential unintended consequences from reduced nicotine cigarettes, how can [the consequences] be determined and monitored, and what needs to be done to mitigate against negative consequences?"

In other words, these “experts” can’t even define a threshold dose for nicotine addiction, and they are clueless about the effects of radically reducing nicotine in cigarettes. Yet, their press release (here ) makes nicotine prohibition sound like the perfect solution. Dr. Hatsukami ignored all those important questions, proclaiming in the release that “Reducing the nicotine in cigarettes to a level that is non-addicting could have a profound impact on reducing death and disability related to cigarettes and improving overall public health.” It appears that she has already reached conclusions before the research is performed.

Lawyer Zeller was even more fanciful: “Imagine a world where the only cigarettes that kids could experiment with would neither create nor sustain addiction.”

Unfortunately, it doesn’t take an active imagination to appreciate the disaster that would result from radical reduction (prohibition) of nicotine in cigarettes. One need only look at the nation’s reaction to alcohol prohibition, as chronicled by Daniel Orient in his outstanding book, Last Call (description here).

In 1914, U.S. per capita beer consumption was 20 gallons. In anticipation of alcohol prohibition, launched in 1920 by the 18th Amendment to the Constitution, breweries produced an alcohol-free drink, informally called near beer. Six months into prohibition, sales of near beer plummeted, and brewers turned to a more attractive and profitable alternative: malt syrup, the key ingredient for making beer. It was sold in grocery stores across the nation, and it spawned a mini-industry offering filters, bottles, bottle stoppers, and most importantly, yeast. It is not a coincidence that California vineyards survived Prohibition in a similar manner. Millions of Americans legally consumed alcohol during Prohibition by making their own beer and wine.

The prohibitionists’ response to home brewing was to call for more prohibition. In 1925, Wayne B. Wheeler, a key prohibition architect (profiled here), asked one of his friends in Congress if “the time is ripe to prohibit the sale and distribution of these malt syrups and malt supplies.” Orient writes, “It wasn’t, nor would it ever be.”

Near beer, which tasted like real beer, didn’t sell precisely because it didn’t provide alcohol, an addictive drug with benefits. Today, neo-prohibitionists, with little research and a lot of imagination, are trying to sell Americans on near cigarettes that are devoid of addictive but rewarding nicotine.

Is the time ripe for such foolishness, especially when smokers have increasing access to vastly safer smokeless alternatives? It isn’t, nor will it ever be.

Does Dual Use Jeopardize Smokeless Tobacco’s Role in Harm Reduction? Absolutely Not

One year ago, I briefly discussed the “dual use” of cigarettes and smokeless tobacco by men in the U.S. (post here). Dual use is the object of persistent complaints by American tobacco control extremists. For example, in 2002, Dr. Jack Henningfield, currently a member of the FDA tobacco products scientific advisory committee, was first author of a commentary describing theoretical adverse consequences of dual use (citation here). Despite his concerns, Henningfield acknowledged that “There are virtually no data that currently exist on the safety of such use or the degree to which such use will foster the perpetuation of smoking or contribute to reduced overall smoking…The issue warrants further study.”

That study has now been done, and the results have been published online in Nicotine & Tobacco Research (abstract available here). In a review of 17 published research studies that had data on the health risks from dual use versus those from smoking, almost all of which have appeared since 2002, Kimberly Frost-Pineda and colleagues conclude that “…there are not any unique health risks associated with dual use of smokeless tobacco products and cigarettes, which are not anticipated or observed from cigarette smoking alone.” The authors further commented that “some data indicate that the risks of dual use are lower than those of exclusive smoking.”

Frost-Pineda and colleagues also found evidence from both American and Swedish longitudinal studies that dual users were more likely than exclusive smokers to quit smoking, but less likely to become completely tobacco-abstinent. For example, one American study (abstract here) found that 11% of dual users were tobacco-abstinent after 4 years of follow-up, compared with 16% of exclusive smokers. However, 80% of exclusive smokers were still smoking at the 4-year follow-up, while only 27% of dual users were smoking; 44% were still dual users and 17% were exclusive smokeless users. The differences between smokers and dual users in Swedish follow-up studies are even more impressive.

This excellent review will present major problems for Henningfield and other FDA panelists, including Greg Connolly, Dorothy Hatsukami, Jonathan Samet and Neal Benowitz, because they have established solid records opposing tobacco harm reduction. Samet, the panel’s chair, summed up this opposition in a 2009 article in the Journal of the American Medical Association (citation here ): “Snus, a moist snuff that is low in tobacco-specific nitrosamines, has received particular attention because it has been widely used in Sweden, apparently with little increase in risks for cancer and cardiovascular disease. However, there is concern that strategies to introduce lower-risk products will diminish efforts to promote prevention and cessation.”

For over 40 years, “prevention and cessation” efforts have largely failed. But tobacco prohibitionists continue to focus on those objectives, while raising a host of largely theoretical concerns about the substitution of smokeless tobacco for cigarettes. Now, scientific research shows that the “problem” of dual use is not a problem at all.

A final note: The authors of the dual use study are employees of Altria Client Services, which is owned by the parent company of Philip Morris and U.S. Smokeless Tobacco. They should be complimented for this contribution to the scientific literature on tobacco harm reduction. The editors of Nicotine and Tobacco Research deserve kudos for reviewing and publishing this manuscript.

Tobacco Harm Reduction: Not During Pregnancy (Revisited)

In May, I discussed a 2003 Swedish study reporting that pregnant women who use snus are at risk for slightly smaller babies, and have modestly elevated risks for premature delivery and preeclampsia (read the post here). Two new studies from Sweden also document that snus use has risks for the developing baby and should be avoided.

Both studies are based on over 600,000 pregnancies documented in the Swedish Medical Birth Register from 1999 to 2006, and both are authored by Anna-Karin Wikström and colleagues from the Karolinska Institute.

The first study, published in the British Journal of Obstetrics and Gynaecology (sic) (abstract here), examined the effect of tobacco use on the risk for very premature (less than 32 weeks) or moderately premature (32-26 weeks) births. It showed that snus users had a modestly elevated risk for a very premature birth (adjusted odds ratio, aOR = 1.38, 95% confidence interval = 1.04 – 1.83). The risk among light smokers (1-9 cigarettes per day) was 1.60 (CI = 1.42 – 1.81), and the risk among heavy smokers (10+ cigarettes) was 1.90 (CI = 1.61 – 2.25). The study also showed that snus users had an elevated risk for a moderately premature birth of 1.25 (CI = 1.12 – 1.40), which was intermediate between light smokers (aOR = 1.18, CI = 1.12 – 1.24) and heavy smokers (aOR = 1.45, CI = 1.35 – 1.56).

The second study, published in Epidemiology (abstract here ), examined the effect of tobacco use on the risk for stillbirth, which is the death of a baby during pregnancy. It showed that women who were snus users had a modestly elevated risk (aOR = 1.57, CI = 1.03 – 2.41), which was again intermediate between light smokers (aOR = 1.15, CI = 0.91 – 1.45) and heavy smokers (aOR = 1.85, CI = 1.39 – 2.46).

The study I discussed in May found that snus use was associated with preeclamsia, but Wikström and colleagues did not report a statistically significant elevated risk. In addition, they reported that snus users did not have elevated risks for bleeding or for infants who were small for their gestational age, both of which are seen in light and heavy smokers.

In general snus use is vastly safer than smoking, but pregnant women should refrain from using all tobacco products.

The American Heart Association Has No Compassion for Smokers

On September 13, the American Heart Association released a policy statement opposing the use of smokeless tobacco (ST) to quit smoking. The statement (available here), based on a selective review of the literature, warns that ST might have risks for cardiovascular disease.

The Heart Association’s rejection of tobacco harm reduction is contradicted by the evidence presented in its review.

Here are the diseases that were reviewed, and the authors’ assessment of the risks among ST users:

Hypertension (high blood pressure): “In summary, data from the majority of studies in this section do not support an increase in the incidence or prevalence of hypertension in ST product users.”

Myocardial Infarction (heart attack): “In summary, data derived from the majority of studies conducted in Sweden, whereby snuff/snus is the major ST product used, have not demonstrated a significant increase risk of nonfatal or fatal MI…Data derived from predominately US populations are equivocal…More research is needed in the United States with currently marketed ST products to assess the potential relationship between ST product use and MI risk in the US population.”

Stroke: “In summary, data from 2 studies (1 from the United States and 1 from Sweden) suggest that ST product use is associated with a slight increase in the risk of stroke mortality…More research is needed in the United States regarding currently marketed ST products to assess the potential relationship between ST use and stroke risk in the US population.”

Other Cardiovascular Risk Factors: “Although the data are limited, most studies have found no relationship between ST use and other biochemical risk factors for [cardiovascular diseases].”

Diabetes and Metabolic Syndrome (a complex disorder involving increases in blood sugar, blood lipids, blood pressure and weight): “Based on data from two of the above studies conducted solely in Swedish populations, heavy use of moist snuff appears to increase the odds of developing [metabolic syndrome] and type 2 diabetes.” This interpretation should be placed in perspective. One Swedish study (abstract here) found that heavy users of snus (5+ cans per week) had modestly elevated risks for metabolic syndrome (odds ratio = 1.5 – 2.0), but moderate users (4 cans or fewer) had no risk. With respect to type 2 diabetes, one Swedish study (here) found an increased risk in users of 3+ cans per week (OR = 2.7, CI = 1.3 – 5.5), while two other studies (here and here) found no risk in snus users; the second study was not included in the Heart Association review. In summary, if the risks are real, they are modest and only present in heavier users.

So, after a comprehensive review, the authors concluded that there were no markedly increased risks for any cardiovascular disease. Yet, on the basis of very limited evidence, “the American Heart Association does not recommend the use of ST as an alternative to cigarette smoking or as a smoking cessation product.”

Each year 118,000 Americans die from cardiovascular diseases attributed to smoking. Why is the Heart Association denying these smokers a vastly safer alternative?

The authors were unable to find any substantially elevated risks related to ST use, yet the Heart Association press release and other materials are decidedly prohibitionist. Here is a media sound bite by first author Mariann Piano: “[Health professionals] need to respond by continuing to emphasize that none of their patients should be using any kind of tobacco product. So that does include all forms and types of ST products. And so they need to absolutely emphasize that their patients should never begin smoking and that smoking cessation, for those who do use cigarettes, or cessation of ST products. We again don’t advocate the use of any tobacco products.”

Piano’s prohibitionist rhetoric is surprising, because in 2001 she was on a Heart Association panel that delivered a balanced message on the impact of alcohol on heart diseases (available here). That report concluded:

“Moderate intake of alcoholic beverages (1 to 2 drinks per day) is associated with a reduced risk of [coronary heart disease] in populations…Although moderate use of wine and other alcohol-containing beverages does not appear to lead to significant morbidity, alcohol ingestion, unlike other dietary modifications, poses a number of health hazards…The American Heart Association maintains its recommendation that alcohol use should be an item of discussion between physician and patient.”

The Heart Association could have issued a similar policy with respect to ST as a substitute for cigarettes, but tobacco prohibition prevailed. The list of authors includes several prohibitionists, most prominently Neal Benowitz, who I discussed previously (here). He has established a clear position against tobacco harm reduction, which is especially disturbing since he is on the FDA’s tobacco products scientific advisory committee.

The Heart Association has rejected ST; what does it recommend for smokers? Its quit smoking website (here) offers smokers these tips, among many others:

• Lie back in a comfortable chair and relax for 10 to 15 minutes. Use a relaxation tape. If you don't have time for a full session, breathe in deeply and slowly while you count to five. Then breathe out slowly for 5 counts.
• Take a short walk.
• Start a hobby that calms you, such as making models, sewing or doing jigsaw puzzles.
• Warn your family and friends that you may be in a bad mood for a few weeks.
• Do something to improve your self-image. For example, shop for clothes to go along with the "new" you, or get a new haircut.

The American Heart Association has rejected tobacco harm reduction for the thinnest of reasons. Yet it wants smokers to manage one of the most powerful of human addictions with a jigsaw puzzle, a relaxation tape or a new haircut. The Heart Association should be expected to take a more positive and compassionate role in preventing the 118,000 cardiovascular disease deaths that result each year from smoking.

Is “Never Recommend A Carcinogen” An Appropriate Policy? Apparently Only For Tobacco

The Wall Street Journal’s “Numbers Guy” Carl Bialik blogged in April on the scientific debate about promoting smokeless tobacco as a substitute for cigarettes (read it here). Bialik’s well-balanced article included expert comments on the science of tobacco harm reduction, in addition to quotes from the usual array of individuals and organizations opposed to offering smokers safer options.

On re-reading Bialik’s article, I was struck by one passage in particular:

“‘We wouldn’t recommend anybody using a product that causes cancer,’ said Cathy Backinger, chief of the tobacco control research branch at the National Cancer Institute.”

At first glance, the comment sounds perfectly reasonable. Surely no one at the NCI would recommend that ANYBODY use a product that causes cancer. Well, it turns out that this is completely false. In fact, the NCI recommends routinely that women take a medication that is known to cause two forms of cancer.

The medication is tamoxifen, which, according to an NCI website (available here), “interferes with the activity of estrogen, a female hormone that can promote the development of cancer in the breast.” The NCI states that “Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) for the prevention of breast cancer and for the treatment of breast cancer, as well as other types of cancer.”

In other words, the NCI endorses the use of tamoxifen by women who don’t have breast cancer but who are at risk of developing it.

But there’s a problem. The NCI acknowledges that “Tamoxifen increases the risk of two types of cancer that can develop in the uterus: endometrial cancer, which arises in the lining of the uterus, and uterine sarcoma, which arises in the muscular wall of the uterus.” The NCI says tamoxifen doubles the risk for endometrial cancer; the magnitude of the sarcoma risk is not specified. The NCI also cautions that “women who took tamoxifen had an increased chance of developing blood clots and an increased chance of stroke.”

The NCI justifies the use of tamoxifen with a straightforward rationale: “The benefits of tamoxifen as a treatment for breast cancer are firmly established and far outweigh the potential risks. Patients who are concerned about the risks and benefits of tamoxifen or any other medications are encouraged to discuss these concerns with their doctor.”

There are legitimate reasons to recommend tamoxifen for women who are at risk for developing breast cancer. Similarly, there is a rock-solid scientific and medical foundation for recommending smokeless tobacco – with cancer risks that are barely measureable by modern epidemiologic methods – to smokers who otherwise face far higher risks of developing a plethora of medical illnesses.

If the Backinger principle was adopted by physicians, they would withhold tamoxifen from women at risk for breast cancer on the grounds that it may cause cancer of the uterus. That application would violate principles of public health and condemn thousands of women to a life with – and perhaps death from – breast cancer. Dr. Backinger’s refusal to consider tobacco harm reduction similarly violates public health principles and condemns millions of inveterate smokers to a disease and death.

Public health policies should be consistent in using scientific evidence of relative risk to promote legitimate life-saving strategies.

Outstanding News Report On Smokeless Products

KMSP Fox 9 in Minneapolis-St. Paul recently aired an excellent news report on new smokeless tobacco products, including dissolvable Camel Orbs, Sticks and Strips and Camel snus (Click on the image above to see the video).

The station focused on a new Minnesota law that puts all tobacco products behind the counter and out of the reach of children. Kelly Valen, a 43-year-old smoker who blames her addiction on easy cigarette availability, is excited about the law but sadly oblivious to what the rest of the story delivers: information about vastly safer smokeless alternatives.

Discussing types of “tobacco you may not even heard of yet,” the station turned to Mike Sheldon of Clearway Minnesota as an authority on “more innovative and new tobacco products.” He presents an informative display of orbs, sticks, strips and snus, saying “they’re smokeless and spitless, and that’s trying to take away the social stigma of smokeless tobacco products of the past” -- an accurate description of the advantages of these new cigarette substitutes.

KMSP says that while these products aren’t for sale yet in Minnesota, the dissolvables are available in test market cities Indianapolis, Portland, Oregon and Cincinnati. (Actually, they’re available in Columbus, not Cincinnati.) Camel snus is sold nationwide.

It is important for smokers to learn about safer, satisfying, spitless smokeless products, but FDA regulations severely restrict what manufacturers can tell smokers about these innovative new products. Clearway Minnesota and KMSP have contributed to public health with this informative new feature.

Snus Use Is Not Associated with Gastrointestinal Problems

A new study (abstract here) published in the European Journal of Epidemiology finds that snus use in Sweden is not associated with gastrointestinal (GI) problems.

A detailed GI symptoms questionnaire was distributed to 3,000 adults age 18 to 80 years in the northern Swedish cities of Kalix and Haparanda. Questions concerned gastroesophageal reflux (GER), dyspepsia (pain above the stomach and/or nausea and feeling uncomfortably full after a meal), irritable bowel syndrome (IBS) and other conditions.

About 1,000 survey respondents were subjected to endoscopic exams of their upper GI tracts, searching for ulcers of the esophagus, stomach and small intestine and for evidence of infection by Helicobacter pylori (bacteria which can cause stomach ulcers). Snus users (n = 96), smokers (n = 165) and dual users (n = 22) were compared with non-users (n = 432).

The percentages of snus users reporting GI symptoms were no different than those among non-users. In contrast, smokers were more likely to report dyspepsia (OR = 1.6, 95% CI = 1.1 – 2.2), and dual users were more likely to report dyspepsia (OR = 2.8, CI = 1.1 – 7.3) and IBS (OR = 3.3, CI = 1.3 – 8.2).

With respect to the endoscopy findings, snus users were no more likely than non-users to have ulcers of the esophagus, stomach or small intestine. Smokers were more likely to have peptic ulcer disease (OR = 2.3, CI = 1.0 – 5.2). The published paper presents detailed findings of numerous other minor studies that were performed. Compared with non-users, neither snus users nor smokers had elevated rates of Helicobacter infections.

It is widely known that Swedish snus users place the tobacco in their upper lip, which results in minimal tobacco juice production, eliminating the need to spit. But a small amount of tobacco extract is swallowed, causing some users to worry about potential effects on the GI tract. This study offers reassurance that snus use is not associated with any significant GI symptoms or disorders.

Federal Agencies Agree: Phrase “Spit Tobacco” Is Inappropriate

Readers of this blog may remember my July 14 post (available here) describing the use of the derogatory term “spit tobacco” on websites run by the FDA and the National Institute of Dental and Craniofacial Research (NIDCR). At that time, I wrote to the directors of the agencies, asking them to remove this offensive language from their sites.

I have just received reply letters from both agencies. Susan Johnson, Director of the Office of Communications and Health Education at NIDCR, wrote that the institute “is in the process of substituting ‘smokeless’ (or product-specific terms) for ‘spit’ in our online materials; we anticipate these changes will be completed by the end of August 2010.”

In a separate letter, Anne Henig, from the Office of the Director of the FDA Center for Tobacco Products, advised: “NIDCR has updated its webpage and changed the title to Smokeless Tobacco: A Guide for Quitting” (here)...FDA has also updated its webpage to reflect NIDCR’s change. I hope these modifications will address your concerns.”

I appreciate the timely responses from NIDCR and FDA. I’m encouraged that officials at these agencies have joined the CDC in resolving to treat smokeless tobacco users with respect and dignity.

New Study Confirms No Significant Risk for Cardiovascular Diseases Among Smokeless Users

A study just released by the American Journal of Epidemiology (abstract here) confirms that smokeless tobacco use is NOT associated with a significantly increased risk of cardiovascular diseases.

Regrettably, this important finding will not dominate the headlines. Authors Hiroshi Yatsuya and Aaron Folsom chose to emphasize a partially analyzed result that vilifies smokeless tobacco, while largely ignoring the most valid estimate of smokeless risks, namely that they are only minimally elevated and not statistically significant.

The research was based on the Atherosclerosis Risk in Communities (ARIC) study, which recruited almost 16,000 people age 45-64 years in 1987-89 from Forsyth County North Carolina; Jackson Mississippi; suburbs of Minneapolis; and Washington County, Maryland. An enormous amount of information about cardiovascular risk factors was collected, and episodes of heart attacks and strokes were recorded up to 2005.

This Yatsuya study reported hazard ratios (interpreted similarly to relative risks, which are described here) for heart attacks and strokes among smokeless tobacco users compared with never users. When reporting risk due to one factor – in this case, smokeless tobacco – investigators must adjust the estimate for differences in other well-recognized risk factors that might affect the results. This is especially important for heart attacks and strokes, which have many risk factors.

The importance of such adjustments is easily explained. In this study, for example, smokeless users had a higher rate than nonusers of diabetes, a potent risk factor for heart attacks that is not related to smokeless use. Therefore, researchers use techniques to adjust the heart attack risk for smokeless tobacco users to account for the difference in the diabetes rate. This process is repeated for all the other risk factors.

After adjustment for age, sex, race, education, income, alcohol use, physical activity and smoking, Yatsuya and Folsom reported that smokeless tobacco users have a 29% excess risk of heart attacks and strokes (95% Confidence Interval, 8 – 55%). Adjusting for all of these factors is appropriate, but not complete.

After further adjusting for pipe/cigar smoking and exposure to secondhand smoke, the excess heart attack and stroke risk among smokeless users was 27% (CI = 6 – 52%). This is the only result that Yatsuya and Folsom chose to highlight in the abstract. It is still only a partial result, because they had information on many other important risk factors, such as blood pressure, use of blood pressure medicines, diabetes, weight, and serum fat levels. The result after adjustment for these factors was buried in the fine print of the paper. The excess risk dropped to 21% (CI = 0 – 45%), which is 22% lower than their touted number and not statistically significant.

Why did Yatsuya and Folsom downplay the most valid result for smokeless tobacco users? Why did the journal’s reviewers and editors not insist that Yatsuya and Folsom report the results in a fair and balanced manner? One possible answer: An unbiased report about smokeless tobacco use would not have offered these strident conclusions in both the paper and the abstract: “Current users of smokeless tobacco should be informed of its harm and advised to quit the practice. Current smokers should also be given sufficient information on safe, therapeutic methods of quitting which do not include switching to smokeless tobacco.”

Can we conclude from this study that smokeless tobacco is not associated with heart attacks and strokes? Of course not. But the most valid risk estimate is so small that the authors had to all but bury it in order to support their abstinence agenda. The bottom line for consumers is that this study confirms that smokeless tobacco use is NOT associated with a significantly increased risk of cardiovascular diseases.

Straight Talk About E-Cigarettes

Electronic cigarettes (e-cigarettes) pose important issues relevant to tobacco harm reduction. This post will review the facts about these products, which have been the subject of exaggerated claims by e-cigarette proponents and nicotine prohibitionists alike. As with most complex issues, the truth about e-cigarettes lies somewhere in between.

When users draw on them, battery-powered e-cigarettes vaporize a mixture of water, propylene glycol, nicotine and flavorings. Nicotine is one of the most intensively studied drugs in history; while it is highly addictive, it is not the primary cause of virtually any of the diseases related to smoking. In fact, long-term nicotine consumption is about as safe as that of caffeine. Propylene glycol is approved by the FDA for use in a large number of consumer products; it, too, is sometimes vaporized, forming artificial smoke in theatrical and other productions.

It is almost certain that e-cigarette use (also called vaping) is vastly safer than cigarette smoking, but this is based on limited scientific evidence. Some questions remain unanswered.

The health effects of long-term exposure of the respiratory tract to propylene glycol vapor are unknown, and unknowable. As a health professional, I am more comfortable recommending a product with a defined risk profile, where a clear risk-benefit analysis can be evaluated. That is why I have been a strong supporter of smokeless tobacco products as cigarette substitutes. I recommend these products knowing that we have 50 years of epidemiology documenting the extremely low level of health risks. E-cigarette consumers must understand that the safety of e-cigarettes can not be guaranteed, despite the likelihood that they pose but a tiny fraction of the health risks of regular cigarettes. But given the paucity of legitimate research, specific safety claims for e-cigarettes can not be made.

There is a lot of uncertainty with respect to the reliability of e-cigarettes, essentially all of which are imported from China. One of my colleagues ordered numerous products with the intent of performing some routine tests; many of these products did not function properly right out of the box. According to a recent clinical study of two brands (abstract here), “…neither of the electronic cigarettes exposed users to measurable levels of nicotine or [carbon monoxide]…” Not inhaling carbon monoxide is a good thing, but for addicted smokers, not getting nicotine may be a problem. Many e-cigarette users know that the devices often don’t deliver enough nicotine to satisfy them, so they re-load cartridges with even higher doses from commercially available concentrated solutions. Concentrated nicotine is dangerous, and this kind of experimentation is bound to lead to injuries.

The same study showed that “…both [brands] suppressed nicotine/tobacco abstinence symptom ratings.” This is impressive, because it indicates that e-cigarettes simulate the behavioral aspects of smoking and therefore may be successful in ways that no other smoking cessation product can match.

E-cigarette cartridges may contain hazardous contaminants. Last year, the FDA conducted laboratory tests on a few e-cigarette cartridges. Although the tests were biased and flawed (as I discussed here), they found in one cartridge traces of diethylene glycol, a poisonous impurity found previously in propylene glycol (reported here).

Consumer products should be free of contaminants. Cartridges, as well as the hardware, should be subjected to independent quality control testing. The FDA tests underscored the need for regulatory oversight. This could be accomplished if the FDA regulated e-cigarettes as recreational tobacco products under authority from the Tobacco Act. Instead, the FDA is attempting, inappropriately according to one federal judge, to regulate them as drug-delivery devices (discussed here). That would effectively remove them from the American market, leaving hundreds of thousands of e-cigarette users with no satisfactory alternative to tobacco combustion.

There is no justification or scientific rationale to ban e-cigarettes. Still, anti-tobacco extremists are campaigning against them, claiming, entirely without proof, that they are a starter tobacco product for children. As with all tobacco products, they should not be available to minors.

Another battle rages over whether e-cigarettes can be used safely indoors. Some militant users object to any indoor restrictions, while prohibitionists claim that second-hand vapor is annoying and/or toxic. The latter claim is preposterous, but e-cigarette users who are courteous and respectful toward bystanders are likely to lead longer, healthier and less stressful lives.