Thursday, December 29, 2011

Low Nitrosamine Levels in Altria and Reynolds Moist Snuff Products, say Minnesota Researchers

I discussed a year ago the tempest-in-a-teapot issue of tobacco specific nitrosamines (TSNAs) in smokeless tobacco products (here). TSNAs are contaminants found only in tobacco, and they are present in vanishingly small concentrations – mainly in the single-digit parts-per-million range. “Regardless of current TSNA levels,” I wrote, “anti-tobacco extremists will call for reductions.”

Last month, the University of Minnesota’s Stephen Hecht, Irina Stepanov and Dorothy Hatsukami (a member of the FDA Tobacco Products Scientific Advisory Committee) published a letter in Tobacco Control (here), demanding TSNA reductions. This, despite the fact that their data showed that TSNA levels in moist snuff products from Altria and Reynolds were at historically low levels in 2010. I have commented on this group’s anti-smokeless-tobacco articles before (here and here).

Hecht et al. list the levels of NNN and NNK in several Altria and Reynolds brands:


NNN + NNK Levels in Moist Snuff and Snus, in Parts Per Million (ppm), Dry Weight
Brand NNN+NNK (ppm)
Altria
Copenhagen 5.6
Copenhagen Long Cut 5.8
Copenhagen LC Wintergreen 4.6
Skoal Long Cut Straight 4.9
Skoal Long Cut Wintergreen 5.2
Skoal Bandits Wintergreen 5.2
Marlboro Snus Rich 0.7
Marlboro Snus Spearmint 0.9
Marlboro Snus Peppermint 0.8
Marlboro Snus Mild 0.8
Reynolds
Grizzly11.1
Kodiak Wintergreen 5.1
Camel Snus Frost 1.5
Camel Snus Mellow 1.7

These NNN and NNK levels are lower, across the board, than those of moist snuff products from the 1980s and 1990s, which I documented in a review article in 2004 (here). Epidemiologic studies from the 1980s and 1990s show that oral cancer risks among moist snuff users were minimally elevated, if at all, when those higher level products were being used.

While Hecht and colleagues assert that “smokeless tobacco is carcinogenic to humans, causing oral, pancreatic and esophageal cancer,” a comprehensive study of cancer risks among smokeless users (here) documented no significant risk for any of these cancers. There is virtually no evidence that current TSNA levels are associated with ANY significant cancer risks. Reducing current levels cannot lower an immeasurable cancer risk.

The article by Hecht et al. indicates that the authors are comfortable with TSNA levels in Marlboro and Camel snus, and that they view these products as acceptable cigarette substitutes. Perhaps Drs. Hecht, Stepanov and Hatsukami will now endorse them in this manner.

Wednesday, December 21, 2011

Allegations and Answers in Owensboro

A letter published in the Owensboro Messenger-Inquirer on December 12 challenged the veracity and ethics of the Switch and Quit Owensboro campaign (described here). The letter, authored by a former administrator of the Kentucky oral/dental health program, reflected the hostility towards tobacco harm reduction that is common among dental organizations (previously described here and here).

The Messenger-Inquirer published this response from me on December 19:

To the Editor,

Dr. Jim Cecil’s December 12 letter criticizing Switch and Quit Owensboro contained serious inaccuracies.

Dr. Cecil states that smokeless tobacco products “are known to cause” a number of diseases. In fact, research shows that the health risks from smokeless use are so minuscule that they are barely measurable, and they are a tiny fraction of the health risks associated with smoking. Dr. Cecil suggests that smokers only be told about “FDA-approved smoking cessation aids,” but those products succeed with only 7% of smokers. Smokeless tobacco works as a cigarette substitute because it satisfies nicotine cravings; it is also more affordable and more widely available than nicotine medicines.

Dr. Cecil incorrectly states that “there is no scientific evidence that smokeless tobacco can help a smoker quit!” Numerous scientific studies published in prestigious medical journals document that smokeless tobacco is an effective quit-smoking tool. These studies are summarized in two comprehensive reviews in Harm Reduction Journal (here and here).

Rather than being an industry ploy, as Dr. Cecil implies, Switch and Quit embodies a smoking cessation concept that has been endorsed by the esteemed British Royal College of Physicians (among others), which found “...that smokers smoke predominantly for nicotine, that nicotine itself is not especially hazardous, and that if nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved.” (available here)

Dr. Cecil believes it is “unconscionable” and “unethical” to inform smokers about vastly safer smoke-free tobacco products. Consider this fact: If all American smokers instead used smokeless tobacco, over 430,000 lives would be saved each year. The Switch and Quit campaign is consistent with the highest medical and ethical standards.

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

Thursday, December 15, 2011

Karolinska Institute Study: Heart of Failure


I have described in detail (here, here, and here) studies from Stockholm’s Karolinska Institute (KI) that have driven smokeless tobacco regulation worldwide. These studies contain important and troubling discrepancies that KI researchers have refused to address. Rather, they continue to defy international scientific principles of data sharing, which stipulate that scientific results are open to challenge by other scientists to determine their accuracy and integrity.

Some of the same KI researchers, led by Gabriel Arefalk, recently authored another study, alleging that snus use causes heart failure (here). The article was published in the European Journal of Cardiovascular Prevention and Rehabilitation.

As in the past, KI focused on snus users in the Swedish Construction workers cohort. This time, construction workers who were snus users didn’t have a significantly higher risk for heart failure than nonusers. But the researchers also analyzed the Uppsala Longitudinal Study of Adult Men (ULSAM), reporting that snus use “was associated with a more than doubled risk for subsequent heart failure” in this group.

It appears that the ULAM analysis was tailor-made to produce the desired result, and it is evident that the KI researchers employed highly unorthodox methods. I attempted to draw attention to these serious problems by submitting a letter to the journal editor. My submission was rejected, “on grounds that this commentary is a re-review of the analyses of the paper.” Ignoring my systematic description of the study’s deficiencies, the editor suggested that I “obtain data and write another scientific paper for the journal.” This is particularly ironic, since I have tried for three years to obtain data from KI.

Following is my letter to the European Journal of Cardiovascular Prevention and Rehabilitation.

To the Editor:
Study of Snus Use and Heart Failure: Problems Requiring Resolution


The article by Arefalk et al. (1) reported that snus use was “a significant predictor of heart failure” among 70 year-old men in the Uppsala Longitudinal Study of Adult Men (ULSAM) (hazard ratio, HR = 2.09, 95% confidence interval, CI = 1.00 – 4.39). However, there are numerous problems that raise questions about the validity of the findings.

Among the 78 snus users at baseline, 62 (79%) were current smokers; in the referent group of 998 snus non-users, only 175 (18%) were current smokers. The large difference in smoking makes it extremely unlikely that the results were fully adjusted for current smoking, which is an important confounding factor (2). This problem was compounded by the authors’ highly unorthodox adjustment procedure.

The authors apparently did not utilize conventional categories of current, former and never smoking, even though it was clearly possible to do so according to the ULSAM questionnaire (3). Instead, they stated that “[s]moking was adjusted for by using a current smoking dose variable [none, < 10 or > 10 cigarettes per day] as well as a pack-year variable [never, < 33 and > 33 pack-years].” But this created a major problem: the 504 former smokers were combined with the 335 never smokers in the current smoking dose variable, and they were combined with the 237 current smokers in the pack-years of smoking variable (Table 1, Column labeled Total Sample). Thus, in the authors’ adjusted models former smokers were simultaneously pooled both with never smokers and with current smokers, two groups that ought to be mutually exclusive.

Although Arefalk et al. failed to define or categorize current and former smokers in the ULSAM cohort, the latter group appeared in the discussion: “…we performed a secondary analysis…further subdividing former smokers into those who quit smoking less than vs. more than 10 years before baseline.” Mentioning former smokers in the last third of the discussion without ever defining them is incomprehensible. In addition, the authors’ 10-year cut-point for smoking cessation was different from the 5-year cut-point in the questionnaire (3). The authors need to provide a complete explanation of the analysis that they employed.

Arefalk et al. reported that there were 78 snus users, which is consistent with the number on the ULSAM website (questionnaire item Z480, “Do you use snus?”; yes, n=79)(3). They also described 237 current smokers (167 moderate and 70 heavy), which was consistent with responses to the question asked during a euglycemic hyperinsulinemic clamp investigation, “Do you smoke?” (Z085; yes, n=245), but not with responses to the questionnaire item “Do you smoke?”(Z158; yes, n=173) (3). It would be helpful to understand the differences in these responses.

Arefalk et al. also estimated the risk of heart failure among snus users in the Swedish Construction Workers Cohort (CWC), and they evaluated the effect of dose among the 75 current snus users with heart failure (Table 4). They concluded that “[n]o clear dose-response relationship was observed…” In contrast, Arefalk et al. reported that “the limited sample size did not permit the study of dose-response relations” in the ULSAM cohort. This important information, which was available for the 14 snus users with heart failure (3), may be very informative even if it was inadequate for a formal analysis. For example, perhaps all 14 cases of heart failure were among users of very low doses. Arefalk et al. should not withhold this information.

There were numerous formatting errors in the tables. For example, in Table 1 the variables Diabetes prevalence, ECG-left ventricular hypertrophy, Body mass index, Office systolic blood pressure and Antihypertensive medication use were listed under Pack-years of smoking, and the variables Myocardial infarction before baseline and Myocardial infarction during follow-up were listed under Alcohol use. There were similar errors in Table 4.

Arefalk et al. concluded that they “observed an increased risk for subsequent heart failure” among male snus users in the ULSAM, but the conclusion is neither legitimate nor persuasive until the authors resolve the fundamental questions about the analysis.

References

1. Arefalk G, Hergens M-P, Ingelsson E, Ärnlöv J, Michaëlsson K, Lind L, Ye W, Nyrén O, Lambe M and Sundström J. Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts. European Journal of Cardiovascular Prevention and Rehabilitation 2011, DOI: 10.1177/1741826711420003 (here).

2. Dunlay SM, Weston SA, Jacobsen SJ, and Roger VL. Risk factors for heart failure: a population-based case-control study. American Journal of Medicine 2009; 122: 1023-1028 (here).

3. ULSAM-70 Questionnaire and Response Statistics (here).

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

Thursday, December 8, 2011

Tobacco Retailer Compliance High, Says FDA Data

The Food and Drug Administration issued a press release on November 10 (here), titled “FDA acts to protect children from illegal tobacco sales.” It advises that “most retail establishments inspected by the FDA have been found to be in compliance with the law” restricting sales of tobacco to minors. The release focused on warning letters sent “to more than 1,200 retailers, the majority of which respond to violations relating to selling tobacco to minors, as part of its ongoing effort to reduce tobacco use among children.”

FDA Commissioner Margaret A. Hamburg is quoted: “It should worry every parent that 20 percent of U.S. high school students smoke cigarettes…Retailers are vital partners in the FDA’s efforts to prevent tobacco use among kids.”

What the FDA didn’t report is that in most states, retailer compliance is outstanding. I downloaded the raw data from the agency’s website and noted compliance statistics for the available states:


FDA Tobacco Retail Compliance Inspections in 16 States
State Number of Inspections Compliance Rate (%)
Alabama 2,12299
Arkansas 68096
Arizona 81894
Colorado 1,68292
Idaho 32399+
Illinois 95093
Kansas 2,01699+
Massachusetts 2,81396
Maryland 1,47799
Maine 3,13799+
Missouri 1,03388
Mississippi 3,41994
New Jersey 1--
Pennsylvania 1,81394
Tennessee 82996
Washington 1,30593
All 24,41896

Retailers in all states combined showed a 96% compliance rate, with every state except Missouri above 90%. Retailers in Alabama, Idaho, Kansas, Maryland and Maine demonstrated compliance rates of at least 99%.

As I noted in an earlier post (here), the principal suppliers of tobacco to underage users are adult friends or relatives, according to a 2004 study (abstract here).

The FDA should continue to monitor retailers, but when it comes to children’s access to tobacco, retailers are clearly not the major problem.