FDA Rejects Plea to Correct Smokeless Tobacco Warnings; A Closer Look at Flawed Interpretations

After two and a half years’ review, the FDA Center for Tobacco Products rejected Swedish Match’s request to eliminate or revise the 30-year-old, egregiously inaccurate warnings that are required to appear on snus products sold in the United States. 

In 2014, Swedish Match sought to:

·         Remove the warning, “This product can cause gum disease and tooth loss”;

·         Remove the warning, “This product can cause mouth cancer”; and,

·         Replace the warning, “This product is not a safe alternative to cigarettes” with this text: “No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.”

I explored this issue earlier (here).

The FDA justified its rejections in a six-page letter to the company (here) in a 115-page supporting document (here), and subsequently in an announcement proclaiming, “FDA Issues Science-Based Decisions on First MRTP Applications.” 

Science-based?  Following is my review of the FDA’s tortured interpretation of the scientific evidence in its decisions on the gum disease/tooth loss and mouth cancer warnings. 

Gum Disease/Tooth Loss Warning Decision

The agency interpreted removal of a warning as a marketing claim, obligating Swedish Match to prove that snus was entirely without risk – a virtually impossible task.  The FDA advised, for example, that “Omission of [the gum disease tooth loss warning] from a subset of smokeless tobacco products indicates that unlike other smokeless tobacco products, the eight General Snus products cannot cause gum disease or tooth loss.” (emphasis in original).

For this decision, the agency reviewed published studies of “dental conditions (e.g., plaque, caries, tooth wear or tooth loss), gingivitis, gingival recession and periodontal disease” that it claimed were related.  Here are the conclusions for each of these, with the FDA findings in bold:

·         Dental conditions: “Overall, the dental conditions data included no studies that evaluated tooth loss over time…The results on caries were mixed, and the only study to examine the association between Swedish snus and tooth wear found an association. No association was seen between Swedish snus and plaque…”

·         Gingivitis: “Overall the results of the studies on gingivitis were mixed.”

·         Gum recession: “Overall, the only adjusted study of gingival recession to include non-users found a significant positive association between Swedish snus and gingival recession, and several unadjusted studies found significant associations between Swedish snus and gingival recession, although the direction of the association was mixed.”

·         Periodontal disease: “Overall, nearly all of the studies which examine the association between Swedish snus and indicators of periodontal disease (plaque, pocket depth, attachment loss, bone loss) found no association…”

Note the repeated finding of “mixed,” suggesting that some studies showed a positive association while others showed no association or a negative one.  For periodontal, or gum, disease, there was no association. 

Despite these equivocal or nil findings, the FDA concluded: “Overall, the totality of the evidence demonstrates that the eight General snus products can cause gum disease and tooth loss, and, correspondingly, does not support the removal of the warning that these products can cause gum disease and tooth loss.”  The FDA's decision is entirely unsupported by the "totality of evidence."

Mouth Cancer Warning Decision

The FDA decision on mouth cancer is based on an improper analysis of six published studies.  Peter Lee in 2010 published a formal meta-analysis of these studies and one more (abstract here).  Here are his findings for mouth cancer:

“No overall association is seen for oropharyngeal cancer, the most studied cancer type.  For the whole population, an increase (RR 3.1, 95% CI 1.5–6.6) seen in the Uppsala county study (Roosaar et al., 2008), based on 11 cases, contrasts with six studies showing no increase, the overall estimate being 0.97 (0.68–1.37). The never smoker estimate, 1.01 (0.71–1.45), based on four studies, is also null. These results are supported by long-term follow-up of 1115 individuals with ‘‘snuff-dippers lesion’’ (Axéll et al., 1976), which observed no oral cancers at the sites of lesions seen initially (Roosaar et al., 2006).”

When Lee included Roosaar with the other studies in his analysis, there was no association of snus and mouth cancer.  The FDA basically agreed with Lee that Roosaar was the lone work that was positive for snus and mouth cancer, but it cited this study as the sole reason for maintaining the warning.  In fact, the FDA is saying it will ignore the broad consensus of scientific research (i.e. the "totality of evidence") if any one study reports a positive finding.

Having set this impossibly high bar for safer tobacco products, the FDA went further by focusing on tobacco-specific nitrosamines in snus.  Research documents that TSNAs exist in vanishingly small concentrations in snus – about two parts per million or lower (here), and there is no scientific evidence directly linking TSNAs to mouth cancer.  Still, the FDA cited “the presence of nitrosamines in the products that are the subject of these applications, the lack of a threshold dose for mouth cancer” as additional reasons to sustain the warning.  The FDA is effectively saying that TSNAs must be reduced to zero for the warning to be removed.

The FDA closed the door on the gum disease tooth loss warning, but it gave Swedish Match the option of submitting a revised application for the other warnings.  It appears that the agency’s revision/amendment pathway is designed to defeat all the but wealthiest and most determined applicants, leaving millions of smokers and future smokers with demonstrably false warnings against the use of safer smoke-free products.

Through with Chew Week: Don’t Be Fooled

Chewers and Dippers: It’s the third week in February, which means it’s time for you to be badgered by the annual Through with Chew public relations campaign.  Across the nation, tobacco prohibitionists are publishing unscientific and unsubstantiated claims about smokeless tobacco.  Here are recent examples from Fallon County, Montana and Boone County, Iowa, followed by the facts

Claim 1: “chew products deliver a higher dose of nicotine than cigarettes, making the product more habit forming.”

The Facts: The amount of nicotine that smokeless tobacco “delivers” is irrelevant, because chewers and dippers use products in ways that satisfy them.  In fact, there is evidence from one of the world’s foremost authorities on nicotine addiction that smokeless tobacco is less habit-forming than cigarettes (here and here).  Most Americans are badly misinformed about the absence of significant health effects of nicotine (here).  

Claim 2: “Smokeless ‘Spit’ tobacco contains over 2,000 chemicals.”

The Facts: Every natural product, including coffee contains thousands of chemicals (here).  A product’s chemical composition is unimportant if it carries little or no risk.  Like coffee, smokeless tobacco fits in that category.

Claim 3: “Chew contains at least 28 chemicals that have been found to cause cancer…”

The Facts: Almost everything we eat contains cancer-causing chemicals, but they are in trace levels that present no risk.  Again, coffee is a prime example (here).  Numerous scientific studies prove that there are vanishingly small levels of carcinogens in modern smokeless tobacco products (here, here, here, here, here). 

Claim 4: “Harmful effects of smokeless tobacco include mouth, tongue, esophageal, and throat cancer…stomach and pancreatic cancer”

The Facts: According to dozens of published epidemiologic studies (reviewed here), the risks for these cancers are not elevated.

Claim 5: “Harmful effects of smokeless tobacco include increased risk of heart disease, heart attacks and stroke.”

The Facts: Among the many risk factors for heart disease and stroke, smoking is one of the biggest.  That is not the case with smokeless tobacco.  When the American Heart Association conducted an extensive investigation of smokeless tobacco and heart disease, it found almost nothing (here).  Large studies from Sweden show that snus users do not have risk for heart attacks (here) and strokes (here), and snus use may even offer benefits for heart attack survival (here).

Claim 6: “Harmful effects of smokeless tobacco include leukoplakia (white sores in the mouth that can become cancer).”

The Facts: White patches are common in chewers and dippers, but they are nearly always benign.  The link with mouth cancer is virtually zero (here).

Claim 7: “Harmful effects of smokeless tobacco include receding gums, bone loss around the roots of the teeth, abrasion (wearing down) of teeth.”

The Facts: There is virtually no scientific evidence that smokeless tobacco is a risk factor for any dental problem (here, here).  In fact, one study shows that snus and moist snuff (dip tobacco) might be protective against cavities (here).

Don’t be fooled by bogus smokeless tobacco health claims.

Snus Use and Gum Disease: No Association

Swedish investigators have just published a study in the Journal of Clinical Periodontology documenting “no significant association between gingivitis, [periodontal pockets] and periodontal disease experience and snus use.” (abstract here). The authors are Anders Hugoson from Jönköping University and Margot Rolandsson from Karlstad University.

The study was based on 1,500 residents of Jönköping who took part in detailed dental health exams in 1983, 1993 and 2003. Hugoson and Rolandsson supervised teams of dentists who collected information on the number of teeth, plaque index, presence of inflammation of the gingiva (gum tissue), periodontal pocket depth, gum recession, calculus, and x-ray examination. The findings were used to classify participants according to the presence and severity of gum, or periodontal, disease. The results were adjusted for factors that might influence the development of periodontal disease, such as age, gender, and socioeconomic class (education, employment and marital status).

In comparison to nonusers of tobacco, smokers were more likely to have severe periodontal disease (odds ratios, OR = 3.0 – 6.5, which were statistically significant). The authors note, “Numerous epidemiological studies have demonstrated that of all the risks identified, cigarette smoking may be the most strongly associated with periodontitis.”

Severe periodontal disease among snus users was about as common as among nonusers of tobacco (OR = 0.8, not statistically significant). This is in essential agreement with a comprehensive review published by Kallischnigg and colleagues in BMC Oral Health in 2008 (available here). Furthermore, it suggests that the federally mandated smokeless tobacco warning, “This product can cause gum disease and tooth loss,” is not relevant to snus, if it is scientifically credible at all.

Hugoson and Rolandsson provide information on tobacco use for each year of the study. Following is the breakdown for men:

Proportion of Men in Jönköping Who Are Snus Users, Smokers and Nonusers
Year	Snus Users (%)	Smokers (%)	Nonusers (%)
1983	9	29	62
1993	13	17	70
2003	17	14	69

The prevalence of snus use among men doubled from 9% in 1983 to 17% in 2003, while the prevalence of smoking was cut in half, from 29% to 14%.

This study provides more evidence that use of snus by Swedish men has resulted in real benefits to their general and oral health.

The Truth About Federal Warnings on Smokeless Tobacco Products

Cigarette smokers who are considering a switch to vastly safer smokeless tobacco are confronted with confusing government-ordered warning labels. Most would be surprised to learn that three of the four mandated warnings were fabricated by tobacco prohibitionists and codified into federal legislation in 1986 by a misinformed U.S. Congress. Despite their obvious flaws, the original warnings were re-confirmed in the 2009 Tobacco Act and a fourth was added.

Here are the underlying facts and fallacies related to the four warnings:

1. “This product can cause mouth cancer.” This warning was mandated in 1986, five years after Dr. Deborah Winn egregiously misinformed Americans about the magnitude and scope of mouth cancer risk from smokeless tobacco (discussed previously in this blog here and here). This warning is highly misleading. Contemporary American and Swedish smokeless products confer vanishingly small risk for mouth cancer. Now that the FDA has been given authority over the warnings, I hope the agency will provide comprehensive information about all health risks, as I did in this blog (here and here).

2. “This product can cause gum disease and tooth loss.” In 1986, prohibitionists were desperate to blame smokeless tobacco for causing something besides mouth cancer, but twenty-five years ago there was virtually no scientific evidence that smokeless tobacco was an independent risk factor for any dental problem. The same is true today. A comprehensive review of the subject was published by Kallischnigg and colleagues in BMC Oral Health in 2008 (available here). The risk for all dental problems is either very low or nonexistent among smokeless tobacco users.

3. “This product is not a safe alternative to cigarettes.” The purpose of this 1986 warning was to deceive smokers into believing that smokeless tobacco was just as dangerous as smoking. As I wrote in my 1995 book, For Smokers Only: How Smokeless Tobacco Can Save Your Life (link), this warning “is simply ludicrous…Not even potato chips or nature hikes are ‘safe.’ If we look at ‘safe’ to mean relatively safe or ‘safer,’ something the government warnings inanely avoid here, then use of smokeless tobacco products is far safer than cigarette smoking.”

To apply an absolute standard of safety to any product or activity is preposterous. It’s worse to use this standard to deny smokers access to life-saving smokeless products and information.

4. “Smokeless tobacco is addictive.” This was added in the 2009 legislation, and it’s the only warning with a legitimate scientific rationale. It is entirely appropriate for consumers to be warned that any product containing nicotine is addictive. But the warning also reinforces what switchers already know -- that smokeless tobacco can be a satisfying cigarette substitute precisely because it provides satisfying doses of nicotine.

Congress was misinformed in 1986, when it dictated the mouth-cancer, gum-disease and not-safe warnings for smokeless tobacco. In view of the extensive relative risk data published since then, Congress should have revised the warnings to reflect the facts, rather than just rubber-stamp them in 2009.

The FDA prides itself on being science-driven; that provides some hope that smokeless tobacco warnings will some day be appropriately and accurately revised. In the meantime, the mouth-cancer, gum-disease and not-safe warnings exaggerate and distort the vanishingly small health impact of smokeless tobacco. Medical ethics and principles of public health dictate that smokers and smokeless tobacco users should not be subject to such health-endangering deception.