June 8, 2014

Stanton A. Glantz, PhD

FDA’s Proposed Exception for Premium Cigars and Weak Warning Labels for Cigars Do Not Protect the Public Health

My colleague Suzaynn Schick and some others just submitted this public comment to FDA.
The FDA should not exempt “premium” cigars from regulation (i.e., reject "Option 2) and should include the fifth FTC warning (Tobacco Use Increases the Risk of Infertility, Stillbirth and Low Birth Weight) on the packaging of all cigars. 
Although large, expensive cigars may be used differently by different sectors of society, there are still plenty of people in the U.S. who can afford to smoke them regularly.  Premium cigar smokers should neither be excluded from the education that health warnings provide, nor spared the emotional distress the warnings may provoke.  All tobacco and nicotine deliver products need to be labeled clearly and consistently.  Failure to do so creates the false impression that products without health warnings are less risky to use than labeled products.  In the case of premium cigars, this is certainly not true. 
It is particularly important to include the warning about reproductive risk on all cigars.  Cigars are a combustible tobacco product and while epidemiological studies have not yet proven that cigar smoking causes reproductive harm, the preponderance of the evidence suggests that it does.  In 2001 the Federal Trade Commission mandated that cigar packaging and advertisements must display the Surgeon General’s Warnings, including the reproductive warning (U.S. Federal Trade Commission 2001).  As the FDA recognizes in the draft rule, a large cigar can contain as much nicotine as a pack of cigarettes (National Cancer Institute 1998) and also emits massive amounts of carbon monoxide, respirable particles, carcinogens and other oxidant chemicals (National Cancer Institute 1998, Klepeis, Ott et al. 1999).  Although the proportional uptake of the total nicotine from cigars is lower than that from cigarettes, even exposure to secondhand cigarette smoke causes reproductive harm (U.S. Dept. of Health and Human Services, Centers for Disease Control and Prevention et al. 2006). 
It is vitally important to include reproductive health warnings on all cigars because of the intersection of cigar use and reproductive risk. Conception is a focal event that can be disrupted by a single toxic assault.  Smoking a large, expensive, celebratory cigar presents a significant risk to conception and to the health of an unborn child.
Smoking by men reduces the number of term pregnancies among couples conceiving by in-vitro fertilization (Fuentes, Munoz et al. 2010).   Exposure to secondhand cigarette smoke in women is associated with the recovery of fewer oocytes during assisted reproductive procedures. According to the 2014 Surgeon General's report:
     Basic characteristics of embryologic and fetal development include cell growth, differentiation, interaction, and migration. Teratogenic factors can disturb one or more of these processes, resulting in abnormalities in fetal structure or function, including growth retardation, malformations due to abnormal growth or morphogenesis, and altered CNS performance (Hacker, Gambone et al. 2010). In addition, there is a growing appreciation that teratogenic substances can have effects throughout the duration of pregnancy, and that those effects can be more subtle than gross anatomic anomalies (Yaffe and Aranda 2010). Thus, for women of reproductive age, a comprehensive exploration of the known and potential harms of the range of available tobacco products, all of which contain nicotine, is needed. (U.S. Department of Health and Human Services, Centers for Disease Control and Prevention et al. 2014)
Here is an overview of the reproductive health effects of cigar use as they relate to health effects caused by the use of tobacco products during pregnancy.

  1. According to the 2014 Surgeon General’s report, “Tobacco use during and after pregnancy remains a major cause of reduced fertility as well as maternal, fetal, and infant morbidity and mortality” (U.S. Department of Health and Human Services, Centers for Disease Control and Prevention et al. 2014).
  2. It is critical that women of reproductive age be warned of health risks associated with use of tobacco products during pregnancy. Adverse reproductive health effects include (but are not limited to):increased risk of sudden infant death syndrome (SIDS) (U.S. Department of Health and Human Services 2004), orofacial clefts (Jia, Shi et al. 2011, Mirilas, Mentessidou et al. 2011, Zandi and Heidari 2011, Zhang, Jiao et al. 2011), anorectal atresia (Miller, Manning et al. 2009, Hackshaw, Rodeck et al. 2011), and ectopic pregnancy (Bouyer, Coste et al. 2003, Karaer, Avsar et al. 2006, Roelands, Jamison et al. 2009).


  1. There is sufficient evidence to infer a causal relationship between smoking and erectile dysfunction in men (U.S. Department of Health and Human Services, Centers for Disease Control and Prevention et al. 2014)
  2. Tobacco smoke has been shown to adversely affect sexual health and erectile function (Bornman and du Plessis 1986, Juenemann, Lue et al. 1987, Mannino, Klevens et al. 1994, Polsky, Aronson et al. 2005, Shiri, Hakkinen et al. 2006).
  3. Several lines of evidence support a causal relationship between smoking and erectile dysfunction (ED):


  1. A review of the literature provides mounting evidence that smoking constitutes a risk factor for erectile dysfunction, including:
    • Case studies (Wabrek et al. 1983; Condra et al. 1986; Tengs and Osgood 2001)
    • Cross-sectional studies (Moreira et al. 2006; Lam et al. 2006b; He et al. 2007)
    • Prospective population-based studies (Kleinman et al. 2000; Bacon et al. 2003; Kupelian et al. 2010)

Stillbirth and perinatal mortality
Studies support a role for nicotine in the effects of smoking on stillbirth and perinatal mortality. Animal models show that nicotine in the fetus causes cell damage, reduces cell number, and impairs synaptic activity (Slotkin, Orband-Miller et al. 1987, Slotkin 1998, Dwyer, Broide et al. 2008). Nicotinic acetylchonine receptors (nAChRs) are receptors that are ordinarily activated by endogenous acetylcholine, but that can also be stimulated by nicotine, resulting in disruption of normal cholinergic signaling (Albuquerque, Pereira et al. 2009).

  1. In the 2001 Surgeon General’s report, it was noted that cigarette smoking was consistently associated with stillbirth (U.S. Department of Health and Human Services, Public Health Service et al. 2001), with an increased risk of 40% (Cnattingius, Haglund et al. 1988)to 60% (Raymond, Cnattingius et al. 1994).


  1. Nicotine exposure in animal models has also been shown to interfere with the fetus’s critical protective response to hypoxia, which would lead to an increased risk of infant mortality (Slotkin 1998).

Low birth weight

  1. Tobacco use during pregnancy leads to reduced birth weight (U.S. Department of Health and Human Services, Centers for Disease Control and Prevention et al. 2014). The 2004 Surgeon General’s report found the evidence sufficient to infer causal relationships between smoking and fetal growth restriction and between smoking and decreased gestation/increased preterm delivery.  Likewise, the 2006 Report on the Health Consequences of Involuntary Exposure to Tobacco Smoke found that secondhand smoke exposure causes sudden infant death syndrome and low birth weight (U.S. Dept. of Health and Human Services, Centers for Disease Control and Prevention et al. 2006).
  2. Maternal smoking is associated with a 27% increase in the risk of preterm delivery compared with nonsmokers (Shah and Bracken 2000). Similarly, Baba et al. 2012 found an increased risk of preterm birth associated with smoking during pregnancy (Baba, Noda et al. 2011).
  3. Studies of gene-environment interactions have shown that genes that encode enzymes associated with the metabolism of compounds found in tobacco smoke, including polycyclic hydrocarbons (PAHs) and nitrosamines, have been associated with restricted fetal growth in smokers (Wang, Zuckerman et al. 2002, Nukui, Day et al. 2004, Grazuleviciene, Danileviciute et al. 2009, Aagaard-Tillery, Spong et al. 2010).

Concluding remarks
            Despite the numerous health risks described above, over 400,000 live-born infants in the United States are exposed in utero to tobacco from maternal smoking annually (Hamilton, Martin et al. 2013, Tong, Dietz et al. 2013). We should not remove the fifth FTC warning from premium cigars, or exclude premium cigars from the FDA regulation (i.e., reject "Option 2) and risk increasing this number.
Aagaard-Tillery, K., C. Y. Spong, E. Thom, B. Sibai, G. Wendel, Jr., K. Wenstrom, P. Samuels, H. Simhan, Y. Sorokin, M. Miodovnik, P. Meis, M. J. O'Sullivan, D. Conway, R. J. Wapner and H. D. M.-F. M. U. N. Eunice Kennedy Shriver National Institute of Child Health (2010). "Pharmacogenomics of maternal tobacco use: metabolic gene polymorphisms and risk of adverse pregnancy outcomes." Obstet Gynecol 115(3): 568-577.
Adaikan, P. G. and S. S. Ratnam (1988). "Pharmacology of penile erection in humans." Cardiovasc Intervent Radiol 11(4): 191-194.
Albuquerque, E. X., E. F. Pereira, M. Alkondon and S. W. Rogers (2009). "Mammalian nicotinic acetylcholine receptors: from structure to function." Physiol Rev 89(1): 73-120.
Baba, S., H. Noda, M. Nakayama, M. Waguri, N. Mitsuda and H. Iso (2011). "Risk factors of early spontaneous abortions among Japanese: a matched case-control study." Hum Reprod 26(2): 466-472.
Bornman, M. S. and D. J. du Plessis (1986). "Smoking and vascular impotence. A reason for concern." S Afr Med J 70(6): 329-330.
Bouyer, J., J. Coste, T. Shojaei, J. L. Pouly, H. Fernandez, L. Gerbaud and N. Job-Spira (2003). "Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France." Am J Epidemiol 157(3): 185-194.
Cnattingius, S., B. Haglund and O. Meirik (1988). "Cigarette smoking as risk factor for late fetal and early neonatal death." BMJ 297(6643): 258-261.
Dwyer, J. B., R. S. Broide and F. M. Leslie (2008). "Nicotine and brain development." Birth Defects Res C Embryo Today 84(1): 30-44.
Fuentes, A., A. Munoz, K. Barnhart, B. Arguello, M. Diaz and R. Pommer (2010). "Recent cigarette smoking and assisted reproductive technologies outcome." Fertil Steril 93(1): 89-95.
Grazuleviciene, R., A. Danileviciute, R. Nadisauskiene and J. Vencloviene (2009). "Maternal smoking, GSTM1 and GSTT1 polymorphism and susceptibility to adverse pregnancy outcomes." Int J Environ Res Public Health 6(3): 1282-1297.
Hacker, F. F., J. C. Gambone and S. J. Hobel (2010). Hacker and Moore's Essentials of obstetrics ang gynecology, 5th edition. Philadelphia, Saunders Elsevier.
Hackshaw, A., C. Rodeck and S. Boniface (2011). "Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls." Hum Reprod Update 17(5): 589-604.
Hamilton, B. E., J. A. Martin and S. J. Ventura (2013). "Births: preliminary data for 2012." Natl Vital Stat Rep 62(3): 1-20.
Harte, C. B. and C. M. Meston (2008). "Acute effects of nicotine on physiological and subjective sexual arousal in nonsmoking men: a randomized, double-blind, placebo-controlled trial." J Sex Med 5(1): 110-121.
Jia, Z. L., B. Shi, C. H. Chen, J. Y. Shi, J. Wu and X. Xu (2011). "Maternal malnutrition, environmental exposure during pregnancy and the risk of non-syndromic orofacial clefts." Oral Dis 17(6): 584-589.
Juenemann, K. P., T. F. Lue, J. A. Luo, N. L. Benowitz, M. Abozeid and E. A. Tanagho (1987). "The effect of cigarette smoking on penile erection." J Urol 138(2): 438-441.
Karaer, A., F. A. Avsar and S. Batioglu (2006). "Risk factors for ectopic pregnancy: a case-control study." Aust N Z J Obstet Gynaecol 46(6): 521-527.
Klepeis, N. E., W. R. Ott and J. L. Repace (1999). "The effect of cigar smoking on indoor levels of carbon monoxide and particles." J Expo Anal Environ Epidemiol 9(6): 622-635.
Mannino, D. M., R. M. Klevens and W. D. Flanders (1994). "Cigarette smoking: an independent risk factor for impotence?" Am J Epidemiol 140(11): 1003-1008.
Miller, E. A., S. E. Manning, S. A. Rasmussen, J. Reefhuis, M. A. Honein and S. National Birth Defects Prevention (2009). "Maternal exposure to tobacco smoke, alcohol and caffeine, and risk of anorectal atresia: National Birth Defects Prevention Study 1997-2003." Paediatr Perinat Epidemiol 23(1): 9-17.
Mirilas, P., A. Mentessidou, E. Kontis, M. Asimakidou, B. J. Moxham, A. S. Petropoulos and E. N. Emmanouil-Nikolousi (2011). "Parental exposures and risk of nonsyndromic orofacial clefts in offspring: a case-control study in Greece." Int J Pediatr Otorhinolaryngol 75(5): 695-699.
National Cancer Institute (1998). Cigars: Health Effects and Trends. Tobacco Control Monograph Series. N. C. Institute. Washington, DC, National Cancer Institute,. 1.
Nukui, T., R. D. Day, C. S. Sims, R. B. Ness and M. Romkes (2004). "Maternal/newborn GSTT1 null genotype contributes to risk of preterm, low birthweight infants." Pharmacogenetics 14(9): 569-576.
Polsky, J. Y., K. J. Aronson, J. P. Heaton and M. A. Adams (2005). "Smoking and other lifestyle factors in relation to erectile dysfunction." BJU Int 96(9): 1355-1359.
Raymond, E. G., S. Cnattingius and J. L. Kiely (1994). "Effects of maternal age, parity, and smoking on the risk of stillbirth." Br J Obstet Gynaecol 101(4): 301-306.
Roelands, J., M. G. Jamison, A. D. Lyerly and A. H. James (2009). "Consequences of smoking during pregnancy on maternal health." J Womens Health (Larchmt) 18(6): 867-872.
Shah, N. R. and M. B. Bracken (2000). "A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery." Am J Obstet Gynecol 182(2): 465-472.
Shiri, R., J. Hakkinen, J. Koskimaki, T. L. Tammela, A. Auvinen and M. Hakama (2006). "Smoking causes erectile dysfunction through vascular disease." Urology 68(6): 1318-1322.
Slotkin, T. A. (1998). "Fetal nicotine or cocaine exposure: which one is worse?" J Pharmacol Exp Ther 285(3): 931-945.
Slotkin, T. A., L. Orband-Miller, K. L. Queen, W. L. Whitmore and F. J. Seidler (1987). "Effects of prenatal nicotine exposure on biochemical development of rat brain regions: maternal drug infusions via osmotic minipumps." J Pharmacol Exp Ther 240(2): 602-611.
Tong, V. T., P. M. Dietz, B. Morrow, D. V. D'Angelo, S. L. Farr, K. M. Rockhill, L. J. England, C. Centers for Disease and Prevention (2013). "Trends in smoking before, during, and after pregnancy--Pregnancy Risk Assessment Monitoring System, United States, 40 sites, 2000-2010." MMWR Surveill Summ 62(6): 1-19.
U.S. Department of Health and Human Services (2004). The health consequences of smoking: a report of the surgeon general. . Atlanta, GA, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention,  National Center for Chronic Disease Prevention and Health Promotion,  Office on Smoking and Health. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion and O. o. S. a. Health (2014). The health consequences of smoking -- 50 years of progres: a report of the Surgeon General. Atlanta GA: 944.
U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health and National Cancer Institute (2001). Women and smoking; A report of the Surgeon General. Atlanta, GA, U.S. Department of Health and Human Services,. U.S. Dept. of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion and National Center for Chronic Disease Prevention and Health Promotion (2006). The health consequences of involuntary exposure to tobacco smoke : a report of the Surgeon General. United States Public Health Service. Office of the Surgeon General and United States Office on Smoking and Health. Atlanta, GA.
U.S. Federal Trade Commission. (2001). "Nationwide Labeling Rules for Cigar Packaging and Ads Take Effect Today." Press Releases  Retrieved 5/21/2014, 2014, from http://www.ftc.gov/news-events/press-releases/2001/02/nationwide-labeling-rules-cigar-packaging-and-ads-take-effect.
Wang, X., B. Zuckerman, C. Pearson, G. Kaufman, C. Chen, G. Wang, T. Niu, P. H. Wise, H. Bauchner and X. Xu (2002). "Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight." JAMA 287(2): 195-202.
Xie, Y., H. Garban, C. Ng, J. Rajfer and N. F. Gonzalez-Cadavid (1997). "Effect of long-term passive smoking on erectile function and penile nitric oxide synthase in the rat." J Urol 157(3): 1121-1126.
Yaffe, S. J. and J. V. Aranda (2010). Neonatal and pediatric pharmacology, therapeutic principles in practice, 4th edition. Philadelphia, Lippincott, Williams and Wilkins.
Zandi, M. and A. Heidari (2011). "An epidemiologic study of orofacial clefts in Hamedan City, Iran: a 15-year study." Cleft Palate Craniofac J 48(4): 483-489.
Zhang, B., X. Jiao, L. Mao and J. Xue (2011). "Maternal cigarette smoking and the associated risk of having a child with orofacial clefts in China: a case-control study." J Craniomaxillofac Surg 39(5): 313-318.
The comment has tracking number 1jy-8cjy-mdi0.

Add new comment

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.