Summary
Smokeless tobacco (snuff) is a finely ground or shredded tobacco that is sniffed through the nose or placed between the cheek and gum. Chewing tobacco is used by putting a wad of tobacco inside the cheek. Smokeless tobacco is widely used by young athletes to enhance performance because nicotine improves some aspects of physiology. However, smokeless tobacco has harmful health effects, including cardiovascular disorders, linked to nicotine physiological effects, mainly through catecholamine release. Nicotine decreases heart rate variability and the ventricular fibrillation threshold, and promotes the occurrence of various arrhythmias; it also impairs endothelial-dependent vasodilation and could therefore promote premature atherogenesis. At rest, heart rate, blood pressure, inotropism, cardiac output and myocardial oxygen consumption are increased by nicotine, leading to an imbalance between myocardial oxygen demand and supply. The same occurs at submaximal levels of exercise. These increases are accompanied by a rise in systemic resistances. At maximal exercise, heart rate, cardiac output and maximal oxygen uptake ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='V˙O2max’>V˙O2maxV˙O2max
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) are unaffected by nicotine. Because endothelial dysfunction is promoted by nicotine, paradoxical coronary vasoconstriction may occur during exercise and recovery. Nicotine induces a decrease in muscular strength and impairs anaerobic performance. However, nicotine is used in sports as it diminishes anxiety, enhances concentration and agility, improves aerobic performance and favours weight control. Importantly, smokeless tobacco, similar to cigarette smoking, leads to nicotine dependence through dopaminergic pathways. Smokeless tobacco has harmful cardiovascular effects and is addictive: it fulfils all the criteria for inclusion in the World Anti-Doping Agency prohibited list as a doping product. Smokeless tobacco use in sporting activities must be discouraged.
Résumé
Le tabac non fumé (TNF) est un tabac finement moulu ou broyé qui peut être placé soit dans le nez ( dry snuff , tabac à priser) ou entre la joue et la gencive ( moist snuff , snus , tabac à chiquer). Le TNF est utilisé couramment par les jeunes athlètes qui pensent ainsi pouvoir augmenter leur performance sportive, la nicotine améliorant certains paramètres physiologiques. Cependant, le TNF a des effets nocifs sur la santé, entraînant notamment des troubles cardiovasculaires, liés aux effets physiologiques de la nicotine, principalement via une libération de catécholamines. La nicotine diminue la variabilité de la fréquence cardiaque (FC), le seuil de fibrillation ventriculaire et favorise la survenue d’arythmies. Elle altère la vasodilatation dépendante de l’endothélium et pourrait donc favoriser le développement prématuré d’athérome. Au repos, la FC et la pression artérielle (PA), ainsi que l’inotropisme, le débit cardiaque et la consommation myocardique d’oxygène sont augmentées par la nicotine, conduisant à un déséquilibre entre la demande et l’apport en oxygène au niveau myocardique. Ceci est également constaté à des niveaux d’effort sous-maximal. Ces modifications sont accompagnées d’une élévation des résistances périphériques. À l’exercice maximal cependant, la FC, le débit cardiaque et à le <SPAN role=presentation tabIndex=0 id=MathJax-Element-2-Frame class=MathJax style="POSITION: relative" data-mathml='V˙O2max’>V˙O2maxV˙O2max
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sont inchangés par la nicotine. Puisqu’un dysfonctionnement endothélial est favorisé par la nicotine, une vasoconstriction coronaire paradoxale peut survenir aussi bien pendant l’exercice que pendant la phase de récupération. La nicotine diminue la force musculaire et altère la capacité d’exercice anaérobie. Cependant, elle est consommée dans certains sports car elle diminue l’anxiété, renforce la concentration, améliore la performance aérobie et favorise le contrôle de la prise de poids. Il est important de savoir que le TNF, à l’instar du tabac fumé, entraîne une dépendance à la nicotine, relevant de mécanismes dopaminergiques. L’usage du TNF possède des effets cardiovasculaires nocifs, et induit une dépendance à la nicotine : le TNF remplit donc les critères pour être incorporé à la liste des produits dopants de l’Agence mondiale antidopage. L’utilisation du TNF doit donc être déconseillée dans le cadre de la pratique sportive.
Background
Over the past two decades, the use of alternative kinds of tobacco consumption, such as smokeless tobacco (SLT) in the form of ‘snuff’, chewing tobacco, snus or ‘tabac à chiquer’ in France, has increased in young athletes. SLT is chewed or sniffed but not smoked. Although the negative health effects of cigarette smoking have been largely documented, those of SLT remain controversial. SLT has been shown to be associated with an increased risk of oral or oropharyngeal cancer and cardiovascular diseases , leading to the strong discouragement of its use . Although no firm association was found between SLT use and the risk of myocardial infarction in a pooled analysis of prospective observational studies , quitting snus, a humid form of powdered tobacco placed under the lip, after myocardial infarction has recently been associated with a better prognosis .
Current guidelines recommend that tobacco, including SLT, must be avoided for 2 hours before and after a sports session or practice . However, given that SLT is mostly used by athletes and that intense physical exercise can induce acute cardiovascular events , it is important to determine whether the cardiovascular effects of nicotine can increase the risk of cardiovascular outcomes, especially during sports activities. Nicotine is currently under evaluation as a doping product by the World Anti-Doping Agency . As nicotine contributes substantially to the cardiovascular effects of tobacco , the debate could be extended to e-cigarettes.
We aim to review current knowledge regarding SLT as a cardiovascular risk factor, considering patterns of consumption of SLT around the world, the pharmacological properties of SLT, the context of SLT use by athletes and SLT safety data. Finally, we review the main findings on the cardiovascular impact of SLT and discuss whether SLT can be classified as a doping agent.
Worldwide consumption patterns
Few data are available on the real use of SLT across the world. In the USA, SLT use is frequent among athletes, especially baseball players . In Scandinavia, SLT use is common both in the community and among athletes , and often starts early in life; more than 15% of boys aged between 14 and 15 years were found to have used snuff . SLT use is even more frequent among individuals participating in sports club activities, especially team sports, such as ice hockey . In Sweden, the only European Union country where the sale of snuff is allowed, SLT represents almost 50% of total tobacco consumption . Cigarette smoking in Sweden is much lower than that in neighbouring countries, and tobacco-related mortality is about 50% lower than in other European countries . However, the interplay between SLT and cigarette smoking is complex. Switching patterns exist in both directions and both types of consumption can be concomitant . The consumption of snus and chewing tobacco is much lower among young Swiss men .
In France, epidemiological data are controversial. Among 920 students from the Alpine region, 11.2% had tried chewing tobacco . However, SLT use has been reported in French ice hockey players and skiers . In France, as in other European countries (except Sweden and Norway), the sale of snuff is prohibited. SLT can be purchased via the Internet or brought in by relatives or friends travelling from countries such as the USA, Norway or Sweden, where the sale of SLT is allowed. In France, the snuff-provider role of team partners and coaches travelling from such countries must not be underestimated. Moreover, chewing tobacco is sold legally in France, which explains why some athletes use it.
Analysis of urine from 2185 athletes worldwide suggests that nicotine is used for reasons other than recreational purposes , especially in certain sports, such as American football, ice hockey and wrestling.
Pharmacology
SLT includes chewing tobacco, spit tobacco, dry snuff, which is sniffed into the nose, and moist snuff (snus), which is placed in the mouth between cheek and gum. Quantitatively, nicotine is the most abundant alkaloid component of tobacco; it is thus assumed that nicotine is one of the major causes of the pharmacological effects of tobacco . The concentration of nicotine in snuff is approximately twice that in chewing tobacco.
Pharmacokinetics
After ingestion of SLT, nicotine absorption by the oral mucosa is rapid and massive , and is increased in some preparations by the adjunction of very small particles of glass. Plasma nicotine concentration shows a peak that is nearly as high as that obtained by cigarette smoking, with a time to peak after snuff intake of about 30 minutes. This peak is then followed by a plateau phase, which lasts about 2 hours, and is thus much longer than with cigarette smoking. Interestingly, nicotine absorption lasts for 1 hour after the SLT has been removed from the mouth. For these reasons, exposure to nicotine after snuff intake is nearly twice that after cigarette smoking. The half-life of nicotine is about 2 hours. Nicotine is mostly metabolized by the liver; the main metabolite, cotinine, is inactive and has a much longer half-life (about 16 hours) than nicotine. Cotinine is found in the blood and urine; this issue is important for biological assessments of consumption.
Pharmacodynamics
Most of the effects of SLT are attributable to nicotine . This alkaloid binds to nicotinic receptors, which are located in the brain, the autonomic ganglia, the adrenals and neuromuscular junctions. The stimulation of these receptors by nicotine induces the release of neuromediators (e.g. norepinephrine, epinephrine, acetylcholine, dopamine, serotonin, vasopressin, nitric oxide, etc.). Most cardiovascular effects are due to the secretion of catecholamines: either norepinephrine by sympathetic nerve terminals or epinephrine by the adrenomedulla . Direct effects can also occur, independently of nicotinic cholinergic receptors and catecholamine release ; nicotine can block ionic channels at nicotine concentrations that are achieved after SLT use . Nicotine may increase carotid and aortic chemoreceptor sensitivity . Some authors have suggested that the sympathetic response may be attributable to a reaction induced by parasympathetic effects . These mechanisms could explain the polyphasic and dose-dependent response to nicotine. The cognitive and addictive effects are mainly caused by dopaminergic stimulation, especially in the nucleus accumbens and prefrontal area .
The tolerance phenomenon is a key issue for the effects of nicotine, as it occurs very early after nicotine exposure. If the blood nicotine peak is progressive, as is the case with nicotine gum or patches, tolerance effects induce less intense cardiovascular effects than other means of administration, such as intravenous infusion, snuff dipping or cigarette smoking.
Use in athletes
Athletes have different motivations for SLT consumption, including enhanced concentration, help with relaxation or for ritual reasons ; sometimes they use SLT for weight control . Athletes also think that SLT can enhance their performance ; however, this belief was not reported in baseball players who answered anonymous questionnaires .
It has been suggested that SLT provides the ‘beneficial’ effects of nicotine without the negative effects of smoke, especially on the respiratory tract. During the 2009 Ice Hockey World Championship, nicotine and its metabolites were detectable in nearly 50% of 72 urine samples, suggesting active tobacco consumption. Moreover, two athletes had quite elevated concentrations, which is highly suggestive of SLT use for doping purposes .
Baseball players use SLT more often during the baseball season than during the off-season . However, long-term SLT use failed to improve physical performance in middle-aged men . Moreover, in this cohort of 144 Swedish firemen, maximal oxygen uptake ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-3-Frame class=MathJax style="POSITION: relative" data-mathml='V˙O2max’>V˙O2maxV˙O2max
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) and maximal workload during a bicycle stress test were similar in SLT users and nonusers of tobacco, but higher than in cigarette smokers. Data from a meta-analysis on the effects of nicotine found that nicotine significantly improved fine motor abilities, alerting attention-accuracy and response time, and orienting attention-response time . However, reaction and movement times were similar in SLT users and nonusers after nicotine absorption . Moreover, anticipation time was also similar in both groups. In contrast, the abilities to face cognitively challenging tasks and to manage stressful situations were better in SLT users, and the anxiety-scale response during tests was lower. Interestingly, with the intake of increasing amounts of SLT , no dose-response effect was found regarding performance and self-reported anxiety. Although some beneficial effects are observed, caution must be taken, given that these tests have major limitations: as tests are often performed in current users during a withdrawal period, it is sometimes difficult to separate what is due to the beneficial effects of the SLT from what is due to correction as a result of withdrawal .
The scoring performances of baseball players were similar for users and nonusers . SLT use induced a decrease in the muscular strength of athletes . In contrast, participation in brief high-intensity exercise (such as the Wingate anaerobic test) was unchanged after SLT . SLT can impair anaerobic performance . In some studies, maximal effort was not improved and lactate accumulation occurred earlier ; this could be deleterious for exercise, with an earlier anaerobic threshold . <SPAN role=presentation tabIndex=0 id=MathJax-Element-4-Frame class=MathJax style="POSITION: relative" data-mathml='V˙O2max’>V˙O2maxV˙O2max
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was found to be similar with and without SLT .
Interestingly, transdermal nicotine administration was found to increase performance during aerobic exercise, probably through delayed central perception of fatigue. Also, nicotine increases pain tolerance; it also reduces appetite and enhances lipolysis , thus promoting weight loss. The potential effects of nicotine on performance are summarized in Table 1 .
