Journal of Consulting and Clinical Psychology 1991, Vol. 59, No. 5, 749-752
Copyright 1991 by the American Psychological Association, Inc. 0022-006X/91/S3.00
BRIEF REPORTS
Metabolic Effects of Nicotine Gum and Cigarette Smoking: Potential Implications for Postcessation Weight Gain? Robert C. Klesges, Kimberly DePue, and Janet Audrain
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
Center For Applied Psychological Research, Memphis State University
Lisa M. Klesges
Andrew W Meyers
Department of Biostatistics and Epidemiology University of Tennessee, Memphis
Center For Applied Psychological Research Memphis State University
The effects of nicotine chewing gum and cigarettes on resting energy expenditure (REE) were evaluated. Twenty smoking women participated in nicotine gum and smoking administration, after which their REEs were measured. Results indicate an acute increase in REE for both nicotine gum and cigarettes. Metabolic rates for nicotine gum slowly returned to baseline, whereas rates for cigarettes quickly dropped and fell significantly below baseline. Thus, the metabolic effect of nicotine gum was greater than the eifect of smoking.
There is ample evidence that there is a relationship between smoking and body weight (Klesges, Meyers, Klesges, & LaVasque, 1989). That is, smokers weigh less than nonsmokers, those who quit smoking gain weight, and those who begin smoking lose weight. Recent studies have also shown that the weight-reducing qualities of smoking are some of the several reasons for smoking initiation, maintenance, and relapse (Klesges et al., 1989). Because these weight-related issues appear to have such a strong impact on smoking behavior, recent efforts have been directed at ways of reducing the weight gain following cessation for those individuals concerned about body weight issues (Gritz, Klesges, & Meyers, 1989). Unfortunately, behavioral approaches to reducing postcessation weight gain have been largely unsuccessful. To date, only three controlled studies have examined behavioral interventions for reducing postcessation weight gain, and none of the studies prevented postcessation weight gain (Bowen, Spring, & Fox, in press; Grinstead, 1981; Mermelstein, 1987). Only one study reduced weight gain (Mermelstein, 1987), and most important, none of the studies were successful in enhancing cessation rates. These failures may be due to the fact that quitting smoking is an extremely difficult and time-consuming process
and that adding additional treatment components to avoid postcessation weight gain may result in a program that is too complex or demanding to follow (Gritz et al., 1989). Nicotine gum is currently being investigated as a method both for enhancing smoking cessation and for preventing weight gain following cessation (Fagerstrom, 1987; Gross, Stitzer, & Maldonado, 1989). The strongest support for the smoking-related weight-reducing qualities of nicotine gum was provided in a recent double-blind, placebo-controlled investigation by Gross and colleagues (1989). Of the 40 subjects who completed the 10-week abstinence trial, subjects in the placebo group gained an average of 7.8 Ib, whereas subjects in the nicotine gum group gained an average of 3.8 Ib. However, the issue of the weight-controlling properties of nicotine gum is not fully resolved given that some investigations have failed to find a relationship between nicotine gum use and weight gain (e.g., Brantmark, 1973). Although there appear to be data suggesting that nicotine gum reduces postcessation weight gain, nothing is known regarding the mechanism (viz., dietary intake, resting energy expenditure [REE]) by which nicotine gum affects weight gain. Based on evidence that nicotine nasal spray increases metabolic rate (Perkins, Epstein, Stiller, Marks, & Jacob, 1989), the purpose of this investigation was to determine whether nicotine gum increases REE as well as to determine whether the metabolic response to chewing nicotine gum was similar to that of smoking cigarettes.
This study was supported by two grants awarded by the National Heart, Lung, and Blood Institute: one awarded to Robert C. Klesges and Andrew W Meyers (HL 39332) and one awarded to Robert C. Klesges (HL 36553). Support was also received from a Centers of Excellence grant awarded to the Department of Psychology, Memphis State University, by the State of Tennessee. Correspondence concerning this article should be addressed to Robert C. Klesges, Center for Applied Psychological Research, Department of Psychology, Memphis State University, Memphis, Tennessee 38152.
Method Subjects were 20 smoking women with an average age of 25 years (SD =5.03; range = 18-35). Subjects in the range of the 15th to the 85th percentile of normal weight (M= 54.0; SD = 25.55) were selected on the basis of the latest US. Department of Health, Education, and Wel-
749
750
BRIEF REPORTS
fare (DHEW, 1979) norms. The mean weight of the participants was 134.4 Ib (SD =21.3). Subjects were screened to ensure that each subject smoked at least 20 cigarettes each day (A/= 23.85; S/> = 5.39). Subjects were excluded if they had a history of cardiovascular disease, if they had any condition that would preclude chewing nicotine gum, or if they had a condition (e.g., diabetes) or were taking any substance known or thought to be associated with elevated REE.
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
Subjects were randomly assigned to either nicotine gum or cigarette administration on the first day in order to control for possible order effects. The independent variables in this design consisted of two levels of nicotine administration (nicotine gum and cigarettes) and time (baseline and ten 10-min blocks of time following drug administration), and the dependent variable was REE. Subjects were evaluated twice over consecutive days. Subjects arrived at the laboratory at 4:00 p.m. the afternoon before their first scheduled testing day. Twelve hoursof alcohol, food, and caffeine abstinence and 2 hr of smoking abstinence were required. Subjects also received a carbon monoxide (CO) level check that had to read a minimum of 20 parts per million (ppm) to verify they were at least moderate smokers. Subjects were given a brief introduction to the study, after which their height and weight measurements and age were obtained. Subjects were asked to come to the laboratory with their own supply of cigarettes at 12:00 noon the following day Subjects were allowed to smoke their own cigarettes to better approximate their true smoking levels and because daily intake of nicotine is identical across most brands of cigarettes, including low-yield cigarettes (flenowitz & Jacob, 1984). Subjects had to have at least a 20% reduction from their previous day's CO level in order to participate in the study. Because there was no precise manner to determine whether subjects complied with the 2-hr abstinence requirement, a 20% reduction, along with a bogus pipeline procedure, was used instead of completely relying on self-reports. Before the first REE measurement, salivary nicotine and cotinine were collected for comparison with a later sample, to determine whether a difference in the amount of nicotine extracted from each treatment contributed to a difference in the REE level between the two treatment conditions. Samples were analyzed by gas chromatography (Jacob, Wilson, & Benowitz, 1981). The subjects were then prepared for metabolic testing by placing them in a ventilated canopy and having them assume a supine position. REE was computed using a Critical Care Monitor by Medical Graphics Corporation, apatented,breath-by-breath, indirect calorimetry metabolic cart system. Two consecutive 20-min baseline metabolic recordings were collected, although the first 5 min of each recording, constituting habituation (Isbell, Klesges, Meyers, & Klesges, 1991), were not analyzed. Following baseline assessments, subjects were randomly assigned to one of two conditions, smoking cigarettes or chewing 4 mg nicotine polacrilex. At this point, subjects were administered nicotine polacrilex or instructed to smoke two cigarettes during the next 30 min. In the nicotine gum condition, subjects were asked to slowly chew two 2-mg pieces of nicotine gum to the sound of a tone. In the smoking condition, subjects were instructed to smoke one cigarette during the first 7 min and one cigarette during the last 7 of the 30 min in order to have parallel time frames for the ingestion of nicotine from the gum and the cigarettes. Subject's REE was then measured for 100 min. Similar to the baseline assessment, a 5-min habituation period preceded actual data collection (Isbell et al., 1991). At the end of metabolic testing, salivary nicotine and cotinine were again collected from each subject. After the first day in the study, subjects were asked to again abstain from smoking for 2 hr and to abstain from food, alcohol, and caffeine for 12 hr before their next laboratory appointment. Subjects were then assigned to the experimental condition they did not receive on the first day, and the experimental procedures were repeated.
Results To assess treatment effects and potential order effects in this crossover design, a 2 X 2 X 11 repeated measures analysis of variance was analyzed. This analytic design included one between-subjects factor of sequence (nicotine gum followed by cigarettes vs. cigarettes followed by nicotine gum), two withinsubjects factors of treatment (nicotine gum vs. cigarettes), and time (baseline and ten 10-min blocks of subsequent REE data). There were no indications of significant sequence effects as evidenced by no main effects for sequence, F(l ,18) = 0.23, p = 0.64, and no significant interactions of sequence with treatment, F(l, 18) = 0.02, p = 0.877; sequence with time, F(\0, 180) = 0.63, p = 0.790; or Sequence X Treatment X Time, FflO, 180) = 0.74, p = 0.687. Thus, the counterbalancing of possible sequence effects was successful. The results of REE over time between nicotine gum and cigarettes indicated a marginally significant main effect for treatment, F(l, 18) = 3.15, p = 0.09; a significant main effect for time, F(10,180) = 31.07, p < 0.001; and a significant interaction between treatment and time, F(\ 0,180) = 2.18, p = 0.021. The differing REE profiles for nicotine gum and cigarettes can be seen in Table 1. Simple main effects analyses were calculated to follow up the Treatment x Time interaction. Both nicotine gum, F(10,180) = 15.41, p < 0.001, and cigarette conditions, F(10,180) = 19.60, p< 0.001, showed significant changes over time. A Dunnett follow-up test was used to determine significant changes over time compared with baseline within a treatment condition (two-tailed a = 0.05). These follow-ups indicated that both chewing nicotine gum and smoking cigarettes produced a significant acute increase in REE from baseline to the first 10 min post-drug administration. Nicotine gum administration resulted in an average 242.6 kcal/day increase (compared with baseline) in metabolic rate, whereas cigarettes resulted in only a 155.6 kcal/day increase. Following these acute increases, subjects receiving nicotine gum returned to baseline levels of resting energy by 20 min post-drug administration. In contrast, when subjects smoked cigarettes, following the initial increase in REE, the drop in REE over time resulted in levels that were significantly below baseline by 30 min post-drug administration. The comparability of baseline REE between nicotine gum and cigarettes was evaluated and found to be similar, /•'(! ,18) = 0.14, p = 0.72. This result indicates that baselines were not significantly different on the day subjects received nicotine gum (M = 1309.7, SD = 140.60) compared with the day they received cigarettes (M= 1339.0, SD = 153.0). Likewise, baseline levels of nicotine, F(l, 18) = 1.70, p = 0.209, and cotinine, F(l, 18) = 2.63, p = 0.122, were similar between the treatment conditions. Salivary nicotine and cotinine levels were analyzed to determine whether there were post-drug differences between the treatments. Cotinine and nicotine at 100 min post-drug administration served as dependent variables in one-way analyses of covariance with respective baseline levels as the covariates, treatment as a within-subjects factor, and sequence as a between-subjects factor. Results indicate no significant cotinine differences between treatments, /•"(', 17) = 1.10, p = 0.308; how-
751
BRIEF REPORTS Table 1 Effects of Resting Energy Expenditure by Treatment Over Time Time (in minutes) Treatment Nicotine gum M SD Cigarettes M SD
Baseline
10
20
30
40
50
60
70
1309.7 140.63
1552.3' 211.5
1370.3 178.8
1340.3 197.1
1326.4 202.3
1321.7 217.5
1328.1 203.1
1310.9 183.1
1339.0 153.03
1494.6' 203.4
1258.5 179.9
1259.4" 172.7
1255.5b 171.1
1215.1" 161.2
1225.5" 172.5
1218.3" 176.6
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
Note. Subjects were 20 women. • Indicates a significant increase (p < .05) from baseline.
90
100
1313.7 202.9
1302.6 209.0
1329.4 188.4
1237.3" 197.0
1266.7" 200.0
1281.6" 207.4
* Indicates a significant decrease (p < .05) from baseline.
ever, nicotine at posttest did differ significantly between groups, F(l, 17) = 5.50, /? = 0.031, with the nicotine gum condi-
rate was lower following smoking than before smoking (Warwick, Chappie, & Thomson, 1987). This pattern of individual
tion yielding higher nicotine levels (adjusted M= 182.5) than did the cigarette condition (adjusted M = 111.3). Although dif-
variability in the metabolic response to smoking may help to explain why very well designed studies can conclude that smok-
ferent amounts of nicotine were extracted from the gum versus the cigarettes, nicotine levels were not significantly correlated to initial acute effects or the subsequent drop in REE within each treatment (Pearson rs range = 0.16-0.34, all ps > 0.05).
ing has either a dramatic (e.g, Hofstetter et al, 1986) or no (Warwick et al., 1987) effect on metabolic rate. It also may explain the great variability in smoking's effects on body weight, with some individuals (e.g., women who smoke a moderate amount of cigarettes; see Klesges et al, 1989) experiencing a marked effect on
Discussion The results of the current investigation indicate that both smoking cigarettes and chewing nicotine gum produced a very similar acute increase in REE. However, following this acute increase in REE, nicotine gum's effects were greater in nicotine gum versus cigarettes. When subjects smoked cigarettes, REE increased 12.5% and then decreased quickly, dropping, on average, significantly below baseline and eventually returning to baseline after 100 min. In contrast, when the same subjects chewed nicotine gum, an acute increase was observed, followed by a gradual return to baseline. This is the first investigation to examine the effects of nicotine gum on metabolic rate. The findings that indicate that nicotine gum increases metabolic rate thus identify a metabolic mechanism that might explain the weight-controlling effects of
body weight and others experiencing no effect on body weight. Taken together, these results indicate that some individuals may experience strong metabolic "benefits" of smoking that, in turn, have a marked effect on their body weights. In contrast, in other individuals, smoking may be hypometabolic following the acute phase of smoking, potentially obviating the metabolic benefits of smoking. Future studies should extend these findings to determine who is more likely to enjoy more of the metabolic benefits of smoking. Finally, it appears from the results that although subjects received nicotine from both nicotine gum and cigarettes, the chronic effects of smoking on REE did not parallel that of chewing nicotine gum over a 100-min test period. Because the metabolic rates of subjects fell significantly below baseline when they smoked, the net metabolic effects of nicotine gum
nicotine gum observed in some studies after quitting smoking (e.g., Fagerstrom, 1987). Future studies should extend the
were greater than those for smoking. Future studies should carefully evaluate what aspects of smoking (e.g, smoking topography, tobacco constituents) are associated with increases versus
current findings by replicating these effects in men. A dosing study in which 2-mg and 4-mg dosages of nicotine gum are
decreases in metabolic rate. It is interesting to note that changes in salivary nicotine were
compared with a placebo and cigarettes is also warranted. These results also indicate that whereas smoking produced
unrelated to changes in REE. Whereas cotinine levels of subjects during nicotine gum administration did not differ from
an acute increase in metabolic rate, the long-term patterns of
smoking, more nicotine was extracted from chewing nicotine
results show that the mean response fell significantly below baseline. However, the individual responses to smoking indi-
gum. Although both smoking cigarettes and chewing nicotine gum produced changes in metabolic rate, changes in salivary nicotine did not correlate with changes in metabolic rate. Thus,
cated great variability, with some subjects' metabolic rates remaining elevated throughout the 100-min test and others falling
within the limited dosage range observed in the current investi-
markedly below baseline. Other recent studies have reported highly variable responses to the metabolic eifects of smoking.
gation, nicotine's effect on REE did not appear to be dose dependent. These findings are consistent with a recent investiga-
For example, whereas one study indicated that smokers smoking had a 10% higher metabolic rate than did the same smokers when they were not smoking (Hofstetter, Schutz, Jequier, &
tion (Perkins et al., 1989), which found that both low and moderate nicotine doses resulted in a similar increase in metabolic rate over baseline. The observation of the metabolic effects of
Wahren, 1986), another recent study reported that metabolic
nicotine gum may have implications for reducing postcessation
752
BRIEF REPORTS
weight gain. Not only does nicotine gum appear to increase cessation rates and decrease withdrawal symptoms across a variety- of investigations (Brantmark, 1973), it may also have a positive effect on an undesirable side effect of quitting smoking— namely, postcessation weight gain. Because weight gain motivates many people to continue smoking (Gritz et al., 1989), judicious use of nicotine chewing gum may be a helpful adjunct to smoking cessation efforts in those individuals who are moti-
ing intervention and controlling postcessation weight gain. Annals n(Behavioral Medicine, 11, 144-153. Gross, J,, Stitzer, M. L., & Maldonado, i. (1989). Nicotine replacement: Effects on postcessation weight gain. Journal of Consulting and Clini-
vated by the weight control properties of smoking. Future stud-
cal Psychology, 57, 87-92. Hofstetter, A., Schutz, Y, Jequier, E., & Wahren, J. (1986). Increased
ies should simultaneously measure both the metabolic effect of
24-hour energy expenditure in cigarette smokers. New England Jour-
nicotine gum and postcessation weight gain to directly test this
nal oj Medicine, 314, 79-82. Isbell, T. R, Klesges, R. C, Meyers, A. W, & Klesges, L. M. (1991). Measurement reliability and reactivity using repeated measurements of resting energy expenditure with a face mask, mouthpiece, and ventilated canopy Journal of Parenleral and Enleral Nutrition, IS, 165-168. Jacob, P., Ill, Wilson, M., & Benowitz, N. L. (1981). Improved gas chromatographic method for determination of nicotine and cotinine in biological fluids. Journal of Chromatography, 222, 61-70. Klesges, R. C, Meyers, A. W, Klesges, L. M., & LaVasque, M. E. (1989). Smoking, body weight, and their effects on smoking behavior: A comprehensive review of the literature. Psychological Bulletin, 106(2), 204-230. Mermelstein, R, (1987, April). Preventing weight gain following smok-
hypothesis. Despite the positive features of the current investigation, care
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
sation: A comparison of behavioral treatment approaches. Unpublished doctoral dissertation, University of California, Los Angeles. Gritz, E. R., Klesges, R. C, & Meyers, A. W (1989). The implications of the smoking and body weight relationship for programmatic smok-
should be exercised in overgeneralizing these results. This study was conducted on normal-weight young women who smoked a moderate number of cigarettes. Therefore, future researchers should
investigate
potential
gender
differences,
wide age
ranges, and subjects who vary in body weight. In summary, nicotine gum and cigarettes both produced an acute increase in resting energy expenditure. However, the metabolic effects were greater in nicotine gum relative to cigarettes. Nicotine gum might have promise as an adjunctive treatment for those subjects who otherwise would not quit because of the weight control properties of smoking.
References Benowitz, N. L., & Jacob, P., III. (1984). Nicotine and carbon monoxide intake from high- and low-yield cigarettes. Clinical Pharmacology and Therapeutics, 38, 265-270. Bowen, D. J., Spring, B., & Fox, E. (in press). Tryptophan and high carbohydrate diets as adjuncts to smoking cessation therapy. Journal of Behavioral Medicine. Brantmark, B. (1973). Nicotine containing chewing gum as an antismoking aid. Psychopltarmacology, 31,191-200. Fagerstrom, K. O. (1987). Reducing weight gain after stopping smoking. Addictive Behaviors, 12, 91-93. Grinstead, O. A. (1981). Preventing weight gain following smoking ces-
ingcessation. Paper presented at the meetingof the Society of Behavioral Medicine Eighth Annual Scientific Sessions, Washington, DC. Perkins, K. A., Epstein, L. H., Stiller, R. L., Marks, B. L., & Jacob, R. G. (1989). Acute effects of nicotine on resting metabolic rate in cigarette smokers. American Journal of Clinical Nutrition, 50, 545-550. United States Department of Health, Education, and Welfare. (1979). Weight by height and age far adults 18-74 years: U.S. 1971-1974 (DHEW Publication No. 791656, Series 11, No. 280). Rockville, MD: Author. Warwick, P. M., Chappie, R. W, & Thomson, E. S. (1987). The effects of smoking two cigarettes on resting metabolic rate with and without food. International Journal of Obesity, 11, 229-237. Received October 19,1990 Revision received March 28,1991 Accepted April 5,1991 •
Copyright 1991 by the American Psychological Association, Inc. 0022-006X/91/S3.00
BRIEF REPORTS
Metabolic Effects of Nicotine Gum and Cigarette Smoking: Potential Implications for Postcessation Weight Gain? Robert C. Klesges, Kimberly DePue, and Janet Audrain
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
Center For Applied Psychological Research, Memphis State University
Lisa M. Klesges
Andrew W Meyers
Department of Biostatistics and Epidemiology University of Tennessee, Memphis
Center For Applied Psychological Research Memphis State University
The effects of nicotine chewing gum and cigarettes on resting energy expenditure (REE) were evaluated. Twenty smoking women participated in nicotine gum and smoking administration, after which their REEs were measured. Results indicate an acute increase in REE for both nicotine gum and cigarettes. Metabolic rates for nicotine gum slowly returned to baseline, whereas rates for cigarettes quickly dropped and fell significantly below baseline. Thus, the metabolic effect of nicotine gum was greater than the eifect of smoking.
There is ample evidence that there is a relationship between smoking and body weight (Klesges, Meyers, Klesges, & LaVasque, 1989). That is, smokers weigh less than nonsmokers, those who quit smoking gain weight, and those who begin smoking lose weight. Recent studies have also shown that the weight-reducing qualities of smoking are some of the several reasons for smoking initiation, maintenance, and relapse (Klesges et al., 1989). Because these weight-related issues appear to have such a strong impact on smoking behavior, recent efforts have been directed at ways of reducing the weight gain following cessation for those individuals concerned about body weight issues (Gritz, Klesges, & Meyers, 1989). Unfortunately, behavioral approaches to reducing postcessation weight gain have been largely unsuccessful. To date, only three controlled studies have examined behavioral interventions for reducing postcessation weight gain, and none of the studies prevented postcessation weight gain (Bowen, Spring, & Fox, in press; Grinstead, 1981; Mermelstein, 1987). Only one study reduced weight gain (Mermelstein, 1987), and most important, none of the studies were successful in enhancing cessation rates. These failures may be due to the fact that quitting smoking is an extremely difficult and time-consuming process
and that adding additional treatment components to avoid postcessation weight gain may result in a program that is too complex or demanding to follow (Gritz et al., 1989). Nicotine gum is currently being investigated as a method both for enhancing smoking cessation and for preventing weight gain following cessation (Fagerstrom, 1987; Gross, Stitzer, & Maldonado, 1989). The strongest support for the smoking-related weight-reducing qualities of nicotine gum was provided in a recent double-blind, placebo-controlled investigation by Gross and colleagues (1989). Of the 40 subjects who completed the 10-week abstinence trial, subjects in the placebo group gained an average of 7.8 Ib, whereas subjects in the nicotine gum group gained an average of 3.8 Ib. However, the issue of the weight-controlling properties of nicotine gum is not fully resolved given that some investigations have failed to find a relationship between nicotine gum use and weight gain (e.g., Brantmark, 1973). Although there appear to be data suggesting that nicotine gum reduces postcessation weight gain, nothing is known regarding the mechanism (viz., dietary intake, resting energy expenditure [REE]) by which nicotine gum affects weight gain. Based on evidence that nicotine nasal spray increases metabolic rate (Perkins, Epstein, Stiller, Marks, & Jacob, 1989), the purpose of this investigation was to determine whether nicotine gum increases REE as well as to determine whether the metabolic response to chewing nicotine gum was similar to that of smoking cigarettes.
This study was supported by two grants awarded by the National Heart, Lung, and Blood Institute: one awarded to Robert C. Klesges and Andrew W Meyers (HL 39332) and one awarded to Robert C. Klesges (HL 36553). Support was also received from a Centers of Excellence grant awarded to the Department of Psychology, Memphis State University, by the State of Tennessee. Correspondence concerning this article should be addressed to Robert C. Klesges, Center for Applied Psychological Research, Department of Psychology, Memphis State University, Memphis, Tennessee 38152.
Method Subjects were 20 smoking women with an average age of 25 years (SD =5.03; range = 18-35). Subjects in the range of the 15th to the 85th percentile of normal weight (M= 54.0; SD = 25.55) were selected on the basis of the latest US. Department of Health, Education, and Wel-
749
750
BRIEF REPORTS
fare (DHEW, 1979) norms. The mean weight of the participants was 134.4 Ib (SD =21.3). Subjects were screened to ensure that each subject smoked at least 20 cigarettes each day (A/= 23.85; S/> = 5.39). Subjects were excluded if they had a history of cardiovascular disease, if they had any condition that would preclude chewing nicotine gum, or if they had a condition (e.g., diabetes) or were taking any substance known or thought to be associated with elevated REE.
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
Subjects were randomly assigned to either nicotine gum or cigarette administration on the first day in order to control for possible order effects. The independent variables in this design consisted of two levels of nicotine administration (nicotine gum and cigarettes) and time (baseline and ten 10-min blocks of time following drug administration), and the dependent variable was REE. Subjects were evaluated twice over consecutive days. Subjects arrived at the laboratory at 4:00 p.m. the afternoon before their first scheduled testing day. Twelve hoursof alcohol, food, and caffeine abstinence and 2 hr of smoking abstinence were required. Subjects also received a carbon monoxide (CO) level check that had to read a minimum of 20 parts per million (ppm) to verify they were at least moderate smokers. Subjects were given a brief introduction to the study, after which their height and weight measurements and age were obtained. Subjects were asked to come to the laboratory with their own supply of cigarettes at 12:00 noon the following day Subjects were allowed to smoke their own cigarettes to better approximate their true smoking levels and because daily intake of nicotine is identical across most brands of cigarettes, including low-yield cigarettes (flenowitz & Jacob, 1984). Subjects had to have at least a 20% reduction from their previous day's CO level in order to participate in the study. Because there was no precise manner to determine whether subjects complied with the 2-hr abstinence requirement, a 20% reduction, along with a bogus pipeline procedure, was used instead of completely relying on self-reports. Before the first REE measurement, salivary nicotine and cotinine were collected for comparison with a later sample, to determine whether a difference in the amount of nicotine extracted from each treatment contributed to a difference in the REE level between the two treatment conditions. Samples were analyzed by gas chromatography (Jacob, Wilson, & Benowitz, 1981). The subjects were then prepared for metabolic testing by placing them in a ventilated canopy and having them assume a supine position. REE was computed using a Critical Care Monitor by Medical Graphics Corporation, apatented,breath-by-breath, indirect calorimetry metabolic cart system. Two consecutive 20-min baseline metabolic recordings were collected, although the first 5 min of each recording, constituting habituation (Isbell, Klesges, Meyers, & Klesges, 1991), were not analyzed. Following baseline assessments, subjects were randomly assigned to one of two conditions, smoking cigarettes or chewing 4 mg nicotine polacrilex. At this point, subjects were administered nicotine polacrilex or instructed to smoke two cigarettes during the next 30 min. In the nicotine gum condition, subjects were asked to slowly chew two 2-mg pieces of nicotine gum to the sound of a tone. In the smoking condition, subjects were instructed to smoke one cigarette during the first 7 min and one cigarette during the last 7 of the 30 min in order to have parallel time frames for the ingestion of nicotine from the gum and the cigarettes. Subject's REE was then measured for 100 min. Similar to the baseline assessment, a 5-min habituation period preceded actual data collection (Isbell et al., 1991). At the end of metabolic testing, salivary nicotine and cotinine were again collected from each subject. After the first day in the study, subjects were asked to again abstain from smoking for 2 hr and to abstain from food, alcohol, and caffeine for 12 hr before their next laboratory appointment. Subjects were then assigned to the experimental condition they did not receive on the first day, and the experimental procedures were repeated.
Results To assess treatment effects and potential order effects in this crossover design, a 2 X 2 X 11 repeated measures analysis of variance was analyzed. This analytic design included one between-subjects factor of sequence (nicotine gum followed by cigarettes vs. cigarettes followed by nicotine gum), two withinsubjects factors of treatment (nicotine gum vs. cigarettes), and time (baseline and ten 10-min blocks of subsequent REE data). There were no indications of significant sequence effects as evidenced by no main effects for sequence, F(l ,18) = 0.23, p = 0.64, and no significant interactions of sequence with treatment, F(l, 18) = 0.02, p = 0.877; sequence with time, F(\0, 180) = 0.63, p = 0.790; or Sequence X Treatment X Time, FflO, 180) = 0.74, p = 0.687. Thus, the counterbalancing of possible sequence effects was successful. The results of REE over time between nicotine gum and cigarettes indicated a marginally significant main effect for treatment, F(l, 18) = 3.15, p = 0.09; a significant main effect for time, F(10,180) = 31.07, p < 0.001; and a significant interaction between treatment and time, F(\ 0,180) = 2.18, p = 0.021. The differing REE profiles for nicotine gum and cigarettes can be seen in Table 1. Simple main effects analyses were calculated to follow up the Treatment x Time interaction. Both nicotine gum, F(10,180) = 15.41, p < 0.001, and cigarette conditions, F(10,180) = 19.60, p< 0.001, showed significant changes over time. A Dunnett follow-up test was used to determine significant changes over time compared with baseline within a treatment condition (two-tailed a = 0.05). These follow-ups indicated that both chewing nicotine gum and smoking cigarettes produced a significant acute increase in REE from baseline to the first 10 min post-drug administration. Nicotine gum administration resulted in an average 242.6 kcal/day increase (compared with baseline) in metabolic rate, whereas cigarettes resulted in only a 155.6 kcal/day increase. Following these acute increases, subjects receiving nicotine gum returned to baseline levels of resting energy by 20 min post-drug administration. In contrast, when subjects smoked cigarettes, following the initial increase in REE, the drop in REE over time resulted in levels that were significantly below baseline by 30 min post-drug administration. The comparability of baseline REE between nicotine gum and cigarettes was evaluated and found to be similar, /•'(! ,18) = 0.14, p = 0.72. This result indicates that baselines were not significantly different on the day subjects received nicotine gum (M = 1309.7, SD = 140.60) compared with the day they received cigarettes (M= 1339.0, SD = 153.0). Likewise, baseline levels of nicotine, F(l, 18) = 1.70, p = 0.209, and cotinine, F(l, 18) = 2.63, p = 0.122, were similar between the treatment conditions. Salivary nicotine and cotinine levels were analyzed to determine whether there were post-drug differences between the treatments. Cotinine and nicotine at 100 min post-drug administration served as dependent variables in one-way analyses of covariance with respective baseline levels as the covariates, treatment as a within-subjects factor, and sequence as a between-subjects factor. Results indicate no significant cotinine differences between treatments, /•"(', 17) = 1.10, p = 0.308; how-
751
BRIEF REPORTS Table 1 Effects of Resting Energy Expenditure by Treatment Over Time Time (in minutes) Treatment Nicotine gum M SD Cigarettes M SD
Baseline
10
20
30
40
50
60
70
1309.7 140.63
1552.3' 211.5
1370.3 178.8
1340.3 197.1
1326.4 202.3
1321.7 217.5
1328.1 203.1
1310.9 183.1
1339.0 153.03
1494.6' 203.4
1258.5 179.9
1259.4" 172.7
1255.5b 171.1
1215.1" 161.2
1225.5" 172.5
1218.3" 176.6
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
Note. Subjects were 20 women. • Indicates a significant increase (p < .05) from baseline.
90
100
1313.7 202.9
1302.6 209.0
1329.4 188.4
1237.3" 197.0
1266.7" 200.0
1281.6" 207.4
* Indicates a significant decrease (p < .05) from baseline.
ever, nicotine at posttest did differ significantly between groups, F(l, 17) = 5.50, /? = 0.031, with the nicotine gum condi-
rate was lower following smoking than before smoking (Warwick, Chappie, & Thomson, 1987). This pattern of individual
tion yielding higher nicotine levels (adjusted M= 182.5) than did the cigarette condition (adjusted M = 111.3). Although dif-
variability in the metabolic response to smoking may help to explain why very well designed studies can conclude that smok-
ferent amounts of nicotine were extracted from the gum versus the cigarettes, nicotine levels were not significantly correlated to initial acute effects or the subsequent drop in REE within each treatment (Pearson rs range = 0.16-0.34, all ps > 0.05).
ing has either a dramatic (e.g, Hofstetter et al, 1986) or no (Warwick et al., 1987) effect on metabolic rate. It also may explain the great variability in smoking's effects on body weight, with some individuals (e.g., women who smoke a moderate amount of cigarettes; see Klesges et al, 1989) experiencing a marked effect on
Discussion The results of the current investigation indicate that both smoking cigarettes and chewing nicotine gum produced a very similar acute increase in REE. However, following this acute increase in REE, nicotine gum's effects were greater in nicotine gum versus cigarettes. When subjects smoked cigarettes, REE increased 12.5% and then decreased quickly, dropping, on average, significantly below baseline and eventually returning to baseline after 100 min. In contrast, when the same subjects chewed nicotine gum, an acute increase was observed, followed by a gradual return to baseline. This is the first investigation to examine the effects of nicotine gum on metabolic rate. The findings that indicate that nicotine gum increases metabolic rate thus identify a metabolic mechanism that might explain the weight-controlling effects of
body weight and others experiencing no effect on body weight. Taken together, these results indicate that some individuals may experience strong metabolic "benefits" of smoking that, in turn, have a marked effect on their body weights. In contrast, in other individuals, smoking may be hypometabolic following the acute phase of smoking, potentially obviating the metabolic benefits of smoking. Future studies should extend these findings to determine who is more likely to enjoy more of the metabolic benefits of smoking. Finally, it appears from the results that although subjects received nicotine from both nicotine gum and cigarettes, the chronic effects of smoking on REE did not parallel that of chewing nicotine gum over a 100-min test period. Because the metabolic rates of subjects fell significantly below baseline when they smoked, the net metabolic effects of nicotine gum
nicotine gum observed in some studies after quitting smoking (e.g., Fagerstrom, 1987). Future studies should extend the
were greater than those for smoking. Future studies should carefully evaluate what aspects of smoking (e.g, smoking topography, tobacco constituents) are associated with increases versus
current findings by replicating these effects in men. A dosing study in which 2-mg and 4-mg dosages of nicotine gum are
decreases in metabolic rate. It is interesting to note that changes in salivary nicotine were
compared with a placebo and cigarettes is also warranted. These results also indicate that whereas smoking produced
unrelated to changes in REE. Whereas cotinine levels of subjects during nicotine gum administration did not differ from
an acute increase in metabolic rate, the long-term patterns of
smoking, more nicotine was extracted from chewing nicotine
results show that the mean response fell significantly below baseline. However, the individual responses to smoking indi-
gum. Although both smoking cigarettes and chewing nicotine gum produced changes in metabolic rate, changes in salivary nicotine did not correlate with changes in metabolic rate. Thus,
cated great variability, with some subjects' metabolic rates remaining elevated throughout the 100-min test and others falling
within the limited dosage range observed in the current investi-
markedly below baseline. Other recent studies have reported highly variable responses to the metabolic eifects of smoking.
gation, nicotine's effect on REE did not appear to be dose dependent. These findings are consistent with a recent investiga-
For example, whereas one study indicated that smokers smoking had a 10% higher metabolic rate than did the same smokers when they were not smoking (Hofstetter, Schutz, Jequier, &
tion (Perkins et al., 1989), which found that both low and moderate nicotine doses resulted in a similar increase in metabolic rate over baseline. The observation of the metabolic effects of
Wahren, 1986), another recent study reported that metabolic
nicotine gum may have implications for reducing postcessation
752
BRIEF REPORTS
weight gain. Not only does nicotine gum appear to increase cessation rates and decrease withdrawal symptoms across a variety- of investigations (Brantmark, 1973), it may also have a positive effect on an undesirable side effect of quitting smoking— namely, postcessation weight gain. Because weight gain motivates many people to continue smoking (Gritz et al., 1989), judicious use of nicotine chewing gum may be a helpful adjunct to smoking cessation efforts in those individuals who are moti-
ing intervention and controlling postcessation weight gain. Annals n(Behavioral Medicine, 11, 144-153. Gross, J,, Stitzer, M. L., & Maldonado, i. (1989). Nicotine replacement: Effects on postcessation weight gain. Journal of Consulting and Clini-
vated by the weight control properties of smoking. Future stud-
cal Psychology, 57, 87-92. Hofstetter, A., Schutz, Y, Jequier, E., & Wahren, J. (1986). Increased
ies should simultaneously measure both the metabolic effect of
24-hour energy expenditure in cigarette smokers. New England Jour-
nicotine gum and postcessation weight gain to directly test this
nal oj Medicine, 314, 79-82. Isbell, T. R, Klesges, R. C, Meyers, A. W, & Klesges, L. M. (1991). Measurement reliability and reactivity using repeated measurements of resting energy expenditure with a face mask, mouthpiece, and ventilated canopy Journal of Parenleral and Enleral Nutrition, IS, 165-168. Jacob, P., Ill, Wilson, M., & Benowitz, N. L. (1981). Improved gas chromatographic method for determination of nicotine and cotinine in biological fluids. Journal of Chromatography, 222, 61-70. Klesges, R. C, Meyers, A. W, Klesges, L. M., & LaVasque, M. E. (1989). Smoking, body weight, and their effects on smoking behavior: A comprehensive review of the literature. Psychological Bulletin, 106(2), 204-230. Mermelstein, R, (1987, April). Preventing weight gain following smok-
hypothesis. Despite the positive features of the current investigation, care
This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
sation: A comparison of behavioral treatment approaches. Unpublished doctoral dissertation, University of California, Los Angeles. Gritz, E. R., Klesges, R. C, & Meyers, A. W (1989). The implications of the smoking and body weight relationship for programmatic smok-
should be exercised in overgeneralizing these results. This study was conducted on normal-weight young women who smoked a moderate number of cigarettes. Therefore, future researchers should
investigate
potential
gender
differences,
wide age
ranges, and subjects who vary in body weight. In summary, nicotine gum and cigarettes both produced an acute increase in resting energy expenditure. However, the metabolic effects were greater in nicotine gum relative to cigarettes. Nicotine gum might have promise as an adjunctive treatment for those subjects who otherwise would not quit because of the weight control properties of smoking.
References Benowitz, N. L., & Jacob, P., III. (1984). Nicotine and carbon monoxide intake from high- and low-yield cigarettes. Clinical Pharmacology and Therapeutics, 38, 265-270. Bowen, D. J., Spring, B., & Fox, E. (in press). Tryptophan and high carbohydrate diets as adjuncts to smoking cessation therapy. Journal of Behavioral Medicine. Brantmark, B. (1973). Nicotine containing chewing gum as an antismoking aid. Psychopltarmacology, 31,191-200. Fagerstrom, K. O. (1987). Reducing weight gain after stopping smoking. Addictive Behaviors, 12, 91-93. Grinstead, O. A. (1981). Preventing weight gain following smoking ces-
ingcessation. Paper presented at the meetingof the Society of Behavioral Medicine Eighth Annual Scientific Sessions, Washington, DC. Perkins, K. A., Epstein, L. H., Stiller, R. L., Marks, B. L., & Jacob, R. G. (1989). Acute effects of nicotine on resting metabolic rate in cigarette smokers. American Journal of Clinical Nutrition, 50, 545-550. United States Department of Health, Education, and Welfare. (1979). Weight by height and age far adults 18-74 years: U.S. 1971-1974 (DHEW Publication No. 791656, Series 11, No. 280). Rockville, MD: Author. Warwick, P. M., Chappie, R. W, & Thomson, E. S. (1987). The effects of smoking two cigarettes on resting metabolic rate with and without food. International Journal of Obesity, 11, 229-237. Received October 19,1990 Revision received March 28,1991 Accepted April 5,1991 •
