Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992), pp. 1544-1547
Cigarette Smoking and Nicotine Delay Postprandial Mouth-Cecum Transit Time A.M. S C O T T , MB, BS, F R A C P , J.E. K E L L O W , MD, F R A C P , G.M. E C K E R S L E Y , RN, J.M. N O L A N , RN, and M.P. J O N E S , BSc
The acute effects o f both cigarette smoking and nicotine on postprandial mouth-cecum transit were studied in 20 habitual smokers, 10 males and 10 females. Mouth-cecum transit time was measured by the breath hydrogen technique, following ingestion o f a standard mixed liquid meal. Each subject was studied on four separate occasions, either (1) sham or actively smoking two standard cigarettes, commencing 20 min after the meal, or (2) chewing two placebo or nicotine tablets over a 60-min period, commencing immediately after the meal. The time of administration o f these stimuli was designed to minimize the effects on mouth-cecum transit time o f alterations in gastric emptying. Mouth-cecum transit time was prolonged in response to both smoking [median and interquartile range: 120 (95, 150) min vs 100 (75, 140) min, P = 0.01] and nicotine [120 (80, 170) min vs 100 (70, 140) min, P = 0.002]. No difference was observed between sexes with respect to nicotine; the effect o f smoking on mouth-cecum transit time, however, was less pronounced in females compared to males [difference active-placebo: 10 (10, 20) min vs 35 (20, 60) min, P = 0.01]. We conclude that acute cigarette smoking delays mouth-cecum transit time, an effect most likely due to nicotine. KEY WORDS: cigarette smoking; nicotine; mouth-cecum transit.
Cigarette smoking has been shown to affect esophageal and gastric motility (1, 2), as well as gastric, duodenal, and pancreatic secretion (3-7). With regard to m o u t h - c e c u m transit time (MCTT), however, although habitual smoking has been shown to have no chronic effect (8), the acute effect of smoking is not known. In addition, the influence of nicotine on M C T T in m a n has not previously been assessed. The aims of this study, in both male and female s m o k e r s , were therefore to determine the acute Manuscript received July 16, 1991; revised manuscript received April 13, 1992; accepted April 13, 1992. From the Departments of Medicine and Health Information Systems, Royal North Shore Hospital, Sydney, Australia. This study was supported by a grant from the Australian Tobacco Research Foundation. Address for reprint requests: Dr. J.E. Kellow, Department of Medicine, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. 1544
effects of cigarette smoking and of nicotine chewing gum on postprandial M C T T .
MATERIALS AND METHODS Subjects. Twenty habitual smokers, mean age 31 --+ 13 years, in two age-matched groups of 10 males and 10 females, participated. No subject had a history of, or symptoms related to, gastrointestinal disease. No subject was taking any medications at the time of the study, and all females were studied within the first 14 days of their menstrual cycle. The number of cigarettes smoked daily, 18 - 6 (mean --- SD), and the duration of smoking history, 13 -+ 15 years, were comparable in the two groups. All subjects gave written informed consent, and the study was approved by the Medical Review Ethics Committee of the Royal North Shore Hospital. Experimental Protocol. Each subject was studied on four separate randomized occasions following an overnight fast and after abstention from smoking for a 12-hr period. After ingestion of a standard liquid test meal of chicken soup (400 ml, 292 kcal), labeled with 10 g Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
0163-2116/92/1000-1544506.50/0 9 1992 Plenum Publishing Corporation
SMOKING DELAYS MOUTH-CECUM TRANSIT lactulose (9), subjects either: (1) sham (placebo) or actively smoked two standard cigarettes (each containing 1.2 mg nicotine) over a 5-min period, with instructions to inhale deeply, commencing 20 min after completion of the meal. The delay time of 20 min was chosen to minimize any effects of alterations in gastric emptying on MCTT (10); or (2) chewed two (consecutive) placebo or 4-mg nicotine tablets (Nicorette, Glaxo Australia Pty. Ltd.) over a 60-min period, commencing immediately after completion of the meal. The timing and duration of this stimulus was chosen so that significant levels of plasma nicotine would be obtained by 20 min and thereafter (11), and because nicotine gum had previously been shown not to affect gastric emptying (12). Mouth-cecum transit time was measured by the breath hydrogen technique. All subjects brushed their teeth and used a 0.2% chlorhexidine mouthwash prior to the meals (9); end expiratory breath samples were obtained every 10 min, commencing just prior to the meal, for a period of 3 hr. Breath hydrogen concentrations (ppm) were measured by an electrochemical breath analyzer (GMI Medical Ltd., Renfew, Scotland). MCTT was defined as the time from ingestion of the meal to a rise in breath hydrogen 5 ppm above the basal value, which was sustained for at least three consecutive samples (13). Statistical Analysis. MCTT values following cigarette smoking and nicotine gum were compared by Wilcoxon signed-rank test (14). The relationship between changes in MCTT and the age of subjects, number of cigarettes smoked per day, and the duration of smoking was assessed by Spearman rank correlation. The influence of sex was investigated by comparisons across male and female groups using Wilcoxon signed-rank test. Statistical significance was determined according to Hochberg's method (15), which accounts for multiple significance testing. Values in the text are median and interquartile range unless otherwise stated.
200
Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
I
150
100
50
0
I
I
Control
Smoking
Smoking Fig 1. M o u t h - c e c u m transit time (MCTT) in r e s p o n s e to control
(sham) or active cigarette smoking in 20 habitual smokers. responses to nicotine within the male group or within the female group. Age of the subjects, number of cigarettes smoked daily, and duration of smoking were found to have no confounding influence on the results. Similarly, the order in which 200
I
I
150
100
RESULTS M C T T was prolonged by cigarette smoking in 17 of the 20 subjects [active smoking: 120 (95,150) min vs placebo smoking: 100 (75, 140) min], and the mean difference between active and placebo smoking was statistically significant (P = 0.01) (Figure 1). M C T T was also prolonged by nicotine gum in all but five subjects [active nicotine: 120 (80, 170) min vs placebo nicotine: 100 (70, 140) min], and the mean difference between active and placebo nicotine was again statistically significant (P = 0.002) (Figure 2). There were no significant differences between the responses to smoking and the responses to nicotine. The effect of smoking was most p r o n o u n c e d in males (Table 1). The effect of nicotine, however, did not differ significantly between males and females (Table 1). T h e r e were no significant differences between the responses to smoking and the
I
50
0
q
I
Control
Nicotine
Nicotine Fig 2. Mouth--cecum transit time (MCTT) in r e s p o n s e to control (placebo) or active nicotine chewing g u m in 20 habitual smokers. TABLE 1. COMPARISON OF M C T T IN RESPONSE TO SMOKING AND TO NICOTINE GUM IN MALES AND FEMALES
Difference in MCTT* between active and placebo stimulus (median and interquartile range, min) Stimulus
Males (N = 10)
Females (N = 10)
P value, males vs females
Smoking Nicotine
35 (20, 60) 20 (10, 40)
10 (10, 20) 30 (10, 40)
0.01 0.93
*MCTT = mouth-cecum transit time.
1545
SCOTT ET AL the four tests were performed did not significantly affect the results. DISCUSSION The results of the present study demonstrate that both cigarette smoking and nicotine, the latter administered in the form of chewing tablets, prolong the mouth-cecum transit of the head of a meal. These effects were of a similar magnitude and were independent of the age of the patient, and the cigarette smoking history. We addressed the possibility of there being confounding effects of smoking (10) or nicotine on rates of gastric emptying, thus influencing MCTT, by delaying the onset of smoking until 20 min after ingestion of the meal; moreover, any effects of nicotine on gastric emptying, because it was given in the form of chewing tablets, would not have been expected to occur until at least a similar time period had elapsed (11). We did not wish to commence the chewing gum at 20 min after ingestion of the meal, as by the time adequate plasma nicotine levels would have been achieved, small bowel transit would have been relatively well advanced. The reported immediate and transient elevation of breath hydrogen levels due to acute cigarette smoking (9, 16, 17) was confined to the actual duration of smoking plus the 5-min period immediately after cessation, and thus did not affect determination of MCTT. Nicotine levels were not measured in the present study because the stress of venipuncture itself may have produced spurious alterations in transit (18). Despite the fact that the breath hydrogen technique assesses only the transit of the head of the meal, consistent effects of smoking and nicotine were observed in the majority of patients. Moreover, although it could be postulated that "dilution" of the lactulose load due to increased pancreaticobiliary secretion may have been a factor in the delay in measured transit, smoking has been shown to decrease, rather than increase, basal and stimulated pancreatic bicarbonate output (3, 5, 19). For this reason, and based on other reported studies (7, 20, 21), we feel that the observed changes in MCTT are likely to reflect primarily modulation of gastrointestinal motor activity. Thus, acute smoking has been shown to cause a reduction in basal antropyloroduodenal motility, an effect that continued for 20-30 min after smoking ceased (7). Likewise, while nicotine has been shown to inhibit duodenal contractile activity in dogs, possibly via an adren1546
ergic mechanism (20, 21), no previous study has examined its effects on the human small intestine. It was of particular interest to study the effects of orally administered nicotine, as it has been suggested that some of the effects of smoking on gut motility could be due to a vagal reflex induced by airway irritation (22). Despite the differing levels of plasma nicotine that may have been produced by the two different forms of stimuli, the similarity in the transit results between nicotine gum and smoking strongly suggests that nicotine is responsible for the observed effects. There is evidence that there may be regional differences in the effects of nicotine on the gastrointestinal tract; nicotine, in contrast to smoking, was shown not to affect gastric emptying in a recent study (12), and yet, at least in the dog, caused inhibition of contractile activity in the colon (23). The reasons for the disparity between sexes in response to smoking, where MCTT was less affected in females than males, is not clear. Comparison of smoking history between sexes demonstrated no appreciable differences, and we studied all females in the first 14 days of the menstrual cycle in order to minimize any confounding effects (24). It is possible that plasma levels of nicotine attained in females when smoking were not comparable to those in males; although all subjects apparently smoked in the same manner, one explanation may lie in a lesser degree of inhalation of the cigarette smoke by females. In conclusion, we have found that acute cigarette smoking delays MCTT by up to 25% of basal values, and the effect is most likely due to nicotine. Whether our observations can be related to the gastrointestinal symptoms sometimes reported by habitual smokers is speculative, but a delay in transit may be compatible with, for example, the common symptom of anorexia. Likewise, it is not inconceivable that the hyperphagia that subjects report after giving up smoking (25) may be associated with a relative acceleration of transit produced by withdrawal. Moreover, such alterations in transit may be a factor in the reported association between smoking and symptoms of irritable bowel syndrome (26-28). REFERENCES 1. Kahrilas PJ, Gupta RR: Mechanisms of acid reflux associated with cigarette smoking. Gut 31:4-10, 1990 2. Scott AM, Kellow JE, Shuter B, Prescott B, Nolan JM, Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
SMOKING DELAYS MOUTH-CECUM TRANSIT
3.
4. 5.
6.
7.
8.
9.
10.
11.
12.
13.
14. 15.
H6schl R: How does cigarette smoking delay solid and liquid gastric emptying? Aust NZ J Med 20(suppl 1):371, 1990 Murthy SNS, Dinoso VP, Clearfield HR, Chey WY: Simultaneous measurements of basal pancreatic, gastric acid secretion, serum gastrin and secretin during smoking. Gastroenterology 73:758-761, 1977 Fung WP, Tye CY: Effect of smoking on gastric acid secretion. Aust NZ J Med 3:251-254, 1973 Bynum JE, Solomon TE, Johnson LR, Jacobsen ED: Inhibition of pancreatic secretion in man by cigarette smoking. Gut 13:361-365, 1973 Mnrthy SNS, Dinoso VP, Harris R, Clearfield HR, Chey WY: Serial pH changes in the duodenal bulb during smoking. Gastroenterology 75:1-4, 1978 Ertel G, Henman B, Murthy SNS, Dinoso VP: The effects of smoking on gastroduodenal motility, pH changes in the proximal duodenum, and gastrointestinal hormones. Gastroenterology 88:1375, 1985 Scott AM, Kellow JE, Shuter B, Nolan JM, H6schl R, Jones MP: Effects of chronic smoking on upper gastrointestinal motor function. J Nucl Med 31(5):801, 1990 Thompson DG, Binfield P, De Belier A, O'Brien J, Warren NA, Wilson M: Extraintestinal influences on exhaled breath hydrogen measurements during the investigation of gastrointestinal disease. Gut 26:1349-1352, 1985 Scott AM, Kellow JE, Shuter B, Nolan JM, H6schl R, Jones MP: Cigarette smoking delays solid and liquid gastric emptying. J Nucl Med 37(5):847, 1990 Russell MAH, Feyerabend C, Cole PU: Plasma nicotine levels after cigarette smoking and chewing nicotine gum. Br Med J 1:1043-1046, 1976 Miller G, Palmer KR, Smith B, Ferrington C, Merrick MV: Smoking delays gastric emptying of solids. Gut 30:50-53, 1989 Kellow JE, Borody TJ, Phillips SF, Haddad AC, Brown ML: Sulfapyridine appearance in plasma after salicylazosulfapyridine. Gastroenterology 91:396-400, 1986 Canover WJ: Practical Non-Parametric Statistics, 2nd ed. New York, John Wiley & Sons, 1980 Hochberg Y, Benjamini Y: More powerful procedures for multiple significance testing. Star Med 9(7):811-818, 1990
Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
16. Rosenthal A, Soloman NW: Time-course of cigarette smoke contamination of clinical hydrogen breath-analysis tests. Clin Chem 29(11): 1980-1981, 1983 17. Tadesse K, Eastwood M: Breath-hydrogen test and smoking. Lancet 2:91-92, 1977 18. Cann PA, Read NW, Cammack J, Childs H, Holden S, Kashman R, Longmore J, Nix S, Simms N, Swallow K, Weller J: Psychological stress and the passage of a standard meal through the stomach and small intestine in man. Gut 24:236-240, 1983 19. Bochenek WJ, Koronczewski R: Effect of cigarette smoking on bicarbonate and volume of duodenal contents. Am J Dig Dis 18:729-733, 1973 20. Carlsen GM, Ruddon RW, Hug CC, Bass P: Effects of nicotine on gastric antral and duodenal contractile activity in the dog. J Pharmacol Exp Ther 172:367-376, 1970 21. Carlsen GM, Ruddon RW, Hug CC, Schmiege SN, Bass P: Analysis of the site of nicotine action on gastric antral and duodenal contractile activity. J Pharmacol Exp Ther 172:377-383, 1970 22. Schnedorf JG, Ivy AC: The effect of tobacco smoking on the alimentary tract. JAMA 112:898-903, 1939 23. Weisbrodt NW, Hug CC, Schmiege SK, Bass P: Effects of nicotine and tyramine on contractile activity of the colon. Eur J Pharmacol 12:310-319, 1970 24. Wald A, Van Thiel DH, Hoechstetter L, Gavaler J, Egler K, Verm R, Scott L, Lester R: Gastrointestinal transit: The effect of the menstrual cycle. Gastroenterology 80:14971500, 1981 25. Hall SM, McGee R, Tunstall C, Duffy J, Benowitz N: Changes in food intake and activity after quitting smoking. J Consult Clin Psychol 58:81-86, 1989 26. Johnsen R, Jacobsen BK, Forde OH: Associations between symptoms of irritable colon and psychological and social conditions and lifestyle. Br Med J 292:1633-1635, 1986 27. Delor CJ: The irritable bowel syndrome. Ann Intern Med 25:427-434, 1967 28. Kirsner JB: The irritable bowel syndrome. A clinical review and ethical considerations. Arch Intern Med 141:635-639, 1981
1547
Cigarette Smoking and Nicotine Delay Postprandial Mouth-Cecum Transit Time A.M. S C O T T , MB, BS, F R A C P , J.E. K E L L O W , MD, F R A C P , G.M. E C K E R S L E Y , RN, J.M. N O L A N , RN, and M.P. J O N E S , BSc
The acute effects o f both cigarette smoking and nicotine on postprandial mouth-cecum transit were studied in 20 habitual smokers, 10 males and 10 females. Mouth-cecum transit time was measured by the breath hydrogen technique, following ingestion o f a standard mixed liquid meal. Each subject was studied on four separate occasions, either (1) sham or actively smoking two standard cigarettes, commencing 20 min after the meal, or (2) chewing two placebo or nicotine tablets over a 60-min period, commencing immediately after the meal. The time of administration o f these stimuli was designed to minimize the effects on mouth-cecum transit time o f alterations in gastric emptying. Mouth-cecum transit time was prolonged in response to both smoking [median and interquartile range: 120 (95, 150) min vs 100 (75, 140) min, P = 0.01] and nicotine [120 (80, 170) min vs 100 (70, 140) min, P = 0.002]. No difference was observed between sexes with respect to nicotine; the effect o f smoking on mouth-cecum transit time, however, was less pronounced in females compared to males [difference active-placebo: 10 (10, 20) min vs 35 (20, 60) min, P = 0.01]. We conclude that acute cigarette smoking delays mouth-cecum transit time, an effect most likely due to nicotine. KEY WORDS: cigarette smoking; nicotine; mouth-cecum transit.
Cigarette smoking has been shown to affect esophageal and gastric motility (1, 2), as well as gastric, duodenal, and pancreatic secretion (3-7). With regard to m o u t h - c e c u m transit time (MCTT), however, although habitual smoking has been shown to have no chronic effect (8), the acute effect of smoking is not known. In addition, the influence of nicotine on M C T T in m a n has not previously been assessed. The aims of this study, in both male and female s m o k e r s , were therefore to determine the acute Manuscript received July 16, 1991; revised manuscript received April 13, 1992; accepted April 13, 1992. From the Departments of Medicine and Health Information Systems, Royal North Shore Hospital, Sydney, Australia. This study was supported by a grant from the Australian Tobacco Research Foundation. Address for reprint requests: Dr. J.E. Kellow, Department of Medicine, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. 1544
effects of cigarette smoking and of nicotine chewing gum on postprandial M C T T .
MATERIALS AND METHODS Subjects. Twenty habitual smokers, mean age 31 --+ 13 years, in two age-matched groups of 10 males and 10 females, participated. No subject had a history of, or symptoms related to, gastrointestinal disease. No subject was taking any medications at the time of the study, and all females were studied within the first 14 days of their menstrual cycle. The number of cigarettes smoked daily, 18 - 6 (mean --- SD), and the duration of smoking history, 13 -+ 15 years, were comparable in the two groups. All subjects gave written informed consent, and the study was approved by the Medical Review Ethics Committee of the Royal North Shore Hospital. Experimental Protocol. Each subject was studied on four separate randomized occasions following an overnight fast and after abstention from smoking for a 12-hr period. After ingestion of a standard liquid test meal of chicken soup (400 ml, 292 kcal), labeled with 10 g Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
0163-2116/92/1000-1544506.50/0 9 1992 Plenum Publishing Corporation
SMOKING DELAYS MOUTH-CECUM TRANSIT lactulose (9), subjects either: (1) sham (placebo) or actively smoked two standard cigarettes (each containing 1.2 mg nicotine) over a 5-min period, with instructions to inhale deeply, commencing 20 min after completion of the meal. The delay time of 20 min was chosen to minimize any effects of alterations in gastric emptying on MCTT (10); or (2) chewed two (consecutive) placebo or 4-mg nicotine tablets (Nicorette, Glaxo Australia Pty. Ltd.) over a 60-min period, commencing immediately after completion of the meal. The timing and duration of this stimulus was chosen so that significant levels of plasma nicotine would be obtained by 20 min and thereafter (11), and because nicotine gum had previously been shown not to affect gastric emptying (12). Mouth-cecum transit time was measured by the breath hydrogen technique. All subjects brushed their teeth and used a 0.2% chlorhexidine mouthwash prior to the meals (9); end expiratory breath samples were obtained every 10 min, commencing just prior to the meal, for a period of 3 hr. Breath hydrogen concentrations (ppm) were measured by an electrochemical breath analyzer (GMI Medical Ltd., Renfew, Scotland). MCTT was defined as the time from ingestion of the meal to a rise in breath hydrogen 5 ppm above the basal value, which was sustained for at least three consecutive samples (13). Statistical Analysis. MCTT values following cigarette smoking and nicotine gum were compared by Wilcoxon signed-rank test (14). The relationship between changes in MCTT and the age of subjects, number of cigarettes smoked per day, and the duration of smoking was assessed by Spearman rank correlation. The influence of sex was investigated by comparisons across male and female groups using Wilcoxon signed-rank test. Statistical significance was determined according to Hochberg's method (15), which accounts for multiple significance testing. Values in the text are median and interquartile range unless otherwise stated.
200
Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
I
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100
50
0
I
I
Control
Smoking
Smoking Fig 1. M o u t h - c e c u m transit time (MCTT) in r e s p o n s e to control
(sham) or active cigarette smoking in 20 habitual smokers. responses to nicotine within the male group or within the female group. Age of the subjects, number of cigarettes smoked daily, and duration of smoking were found to have no confounding influence on the results. Similarly, the order in which 200
I
I
150
100
RESULTS M C T T was prolonged by cigarette smoking in 17 of the 20 subjects [active smoking: 120 (95,150) min vs placebo smoking: 100 (75, 140) min], and the mean difference between active and placebo smoking was statistically significant (P = 0.01) (Figure 1). M C T T was also prolonged by nicotine gum in all but five subjects [active nicotine: 120 (80, 170) min vs placebo nicotine: 100 (70, 140) min], and the mean difference between active and placebo nicotine was again statistically significant (P = 0.002) (Figure 2). There were no significant differences between the responses to smoking and the responses to nicotine. The effect of smoking was most p r o n o u n c e d in males (Table 1). The effect of nicotine, however, did not differ significantly between males and females (Table 1). T h e r e were no significant differences between the responses to smoking and the
I
50
0
q
I
Control
Nicotine
Nicotine Fig 2. Mouth--cecum transit time (MCTT) in r e s p o n s e to control (placebo) or active nicotine chewing g u m in 20 habitual smokers. TABLE 1. COMPARISON OF M C T T IN RESPONSE TO SMOKING AND TO NICOTINE GUM IN MALES AND FEMALES
Difference in MCTT* between active and placebo stimulus (median and interquartile range, min) Stimulus
Males (N = 10)
Females (N = 10)
P value, males vs females
Smoking Nicotine
35 (20, 60) 20 (10, 40)
10 (10, 20) 30 (10, 40)
0.01 0.93
*MCTT = mouth-cecum transit time.
1545
SCOTT ET AL the four tests were performed did not significantly affect the results. DISCUSSION The results of the present study demonstrate that both cigarette smoking and nicotine, the latter administered in the form of chewing tablets, prolong the mouth-cecum transit of the head of a meal. These effects were of a similar magnitude and were independent of the age of the patient, and the cigarette smoking history. We addressed the possibility of there being confounding effects of smoking (10) or nicotine on rates of gastric emptying, thus influencing MCTT, by delaying the onset of smoking until 20 min after ingestion of the meal; moreover, any effects of nicotine on gastric emptying, because it was given in the form of chewing tablets, would not have been expected to occur until at least a similar time period had elapsed (11). We did not wish to commence the chewing gum at 20 min after ingestion of the meal, as by the time adequate plasma nicotine levels would have been achieved, small bowel transit would have been relatively well advanced. The reported immediate and transient elevation of breath hydrogen levels due to acute cigarette smoking (9, 16, 17) was confined to the actual duration of smoking plus the 5-min period immediately after cessation, and thus did not affect determination of MCTT. Nicotine levels were not measured in the present study because the stress of venipuncture itself may have produced spurious alterations in transit (18). Despite the fact that the breath hydrogen technique assesses only the transit of the head of the meal, consistent effects of smoking and nicotine were observed in the majority of patients. Moreover, although it could be postulated that "dilution" of the lactulose load due to increased pancreaticobiliary secretion may have been a factor in the delay in measured transit, smoking has been shown to decrease, rather than increase, basal and stimulated pancreatic bicarbonate output (3, 5, 19). For this reason, and based on other reported studies (7, 20, 21), we feel that the observed changes in MCTT are likely to reflect primarily modulation of gastrointestinal motor activity. Thus, acute smoking has been shown to cause a reduction in basal antropyloroduodenal motility, an effect that continued for 20-30 min after smoking ceased (7). Likewise, while nicotine has been shown to inhibit duodenal contractile activity in dogs, possibly via an adren1546
ergic mechanism (20, 21), no previous study has examined its effects on the human small intestine. It was of particular interest to study the effects of orally administered nicotine, as it has been suggested that some of the effects of smoking on gut motility could be due to a vagal reflex induced by airway irritation (22). Despite the differing levels of plasma nicotine that may have been produced by the two different forms of stimuli, the similarity in the transit results between nicotine gum and smoking strongly suggests that nicotine is responsible for the observed effects. There is evidence that there may be regional differences in the effects of nicotine on the gastrointestinal tract; nicotine, in contrast to smoking, was shown not to affect gastric emptying in a recent study (12), and yet, at least in the dog, caused inhibition of contractile activity in the colon (23). The reasons for the disparity between sexes in response to smoking, where MCTT was less affected in females than males, is not clear. Comparison of smoking history between sexes demonstrated no appreciable differences, and we studied all females in the first 14 days of the menstrual cycle in order to minimize any confounding effects (24). It is possible that plasma levels of nicotine attained in females when smoking were not comparable to those in males; although all subjects apparently smoked in the same manner, one explanation may lie in a lesser degree of inhalation of the cigarette smoke by females. In conclusion, we have found that acute cigarette smoking delays MCTT by up to 25% of basal values, and the effect is most likely due to nicotine. Whether our observations can be related to the gastrointestinal symptoms sometimes reported by habitual smokers is speculative, but a delay in transit may be compatible with, for example, the common symptom of anorexia. Likewise, it is not inconceivable that the hyperphagia that subjects report after giving up smoking (25) may be associated with a relative acceleration of transit produced by withdrawal. Moreover, such alterations in transit may be a factor in the reported association between smoking and symptoms of irritable bowel syndrome (26-28). REFERENCES 1. Kahrilas PJ, Gupta RR: Mechanisms of acid reflux associated with cigarette smoking. Gut 31:4-10, 1990 2. Scott AM, Kellow JE, Shuter B, Prescott B, Nolan JM, Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
SMOKING DELAYS MOUTH-CECUM TRANSIT
3.
4. 5.
6.
7.
8.
9.
10.
11.
12.
13.
14. 15.
H6schl R: How does cigarette smoking delay solid and liquid gastric emptying? Aust NZ J Med 20(suppl 1):371, 1990 Murthy SNS, Dinoso VP, Clearfield HR, Chey WY: Simultaneous measurements of basal pancreatic, gastric acid secretion, serum gastrin and secretin during smoking. Gastroenterology 73:758-761, 1977 Fung WP, Tye CY: Effect of smoking on gastric acid secretion. Aust NZ J Med 3:251-254, 1973 Bynum JE, Solomon TE, Johnson LR, Jacobsen ED: Inhibition of pancreatic secretion in man by cigarette smoking. Gut 13:361-365, 1973 Mnrthy SNS, Dinoso VP, Harris R, Clearfield HR, Chey WY: Serial pH changes in the duodenal bulb during smoking. Gastroenterology 75:1-4, 1978 Ertel G, Henman B, Murthy SNS, Dinoso VP: The effects of smoking on gastroduodenal motility, pH changes in the proximal duodenum, and gastrointestinal hormones. Gastroenterology 88:1375, 1985 Scott AM, Kellow JE, Shuter B, Nolan JM, H6schl R, Jones MP: Effects of chronic smoking on upper gastrointestinal motor function. J Nucl Med 31(5):801, 1990 Thompson DG, Binfield P, De Belier A, O'Brien J, Warren NA, Wilson M: Extraintestinal influences on exhaled breath hydrogen measurements during the investigation of gastrointestinal disease. Gut 26:1349-1352, 1985 Scott AM, Kellow JE, Shuter B, Nolan JM, H6schl R, Jones MP: Cigarette smoking delays solid and liquid gastric emptying. J Nucl Med 37(5):847, 1990 Russell MAH, Feyerabend C, Cole PU: Plasma nicotine levels after cigarette smoking and chewing nicotine gum. Br Med J 1:1043-1046, 1976 Miller G, Palmer KR, Smith B, Ferrington C, Merrick MV: Smoking delays gastric emptying of solids. Gut 30:50-53, 1989 Kellow JE, Borody TJ, Phillips SF, Haddad AC, Brown ML: Sulfapyridine appearance in plasma after salicylazosulfapyridine. Gastroenterology 91:396-400, 1986 Canover WJ: Practical Non-Parametric Statistics, 2nd ed. New York, John Wiley & Sons, 1980 Hochberg Y, Benjamini Y: More powerful procedures for multiple significance testing. Star Med 9(7):811-818, 1990
Digestive Diseases and Sciences, Vol. 37, No. 10 (October 1992)
16. Rosenthal A, Soloman NW: Time-course of cigarette smoke contamination of clinical hydrogen breath-analysis tests. Clin Chem 29(11): 1980-1981, 1983 17. Tadesse K, Eastwood M: Breath-hydrogen test and smoking. Lancet 2:91-92, 1977 18. Cann PA, Read NW, Cammack J, Childs H, Holden S, Kashman R, Longmore J, Nix S, Simms N, Swallow K, Weller J: Psychological stress and the passage of a standard meal through the stomach and small intestine in man. Gut 24:236-240, 1983 19. Bochenek WJ, Koronczewski R: Effect of cigarette smoking on bicarbonate and volume of duodenal contents. Am J Dig Dis 18:729-733, 1973 20. Carlsen GM, Ruddon RW, Hug CC, Bass P: Effects of nicotine on gastric antral and duodenal contractile activity in the dog. J Pharmacol Exp Ther 172:367-376, 1970 21. Carlsen GM, Ruddon RW, Hug CC, Schmiege SN, Bass P: Analysis of the site of nicotine action on gastric antral and duodenal contractile activity. J Pharmacol Exp Ther 172:377-383, 1970 22. Schnedorf JG, Ivy AC: The effect of tobacco smoking on the alimentary tract. JAMA 112:898-903, 1939 23. Weisbrodt NW, Hug CC, Schmiege SK, Bass P: Effects of nicotine and tyramine on contractile activity of the colon. Eur J Pharmacol 12:310-319, 1970 24. Wald A, Van Thiel DH, Hoechstetter L, Gavaler J, Egler K, Verm R, Scott L, Lester R: Gastrointestinal transit: The effect of the menstrual cycle. Gastroenterology 80:14971500, 1981 25. Hall SM, McGee R, Tunstall C, Duffy J, Benowitz N: Changes in food intake and activity after quitting smoking. J Consult Clin Psychol 58:81-86, 1989 26. Johnsen R, Jacobsen BK, Forde OH: Associations between symptoms of irritable colon and psychological and social conditions and lifestyle. Br Med J 292:1633-1635, 1986 27. Delor CJ: The irritable bowel syndrome. Ann Intern Med 25:427-434, 1967 28. Kirsner JB: The irritable bowel syndrome. A clinical review and ethical considerations. Arch Intern Med 141:635-639, 1981
1547
