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Reprinted frq~ ~e Archives of Environmental Health ~ rch 1970, Volume 20 Copyright~, O, American Medical Association Metabolic Changes Associated With the Cessation of Cigarette Smoking Stanley C. Glauser, MD, Phl); Elinor M. Glauser, MD; Marcus M. Reidenberg, MD; Ben F. Rusy, M D; and Ronald J. Tallarida, PhD, Philadelphia

377 Metabolic Changes Associated With the Cessation of Cigarette Smoking Stanley C. Glauser, M D , P h D ; E linor M. Glauser, M D ; Marcus M. Reidenberg, M D ; Ben F. Rusy, M D; and Ronald J. Tallarida, PhD, Philadelphia The person who stops smoking frequently gains weight in the succeeding weeks. To study this phenomenon, subjects were observed before and one month after the cessation of smoking. Slatis- tically significant increases were found in the body weight and body surface area while there were statistically significant decreases in the pro- rein-bound iodine level (PBI), oxygen consump- tion, heart rate, 30-minute postprandial blood glucose level, and the serum calcium level. These metabolic changes following the cessation of smoking may be one of ths rsasons for the weight gain observed. THE adverse effects of cigarette smoking on the health of the individual have been well established.1 Much effort has gone into convincing cigarette smokers that they should stop smoking, since the cessation of smoking has been shown to reverse some of the adverse effects of smoking.~ The person who stops smoking frequently gains weight in the succeeding weeks or months. This unwanted weight gain is often attributed to increased food intake due to psychological factors related to the cessation of smoking. The cause of this weight gain is, in fact, unknown. Our study was carried out to see if the cessation of smoking was associated with any gross metabolic changes that could be, in part, responsible for the weight gain. Submitted for publication May 25, 1969; accepted Sept 30. From the Department of Pharmacology, Temple University School of Medicine. Philadelphia. Reprint requests to 3400 N Broad St, Philadel- phia 19140 (Dr. Glauser). Methods Seven male cigarette smoking scientists vol- unteered to participate in this study. Each had previously participated in pulmonary studies and was thoroughly familiar with the testing procedure. The entire battery of tests was car- tied out on each subject at two different times. Tests were made during the period in which the volunteer was smoking and again after he had not smoked for one month. The subjects fasted and did not smoke for 12 hours prior to the battery of tests. They came to the laboratory and assumed a supine posi- tion for a one-half hour rest. This position was maintained for the entire experimental period. Following the initial rest, the subject breathed through a Hans Rudolph high velocity one-way breathing valve. A three-minute period of quiet breathing of room air through the apparatus was followed by a seven-minute collection peri- od. During this test period, air was inspired from a Tissot spirometer and expired gas was collected in a Douglas bag. The respiratory rate was determined during this test period. Sam- ples of inspired and expired gas were collected Table 1.--Smoking History of Subiects in Study Subjects Years Smoked Packs per Day Cough 1 13 1.5 none 2 I 0 1 .O none 3 22 1.0 none 4 8 1.5 positive 5 18 2.0 positive 6 8 1.25 none 7 I0 1.5 none Average 12.7 1.4 SD 5.0 0.3 Arch, Enuiron Health--Vol 20, March 1970

378 ( ( CESSATION OF CIGARETTE SMOKING--GLAUSER ET AL Table 2.--Measurement of Age, Height, Weight, BSA,* Temperature, Blood Pressure, and Weight,? Ib (kg) BSA (meters squared)~: Height, Subject Age in (cm) Before After Before After 1 30 72.25 (180.6) 209.5 (104.8) 214,0 (107) 2.16 2.19 2 27 70.25 (175.6) 191.0 (95.5) 194,0 (97) 2.05 2.06 3 43 71.50 (178.8) 213.0 (106.5) 214,0 (107) 2.17 2.17 4 28 67.50(168.8) 154.5 (77.3) 164,0 (82) 1.82 1.86 5 35 69.75 (174.3) 167.0 (83.5) 172.0 (89) 1.92 1.94 6 30 70.00(175.0) 167.0 (83.5) 167,0 (83.5) 1.92 1.92 7 27 70.25 (175.6) 216.0 (108) 238.0 (I 19) 2.15 2.24 Average 31.4 70.21 (175.5) 188.3 (94.2) 194.7 (97.4) 2.03 2.05 SD 5.4 1.38 23.6 26.3 0.13 0.14 * BSA, body surface area. t Both values are statistically significant and different (P < 0.05). ~ Both values are statistically significant and highly different (P < 0.025). Table 3.--Measurement of Hematocrit, Glucose, Serum Cholesterol, PBI, Hemoglobin, Serum Fasting Blood Glucose, 30-rain Blood Glucose, Serum Cholesterol, Hematocrit rag/100 ml mg/100 ml* rag/100 ml Subject Before After Before After Before After Before After 1 42.0 46.3 80 85 108 76 282 213 2 44.0 44.4 82 92 137 150 185 199 3 43.7 46.3 100 95 175 161 310 312 4 43 42 82 79 120 109 226 263 5 46.1 44.8 83 85 122 122 308 265 6 43.8 41.4 90 86 148 118 182 126 7 46.7 44.2 92 86 148 130 204 209 Average 44.2 44.2 87 87 ] 37 123 242 227 SD 1.5 1.8 6.7 4.8 20.8 25.8 52 55 * Both values are statistically significant and different (P < 0.05). % Both values are statistically significant and highly different (P < 0.025). Table 4.~Measurement of 0~_ Consumption, CO~ Production, RespiratorF Quotient and Rate, and Oxygen Oxygen Consumption, (ml Oz/min at STPD)* Carbon Dioxide Production, (ml COz/min at STPD) Respiratory Quotient* Subject Before After Before After Before After 1 295 273 199 233 0.67 0.85 2 284 204 210 176 0.74 0.86 3 311 275 237 191 0.73 0.69 4 214 247 185 213 0.86 0.86 5 298 256 231 206 0.78 0.80 6 262 249 179 183 0.68 0.73 7 317 315 251 269 0.79 0.85 Average 283 260 213 210 0.75 0.81 SD$ 33 31 25 30 0.06 0.06 * Both values are statistically significant and different (P < 0.05). STPD, standard temperature and pressure, dry. Arch Enuiron Health--VoZ 20, March 1970

CESSATION OF CIGARETTE SA{OKING--GLAUSER ET AL Heart Rate Before and After Cessation of Smoking 379 Temperature, F (C) Blood Pressure (mm Hg) Heart Rate (Beats/min)¢ Before After Before After Before After 97.0 (36.1) 97.2 (36.2) 126/88 122/90 65 65 97.6 (36.4) 97.8 (36.6) 100/60 112/58 43 42 98.2 (36.8) 97.6 (36.4) 124/86 126/86 65 52 97.6 (36.4) 97.4 (36.3) 110/66 112/60 68 68 97.6 (36.4) 97.6 (36.4) 108/68 122/78 62 58 97.8 (36.6) 98.0 (36.7) 112/70 108/64 53 53 97.6 (36.4) 97.4 (36.3) 110/70 116/78 65 60 97.6 (36.4) 97.6 (36.4) 113/73 117/73 60 57 0.3 0.2 8/10 6/12 8 8 Calcium, and Difference Between 30-minute and Fasting Blood Glucose Serum Calcium, PBI, #g/100 ml* Hgb, gm/100 ml mg/100 ml¢ 30-min Blood Glucose-Fasting Blood Glucose, mg/100 ml* Before After Before After Before After Before After 4.8 4.7 12.1 16.3 10.84 10.00 28 4.7 3.7 13.9 14.5 9.84 9.66 55 58 4.2 4.4 13.6 14.8 10.20 10.42 75 66 6.2 6.3 13.0 13.7 10.04 10.10 38 30 5.6 4.5 13.6 13.3 10.50 9.32 39 37 3.7 3.7 13.7 13.2 9.22 8.40 58 32 6.2 4.7 13.1 12.3 10.74 9.84 56 44 5.1 4.6 13.3 14.0 10.20 9.70 50 37 0.9 0.8 0.6 1,2 0.50 0.60 14.6 22,4 Consumption Before and After Cessation of Smoking Respiratory Rate, Oz Consumption/meters (Breaths/min) squared Before After Before After 8 6 137 125 7 10 139 99 4 4 143 127 13 16 118 133 10 8 155 132 12 16 ]36 130 10 8 147 141 9 10 139 127 3 4 11 12 under mercury in a tonometer and analyzed in a Scholander:~ gas analyzer. Inspired and ex- pired gas volumes were measured in a W~ssot spirometer and corrected to standard condi- tions. Oral temperatures were measured with a clinical thermometer. Blood pressure readings were made on an aneroid type sphygmomanom- eter. A six-lead electrocardiogram was taken using the limb leads. Venous blood samples were collected. Tubes without anticoagulant were used 5o collect blood for serum cholester- ol, serum calcium, and serum protein-bound iodine (PBI) levels. Anticoagulated blood was used fasting to obtain the following values: blood glucose, hemoglobin, and hematocrit. The volunteer was then given 150 ml of a 50% glucose solution in ice. Thirty minutes later, another venous blood sample was drawn for Arch Environ Health--Vd 20, March 1970

380 CESSATION OF CIGARETTE glucose determination. The subjects were then permitted to stand up and their height and weight were measured. The blood glucose analysis was done by the ferricyanide reduction method as adapted for the autoanalyzer. The PBI analysis was done by the wet ash and ceric ammonium sulfate-ar- senous acid method, as adapted for the autoan- alyzer. The analysis of cholesterols was done by the method of Pauvionsky.4 The hemoglobin concentration was determined spectrophoto- metrically, using Drabkin's reagent.5 The hema- tocrit readings were done using microcapfllary tubes. The serum calcium levels were determined by atomic absorption spectroscopy,s The analysis of data was done by means of a paired comparison, with each subject serving as his own control. Table 1 identifies the seven male scientist volunteers and shows that they smoked an average of 12.7 years and consumed as aver- age of 1.4 packs of cigarettes per day. By history, only two acknowledged having a chronic cough. Table 2 gives the age and height of the subjects, and weight before and after cessa- tion of snmking. The mean age was 31.4 years, the mean height was 178.7 cm (70.21 inches). The mean weight before cessation of smoking was 83.29 kg (188.3 lb), while after cessation of smoking it increased to 87.33 kg (194.7 lb). Table 2 also gives the body surface area, temperature, blood pres- sure, and heart rate before and after the cessation of smoking. The body surface area was determined from the nomogram of DuBois.z The mean body surface area before cessation of smoking was 2.03 meters squared, while after cessation of smoking, it rose to 2.05 meters squared. This difference is due to the increase in body weight. The mean body temperature both before and af- ter cessation of smoking was 97.6 F (36.4 C). The mean blood pressure before cessation of smoking was 113/73 mm Hg, while after cessation of smoking, it was 117/73. The mean heart rate before cessation of smoking, as determined from the ECG record, was 60 beats per minute, while after cessation of smoking, this decreased to 57 beats per min- ute. In Table 3, values are given for hemato- crit, fasting blood glucose, 30-minute post- SMOKING--GLAUSER ET AL prandial blood glucose, serum cholesterol, PBI, hemoglobin concentration of blood, and serum calcium. The mean hematocrit reading before and after cessation of smok- ing was 44.2~. The mean fasting blood glucose level before and after cessation of smoking was 87 mg/100 ml. The mean 30- minute postprandial blood glucose level was 137 mg/100 ml before cessation of smoking, while after cessation of smoking this value dropped to 123 rag/100 ml. The mean serum cholesterol level before cessation of smoking was 242 rag/100 ml and after cessation of smoking was 10.2 mg/100 ml, while after level before cessation of smoking was 5.1~g/100 ml while after cessation of smok- ing, it was 4.6ttg/100 ml. Before cessation of smoking, the mean hemoglobin value was 13.3 gm]100 ml, while after cessation of smoking it was 14.0 gm/100 ml. The mean sertan calcium level before cessation of smoking was 10.2 mg/100 ml, while after cessation of smoking this had declined to 9.7 rag/100 ml. Table 4 summarizes the respiratory data and lists the oxygen consumption, carbon dioxide production, respiratory quotient, and respiratory rate. The mean oxygen con- sumption before cessation of smoking was 283 ml/min, while after cessation of smok- ing the value had dropped to 260 ml/min. The average carbon dioxide production be- fore cessation of smoking was 213 ml/min, while after cessation of smoking it was 210 ml/min. The respiratory quotient was calcu- lated for each individual by dividing his carbon dioxide production by his oxygen consumption. The mean respiratory quotient before cessation of smoking was 0.75, while after cessation of smoking this value had risen to 0.81. The average respiratory rate before cessation of smoking was 9 breaths per minute and after cessation of smoking was 10 breaths per minute. The electrocar- diographic pattern of each patient taken after the cessation of smoking was the same as that taken during smoking. Conunent The following factors were significantly changed following the cessation of smoking: body weight increased, body surface area increased, heart rate decreased, 30-minute postprandial blood glucose level decreased, Arch Environ HeaIth--Vol 20. March 1970

CESSATION OF C RETTE SMOKING--GLAUSER ET AL ~ 381 PBI decreased, serum calcium level de- creased, oxygen consumption decreased, and the respiratory quotient increased. There was also a significant drop in the increase in blood glucose following a glucose meal. Each of the subjects, with one exception, gained weight during the month between tests. The subject who maintained a con- stant weight had a marked increase in activ- ity levels. All but one subject had a decrease in their basal oxygen consumptions. It is commonly accepted that the weight gain following the cessation of smoking is due to an increase in food consumption without a parallel increase in physical activity. We interpret our results to indicate that a meta- bolic change occurs following the cessation of smoking. This change causes a decreased basal oxygen consumption. With no change in caloric intake or physical activity, this metabolic change would cause weight gain. We think that this metabolic change is par- tially responsible for the weight gain ob- served in our subjects. Other evidence for a metabolic change was the decreased hyper- glycemic response to a glucose meal while the fasting blood glucose level remained con° stant; the decreased PBI level; the de- creased serum calcium level; and a small, but statistically significant, decreased heart rate. Other known changes produced by smok- ing include an increased heart rate,S,9 block- age of normal metabolism of tryptophan,TM induction of benzpyrene hydroxylase in pla- cental tissue,11 and decrease in carbonic an- hydrase in fetuses.12 Nicotine has been shown to cause an increase in tryptophan pyrrolase and in the rate of metabolism of ethylmorphine, norcodeine, and aniline.TM The metabolic changes following the ces- sation of smoking described in this study may be one of the reasons for the weight gain observed. The idea that weight gained after smoking is stopped is due solely to increased caloric intake without parallel in- creased physical activity is not necessarily true. This work was supported in part by PHS grants AM-10072, He-08752, and FR~)0349, and a grant- in-aid from the Southeastern Pennsylvania Hear~ Association. References 1. The Health Consequences of Smoking. Surgeon Genemrs Report, a Public Health Service Review, 1967. 2. Hammond EC: The effects of smoking. Sci Amer 207:39-51, 1962. 3. Scholander PE: Analyzer for accurate estima- tions of respiratory gases in one half cubic centime- tar samples. J Biol Chem 167:235-250, 1947. 4. Pauvionsky P: Moderately simple cholesterol method eliminating intermediate extractions. Clin Chern 8:444, 1962. 5. Drabkin DL, Austin JH: Spectrophotometric studies: Preparation from washed blood cells; nitric oxide hemoglobin and sulfhemoglobin. J Biol Chem 112:51-65, 1935. 6. Willis JB: Determination of calcium and mag- nesium in urine by atomic absorption spectroscopy. Anal Chem 33:556-559, 1961. 7. DuBois EF: Basal Metabolism in Health and Disease, ed 3. Philadelphia, Lea & Febiger Publish- ers, 1924, pp 145-200. 8. Krumholz RA, Chevalier RB, Ross JC: Changes in cardiopulmonary functions related to abstinenco from smoking. Ann Intern Med 62:197- 207, 1965. 9. Chevalier RB, Bowers, JA, Bondurant S, et al: Circulatory and venti!atory effects of exercise in smokers and nonsmokers. J Appl Physiol 18:357- 360, 1963. 10. Kerr WK, Barkin M, Levers PE, et al: The effect of cigarette smoking on bladder carcinogens in man. Canad Med Assoc J 93:1-7, 1965. 11. Welch RM, Harrison YE, Conney AH, et al: Cigarette smoking: Stimulatory effect on metabo- lism of 3, 4-Benzpyrene by enzymes in human placenta. Science 160:541-542, 1968. 12. Mantell CD: Smoking in pregnancy: The role played by carbonic anhydrase. New Zeal Med J 63:601-603, 1964. 13. Ruddon RW, Cohen AM: Alteration of en- zvmo activity in rat liver after nicotine administra- tion. Fed Proc 28:418, 1969. Arch Ent,iron ttealth--Vol 20, March 1970 Printed and Publisned in the United States of America

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