Smoking cessation and weight gain

Smoking cessation and weight gain David McFadden, MD, MPH Mayo Clinic Nicotine Dependence Center 2012 MFMER slide-1

Disclosures I presented lectures for Pfizer-sponsored tobacco treatment seminars in Brazil, Mexico and Chile I received no direct fees, but Mayo Clinic Nicotine Dependence center was reimbursed for my services. 2012 MFMER slide-2

Objectives 1. Understand the relationship of smoking cessation to weight gain 2. Understand the proposed mechanism of weight gain post smoking cessation 3. Understand the impact of weight gain concerns on tobacco use 4. To review the pharmaceutical approach to treating nicotine dependence with weight neutralizing drugs. 2012 MFMER slide-3

Tobacco mortality annual WHO estimates 6 million deaths annually worldwide due to smoking By 2030 estimated 8 million deaths 80% will occur in less developed countries (China and India) Since 1964 smoking prevalence in the USA declined dramatically, BUT it s decline has stalled over the last 6 years. 2012 MFMER slide-4

Obesity problem 1/3 of the American population 2 nd most important cause of preventable mortality in the USA (after smoking) Risk factor for Diabetes, Cardiovascular disease, Obstructive Sleep Apnea, Hypertension, Dyslipidemia 2012 MFMER slide-5

Challenges Weight gain is very common after smoking cessation Weight gain concern-barrier to quitting cigarette smoking and obesity are both risk factors for several highly prevalent lifestyle diseases (cardiovascular disease and diabetes) 2012 MFMER slide-6

Weight smokers vs. nonsmokers On average smokers weigh 5 kg (10.4 lbs.) less than nonsmokers Smokers gain an average for 4-5 kg. within 6-12 months of quitting 13% of smokers gain >10 kg.(22 lbs.) African American smokers Age <55 Low social-economic status 2012 MFMER slide-7

Weight gain with smoking cessation Average gain 7 to 19 lbs within 8 years of quitting Continued smokers gain 4-5 lbs. Most weight gain --within 6 months of quitting; greatest within the first month 10% of smokers may gain up to 30 lbs. (ref. 1) 2012 MFMER slide-8

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Weight gain Underweight smokers (BMI 18) or overweight smokers (BMI >29) have the greatest weight gain after quitting smoking Only 25% of former smokers maintain a healthy weight after quitting 2012 MFMER slide-11

Trajectories of cigarette smoking as predictor of obesity Heavy/continuous smokers compared with nonsmokers had a significantly lower likelihood of obesity. Also Heavy/continuous smokers had a significantly lower likelihood of being overweight or obese compared with non-daily occasional smokers. (ref. 3) 2012 MFMER slide-12

A Paradox the Obese smoker 20% of smokers are obese (BMI>30) Higher ratio of visceral to SQ fat risk of Diabetes and CVD Those who smoke the most cigarettes per day had the highest weight. (ref. 1) 2012 MFMER slide-13

Longitudinal change in weight related to smoking cessation EPIC-PANACEA study (European Prospective Investigation into Cancer and Nutrition-Physical Activity, alcohol, cessation of smoking) 300,000 healthy volunteers from 9 European countries followed for 5 years. Anthropometric and smoking habit data obtained (ref. 4) 2012 MFMER slide-14

results Smoking cessation resulted in annual weight gain; men (0.44 kg.), women (0.36 kg.) However when smokers who quit at least 1 year before study recruitment were compared with never smokers, there was no difference in annual weight gain Weight gain occurs mainly in the first year after smoking cessation (ref.4) 2012 MFMER slide-15

Why does it happen? Why do smokers gain weight after quitting smoking? Physiologic?? Psychologic?? 2012 MFMER slide-16

weight gain after smoking cessation Mechanisms are complex and NOT completely understood: two hypothesis 1.physiologic- mechanism due to action of nicotine 2.behavioral --smoking a cigarette -- alternative to eating. 2012 MFMER slide-17

Pathophysiology Body weight is determined by balance of caloric (energy) intake vs. daily energy calorie (energy) expenditure Daily energy expenditure is a combination of resting metabolic rate, physical activity and thermic effects of food. 2012 MFMER slide-18

Nicotine action Nicotine raises resting metabolic rate while suppressing appetite. Nicotine is a sympathomimetic drug similar to other antiobesity drugs. Sympathomimetic drugs increase energy expenditure. 2012 MFMER slide-19

Nicotine action Acts on nicotinic cholinergic brain receptor and autonomic ganglia which results in release of several neurotransmitters Dopamine, norepinephrine, serotonin, acetylcholine, glutamate and GABA 2012 MFMER slide-20

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Nicotine action Increases thermogenesis in adipose tissue by increasing lipolysis and recycling of fatty acids into triglycerides Increases 24 hr. energy expenditure by 10%= 200kcal per 24 hrs. This amount of energy expenditure 10 kg. weight loss in 1 year if steady state metabolism maintained. 2012 MFMER slide-22

Nicotine CNS effects Eating behavior and metabolic rate are regulated by the hypothalamus which integrates signals of satiety and adiposity as well as central motivational and emotional influences. Leptin plays a role in these mechanisms 2012 MFMER slide-23

Nicotine CNS action Norepinephrine, dopamine, serotonin and GABA influence other brain chemicals that suppress appetite and increase metabolic rate such as Pro-opiomelanocortin, cocaine-amphetamine-regulated transcript other drugs with similar action phentermine, sibutramine and bupropion (ref. 1) 2012 MFMER slide-24

Smoking and Diabetes Increased insulin resistance increase visceral fat. Adiponectin (adipose-derived protein) modulates insulin sensitivity and is lower in smokers. Smokers have increased risk of Diabetes, but smoking cessation leads to higher short-term risk. (ref.10) 2012 MFMER slide-25

Mechanism of weight gain with cessation Decreased metabolic rate Increased caloric intake Just the opposite effects of nicotine In one study average increase in caloric intake in exsmokers was 227 calories/day Nicotine s appetite suppressant effect --reversed upon quitting 2012 MFMER slide-26

2 nd mechanism of weight gain Smoking and overeating are both compulsory habits Substitute nicotine reward with food reward Eating becomes alternative to smoking Increased desire for comfort foods usually fats and sweets 2012 MFMER slide-27

Smoking cessation and gastric emptying In a Japanese study of 53 habitual smokers Smoking cessation temporarily accelerated gastric emptying which may lead to temporary increase in appetite resulting in weight gain (ref. 2) 2012 MFMER slide-28

Smoking to control weight Concept barrier to smoking cessation especially for women Even in 1930s, cigarette advertisements to women reach for a cigarette instead of a sweet 2012 MFMER slide-29

Weight gain concern A common and significant barrier to smoking cessation for many smokers resulting in smoking relapse (ref. 11) In a large population-based study, 52% of women and 32% of men reported weight gain was one of the reasons for relapse (Ref 5) 2012 MFMER slide-30

Weight gain concern Stronger predictor of relapse than actual weight gain 1. SCP + counseling to reduce concerns about weight gain 2. SCP + diet advice to prevent weight gain 3. one group of smokers-- standard smoking cessation counseling (SCP) 2012 MFMER slide-31

1 year follow up results 21% of weight concerns group abstinent weight gain 5.5 lbs. 13% of weight control abstinent weight gain 11.9 lbs. 9% of standard smoking cessation abstinent -- weight gain 16.9 lbs (ref 6) 2012 MFMER slide-32

Weight gain concerns In a similar more recent study with cognitive behavioral therapy (CBT) Bupropion +CBT for weight concerns had higher 6 month abstinence rates (34%) vs. Bup + standard counseling(21%) or CBT for weight concerns + placebo (11.5%) There was no difference among these groups in post cessation weight gain (ref. 7) 2012 MFMER slide-33

Adolescence smoking Smoking perceived as weight control method by adolescent girls. Not proven in this age group, but perception is real Tracks into adulthood Young adults trying to lose weight --40% more likely to smoke cigarettes 2012 MFMER slide-34

Smoking and weight concerns in adolescents Survey of 4,523 US high school students Heavy smokers most likely to consume unhealthy diet All smokers (light and heavy) more likely to engage in unhealthy dietary restrictions Dietary restrictions were related to smoking-related weight concerns (ref 8): 2012 MFMER slide-35

Medications to prevent weight gain Bupropion one of 7 FDA approved drugs for smoking cessation has been shown to attenuate food reward and suppress weight gain In a Cochrane Database review, Buproprion (300mg/day) was found to limit post cessation weight gain (-0.76 kg.) at the end of treatment. However after one year there was no effect. NRT limited weight gain post cessation (-0.45 kg.) No effect after one year There was no evidence that Varenicline reduced post cessation weight gain (Ref. 12) 2012 MFMER slide-36

Exercise In the Cochrane Data review, there was no evidence that exercise reduced post-cessation weight at the end of treatment BUT there was evidence for an effect at 12 months (-2.07 kg.) (95% CI -3.78 kg 0.36 kg) (ref. 12) 2012 MFMER slide-37

Medications to prevent weight gain Standard smoking cessation pharmacotherapy with NRT, bupropion appear to delay rather than prevent post-cessation weight gain. Bupropion may be the most effective especially if combined with a program that includes counseling for weight gain concerns (ref. 1) 2012 MFMER slide-38

Rimonabant Effective treatment for both tobacco dependence and obesity. A cannabinoid receptor antagonist. Adverse psychiatric effects--not FDA approved 2012 MFMER slide-39

Tobacco company role in weight control A systematic search of the archives of 6 major US and UK tobacco companies Appetite- suppressant molecules such as tartaric acid and 2-acetylpyridein were added to some cigarettes. Tobacco industry played an active role in adding appetite-suppressants to cigarettes (ref 9) 2012 MFMER slide-40

Intervention/treatment Behavioral interventions to maintain energy balance Manage calorie intake Increase physical activity Deal with concerns about weight gain counseling group gained less weight than both standard therapy group and weight control group 2012 MFMER slide-41

Future treatments Topiramate (TPM) an anticonvulsant known to produce weight loss (6.5% vs. placebo at 6 months). Consider combined TPM with NRT Phentermine/TPM to be approved soon by FDA for treatment of obesity-could also be combined with standard smoking cessation pharmacotherapy 2012 MFMER slide-42

Summary --Cigarette smokers are more likely to have normal weights or body mass index (BMI) --Nicotine has been the most effective long-term weight control drug over the last century. --Unfortunately when it s delivered via cigarette smoke it is extremely toxic resulting in premature deaths of half of those who are lifelong smokers. (Ref. 1) 2012 MFMER slide-43

Summary --smoking cessation does result in a small but significant weight gain --Further studies need to be done to better understand the mechanism of weight gain and explore new treatment strategies --Weight gain concerns should be addressed in smoking cessation programs Future studies should consider combining established weight loss medications with standard smoking cessation pharmacotherapy 2012 MFMER slide-44

References 1. Cigarette Smoking, Nicotine, and Body Weight J. Audrain-McGovern and N. L Benowitz Clinical Pharmacology & Therapeutics (2011) 90, 164-168 Published online June 1, 2011 (Pub Med) 2. Kadota K et al, J. Clin Gastroenterol. 2010, April; 44(4) 2012 MFMER slide-45

References 3. Brook DW, Zhang C et al; NTR 2010 March; 122 (3); 263 4. EPIC/PANACEA study, Travier N, Prev Med, Sept 12, 2011) 5.Psinger C.. Prev. Med. April 2007;44(4):290-95) 6. Meyers AW, J. consult Clin. Psychol. 1997; 65:448) 7. Levine, Arch Intern Med, 2010 mar 22; 170(6): 543 8. Cavallo Da et al; Pediatrics 2010 Jul.) 2012 MFMER slide-46

References 9. Eur J Public health 2011, April 7 10. Yeh HC et al, Ann Intern Meds, 2010, Jan. 5 11. Borrelli B, Addict. Behav. 1998;23(5):609 12. Parsons AC, Cochrane Database Syst Rev. 2012;1:CD006219 2012 MFMER slide-47