Metabolic effects of smoking cessation

An Erratum to this article was published on 30 September 2016

This article has been updated

Key Points

  • In general, an inverse relationship between smoking and BMI exists

  • Post-cessation-related obesity might contribute to insulin resistance

  • The number one reason for not wanting to quit smoking or quitting and then relapsing is fear of post-cessation weight gain, especially in women and in individuals with obesity

  • Future smoking cessation programs and therapies need to be designed with an emphasis on reducing post-cessation weight gain

  • The benefits of smoking cessation outweigh the risks


Smoking continues to be the leading cause of preventable death in the USA, despite the vast and widely publicized knowledge about the negative health effects of tobacco smoking. Data show that smoking cessation is often accompanied by weight gain and an improvement in insulin sensitivity over time. However, paradoxically, post-cessation-related obesity might contribute to insulin resistance. Furthermore, post-cessation weight gain is reportedly the number one reason why smokers, especially women, fail to initiate smoking cessation or relapse after initiating smoking cessation. In this Review, we discuss the metabolic effects of stopping smoking and highlight future considerations for smoking cessation programs and therapies to be designed with an emphasis on reducing post-cessation weight gain.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Mechanisms by which cigarette smoking reduces body weight.
Figure 2: Mechanisms by which nicotine leads to insulin resistance.
Figure 3: Prevalence of smoking and obesity.
Figure 4: Weight gain within the first year of attempting to quit smoking.
Figure 5: Changes in BMI over 10 years with smoking status.

Change history

  • 30 September 2016

    On page 302 of the above article, VLDL in Figure 2 was incorrectly labelled as VDL. This has been corrected online.


  1. 1

    World Health Organization. Tobacco. Fact sheet N°339. [online], (2015).

  2. 2

    Yuen, B. G. et al. Association between smoking and uveitis: results from the Pacific Ocular Inflammation Study. Ophthalmology 122, 1257–1261 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3

    Roura, E. et al. Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort. Int. J. Cancer 135, 453–466 (2014).

    Article  CAS  Google Scholar 

  4. 4

    Jaramillo, J. D. et al. Reduced bone density and vertebral fractures in smokers. Men and COPD patients at increased risk. Ann. Am. Thorac. Soc. 12, 648–656 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5

    US Department of Health and Human Services. The health consequences of smoking—50 years of progress: a report of the Surgeon General, 2014 [online], (2014).

  6. 6

    Practice Committee of the American Society for Reproductive Medicine. Smoking and infertility: a committee opinion. Fertil. Steril. 98, 1400–1406 (2012).

  7. 7

    Ruan, X. & Mueck, A. O. Impact of smoking on estrogenic efficacy. Climacteric 18, 38–46 (2015).

    Article  CAS  Google Scholar 

  8. 8

    Pedone, C. & Incalzi, R. A. Smoking and mortality — beyond established causes. N. Engl. J. Med. 372, 2169 (2015).

    PubMed  Google Scholar 

  9. 9

    Grando, S. A. Connections of nicotine to cancer. Nat. Rev. Cancer 14, 419–429 (2014).

    Article  CAS  Google Scholar 

  10. 10

    Kowall, B. et al. Association of passive and active smoking with incident type 2 diabetes mellitus in the elderly population: the KORA S4/F4 cohort study. Eur. J. Epidemiol. 25, 393–402 (2010).

    Article  CAS  Google Scholar 

  11. 11

    Kermah, D., Shaheen, M., Pan, D. & Friedman, T. C. Multivariate data analysis from the National Health and Nutrition Examination Survey (NHANES) 2001–2006 shows that second-hand smoke is associated with both obesity and diabetes mellitus. Endocrine Society [online], (2012).

  12. 12

    Facchini, F. S., Hollenbeck, C. B., Jeppesen, J., Chen, Y. D. & Reaven, G. M. Insulin resistance and cigarette smoking. Lancet 339, 1128–1130 (1992).

    Article  CAS  Google Scholar 

  13. 13

    Assali, A. R., Beigel, Y., Schreibman, R., Shafer, Z. & Fainaru, M. Weight gain and insulin resistance during nicotine replacement therapy. Clin. Cardiol. 22, 357–360 (1999).

    Article  CAS  Google Scholar 

  14. 14

    Attvall, S., Fowelin, J., Lager, I., Von Schenck, H. & Smith, U. Smoking induces insulin resistance — a potential link with the insulin resistance syndrome. J. Intern. Med. 233, 327–332 (1993).

    Article  CAS  Google Scholar 

  15. 15

    Hautanen, A. & Adlercreutz, H. Hyperinsulinaemia, dyslipidaemia and exaggerated adrenal androgen response to adrenocorticotropin in male smokers. Diabetologia 36, 1275–1281 (1993).

    Article  CAS  Google Scholar 

  16. 16

    Janzon, L., Berntorp, K., Hanson, M., Lindell, S. E. & Trell, E. Glucose tolerance and smoking: a population study of oral and intravenous glucose tolerance tests in middle-aged men. Diabetologia 25, 86–88 (1983).

    Article  CAS  Google Scholar 

  17. 17

    Kong, C. et al. Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in type 2 diabetes. Atherosclerosis 156, 373–378 (2001).

    Article  CAS  Google Scholar 

  18. 18

    Ronnemaa, T., Ronnemaa, E. M., Puukka, P., Pyorala, K. & Laakso, M. Smoking is independently associated with high plasma insulin levels in nondiabetic men. Diabetes Care 19, 1229–1232 (1996).

    Article  CAS  Google Scholar 

  19. 19

    Targher, G. et al. Cigarette smoking and insulin resistance in patients with noninsulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 82, 3619–3624 (1997).

    CAS  PubMed  Google Scholar 

  20. 20

    Laws, A. & Reaven, G. M. Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J. Intern. Med. 231, 25–30 (1992).

    Article  CAS  Google Scholar 

  21. 21

    Steinberg, H. O. et al. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J. Clin. Invest. 97, 2601–2610 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Sinha-Hikim, I. et al. Nicotine in combination with a high-fat diet causes intramyocellular mitochondrial abnormalities in male mice. Endocrinology 155, 865–872 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Farrell, G. C., Teoh, N. C. & McCuskey, R. S. Hepatic microcirculation in fatty liver disease. Anat. Rec. (Hoboken) 291, 684–692 (2008).

    Article  Google Scholar 

  24. 24

    Postic, C. & Girard, J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J. Clin. Invest. 118, 829–838 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Trauner, M., Arrese, M. & Wagner, M. Fatty liver and lipotoxicity. Biochim. Biophys. Acta 1801, 299–310 (2010).

    Article  CAS  Google Scholar 

  26. 26

    Liu, R. H., Mizuta, M. & Matsukura, S. Long-term oral nicotine administration reduces insulin resistance in obese rats. Eur. J. Pharmacol. 458, 227–234 (2003).

    Article  CAS  Google Scholar 

  27. 27

    Nakhate, K. T., Dandekar, M. P., Kokare, D. M. & Subhedar, N. K. Involvement of neuropeptide YY1 receptors in the acute, chronic and withdrawal effects of nicotine on feeding and body weight in rats. Eur. J. Pharmacol. 609, 78–87 (2009).

    Article  CAS  Google Scholar 

  28. 28

    Seeley, R. J. & Sandoval, D. A. Neuroscience: weight loss through smoking. Nature 475, 176–177 (2011).

    Article  CAS  Google Scholar 

  29. 29

    Chen, H. et al. Long-term cigarette smoke exposure increases uncoupling protein expression but reduces energy intake. Brain Res. 1228, 81–88 (2008).

    Article  CAS  Google Scholar 

  30. 30

    Ypsilantis, P. et al. Effects of cigarette smoke exposure and its cessation on body weight, food intake and circulating leptin, and ghrelin levels in the rat. Nicotine Tob. Res. 15, 206–212 (2013).

    Article  CAS  Google Scholar 

  31. 31

    Audrain-McGovern, J. & Benowitz, N. L. Cigarette smoking, nicotine, and body weight. Clin. Pharmacol. Ther. 90, 164–168 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Bajaj, M. Nicotine and insulin resistance: when the smoke clears. Diabetes 61, 3078–3080 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

    Hankey, C. & Leslie, W. Obesity: is weight gain after smoking cessation an important concern? Nat. Rev. Endocrinol. 8, 630–632 (2012).

    Article  Google Scholar 

  34. 34

    Clair, C. et al. Dose-dependent positive association between cigarette smoking, abdominal obesity and body fat: cross-sectional data from a population-based survey. BMC Public Health 11, 23 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35

    Tsuji, T. et al. Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking. Am. J. Respir. Cell Mol. Biol. 51, 822–829 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    McGrath-Morrow, S. A. et al. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice. PLoS ONE 10, e0118344 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Martinez de Morentin, P. B. et al. Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase. Diabetes 61, 807–817 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Schoenberg, N. E., Huang, B., Seshadri, S. & Tucker, T. C. Trends in cigarette smoking and obesity in Appalachian Kentucky. South. Med. J. 108, 170–177 (2015).

    Article  Google Scholar 

  39. 39

    Jamal, A. et al. Current cigarette smoking among adults — United States, 2005–2013. MMWR Morb. Mortal. Wkly Rep. 63, 1108–1112 (2014).

    PubMed  PubMed Central  Google Scholar 

  40. 40

    Centers for Disease Control and Prevention. Quitting smoking [online], (2015).

  41. 41

    Bilano, V. et al. Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control. Lancet 385, 966–976 (2015).

    Article  Google Scholar 

  42. 42

    US Department of Health and Human Services. Treating tobacco use and dependence: 2008 update. National Center for Biotechnology Information [online], (2008).

  43. 43

    Fiore, M. C., Fleming, M. F. & Burns, M. E. Tobacco and alcohol abuse: clinical opportunities for effective intervention. Proc. Assoc. Am. Physicians 111, 131–140 (1999).

    Article  CAS  Google Scholar 

  44. 44

    Casella, G., Caponnetto, P. & Polosa, R. Therapeutic advances in the treatment of nicotine addiction: present and future. Ther. Adv. Chronic Dis. 1, 95–106 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Siahpush, M. et al. It is better to be a fat ex-smoker than a thin smoker: findings from the 1997–2004 National Health Interview Survey-National Death Index linkage study. Tob. Control 23, 395–402 (2014).

    Article  Google Scholar 

  46. 46

    Tian, J., Venn, A., Otahal, P. & Gall, S. The association between quitting smoking and weight gain: a systemic review and meta-analysis of prospective cohort studies. Obes. Rev. 16, 883–901 (2015).

    Article  CAS  Google Scholar 

  47. 47

    Klesges, R. C., Meyers, A. W., Klesges, L. M. & La Vasque, M. E. Smoking, body weight, and their effects on smoking behavior: a comprehensive review of the literature. Psychol. Bull. 106, 204–230 (1989).

    Article  CAS  Google Scholar 

  48. 48

    Williamson, D. F. et al. Smoking cessation and severity of weight gain in a national cohort. N. Engl. J. Med. 324, 739–745 (1991).

    Article  CAS  Google Scholar 

  49. 49

    Aubin, H. J., Farley, A., Lycett, D., Lahmek, P. & Aveyard, P. Weight gain in smokers after quitting cigarettes: meta-analysis. BMJ 345, e4439 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50

    Lichtenstein, E., Zhu, S. H. & Tedeschi, G. J. Smoking cessation quitlines: an underrecognized intervention success story. Am. Psychol. 65, 252–261 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51

    Levine, M. D., Bush, T., Magnusson, B., Cheng, Y. & Chen, X. Smoking-related weight concerns and obesity: differences among normal weight, overweight, and obese smokers using a telephone tobacco quitline. Nicotine Tob. Res. 15, 1136–1140 (2013).

    Article  Google Scholar 

  52. 52

    Bush, T. M. et al. Impact of baseline weight on smoking cessation and weight gain in quitlines. Ann. Behav. Med. 47, 208–217 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53

    Lycett, D., Munafò, M., Johnstone, E., Murphy, M. & Aveyard, P. Associations between weight change over 8 years and baseline body mass index in a cohort of continuing and quitting smokers. Addiction 106, 188–196 (2011).

    Article  Google Scholar 

  54. 54

    Locatelli, I., Collet, T. H., Clair, C., Rodondi, N. & Cornuz, J. The joint influence of gender and amount of smoking on weight gain one year after smoking cessation. Int. J. Environ. Res. Public Health 11, 8443–8455 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55

    Komiyama, M. et al. Analysis of factors that determine weight gain during smoking cessation therapy. PLoS ONE 8, e72010 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Prod'hom, S. et al. Predictors of weight change in sedentary smokers receiving a standard smoking cessation intervention. Nicotine Tob. Res. 15, 910–916 (2013).

    Article  CAS  Google Scholar 

  57. 57

    Hur, Y. N., Hong, G. H., Choi, S. H., Shin, K. H. & Chun, B. G. High fat diet altered the mechanism of energy homeostasis induced by nicotine and withdrawal in C57BL/6 mice. Mol. Cells 30, 219–226 (2010).

    Article  CAS  Google Scholar 

  58. 58

    Lerman, C. et al. Changes in food reward following smoking cessation: a pharmacogenetic investigation. Psychopharmacology (Berl.) 174, 571–577 (2004).

    Article  CAS  Google Scholar 

  59. 59

    Volkow, N. D., Wang, G. J., Fowler, J. S. & Telang, F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Phil. Trans. R. Soc. B 363, 3191–3200 (2008).

    Article  Google Scholar 

  60. 60

    Johnson, P. M., Hollander, J. A. & Kenny, P. J. Decreased brain reward function during nicotine withdrawal in C57BL6 mice: evidence from intracranial self-stimulation (ICSS) studies. Pharmacol. Biochem. Behav. 90, 409–415 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    White, M. A., Masheb, R. M. & Grilo, C. M. Self-reported weight gain following smoking cessation: a function of binge eating behavior. Int. J. Eat. Disord. 43, 572–575 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  62. 62

    Brook, J. S., Zhang, C., Brook, D. W. & Finch, S. J. Voluntary smoking bans at home and in the car and smoking cessation, obesity, and self-control. Psychol. Rep. 114, 20–31 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63

    Stadler, M. et al. Effects of smoking cessation on β-cell function, insulin sensitivity, body weight, and appetite. Eur. J. Endocrinol. 170, 219–227 (2014).

    Article  CAS  Google Scholar 

  64. 64

    Centers for Disease Control and Prevention. Vital signs: nonsmokers' exposure to secondhand smoke — United States, 1999–2008. MMWR Morb. Mortal. Wkly. Rep. 59, 1141–1146 (2010).

  65. 65

    Biedermann, L. et al. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PLoS ONE 8, e59260 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Biedermann, L. et al. Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH. Inflamm. Bowel Dis. 20, 1496–1501 (2014).

    Article  Google Scholar 

  67. 67

    Farley, A. C., Hajek, P., Lycett, D. & Aveyard, P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst. Rev. 1, CD006219 (2012).

    PubMed  Google Scholar 

  68. 68

    Love, S. J. et al. Offer of a weight management program to overweight and obese weight-concerned smokers improves tobacco dependence treatment outcomes. Am. J. Addict. 20, 1–8 (2011).

    Article  Google Scholar 

  69. 69

    Perkins, K. A. et al. Cognitive-behavioral therapy to reduce weight concerns improves smoking cessation outcome in weight-concerned women. J. Consult. Clin. Psychol. 69, 604–613 (2001).

    Article  CAS  Google Scholar 

  70. 70

    Meyers, A. W. et al. Are weight concerns predictive of smoking cessation? A prospective analysis. J. Consult. Clin. Psychol. 65, 448–452 (1997).

    Article  CAS  Google Scholar 

  71. 71

    Parsons, A. C., Shraim, M., Inglis, J., Aveyard, P. & Hajek, P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst. Rev. 1, CD006219 (2012).

    Google Scholar 

  72. 72

    Levine, M. D. et al. Bupropion and cognitive behavioral therapy for weight-concerned women smokers. Arch. Intern. Med. 170, 543–550 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  73. 73

    Schnoll, R. A., Wileyto, E. P. & Lerman, C. Extended duration therapy with transdermal nicotine may attenuate weight gain following smoking cessation. Addict. Behav. 37, 565–568 (2012).

    Article  Google Scholar 

  74. 74

    Taniguchi, C. et al. Varenicline is more effective in attenuating weight gain than nicotine patch 12 months after the end of smoking cessation therapy: an observational study in Japan. Nicotine Tob. Res. 16, 1026–1029 (2014).

    Article  CAS  Google Scholar 

  75. 75

    Heffner, J. L., Lewis, D. F. & Winhusen, T. M. Osmotic release oral system methylphenidate prevents weight gain during a smoking-cessation attempt in adults with ADHD. Nicotine Tob. Res. 15, 583–587 (2013).

    Article  CAS  Google Scholar 

  76. 76

    Vergnaud, A. C. et al. Fruit and vegetable consumption and prospective weight change in participants of the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home, and Obesity study. Am. J. Clin. Nutr. 95, 184–193 (2012).

    Article  CAS  Google Scholar 

  77. 77

    Leslie, W. S. et al. Changes in body weight and food choice in those attempting smoking cessation: a cluster randomised controlled trial. BMC Public Health 12, 389 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  78. 78

    Deputy, N. P., Sharma, A. J., Kim, S. Y. & Hinkle, S. N. Prevalence and characteristics associated with gestational weight gain adequacy. Obstet. Gynecol. 125, 773–781 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  79. 79

    Suzuki, K. et al. Effect of maternal smoking cessation before and during early pregnancy on fetal and childhood growth. J. Epidemiol. 24, 60–66 (2014).

    Article  Google Scholar 

  80. 80

    Wang, L., Mamudu, H. M. & Wu, T. The impact of maternal prenatal smoking on the development of childhood overweight in school-aged children. Pediatr. Obes. 8, 178–188 (2013).

    Article  CAS  Google Scholar 

  81. 81

    Hawkins, S. S., Baum, C. F., Oken, E. & Gillman, M. W. Associations of tobacco control policies with birth outcomes. JAMA Pediatr. 168, e142365 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82

    Lee, K. et al. Associations of smoking and smoking cessation with CT-measured visceral obesity in 4,656 Korean men. Prev. Med. 55, 183–187 (2012).

    Article  Google Scholar 

  83. 83

    Matsushita, Y. et al. Associations of smoking cessation with visceral fat area and prevalence of metabolic syndrome in men: the Hitachi health study. Obesity (Silver Spring) 19, 647–651 (2011).

    Article  Google Scholar 

  84. 84

    Huang, P. L. A comprehensive definition for metabolic syndrome. Dis. Model. Mech. 2, 231–237 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Lihn, A. S., Pedersen, S. B. & Richelsen, B. Adiponectin: action, regulation and association to insulin sensitivity. Obes. Rev. 6, 13–21 (2005).

    Article  CAS  Google Scholar 

  86. 86

    Maeda, K. et al. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). 1996. Biochem. Biophys. Res. Commun. 425, 556–559 (2012).

    Article  CAS  Google Scholar 

  87. 87

    Shapiro, L. & Scherer, P. E. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr. Biol. 8, 335–338 (1998).

    Article  CAS  Google Scholar 

  88. 88

    Díez, J. J. & Iglesias, P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur. J. Endocrinol. 148, 293–300 (2003).

    Article  Google Scholar 

  89. 89

    Chen, J. et al. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia 49, 1292–1302 (2006).

    Article  CAS  Google Scholar 

  90. 90

    Kaur, J. A comprehensive review on metabolic syndrome. Cardiol. Res. Pract. 2014, 943162 (2014).

    PubMed  PubMed Central  Google Scholar 

  91. 91

    Inoue, K. et al. Early effects of smoking cessation and weight gain on plasma adiponectin levels and insulin resistance. Intern. Med. 50, 707–712 (2011).

    Article  CAS  Google Scholar 

  92. 92

    Matthews, D. R. et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419 (1985).

    Article  CAS  Google Scholar 

  93. 93

    Benowitz, N. L. Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog. Cardiovasc. Dis. 46, 91–111 (2003).

    Article  CAS  Google Scholar 

  94. 94

    Nakanishi, K., Nishida, M., Ohama, T., Moriyama, T. & Yamauchi-Takihara, K. Smoking associates with visceral fat accumulation especially in women. Circ. J. 78, 1259–1263 (2014).

    Article  CAS  Google Scholar 

  95. 95

    Yun, J. E., Kimm, H., Choi, Y. J., Jee, S. H. & Huh, K. B. Smoking is associated with abdominal obesity, not overall obesity, in men with type 2 diabetes. J. Prev. Med. Public Health 45, 316–322 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  96. 96

    Kirilly, E., Gonda, X. & Bagdy, G. CB1 receptor antagonists: new discoveries leading to new perspectives. Acta Physiol. (Oxf.) 205, 41–60 (2012).

    Article  CAS  Google Scholar 

  97. 97

    Gamaleddin, I. H. et al. Role of the endogenous cannabinoid system in nicotine addiction: novel insights. Front. Psychiatry 6, 41 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  98. 98

    Silvestri, C. & Di Marzo, V. Second generation CB1 receptor blockers and other inhibitors of peripheral endocannabinoid overactivity and the rationale of their use against metabolic disorders. Expert Opin. Investig. Drugs 21, 1309–1322 (2012).

    Article  CAS  Google Scholar 

  99. 99

    Garwood, C. L. & Potts, L. A. Emerging pharmacotherapies for smoking cessation. Am. J. Health Syst. Pharm. 64, 1693–1698 (2007).

    Article  CAS  Google Scholar 

  100. 100

    Bruin, J. E., Gerstein, H. C., Morrison, K. M. & Holloway, A. C. Increased pancreatic β-cell apoptosis following fetal and neonatal exposure to nicotine is mediated via the mitochondria. Toxicol. Sci. 103, 362–370 (2008).

    Article  CAS  Google Scholar 

  101. 101

    Yoshikawa, H., Hellstrom-Lindahl, E. & Grill, V. Evidence for functional nicotinic receptors on pancreatic β cells. Metabolism 54, 247–254 (2005).

    Article  CAS  Google Scholar 

  102. 102

    Woynillowicz, A. K., Raha, S., Nicholson, C. J. & Holloway, A. C. The effect of smoking cessation pharmacotherapies on pancreatic β-cell function. Toxicol. Appl. Pharmacol. 265, 122–127 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Tjalve, H. & Popov, D. Effect of nicotine and nicotine metabolites on insulin secretion from rabbit pancreas pieces. Endocrinology 92, 1343–1348 (1973).

    Article  CAS  Google Scholar 

  104. 104

    Wu, Y. et al. Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo. Nat. Med. 21, 373–382 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. 105

    Hsia, S., DesNoyers, M., Lee, M. L., Goldstein, C. & Friedman, T. C. Metabolic effects of smokers undergoing smoking cessation. Endocrine Society [online], (2015).

  106. 106

    Bergman, B. C. et al. Novel and reversible mechanisms of smoking-induced insulin resistance in humans. Diabetes 61, 3156–3166 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. 107

    Voulgari, C., Katsilambros, N. & Tentolouris, N. Smoking cessation predicts amelioration of microalbuminuria in newly diagnosed type 2 diabetes mellitus: a 1-year prospective study. Metabolism 60, 1456–1464 (2011).

    Article  CAS  Google Scholar 

  108. 108

    Athyros, V. G., Katsiki, N., Doumas, M., Karagiannis, A. & Mikhailidis, D. P. Effect of tobacco smoking and smoking cessation on plasma lipoproteins and associated major cardiovascular risk factors: a narrative review. Curr. Med. Res. Opin. 29, 1263–1274 (2013).

    Article  Google Scholar 

  109. 109

    Legislative Analyst's Office. 2011 Cal Facts. California's economy and budget in perspective. [online], (2011).

  110. 110

    Tweed, J. O., Hsia, S. H., Lutfy, K. & Friedman, T. C. The endocrine effects of nicotine and cigarette smoke. Trends Endocrinol. Metab. 23, 334–342 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references


Salary support for T.C.F. was provided by the Diversity-promoting Institutions Drug Abuse Research Development Program (grant R24DA017298) and the National Institute on Minority Health and Health Disparities (grant U54MD007598). The authors acknowledge the professional development core of the Charles R. Drew University Accelerating Excellence in Translational Science (AXIS) (grant U54MD007598) for help with editing the manuscript.

Author information




K.K.H., M.Z. and T.C.F. researched data for the article. K.K.H. and T.C.F. provided substantial contributions to discussions of the content. K.K.H., M.Z. and T.C.F. wrote the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Theodore C. Friedman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Harris, K., Zopey, M. & Friedman, T. Metabolic effects of smoking cessation. Nat Rev Endocrinol 12, 299–308 (2016).

Download citation

Further reading


Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing