When smokers stop smoking, they typically gain weight, which might negate some of the health benefits of quitting. We examine the efficacy of behavioral and pharmacological approaches to preventing weight gain after quitting smoking, as well as processes that could explain the effects of smoking and nicotine on body weight. Understanding how nicotine affects body weight could lead to new pharmacological and behavioral treatments for obesity, as well as obesity and nicotine dependency in combination.
The Health Consequences of Smoking and Obesity
In the United States, about 19 percent of women and 23 percent of men are current smokers. Cigarette smoking is responsible for about 400,000 premature deaths in the United States each year due to cardiovascular and respiratory disorders, as well as cancer.
Excess body weight caused by inadequate food and insufficient physical activity is the second largest cause of premature illness and mortality. In the United States, 30% of women and 43% of men are overweight, while 26% of women and 29% of men are obese. Obesity and overweight are linked to an increased risk of heart disease, hypertension, type 2 diabetes, respiratory issues, musculoskeletal disorders, and some malignancies.
For many years, the notion that cigarette smoking aids in weight loss has been part of popular culture. In the 1930s, cigarette commercials advised ladies to “reach for a cigarette instead of a sweet.” For many smokers, the fear of gaining weight might make quitting smoking difficult. The reduction in morbidity and death associated with smoking cessation substantially outweighs the health hazards associated with post-cessation weight gain, according to most health-care practitioners.
Weight gain, on the other hand, can negate some of the health benefits of quitting smoking. Weight gain after quitting smoking, for example, increases the risk of type 2 diabetes and hypertension, as well as reducing the benefits of quitting smoking on lung function. When you’re 45–64 years old, you’re most likely to be overweight or obese. This is also a time when quitting smoking is more likely to happen.
44 percent of overweight males and 48 percent of obese men in the population over 50 years old are past smokers, whereas 27 percent of overweight women and 27 percent of obese women are former smokers. To minimize weight gain after quitting smoking and maximize the health advantages of quitting, a better knowledge of the behavioral and biological links between smoking and eating behaviors is required.
Smoking’s Physiological Effect on Body Weight
The mechanisms by which smoking causes weight loss are complex and poorly understood. Nicotine is responsible for the majority of the effects of cigarette smoking on body weight, while smoking can also be used as a behavioral alternative to eating, resulting in reduced food consumption. Nicotine affects the brain and autonomic ganglia through nicotinic cholinergic receptors.
Nicotine binds to nicotinic receptors, which opens ion channels and allows sodium and calcium to enter, increasing the release of different neurotransmitters. Catecholamines are released systemically, and dopamine, norepinephrine, serotonin, acetylcholine, glutamate, -aminobutyric acid, and other neurotransmitters are released in the central nervous system.
The mechanisms through which cigarette smoking causes weight loss. Smoking reduces body weight through boosting energy expenditure and preventing the compensatory increase in calorie intake that would otherwise occur. Nicotine increases energy expenditure through both direct effects on peripheral tissues (mediated primarily by catecholamines) and indirect effects on central nervous system neuroendocrine circuits.
Nicotine’s actions on the brain also cause appetite suppression, therefore smoking can be used as a behavioral substitute for eating. AgRP stands for Agouti-related peptide; CART stands for cocaine amphetamine-regulated transcript; DA stands for dopamine; Epi stands for epinephrine; GABA stands for -aminobutyric acid; NEpi stands for norepinephrine; NPY stands for neuropeptide Y; POMC stands for proopiomelanocortin.
The balance between caloric intake and daily energy expenditure determines body weight. Resting metabolic rate, physical activity, and thermic effects of meals all contribute to daily energy expenditure. Nicotine decreases body weight by increasing resting metabolic rate while dampening the expected rise in food intake as a result of the metabolic rate increase.
Nicotine, like many other anti-obesity medications, is a sympathomimetic substance. Sympathomimetic medicines enhance energy expenditure through peripheral tissue action and brain metabolic modulation. Nicotine stimulates local norepinephrine release in bodily tissues as well as systemic epinephrine release from the adrenal glands.
Nicotine stimulates thermogenesis in adipose tissue by enhancing lipolysis and subsequent fatty acid recycling into triglycerides. Smoking raises energy expenditure by 10% over a 24-hour period and increases it more during exercise and after eating than at rest.
A 10% increase in metabolic rate, equating to an expenditure of 200 kcal per 24 hours, may appear insignificant; but, assuming no change in caloric intake, this increase in energy expenditure caused by nicotine might result in a weight loss of 10 kg in a year.
Nicotine has a variety of possible impacts on eating and energy expenditure regulation in the central nervous system. The hypothalamus, which integrates peripheral cues of satiety and adiposity as well as cerebral motivational and emotional stimuli, regulates eating behavior and metabolic rate.
Leptin is a hormone that is secreted in proportion to the amount of fat tissue in the body and operates centrally to decrease food intake and boost metabolic rate. The results of studies comparing the levels of leptin in smokers and nonsmokers are mixed. However, it has been claimed that nicotine may enhance the effects of leptin in the brain by raising the sensitivity of downstream transduction cascades or improving leptin binding.
The central nervous system’s release of hormones such as norepinephrine, dopamine, serotonin, and -aminobutyric acid influences brain chemicals that suppress eating and increase metabolic rate (such as pro-opiomelanocortin and cocaine-amphetamine-regulated transcript) as well as those that suppress eating and decrease metabolic rate (such as pro-opiomelanocortin and cocaine-amphetamine-regulated transcript) (such as neuropeptide Y, Agouti-related peptide, melanin-concentrating hormone, and orexin).
Nicotine has a complex influence on these hormones; the acute reaction is compatible with the activation of systems that decrease appetite and boost body metabolism, whilst the chronic changes are consistent with the activation of systems that raise appetite and slow metabolic rate. Drugs that enhance norepinephrine, dopamine, and/or serotonin levels in the central nervous system (such as phentermine, sibutramine, and bupropion) decrease hunger and aid weight reduction, similar to nicotine.
Nicotine also has other metabolic impacts on body weight and composition, such as insulin resistance, which is most likely linked to catecholamine release. Smokers have lower levels of the adipose-derived protein adiponectin, which controls insulin sensitivity and has anti-inflammatory properties, than nonsmokers.
Insulin resistance is linked to changes in body composition, such as an increase in visceral fat. In comparison to total fat, smokers have a larger percentage of visceral fat and, as a result, a higher waist-to-hip ratio than nonsmokers.
The cause of the association between smoking and increased visceral fat is unknown, however it could be related to nicotine’s effects, which increase cortisol production and change the balance of male and female sex hormones. A high waist-to-hip ratio is a risk factor for atherosclerotic cardiovascular disease, and it appears to be linked to smoking frequency and the number of cigarettes smoked per day/packs smoked annually.
Nicotine’s rewarding and reinforcing effects are mediated by the endocannabinoid system. Food intake and other appetite-related behaviors are influenced by endogenous cannabinoids. Cannabinoids interact with opioid and dopamine systems in reward circuits in the brain. Cannabinoid receptor antagonists have been demonstrated to lower body weight and promote smoking cessation, as detailed below.
Weight Gain After Smoking Cessation, Natural History, Physiological Changes, and Weight Gain
As previously stated, smokers weigh 4–5 kg less than nonsmokers on average. When smokers stop smoking, they acquire 4.5 kg on average within 6–12 months, and their weight recovers to the same weight-age trajectory as nonsmokers (Figure 1).
However, some smokers acquire significantly more weight after quitting; 13% gain more than 10 kg. African-American race, age 55, being a heavy smoker (more than 25 cigarettes per day), and lower socioeconomic status are all risk factors for weight increase after quitting smoking. Weight gain after quitting smoking is also influenced by genetic variables, as evidenced by twin studies.
Figure 2 shows that weight gain is greatest in the first 1–2 months after quitting smoking, but it continues to rise for 6 months or longer. Some smoking cessation pharmacotherapies (nicotine replacement medications and bupropion, for example) reduce weight gain after quitting. When these prescriptions are withdrawn, however, body weight returns to where it would have been if the medication had not been taken. Increased body fat is the primary cause of weight gain after quitting smoking.
Weight gain after quitting smoking is caused by a decrease in metabolic rate and an increase in caloric intake, which are the opposing effects of nicotine. In one study, respondents who had quit smoking consumed an additional 227 calories per day on average, which might account for 69 percent of the weight gain reported after three months. Lower socioeconomic position has been linked to weight gain after quitting smoking, maybe because it is linked to less physical activity and the intake of high-fat, high-calorie meals.
There are a variety of reasons for increased food intake after quitting smoking. One is that nicotine’s appetite-suppressing effects on the brain are reversed, resulting in an increase in appetite. However, at least temporarily, the higher consumption of favorite snacks linked with smoking cessation cannot be explained by overall changes in hunger.
Overeating or compulsive eating may have been aided by smoking and/or nicotine, but these behaviors are unrestrained following smoking cessation. Smokers who have a history of binge eating or who binge eat during treatment for quitting smoking have worse stop rates and gain more weight.
Another explanation for the link between smoking and eating is that the pleasurable effects of food replace the pleasurable effects of smoking (that is, substitutable reinforcers). According to research, the absence of nicotine improves the rewarding value of food, and that hereditary variables contribute to individual variances in food reward. Increased consumption of high-fat, high-sugar foods stimulates reward circuits in the brain, which are comparable to those activated by smoking. Nicotine withdrawal raises the reward threshold, resulting in reduced pleasure from traditional reinforcers. As a result, increased amounts of highly rewarding foods (snacks high in sugar and carbs, known as “comfort foods”) may be sought to replace the pleasure previously had from smoking.
Bupropion has been proven to lower the reward threshold, suppress weight gain, and reduce food reward. It is critical to discover processes that account for overeating among smokers within the first 6 months after quitting to optimize the health advantages of smoking cessation and to inform behavioral and pharmacologic therapies to minimize post-cessation weight gain.
Weight Gain and Smoking Cessation Treatment Implications
When smokers stop smoking, they often experience an increase in calorie intake but no increase in physical activity as a result of the loss of nicotine’s metabolic boost and appetite suppression. Weight gain results from this positive energy balance. Behavioral therapies to prevent post-cessation weight gain have so focused on calorie restriction, increased physical activity, or a combination of the two.
Despite the fact that more than 90% of the participants in these trials were women, the findings were mixed when it came to whether the subjects were concerned about post-cessation weight gain. A recent meta-analysis looked at whether weight-related behavioral therapies can help people lose weight after quitting smoking.
The findings of the systematic review showed that weight-management components in smoking cessation programs have a short-term benefit for both smoking abstinence and weight control. The favorable effects of these weight-control strategies, however, were no longer significant after 6 months.
These findings support the short-term benefits of a combined (smoking cessation and weight control) treatment and, more crucially, refute the long-held belief that quitting smoking while also trying to limit caloric intake would be counterproductive to quitting smoking. 36 Longer-term behavioral therapies, which have yet to be studied, may have stronger long-term benefits on body weight.
A weight control/smoking cessation treatment that simply addresses the worries about post-cessation weight gain, rather than the weight gain itself, is an alternative. Concerns about weight increase are a stronger predictor of relapse than actual weight gain, according to this therapy method.
A group of smokers received conventional smoking-cessation therapy, a second group received this counseling plus food recommendations to prevent weight gain (weight control), and a third group received the standard smoking-cessation program plus counseling to lessen their weight-growth concerns.
At the one-year follow-up, 21% of the women in the weight-concerns group were smoking-free, compared to 13% in the weight-control group and 9% in the typical smoking-cessation counseling group. Women in the weight-concerns group also gained less weight (5.5 pounds) than women in the weight-control or routine smoking-cessation counseling groups (11.9 pounds) (16.9 pounds). As a result, for smokers who wish to quit smoking but are concerned about gaining weight after quitting, lowering anxieties about weight increase, rather than managing weight gain, may be more effective.
Several pharmacotherapies have been studied to prevent weight gain after quitting. Bupropion, nicotine-replacement medicines, fluoxetine, and varenicline are among them. Overall, these drugs tend to delay rather than prevent weight gain after quitting smoking. That is, once the drug regimens are ended, the weight returns to the level that would have occurred if no medicine had been used.
A brief suppression of weight growth, on the other hand, may improve smokers’ incentive to stop, giving smokers who are concerned about weight gain time to focus on quitting first and then addressing nutritional consumption and physical activity.
In a recent study, researchers discovered that combining bupropion medication with a weight-concerns smoking-cessation intervention resulted in higher levels of smoking abstinence at 6 months than normal smoking-cessation counseling with either bupropion or placebo (34 percent , 21 percent , and 12 percent , respectively). At 3, 6, or 12 months after quitting, there were no significant variations in weight gain across women.
Implications for New Drug Development in the Treatment of the Obese Smoker
Despite the fact that smoking reduces weight in general, many smokers have metabolic syndrome, which includes obesity, in addition to tobacco dependence. Smoking and obesity are two major cardiovascular risk factors that work together to cause heart disease. Smoking induces a chronic inflammatory state, endothelial dysfunction, increased thrombogenesis, insulin resistance, diabetes, and is linked to an atherogenic lipid profile.
Obesity raises blood pressure, causes or worsens diabetes, causes hyperlipidemia, and triggers a persistent inflammatory response. Despite the fact that smokers weigh less than nonsmokers, their ratio of visceral to subcutaneous fat is high, which is a cardiovascular risk factor. According to estimates, 20% of smokers are overweight.
Surprisingly, epidemiological studies have discovered that people who smoke the most cigarettes per day weigh more and are more likely to be obese than people who smoke less cigarettes per day. Obesity is more common in high-level smokers, which may be due to an appetite-related behavior issue that causes them to over consume both nicotine and food.
Obese smokers are less able to distinguish between nicotinized and de-nicotinized cigarettes (those with less nicotine reinforcing effects) than their normal-weight counterparts, according to research.
The concept of treating tobacco addiction and obesity combined is intriguing. Rimonabant, a cannabinoid receptor antagonist, was the first medicine to give such a treatment. The cannabinoid 1 receptor appears to be implicated in nicotine and food reward pathways. Rimonabant has been proven to be successful in clinical trials for smoking cessation, weight loss, and metabolic syndrome control.
Unfortunately, the medicine was not licensed for usage in the United States due to its negative psychiatric side effects. As previously stated, bupropion is effective for quitting smoking and has also been used for weight loss. Bupropion mimics the effects of nicotine by increasing dopamine and norepinephrine levels in the brain. Indeed, nicotine itself may be considered a long-term weight-control strategy. The most serious issue with utilizing nicotine (and other sympathomimetic substances) as a treatment is the risk of cardiovascular damage. Nicotine can cause endothelial damage and insulin resistance by increasing heart rate and cardiac activity. However, oxidants and particulates, not nicotine, cause the majority of the cardiovascular risk associated with smoking.
The usage of snus, a type of smokeless tobacco, by men in Sweden is an interesting test of nicotine’s long-term safety. In Sweden, a substantial number of men consume snus and do not smoke.
Snus users are exposed to the same amount of nicotine as smokers, although most epidemiological studies in Sweden have indicated little or no increased risk of cardiovascular events in snus users. The efficacy and safety of long-term nicotine therapy for weight loss are still being researched.
To summarize, nicotine has unquestionably been the most effective long-term weight management medicine in use during the previous century across the population. Unfortunately, the majority of people receive nicotine through cigarette smoke, which is extremely hazardous, resulting in the premature death of half of all lifetime smokers. Understanding how nicotine impacts body weight in the brain could lead to novel pharmacological methods, not just for obesity but also for obesity associated with substance misuse.