Arya M. Sharma, MD

Readers of these pages will be quite familiar with my previous posts on food addiction.

A new paper by Paul Johnson and Paul Kenny from the Scripps Research Institute, Jupiter, FL, just released online in Nature Neuroscience, demonstrates that in rats development of obesity is coupled with a progressively worsening deficit in neural reward responses (as seen in cocaine or heroin abuse).

In drug users, this decreased neural reward response is considered crucial in triggering the transition from casual to compulsive drug-taking.

In their experiments, the researchers found compulsive-like feeding behavior in obese but not lean rats, and showed that this compulsive overeating was even resistant to disruption by an aversive conditioned stimulus.

The researchers also found down regulation of dopamine D2 receptors in the striatum (an area of the brain involved in reward behaviours) in a manner similar to what has been reported in humans addicted to drugs.

Genetic knockdown of striatal D2 receptors also rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with access to palatable high-fat food.

Together these data clearly demonstrate that overconsumption of highly palatable foods can trigger addiction-like neuroadaptive responses in brain reward circuits that can drive the development of compulsive overeating.

As I noted in several media interviews on this article yesterday,

“while not all forms of obesity can be reduced to food addiction, anyone dealing with obesity needs to be aware of the possibility that they may be addicted to certain foods and must therefore approach their obesity in the same manner as they would approach any other addiction. Unfortunately, in contrast to substance abuse, food abstinence is not an option“.

I can certainly now see why diet plans for treating food addiction are about as successful as drinking plans are for managing alcoholism.

AMS
Edmonton, Alberta

Regular readers of these pages are well aware of the close link between addictions and some forms of overeating. This topic is now nicely addressed in a commentary by Valerie Taylor (McMaster, Hamilton), Claire Curtis and Caroline Davis (both York University, in this week’s edition of CMAJ.

As they discuss,

“The concept of food addiction, which more accurately may reflect addiction to specific components of food, can be described in much the same way as other addictive behaviours. Both food and drugs induce tolerance over time, whereby increasing amounts are needed to reach and maintain intoxication or satiety. In addition, withdrawal symptoms, such as distress and dysphoria, often occur upon discontinuation of the drug or during dieting. There is also a high incidence of relapse with both types of behaviour.“

To further support their arguments, they cite the many imaging studies showing that specific areas of the reward or mesolimbic system, such as the caudate nucleus, the hippocampus and the insula, are activated both by drugs and by food.

Thus, the easy accessibility of highly palatable foods together with our innate preferences for such foods, can increase the likelihood that vulnerable people will “misuse” food, in much the same way that addicts misuse other drugs to blunt negative emotional states, such as depression, anxiety, loneliness, boredom, anger orinterpersonal conflict.

While the concept of addiction should not negate the role of free will and personal choice, it does provide a rationale for the including addiction screens as a routine part of assessment for obesity. It may also help explain the success of lifestyle programs that incorporate pharmacotherapy or behavioural strategies specifically designed to address the addictive component of this illness.

Thus, as pointed out by Taylor and colleagues, there is not only considerable overlap among the medications shown to interfere with food and drug abuse in animal models, but the many behavioural interventions developed for managing addictions (motivational interviewing, cognitive behavioural therapy and 12-step programs), are increasingly recognised as also being helpful in managing obesity.

Health professionals and decision makers charged with tackling the obesity epidemic would do well to familiarise themselves with the science of addictions and utilize learnings from addiction management in their counseling of patients presenting with excess weight.

AMS
Edmonton, Alberta

Hedonic hyperphagia (overeating controlled by reward rather than need for calories) often underlies excess caloric intake. As the reward centres that regulate drug and other forms of addiction are the same that are stimulated by highly palatable foods, it is not surprising that genes associated with substance and other addictions may also be linked with obesity.

This assumption finds new support in a study published this month in PLoS Genetics by Nancy Heard-Costa from Boston University School of Medicine on behalf of the CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) consortium .

The researchers performed genetic analyses on more than 30,000 subjects participating in 8 large cohort studies, including the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES- Reykjavik Study), the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), the European Special Population Network consortium (EUROSPAN), the Family Heart Study, the Framingham Heart Study, Old Order Amish (OOA), and the Rotterdam Study (RS).

Genetic loci studied included those identified in previous studies as well as new candidate loci for abdominal fat deposition.

In addition to confirming significant associations with the previously reported FTO and MC4R genes, the researchers found a novel locus in the NRXN3 gene associated with waist circumference, BMI and obesity.

NRNX3 has previously been associated with addiction (alcohol dependence, cocaine addiction, and illegal substance abuse) and is part of a family of central nervous adhesion molecules, which are highly expressed in sub-cortical regions of the brain in involved with learning and reward training.

Although the odds ratio for obesity per copy of the implicated G Allele was only 1.13, this small effect at a population level can be substantial.

More importantly, this finding clearly supports the notion that some individuals may be more susceptible to obesity because of an increased genetic predisposition to reward-seeking behaviours, that obviously include seeking out highly-palatable (addictive) foods.

Punitive approaches to drug addictions have not worked - neither will punitive approaches to obesity resulting from hedonic overeating.

AMS
Edmonton, Alberta

Smoking cessation is one of the most common risk factors for weight gain and there is little doubt that in some people food activates exactly the same hedonic pathways as does nicotine and other drugs - this is why for some people, food is very much an addiction.

In fact, previous studies have shown that people who abstain from smoking, not only tend to give in to food cravings more often, but as cravings for cigarettes become more intensified, so do cravings for starchy carbohydrates and fats. These food are also well know to improve dysphoric moods (anxiety, depression, and irritability) that typically accompany nicotine withdrawal.

A new study published this month in OBESITY further illustrates these striking similiarities in food cravings and mood states between obese women and women who smoke tobacco.

In this study, Yanina Pepino and colleagues form the Monell Chemical Senses Center, Philadelphia, PA, USA, assessed food cravings in 229 women who differed in smoking history (i.e., never smoker, former smoker, and current smoker) and body weight (i.e., normal weight, overweight, and obese).

Each subject completed the Food Craving Inventory (FCI), which measures cravings for sweets, high fats, carbohydrates/starches, and fast-food fats, and the Profile of Mood States (POMS), which measures psychological distress.

Both smoking and obesity were found to be independently associated with specific food cravings and mood states (particularly depression and anger). Current smokers clearly craved high fats more frequently than former and never smokers. They also craved starches more frequently and felt more depressed and angry than never smokers, but not former smokers.

From these findings the authors conclude that while cravings for starchy foods and poor mood may be characteristic of women who are likely to smoke, more frequent cravings for fat among smokers is related to smoking per se.

Similarly, obese women craved high fats more frequently than nonobese women and depression symptoms were intensified with increasing body weights.

The overlapping neuroendocrine alterations associated with obesity and smoking and the remarkable similarities in food cravings and mood states between women who smoke and women who are obese suggest that common biological mechanisms modulate cravings for fat in these women.

Unfortunately, while smoking can be addressed by “smoking cessation” programs it is highly unlikely that we will be able to address the obesity epidemic with “eating cessation” programs.

Nevertheless, the recognition that smoking and food cravings interact with mood and involve the same hedonic neuronal pathways, may well lead to treatments that can target both nicotine and food addiction.

AMS
Edmonton, Alberta

Most people who stop smoking gain weight, on average about 7kg in the long term. Indeed, weight control is one of the most common reasons I hear in my practice for people continuing to smoke.

So how can the weight gain associated with smoking cessation be prevented?

This was the topic of an exhaustive literature analysis published in the Cochrane Database of Systematic Reviews by Amanda Parsons and colleagues from the University of Birmingham, UK.

The review looked both at interventions designed specifically to aid smoking cessation and limit post-cessation weight gain and interventions designed to aid smoking cessation that may also plausibly have an effect on weight

Using the rigorous Cochrane methodolgy, the authors found evidence that compared to lifestyle interventions alone, pharmacological interventions aimed at reducing post-cessation weight gain resulted in a significant reduction in weight gain at the end of treatment (dexfenfluramine (-2.50 kg), fluoxetine (-0.80 kg], phenylpropanolamine (-0.50 kg), naltrexone (-0.76 kg). However, there was no evidence of any maintenance of these effects at 6 or 12 months after treatment.

In cases, where the intervention was limited to behavioural advice to control weight, not only was there no reduction in weight gain, there was also a trend towards less abstinence. In contrast, when programmes were individualized, there was reduced weight gain at end of treatment and at 12 months (-2.5 8 kg) without a reduction in abstinence rates. Exercise intervention alone did not limit weight gain at 12 months.

Very low calorie diets (-1.30kg at 12 months) and cognitive behavioural therapy (-5.20 kg at 12 months) were both associated with improved abstinence and reduced weight gain at end of treatment and at long-term follow up.

While both bupropion (-0.76 kg) and fluoxetine (-1.30 kg), when used for smoking cessation, limited post-cessation weight gain at the end of treatment, these effects were not maintained at one year.

Nicotine-replacement treatments resulted in attenuation of post-cessation weight gain (-0.45 kg) at the end of treatment and at 12 months (-0.42 kg).

One study randomized successful quitters to 12 more weeks of varenicline treatment resulting in a weight reduction of 0.71 kg. In three studies, participants taking bupropion gained significantly less weight at the end of treatment than those on varenicline.

Apparently, there were no studies on anti-obesity drugs (sibutramine or orlistat) to prevent post-cessation weight gain.

From this analysis, the authors conclude that general behavioural interventions that fall short of formal CBT are largely ineffective in preventing smoking cessation-related weight gain, and may in fact reduce abstinence.

Individualized interventions, very low calorie diets, and CBT may be effective without reducing abstinence. Bupropion, fluoxetine, nicotine replacement therapy, and probably varenicline all reduced weight gain while being used.

Currently, there does not appear to be any effective way to curtail the long-term weight gain associated with smoking cessation.

Nevertheless, given the substantial risks associated with smoking, the risk/benefit relationship of smoking cessation, i.e. the potential health risks from weight gain vs. the potential health risks from continued smoking are clearly in favor of smoking cessation.

This said, it appears that there is considerable room (and need) for more effective interventions to prevent cessation-associated weight gain.

AMS
Edmonton, Alberta
p.s. interestingly, OBESITY PANACEA also had a post yesterday on the issue of obesity and smoking.