Addiction Gene Linked to Common Obesity
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
Food Cravings, Mood, and Nicotine Addiction
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… Read More »
Preventing Smoking Cessation-Related Weight Gain
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… Read More »
Does High-Glycemic Index Promote Food Addiction?
Yesterday, I was widely quoted in national media on the issue of food addiction. The background for this was an interview done by CanWest’s Sharon Kirkey regarding a recent paper by Simon Thronley and colleagues from Auckland, New Zealand, published in Medical Hypothesis. The basic tenor of their article is that food consumption shows many similarities to features of other addictive behaviours, such as automaticity and loss of control. They hypothesize that Glycemic Index (GI) is perhaps the key element of food that predicts its addictive potential. They quote reports of a withdrawal syndrome from high glycemic food abstinence and argue that both empirical and clinical studies support an addictive component of eating behaviour, with similar neurotransmitters and neural pathways triggered by food consumption, as with addictive drugs. Specifically, they argue that the short time to peak arterial concentration of glucose (similar to the short time to peak concentrations of nicotine in smokers) associated with high GI-foods, essentially ‘spikes’ the addictive potential of palatable foods – thereby making them more addictive than low-GI foods. The authors suggest that subtle changes in the preparation and manufacturing of commonly consumed food items and/or reducing glycemic index through regulatory channels, may help break a cycle of [food-] addiction and draw large public health benefits. While I much like their concept, and certainly buy into the fact that some folks demonstrate features akin to food addiction, this is certainly not a universal thruth that applies to all people with excess weight – in fact, I know a couple of normal weight people, who probably have “sweet addiction” as well. Nevertheless, I do think that this paper should once again remind us of the important mental health component to ingestive behaviour and certainly explains why for some people kicking doughnuts and chocolate is apparently as hard as kicking alochol or cocaine. AMS Edmonton, Alberta.
Another Addiction Drug for Obesity?
I have often blogged on the close link between certain forms of obesity and addiction. Not only do many patients battling with obesity openly admit to a “food addiction”, several drugs targeting obesity such as rimonabant (a CB-1 receptor antagonist) or contrave (a combination of buproprion and naltrexone) specifically target the neurocircuitary of the brain’s addiction system. A new addition to this approach may be Gaba-vinyl-GABA (GVG) or vigabatrin, an epilepsy drug currently undergoing Phase II trials for patients with cocaine and methamphetamine dependence. In a study published by Amy deMarco and colleagues from Brookhaven National Laboratory, Upton, NY, in the journal Synapse last week, vigabatrin resulted in a dose-dependent 12-20% reduction in body weight in Sprague Dawley and adolescent and adult Zucker fatty rats. Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. The mechanism of action of vigabatrin is attributed to irreversible enzyme inhibition of GABA-T, and consequent increased levels of the inhibitory neurotransmitter, GABA. Vigabatrin is sold as Sabril in Canada by Ovation Pharmaceuticals Inc for the adjunctive management of epilepsy which is not satisfactorily controlled by conventional therapy. Its major neurological side effects include somnolence, impairment of peripheral vision and risk for seizures. Increases in liver enzymes have also been reported. No doubt, it will be interesting to see how the clinical trials of this compound for obesity pan out. Apparently, Brookhaven Labs have licensed out the compound to Catalyst Pharmaceutical Partners, (Coral Gables, Florida), who plan to test it for binge-eating disorder (BED). I am not sure why exactly the researchers (and Catalyst Pharmaceuticals) believe that BED is the best population to test this in, as this disorder (as blogged before) readily responds to CBT and does not actually present with typical features of addiction. In fact one of the key features of BED, the sense of dispair and failure that follows a binge episode is the exact opposite of a “high” experienced by drug users. In any case, to me, patients with BED seem the least likely obese population to respond to an addiction drug – but who knows, we’ll find out soon enough (always happy to eat my words). AMS Edmonton, Alberta
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