Dr. Sharma's Obesity Notes

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

On Tuesday, the Hong Kong-based Shaw Prize foundation awarded Ontario-born Douglas Coleman, an emeritus scientist with Jackson Laboratories in Maine, and Jeffrey Friedman of Rockefeller University in New York, this year’s $1 Million prize for their work on the hormone leptin (for CBC report click here).

Coleman first identified a hormone that governs food intake and body weight while working on mice in the 1970s. From the 1990s and into this decade, Friedman, using gene mapping techniques, isolated that hormone — leptin, finding it was active only in body fat, a surprising and significant finding, given fat cells were not previously known to secrete major hormones.

The discovery of leptin was arguably the most significant stimulus for the modern biology of obesity leading not only to a renewed interest in adipocyte biology but also to a better understanding of central regulation of food intake and energy balance.

Last Fall, I had the privilege of introducing Friedman to an audience here at the University of Alberta. I have unfortunately never had the chance to meet Coleman.

Congratulations to both winners!

AMS
Washington DC

Starting this week I will be occasionally posting interviews with researchers from the Canadian Obesity Network, which are now posted on YouTube.

You can watch these videos either by clicking on the video below, but remember, those of you, who get this blog by e-mail will have to actually visit the blog site by clicking here.

Those of you, who have YouTube blocked at work, will have to wait till you get home to view.

So here we go:

The first post in this series is Dr. William Colmers from the Department of Pharmacology, University of Alberta, Edmonton, talking about his research on the neurobiology of appetite regulation:

AMS
Edmonton, Alberta

There is now ample evidence to suggest that headaches are more common in people with overweight and obesity than in people with normal weight.

Thus, for example in a recent paper by Winter and colleagues from the University of Münster, Germany, published in Cephalalgia, reporting on a cross-sectional study of over 63,000 women, a BMI greater than 35 was associated with a 3-fold increased risk of daily migraine as well as increased risk of phonophobia and photophobia but decreased risk of a unilateral pain and aura.

These findings on obesity and headaches were recently extended to kids, in a paper just published in Headache, Andrew Hershey and colleagues on behalf of the American Headache Society Pediatric Adolescent Section. These investigators reported data in 913 consecutive kids seen at 7 pediatric headache centers in the US. While the prevalence of overweight at initial visit did not significantly differ from the general pediatric population, the higher the BMI percentile, the greater the headache frequency and associated disability. Furthermore, any increase in BMI at 3- and 6-month follow-up was significantly correlated with a further increase in headache frequency.

While the exact reasons for the link between obesity and headaches remains unclear, Marcelo Bigal and colleagues from Albert Einstein College of Medicine, Bronx, NY, USA have previously reviewed some of the putative mechanisms in an article published in Neurology. Firstly, several of the inflammatory mediators that are increased in obese individuals are important in migraine pathophysiology, including interleukins and calcitonin gene-related peptide (CGRP). Obesity is also a state of sympathetic activation, which may contribute to increase in headache frequency. Orexins modulate both pain and metabolism and dysfunction in the orexins pathways appears to be a risk factor for both conditions. Finally, conditions that are comorbid to both states (e.g., depression, sleep apnea) may also promote headaches.

Whatever the exact mechanism, clinicians should be aware of the relationship between headaches and excess weight. Whether headaches promote obesity (i.e. treatment of headaches will prevent obesity) or whether obesity promotes headaches (i.e. treatment of obesity will reduce headaches) remains to be seen.

AMS
Edmonton, Alberta

Orexigen Therapeutics Inc on Thursday reported the results of their first 56-week phase III study on contrave, a combination of the antidepressant bupropion and the opioid-antagonist naltrexone (both drugs have been on the market for other indications for over 20 years).

Although participants in this almost 800 patient study lost an average of 9.3% of their initial body weight on contrave vs. only 5.1% on placebo, the difference falls just short of the 5% placebo-corrected weight loss generally considered by the FDA as a threshold for approval.

Drop-out rates on contrave were 26% vs. 13% on placebo - the major side effects being nausea, hives, anxiety, headache, constipation and dizziness (nothing alarming or unexpected here).

Participants on contreve experienced significant improvement in quality of life and markers of cardiovascular risk as well as reductions in food cravings.

Despite falling just short of the FDA criteria in this study, the company still expects that the results of their remaining three phase III trials (expected to be completed later this year) will meet the mark.

It will certainly be interesting to see if there are certain subsets of patients who will respond better to this drug than to existing treatments.

As I have frequently said before, I do not expect any single drug to be effective in all obese patients. Given the mode of action of this drug, I would expect to see the greatest effect in individuals with emotional eating and food addictions.

Matching the right patient with the right medication will remain the single biggest challenge in the future development of anti-obesity medications.

AMS
Edmonton, Alberta