Obesity and bariatric medicine interview with Denise Bruner, M.D.

Written by MICANS, MS, PharmB, Philip A

AAM: Dr. Bruner, I would like to thank you so much for your time today- to share your thoughts with the readers of the Antiaging Magazine. Perhaps I should start by asking you to please tell us about your experience and your credentials?

DB: I am a second-generation physician who attended Howard University College of Medicine, which was my father’s alma mater. My internship and residency training was in the field of internal medicine. I am a diplomat of the American Board of Bariatric Physicians and the American Board of Anti-aging Medicine. I was the past president of the American Society of Bariatric Physicians (ASBP) and also hold the honor of being a Fellow of the American Society of Bariatric Physicians. My practice, which includes both Bariatric and anti-aging medicine, is located in Arlington, Virginia.

AAM: What was it that made you specifically interested in the field of Bariatric medicine? [Ed.- weight control].

DB: My passion for Bariatric medicine originates from my personal battle with obesity. There was a strong paternal history of obesity; however I did not have a serious weight issue until the time of my internship and residency. Over the course of my internship and first few months of residency, I gained 70 pounds. The combination of sleep deprivation, lack of physical activity, proper water intake, consumption of hospital along with vending machine food, living in expandable clothing (scrubs) led to my weight explosion!

But I had the good fortune to meet a Bariatric physician who was a member of the ASBP and was gracious enough to employ me in his practice. With his assistance along with the educational courses sponsored by the ASBP, I learned how to manage my metabolic problem of insulin resistance. I have been successfully maintaining my weight loss for the past 20 years and helping others to achieve success in modifying their metabolic risk factors through weight loss gives me great joy each day.

AAM: I imagine that with the growing rates of obesity to be found in nearly all parts of the world today that this worries you?

DB: Yes, today over 60% of Americans are either overweight or obese. One need only to observe people walking down the street to see that almost every other person has some degree of a weight problem. I am also dismayed to see the growing number of children who are also affected. Until 10 years ago this problem seemed confined to the States. As I travel throughout the world, I see that the increased availability of fast and processed foods through Americanization, the abundance of sugary snacks and a more sedentary lifestyle has resulted in the exponential increase adult and children’s waistlines. The rate of overweight and obesity in American children has doubled over the past 20 years and currently 1 in 5 children in Europe are overweight. Obesity is associated with a myriad of diseases and disabilities which include: metabolic syndrome, type-II diabetes, hypertension, cardiovascular disease, dyslipidemias, arthritis, cancer, sleep apnea, stroke, steatohepatitis, PCOS, infertility, depression, and premature death. When I attended medical school, type-II diabetes was also known as adult onset diabetes. Not now. The rise in incidence of type-II diabetes is directly correlated to the rise in incidence of obesity. We are now diagnosing children aged 3 and older with type-II diabetes! The WHO projects that the global prevalence of diabetics will increase from 171 million in 2000 to 366 million by 2030.

AAM: So the $64 Billion question is- what can be done to help counteract this trend?

DB: I think we are talking about 2 separate strategies. The first is treatment of those who are already overweight or obese and the second one is prevention. The treatment portion involves helping patients achieve and maintain a weight loss that successfully ameliorates their metabolic risk factors. This entails prescribing a food plan that addresses specific metabolic needs and is practical for an individual’s lifestyle. Elimination of the “white” things, like sugar, rice, bread, and potatoes is a part of all of my food plans. Regular physical activity, i.e. 5 days per week is also critical, but again it must be practical for that person. You cannot expect a person to regularly spend 20-30 minutes traveling to an exercise facility and then exercise for 1 hour. Convenience ensures compliance. It is also important to stress the simplicity of adding activities in one’s daily life. A simple example of this would be taking a 15 minute walking break every 2 hours rather than sitting at the computer for 4 continuous hours. Drinking at least 1.5 liters of water daily and minimize consumption of those diet sodas. Adding prescription appetite suppressants can certainly be a helpful adjunct in Bariatric treatment provided that the components of a food plan and activity are being implemented. The preventive side is genesis of our ability to decrease this growing obesity epidemic in our children. We must start with the family unit and encourage the parents to serve as positive examples, so that their children can emulate their behaviors. Encourage the children to be physically active by having family activities and not just play computer games. Work with the schools systems to offer healthy not obesigenic lunches for children. Remember not to use food as a reward for good behaviors. Offer fruit not fruit juices for snacks.

AAM: Indeed. Can I ask you what kinds of patients come to you and what are they looking for in the way of help?

DB: Patients come for varying amounts of weight loss and some just to help them consume a healthier diet. They are basically looking for tools to help them sustain lifestyle changes that improve their quality of life and their longevity. The patient is questioned regarding weight and nutritional intake, activity level, any medications either OTC or prescribed, allergies, family, medical, surgical, sexual and psychological history and their personal health objectives. With this information along with laboratory assessments and physical examination, I can design a personalized program for that individual.

AAM: Could you please describe some of the most useful nutrients and drugs, which in your experience have been the most helpful for your patients?

DB: The most nutrients I find most useful in my practice are as follows: L-carnitine, CLA, chromium, CoQ10, OmegaPro 3 Fatty Acids, vanadium, alpha lipoic acid, zinc, calcium magnesium, multivitamin, B complex especially pyridoxine, pyridoxal-5-phosphate, B12, folic acid, niacinamide, vitamin C, taurine, 5-HTP, tyrosine, phenylalanine and Rhodiola Rosea. In terms of pharmaceutical agents, phentermine is a re-uptake inhibitor which helps to decrease appetite. Reductil® [Ed.- Sibutramine] is both and selective serotonin re-uptake inhibitor- therefore it should help with both appetite and cravings. I prefer using phentermine in my practice as there is a great deal of flexibility with dosing and has a rapid onset of action as compared with at times a 4 week period before the effect of Reductil is noted. Phentermine is affordable as contrasted with the expense of Reductil and works well in people who have issues with their overactive appetite. In my experience and discussion with my colleagues, Reductil seems to work in only about 20% of those for whom it is prescribed. Bupropion has been helpful with decreasing appetite and cravings. Topiramate is useful in those with binge eating disorders and has been involved in a clinical trial in combination with phentermine. The results look promising. Xenical® blocks fat absorption when the food consumed has a fat percentage greater than 30%. It is analogous to using the drug, antabuse, in alcoholics…definitely aversive conditioning. I use it primarily in the maintenance phase, because it helps to keep patients on their food plan especially when in social gatherings. Many of my patients have metabolic syndrome, so I use metformin to help improve their insulin resistance.

AAM: How do you decide on the combination, or how one particular program may be more preferable for one patient over another?

DB: My father who was a very wise physician always told me to listen to the patient and they will guide you in discovering solutions for their treatment. In my practice, I spend a lot of time gathering information and listening to what components of other programs have and have not been successful for that patient. One of the first things that I do is a body composition analysis via bio-electrical impedance. This test gives me a relatively accurate weight loss goal for that patient. If the patient has unrealistic weight loss goals at the outset, the patient is setting himself or herself up for certain failure. At the outset, we agree on the goal. If a patient has gone through a variety of programs that did not involve the use of any appetite suppressants, but was fairly compliant with food and activity plans, but complains of hunger and or cravings, I would prescribe one of the appetite suppressants. If a patient has metabolic syndrome, I would recommend a food plan that concentrates on lean proteins, vegetables and fruits with low-glycemic indices and restricting fat to no more than 30% of total calories. Many patients in their attempt to lose weight think that the fewer calories that they consume, the greater the weight loss, so it is important to make certain that the patient is consuming the proper amount of calories especially in the protein category. People tend to automatically decrease their protein consumption because they equate protein with fat, and through protein deprivation produce sarcopenia. Also when the body perceives starvation, its survival mechanisms kick in to slow down your metabolism, so it is important for many people who have done this in the past, to eat 5-6 small meals per day.

AAM: I can appreciate that weight loss/ control is a complex area, just how much do genes in your experience influence one’s size and proportions?

DB: Genetics are in part responsible for about 40% of obesity that we see, and the environment is responsible for the remainder. In the April 2006 issue of Science Magazine, researchers reported the first study to actually identify a specific genetic factor in obesity, a sequence variation close to the INSIG2 gene. So for those of us like myself who had a strong genetic predisposition for obesity, controlling food intake and regular physical exercise are crucial components necessary to modifying one’s overall genetic predispositions. These behavioral changes however need to be sustained, as our genes are certainly not going to change. Parents who are obese have a special challenge with their children. These parents need to exercise vigilance over food selections and physical activity for both themselves and their offspring. We certainly learn by example and if parents are not good role models, the children’s ability to overcome their obesigenic environment is compromised. Studies have shown that when infants are overfeed to stop their crying or to induce sleep etc., that their normal feeding feedback mechanisms can be altered. In other words, their neurochemistry can be short circuited, and they continue to overeat as they mature.

AAM: Perhaps more so than any other area, there are many people looking for the magic bullet to weight loss, are there any new developments on the immediate horizon that hold promise?

DB: Currently there are more than 100 potential anti-obesity drugs in various stages of clinical trials. We live in a society of instantaneous results, i.e., text messages, e-mails, so we also would like immediate results with regards to weight loss. Companies promoting products that produce rapid weight loss with no regard to food intake or physical activity exploit the vulnerability of those who desperately want to believe that they have found the proverbial magic bullet. Unfortunately, there is no magic bullet, but there are some very interesting drugs on the horizon. These drugs are primarily modulators of the neuro-endocrine pathways, which I believe will become the primary drugs of choice in Bariatric medicine. AOD-9604 developed by Metabolic Pharmaceuticals, is a growth hormone fragment that is orally absorbed and can certainly be used in combination with other anti-obesity agents. It produces weight loss by promoting lipolysis and inhibiting lipogenesis without the negative side effects of growth hormone. Another rising star is a 5-HT2C agonist, APD356, developed by Arena Pharmaceuticals. Fenfluramine, the drug that was withdrawn due to its association with valvular heart disease and PPH was a 5-HT2C receptor agonist. Because of its different receptor site activity, APD356 has not been associated with the development of any cardiovascular disease. The emerging star is Rimonabant, or branded Acomplia, this is the first anti-obesity agent that has been in approved since 1997- at least in Europe, however the FDA of the United States denied the request to fast track approval by Sanofi-Aventis earlier this year, and placed additional requirements on the company before approving the drug for use in the United States.

AAM: Yes indeed a lot has been made of Acomplia in the press recently, particularly as you say- it has just been approved in Europe for use in weight loss. What makes it different to other methods that have come before it?

DB: Well Rimonabant is a CB1 receptor antagonist that has been shown to produce weight loss, improve metabolic and cardiovascular risk factors and assist in smoking cessation. Cannabinoid 1 receptors are expressed in several areas of the brain including the basal ganglia, hippocampus and cerebellum and other sites including the autonomic nervous system, liver, muscle, GI tract, and adipose tissue. Nicotine and the primary psychoactive ingredient in marijuana, THC, produce activation of these receptors. That is why people get the “munchies” after smoking marijuana.

AAM: So what do you make of the clinical trials with Acomplia that show 10% loss of bodyweight and an average of 3 inches off the waist, is this a breakthrough?

DB: The results of the RIO [Ed.- Rimonabant in Obesity], Europe study noted that with a weight loss of 10%, there was an elevation in the HDL cholesterol, a decrease in the LDL cholesterol, a reduction in triglycerides and waist circumference, an increase in the Adiponectin level, and an improvement in glycemic control. I must say that if I told a patient who weighed 200 pounds that I could help her lose 20 pounds with the help of a drug, I think that she would promptly leave my office in a huff. Although the medical literature supports the fact that a 5-10% reduction in baseline weight improves if not reverses co-morbidities associated with obesity, in the real world, patients’ expectations for weight loss are much higher. The study could not permit individualization of treatment modalities. I believe that a patient who is involved in a structured program under the supervision of an experienced practitioner would attain a far superior weight loss as compared to those in the RIO-Europe study. Studies that involved other anti-obesity drugs such as Reductil, Xenical® and phentermine did show a statistically significant reduction in weight approaching the Rimonabant data, but none of the studies showed such overall improvement of metabolic and cardiovascular risk factors.

The release of this drug has met with great excitement in the field of Bariatric medicine as this marks the first release of a new anti-obesity agent in almost 10 years. I am excited to have a new agent although I have a few reservations about my unconditional support for Rimonabant. First of all, since we are meant to survive, our bodies do everything to protect our survival. To explain this concept another way, the body’s orexigenic pathways- those that stimulate eating- are far stronger and can overcome the anorexigenic pathways- those that inhibit eating. An example of this would be the recent experience with Axokine, a drug that by-passes leptin resistance and showed great promise as an anti-obesity drug. During phase 3 clinical trials, the majority of subjects developed neutralizing antibodies to Axokine resulting in the discontinuation of the trial. Are we going to see that over time, Rimonabant loses its effectiveness? Secondly, I am fearful that patients will rely solely on the drug and forget about the importance of maintaining sensible food consumption and regular physical activity and blame the drug for their failure, when in fact the failure is due to their non-compliance.

AAM: One imagines this discovery will take Bariatric medicine off into new directions that were previously unexplored; do you hold out that we can crack weight control one of these days?

DB: I believe the foundation of successful Bariatric treatment lies in the food and physical activity plan, correcting hormonal imbalances, nutritional and micronutrient deficiencies, and gut dysbiosis. The addition of pharmacological agents provides an extremely useful adjunct to our treatment armamentarium. I have witnessed the numerous beneficial effects that anti-obesity medications have had on the improving co-morbidities in so very many patients. The future holds great promise for agents that control appetite signaling pathways through neuro-endocrine pathways and even agents that help to boost metabolic rates. We will probably use a combination of agents, much as we do for the treatment of hypertension. These agents will assure the successful treatment of obesity, but more importantly, facilitate maintenance of weight loss. The future may even hold a vaccine to prevent obesity. I feel that this is one of the most exciting times to be involved in Bariatric medicine because caloric restriction is critical to enhancing our longevity.

AAM: Thanks very much Dr. Bruner, you’ve given hope for us all!

DB: That’s good to know!