Phenotype-tailored diets ‘set patients up for success’ in weight loss, health outcomes
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It has long been said that the best way to treat obesity is to eat a healthy, reduced-calorie diet and exercise regularly.
This method of intervention paints patients with a broad brush and overlooks their unique phenotype for weight loss, contributing to variability in treatment outcomes. Phenotyping classifies a patient’s specific type of obesity based on biological mechanisms. By understanding a phenotype, a physician can identify what is driving a patient’s weight gain and limiting their ability to lose weight.
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While phenotype-based diets have historically not been well understood, new research from the Mayo Clinic — recently presented at the Fall Obesity Summit by the Obesity Medicine Association — is showing that phenotype-tailored approaches to lifestyle modification can produce significant weight loss and health improvement in adults with obesity.
Phenotypes Can Guide Patient Interventions, Treatments
Pathophysiology and behavioral science have allowed us to classify obesity into four phenotypes: abnormal satiation (hungry brain), abnormal postprandial satiety (hungry gut), emotional hunger (hedonic eating) and abnormal resting energy expenditure (slow burn). These four phenotypes account for at least 85% of patients’ obesity.
Based on a patient’s phenotype, a physician has a clearer understanding of which interventions and treatments will best suit their patient. Our research published in Obesity found that 79% of phenotype-understood patients lost more than 10% of total body weight when using anti-obesity medications, compared with only 35% of non-phenotype patients. Weight loss improves by 1.75 times when anti-obesity medications are selected based on a patient’s phenotype compared with standard-of-care medication selection.
Research shows that beyond weight loss, patients who followed a phenotype-tailored diet and lifestyle saw improvement in different biological and behavioral factors that contribute to obesity, which hasn’t been seen with other diets. Diet interventions based on macronutrients, genetic predisposition or meal timing have shown no benefit compared with standard treatment and have mainly focused on obesity-related complications, such as managing and preventing type 2 diabetes, hypertension or cardiovascular risk. However, none have been tailored to the underlying pathophysiological and behavioral abnormalities identifiable in patients with obesity.
This latest research featured a non-randomized study of 165 patients over the course of 12 weeks. The phenotype-tailored diet was derived from nutritional studies that showed targeted-specific physiological or metabolic benefits after and during a unique intervention. One group of patients in the study followed the Mayo Clinic diet with a 500 kcal deficit, combined with 150 minutes of moderate exercise per week and a recommendation to reach 10,000 steps daily. The other group was given a low-calorie diet and recommendations tailored to their specific phenotype, along with exercise and step recommendations.
Participants identified to have the “abnormal satiation” phenotype were instructed to restrict their meals to one or two per day with a volumetric, high-fiber diet. The “abnormal satiety” phenotype participants were instructed to have three meals per day with a pre-meal protein supplement. The “emotional eating” phenotype participants followed a Mayo Clinic diet, avoided snacks and participated in behavioral group therapy with clinical health psychologists, along with a weekly check-in with their wellness coach. The “abnormal resting energy expenditure” phenotype participants were directed to follow a Mayo Clinic diet combined with a post-workout protein supplement. They were instructed to do at least 30 minutes of high-intensity interval training four to five times per week and check in weekly with their physical therapist.
Patients in the phenotype-guided diet and exercise program lost twice as much weight as patients who were on the Mayo Clinic diet. They also saw a greater decrease in waist circumference, fat mass, gastric emptying, anxiety score and triglycerides level. This finding can reach far beyond patients who are obese and also help those who are overweight and trying to lose weight that creeps up year over year.
Precision Medicine vs. Traditional Guidance
A one-size-fits-all treatment for obesity will not work for many patients due to the complexity, heterogeneity and multifactorial nature of the disease. Using precision medicine to target treatments for individuals based on the causes behind their disease is providing better outcomes than traditional guidance. Using personalized approaches to treating disease has become much more common as we have gained a deeper understanding of diseases.
Consider how our understanding of cancer treatment has evolved over time. Each case is unique to the individual and needs to be treated as such — the same goes for obesity. We have been calling obesity a disease for more than a decade, and until now, we have not been able to explain to a patient why they are suffering from this disease.
We have a lot more to discover about phenotyping, and there are ongoing studies to examine different drug responses and outcomes as they relate to obesity treatment and phenotypes. We are also looking at other procedure interventions and how phenotyping could improve outcomes.
By using obesity phenotyping to understand exactly why patients have not been able to lose weight in the past, we are able to set patients up for success in weight loss and improve their overall health.
- For more information:
- Andres Acosta, MD, PhD, is a consultant and assistant professor of medicine in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minnesota. He also co-founded Phenomix Sciences.
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