Comparing the Metabolic Effects of Different Weight Loss Diets

Summary

Obesity is a common chronic disease affecting more than 40% of Americans. It is associated with an increased risk of diabetes and poor metabolic health. Dietary modification is the primary therapy for reducing the risk of diabetes and improving metabolic health in individuals with obesity. Three dietary patterns commonly prescribed for this purpose are the very-low-carbohydrate ketogenic diet, plant-based low-fat diet, and Mediterranean diet. While all three of these diets can lead to weight loss, their distinct compositions require the body to process them in different ways. For example, the high carbohydrate content of a plant-based low-fat diet activates a different set of pathways than the high fat content of a ketogenic diet. Given these differences, the metabolic effects of each diet may vary. Organ systems in the body, such as muscle tissue, fat tissue, and the liver, may also respond differently across diets. 

It is currently unknown whether specific diets have the ability to enhance or impair the metabolic benefits of weight loss, such as improved insulin sensitivity of muscle tissue and reduced liver fat. Understanding the metabolic effects of different diets could help inform personalized dietary counseling, a key component of obesity treatment programs. 

In order to better understand the metabolic effects of these specific diets, Dr. Max Petersen and Dr. Samuel Klein at Washington University are conducting a randomized controlled trial. Dr. Petersen is a Washington University endocrinologist, and Dr. Klein directs the Center for Human Nutrition, which has led clinical trials in obesity and nutritional science at Washington University for over 30 years. In this study, people with obesity and prediabetes from the St. Louis area are randomized to either a ketogenic (high fat, very low carbohydrate, adequate protein), plant-based low-fat (high carbohydrate, adequate protein), or Mediterranean (balanced nutrient profile) diet, with all food provided to achieve 10% weight loss over 3 to 6 months. Before and after weight loss,  several key aspects of metabolic health that affect future risk of diabetes, liver disease, and cardiovascular disease are measured. These include the sensitivity of muscle tissue to insulin, the metabolic and hormonal response to meals, and body composition (including fat distribution and muscle mass). Biopsies of adipose (fat) tissue are taken to measure the activation of specific pathways that are important for metabolic health.   

Significance

Individualized dietary counseling is the foundation of obesity treatment programs and enhances the benefits of other therapies, such as medications or surgeries. Understanding how different diets affect metabolic health during weight loss could have important clinical implications for dietary management in people with obesity and prediabetes. For example, if a specific diet is found to be particularly beneficial for improving insulin sensitivity, doctors may prescribe that diet to people with very low insulin sensitivity over other diets. In addition to direct clinical benefits, insights from this research could be used to develop educational resources that support the implementation of the most beneficial dietary interventions for people with obesity. 

Obesity is a disease that disproportionately impacts Americans with low socioeconomic status and those who are Black or of Hispanic/Latino ethnicity. Moreover, the most potent medications available for obesity treatment are prohibitively expensive for most Americans with obesity. However, everybody eats. Our study population includes adult men and women from the St. Louis area with diverse backgrounds to ensure our research is able to equitably benefit all people.

Benefits

Demonstrated benefits are those that have been observed and are verifiable.

Potential benefits are those logically expected with moderate to high confidence.

Robust data regarding the metabolic effects of specific diets during weight loss could lead to insights that inform national and international guidelines for nutrition and obesity. potential.

Clinical

Guidelines

Educational resources could be generated based on the study results to advocate for the most beneficial dietary interventions.  potential.

Community

Health education resources

A better understanding of the metabolic effects of specific diets during a weight loss intervention could lead to more cost-effective weight loss programs.   potential.

Economic

Cost effectiveness

Optimizing dietary strategies for weight loss could offer a more accessible alternative to expensive anti-obesity medications. potential.

Economic

Societal & financial cost of illness

Clinical

The question of what diet is best for weight loss can be considered from various angles: preference, ease of adherence, cost, environmental, and cultural. Our study asks the question from a purely physiological perspective: if adherence is perfect, what are the differential metabolic effects of several popular diets (ketogenic, Mediterranean, plant-based) during weight loss in people with obesity and prediabetes?

Community

Obesity afflicts more than 40% of Americans and increases the risk for many other common and important chronic illnesses. Dietary modifications are the foundation for all effective obesity therapies and can be employed even if more potent therapies, such as anti-obesity medications and bariatric surgeries, are inaccessible. Therefore, it is critical to understand the specific metabolic effects of the major diets commonly used for weight loss. 

Economic

An intensive lifestyle intervention combined with medication for obesity leads to greater weight loss and health benefits than medication alone. Further, highly effective obesity treatments such as newer anti-obesity medications and bariatric surgery can be expensive. Understanding the metabolic effects of specific diets could lead to more cost-effective weight loss programs.

The high prevalence of obesity and cost of anti-obesity medications have raised ethical and economic concerns about healthcare access. By optimizing dietary strategies for weight loss, we can help address these concerns.