The carbohydrate-insulin model: a physiological perspective on the obesity pandemic

Ludwig, David S
Aronne, Louis J
Astrup, Arne
de Cabo, Rafael
Cantley, Lewis C
Friedman, Mark I
Heymsfield, Steven B
Johnson, James D
King, Janet C
Krauss, Ronald M
Lieberman, Daniel E
Taubes, Gary
Volek, Jeff S
Westman, Eric C
Willett, Walter C
Yancy, William S Jr
Ebbeling, Cara B

¹New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, Boston, MA, USA
²Department of Pediatrics, Harvard Medical School, Boston, MA, USA
³Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
⁴Comprehensive Weight Control Center, Weill Cornell Medicine, New York, NY, USA
⁵Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark
⁶Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA
⁷Department of Medicine, Weill Cornell Medicine, New York, NY, USA
⁸Monell Chemical Senses Center, Philadelphia, PA, USA
⁹Nutrition Science Initiative, San Diego, CA, USA
¹⁰Metabolism & Body Composition Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA
¹¹Diabetes Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
¹²Institute for Personalized Therapeutic Nutrition, Vancouver, British Columbia, Canada
¹³Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, CA, USA
¹⁴Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
¹⁵Department of Medicine, University of California San Francisco, San Francisco, CA, USA
¹⁶Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA
¹⁷Department of Human Sciences, Ohio State University, Columbus, OH, USA
¹⁸Department of Medicine, Duke University School of Medicine, Durham, NC, USA
¹⁹Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA

Address correspondence to DSL (e-mail: [email protected])

Received June 25, 2021; Accepted July 26, 2021

The American Journal of Clinical Nutrition 114(6):p 1873-1885, December 2021. | DOI: 10.1093/ajcn/nqab270

ABSTRACT

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.