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Fierce debate over a new theory to tackle the global obesity pandemic

A bold challenge to the dominant theory explaining obesity has been launched by Harvard University Professor David S Ludwig and 16 fellow researchers from the United States, Canada and Denmark. Their proposed Carbohydrate-Insulin Model, published in the American Journal of Clinical Nutrition, has sparked fierce scientific debate and may change medical responses to the global obesity pandemic, writes MedicalBrief.

The dominant theory on obesity is that it is caused by overeating and should be managed by consuming fewer calories and exercising more. This is the approach that doctors around the world impart to patients, and that informs public health campaigns and policy-making.

Ludwig and colleagues suggest that this ‘energy balance’ theory is an insufficient explanation for obesity, and has failed adequately to tackle the public health problem.

The Carbohydrate-Insulin Model (CIM) suggests that eating processed, rapidly digestible (high glycaemic) carbohydrates raises insulin levels and suppresses glucagon levels. The body responds by directing an excessive amount of calories to fat tissue. The result is conservation of energy, increased hunger and, longer term, more fat storage. The focus should be more on what a person eats, than how much.

Aside from Harvard University and nutrition-related institutions, the researchers are from Weill Cornell Medicine, the University of California – Berkeley and San Francisco – Ohio State University and Duke University in the United States, as well as the University of British Columbia in Canada and University of Copenhagen in Denmark.

In a 12 October 2021 article in MedPage Today, Sophie Putka reports Ludwig as saying that the journal paper attracted more than 140,000 views in its first few weeks, “exceptional” for an academic journal. She describes and investigates the fierce academic battle that followed its publication on 13 September. (See below.)

Before that, Ludwig summarises the position of the 17 researchers in an Oxford University Press Blog published last month. Also below are the study details and abstract of the American Journal of Clinical Nutrition article, and a Consensus Statement on “Ending weight bias and the stigma of obesity” published by Nature Reviews in March last year.


Oxford University Press Blog

Does “overeating” cause obesity? The evidence is less filling

The usual way of thinking considers obesity a problem of energy balance. Take in more calories than you expend – in other words, ‘overeat’– and weight gain will inevitably result. The simple solution, according to the prevailing Energy Balance Model (EBM), is to eat less and move more, writes David S Ludwig in an Oxford University Press Blog published on 28 September 2021.

Variations on this recommendation have been advocated to the public by government and professional health organisations for decades. For instance, the USDA Dietary Guidelines for Americans state: “Losing weight … requires adults to reduce the number of calories they get from foods and beverages and increase the amount expended through physical activity”.

Health care providers almost invariably prescribe low-calorie diets (typically restricted in fat, the most calorie-dense nutrient) and exercise to their patients.

In a new Perspective article in American Journal of Clinical Nutrition, my 16 co-authors and I argue that viewing body weight control as an energy balance problem is fundamentally wrong, or at least not helpful, for three reasons:

  1. It hasn’t worked

The obesity pandemic continues to worsen worldwide despite an incessant focus on calorie balance. Of particular concern is an emerging pandemic vicious cycle. Obesity is among the most important risk factors for COVID-19 susceptibility and severity, after advanced age. Conversely, the COVID-19 pandemic may exacerbate obesity, at least according to preliminary data in children. We need a more effective approach to weight control, now more than ever.

  1. It doesn’t consider biology

The relationship between energy balance and body fat reflects a law of physics (conservation of energy), providing no information about biology. It’s like considering fever a problem of ‘heat balance’ – too much heat being generated by the body, not enough heat dissipated. Although technically true, this view doesn’t address the critical questions: what’s causing the fever and how we can cure it?

  1. It can’t distinguish cause from effect

The law of energy conservation holds that the relationship between energy balance and body weight is inseverable but provides no information about the direction of cause and effect. During the growth spurt, an adolescent may consume hundreds of calories more than he burns. But does this ‘overeating’ make him grow taller, or does the rapid growth make him hungry and eat more? Clearly, the latter … as no amount of ‘overeating’ will make an adult grow any taller.

The Carbohydrate-Insulin Model, an alternative obesity paradigm considered in our Perspective, makes a bold claim: we’ve had it backwards all along! Overeating doesn’t cause obesity; rather, increasing body fatness – resulting from the effects of diet on hormones and metabolism – drives overeating.

The processed, rapidly digestible carbohydrates that flooded the food supply during the low-fat diet craze (think Fat-Free Snackwells Cookies) have raised insulin and suppressed glucagon levels.

This highly anabolic hormonal state after a meal directs an excessive amount of incoming calories toward storage in fat tissue. As a result, too few calories are available to fuel the needs of metabolically active organs, like muscle.

The brain responds by increasing hunger in an attempt to solve this ‘energy crisis’ – driving us to consume extra calories to replace those being diverted into fat tissue. If we try to resist hunger, and cut back calories, energy expenditure (calorie burn) may slow down, explaining why so few people succeed on low-calorie diets over the long term. Eventually, biology trumps willpower.

If the CIM is right, then a focus on what you eat will be more effect than on how much. By replacing processed carbohydrates (white bread, white rice, potatoes, cookies, cakes, sugary beverages) with healthy high-fat foods (nuts and nuts butters, full fat dairy, avocado, oil olive, even dark chocolate), we can lessen the drive to ‘overeating’ at the source, by shifting calories away from deposition in fat tissue.

As a result, hunger naturally decreases, and weight loss may occur more easily, like the reduction in body temperature that follows treatment of fever with aspirin. For individuals with more severe metabolic dysfunction, such as type 2 diabetes, more intensive carbohydrate restriction (such as a ketogenic diet) may be optimal.

Although rapidly digestible carbohydrates (technically, high-glycaemic load) play a key role in the CIM, the model provides a way of understanding how many dietary factors (amount and type of protein, type of fat, micronutrients fiber, pre- and probiotics) and other environmental factors can influence body fat storage, other than directly through ‘overeating’.

Although the CIM is not proven, our Perspective highlights the extensive supportive basic and clinical research that already exists. We argue that the CIM better reflects a century of accumulated knowledge on the biology of obesity than the energy balance model. And we call for better funding to conduct the definitive research. As highlighted in our Perspective, versions of this debate have raged for a century.

Professor David S Ludwig is an endocrinologist and researcher at Boston Children’s Hospital. He holds the rank of professor of paediatrics at Harvard Medical School and professor of nutrition at Harvard TH Chan School of Public Health.


Obesity paper has diet researchers riled up

Last month, the American Journal of Clinical Nutrition (AJCN) published a perspective piece that stirred up tensions in the worlds of epidemiology, physiology and nutrition, writes Sophie Putka for MedPage Today, in an article published on 12 October 2021.

Doctors and researchers argued on Twitter; commenters defended and derided related opinion pieces; and lay audiences read headlines such as “Overeating isn't the primary cause of obesity” and “Study finds primary cause of current obesity epidemic”.

The paper's lead author, Dr David Ludwig of Harvard University, says the journal saw more than 140,000 views on the paper in its first few weeks of publication, which he said, "for an academic nutrition journal, is exceptional”.

This is a shortened version of the MedPage Today article. Find a link to the full story below.

But there's more to this perspective piece than its reception. While supporters applauded what they say is a long-overdue reset of the narrative on weight and metabolism, the model and its central premises prompted fierce criticism.

The controversy reveals just how much more there is to learn about how the body responds to food, even as all sides ultimately agree on basic nutritional and metabolic interventions.

Sophie Putka goes on to describe the Carbohydrate-Insulin Model, outlined above.

Increased hunger and diminished energy expenditure begets a vicious cycle that can be averted with a low-carb, low glycaemic diet. “Given the choice between bread and butter, for years we focused on getting rid of the butter,” said Ludwig. “But maybe between the two, the bread is the bigger issue.”

The argument against 'calories in, calories out'

The current leading mechanistic model – the energy balance theory – Ludwig said, is "not addressing the cause, it's addressing a downstream effect, and so we'd be like somebody with fever, trying to treat the problem by getting into an ice bath."

According to Putka in MedPage Today, Ludwig and co-authors say that the obesity treatment community is still operating within a framework that goes hand-in-hand with the energy balance model. An energy imbalance comes from the law of physics that state energy cannot be created or destroyed – so if you take in more than you expend, it has to go somewhere.

They say the theory is still missing the ‘why’. Energy balance explains what happens when people gain weight, but not why is it happening.

“The whole world thinks obesity is about energy balance,” said Professor Robert Lustig, a professor of paediatrics in the division of endocrinology at the University of California San Francisco, who outlined a similar model of hyperinsulinaemia leading to weight gain in 2006.

“Therefore, it's calories in, calories out. Therefore, it's about two behaviours, gluttony and sloth. Therefore, if you're fat, it's your fault. Therefore, diet and exercise. Therefore, any calorie can be part of a balanced diet.”

And indeed, recent studies and reports suggest that stigmatisation of people with obesity is alive and well, negatively impacting upon almost every aspect of life, especially healthcare.

Criticisms: Argument framing and energy balance

Putka writes in MedPage Today that critics say the authors use the energy balance model in a misleading way for their argument's purposes, conflating the principle with what amounts to ineffective dietary advice.

“The common recommendation, 'eat less, be more physically active’, that we tell people doesn't work very well. Results are not that successful,” said Dr Samuel Klein, director of the Centre for Human Nutrition at the Washington UniversitySchool of Medicine in St Louis.

“But the 'why' doesn't mean that energy balance is wrong. We're unable to get people to actually reduce their energy intake adequately in order to do that.”

Klein and others point to the Endocrine Society’s 2017 scientific statement on obesity pathogenesis for a more full explanation of the theory.

The authors address this in their ‘criticisms’ section, writing that none of “the recent dismissals of the CIM [carbohydrate-insulin model], provide a mechanistically oriented, testable model addressing dietary drivers of obesity, beyond the recurring focus on widely available, inexpensive, energy-dense, highly palatable, processed foods.”

Ludwig said what influences palatability isn't universal or well defined yet, either, and that this explanation of the rise of obesity isn't adequate.

Many say their perspective pushes the conversation forward, writes Putka in MedPage Today.

"I think one of the main arguments in the paper is, obesity is a huge problem, and we obviously have not been good at fixing it because of how prevalent it is," said Dr Jorge Moreno, MD, an internal medicine physician at Yale who specialises in obesity.

He said while low-carb for weight loss isn't new, linking low-glycaemic diets directly to weight loss is compelling. "We can't use the old model as our driver for change."

The landscape today

Others who have joined the conversation say that the research has been trying to quantify what actually drives energy intake and expenditure that leads to an energy imbalance, and that they're not just pushing the outdated agenda of a bygone low-fat era.

“Obesity pathophysiology is very complicated, and it doesn't fit in a sort of energy-in-energy-out perfect little equation because the complexities of both sides of that equation are so vast,” said Karl Nadolsky, an endocrinologist specialising in diabetes, metabolism, and obesity.

"They [Ludwig et al] use the real complexities to try to push this model that really ultimately supports their dietary bias for some reason," but one diet or another doesn't have to be mutually exclusive, he said, according to Putka in MedPage Today.

The carb conundrum

That's where the carbohydrates come into play. The authors conclude that based on their model, a low-carb diet would “decrease the insulin-to-glucagon ratio, enhance lipolysis and fat oxidation, and result in lower spontaneous food intake”.

They also disclose in their acknowledgements that five of the authors receive royalties from books on low-carb diets, and consulted for or started companies that promote low-carb diets. Among them, Ludwig has written a book that promotes a low-carb diet, although he said he has never accepted money from the food industry.

Regarding the conflicts of interest, Ludwig said: “There's nothing unusual about this," and pointed to drug studies where authors are closely tied to pharmaceutical companies, and food industry interests that fuelled much of the ‘low-fat’ wave of the 80s and 90s.

“Writing books, including for the public, is what academics have been encouraged to do for centuries, and selectively impugning a controversial idea … because people are writing books, I don't think advances the dialogue,” he said.

The mechanism itself

Central to the debate, writes Putka in MedPage Today, is a disagreement about the role of insulin. In the paper, insulin is a key driver (although not the only one) of food intake, leading us to store more fat, which in turn lowers our energy expenditure, and makes us hungrier. In the energy balance theory, insulin plays a role, but not the lead.

Critics also say that there's not enough evidence that low-carb diets cause the body to expend more energy, or that increased insulin is a direct cause of increased food intake.

“Stimulating fuel uptake by adipose tissue – there's no evidence that goes back to stimulate your brain to eat more food,” said Klein. What's more, he said the initial insulin spike doesn't just happen with high-glycaemic foods – it happens with small amounts of any carbohydrate.

Lustig, who pioneered the earlier paper on a model similar to the CIM in 2006, said it's clear: insulin is what influences energy expenditure – but it's driven by leptin. He said he thought a discussion of leptin's role, fructose and its conversion of fat in the liver, and how insulin release might affect three fat depots (subcutaneous, visceral, and liver) were missing. “Those are the things that would have made this paper much better. But the concept is right.”

Agreement and an individualised approach

Ludwig says he welcomes a debate, and hopes to push the conversation forward. “We explicitly leave open the possibility of common ground, but I think that it's likely that the truth will be in the middle," he told Putka, writing in MedPage Today. “And we call on opponents to be civil with each other. “That is to me, what science is about … to consider new ideas, even if those ideas are provocative."

Still, it can be easy to miss what specialists in obesity, nutrition and endocrinology agree on. For one, cutting back on sugar and highly processed foods, and recommending low-glycaemic foods to patients.

"Replacing the high-saturated-fat foods and refined processed foods that have both types of fat with nuts and seeds and olive oil, improves, not only the weight, but also the cardiometabolic data," Nadolsky said. "So these things all go together, and they don't have to be mutually exclusive."

He said helping individuals find the right approach for them is most important of all – and it might be low-carb, or it might be something else.

Although there's disagreement in the framing of ‘easily available, highly palatable’ foods as the main cause of obesity, most agree that easily available, highly processed carb-rich foods contribute in a big way. There are also more effective, non-diet interventions for obesity than ever before, like bariatric surgery, said Klein, and weight management medication.

The truth is, there's still much to be learned about the complexities of how food interacts with human metabolism. “The regulation of food intake is really still very much an emerging science that we don't know a lot about,” said Klein.


Study details

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

David S Ludwig,  Louis J Aronne,  Arne Astrup,  Rafael de Cabo, Lewis C Cantley,  Mark I Friedman,  Steven B Heymsfield,  James D Johnson, Janet C King,  Ronald M Krauss,

Daniel E Lieberman,  Gary Taubes,  Jeff S Volek, Eric C Westman,  Walter C Willett,  William S Yancy, Jr,  Cara B Ebbeling

Author affiliations: Harvard University; Weill Cornell Medicine; University of California Berkeley; University of California San Francisco; Ohio State University; Duke University; University of Copenhagen in Denmark; University of British Columbia in Canada; New Balance Foundation Obesity Prevention Center at Boston Children's Hospital; National Institute on Aging at the National Institutes of Health or NIH; Monell Chemical Senses Centre in Philadelphia; Pennington Biomedical Research Centre in Baton Rouge; and the Nutrition Science Initiative in San Diego.

Published in The American Journal of Clinical Nutrition on 13 September 2021.


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. Conceptualising 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-glyacemic-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 two models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.


Consensus statement

Ending weight bias and the stigma of obesity

Published in Nature Reviews Endocrinology, Volume 16, on 10 March 2020.

A Consensus Statement published last year in Nature Medicine calls for the end to weight bias and the stigma of obesity. Nature Reviews Endocrinology writes that is proud to support this initiative.

There is a link to the full Consensus Statement below. This article provides a summary.

Obesity and overweight have increased in prevalence in the past few decades, reaching pandemic levels in many countries. People with overweight and obesity are known to be at increased risk of a range of medical complications.

In addition, it is becoming increasingly clear that people with obesity and overweight are also facing stigma in many aspects of their lives, which not only has a damaging effect on the individual’s mental health but can also influence the quality of health care that affected people receive.

In a Consensus Statement published in Nature Medicine, Professor Francesco Rubino of King’s College London and colleagues call for an end to weight bias and obesity stigma and set out a pledge to help achieve this aim.

Weight bias and obesity stigma are rooted in the misconception that body weight is easily controlled by making changes to the diet and physical activity levels. In reality, the factors that influence body weight are complex and include genetics, epigenetics, the environment, societal factors and medications.

Indeed, lifestyle and behavioural interventions that involve reduced calorie intake and increased physical activity levels rarely result in long-lasting changes in body weight, owing to complex hormonal and metabolic adaptations for maintaining body weight. In short, altering body weight is not as simple as eating less and moving more.

Despite obesity being generally accepted as a chronic disease, obesity stigma is highly prevalent and has far reaching effects. Weight bias and obesity stigma can affect an individual’s everyday life – from their salary to the likelihood that they will seek health care and the care that they then receive.

In their Consensus Statement, the international panel of 36 experts, including representatives from a range of institutions and organisations, such as the World Obesity Federation and the American Diabetes Association, suggest that weight bias and obesity stigma can also have much wider negative effects, informing public health policies, limiting access to appropriate treatments and influencing the direction of research.

The Consensus Statement was developed to inform health-care professionals, policy-makers and the public about the factors that have led to obesity stigma and the resulting negative effects.

The authors of the Consensus Statement recognise that body weight regulation is not something an individual can easily control. Furthermore, they condemn the use of stigmatising language, images, attitudes, policies and weight-based discrimination wherever they occur.

Several recommendations have been included to help end obesity stigma, such as updating the curricula of health-care providers to ensure a more complete understanding of the causes of obesity and ensuring public health authority policies do not promote weight-based stigma.

The Consensus Statement also includes a pledge, which organisations and individuals are invited to sign up to pledge. The Nature Research journals have signed up to this pledge. We pledge:

  • To treat individuals with overweight and obesity with dignity and respect.
  • To refrain from using stereotypical language, images and narratives that unfairly and inaccurately depict individuals with overweight and obesity as lazy, gluttonous and lacking willpower or self-discipline.
  • To encourage and support educational initiatives aimed at eradicating weight bias through dissemination of modern-day knowledge of obesity and body-weight regulation.
  • To encourage and support initiatives aimed at preventing weight-based discrimination in the workplace, education and health care settings.

We feel strongly that everyone deserves to be treated with dignity and respect and that a person’s body weight should not influence how they are treated in society. We hope that our readers will join us in supporting this pledge to end weight bias and obesity stigma, ensuring a fairer society for all.


Oxford University Press Blog – Does “overeating” cause obesity? The evidence is less filling (Open access)


MedPageToday story – Obesity paper has diet researchers riled up (Open access)


The American Journal of Clinical Nutrition article – The carbohydrate-insulin model: a physiological perspective on the obesity pandemic (Open access)


Statement in Nature Reviews – Endocrinology – Ending weight bias and the stigma of obesity (Open access)


Nature Medicine – Consensus Statement – Joint international consensus statement for ending stigma of obesity (Open access)


See also from the MedicalBrief archives


Noakes: Iconic study hid findings, reached unjustifiable and possibly unethical conclusions


Governments failing to curb 'big food' fuelling obesity — Lancet Commission


The Lancet Commission on Obesity recommendations 'deeply problematic'


WHO studies: Europe's problems with breastfeeding and child obesity


Is food addiction to blame for obesity? Not entirely, say researchers


Americans are exporting their obesity to SA — Health department director




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