It’s the trillion dollar question: What causes obesity?
Most people will tell you it’s a simple energy imbalance. In other words, weight gain = calories in – calories out.
On the surface, this makes perfect sense. The laws of thermodynamics must apply to humans. Therefore, if we “eat less” (calories in) and “move more” (calories out) we should be able to lose weight and maintain and healthy body weight.
The trouble is, while the energy balance model works in theory, it fails in practice.
Society has been pushing the “eat less, move more” calorie-centric approach to weight management for decades without success. “Eat less, move more” hasn’t slowed the rising tide of obesity.
So, maybe, the way to solve the obesity problem requires a different approach.
The “carbohydrate-insulin model” (CIM) contrasts with the calorie focused standard model of obesity, in which an imbalance between calorie intake and output leads to weight gain.
In the CIM, proposed by Professor David Ludwig MD PhD [Ludwig 2018], excessive intake of high glycemic carbohydrates alters the metabolic and hormonal environment in the human body, which drives overeating and fat gain.
The CIM makes several predictions.
First, it predicts that high-glycemic carbohydrates spike insulin, lowering the total amount of energy in the blood around 3 – 5 hours after a meal, potentially making you feel hungry within a few hours. This hypothesis makes sense from first principles. Insulin drives glucose into fat and muscle cells, inhibits the release of fatty acids from fat cells, and blocks the production of ketone bodies by the liver.
A randomized controlled feeding trial, indeed, did demonstrate that the hypothesis holds true. The more carbohydrates individuals ate, the higher their insulin spiked and, consequently, the lower the total energy in their blood stream (glucose, fatty acids, and ketone bodies) 3 – 5 hours after eating [Shimy 2020].
The practical implication of this late-postprandial low energy availability phenomenon is that high-carbohydrate diets could challenge a person’s ability to maintain weight loss through caloric restriction over long-term.
There is further evidence to support the notion that higher carbohydrates diets are inferior to low-carbohydrate diets for maintaining weight loss. After weight loss, high-carbohydrate weight maintenance diets are associated with a 43-51% increased blood flow to the brain’s reward center, the nucleus accumbens, months as compared to higher fat low-carbohydrate diets [Holsen 2021].
(DietDoctor has an excellent video covering this research entitled “Are Carbohydrates Addictive.” )
These early data are consistent with the idea that therapeutic carbohydrate reduction is beneficial for, not only losing weight, but also keeping the weight off.
Second, the CIM predicts that high-carbohydrate diets may decrease energy expenditure as a means to defend a higher weight set point.
This prediction was examined in the Framingham State Food Study, a 20-week randomized controlled trial in which individuals who had lost weight were randomly assigned to diets controlled for protein (20% calories from protein) but in which calories from carbohydrates were swapped for those from fat. The low-fat group ate 20% calories from fat and 60% from carbs, and the high fat group are 60% calories from fat and 20% from carbs. The study found that, among 120 persons on average, the low carb group required 278 more calories per day to maintain weight as compared to the low fat group [Ebbeling 2018, Ebbeling 2020].
Third, the CIM predicts that high insulin levels can bias fuel partitioning towards fat, as opposed to lean mass, even when calories are controlled.
This has been demonstrated in rats in which administration of insulin leads to fat gain even when caloric intake and activity are controlled to prevent excessive weight gain [Torbay 1985] and in rodents with high vs low-carbohydrate, calorie-controlled diets [Pawlak Lancet 2004]. While the concept of insulin-driven fuel mispartitioning is difficult to test experimentally in humans (beyond the natural experiment of exogenous insulin treatment), is consistent with other data showing that hypothalamic insulin resistance is associated with weight regain at nine months and two years after lifestyle intervention, as well as the preferential partitioning of excess fuel into inflammatory abdominal visceral fat, even when body mass index is controlled [Kullmann 2020]. (If you want more on visceral fat, listen to this podcast.
There are, admittedly, criticisms of the CIM. For example, the doubly labeled water method used in the Framingham State Food study was criticized on “theoretical possibility that … [differential] fluxes through biosynthetic pathways” could limit the accuracy of the methodology used in that trial [Hall 2019]. However, this challenge was met in a secondary analysis that confirmed that individuals eating a low-carb diet required 200 – 300 more Calories per day to maintain their weight [Ebbeling 2020]. Additionally, some researchers note that low-carbohydrate diets don’t appear to increase energy expenditure as compared to low-fat diets in short-term trials. However, this might not be an entirely fair assessment, given that biological adaptation to a low carbohydrate diets takes several weeks [Vazquez 1992].
Indeed, a 2021 meta-analysis of 29 controlled feeding studies found that studies shorter than 2.5 weeks duration showed a small disadvantage of low-carbohydrate diets for total energy expenditure, whereas those longer than 2.5 weeks showed a larger advantage for low-carbohydrate diets [Ludwig 2021]. Therefore, it is important that all trials designed to properly test the CIM be of sufficient duration, ideally at least 1 months for energy expenditure and at least 6 months for body composition.
The CIM is not a proven model by any means, nor is it the entire picture. The obesity epidemic is a complex issue that involves economic and sociocultural factors as well, including food inequality, large portion sizes, food processing, low physical activity levels, environmental endocrine disruptors, etc. However, the CIM does provide a novel foundation for innovating solutions to tackle the obesity crisis. It’s something different. And we need different because “eat less, move more” hasn’t worked.