• The number of people with obesity has increased rapidly over the past 50 years.
• Probable causes are an energy imbalance, where energy intake exceeds energy used, or diets high in fat, or carbohydrates.
• However, a new study suggests a different hypothesis — that fructose, a simple sugar found in many foods, may be the driver of obesity.
• The authors propose that fructose resets cell metabolism, increasing hunger and driving the desire for energy-rich foods, such as fats and carbohydrates, which results in weight gain.

Obesity is a growing problem worldwide. According to the World Health Organization (WHO), obesity rates have tripled since 1975, with 13% of all adults now classified as having obesity.

In the United States, between 1980 and 2008, obesity rates rose from 13.4% to 34.3% of adults, and by 2020, the Centers for Disease Control and Prevention (CDC) reported that 41.9% of adults in the U.S. had obesity.

Having obesity increases the risk of many health conditions and adverse events, such as sleep apnea, heart disease, type 2 diabetes, and stroke.

It may also increase the likelihood of developing certain cancers, and is linked to issues with the digestive system, skin, fertility, and mental health.

What are the drivers of obesity?

But what is causing this huge increase in obesity cases globally? Theories include:

• the energy balance hypothesis — energy intake exceeds energy expenditure
• the carbohydrate-insulin model — diets high in carbohydrates are particularly fattening as they elevate insulin secretion
• the protein-leverage hypothesis — low protein intake can lead to higher overall energy consumption
• the seed oil hypothesis — the increase in obesity over the past 50 years is highly correlated with an increase in seed oil usage and intake, including soy, corn, sunflower and canola (rapeseed) oils.

Now, a paper from the University of Colorado Anschutz School of Medicine proposes that a single substance — fructose — may drive all of these models of weight gain.

The authors have built on their previous work about the effect of fructose on cells, formulating the “fructose survival hypothesis” to explain the rapid increase in obesity rates.

The paper is published in Obesity.

Kelsey Costa, a registered dietitian and nutrition consultant for the National Coalition on Healthcare, not involved in this research, commented on this emerging hypothesis for Medical News Today:

“The study introduces a compelling integration of existing obesity theories, suggesting that obesity is not merely a result of consuming excessive energy but, instead, a condition of low energy, marked by insufficient ATP [adenosine triphosphate], due to the types and amounts of food consumed.”

The fructose survival hypothesis

When a person eats food, most of the energy ingested is converted to adenosine triphosphate (ATP), the molecule that supplies energy to cells. If too much food is eaten, that excess energy is stored as fat.

If the food contains fructose, the fructose initially undergoes the same conversion to ATP to fuel all the body’s functions.

However, as more fructose is ingested, it suppresses the activity of mitochondria — the organelles that produce ATP — in the cells, reducing levels of ATP.

When ATP levels drop, this sends an alarm signal that the cell might run out of energy, which stimulates a number of biological responses, among them hunger, thirst, increased energy intake, insulin resistance, increased food absorption and reduced resting metabolism.

Where food is abundant, and much of it contains fructose, these changes are likely to lead to weight gain.

What foods contain fructose?

Fructose is the naturally occurring sugar in fruit and vegetables. However, Costa advised that this should not discourage people from eating whole fruits.

“While most whole fruits naturally contain fructose, their consumption is not associated with obesity or weight gain in humans, as the presence of dietary fibers, bioactive compounds, and essential nutrients counteracts the effects of fructose on satiety and insulin sensitivity,” she told us.

“As such, whole fruits can still be enjoyed as part of a healthy, balanced diet for weight management,” Costa added.

The problem arises when fruits are processed, or fructose is added to foods, often in the form of high fructose corn syrup (HFCS).

HFCS is a sweetener produced cheaply from corn starch. It is found in most processed foods, so the more processed, and particularly ultra-processed food there is in your diet, the higher your intake of fructose is likely to be.

And it is not only sweet foods, such as sodas, sweetened juices and packaged desserts and cakes, that contain it. Foods that we regard as savoury, including bread, canned soups, prepackaged meals, cereals and many fast foods are all likely to contain HFCS.

“The proposed ‘fructose survival switch’ potentially underlies the influence of ultra-processed foods on energy intake and weight gain. High salt content often found in these foods could further stimulate fructose production, exacerbating the energy imbalance and contributing to obesity.”

– Kelsey Costa

Fructose is also present in table sugar, or sucrose — which is made up of glucose and fructose — and it is made in the body from glucose and other carbohydrates, as Costa explained.

“The body can also convert glucose to fructose through the polyol pathway, activated by various triggers such as diabetes, high glycemic or high carbohydrate diets, high salt intake, low water intake, purine-rich foods, or stress conditions, leading to obesity and other metabolic effects. Alcohol intensifies this process, stimulating more fructose production,” she told MNT.

Unifying the theories on obesity drivers

So how does the fructose theory bring together all these different ideas about the causes of obesity?

Lead author Prof. Richard Johnson, professor of medicine – renal diseases and hypertension in the School of Medicine at the University of Colorado Anschutz Medical Campus, explained in a press release that “[f]ructose is what triggers our metabolism to go into low power mode and lose our control of appetite, but fatty foods become the major source of calories that drive weight gain.”

“This theory views obesity as a low-energy state,” he added. “Identifying fructose as the conduit that redirects active energy replacement to fat storage shows that fructose is what drives energy imbalance, which unites theories.”

Moderate fructose intake to help manage weight

Costa advised that moderating overall fructose consumption may be an essential strategy for weight management and obesity prevention.

She recommended:

• increasing your intake of lower glycemic, fiber-rich foods like non-starchy vegetables, whole fruits, and legumes
• drinking enough water to keep your body hydrated and facilitate proper metabolic function
• limiting intake of high-fructose foods and drinks, such as sugary beverages, sweets, and ultra-processed foods
• reducing consumption of sodium, refined and high-glycemic carbohydrates, purine-rich foods like red processed meats, and alcohol to limit fructose production in the body.

“Whether the fructose survival hypothesis holds true or not, these dietary recommendations can help individuals maintain a healthy weight and reduce the risk of obesity and chronic diseases,” she advised.

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