Increased fructose intake from processed foods triggers a genetic trait to store fat. This used to help us survive but now it leads to weight gain.
By Sneha Bhadti
Human beings evolved over millions of years during periods of scarcity. We developed genes that kept us alive during famines. While these genes were highly beneficial when food was limited, in the modern world this is proving to be disadvantageous to our health.
As the prevalence of obesity increases, researchers consider how lifestyle factors contribute to this global trend of weight gain. One such factor is fructose. Fructose is a sugar molecule that is found in many foods, including fruits, honey, and table sugar. Glucose, the more commonly known sugar, can be converted to fructose as well.
Researchers based at the University of Colorado Anschutz Medical Campus have suggested that two events are contributing to higher levels of obesity: First, over time we’ve gained genes that keep us alive during famine (thrifty genes). Second, the larger quantity of food in modern diets either contain fructose or increase the production of fructose in our bodies. Dr. Richard Johnson and fellow researchers published a review article in July 2023 to explain how the combination of these genes with excess fructose contributes to obesity and weight-related health concerns.
The survival switch worsens our health
Johnson and colleagues explained that the tendency of humans towards weight gain could be due to a combination of nurture and nature—while diet is a major cause of weight gain, we also have genes that lead to the storage of the fuel we eat.
The researchers described a genetic mutation that is highly useful in keeping us alive in times of food scarcity called the survival switch. The survival switch is activated by fructose and leads to a greater amount of fat storage while simultaneously inhibiting fat burning. It also makes us hungrier, elevates blood pressure, raises blood sugar levels, and increases inflammation in the body. This fat storage was useful for humans to store energy, have enough energy to hunt or forage for food, improve circulation, and even prevent infection by activating the immune system.
Food is now more readily available without hunting or gathering. The types of foods we eat, such as processed fast food that is high in added sugar and salt, generate more fructose and contribute to the activation of the survival switch. In modern times, this may be worsening our health.
More glucose leads to more fructose
Another source of elevated fructose production is glucose. Glucose can be converted to fructose in our bodies. In the review, Johnson’s team described the polyol pathway, which is activated by a high concentration of glucose.
In the polyol pathway, glucose is transformed into sorbitol, catalyzed by an enzyme called aldose reductase. Sorbitol dehydrogenase then acts on sorbitol to produce fructose. The more glucose we eat, the more fructose is made using this pathway. Eating an abundance of simple carbohydrates and sugars provides glucose, which then leads to the body generating more fructose and activating the survival switch.
However, high glucose levels are not the only culprit of more fructose production. Salt is also a major player. A high salt diet influences aldose reductase to produce more sorbitol, which eventually leads to more fructose. Interestingly, aldose reductase is also activated by umami foods, alcohol, and bodily stresses such as dehydration, which is also increased by salty foods.
The long term impacts of increased fructose intake
In the review, the researchers compiled data linking the survival switch to multiple metabolic disorders that are associated with weight gain, such as diabetes and high blood pressure. Further down the line, the survival switch has been linked to coronary heart disease, some cancers, faster aging, and psychological disorders such as Alzheimer’s disease.
What can we do now?
While the long-term consequences of our own genes and dietary habits can be daunting, this research can benefit us today by reminding us to be more conscious of our food choices. Instead of opting for overly processed fast food, we can choose fruits, vegetables, and complex carbohydrates. Reducing the quantity of simple carbohydrates, sugars, and salt in our diets is likely to have a profound impact on our future health and will help us avoid metabolic diseases.
This study was published in Philosophical Transactions of the Royal Society B, Biological Sciences.
The information contained in this article is for educational and informational purposes only and is not intended as health or medical advice. Always consult a physician or other qualified health provider regarding any questions you may have about a medical condition or health objectives.
Johnson, R. J., Lanaspa, M. A., Sanchez-Lozada, L. G, Tolan, D., Nakagawa, T., Ishimoto, T., Andres-Hernando, A., Rodriguez-Iturbe, B., Stenvinkel, P. (2023). The fructose survival hypothesis for obesity. Philosophical Transactions of the Royal Society B, Biological Sciences, 378(1885), 20220230. http://doi.org/10.1098/rstb.2022.0230
About the Author
Sneha Bhadti has earned a bachelor’s degree in Biomedical Sciences and a master’s degree in Health Economics. She currently works as a systematic reviewer and loves reading about the latest medical research. Sneha enjoys communicating science, especially translating complex science for the general public and decision makers.