Fructose's metabolic effects and links to modern disease
What it found
Fructose has unique metabolic effects that can promote fat storage, insulin resistance and other features of metabolic syndrome, especially when eaten in excess.
The evidence comes from lab studies, animals and some human trials.
What they found
Studies in people
Triglycerides and insulin
In people, fructose-sweetened drinks raised triglycerides and reduced insulin sensitivity compared with glucose drinks, especially in overweight individuals.
Animal and lab studies
Fat production
Fructose stimulates de novo lipogenesis (making new fat) more than glucose does. This occurs through signals like F1P and ChREBP.
Studies in people and animals
Fatty liver
Animal studies show that fructose can cause fatty liver, and blocking its metabolism protects against this. In humans, reducing fructose intake can decrease liver fat.
Blood pressure and uric acid
Fructose raises uric acid and stimulates vasopressin, which can increase blood pressure. Mice lacking the ability to metabolise fructose are protected from salt-induced hypertension.
Cancer and brain
Fructose metabolism has been linked to cancer growth in several tissues, and to brain effects like cognitive decline in animal models. Human evidence is still emerging.
Other findings
Fructose metabolism
Fructose is broken down by a different pathway than glucose, bypassing the main regulated step of glycolysis. This leads to rapid use of ATP, production of uric acid and fat synthesis.
What the authors conclude
“In the context of consistently abundant food, fructose intake is a hazard, promoting insulin resistance, hypertriglyceridemia, fatty liver, and elevated blood pressure.”
Also in their conclusions
- They conclude that fructose has multiple distinctive metabolic effects beyond standard carbohydrate metabolism.
- They say that in the context of consistently abundant food, fructose intake is a hazard, promoting insulin resistance, hypertriglyceridemia, fatty liver, and elevated blood pressure.
- They suggest that targeting fructose metabolism could be a future approach for improving metabolic health.
How it was done
The authors wanted to explain how fructose, a sugar in table sugar and high-fructose corn syrup, might contribute to obesity and metabolic disease, beyond just its calories.
They reviewed biochemical, molecular and physiological studies on how fructose is metabolised differently from glucose, including studies in cells, animals and people.
What it can’t tell you
- Many of the findings come from animal or lab studies, so they cannot prove what happens in people.
- Human trials often use high doses of fructose in drinks, which may not reflect typical consumption from whole foods.
- It is still unclear how much endogenously produced fructose contributes to disease in people.
Who paid
- Funding
- Funded by NCI NIH HHS; NIDDK NIH HHS; NIAAA NIH HHS (from the PubMed record).
- Conflicts
- Competing interests: R.J.J., M.A.L., D.R.T. and J.D.R. have equity with Colorado Research Partners, which is developing KHK inhibitors. R.J.J. also consults for Amgen, Dynamicure, Soba Pharmaceuticals and Kibow and is on the Scientific Board of Blue Oak Nutraceuticals, Santa Barbara Nutrients and RxSugar. M.D.G. holds equity in Faeth Therapeutics and Skye Biosciences; reports consulting or advisory roles with Almac Discovery, Genentech, Faeth Therapeutics, Scorpion Therapeutics and Skye Biosciences; patents, royalties and other intellectual property with Weill Cornell Medicine and Faeth Therapeutics. J.D.R. is a member of the Rutgers Cancer Institute (RCI) and the University of Pennsylvania Diabetes Research Center (U Penn DRC); director of the U Penn DRC-Princeton inter-institutional metabolomics core and RCI metabolomics core; advisor and stockholder in Bantam Pharmaceuticals, Rafael Pharmaceuticals and Empress Therapeutics; a founder, director and stockholder of Farber Partners and Raze Therapeutics; a founder, advisor and stockholder in Marea Therapeutics and Fargo Biotechnologies; and inventor of patents held by Princeton University. S.S., K.L.S., L.G.S-L. and M.A.H. declare no competing interests.
- Authors work at
- University of Colorado Anschutz Medical Center, USA; Boston University, USA; NYU Grossman School of Medicine, USA
The paper
- Title
- Fructose: metabolic signal and modern hazard
- Type
- ReviewThe authors read earlier studies and describe what they found. It isn’t a new study.
- Evidence
- Studies in people · animals · lab
- Summarised from
- Full text
- Cite
- Johnson RJ, Lanaspa MA, Tolan DR, et al (2026). Fructose: metabolic signal and modern hazard. Nature metabolism. doi:10.1038/s42255-026-01506-yFree full textPubMed 41998215DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error