Fructose metabolism and its link to metabolic disease
What it found
In people, animals and lab studies, eating too much fructose is linked to weight gain, liver fat, insulin resistance and higher blood triglycerides.
The authors say fructose metabolism through the enzyme KHK is needed for these effects.
What they found
Studies in people
Fructose and liver fat
In people with obesity, 75 g of fructose per day for 12 weeks increased body weight, liver fat and new fat production in the liver. A 6-month study found that one liter of sugar-sweetened beverage daily increased visceral, liver and ectopic fat.
Fructose vs glucose
In adults who were overweight or obese, drinks sweetened with fructose at 25% of energy needs for 10 weeks increased visceral fat, new fat production and signs of insulin resistance, while glucose drinks did not. Both increased body weight similarly.
Animal and lab studies
Intestinal fructose metabolism
In mice, about 90% of absorbed fructose was broken down in the small intestine, with little reaching the liver. The intestine may shield the liver from fructose.
Studies in people and animals
Fructose and uric acid
Fructose metabolism in the liver uses ATP and produces uric acid. This may explain links between sugary drink consumption and gout.
KHK enzyme and disease
Mice without the KHK enzyme were protected from fructose-induced weight gain, fat mass, high insulin and fatty liver. People with a condition called benign essential fructosuria lack KHK and have no reported health problems.
Other findings
Fructose in drinks and food
Sugar is added as sucrose or high-fructose corn syrup, both of which contain nearly equal amounts of glucose and fructose. HFCS 55, the most common form in drinks, is 55% fructose and 45% glucose.
What the authors conclude
“Thus, fructose metabolism via KHK is essential for fructose-induced metabolic disease.”
Also in their conclusions
- They conclude that fructose metabolism via KHK is essential for fructose-induced metabolic disease.
- They suggest that inhibiting KHK may be a new therapeutic strategy for treating cardiometabolic disease.
- They note that a KHK inhibitor reduced liver fat by 18.7% in adults with NAFLD after 6 weeks.
How it was done
The authors wanted to understand how excessive sugar consumption, especially fructose, might contribute to obesity and cardiometabolic disease. They also looked at new treatment options based on this knowledge.
They reviewed the biochemistry, genetics and physiology of fructose metabolism. They examined studies in people, animals and cells, including trials where people consumed fructose-sweetened drinks for weeks to months.
What it can’t tell you
- Most studies in people are short-term and cannot show whether fructose causes long-term heart disease or diabetes.
- Animal studies cannot prove what happens in people.
- The review cannot say whether natural fructose in fruit has the same effects as added fructose.
Who paid
- Funding
- Funded by American Heart Association-American Stroke Association; NIDDK NIH HHS (from the PubMed record).
- Conflicts
- Declaration of interests M.A.H. received research support from Eli Lilly and Co. M.J.B. is an employee and shareholder of Pfizer, which holds patent US20170183328A1.
- Authors work at
- Duke University, USA
The paper
- Title
- Molecular aspects of fructose metabolism and metabolic disease
- 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
- Herman MA, Birnbaum MJ (2021). Molecular aspects of fructose metabolism and metabolic disease. Cell metabolism. doi:10.1016/j.cmet.2021.09.010Free full textPubMed 34619074DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error