Review · Critical reviews in clinical laboratory sciences · 2020

Fructose and insulin resistance in the liver

Softic S, Stanhope KL, Boucher J, et al · Free full text

In people, fructose intake is linked to insulin resistance in the liver, often before it shows up in the whole body.

Animal and lab studies suggest several ways fructose may cause this, including direct effects on insulin signalling.

What they found

Studies in people

Short-term human studies

Several small trials found that fructose supplements for 6 to 14 days reduced insulin sensitivity or increased liver glucose production in healthy people. One study found no change in a simple insulin resistance score after 14 days of extra fructose in overweight men, but the score rose after two weeks of fructose without extra calories.

Longer human studies

Drinks sweetened with fructose for 3 to 12 weeks increased fasting insulin, blood glucose or liver glucose production in overweight and obese people. A 10-week study giving 25% of daily calories as fructose found a 17% drop in an insulin sensitivity measure.

Large population studies

In 70,000 women followed for 18 years, those having 2 to 3 sugar-sweetened drinks a day had a 31% higher risk of type 2 diabetes than those having less than one a month. A meta-analysis of 17 studies found each extra daily serving of sugary drinks was linked to an 18% higher risk of type 2 diabetes, or 13% after adjusting for body fat.

Animal and lab studies

Mitochondria and energy

Fructose reduced fat burning and lowered energy levels in liver cells in animal and lab studies. It also changed the number and shape of mitochondria in mice.

Direct effects on insulin signalling

In rats and hamsters, fructose lowered insulin receptor and IRS2 levels and increased PTP1b activity, all of which can blunt insulin signals. Knocking down the enzyme that breaks down fructose improved insulin sensitivity in mice.

Studies in people and animals

Liver fat and insulin

Fructose increased fat-making in the liver more than glucose in human and animal studies. In mice, fructose also changed the types of fats made, which are linked to insulin resistance.

What the authors conclude

“The current evidence shows that the fructose, but not glucose, component of dietary sugar drives metabolic complications and contradicts the notion that fructose is merely a source of palatable calories that leads to increased weight gain and insulin resistance.”

Softic S, Stanhope KL, Boucher J, et al, 2020

Also in their conclusions

They conclude that dietary fructose strongly promotes liver insulin resistance through a complex mix of pathways, some of which are independent of weight gain and total calories.
They say the current evidence contradicts the idea that fructose is merely a source of palatable calories that leads to weight gain.
They suggest that if direct effects are confirmed, reducing excess fructose intake should take priority over cutting total calories to improve liver insulin sensitivity.

How it was done

The authors wanted to work out whether fructose itself drives liver insulin resistance, or whether it is simply a source of extra calories that leads to weight gain.

They reviewed human studies, animal experiments and lab studies on fructose intake and liver insulin resistance. The human studies ranged from a few days to 18 years, and included healthy adults, overweight or obese people, and some with a family history of type 2 diabetes.

What it can’t tell you

Many of the human studies were short and small, so they cannot show what happens over years.
The population studies can show a link between fructose and insulin resistance, but not that fructose causes it.
Most of the evidence for direct effects on insulin signalling comes from animals and cells, so it may not apply to people.

Who paid

Funding: Funded by NIDDK NIH HHS; NIGMS NIH HHS (from the PubMed record).
Authors work at: University of Kentucky College of Medicine and Kentucky Children's Hospital, USA; Joslin Diabetes Center, USA; University of California, USA

The paper

Title: Fructose and hepatic insulin resistance
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: Softic S, Stanhope KL, Boucher J, et al (2020). Fructose and hepatic insulin resistance. Critical reviews in clinical laboratory sciences. doi:10.1080/10408363.2019.1711360Free full text PubMed 31935149 DOI

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