Feature articles

Is fructose bad for the liver?

Bowl of fresh fruit Fructose has developed a bad name, with some products even boasting they are free-from fructose. While there are varied concerns around fructose, we’ve chosen to focus on claims around adverse affects on the liver.

Food chemistry basics
Fructose is a monosaccharide, or one of the most fundamental of sugars. Fructose has a low GI (19) and is around 70% sweeter than sucrose so less is needed. Table sugar, or sucrose, is made up of one molecule of fructose and one molecule of glucose. Some of the adverse publicity about sucrose is based on the fact that it yields fructose during digestion. 

How much fructose do we eat?
Most fructose comes from the digestion of sucrose but fructose exists naturally in fruit, fruit juices and fruit concentrates, honey, most root vegetables and some grains. Pure fructose is available as a table-top sweetener although it’s not commonly used. Fructose is perhaps most well known in high fructose corn syrup (HFCS) used in US food manufacturing, but in Australia and New Zealand, locally grown cane sugar is the preferred sweetener. Small amounts of HFCS are present in a limited number of foods, usually imported foods. Based on 1995 National Nutrition Survey data, it is estimated 95% of Australian adults (25-64 years of age) consumed less than 60 grams of total fructose a day from all sources (1). As total and added sugars intake declined between the 1995 and 2011 dietary surveys it may be assumed fructose consumption has declined also (2).

How is fructose implicated in liver disease?
Non alcoholic fatty liver disease (NAFLD) has been increasing globally and the leading cause of chronic liver failure (3). Research looking into associations between sugar sweetened beverage intake and development of NAFLD are limited and show mixed results. The argument goes that eating fructose causes de-novo lipogenesis which leads to fatty liver and insulin resistance.

How is fructose different to glucose?
Fructose is handled differently to glucose, with most fructose being metabolised in the liver while glucose can be metabolised in many different cells throughout the body. Unlike glucose, fructose does not stimulate insulin release or use insulin for transport into cells. Once in the liver, Fructose metabolism bypasses the rate limiting phosphofructokinase step of glycolysis and is instead shunted into Free Fatty Acid (FFA) production. Enhanced De-novo lipogenesis has been shown in both humans and animals during overfeeding however with usual daily intake, less than 1% of ingested fructose is directly converted to plasma triglycerides (4). It has been suggested there may be other lipogenic metabolic pathways involved (5).

What happens to fructose during metabolism?
Once in the liver, because fructose can only be used by liver cells, more than half of fructose is converted into glucose to make it more universally available.

Isotropic tracer studies in humans show:

• 45% fructose is oxidised within 3-6 hours (non-exercising subjects)
• 45.8% is oxidised within 2-3 hours (exercising subjects)
• 41% of fructose is converted to glucose in 3-6 hours
• 25% is converted to lactate
• Conversion of fructose to glycogen is unclear (previous studies suggest 15% (6))

While a small percentage of fructose can ultimately be converted into free fatty acids (FFA) which can then convert to triglycerides (de-novo lipogenesis) and can be carried in very low density lipoprotein (VLDL) particles (7), the de-novo pathway is considered to be a minor contributor to serum lipid homeostasis (8).

Studies estimate 1-5% of fructose ends up
in the de-novo lipogenesis pathway,
resulting in one gram of fat (9).


Does fructose cause fatty liver?
While some studies have shown large doses of fructose can increase fat deposition in the liver, the amounts of fructose have been far more than is normally consumed in the diet and other studies have not shown such effects (10). Fat accumulation is associated with hypercaloric feeding and there are no differences between fructose and glucose in isocaloric conditions (1).

High Fructose Corn Syrup
HFCS is the preferred sweetener in food manufacturing in the USA because it is cheap and functional. It is cheap because it is derived from corn and corn farming is subsidised by the US government. HFCS is strongly criticised because of its fructose content. In reality - and despite the name - HFCS has a similar proportion of fructose than cane sugar and honey.
 

What is HFCS?
HFCS doesn’t actually contain high fructose levels but was named as such to distinguish it from corn syrup that contains no fructose. Most HFCS ends up in soft drinks (soda) – all soda in the USA is sweetened with HFCS. It is produced from corn starch after treatment with enzymes that can produce varying fructose content; the most common types are 55% fructose (HFC55) and 42% (HFC42). Similarly, sucrose is 50% fructose, and honey has a similar proportion of glucose and fructose (depending on the source). During digestion, HFCS, honey and sucrose produce glucose and fructose in very similar amounts.



What does the evidence say about fructose?
There seems to be no difference between glucose and fructose in human studies examining liver triglycerides or liver enzymes, even when provided as 25% of energy intake; both contribute to liver changes during hypercaloric conditions and these liver changes are associated with weight gain (11). A systematic review and meta-analysis of fructose, HFCS and sucrose on NAFLD and indexes of liver health found the evidence does not support the conclusion that these sugars contribute to liver disease, and associations are confounded by excessive energy intake (12).

NEXT: Diet and the microbiome 

Sign up to our newsletter

Receive the latest newsletter with research on sugar. Plus insights from scientific experts.


View previous issues

MORE ABOUT SUGAR

resources.jpg

Resources

Latest resources, fact sheets and scientific studies.

appleIco.jpg

Sugar and health

View and download articles, reports and fact sheets containing current findings about the role of sugar in our diets.

askQuestionIco.jpg

Frequently asked questions

Explore the most common questions asked about sugar, and read up on some of the prevailing misconceptions.