Fructose: Too much in diet associated with INSULIN resistance /T2D/obesity, fatty liver and CVD

About fructose

Fructose is one of only 3 monosaccharides (single sugar molecules; the others being glucose and galactose).  Fructose makes up half of the sucrose (table sugar) molecule. In this diagram, that's a glucose molecule on the left, covalently linked (in the case of sugar molecules, called a disaccharide bond) to a fructose molecule (on the right):

Fructose is naturally present in honey, sugar cane, fruits, flowers, berries and most root vegetables (especially sugar beets).  Fructose is present both as a single molecule and as 50% of sucrose (table sugar), bonded to a glucose molecule.  A cup of strawberries contains ~4g of fructose, a teaspoon of honey ~3.5g .

Fructose ranks high on the sweetness scale.  Rated from 1.2 to 1.8 times sweeter than sucrose.

Fructose ranks low on the glycemic index at 19 (doesn't much raise blood glucose), but it does raise blood fructose levels - which is worse.   Fructose binds to cellular proteins 7 times faster than glucose. This creates 100 times more reactive oxygen species (ROS) than glucose, which can cause significant cellular damage. E.g. to arterial or pancreatic cells

Fructose digestion / metabolism

The monsaccharides are directly absorbed into the bloodstream during digestion.   If fructose is consumed in sugar (i.e. attached to a glucose molecule), the enzyme sucrase cleaves them apart in the small intestines, ready for individual absorption. Once in the blood, fructose enters the hepatic portal vein en route to the liver to be metabolized.

The use of mixed sugars are more metabolically predictive of dietary consequences than that from single monosaccharides studied individually. Studies show the greatest absorption rate occurs when glucose and fructose are administered in equal quantities Wikipedia When fructose and glucose are ingested together (e.g. as in sucrose), the oxidation rates of the mixed sugars are faster than that of either one of them ingested alone at the same dosage.  A meta-analysis of various studies shown here:

• Non-exercise subjects: The oxidation rate from fructose to glucose had a mean average of 45% (mean conversion rate 41%)  within a period of 3-6 hours after ingestion.
• With exercise:  The mean average oxidation rate of fructose was about 45.8% within 2-3 hours. Ingesting fructose with glucose, the oxidation rate increased to ~66%

Oxidation rates (represents conversion) of fructose & glucose Sun, 2012

The data of obese or diabetic subjects were not included in this figure. 

Metabolic fate of dietary fructose carbons. 

The data obtained within study periods <= 6 hours after 50-150 gm fructose ingestion by non-diabetic or obese persons. Sun, 2012

Some people are unable to fully metabolize / absorb fructose, which causes digestive gas / discomfort.    In these cases fructose is considered a FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) - - -short-chain carbs, which resist digestion. 

As always, study results depend on the details

Fructose administered on its own (as often the case in studies) is poorly absorbed.  It will therefore have little effect, other than causing GI pain, bloating or diarrhea. Dietary fructose is usually present with other sugars and fiber.

Some studies attempt to skew the data,  for example, showing that consumed fructose generates liver fat at a slow rate of <5%.  This is likely the case for someone who is thin, not INSULIN-resistant, has not consumed anything in the last few hours (i.e. has depleted glycogen /glucose storage in liver), and then consumes only fructose. However, it would be a very different outcome for someone well-fed, INSULIN-resistant, overweight and consuming a more natural combination of fructose together with glucose, which reveals fructose converting to fat at a rate closer to 30%.

The dose matters.  E.g. Studies supplying fructose as a high percentage of dietary calories do show increased blood TGs and LDL cholesterol, INSULIN resistance and weight gain

How much fructose are we consuming?

Foods containing the highest amount of fructose per serving include: foods containing sucrose, HFCS, agave nectar, honey, molasses, maple syrup, fruit and their juices. 

 1977-1978: Estimated that mean fructose consumption in U.S. was 37 g/day (8% of total caloric intake) and 54 g/day among those age 15-18 years  (Park &Yetley, 1993)

Some "food for thought"

• Sugar-sweetened beverages (SSBs) were the source of 30% of fructose for all age groups and almost 50% of fructose for adolescents. Grains (including breads, cereal, cakes, pies, and snacks) were the second-largest source (11-12%). 
• 74% of fructose came from foods and beverages other than whole fruits and vegetables. 
• Fruits / 100% fruit juice was the largest source of fructose for over 51 year olds

Chart: How much fructose in fruit

• If all fructose sources except whole fruit and vegetables were removed:  children would eliminate 82% dietary fructose, and adults 75%.
• Underreporting of total calorie intake is known to increase as BMI increases.  Neuhouser, 2008
• Adults ate ~ 50% higher percentage of whole fruit  and 33% less percentage of sweetened beverages than teens

Pie chart of fructose-source consumed by adults (2008)

Dietary Fructose Consumption Among US Children and Adults: National Health and Nutrition Examination Survey III (n=21,483)

RTE=Ready to eat        Beverages= sugar-sweetened beverages

So - is consuming fructose harmful or not?

Excessive fructose intake elevates plasma triglycerides (TGs) and LDL cholesterol, and lowers HDL cholesterol

"Our study shows for the first time the surprising speed with which humans make body fat from fructose. Once you start the process of fat synthesis from fructose, it's hard to slow it down. The bottom line of this study is that fructose very quickly gets made into fat in the body."

- Dr. Elizabeth Parks, associate professor of clinical nutrition,UT Southwestern Medical Center

Author of a fructose study reported in the Journal of Nutrition (2008).