Invisible to the eye, sugar is a disaccharide consisting of two molecules in equal amounts, namely glucose, and fructose.  They get separated early in the digestive process and both get absorbed into the bloodstream but are processed quite differently.  While glucose is the currency of energy in the body, fructose is the currency of energy storage. 

When consuming moderate amounts of sugar, concentrations of glucose and fructose circulating in the blood are low.  Most glucose gets delivered to cells in the body to provide fuel for the generation of energy in the cells, while about 20% ends up in the liver and gets converted into glycogen.  Glucose levels are constantly controlled in the body, mainly through the hormone, insulin.  Virtually all the fructose in the bloodstream is readily extracted by the liver, where it is metabolized, and most fructose is cleared in a single pass through the liver. 

What is fructose?

Fructose is one of nature’s natural sweeteners and a simple sugar, called a monosaccharide, which is made up of a single molecule, which the body cannot digest into smaller molecules.  Fructose occurs naturally in fruit and honey, as well in small amounts in certain vegetables, such as asparagus, onions, and peppers.  It is the sweetest of all natural carbohydrates, which is probably why we like it so much.

Before the mass production of refined sugar, humans consumed fructose in relatively small amounts.  While excess fructose can be harmful, there is not enough fructose in fruit to be of concern as it is absorbed slowly due to the presence of fiber.  In addition to fiber, fruit contains healthy minerals, vitamins, and antioxidants. 

In contrast, sugar-based sweeteners such as cane sugar and sugar from high-fructose corn syrup (popular in the USA) are widely used in processed foods, often hidden and unhealthy, due to the large amounts of glucose and fructose they contain.  Interestingly, while honey is popularly regarded as a healthy alternative to sugar, it is higher in fructose (38%) than in glucose (31%), while the remaining sugars include sucrose, maltose, and a few others.

Effects of excess amounts of sugar:

Once glucose and fructose are separated during digestion in the small intestine, these two monosaccharides are metabolised quite differently, with fructose regarded in some circles as the evil twin of glucose. 

When glucose is absorbed in the small intestine, it gets absorbed into the bloodstream and delivered to cells throughout the body, raising “blood sugar” during this process.  Glucose in the bloodstream triggers the pancreas to release the hormone insulin, which facilitates the take-up of glucose in the cells to produce energy.  Elevated glucose levels after a meal prompts the pancreas to secrete insulin, which makes its way through the bloodstream and then activates a specific receptor in body cells to allow blood sugar to be absorbed into the cell as fuel for energy production.  

When consuming too much sugar too often, cells lose their sensitivity to insulin, a condition called “insulin resistance”.  As a result, cells are less able to absorb glucose, leading to much more glucose in the bloodstream being stored as fat in fat cells.  Regular elevated blood sugar levels can result in diabetes and obesity.

Fructose, on the other hand, is primarily taken up and metabolised by the liver. Unlike glucose, fructose does not prompt the pancreas to release insulin and does not have an immediate effect on blood sugar levels.  Small amounts of fructose, such as from eating fruit, are easily processed by the body, but excessive amounts can cause several problems.

An enzyme called fructokinase enables the metabolism of fructose in liver cells, using a substance called adenosine triphosphate (ATP), an energy carrying molecule made in the mitochondria inside the cells in the body.  The chemical interaction between high levels of fructose and ATP is not regulated, rapidly depleting 40-50% of the ATP available in cells in the liver. During this interaction, ATP gets converted into the molecule AMP (adenosine monophosphate) as part of a complicated chain of chemical events and ultimately generates uric acid as an end-product.  While ATP ends up as uric acid, the fructose in the liver is converted into fat.

Liver cells, if flooded by excess amounts of fructose, converts most of this excess to fat, called triglycerides, which are reflected as rising triglyceride levels in the bloodstream.  This fat is lodged in liver cells and via the bloodstream in fat cells in the body.  Regular overloading with fructose intake may result in a fatty liver. Fat build-up in the liver can lead to insulin resistance in the liver and non-alcoholic fatty liver disease. 

Effects of high levels of fructose in the diet:

Research has linked excessive fructose consumption with various adverse health conditions such as insulin resistance, diabetes, obesity, metabolic syndrome, and an increased risk for cardiovascular disease and cognitive decline, with the high levels of uric acid acting as instigator and primary contributor to human disease.   

Insulin resistance in the liver:  Although fructose does not affect insulin directly, the metabolism of excess amounts of fructose can promote insulin resistance through the build-up of fat in the liver.  Animal studies have indicated that fructose may also directly cause hepatic (liver related) insulin resistance by interfering with insulin signalling.  The development of insulin resistance in the liver is a feature of non-alcoholic fatty live disease and can lead to Type 2 diabetes. 

A human study by the University of Zurich found that even moderate amounts of fructose lead to higher production of fat in the liver.

Inflammation and microbiome changes:  Studies have found that fructose is associated in multiple ways to inflammation, starting in the gut.  Animal studies indicate that fructose metabolism may reduce the proteins that maintain the integrity of the gut barrier, which consists of a mucus-covered layer of cells that prevents toxins from leaking out of the intestines into the bloodstream.  A weakened gut barrier becomes permeable, which allows the leaking of endotoxins, causing inflammation in the body, and in the liver.  This may affect the ability of the immune system to fight certain infections, as well as damaging cells and tissues.  Excess fructose consumption can also reduce the levels of healthy bacteria in the gut.

Cancer:  Studies have linked high intake of fructose with the development of cancer, indicating that fructose transporter receptors are expressed on cancer cells, such as breast and colorectal cancers, which means fructose is used as fuel for cancer cells.  Lactate is an end-product of fructose metabolism and is likely needed at various steps during cancer growth.  Lactate levels were found to be up to 40-fold higher in certain tumors.  Lactate also promotes the growth of new blood vessels (angiogenesis) to supply oxygen-rich blood to tumors by inducing vascular endothelial growth factor in the endothelial cells in the lining of vascular vessels.  In addition, fructose intake is associated with more aggressive cancer behavior and may also promote the spreading of cancer.

Appetite:  Two hormones control our appetite, namely ghrelin (triggers feelings of hunger) and leptin (triggers a sense of fullness).  

  • When the stomach is empty, ghrelin is secreted by the stomach and sends a message to the brain that you need to eat. 
  • When the stomach is full, fat cells release leptin, which sends a message to the brain to stop eating.

When these two hormones are in balance you don’t undereat or overeat.  Fructose, however, upsets this balance by reducing leptin and blunting the suppression of ghrelin, which prevents you from reaching a feeling of fullness when eating a meal.  This results in greater appetite and more eating. 

Animal studies found that high levels of fructose induce resistance to leptin.  As the body gets overloaded and overwhelmed by fructose, causing continual surges in leptin, the receptors for leptin start to turn off, leading to leptin-resistance.

Leptin resistance is associated with weight gain and obesity, in combination with eating food high in calories and fat.  As excessive fructose intake also leads to higher levels of triglycerides, scientists suspect that elevated levels of triglycerides may prevent leptin from reaching the brain, and as such prohibit signals that the body has reached satiety levels.

Uric acid buildup:  As a byproduct of the metabolism of fructose, increased consumption of fructose generates increased levels of uric acid in the bloodstream, with damaging effects in the body.   In addition, increases in uric acid due to increased fructose metabolism may stimulate the liver to generate more fructose, as uric acid stimulates an enzyme (aldose reductase), which is involved in the conversion of glucose to fructose (polyol pathway), worsening the accumulation of fat.

High levels of uric acid, a condition called hyperuricemia, has long been established as the major cause of gout, and evidence from many recent studies has indicated that asymptomatic hyperuricemia plays a role in the development of diseases such as metabolic syndrome, hypertension, stroke, atherosclerosis, and others.

For more information on the devastating effects of uric acid in the body, please see the Health Insight blog “URIC ACID”. 


Excessive intake of fructose may directly or indirectly promote the development of metabolic disorders.  Research over the past decade suggests that the imbalance between high fructose intake and low physical energy consumption, due to a lack of exercise, may also be a possible reason for the adverse health effects of fructose.

Hidden added sugars in most supermarket food products are the main sources of excessive fructose in the diet, while fruit itself is a minor source, with the added benefits of containing fiber, minerals, and vitamins.  As fruit juice contains high levels of fructose, the golden rule is: “Eat the fruit and skip the juice!”


Is fructose bad for you?  The surprising truth.  Published 23 April 2018.  Healthline.  (

Is fruit good or bad for your health?  Published 31 May 2018.  Healthline.  (

High-fructose corn syrup: just like sugar, or worse?  Published 20 August 2020.  Healthline.  (

Why fructose is bad for metabolic health.  Published 28 April 2021.  Expert review by Dr David Perlmutter.  Levels.  (

Fructose, uric acid, and diabetes.  Published 19 January 2022.  Blog by Dr David Perlmutter.  (

Fructose intake: metabolism and role in disease.  Published 3 February 2021.  Book by Luke He et. al.  IntechOpen Book Series.  (

Fructose: absorption and metabolism.  Article by Keim N.L. et. al. in Encyclopedia of Human Nutrition.  (Third Edition), 2013.

Drop Acid.  Book by Dr. David Perlmutter.  Published 2022 by Little, Brown, Spark. USA.  P.324.


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