From being an integral part of a well-balanced diet, fructose has become one of the leading factors in the development of many metabolic disorders that are on a continuous rise. How did the changes in our dietary patterns and the development of the food industry lead to that? Can we change the course? It all comes down to our choices, and by the end of this article, you will get the tools to make the best ones!

What is fructose?

Fructose is a type of sugar that has always been present in our diets. It is the sweetest naturally occurring carbohydrate, 1.5x sweeter than sucrose (white table sugar). The best-known natural sources are fruits like apples, grapes, pears, blueberries, bananas or nectars and nectar products like honey and agave syrup. In smaller amounts, it is also present in vegetables like onions, peppers, carrots, sweet potatoes, etc.

History of fructose consumption

You can imagine that our hunter-gatherer ancestors’ intake was low and strictly limited to these natural resources. Fast forward to our days, and that intake has climbed up to nearly 50 g/ day, representing 10% of our total energy intake, mostly due to fructose being present in a wide range of processed foods like soft drinks, juices, baked goods, yoghurts, ready-to-eat soups, etc. Let’s find out how it came to that and how that increase, together with an ever-growing sedentary lifestyle, influences our health.

For a long time, sucrose (white table sugar, composed of a glucose molecule linked to a fructose molecule) was marked as the only one whose excessive consumption caused metabolic confusion in the body. At the same time, glucose and fructose, as naturally present in food, were viewed as “better”.

Then, in the search for an effective treatment for diabetes, fructose showed to be a promising candidate. Because of a different metabolic pathway to glucose, it wasn’t suddenly raising the blood sugar levels, which meant a beneficial lower glycemic index (GI).

Based on those limited findings, it was immediately given the green light as a “useful therapeutic agent” in diabetic patients, which was, as we see it today, a great mistake.

Beginning in the 1960s, the food industry started replacing sucrose (the white table sugar) with syrups like glucose-fructose or high fructose corn syrup (HFCS), mixes of free fructose and free glucose molecules in different ratios. You guessed it, these solutions were cheaper than sucrose but unfortunately were metabolised even faster than the white table sugar.

A few decades later, with a global increase in obesity, diabetes and a range of metabolic disorders, the perspective of fructose as a “useful therapeutic agent” has shifted to being considered one of the risk factors for those conditions.

What are sugars?

When we talk about sugar, we can actually mean a lot of things. Are we talking about the ingredient white table sugar or molecules like glucose or sucrose?

All carbohydrates are made from monosaccharides, forming chains of different lengths and combinations.
Chains with one (monosaccharides) or two molecules (disaccharides) form a subgroup called “simple carbohydrates”. In contrast, chains longer than 2 molecules all fall into the second subgroup called “complex carbohydrates”.

The most common monosaccharides are:

• glucose (body’s direct source of energy)
• fructose (also known as fruit sugar)
• galactose (primarily found in dairy products)

These are some of the combinations of two monosaccharides that form disaccharides:

• sucrose (glucose + fructose) – white table sugar
• maltose (glucose + glucose)
• lactose (glucose + galactose)

These “simple carbohydrates” are the ones typically referred to as sugars. Those sugars can be naturally present in food, such as fruit, vegetables and nectar products or added in the production process. But even though we all call them sugars, the way they affect our bodies is quite different.

Metabolism of fructose is different than glucose’s

Glucose is a direct energy source for our cells and the brain’s primary one. Once it enters the bloodstream, its destiny depends on the hormonal response it triggers, where insulin is the best-known hormone in action. A big part of it goes into the muscles, adipose tissue (body fat) and other tissues in the body, where it is immediately used as a source of energy.

Fructose takes a slightly slower path than glucose, and it greatly depends on the amount that we consume. A smaller amount will be metabolised in the gut cells, entering the bloodstream as glucose or lactate, which will be used as energy sources by our cells. But in larger amounts, a bigger part will end up in the liver, where it will be processed into glucose, lactate and fatty acids.

Physical activity

In people with a sedentary lifestyle, a fructose-rich diet lasting several days stimulated the formation of fatty acids in the liver and increased blood triglyceride concentrations.
Studies indicate that these negative effects could be diminished with increased physical activity. That essentially happens because of the body’s higher need for energy, but we’ll talk about that in the next lines.

Concentration

Studies on rodents indicate that when the fructose intake is low, most of it gets metabolised in the gut, and as we said, lactate and glucose enter the bloodstream. But when the amount entering the gut is high, the previously mentioned metabolic pathway becomes saturated, and the remaining fructose gets transported to the liver.

Suppose we are active and our body needs energy. In that case, it will still be predominantly metabolised into lactate and glucose. But if our energy requirements are lower due to our sedentary lifestyle, fructose stimulates the production of fat in the liver, known as hepatic DNL (de novo lipogenesis).

Hormonal response

Compared to glucose, which metabolism is highly regulated in healthy, active individuals, fructose follows a metabolic pathway independent of insulin and other important regulating hormones.
It also doesn’t activate the same hormonal response to satiety as glucose, leading to overeating. In plain terms, we can eat more without our bodies signalling that we are no longer hungry.

Uric acid

Interestingly, it looks like fructose is the only type of carbohydrate that can produce uric acid during its metabolism. The accumulation of uric acid crystals in the joints can cause a painful form of arthritis called gout. Uric acid is usually a product of the breakdown of purines, one of the two chemical compounds that cells use to make the building blocks of DNA and RNA. Meat and meat products are also good sources of purines.

Now let’s have a look at some other interesting research investigating the link between high fructose intake and health problems.

High intake links to health problems

Fructose and non-alcoholic fatty liver disease (NAFLD)

An indication of this chronic liver disease is the accumulation of triglycerides (a form of fat) in the liver. It develops when the liver runs out of possible ways to get rid of fat.
A significant increase in this disease has been seen in recent decades, and carbohydrates, particularly fructose, have shown to stimulate fatty acid formation (hepatic de novo lipogenesis-DNL) with the increase of liver fat. Further research will show if this is happening only due to the excess amount of fructose or to the total energy excess.

Fructose and pancreatic cancer

Researchers from the University of California and Los Angeles found that pancreatic tumour cells use fructose to divide and reproduce. This finding further contradicts the earlier belief that all sugars are equal.
As shown in a study, tumour cells that were fed glucose and fructose used these sugars in two different ways. The results, published in the journal Cancer Research, could help explain earlier studies linking fructose intake to pancreatic cancer, one of the deadliest forms of the disease.

“These results show that cancer cells can easily metabolise fructose to increase proliferation”, wrote Dr Anthony Heaney and colleagues at UCLA’s Jonsson Comprehensive Cancer Center in 2010.
“Fructose is dangerous for cancer patients with diabetes who are prescribed a refined fructose diet, and reducing the intake of refined fructose or stopping consuming fructose-treated diets can slow the growth of cancer.”

Fructose and irritable bowel syndrome (IBS)

Irritable bowel syndrome is an inflammatory condition showing symptoms like abdominal pain, diarrhoea and bloating. Human studies on patients with IBS found that 65% of participants have fructose malabsorption, a metabolic disorder where intestinal cells can’t break down fructose effectively.

Fructose and inflammation

Fructose also seems to help raise inflammation in our body when present in excessive quantities in the gut. It generates compounds called AGE’s (advanced glycation end products) that are connected to the build-up of plaque in your arteries, neurodegenerative diseases (Alzheimer’s, Parkinson’s) and some chronic inflammatory diseases like diabetes or asthma.

AGE’s form in a non-enzymatic reaction between proteins and sugars (Maillard reaction). The reaction happens in food when high heat is applied (like when you cook a steak in your pan) but also in our body.

Fructose and pro-inflammatory microbiota

Gut microbiota relates to all the microorganisms present in our digestive tract. The gut microbiota, as well as its metabolites, have an important role in our immune system, digestion and metabolism. It can produce essential vitamins and a range of nutrients, including extremely beneficial short-chain fatty acids (SCFA). The composition is highly dependent on our diet, and it can change in a matter of days.
An imbalanced composition has been linked to a range of metabolic disorders.

Higher concentrations of fructose in our intestine promote so-called “pro-inflammatory microbiota”. It is manifested in the production of endotoxins and the suppression of the production of short-chain fatty acids. The inflammation leads to a leaky barrier, enabling pathogens and endotoxins to enter the bloodstream. This way, one of the most critical functions of our intestine, which is to select what goes into the bloodstream and what does not, is disabled.

What is glucose-fructose syrup?

Glucose-fructose syrup is a type of sweetener obtained from starch (very often coming from corn). The production process basically mimics the way our body would break down complex carbohydrates into sugars. Finally, the product is a mixture of free fructose and free glucose molecules. Depending on the ratio of those two, it can be also called isoglucose, fructose-glucose or high fructose corn syrup (HFCS). These syrups are highly common and widely present in processed foods because they are cheap and easily substituted for sucrose, still bringing that wanted acceptance to the consumer.

The biggest problem lies in the amount that we consume, specifically because of their widespread use. According to a report of an article in the April 2004 issue of the American Journal of Clinical Nutrition, the consumption of high fructose corn syrup alone increased by over 1000 % only between 1970 to 1990.

Unfortunately, these syrups are not the only ingredients containing fructose in high concentrations that manufacturers add to our food. Here is a list of other very common ones that you will likely find in the ingredients list of many products:

• Organic cane sugar
• Brown sugar
• Raw sugar
• Corn syrup
• Caramel
• Maple syrup
• Honey
• Molasses
• Cane juice and syrup
• Fruit juice
• Fruit juice concentrate
• Fruit purees
• Fruit nectars
• Evaporated cane juice

Final thoughts

It would be wrong to point the finger only at fructose when talking about the rise of many chronic metabolic conditions in our communities. When fructose intake is linked to moderate consumption of nutritious foods like fruit and vegetables, it doesn’t show any adverse effects, but when consumed in high amounts and coming from nutritionally poor choices, it contributes to the development of the previously mentioned conditions. Additionally, our physical activity level and total energy intake are also very important factors that should not be forgotten!

Drinking 500 ml of a beverage sweetened with HFCS with a composition of 55% of fructose, you will end up ingesting 27,5 g of it.
Eating an apple which on average weighs 200 g, you will be ingesting around 12 g of fructose together with essential vitamins, fibre, a range of antioxidants and other beneficial nutrients.
It is easy to guess what would be a better option!

Choosing nutrient-rich food, preparing meals at home and being smart about your choices when it comes to processed foods containing high amounts of sugar will take you a long way and help you live a healthy life.

Prepared by Marijan Katalenić