Fructose: Sweet poison?

Fructose is a simple sugar (such as glucose and maltose) that occurs naturally in foods. When one molecule of fructose combines with one molecule of glucose, it forms sucrose (a.k.a. table sugar).

Years ago, agave syrup was all the rage because it was high in fructose. Fructose is known to have a low glycaemic index, meaning it does not raise blood sugar as much as glucose. Back in the 1960s, fructose was used to treat diabetes because it does not need insulin to be metabolised (1, 2, 3). That’s good, right?

Not so fast! There has been plenty of scientific research on how fructose affects metabolic health. Science seems to indicate that a high consumption of fructose is detrimental to health and particularly linked with non alcoholic fatty liver disease (NAFLD).

I thought the debate was settled and this was common knowledge, at least among the medical profession. However, it was recently brought to my attention that most people, clinicians included, still think that we should be shoving as much fructose as possible into our bodies. I hope this article sheds a light in this very important health topic.

Fructose in foods

Fructose is naturally present in many foods, such as fruits, vegetables and honey. As mentioned above, sucrose is 50% fructose, 50% glucose. High fructose corn syrup (HFCS) is commonly used as a sweetener in food products, mainly in the US. This is because it’s cheap, sweeter than table sugar, and confers desirable properties to the end product. HFCS typically contains 55% fructose and 45% glucose (2).

It is important to note that the total sugar in any given food will be a combination of fructose, glucose and/or other sugars. The table below shows the amount of fructose and glucose in some common foods (4).

Fructose metabolism

Fructose follows a different pathway than glucose in our bodies. While glucose is used as fuel by cells, fructose goes to the liver. This means that fructose does not require insulin to be metabolised (5), which is the core argument of pro-fructose argument. However, this also means that there is no delay to proceed with the steps that lead to glycolysis (breakdown of glucose), gluconeogenesis (generation of glucose), glycogenesis (generation of glycogen) and lipogenesis (generation of lipids) (5).

The actual compounds that get produced following fructose intake depend on factors such as nutritional status, dietary patterns and genetics (6).

Fructose and lipids

Excessive fructose consumption is associated with increased accumulation of fatty acids in the liver and skeletal muscle. It is also associated with increased generation of fatty acids in the liver and higher concentration of triglycerides (TG) in plasma (2, 5, 6, 7)

Fructose acts both as a substrate and an activator of de novo lipogenesis (8).

Fructose metabolism may also increase the production of uric acid in the body, which may lead to high blood pressure, gout and other conditions (7). This assumption, however, has been contended by other researchers (9).

Fructose ingestion may also inhibit fat oxidation. In addition, if insulin resistance is present, there is reduced uptake of lipids that are circulating in blood and increased hydrolysis of stored TG, resulting in more TG in blood (2).

There is some evidence that consuming plausible amounts of fructose can lead to increases in total and LDL-cholesterol in serum (2).

Metabolic syndrome and weight gain

Some research indicates that high fructose diets can induce systemic insulin resistance and high fasting blood sugar (6).

The link between fructose and weight gain has not been clearly established. Fructose may affect satiety by altering normal secretion of ghrelin (the hunger hormone) (10). This means that you may feel less full when eating fructose-containing foods, which can lead to over-consumption of calories, overweight and obesity.

Similarly, the link between fructose consumption and cholesterol, blood pressure (11) and insulin resistance (2, 11) is not clear yet.

Liver health

Fructose can not only stimulate the generation of lipids within the gut but also in the liver (2).

Many scientists consider excessive fructose consumption as a key risk factor for the development of NAFLD (1, 5, 8). NAFLD is a spectrum of disorders ranging from simple steatosis (accumulation of fat within an organ, in this case the liver) to non-alcoholic steatohepatitis (NASH) (6). NASH can progress to fibrosis, cirrhosis, and liver cancer (1, 8). The link is potentially due to the effect of fructose due to its effects in the gut microbiota (1).

Increased fructose intake has also been linked to hepatic insulin resistance (6).

Ageing and inflammation

Advanced Glycation Endproducts (AGEs) are toxic compounds that are produced by the reaction between sugars and proteins. The acronym is fitting as AGEs play a role in age-related conditions such as neurodegenerative diseases, atherosclerosis, and chronic inflammatory diseases. Fructose, being a sugar, reacts with proteins to produce AGEs at a 7.5 to 10-fold higher rate than glucose (5).

High fructose intake is associated with increased inflammation and oxidative stress (5). This is potentially due to the activation of neutrophils by increased TG and glucose after meals. Neutrophils are immune cells responsible for generation of pro-inflammatory chemicals called cytokines (2). Excessive fructose intake is also associated with increased intestinal permeability, which facilitates microbial toxins to enter circulation (1).

Fructose malabsorption

Fructose is incompletely absorbed in the gut. When more fructose is consumed than what can be absorbed, it can cause diarrhoea and flatulence (2).

In addition, some individuals also have issues absorbing modest quantities of fructose. They normally exhibit symptoms of irritable bowel syndrome (IBS) and benefit from reducing fructose (and potentially other FODMAPs from their diets.

Effects in the gut microbiome

There is some evidence that excess fructose consumption might lead to changes in the composition of the gut microbiome. As a result, this might lead to increased permeability in the gut barrier and inflammation (1). I’m sure a lot more research will come in the next few years on this topic.

Benefits for athletes

Fructose can be beneficial for athletes because it helps in carbohydrate absorption (2, 12) and oxidation (2) during exercise. Fructose may also help reduce the perception of fatigue and therefore improve performance (2). Finally, the ingestion of sucrose can minimise gastrointestinal distress compared to just glucose (12).

Bottom line

Research on the health effects of fructose has been done on animals and humans. Some of the studies show detrimental results when using amounts of fructose that exceed normal intake. The most consistent effect of consuming high amounts of fructose seems to be elevated TG production, followed by the risk of developing NAFLD. If you already have elevated TG, NAFLD, insulin resistance or other metabolic disorders, you should watch your total sugar and fructose intake.

Recommendations

• Eating fruit is still healthy! Fructose is present in fruit, yes, but so do many other nutrients that are essential for health, such as vitamins, phytochemicals and fibre. If you have diabetes, insulin resistance or specific body composition goals, you should limit your fruit intake and choose fruits with lower sugar content. Same if you have intolerance to some FODMAPs.
• Avoid concentrated forms of sugar that are not great sources of nutrition, i.e. sweetened beverages.
• If you have insulin resistance and/or NAFLD, stop consuming sugar-containing processed foods such as biscuits, chocolate bars, cakes and soft drinks on a regular basis. Assuming you’re an adult, you make your own choices when it comes to feeding yourself. Be responsible.
• Exercise. Some of the adverse effects of fructose can be minimised by physical activity. Active muscles can uptake mobilise and burn more fatty acids (2). Having said that, there is no consensus as to what type and intensity of exercise is effective (1, 2, 8, 7). I would advise incorporating different exercise modalities into your lifestyle.

References

1. Lambertz J, Weiskirchen S, Landert S, Weiskirchen R. Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease. Frontiers in immunology. 2017;8:1159-.
2. Bidwell AJ. Chronic Fructose Ingestion as a Major Health Concern: Is a Sedentary Lifestyle Making It Worse? A Review. Nutrients. 2017;9(6):549.
3. Dornas WC, de Lima WG, Pedrosa ML, Silva ME. Health implications of high-fructose intake and current research. Advances in nutrition (Bethesda, Md). 2015;6(6):729-37.
4. US Department of Agriculture (USDA), Agricultural Research Service, Nutrient Data Laboratory. USDA National Nutrient Database for Standard Reference, Legacy. Version Current: April 2018. Internet: http://www.ars.usda.gov/nutrientdata
5. Aragno M, Mastrocola R. Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease. Nutrients. 2017;9(4):385.
6. Ter Horst KW, Serlie MJ. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease. Nutrients. 2017;9(9):981.
7. Pereira RM, Botezelli JD, da Cruz Rodrigues KC, Mekary RA, Cintra DE, Pauli JR, et al. Fructose Consumption in the Development of Obesity and the Effects of Different Protocols of Physical Exercise on the Hepatic Metabolism. Nutrients. 2017;9(4):405.
8. Jegatheesan P, De Bandt J-P. Fructose and NAFLD: The Multifaceted Aspects of  Fructose Metabolism. Nutrients. 2017;9(3):230.
9. Caliceti C, Calabria D, Roda A, Cicero AFG. Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review. Nutrients. 2017;9(4):395.
10. Basaranoglu M, Basaranoglu G, Sabuncu T, Sentürk H. Fructose as a key player in the development of fatty liver disease. World journal of gastroenterology. 2013;19(8):1166-72.
11. Rippe JM, Angelopoulos TJ. Fructose-containing sugars and cardiovascular disease. Advances in nutrition (Bethesda, Md). 2015;6(4):430-9.
12. Gonzalez JT, Fuchs CJ, Betts JA, van Loon LJC. Glucose Plus Fructose Ingestion for Post-Exercise Recovery-Greater than the Sum of Its Parts? Nutrients. 2017;9(4):344.

[Photo by nabil boukala on Unsplash]

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