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Fructose: hidden dangers

Recently “Nature” - one of the most influential peer review journals and the gold standard publication for medical research - published a new study on the effects of fructose on the intestine walls and the resulting weight gain.

Read here: https://www.nature.com/articles/d41586-021-02195-1 The research found that mice consuming fructose as part of their meals had such changes in their gut wall that more nutrients were allowed to be absorbed, which lead to increase in weight.

The first time I came across the potential detrimental effects of fructose on our health was back in 2009 when I watched a Youtube documentary by Robert Lustig. Lustig is Professor Emeritus at the University of California (UCSF) specialising in paediatric endocrinology. In 2009 Lustig recorded a lecture to his students about fructose and its effects on the liver which he shared on Youtube. Called “Sugar: the bitter truth”, the film has by now been watched 13 million times, and the Financial Times called it the “sugar’s tobacco moment”.

https://www.youtube.com/watch?v=dBnniua6-oM In the film Lustig shows the research he and his colleagues conducted on fructose, and high fructose corn syrup in particular, to demonstrate that fructose added to a variety of foods leads to the development of diseases of metabolic syndrome. Metabolic syndrome diseases are obesity, diabetes type 2, hypertension, heart disease.

Fructose is one of the two components of table sugar, honey, it is the main part in fruit, and it is now being added to many sweet and savoury products by food manufacturers.

Lustig documented that the role of fructose in its natural state (such as part of fruit) can be eaten safely, as the fibre in the fruit slows down the absorption of fructose. However, fructose without the fibre is metabolised by the liver, which having to deal with large amount of fructose gets over burdened. As a result, the overconsumption of fructose leads to liver damage seen in fatty liver disease (non-alcoholic fatty liver disease). High-fructose corn syrup (HFCS) - a manufactured fructose - is now a constant component in soft drinks, fizzy drinks, fruit juices, fruit pastilles, sweets and many savoury foods too.

At the time, 12 years ago, Lustig was a pioneer in his field, he was one of the first people to claim that sugar was “not just simply empty calories” and rejected the idea that ‘a calorie is just a calorie’. 12 years on, not much has changed in the public consumption of sugary drinks. Soft drinks are still the main culprit of high rates of overweight and obesity. In Britain, 62% of the population are either clinically overweight or have type 2 diabetes. Every third child has obesity or diabetes type 2.



So what exactly are the dangers of fructose?

In the 1960s, fructose was used as a type of treatment of diabetes, because it did not need insulin to be metabolised. Feeding fructose to people at the time was shown to have no influence on fasting blood glucose and its excretion into urine. This type of sugar was described as a “useful therapeutic agent stabilising blood glucose in diabetic patients to the normal fasting level, improving the overproduction of acetone, restoring the nitrogen balance, and decreasing the loss of water”. Read more:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609573/#B9

Around the same time, in the 60s, high fructose corn syrup (HFCS) was introduced by the food industry as a substitute of sugar. The intake of foods containing HFCS by the public has increased dramatically since the 90s, and research since the early 2000s has identified fructose as the type of sugar responsible for the high rates of obesity.

Research on fructose has been controversial. Fructose is associated with weight gain and onset of obesity, however, the exact mechanisms are not yet fully understood. Most research that points to the detrimental effects of fructose has been done on mice. As it is a type of prospective study (where researchers set up an experiment and watch out for its outcomes, such as development of a disease), it is quite difficult for ethical considerations to set up an experiment which may induce obesity in people.



Retrospective studies done on humans are conflicted. Many report fructose does not lead to weight gain, others point it does. The task for researchers is quite difficult, as they need to isolate fructose from other sugars at the same time controlling for a range of lifestyle habits and confounding dietary patterns.

Among ill effects, fructose is attributed to the negative changes in the gut microbiome. Healthy gut bacteria are responsible for the health of our immune system, where they protect us against harmful pathogens and act as the gatekeepers in intestinal barrier function. The gut microbiota produce vitamins and a variety of nutrients, including important short-chain fatty acids that help fight inflammation.

Fructose affects the gut microbiota in such a way as it is often reported to worsen the symptoms of irritable bowel syndrome (IBS), with prevailing symptoms such as abdominal pain, diarrhea, bloating. Studies on humans suffering from IBS show a high presence of fructose malabsorption and intolerance.

Read here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040818/

It is often the change in the gut bacteria composition that leads to insulin resistance that further entails metabolic syndrome diseases. Gut bacteria have a strong impact on our body weight. When transplants of the gut bacteria from obese mice are placed into germ-free recipient mice, the latter develop visceral fat, associated with obesity, within as little as 2 weeks. Transplants of the healthy gut bacteria from lean people to obese people is now showing good results as a weight reduction treatment in clinically overweight people.

Fructose consumption is linked to the development of non-alcoholic fatty liver disease (NAFLD). Fructose metabolism causes the hepatic (that of the liver) de novo lipogenesis. In simple terms, this is the liver taking on fructose to metabolise it, converting it first to glycogen for later use as energy, but soon with the high load of glycogen stored and fructose still coming, the liver starts converting it triglycerides - fat that gets stored in our cells. The level of triglycerides in the blood is often referred to as high cholesterol levels.

One study of obese children pointed out that the fatter group of children had the smaller LDL particle size, and after controlling for body composition, the intake of fructose was the only dietary factor related to the LDL particle size. LDL is often labelled ‘bad’ cholesterol, however, more recently doctors and researchers are urging that it is the LDL particle size that matters whether the person will have a high risk of cardiovascular disease. The small dense LDL are more harmful than the larger, fluffy type of LDL.

Read more:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372893/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832395/

Fructose may induce sarcopenia. Sarcopenia is loss of muscle associated with ageing.

Studies on mice showed that when ageing rodents were fed fructose, they lost significantly more lean body mass and instead had more fat mass than starch-fed mice. The animals also had lower levels of muscle protein synthesis after the meals.

The conflicts in the studies reporting negative changes or no changes due to fructose consumption are difficult to separate for the public and media. Even researchers themselves argue that studies often get mixed up whether the effects on the metabolic markers are attributed to pure glucose versus fructose or to HFCS, which contains both.

The new piece of research published in Nature “Fructose in the Diet Expands the Surface of the Gut and Promotes Nutrient Absorption”

(read: https://www.nature.com/articles/d41586-021-02195-1) examines the changes fructose causes in the lining of the gut of mice. In this study the researchers demonstrate that the walls of the small intestine act as the gatekeeper against the harmful effects of fructose. The fructose when eaten as part of fruit is taken up and broken down by the intestinal cells. However, when fructose is ingested in excess amounts, it starts leaking into the bloodstream to reach the liver intact. It may also “spill over from the small intestine and reach the colon” - the researchers suggest. But most interestingly, this current study indicates that the changes that occur in the intestine after consumption of fructose alter the gut bacteria to change the metabolism of fats that causes weight gain.

The absorption of nutrients in the intestine happens with the help of micro structures called villi, or microvilli. Nutrients from the gut pass into the bloodstream after they go through the villi. The researchers report that if mice received high-fructose corn syrup in their diet, they developed longer villi and higher levels of lipids in their blood compared with the animals that did not receive HFCS. The authors propose that villus lengthening happens due to the survival of the cells at the tips of the villi that was triggered by the presence of fructose.

This elongation of the villi may have caused leaky gut in mice - the condition where nutrients, such as excess dietary fat bypass intestinal cells and leach into the bloodstream.

Having read numerous studies on fructose over the years, one thing becomes very clear, avoiding sugary drinks, such as soft, fizzy drinks and fruit juices, where fructose is the main sweetener, is definitely a good start to prevent and curb overweight and obesity.