Fructose and oxidative stress

Fructose is a sugar found in fruit and honey and also in some processed foods and sweetened drinks like coke. It sounds harmless, but eating too much fructose can be damaging, particularly in conditions like ME/CFS, Long Covid and Fibromyalgia.  

Unlike glucose, fructose is absorbed in the liver and the particular way it is metabolised leads to mitochondrial stress, fat accumulation, inflammation and reduced energy levels. In this post, we explore the difference between fructose and other sugars, its link to uric acid and oxidative stress, and practical ways to reduce your fructose intake.

What Is Fructose?

Fructose is a monosaccharide—a simple sugar—commonly known as “fruit sugar.” It occurs naturally in fruits and vegetables but is also a major component of added sugars like sucrose (table sugar), which is 50% fructose and 50% glucose. With 4 calories per gram and a sweetness level 1.2 to 1.8 times greater than sucrose, fructose is the sweetest naturally occurring carbohydrate.

Glucose vs. fructose metabolism - the fundamental difference

Fructose is unique in the way it is absorbed in the body, and differs from glucose as shown in the diagram below. Crucially, it does not raise blood glucose or trigger insulin release. Instead, fructose is processed by an enzyme called fructokinase, which consumes ATP (adenosine triphosphate)—our cellular energy currency.

The Mitochondrial Cost of Fructose Metabolism

The trouble with fructose is that the process of its metabolism depletes energy:

• Normally we use some energy (ATP) to metabolise food, but we produce more energy from that food – i.e more ATPs, so their is a net gain in energy after eating

• But the metabolism of fructose causes a depletion of ATP:

  • Fructose is metabolised by an enzyme called fructokinase which uses ATP to generate ADP

  • Whilst ADP is usually converted back into ATP, in fructose metabolism ADP is converted instead to AMP, and then to Uric Acid

  • This depletes ATP and therefore energy is reduced

    
    

• This pathway leads to energy depletion and oxidative stress—particularly in the mitochondria, the powerhouses of the cell.

  
  

Mitochondrial Dysfunction and Oxidative Stress

Uric acid, a byproduct of fructose metabolism, plays a key role in inducing oxidative stress within the mitochondria, the energy producing components of all of our cells. This contributes to fatigue, hunger, and fat accumulation. It also increases the risk for gout, a painful form of arthritis, and is strongly associated with metabolic syndrome.

Fructose and metabolic health

The liver converts excess fructose into fat through a process called de novo lipogenesis, contributing to the development of Non-Alcoholic Fatty Liver Disease (NAFLD), which is a major driver of insulin resistance, which can lead to Type 2 Diabetes and other metabolic disorders.

High fructose intake is also linked to leptin resistance—a condition where the brain no longer responds properly to the hormone leptin, which signals fullness. This leads to dysregulated appetite and overconsumption of food.

Fructose, Gut Health, and Inflammation

Research also suggests that fructose can cause damage to the gut and the immune function:

• It promotes inflammation.

• It disrupts gut barrier integrity.

• High fructose corn syrup (HFCS), which is found in foods like ice-cream and sweetened drinks negatively alters the gut microbiome, reducing beneficial bacteria.

Evolution and the "Survival Switch" Theory

The Survival Switch Theory has been suggested by Dr Richard Johnson to explain how humans evolved to metabolise fructose using fructokinase to support our survival when food was scarce. By enabling the conversion of fruit sugar into bodily fat, fructokinase helped humans to survive during winter when food was scarce. However, in today's world when we're surrounded by food all year around, this evolutionary adaptation is no longer helpful, and instead, contributes to chronic diseases.

How to reduce fructose in your diet

1. Avoid high fructose corn syrups or equivalents

• Common in U.S. processed foods and soft drinks

• Known as glucose-fructose syrup (GFS) in the UK and Europe

• Found in: cereals, biscuits, cakes, sauces, ice cream

2. Cut Back on Added Sugars

• Avoid: table sugar, honey, jams, sweetened drinks such as Coco-cola, Sprite etc.

• Limit: cakes, sweets, ice creams

• Read labels and look out for hidden sugars

• Remember - table sugar is 50% fructose!

  
  

3. Eat Fruit, But Don’t Drink It

• Just eat whole fruit which is have beneficial nutrients, including phytonutrients, and also fibre, which slows down digestion fruits contain fibre and nutrients that slow sugar absorption

• Limit tropical fruits which have a high sugar content

• Avoid fruit juices and dried fruits, which can spike fructose intake

Below you can see how the fructose content of fruits varies, with some fruit containing very little - eg apricots and strawberries, whilst others such as grapes being much higher. Dried fruits such as dates and raisens are very high in fructose, as are fruit juices.

Final Thoughts

While fructose from whole fruits can be part of a healthy diet, eating too much fructose, especially from added sugars and processed foods, can lead to significant metabolic harm.

Understanding how fructose effects our biochemistry is important as this type of sugar is very different from other sugars. Keeping fructose down will help to reduce oxidative stress and inflammation in ME/CFS, Long Covid and Fibromyalgia and help to preserve energy. Reducing fructose will support better mitochondrial function, hormonal balance, and overall metabolic health.