Fructose intolerance: causes, symptoms and effective treatment methods

Fructose intolerance: a growing problem in modern Western society.

Fructose occurs naturally mainly in fruit. However, the main problem is the excessive consumption of industrially produced fructose. This is hidden in many processed foods and is not declared. As a result, fructose intake in the population has increased considerably. This article explains various forms of fructose intolerance, their causes, symptoms, diagnostic possibilities and treatment options.

What is fructose intolerance?

Fructose is a monosaccharide (simple sugar) that is naturally found in fruits and honey. Fructose has a high sweetening power and has therefore been increasingly produced industrially in recent decades. This type of fructose is called "high-fructose corn syrup" and is used in processed foods and sweetened drinks. Due to the increasing consumption, fructose consumption has also increased, which in turn leads to an increase in cases of fructose intolerance (1).

In order to understand the development and effects of fructose intolerance, three terms need to be differentiated. In addition to the congenital and rare so-called hereditary fructose intolerance, there is fructose malabsorption and intestinal fructose intolerance. These clinical pictures differ in some important aspects:

Hereditary fructose intolerance

• Caused by a congenital defect in the enzyme aldolase B, which is found in the liver, kidneys and small intestine
• Even small amounts of fructose can cause serious health damage, so a complete avoidance of foods containing fructose is necessary
• Often discovered in infancy, later those affected develop an aversion to sweets
• Prevalence 1: 26000

Fructose malabsorption

• Physiological disorder of the body's ability to absorb fructose from food
• Insufficient absorption of fructose from the intestine
• Often causes no symptoms

Intestinal fructose intolerance

• Fructose malabsorption with associated symptoms (1, 2)

What symptoms indicate fructose intolerance?

If fructose intolerance is present, the body reacts to fructose consumption primarily with gastrointestinal complaints. These occur when the physiological capacity for fructose absorption of 35 to 50 g of fructose per hour is exceeded. In those affected by fructose malabsorption, the symptoms occur even with low amounts of fructose of less than 25 g (1, 3).

Common symptoms of fructose intolerance include:

• An excessive accumulation of gases in the intestines
• Flatulence
• Abdominal cramps
• Diarrhea
• depression

In the case of hereditary fructose intolerance, fructose should be avoided completely, as fructose is intolerant in any amount. If fructose is consumed, further acute symptoms can occur. These include sweating, nausea, vomiting, paleness and seizures. Chronic symptoms can lead to ascites (dropsy), jaundice and liver cirrhosis. If no treatment is undertaken after taking fructose, the consumption of fructose can even be fatal.

In addition, fructose intolerance can have a negative effect on the psyche. People who suffer from fructose malabsorption tend to suffer from depression. This is due to a lack of the amino acid L-tryptophan. L-tryptophan is the biochemical precursor of the neurotransmitter serotonin. When there is an excess of fructose in the body, L-tryptophan is removed from the metabolism. This can then no longer be made available for serotonin synthesis (2). In addition to depression, a deficiency in this amino acid can cause other side effects. These include panic attacks, sleep disorders and muscle pain (4).

Fructose intolerance can also cause symptoms on the skin. Excessive sugar consumption changes the intestinal flora. If this is not balanced, it can have a negative effect on the skin, causing dryness, pimples, inflammation and wrinkles (5). An unbalanced intestinal flora caused by fructose intolerance can also cause eye problems. These include eye diseases such as uveitis, age-related macular degeneration, glaucoma and chalazion (6).

What causes fructose intolerance?

In order to understand fructose intolerance, it is worth first looking at the metabolism of fructose in the body. Fructose first reaches the small intestine via food. This is where the enzymatic breakdown of carbohydrates takes place. In the small intestine, fructose is transported to the brush border cells in the small intestinal lumen by two membrane transport proteins called "GLUT" and "SGLT".

GLUT-5 transporters transport fructose into the brush border cells. Since GLUT-5 has only a low capacity, GLUT-2 is activated in the presence of glucose to support fructose uptake. From the brush border cells, fructose enters the bloodstream and is transported further to the liver.

Due to this mechanism, fructose can be better absorbed in combination with glucose. For this reason, fruits with a high glucose content are better tolerated than those with more fructose. In contrast to glucose, the presence of sorbitol, a sugar alcohol, inhibits the absorption of glucose. Sorbitol competes with fructose for the GLUT-5 transporter, which inhibits its activity and prevents fructose from being metabolized efficiently. Like fructose, sorbitol is also found in fruit.

In summary, if the fructose transporters are not functioning properly, fructose cannot be absorbed efficiently. The unabsorbed portion of fructose is transported from the small intestine to the large intestine. There, fructose is metabolized by fermentation into hydrogen, carbon dioxide and short-chain fatty acids. This process causes the symptoms mentioned in the previous chapter.

In hereditary fructose intolerance, the metabolic process in the liver is restricted. Normally, fructose is converted into fructose-1-phosphate in the liver via the enzyme fructokinase. Fructose-1-phosphate is then split into two further parts by the enzyme aldolase B: glyceraldehyde and dihydroxyacetone phosphate. However, since hereditary fructose intolerance is genetically deficient in aldolase B, this conversion is not possible. Fructose accumulates in the liver, which can have a toxic effect in large quantities. Furthermore, this inhibits the so-called glycolysis and gluconeogenesis. This limits ATP synthesis for energy provision and can lead to life-threatening hypoglycemia (2).

Diagnosis of fructose intolerance

There are several ways to diagnose fructose intolerance, which are described below. However, not all methods are suitable for all forms of fructose intolerance. In the case of hereditary fructose intolerance, the so-called self-test and the hydrogen breath test are not even allowed to be used. If there is a suspicion, the diagnosis must therefore be carried out in close consultation with a doctor.

The self-test is a simple way to check for fructose intolerance yourself. It is based on the principle of an elimination diet. In the "elimination phase", which lasts several days, you completely avoid foods that contain fructose and sorbitol. No symptoms should appear during this period. Then the "provocation" begins with fruit that contains fructose, such as apples and watermelon, which have an unfavorable glucose-fructose ratio. To rule out pure malabsorption of sorbitol, the amount of sorbitol should initially be kept as low as possible. If fructose intolerance is actually present, symptoms will appear after 6 to 8 hours at the latest. If no symptoms appear, you should eat foods that contain sorbitol, such as prunes.

As the name suggests, the hydrogen breath test can be used to test for fructose intolerance via the breath. In this test, those affected are given a fructose solution of 25 g in 250 ml of water. If there is a disorder in fructose absorption, more fructose remains in the intestine. The fermentation of fructose produces gases that diffuse through the intestinal wall into the bloodstream. These gases eventually end up in the alveoli, where they are exhaled. This makes them measurable. The results are measured every three hours (2).

In the case of hereditary fructose intolerance, a blood test is carried out to test for gene mutations of the enzyme aldolase B. If this enzyme is mutated, hereditary fructose intolerance can be diagnosed very precisely (1).

Which foods can (not) be consumed if you have fructose intolerance?

The following table lists selected foods that contain fructose. The glucose content is also noted. Ideally, the ratio of fructose to glucose is 1:1 to enable effective absorption of fructose.

Food (100 g)	Fructose (g)	Glucose (g)
Raisins	33.2	32.0
Apple, dried	27.8	9.8
Pear	6.7	1.7
Apple	5.7	2.0
Watermelon	3.9	2.0
Honey	38.8	33.9

 Tab. 1: Fructose and glucose content in selected foods (1, 2)

The amount of fructose in high-fructose corn syrup varies depending on the manufacturer. The figures fluctuate between 42 and 90 percent fructose. Sorbitol is found in large quantities primarily in dried fruit. For example, 100 g of plums contain 6.6 g of sorbitol and 5.3 g of peaches (2).

If you have fructose intolerance, changing your diet is the most effective way to alleviate the symptoms. The FODMAP diet was developed to make this easier and to keep an overview of the large number of foods. It involves avoiding certain foods and replacing them with suitable alternatives. In addition to fructose, attention is also paid to polyols such as sorbitol, disaccharides such as lactose and oligosaccharides. The following table compares foods that are low in fructose and foods that are high in fructose.

Groceries	Rich in fructose	Low-fructose alternative
Fruit	(see Table 1)	Avocado, cranberries, lime, lemon, cantaloupe melon, pineapple, strawberries, bananas, tangerines
Vegetables	Artichoke, asparagus, broccoli, mushrooms, onions, peas, tomatoes and tomato products	Beetroot, pak choi, celery, kale, parsnip, spinach, sweet potato, radish
Cereals and cereal products	Foods with wheat as the main ingredient: wheat bread, pasta, couscous	Buckwheat flour, corn flour, semolina, oat flakes, quinoa, rice
Animal products	Marinated and processed meat, dairy products with HFCS, especially found in yoghurts and flavored milk (chocolate, vanilla)	Unprocessed meats, dairy products such as cheese, yoghurt, also rice and almond milk

Tab. 2: Fructose intolerance: what can I (not) eat? (7)

How is fructose related to table sugar (sucrose)? Are natural products such as honey or agave syrup better alternatives? According to the Max Planck Institute for Polymer Research, the differences between natural sweeteners and refined table sugar are minimal. The traces of vitamins and minerals in honey, for example, are so small that they are irrelevant to health.

The various sweeteners such as honey, granulated sugar and maple syrup have a fructose to glucose ratio of approximately 50:50. In agave syrup, fructose predominates at 82:18. The total sugar per teaspoon is highest in honey at 5.7 g. In maple syrup it is 4.0 g and rice syrup has the lowest value at 3.7 g. Rice syrup is the only natural sweetener that consists of 100% glucose. In summary, the source of sugar does not make a decisive difference in the effect on the body. Sugar consumption, regardless of its origin, should be a minimal proportion in a balanced overall diet (8).

The most common method for treating fructose intolerance is to change your diet. However, medication can be helpful. The enzyme xylose isomerase is taken in tablet form. This can alleviate symptoms by converting unabsorbed fructose into glucose in the small intestine. However, researchers point out that further research is needed to confirm previous results (7, 9).

Nutritional tips and recommendations for fructose intolerance

Based on this information, one might think that eating fruit is harmful. However, in today's Western diet, only a third of the fructose consumed comes from fruit and vegetables. The rest comes from processed foods enriched with industrially produced fructose. This type of food is increasingly dominating the diet, while the consumption of fresh food is decreasing (2).

When it comes to metabolizing fructose, it is crucial that processed fructose such as corn syrup enters the bloodstream directly. When eating raw fruit, the sugar must first be released from the cells, which usually does not happen 100%. In contrast to artificially produced fructose, fruit also has numerous health-promoting ingredients such as fiber, vitamins and polyphenols (8).

Completely avoiding fructose is counterproductive in cases of fructose malabsorption. In the short term, symptoms would improve, but in the long term, sensitivity to fructose would increase. This would result in reduced activity of GLUT-5, which would make fructose absorption less efficient and could lead to serious symptoms. However, it is recommended to avoid sorbitol, as this substance inhibits fructose absorption (9).

A dietary change to improve fructose malabsorption can be divided into three phases:

1. Low-fructose diet with the aim of reducing symptoms. Fructose and sugar alcohols should be avoided.
2. In the second phase, fructose consumption is increased to determine individual fructose tolerance. In addition, a balanced diet is adopted, paying attention to fat and protein intake, in order to improve fructose absorption.
3. Long-term nutrition: From this point on, a balanced diet should be aimed for. Fructose can be consumed within tolerable limits.

The above-mentioned steps of dietary change should, if possible, be carried out with the support of an experienced nutritionist. The long-term goal is not to avoid fructose, but to have a balanced diet with a tolerable level of fructose consumption. In this way, those affected can be given tailored recommendations to make the big step of dietary change easier. In this way, the necessary intake of essential nutrients is also taken into account (3).

To get a better picture of a balanced diet, a daily FODMAP meal plan with low fructose content is presented below:

• Breakfast: 40 g oatmeal, half a cup of lactose-free milk, 200 g lactose-free yoghurt
• Snack: 1 slice of cantaloupe melon
• Lunch: Chicken Risotto (without garlic and onions)
• Snack: 2 chocolate cookies, 1 cup of black tea
• Dinner: half cup ratatouille (low FODMAP), 1 cup gluten-free pasta
• Snack: 1 cup of grapes, 1 cup of black tea (10)

Lifestyle adjustments with fructose intolerance

It is often a challenge to shop and eat out appropriately if you have fructose intolerance. The labeling of fructose and high-fructose corn syrup on food is not sufficiently regulated, which means that these ingredients often go undetected. In restaurants, fructose does not have to be labeled, unlike lactose or other allergens.

In recent years, apps have been developed that make it possible to quickly assess whether foods are suitable for an adapted diet. These apps can be used to evaluate foods according to the FODMAP principle. This gives you a quick overview of whether the food/product is compatible or not (10).

Nevertheless, eating out can be a challenge when you have fructose intolerance. However, you don't have to give it up. A magazine for people with fructose intolerance has described possible measures that should make eating out easier:

• Speak to the waiter, possibly talk to the chef himself
• Find out whether dishes are prepared using fresh ingredients or ready-made products
• Avoid “system catering” as industrially produced ingredients are often used and no changes can be made

When choosing drinks, water is a safe alternative (11)

Conclusion

Fructose intolerance is a condition that is becoming increasingly common. Hereditary fructose intolerance is a genetic defect that requires a lifelong avoidance of fructose. Fructose malabsorption occurs when the physiological capacity to absorb fructose is exceeded. Fructose accumulates excessively in the intestines and causes unpleasant symptoms such as bloating, abdominal cramps and diarrhea. While hereditary fructose intolerance is untreatable, there are various methods to improve fructose absorption in the case of fructose malabsorption. This involves a change in diet by initially avoiding fructose. In a later step, fructose is gradually increased again until the individual tolerance limit is reached. An important factor in the treatment of fructose intolerance is avoiding high-fructose corn syrup. To do this, processed foods in particular should be limited.

Sources

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