Incompletely absorbed (malabsorbed) fructose is fermented by the flora in the lower bowel resulting in the formation of gas and chemical substances, including short-chain fatty acids. The threshold of fructose malabsorption varies individually and widely. Most individuals will show malabsorption of sugars, including fructose, when very large quantities are consumed, without necessarily resulting in symptoms.
In pre-disposed individuals symptoms may be caused by an increased production of gas, increased sensitivity to gas-induced distension or some of the chemical compounds produced by fermentation, or an abnormal gut flora (microbiome).
The activity of the transport proteins determining gut absorption of fructose, such as GLUT5, is genetically determined and may be changed by inflammation or stress. Inflammation in the intestine, due to e.g. Crohn’s Disease, gastroenteritis or Celiac’s Disease, can therefore result in fructose intolerance. The microbiome can change after intestinal infections or antibiotic use. Intolerance to fructose often only becomes apparent in adulthood and must be distinguished from the rare and potentially dangerous hereditary fructose intolerance (HFI) (See below).
Fructose is found in honey, various fruit and often in sweetened snacks or drinks in daily amounts of at least 20 to 70g, depending on the local diet. Some sports and fruit drinks contain over 50g of fructose per 1000ml.
Fructose consumption has increased markedly in the last decades and high levels of consumption appear to be implicated in obesity, the metabolic syndrome (diabetes, cardiovascular and blood lipid diseases) and certain liver diseases. Fructans are not sweet and occur predominantly in vegetables and grains.
Fructose and fructan intolerances often overlap, but are not identical.
Frequency in population
Approximately 30% of healthy adults show malabsorption of fructose doses below 50g and around 10% have symptomatic intolerance. There appear to be no major racial differences.
Up to 70% of patients with Irritable Bowel Syndrome have fructose intolerance.
This intolerance commonly appears only in adults and may be triggered by stress, inflammation, infection and antibiotic use.
Bloating, abdominal cramps and pain, diarrhea or constipation, increased intestinal sounds and gas production, reflux (e.g. acid taste in mouth, heartburn), nausea or vomiting.
The symptoms resemble those of functional disorders or Irritable Bowel Syndrome (IBS).
Up to 70% of patients with IBS have intolerance to normal amounts of fructose. Depression may be more common in both adults and children with fructose malabsorption, and can improve with dietary reduction in fructose intake. This may be due to lowered tryptophan levels in the blood. Skin rashes or hives, itching are not typical. Zinc and folic acid blood concentrations have been reported to be decreased in a proportion of fructose intolerant.
Testing & diagnosis
The most reliable diagnostic test is the fructose breath test.
Self-diagnosis of fructose intolerance is often difficult due to the presence of fructose not only in fruit, but also in other food. A careful history should be taken in very case, especially in case of suspicion of severe fructose intolerance in young children, in whom specific genetic tests are performed to exclude hereditary fructose intolerance before performing the fructose breath test. This is recommended to prevent serious reactions to the ingested fructose.
Breath tests are the most useful and non-invasive tests for determining the various sugar (e.g. fructose, lactose, sucrose) and sugar alcohol (e.g. sorbitol, xylitol) intolerances. They are well validated, widely used, but some discussion still exists about the ideal test conditions. These tests should not be used in infants and reduced doses of test compound are used in children. The tests procedures are identical for all the intolerances.
The following are important details regarding the test procedure.
- Dietary restrictions, no smoking or excessive exercise from the day before testing and no antibiotics or colonoscopy in the last week pre-test.
- Ingestion of a specific amount of the sugar or sugar alcohol to be tested for intolerance.
- Regular breath samples taken for a standardized period.
- Diary of symptoms during the next day for calculation of the symptom index.
- Measurement of specific gases, e.g. hydrogen and methane, in the breath samples.
An intolerance is diagnosed based on the symptoms following the test and the gas concentrations in the breath samples. The diagnosis is confirmed by a significant decrease in symptoms whilst on a diet low in the poorly tolerated sugar or sugar alcohol. Expert dietary advice is very helpful for the identification of food and drink containing the difficult-to-spot offending ingredient. Examples of such ingredients are so-called hidden lactose or fructans in vegetables or whole-meal products.
Fructose intolerance due to malabsorption (common fructose intolerance): no specific genetic test is currently available. Testing is by breath test (contact us if you have problems accessing tests locally).
Hereditary fructose intolerance (HFI): about 70% of genetic aberrations (polymorphisms) associated with HFI can currently be identified and these should be determined in case of clinical suspicion, due to the lifelong and possibly severe consequences of not excluding fructose meticulously from the diet.
Reduction of the intake of fructose and often also of fructo-oligosaccharides (fructans) to individually tolerated levels will rapidly lead to symptom relief in most individuals (within a few days).
The identification of fructose and fructan content is not intuitive and requires specialist advice to ensure adequate vitamin, fruit and vegetable intake. Generally, the foods identified as ‘healthy’ contain fructose or fructans and replacement with other equally healthy alternatives or the addition of supplements constitute the dietician’s challenge. Sorbitol and xylitol consumption should be reduced to a minimum, due to the high degree of concurrent intolerance and symptom exacerbation.
Concurrent glucose consumption increases fructose absorption and hence tolerability.
Consequently, foods with high glucose content are better tolerated and glucose taken just before meals may reduce symptoms. Small amounts of fructose eaten after meals are better tolerated than a single dose on an empty stomach. In some patients the overlap of intolerances to several classes of poorly absorbed carbohydrates (FODMAP’s) necessitates a general reduction of these carbohydrates.
An enzyme-containing preparation (xylose isomerase), Fructosin®, has shown anecdotal effectiveness, but is without an adequate evidence base and is not generally recommended.
Fructose has been reported to increase intestinal permeability.
Lactose and fructose intolerance co-exist in approximately 20-30% of individuals.
Hereditary fructose intolerance (HFI)
In distinction to the fructose malabsorption described above, HFI is a severe fructose intolerance due to genetic defects (aldolase B) mainly affecting children at the time of introduction of sugars, but also rarely manifesting in adults.
Besides the same symptoms as fructose malabsorption (see above), metabolic disturbances, such as hypoglycemia, and permanent liver and kidney damage can ensue. In infants the disease may be lethal due to seizures and coma. There is even sensitivity to the fructose component of sucrose, household sugar, as well as to infusions containing fructose. All forms of sucrose and fructose, and probably also sorbitol, should be strictly avoided. A positive family history of sugar intolerance or an aversion against sweets / candies is a useful clue. Diagnosis is by careful history taking, blood sampling for metabolic, liver and kidney disease, and, specifically, genetic testing. At present not all forms of HFI can be identified using genetic blood tests.
Wilder-Smith CH et al.
Fructose and lactose intolerance and malabsorption testing: the relationship with symptoms in functional gastrointestinal disorders.
Aliment Pharmacol Ther 2013
Wilder-Smith CH et al.
Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance.
United European Gastroenterol J. 2014