Fructose intolerance (also known as fructose malabsorption) and HFI (Hereditary Fructose Intolerance) are two very distinct metabolic disorders, in which fructose is not well tolerated.

Both are often described wrongly as fructose allergy, which has not been described in medical literature and which is very unlikely to exist.

HFI (or Fructose 1-Phosphate Aldolase Deficiency)

Hereditary fructose intolerance is an inherited condition where the body does not produce the chemical needed to metabolise fructose (fruit sugar) in the liver. The fructose is normally absorbed by the body from the small intestine, but in the liver the body misses the enzyme fructose 1-phosphate aldolase (Enzyme Classification Code EC 2.1.2.13), which is a key enzyme in the further metabolism of fructose. Ingested fructose is converted to fructose-1-phosphate, which is further metabolised to glyceraldehyde-3-phosphate. This compound is part of the normal metabolism of sugars, known as glycolysis, which is the main energy-generating mechanism in the body (figure below).

Pathway of metabolism of fructose to glyceraldehyde-3-phosphate 

The lack of this enzyme results in an accumulation of fructose-1-phosphate in the liver, kidney, and small intestine. The accumulated fructose-1-phosphate inhibits glycogen breakdown and glucose synthesis, thereby causing severe hypoglycemia following ingestion of fructose. Hypoglycemia is a condition normally observed in diabetes and indicates a very low blood sugar level.

Further symptoms include severe abdominal pain and vomiting following ingestion of fructose or other sugars metabolized through fructose-1-phosphate. Prolonged fructose ingestion in infants leads ultimately to hepatic and/or renal failure and death.

HFI is therefore a very serious metabolic disorder, unlike fructose metabolism (see below).

The incidence of HFI among the population is not very clear, due to the difficulty of HFI diagnosis. A recent study in the UK using DNA testing indicated an incidence rate of 1 in 22,000 where the range would be between 1 in 12,000 to 1 in 58,000. HFI is (or seems) more common in North-West Europe and in areas with many people of North-West European descent (USA, Australia). However data among other populations are scarce, and there may be other populations with similar or higher incidences.

Diagnosis of HFI is difficult and (in small children) dangerous. The only definitive way to ascertain if one is suffering from HFI is to have one of two tests:

• An enzymatic assay to determine aldolase activity. The aldolase is obtained from patient liver tissue in an invasive surgical procedure called a liver biopsy.
• A fructose tolerance test. Fructose is injected intravenously under controlled conditions where acute glucose, fructose, and phosphate levels are monitored.

A newer, non-invasive DNA test is readily becoming more available. While the DNA test is not diagnostic because negative results do not guarantee that one does not have HFI, positive results, along with clinical symptoms, are strong indicators of disease. A presumptive diagnosis can be made.

The hydrogen breath test, which is used for fructose malabsorption, is not an effective detection method for HFI.

The treatment for HFI, is a strict fructose free diet. This involves exclusion of anything containing fructose, sucrose, or sorbitol. Implementation and adherence to this diet is often difficult, but not impossible. People on this diet live normal and healthy lives, although the danger of inadvertent fructose ingestion remain. See below for more details on the diet.

The diet also excludes sorbitol. Although sorbitol does not contain fructose and is poorly absorbed by the body, the absorbed sorbitol may be converted in the body to fructose by the so-called sorbitol pathway.

Fructose malabsorption or normal fructose intolerance.

The much more common type of fructose intolerance is very similar to lactose intolerance. In this case the ingested fructose is not absorbed by the body in the small intestine. Fructose is absorbed from the intestine using a specific transporting protein. When this protein is either not present, or has become inactive, fructose is not absorbed and reaches the large intestine.

In the large intestine fructose is rapidly fermented by the intestinal bacteria (intestinal microflora) to acids and gases, predominantly hydrogen and carbon dioxide. These gases cause the main problems; flatulence, bloating and abdominal pain. Diarrhoea is common.

Fructose intolerance may be inherited, but non-genetic factors also play a role. It is much more common than HFI, with 1 in 3 persons having some problem in digesting simple carbohydrates, such as fructose.

As with lactose intolerance and other carbohydrate intolerances, most people will have no problems with small amounts of fructose. The threshold for the symptoms varies widely among individuals, some people have problems with less than 1 gram of fructose, others can easily eat 20 grams without any problem.

Fructose intolerance is certainly not pleasant, but not as serious or life threatening as HFI. It is diagnosed by the breath hydrogen test, similar as for other carbohydrate intolerances. The body does not produce hydrogen by itself. When hydrogen is detected in the breath within 1 hour after ingestion of a test carbohydrate on an empty stomach, the person is regarded intolerant.

The treatment is a diet low in fructose or a fructose free diet, depending on the threshold of the individual. Symptoms will occur with fructose and sucrose. People with fructose intolerance are generally more sensitive to other non-digestable carbohydrates, such as polyols (sorbitol, xylitol), raffinose (beans) and inulin (polyfructose) than normal people, see the list below.

Sugars that may or may not be used by HFI or fructose intolerant people

The following tables show different sugars that can be found in the diet and whether or not they cause problems in patients with HFI or fructose intolerance.

Table 1 : carbohydrates that contain or liberate fructose in the small intestine

Other syrups are generally no problem, as they are derived from starch (=glucose). However, sometimes part of the syrup is enzyme treated to make it sweeter. In this process glucose is converted into fructose. HFI patients thus should avoid syrups, unless they are sure that no fructose is formed. This information can be obtained from the producer.

People with normal fructose intolerance often tolerate small amounts of sugar and honey, depending on their individual threshold.

Table 2 : carbohydrates that contain or liberate fructose in the large intestine*

* people with fructose intolerance normally can tolerate some of these compounds, but the threshold is generally low.
** the fructose is not liberated in the small intestine, therefore not absorbed. However, a very small percentage of raffinose may be absorbed. It is thus recommended to avoid these.

In some references it is recommended to avoid ‘oligosaccharides'. Although fructo-oligosaccharides are the most widely used oligosaccharides, they are the only oligosaccharides to avoid. Xylo- and galacto-oligosaccharaides are no problem.

Table 3 : Non-digestible carbohydrates to which everybody is intolerant, but which may cause more problems in people with fructose intolerance than in normal people.

Table 4 : carbohydrates that cause no problems

Non carbohydrate sweeteners : aspartame, acesulfam K, saccharin, cyclamate, thaumatin are no problem for HFI or fructose intolerant people.

For the E-numbers the following should be avoided for HFI patients. For fructose intolerant persons none should be avoided, but people may be more intolerant to the polyols (see table 3).

• E420 : sorbitol
• E473 and E474 : sugar esters
• E491-E495 : sorbitan esters, some sorbitol may be liberated
• E953 : Isomalt

Diet

For an appropriate diet for either HFI or fructose intolerance people should avoid the carbohydrates according to the above tables. As many of these carbohydrates are present in natural sources and are thus not listed on the label, patients should consult a dietician as soon as the diagnosis has been confirmed. HFI patients should always consult a dietician.

Below some natural products that should be avoided, but this list is not conclusive. In doubt ask a dietician or avoid the product.

Some products with fructose and/or sucrose and/or raffinose

• All soft fruits
• All naturally sweet products
• Beans
• Honey
• Banana has some fructose, but can be used by many fructose intolerant people (non HFI)

And all products made with/derived from the above products

Some products high in sorbitol :

• Apples
• Apricots
• Gooseberries
• Grapes (raisins)
• Peaches
• Pears
• Plums
• Raspberries
• Strawberries
• And juices of the above fruits.

Further reading on HFI : http://www.bu.edu/aldolase/HFI/