Allergy Advisor - Allergy and Intolerance Newsletter

Contents
A. Case study
B. Diagnostic testing
C. Treatment
D. More information
E. Editors' comments
F. References
G. CPD questions (South Africa)

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Index

A.Case study
Lactose intolerance is probably one of the most common pediatric referrals dietitians receive. But what if all the typical symptoms are present but the child does not respond to the dietary treatment?

A 2-year-old boy was referred because of lactose intolerance. Even though the patient was referred with a specific diagnosis, the same detailed clinical history as is done at any first consultation was taken. This included anthropometry, a medical history and a dietary history, including recent dietary changes and ensuring dietary adequacy. The patient's mother was also questioned about her son's bowel patterns (including recent changes, consistency and frequency), as well as all the symptoms experienced. The patient presented with chronic diarrhoea and flatulence.

Because lactose intolerance fitted into the picture, a lactose-free diet was introduced, as requested by the doctor. But the diarrhoea did not subside. On the follow-up visit, it was established that the diet was followed strictly at home as well as at the playschool, which the patient had started attending the previous week. It was noted that the symptoms were now more severe over weekends than during the week.

Could this be a food allergy? No immediate reactions to food were experienced, so it was unlikely, but delayed reactions to food should always be considered as a possibility. Tests for allergy were done, but were negative. (This topic will be discussed further in a future newsletter.) The presence of flatulence in addition to diarrhoea indicated that intolerance was a more likely cause.

The mother was asked to complete a food-and-symptom diary while her son still followed the lactose-free diet. At the next visit the diary was scrutinised, and there appeared to be a difference between the amount of fruit juice (mostly apple juice) intake at the playschool and at home. The mother saw fruit juice as a healthy and convenient beverage to offer her son whenever he asked for something to drink. Because apple juice is sweet-tasting, her son liked it. A win-win situation?

What do we know about allergies and fruit juice? Most commercially available fruit juices are manufactured with aseptic heat packaging, a process through which most allergens will be denaturated, except for lipid transfer protein, which occur in apples and other fruit. Thus, an allergy is unlikely. What about intolerance? Apple juice has one of the highest fructose contents among fruit juices and can cause gastro-intestinal (GI) symptoms such as flatulence and diarrhoea, especially in young children, due to malabsorption of fructose. Malabsorption has been found in children with intakes of as little as 15ml fruit juice/kg body weight. So, a case of fructose intolerance?

When fructose was excluded from the diet and lactose reintroduced, the diarrhoea disappeared immediately. Fructose intolerance was diagnosed, and it was then left up to the mother to determine what level of fructose (in diluted form) her son could tolerate.

TIP for Allergy Advisor users:
In Menu I, a search under "apple juice" reveals fructose as a constituent. Clicking on "fructose" brings up a list of symptoms associated with this substance. A quick diagnosis can be made in this way. In dietary management, Allergy Advisor's list of fructose levels in various foods can be used. More information on lipid transfer protein can also be found.

B. Diagnostic testing
One method of confirming fructose malabsorption is to test the breath hydrogen response to a challenge with fructose (although this method is not supported by all).¹ But whereas relatively low doses of fructose may cause an increased breath hydrogen response in a person with fructose intolerance, it should be noted that if a normal person has an abnormally high intake, the response will also be increased. Sensitivity and specificity of the fructose hydrogen breath test were shown in one study to be 98% and 86% respectively. The fructose hydrogen breath test was described as a simple, sensitive and non-invasive method for the diagnosis for this disorder.² Another quick screening test is to check for reducing substances in the stools.

Pathophysiologic causes of acute diarrhoea (e.g., Giardia lamblia infection, antibiotic use) are different from those of chronic diarrhoea (e.g., lactose or fructose intolerance).³ Before embarking on expensive and time-consuming evaluations, a thorough diet history and brief restriction of fruit juice intake may be warranted.⁴

C. Treatment

In many cases removing fruit juice from the diet will be sufficient to alleviate symptoms, but in more severe and prolonged cases dietary exclusion of fructose, sucrose (which is broken down into glucose and fructose) and sorbitol (which converts to fructose) is necessary.^5,6 This should then be followed by a gradual re-introduction of fruit. Initially fruit with a fructose:glucose ratio of 1:1 or less and low sorbitol concentrations (for example grapes) should be allowed. As fructose intolerance can cause symptoms other than diarrhoea, the tolerance threshold needs to be determined gradually.

If tolerated, juices with equivalent fructose-glucose concentrations and low sorbitol concentrations or no sorbitol may be a good substitute for juices containing sorbitol and high concentrations of fructose along with low concentrations of glucose (see below).⁷Juices, because of the relatively high sugar/volume load, are best introduced after a reasonable fruit intake has been established. Because fruit intake is reduced with such a diet, vitamin supplementation might be necessary.

Examples of basic fructose-free diets for HFI can be found on the following web sites: www.bu.edu/aldolase/HFI/treatment/ and www.hfi.ch/eng/diat.htm. Diets for fructose intolerance do not need to be as restricted. Allergy Advisor has a list of fructose levels in foods as well as a fructose-free diet sheet, which lists foods allowed and foods restricted, names on labels indicating fructose, recommended supplements, etc.

D. More information

The over-hasty diagnosis of lactose intolerance in infants and toddlers has probably caused many cases of fructose intolerance to be overlooked. Fruit juice has become a significant part of young children's diets. Many factors may be responsible for this, including children's innate preference for sweetness, parents' perception of fruit juice as a "natural" and "healthy" food, and the convenience of a single-serving juice bottle or box. Marketing surveys have shown that infants consume, on average, 150ml of juice per day, and about 1% consume more than 600ml daily. It was also found that 50% of juice consumed is apple juice.⁸ Even at intakes of 15ml/kg (or 240ml in another study) at a time, which is generally seen as an acceptable serving size, apple juice has been associated with symptoms. Most packaged fruit juices contain between 125ml and 340ml and these would be the amounts a child would drink at one time. Fructose malabsorption can occur as frequently in normal, healthy children and adults as in those with functional bowel disease (such as irritable bowel disease).⁷

This type of fructose intolerance is not to be confused with hereditary fructose intolerance (dicussed below).

How is fructose (mal)absorbed?
The mechanism of fructose absorption is not completely understood. It is proposed that fructose is absorbed by a facilitated transport mechanism via a carrier, but not against a concentration gradient. Another hypothesis (and a mechanism that could operate at the same time as the one described above) is that fructose is absorbed by a disaccharidase-related transport system. This is surmised because the absorption of fructose is more efficient in the presence of glucose, with maximal absorption occurring when fructose and glucose are present in equimolar concentrations. The absorption capacity of fructose is much more complete when fructose is given either as sucrose to be broken down or with glucose than when it is ingested alone. Clinical studies have demonstrated this, with malabsorption being more apparent when the fructose concentration exceeds that of glucose (e.g., in apple and pear juice) than when the 2 sugars are present in equal concentrations (e.g., in white grape juice). However, when provided in appropriate amounts (10 ml/kg body weight), these different juices are absorbed equally well.⁶ As mentioned above, total fruit juice consumption of children has increased, but at the same time the type of juice consumed has also changed. Whereas orange juice was the major juice produced fifty years ago (primarily to prevent scurvy), now apple juice is the juice of choice for the under-5 age group - the result is a higher fructose intake.⁹ Also, fruit juice manufacturers use deflavoured apple juice to flavour many other fruit juices, which increases their fructose content.

It should be noted, however, that a study has shown that freshly pressed and unprocessed ("cloudy") apple juice did not influence stool frequency and consistency, compared with normal, enzymatically processed ("clear") apple juice, which significantly promoted diarrhoea. It was suggested that, in addition to fructose, the increased availability of non-absorbable monosaccharides and oligosaccharides as a result of the enzymatic processing of apple pulp is an important aetiological factor in apple juice-induced chronic non-specific diarrhoea (see below).¹⁰ It should be noted that not all countries use this method of processing fruit juice.

It can therefore be said that a combination of high fructose intake, a high ratio of fructose to glucose, and an individual's relative inability to absorb fructose all contribute to incomplete absorption and loose stools.¹

Sorbitol is a sugar alcohol that also naturally occurs in fruits (and is added to other foods, but not to fruit juice, during commercial processing). Sorbitol is absorbed via passive diffusion at slow rates, resulting in much of the ingested sorbitol being unabsorbed. This is a further possible cause of loose stools, although the quantity of sorbitol in fruits is generally less than that of fructose. ^1,6,11

It has also been shown that chilled fluids stimulate colonic propulsion and the urge to defecate. This may play a role in diarrhoea, as fruit juice is usually given chilled.⁴

Other GI symptoms may be experienced
Unexplained bloating, flatus, and distension are common GI complaints. As already noted, much attention has been paid to lactose intolerance as a potential cause, and fructose intolerance has been neglected. It is suggested that many people with unexplained GI symptoms, including irritable bowel syndrome, have fructose intolerance.¹²

Malabsorbed carbohydrates are osmotically active molecules that draw water inside the lumen of the gut in direct proportion to their amount. The increased volume leads to an increased peristaltic movement and a reduced transit time, decreasing the chance of digestion and/or absorption. The undigested carbohydrates reach the colon and are fermented by bacteria. This bacterial fermentation results in the production of hydrogen, carbon dioxide, methane, and the short-chain fatty acids (acetic, propionic, and butyric). Some of these substances are reabsorbed in the colon, but those remaining unabsorbed can lead to abdominal pain, bloating, cramps, vomiting, malabsorption and metabolic disturbances, including hypoglycemia. Unabsorbed carbohydrates present an osmotic load to the gastrointestinal tract, which causes diarrhoea. If the pH decreases below 5.5, Na+ absorption by the colonic mucosa is disturbed, which further increases stool volume.^13,14

In infants, the main clinical feature of intolerance is the passage of watery stools with an acidic pH, often passed with flatus. Volume is variable and roughly proportional to the amount of malabsorbed carbohydrate that has been ingested.¹³ The intestinal transit in young infants is rapid in any case. Watery stools can thus be passed very frequently. Undigested or unabsorbed sugars, because of their osmotic effect, attract water into the intestine, where they are dissolved into a fluid that distends the gut wall. Increased peristalsis causes the passage of frequent fluid stools. This can quickly cause dehydration and metabolic acidosis. In older children and adults, the capacity to salvage carbohydrates from the large intestine is better developed. Adults with intolerance are thus more likely to complain of abdominal discomfort, borborygmi (rumblings) and flatulence and possibly less likely to have acute, watery diarrhoea.⁶

Non-GIT effects related to fructose intolerance:
Persons with fructose intolerance often develop a powerful aversion to sweet-tasting foods and drinks, including fruit. A reduced incidence of dental caries has also been noted.¹⁴

In isolated studies, fructose malabsorption has been associated with early signs of mental depression and low serum tryptophan concentration. Following a fructose- and sorbitol-reduced diet has been shown to improve mood and early signs of depression.¹⁵

It has been suggested that increases in crying and fussing duration may be an important clinical indicator of carbohydrate malabsorption in infants and that infant colic may be a important factor affecting carbohydrate malabsorption from fruit juices containing sorbitol and a high fructose-to-glucose ratio.¹⁶

Other dietary causes of chronic diarrhoea:
Chronic non-specific diarrhoea (CNSD), also known as toddlers' diarrhoea, is one of the most common problems encountered in pediatric medicine and is most often seen between the ages of 6 and 36 months. The diarrhoea is often brown and watery, at times containing undigested food particles. More than 90% of cases spontaneously resolve before the age of 39 months, and the children grow and develop normally. Some examples of dietary factors that have also been shown to contribute to chronic diarrhoea are malabsorption of carbohydrates (e.g., fructose intolerance), a low fat intake*, excessive fluid intake, food poisoning, excessive intake of carbonated fluids, dietary salicylates, protein intolerance (e.g. cow's milk, soya, and lysinuric protein intolerance#), disaccharide deficiency following gastroenteritis and an excessive intake of nonabsorbable solutes such as sorbitol, magnesium hydroxide, and lactulose. Physical factors such as GI resections may also cause diarrhoea.^7,13,17,18

*Although high fat intake is sometimes implicated as a cause or aggravation of diarrhoea, low fat intake has also been implicated; the suspected mechanism being associated with fat's role in gastric emptying and alteration in intestinal motility (mouth-to-anus transit time).¹⁸

# For more information: www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?222700

What level of fructose is tolerated?
As discussed above, there are many factors that influence whether a person will react adversely to a fructose load. Studies have shown that intakes of 15 ml/kg body weight of fruit juice (with a maximum dose of 375 ml)^19,20 have been associated with increased breath H2 and/or fructose malabsorption symptoms. In other studies the dosages associated with reactions were 240ml⁴ and 250ml.²¹ One out of 3 healthy adults and 2 out of 3 children have been shown to incompletely absorb orally administered 0.7 - 2 g/kg of fructose.⁸ Apple juice was used in most of these studies.

In another study, fructose absorption was studied by the breath hydrogen test in 114 healthy children aged 0.1-6 years. These were given either 2 g/kg or 1 g/kg of fructose. All 57 children given 2 g/kg had peak breath hydrogen excretions > or = 20 ppm. At 1 g/kg, only 25/57 (44%) showed incomplete absorption. The percentage incompletely absorbing fructose and the peak breath hydrogen value were significantly higher in children aged 1-3 years. Interestingly, this age distribution correlates with that of toddlers' diarrhoea.²²

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Index