Fructose Malabsorption

In this article, fructose malabsorption, also known as Dietary Fructose Intolerance (DFI), which is a common cause of diarrhea, is described. Another, rare, Hereditary Fructose Intolerance (HFI), which causes impairment of liver, kidneys and small intestine is much more severe. DFI and HFI are NOT allergies.

In fructose malabsorption fructose can’t be efficiantly absorbed from unknown reason. Transport protein GLUT5, responsible for fructose absorption in the small intestine, may not be present or becomes inactive. People with fructose intolerance have fructose absorption limit lower than 25 grams per serving, but this may differ a lot from person to person. Fructose, unabsorbed in the small intestine, reaches the colon, where bacteria ferment it and yield short chain fatty acids, carbon dioxide (CO2), hydrogen and methane, which cause symptoms. It is estimated that about 1/3 of people are fructose intolerant, and about half of them have symptoms. People with fructose intolerance may be also sensitive to other non-digestable carbohydrates, such as sorbitol and xylitol, raffinose (beans) and inulin (polyfructose), (5).

Who Can Get Fructose Intolerant?

Anyone at any time can develop fructose intolerance. Abnormality or lack of GLUT-5, a fructose transporting protein, may be inherited (5). Other causes, suggested so far:

• family predisposition; 
• overuse of High Fructose Corn Syrup (HFCS), or fruit juices in children (toddler’s diarrhea); 
• small intestinal bacterial overgrowth (SIBO);
• celiac disease; 
• chemotherapy or radiation;
• dumping syndrome (rapid stomach emptying).

What is Fructose? 

Fructose is a monosacharide or single sugar, also called fruit sugar, which naturally occurs in fruits, some vegetables, wheat, honey, sugar cane, sugar beets, and some other plants. Because of wide use of high fructose corn syrup (HFCS) as a sweetener, fructose in now contained in many commercial foods and drinks.

Fructose and glucose have the same cemical formula (C6H12O6), but different molecular structure. They both have  about the same caloric value, but fructose is sweeter. Glucose is metabolised in many tissues, but fructose mainly in the liver. Fructose doesn’t trigger the release of insulin and doesn’t require insulin to enter the cells, so it can be safely used by diabetics. Fructose is not essential nutrient for human though. Foods, high in fructose.

High Fructose Corn Syrup (HFCS)

HFCS can cause diarrhea in some persons with DFI. 

HFCS is a mixture of fructose and glucose, which became widely used as a sweetener, because of increased amount of fructose, which is sweeter than sucrose, and easily blends with foods and drinks. It is derived from corn, by a procedure which converts some glucose into fructose. HFCS55, mostly used in soft drinks, contains 55% of fructose and 45% of glucose, while HFCS42, used in baked and other products, contains 42% of fructose and 58% of glucose.

HFCS is present in soft, fruit and sports drinks, baked goods, candies, jams, yogurts, condiments, canned and packaged foods, and other sweetened foods.

HFCS was “generally recognisied as safe” (GRAS) by FDA, US Federal Drug Administration (6). HFCS can cause diarrhea in fructose intolerant persons though.

Sucrose

Sucrose is generally well tolerated by most persons with DFI.

Sucrose, known as table or white sugar, is a disaccharide that contains equal parts of glucose and fructose, and is found naturally in sugar cane and sugar beets.

Fructans

Fructans can irritate the DFI person the same way as fructose. Fructans are molecules composed from several molecules of fructose with glucose on the end. Foods high in fructans.  

Sorbitol

Sorbitol, when ingested in excess can cause diarrhea at anyone, especially in persons with DFI. 

Sorbitol (C6H14O6), also named glucitol, is a sugar alcohol derived from glucose. It is used as an artificial sweetener in ”diet soda”, ice cream, chocolate, and other sweets, in “sugar free” chewing gum, gels, or as a moisture stabilisator in baked products. On labels it can be referred as humectant, sweetener, emulsifier, or as E420. It’s calory value is 2.6 calories/g (sugar has 4 cal/g). It is also in the cough syrup, and it is used as a laxative. Sorbitol naturally occurs in stone fruits, apples, pears, raisins, and in some fruit juices (foods high in sorbitol), (9,10). It is poorly absorbed in the small intestine. Excessive amount of ingested sorbitol drags water into intestine and causes osmotic diarrhea; even 10g of sorbitol (1 stick of chewing gum contains 1.25g of sorbitol) can cause prominent diarrhea in a child. Consuming 20g of sorbitol daily was reported to cause chronic diarrhea and weight loss in adult (13). Persons with fructose intolerance are often excessively sensitive to sorbitol. Sorbitol, absorbed in the small intestine may be partly converted to fructose in the cells, so persons with hereditary fructose intolerance (HFI) should avoid it. Other sugar alcohols (polyols) are mentioned below in FODMAPs.

FODMAPs

FODMAPs stands for Fermentable Oligo-, Di- and Mono-saccharides And Polyols. Oligosacharides and polyols are generally poorly absorbed in any healthy person, but disaccharides and monosaccharides are poorly absorbed only in persons with sugar intolerances. FODMAPs, when not absorbed in small intestine, reach the colon, where they are fermented by bacteria, which break them down and produce gas. They also cause osmotic diarrhea.

Main FODMAPS used in diet:

• Oligosaccharides: fructans, galactans (galactose chain + glucose, in legumes), raffinose (composed of galactose, fructose, and glucose; can’t be digested by human, found in beans, cabbage, brussels sprouts, broccoli, asparagus, and whole grains)
• Disaccharides: sacharose (sucrose), lactose (milk sugar), maltose (from malt, in beer)
• Monosaccharides: glucose (dextrose), fructose, galactose
• Polyols (sugar alcohols): sorbitol, mannitol, xylitol, isomalt, maltitol, and less frequetly used: arabitol, erythritol, glycol, glycerol, lactitol, ribitol

Fructose Absorption

Fructose can be absorbed in the small intestine without the help of any enzyme. In the clinical trial, performed in University of Iowa, it was shown, that a small intestine of a healthy person can absorb about 25 g of fructose at one time (glass of orange juice or a can of Coke contain about 15 g of fructose) (1). Glucose enhances absorption of fructose, so fructose from table sugar, which is composed from equal amounts of fructose and glucose is generally well absorbed. Greater the fructose/glucose ratio in the food, harder the fructose will be absorbed (2).

Symptoms of DFI 

Symptoms of DFI may show up at any age. They appear within few hours after the meal, containing fructose. The threshold for the symptoms may be as low as 1g of fructose in some persons with DFI, or as high as 20 g in others. Bloating, abdominal gurgling, flatulence, pain, diarrhea, and aversion to sweet-tasting foods are most common symptoms. Less frequently depression, fatigue, headache, craving for sugar, and weight loss appear.

Since fructose in absence of glucose is slowly absorbed, it waits in the small intestine for a long time and attracts water from intestinal wall, what causes osmotic diarrhea. This shorten the intestinal transit time, and some micronutrients (iron, vitamins) may have not enough time to be absorbed, so anemia and various nutrient deficiences may appear. 

Picture 1. Apples and pears have a high fructose/glucose ratio

Lab Findings in DFI 

Fructose malabsorption was found to be correlated with folate deficiency (low plasma folic acid levels) in some cases, supposedly due to changed intestinal flora (intestinal bacteria produce considerable amount of folic acid), (3). Plasma zinc, iron, calcium, vit C and E, triptophane and glutathione may also be lowered, and amylase, lipase and triglicerides may be elevated (4,7). ”Fructose deficiency”, on the other hand, doesn’t exist since fructose isn’t an essential nutrient in human.       

Toddler’s Diarhea

Small children between 2 and 5, which are fed with large amounts of fruit juices, can develop the so called toddler’s diarrhea. This occurs, because a not fully developed intestine of a small child can’t absorb great amounts of fructose, which then stays in the intestine, drags water from the intestinall wall and causes diarrhea. The child is otherwise healthy, grows normally, and does not lose weight. The treatment is with limiting fruit juices and offering milk and other fructose-free drinks instead. Some weeks or few monts may be needed before the normal bowel habit is established.

Fructose Intolerance or IBS?

In another clinical trial, a group of persons with a diagnosis of IBS, were tested with hydrogen breath test with fructose, and 30% of them were found to be fructose intolerant (1,12). Many people with IBS complain that they cannot digest fruits properly, and also have problems with other foods. For such persons a fructose-free diet would be worth to try.

Diagnosis by Hydrogen Breath Test with Fructose

Hydrogen breath test with fructose is the most accurate test for fructose intolerance. 98% sensitivity and 86% specificity of the fructose hydrogen breath test were shown in one study (7). A meal, rich in fructose, is ingested. If fructose isn’t absorbed in the small intestine, it will reach the colon, where bacteria will break it down and produce hydrogen and methane. These gases will be absorbed into the blood and will appear in expired air. 

Procedure. After fructose meal, patient breaths into a testing machine in 30 min intervals; test takes about three hours to be completed (1). From amount of hydrogen and methane in exhalled air, the extent of fructose intolerance can be determined. 

How to prepare for the test?

Additional hydrogen breath tests can be done to exclude other causes of diarrhea:

• lactose breath test to exclude lactose intolerance
• lactulose breath test to exclude small intestinal bacterial overgrowth (SIBO);
• sucrose breath test;
• 3C stable Radioisotope breath tests for children and pregnant women.

Reducing Substances

Reducing substances in the stool (lactose, fructose, glucose, lactose) is a screening test for carbohydrate malabsorption.

Treatment 

Treatment of the cause doesn’t exist at the time. Enzymes, which would help in absorbing fructose are investigated.

Diet in Fructose Intolerance

The basis of diet in Fructose intolerance is avoiding foods wit high fructose, high fructose : glucose ratio, fructans or sorbitol. 

In toddlers, eliminating fruit juices, especially apple and pear juice, may be enough to releave diarrhea.

Foods to eliminate in Dietary Fructose Intolerance:

• most fruits and fruit juices;
• High Fructose Corn Syrup - HFCS (sweetened carbonated/milk/soy beverages, breakfast cereals, and yogurts, flavoured water, beer, sweetened wine);
• low calory and diabetic products
• honey;
• commercialy baked products and breaded meats;

 Additional foods to eliminate in more prominent Dietary Fructose Intolerance:

• table sugar (sucrose, sacharose), inverted sugar (F:G=1:1); 
• wheat (pasta and white bread)
• whole grain bread

Foods generally well tolerated in DFI:

• meats (unbreaded and non-processed), poultry, fish and shellfish, crab, crayfish; 
• green leafy vegetables, potatoes, white rice, green beans, broccoli, cauliflower, lettuce (except iceberg), white cabbage without added sauces;
• cranberries, avocado, bananas;
• dairy products (except in lactose intolerance)
• sucrose (small amounts)

Details of low fructose and fructose free diet 

Vitamins and Mineral Replacement in DFI

A person with DFI often has deficiency of vitamins C, E, and folate, and minerals calcium, iron, and zinc. These nutrients have to be replaced with supplements, which (read labels!) don’t contain fructose or sorbitol as a sweetener (often in supplements for children).  

Dextrose

Dextrose is commercially available pure glucose. Dextrose can be used by fructose intolerant persons to help in fructose absorption when eating fructose containing foods.

References:

1. http://www.uihealthcare.com/kxic/2008/06/fructose.html  FRUCTOSE INTOLERANCE CLINICAL TRIAL
2. http://www.healthsystem.virginia.edu/internet/digestive-health/nutrition/BarrettArticle.pdf TABLE SUGAR, FRUCTOSE/GLUCOSE RATIO
3. http://www.clinchem.org/cgi/content/full/45/11/2013  FRUCTOSE MALABSORPTION AND FOLATE DEFICIENCY
4. http://www.uihealthcare.com/topics/medicaldepartments/foodandnutrition/dfi/whatisdfi.html  LAB FINDINGS IN DFI
5. http://www.food-info.net/uk/intol/hfi.htm  GLUTE5, FRUCTOSE TRANSPORTER
6. http://www.ific.org/publications/qa/fructoseqa.cfm?renderforprint=1  FDA about HFCS, AND OTHER FACTS ABOUT FRUCTOSE
7. http://www.foodintol.com/sugar.asp  DFI MAY CAUSE CALCIUM DEFICIENCY AND OSTEOPOROSIS
8. http://www.allergyadvisor.com/Educational/sept2002.htm SPECIFITY AND SENSITIVITY OF HYDROGEN BREATH TEST
9. http://www.fructose.at/pdf/booklets/fructose_tabelle.pdf  FRUITS HIGH IN SORBITOL
10. http://www.food-info.net/uk/intol/hfi.htm  PROBLEMATIC SUGARS IN DFI
11. http://www.healthsystem.virginia.edu/internet/digestive-health/nutrition/low-fructose-diet.pdf DIET IN DFI
12. http://www.ncbi.nlm.nih.gov/pubmed/18223504  IBS vs DFI
13. http://www.medscape.com/viewarticle/568700  SORBITOL CAN CAUSE WEIGHT LOSS