Today's Dietician - Not So Sweet: Fructose Malabsorption

Here is a great article from this month's issue of Today's Dietician...

September 2011 Issue

Not So Sweet: Fructose Malabsorption 

By Lisa S. Brown, PhD, RD, and Nina 

Current Today’s Dietitian Vol. 13 No. 9 P. 70

Suggested CDR Learning Codes: 2000, 3005, 5110, 5220, 5290; Level 2

An 87-year-old woman presented with a history of gastric distress. She’d been experiencing chronic diarrhea for the past 30 years, with bouts increasing from a few times per month to several times per week. Previously she’d screened negative for celiac disease and a trial gluten-free diet had no effect. She’d tested positive for lactose intolerance and had been on a low-lactose diet for approximately 10 years, which had been helpful, though symptoms persisted.

As a last resort, her doctor sent her to a dietitian who, based on the medical history and symptoms, immediately initiated a low-fructose diet to see whether the client might have fructose malabsorption (FM). Almost immediately, the woman experienced reduced symptoms, which cleared up completely within a few months as the dietitian continued to work with the woman and her family to reduce her dietary fructose exposure.

This case shows how FM, formerly known as dietary fructose intolerance, often goes undiagnosed. Although it affects between 30% and 80% of the adult population and an unknown percentage of children, it has stayed beneath the radar.

Dietitians can play an important role in identifying individuals who should be tested for FM and an even more important role in treating the condition. This article will evaluate the pathophysiology of FM, the profile of those most likely to suffer from it, and the symptoms, diagnosis, and treatment of the disorder.

Fructose Explained
Fructose is a monosaccharide commonly found in naturally sweet foods, foods with added sugar, and as part of an oligosaccharide chain called a fructan. Foods that naturally contain relatively high amounts of fructose include honey, fruit, fruit juices, molasses, maple sugar, agave nectar, and some root vegetables such as sweet potatoes. Fructose is also found in refined sugars commonly added to food, including sucrose and high-fructose corn syrup (HFCS).

Sucrose (table sugar) is derived from sugar cane and sugar beets and contains approximately half glucose and half fructose. HFCS is an artificially created sugar that also contains glucose. The percentage of glucose and fructose varies depending on the application in a food product. Soft drinks, for example, generally contain a HFCS solution of 55% fructose and 42% glucose, while HFCS found in baked goods most commonly contains a ratio of 42% fructose and 53% glucose.

Fructans, the most common of which is inulin, are found in wheat and certain vegetables, including onions, leeks, and asparagus.1

Although fructose has been part of the human diet for thousands of years, the amount consumed by the average American has increased considerably over the past 40 years. This is due to an overall increase in the total amount of refined sugar that Americans consume as well as an exponential increase in the amount of HFCS as a percentage of that total.

Between 1970 and 1999, the consumption of total caloric sweeteners per person per year increased by approximately 27%—from 119.1 lbs to 151.3 lbs. The amount of total caloric sweeteners consumed has decreased since its peak in 1999, with the latest available figures for 2010 showing that the average American consumed 131.9 lbs, but the amount of HFCS consumed remains significantly higher than in the 1970s when it was virtually nonexistent. HFCS consumption grew from 0.5 lbs per person in 1970 to 63.7 lbs in 1999, its peak year. In 2010, the latest year for which statistics are available, consumption of HFCS dropped to a 21-year low of 48.9 lbs per capita. But that still represents a nearly 10,000% increase over 1970 levels.2

These statistics illustrate a dramatic rise in fructose consumption over the past several decades; however, studies show that the human ability to absorb fructose hasn’t changed and that most individuals have a limited ability to process fructose in the small intestine.1,3 Given the clash of food technology with human biology, we should expect, and are seeing, a corresponding rise in symptoms of fructose malabsorption—the 87-year-old patient in our example illustrates this well. Dietitians are likely to see more patients like this one and are uniquely qualified to treat them.

Pathophysiology
It’s important to distinguish FM from the genetic disorder hereditary fructose intolerance (HFI). FM occurs when an individual doesn’t absorb all the fructose present in the small intestine. The primary problem is a limited absorptive capacity for dietary fructose in the small intestine, but in some individuals, the problem appears to be caused or exacerbated by a secondary problem of bacterial overgrowth in the small intestine.1 FM is generally diagnosed in adulthood but also has been observed in children.

It’s thought that limited absorptive capacity for fructose is actually the norm based on the observation of the transport systems available for fructose. Fructose is transported in the intestine primarily by the facilitative glucose transporters type 2 and 5 (GLUT2 and GLUT5). GLUT2 is the preferred carrier when fructose is linked to glucose, while GLUT5 is utilized by free fructose. GLUT5 capacity appears to be more limited than GLUT2, causing free fructose to be more difficult to absorb than fructose bound to glucose.

People with FM can tolerate some amount of fructose each time they eat, but if the amount they consume is greater than the number of transporters available, a portion of the fructose continues on to the large intestine. This unabsorbed fructose creates an osmotic load and is fermented by bacteria in the large intestine, causing a wide range of primarily gastrointestinal symptoms.1,3

If an individual has significant bacterial overgrowth in the small intestine, fermentation may occur regardless of whether there are enough transporters for the fructose load. In this case, all fermentable carbohydrates are a potential problem for the individual, not just fructose. It’s important to determine whether such bacterial overgrowth is part of a patient’s etiology because if so, it would modify the treatment plan to include the limitation of a broader group of carbohydrates known as Fermentable Oligo-, Di-, and Mono-saccharides, and Polyols (FODMAPs). These include lactose, fructose, fructans, sugar alcohols, and galactans1 and will be discussed briefly in the Treatment section.

HFI is distinct from FM and must be differentiated as a separate disease state. HFI is an autosomal recessive genetic disorder usually identified in infancy. It’s caused by a lack of the enzyme aldolase-B, which 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, leading to severe hypoglycemia following the consumption of fructose. If left untreated, it can lead to organ failure and death. The only treatment for HFI is avoiding dietary fructose to as great a degree as possible.4

Demographics
All population subgroups appear to be equally afflicted by FM, although women and individuals with lactose intolerance appear to be more susceptible.5

As mentioned, FM has been estimated to affect from 30% to 80% of the adult American population (this wide range is discussed later), but it’s also been observed in children with a history of chronic gastric distress. It’s possible that healthy children also experience FM if the load is great enough, but there are currently no peer-reviewed studies that have investigated this.

A 2011 study investigated the prevalence of FM in a symptomatic pediatric population and found that many children who present with common gastrointestinal complaints test positive for FM.6 The researchers also found that a positive hydrogen breath test (discussion follows) was strongly related to age of the child, with younger children more likely to test positive. In this study, positive tests were recorded as follows:

• 88.2% of symptomatic infants under age 1;
• 66.6% of 1- to 5-year-olds;
• 40.4% of 6- to10-year-olds; and
• 27.1% of 10- to 15-year-olds.

The prevalence of FM in a healthy pediatric population is undetermined.

It’s currently unclear whether adults’ capacity to absorb fructose decreases over time, but the study discussed previously showed that the ability to tolerate fructose may increase with age from infancy through age 15.6 The mode of diagnosis and application of different testing procedures most likely accounts for the wide range of estimates in adults. A diagnosis may be based solely on clinical symptoms or a formal diagnosis may be done based on a hydrogen breath test. If testing is based on clinical symptoms, approximately 30% of adults appear to be affected. However, randomized testing using a breath test in a healthy population has found the prevalence to be somewhere between 66% and 80%, although most subjects who test positive aren’t clinically symptomatic.3,7

One small study published in 2005 tested 15 healthy volunteers to determine whether average amounts of ingested fructose resulted in excess hydrogen production in their intestinal tracts, a sign that some fructose was fermented by bacteria instead of absorbed in the small intestine. Of the 15 subjects, one-half showed signs of malabsorption following a 25-g fructose load, and two-thirds were affected by a 50-g load.8 A 2007 study of 20 subjects found that only two individuals tested positive with a 25-g load but had no clinical symptoms, while a 50-g load resulted in 16 subjects (80%) testing positive, although only 55% of these subjects were clinically symptomatic.3

Based on available food consumption data, it wouldn’t be unusual for an individual to consume 50 g of fructose per day or more. A 2009 study by Marriott and colleagues used 1999-2004 National Health and Nutrition Examination Survey data to estimate that fructose intake in the American diet is 48.6 g/day on average for women and 62.8 g/day for men, with some individuals consuming more than twice the average.8 Major sources of fructose were sugar-sweetened beverages and other foods with added sugar.

Diagnostic Procedures
• Breath test: Although hydrogen breath testing is considered the gold standard, results differ based on the dose of the fructose load given. Dosage may vary from 15 g to 100 g; 25 g and 50 g are most commonly used. To further complicate matters, no standard cutoff has been established for the level of hydrogen exhaled, so a diagnosis is left to the discretion of the individual doctor.9

A 2008 article by Eisenmann and colleagues described best practices in hydrogen breath testing. The authors advised patients to fast for at least 12 hours before undergoing a test and avoid both smoking and chewing gum. The authors further cautioned that taking antibiotics or having a colonoscopy up to one month before the test and taking laxatives up to three days before could distort the results.

Overall, an increase of more than 20 ppm indicates a positive test. If a test is negative but the individual still experiences symptoms, it’s possible the duration of the test wasn’t sufficient (tests are generally two hours) or that the individual didn’t produce hydrogen. Trial diets may be helpful in these cases to determine if there’s a link between the suspected nutrients and the symptoms.

Your client’s doctor also may use hydrogen breath tests to determine if the individual has significant small intestine bacterial overgrowth and lactose intolerance. A load of oral lactulose is given to test for bacterial overgrowth and a load of lactose may be used to determine lactose intolerance. Finally, a test to determine if the individual has celiac disease can help the dietitian figure out which carbohydrates to restrict.

• Elimination diet: If the dietitian initiates an elimination diet for the purposes of diagnosis, strict protocols should be set up to ensure the client doesn’t spend an extended amount of time on a severely restricted diet. The dietitian should begin by removing all identified sources of fructose and monitoring symptoms. You also may choose to restrict other carbohydrates if broader intolerance is suspected and slowly reintroduce classes of carbohydrates to determine which, if any, cause symptoms. Generally this will mean a low-carbohydrate diet for the client until it’s determined which carbohydrates are “safe.”

You may recommend a multivitamin and possibly fiber supplementation if the restricted diet will last more than a few weeks. Coordination with the client’s medical doctor is extremely important in these early stages.

To avoid fructose, all sources of wheat, fruits, and some vegetables are restricted in addition to any sources of added sugar. If no other carbohydrate restrictions are indicated, then the client can continue consuming dairy products and some grains, including rice. If all potential sources of fermentable carbohydrates are restricted, then the client shouldn’t have lactose-containing dairy, beans, any kind of sugar, wheat (including pasta), fruits, or vegetables. (More information on a low-fructose diet is given in the Treatment section.)

Having the client keep a food/symptom diary is very helpful during this stage. Meeting with the client weekly will help ensure that he or she is following the diet correctly and will minimize the time spent on the restricted diet. If it’s not possible to meet with the client weekly, the follow-up shouldn’t be delayed for more than one month, and, if possible, the dietitian should use an alternative means of communication with the client such as e-mail.

If the client has FM, symptoms likely will abate within one week; however, a client may need up to six to eight weeks to determine if fructose restriction is helpful, especially if other carbohydrates also cause symptoms.1 If no change occurs after six to eight weeks, the diet should be discontinued. Symptoms of FM can vary from common gastrointestinal complaints, such, as reflux, bloating, gas, nausea, diarrhea, and constipation, to less obviously associated complaints such as depression.10 In children, FM is associated with similar gastrointestinal symptoms and may be an underlying cause of infant/toddler diarrhea once they begin consuming juice in addition to other fruits and vegetables.

Treatment 
Despite a straightforward-sounding diagnosis, understanding the treatment of FM can be complex. One complicating factor is the need to modify the treatment plan for individual factors, including the client’s unique threshold for fructose, as well as limiting or eliminating other carbohydrates to which an individual may be sensitive.

It’s not clear what percentage of individuals have more than one form of carbohydrate intolerance, but it appears likely that many symptomatic individuals are at high risk for multiple problems. Even if the diagnosis is limited to FM, currently there’s no standardized treatment protocol and the information on what to avoid is often contradictory. Here, dietitians have a great opportunity to add to the establishment of evidence-based protocols by keeping scrupulous records, closely following their patients, and sharing their information with others.

The focus of treatment should be on relieving symptoms while maintaining a nutritionally adequate diet. However, you must begin by establishing the severity of the condition. If available, find out from the doctor the precise fructose load used in testing. A client who malabsorbs and is symptomatic after a 25-g load will need more severe restriction; a client who malabsorbs on a 50-g load but is fine with a 25-g load can tolerate fairly generous amounts of fructose and may need to avoid only highly concentrated sources, such as soft drinks and juice.

Once the level of FM has been determined by a breath test or dietary manipulation, the dietitian should work with the client to set up a diet plan in which healthy food sources of fructose, such as fruits, vegetables, and whole grain wheat, are spread evenly throughout the day. Unlike lactose intolerance, individuals don’t appear to adapt to consuming dietary fructose, so treatment shouldn’t include a regular dietary dose of fructose designed to enhance ability to tolerate it.11

The dietitian needs to educate clients and their families about dietary sources of fructose and screen their diet to determine the major sources of fructose and help them identify acceptable substitutions. Once this has been accomplished, you should continue to work with clients to establish a dietary pattern that controls symptoms while allowing the broadest range of nutrient-dense foods possible.

Diet therapy begins with removing any foods high in added sugar. Sugar-sweetened beverages, especially soft drinks, sports drinks, and juices, are primary sources of fructose.7 Any food with added sugar, including baked goods, candy, and ice cream, also should be identified and limited from the start. It’s least desirable to limit fruits and vegetables, but if the client continues to be symptomatic after removing refined sugar or if he or she is following a restricted diet for diagnostic purposes, you may want to conduct a trial period in which fruits and vegetables are limited as well.

Once symptoms subside, you can slowly reintroduce foods, beginning with the fruits and vegetables eliminated during the trial period. If the client wishes, you also may reintroduce foods with added sugar once the client’s symptoms are under control. It’s helpful if they avoid HFCS and focus on foods with cane or beet sugar instead, since fructose is better tolerated when it’s bound to glucose, as is the case with sucrose.

Sources give conflicting information regarding which fruits to restrict based on whether they are giving recommendations for total fructose content or free fructose content (fructose that’s not bound to glucose). Barrett recommends focusing on fruits high in free fructose, which include watermelon, pineapple, peaches, mangoes, apples, pears, and honeydew.1 Fruits that may be better tolerated include berries, plums, kiwi, bananas, and most citrus fruits.1

Clients should be encouraged to consume fruit in its whole form instead of dried or juiced to avoid an overconcentration of fructose in the gut at one time. The same controversy exists regarding which vegetables to restrict. Some sources recommend restricting root vegetables such as sweet potatoes. Advocates of restriction based on free fructose content target only onions, leeks, asparagus, and artichokes. Concentrated tomato products also should be limited, including sauce and salsa.

Clients should be warned that sauces and condiments may be a problem because they often contain added sugar and because tomato has been associated with symptoms. Avoiding inulin, which is commonly added to processed food products, including yogurt, may also be helpful because it’s a fructan.

Some individuals find it helpful to limit foods in which wheat is a primary ingredient, since wheat contains fructans, but individual toleration varies. Many individuals can tolerate some fructose as long as they don’t get too much at one time. Eating fructose in forms where it’s combined in an equal balance with glucose and eating fructose with other foods to slow the absorption may also help reduce symptoms of malabsorption.

Finally, there’s some information available from Internet blogs that suggests using a concentrated glucose dose, which can be found in certain candies, to offset fructose consumed. At this time, there’s no evidence to support this practice and more research is necessary to see if it has a biological effect or simply creates a placebo effect. Dietitians should caution someone trying this technique.

Patients with gastrointestinal problems of long duration are some of the unhappiest people you’ll encounter in your professional career. The bewildering variety of debilitating symptoms, the multiplicity of potential causes, and the still-incomplete protocols for treatment can frustrate patients and lead them to try unsound and perhaps dangerous self-treatment. Or they may simply tolerate a curable condition for years, like our 87-year-old diarrhea sufferer. It’s understandable but regrettable that no one suspected FM earlier in this patient’s treatment.

As dietitians, we can play a vital role in helping such people. With the unprecedented increase in fructose consumption over the past four decades, there are many people who need our help. It’s an opportunity to refine our skills, interact with medical professionals, care for patients, and improve the overall practice of dietetics by adding to the growing body of evidence on this disorder.

— Lisa S. Brown, PhD, RD, is an assistant professor of nutrition at Simmons College in Boston.

— Nina Current is a graduate student in the nutrition and health promotion program at Simmons College.

Learning Objectives
After completing this continuing education activity, the student should be able to:
1. Evaluate several common symptoms of fructose malabsorption (FM).
2. Assess the reasons for the increased prevalence of FM in American adults.
3. Distinguish between FM and hereditary fructose intolerance.
4. Provide basic dietary guidance necessary for the treatment of FM.

Examination
1. The reason more American adults are likely presenting with symptoms of fructose intolerance is:
a. an increase in the amount of dietary fructose consumption over the past 40 years.
b. an increased prevalence of autoimmune disease in the American population.
c. increased damage to the gut due to exposure to toxic heavy metals.
d. All of the above

2. Fructose malabsorption (FM) was formerly known as:
a. dietary fructose intolerance.
b. hereditary fructose intolerance.
c. dietary fructose rejection.
d. inherited fructose disease.

3. FM is formally diagnosed using:
a. a fructose-free diet with symptom assessment.
b. a blood test measuring free fructose in the blood.
c. a sugar-free diet with symptom assessment.
d. a hydrogen breath test following a fructose test load.

4. The treatment of FM includes:
a. limiting all dairy products in the diet.
b. limiting milk and soft cheeses in the diet.
c. limiting refined sugars in the diet.
d. timing medication with meals.

5. The most common source of dietary fructose in the American diet is:
a. bacon.
b. milk.
c. rice.
d. soft drinks.

6. A fruit that’s relatively low in fructose is:
a. apples.
b. strawberries.
c. peaches.
d. watermelon.

7. Symptoms of FM may include:
a. gastrointestinal upset, including nausea and diarrhea.
b. constipation.
c. depression.
d. All of the above

8. Dietitians should alert their clients to hidden sources of fructose, including:
a. spices.
b. condiments and sauces.
c. food preservatives.
d. soy products.

9. A diagnosis of FM is:
a. based on clear guidelines from the American Medical Association.
b. not currently standardized.
c. difficult because of the association with lactose intolerance.
d. not possible in older individuals.

10. Dietary intake of fructose is better tolerated if:
a. the fructose is consumed when linked to glucose.
b. the fructose is consumed with sorbitol.
c. the fructose is consumed alone.
d. the fructose is consumed with lactose.

References
1. Barrett JS, Gibson PR. Clinical ramifications of malabsorption of fructose and other short-chain carbohydrates. Nutrition Issues in Gastroenterology. 2007:51-65. Available at: http://www.mecfs-vic.org.au/sites/www.mecfs-vic.org.au/files/Article-BarrettPractGastro.pdf. Accessed April 25, 2011.

2. U.S. Department of Agriculture Economic Research Service. Sugar and sweeteners: Recommended data, Table 50: U.S. per capita caloric sweeteners estimated deliveries for domestic food and beverage use, by calendar year. Updated July 18. Available at: http://www.ers.usda.gov/Briefing/Sugar/Data.htm#. Accessed July 20, 2011.

3. Rao SS, Attaluri A, Anderson L, Stumbo P. Ability of the normal human small intestine to absorb fructose: Evaluation by breath testing. Clin Gastroenterol Hepato. 2007;5(8):959-963.

4. Mayatepek E, Hoffmann B, Meissner T. Inborn errors of carbohydrate metabolism. Best Pract Res Clin Gastroenterol. 2010;24(5):607-618.

5. Mishkin D, Sablauskas L, Yalovsky M, Mishkin S. Fructose and sorbitol malabsorption in ambulatory patients with functional dyspepsia: Comparison with lactose maldigestion/malabsorption. Dig Dis Sci. 1997;42(12):2591-2598.

6. Jones HF, Burt E, Dowling K, Davidson G, Brooks DA, Butler RN. Effect of age on fructose malabsorption in children presenting with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. 2011;52(5):581-584.

7. Beyer PL, Caviar EM, McCallum RW. Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults. J Am Diet Assoc. 2005;105(10):1559-1566.

8. Marriott BP, Cole N, Lee E. National estimates of dietary fructose intake increased from 1977 to 2004 in the United States. J Nutr. 2009;139(6):1228S-1235S.

9. Eisenmann A, Amann A, Said M, Datta B, Ledochowski M. Implementation and interpretation of hydrogen breath tests. J Breath Res. 2008;2(4):046002.

10. Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG. Review article: Fructose malabsorption and the bigger picture. Aliment Pharmacol Ther. 2007;25(4):349-363.

11. Szilagyi A, Malolepszy P, Yesovitch S, et al. Fructose malabsorption may be gender dependent and fails to show compensation by colonic adaptation. Dig Dis Sci. 2007;52(11):2999-3004.