C H A P T E R

13Specialty Foods for Children with Cystic

FibrosisMegan Elizabeth McGuckin1, Ronald Ross Watson2

1University of Arizona, Department of Immunobiology, USA; 2University of Arizona, Mel and Enid Zuckerman College of Public Health, Tucson, AZ, USA

13.1 CYSTIC FIBROSIS

Cystic fibrosis (CF) is a chronic, heritable disease that mainly affects the lungs and digestive system. A mutation of the Cystic Fibrosis Transmembrane Regu-lator (CFTR) gene causes the body to produce unusu-ally thick, sticky mucus. This mucus can clog the lungs, leading to life-threatening lung infections, and obstruct the pancreas, stopping natural enzymes from helping the body break down and absorb food. The CFTR gene provides instructions for making a chan-nel that transports negatively charged particles called chloride ions in and out of cells [1]. Chloride has important functions in cells; for example, the flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. Mutations in the CFTR gene disrupt the function of the chloride channels, prevent-ing them from regulating the flow of chloride ions and water across cell membranes. As a result, cells that line the passageways of the lungs, pancreas, and other organs produce mucus that is unusually thick and sticky. This mucus clogs the airways and various ducts, causing the characteristic signs and symptoms of cystic fibrosis [2]. Symptoms of CF include delayed growth, cough, sputum production, wheeze, chest tightness, difficulty breathing/shortness of breath, fever, and repeated inflammation of the pancreas (pancreatitis) [3]. CF affects about 70,000 children worldwide without a cure, so there are major focuses on reducing symptoms in children with foods, supple-ments, and nutrients.

Diet and Exercise in Cystic Fibrosishttp://dx.doi.org/10.1016/B978-0-12-800051-9.00013-4

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13.2 NUTRITIONAL AND GROWTH PROBLEMS ASSOCIATED WITH CYSTIC

FIBROSIS

Children with CF are diagnosed in early childhood by poor growth and lack of development. Weight loss and difficulty gaining or maintaining weight are common problems for many people of all ages who have CF [4]. This is due to the mutation on the CFTR gene, which reg-ulates negatively charged chloride ions in cells that allow the movement of water, which creates thin, free-flowing mucus. However, the mutation on the CFTR gene dis-rupts the function of the chloride channels, which essen-tially disrupts the body’s ability to produce thin mucus [2]. Cells that line organs, such as the pancreas, produce mucus that is unusually thick and sticky [2]. As a result, the pancreas is unable to release enzymes that aid in digestion, and hormones such as insulin. Because of the inability of the pancreas to release sufficient digestive enzymes, children with CF have very reduced absorption of proteins, vitamin A, vitamin C, vitamin E, zinc, omega 3 fatty acids, docosahexaenoic acid, garlic, ginseng, and curcumin, all of which may help absorption by supple-mentation [5]. The reduced pancreatic enzymes usually cause digestive problems in people with CF, and can lead to diarrhea, malnutrition, poor growth, and weight loss [2]. CF patients also have an inability to retain salt. A common indication of CF in infants is that they may have a salty frosting on their skin or their skin tastes salty. They also may lose abnormally large amounts of body salt when they sweat on hot days [6]. This is due to altered epithelial cell function in the sweat glands. This genetic

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13. SPECIALTY FOODS FOR KIDS WITH CYSTIC FIBROSIS102

mutation not only affects the dietary needs of children with CF, but it also affects their basic daily requirements.

13.3 CYSTIC FIBROSIS-RELATED DIABETES MELLITUS

As a result of the thick, sticky mucus, the pores and ducts of the pancreas become clogged. This pre-vents not only the release of digestive enzymes but also the release of hormones like insulin. When the mucus blocks the ducts of the pancreas, production of insulin is halted. In adolescence or adulthood, a short-age of insulin can cause a form of diabetes known as cystic fibrosis-related diabetes mellitus (CFRDM) [2]. CF patients usually develop this type of diabetes in their 20s, and more develop the disease after 30 years of age [7]. CFRDM has features of both type I diabe-tes (insulin-dependent diabetes) and type II diabetes (noninsulin-dependent diabetes). People with CF are unable to make enough insulin, as a result of scarring and excess, thick mucus on the pancreas. Insulin resis-tance develops in CFRDM [8]. Insulin resistance can develop as a result of chronic infections, high levels of cortisol (a hormone that the body secretes in response to stress), and frequent exposure to corticosteroids, which are anti-inflammatory drugs sometimes used in the treatment of lung conditions that mimic the action of cortisol [8]. Treatment of CFRDM includes a combi-nation of insulin, exercise, and diet. The diet for peo-ple with CFRDM is different than the calorie-restricted diet typically prescribed for people with other types of diabetes. Despite their diabetes, people with CF must maintain a high-calorie, high-fat diet and compensate by adjusting insulin doses [8]. This treatment allows sugars and proteins to move from the blood into the body’s cells. It is used for energy and to build muscle. Keeping blood glucose levels at a normal level (or near normal levels) helps in weight gain and the produc-tion of more energy. It also lowers the risk of problems that diabetes can cause [9]. So, due to the effects of the mutation on the CFTR gene, people with CF are forced to alter their diets—regardless of the presence or lack of CFRDM.

The ducts in the pancreas of children with CF become clogged with thick, sticky mucus, reducing the released enzymes necessary for digestion. Not only is the body unable to digest sufficient essential nutrients, but also the body cannot adequately collect and use these essential nutrients for growth and daily functions. Without these essential digestive enzymes, the body cannot absorb key nutrients such as carbohy-drates, proteins, and fats, the three parts of food that supply calories [10]. Thus, patients with CF require specific diets, such as high-calorie diets, high-fat diets, and several other diets.

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13.4 SPECIALTY FOODS AND DIETS

For children with CF, there are options available to cope with the nutritional problems associated with thick, sticky mucus covering the pancreas. Some options include supplemental vitamins, enzyme supplements, gastrostomy tube (G-tube) feeding, and nasogastric (NG) tube feeding [11]. A change in the diet may have beneficial results without these invasive techniques (see Table 13.1).

13.4.1 Increased Fat and Calorie Diets

One of the major issues for children with CF is the amount of fat present in their diet. The fat present in foods is important for normal weight gain and growth in chil-dren. A benefit of a diet high in fat is that it allows a per-son with CF to absorb more fat-soluble vitamins, which are required for a number of important functions in the human body. Due to the lack of digestive enzymes, there are precautions that children with CF must take into con-sideration before starting a high-fat diet. First, fatty foods may require an extra dose of pancreatic enzymes to aid in digestion. Children are less likely to eat fats because of this need for extra enzymes [12]. Children with CF tend to become dependent on saturated fats, potentially increas-ing the risk of cardiovascular disease [13]. Macronutrient intakes do not change significantly in the population of CF children, but there is a consistent imbalance of fat sources, with overdependence on saturated fats, which, in the con-text of increased survival in CF may potentially increase risk of cardiovascular disease [13]. Thus, by eating diets high in bad fats, children with CF have a higher chance of becoming more ill. Moreover, children with CF are highly encouraged to consume diets that are high in calories. Children with CF need more calories to compensate for the low absorption of nutrients; more specifically, they need to increase their body mass index (BMI) to greater than 25 [14]. The extra calories in this type of diet help them meet the greater energy needed for breathing [15]. High-calorie diets are good for normal growth and development, as well as for gastrointestinal comfort [16]. Unfortunately, a high-calorie diet that contains many carbohydrates may increase the risk of diabetes, where the prevalence of dia-betes in the population of people with cystic fibrosis is about 36% already [17,18]. Alternative foods have been researched as options for children with CF.

13.4.2 Breastfeeding and Whey Protein

One major concern of mothers who have infants with CF is the decision on breastfeeding. Is it beneficial for the spe-cific dietary needs of CF patients? Human breast milk has two main proteins, whey and casein, both of which allow easy digestion. Exclusive breastfeeding for infants with CF does not compromise growth, and it provides a respiratory

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13.4 SPECiAlTy FoodS And diETS 103

TABLE 13.1 Fruits and Vegetables for Children with Cystic Fibrosis: Benefits and Risks

Diet Benefits Risks

Carrot juice High amount of bioaccessible provitamin A High sugar content

Broccoli juice Substantial amount of health-promoting compounds: vitamins, glucosinolates, phenolic compounds, and dietary essential minerals

Possible genotoxic activities

Tomato juice Contains lycopene, an antioxidant that protects cells and organs from oxygen damageHigh in vitamins

Extra dose of pancreatic enzymes for digestion

Cucumber juice Reversed changes in serum glucose, insulin, total cholesterol, triglyceridePossible role in ameliorating diabetes mellitus

Low cellular antioxidant activity levels

Pineapple juice Enzyme bromelaine: promotes good digestionThiamine improves glucose tolerance

High amounts of natural sugar

Acai berry Reduces the negative effects of a high-fat dietReduced levels of metabolic disease riskHigh nutritional valueContains antioxidant compounds

Does not significantly alter the nutrient tract digestibilityProtein levels decline

Watermelon Increases arginine availabilityReduces serum concentrations of cardiovascular risk factorsImproves glycemic controlAmeliorates vascular dysfunction in type II diabetes

Must have specific genetic variants of β-carotene 15,15′-monooxygenase 1

Celery Highly toxic toward fungi and bacteriaDisplays neurotoxic, anti-inflammatory and antiplatelet-aggregatory effects

Protects the gastric mucosaSuppresses the basal gastric secretion

Raspberries Increase the metabolism in the body’s fat cellsTiliroside improves insulin balance, and blood sugar balance

Rheosmin decreases the activity of a fat-digesting enzyme

Strawberries Lowers blood glucose levelsAnti-inflammatory and blood glucose-regulating capacityContains flavonoids: potent antioxidant power

High in sugar

Blueberries Able to decrease cholesterolLow in sugar

Blueberries and diabetes medicines can lead to extremely low blood sugar levels

Cranberries Provides novel cardiovascular benefits Commercially processed products contain lower levels of polyphenols

Avocado Contains fats, fiber, vitamins, and potassiumLow added sugarBioactive compounds: monounsaturated fatty acids and sterols

Extra dose of pancreatic enzymesGenitourinary ailments, inflammatory ailments in respiratory tract, gastrointestinal tract ailments

benefit [19]. Although breast milk acts as a source for rel-evant nutritional items, it may be inadequate in caloric density, protein, essential fatty acids, and sodium to meet the increased requirements of CF infants [20]. Therefore, a food supplement like whey protein, rich in sulfhydryl groups, is recognized for its ability to increase glutathione and reduce oxidative stress. Supplementation with whey increased intracellular glutathione levels in patients with CF [21]. Pressurized whey supplementation in children and adults with CF could have significant nutritional and anti-inflammatory benefits [21]. Whey protein improves glucose levels and insulin response, promotes a reduc-tion in blood pressure and arterial stiffness, and improves lipid profile [22]. The main side effects of consumption of whey protein include bloating, and 43% of participants

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experienced nausea and some vomiting [23]. In a study on whey protein, 27 patients with CF were treated with 20 g of whey protein per day. Anthropometric measures, pul-monary function, serum C-reactive protein, whole blood glutathione, and whole blood IL-8 and IL-6 responses to phytohemagglutinin stimulation were measured at baseline and at one month. Children showed improvement in lung function. For both children and adults, enhancements in nutritional status, as assessed by BMI, were observed [21].

13.4.3 Juices

A major problem that comes with a change in diet for children is the success of the child actually eating the new foods. One way to solve this problem is to use juices.

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13. SPECIALTY FOODS FOR KIDS WITH CYSTIC FIBROSIS104

For children with CF, not only are the juices healthy, but they are also easy to eat and tasty. Carrot juice contains a lot of beta-carotene, vitamins, and minerals, providing a great amount of bioaccessible provitamin A [24]. Carrot juice is also rich in potassium, calcium, sodium, magne-sium, iron, and phosphorus. On the other hand, people with diabetes should avoid drinking carrot juice, due to the high sugar content—it has about an 85 on the gly-cemic index [25,26]. Broccoli juice contains a substantial amount of health-promoting compounds such as vita-mins, glucosinolates, phenolic compounds, and dietary essential minerals [27]. These compounds are important, not only in children with CF, but in healthy people as well. Broccoli consumption mediates a variety of physi-ological functions, including acting as an antioxidant, regulating enzymes, and controlling apoptosis and the cell cycle [28]. In vitro and experimental animal studies indicate that broccoli, its extracts, and the glucosinolate-derived degradation products have genotoxic activi-ties; however, the relevance of the genotoxic activities to human health is not yet known. A quantitative com-parison of the benefit and risk of broccoli consumption shows that the benefit from intake in modest quantities and in processed form outweighs the potential risks [29]. Tomato juice has a major organic compound called lycopene. It acts as an antioxidant by protecting cells and organs from oxygen damage. Tomato juice is also very high in vitamins that are essential to a CF diet [30]. However, tomato juice can require another dose of pan-creatic enzymes to aid in digestion [12]. Cucumber juice can also be beneficial to children with CF. In an experi-ment, cucumber peels were fed to male mice in doses of 250 and 500 mg for 15 days. The alterations in serum glucose and hepatic lipid peroxidation were measured. Cucumber juice is high in vitamin A, and cucumber juice’s effects on alterations in serum glucose, insulin, triiodothyronine, thyroine, total cholesterol, triglycer-ide, high-density lipoprotein, low-density lipoprotein, hepatic lipid peroxidation, superoxide dismutase, and catalase were studied [31]. The cucumber extracts nearly reversed most of these changes introduced by alloxan, suggesting its possible role in ameliorating diabetes mel-litus [31]. On the other hand, cucumbers had one of the lowest antioxidant activity levels of all the fruits and vegetables tested [32]. A very sweet juice that children may enjoy is pineapple juice. Pineapple juice contains an enzyme, bromelaine, which promotes good digestion by helping the body break down proteins [33]. Also, sup-plementation with thiamine has been found to improve glucose tolerance in patience with hyperglycemia [34]. Unfortunately, like many fruit juices, pineapple juice contains high amounts of natural sugar, called fructose. When consuming pineapple juice, a large amount of sugar—about 35% more sugar—becomes available for absorption immediately after consumption, with little

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digestion required [35,36]. This would be a risky food for children who are prone to CFRDM.

13.4.4 Watermelon and Celery

Watermelons work to increase the availability of argi-nine by reducing serum concentrations of cardiovascular risk factors. They also improve glycemic control and ame-liorate vascular dysfunction in obese animals with type II diabetes [37]. Unfortunately, the bioavailability of carot-enoids found in watermelon involve specific genetic vari-ants of β-carotene 15,15′-monooxygenase 1. This means that the ability of a child with CF to digest and process some of the nutrients in watermelon is limited—the nutri-ents must be in the correct form in order for a child with CF to digest them properly. Celery is highly toxic toward fungi, bacteria, and mammalian cells. It also displays neu-rotoxic, anti-inflammatory and antiplatelet-aggregatory effects [38]. Due to its anti-inflammatory effects, celery is a good choice for CF children. Celery protects the gas-tric mucosa and suppresses the basal gastric secretion in rats; thus it promotes the production of mucus [39]. Cel-ery would be counteractive in children with CF, as their glands already produce excess mucus.

13.4.5 Berries

Raspberries’ phytonutrient rheosmin increases the metabolism in the body’s fat cells. Also, by activating adi-ponectin, the tiliroside in raspberries can help improve insulin balance, blood sugar balance, and blood fat, thus making raspberries great for children at risk for CFRDM [17]. On the other hand, in some cases, rheosmin can decrease the activity of a fat-digesting enzyme released by the pancreas called pancreatic lipase. This decrease in enzyme activity may result in less digestion and absorp-tion of fat [17]. There are several health factors in straw-berries, with the most abundant of these being ellagic acid and certain flavonoids: anthocyanin, catechin, quercetin, and kaempferol. These compounds have potent antioxi-dant power, helping lower risk of cardiovascular events by inhibition of LDL-cholesterol oxidation, promotion of plaque stability, improved vascular endothelial func-tion, and decreased tendency for thrombosis [40]. In an experiment researching the anti-inflammatory and blood glucose-regulating capacity of strawberries with mice, blood glucose values were approximately 6.5% lower in the supplemented mice [41]. These results of low blood glucose levels encourage the consumption of strawberries for children with CF who are also at a risk for CFRDM. However, strawberries are also a fruit that is high in sugar content, about 217 mmol in the vacuole alone [42,43].

Blueberries are extremely low on the glycemic index, meaning they are low in sugar. This makes blueberries a great choice for those with diabetes or those at risk

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CluSion 105

13.5 Con

for diabetes [44]. In a double-blinded, randomized, and placebo-controlled clinical study, the bioactives in blue-berries increased the participants’ insulin sensitivity [45]. Because blueberries are so low in sugar, mixing blueber-ries and diabetes medications can lead to extremely low insulin levels; in fact, a study found that consumption of blueberries resulted in a lower insulin response [46].

Acai berries contain anthocyanins and flavonoids, which are powerful antioxidants that help defend the body [47]. This berry also has the ability to reduce the negative effects of a high-fat diet in laboratory studies on flies [47]. Consumption of acai fruit pulp can reduce the levels of selected markers of metabolic disease risk [48]. Acai berries have high nutritional values and con-tain antioxidant compounds [49]. These antioxidant compounds were tested by in vitro antioxidant assays using a macrophage model and in vivo hypolipidemoc activity using zebra fish. In assays in vitro, all extracts demonstrated potent ferric ion reductive capacity, radical-scavenging activity, and inhibition of low-density lipo-protein oxidation at a final concentration of 0.1 mg/mL; the extracts could also abrogate fructose-mediated pro-tein gycation and mildly inhibit cholesteryl ester trans-fer protein [50]. However, increased consumption of acai berries does not significantly alter the nutrient tract digestibility, and protein levels decline [51]. The decline in protein means the children do not need an extra dose of pancreatic enzymes to aid in digestion, with less needed protein in the overall diet.

Cranberries are another great fruit to consider adding to a child’s diet. They have properties that provide novel cardiovascular benefits, improving both vascular function and cholesterol profiles [52]. Processed cranberry prod-ucts contain significantly lower levels of polyphenols and higher levels of artificial sugar. The commercial process-ing can alter the levels of biologically active flavonoids (especially anthocyanins and proanthocyanidins) [53].

13.4.6 Avocado

Lastly, avocado is a well-known food, which is a great addition to a CF diet. Avocados contain monounsaturated and polyunsaturated fats, dietary fiber, vitamins E, K, magnesium, and potassium, and lower levels of sugar. There is no significant increase in calories or sodium in this food [54]. Avocados are also a good source of bioac-tive compounds such as unsaturated fatty acids and ste-rols [55]. However, because of the high amount of fats in avocado, an extra dose of pancreatic enzymes may be needed to aid in digestion; it is recommended to start out taking 500 units lipase/kg/meal until fat malabsorption is corrected [12]. Also, avocados have been associated with genitourinary aliments, inflammatory ailments in the respiratory tract, and gastrointestinal tract ailments [56]. These factors make it a risky choice for children with CF.

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13.5 CONCLUSION

Cystic fibrosis, a heritable disease that mainly affects the lungs and the digestive system, is a result of a mutation of the CFTR. This mutation causes the body to produce unusually thick mucus that can clog the lungs and obstruct the pancreas, thus preventing natural enzymes from break-ing down and absorbing essential nutrients. Because of these functional issues, children with CF have difficulty maintaining their weight and are unable to absorb proteins and vitamins. Also, as a result of the thick sticky mucus on the pancreas, insulin is unable to perform its job, so chil-dren with CF are also at a high risk for CFRDM. It is due to these vital side effects of the mutation of the CFTR gene that the diet of children with CF is so important.

Of the specialty foods discussed, one of the major contributors to the health of children with CF would be whey protein. Not only does whey protein have impor-tant anti-inflammatory benefits but it also improves glucose levels, insulin response, and lipid profile [21]. Because children with CF are at such a high risk for infections, including whey protein in their diet can help their immune system protect them. Also, for children who have CFRDM, the improved insulin response and glucose levels are a huge benefit of this specialty food.

Although calories and proteins are a huge factor in the diets of children with CF, fruits provide many of the essen-tial vitamins and nutrients that are important for normal growth and functioning of the body. A major fruit to con-sider is the acai berry. Acai berries contain anthocyanins and flavonoids, which are powerful antioxidants that help defend the body [47]. This berry also has the ability to reduce the negative effects of a high-fat diet [47]. Another specialty fruit is the blueberry, which has bioactives that can improve insulin sensitivity [45]. This is a huge factor for children with CFRDM—not only are blueberries an easy snack, but they have monumental effects for controlling a major side effect of CF. Pineapples are another great fruit for children with CF. Pineapples contain an enzyme called bromelaine, which promotes digestion by helping the body break down proteins [33]. This is a huge factor for children with CF—this enzyme could help the body compensate for the lack of release of natural enzymes by the pancreas.

Vegetables are another great source for vitamins for chil-dren with CF. The main vegetable to consider adding to a child’s diet is broccoli juice. This super vegetable contains a substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals [27]. These components function to mediate a variety of physiological pathways in the body, such as antioxidant-regulating enzymes, and controlling apoptosis in the cell cycle [28]. Minor changes in the diets for children with CF can have incredible results—just by adding a few different fruits and vegetables, and more pro-tein, the daily lives of children with CF can be improved.

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Further ReadingWang TT, Edwards AJ, Clevidence BA. Strong and weak plasma re-

sponse to dietary carotenoids identified by cluster analysis and linked to beta-carotene 15,15’-monooxygenase 1 single nucleo-tide polymorphisms. National Center for Biotechnology Infor-mation. U.S. National Library of Medicine; Aug 24, 2013. Web Sep 8, 2013.

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WTH AND HEALTH IN CHILDREN WITH CYSTIC FIBROSIS