European Journal of Clinical Nutrition (2002) 56, 755–764 ß 2002 Nature Publishing Group All rights reserved 0954–3007/02 $25.00 www.nature.com/ejcn ORIGINAL COMMUNICATION The comparative gastrointestinal responses of children and adults following consumption of sweets formulated with sucrose, isomalt and lycasin HBC

A Lee1, D Wils2, A Zumbe´1 and DM Storey1*

1Bioscience Research Institute, The University of Salford, Greater Manchester, UK; and 2Roquette Fre`res, Lestrem, France

Objectives: To determine the gastrointestinal responses of children and adults following consumption of sucrose, isomalt and lycasin HBC and to compare these at two different dose levels in adults. Design: Both studies were randomised, double-blind, cross-over designs. Subjects: Fifty-one children aged 6 – 9 y were recruited from primary schools in the Salford area of Greater Manchester. Forty- eight children completed the study. Fifty healthy adult volunteers aged 18 – 24 y were recruited from the student population of the University of Salford. All subjects completed the study. Interventions: Children consumed either 25 g of sucrose, isomalt or lycasin HBC and adults 25 and 40 g in hard boiled sweets per day for two consecutive test days. Test periods of 2 days were separated by 7 day washout periods. Children consumed sweets throughout test days and adults in no less than 30 min but no more than 90 min. Subjects reported the prevalence and magnitude of flatulence, borborygmi, bloating, colic, bowel movements and watery faeces. Results: Consumption of 25 g isomalt provoked a mild laxative effect in children but not in adults. Consumption of 25 g isomalt significantly increased the prevalence and magnitude of gastrointestinal responses in both children and adults. Consumption of 25 g lycasin HBC significantly increased borborygml in children and adults but no other gastrointestinal responses. Consumption of 40 g lycasin HBC or isomalt by adults significantly increased the mean frequency of bowel movements and the number of subjects passing watery faeces. In adults, 40 g isomalt and lycasin HBC provoked significantly more gastrointestinal responses compared to 25 g of either product. Conclusions: Consumption of 25 g lycasin HBC does not provoke an unacceptable laxative effect or gastrointestinal response in children or adults compared to 25 g isomalt, which is associated with a mild laxative effect and increase in gastrointestinal responses. In adults gastrointestinal responses following consumption of products were found to be dose dependent. Sponsorship: Roquette Fre`res, Lestrem, France. European Journal of Clinical Nutrition (2002) 56, 755 – 764. doi:10.1038=sj.ejcn.1601389

Keywords: gastrointestinal responses; humans; children; adults; sucrose; isomalt; lycasin; polyols; tolerance; maltitol syrup

Introduction have excellent organoleptic, technological and physico- Isomalt and maltitol syrups are widely used to replace chemical properties, making them ideal for formulation sucrose in confectionery because of their cariostatic and into ‘toothfriendly’, ‘reduced calorie’ and or ‘sugar-free’ hypocaloric properties compared to sucrose (Grenby & Sal- products suitable for both adults and children (Zumbe´ danha, 1988; Ziesenitz & Siebert, 1987). These polyol sugars et al, 1994, 2001; Sicard & Le Bot, 1994). Isomalt, an equimolar mixture of the disaccharide polyols D-glucosyl-a(1?1)-D-mannitol and D-glucosyl-a(1?6)-D-glu- *Correspondence: DM Storey, Bioscience Research Institute, The citol is produced by the catalytic hydrogenation of isomal- University of Salford, Salford, Greater Manchester, M5 4WT, UK. 1 E-mail: [email protected] tulose. Lycasin 80=55 (lycasin 80=55) is one member of the Guarantor: DM Storey and A Lee family of maltitol syrups and is produced by the catalytic Contributors: All authors were equally responsible for initiating and hydrogenation of glucose syrup. Lycasin 80=55 typically designing the study and writing the report. A Lee collected the data contains 5% monosaccharides, 55% of the disaccharide and performed the statistical analysis. Received 9 June 2000; revised 17 September 2001; maltitol, 19% maltotriitols and 21% hydrogenated oligosac- accepted 24 September 2001 charides with the degree of polymerisation ranging from 4 to Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 756 20 sub-units (Sicard & Le Bot, 1994). The recently developed of 25 g of sweets containing sucrose, isomalt or lycasin HBC bulk sweetener ‘lycasin hard boiled candy’ (lycasin1 HBC) and those of 50 young adults aged 18 – 24 following con- contains a higher proportion of hydrogenated polysacchar- sumption of 25 or 40 g of sweets containing sucrose, isomalt ides compared to standard lycasin 80=55. In humans, iso- or lycasin HBC. malt, maltitol and maltitol syrups produce low glycaemic and insulinaemic responses compared to glucose and sucrose (Pelletier et al, 1994; Thiebaud et al, 1984). It is estimated Subjects and methods that 44 and 40% of a 20 g dose of maltitol and isomalt are Child study unabsorbed in the upper intestine respectively (Beaugerie Children were recruited from the Alder Park and Westwood et al, 1991). However, the degree of upper intestinal absorp- Park primary schools in the Salford area of Greater Manche- tion of isomalt is inversely proportional to the dose of ster, UK. Individual classes of children aged 6 – 9 y were isomalt ingested (Langkilde et al, 1994; Kruger et al, 1991). chosen by the head teachers of schools for potential recruit- Both maltitol and lycasin 80=55 are digested to a similar ment to the study. The purpose and nature of the study was extent in the upper intestine of humans (Beaugerie et al, explained to children in each class with the co-operation of 1990). Isomalt and maltitol are only partly hydrolysed in the teaching staff. Parents and=or guardians of children were upper intestine because of the low affinity of upper intestinal invited by letter to allow their children to participate and disaccharidases for these substrates (Nilsson & Jagerstad, discuss the study with the investigators in meetings at home 1987). Hydrolysis of maltitol results in 50% glucose and or at school. Parents provided written informed consent for 50% sorbitol, (Ziesenitz & Siebert, 1987) and hydrolysis of their children to participate in the study and could withdraw isomalt, 50% glucose, 25% sorbitol and 25% mannitol their children at any time and for any reason. Children gave (Grupp & Siebert, 1978). Thus consumption of isomalt, verbal consent and were free to leave the study at any time maltitol or a product rich in maltitol such as lycasin 80=55 and for any reason. Approval was given by Salford Local or lycasin HBC results in a mixture of intact polyol molecules Education Authority and Head teachers of schools. Ethical and their hydrolysates entering the colon where they con- approval was granted by Salford and Trafford Health Author- tribute to the carbohydrate pool available for bacterial fer- ity Local Regional Ethics Committee. mentation. Colonic fermentation produces short chain fatty No inclusion=exclusion criteria other than parental con- acids, hydrogen, carbon dioxide and, in some individuals, sent, the consent of the child and screening of children were methane (Macfarlane & Cummings, 1991). Colonic gas for- employed in selecting children for the study. Parents com- mation following ingestion of poorly absorbed carbohy- pleted screening questionnaires for their children. Screening drates may lead to increased gastrointestinal (GI) of children ensured that they had no history of gastrointest- symptoms, notably flatulence and abdominal discomfort. If inal or metabolic disease, did not have any dietary restric- the fermentative capacity of the colon is exceeded, watery tions or prescribed diets, did not suffer from a food allergy faeces may occur because of the osmotic effect exerted by and did not regularly consume polyol-containing confec- malabsorbed low molecular weight carbohydrates (Saunders tionery products. It was also ensured that children had not & Wiggins, 1981; Menzies, 1983). Consumption of polyol received antibiotics, steroids, laxatives or any other drugs 6 sugars has been shown to provoke dose-dependent increases months prior to the study. Screening was based upon inclu- in GI symptoms as well as elevated exhaled breath hydrogen sion and exclusion criteria employed in previous studies profiles, indicating active colonic fermentation (Storey et al, with young adults (Lee et al, 1994; Storey et al, 1998). The 1998; Koutsou et al, 1996; Storey & Zumbe´, 1996; Lee et al, prescription of medication given to children was monitored 1994; Fritz et al, 1985; Hyams, 1983). throughout the study enabling the child’s suitability for Although the occurrence of GI symptoms following continued participation to be assessed. No child was polyol ingestion is regarded as a transient phenomenon excluded from the study on such grounds. and mitigated by reducing one’s intake (Cummings et al, In all, 122 children were invited to take part in the study 2001), they are not attractive to the consumer and could be (four classes) and 77 were given parental consent to do so. Of regarded as a highly sensitive issue when considering such these, 24 did not pass the screening stage of the study and effects in children. Little is known about the GI effects of two decided not to take part. Forty-eight out of 51 children polyol consumption in children, although studies with iso- who started the study completed it satisfactorily. One child malt indicate that doses of up to 35 g are tolerated well by was withdrawn by their parents, who reported that the child children (Paige et al, 1992). Because lycasin HBC contains a had experienced abdominal pain following consumption of higher proportion of hydrogenated polysaccharides com- test sweets. One child consumed insufficient product and pared to mono- and disaccharide polyols and lycasin 80=55 one did not consume product on the days instructed. it should exert a lower osmotic potential in the gut and Twenty-three boys and 25 girls aged between 6 y 11 reduce the potential for laxation. To date, there are no months and 9 y 9 months (meanÆ s.d. ¼ 8.40Æ 0.9 and published studies concerning the GI effects of lycasin HBC 8.30Æ 0.8 y, respectively) completed the study satisfactorily. in adults or children. This paper reports the comparative GI Body mass indices (meanÆ s.d.) were 17.08Æ 2.49 kg=m2 and responses of 48 children aged 6 – 9 y following consumption 17.57Æ 2.67 kg=m2 for boys and girls, respectively. There

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 757 were no significant differences in age or body mass index children consumed them during school hours, allowing (BMI) between either boys or girls. supervision by class teachers and=or the study investigators. Following consumption of sweets on test day 1, children were given the choice of consuming the same product for a Adult study second test day or consuming an alternative product once Fifty healthy volunteers aged 18 – 24 y were recruited from only. All of the children chose to consume each of the the student population of the University of Salford by means sucrose, isomalt and lycasin HBC products for a second day. of publicity posters. The purpose and nature of the studies Consumption of fresh milk and fresh fruit juice by chil- were explained and volunteers screened for the same inclu- dren was limited to no more than one 200 ml glass of each sion and exclusion criteria employed in the child study. during test days, for the preceding 12 h of the previous day Written consent was obtained from all volunteers, who and for the first 12 h of the day thereafter. This restriction were free to leave the study at any time and for any reason. was made to avoid GI intolerance symptoms arising from Approval for the study was given by the University of Salford malabsorption of lactose or fructose in milk and fresh fruit Occupational Health and Hygiene Service. Twenty-four male juice, respectively, as in Lee et al (1994). subjects and 26 female subjects participated in the study Children were interviewed individually 24 h after con- with body mass indices (meanÆ s.d.) of 23.59Æ 3.80 kg=m2 sumption of each product to determine if they had adhered and 20.81Æ 1.68 kg=m2 for males and females, respectively. to study restrictions, what consumption pattern they fol- lowed and if they had experienced any GI sensations. Ques- tions relating to the sensorial perception of the products and Test materials the incidence of the minor symptoms of thirst and loss of Test sweets were identical except for their carbohydrate appetite were included in the protocol as distracter questions content and were manufactured by Cadbury Dulciora, Valla- and as a means of building up children’s confidence. Chil- dolid, Spain, a subsidiary of Cadbury Schweppes plc, Bourn- dren were asked what they had eaten during test days. ville, Birmingham, UK. The bulk sweeteners incorporated into the sweets were lycasin1 HBC (Roquette Fre`res, Lestrem, France), isomalt (Palatinit Sussungsmittel GmbH, Man- Adult study nheim, Germany), glucose syrup and sucrose. Products for In a double-blind, controlled, cross-over study, subjects were the child study were supplied as 25 g bags of hard-boiled, tested with each product in randomised order determined by fruit-flavoured sweets containing 10 pieces each with an a Latin square design applied to each leg of the cross-over assortment of orange, lemon, strawberry and cherry flavours. study. Subjects consumed 25 and 40 g of either sucrose, Products for the adult study were supplied as 25 and 40 g isomalt or lycasin HBC sweets during test periods separated bags of hard-boiled, menthol and eucalyptus flavoured by washout periods of one week (Figure 2). Dietary restric- sweets identical in carbohydrate content to those used for tions were enforced according to Lee et al (1994), and Storey the child study. Products for each study were identified by 12 et al (1998), although fasting previous to the day of product different code numbers, the identity of which was not ingestion and consumption of the product at breakfast time revealed to study investigators until after both studies were were not prescribed. Instead, subjects were requested not to completed. consume products at extreme times of day or as a replace- ment breakfast, lunch or dinner. Subjects were required to consume all of the sweets given in no less than 30 min but Study design and restrictions no more than 90 min, preferably as a mid-morning snack Child study before lunch. Subjects were individually debriefed 24 h after Children were tested with each product in a double-blind, product consumption according to a set protocol to deter- controlled, cross-over study with each coded product allo- mine adherence to dietary restrictions and consumption cated in random order determined by a Latin square design regime and to assess GI responses. applied to each leg of the study. Children received either 25 g sucrose, isomalt or lycasin sweets per day for 2 day periods separated by 7 day washout periods (Figure 1). Children were GI responses not given 40 g of polyol based sweets to consume as in the Child study adult study because of the risk of unacceptable GI responses Questions relating to GI responses were asked after an and because 25 g sweets is considered a reasonable portion informal discussion with the child about the school day size for children to consume (Zumbe´ et al, 1994). Test and their sensorial perception of the sweets. Children were products were supplied daily to avoid over-consumption. asked if they wanted to tell the study investigator anything Children were instructed and encouraged to consume all about the sweets and whether they had experienced any the sweets in each packet given to them but they were not unusual feelings in the 24 h period following consumption forced to do so. They were informed that they could con- of sweets. Any reports of GI responses at this stage were sume the sweets as a snack over any period of time, but most classed as unprompted. Children were then prompted by

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 758

Figure 1 Child study design.

asking them if they had experienced any GI response they visits and therefore information regarding faecal volume was had not already mentioned. Familiar terms were used to not determined. describe GI responses to children, these being ‘tummy- ache’ (colic), ‘rumbly tummy’ (borborygmi), ‘farting’ (flatu- Adult study lence) and ‘feeling full up and bloated’ (bloating). Children Subjects were given printed sheets on which to record the were asked how many times they had visited the toilet to incidence and magnitude of GI responses and details of their open their bowels and whether their faeces were normal, bowel movements for the 24 h period following consump- ‘runny’ (watery) or hard. Children were asked to rank any tion of each product. Notifiable responses were borborygmi, positive response using the terms ‘a little’, ‘some’ or ‘lots’, colic, bloating and flatulence. Each response was ranked on a which were subsequently assigned scores of 1, 2 and 3, hedonic scale where 0 indicated ‘normal’ function, 1 indi- respectively. Children had an extensive vocabulary for the cated ‘slightly more than usual’, 2 indicated ‘noticeably description of their GI responses and, in particular, the more than usual’ and 3 indicated ‘considerably more than consistency of their faeces. No child refused to answer any usual’. The number of bowel movements to pass normal questions asked by the study investigators. Because of ethical faeces, hard faeces and watery faeces was recorded. Informa- considerations children could not be monitored during toilet tion regarding faecal volume was not determined.

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 759

Figure 2 Adult study design.

Statistics scores were assumed to be parametric and analysed by GI responses for both children and adults were regarded as paired t-tests after one-way ANOVA. categorical (yes=no), and considered to be non-parametric. Products were compared by 2Â2 contingency table analysis according to the methods of McNemar (1947) to test for Results and discussion differences in responses following product consumption but The perceived benefits of polyol ingestion should be without accounting for the order of product presentation. balanced against their potential to cause increased abdom- The binomial test was used when four subjects reported GI inal discomfort and laxation (Livesey, 2001). This is espe- responses or when the expected frequency in each cell of the cially true in sensitive groups such as children, where contingency table was less than 5. A second 2Â2 contin- consumption of traditional sucrose-based confectionery gency table analysis was performed as described by Gart would not normally be expected to provoke such responses. (1969) to test for both product effects and for any effect of Thus, our investigation compares the GI responses of children the order of product presentation, thereby testing the effi- and adults following consumption of traditional sucrose- cacy of the cross-over design. Differences between subjects in based confectionery with alternative confectionery contain- the frequency of bowel movements and mean symptom ing isomalt or lycasin HBC.

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 760 Child study with those of Koutsou et al (1996), who reported no signifi- There was no significant increase in the mean number of cant laxation in young adults following consumption of 30 g bowel movements to pass normal or watery faeces following maltitol (the main constituent of lycasin 80=55) and only consumption of lycasin HBC sweets compared to sucrose mild laxation after consumption of 30 g isomalt in milk sweets (Table 1). Conversely, consumption of isomalt sweets chocolate. Conversely, Paige et al (1992) reported only one was associated with a significant increase in the mean incidence of ‘diarrhoea’ following consumption of 15 and number of bowel movements to pass watery faeces 25 g isomalt in children under 12 y. (P < 0.025) and in overall mean bowel movement frequency Consumption of isomalt sweets was associated with a (P < 0.05). Consumption of isomalt sweets was associated significant increase in the total number of GI responses for with a significant increase in the total number of bowel bloating and borborygmi made by children over 2 days movements made by children to pass watery faeces com- compared to sucrose sweets (P < 0.05 and P < 0.25 respec- pared to sucrose and lycasin HBC sweets (P < 0.001 and tively; Table 2). P < 0.05 respectively; Table 2). These results were influenced Consumption of lycasin HBC sweets was not associated by one child who made seven bowel movements to pass with any significant increase in the total number of GI watery faeces, and two children, each of whom made five responses made by the study group over two days. Table 3 bowel movements to pass watery faeces following consump- partitions data into numbers of children reporting GI tion of isomalt sweets over 2 days. responses rather than overall incidence of GI responses as Table 3 partitions tolerance data in terms of grade of GI shown in Table 2. Consumption of isomalt sweets was response and if children experienced responses on only 1 associated with a significant increase in the number of day, or both days of product consumption. Using the cate- children reporting bloating, borborygmi and colic on one gories adopted in this study, those children experiencing grade 3 responses and on both days of product consumption could be considered as those most sensitive to the effects of Table 2 Gastrointestinal responses by children after consumption over polyol ingestion out of the study group. No child made more two days of sweets containing 25 g sucrose, isomalt or lycasin HBC, (total than three bowel movements to pass watery faeces on both number of responses reported by children, n ¼ 48) 1 days of consumption of any product. However, four children GI response Sucrose Isomalt Lycasin HBC made three or more bowel movements to pass watery faeces following consumption of isomalt sweets on one test day Bloating Total 24 37* 21a compared to none for lycasin HBC. This result is not statis- A little 11 19 16 tically significant. If laxation is defined in terms of bowel Some 5 7 3 movement frequency and faecal consistency, results demon- Lots 8 11 2 strate that lycasin HBC is tolerated well by children with no Borborygmi significant increase in laxation. Where it is not possible to Total 15 36** 25 record faecal volume, diarrhoea (increased laxation) may be A little 10 20 14 Some 3 6 7 defined as ‘one or more watery stools or more than three Lots 2 10 4 stools per day’ (Marteau & Flourie´, 2001). This study con- siders mild laxation to be the passage of watery faeces on Flatulence Total 12 20 20 only one occasion, or the passage of more than three faeces A little 7 7 5 of normal consistency in 24 h following consumption of Some 3 5 6 products. In this study, consumption of isomalt sweets was Lots 2 8 9 associated with a significant but mild laxative effect com- Colic pared to sucrose controls. These observations are in keeping Total 16 26 12a A little 8 7 7 Some 2 6 3 Lots 6 13 2 Table 1 Frequency of bowel movements by children to pass hard, Number of bowel movements to pass watery faeces normal or watery faeces after consumption over two days of sweets a { containing 25 g sucrose, isomalt or lycasin HBC; meanÆ s.d. (n ¼ 48). Total 2 43*** 11 1274 1 Sucrose Isomalt Lycasin HBC 2032 3031 Hard 0.04 þ 0.29 0.00 þ 0.00 0.00 þ 0.00 4010 Normal 0.29 þ 0.59 0.36 þ 0.62 0.33 þ 0.61 5020 Watery 0.02 þ 0.10 0.45 þ 1.20** 0.11 þ 0.44 6000 Total bowel movements 0.35 þ 0.67 0.81 þ 1.24* 0.45 þ 0.74 7010

*Significant increase in mean frequency of bowel movements compared to Significant increase in GI responses compared to sucrose product *P < 0.05, sucrose product (P < 0.05). **P < 0.025, ***P < 0.001. { **Significant increase in mean frequency of bowel movements to pass watery Significant decrease in GI responses compared to isomalt product (P < 0.05). faeces compared to sucrose product (P < 0.025). aTotal bowel movements made to pass watery faeces over two days.

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 761 Table 3 Number of children reporting gastrointestinal responses following consumption over two days of sweets containing 25 g sucrose, isomalt or lycasin HBC (n ¼ 48)

1 Sucrose Isomalt Lycasin HBC

GI responsea 1 day 2 days Total 1 day 2 days Total 1 day 2 days Total

Bloating 1 þ 2 þ 3 10 7 17 19 9 28* 13 4 17{ 2 þ 392116612314 3617347202

Borborygmi 1 þ 2 þ 3 7 4 11 12 12 24*** 11 7 18* 2 þ 350510313729 3213437202

Flatulence 1 þ 2 þ 3639124168614 2 þ 3123111125510 3202617527

Colic 1 þ 2 þ 3 6 5 11 10 8 18* 8 2 10{ 2 þ 3 6179514505 3202358415 Bowel movements to pass faeces of any consistency 1 þ 19322121628101121 2 þ 7079413426 3 þ 000404000

Bowel movements to pass watery faeces 1 þ 2 0 2 9 4 13** 1 3 4{ 2 þ 000628112 3 þ 000404000

Significant increase in number of children reporting GI responses over two days compared to sucrose product, * (P < 0.05, ** P < 0.01, *** P < 0.005). {Significant decreases in number of children reporting GI responses over two days compared to isomalt products (P < 0.05). aChildren’s GI response where: 1 ¼ a little; 2 ¼ some; 3 ¼ lots.

day or both days compared to sucrose sweets (P < 0.05, nition by the study investigator of the response or its P < 0.005 and P < 0.05, respectively). Consumption of lycasin magnitude. In total there were 15 unprompted GI responses HBC sweets was only associated with a significant increase in out of a possible 96 following consumption of sucrose sweets the number of children reporting borborygmi on one or two compared to 19 for lycasin HBC sweets (P > 0.05) and 31 for days compared to sucrose sweets. Borborygmi (tummy rum- isomalt sweets (P < 0.05). This result is probably a function of bling in children) could be classed as the least severe GI the increased number of children experiencing GI responses, response in comparison to colic (tummy ache in children) and of a greater magnitude, following consumption of iso- and diarrhoea, which may be distressing to children. malt sweets compared to sucrose and lycasin HBC sweets. Furthermore, the total number of children reporting colic Only one child was withdrawn from the study because of and bloating was significantly less compared to the number adverse GI responses following consumption of isomalt reporting GI responses following consumption of isomalt sweets and even in the event of children reporting responses sweets (P < 0.05 in both cases). These results presumably as ‘lots’, no child wished to discontinue the study. Most reflect differences in the extent of upper intestinal hydrolysis children reported only grade 1 GI responses, and few grade 3 and absorption, the osmotic potential and fermentability of GI responses following consumption of isomalt or lycasin isomalt and lycasin HBC in the GI tract of children. HBC products, the majority of GI responses occurring only Although potentially useful, breath hydrogen techniques to after one day’s consumption of product rather than on both assess upper intestinal absorption and colonic fermentation days. Consumption of isomalt and lycasin HBC sweets was of polyols could not be used with healthy, non-hospitalised not associated with a significant number of children report- children in this study because of ethical considerations. ing grade 3 responses on both consumption occasions com- Of some interest is the number of children who gave pared to controls. Every child who completed the study unprompted GI responses following consumption of pro- chose to consume products for a second day, even if GI ducts over two days. An unprompted GI response was one responses were reported on the first day of consumption, where the child volunteered information without prior defi- indicating positive acceptance of products.

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 762 Adult study Table 5 Gastrointestinal responses of adults after consumption of Consumption of 25 g isomalt or lycasin HBC sweets was not sweets containing 25 g or 40 g sucrose, isomalt or lycasin HBC (number of subjects reporting symptoms, n ¼ 50) associated with any significant increase in overall mean 1 frequency of bowel movements (Table 4). However, con- Sucrose Isomalt Lycasin HBC sumption of 40 g isomalt sweets was associated with a sig- a nificant increase in the overall mean frequency of bowel GI response 25 g 40 g 25 g 40 g 25 g 40 g movements compared to the sucrose control (P < 0.005). The Bloating number of subjects reporting bowel movements to pass 0 403728313625 { watery faeces on one or more occasions following consump- 1 þ 2 þ 3 10 13 22**** 19 14 25*** 2 þ 3 539658 tion of both 40 g isomalt and 40 g lycasin HBC sweets was 3 223213 significantly higher compared to sucrose sweets (P < 0.005 and P < 0.05, respectively; Table 5). Only consumption of Borborygmi 0 454129233532 40 g isomalt sweets was associated with a greater number of 1 þ 2 þ 3 5 9 21**** 27***** 15* 18* subjects making bowel movements to pass watery faeces on 2 þ 3 2 0 8 15***** 2 6* two or more occasions compared to sucrose controls 30026*11 (P < 0.05). Flatulence Consumption of 25 g isomalt sweets led to significantly 0 333519142421 more adults reporting bloating (P < 0.005), borborygmi 1 þ 2 þ 3 17 15 31* 36***** 26 29* 2 þ 3 4 2 29***** 16**** 10 18***** < < < P 0.005), flatulence (P 0.05) and colic (P 0.005) com- 3 002525 pared to sucrose sweets (Table 5) and to a significant increase in the number reporting colic compared to lycasin HBC Colic 0 464133334438 sweets (P < 0.05). As with children, consumption of 25 g 1 þ 2 þ 3 4 9 17****{ 17 6 12 lycasin HBC sweets provoked only increased borborygmi 2 þ 301510*15 (P < 0.05). Forty grams of isomalt sweets provoked grades 1, 3 002311 2 and 3 borborygmi and flatulence (P < 0.001) and grades 2 Bowel movements to pass and 3 borborygmi, flatulence and colic (P < 0.001, P < 0.005 watery faeces and P < 0.05, respectively). More subjects reported any grade None 43 44 40 31 41 35 1 þ 7 6 10 19**** 9 15* of bloating, borborygmi and flatulence following consump- 2 þ 22 3 9*3 5 tion of lycasin HBC sweets compared to sucrose sweets 3 þ 10 2 5 1 0 (P < 0.025, P < 0.05 and P < 0.05, respectively) and grades 2 4 þ 00 0 2 0 0 and 3 flatulence and borborygmi (P < 0.001 and P < 0.05). 5 000100 These results are similar to those observed in children in that a0 ¼ normal gastrointestinal function; 1 ¼ slightly more than usual; the majority of GI responses reported following consump- 2 ¼ noticeably more than usual; 3 ¼ considerably more than usual. tion of both lycasin HBC and isomalt sweets were classed as Significant increase in GI response compared to sucrose product, *P < 0.05, grade 1 responses. **P < 0.025, ***P < 0.005, *****P < 0.001. {Significant increase in GI response compared to 25 g Lycasin HBC (P < 0.05). In this study bowel movement frequency was far higher in adults compared to children (Tables 1 and 4). Bowel move- ment frequency varies considerably in adults, a normal range 6.8 þ 2.5 (Bloom et al, 1993). When converted to a mean of being three bowel movements per week to three per day, 0.971 bowel movements per day this value is still high with a modal frequency of one per day (Cummings et al, compared to the mean bowel movement frequency of chil- 2001). In children aged 3 – 12 y, bowel movement frequency dren following consumption of sucrose based sweets in this is reported as ranging from 1 to 21 per week with a mean of study (Table 1). This may indicate a diet low dietary fibre for

Table 4 Frequency of bowel movements by adults to pass hard, normal or watery faeces after consumption of sweets containing 25 g or 40 g sucrose, isomalt or lycasin HBC=mean þ s.d.

1 Sucrose Isomalt Lycasin HBC

25 g 40 g 25 g 40 g 25 g 40 g

Hard 0.02Æ 0.14 0.08Æ 0.04 0.08Æ 0.27 0.4Æ 0.20 0.06Æ 0.24 0.14Æ 0.40 Normal 1.10Æ 0.67 1.08Æ 0.84 1.04Æ 0.87 1.00Æ 0.96 0.96Æ 0.75 0.98Æ 0.84 Watery 0.20Æ 0.57 0.16Æ 0.46 0.30Æ 0.70 0.72Æ 1.17* 0.26Æ 0.63 0.40Æ 0.66***

Total 1.32Æ 0.76 1.32Æ 0.76 1.42Æ 0.12 1.76Æ 1.14** 1.28Æ 0.69 1.52Æ 0.70

*Significant increase in mean frequency of bowel movements to pass watery faeces compared to 40 g sucrose (P < 0.005). **Significant increase in mean frequency of total bowel movements compared to 40 g sucrose (P < 0.025). ***Significant increase in mean frequency of bowel movements to pass watery faeces compared 40 g sucrose product (P < 0.05).

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 763 schoolchildren in this study as previously indicated in other significantly higher score compared to 25 g isomalt, studies with schoolchildren (Johnson & Hackett, 1997; (P < 0.05), as did 40 g lycasin HBC compared with 25 g of Adamson et al, 1992). lycasin HBC (P < 0.005) These results are in keeping with The effect of age upon GI tolerance of polyols is unclear Koutsou et al (1996), who demonstrated the dose-depen- and data based upon grams intake per kilogram body weight dency of GI symptoms following polyol ingestion. However may give a false impression of tolerance in children com- scores following consumption of 25 g lycasin HBC by both pared to adults (Livesey, 2001). Previous studies with isomalt adults and children were not significantly different from given to children suggest there is no difference in the those following consumption of sucrose sweets, whereas tolerance of children aged 8 – 12 y and those aged up to 18 consumption of 25 g isomalt sweets increased the score in (Paige et al, 1992). In order to compare results from children both children and adults (P < 0.01 and P < 0.005, respec- and adults in this study, a mean symptom score has been tively). There were no significant differences in mean symp- calculated following consumption of products in each case. tom scores following consumption of 25 g of any product The mean symptom score for children consuming products between adults and children. Considering that both double- over two days and adults consuming 25 and 40 g products on blind studies were conducted with different groups, in dif- one day each were derived by summing each subject’sGI ferent sites, at different times and the subjective nature of responses for colic, bloating, borborygmi, flatulence and the data, there is a remarkable correlation in the mean watery faeces using the hedonic, 0, 1, 2, 3 grade scales symptom scores of both children and adults following con- described earlier. For both children and adults, bowel move- sumption of sucrose based products (Figure 1). Overall, ments to pass watery faeces were scored as none ¼ 0, one ¼ 1, results strongly suggest that both children and adults toler- two ¼ 2, three or more ¼ 3. ate 25 g doses of isomalt and of lycasin HBC in sweets equally Figure 3 shows the mean symptom scores of children and well. adults following consumption of sucrose, isomalt and lyca- However, the mean symptom scores of children following sin HBC sweets. In adults, the score increased significantly consumption of 25 g lycasin HBC and isomalt sweets were following consumption of 40 g isomalt and 40 g lycasin HBC slightly lower than those of adults. This is probably due to sweets compared to sucrose sweets (P < 0.001 in both cases). differences in the time taken to consume sweets between Forty grams of isomalt consumed by adults resulted in a adults and children. Because of ethical considerations chil-

1 Figure 3 Symptom scores following consumption by children and adults of sweets containing sucrose, isomalt and lycasin HBC=meanÆ s.e.m.

European Journal of Clinical Nutrition Tolerance of isomalt and lycasin HBC in children and adults A Lee et al 764 dren were given the opportunity to consume sweets Koutsou GA, Storey DM, Lee A, Zumbe´ A, Flourie´ B, Le Bot Y & throughout the day rather than adhere to the strict con- Olivier Ph (1996): Dose-related gastrointestinal response to the ingestion of either isomalt, lactitol or maltitol in milk chocolate. sumption pattern enforced on adults. It is quite possible that Eur. J. Clin. Nutr. 50,17– 21. differences in the consumption time of sweets influenced the Kruger D, Grossklaus R, Klingebiel L, Ziese T & Kochgensecke S occurrence of gastrointestinal symptoms in both study (1991): Caloric availability of palatinit in the small intestine of groups. A longer consumption time theoretically partitions rats: implications of dose dependancy on the energy value. Nutr. Res. 11, 669 – 678. the dose of polyol entering the colon thereby limiting the Langkilde AM, Anderson H, Schweizer TF & Wursch P (1994): Diges- osmotic and=or fermentative effect. In studies with young tion and absorption of sorbitol, maltitol and isomalt from the adults, ingestion of up to 50 g polyol sweets has been shown small bowel. A study in ileostomy subjects. Eur. J. Clin. Nutr. 48, to cause dose-dependent increases in GI symptoms and 768 – 775. Lee A, Zumbe´ A & Storey DM (1994): Breath hydrogen after ingestion laxation, the response being dependent on the period of of the bulk sweeteners sorbitol, isomalt and sucrose in chocolate. time over which products were consumed (Storey & Zumbe´, Br. J. Nutr. 71, 731 – 737. 1996). Double-blind, controlled cross-over studies similar to Livesey G (2001): Tolerance of low-digestible carbohydrates: a gen- Br. J. Nutr. this investigation are recommended to assess the subjective eral view. 85,S7– S16. Macfarlane GT & Cummings JH (1991): The colonic flora, fermenta- symptoms of intolerance following ingestion of poorly tion and large bowel function. In: The Large Intestine: Physiology, absorbed carbohydrates (Cummings et al, 2001; Marteau & Pathophysiology and Disease, ed. SF Phillips, JH Pemberton & RG Flourie´, 2001). However, experimental conditions and inter- Shorter, pp 51 – 92. New York: Raven Press. Marteau P & Flourie´ B (2001): Tolerance to low-digestible carbohy- subject variability in GI tolerance due to differences in drates: symptomatology and methods. Br. J. Nutr. 85,S17– S21. absorption capacity, motility pattern, colonic response and McNemar Q (1947): Note on the sampling error of the difference intestinal sensitivity may influence results (Marteau & between correlated proportions or percentages. Psychometrica 12, Flourie´, 2001). 153 – 157. Menzies IS (1983): Medical importance of sugars in the alimentary tract. In: Developments in Sweeteners — 2, ed. TH Grenby, KJ Parker Acknowledgements & MG Lindley, pp 89 – 118. London: Applied Science. The investigators thank the children, parents and staff of the Nilsson U & Jagerstad M (1987): Hydrolysis of lactitol, maltitol and Alder Park and Westwood Park County Primary Schools, palatinit by human intestinal biopsies. Br. J. Nutr. 58, 199 – 206. Paige DM, Bayless TM & Davis LR (1992): Palatinit digestibility in Salford, Greater Manchester. children. Nutr. Res. 12,27– 37. References Pelletier X, Hanesse B, Bornet F & Debry G (1994): Glycaemic and insulinaemic responses in healthy volunteers upon ingestion of Adamson A, Rugg-Gunn AJ, Butler T, Appleton DR & Hackett AF maltitol and maltitol syrups. Diabetes & Metab. 20, 291 – 296. (1992): Dietary sources of energy protein, unavailable carbohy- Saunders DR & Wiggins HS (1981): Conservation of mannitol, drate and fat in 11 – 12-year-old English children compared with lactulose and raffinose by the human colon. Am. J. Physiol. 241, results in 1980. J. Hum. Nutr. Diet. 5, 371 – 385. G397 – G402. Beaugerie L, Flourie´ B, Marteau P, Pellier P, Franchisseur C & Ram- Sicard PJ & Le Bot Y (1994): Manufacturing opportunities with non- baud JC (1990): Digestion and absorption in the human intestine sugar sweeteners. In: Sugarless — Towards the Year 2000, ed. AJ of three sugar alcohols. Gastroenterology 99,717– 723. Rugg-Gunn, pp 112 – 135. Cambridge: Royal Society of Chemistry. Beaugerie L, Flourie´ B, Pellier P, Achour L, Franchisseur C & Rambaud Storey DM & Zumbe´ A (1996): Physiology, metabolism and tolerance JC (1991): Tolerance clinique, absorption intestinale et valeur of digestible and low-digestible carbohydrates. In: Handbook of energetique de quatre polyols pris a jeun. Gastroenterol. Clin. Biol. Starch Hydrolysis Products and Their Derivatives, ed. M Kearsley, pp 15, 929 – 932. 178 – 229. Glasgow: Blackie. Bloom DA, Seeley WW, Ritchey ML & McGuire EJ (1993): Toilet Storey DM, Koutsou G, Lee A, Zumbe´ A, Olivier P, Le Bot Y & Flourie´ habits and continence in children — an opportunity sampling in B (1998): Tolerance and breath hydrogen excretion following search of normal parameters. J. Urol. 149, 1087 – 1090. ingestion of maltitol incorporated at two levels into milk choco- Cummings JH, Lee A & Storey D (2001): Workshop: physiology and late consumed by healthy young adults with and without fasting. tolerance of LDCs. Br. J. Nutr. 85,S59– S60. J. Nutr. 128, 587 – 592. Fritz M, Siebert G & Kaspar H (1985): Dose dependence of breath Thiebaud D, Jacot E, Schmitz H, Spengler, M & Felber JP (1984): hydrogen and methane in healthy volunteers after ingestion of a Comparative study of isomalt and sucrose by means of continuous commercial disaccharide mixture Palatinit. Br. J. Nutr. 54, 389 – indirect calorimetry. Metabolism 33,808– 813. 400. Ziesenitz SC & Siebert G (1987): The metabolism and utilisation of Gart JJ (1969): An exact test for comparing matched proportions in polyols and other bulk sweeteners compared with sugar. In: cross-over designs. Biometrica 56:75– 80. Developments in Sweeteners, Vol 3, ed. TH Grenby, pp 109 – 149. Grenby TH & Saldanha MG (1988): Comparison of lycasin versus Barking: Elsevier. sucrose sweets in demineralisation studies of human enamel and Zumbe´ A, Lee A & Storey DM (1994): Manufacture and marketing of hydroxylapatite. Caries Res. 22, 269 – 275. non-sugar chocolate. In: Sugarless — Towards the Year 2000, ed. AJ Grupp U & Siebert G (1978): Metabolism of hydrogenated palatinose, Rugg-Gunn, pp 147 – 171. Cambridge: Royal Society of Chemistry. an equimolar mixture of a-D-glucopyranosido-1-6-sorbitol and a- Zumbe´ A, Lee A & Storey DM (2001): Polyols in confectionery: the D-glucopyranosido-1-6-mannitol. Res. Exp. Med. (Berlin) 173, 261 – route to sugar-free, reduced sugar and reduced calorie confection- 278. ery. Br. J. Nutr. 88,S31– S45. Hyams JS (1983): Sorbitol intolerance: an unappreciated cause of functional gastrointestinal complaints. Gastroenterology 84,30– 33. Johnson B & Hackett AF (1997): Eating habits of 11 – 14-year-old schoolchildren living in less affluent areas of Liverpool, UK. J. Hum. Nutr. Diet. 10, 135 – 144.

European Journal of Clinical Nutrition