A tolerance study of maltitol in Chinese healthy subjects: a multicenter, simple-blind, placebo-controlled study

A tolerance study of maltitol in Chinese healthy subjects: a multicenter, simple-blind, placebo-controlled study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A tolerance study of maltitol in Chinese healthy subjects: a multicenter, simple-blind, placebo-controlled study Xuesong Xiang, Siyu Wang, Xiaobing Liu, Jun Wang, Zihan Xu, Mingyu Zhu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4015055/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives: Our aim was to evaluate the gastrointestinal tolerance of maltitol in Chinese individuals, and to explore the gastrointestinal reactions, and small intestine bacterial overgrowth (SIBO). Methods: 132 healthy subjects from three cities were enrolled in the 6 weeks’ study. All subjects were prescribed a lactulose hydrogen breath test to determine SIBO before the study. The maltitol-containing cookies (MC) with each piece of MC containing 2.5 g maltitol and sucrose-containing cookies (SC) with each piece of SC containing 3.6 g sucrose were prepared and provided. Half of subjects firstly consumed 3 pieces MC and the others consumed 3 pieces SC at the first week, then switched at the second week. All subjects consumed 5 pieces MC at the third week and consumed 7 pieces MC at the fourth week. Half of subjects consumed 10 pieces MC and the others consumed 10 pieces SC at the fifth week, then switched at the sixth week. After consuming the cookies each time, all subjects were asked to fill questionnaire to record if they experienced any gastrointestinal reactions. Results: The incidence of gastrointestinal reactions increases with the intake of maltitol dose and no significant difference in gastrointestinal reactions between maltitol cookies and sucrose cookies with the 3 pieces consumed. There was a significant difference in gastrointestinal reaction between the two types of cookies when the intake reached 10 pieces ( P <0.0001). The incidence of gastrointestinal reactions was significantly different between the positive and negative lactulose hydrogen breath conditions ( P <0.0001) and negative hydrogen breath test were more likely to experience gastrointestinal reactions (Z=5.2088). Conclusion: Chinese individuals have the lower tolerance threshold for maltitol (17.5 g) as compared to the individuals in other countries. The ethnic differences should be taken into account in the evaluation ad regulations of safe dosages for maltitol in future. Health sciences/Health care/Nutrition Health sciences/Signs and symptoms/Digestive signs and symptoms maltitol tolerance study small intestine bacterial overgrowth (SIBO) Chinese subjects evaluation Figures Figure 1 Figure 2 Introduction Maltitol is a non-reducing sugar and disaccharide polyol that is listed as an alternative sweetener for sucrose. It has a sweetness that is 75–90% of sucrose [ 1 ] . Compared to sucrose and glucose, polyols are relatively low in calories and have a low glycemic index (GI), which may reduce insulin resistance and benefit individuals with obesity or metabolic syndrome [ 2 – 4 ] . As a suitable substitute for sucrose, maltitol has been widely used in chocolate, yogurt and baked goods [ 5 , 6 ] . A small amount of maltitol is digested in the small intestine, and most can enter the colon and be fermented by bacteria [ 7 , 8 ] . Maltitol is absorbed dose-dependently in the small intestine [ 9 ] . However, due to the permeability in the intestine and the fermentation [ 10 ] , the slow-digesting character can cause side effects involving flatulence and diarrhea [ 11 ] . In general, maltitol’s use in food is considered safe and does not produce severe adverse reactions [ 10 ] . So far, the study on the tolerance dose of maltitol had been conducted in European studies [ 12 ] . Further, several studies confirmed that maltitol does not cause gastrointestinal reactions, or severe gastrointestinal reaction when consumed to a daily dosage of 90 g in the European populations [ 13 – 15 ] . Nevertheless, the findings of study in young Japanese women had pointed out that 85.3% subjects occurred diarrhea when taking an aqueous solution containing 45 g of maltitol [ 16 ] . Given that there was a great difference in maltitol tolerance dose between Asian and European populations, in addition, there was a paucity of studies on the maltitol tolerance dose in China. So it is extremely necessary to explore the maltitol tolerance dose in healthy Chinese populations, particularly in confections and baked goods with maltitol increasingly used [ 17 ] . Therefore, this study was performed to investigate the maltitol tolerance dose in healthy Chinese populations. In addition, the lactulose hydrogen breath test was added to examine whether excessive growth of small intestinal bacteria could have some influence on maltitol tolerance. Materials and methods Study subjects The current study was conducted in three major cities in China, including Beijing, Shanghai and Shenzhen. The subjects aged 18−45 years and with BMI of 18.5-23.9 Kg/m 2 were recruited by printed advertisements. They were excluded if they suffered from any functional, metabolic or inflammatory disease, had food allergies, such as wheat, milk, eggs, nuts; were taking medication that could affect nutrition absorption; had used antibiotics within the past 3 months; had participated in any other pilot study in the past month; drank more than 25 g of alcohol per day (men) or more than 15 g of alcohol per day (women); smoked more than 4 cigarettes per day; or had history of taking antibiotics or laxatives within 3 months. All subjects provided informed assent or consent after the nature of study explained. The lactulose hydrogen breath test The lactulose hydrogen breath test was arranged before the experiment to examine the SIBO [18] . The subjects were instructed to follow a low-carbohydrate diet and were asked to abstain from food, drink, or smoking before 12 hours. All subjects were required to rinse their mouth with at least 20 mL water prior to the test. Baseline breath samples were first obtained from the subjects, who were provided with 10 g lactulose and 250 mL of water. Breath samples were collected at 15 min intervals within the 105 min using a Breath Analyzer (QuinTron Instrument Co. Milwaukee, Wisconsin, USA). The H 2 content in the breath samples were measured using the Breath Analyzer. A level of H 2 above 20 ppm or a rise of at least 20 ppm within the 90 min was considered as a positive. Study design This study was designed as a multicenter, -single blinded, placebo-controlled trial. During the experiment, all subjects were provided with 2 kinds of cookies. One is the sucrose-containing cookies (SC), containing 3.6 g sucrose per piece, and another is the maltitol-containing cookies (MC), containing 2.5 g maltitol and 0.6 g polydextrose per piece. The cookies were required of identical in taste, appearance and other sensory characteristics, and they were distinguished by codes and were not revealed to the investigators. The experiment was arranged as follows: (1) From the 1st to 2nd week, there was a controlled period for 3 pieces of cookies. Half of the subjects consumed SC, while the other half consumed MC at the 1st week. Then they switched at the 2nd week. (2) From the 3rd to 4th week, all subjects were given 5 pieces and 7 pieces MC. (3) From the 5th to 6th week was another controlled period, all subjects were given 10 pieces cookies. Subjects only consumed cookies while they were fasting on Thursday’s morning of every week. Once the subjects consumed cookies, they were asked to complete the gastrointestinal symptom questionnaire at the 1st hour, 2nd hour, 4th hour, 6th hour, 10th hour, 24th hour, and 48th hour. All subjects would then enter a 6-day washout period. The Gastrointestinal Tolerance Questionnaire (GITQ) captured 9 symptoms, including diarrhea, gas flatulence, abdominal bloating, abdominal pain/discomfort, burping, reflux (heartburn), borborygmus/stomach rumbling, nausea, and vomiting. The stool consistency was captured in the Bowel Habits Diary (BHD) with Bristol Stool Scale (BSS) to assess the occurrence of diarrhea. By comparing the records of the subjects in GITQ, we can objectively evaluate the incidence of diarrhea under different levels of cookie intake . Statistical analysis Statistical analysis was conducted using SAS software 9.4 ( SAS Inc., Cary, N.C., USA) and GraphPad Prism 8.0. A one-way ANOVA was performed to compare the basic subject information from different cities. The rates of gastrointestinal reactions among 4 MC groups were compared using the Chi-square test, followed by Bonferroni’s test for post hoc pairwise comparison. The rates of gastrointestinal reactions between the MC groups and the SC groups were analyzed using the Chi-square test and Fisher exact probability test. To detect a potential relationship between the results of the lactulose hydrogen breath test and the rates of gastrointestinal reactions, both the Chi-square test and logistic regression model were performed. Additionally, to detect the trend of the occurrence of gastrointestinal reactions in relation to positive lactulose hydrogen breath test results, a trend test was conducted using the Cochran-Armitage trend test. A significance level of P < 0.05 was considered statistically significant. Ethics statement All procedures were conducted in accordance with the “China Ethics Committee of Registering Clinical Trials” (ChiECRCT20210092) and were consented to by all subjects. Results The basic information of subjects The basic information of subjects was summarized in Table 1. A total of 132 subjects (44, 45 and 43) were recruited from Beijing, Shanghai, Shenzhen, respectively. The average age and BMI of subjects were 29.6 ± 5.1 years, and 21.8 ± 2.5 kg/m². There were no significant differences in age and BMI among the three cities ( P >0.05). Table 1 Basic characteristics of the subjects Variables Total (`x ± s) Beijing Shanghai Shenzhen N 132 44 45 43 Male 66 23 23 20 Female 66 21 22 23 Age (years) 29.6±5.1 29.7±5.0 30.2±5.2 28.8±5.1 Weight (Kg) 62.2±10.6 64.9±10.9 60.8±8.9 60.9±11.5 Height (cm) 168.6±8.9 169.4±8.4 168.9±9.4 167.3±9.0 BMI (Kg/m2) 21.8±2.5 22.5±2.5 21.2±1.8 21.6±2.9 The lactulose hydrogen breath test As shown in Table 2, 53 subjects tested were positive and 79 tested were negative. Among those who tested positive, 17 out of 44 were from Beijing, 20 out of 45 were from Shanghai, and 16 out of 43 were from Shenzhen. There was no statistical difference in the positive rate among three cities ( P >0.05). Moreover, there was no significant difference in the prevalence of SIBO among the three cities ( P >0.05). Table 2 The lactulose hydrogen breath test in the three cities Centers N Positive (+) Negative (-) χ 2 P Total 132 53 79 / / Beijing 44 17 27 0.726 0.542 Shanghai 45 20 25 Shenzhen 43 16 27 Note: positive (+) indicates an individual has SIBO, negative (-) indicates an individual has no SIBO. Gastrointestinal reactions Associate with cookies consumption Table 3 and Table 4 present the number of subjects who reported gastrointestinal reactions after consuming different doses of MC and SC. The data reveals that the number of subjects who experienced gastrointestinal reactions increased with higher intake of MC in all three cities. Table 3 The number of subjects with gastrointestinal reactions of MC in three cities City N 3 pieces (7.5g) 5 pieces (12.5g) 7 pieces (17.5g) 10 pieces (25.0g) + - + - + - + - Beijing 44 2 42 8 36 11 33 11 32 Shanghai 45 3 42 3 42 4 41 9 35 Shenzhen 43 1 42 5 38 8 35 20 21 Total 132 6 126 16 116 23 109 40 88 Note: 7.5g, 12.5g, 17.5g, 25.0g are the weight of maltitol in the corresponding number of MC. Table 4 The number of subjects with gastrointestinal reactions of SC in three cities City N 3 pieces 10 pieces + - + - Beijing 44 1 43 8 35 Shanghai 45 2 43 2 43 Shenzhen 43 0 43 3 38 Total 132 3 129 13 117 Significant differences were observed in the number of subjects reporting gastrointestinal reactions between MC groups consuming 7.5 g vs 17.5 g ( P =0.0035), 7.5 g vs 25.0 g ( P <0.0001), and 12.5 g vs 25.0 g ( P =0.0009). However, no significant difference was observed between 17.5 g and 25.0 g doses( P =0.0559). As there was no difference obtained between cities, the data were pooled for the analysis of the GITQ parameters ( P =0.4000). Table 5 shows the result of the GITQ, which identified subjects with gastrointestinal reactions. The most common symptoms were diarrhea, bloating and flatulence. Pairwise comparisons were made to investigate statistical differences in the number of subjects reporting bloating and flatulence between the four MC groups: 7.5 g vs 17.5 g ( P =0.0217), 7.5 g vs 25.0 g ( P <0.0001), 12.5 g vs 25.0 g ( P =0.0004) and 17.5 g vs 25.0 g ( P =0.0257). The number of subjects with diarrhea in the MC group was compared in pair-wised comparison. There were statistical differences between 7.5 g vs 25.0 g ( P <0.0001), 12.5 g vs 25.0 g ( P =0.0025) and 17.5 g vs . 25.0 g ( P =0.0353). Table 5 Specific gastrointestinal reaction rates of different symptoms Dose Total (%) Diarrhea (%) Bloating or flatulence (%) Abdominal pain (%) Gastrointestinal pain (%) Nausea (%) Stomachache (%) 3 pieces (7.5g) 4.8 1.5 3.8 1.5 0.8 0 0 5 pieces (12.5g) 13.8 4.5 9.1 0.8 0.8 0 0 7 pieces (17.5g) 21.1 6.1 16.7 1.5 0.8 0.8 0 10 pieces (25.0g) 59.3 17.8 27.9 3.9 0 0.8 0.8 The comparison of gastrointestinal reaction was conducted between the MC group and the SC group with 3 pieces and 10 pieces cookies. The incidence of different gastrointestinal reactions with 3 pieces cookies in two groups from the three cities were showed in Figure 1. No statistical differences were observed between the MC groups and SC groups when eating 3 pieces cookies. When the intake of cookies reaches 10 pieces, the incidence of gastrointestinal reactions was significantly higher in the MC group compared to the SC group ( P <0.0001) (Figure 2). The rate of diarrhea and bloating were higher in the MC group compared to the SC group when consuming 10 pieces of cookies ( P <0.0001). Table 6 Relationship between lactulose hydrogen Breath Test and Number of Occurrences of Gastrointestinal Reactions When eat Maltitol-containing Cookies Lactulose hydrogen breath test results Gastrointestinal reaction + - Positive (+) 31 173 Negative (-) 116 205 χ 2 27.13 P <0.0001 Table 6 demonstrates the number of subjects with gastrointestinal reactions with negative and positive at lactulose hydrogen breath test during 4 times of consumptions with MC. The Chi-square test and logistic regression model results showed that the incidence of gastrointestinal reactions was statistically different ( P <0.0001) under positive and negative lactulose hydrogen breath conditions. The Cochran-Armitage test was used to conduct trend test, Z=5.2088, indicating that negative hydrogen respiration test was more likely to have gastrointestinal reactions. Discussion This study investigated the gastrointestinal tolerance of maltitol in Chinese population using a multicenter, randomized, double-blinded, placebo-controlled study design. The results showed that the incidence of gastrointestinal reactions increased as the intake of maltitol increased, with bloating or flatulence being the most frequent gastrointestinal reaction. The results showed that the incidence of gastrointestinal symptoms increased as the MC intake increased. 4.8% of subjects experienced gastrointestinal reactions when consuming 7.5g maltitol. Moreover, the incidence of gastrointestinal reactions increased significantly (21.2–59.3%) when the range of taking maltitol was changed (17.5 g to 25.0 g). The most common gastrointestinal reaction is bloating or flatulence (3.8–27.9%) and diarrhea followed (1.5–17.8%), while only a few other gastrointestinal reactions were reported (< 4%). Previous studies on maltitol tolerance in general populations, have mainly focused on Europeans. In a study conducted in Europe involving 12 healthy subjects showed that when consumed maltitol-containing chocolate, the threshold of maltitol induce diarrhea or severe gastrointestinal reactions was up to 92 ± 6 g with maltitol per day [ 13 ] . Another study conducted on 40 volunteers showed that they were well tolerated in bowel habit or intestinal symptoms at a daily dose of 45.6 g of maltitol [ 14 ] . Likewise, Olivier’s study, which included 59 healthy subjects aged 18–24 years, showed that maltitol-containing chocolate did not have any laxative effect when ingested at either 30 g or 40 g maltitol [ 19 ] . However, there was a large discrepancy between our study and those in Europe. The current studies on the tolerance of maltitol in Chinese populations are relatively limited. Notably, a study carried out on 27 healthy Japanese women showed the intake range of maltitol was between 15 g to 45 g, 22 out of 27 subjects had osmotic diarrhea [ 17 ] . The findings in Japanese study are closer to those obtained in our current study. In summary, maltitol tolerance is lower in Asian populations compared to European populations, perhaps due to the different ethnic or regional lifestyle including food habits. In a study involving 12 healthy Chinese subjects, it was found that 25 g of maltitol did not cause more severe gastrointestinal reactions than the same dose of glucose [ 20 ] . In addition, the difference in results could be due to the different carriers used for maltitol ingestion. In our study, cookies were used as a maltitol-carrier, which may result in a certain food mixing effect, thereby reducing the tolerance threshold for maltitol. The impact of maltitol-carriers should be considered when maltitol is used as sweetener and sugar substitute. In our study, the baseline results of lactulose hydrogen breath test were correlated with the incidence of maltitol gastrointestinal reactions. This correlation might indicate that the individuals with SIBO are less likely to experience gastrointestinal reactions when they consume maltitol, although the digestion mechanism at the small intestinal is still unclear [ 21 ] . There are some limitations to be noted in our study. First, the current study was only performed on a group of Chinese healthy subjects, and the generalization and application of study results could be difficult in the general population. Second, there is a lack of sufficient research on colon microbiota, which could provide some clues to examine differences in ethnic tolerance. Third, a small amount of polydextrose was added to maltitol-containing cookies in our study. Polydextrose can improve the maltitol-containing cookies taste to some extent, and can make them more comparable to the traditional sucrose-containing cookies. The addition of small amounts of polydextrose (0.65g/100g) could have an interference on our results. Polydextrose is a high molecular weight polyol that is much more tolerated by subjects than other polyols, current reports suggest that consuming no more than 50g of polydextrose per day does not lead to more frequent diarrhea [ 22 ] . Since polydextrose is well tolerated, it’s reasonable to assume that the addition of small amounts of polydextrose had a limited effect on our results. Conclusion In conclusion, our study indicated that a single intake of more than 17.5 g maltitol in Chinese healthy population could increase the probability of gastrointestinal reactions, which was much lower than the existing threshold reported in previous studies. The results of this study provide the valuable reference material for the reasonable application of maltitol and the formulate some time-efficient regulations in future. Declarations Data Availability Statement: The data used in this study are available upon request from the corresponding author. Author Contribution Statement: Professor Xuesong Xiang was responsible for project organization and design. Professor Zhengyuan Wang provided statistical guidance and supervised the implementation of certain field experiments. Siyu Wang supervised specific field experiments and authored the main sections of the paper. Professor Liu Xiaobing conducted article revisions and performed statistical analyses. Professor Wang Jun offered guidance for select field experiments. Xu Zihan managed the collection of experimental data. Zhu Mingyu and Li Baolong were responsible for manuscript formatting and verifying statistical data. Funding: This study was supported by the Health Food Evaluation Center of State Food and Drug Administration (Grants No. ZBW-2017-BJSP-09). This research was supported in part by Mondelez SH Food Corp Mgt Co, Ltd. Acknowledgements: We would like to thank all the scientists, technicians and assistants who helped carry out this study. We are especially grateful to the volunteers involved in the study. The authors would like to thank Professor Liu Xiaobing's guidance to us. Ethical Approval: The study followed the Declaration of Helsinki and was approved by Chinese Ethics Committee of Registering Clinical Trials (APPROVAL No.: ChiECRCT20210092). Competing Interests: This study was conducted under the collaborative framework between national institute for nutrition and health in Chinese center for disease control and prevention. and Mondelez SH Food Corp Mgt Co, Ltd. The research funding was partially or fully provided by Mondelez SH Food Corp Mgt Co, Ltd. Nevertheless, Mondelez SH Food Corp Mgt Co, Ltd did not participate in the experimental design, data analysis, manuscript writing, or decision to publish. As the principal investigator and author of this study, I declare that there is a collaborative relationship with Mondelez SH Food Corp Mgt Co, Ltd, but I assure the independence and objectivity of the research. It should be noted that the experimental data generated in this study are currently used solely for academic research purposes and cannot be used for commercial purposes without the consent of Mondelez SH Food Corp Mgt Co, Ltd. All experimental procedures complied with relevant legal and ethical standards. References Ding, S., et al. (2019). "Evaluation of specific volume, texture, thermal features, water mobility, and inhibitory effect of staling in wheat bread affected by maltitol." Food Chem 283 : 123-130. Minehira, K. and L. Tappy (2002). 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4015055","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":278232591,"identity":"1551e072-9c14-4136-8459-c4cf576a1312","order_by":0,"name":"Xuesong Xiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYDACZgglB2SwAekDPCCeBDFajEnQAgWJDQwQLQwEtRgcZ3728GtbXfp2dt5jDxhq7siYsx9+eOMHg10eLi2SzWzmxjJnDufubOZLN2A49ozHsifN2LKHIbkYlxZ+ZgYzaYmKA7kbDvOYSTA2HOYxOJDDJg10IcipWAEbM/s3aQmDunQDuJbzb/Br4WfmMZP8UMGcgNByg4Atks08ZdIMZw4bgh2WcAyk5RnQLwbJOLUYnD++TfJnW528wfkzZhIfag7bG5xPBoZYhR1OLSDAzANjJSCMwqMeCBh/4JcfBaNgFIyCkQ4AuFRPmLkwHvsAAAAASUVORK5CYII=","orcid":"","institution":"China CDC","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xuesong","middleName":"","lastName":"Xiang","suffix":""},{"id":278232592,"identity":"73c6705d-883f-4d00-98be-a273bc005d62","order_by":1,"name":"Siyu Wang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Siyu","middleName":"","lastName":"Wang","suffix":""},{"id":278232593,"identity":"31782029-6fdd-4579-a8f0-0ecb2f34c500","order_by":2,"name":"Xiaobing Liu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaobing","middleName":"","lastName":"Liu","suffix":""},{"id":278232594,"identity":"0f5f49fa-2c7b-4bb4-a2a1-5e280dad93ee","order_by":3,"name":"Jun Wang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Wang","suffix":""},{"id":278232595,"identity":"1d93f87e-3f24-4a90-9ba6-2074e101f16a","order_by":4,"name":"Zihan Xu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zihan","middleName":"","lastName":"Xu","suffix":""},{"id":278232596,"identity":"dbf15af1-b807-4064-b661-e72cf76f8ba9","order_by":5,"name":"Mingyu Zhu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mingyu","middleName":"","lastName":"Zhu","suffix":""},{"id":278232597,"identity":"9e071749-b747-4577-93d9-b433e5ac3ec5","order_by":6,"name":"Baolong Li","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Baolong","middleName":"","lastName":"Li","suffix":""},{"id":278232598,"identity":"2fb83324-4925-42c4-9bf2-8b29c0f8b956","order_by":7,"name":"Zhengyuan Wang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhengyuan","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-03-05 03:36:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4015055/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4015055/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53019045,"identity":"b1869c14-9234-4780-9332-a2e9a358aaed","added_by":"auto","created_at":"2024-03-19 16:19:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":62215,"visible":true,"origin":"","legend":"\u003cp\u003eThe flow diagram of this study.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4015055/v1/3cc729bec427447f5354df12.png"},{"id":53019044,"identity":"23c3f593-141b-4e55-b27d-f33620ba4859","added_by":"auto","created_at":"2024-03-19 16:19:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":39257,"visible":true,"origin":"","legend":"\u003cp\u003eSpecific gastrointestinal reaction rate of different symptoms between SC group and MC group\u003cstrong\u003e A\u003c/strong\u003e: Specific gastrointestinal reaction rate of different symptoms in subjects who eat 3 pieces cookies; \u003cstrong\u003eB\u003c/strong\u003e: Specific gastrointestinal reaction rate of different symptoms in subjects who eat 10 pieces cookies\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4015055/v1/b3b44ea1d26925c6e49e4d39.png"},{"id":76016121,"identity":"7eeb7129-1889-4631-a284-1980f1cab912","added_by":"auto","created_at":"2025-02-11 13:04:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":817788,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4015055/v1/8ec5bd4d-95a3-4394-9a56-734e73c29097.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential conflict of interest.","formattedTitle":"A tolerance study of maltitol in Chinese healthy subjects: a multicenter, simple-blind, placebo-controlled study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMaltitol is a non-reducing sugar and disaccharide polyol that is listed as an alternative sweetener for sucrose. It has a sweetness that is 75\u0026ndash;90% of sucrose \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Compared to sucrose and glucose, polyols are relatively low in calories and have a low glycemic index (GI), which may reduce insulin resistance and benefit individuals with obesity or metabolic syndrome \u003csup\u003e[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. As a suitable substitute for sucrose, maltitol has been widely used in chocolate, yogurt and baked goods \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. A small amount of maltitol is digested in the small intestine, and most can enter the colon and be fermented by bacteria \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Maltitol is absorbed dose-dependently in the small intestine \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. However, due to the permeability in the intestine and the fermentation \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, the slow-digesting character can cause side effects involving flatulence and diarrhea \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn general, maltitol\u0026rsquo;s use in food is considered safe and does not produce severe adverse reactions \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. So far, the study on the tolerance dose of maltitol had been conducted in European studies \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Further, several studies confirmed that maltitol does not cause gastrointestinal reactions, or severe gastrointestinal reaction when consumed to a daily dosage of 90 g in the European populations \u003csup\u003e[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, the findings of study in young Japanese women had pointed out that 85.3% subjects occurred diarrhea when taking an aqueous solution containing 45 g of maltitol \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Given that there was a great difference in maltitol tolerance dose between Asian and European populations, in addition, there was a paucity of studies on the maltitol tolerance dose in China. So it is extremely necessary to explore the maltitol tolerance dose in healthy Chinese populations, particularly in confections and baked goods with maltitol increasingly used \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTherefore, this study was performed to investigate the maltitol tolerance dose in healthy Chinese populations. In addition, the lactulose hydrogen breath test was added to examine whether excessive growth of small intestinal bacteria could have some influence on maltitol tolerance.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003eStudy subjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe current study was conducted in\u0026nbsp;three major cities in China, including Beijing, Shanghai and Shenzhen. The subjects aged 18\u0026minus;45 years and with BMI of 18.5-23.9 Kg/m\u003csup\u003e2\u003c/sup\u003e were recruited by printed advertisements. They were excluded if they suffered from any functional, metabolic or inflammatory disease, had food allergies, such as wheat, milk, eggs, nuts; were taking medication that could affect nutrition absorption; had used antibiotics within the past 3 months; had participated in any other pilot study in the past month; drank more than 25 g of alcohol per day (men) or more than 15 g of alcohol per day (women); smoked more than 4 cigarettes per day; or had history of taking antibiotics or laxatives within 3 months. All subjects provided informed assent or consent after the nature of study explained.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;lactulose hydrogen breath test\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe lactulose hydrogen breath test was arranged before the experiment to examine the SIBO\u003csup\u003e[18]\u003c/sup\u003e.\u0026nbsp;The subjects were instructed to follow a low-carbohydrate diet and were asked to abstain from food, drink, or smoking before 12 hours.\u0026nbsp;All subjects were required to rinse their mouth with at least 20 mL water prior to the test. Baseline breath samples were first obtained from the subjects, who were provided with 10 g lactulose and 250 mL of water. Breath samples were collected at 15 min intervals within the 105 min using a\u0026nbsp;Breath Analyzer (QuinTron Instrument Co. Milwaukee, Wisconsin, USA). The H\u003csub\u003e2\u0026nbsp;\u003c/sub\u003econtent in the breath samples were measured using the Breath Analyzer. A level of H\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eabove 20 ppm or a rise of at least 20 ppm within the 90 min was considered as a positive.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was designed as a multicenter, -single blinded, placebo-controlled trial. During the experiment, all subjects were provided with 2 kinds of cookies. One is the sucrose-containing cookies (SC), containing 3.6 g sucrose per piece, and another is the maltitol-containing cookies (MC), containing 2.5 g maltitol and 0.6 g polydextrose per piece. The cookies were required of identical in taste, appearance and other sensory characteristics, and they were distinguished by codes and were not revealed to the investigators. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe experiment was arranged as follows: (1) From the 1st to 2nd week, there was a controlled period for 3 pieces of cookies. Half of the subjects consumed SC, while the other half consumed MC at the 1st week. Then they switched at the 2nd week. (2) From the 3rd to 4th week, all subjects were given 5 pieces and 7 pieces MC. (3) From the 5th to 6th week was another controlled period, all subjects were given 10 pieces cookies. Subjects only consumed cookies while they were fasting on Thursday\u0026rsquo;s morning of every week.\u003c/p\u003e\n\u003cp\u003eOnce the subjects consumed cookies, they were asked to complete the gastrointestinal symptom questionnaire at the 1st hour, 2nd hour, 4th hour, 6th hour, 10th hour, 24th hour, and 48th hour. All subjects would then enter a 6-day washout period. The Gastrointestinal Tolerance Questionnaire (GITQ) captured 9 symptoms, including diarrhea, gas flatulence, abdominal bloating, abdominal pain/discomfort, burping, reflux (heartburn), borborygmus/stomach rumbling, nausea, and vomiting. The stool consistency was captured in the Bowel Habits Diary (BHD) with Bristol Stool Scale (BSS) to assess the occurrence of diarrhea. By comparing the records of the subjects in GITQ, we can objectively evaluate the incidence of diarrhea under different levels of cookie intake\u003cu\u003e.\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was conducted using \u003cstrong\u003eSAS\u003c/strong\u003e software 9.4 (\u003cstrong\u003eSAS\u003c/strong\u003e Inc., Cary, N.C., USA) and GraphPad Prism 8.0. A one-way ANOVA was performed to compare the basic subject information from different cities. \u0026nbsp;The rates of gastrointestinal reactions among 4 MC groups were compared using the Chi-square test, followed by Bonferroni\u0026rsquo;s test for post hoc pairwise comparison. The rates of gastrointestinal reactions between the MC groups and the SC groups were analyzed using the Chi-square test and Fisher exact probability test. To detect a potential relationship between the results of the lactulose hydrogen breath test and the rates of gastrointestinal reactions, both the Chi-square test and logistic regression model were performed. Additionally, to detect the trend of the occurrence of gastrointestinal reactions in relation to positive lactulose hydrogen breath test results, a trend test was conducted using the Cochran-Armitage trend test. A significance level of \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures were conducted in accordance with the \u0026ldquo;China Ethics Committee of Registering Clinical Trials\u0026rdquo; (ChiECRCT20210092) and were consented to by all subjects.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eThe basic information of subjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe basic information of subjects was summarized in Table 1. A total of 132 subjects (44, 45 and 43) were recruited from Beijing, Shanghai, Shenzhen, respectively. The average age and BMI of subjects were 29.6\u0026nbsp;\u0026plusmn;\u0026nbsp;5.1 years, and 21.8\u0026nbsp;\u0026plusmn;\u0026nbsp;2.5 kg/m\u0026sup2;. There were no significant differences in age and BMI among the three cities (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBasic characteristics of the subjects\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003eTotal (`x \u0026plusmn; s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003eBeijing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\" colspan=\"3\"\u003e\n \u003cp\u003eShanghai\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003eShenzhen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003e29.6\u0026plusmn;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e29.7\u0026plusmn;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e30.2\u0026plusmn;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e28.8\u0026plusmn;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\"\u003e\n \u003cp\u003eWeight (Kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003e62.2\u0026plusmn;10.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e64.9\u0026plusmn;10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e60.8\u0026plusmn;8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e60.9\u0026plusmn;11.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\"\u003e\n \u003cp\u003eHeight (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003e168.6\u0026plusmn;8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e169.4\u0026plusmn;8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e168.9\u0026plusmn;9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e167.3\u0026plusmn;9.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.8659793814433%\"\u003e\n \u003cp\u003eBMI (Kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003e21.8\u0026plusmn;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e22.5\u0026plusmn;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e21.2\u0026plusmn;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" colspan=\"2\"\u003e\n \u003cp\u003e21.6\u0026plusmn;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eThe\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;lactulose\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ehydrogen\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;breath test\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 2, 53 subjects tested were positive and 79 tested were negative. Among those who tested positive, 17 out of 44 were from Beijing, 20 out of 45 were from Shanghai, and 16 out of 43 were from Shenzhen. There was no statistical difference in the positive rate among three cities (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). Moreover, there was no significant difference in the prevalence of SIBO among the three cities (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eThe lactulose hydrogen breath test in the three cities\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.587628865979383%\"\u003e\n \u003cp\u003eCenters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003ePositive (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\"\u003e\n \u003cp\u003eNegative (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003c/em\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"bottom\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"bottom\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"bottom\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"bottom\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"bottom\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" valign=\"bottom\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"bottom\"\u003e\n \u003cp\u003eBeijing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"bottom\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"bottom\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"bottom\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" rowspan=\"3\" valign=\"bottom\"\u003e\n \u003cp\u003e0.726\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" rowspan=\"3\" valign=\"bottom\"\u003e\n \u003cp\u003e0.542\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.027397260273972%\" valign=\"bottom\"\u003e\n \u003cp\u003eShanghai\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.698630136986301%\" valign=\"bottom\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.136986301369863%\" valign=\"bottom\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.136986301369863%\" valign=\"bottom\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.027397260273972%\" valign=\"bottom\"\u003e\n \u003cp\u003eShenzhen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.698630136986301%\" valign=\"bottom\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.136986301369863%\" valign=\"bottom\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.136986301369863%\" valign=\"bottom\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eNote:\u0026nbsp;\u003c/em\u003epositive (+) indicates an individual has SIBO, negative (-) indicates an individual has no SIBO.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGastrointestinal reactions Associate with cookies consumption\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 and Table 4 present the number of subjects who reported gastrointestinal reactions after consuming different doses of MC and SC. The data reveals that the number of subjects who experienced gastrointestinal reactions increased with higher intake of MC in all three cities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eThe number of subjects with gastrointestinal reactions of MC in three cities\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.26530612244898%\" rowspan=\"2\"\u003e\n \u003cp\u003eCity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.183673469387756%\" rowspan=\"2\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" colspan=\"2\"\u003e\n \u003cp\u003e3 pieces (7.5g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" colspan=\"2\"\u003e\n \u003cp\u003e5 pieces (12.5g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" colspan=\"2\"\u003e\n \u003cp\u003e7 pieces (17.5g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" colspan=\"2\"\u003e\n \u003cp\u003e10 pieces (25.0g)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.829787234042554%\"\u003e\n \u003cp\u003eBeijing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.829787234042554%\"\u003e\n \u003cp\u003eShanghai\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.829787234042554%\"\u003e\n \u003cp\u003eShenzhen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.829787234042554%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eNote:\u003c/em\u003e 7.5g, 12.5g, 17.5g, 25.0g are the weight of maltitol in the corresponding number of MC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eThe number of subjects with gastrointestinal reactions of SC in three cities\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.510204081632654%\" rowspan=\"2\"\u003e\n \u003cp\u003eCity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" rowspan=\"2\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" colspan=\"2\"\u003e\n \u003cp\u003e3 pieces\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" colspan=\"2\"\u003e\n \u003cp\u003e10 pieces\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.510204081632654%\" valign=\"top\"\u003e\n \u003cp\u003eBeijing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.510204081632654%\" valign=\"top\"\u003e\n \u003cp\u003eShanghai\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.510204081632654%\" valign=\"top\"\u003e\n \u003cp\u003eShenzhen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.510204081632654%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" valign=\"top\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSignificant differences were observed in the number of subjects reporting gastrointestinal reactions between MC groups consuming 7.5 g \u003cem\u003evs\u003c/em\u003e 17.5 g (\u003cem\u003eP\u003c/em\u003e=0.0035), 7.5 g \u003cem\u003evs\u0026nbsp;\u003c/em\u003e25.0 g (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001), and 12.5 g \u003cem\u003evs\u0026nbsp;\u003c/em\u003e25.0 g (\u003cem\u003eP\u003c/em\u003e=0.0009). However, no significant difference was observed between 17.5 g and\u003cem\u003e\u0026nbsp;\u003c/em\u003e25.0 g doses(\u003cem\u003eP\u003c/em\u003e=0.0559).\u0026nbsp;As there was no difference obtained between cities, the data were pooled for the analysis of the GITQ parameters (\u003cem\u003eP\u003c/em\u003e=0.4000).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 5 shows the result of the GITQ, which identified subjects with gastrointestinal reactions. The most common symptoms were diarrhea, bloating and flatulence. Pairwise comparisons were made to investigate statistical differences in the number of subjects reporting bloating and flatulence between the four MC groups: 7.5 g \u003cem\u003evs\u003c/em\u003e 17.5 g (\u003cem\u003eP\u003c/em\u003e=0.0217), 7.5 g \u003cem\u003evs\u003c/em\u003e 25.0 g (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001), 12.5 g \u003cem\u003evs\u003c/em\u003e 25.0 g (\u003cem\u003eP\u003c/em\u003e=0.0004) and 17.5 g \u003cem\u003evs\u003c/em\u003e 25.0 g (\u003cem\u003eP\u003c/em\u003e=0.0257). The number of subjects with diarrhea in the MC group was compared in pair-wised comparison. There were statistical differences between 7.5 g \u003cem\u003evs\u003c/em\u003e 25.0 g (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001), 12.5 g \u003cem\u003evs\u003c/em\u003e 25.0 g (\u003cem\u003eP\u003c/em\u003e=0.0025) and 17.5 g \u003cem\u003evs\u003c/em\u003e. 25.0 g (\u003cem\u003eP\u003c/em\u003e=0.0353).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u0026nbsp;\u003c/strong\u003eSpecific gastrointestinal reaction rates of different symptoms\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.541666666666666%\"\u003e\n \u003cp\u003eDose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003eTotal (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003eDiarrhea (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003eBloating or flatulence (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003eAbdominal pain (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003eGastrointestinal pain (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003eNausea\u003c/p\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003eStomachache\u003c/p\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.541666666666666%\"\u003e\n \u003cp\u003e3 pieces\u003c/p\u003e\n \u003cp\u003e(7.5g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.541666666666666%\"\u003e\n \u003cp\u003e5 pieces\u003c/p\u003e\n \u003cp\u003e(12.5g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.541666666666666%\"\u003e\n \u003cp\u003e7 pieces\u003c/p\u003e\n \u003cp\u003e(17.5g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e21.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.541666666666666%\"\u003e\n \u003cp\u003e10 pieces\u003c/p\u003e\n \u003cp\u003e(25.0g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e59.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.75%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe comparison of gastrointestinal reaction was conducted between the MC group and the SC group with 3 pieces and 10 pieces cookies. The incidence of different gastrointestinal reactions with 3 pieces cookies in two groups from the three cities were showed in Figure 1. No statistical differences were observed between the MC groups and SC groups when eating 3 pieces cookies. When the intake of cookies reaches 10 pieces, the incidence of gastrointestinal reactions was significantly higher in the MC group compared to the SC group (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001) (Figure 2).\u0026nbsp;The rate of diarrhea and bloating were higher in the MC group compared to the SC group when consuming 10 pieces of cookies (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6\u003c/strong\u003e Relationship between lactulose hydrogen Breath Test and Number of Occurrences of Gastrointestinal Reactions When eat Maltitol-containing Cookies\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.515151515151516%\" rowspan=\"2\"\u003e\n \u003cp\u003eLactulose hydrogen breath test results\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.484848484848484%\" colspan=\"2\"\u003e\n \u003cp\u003eGastrointestinal reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.680851063829785%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.319148936170215%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003ePositive (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e173\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eNegative (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.515151515151516%\"\u003e\n \u003cp\u003e\u0026chi;\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.484848484848484%\" colspan=\"2\"\u003e\n \u003cp\u003e27.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.515151515151516%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.484848484848484%\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 6 demonstrates the number of subjects with gastrointestinal reactions with negative and positive at lactulose hydrogen breath test during 4 times of consumptions with MC.\u0026nbsp;The Chi-square test and logistic\u0026nbsp;regression\u0026nbsp;model results showed that the incidence of gastrointestinal reactions was statistically different (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001) under positive and negative lactulose hydrogen breath conditions. The Cochran-Armitage test was used to conduct trend test, Z=5.2088, indicating that negative hydrogen respiration test was more likely to have gastrointestinal reactions.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the gastrointestinal tolerance of maltitol in Chinese population using a multicenter, randomized, double-blinded, placebo-controlled study design. The results showed that the incidence of gastrointestinal reactions increased as the intake of maltitol increased, with bloating or flatulence being the most frequent gastrointestinal reaction. The results showed that the incidence of gastrointestinal symptoms increased as the MC intake increased. 4.8% of subjects experienced gastrointestinal reactions when consuming 7.5g maltitol. Moreover, the incidence of gastrointestinal reactions increased significantly (21.2\u0026ndash;59.3%) when the range of taking maltitol was changed (17.5 g to 25.0 g). The most common gastrointestinal reaction is bloating or flatulence (3.8\u0026ndash;27.9%) and diarrhea followed (1.5\u0026ndash;17.8%), while only a few other gastrointestinal reactions were reported (\u0026lt;\u0026thinsp;4%).\u003c/p\u003e \u003cp\u003ePrevious studies on maltitol tolerance in general populations, have mainly focused on Europeans. In a study conducted in Europe involving 12 healthy subjects showed that when consumed maltitol-containing chocolate, the threshold of maltitol induce diarrhea or severe gastrointestinal reactions was up to 92\u0026thinsp;\u0026plusmn;\u0026thinsp;6 g with maltitol per day\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Another study conducted on 40 volunteers showed that they were well tolerated in bowel habit or intestinal symptoms at a daily dose of 45.6 g of maltitol \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Likewise, Olivier\u0026rsquo;s study, which included 59 healthy subjects aged 18\u0026ndash;24 years, showed that maltitol-containing chocolate did not have any laxative effect when ingested at either 30 g or 40 g maltitol \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, there was a large discrepancy between our study and those in Europe. The current studies on the tolerance of maltitol in Chinese populations are relatively limited. Notably, a study carried out on 27 healthy Japanese women showed the intake range of maltitol was between 15 g to 45 g, 22 out of 27 subjects had osmotic diarrhea \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. The findings in Japanese study are closer to those obtained in our current study. In summary, maltitol tolerance is lower in Asian populations compared to European populations, perhaps due to the different ethnic or regional lifestyle including food habits. In a study involving 12 healthy Chinese subjects, it was found that 25 g of maltitol did not cause more severe gastrointestinal reactions than the same dose of glucose \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. In addition, the difference in results could be due to the different carriers used for maltitol ingestion. In our study, cookies were used as a maltitol-carrier, which may result in a certain food mixing effect, thereby reducing the tolerance threshold for maltitol. The impact of maltitol-carriers should be considered when maltitol is used as sweetener and sugar substitute.\u003c/p\u003e \u003cp\u003eIn our study, the baseline results of lactulose hydrogen breath test were correlated with the incidence of maltitol gastrointestinal reactions. This correlation might indicate that the individuals with SIBO are less likely to experience gastrointestinal reactions when they consume maltitol, although the digestion mechanism at the small intestinal is still unclear \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThere are some limitations to be noted in our study. First, the current study was only performed on a group of Chinese healthy subjects, and the generalization and application of study results could be difficult in the general population. Second, there is a lack of sufficient research on colon microbiota, which could provide some clues to examine differences in ethnic tolerance. Third, a small amount of polydextrose was added to maltitol-containing cookies in our study. Polydextrose can improve the maltitol-containing cookies taste to some extent, and can make them more comparable to the traditional sucrose-containing cookies. The addition of small amounts of polydextrose (0.65g/100g) could have an interference on our results. Polydextrose is a high molecular weight polyol that is much more tolerated by subjects than other polyols, current reports suggest that consuming no more than 50g of polydextrose per day does not lead to more frequent diarrhea\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Since polydextrose is well tolerated, it\u0026rsquo;s reasonable to assume that the addition of small amounts of polydextrose had a limited effect on our results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study indicated that a single intake of more than 17.5 g maltitol in Chinese healthy population could increase the probability of gastrointestinal reactions, which was much lower than the existing threshold reported in previous studies. The results of this study provide the valuable reference material for the reasonable application of maltitol and the formulate some time-efficient regulations in future.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e The data used in this study are available upon request from the corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution Statement:\u0026nbsp;\u003c/strong\u003eProfessor Xuesong Xiang was responsible for project organization and design. Professor Zhengyuan Wang provided statistical guidance and supervised the implementation of certain field experiments. Siyu Wang supervised specific field experiments and authored the main sections of the paper. Professor Liu Xiaobing conducted article revisions and performed statistical analyses. Professor Wang Jun offered guidance for select field experiments. Xu Zihan managed the collection of experimental data. Zhu Mingyu and Li Baolong were responsible for manuscript formatting and verifying statistical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study was supported by the Health Food Evaluation Center of State Food and Drug Administration (Grants No. ZBW-2017-BJSP-09). This research was supported in part by Mondelez SH Food Corp Mgt Co, Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe would like to thank all the scientists, technicians and assistants who helped carry out this study. We are especially grateful to the volunteers involved in the study. The authors would like to thank Professor Liu Xiaobing\u0026apos;s guidance to us.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u003c/strong\u003e The study followed the Declaration of Helsinki and was approved by Chinese Ethics Committee of Registering Clinical Trials (APPROVAL No.: ChiECRCT20210092).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u0026nbsp;\u003c/strong\u003eThis study was conducted under the collaborative framework between national institute for nutrition and health in Chinese center for disease control and prevention. and Mondelez SH Food Corp Mgt Co, Ltd. The research funding was partially or fully provided by Mondelez SH Food Corp Mgt Co, Ltd. Nevertheless, Mondelez SH Food Corp Mgt Co, Ltd did not participate in the experimental design, data analysis, manuscript writing, or decision to publish. As the principal investigator and author of this study, I declare that there is a collaborative relationship with Mondelez SH Food Corp Mgt Co, Ltd, but I assure the independence and objectivity of the research. It should be noted that the experimental data generated in this study are currently used solely for academic research purposes and cannot be used for commercial purposes without the consent of Mondelez SH Food Corp Mgt Co, Ltd. All experimental procedures complied with relevant legal and ethical standards.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDing, S., et al. (2019). \u0026quot;Evaluation of specific volume, texture, thermal features, water mobility, and inhibitory effect of staling in wheat bread affected by maltitol.\u0026quot; \u003cu\u003eFood Chem\u003c/u\u003e \u003cstrong\u003e283\u003c/strong\u003e: 123-130.\u003c/li\u003e\n\u003cli\u003eMinehira, K. and L. 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Its measurement and its contribution to diarrhea. .\u0026quot; \u003cu\u003eJ Clin Invest\u003c/u\u003e \u003cstrong\u003e86\u003c/strong\u003e(6): 1936-1944.\u003c/li\u003e\n\u003cli\u003eOku., T., et al. (1991). \u0026quot;Metabolic fate of ingested [14C]-maltitol in man.\u0026quot; \u003cu\u003eJournal of nutritional science and vitaminology \u003cstrong\u003e37(5)\u003c/strong\u003e: 529\u0026ndash;544.\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eSaraiva, A., et al. (2020). \u0026quot;Maltitol: Analytical Determination Methods, Applications in the Food Industry, Metabolism and Health Impacts.\u0026quot; \u003cu\u003eInt J Environ Res Public Health\u003c/u\u003e \u003cstrong\u003e17\u003c/strong\u003e(14).\u003c/li\u003e\n\u003cli\u003eRuskon\u0026eacute;-Fourmestraux., A., et al. (2003). \u0026quot;A digestive tolerance study of maltitol after occasional and regular consumption in healthy humans.\u0026quot;\u003cu\u003e European journal of clinical nutrition\u003c/u\u003e \u003cstrong\u003e57(1)\u003c/strong\u003e: 26\u0026ndash;30.\u003c/li\u003e\n\u003cli\u003eBeards, E., et al. (2010). \u0026quot;A human volunteer study to assess the impact of confectionery sweeteners on the gut microbiota composition.\u0026quot; \u003cu\u003eBr J Nutr\u003c/u\u003e \u003cstrong\u003e104\u003c/strong\u003e(5): 701-708.\u003c/li\u003e\n\u003cli\u003eSaraiva, A., et al. (2020). \u0026quot;Maltitol: Analytical Determination Methods, Applications in the Food Industry, Metabolism and Health Impacts.\u0026quot; \u003cu\u003eInt J Environ Res Public Health\u003c/u\u003e \u003cstrong\u003e17\u003c/strong\u003e(14): 5227.\u003c/li\u003e\n\u003cli\u003eStorey DM, K. G., Lee A, Zumbe A, Olivier P, Le Bot Y, Flourie B. (1998). \u0026quot;Tolerance and breath hydrogen excretion following ingestion of maltitol incorporated at two levels into milk chocolate consumed by healthy young adults with and without fasting.\u0026quot;\u003cu\u003e J Nutr\u003c/u\u003e \u003cstrong\u003e128\u003c/strong\u003e(3): 587-592.\u003c/li\u003e\n\u003cli\u003eOku T, H. R., Nakamura S. (2008). \u0026quot;Suppressive effect of cellulose on osmotic diarrhea caused by maltitol in healthy female subjects.\u0026quot; \u003cu\u003eJ Nutr Sci Vitaminol (Tokyo)\u003c/u\u003e \u003cstrong\u003e54\u003c/strong\u003e(4): 309-314.\u003c/li\u003e\n\u003cli\u003eRezaie, A., et al. (2017). \u0026quot;Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus.\u0026quot; \u003cu\u003eAm J Gastroenterol\u003c/u\u003e \u003cstrong\u003e112\u003c/strong\u003e(5): 775-784.\u003c/li\u003e\n\u003cli\u003eKoutsou GA, S. D., Lee A, Zumbe A, Flourie B, leBot Y, Olivier Ph (1996). \u0026quot;. Dose-related gastrointestinal response to the ingestion of either isomalt, lactitol or maltitol in milk chocolate.\u0026quot; \u003cu\u003eEur J Clin Nutr\u003c/u\u003e \u003cstrong\u003e50\u003c/strong\u003e(1): 17-21.\u003c/li\u003e\n\u003cli\u003e李佳, et al. (2022). \u0026quot;麦芽糖醇在健康人群的胃肠道耐受反应.\u0026quot; \u003cu\u003eFood and Nutrition in China\u003c/u\u003e \u003cstrong\u003e28(08):49-52\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eStaudacher, H. M. and K. Whelan (2017). \u0026quot;The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.\u0026quot; \u003cu\u003eGut\u003c/u\u003e \u003cstrong\u003e66\u003c/strong\u003e(8): 1517-1527.\u003c/li\u003e\n\u003cli\u003eFlood, M. T., et al. (2004). \u0026quot;A review of the clinical toleration studies of polydextrose in food.\u0026quot; \u003cu\u003eFood Chem Toxicol\u003c/u\u003e \u003cstrong\u003e42\u003c/strong\u003e(9): 1531-1542.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"maltitol, tolerance study, small intestine bacterial overgrowth (SIBO), Chinese subjects, evaluation","lastPublishedDoi":"10.21203/rs.3.rs-4015055/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4015055/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e Our aim was to evaluate the gastrointestinal tolerance of maltitol in Chinese individuals, and to explore the gastrointestinal reactions, and small intestine bacterial overgrowth (SIBO).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003e132 healthy subjects from three cities were enrolled in the 6 weeks’ study. All subjects were prescribed a lactulose hydrogen breath test to determine SIBO before the study. The maltitol-containing cookies (MC) with each piece of MC containing 2.5 g maltitol and sucrose-containing cookies (SC) with each piece of SC containing 3.6 g sucrose were prepared and provided. Half of subjects firstly consumed 3 pieces MC and the others consumed 3 pieces SC at the first week, then switched at the second week. All subjects consumed 5 pieces MC at the third week and consumed 7 pieces MC at the fourth week. Half of subjects consumed 10 pieces MC and the others consumed 10 pieces SC at the fifth week, then switched at the sixth week. After consuming the cookies each time, all subjects were asked to fill questionnaire to record if they experienced any gastrointestinal reactions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The incidence of gastrointestinal reactions increases with the intake of maltitol dose and no significant difference in gastrointestinal reactions between maltitol cookies and sucrose cookies with the 3 pieces consumed. There was a significant difference in gastrointestinal reaction between the two types of cookies when the intake reached 10 pieces (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001). The incidence of gastrointestinal reactions was significantly different between the positive and negative lactulose hydrogen breath conditions (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001) and negative hydrogen breath test were more likely to experience gastrointestinal reactions (Z=5.2088).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Chinese individuals have the lower tolerance threshold for maltitol (17.5 g) as compared to the individuals in other countries. The ethnic differences should be taken into account in the evaluation ad regulations of safe dosages for maltitol in future.\u003c/p\u003e","manuscriptTitle":"A tolerance study of maltitol in Chinese healthy subjects: a multicenter, simple-blind, placebo-controlled study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-19 16:19:44","doi":"10.21203/rs.3.rs-4015055/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"37032fcb-373f-4d0d-8a96-7dbd250f5db2","owner":[],"postedDate":"March 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29305457,"name":"Health sciences/Health care/Nutrition"},{"id":29305458,"name":"Health sciences/Signs and symptoms/Digestive signs and symptoms"}],"tags":[],"updatedAt":"2025-02-11T12:56:47+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-19 16:19:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4015055","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4015055","identity":"rs-4015055","version":["v1"]},"buildId":"ApUGefWb6u5IBVtyqm6d5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}