{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:03:11Z","timestamp":1790172191842,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission, Adminitrative Commission of Zhongguancun Science Park","doi-asserted-by":"publisher","award":["Z231100004523001"],"award-info":[{"award-number":["Z231100004523001"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Long\u2010term safety, tolerance, and population\u2010specific effects of innovatively fermented\n                    <jats:italic>D<\/jats:italic>\n                    \u2010allulose are lacking in the Chinese population. This study aimed to address these gaps and support its application as a novel food ingredient in China. A 30\u2010day randomized, double\u2010blind, parallel\u2010group design with pre\u2010post comparison trial was conducted, enrolling 50 healthy Chinese adults (high\u2010dose group: 36\u2009g\/day, 0.6\u2009g\/kg body weight,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200926; low\u2010dose group: 24\u2009g\/day, 0.4\u2009g\/kg body weight,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200924). Gastrointestinal tolerance was monitored via daily questionnaires; systemic safety was evaluated using hematological tests, serum biochemical tests, urinalysis, fecal analysis, and body composition measurements. The incidence of gastrointestinal symptoms was 48.0%, which were mild, transient, and most frequent on Days 1\u20133, with no significant intergroup differences. All statistically significant changes in safety indicators remained within normal clinical reference ranges. Compared with baseline, the 30\u2010day intervention resulted in reduced red blood cell count, hematocrit, and platelet count, as well as elevated mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in both groups. For serum biochemical parameters, levels of alkaline phosphatase, gamma\u2010glutamyl transferase, uric acid, total cholesterol, and high\u2010density lipoprotein cholesterol decreased in both groups, while fasting blood glucose was reduced only in high\u2010dose group. Notably, high\u2010dose\n                    <jats:italic>D<\/jats:italic>\n                    \u2010allulose intervention decreased bone mineral density T\u2010scores in participants aged 35\u2009years and older. All statistically significant alterations in the measured indicators remained within normal clinical ranges and were clinically insignificant. This study provides critical safety data to support the planned approval of\n                    <jats:italic>D<\/jats:italic>\n                    \u2010allulose as a novel food ingredient in China in 2025. Its modulation of hematological and serum biochemical parameters suggests effects on hematopoiesis and glycolipid metabolism. Given the limitations of the 30\u2010day intervention duration, relatively modest sample size, and restriction to healthy normal\u2010BMI adults, a provisional safe intake limit of 0.4\u2009g\/kg body weight per day is proposed for Chinese adult population, requiring validation in longer\u2010term and larger\u2010scale studies.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.72042","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:24:21Z","timestamp":1782732261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>D<\/i>\n                    \u2010Allulose as a Low\u2010Calorie Sweetener: A 30\u2010Day Randomized, Double\u2010Blind Study on Gastrointestinal Tolerance and Systemic Safety to Support Its Application in Healthy Diets"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8858-883X","authenticated-orcid":false,"given":"Lijuan","family":"Qi","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Ning","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"},{"name":"School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangli","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Nie","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Jing","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"},{"name":"School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3631-3653","authenticated-orcid":false,"given":"Shan","family":"Gao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Trace Ability Technologies for Food Poisoning Beijing Center for Disease Prevention and Control  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1163\/18762891\u2010bja00071"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.117.015560"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2019.104485"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026\u20100495(98)90208\u20106"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf204050w"},{"key":"e_1_2_13_7_1","unstructured":"Food Standards Australia New Zealand (FSANZ).2023.\u201cTechnical and Risk Assessment\u2010Application A1247 D\u2010Allulose as a Novel Food.\u201dhttps:\/\/www.foodstandards.gov.au\/sites\/default\/files\/2024\u201008\/A1247%20Approval%20Report.pdf."},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.032"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408390802067126"},{"key":"e_1_2_13_10_1","unstructured":"GRAS Associates LLC (Agent for L&P Food Ingredient Co. Ltd).2021.\u201cGRAS Notice No. 001029: D\u2010Allulose With Amendments.\u201dCollege Park MD USA: U.S. Food and Drug Administration (FDA).https:\/\/www.fda.gov\/media\/170990\/download."},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10122010"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102011\u201007\u2010356006"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.90707"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2025.105890"},{"key":"e_1_2_13_15_1","first-page":"15","article-title":"Estimation of Maximum No\u2010Effect Level of D\u2010Psicose in Causing Diarrhea in Human Subjects (Japanese)","volume":"10","author":"Iida T.","year":"2007","journal-title":"Journal of Japan Council for Advanced Food Ingredients Research"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.07.018"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.54.511"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3772"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/1750\u20103841.12908"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.08\u2010191"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.05.056"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114523001113"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.132415"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.48.77"},{"key":"e_1_2_13_25_1","first-page":"225","article-title":"Metabolic Effects of D\u2010Psicose in Rats: Studies on Faecal and Urinary Excretion and Caecal Fermentation","volume":"12","author":"Matsuo T.","year":"2003","journal-title":"Asia Pacific Journal of Clinical Nutrition"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.5650\/jos.ess24099"},{"key":"e_1_2_13_27_1","unstructured":"National Health Commission of the People's Republic of China.2025.\u201cAnnouncement on 20 New Foods Including D\u2010Allulose (2025 No. 4).\u201dhttps:\/\/zwfw.nhc.gov.cn\/kzx\/tzgg\/sptjjxpzsp_224\/202507\/t20250702_3106.html."},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13374"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.06.002"},{"issue":"5","key":"e_1_2_13_30_1","first-page":"2308","article-title":"Control of Growth, Morphology, and Alkaline Phosphatase Activity by Butyrate and Related Short\u2010Chain Fatty Acids in the Retinoid\u2010Responsive 9\u20101C Rat Prostatic Adenocarcinoma Cell","volume":"45","author":"Reese D. 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