Evaluation of the Effects of Orange Consumption on Carbohydrate and Lipid Metabolism in Subjects With MAFLD (Metabolic Associated Fatty Liver Disease)

Given the current increase in the incidence of dyslipidemia and obesity in the general population, there is a strong interest in identifying dietary factors capable of preventing the onset of metabolic diseases or at least capable of reducing metabolic risk. Several experimental evidences have shown that improving the carbohydrate and lipid profile in subjects at risk can reduce mortality linked to cardiovascular, neurodegenerative diseases and cancer. The diet is, therefore, an effective prevention tool in combating diseases related to metabolism, such as MAFLD (Metabolic Associated Fatty Liver Disease). In particular, fruit with its high content of polyphenols has been shown to exert a high anti-inflammatory, antithrombotic and antiproliferative action.

Polyphenols extracted from oranges of the "Tacle" variety have demonstrated in vitro an inhibitory action of cholesterol synthesis. In addition, the consumption of orange juice has been shown to improve the serum lipid profile of obese subjects, as well as "hesperedine", a flavonoid mainly present in oranges is able to reduce the proliferative activity of MCF-7 (human breast cancer cell line with estrogen, progesterone and glucocorticoid receptors) cells.

Study Overview

• Status: Completed
• Conditions: Metabolic Disease; Fatty Liver, Nonalcoholic
• Intervention / Treatment: Dietary supplement: Dietary supplementation with fresh oranges; Dietary supplement: Balanced Diet without oranges

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • BARI
    • Castellana Grotte, BARI, Italy, 70013
      • Irccs Saverio de Bellis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age > 30 years and <65 years
• diagnosis of MAFLD on the basis of clinical and instrumental parameters

Exclusion Criteria:

• gastroesophageal reflux diseases;
• inflammatory bowel diseases; oncological diseases;
• serious medical conditions that may impair participation in the trial;
• people who follow a special diet or who use anticoagulants;
• subjects unable to follow a diet for religious or other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment_group	Dietary supplement: Dietary supplementation with fresh oranges; the subjects enrolled in this group, will have to consume 400gr of oranges "Navelina" net of waste / day / per person for a month. The oranges will be provided, to each participant, by the IRCCS "Saverio de Bellis".
Active Comparator: Control_group	Dietary supplement: Balanced Diet without oranges; the subjects enrolled in this group, will have to consume 400 gr of fruit (with the exception of citrus fruits) net of waste / day / per person for a month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
variation in lipidomic profile	change in membrane lipidomic profile and	1 year
changes in MAFLD score	changes in MAFLD score at the end of the treatment period from baseline - this score is evaluated as change in grade of steatosis Measurement of steatosis: The Controlled Attenuation Parameter (CAP) measurement was performed by a vibration-controlled elastography (VCTE) implemented on FibroScan® (Echosens, Paris, France). The CAP score is measured in decibels per meter (dB/m). Values < 215 dB/m corresponded to the absence of NAFLD; values between 215 and 250 dB/m indicated a mild NAFLD; values between 251 and 299 dB/m indicated a moderate NAFLD, while values ≥ 300 dB/m corresponded to a severe NAFLD.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
variation in antioxidant status	evaluation of antioxidant status and improvement of inflammatory parameters in order to reduce metabolic risk in subjects with MAFLD	1 year
changes in inflammatory parameters	and improvement of inflammatory parameters in order to reduce metabolic risk in subjects with MAFLD	1 year

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
• Collaborators: Cisternino Anna Maria; Valeria Tutino; Valentina De Nunzio; Roberta Rinaldi

Publications and helpful links

General Publications

• Ammollo CT, Semeraro F, Milella RA, Antonacci D, Semeraro N, Colucci M. Grape intake reduces thrombin generation and enhances plasma fibrinolysis. Potential role of circulating procoagulant microparticles. J Nutr Biochem. 2017 Dec;50:66-73. doi: 10.1016/j.jnutbio.2017.08.012. Epub 2017 Sep 1.
• Tutino V, Gigante I, Milella RA, De Nunzio V, Flamini R, De Rosso M, Scavo MP, Depalo N, Fanizza E, Caruso MG, Notarnicola M. Flavonoid and Non-Flavonoid Compounds of Autumn Royal and Egnatia Grape Skin Extracts Affect Membrane PUFA's Profile and Cell Morphology in Human Colon Cancer Cell Lines. Molecules. 2020 Jul 23;25(15):3352. doi: 10.3390/molecules25153352.
• Tutino V, De Nunzio V, Milella RA, Gasparro M, Cisternino AM, Gigante I, Lanzilotta E, Iacovazzi PA, Lippolis A, Lippolis T, Caruso MG, Notarnicola M. Impact of Fresh Table Grape Intake on Circulating microRNAs Levels in Healthy Subjects: A Significant Modulation of Gastrointestinal Cancer-Related Pathways. Mol Nutr Food Res. 2021 Nov;65(21):e2100428. doi: 10.1002/mnfr.202100428. Epub 2021 Sep 21.
• Simpson EJ, Mendis B, Macdonald IA. Orange juice consumption and its effect on blood lipid profile and indices of the metabolic syndrome; a randomised, controlled trial in an at-risk population. Food Funct. 2016 Apr;7(4):1884-91. doi: 10.1039/c6fo00039h.
• Akiyama S, Katsumata S, Suzuki K, Ishimi Y, Wu J, Uehara M. Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. J Clin Biochem Nutr. 2010 Jan;46(1):87-92. doi: 10.3164/jcbn.09-82. Epub 2009 Dec 29.
• Notarnicola M, Tutino V, De Nunzio V, Cisternino AM, Cofano M, Donghia R, Giannuzzi V, Zappimbulso M, Milella RA, Giannelli G, Fontana L. Daily Orange Consumption Reduces Hepatic Steatosis Prevalence in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Exploratory Outcomes of a Randomized Clinical Trial. Nutrients. 2024 Sep 20;16(18):3191. doi: 10.3390/nu16183191.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): July 30, 2023
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Nutritional and Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Metabolic Diseases; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Supplements
• Other Study ID Numbers: RC2022_prg.15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No