Evidence map›Paper›PMID 21346065›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2011

Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome.

Stefano Rizza, Ranganath Muniyappa, Micaela Iantorno, Jeong-a Kim, Hui Chen, Philomena Pullikotil, Nicoletta Senese, Manfredi Tesauro, Davide Lauro, Carmine Cardillo and 1 more

3 registry-linked trialsOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 127 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 6 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01773486 phase2withdrawnnot on this mapstarted 2015, after this paper: background citation

An Exploratory Study to Evaluate the Ability of the Citrus Polyphenol Hesperidin to Improve Insulin Sensitivity in Healthy Subjects and to Ameliorate Insulin Resistance in Obese Subjects

TypeinterventionalSponsorUniversity of Maryland, BaltimoreRan2015 to 2015Enrolled0ConditionsObesity, Insulin ResistanceArmsHesperidin, Placebo
NCT03372109 nacompletednot on this mapstarted 2017, after this paper: background citation

A Randomized Controlled Trial to Evaluate the Effects of Repeated Periods of Modified Fasting to Support Healthy Natural Weight Management and Prevention of Weight Gain in Overweight But Generally Healthy Adults Over the Winter Holiday Period

TypeinterventionalSponsorSupplement Formulators, Inc.Ran2017 to 2018Enrolled23ConditionsBody Weight ChangesArmsMeal replacement shake, Multivitamin and mineral capsules, Fish oil with sesame lignans and olive extract softgel, Prebiotic Chewable tablet, Clove Extract and Maqui Berry extract capsule
NCT04107155 nacompletednot on this mapstarted 2019, after this paper: background citation

A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of a Weight Management Program on Body Weight in Individuals Who Are Overweight and Otherwise Healthy

TypeinterventionalSponsorSupplement Formulators, Inc.Ran2019 to 2019Enrolled54ConditionsBody WeightArmsWeight Management Formulation, Placebo, Handout with Suggestions for Healthy Eating and Overall Health
3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 6 syntheses or guidelines pooled it, 317 citations in OpenAlex.

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67 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Stefano RizzaDepartment of Internal Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Ranganath Muniyappa
Micaela Iantorno
Jeong-a Kim
Hui Chen
Philomena Pullikotil
Nicoletta Senese
Manfredi Tesauro
Davide Lauro
Carmine Cardillo
Michael J Quon
National Center for Complementary and Integrative Health · USUniversity of Rome Tor Vergata · ITNational Institutes of Health · USUniversità Cattolica del Sacro Cuore · ITUniversity of Alabama at Birmingham · US

Funding

Intramural NIH HHS
6 · The paper itself

Abstract

contextHesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown.

objectiveWe tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. DESIGN, SETTING, AND

interventionsCellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24).

main outcome measureWe measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods.

resultsTreatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H(2)O(2). Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin).

conclusionsNovel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption.

Indexed as

Adenylate KinaseAnimalsCattleCell AdhesionCells, CulturedCross-Over StudiesDouble-Blind MethodEndothelial CellsEndothelium, VascularFemaleHesperidinHumansInflammationMaleMetabolic SyndromeMiddle AgedAdenylate KinaseHesperidinNitric OxideNitric Oxide Synthase Type IIIOncogene Protein v-aktTumor Necrosis Factor-alpha

Identifiers

PMID21346065
PMCPMC3085197
OpenAlexW2031034395

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.