---
title: "Citrus polyphenol hesperidin stimulates nitric oxide production…"
description: "Hesperidin improves blood vessel function and reduces inflammation in people with metabolic syndrome, potentially through its metabolite hesperetin…"
url: "https://magellanlongevity.com/study/d21346065.md"
canonical: "https://magellanlongevity.com/study/d21346065.html"
html: "https://magellanlongevity.com/study/d21346065.html"
type: "study"
study_key: "d21346065"
journal: "J Clin Endocrinol Metab"
year: 2011
pmid: "21346065"
doi: "10.1210/jc.2010-2879"
citations: 1
updated: 2026-09-02
author: "Gabriel Radu, DO"
author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765."
publisher: "Magellan Longevity"
content_format: "markdown"
---

# Citrus polyphenol hesperidin stimulates nitric oxide production while improving endothelial function and reducing inflammatory markers in metabolic syndrome

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**HTML version:** https://magellanlongevity.com/study/d21346065.html · **In the Magellan app:** https://magellanlongevity.com/#/study/d21346065

## Citation

| Field | Value |
| --- | --- |
| Journal | J Clin Endocrinol Metab |
| Year | 2011 |
| PMID | [21346065](https://pubmed.ncbi.nlm.nih.gov/21346065/) |
| DOI | [10.1210/jc.2010-2879](https://doi.org/10.1210/jc.2010-2879) |
| Study key | d21346065 |

## Takeaway

Hesperidin improves blood vessel function and reduces inflammation in people with metabolic syndrome, potentially through its metabolite hesperetin stimulating nitric oxide production.

## The question

Does hesperetin stimulate nitric oxide production from vascular endothelium, and does oral hesperidin therapy improve endothelial function and reduce inflammatory markers in individuals with metabolic syndrome?

## Hypothesis

Hesperetin, a citrus flavonoid metabolite, may stimulate nitric oxide production and improve vascular function, while oral hesperidin therapy may improve endothelial function and reduce inflammatory markers in subjects with metabolic syndrome.

## Methods

Cellular mechanisms of hesperetin were studied in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial was conducted in 24 individuals with metabolic syndrome, who received oral hesperidin (500 mg once daily for 3 weeks) or placebo. Brachial artery flow-mediated dilation and circulating inflammatory biomarkers were measured.

## Results

In BAEC, hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase, leading to NO production, which required H2O2. Hesperetin pretreatment reduced monocyte adhesion to BAEC and vascular cell adhesion molecule-1 expression induced by TNF-α. In the clinical study, hesperidin treatment increased flow-mediated dilation (10.26% vs. 7.78% with placebo) and reduced concentrations of high-sensitivity C-reactive protein, serum amyloid A protein, and soluble E-selectin.

## Conclusion

Hesperetin has vasculoprotective actions, including stimulating NO production and reducing inflammation in endothelial cells. Oral hesperidin treatment improves endothelial dysfunction and reduces circulating inflammatory markers in individuals with metabolic syndrome.

## Limitations

The clinical trial was exploratory with a small sample size (n=24) and a relatively short intervention period (3 weeks).

## Verbatim from the abstract

> hesperidin increased flow-mediated dilation and reduced circulating inflammatory biomarkers

## Flow-Mediated Dilation (FMD) in Metabolic Syndrome Patients

| Measure | FMD (%) |
| --- | --- |
| Placebo | 7.78 |
| Hesperidin | 10.26 |

*Flow-mediated dilation was significantly higher after hesperidin treatment compared to placebo in individuals with metabolic syndrome.*

## Where this study is used on Magellan

This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions.

| Compound or device | Evidence grade | Graded pages |
| --- | --- | --- |
| Hesperidin Citrus Flavonoid | Moderate evidence | [Hesperidin Citrus Flavonoid](https://magellanlongevity.com/p/113.md) |

## Reference

1. **Citrus polyphenol hesperidin stimulates nitric oxide production while improving endothelial function and reducing inflammatory markers in metabolic syndrome**
   J Clin Endocrinol Metab 2011 · [PMID 21346065](https://pubmed.ncbi.nlm.nih.gov/21346065/) · [DOI 10.1210/jc.2010-2879](https://doi.org/10.1210/jc.2010-2879)

   > hesperidin increased flow-mediated dilation and reduced circulating inflammatory biomarkers

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## Related on Magellan Longevity

- [Hesperidin Citrus Flavonoid](https://magellanlongevity.com/p/113.md) — product graded on this and related evidence
- [Evidence: lowers adhesion molecules, BP](https://magellanlongevity.com/study/s113.md)
- [Longevity research map](https://magellanlongevity.com/longevity-research-map.html)
- [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md)

## Scope and disclosures

Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication.

Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases.

Reviewed for accuracy by a board-certified physician (DO).