Hesperidin
Summary
Hesperidin is the main flavonoid in orange juice. Evidence on heart markers is mixed (grade C): a 2019 analysis of 10 trials found no effect on cholesterol or blood pressure, while a 2024 analysis found lower LDL and total cholesterol but no blood-pressure change. Two 6-week trials found no change in blood vessel function. EFSA found glucosyl hesperidin safe at proposed food and supplement levels.
Key facts
- A flavanone found mainly in citrus fruits; in the body it is broken down to hesperetin, which circulates as conjugates[1][9]
- About 210–500 mg/day in recent trials; glucosyl hesperidin up to 3 g/day for 12 weeks in safety data[7][4][8][1]
- EFSA (2024): glucosyl hesperidin safe at proposed uses up to 364 mg/day for adults; hesperidin supplements in the EU usually did not exceed 600 mg/day[1]
- The Florida Department of Citrus funded the 12-week orange juice trial and Ferrer HealthTech donated its hesperidin; HTBA funded the bioavailability study[6][8]
- 6 graded human outcomes on this page
- October 10, 2026
How it works
ProposedHesperidin is poorly soluble and mostly broken down by gut bacteria to hesperetin, which is absorbed and conjugated. Proposed effects on blood vessels and lipids come largely from laboratory and animal work.[1][9]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Heart markers | Grade C | Mixed | Meta-analysis of 9 trials · n = 2,414 · 2024 | 2 rows |
| Blood pressure | Grade D | Improved | RCT · n = 159 · 2021 | 2 rows |
| Blood vessels | Grade D | No effect | RCT · n = 68 · 2016 | 2 rows |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Cholesterol and blood pressure | Mixed | Grade C | Meta-analysis · n = 2,414 · 2024 Healthy people and people with cardiometabolic conditions in 9 trials Form: Hesperidin supplements · Dose: Varied across trials · Duration: Varied across trials Hesperidin lowered LDL, total cholesterol and triglycerides versus placebo or control, with no change in systolic or diastolic blood pressure or HDL; heterogeneity was high for LDL and total cholesterol. | 38462779 (opens PubMed)Source [2] |
| Cholesterol, triglycerides and blood pressure | No effect | Grade C | Meta-analysis · n = 577 · 2019 Adults in 10 randomized trials Form: Hesperidin supplements · Dose: Varied across trials · Duration: Varied across trials Hesperidin had no effect on total, LDL or HDL cholesterol, triglycerides, or systolic and diastolic blood pressure compared with control. | 30632207 (opens PubMed)Source [3] |
| Systolic blood pressure and pulse pressure | Improved | Grade D | RCT · n = 159 · 2021 Adults with pre- or stage-1 hypertension Form: Orange juice or hesperidin-enriched orange juice · Dose: 500 mL/day · Duration: 12 weeks Systolic blood pressure and pulse pressure fell in step with the drinks' hesperidin content over 12 weeks; enriched juice also lowered diastolic pressure. | 32661681 (opens PubMed)Source [6] |
| Blood vessel function (flow-mediated dilation) | No effect | Grade D | RCT · n = 68 · 2016 Healthy adults with overweight or obesity Form: Hesperidin 2S · Dose: 450 mg/day · Duration: 6 weeks Fasting and after-meal flow-mediated dilation did not change versus placebo; blood pressure and adhesion molecules showed only non-significant trends in the full group. | 27797708 (opens PubMed)Source [4] |
| Blood vessel function (flow-mediated dilation) | No effect | Grade D | Crossover RCT · n = 37 · 2026 Men with central overweight Form: Hesperidin-enriched drink or 100% orange juice · Dose: 210 mg hesperidin/day, or 330 mL orange juice · Duration: 6 weeks per period Neither orange juice nor hesperidin changed fasting or after-meal flow-mediated dilation, or other vascular, metabolic or body measures, versus control, despite similar hesperetin exposure. | 42605853 (opens PubMed)Source [7] |
| Diastolic blood pressure | Improved | Grade D | Crossover RCT · n = 24 · 2011 Healthy men aged 50–65 with overweight Form: Control drink plus hesperidin, compared with orange juice and placebo drink · Dose: Hesperidin amount matched to 500 mL orange juice (not stated in the abstract) · Duration: 4 weeks per period Diastolic blood pressure was lower after orange juice or the hesperidin drink than after placebo; fasting microvascular reactivity did not change, but after-meal reactivity improved. | 21068346 (opens PubMed)Source [5] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| Standard hesperidin (2S/2R mixture from citrus peel) | Varies[8][9] | About 43% relative urinary recovery of hesperidin compounds in one crossover study; absorption is low and variable.[8][9] | No adverse effects reported in the abstracts of the trials cited here.[4][7] | Most supplement trials |
| Micronized or 2S-hesperidin | Varies[4][8] | Micronized 2S-hesperidin had higher relative bioavailability (70%) than the standard mixture (43%).[8] | No adverse effects reported in the abstract.[4] | Vessel-function trial at 450 mg/day; bioavailability study |
| Glucosyl hesperidin (enzymatically modified, water-soluble) | Varies[1] | Converted to hesperidin in the gut; blood hesperetin exposure was about 3.7 times higher than with hesperidin in rats.[1] | No relevant changes in blood tests at up to 3 g/day for 12 weeks in human studies reviewed by EFSA.[1] | Japanese blood lipid, blood pressure and body fat studies |
Studied doses
Doses studied in human trials ranged from 210 mg/day for 6 weeks to 450–500 mg/day, and to the hesperidin in 500 mL/day of orange juice for 12 weeks. Glucosyl hesperidin was given at up to 3 g/day for 12 weeks in studies reviewed by EFSA.[7][4][8][6][1]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Medicines
- Blood pressure medicinesRCTHesperidin-rich orange juice lowered systolic pressure in mildly hypertensive adults, so effects could add to these medicines; no interaction studies exist.[6]
Who should be careful
- Pregnancy and breastfeeding
- The trials cited here enrolled non-pregnant adults; EFSA's assessment covered proposed food-supplement levels only.[1][4]
- High-dose use
- EFSA derived a margin of safety from a 90-day animal study and noted changes at the highest dose tested; most supplements stay below 600 mg/day.[1]
- Children
- EFSA assessed glucosyl hesperidin supplements for children at lower maximum levels (60–115 mg/day by age).[1]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
Safety
Hesperidin is a common dietary flavonoid, and trials reported few side effects.
- Regulatory assessment
- EFSA concluded glucosyl hesperidin is safe at proposed uses (up to 364 mg/day for adults).[1]
- Human data
- Human studies of glucosyl hesperidin up to 3 g/day for 12 weeks showed no clinically relevant blood-test changes.[1]
- Diet comparison
- Dietary hesperidin intake can reach up to 8 mg/kg body weight per day in adults, according to EFSA.[1]
How to read the label
- Form mattersStandard citrus hesperidin is poorly absorbed; micronized 2S or glucosyl forms are absorbed better.[8][1]
- Label dose vs clinical doseRecent trials used 210–500 mg/day; EU supplements historically did not exceed 600 mg/day.[7][4][1]
- Juice vs supplementSeveral positive blood pressure results come from orange juice, which contains other compounds besides hesperidin.[6][5]
Cost per studied dose, without the sales pitch
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Cost per studied dose
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Frequently asked questions
Does hesperidin lower blood pressure?
Results are mixed. Pooled supplement trials found no blood pressure change, while hesperidin-rich orange juice lowered systolic pressure in mildly hypertensive adults.[3][2][6]
Does hesperidin lower cholesterol?
A 2024 meta-analysis found lower LDL and total cholesterol, but a 2019 meta-analysis found no effect.[2][3]
Is hesperidin safe?
EFSA found glucosyl hesperidin safe at proposed uses, and human studies up to 3 g/day for 12 weeks showed no relevant blood-test changes.[1]
Which form of hesperidin is best absorbed?
Micronized 2S-hesperidin was absorbed better than the standard mixture in a crossover study, and glucosyl hesperidin is more water-soluble.[8][1]
Is orange juice the same as a hesperidin supplement?
Not quite. Hesperetin exposure was similar from 330 mL of orange juice and a 210 mg hesperidin drink, but juice also has other compounds.[7]
Sources
- [1]Safety of glucosyl hesperidin as a Novel food pursuant to Regulation (EU) 2015/2283 (EFSA Journal 2024;22(8):e8911). European Food Safety Authority (EFSA) NDA Panel, 2024. guideline
- [2]Effect of hesperidin on blood pressure and lipid profile: A systematic review and meta-analysis of randomized controlled trials.. Phytother Res, 2024. meta-analysis
- [3]Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled clinical trials.. Phytother Res, 2019. meta-analysis
- [4]Randomized clinical trial on the efficacy of hesperidin 2S on validated cardiovascular biomarkers in healthy overweight individuals.. Am J Clin Nutr, 2016. RCT
- [5]Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers.. Am J Clin Nutr, 2011. crossover-RCT
- [6]Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study).. Eur J Nutr, 2021. RCT
- [7]Orange juice and hesperidin increase flavanone exposure without detectable short-term vascular benefits: a randomized crossover trial.. Food Funct, 2026. crossover-RCT
- [8]Hesperidin Bioavailability Is Increased by the Presence of 2S-Diastereoisomer and Micronization-A Randomized, Crossover and Double-Blind Clinical Trial.. Nutrients, 2022. PK-study
- [9]Bioavailability of Hesperidin and Its Aglycone Hesperetin-Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)-Mini-Review.. Nutrients, 2022. review
What changed
- First draft. Every PMID checked against NCBI E-utilities esummary (title and year taken from the record) and abstracts read for the cited rows.
- Adversarial review pass: every evidence row re-read against its PubMed abstract. Official source opened before citing: EFSA Safety of glucosyl hesperidin as a Novel food (EFSA Journal 2024;22(8):e8911). No NIH ODS or NCCIH fact sheet covers hesperidin. Industry ties: Florida Department of Citrus grant and drinks plus Ferrer HealthTech hesperidin (2021 trial, PMC7987641); HTBA-funded bioavailability study (PMC9231284); a BioActor BV author on the 2016 trial; the EFSA applicant was Hayashibara (now Nagase Viita). Rat drug-interaction data (metoprolol) were not used. Retraction, expression-of-concern, erratum and withdrawn checks on all 8 PMIDs: none flagged. Page set indexable. Independent browser review (4 parallel reviewers, every evidence row checked against its abstract and official sources on the Vercel preview) found issues that were fixed: evidence direction now follows the site convention (up = improved, down = worsened), plus wording and disclosure corrections listed in the batch-14 PR review comment.
