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Hesperidin

Hesperidin is a compound in orange peels that gives the flavonoid hesperitin to the body, and this flavonoid mediates most benefits of hesperidin including a possible increase in circulation (but unclear effects on blood pressure) and possible brain protective effects. Hesperidin, alongside naringenin, are known as the main citrus flavonoids.

Our evidence-based analysis on hesperidin features 235 unique references to scientific papers.

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Summary of Hesperidin

Primary information, health benefits, side effects, usage, and other important details

Hesperidin is a bioflavonoid glycoside commonly found in citrus fruits (most notoriously oranges) and is a sugar-bound form of the flavonoid hesperitin. Hesperitin is known to mediate the actions of hesperidin in the body, and since hesperidin needs to progress to the colon to be 'released' by intestinal bacteria it acts as a time-release for hesperitin; one serving of hesperidin seems to increased blood levels for over the course of a day or so when consumed in this manner.

If we are to look at the human evidence on orally ingested hesperidin, it appears to promote blood flow (minorly to moderately) although it's unclear if it has a notable influence on blood pressure; the current research isn't supportive overall, though it hasn't been studied in severe hypertension yet. It is pretty much ineffective for cholesterol and triglycerides from the available evidence. Not much other human evidence exists aside from the cardiovascular parameters mentioned above, and it seems pretty weak at improving parameters of diabetes as well (with exception to the eyes, diabetic retinopathy, as preliminary evidence suggests that hesperidin is quite protective of them).

That being said, in animal studies oral intake of hesperidin at a dose similar to that used in humans seems to be a very potent cardioprotection agent and is quite protective of the brain in response to various stressors; the protection is antioxidative in nature, but it seems to work through a currently not identified antioxidant responses from the genome. Aside from the protective effects (most notable in the heart and brain, but extend to every organ), hesperidin may be able to reduce a lack of appetite and have minor anti-allergic properties.

Orange peels can actually be used to get the supplemental dosage of hesperidin seen in the human studies, and hesperidin is known to interact with a variety of drug metabolizing enzymes so it should be approached cautiously if also using pharmaceuticals.

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How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

Most studies using hesperidin tend to use 500mg of supplemental hesperidin, and use the standard form of hesperidin if taking it as a daily preventative.

If using it for acute improvements in blood flow (ie. before a workout) then the form of G-Hesperidin may be preferred since it is absorbed faster and reaches higher levels in the blood. It does not have significantly better absorption overall, but it is faster at peaking in the blood.

Supplementation of hesperidin should be around 500mg and preferably taken with food

In regards to food products, the lowest known beneficial dose of hesperidin in rodent studies is around 25mg/kg oral intake daily. This is approximately 4mg/kg oral intake for an adult human which may be a bit too high to consume via orange juice products (in optimal conditions, a 150lb man would need to consume 1,800mL) and orange fruits (1,800g of the fresh fruit). The exception to the above is the antiallergic effects, which have occurred at a fifth of the aforementioned dose.

The peels of tangerines, however, appear to have 5-10% of their weight as hesperidin after 5-7 days of drying (to remove water content and concentrate the hesperidin) and as such a 500mg supplemental dose of hesperidin can be achieved by 5-10g of the dried tangerine peel. This is a low cost alternate assuming that the peel is thoroughly scrubbed prior to drying to remove possible contamination and grime collected on the peel.

When looking at food products, it is unlikely that the benefits of hesperidin can be mediated by standard orange consumption except maybe for antiallergic effects. Sundrying the peels of tangerines or oranges, however, can yield enough hesperidin for supplemental purposes

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Human Effect Matrix

Unlocked for Examine members

The Human Effect Matrix summarizes human studies to tell you what effects Hesperidin has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-a - Very High See all 7 studies
There is no significant influence on triglycerides noted with supplementation of hesperidin; if an effect occurs, it is of very minor magnitude and only lasts for as long as supplementation persists.
grade-b Minor High See all 3 studies
There is a decrease in C-Reactive Protein (inflammatory biomarker) in those with higher baseline inflammation or inflammatory disease conditions, but not in healthy persons.
grade-b - Very High See all 3 studies
Overall, studies don't suggest a notable effect on blood pressure. Some studies have found small reductions, and one has found a large reduction, but the evidence is inconsistent. A meta-analysis didn't find a notable influence of dose or study duration. More research is needed, particularly in people with severe hypertension.
grade-b - Very High See all 6 studies
There is no significant or long lasting effect on HDL cholesterol seen with hesperidin, except maybe a very small (less than 5%) increase in those with the lowest levels of HDL which fades after cessation of supplementation.
grade-b - Very High See all 6 studies
Similar to total cholesterol, while there may be a minor reduction in those at the worst levels of LDL cholesterol those with minor increases fail to find benefit.
grade-b - Very High See all 6 studies
While there may be a slight decrease which only applies to those with very elevated cholesterol at baseline, in normal persons or those with mild to moderately high cholesterol there is no significant influence.
grade-c Notable Very High See 2 studies
An increase in blood flow has been noted in persons with metabolic impairments, and was fairly notable in the lone study due to reaching 24.5% over placebo.
grade-c Minor Very High See all 3 studies
There appear to be mild decreases of circulating Apolipoprotein B seen with supplementation of hesperidin in the populations with poor baseline cholesterol that actually see benefit from supplementation.
grade-c Minor Very High See 2 studies
There is a mild decrease in E-selectin and perhaps sCAM-1 seen with oral supplementation of hesperidin, but not ICAM or VCAM; this is thought to be a mechanism underlying atherogenesis prevention.
grade-c Minor - See study
In men with high triglycerides and cholesterol, the serum liver enzymes appear to be reduced suggesting protective effects at the level of the liver.
grade-c Minor - See study
While hesperidin does not influence basal (fasting) microcirculation, there is an acute increase in circulation seen with supplementation of hesperidin at the time of peak blood concentrations.
grade-c Minor - See study
There is a mild increase in particulate size of LDL cholesterol, indicative of less oxidation of these particulates and less atherogenecity, with hesperidin supplementation.
grade-c Minor - See study
Preliminary evidence suggests a mild decrease in symptoms of rheumatoid arthritis seen with high (3,000mg) supplemental doses of G-hesperidin.
grade-c - - See study
No significant influence on Apolipoprotein A seen with supplementation of hesperidin.
grade-c - - See study
Overall B-cell count does not appear to be influenced with supplementation of hesperidin.
grade-c - Very High See 2 studies
There are no known significant alterations in blood glucose seen with supplementation of hesperidin
grade-c - - See study
No significant alterations in fibrinogen content have been noted with oral supplementation of hesperidin
grade-c - - See study
General oxidative parameters do not appear to be significantly altered with supplementation of hesperidin under resting conditions.
grade-c - - See study
Alongside a failure to improve insulin sensitivity or to reduce glucose was a failure to reduce HbA1c concentrations in the plasma of those with metabolic syndrome given 500mg hesperidin.
grade-c - - See study
There was no influence on homocysteine seen with supplementation of hesperidin relative to placebo, despite subjects being in an inflammatory state.
grade-c - Very High See 2 studies
Similar to blood glucose, there is no significant influence on basal insulin concentrations in otherwise healthy persons or those with metabolic diseases.
grade-c - - See study
There is no significant change in insulin sensitivity in persons with metabolic syndrome given 500mg of hesperidin daily.
grade-c - - See study
No significant influence on interleukin 6 (IL-6) is seen with oral supplementation of hesperidin.
grade-c - - See study
Natural Killer (NK) cell activity does not appear to be influenced with supplementation of hesperidin, with the count also remaining unchanged.
grade-c - - See study
The overall cell population of Natural Killer (NK) cells does not appear to be influenced with supplementation of Hesperidin
grade-c - - See study
The activity of neutrophils taken from subjects consuming hesperidin does not appear to be significantly altered when stimulated relative to placebo.
grade-c - - See study
There are no significant alterations in the amount of neutrophils seen in subjects consuming hesperidin.
grade-c - - See study
The increase in nitric oxide (and nitrate) seen with supplementation of hesperidin failed to reach statistical significance.
grade-c - - See study
There do not appear to be any significant influence on the overall count of T Lymphocytes (collectively referring to Th1 and Th2 cells) with hesperidin supplementation.
grade-c - Very High See 2 studies
In studies measuring weight as well as other parameters, weight is not influenced by supplementation of hesperidin relative to placebo
grade-c - - See study
No significant influence on total white blood cell count is seen with supplemental hesperidin.

Studies Excluded from Consideration

Note: This Table contains information on Hesperitin (flavonoid), Hesperidin (the food-bound for of Hesperitin), and G-Hesperiin (A synthetic variant) collectively

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Things to Note

Is a Form Of

Primary Function:

Also Known As

5, 7, 3'-trihydroxy-4'-methoxyflavanone, hesperitin-7-O-rutinoside, Hesperitin glycoside, glucosyl hesperidin, Vitamin P, hesperitin, G-hesperidin

Do Not Confuse With

Hesperitin (its aglycone), Eriodictyol (another flavonoid known as Vitamin P)

Goes Well With

  • Nitric oxide synthase inhibitors (for neuroprotective effects)

  • Synephrine (may increase metabolic rate increase from synephrine, naringenin is a confound)

Caution Notice

Known to interact with enzymes of Drug Metabolism

  • Appears to inhibit CYP3A4 at oral doses which are likely relevant to oral supplementation

  • Appears to inhibit both CYP2C8 and CYP2C9, whereas only the latter may be relevant due to inhibition of CYP2C8 needing a large concentration to occur

  • Hesperidin (and orange juice in general) may inhibit the OAT2B1 transporter to a relevant degree

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Click here to see all 235 references.