When you peel an orange, you almost certainly carefully remove the white, spongy layer left attached to the segments. It is called albedo, it has a slightly bitter taste and ends up in the bin along with the peel. A shame, because it is where a good part of the hesperidin is concentrated, the flavonoid that has made citrus fruits one of the fruit families most studied by research on polyphenols.
If you live in a region facing the Mediterranean, you have oranges, mandarins, lemons and bergamots at hand for much of the year, and you have always eaten them without asking yourself what they contain. The Mediterranean diet has made citrus fruits a daily habit before anyone isolated their individual compounds. Today research studies their individual compounds, and hesperidin is among the most investigated.
Below you will find what you need to orient yourself: what hesperidin is and in which family of molecules it is placed, in which fruits (and in which parts of the fruit) it is found, what studies have observed about its antioxidant properties and its relationship with the microcirculation, how it differs from diosmin and why in supplements it often appears alongside pineapple and its bromelain.
What hesperidin is: the symbol flavanone of citrus fruits
Hesperidin is a flavonoid of the flavanone subclass, present in a characteristic way in the fruits of the Citrus genus and considered the most representative phenolic compound of sweet oranges and mandarins [1]. The name comes from "hesperidium", the term with which botany indicates the fruit of citrus fruits, which in turn recalls the Hesperides of Greek mythology, guardians of the garden of golden apples.
Chemically hesperidin is a glycoside: a molecule formed by an active part, hesperetin, linked to a sugar composed of rhamnose and glucose (rutinose). It was isolated for the first time in 1828, and precisely from the albedo of oranges. In the Thirties of the Twentieth century the Nobel Prize group Albert Szent-Györgyi included it among the substances baptized "vitamin P", for the effects observed on the permeability of capillaries [4]. The vitamin label fell away long ago, the interest for the link between hesperidin and small vessels no.
Flavonoids, flavanones and bioflavonoids: let's clarify the terms
Online the three terms circulate almost as synonyms, and the confusion is understandable. A short glossary will help you read what follows with more confidence.
● Flavonoids: the great family of polyphenolic compounds produced by plants, responsible for many colors of flowers and fruits and studied for their antioxidant properties. There are several thousand of them.
● Flavanones: a subclass of flavonoids, almost exclusive to citrus fruits, which includes hesperidin, naringin, eriocitrin and narirutin [1].
● Bioflavonoids: a colloquial and commercial term, not a chemical category. It is used as a generic synonym for flavonoids and, on the label, it usually refers to those of citrus fruits.
When on a label you read "citrus bioflavonoids", you are actually reading about hesperidin and its close relatives.
Hesperidin and hesperetin: from the natural form to the absorbed one
In nature hesperidin is found linked to sugar, in the so-called glycosylated form. As it is the molecule it is poorly soluble and crosses almost intact the stomach and small intestine. It is in the colon that the intestinal bacteria detach the sugar portion and release the aglycone, hesperetin, which at that point the intestinal wall manages to absorb [2].
The practical consequences are two. The first concerns the times: after a glass of orange juice, the peak of hesperetin in the blood appears after a few hours, not minutes, because the passage through the microbiota takes time [2]. The second concerns the differences between people: the composition of the bacterial flora changes from individual to individual, and with it the quantity of hesperetin that each absorbs. It is the reason why, when talking about hesperidin, bioavailability is a recurring theme.
Where is hesperidin found?
In citrus fruits, and in the parts we do not eat.
Scientific databases on the content of polyphenols in foods, such as Phenol-Explorer, put sweet orange and mandarin at the top of the ranking of food sources of hesperidin [3]. The way you consume them, however, changes a lot the quantity that arrives on your table.
Which citrus fruits contain the most?
Every citrus fruit has its own profile of flavanones, a sort of fingerprint that distinguishes one species from another.
Here is a comparison between the most widespread species in the Mediterranean basin.
● Sweet orange (Citrus sinensis): prevailing flavanone hesperidin; hesperidin content high.
● Mandarin and clementine (Citrus reticulata): prevailing flavanone hesperidin; hesperidin content high.
● Lemon (Citrus limon): prevailing flavanones hesperidin and eriocitrin; hesperidin content medium-high.
● Grapefruit (Citrus paradisi): prevailing flavanone naringin; hesperidin content low.
● Bergamot (Citrus bergamia): prevailing flavanones neohesperidin, naringin and neoeriocitrin; hesperidin content low (neohesperidin form prevails).
According to Phenol-Explorer data, in a sweet orange juice hesperidin is around some tens of milligrams every 100 ml, with a variability linked to variety, degree of ripeness and extraction method [3]. Grapefruit, however bitter and "healthy" in the common imagination, contains little: its characteristic flavanone is naringin. bergamot follows an even different path, with a profile dominated by neohesperidin and naringin.
A detail that concerns closely those who live in Italy: Sicily and Calabria cover the majority of the national production of oranges and clementines, with a season that goes roughly from November to May. Eating citrus fruits in their season means choosing local fruits, harvested at ripeness.
Peel, albedo, pulp and juice
We return to the peeled orange from the beginning. In section you recognize three layers: the colored outer part (flavedo), the white spongy layer (albedo) and the segments with their membranes. The concentration of hesperidin follows a precise gradient: maximum in flavedo and albedo, still high in the membranes that wrap the segments, decreasing in the juice [1].
There is also a physical reason. Hesperidin is poorly soluble in water, so it stays linked to the fibrous parts of the fruit instead of dissolving in the liquid. In the glass, a relevant part of the hesperidin is in the cloudy fraction (the "cloud" of fine pulp in suspension) and not in the clear part. Eating the whole fruit, albedo included, or at least not filtering the juice, makes the difference.
Freshly squeezed and packaged juice: what changes?
A homemade juice made and drunk immediately preserves the pulp and with it a good part of the flavanones. In industrial juices centrifugation, filtration and pulp removal come into play: steps that lighten the product but cut the insoluble fraction in which hesperidin is concentrated. Pasteurization, by itself, affects less than believed, because flavanones withstand heat well. It is clarification that removes the most.
No alarms, therefore, but a choice criterion: if you look for hesperidin in the glass, orient yourself on juices with pulp, not from concentrate, and when you can still prefer the whole fruit. A segment with a little albedo is worth more than a glass of clear juice.
Hesperidin: why research deals with it
Hesperidin is studied especially on two fronts: the antioxidant properties, common to many polyphenols, and the relationship with the microcirculation, that is the network of small vessels that brings oxygen and nutrients to the tissues [4]. It is largely laboratory studies and on experimental models, which we will see later together with their limits.
Before entering the evidence it is convenient to understand what the microcirculation is and why it is linked to the sensation of heavy legs. For a broader in-depth you find our complete guide to the microcirculation.
Microcirculation and heavy legs: the physiological link explained simply
Imagine the circulatory system as a road network. Arteries and veins are the highways; the microcirculation is the set of neighborhood streets, the capillaries, where the real exchange happens: oxygen and nutrients leave the blood towards the tissues, liquids and waste substances re-enter to be brought back towards the heart. Every day a small part of liquid leaves the capillaries and is collected by the lymphatic system and the veins, which put it back in circulation.
In the legs the return works against the force of gravity and relies on the calf muscle pump, which at every step pushes the blood upwards. When you stay still for a long time, standing or sitting, the pump stops, the liquids stagnate in the tissues and appear the signs you know well: ankles a bit swollen in the evening, sense of heaviness, socks that leave the mark. They are common and physiological discomforts, of which we speak in depth in the article dedicated to heavy legs.
Heat, sedentary lifestyle and long hours standing: when the legs ask for attention
Probably you recognize yourself in at least one of these scenes. Eight hours at the desk with the legs bent under the table. A shift standing behind a counter or in the ward. A long trip in a plane or in a train. A summer with temperatures that dilate the vessels and slow down the return of liquids, as we tell in the article on swollen legs in summer.
They are ordinary life conditions, not health problems, and the first answer passes through the habits: move as soon as possible, interrupt the long stays standing or sitting, drink enough and take care of the diet. If you are also interested in the theme of theintegration in the warm months, we have a dedicated guide.
Hesperidin properties: what scientific research says
The properties of hesperidin are at the center of hundreds of publications, mostly laboratory studies and studies on experimental models, with a smaller number of studies on humans [4]. The following results should be read with this caution: they describe what research has observed, not the effects expected by those who consume citrus fruits or take a supplement. The complete bibliography is at the end of the article.
Antioxidant action against free radicals
Metabolism constantly produces unstable molecules, free radicals, which try to stabilize themselves by taking electrons from nearby structures. When their production exceeds the body's ability to neutralize them, oxidative stress occurs, favored by smoking, pollution, UV rays, intense exertion, and simply aging.
Available reviews describe for hesperidin and hesperetin, especially in experimental models, a multi-faceted antioxidant activity: they directly neutralize free radicals, bind metal ions that would favor their formation, and stimulate the body's own antioxidant defense systems [4]. Hesperetin, without sugar, shows superior activity in in vitro tests compared to the glycosylated form, thus returning to the issue of absorption [4].
Capillaries and collagen: what the literature reports
This is the historical field of hesperidin, which almost a century ago earned flavanones the name of "vitamin P". Reviews that review the literature report studies in which hesperidin has been associated with parameters of resistance and capillary permeability, that is, the ability of small vessels to let through what is needed without dispersing excess liquids into the tissues [4].
One part of the hypotheses calls into question collagen, the protein that gives structure to the vessel wall: in experimental models, hesperidin inhibited the activity of some enzymes that degrade the connective tissue matrix, including hyaluronidase [4]. This is preclinical data, useful to understand why research continues to be interested in this flavonoid, but not directly transferable to humans or a supplement.
Diosmin and hesperidin: differences and areas of use
Anyone looking for information on hesperidin almost always encounters a second name: diosmin. The two flavonoids are continuously cited together, and for good reason, but they are not the same thing. Here you find their relationship and the context in which each is used, with a clear warning: the purpose is purely informative and does not enter into therapeutic uses, which are the responsibility of the doctor.
From hesperidin to diosmin: a chemical relationship
Diosmin is a flavone, not a flavanone. The difference lies in a double bond in the central ring of the molecule: by adding it to hesperidin, with a dehydrogenation reaction, diosmin is obtained [5]. This is how almost all diosmin on the market is produced, starting from hesperidin extracted from citrus waste. In nature, diosmin exists, but in modest quantities, in some plants and in the same citrus fruits [5].
A summary comparison between the two molecules:
● Chemical class: hesperidin is a flavanone (glycoside); diosmin is a flavone (glycoside).
● Aglycone: hesperetin for hesperidin; diosmetin for diosmin.
● Main source: hesperidin is natural, extracted from the albedo and peel of oranges and mandarins; diosmin is semi-synthetic, obtained from hesperidin.
● Presence in nature: hesperidin is abundant in citrus fruits; diosmin is scarce (citrus, Teucrium, Scrophularia).
● Where you find it: hesperidin in foods and food supplements; diosmin in medicines and, in some cases, supplements.
Supplements and medicines: why they are two different worlds
A passage of transparency is mandatory. Diosmin is the active ingredient of several medicines, with precise indications that are evaluated and prescribed only by the doctor. A food supplement, by law definition, is a food: it contributes to supplementing the normal diet and supporting physiological functions, and it cannot in any way replace a pharmacological therapy.
If you are already following a treatment, or if the discomfort in your legs worries you, the first interlocutor remains your doctor.
Diosmin and hesperidin together: what the literature reports
Many of the scientific works that cite "diosmin and hesperidin" concern a flavonoid fraction in which the two compounds are associated in a fixed proportion, generally with diosmin as the prevailing component [5]. That fraction belongs to the field of medicines, and its indications are a medical matter. In the field of supplements, hesperidin is instead used alone or in combination with other plant ingredients, as in the case of bromelain that we will see shortly. They are two different paths, better not to confuse them.
Hesperidin and pineapple: why they can be found in the same supplements
In some supplements dedicated to leg wellness, hesperidin appears next to an ingredient that has nothing to do with citrus fruits: pineapple, present as fruit juice and as bromelain, the enzyme obtained from the stem. They are ingredients with different roles, and it is useful to distinguish them.
What is bromelain and where is it obtained
Bromelain is a complex of proteolytic enzymes, that is, capable of breaking down proteins, extracted mostly from the pineapple stem (Ananas comosus). Its activity is not measured in milligrams but in enzymatic units: the acronym GDU/g (Gelatin Digesting Units per gram) indicates how much gelatin the enzyme can digest under standard conditions. At the same weight, a higher GDU value indicates greater enzymatic activity: it is the data you find on the label.
The properties of bromelain deserve a separate treatment, which you find in our in-depth look at bromelain.
Pineapple and hesperidin: different roles in the same formula
The difference can be told in a few lines. Pineapple (Ananas comosus) contributes to the drainage of body liquids, is useful in case of heavy legs and promotes the functionality of the microcirculation. Hesperidin instead represents the citrus component of the formula: what we know about its properties comes from the scientific literature described above [4].
Bringing the two ingredients together is a formulation choice that unites two culinary traditions, that of Mediterranean citrus fruits and that of pineapple, in line with the approach of nutraceuticals: starting from what the table already knows. If you want to deepen the topic of liquids that accumulate during sedentary periods or in the hot months, you find an article dedicated to water retention.
Flomel 500: hesperidin in the MNS-58 Complex
The two ingredients we have talked about so far are found together in Flomel 500, the food supplement of Esserre with MNS-58 Complex, based on bromelain and hesperidin, with dehydrated pineapple juice. Hesperidin comes from the sweet orange fruit; bromelain from the pineapple stem. Flomel 500 is available in the format of 20 sachets and in the format of 40 sachets.
The MNS-58 Complex: a formula inspired by the Mediterranean diet
The MNS-58 Complex was born from the approach of MNS Nutrition of Esserre: starting from ingredients of plant origin with a long culinary history, such as Mediterranean citrus fruits and pineapple, now at home also on our tables, and developing them into a formula through the work of Esserre's scientific research and development. A philosophy that puts plant-based ingredients and transparency on composition at the center.
The ingredients of Flomel 500
The characterizing ingredients of Flomel 500 are three:
● Bromelain 2500 GDU/g, from the pineapple stem.
● Dehydrated pineapple juice, from the fruit.
● Hesperidin, from the sweet orange fruit.
Flomel 500, thanks to the presence of pineapple juice (Ananas comosus), contributes to the drainage of body liquids and is useful in case of heavy legs. Pineapple juice also promotes the functionality of the microcirculation and contributes to counteract the aesthetic issues of cellulite. Bromelain and hesperidin complete the composition: the first is the enzymatic complex obtained from the pineapple stem, the second the characteristic flavonoid of the sweet orange.
Formula characteristics and mode of use
Flomel 500 is gluten-free, lactose-free, preservative-free and suitable for vegans.
The sweetener is natural, based on steviol glycosides from stevia. The ingredients, as reported on the label, are: maltodextrins; bromelain 2500 GDU/g (from Ananas comosus (L.) Merr., stems); dehydrated pineapple juice (from Ananas comosus (L.) Merr., fruit); flavoring; acidifier: citric acid; hesperidin (from Citrus sinensis (L.) Osbeck, fruit); anti-caking agent: silicon dioxide; sweetener: steviol glycosides from stevia.
For the mode of use, follow to the letter the indications reported on the label.
Food supplements should not be understood as substitutes for a varied and balanced diet and a healthy lifestyle. The food supplement cannot in any way replace a pharmacological therapy. Do not exceed the recommended daily dose; keep out of reach of children under three years. In pregnancy, in breastfeeding, if you follow pharmacological therapies or if you are allergic to pineapple or citrus fruits, consult your doctor or the reference specialist before taking.
Flomel 500 is part of the Flomel range, which includes various formulations and formats, as well as Flomel Cream Gel for local application.
Frequently Asked Questions (FAQ)
What is the difference between diosmin and hesperidin?
They are two citrus flavonoids, closely related but not identical. Hesperidin is a flavanone found in abundance in oranges and mandarins; diosmin is a flavone that occurs naturally in small quantities and is produced from hesperidin. Diosmin is also the active ingredient in some medicines, the use of which is at the discretion of the doctor.
Which foods contain the most hesperidin?
The main sources are sweet oranges and mandarins, followed by clementines and lemons. Grapefruit and bergamot contain less, because their characteristic flavanone is different. The highest concentration is in the peel and the albedo (the white part): whole fruit and pulp-containing juice beat filtered juice.
Can hesperidin and bromelain be taken together?
Hesperidin and bromelain are found together in several supplements, often alongside pineapple juice. Pineapple contributes to the drainage of body fluids and microcirculation functionality, while the available information on hesperidin comes from scientific literature. Always follow the directions for use on the label and ask your doctor for advice, especially if you are allergic to pineapple or citrus fruits or if you are undergoing pharmacological treatments.
Can hesperidin be taken at any time of the year?
Through diet, yes: citrus fruits are available for much of the year, with a harvest that runs from autumn to spring. For supplements containing it, there are no "right" or "wrong" periods: follow the directions on the label and consult your doctor or pharmacist.
Scientific References
- Tomás-Barberán FA, Clifford MN. Journal of the Science of Food and Agriculture. 2000;80(7):1073-1080.
- Manach C, Morand C, Gil-Izquierdo A, Bouteloup-Demange C, Rémésy C. European Journal of Clinical Nutrition. 2003;57(2):235-242.
- Neveu V, Perez-Jiménez J, Vos F, et al. Database (Oxford). 2010;2010:bap024. Available at phenol-explorer.eu.
- Li C, Schluesener H. Critical Reviews in Food Science and Nutrition. 2017;57(3):613-631.
- Bogucka-Kocka A, Woźniak M, Niewiadomy A, Kocki J. Natural Product Communications. 2013;8(4):545-550.
Regulatory References
The effects reported for pineapple juice (Ananas comosus, fruit) correspond to those expected by the ministerial guidelines on the physiological effects of substances and plant preparations, referring to the list of permitted plants as set out in the Ministerial Decree of 10 August 2018. The information on hesperidin is reported as literary evidence and does not constitute health indications.
