Hesperidin, leg wellness & cellulite

Antioxidant protection, circulation enhancement, anti-ageing, cellulite

The flavonoid hesperidin (typically derived from citrus fruits, such as bitter orange) has been widely researched for decades and has been found in numerous studies to help boost circulation and thereby fight water retention. It is also a well-known antioxidant. 



Hesperidin is therefore of great importance as active ingredient in anti-cellulite, leg wellness and under-eye creams [the Celluence® cellulite / leg wellness creams are the only creams in the world with high concentrations of 95% pure, bioavailable hesperidin plus 39 other natural anti-cellulite actives. 


10+ ways Hesperidin...

...helps fight poor circulation / water retention, oxidative damage, skin, ageing and cellulite



3/ Hesperetin and hesperidin stimulate fat release and fat breakdown - ideal for cellulite reduction

Hesperetin was found to decrease the expression of resistin, adiponectin, aP2, LPL, PPAR-γ, and TNF-α in mesenchymal stem cells (hMSCs) and to significantly inhibit adipocyte differentiation and to increase the proapoptotic gene expression levels in preadipocytes (the water-insoluble flavonoid hesperidin (hesperetin 7-rutinoside) becomes hesperetin in the body).

Source: Hesperetin Inhibit Adipocyte Differentiation and Enhance Bax- and p21-Mediated Adipolysis in Human Mesenchymal Stem Cell Adipogenesis.



2/ Hesperidin protects fat cells from inflammation, helps fight cellulite

Inflammation and oxidative damage are key components of cellulite, as well as diabetes and several other so-called civilisation diseases, such as heart disease and arthritis. Recent research has now looked into 28 polyphenols (such as hesperidin, resveratrol, epigallocatechin gallate and curcumin) and concluded that those polyphenols protect fat cells from both oxidative damage and inflammation, by reducing inflammatory hormones, such as IL-6. This practically means that polyphenols (either as foods or as supplements) can be used in the fight against fat tissue inflammation for the prevention of diabetes and cellulite

[Source: Evaluation of antioxidant properties of major dietary polyphenols and their protective effect on 3T3-L1 preadipocytes and red blood cells exposed to oxidative stress]



1/ Review paper suggests hesperidin for the treatment of varicose veins

The loss of vascular integrity is associated with the pathogenesis of varicose veins. Several botanical extracts (horse chestnut/aesculus, butcher's broom/ruscus, gotu kola, flavonoids and pine bark) have been shown to improve microcirculation, capillary flow and vascular tone, and to strengthen the connective tissue of the perivascular amorphous substrate. Oral supplementation with may prevent time-consuming, painful, and expensive complications of varicose veins and hemorrhoids

[Source: Hemorrhoids and varicose veins: a review of treatment options]



Screening of potential anti-adipogenic effects of phenolic compounds showing different chemical structure in 3T3-L1 preadipocytes

This study was designed to analyze the anti-adipogenic effect of fifteen phenolic compounds from various chemical groups in 3T3-L1 pre-adipocytes. Cells were treated with 25 μM, 10 μM or 1 μM of apigenin, luteolin, catechin, epicatechin, epigallocatechin, genistein, daizein, naringenin, hesperidin, quercetin, kaempferol, resveratrol, vanillic acid, piceatannol and pterostilbene for 8 days. At 25 μM lipid accumulation was reduced by all the compounds, with the exception of catechin, epicatechin and epigallocatechin. At a dose of 10 μM apigenin, luteolin, naringenin, hesperidin, quercetin and kaempferol induced significant reductions, and at 1 μM only naringenin, hesperidin and quercetin were effective. The expression of c/ebpα was not. C/ebpβ was significantly reduced by genistein and kaempferol, pparγ by genistein and pterostilbene, srebp1c by luteolin, genistein, hesperidin, kaempferol, pterostilbene and vanillic acid, and lpl by kaempferol. In conclusion, the most effective phenolic compounds are naringenin, hesperidin and quercetin. Differences were found in terms of effects on the expression of genes involved in adipogenesis among the analyzed compounds.



Hesperidin, ascorbic acid and butcher's broom improve vein function and circulation

The combination of ruscus aculeatus, vitamin C (ascorbic acid) and hesperidin has been found to improve capillary structure and chronic venous hypertension, and for these reasons it is ideal for inclusion in anti-cellulite / leg wellness creams.

Source 1: Use of microcirculatory parameters to evaluate clinical treatments of chronic venous disorder (CVD).

Abstract 1: OBJECTIVES: To evaluate changes on cutaneous microangiopathy in chronic venous disorder (CVD) after use of Cirkan [venotonic drug containing Ruscus aculeatus (plant extract), hesperidine methylchalcone (flavonoid) and vitamin C], elastic compression stockings (ECS) or no treatment for four weeks. PATIENTS AND METHODS: Fifty-five female patients (85 legs), 25 to 57 years, with at least one limb classified as C2,s or C2,3,s (CEAP classification), were allocated consecutively, according to entrance order, in these three groups. Ten healthy women age-matched were also investigated. Using orthogonal polarization spectral technique (noninvasive method), measurements of functional capillary density (FCD, number of capillaries with flowing red blood cells/mm(2)), capillary morphology (CM, % of abnormal capillaries/mm(2)) and diameters (mum) of dermal papilla (DDP), capillary bulk (DCB) and capillary limb (CD) were obtained on the medial perimalleolar region and later analyzed using CapImage software. RESULTS AND CONCLUSIONS: CVD patients showed significant changes on CD and CM compared to healthy subjects in agreement with our previous findings (J Vasc Surg 43:1037-1044, 2006). On Cirkan-treated patients, after 4 weeks, CD decreased on both limbs and CM improved on the left one, suggesting an amelioration of the chronic venous hypertension. No significant changes could be detected on other patient groups. These results confirm the existence of microcirculatory dysfunction in early stages of CVD, probably due to post-capillary hypertension, and further support the venotonic action of Cirkan.

Source 2: Clinical and capillaroscopic evaluation in the treatment of chronic venous insufficiency with Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid in venous insufficiency treatment of ambulatory patients.

Abstract AIM: Clinical and capillaroscopic evaluation of an association of Ruscus aculeatus, hesperidin methylchalcone (HMC) and ascorbic acid in chronic venous insufficiency METHODS: A prospective, multicenter and open clinical study. Chronic venous insufficiency patients were studied using clinical, etiological, anatomical, physiological classification (CEAP) symptom scale. Symptomatology, CEAP scale, and baseline, 2-, 4-, 6- and 8-week skin capillaroscopy were assessed. Treatment consisted of two capsules per day of Ruscus aculeatus 150 mg/HMC 150 mg/ascorbic acid 100 mg during 8 weeks. RESULTS: A total of 124 patients were studied, 109 female (89.28%), with a mean age of 52.5 (33-80+9.8). Initial intense reports were 79% pain, 85% heaviness, 74% cramps, 82% edema, decreasing to 20%, 12%, 8% and 14%, respectively, within two weeks, and symptomatology being absent at the end of treatment. Capillaroscopy changes at treatment completion were: 98% to 20% inter-capillary fluid decrease; 80% to 20% efferent loop thickening; 5% to 2% peri-capillary bed, and 5% to 4% mega-capillaries. CONCLUSION: Severe symptom decrease started from the second week until there were no symptoms at the end of treatment. It is the first time morphologic changes were observed in chronic venous insufficiency through capillaroscopy following a pharmacological intervention. Capillary-level effect was proportional to symptom decrease. Improvement was seen from the second week of treatment.



Pycnogenol (red pine bark extract) is as effective as hesperidin/diosmin (Daflon) for the healing for venous ulcers and swelling reduction

Comment: The venotonic and circulation-enhancing medication Daflon (450m Diosmin + 50g hesperidin) has been effectively used for decades for the relief of poor circulation and vein disease in general. This new paper shows that just 50mg of Pycnogenol, a branded red pine bark extract, has the same effect of vein ulcer healing and circulation improvement / oedema reduction.

Source: Effect of Pycnogenol on the Healing of Venous Ulcers.

Abstract: BACKGROUND: Venous ulcers are common complications of chronic venous insufficiency that result in severe physical and mental suffering to patients. The oral administration of diosmin/hesperidin has been used as adjuvant therapy in the treatment of chronic venous insufficiency. The purpose of this study was to evaluate and compare the effect of pycnogenol and diosmin/hesperidin on the healing of venous ulcers. METHODS: This longitudinal, prospective, randomized clinical trial was conducted with 30 adult patients with venous ulcers from a vascular surgery outpatient clinic of a university hospital. The patients were randomly allocated to two groups: group 1 (n=15) was treated with pycnogenol (50 mg orally, three-times daily), and group 2 (n=15) was treated with diosmin/hesperidin (450/50 mg orally, twice daily). They were assessed every 15 days for 90 days. During follow-up visits, photo-documentation was obtained and the ulcer area and circumference of the affected limb were measured. Friedman's test and the Mann-Whitney test were used to compare ulcer areas and circumference of affected limbs between and within groups at the different time points. The level of significance was set at 5% (P<0.05) for all tests. RESULTS: Both the pycnogenol and diosmin/hesperidin treatments had a similar effect on the healing of venous ulcers and led to a significant decrease in the circumference of affected limbs (P<0.0001). CONCLUSION: The results suggest that pycnogenol has an adjuvant effect on the healing of venous ulcers, similar to diosmin/hesperidin.



How the butcher's broom extract ruscogenin, together with hesperidin and vitamin C improves quality of life in patients with chronic circulation problems

The combination of Ruscus aculeatus (butcher's broom), hesperidin methyl chalcone (HMC) and ascorbic acid has been tested before on patients with lower limb chronic venous insufficiency and was found effective in reducing water retention and improving vein tone. In this study patients with chronic venous disorders (CVD) were assessed after 12 weeks of taking a nutritional supplement comprising of the three actives mentioned above. At the  conclusion of the study it was found that "all clinical symptoms significantly improved with treatment, especially for patients with higher body mass index and heavier pathology. Ankle circumference, which reveals the extension of water retention decreased over time, gradually decreased and both the physical and psychological dimensions of quality of life significantly increased over time and improved in all types of patients. The researchers concluded that" "A 12-week treatment with ruscus aculeatus,  HMC and ascorbic acid showed a significant decrease in clinical symptoms and a significant improvement in the quality of life of patients with chronic venous disorder". The results are unsurprising, given the well-studied circulation-enhancing and blood vessel-protecting effects these separate actives have on their own. Given that poor circulation is an important aspect of cellulite, this combination is also ideal for the treatment of cellulite, both when taken orally (food supplement) or applied locally (cellulite cream). Other active ingredients, in addition to the above three, would offer enhanced synergy and maximum results.

Source: Quality of life improvement in Latin American patients suffering from chronic venous disorder using a combination of Ruscus aculeatus and hesperidin methyl chalcone and ascorbic acid (quality study).

Abstract: AIM: The present study assessed the effect of Ruscus aculeatus, hesperidin methyl-chalcone and ascorbic acid (HMC-AA), in the treatment of chronic venous disorders (CVD) in Latin American patients. METHODS: This study is an observational, single arm, multicentric and prospective trial. Patients suffering from CVD and belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological (CEAP) classes were included. Patient profiles, risk factors, clinical symptomatology and quality of life (QoL) assessed by SF-12 and CIVIQ questionnaires were evaluated at inclusion and after 12-week treatment. RESULTS: The main factors influencing the previous management of patients were age, gender, body mass index (BMI), familial history, physical activity, exposure to heat, heavy loads lifting, profession and clinical characteristics. All clinical symptoms significantly improved with treatment and, as BMI and CEAP classes increased. Ankle circumferences decreased over time, correlating with BMI and CEAP classes. The physical and psychological dimensions of the SF-12 score significantly increased over time and improved within each CEAP class. The CIVIQ score significantly improved over time, correlating with age and CEAP classes. CONCLUSION: A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant decrease in the clinical symptoms and a significant improvement in the QoL of patients with CVD.



Hesperidin and butcher's broom improve circulation on lower legs / calves

In a double blind, cross over clinical trial, it was found that the combination of Ruscus aculeatus / (butcher's broom), hesperidin and ascorbic acid (vitamin C) improved vein function and venous disease in the lower legs (calves), especially after taking the supplement. Those three natural actives are well known for their vein / circulation supporting action and they are already used in anti-cellulite creams for this purpose.

Source: Use of extract of Ruscus aculeatus in venous disease in the lower limbs

Abstract: The effectiveness and tolerability of a venotropic drug (RAES) composed of an extract of Ruscus aculeatus (16.5 mg), hesperidin (75 mg) and ascorbic acid (50 mg) were evaluated in 40 patients (30 female, 10 male) aged between 28 and 74 years, suffering from chronic phlebopathy of the lower limbs. The cross-over, double-blind trial involved two periods of treatment of 2 months with the drug (2 capsules, 3 times/day) or with placebo, and an interim period of 15 days for wash-out. An overall tendency for improvement occurred that was more distinct during the periods of treatment with the drug. In fact, symptoms and plethysmographic parameters (in particular MVIV 40 and 60) immediately changed significantly in correspondence with the administration of RAES. The biological and clinical tolerability were excellent.



Patient satisfaction with hesperidin, ascorbic acid and ruscogenin for the treatment of chronic venous disease (clinical study)

In a study comparing patient satisfaction of different therapies of advanced stage chronic venous disease it was found that of the 780 patients studied, and after six weeks of treatment, 71.3% were satisfied after surgical intervention; 51.4% with a natural vasoactive drug (supplement) consisting of ruscus aculeatus (butcher's broom), HMC (hesperidin) and ascorbic acid (vitamin C); and 43% with compression therapy (pressotherapy / bandaging). In the drug/supplement group,  "out of 377 patients with active venous ulcers smaller than 200 cm2, 18% have been cured, and 66.6% have improved during 6-week period of observation! The researchers concluded that effects exerted on veins, capillaries and lymphatic vessels by the vasoactive supplement/drug explain the positive results observed in this study. All three components of the drug, i.e. ruscus, ascorbic acid and hesperidin are well researched and widely established for their natural and safe vein / circulation / lymphatic drainage supporting action, and they are valuable ingredients, taken either orally (supplements) or locally (creams) in the fight against venous insufficiency, water retention, poor circulation and cellulite. Given that new, more advanced vasoactive supplements exist today, if those newer, more advanced products were used, most probably an even higher number of customer satisfaction would have been recorded.

Source: Patients' satisfaction with therapy methods of advanced chronic venous disease.

Abstract AIM: To assess patients' satisfaction from the therapy of advanced chronic venous disorders (CVD) in everyday clinical practice in Poland, and to compare the efficacy of various venoactive drugs (VADs) in venous ulcers healing process. METHODS: 780 unselected adult patients with active (N=441) or healed (N=339) venous ulcers participated in the non-interventional observational 6-week study. RESULTS: Compression therapy and VADs were utilized by 81.5% and 89.2% of patients respectively. 31.2% of all patients underwent surgical procedures for vein incompetence, 61.3% were satisfied with surgical methods, 43% with compression therapy, and 32.6% with VADs - with highest rate of satisfied patients in the group taking Ruscus aculeatus and HMC and ascorbic acid (51.4%). Of 377 patients with active venous ulcers smaller than 200 cm2, adherent to VADs, 18.0% have been cured, and 66.6% have improved during 6-week period of observation. Multiple logistic regression analysis revealed that the compression therapy [OR=2.74], the size of ulcer ≤ 10 cm2 [OR=2.70] were increasing the change of ulcer healing. No VADs was better than another in the healing process. CONCLUSIONS: 1) Compression therapy and VADs are highly utilized by patients with advanced CVD. 2) Patients are more satisfied with surgical than conservative treatment of advanced CVD. 3) More than half of the patients with the advanced stage CVD taking Ruscus aculeatus and HMC and ascorbic acid is satisfied with the obtained improvement. 4) Ruscus aculeatus and HMC and ascorbic acid is similarly effective as other frequently used VADs in venous ulcer healing. 5. Ruscus aculeatus and HMC and ascorbic acid exerting effects on veins, capillaries and lymphatic vessels may explain the positive results observed in this study.



Hesperidin improves vasodilation in hypertension

Source: Long-term Treatment with Hesperidin Improves Endothelium-dependent Vasodilation in Femoral Artery of Spontaneously Hypertensive Rats: The Involvement of NO-synthase and Kv Channels.

Abstract: Hesperidin is the most common flavonoid found in citrus fruits and is expected to exert vasodilation action relevant to its health benefits. The present study aimed to explore the effect of hesperidin on the vascular responses in normotensive and hypertensive rats and the involvement of NO-synthase and Kv channels. The 15-week-old Wistar and spontaneously hypertensive rats (SHR) were randomized to orally receive either hesperidin (50 mg/kg/day) or a corresponding volume of the water for 4 weeks. Vascular responses of isolated femoral arteries were studied with myograph in control conditions and during inhibition of NO-synthase with l-NNA and Kv channels with 4-AP. Hesperidin had no effect on blood pressure. Endothelium-dependent vasodilation in Wistar and SHR was significantly improved by the treatment with hesperidin. The contraction responses after l-NNA were increased in all groups of rats to similar extent, but relaxatory responses were significantly attenuated only in SHR. The inhibition of Kv channels significantly reduced endothelium-dependent vasodilatory responses in only in SHR administered with hesperidin. The results of our experiment indicate that hesperidin might improve the endothelium-dependent vasodilation during hypertension, possibly through the enhancement of Kv channels function.