| Ingredients | Amount Per Serving |
|---|---|
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(90% diosmin)
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600 mg |
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Beautiful Legs Proprietary Blend
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100 mg |
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(Ruscus aculeatus Root Extract)
(20:1)
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(Polygonum cuspidatum Rhizome Extract, Polygonum cuspidatum Root Extract)
(standardized to contain 48.5% trans-resveratrol)
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|
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(Vitis vinifera, Vitis vinifera, Vitis vinifera)
(french whole red grape)
|
|
|
(whole)
(Vitis rotundifolia, Vitis rotundifolia)
|
|
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(Aesculus hippocastanum )
(seed)
(Escin)
(standardized to 20% escin)
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|
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(Vitis vinifera )
(seed)
(Polyphenols)
(standardized to 95% polyphenols)
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|
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(Citrus aurantium)
(hesperidin complex)
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Cellulose, Silica
Below is general information about the effectiveness of the known ingredients contained in the product Beautiful Legs. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Beautiful Legs. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately short-term. A specific butcher's broom rhizome extract (Fagorutin Ruscus Kapseln, GlaxoSmithKline Consumer Healthcare) has been used with apparent safety at a dose of 75 mg daily for up to 3 months (9932,37502). A specific combination product (Cyclo 3 Fort, Pierre Fabre Medicament) containing butcher's broom root extract, hesperidin methyl chalcone, and vitamin C has been used with apparent safety in doses providing butcher's broom root extract 150 mg twice daily for up to 3 months or 300 mg three times daily for up to 1 month (10068,37494,94779). There is insufficient reliable information available about the safety of butcher's broom when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts found in foods.
POSSIBLY SAFE ...when supplements are used orally and appropriately, short-term. Diosmin seems to be safe when used alone or in combination with other flavonoids in doses of up to 1350 mg daily for up to 6 months (4861,4898,10227,10229,93885,105283,105286,105287,105293,105294)(105296,108150).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods.
PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally in doses of up to 900 mg daily for 30 days in combination with other flavonoids, such as hesperidin.
Some evidence suggests that taking this combination may be associated with placental insufficiency when used during the third trimester of pregnancy; however, the combination does not seem to induce fetal abnormalities, retard fetal growth, increase the risk of intrauterine death, or affect birth weight. Also, when breastfeeding, this combination does not seem to affect infant growth or feeding (54970).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY SAFE ...when the whole fruit of the grape, or extracts of the fruit, seed, or leaf, are used orally and appropriately in medicinal amounts. Grape seed extracts have been used with apparent safety in doses up to 200 mg daily for up to 11 months (9182,53016) and in doses up to 2000 mg daily for up to 3 months (53149,53190). Specific grape fruit extracts (Stilvid, Actafarma; Cognigrape, Bionap srl) have been used with apparent safety in doses up to 250-350 mg daily for 3-12 months or 700 mg daily for 6 months (53254,53256,96198). A specific grape leaf extract (AS 195, Antistax, Boehringer Ingelheim) has been used with apparent safety in doses up to 720 mg daily for up to 3 months (2538,52985,53005,53206). A preparation of dehydrated whole grapes, equivalent to 250 grams of fresh grapes daily, has also been used with apparent safety for up to 30 days (18228). A specific grape seed extract (Enovita; Indena SpA) 150 mg twice daily, standardized to provide at least 95% oligomeric proanthocyanins, has been used with apparent safety for up to 16 weeks (108091) ...when used topically and appropriately. Creams and ointments containing grape seed extract 2% or 5% have been used topically with apparent safety for up to 3 weeks (91539,100955). There is insufficient reliable information available about the safety of other grape plant parts when used topically.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods.
Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). However, whole grapes should be eaten with caution in children aged 5 years and under. Whole grapes can be a choking hazard for young children (96193). To reduce the risk of choking, whole grapes should be cut in half or quartered before being given to children. There is insufficient reliable information available about the safety of grape when used in medicinal amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the safety of medicinal amounts during pregnancy and breast-feeding; avoid using in amounts greater than what is commonly found in foods.
LIKELY SAFE ...when used orally in amounts found in foods.
POSSIBLY SAFE ...when supplements are used orally and appropriately, short-term. Doses of up to 3 grams daily have been used with apparent safety for up to 3 months (37494,54850,94544,105275,105276).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods.
PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally in doses of up to 100 mg daily for 30 days in combination with diosmin.
Some evidence suggests that taking this combination may be associated with placental insufficiency when used during the third trimester of pregnancy; however, the combination does not seem to induce fetal abnormalities, retard fetal growth, increase the risk of intrauterine death, or affect birth weight. Also, when breastfeeding, this combination does not seem to affect infant growth or feeding (54970).
LIKELY SAFE ...when standardized horse chestnut seed extracts are used orally and appropriately, short-term. These extracts, from which esculin, a toxic constituent, has been removed (9420), have been used with apparent safety for 2-12 weeks (281,282,283,284,285,12113,95429,95430).
UNSAFE ...when the raw seed, bark, flower, or leaf is used orally. Horse chestnut contains significant amounts of the toxin esculin, and can be lethal (17). There is insufficient reliable information available about the safety of horse chestnut when used topically, intravenously, or intramuscularly.
CHILDREN: UNSAFE
when the raw seeds, bark, flower, or leaves are used orally.
Poisoning has been reported from children drinking tea made with twigs and leaves (9,55528).
PREGNANCY AND LACTATION: UNSAFE
when the raw seed, bark, flower, or leaf are used orally.
Horse chestnut preparations can be lethal (17); avoid using. There is insufficient reliable information available about the safety of horse chestnut seed extract when used during pregnancy and lactation; avoid using.
There is insufficient reliable information available about the safety of hu zhang.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Beautiful Legs. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, butcher's broom might increase the effects and adverse effects of alpha-adrenergic agonists.
 Details
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Theoretically, butcher's broom might reduce the effects of alpha-adrenergic antagonists.
Details
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Theoretically, diosmin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
A case of spontaneous intraventricular hemorrhage has been reported for a 77-year-old female after 6 weeks of warfarin therapy, despite an international normalized ratio (INR) of only 1.8. The patient had also been taking aspirin and diosmin for several years. Experts speculate that chronic intake of diosmin predisposed the patient to spontaneous intraventricular hemorrhage by inducing chronic microcirculatory hypertension and inhibiting platelet aggregation. The presence of aspirin was also thought to play a role in this event (93886).
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Theoretically, diosmin might reduce the effects of carbamazepine and increase the risk for convulsions.
Details
A pharmacokinetic study in humans shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of carbamazepine 200 mg increases blood levels of carbamazepine by approximately 58% and decreases carbamazepine clearance by 42%. It also decreases the formation of carbamazepine's active metabolite. It is speculated that diosmin reduces the metabolism of carbamazepine by inhibiting cytochrome P450 3A4 (CYP3A4) (95041).
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Theoretically, diosmin might increase the levels and clinical effects of chlorzoxazone.
Details
A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of chlorzoxazone 250 mg increases blood levels of chlorzoxazone by 53% and decreases chlorzoxazone clearance by 40%. It is speculated that diosmin reduces the metabolism of chlorzoxazone by inhibiting cytochrome P450 2E1 (CYP2E1) (93889).
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Theoretically, diosmin might inhibit the metabolism of CYP2C9 substrates.
Details
Diclofenac is metabolized by CYP2C9 enzymes. Clinical and laboratory research shows that diosmin inhibits the metabolism of diclofenac (93888,98596). A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of diclofenac 100 mg increases blood levels of diclofenac and decreases diclofenac clearance (93888).
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Theoretically, diosmin might inhibit the metabolism of CYP2E1 substrates.
Details
Chlorzoxazone is metabolized by CYP2E1 enzymes. A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of chlorzoxazone (Paraflex 250) 250 mg increases blood levels of chlorzoxazone by 34% and decreases chlorzoxazone clearance by 40%. It is speculated that diosmin reduces the metabolism of chlorzoxazone by inhibiting CYP2E1 (93889).
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Theoretically, diosmin might inhibit the metabolism of CYP3A4 substrates.
Details
Laboratory research is conflicting with respect to the effects of diosmin on CYP3A4. Some research suggests that diosmin does not affect CYP3A4 activity (95040). However, other research suggests that diosmin alters the metabolism of carbamazepine, a CYP3A4 substrate. Laboratory and animal research show that oral administration of diosmin for 7 days prior to oral administration of carbamazepine increases plasma concentrations of carbamazepine, decreases the clearance of carbamazepine, and decreases the formation of carbamazepine's active metabolite (95039). Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of carbamazepine 200 mg increases blood levels of carbamazepine by approximately 58% and decreases carbamazepine clearance by 42% (95041). It is speculated that diosmin reduces the metabolism of carbamazepine by inhibiting CYP3A4 (95039,95041). Diosmetin, a metabolite of diosmin, may also inhibit CYP3A4 (95041).
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Theoretically, diosmin might increase the levels and clinical effects of diclofenac.
Details
Clinical and laboratory research shows that diosmin inhibits the metabolism of diclofenac (93888,98596). A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of diclofenac 100 mg increases blood levels of diclofenac and decreases diclofenac clearance. It is speculated that diosmin reduces the metabolism of diclofenac by inhibiting cytochrome P450 2C9 (CYP2C9) (93888).
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Theoretically, diosmin might increase the levels and clinical effects of fexofenadine.
Details
A pharmacokinetic study in humans shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of fexofenadine 120 mg increases blood levels of fexofenadine by approximately 49% and decreases the apparent oral clearance of fexofenadine by 41%. The time taken to reach maximum plasma concentration, the half-life, and the apparent renal clearance of fexofenadine are not affected. For this reason, it is speculated that diosmin alters the pharmacokinetics of fexofenadine via inhibition of P-glycoprotein in the intestine, but not in the kidney or liver (95042).
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Theoretically, diosmin might increase levels of drugs that are substrates of P-glycoprotein (P-gp).
Details
Preliminary laboratory research suggests that diosmin inhibits P-gp (93890). Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of fexofenadine 120 mg increases blood levels of fexofenadine, a P-gp substrate, by approximately 49% and decreases the apparent oral clearance of fexofenadine by 41%. The time taken to reach maximum plasma concentration, the half-life, and the apparent renal clearance of fexofenadine are not affected. For this reason, it is speculated that diosmin inhibits P-gp in the intestine, but not in the kidney or liver (95042).
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Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
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Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
Details
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water (53177). Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.
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Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
Details
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2 (2539).
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It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
Details
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes (11094,53011,53089). However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism (11094). The effects of continued grape juice consumption are unclear.
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Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
Details
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes (53011). However, this interaction has not been reported in humans.
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Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
Details
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes (52949). However, this interaction has not been reported in humans.
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It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
Details
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Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Details
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination (53011).
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Grape juice might decrease phenacetin absorption.
Details
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2) (2539).
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Theoretically, hesperidin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Animal research suggests that hesperetin, a bioflavonoid aglycone derivative of hesperidin, may have antiplatelet activity (54822).
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Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension.
Details
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Theoretically, hesperidin may decrease the levels and clinical effects of celiprolol.
Details
Animal research shows that concomitant use of hesperidin may reduce the plasma area under the curve of celiprolol by up to 75% (91760). This effect has not been reported in humans.
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Theoretically, concomitant use with CNS depressants may cause additive sedative effects.
Details
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Theoretically, hesperidin may increase the levels and clinical effects of diltiazem.
Details
Animal research suggests that hesperidin may enhance the bioavailability of diltiazem, increasing the plasma area under the curve of diltiazem by up to 65.3% (91761). This effect has not been reported in humans.
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Theoretically, hesperidin might inhibit P-glycoprotein-mediated drug efflux and potentially increase levels of drugs that are substrates of P-glycoprotein.
Details
In vitro research shows that hesperidin can inhibit P-glycoprotein efflux (54908). This effect has not been reported in humans.
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Theoretically, hesperidin might increase the levels and clinical effects of verapamil.
Details
Animal research suggests that hesperidin may enhance the bioavailability of verapamil, increasing the plasma area under the curve of verapamil by 96.8% (91762). This effect has not been reported in humans
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Horse chestnut may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Horse chestnut contains the constituent esculin which has been shown to have antithrombotic effects. Therefore, horse chestnut might have antiplatelet effects (19). This has not been shown in humans.
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Theoretically, hu zhang might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
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Theoretically, hu zhang might increase the effects and adverse effects of carbamazepine.
Details
In animals, blood and tissue levels of carbamazepine were increased when given in combination with hu zhang. It is thought that increased levels of carbamazepine are due to cytochrome P450 3A4 (CYP3A4) inhibition (101418). This interaction has not been reported in humans.
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Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A1.
Details
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Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A2.
Details
Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A2 enzyme (21733). This interaction has not been reported in humans.
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Theoretically, hu zhang might increase levels of drugs metabolized by CYP1B1.
Details
Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1B1 enzyme (70834). This interaction has not been reported in humans.
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Theoretically, hu zhang might increase levels of drugs metabolized by CYP2C19.
Details
Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2C19 enzyme (70896). This interaction has not been reported in humans.
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Theoretically, hu zhang might increase levels of drugs metabolized by CYP2E1.
Details
Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2E1 enzyme (7864,70896). Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35% (95824). Chlorzoxazone is used as a probe drug for CYP2E1.
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Theoretically, hu zhang might increase levels of drugs metabolized by CYP3A4.
Details
Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP3A4 enzyme (7864,70896). However, a clinical study in adults with NAFLD found that adding resveratrol 3000 mg daily for 8 weeks did not necessitate dose adjustments to any established medications metabolized by CYP3A4 (91327).
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Theoretically, hu zhang might competitively inhibit the effects of estrogen replacement therapy.
Details
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Below is general information about the adverse effects of the known ingredients contained in the product Beautiful Legs. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, butcher's broom seems to be well tolerated, short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastritis, heartburn, nausea, and vomiting.
Topically: Contact dermatitis in sensitive individuals.
Dermatologic ...Topically, butcher's broom may cause contact dermatitis (37487,94780). A 30-year-old female developed an erythematous, papular, pruritic rash on both legs after applying a cream containing butcher's broom root extract (Fabroven, Pierre Fabre Iberica) to varicose veins for 2 months. The rash spread to the entire body, and the patient had positive patch tests to ethanol extracts of butcher's broom (37487). In another report, a 34-year-old female developed pruritic eczematous lesions in the perianal area after using an antihemorrhoidal cream containing a butcher's broom extract (Proctolog, Desma Pharmaceutical). Several months later, the patient developed a generalized eczematous rash after applying another cream containing butcher's broom extract to the legs. The patient had positive patch tests to ruscogenins, which are constituents of butcher's broom (94780).
Gastrointestinal ...Orally, butcher's broom may cause nausea, vomiting, diarrhea, dyspepsia, heartburn, and gastritis (10068,37494,37498,94778). A 39-year-old female with poorly-controlled diabetes reported severe vomiting and diarrhea after taking butcher's broom for 5 days and was ultimately hospitalized with dehydration, hyperkalemia, acidosis, and sinus tachycardia (94778).
General
...Orally, diosmin is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, dizziness, gastritis, nausea, skin inflammation, and skin redness.
Serious Adverse Effects (Rare):
Orally: Cardiac arrhythmias and hemolytic anemia.
Cardiovascular ...Orally, diosmin can cause cardiac arrhythmias (93887,105293).
Dermatologic ...Orally, diosmin can cause skin redness, hives, itchiness, and inflammation (93887).
Gastrointestinal ...Orally, diosmin can cause gastrointestinal side effects, including abdominal pain, diarrhea, nausea, flatulence, and gastritis (4861,4898,4900,10229,54935,54970,93887,105287,105293,105296)(112796). In one case, exacerbation of chronic colopathy was reported after taking a specific diosmin-containing product (Daflon 500, Les Laboratoires Servier) (10229).
Hematologic ...Orally, diosmin can cause hemolytic anemia (93887).
Musculoskeletal ...Orally, one case report of muscle pain was thought to be related to diosmin use (93887).
Neurologic/CNS ...Orally, diosmin can cause headache, low energy, and dizziness in some patients (4861,4898,4900,10229,93887,105293,112796).
General
...Orally, the whole fruit, as well as the seed, fruit, and leaf extracts, seem to be well tolerated.
Topically, grape seed extracts seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, dry mouth, dyspepsia, headache, joint pain, and nausea.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to grape skin has been reported.
Dermatologic ...Orally, mild hair thinning has been reported in a patient taking a specific grape leaf extract AS195 KG) (2538). Urticaria (hives) has also been reported with this same extract (53206). Cases of contact dermatitis have been reported in grape workers, including those working in California vineyards (53270,53272,53275).
Gastrointestinal ...Orally, abdominal pain and nausea have been reported with use of grape seed extract, but these effects typically occur at rates similar to placebo (9182,13162). In a case report of a 57-year-old man, intermittent nausea, vomiting, and diarrhea occurred over a 10-day period and improved once grape seed extract was stopped (96764). Gastrointestinal adverse effects have also been reported with use of a different grape seed extract (Entelon, Hanlim Pharm). However, the specific types of gastrointestinal effects were not described (100954). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused flatulence, mild constipation, gastrointestinal discomfort, diarrhea, dyspepsia, dry mouth, and retching (2538,52985,53206). Diarrhea, gastrointestinal distress, indigestion, and aversion to taste have been reported with use of Concord grape juice (52972,53166,53175,53181,53199). Loose stools have been reported in a clinical trial of grape pomace (99270). Bowel obstruction caused by intact grapes and grape seeds has been described in case reports (53241,53284,53278). Excessive consumption of grapes, dried grapes, raisins, or sultanas might cause diarrhea due to laxative effects (4201).
Hematologic ...Orally, one case of leg hematoma following a minor trauma was reported in a person using grape leaf extract (2538). Also, one case of bruising was reported in a person drinking Concord grape juice daily for 2 weeks (52972).
Immunologic ...Orally, there is one report of an anaphylactic reaction to oral grape skin extract, which included urticaria and angioedema (4073).
Musculoskeletal ...Orally, musculoskeletal disorders, including back pain, have been reported with use of a specific grape leaf extract AS195 KG) (2538,53206). Joint pain and lumbago have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (91541).
Neurologic/CNS ...Orally, headache has been reported with use of grape seed extract, but this effect occurs at rates similar to placebo (9182,91541). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused dizziness, tiredness, headache, and sleep problems (2538,53206). As a class, nervous system adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of adverse neurologic effects were not described (100954).
Ocular/Otic ...Orally, ocular adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of ocular adverse effects were not described (100954).
Pulmonary/Respiratory ...Orally, nasopharyngitis and oropharyngeal pain have been reported with use of a specific grape leaf extract AS195 KG) (53206). Sore throat, cough, allergic rhinitis, and nasopharyngitis have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (9182,91541). One case report describes a 16-year-old female who developed increased levels of immunoglobulin E (IgE) following skin-prick exposure to grape vine pollen, as well as positive test responses following bronchial and conjunctival provocation (53301). Reduced forced vital capacity has been described in California grape workers (53080,53081). Occupational eosinophilic lung was diagnosed in a grape grower with a history of asthma. Respiratory exposure to sulfites in grape was implicated as the cause of the adverse reaction (53285).
Other
...Orally, grape products can cause adverse effects due to contamination with pesticides or mycotoxins.
Some evidence has shown that pesticides used in vineyards may remain on grape surfaces post-harvesting. For example, the fungicide folpet sprayed on grapevines has been shown to remain on the grape surface. Although there was minimal penetration of the epicuticular wax, it showed high resistance to washing (52935). Carbaryl has been identified in over 58% of juice samples collected in Canada. This pesticide reportedly occurred more frequently in grape than in other juices. However, estimates of short-term intake were below proposed acute reference doses (53003).
Ochratoxin A is a mycotoxin that is suspected to be nephrotoxic, teratogenic, hepatotoxic and carcinogenic and has been identified in grape juice, frozen grape pulps, and red and white wine sold in Rio de Janeiro, Brazil. However, the highest levels identified in grape products were lower than the established virtually safe dose of 5 ng/kg of body weight daily (53010,53004). Ochratoxin A has also been identified in red, but not white, grape juice marketed in Switzerland, Canada, and the U.S. (53292,53020).
General ...Orally, hesperidin is generally well tolerated.
Dermatologic ...A case of recurrent allergic dermatitis was reported in a 70-year-old female with no known allergies who applied topical hesperidin methyl chalchone (94538).
Immunologic ...A case of recurrent allergic dermatitis was reported in a 70-year-old female with no known allergies who applied topical hesperidin methyl chalchone (94538).
General
...Orally, horse chestnut seed extract, from which the toxic constituent esculin has been removed, seems to be well-tolerated.
Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally (extract): Dizziness, gastrointestinal upset, headache, and pruritus.
Orally (seed or bark): Gastrointestinal irritation and toxic nephropathy.
Cardiovascular ...Orally, there is one case report of pericardial tamponade following exudative pericardial effusion in a previously healthy 32-year-old male who consumed three boxes of horse chestnut paste over 6 weeks. The patient was treated with steroid therapy for 2 months, as well as colchicine 0.5 mg twice daily and ibuprofen 600 mg twice daily for 3 months. These cardiovascular events were considered to be possibly related to the antiplatelet activity of horse chestnut or to an immunologic response to antigens present in horse chestnut paste (91972). A case of atrial fibrillation is also reported in a previously healthy 46-year-old male after accidental ingestion of a horse chestnut seed. The patient also presented with abdominal pain, nausea, sweating, and palpitations. The arrhythmia resolved within a few hours without medical intervention (110439).
Dermatologic ...Orally, horse chestnut seed extract has been reported to cause pruritus (282,12113,55486).
Gastrointestinal ...Orally, horse chestnut seed extract has been reported to cause nausea, vomiting, diarrhea, abdominal pain, constipation, dry mouth, gastrointestinal upset, and dyspepsia (282,12113,55477,55486,55493,55520,110439).
Hepatic
...Orally, there is one case report of hepatotoxicity in a 69-year-old female who took 6-15 tablets of a specific product (Venencapsan) containing horse chestnut leaf, milfoil, celandine, sweet clover, milk thistle, and dandelion root daily for 6 weeks.
The patient's symptoms disappeared 6 weeks after discontinuing the product and reappeared following re-initiation (55518). Another case report describes a 70-year-old male presenting with acholia, choluria, and jaundice after 3 weeks of self-treatment with an unspecified dose of a specific combination product (Venenkraft) containing horse chestnut. The patient presented with elevated liver transaminase and bilirubin levels, and was diagnosed with drug-induced liver injury. Following discontinuation, laboratory values and symptoms progressively resolved (107702). In both of these case reports, it is unclear if hepatotoxicity was due to horse chestnut, another ingredient, or the combination.
Intravenously and intramuscularly, isolated cases of liver toxicity have occurred after administration of horse chestnut extract containing aescin (2,512,552).
Immunologic
...Pollen from the horse chestnut flower can cause allergic reactions in children (7775).
Horse chestnut can also cause hypersensitivity reactions, which occur more commonly in people who are allergic to latex (7853,8418).
Rectally, the horse chestnut constituent esculin has caused severe allergic contact dermatitis and proctitis in a 38-year old man (10383).
Intravenously, administration of aescin can cause anaphylaxis (18,553).
Musculoskeletal ...Orally, calf spasms have been reported in patients with CVI who took horse chestnut seed extract (282).
Neurologic/CNS ...Orally, horse chestnut seed extract has been reported to cause headache or dizziness (55486,55520).
Renal
...Orally, high doses of aescin have been reported to cause kidney toxicity (55525).
Horse chestnut seed and bark can cause toxic nephropathy (4). A case of life-threatening kidney rupture occurred in a patient who was taking horse chestnut seed extract and had been diagnosed with angiomyolipoma, a condition characterized by increased risk of kidney rupture with hemorrhage. The rupture was attributed to the anticoagulant effects of horse chestnut seed extract, which may have increased the risk of hemorrhage (55496).
Intravenously, isolated cases of kidney toxicity have occurred after administration of horse chestnut containing aescin (512).
General ...There is currently a limited amount of information on the adverse effects of hu zhang.
