| Ingredients | Amount Per Serving |
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((6.8 g) (Blend supplies an herbal equivalent of 15,000 mg.))
(Proprietary Bioflavonoids Extract Blend Note: (6.8 g) (Blend supplies an herbal equivalent of 15,000 mg.) )
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6800 mg |
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(Rosa canina )
(hip)
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(Citrus sinensis )
(peel)
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(Citrus x limon )
(peel)
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purified Water, Vegetable Glycerin, 12-15% certified organic Alcohol
Below is general information about the effectiveness of the known ingredients contained in the product Bio-Flavonoids. 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
Below is general information about the safety of the known ingredients contained in the product Bio-Flavonoids. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
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 in amounts commonly found in foods. Lemon has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when inhaled in amounts used for aromatherapy, short-term. Lemon essential oil has been used with apparent safety as aromatherapy for up to 2 weeks in clinical research (93475,98128,98129). There is insufficient reliable information available about the safety of lemon when used topically, or when used orally or intranasally in medicinal amounts.
PREGNANCY AND LACTATION:
Insufficient reliable information available.
Avoid using in amounts greater than those typically found in foods.
LIKELY SAFE ...when rose hip extract is used orally in the amounts found in foods. Rose hip extract has Generally Recognized as Safe (GRAS) status in the US (4912). ...when rose hip from Rosa canina is used orally and appropriately in medicinal amounts. A specific formulation of rose hip powder from Rosa canina (LitoZin/i-flex, Hyben Vital), taken in doses of up to 2.5 grams (5 capsules) twice daily, has been safely used for up to 6 months (17416,71641,71646,71658,71660,71661,104557). Rose hip powder from Rosa canina, 40 grams daily mixed in apple juice, has been used safely for up to 6 weeks (18104). Rose hip powder from Rosa canina, 500 mg twice daily for 20 days, has also been safely used (97938).
POSSIBLY SAFE ...when rose hip from Rosa damascena is used orally and appropriately in medicinal amounts. Rose hip extract from Rosa damascena has been used safely in doses of 200 mg every 6 hours for 3 days (104555). There is insufficient reliable information available about the safety of medicinal amounts of rose hip from other Rosa species. There is also insufficient reliable information available about the safety of rose hip when used topically.
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of rose hip when used orally or topically in medicinal amounts; avoid using in amounts greater than those found in foods.
LIKELY SAFE ...when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340,15171,92309).
POSSIBLY SAFE ...when the essential oil of sweet orange is inhaled as aromatherapy, short-term (35735,58060,90505,105455). There is insufficient reliable information available about the safety of sweet orange peel when used orally.
CHILDREN: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods.
CHILDREN: POSSIBLY UNSAFE
when the sweet orange peel is used orally in excessive amounts.
There have been reports of intestinal colic, convulsions, and death in children given large amounts of sweet orange peel (11).
PREGNANCY AND LACTATION: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340).
Below is general information about the interactions of the known ingredients contained in the product Bio-Flavonoids. 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, 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, taking itraconazole capsules or tablets with a beverage containing lemon might increase the levels and clinical effects of itraconazole.
Details
In one case report, dissolving itraconazole tablets in a small amount of specific beverages containing lemon prior to administration increased the level of itraconazole in a lung transplant patient. In this case, the increased bioavailability was desirable and was likely due to improved tablet dissolution in the acidic beverage (110781).
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Theoretically, the antioxidant effects of rose hip might reduce the effectiveness of alkylating agents but might also reduce the oxidative damage caused by certain alkylating agents.
Details
Rose hip contains vitamin C. The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). Further, some animal research suggests that the antioxidant effects of rose hip might attenuate cyclophosphamide-induced testicular toxicity (111413). More evidence is needed to determine what effect, if any, antioxidants found in rose hip, such as vitamin C, have on the effectiveness and adverse effects of chemotherapy.
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Theoretically, rose hip might increase the amount of aluminum absorbed from aluminum compounds.
Details
Rose hip contains vitamin C. Theoretically, vitamin C increases the absorption of aluminum. Concomitant use might increase aluminum absorption, but the clinical significance of this is unknown (3046). Administer rose hip two hours before or four hours after antacids.
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Theoretically, rose hip might reduce the effectiveness of anticoagulant or antiplatelet drugs.
Details
In vitro and animal research suggests that a constituent of rose hip, rugosin E, can induce platelet aggregation (71653). This has not been shown in humans. Theoretically, concomitant use of rose hip might reduce the effectiveness of antiplatelet or anticoagulant drugs.
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Theoretically, the antioxidant effects of rose hip might reduce the effectiveness of antitumor antibiotics.
Details
Rose hip contains the antioxidant vitamin C. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as antitumor antibiotics (391). In contrast, other researchers theorize that antioxidants might make antitumor antibiotic chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on antitumor antibiotic chemotherapy.
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Theoretically, rose hip might reduce the clearance of aspirin; however, its vitamin C content is likely too low to produce clinically significant effects.
Details
Rose hip contains vitamin C. It has been suggested that acidification of the urine by vitamin C can decrease the urinary excretion of salicylates, increasing plasma salicylate levels (3046). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589). The vitamin C content of rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and aspirin is unlikely.
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Theoretically, rose hip might increase blood levels of estrogens.
Details
Rose hip contains vitamin C. Increases in plasma estrogen levels of up to 55% have occured under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products (129,130,11161). It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall (129,11161). When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. However, increases in plasma estrogen levels may occur when women who are deficient in vitamin C take supplements (11161).
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Theoretically, rose hip might increase blood levels of lithium.
Details
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Theoretically, rose hip might reduce the effectiveness of warfarin; however, its vitamin C content is likely too low to produce clinically significant effects.
Details
Rose hip contains vitamin C. High doses of vitamin C may reduce the response to warfarin, possibly by causing diarrhea and reducing warfarin absorption (11566). This occurred in two people who took up to 16 grams daily of vitamin C, and resulted in decreased prothrombin time (9804,9806). Lower doses of 5-10 grams daily of vitamin C can also reduce warfarin absorption, but this does not seem to be clinically significant (9805,9806,11566,11567). The vitamin C content of rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and warfarin is unlikely.
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Consuming sweet orange with celiprolol can decrease oral absorption of celiprolol.
Details
A pharmacokinetic study in healthy volunteers shows that celiprolol levels, after a single dose of 100 mg, are decreased by up to 90% in people who drink sweet orange juice 200 mL three times daily. It's not known if lower consumption of sweet orange juice will have the same effect. Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (12115,17603,17604). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).
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Consuming sweet orange juice with fexofenadine can decrease oral absorption of fexofenadine.
Details
Clinical research shows that coadministration of sweet orange juice 1200 mL decreases bioavailability of fexofenadine by about 72% (7046,17604). In an animal model, sweet orange juice decreased bioavailability of fexofenadine by 31% (17605). Fexofenadine manufacturer data indicates that concomitant administration of sweet orange juice and fexofenadine results in larger wheal and flare sizes in research models. This suggests that sweet orange reduces the clinical response to fexofenadine (17603). Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (7046). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).
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Consuming sweet orange juice with ivermectin can decrease the oral absorption of ivermectin.
Details
A pharmacokinetic study in healthy volunteers shows that taking ivermectin orally with sweet orange juice 750 mL over 4 hours reduces the bioavailability of ivermectin. This effect does not seem to be related to effects on P-glycoprotein. The effect on ivermectin is more pronounced in males compared to females (12154).
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Consuming sweet orange juice can decrease oral absorption of OATP substrates. Separate administration by at least 4 hours.
Details
Clinical research shows that consuming sweet orange juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP (17603,17604). For example, sweet orange juice decreases bioavailability of fexofenadine, a substrate of OATP, by about 72% and of celiprolol, another OATP substrate, by up to 90% (7046,12115). Since sweet orange juice seems to affect OATP for a short time, recommend separating drug administration and consumption of sweet orange juice by at least 4 hours (17603,17604).
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Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.
Details
Animal and in vitro research suggest that orange juice extract inhibits drug efflux by P-gp, increasing absorption and levels of P-gp substrates (12116,15327). In contrast, pharmacokinetic research in humans shows that drinking large amounts of sweet orange juice decreases absorption and levels of the P-gp substrate celiprolol. This suggests that orange juice actually induces drug efflux by P-gp or affects drug levels by another mechanism such as inhibiting the gut drug transporter called organic anion transporting polypeptide (OATP) (7046,12115). Until more is known, sweet orange juice should be used cautiously in people taking P-gp substrates.
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Consuming sweet orange juice with pravastatin can increase the absorption of pravastatin.
Details
A small pharmacokinetic study in healthy volunteers shows that consuming sweet orange juice 800 mL over 3 hours, including before, during, and after taking pravastatin 10 mg, increases pravastatin levels by about 149%, without affecting pravastatin elimination. Theoretically this effect might be due to modulation of organic anion transporting polypeptides (OATPs) by sweet orange juice (14348). Sweet orange juice does not seem to affect simvastatin levels, but it is not known if sweet orange affects any of the other statins.
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Calcium-fortified sweet orange juice might reduce quinolone absorption.
Details
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Below is general information about the adverse effects of the known ingredients contained in the product Bio-Flavonoids. 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, 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, lemon is well tolerated in amounts commonly found in foods.
A thorough evaluation of safety outcomes has not been conducted on the use of larger amounts.
Most Common Adverse Effects:
Orally: Epigastralgia and heartburn with the regular consumption of fresh lemon juice.
Dermatologic ...Topically, the application of lemon oil might cause photosensitivity, due to furocoumarin derivative content. This occurs most often in fair-skinned people (11019).
Gastrointestinal ...Orally, fresh lemon juice, taken as 60 mL twice daily, has been reported to cause gastrointestinal disturbances in 37% of patients in one clinical trial, compared with 8% of patients in the placebo group. Specifically, of the patients consuming lemon juice, 21% experienced heartburn and 8% experienced epigastralgia, compared to 1% and 3%, respectively, in the placebo group (107489).
General
...Orally, rose hip from Rosa canina is well tolerated.
Rose hip from Rosa damascena also seems to be well tolerated. A thorough evaluation of safety outcomes has not been conducted for rose hip derived from other species.
Most Common Adverse Effects:
Orally: Flatulence, loose stools.
Dermatologic ...Orally, one case of mild urticaria has been reported in a clinical trial for a patient taking a specific rose hip powder product (LitoZin/i-flex, Hyben Vital) 2. 5 grams twice daily (71646).
Gastrointestinal
...Orally, gastrointestinal reactions have been reported.
These include abdominal cramps, acid reflux, constipation, diarrhea, flatulence, nausea, vomiting, gastrointestinal obstruction, esophagitis, heartburn, acid reflux, and water brash. However, in most cases, these adverse effects occurred at the same frequency in patients taking placebo (15,18104,71641,71646,97938).
Rose hip powder is a source of vitamin C. Osmotic diarrhea and gastrointestinal upset have been reported with doses of vitamin C greater than the tolerable upper intake level (UL) of 2000 mg daily (4844). However, most rose hip products contain only 500 mg of vitamin C per 100 grams.
Genitourinary ...Orally, a few mild cases of frequent voiding have been reported in clinical trials. However, the frequency of occurrence does not seem to differ from those taking placebo (71641,71646).
Immunologic ...When inhaled in the workplace, rose hip dust has caused mild to moderate anaphylaxis (6).
Neurologic/CNS ...Orally, vertigo and headache have been reported rarely (97938).
Ocular/Otic ...A case of keratoconjunctivitis secondary to contact with rose hip has been reported. The adverse effect was attributed to irritant hairs found on the fruit of rose hip. Symptoms resolved after treatment with topical prednisolone 1% eye drops (71642).
General ...Orally, sweet orange juice or fruit seem to be well tolerated. Large amounts of sweet orange peel may be unsafe, especially for children. When inhaled, sweet orange essential oil seems to be generally well tolerated.
Gastrointestinal ...There have been reports of intestinal colic in children following ingestion of large amounts of sweet orange peel (11).
Neurologic/CNS ...There have been reports of convulsions in children following ingestion of large amounts of sweet orange peel (11).
