| Ingredients | Amount Per Serving |
|---|---|
|
Calories
|
5 {Calories} |
|
Total Carbohydrates
|
2 Gram(s) |
|
Dietary Fiber
|
<1 Gram(s) |
|
Sugar
|
<1 Gram(s) |
|
(Vaccinium macrocarpon )
(fruit)
(standardized to min. 1.5% PACs)
(1,000 mg)
(PACran(R) Cranberry (Form: standardized to min. 1.5% PACs) PlantPart: fruit Genus: Vaccinium Species: macrocarpon Note: 1,000 mg )
|
1 Gram(s) |
|
(Arctostaphylos uva-ursi )
(leaf)
(standardized to min. 15% Arbutin)
(Uva Ursi extract (Form: standardized to min. 15% Arbutin) PlantPart: leaf Genus: Arctostaphylos Species: uva-ursi )
|
300 mg |
|
(Vitis vinifera )
(seed)
(standardized for Polyphenols)
(Grape seed extract (Form: standardized for Polyphenols) PlantPart: seed Genus: Vitis Species: vinifera )
|
45 mg |
Cellulose Note: capsule, Silica, Magnesium Stearate Note: vegetable source, Cellulose powder
Below is general information about the effectiveness of the known ingredients contained in the product Standardized Cranberry Extract. 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
Below is general information about the safety of the known ingredients contained in the product Standardized Cranberry Extract. 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 and appropriately. Cranberry juice up to 300 mL daily and cranberry extracts in doses up to 800 mg twice daily have been safely used in clinical trials (3333,3334,6758,6760,7008,8252,8253,8254,8995,11328) (16415,16720,17100,17126,17176,17210,17524,46379,46388,46389)(46390,46425,46439,46443,46465,46456,46466,46467,46469,46471)(46496,46499,90044,102847,111407).
CHILDREN: LIKELY SAFE
when cranberry juice is consumed in amounts commonly found in the diet (2811,6759,46441,46452,46470,111407).
There is insufficient reliable information available about the safety of cranberry when used in medicinal amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in the diet.
There is insufficient reliable information available about the safety of cranberry when used therapeutically during pregnancy or lactation; avoid using.
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.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Uva ursi has been used with apparent safety in doses of up to 3600 mg daily for 3-5 days (101815).
POSSIBLY UNSAFE ...when used orally long-term or in high doses. There is concern about the safety of long-term or high-dose use because of the hydroquinone content of uva ursi. Hydroquinone is thought to have mutagenic and carcinogenic effects (7). At high doses (around 20 grams of dried herb) it can cause convulsions, cyanosis, delirium, shortness of breath, and collapse. At very high doses (30 grams of dried herb or more) it can be fatal (4).
CHILDREN: POSSIBLY UNSAFE
when used orally by children.
Uva ursi contains hydroquinone and high tannin levels, which can cause severe liver problems in children (4,18); avoid using.
PREGNANCY: LIKELY UNSAFE
when used orally.
Uva ursi can have oxytocic effects, increasing the speed of labor (4,7,19); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Standardized Cranberry Extract. 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, cranberry might increase levels and adverse effects of atorvastatin.
 Details
In one case report, a patient taking atorvastatin experienced upper back pain, rhabdomyolysis, and abnormal liver function after drinking cranberry juice 16 ounces daily for 2 weeks. Theoretically, this may have been caused by inhibition of cytochrome P450 3A4 (CYP3A4) enzymes by cranberry juice, as atorvastatin is a CYP3A4 substrate. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice (90042). Patients taking atorvastatin should avoid large quantities of cranberry juice.
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Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.
Details
There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes (10452,11115,90048). However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac (11094,90048). Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate (15374). Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin (15393).
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Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.
Details
A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice (90042). Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control (46420).
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Theoretically, cranberry might modestly increase the levels and adverse effects of diclofenac.
Details
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Theoretically, cranberry might increase the levels and adverse effects of nifedipine.
Details
Animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine treatment, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control (46420). This interaction has not been reported in humans.
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Theoretically, cranberry might increase the levels and adverse effects of warfarin. However, research is conflicting.
Details
There is contradictory evidence about the effect of cranberry juice on warfarin. Case reports have linked cranberry juice consumption to increases in the international normalized ratio (INR) in patients taking warfarin, resulting in severe spontaneous bleeding and excessive postoperative bleeding (10452,12189,12668,21187,21188,21189,46378,46396,46411)(46415,90043). Daily consumption of cranberry sauce for one week has also been linked to an increase in INR in one case report (16816). In a small study in healthy young males, taking a high dose of 3 grams of cranberry juice concentrate capsules, equivalent to 57 grams of fruit daily, for 2 weeks produced a 30% increase in the area under the INR-time curve after a single 25-mg dose of warfarin (16416). However, 3 very small clinical studies in patients stabilized on warfarin reported that cranberry juice 250 mL once or twice daily for 7 days (27% cranberry juice or pure cranberry juice) or 240 mL once daily for 14 days does not significantly increase INR or affect plasma warfarin levels (15374,17124,90045). The reasons for these discrepant findings are unclear. It is possible that the form and dose of cranberry may play a role, as cranberry extracts and juices contain different constituents. Additionally, an in vitro study evaluating 5 different cranberry juices found varying effects, with only a cranberry concentrate, and not diluted cranberry juices, inhibiting CYP2C9. However, this concentrate did not inhibit CYP2C9 activity in humans (108062).
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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, uva ursi may decrease the metabolism of CYP2C19 substrates.
Details
In vitro, uva ursi appears to inhibit cytochrome CYP2C19 (98550). This effect has not been reported in humans.
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Theoretically, uva ursi may decrease the metabolism of CYP3A4 substrates.
Details
In vitro, uva ursi appears to inhibit CYP3A4 (98550). This effect has not been reported in humans.
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Theoretically, uva ursi may increase levels of drugs metabolized by glucuronidation.
Details
In vitro, uva ursi extract appears to strongly inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1). However, uva ursi extract does not appear to inhibit UGT1A1 in animal models (98549). This effect has not been reported in humans.
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Theoretically, uva ursi may increase lithium levels, necessitating a decrease in dose.
Details
Uva ursi may have diuretic properties (81637). Diuretics may increase lithium reabsorption with sodium in the proximal tubule of the kidney. Theoretically, uva ursi might reduce excretion and increase levels of lithium.
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Theoretically, uva ursi may alter the levels of drugs transported by P-glycoprotein.
Details
In vitro, uva ursi appears to inhibit the multi-drug transporter protein, P-glycoprotein (98550). This effect has not been reported in humans.
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Effects of uva ursi in the urinary tract may be reduced by urinary acidifying agents.
Details
Uva ursi seems to work best in alkaline urine. Theoretically, taking uva ursi with medications known to acidify the urine may decrease any effects of uva ursi on the urinary tract (19).
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Below is general information about the adverse effects of the known ingredients contained in the product Standardized Cranberry Extract. 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, cranberry seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea and gastrointestinal discomfort.
Dermatologic ...Orally, skin redness and itching has been reported in one patient (46389).
Gastrointestinal ...In very large doses, for example 3-4 L per day of juice, cranberry can cause gastrointestinal upset and diarrhea, particularly in young children (46364). There are reports of abdominal and gastrointestinal discomfort after taking cranberry tablets, extracts, and juice in clinical trials (16720,46379,111407). Nausea, vomiting, and diarrhea have also been reported with consumption of lower doses of cranberry juice cocktail, 16 ounces per day, equivalent to about 4 ounces cranberry juice, for several weeks (16415).
Genitourinary ...Vulvovaginal candidiasis has been associated with ingestion of cranberry juice (46374). Clinical research suggests that ingestion of cranberry juice may be associated with vaginal itching and vaginal dryness (46471). One patient in clinical research stopped taking dried cranberry juice due to excessive urination (46437), and an isolated case of nocturia following ingestion of cranberry tablets has been reported (16720).
Hematologic ...Thrombocytopenia has been reported as an adverse event to cranberry juice (46459).
Other ...An isolated case of sensitive swollen nipples after taking cranberry tablets has been reported (16720).
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
...Uva ursi is generally well tolerated in low doses, short-term.
Most Common Adverse Effects:
Orally: Diarrhea, nausea, stomach upset, and vomiting.
Serious Adverse Effects (Rare):
Orally: At high doses (20 grams of dried herb), uva ursi has been reported to cause collapse, convulsions, cyanosis, delirium, shortness of breath, and tinnitus. Very high doses of 30 grams or more may be fatal.
Gastrointestinal ...Orally, uva ursi may cause nausea, vomiting, diarrhea, and stomach upset (92148). It can also irritate the gastrointestinal tract (19).
Genitourinary ...Orally, uva ursi may cause the urine to be greenish-brown. It may also cause irritation and inflammation of the urinary tract mucous membranes (18).
Hepatic ...Uva ursi may be hepatotoxic. Theoretically, chronic use, especially in children, can cause liver impairment due its hydroquinone and high tannin content (4,18).
Neurologic/CNS ...Orally, around 20 grams of uva ursi is reported to supply up to one gram of hydroquinone, which can theoretically cause convulsions and delirium (4).
Ocular/Otic
...Orally, uva ursi may potentially cause retinal toxicity due to its hydroquinone content, which reduces melanin synthesis.
A 56-year-old female developed bilateral bull's-eye maculopathy, paracentral scotomas, and retinal thinning after 3 years of uva ursi tea ingestion (16900).
Taking around 20 grams of uva ursi orally is reported to supply up to one gram of hydroquinone, which can theoretically cause tinnitus (4).
Pulmonary/Respiratory ...Orally, around 20 grams of uva ursi is reported to supply up to one gram of hydroquinone, which can theoretically cause shortness of breath and cyanosis (4).
