Ingredients | Amount Per Serving |
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Proprietary Extract Blend
(Extraction rate: about 1/3-4 (up to 333 mg of dry raw material per 1 ml of extract).)
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983 mg |
(Valeriana officinalis Root Extract, Dry)
(Organic raw material.)
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(Thymus vulgaris Leaf Extract, Dry)
(Organic raw material. )
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(Cinchona officinalis Bark Extract, Dry)
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Alcohol, Water, Glycerin
Below is general information about the effectiveness of the known ingredients contained in the product Legs Relax. 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 Legs Relax. 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 as a flavoring in tonic water and alcoholic beverages. The US Code of Federal Regulations allows not more than 83 parts per million (ppm) of total cinchona alkaloids in finished beverages (93229).
POSSIBLY UNSAFE ...when used orally in medicinal amounts. Cinchona derivatives marketed as over-the-counter (OTC) medicines are required to carry the warning, "Caution - discontinue use if ringing in the ears, deafness, skin rash, or visual disturbances occur" (93231). Cinchona contains the alkaloid quinine that was previously available OTC in the US for treatment and prevention of nocturnal leg muscle cramps. In 1994 the US Food and Drug Administration (FDA) determined that quinine was not generally recognized as safe and effective for this indication, citing serious adverse reactions and its narrow therapeutic index (93232,93233). A final ban on marketing of OTC quinine products was implemented by the FDA in 2007, and a Risk Evaluation and Mitigation Strategy (REMS) to reduce off-label use of prescription quinine products for night-time leg cramps was introduced in 2010 (93232).
LIKELY UNSAFE ...when excessive amounts are used orally. Cinchona contains the alkaloids quinine and quinidine, which are used as prescription medicines and have been associated with significant adverse effects at doses of 2 grams per day or more (505). The amount of these constituents in cinchona products is variable (13).
PREGNANCY: LIKELY UNSAFE
when used orally.
Cinchona is reported to have uterine stimulant and abortifacient activity, and to be fetotoxic and teratogenic, causing visual and auditory defects (12,19). Avoid using.
LACTATION: POSSIBLY UNSAFE
when used orally.
The cinchona alkaloids quinine and quinidine are reported to be excreted in breast milk and may be toxic to infants (19).
LIKELY SAFE ...when used in amounts commonly found in foods. Thyme has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when thyme is used orally and appropriately in supplemental amounts. Orally, thyme, in combination with other herbs, has been used safely for up to 23 days (13557,49219,49223,78133). ...when diluted thyme oil is used topically, short-term. Diluted thyme oil has been used with apparent safety for up to 7 months (5177). There is insufficient reliable information available about the safety of thyme oil when used orally or when inhaled.
CHILDREN: LIKELY SAFE
when used in amounts commonly found in foods.
Thyme has Generally Recognized as Safe (GRAS) status in the US (4912).
CHILDREN: POSSIBLY SAFE
when thyme is used orally in medicinal amounts in combination with English ivy.
Thyme has been used with apparent safety in combination with English ivy for up to 10 days (78181).
There is insufficient reliable information available about the safety of thyme oil when used orally or topically in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts commonly found in foods.
Thyme has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of thyme when used in medicinal amounts during pregnancy and breast-feeding; avoid using.
LIKELY SAFE ...when used orally and appropriately, short-term. Valerian 300-600 mg daily has been safely used in clinical studies in over 12,000 patients for up to 6 weeks (2074,3484,3485,4032,15018,17577,17578,19409,96242,103221)(104010,105718). There is insufficient reliable information available about the safety of valerian when used orally for longer than 6 weeks.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Valerian 160-320 mg has been used with apparent safety in children under 12 years of age for 4-8 weeks (14416).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Legs Relax. 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, taking cinchona might decrease the effectiveness of antacids. Theoretically, taking antacids might also increase the risk of adverse effects from cinchona.
Details
Some research shows that taking cinchona lowers stomach acid pH (19). In addition, some research shows that taking antacids might increase urinary pH. Theoretically, this may increase the amount of quinidine, a constituent of cinchona, reabsorbed in the renal tubules and increase the risk of quinidine toxicity (3046).
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Theoretically, taking cinchona might increase the drug effects and risk of bleeding with anticoagulant and antiplatelet drugs.
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Theoretically, taking cinchona might increase the adverse effects of carbamazepine.
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Clinical research shows that taking quinine, a constituent of cinchona, increases the peak plasma concentration and area under the curve of carbamazepine (11016).
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Theoretically, taking cinchona might inhibit cytochrome P450 2D6 (CYP2D6) and increase levels of drugs metabolized by this enzyme.
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Theoretically, taking cinchona might increase serum levels of digoxin.
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Quinine and quinidine, which are constituents of cinchona, decrease clearance of digoxin and increase serum digoxin levels in humans (3046).
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Theoretically, taking cinchona might decrease the effectiveness of H2-blockers.
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Some research shows that taking cinchona lowers stomach acid pH (19).
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Theoretically, taking cinchona might increase the adverse effects of phenobarbital.
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Theoretically, taking cinchona might decrease the effectiveness of PPIs.
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Some research shows that taking cinchona lowers stomach acid pH (19).
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Theoretically, taking cinchona with other QT interval-prolonging drugs might cause an additive effect and increase the risk of ventricular arrhythmias.
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Quinidine and quinine, which are constituents of cinchona, prolong the QT interval (3046).
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Theoretically, taking cinchona might increase plasma levels and adverse effects of quinidine.
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Cinchona contains quinidine (505).
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Theoretically, taking cinchona might increase plasma levels and adverse effects of quinine.
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Cinchona contains quinine (505).
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Theoretically, concurrent use of anticholinergic drugs and thyme essential oil might reduce the effects of anticholinergic drugs.
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In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.
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Theoretically, thyme leaf extract might have additive effects with anticoagulant or antiplatelet drugs.
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Theoretically, concurrent use of cholinergic drugs and thyme essential oil might cause additive cholinergic effects.
Details
In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.
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Theoretically, thyme might competitively inhibit the effects of estrogen replacement therapy.
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In vitro research shows that thyme has estrogen receptor-binding activity and phytoestrogen content (3701). However, this effect has not been observed in humans.
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Valerian can have additive sedative effects when used concomitantly with alcohol.
Details
Valerian has sedative effects (9894). Theoretically, valerian might have an additive sedative effect when combined with alcohol. Excessive sedation has been reported in an alcohol-abusing individual who took valerian and Gingko biloba (19426). However, the potential interaction between valerian and alcohol has been disputed in other research. Limited evidence suggests that a combination of valerian 160 mg and lemon balm 80 mg (Euvegal) does not cause further deterioration in reaction ability and reaction rate when taken with alcohol as compared to the effects of alcohol alone (19427).
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Valerian can have additive sedative effects when used with alprazolam. Also, valerian in high doses might modestly increase alprazolam levels, though this is not likely to be clinically significant.
Details
Valerian has sedative effects (9894). Theoretically, valerian might cause additive sedation when combined with alprazolam. Also, a small pharmacokinetic study shows that taking valerian extract 1000 mg daily (providing 11 mg valerenic acid) might increase alprazolam levels by about 19%. This might be due to valerian's mild inhibition of cytochrome P450 3A4 (CYP3A4) (13014). Despite being statistically significant, this increase is not likely to be clinically significant.
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Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
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Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP2D6.
Details
Although some in vitro evidence suggests that valerian affects CYP2D6, clinical pharmacokinetic (PK) studies show that valerian is unlikely to affect the CYP2D6 enzyme (13014,13536,19430,19431). In one PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days did not affect the metabolism of dextromethorphan, a CYP2D6 substrate. In another PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of debrisoquine, an accepted CYP2D6 probe-substrate (13014,13536).
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Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
Details
Although some in vitro evidence suggests that valerian extract might inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show that valerian does not have a clinically significant effect on the CYP3A4 enzyme (6450,12214,13014,13536,19431). In one PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of midazolam, an accepted CYP3A4 probe-substrate. In another PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days modestly increases levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of CYP3A4 (13014,13536). However, this mild inhibition is unlikely to be clinically relevant.
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Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
Details
In vitro research shows that methanolic valerian extract and valerenic acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) and UGT2B7 (81685).
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Below is general information about the adverse effects of the known ingredients contained in the product Legs Relax. 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
...Information on the adverse effects of cinchona is limited.
Orally, prolonged use of high doses of cinchona can cause severe adverse effects. Topically, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, nausea, ringing ears, vomiting.
Topically: Contact dermatitis, urticaria.
Serious Adverse Effects (Rare):
Orally: Arrhythmias, cinchonism syndrome, hemolytic uremic syndrome, QT prolongation, thrombotic thrombocytopenic purpura.
Cardiovascular ...Cinchona contains the alkaloids quinidine and quinine that can prolong the QT interval on the electrocardiogram, and cause potentially fatal cardiac arrhythmias such as torsades de pointes (3046,93232)
Dermatologic ...Topical use of cinchona bark extracts and occupational exposure to cinchona bark dust can cause contact dermatitis and other urticarial reactions (11,93234). A 31-year old man developed itching, erythema, and edema of the face and upper chest after occupational exposure to dust from cinchona bark. Skin testing produced reactions to ethanol and ether extracts of the bark, but not to the individual alkaloids quinine and quinidine (93234).
Gastrointestinal ...Cinchona stimulates secretion of stomach acid and has been associated with nausea, vomiting, and diarrhea (6,19).
Hematologic ...Quinine, which is present in cinchona, has been associated with serious, sometimes fatal, hematological disorders including thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (hemolytic anemia, acute renal failure, and thrombocytopenia) (93232,93233). Initial symptoms may include bleeding from the gums, nose or gastrointestinal tract, easy bruising, and petechiae (93233). Bone marrow depression and thrombocytopenia have also been associated with quinidine (505).
Immunologic ...Oral use of quinine, an alkaloid present in cinchona, has been associated with severe allergic skin reactions, as well as anaphylaxis (19,93232).
Ocular/Otic ...Cinchona contains quinine that can cause dose-related adverse effects on hearing and vision, including tinnitus, deafness, vision changes, and blindness (6,8,12,93232).
Other ...Orally, prolonged use of high doses of cinchona or its alkaloids, or a single dose of 3 grams or more of the alkaloid quinine are associated with a toxicity syndrome known as cinchonism. Symptoms include headache, dizziness, nausea and vomiting, diarrhea, hemolysis, hypotension, cardiac arrhythmias, tinnitus, deafness, vision changes, blindness, abdominal pain, delirium, convulsions, paralysis, and collapse (6,12,19,505,93232). Doses of 10-15 grams of quinine may be fatal (18).
General
...Orally, thyme is well tolerated when used in food and seems to be well tolerated when used medicinally.
Topically, thyme seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic reactions, diarrhea, dizziness, headache, heartburn, nausea, or vomiting.
Topically: Contact dermatitis and skin irritation.
Dermatologic ...Topically, thyme, thyme oil, or the constituent thymol can cause contact dermatitis and skin irritation (13463,78252,78362,78384,77982,78154,78310,78313,78384). In one study of 100 patients with contact allergies, 5% were attributed to thyme oil as an allergen contained in wound dressings (78362). Toothpastes containing thymol have been associated with cheilitis and glossitis (13463).
Gastrointestinal
...Orally, thyme and thyme oil may cause heartburn, nausea, vomiting, stomach upset, or diarrhea (13557,94033).
In a clinical study, two patients using extracts of thyme herb and ivy leaves experienced temporary stomach ache and mild nausea (78181).
Intravaginally, cream containing thyme and garlic has been associated with reports of nausea and vomiting in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.
Genitourinary ...Intravaginally, cream containing thyme and garlic has been associated with reports of vaginal dryness and vaginal irritation in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.
Immunologic ...Orally, thyme can cause allergic reactions; however, this is uncommon (13463). Allergic reactions to thyme might be more common in people who are also allergic to oregano and other Lamiaceae species (3808).
Neurologic/CNS ...Orally, thyme may case headache or dizziness (94033).
Pulmonary/Respiratory ...By inhalation, occupational exposure to thyme dust can cause acute airway obstruction (783,13463,13464,77982,78098).
General
...Orally, valerian is generally well-tolerated.
Most Common Adverse Effects:
Orally: Dizziness, drowsiness, and mental slowness. Other reported side effects include headache, gastrointestinal upset, excitability, and vivid dreams. When used chronically and abruptly stopped, symptoms of withdrawal such as tachycardia, anxiety, irritability, and insomnia might occur. Advise patients to taper doses slowly after extended use.
Serious Adverse Effects (Rare):
Orally: Several case reports raise concerns about hepatotoxicity after the use of valerian and valerian-containing multi-ingredient dietary supplements. Withdrawal from chronic valerian use has been associated with cases of cardiac failure and hallucinations.
Cardiovascular ...When used orally in high doses for an extended period of time, valerian withdrawal has been associated with tachycardia and high output cardiac failure in one patient with a history of coronary artery disease (3487). Chest tightness has been reported for an 18-year-old female who took 40-50 capsules containing valerian 470 mg/capsule (659). A case of severe hypotension, suspected to be due to vasodilation, hypocalcemia, and hypokalemia, has been reported for a patient who injected an unknown quantity of a crude tap water extract of raw valerian root (81734).
Dermatologic ...Orally, valerian might rarely cause a rash. A case of valerian-related rash that resolved after valerian root discontinuation was reported in clinical research (19422).
Gastrointestinal ...Orally, valerian has been associated with increased incidence of gastrointestinal problems including diarrhea, nausea, vomiting, and stomach pain (15046,19406,19407,19422,110712). In one individual, taking 20 times the normal dose caused abdominal cramping (659).
Hepatic
...There have been several case reports of hepatotoxicity associated with the use of multi-ingredient oral preparations containing valerian (8243,96241).
In one case report, a 57-year-old man presented with acute hepatitis after consuming a cold and flu remedy containing valerian 2 grams for 3 days; the remedy also contained white willow, elderberry, and horseradish. Although the use of the cold and flu remedy was discontinued one month prior to symptom presentation, the acute hepatitis was attributed to valerian root and treated with steroids (96241). It is possible, however, that some of these preparations may have been adulterated with hepatotoxic agents (8243).
Hepatotoxicity involving long-term use of single-ingredient valerian preparations has also been reported (3484,17578). Also, a case of a 38-year-old female with liver insufficiency and cirrhosis of a vascular parenchymal nature who developed hepatotoxic symptoms following valerian and ethyl-alcohol abuse has been reported (81697). Symptoms resolved and laboratory values normalized following intense plasmapheresis treatment. Another case of acute hepatitis characterized by elevated aminotransferases, mild fibrosis, and liver inflammation has been reported for a 50-year-old female who consumed valerian root extract 5 mL three times weekly along with 10 tablets of viamine, a product containing dry valerian extract 125 mg/tablet, for 2 months (81696). Because a variety of doses were used in these cases, and many people have used higher doses safely, these hepatotoxic reactions might have been idiosyncratic. Tell patients the long-term effect of valerian on liver function is unknown.
Musculoskeletal ...In a case report, combined intake of valerian and passionflower caused throbbing and muscular fatigue when taken concomitantly with lorazepam (19429).
Neurologic/CNS ...Orally, valerian might cause dizziness, headaches, fatigue, sleepiness, and mental dullness (3484,17578,19411,19422,81723,89407). The severity of adverse effects appears to increase with higher doses (19411). However, taking valerian extracts in doses up to 1800 mg does not appear to significantly affect mood or psychomotor performance (10424,15044). Valerian does not usually have a negative impact on reaction time, alertness, and concentration the morning after intake (2074,8296). Clinical research shows that a single dose of valerian root 1600 mg is not associated with any changes in sleepiness, reaction time, or driving performance within 1-4 hours after intake (96240). More serious side effects may occur when valerian is taken at higher doses. In one individual, 20 times the normal dose caused tremor of the hand and foot and lightheadedness (659). In a case report, combined intake of valerian and passionflower caused shaking of the hands and dizziness when taken concomitantly with lorazepam (19429).
Psychiatric ...Orally, valerian has been associate with reports of restlessness, excitability, uneasiness, agitation, and vivid dreams (3484,17578,19411,19422). Chronic use and rapid cessation can lead to withdrawal syndrome with symptoms of agitation, insomnia, and hallucinations (104003). There appears to be a trend towards increased severity of adverse effects with higher doses (19411). A case of acute hypomania has been reported for a 21-year-old female patient who took a valerian decoction in water each night for one month to treat subclinical anxiety. Symptoms included euphoric mood, rapid speech, and increased sociability and sexual interest. Following cessation of valerian use and treatment with quetiapine 100 mg daily for two weeks, the patient recovered (89405). In another case report, an 85-year-old male with mild cognitive impairment, major depression, anxiety, and chronic kidney disease presented to the emergency department with hallucinations, confusion, and agitation thought to be due to abrupt cessation after taking valerian 600 mg daily for about 6 months. The symptoms resolved in about 5 days (104003).