| Ingredients | Amount Per Serving |
|---|---|
|
Proprietary Blend
|
1000 mg |
|
Eclipta
(Eclipta alba)
(Bhringaraj, certified organic)
|
|
|
(Valeriana officinalis )
(root)
(certified organic)
|
|
|
(Scutellaria lateriflora)
(certified organic)
|
|
|
(Passiflora incarnata)
(certified organic)
|
|
|
(Tinospora cordifolia )
(stem)
(Guduchi, certified organic)
|
|
|
(flower)
(Matricaria recutita)
(certified organic)
|
|
|
(Withania somnifera )
(root)
(certified organic)
|
|
|
Finger-leaf Morning Glory
(Ipomoea digitata )
(root)
(Vidari Kanda)
(certified organic)
(Vidari Kanda, certified organic)
|
|
|
(Foeniculum vulgare )
(seed)
(certified organic)
|
|
|
(Piper longum )
(fruit)
(Pippali, certified organic)
|
|
|
(Myristica fragrans )
(seed)
(certified organic)
|
Gum Acacia, Rice Flour
Below is general information about the effectiveness of the known ingredients contained in the product I Sleep Soundly. 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
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 I Sleep Soundly. 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. Ashwagandha has been used with apparent safety in doses of up to 1250 mg daily for up to 6 months (3710,11301,19271,90649,90652,90653,97292,101816,102682,102683) (102684,102685,102687,103476,105824,109586,109588,109589,109590). ...when used topically. Ashwagandha lotion has been used with apparent safety in concentrations up to 8% for up to 2 months (111538).
PREGNANCY: LIKELY UNSAFE
when used orally.
Ashwagandha has abortifacient effects (12).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral Baikal skullcap 0.5-3.52 grams daily has been used with apparent safety for up to 8 weeks (92776,101738,101739,110023). However, a high quality assessment of safety has not been conducted. A specific product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been associated with an increased risk for liver and lung injury. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination. There is insufficient reliable information available about the safety of Baikal skullcap when used intravenously or topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).
CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week.
Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).
LACTATION: POSSIBLY UNSAFE
when used orally.
Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. German chamomile has Generally Recognized as Safe (GRAS) status in the US (4912,110318).
POSSIBLY SAFE ...when used orally, for medicinal purposes, short-term. German chamomile has been used with apparent safety at doses of up to 1500 mg daily for up to 26 weeks (6655,12724,12729,13089,19377,19716,104806,111380). ...when applied topically. A lotion containing 0.2% microencapsulated German chamomile extract has been applied to the skin with apparent safety for up to 35 days (108993). ...when used topically as an oral rinse (99853).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Preliminary clinical research suggests that several multi-ingredient products containing German chamomile are safe in infants when used for up to 4 weeks (16735,19705,19715,96278). ...when used topically and appropriately, short-term. Six drops of oil infused with German chamomile flower has been applied nightly with apparent safety for up to 6 weeks in children 6-18 years old (98621).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in food amounts. The fruit is commonly used in foods (101151). There is insufficient reliable information available about the safety of Indian long pepper when used in medicinal amounts.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in medicinal amounts.
LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods. Nutmeg is commonly used as a spice. Nutmeg and nutmeg oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of nutmeg when used orally in larger doses, up to 120 mg daily. These doses have not been adequately evaluated in clinical research. However, doses at or above 120 mg daily have been associated with serious adverse effects (19292).
POSSIBLY UNSAFE ...when used orally in doses of 120 mg or greater. Chronic use of nutmeg in these doses has been associated with psychotic episodes and hallucinations (19292,19296,19487). Acute intoxication from nutmeg has been described in several case reports in which subjects ingested a single dose of 5-80 grams (2563,19297,19300,19491,111750). Symptoms of toxicity ranged from nausea, dry mouth, and dizziness to palpitations, agitation, and hallucinations (2563,3494,19293,19294,19295,19297,19298,19299,19489,19490)(19491,103373,111750). Two deaths involving nutmeg intoxication have also been reported (19300,112016) . Symptoms generally start 0.5-8 hours after ingestion and last up to 24-48 hours (19298,19488,19491,103372,103373). There is insufficient reliable information available about the safety of nutmeg when used topically.
PREGNANCY: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Nutmeg might have abortifacient activity, and its safrole content might be mutagenic (12).
LACTATION: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.
There is insufficient reliable information available about the safety of nutmeg when used in larger, medicinal amounts during lactation; avoid using.
LIKELY SAFE ...when used orally as a flavoring in foods. The US Food and Drug Administration (FDA) lists passion flower as a permitted food flavoring additive, to be used in the minimum quantity necessary (91203).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Passion flower extract has been used with apparent safety at doses up to 800 mg daily for up to 8 weeks (88198,102866). A specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) has been safely used at a dose of 45 drops daily for up to one month (8007,95036). Also, a tea prepared by steeping 2 grams of the dried aerial parts of passion flower in 250 mL of boiling water for 10 minutes has been used nightly for 7 nights (17374). There is insufficient reliable information available about the safety of passion flower when used topically.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
A specific passion flower product (Pasipay, Iran Darouk Pharmaceutical Company) has been used safely in children aged 6-13 years at a dose of 0.04 mg/ kg daily for 8 weeks (88197).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Some case reports suggest that passion flower use during the first and second trimesters of pregnancy may be associated with an increased risk for premature rupture of membranes and meconium aspiration syndrome; however, causality has not been confirmed (97279). The alkaloids harman and harmaline, which are sometimes found in passion flower, have been reported to have uterine stimulant activity (4,11020,95037). It is not known whether these constituents are present in sufficient quantities to have an effect.
LACTATION:
Insufficient reliable information available; avoid using.
There is insufficient reliable information available about the safety of skullcap.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when the stem extract is used orally and appropriately, short-term. Tinospora cordifolia aqueous stem extract has been used with apparent safety at a dose of 900 mg daily for up to 8 weeks (15085). Powdered stem extract has also been used with apparent safety at a dose of up to 3 grams daily for up to 2 weeks or a dose of 1500 mg daily for up to 26 weeks (92230,106846,111503). There is insufficient reliable information available about the safety of other parts of Tinospora cordifolia when used orally or when any part of the plant is used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; 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 I Sleep Soundly. 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 ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.
 Details
|
Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.
Details
Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure (19279). Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.
|
Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.
Details
There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin) (3710). This may also occur with other benzodiazepines.
|
Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.
Details
Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics (3710).
|
Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research shows that ashwagandha extract induces CYP1A2 enzymes (111404).
|
Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
Details
In vitro research shows that ashwagandha extract induces CYP3A4 enzymes (111404).
|
Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
Details
|
Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.
Details
|
Ashwagandha might increase the effects and adverse effects of thyroid hormone.
Details
Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion (19281,19282,97292). In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism (97292).
|
Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.
Details
In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.
|
Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.
Details
Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily (33075). It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.
|
Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.
Details
Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro (6292). Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin (33408). However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT) (101738). Until more is known, use cautiously.
|
Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.
Details
Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure (33374).
|
Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.
Details
In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) (101736). The clinical significance of this effect is unclear.
|
Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.
Details
In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.
|
Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.
Details
|
Theoretically, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.
Details
In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes (33484). This effect has not been reported in humans.
|
Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.
Details
In vitro evidence suggests that Baikal skullcap has estrogenic activity (16061).
|
Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.
Details
Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion (5541). The dose of lithium might need to be decreased.
|
Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.
Details
Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual (16395). Baikal skullcap might also affect other OATP1B1 substrates (16396,16397,16398).
|
Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.
Details
|
Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Details
|
Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.
Details
Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135). |
Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.
Details
|
Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.
Details
|
Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.
Details
|
Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.
Details
Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen. |
Theoretically, German chamomile might have additive effects when used with CNS depressants.
Details
|
Theoretically, large amounts of German chamomile might reduce the effectiveness of oral contraceptives.
Details
In vitro, German chamomile has demonstrated antiestrogenic activity (12728). Theoretically, concomitant use of large amounts of German chamomile might interfere with contraceptive drugs through competition for estrogen receptors.
|
Theoretically, German chamomile might inhibit CYP1A2 and increase levels of drugs metabolized by these enzymes.
Details
|
Theoretically, German chamomile might inhibit CYP2C9 and increase levels of drugs metabolized by these enzymes.
Details
In vitro evidence shows that German chamomile might inhibit CYP2C9 (19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2C9 in patients taking German chamomile.
|
Theoretically, German chamomile might inhibit CYP2D6 and increase levels of drugs metabolized by these enzymes.
Details
In vitro evidence shows that German chamomile might inhibit CYP2D6 (19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2D6 in patients taking German chamomile.
|
Theoretically, German chamomile might inhibit CYP3A4 and increase levels of drugs metabolized by these enzymes.
Details
|
Theoretically, large amounts of German chamomile might reduce the effectiveness of estrogens.
Details
In vitro, German chamomile has demonstrated antiestrogenic activity (12728). Theoretically, large amounts of German chamomile might interfere with hormone replacement therapy through competition for estrogen receptors.
|
Theoretically, large amounts of German chamomile might interfere with the activity of tamoxifen.
Details
In vitro, German chamomile has demonstrated antiestrogenic activity (12728).
|
German chamomile might increase the effects of warfarin and increase the risk of bleeding.
Details
In one case, a 70-year-old female taking warfarin developed retroperitoneal hematoma and bilateral recti muscle bleeding along with an INR of 7.9 following ingestion of German chamomile tea 4-5 cups daily and use of a topical chamomile-based lotion applied 4-5 times daily (14309).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of amoxicillin.
Details
Evidence from animal research shows that piperine, a constituent of Indian long pepper, increases the plasma levels of amoxicillin when taken concomitantly (29269).
|
Theoretically, Indian long pepper might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
Details
In vitro research shows that Indian long pepper extract inhibits platelet aggregation (101151).
|
Theoretically, Indian long pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
Animal research shows that piperine, a constituent of Indian long pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.
|
Theoretically, Indian long pepper might increase blood levels of carbamazepine.
Details
A small pharmacokinetic study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that a single 20 mg dose of purified piperine, which is a constituent of Indian long pepper, increases carbamazepine levels. Piperine may increase absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or by cytochrome P450 3A4 (CYP3A4) inhibition in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects (16833).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of cefotaxime.
Details
Animal research shows that piperine, a constituent of Indian long pepper, increases the plasma levels of cefotaxime when taken concomitantly (29269).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of cyclosporine.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, increases the bioavailability of cyclosporine (29282).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of CYP1A1 substrates.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP1A1 (29213).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of CYP2B1 substrates.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP2B1 (29332).
|
Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.
Details
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP3A4 (14375).
|
Theoretically, Indian long pepper might increase blood levels of nevirapine.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, increases the plasma concentration and systemic exposure of nevirapine. However, no adverse effects were associated with the elevated plasma levels of nevirapine (29209).
|
Theoretically, Indian long pepper might increase levels of P-glycoprotein substrates.
Details
|
Theoretically, Indian long pepper might increase the sedative effects of pentobarbital.
Details
Animal research shows that piperine, a constituent of Indian long pepper, can increase pentobarbitone-induced sleeping time (29214).
|
Theoretically, Indian long pepper might increase blood levels of phenytoin.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, increases phenytoin serum levels and slows its elimination (537).
|
Theoretically, Indian long pepper might increase blood levels of propranolol.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, accelerates absorption and increases serum concentrations of propranolol (538).
|
Theoretically, Indian long pepper might increase blood levels of rifampin.
Details
|
Indian long pepper might increase blood levels of theophylline.
Details
A small pharmacokinetic study shows that piperine, a constituent of Indian long pepper, increases serum concentrations and slows elimination of theophylline (538).
|
Theoretically, concomitant use of nutmeg and anticholinergic drugs might decrease the effectiveness of either agent.
Details
Animal research suggests that nutmeg extract can inhibit acetylcholinesterase and might increase acetylcholine levels (25549).
|
Theoretically, concomitant use of nutmeg with other cholinergic drugs might have additive effects and increase the risk of cholinergic side effects.
Details
Animal research suggests that nutmeg extract can inhibit acetylcholinesterase and might increase acetylcholine levels (25549).
|
Theoretically, nutmeg might increase the risk of additive sedation when taken with CNS depressants.
Details
Animal studies suggest that nutmeg extracts and several volatile oils in nutmeg, such as methyleugenol, isoeugenol, safrole, myristicin, trimyristin, 1,8-cineole, and geranyl acetate, have sedative effects (2563,25544,25545,25547,25548). One animal study shows that petroleum ether extracts of nutmeg can potentiate the effects of pentobarbital or phenobarbital (25547). However, evidence from other animal research suggests that the nutmeg constituent myristicin can actually reduce sleeping time in rats pretreated with phenobarbital (3492,3493).
|
Theoretically, nutmeg might decrease the levels and clinical effects of drugs metabolized by CYP1A1.
Details
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP1A1 (3493).
|
Theoretically, nutmeg might decrease levels of drugs metabolized by CYP1A2.
Details
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP1A2 (3493).
|
Theoretically, nutmeg might decrease levels of drugs metabolized by CYP2B1.
Details
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP2B1 (3493).
|
Theoretically, nutmeg might increase or decrease the effects and adverse effects of phenobarbital.
Details
|
Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.
Details
|
Theoretically, passion flower might decrease the effects of CYP3A4 substrates.
Details
In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer (110704).
|
Theoretically, passion flower might reduce the bioavailability of OATP2B1 and OATP1A2 substrates.
Details
In vitro research shows that the passion flower constituents apigenin and vitexin inhibit OATP2B1 and OATP1A2. This inhibition may be dose-dependent. One specific high-flavonoid passion flower extract (Valverde) seems to inhibit OATP2B1 and OATP1A2, while another extract with a lower flavonoid concentration (Arkocaps) shows less potent inhibition (105095). OATPs are responsible for the uptake of drugs and other compounds into the body; however, the specific activities of OATP2B1 and OATP1A2 are not well characterized.
|
Theoretically, skullcap can have additive effects when used with other CNS depressants.
Details
|
Theoretically, Tinospora cordifolia might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
|
Theoretically, Tinospora cordifolia might increase levels of drugs metabolized by CYP1A2.
Details
In vitro research shows that Tinospora cordifolia extract inhibits CYP1A2 at high concentrations (98225). However, this interaction has not been reported in humans.
|
Theoretically, Tinospora cordifolia might increase levels of drugs metabolized by CYP2C19.
Details
In vitro research shows that Tinospora cordifolia extract inhibits CYP2C19 at high concentrations (98225). However, this interaction has not been reported in humans.
|
Theoretically, Tinospora cordifolia might increase levels of drugs metabolized by CYP2C9.
Details
In vitro research shows that Tinospora cordifolia extract inhibits CYP2C9. Animal research shows that Tinospora cordifolia extract 400 mg/kg twice daily for 14 days reduces the clearance and increases plasma levels of glyburide, a CYP2C9 substrate (98225). However, this interaction has not been reported in humans.
|
Theoretically, Tinospora cordifolia might increase levels of drugs metabolized by CYP2D6.
Details
In vitro research shows that Tinospora cordifolia extract inhibits CYP2D6 at high concentrations (98225). However, this interaction has not been reported in humans.
|
Theoretically, Tinospora cordifolia might reduce the effectiveness of immunosuppressants.
Details
|
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).
|
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.
|
Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
Details
|
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).
|
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.
|
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).
|
Below is general information about the adverse effects of the known ingredients contained in the product I Sleep Soundly. 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, ashwagandha 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: Diarrhea, gastrointestinal upset, nausea, and vomiting. However, these adverse effects do not commonly occur with typical doses.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about acute hepatitis, acute liver failure, hepatic encephalopathy, the need for liver transplantation, and death due to liver failure with ashwagandha treatment.
Dermatologic ...Orally, dermatitis has been reported in three of 42 patients in a clinical trial (19276).
Endocrine ...A case report describes a 73-year-old female who had taken an ashwagandha root extract (unspecified dose) for 2 years to treat hypothyroidism which had been previously managed with levothyroxine. The patient was diagnosed with hyperthyroidism after presenting with supraventricular tachycardia, chest pain, tremor, dizziness, fatigue, irritability, hair thinning, and low thyroid stimulating hormone (TSH) levels. Hyperthyroidism resolved after discontinuing ashwagandha (108745). Additionally, an otherwise healthy adult who was taking ashwagandha extract orally for 2 months experienced clinical and laboratory-confirmed thyrotoxicosis. Thyrotoxicosis resolved 50 days after discontinuing ashwagandha, without other treatment (114111). Another case report describes a 37-year-old female who presented with moderate symptomatic hyponatremia secondary to adrenal insufficiency after chronic consumption of ashwagandha for 2 years. This subject was effectively managed with oral hydrocortisone (114790).
Gastrointestinal ...Orally, large doses may cause gastrointestinal upset, diarrhea, and vomiting secondary to irritation of the mucous and serous membranes (3710). When taken orally, nausea and abdominal pain (19276,110490,113609) and gastritis and flatulence (90651) have been reported.
Genitourinary ...In one case report, a 28-year-old male with a decrease in libido who was taking ashwagandha 5 grams daily over 10 days subsequently experienced burning, itching, and skin and mucous membrane discoloration of the penis, as well as an oval, dusky, eroded plaque (3 cm) with erythema on the glans penis and prepuce (32537).
Hepatic ...Orally, ashwagandha in doses of 154 mg to 20 grams daily has played a role in several case reports of cholestatic, hepatocellular, and mixed liver injuries. In most of these cases, other causes of liver injury were excluded, and liver failure did not occur. Symptoms included jaundice, pruritus, malaise, fatigue, lethargy, weight loss, nausea, diarrhea, abdominal pain and distension, stool discoloration, and dark urine. Symptom onset was typically 5-180 days from first intake, although in some cases onset occurred after more than 12 months of use (102686,107372,110490,110491,111533,111535,112111,113610,114113). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, serum bilirubin, and international normalized ratio (INR) (112111,113610,114113). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111,114113). However, treatment with corticosteroids, lactulose, ornithine, ursodeoxycholic acid, and plasmapheresis, among other interventions, was required in one case (111533). Rarely, use of oral ashwagandha has been reported to cause hepatic encephalopathy, liver failure requiring liver transplantation, and acute-on-chronic liver failure resulting in death (110490,113610).
Neurologic/CNS ...Orally, ashwagandha has been reported to cause drowsiness (110492,113609). Headache, neck pain, and blurry vision have been reported in a 47-year-old female taking ashwagandha, cannabis, and venlafaxine. Imaging over the course of multiple years and hospital admissions indicated numerous instances of intracranial hemorrhage and multifocal stenosis of intracranial arteries, likely secondary to reversible cerebral vasoconstriction syndrome (RCVS) (112113). It is unclear whether the RCVS and subsequent intracranial hemorrhages were precipitated by ashwagandha, cannabis, or venlafaxine.
General
...Orally, Baikal skullcap seems to be well-tolerated.
There is currently a limited amount of information on the adverse effects of intravenous and topical Baikal skullcap.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, erythema, nausea, pruritus, and vomiting.
Intravenously: Skin reactions.
Topically: Dermatitis.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity and hypersensitivity pneumonitis have been reported with a specific combination product (Limbrel, Primus Pharmaceuticals) containing extracts of Baikal skullcap and catechu.
Cardiovascular ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, elevated triglyceride levels occurred in 1 of 10 patients who received 400 mg every 8 hours and 2 of 10 patients treated with 600 mg every 8 hours, compared with 0 of 10 patients who received 200 mg every 8 hours and 0 of 6 patients who received placebo. Triglyceride elevations were considered mild and resolved after discontinuation (110023).
Dermatologic
...Orally, taking Baikal skullcap may cause erythema and pruritus (105867).
Intravenously, Baikal skullcap as part of a Tanreqing injection has been associated with reports of skin reactions in some pediatric patients (96281).
Topically, several cases of allergic contact dermatitis have been reported after applying sunscreen containing Baikal skullcap extract (105869,105870). Allergic contact dermatitis has also been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing Baikal skullcap root extract 0.5% and resveratrol 1%. Patch testing identified a positive reaction to both ingredients (110024). Baikal skullcap-induced dermatitis appears to respond to treatment with a topical corticosteroid and calcineurin inhibitor (105870).
Gastrointestinal ...Orally, use of Baikal skullcap has been associated with epigastric pain, abdominal pain, constipation, diarrhea, nausea, and vomiting (101738,105867).
Hepatic
...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of acute liver damage.
There have been at least five published reports of liver damage associated with this product. In all cases, the patients were females aged 54-68 years taking doses of 250-500 mg twice daily for 1-3 months. Signs and symptoms included jaundice, pruritus, abdominal pain, fever, rash, and elevated serum bilirubin and liver transaminase levels. All patients fully recovered and levels normalized within 3 months after discontinuation (18009,96282). In addition to these published case reports, approximately 30 liver-related adverse events have been reported to the manufacturer of this product (18009). The mechanism of hepatotoxicity is unclear (18009,18010); it is estimated that the incidence of hepatotoxicity with this product is around 1 in 10,000, although the actual incidence is unknown (18010). In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Hepatotoxicity has also been reported in two patients taking a specific dietary supplement (Move Free Advanced, Reckitt Benckiser) containing Baikal skullcap, black catechu, glucosamine, chondroitin, and hyaluronic acid (33460) and in a patient taking Baikal skullcap, elderflower, horseradish, and white willow (101737). The investigators determined that the hepatotoxicity was likely caused by Baikal skullcap in these cases (33460,101737). Additionally, cases of liver injury are reported in 4 of 37 patients taking various Kampo formulations containing Baikal skullcap and other herbs daily. Patients presented with elevated liver function tests 7 to 38 days after consumption (112179). It is unclear if this adverse effect is from Baikal skullcap, other ingredients, or the combination.
In a small study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, liver transaminase elevations occurred in 2 of 10 patients who received 400 mg every 8 hours for 6 days, compared with 0 of 6 patients who received placebo. No patients receiving either 200 mg or 600 mg every 8 hours experienced liver transaminase elevations. The elevations were considered mild and resolved after discontinuation (110023).
Pulmonary/Respiratory ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of hypersensitivity pneumonitis. Symptoms include fever, chills, headache, cough, chronic bronchitis, shortness of breath, weight loss, and fatigue. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Renal ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, proteinuria of undefined severity occurred in 1 of 10 patients who received 200 mg every 8 hours for 6 days, 3 of 10 patients who received 400 mg every 8 hours for 6 days, and 5 of 10 patients who received 600 mg every 8 hours for 6 days, compared with 1 of 6 patients who received placebo. The proteinuria was considered mild and resolved after discontinuation (110023).
General
...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.
Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).
Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).
Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).
Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).
Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.
Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).
General
...Orally and topically, German chamomile is well tolerated.
Most Common Adverse Effects:
Orally and topically: Allergic reactions and irritation.
Dermatologic ...Topically, German chamomile may cause allergic dermatitis and eczema (9766,9768,10377,110318).
Gastrointestinal ...When used topically as an oral rinse, German chamomile has been reported to cause nausea and burning in the mouth in some patients (99853).
Immunologic ...Orally, German chamomile tea can cause allergic reactions including severe hypersensitivity reactions and anaphylaxis in some patients (567). In one case report, a 47-year-old female who tolerated drinking chamomile tea, reported sneezing, nasal and ocular itching, red and watery eyes, and severe rhinorrhea after 10 years of occupational exposure to German chamomile dust (90542).
Ocular/Otic ...If used near the eyes, German chamomile can cause irritation (10377).
General ...Orally, Indian long pepper is well tolerated when used in food (101151). No adverse effects have been reported when Indian long pepper is used as medicine. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, nutmeg is generally well tolerated when used as a spice in foods.
Acute or chronic use of nutmeg at high doses is unsafe.
Most Common Adverse Effects:
Topically: Allergic contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Accidental or intentional overdose with nutmeg has been associated with several serious adverse cardiovascular, gastrointestinal, neurological, and psychiatric events. Death due to overdose has also been reported.
Cardiovascular ...Orally, in cases of nutmeg overdose, tachycardia, palpitations, weak pulse, hypotension, and nonspecific electrocardiographic changes have been reported (3494,19293,19295,19299,19300,19488,19489,25943,103372,103373)(111750).
Dermatologic ...Topically, allergic contact dermatitis to nutmeg has been reported (25945,25946).
Gastrointestinal ...Orally, nausea was reported in a 13-year-old female consuming nutmeg capsules while smoking cannabis (2563). Vomiting was reported in a case of a 19-year-old female using high doses of nutmeg with a history of lysergic acid diethylamide (LSD) and cannabis use (19294). Burning epigastric pain, gastroenteritis, diarrhea, nausea, and increased thirst have been reported in other cases of intentional or unintentional nutmeg overdose (19293,19299,19300,19489,19490,103372,103373). Vomiting has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Hematologic ...Orally, hyponatremia and leukocytosis with neutrophilia associated with nutmeg overdose have been rarely reported (103372).
Hepatic ...Orally, elevated liver enzymes associated with nutmeg overdose have been reported rarely (103372).
Immunologic ...Topically, allergic contact dermatitis to nutmeg has been reported (25945,25946).
Musculoskeletal ...Orally, muscle weakness, numbness, and ataxia were reported in a 13-year-old female consuming nutmeg capsules while smoking cannabis (2563). An ataxic gait has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Neurologic/CNS ...Orally, headache, dizziness, and drowsiness were reported in a 13-year-old female consuming nutmeg capsules while smoking cannabis (2563). Adverse effects associated with high intake of nutmeg have included confusion, dizziness, drowsiness, hallucinations, headache, incoherent speech, hot and cold sensations, sensations of limb loss, convulsions, and coma (19294,19299,19300,19487,19489,19490,103372,103373,111750). Sweating and hypothermia have also been reported following intake of high doses of nutmeg (19293,19294). Lethargy has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Ocular/Otic ...Orally, a case of double, triple, and blurred vision has been reported for a 13-year-old female who consumed nutmeg capsules while smoking cannabis (2563). Pupil dilation and pupil constriction has been reported from exposure to nutmeg (25948). Involuntary eye movement has been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Psychiatric ...Orally, visual, auditory, and tactile hallucinations, depression, suicidal ideation, insomnia, restlessness, and bizarre behavior have been reported following nutmeg intoxication in various reports (12,2563,19300,19492,103372,103373). Other adverse effects associated with high intake of nutmeg have included disorientation, stupor, euphoria, anxiety, and agitation (19300,19489,103373,103374). Chronic psychosis has been associated with rare cases of prolonged abuse of nutmeg (103372). However, some researchers suggest that nutmeg does not have significant psychological or behavioral effects, even when taken at high doses (25939,25947). Restlessness and anxiety have been reported in a 17-year-old male who snorted at least 15 grams of nutmeg powder (103372).
Other ...Orally, fatal poisoning associated with nutmeg is rare (19300,103372,103373).
General
...Orally, passion flower is well tolerated.
Most Common Adverse Effects:
Orally: Confusion, dizziness, hypersensitivity, and sedation.
Cardiovascular ...There is a case report involving a 34-year-old female who was hospitalized with severe nausea, vomiting, drowsiness, prolonged QT interval, and episodes of nonsustained ventricular tachycardia following use of passion flower extract tablets (Sedacalm, Bioplus Healthcare), 1500 mg on day 1 and 2000 mg on day 2 to relieve stress. All symptoms resolved within one week after passion flower was discontinued (6251).
Genitourinary ...The alkaloids harman and harmaline, which are sometimes found in small amounts in passion flower, have been reported to have uterine stimulant activity (4,11020,95037).
Hematologic ...Orally, passion flower has been reported to cause epistaxis in one clinical trial (95038). Vasculitis has also been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).
Hepatic ...There is debate about whether passion flower contains cyanogenic glycosides. Several related Passiflora species do contain these constituents (3), including Passiflora edulis, which is associated with liver and pancreatic toxicity (7).
Immunologic
...An idiosyncratic hypersensitivity reaction characterized by urticaria and cutaneous vasculitis has been reported in a 77-year-old male with rheumatoid arthritis after taking a specific combination product that included passion flower extract (Naturest) (68308).
It is unclear if these effects were caused by passion flower or other ingredients.
In clinical trials, passion flower has been reported to cause allergy symptoms including sinus irritation; however, the frequency of these events was statistically nonsignificant when compared to treatment with midazolam 15 mg (95038).
Musculoskeletal ...Orally, passion flower has been reported to cause muscle relaxation in a clinical trial (95038).
Neurologic/CNS ...Orally, sedation, dizziness, ataxia, and confusion have been reported in clinical trials. However, these events generally do not necessitate discontinuation (8007,15391,15392,95036,95038). Altered consciousness has been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).
General
...There is currently a limited amount of information available on the adverse effects of skullcap.
Most Common Adverse Effects:
Orally: Cognitive impairment, digestive disturbances, sedation.
Gastrointestinal ...Orally, mild digestive disturbances were reported in around 9% of patients taking skullcap 350 mg three times daily for 2 weeks (91690).
Hepatic ...There are four reports of hepatotoxicity associated with products thought to contain skullcap. However, it is uncertain whether the products actually contained skullcap. It is thought that the products might have been contaminated with an adulterant such as germander (515), which is known to cause liver damage.
Neurologic/CNS ...A single skullcap extract dose of 100 mg does not seem to have adverse CNS effects. However, a higher dose of 200 mg might cause sedation and cognitive impairment (12216). One patient taking skullcap 350 mg three times daily for 2 weeks reported vivid dreams (91690). It is unclear if this event was associated with skullcap.
General
...Orally, Tinospora cordifolia seems to be well tolerated.
Topically, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Headache and nasal pain.
Topically: Burning, erythema, and pruritus.
Serious Adverse Effects (Rare):
Orally: Liver injury has been reported.
Dermatologic ...Topically, Tinospora cordifolia has been reported to cause pruritus, erythema, and burning (92220).
Hepatic
...Orally, liver injury is reported after consumption of Tinospora cordifolia.
In 2 case series, autoimmune hepatitis, acute hepatitis, worsening of chronic liver disease, or acute liver failure is reported in 49 patients after consuming various forms and doses of Tinospora cordifolia alone or in combination with other ingredients for a median of 42-90 days. Of these patients, 2 required a liver transplant and 4 died (110533,110534).
Liver injury is also reported in patients taking combination supplements containing Tinospora cordifolia. One case reports a 50-year-old female who presented with a 2-week history of constant right upper quadrant abdominal pain, nausea, loss of appetite, and fatigue, along with severely elevated alanine transaminase (ALT) and aspartate aminotransferase (AST), after taking a specific combination product containing Tinospora cordifolia 900 mg, stinging nettle 600 mg, and quercetin 600 mg (HistaEze) daily for 4 to 5 weeks (112404). Another case reports a 54-year-old female who developed acute hepatitis with elevated ALT, AST, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin after consuming a multi-ingredient product containing approximately 1900 mg of Tinospora cordifolia and 11 other Ayurvedic herbals daily for 2.5 months (112405). In both cases, liver function returned to normal within 3 months of discontinuing the supplement (112404,112405). It is unclear whether the liver injury in these cases is due to Tinospora cordifolia, other ingredients, or the combination.
Neurologic/CNS ...Orally, Tinospora cordifolia has been reported to cause headache in a clinical trial (15085).
Pulmonary/Respiratory ...Orally, Tinospora cordifolia extract has been reported to cause nasal pain in a clinical trial (15085).
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).
