| Ingredients | Amount Per Serving |
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Proprietary Blend (Combination)
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550 mg |
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(root)
(extract)
(Valerian PlantPart: root Note: extract )
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(flower)
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(herb)
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(from Yeast)
(RNA (Form: from Yeast) )
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(as Lithium Orotate)
(Lithium (Form: as Lithium Orotate) )
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Rice Flour, Magnesium Stearate, Gelatin
Below is general information about the effectiveness of the known ingredients contained in the product Kalmz. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Kalmz. 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 consumed in amounts commonly found in foods. Hops extract and hops oil have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when hops extract and hops-derived bitter acids are used orally and appropriately for medicinal purposes, short-term. Hops extract has been used with apparent safety in doses of up to 300 mg daily for 2-3 months. Hops-derived bitter acids have been used with apparent safety at a dose of 35 mg daily for 3 months (12,55338,55370,102899,105953,107813).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when lithium carbonate or lithium citrate is used orally and appropriately. Lithium carbonate and lithium citrate are FDA-approved drugs and have been used safely in clinical studies (15,97770). Lithium has a narrow therapeutic window and plasma levels must be monitored to avoid toxicity (15). Lithium levels should be drawn 12 hours after the last dose of lithium after steady state concentrations have been attained (approximately 3 days). Toxicity is most common at levels of 1.5 mEq/L, although some patients develop toxicity at levels less than 1 mEq/L (15,97770). There is insufficient reliable information available about the safety of lithium aspartate, lithium orotate, or other forms of supplemental lithium.
CHILDREN: POSSIBLY SAFE
when prescription lithium carbonate or lithium citrate is used orally and appropriately under medical supervision in children 7 years of age and older (15).
There is insufficient reliable information available about the safety of lithium aspartate, lithium orotate, or other forms of supplemental lithium.
PREGNANCY: POSSIBLY UNSAFE
when lithium carbonate and lithium citrate are used orally (15).
Lithium can cause fetal toxicity and increases the risk for cardiac and other abnormalities, including neural tube and urethral defects. However, it does not seem to increase the risk for preterm birth or low birth rate (15,9166,97770,104266). Some research suggests lithium might increase the risk for spontaneous abortion. Based on a meta-analysis of 2 population studies, taking lithium during pregnancy may increase the risk for spontaneous abortion when compared with the general population, but not when compared with patients with affective disorders not taking lithium during pregnancy (104266). This suggests that it may be the presence of affective disorder itself, or the possible associated use of other teratogenic drugs or substances during pregnancy, which may increase the risk for spontaneous abortion.
When the potential benefits to the mother and child outweigh the possible risk to the fetus, prescription lithium may be used with close monitoring by a healthcare professional (15,9166,97770,104266). The safety of lithium supplements during pregnancy is unknown.
LACTATION: LIKELY UNSAFE
when used orally.
Lithium is secreted into breast milk and may cause adverse effects in the nursing infant (15). Prescription lithium may be used in circumstances when the potential maternal benefits outweigh the possible risk to the infant. The infant should be closely monitored for signs of lithium toxicity (97770).
LIKELY SAFE ...when used orally in the amounts commonly found in foods. L-tryptophan is an essential amino acid that must be obtained from the diet. A typical diet in the United States supplies 0.5-2 grams of L-tryptophan daily (1146).
POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. L-tryptophan 5 grams daily for 21 days has been used with apparent safety (91460,97243). In 1989, L-tryptophan was linked to over 1500 reports of eosinophilia-myalgia syndrome (EMS) and several deaths (7067,8053,10085,11474,11478), leading to its removal from the U.S. market in 1990 (7067). The exact cause of EMS in patients taking L-tryptophan is unknown, but some evidence suggests that nearly all cases were due to contaminated L-tryptophan products from a single manufacturer (8050,8051,11477,11478). Under the Dietary Supplement Health and Education Act (DSHEA) of 1994, L-tryptophan is currently available and marketed as a dietary supplement. There is insufficient reliable information available about the safety of L-tryptophan when used orally, long-term.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods.
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts because it may cause respiratory depression in utero (1142).
Avoid using in amounts greater than those found in foods.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the safety of larger medicinal amounts; 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.
LIKELY SAFE ...when RNA and DNA are consumed in food. ...when RNA is used in enteral nutrition along with omega-3 fatty acids and L-arginine (5531,5533,5534,5535,5536,7819).
POSSIBLY SAFE ...when RNA is injected subcutaneously (5538) . ..when nucleotides are used sublingually at doses of up to 50 mg daily for up to 14 days (100724,100727). There is insufficient reliable information available about the safety of RNA/DNA supplement combinations.
CHILDREN: LIKELY SAFE
when infant formulas contain nucleotide supplements (5900).
Infant formulas containing RNA or DNA at a dose of up 72 mg/L for up to the first 12 months of life have been used with apparent safety (100729,100730,100731).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally as supplements.
Some evidence suggests some orally ingested DNA might cross the placenta and be mutagenic (5539).
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 Kalmz. 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, concomitant use of hops with sedative drugs might cause additive sedation.
 Details
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Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
Details
In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity (10686). However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate (105954).
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Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.
Details
Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity (55325). However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant (105954).
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Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.
Details
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Theoretically, taking lithium supplements with ACEIs might increase levels and adverse effects of lithium.
Details
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Theoretically, taking lithium supplements with anticonvulsants might increase the risk of neurotoxicity.
Details
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Theoretically, taking lithium supplements with antipsychotic drugs might increase the risk of encephalopathic syndrome.
Details
Encephalopathic syndrome has been reported in multiple patients taking prescription lithium and antipsychotics concomitantly. Symptoms have included weakness and lethargy, fever, confusion, and extrapyramidal symptoms. In some patients, resulting brain damage was irreversible. Although there is no established causal relationship between these symptoms and the combination of lithium and antipsychotic medications, there is a theoretical relationship (97770). It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
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Theoretically, taking lithium supplements with calcium channel blockers might reduce lithium levels and might also increase the risk of certain adverse effects.
Details
Calcium channel blockers might reduce lithium concentrations. Monitor lithium levels with concurrent use. Calcium channel blockers might also increase the adverse neurological and gastrointestinal adverse effects of lithium (9,15). It is unclear if these interactions would occur with the smaller doses found in lithium supplements.
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Theoretically, taking lithium supplements with loop diuretics might increase lithium levels and adverse effects.
Details
Thiazide diuretics and loop diuretics might reduce lithium excretion, particularly in sodium-restricted patients (9,15). If lithium is clinically indicated and other treatment options are unavailable or inadequate in patients using diuretics, lithium treatment can be initiated with extreme caution. Serum lithium should be measured frequently and the doses used should be the lowest dose ordinarily tolerated (97770). It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.
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Theoretically, taking lithium supplements with methyldopa might increase the risk of lithium toxicity.
Details
Concurrent use of methyldopa with lithium increases the risk of lithium toxicity (9). It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.
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Theoretically, taking lithium supplements with methylxanthines might decrease lithium levels.
Details
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Theoretically, taking lithium supplements with NSAIDs might increase lithium levels and adverse effects.
Details
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Theoretically, taking lithium supplements with phenothiazines might decrease the levels and clinical effects of phenothiazines.
Details
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Theoretically, taking lithium supplements with serotonergic drugs might both mask and increase the risk of serotonin syndrome.
Details
In a case report, a 67-year-old female with depression and bipolar disorder using lithium in combination with selective serotonin reuptake inhibitors (SSRIs) and other medications developed serotonin syndrome with symptoms of deep tendon hyperreflexia, muscle rigidity, tremor, and hyperthermia. However, agitation, one classical symptom of serotonin syndrome, was lacking. This was thought to be due to masking by lithium toxicity (105343). Lithium can increase serotonin levels (9,15), thus, combining serotonergic drugs with lithium might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
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Theoretically, taking lithium supplements with skeletal muscle relaxants might prolong neuromuscular blockade.
Details
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Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.
Details
Clinical research shows that L-tryptophan can cause fatigue and drowsiness (1143).
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Theoretically, combining L-tryptophan with serotonergic drugs might cause additive serotonergic effects.
Details
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Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.
Details
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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).
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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.
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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.
Details
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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 Kalmz. 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, hops extract and oil are generally well tolerated when used in food amounts.
Hops extract also seems to be well tolerated when used in supplemental amounts.
Most Common Adverse Effects:
Orally: Drowsiness, sedation.
Dermatologic ...Topically, allergic reactions have been reported after contact with the fresh hops plant and plant dust. Contact dermatitis is attributed to the pollen (4,12,105930).
Genitourinary ...Orally, supplements containing hops and soy have been associated with 4 cases of postmenopausal bleeding (55404). It is unclear if this effect is due to hops, soy, or the combination. Also, menstrual disturbances have been reported in female workers harvesting hops (10684,55405).
Neurologic/CNS ...Orally, hops might cause drowsiness and sedation. Historically, hops are thought to have sedative effects, since workers harvesting hops were observed to tire easily after oral contact with hop resin. The European Medicines Agency states that hops may have sedative effects; however, there is a lack of clinical research confirming that hops extract causes drowsiness and sedation (105930).
Pulmonary/Respiratory ...Occupational exposure to dust from hops, usually in combination with dust from other products, is associated with chronic respiratory symptoms such as dry cough, dyspnea, chronic bronchitis, and other occupational respiratory diseases (55333,55414).
General
...Orally, prescription forms of lithium are generally well tolerated when used as prescribed.
Plasma levels must be monitored to avoid toxicity. It is unclear how the lower doses of lithium found in supplements may alter the occurrence and likelihood of these adverse effects.
Most Common Adverse Effects:
Orally: Edema, fatigue, fine tremor, gastrointestinal symptoms, lethargy, muscle weakness, polydipsia, polyuria, skin conditions, vertigo, and weight gain.
Cardiovascular ...Orally, lithium has been reported to cause bradyarrhythmia. A case of symptomatic bradycardia due to sinoatrial node dysfunction is reported in a patient with bipolar disorder who took lithium orotate 20 mg daily for 5 years, despite a serum lithium level in the therapeutic range (111327). Deep vein thrombosis is also reported in 2 patients with bipolar disorder who experienced toxic serum levels of lithium (111329). It is unclear if these effects are a concern with the smaller doses found in lithium supplements.
Dermatologic ...Orally, lithium can cause or exacerbate skin disorders such as hair loss, acne, psoriasis, and rash (9,15,97770). A case of Stevens-Johnson syndrome is also reported in a patient with bipolar disorder who took lithium carbonate at an unknown dose for 17 days (111317).
Endocrine ...Orally, chronic use of lithium has been reported to cause various endocrine disorders. Case reports associate chronic lithium use with hypothyroidism, hyperthyroidism, goiter, hyperparathyroidism, and diabetes insipidus (9,15,104267,104269,104270,104271,111320). In one case report, a 68-year-old male with schizophrenia developed severe hypothyroidism resulting in myxedema coma after taking oral lithium carbonate. He recovered after discontinuation of lithium and administration of levothyroxine. At least two other cases of lithium-associated myxedema coma have been reported (97740). At least 4 cases of lithium-associated hyperparathyroidism have been reported in females aged 53-68 years that had taken lithium for 24 years or more. These patients presented with hypernatremia, hypercalcemia, elevated serum creatinine, thyroid or parathyroid abnormalities, and nephrogenic diabetes insipidus (104269,105344). It is unclear if these effects are a concern with the smaller doses found in lithium supplements.
Gastrointestinal ...Orally, lithium can cause gastrointestinal symptoms. These adverse effects often improve with continued use (9). It is unclear if this effect would occur with the smaller doses found in lithium supplements.
Musculoskeletal ...Orally, lithium can cause muscle weakness. This adverse effect often improves with continued use (9). It is unclear if this effect would occur with the smaller doses found in lithium supplements.
Neurologic/CNS ...Orally, lithium can cause vertigo, muscle weakness, lethargy, fatigue, and a dazed feeling. These adverse effects often improve with continued use. Fine tremor can occur and may persist with continued use. Chronic use of lithium can cause mild cognitive and memory impairment, particularly in the presence of dehydration or hyponatremia (9,15,97745). These long-term neurological adverse effects of lithium are potentially due to accumulation in the central nervous system even when blood levels appear within the therapeutic range (97745). Lithium-associated hyperparathyroidism-induced hypercalcemia has resulted in hallucinations, confusion, insomnia, and agitation (105344). A case of delirium and transient difficulty with word finding is reported in a patient with bipolar disorder treated with lithium 250-500 mg twice daily and 9 sessions of electroconvulsive therapy (111316). A case of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is also reported in a patient with bipolar disorder who had a toxic lithium level of 1.94 mEq/L (111318). It is unclear if these effects would occur with the smaller doses found in lithium supplements.
Psychiatric ...Abrupt discontinuation of lithium resulting in a rapid reduction in serum lithium levels can precipitate recurrence of bipolar symptoms (9165). Lithium should be tapered gradually over at least 14 days (9165).
Renal ...Orally, lithium can cause polyuria, polydipsia, and edema (9). Chronic lithium use has been reported to cause central or nephrogenic diabetes insipidus, hypocalciuric hypercalcemia, and nephrotic syndrome (104269,104271,111314,111319). Long-term lithium use is estimated to increase the odds of chronic kidney disease (CKD) by at least 2-fold and may contribute to CKD progression (111315,111324). It is unclear if these effects would occur with the smaller doses found in lithium supplements.
Other ...Orally, chronic use of lithium has been reported to cause an irreversible reduction in taste and smell in a patient with bipolar disorder who took 400-1000 mg/day for 4 months (111313). Chronic use of lithium 1200 mg/day has also been reported to cause dysphagia in a 17-year-old patient with bipolar disorder; however, the patient's serum lithium level was in the toxic range and the adverse effect resolved once the level normalized (111328). It is unclear if these effects would occur with the smaller doses found in lithium supplements.
General
...Orally, L-tryptophan is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, diarrhea, drowsiness, dry mouth, flatulence, headache, heartburn, lightheadedness, nausea, stomach pain, visual blurring, and vomiting.
Serious Adverse Effects (Rare):
Orally: L-tryptophan has been associated with the neurological disorder eosinophilia-myalgia syndrome (EMS). However, almost all cases were traced to L-tryptophan produced by a single manufacturer in Japan and are likely related to contamination.
Cardiovascular ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include cardiovascular symptoms such as myocarditis, arrhythmias, and palpitations (8053,11477).
Dermatologic ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include dermatological symptoms such as sclerodermiform skin changes, alopecia, and rash (8053,11477).
Gastrointestinal ...Orally, L-tryptophan can cause gastrointestinal side effects such as heartburn, stomach pain, belching and flatulence, nausea, vomiting, diarrhea, dry mouth, and anorexia (10853,99884).
Hematologic ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include hematologic symptoms such as eosinophilia (8053,11477).
Hepatic ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include hepatic symptoms such as hepatomegaly (8053,11477).
Musculoskeletal ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include musculoskeletal symptoms such as myalgia and inflammation of the joints and connective tissue (8053,11477).
Neurologic/CNS
...Orally, L-tryptophan can cause headache, lightheadedness, and ataxia (10853,99884).
In 1989, more than 1500 cases of the neurological disorder EMS were associated with oral L-tryptophan use in the US. About 95% of all EMS cases were traced to contaminated L-tryptophan produced by a single manufacturer in Japan (8054,10288,10289,11475,11476). In 1990, L-tryptophan was recalled in the U.S. and an FDA alert was put into force limiting the importation of all over-the-counter L-tryptophan products (7067,11477,11478). After the limitation of L-tryptophan products, the incidence of EMS dropped abruptly (11474). Symptoms of EMS associated with L-tryptophan use include intense eosinophilia; fatigue; myalgia; neuropathy; sclerodermiform skin changes; alopecia; rash; and inflammatory disorders affecting the joints, connective tissue, lungs, heart, and liver (8053,11477). Symptoms tend to improve over time, however some individuals may still experience symptoms up to 2 years after the onset of EMS and complete resolution of symptoms may not occur (8053,10287).
There is some evidence of an association between L-tryptophan-related EMS and the occurrence of chronic B-cell lymphocytic leukemia (8055).
Ocular/Otic ...Orally, L-tryptophan can cause side effects such as visual blurring (10853).
Pulmonary/Respiratory ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include respiratory symptoms such as dyspnea and cough (8053,11477).
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 ...Orally, RNA and DNA are well tolerated when consumed in food or enteral nutrition (5531,5533,5534,5535,5536,7819). Nucleotides seem to be well tolerated when consumed in medicinal amounts for up to 14 days. No adverse effects have been reported. Subcutaneously, RNA can cause itching, redness, and swelling at the injection site (5538).
Dermatologic ...Subcutaneously, an injection of RNA can cause itching, redness, and swelling at the injection site. In one review, these reactions occurred in 3 out of 83 patients (5538).
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).
