MSM (methylsulfonylmethane) • Pregnenolone • Wolfberry seed Oil (lycium barbarum) • Aloe Vera gel • Calendula extract • Roman Chamomile extract • Green Tea extract • St. John's Wort extract • Ginkgo biloba extract • Grapeseed extract • Algae extract • Dehydroepiandrosterone (dehydroepiandrosterone) • Ylang Ylang (canaga odorata) • Clary Sage (salvia sclarea) • Rose Geranium (pelargonium graveolens) • Bergamot (citrus bergamia) • fennel (foeniculum vulgarae) • Sage (salvia officinalis) • Yarrow (achillia millefolium). Other Ingredients: Deionized Water, Carpylic/Capric Triglyceride, Sorbitol, Lecithin, Glyceryl Stearate, Sodium PCA, Stearic Acid, Rosebud Extract, Algae Extract, Tocopheryl Acetate, Linoleate (vitamin E), Hydrolyzed Wheat Protein, Locust Bean Gum, Ioconic Trace Minerals, Organic Flaxseed Oil, Wheat Germ Oil, Allantoin, Wild Yam, Eleuthero Extract(eleutherococcus senticosus), Blue Cohosh, Black Cohosh, Kelp, Retinyl Palmitate (vitamin A), Progesterone from Soy Bean Extract, Ascorbic Acid (vitamin C).
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Prenolone + (with DHEA). 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
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 Prenolone + (with DHEA). 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 aloe gel is used topically and appropriately. Aloe gel-containing formulations have been safely applied in clinical trials (101,11982,12096,12098,12159,12160,12163,12164,17418)(90123,90124,90127,90128,90129,90131,97320,98816,103305). When included in topical cosmetics, the Cosmetic Ingredient Review Expert Panel concluded that aloe-derived anthraquinone levels should not exceed 50 ppm (90122).
POSSIBLY SAFE ...when aloe gel is used orally and appropriately, short-term. Aloe gel has been safely used in a dose of 15 mL daily for up to 42 days or 100 mL of a 50% solution twice daily for up to 4 weeks (11984,12164). Also, a specific aloe gel complex (Aloe QDM complex, Univera Inc.) has been safely used at a dose of approximately 600 mg daily for up to 8 weeks (90121). ...when aloe extract is used orally and appropriately, short-term. Aloe extract has been used with apparent safety in a dose of 500 mg daily for one month (101579). Also, an aloe extract enriched in aloe sterols has been used with apparent safety in a dose of 500 mg daily for 12 weeks (101577).
POSSIBLY UNSAFE ...when aloe latex is used orally. There is some evidence that anthraquinones in aloe latex are carcinogenic or promote tumor growth, although data are conflicting (6138,16387,16388,91596,91597). In 2002, the US FDA banned the use of aloe latex in laxative products due to the lack of safety data (8229). ...when aloe whole-leaf extract is used orally. Aloe whole-leaf extract that has not been filtered over charcoal still contains anthraquinones. This type of aloe whole-leaf extract is referred to as being "nondecolorized". The International Agency for Research on Cancer has classified this type of aloe whole-leaf extract as a possible human carcinogen (91598,91908). Although filtering aloe whole-leaf extract over charcoal removes the anthraquinones, some animal research suggests that this filtered extract, which is referred to as being "decolorized", may still cause gene mutations (91598). This suggests that constituents besides anthraquinones may be responsible for the carcinogenicity of aloe whole-leaf extract. It should be noted that commercial products that contain aloe whole-leaf extract may be labeled as containing "whole leaf Aloe vera juice" or "aloe juice" (91908).
LIKELY UNSAFE ...when aloe latex is used orally in high doses. Ingesting aloe latex 1 gram daily for several days can cause nephritis, acute kidney failure, and death (8,8961).
CHILDREN: POSSIBLY SAFE
when aloe gel is used topically and appropriately.
Aloe gel-containing formulations have been safely applied in clinical trials (90124,90131).
CHILDREN: POSSIBLY UNSAFE
when aloe latex and aloe whole leaf extracts are used orally in children.
Children younger than 12 years may experience abdominal pain, cramps, and diarrhea (4).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Anthraquinones present in aloe latex and aloe whole leaf extracts have irritant, cathartic, and possible mutagenic effects (4,16387,16388,90122). There are also anecdotal reports and evidence from animal research that anthraquinones or aloe whole leaf extracts might induce abortion and stimulate menstruation; avoid using (4,8,19,90122).
LACTATION: POSSIBLY UNSAFE
when aloe preparations are used orally.
Cathartic and mutagenic anthraquinones present in aloe latex and aloe whole leaf extracts might pass into milk; avoid using (4,19).
LIKELY SAFE ...when bergamot essential oil is used orally in amounts commonly found in foods. Bergamot oil has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY SAFE ...when bergamot extract is used orally, short-term. A bergamot extract (Bergamot Polyphenolic Fraction BPF, H&AD SRL) has been used with apparent safety at a dose of 650 mg daily for up to 120 days (96355,105318). Another bergamot extract providing 150 mg of flavonoids (Bergavit, Bionap) daily has been used with apparent safety for up to 6 months (102599). Bergamot phytosome (Vazguard, Indena SpA) has been used with apparent safety at a dose of 500 mg twice daily for 12 weeks (105317). ...when inhaled as aromatherapy, short-term. Bergamot oil 3% has been used with apparent safety as 2 drops poured on a cotton ball, attached to the collar, and breathed in for 20 minutes (105319).
POSSIBLY UNSAFE ...when used topically. Bergamot essential oil that is not free of furocoumarins or psoralens can act as a photosensitizer and can induce malignant changes (6,96370).
CHILDREN: LIKELY SAFE
when bergamot essential oil is used orally in amounts commonly found in foods.
Bergamot oil has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
CHILDREN: POSSIBLY UNSAFE
when large amounts of the oil are ingested.
Bergamot essential oil can cause intestinal colic, convulsions, and death (12). There is insufficient reliable information available about the safety of bergamot extract when used orally.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when the oil is used topically (6).
There is insufficient reliable information available about the safety of bergamot when taken by mouth in medicinal amounts; avoid use.
POSSIBLY SAFE ...when non-contaminated species of spirulina blue-green algae are used orally and appropriately (91713). The blue-green algae species Arthrospira platensis has been used with apparent safety in doses up to 19 grams daily for 2 months, or 10 grams daily for 6 months (18296,18300,18306,75944,91705,99703,104567,109965). The blue-green algae species Arthrospira fusiformis has been used with apparent safety in doses up to 4 grams daily for 3 months, or 1 gram daily for 12 months (15782,91717). Another blue-green algae species, Arthrospira maxima, has been used with apparent safety in a dose of 4.5 grams daily for up to 12 weeks (18297,99654,99655,102688). ...when non-contaminated, non-toxin producing strains of blue-green algae from the Aphanizomenon flos-aquae species are used orally and appropriately. Doses up to 1.6 grams daily have been used with apparent safety for up to 6 months (14842,18310). Some blue-green algae species can produce toxins called microcystins. According to the World Health Organization (WHO), the tolerable daily intake of microcystins in adults is 0.04 mcg/kg (96549).
POSSIBLY UNSAFE ...when contaminated blue-green algae are used orally. Blue-green algae can be contaminated with heavy metals (including mercury, cadmium, lead, or arsenic), neurotoxins, and toxic microcystin-producing cyanobacteria such as Microcystis aeruginosa (9171,75966,91704,91711,96550). Microcystins are most commonly reported in the blue-green algae species Aphanizomenon flos-aquae harvested from Upper Klamath Lake in Oregon. The Oregon Department of Health has set a limit of 1 mcg of microcystin-LR equivalents per gram dry weight of blue-green algae, assuming consumption of about 2 grams/day by adults (91704,91713). However, many samples of Aphanizomenon flos-aquae have been reported to contain higher levels than this (9171,91704). According to the World Health Organization (WHO), the tolerable daily intake of microcystins in adults is 0.04 mcg/kg (96549). When consumed orally, microcystins accumulate in the liver, binding to and inhibiting protein phosphatases, causing hepatocyte damage and possible tumor promotion (9171). Aphanizomenon flos-aquae can also produce neurotoxic compounds that may be present in supplements containing this organism (91704).
CHILDREN: POSSIBLY UNSAFE
when blue-green algae products are used orally.
Blue-green algae can accumulate heavy metals such as lead and mercury (91704,91711). They can also contain toxic microcystins produced by contaminating species of cyanobacteria such a Microcystis aeruginosa (91704). Children are more sensitive to poisoning by microcystins (3536). The Oregon Department of Health has set a limit for microcystins of 1 mcg per gram dry weight of blue-green algae, but some countries have set very low exposure limits of 0.2 mcg per day and 0.8 mcg per day for infants and children, respectively (91704).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Some blue-green algae products, specifically those of the species Aphanizomenon flos-aquae, have been found to contain low amounts of beta-methylamino-L-alanine (BMAA). BMAA is associated with neurodegenerative diseases, and breast milk has been shown to be a potential source of BMAA exposure in infants (96550).
LIKELY SAFE ...when the flower preparations are used orally or topically and appropriately (4,19779,36931,39503,93552,93557,96647,105088).
PREGNANCY: LIKELY UNSAFE
when used orally; contraindicated due to spermatocide, antiblastocyst, and abortifacient effects.
There is insufficient reliable information available about the safety of calendula when used topically during pregnancy (4).
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Clary sage has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912). There is insufficient reliable information available about the safety of clary sage when used as medicine.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Most studies have been small and lasted from a few weeks to 6 months, with usual doses of 50 mg daily (793,1635,2133,3231,4249,4251,4252,4253,4254,4255,9691)(9692,10986,12215,12564,14277,21416,88726,90304,99925). Some studies have also used oral DHEA with apparent safety for 12-24 months (2113,6446,10406,11464,12561,15027,88492). ...when used intravaginally and appropriately. Intravaginal ovules of DHEA 3.25 mg to 13 mg have been safely used for up to 12 weeks (21320,21429,21430). ...when used topically and appropriately. A DHEA cream 1% to 10% has been safely used for up to 12 months (4242,21428).
POSSIBLY UNSAFE ...when used orally in high doses or long-term. There is concern that long-term use or use of amounts that cause higher than normal physiological DHEA levels might increase the risk of prostate cancer (2111,12565), breast cancer (10370,10401,10403), or other hormone-sensitive cancers (6445). In some cases, 50-100 mg daily can produce slightly higher than normal physiological DHEA levels (4249,4251). There is insufficient reliable information available about the safety of using DHEA intravenously or intramuscularly.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally.
DHEA can cause higher than normal androgen levels (2133,4249,4251,4253), which might adversely affect pregnancy or a nursing infant.
POSSIBLY SAFE ...when a specific Ecklonia cava phlorotannin extract (SeaPolynol) is used orally and appropriately. Doses of up to 400 mg daily have been used with apparent safety for 12 weeks (106334,106336). According to the European Food Safety Authority (EFSA), doses of up to 263 mg daily are considered safe based on extrapolation from animal toxicity research (106333). ...when other sources of Ecklonia cava polyphenols are used orally, short-term. Doses up to 144 mg daily have been used with apparent safety for up to 12 weeks (96376). ...when a specific Ecklonia cava polyphenol-rich extract (AG-dieckol, Aqua Green Tech Co.) is used orally and appropriately. Doses of up to 1500 mg daily have been used with apparent safety for up to 12 weeks (96375).
CHILDREN: POSSIBLY SAFE
when a specific Ecklonia cava phlorotannin extract (SeaPolynol) is used orally and appropriately in children 12 years and older.
According to the EFSA, doses of up to 163 mg daily are considered safe in children aged 12-14 years, and 230 mg daily is considered safe in children aged 14 years and above, based on extrapolation from animal toxicity research (106333). There is insufficient reliable information available about the safety of Ecklonia cava in children under 12 years of age.
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 and appropriately. Standardized ginkgo leaf extracts have been used safely in trials lasting for several weeks up to 6 years (1514,1515,3461,5717,5718,6211,6212,6213,6214,6215)(6216,6222,6223,6224,6225,6490,14383,14499,16634,16635)(16636,16637,17402,17716,17718,87794,87819,87826,87848,87864)(87888,87897,87901,87904,89701,89707,107359,107360). There have been some reports of arrhythmias associated with ginkgo leaf extract. However, it is not yet clear if ginkgo might cause arrhythmia (105253,105254). There is some concern about toxic and carcinogenic effects seen in animals exposed to a ginkgo leaf extract containing 31.2% flavonoids, 15.4% terpenoids, and 10.45 ppm ginkgolic acid, in doses of 100 to 2000 mg/kg five times per week for 2 years (18272). However, the clinical relevance of this data for humans, using typical doses, is unclear. The content of the extract used is not identical to that commonly used in supplement products, and the doses studied are much higher than those typically used by humans. A single dose of 50 mg/kg in rats is estimated to be equivalent to a single dose of about 240 mg in humans (18272).
POSSIBLY SAFE ...when used intravenously, short-term. A standardized ginkgo leaf extract called EGb 761 ONC has been safely administered intravenously for up to 14 days (9871,9872,107360,107452). A Chinese preparation containing ginkgo leaf extract and dipyridamole has been safely administered intravenously for up to 30 days (102881,102882). ...when applied topically, short-term. There was no dermal irritation during a 24-hour patch test using the leaf extract, and no sensitization with repeat applications (112946). When used topically in cosmetics, extracts of ginkgo leaves are reported to be safe, but there is insufficient data to determine the safety of nut and root extracts, and isolated biflavones and terpenoids (112946).
POSSIBLY UNSAFE ...when the roasted seed or crude ginkgo plant is used orally. Consuming more than 10 roasted seeds per day can cause difficulty breathing, weak pulse, seizures, loss of consciousness, and shock (8231,8232). Crude ginkgo plant parts can exceed concentrations of 5 ppm of the toxic ginkgolic acid constituents and can cause severe allergic reactions (5714).
LIKELY UNSAFE ...when the fresh ginkgo seed is used orally. Fresh seeds are toxic and potentially deadly (11296).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
There is concern that ginkgo might have labor-inducing and hormonal effects. There is also concern that the antiplatelet effects of ginkgo could prolong bleeding time if taken around the time of labor and delivery (15052). Theoretically, ginkgo might adversely affect pregnancy outcome; avoid using during pregnancy.
LACTATION:
Insufficient reliable information available; avoid using.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term (87790,89708).
A specific ginkgo dried extract (Ginko T.D., Tolidaru Pharmaceuticals), has been safely used in doses of 80-120 mg daily for 6 weeks in children aged 6-14 years (17112,95669). Another specific combination product containing ginkgo leaf extract and American ginseng extract (AD-FX, CV Technologies, Canada) has also been safely used in children aged 3-17 years for up to 4 weeks (8235).
CHILDREN: LIKELY UNSAFE
when ginkgo seed is used orally.
The fresh seeds have caused seizures and death in children (8231,11296).
POSSIBLY SAFE ...when goji fruit preparations are used orally and appropriately, short-term. Goji berry whole fruit, boiled or steamed, has been used with apparent safety at a dose of 15 grams daily for 16 weeks (105489). Other goji berry products have also been used with apparent safety in clinical research, including a specific goji fruit juice (GoChi, FreeLife International) 120 mL daily for 30 days (52532), a goji fruit polysaccharide 300 mg daily for 3 months (92117), and a specific milk-based formulation of goji berry (Lacto-Wolfberry, Nestlé Research Center) for 3 months (52539). There has been some concern about the atropine content of goji; however, most analyses show that levels of atropine in goji berries from China and Thailand are far below potentially toxic levels (52524,94667). There is insufficient reliable information available about the safety of oral use of other parts of the goji plant.
PREGNANCY AND LACTATION:
Insufficient reliable information available.
Some animal research shows that goji fruit may stimulate the uterus (12). However, this has not been reported in humans. Until more is known, avoid using during pregnancy or lactation.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY SAFE ...when the whole fruit of the grape, or extracts of the fruit, seed, or leaf, are used orally and appropriately in medicinal amounts. Grape seed extracts have been used with apparent safety in doses up to 200 mg daily for up to 11 months (9182,53016) and in doses up to 2000 mg daily for up to 3 months (53149,53190). Specific grape fruit extracts (Stilvid, Actafarma; Cognigrape, Bionap srl) have been used with apparent safety in doses up to 250-350 mg daily for 3-12 months or 700 mg daily for 6 months (53254,53256,96198). A specific grape leaf extract (AS 195, Antistax, Boehringer Ingelheim) has been used with apparent safety in doses up to 720 mg daily for up to 3 months (2538,52985,53005,53206). A preparation of dehydrated whole grapes, equivalent to 250 grams of fresh grapes daily, has also been used with apparent safety for up to 30 days (18228). A specific grape seed extract (Enovita; Indena SpA) 150 mg twice daily, standardized to provide at least 95% oligomeric proanthocyanins, has been used with apparent safety for up to 16 weeks (108091) ...when used topically and appropriately. Creams and ointments containing grape seed extract 2% or 5% have been used topically with apparent safety for up to 3 weeks (91539,100955). There is insufficient reliable information available about the safety of other grape plant parts when used topically.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods.
Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). However, whole grapes should be eaten with caution in children aged 5 years and under. Whole grapes can be a choking hazard for young children (96193). To reduce the risk of choking, whole grapes should be cut in half or quartered before being given to children. There is insufficient reliable information available about the safety of grape when used in medicinal amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the safety of medicinal amounts during pregnancy and breast-feeding; avoid using in amounts greater than what is commonly found in foods.
LIKELY SAFE ...when green tea is consumed as a beverage in moderate amounts (733,6031,9222,9223,9225,9226,9227,9228,14136,90156)(90159,90168,90174,90184,95696). Green tea contains caffeine. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 8 cups of green tea daily, or approximately 400 mg of caffeine, is not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806). ...when green tea extract cream or ointment is used topically and appropriately, short-term. A green tea extract 3% cream, applied twice daily, has been used with apparent safety for up to 8 weeks, and a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins has been safely used for up to 16 weeks (15067). The safety of treatment for longer durations or multiple treatment courses is not known.
POSSIBLY SAFE ...when green tea extract is used orally. Green tea extract containing 7% to 12% caffeine has been used safely for up to 2 years (8117,37725). Also decaffeinated green tea extract up to 1.3 grams daily enriched in EGCG has been used safely for up to 12 months (90158,97131). In addition, green tea extract has been safely used as part of an herbal mixture also containing garcinia, coffee, and banaba extracts for 12 weeks (90137). ...when used topically and appropriately as a cream or mouthwash (6065,11310,90141,90150,90151).
POSSIBLY UNSAFE ...when consumed as a beverage in large quantities. Green tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, psychological dependence, and other significant adverse effects. Doses of caffeine greater than 600 mg per day, or approximately 12 cups of green tea, have been associated with significant adverse effects such as tachyarrhythmias and sleep disturbances (11832). These effects would not be expected to occur with the consumption of decaffeinated green tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. There is also some speculation that green tea products containing higher amounts of the catechin epigallocatechin gallate (EGCG) might have increased risk of adverse events. Some research has found that taking green tea products containing EGCG levels greater than 200 mg is associated with increased risk of mild adverse effects such as constipation, increased blood pressure, and rash (90161). Other research has found that doses of EGCG equal to or above 800 mg daily may be associated with increased risk of liver injury in humans (95440,95696,97131).
LIKELY UNSAFE ...when used orally in very high doses. The fatal acute oral dose of caffeine is estimated to be 10-14 grams (150-200 mg per kilogram). Serious toxicity can occur at lower doses depending on variables in caffeine sensitivity such as smoking, age, and prior caffeine use (11832).
CHILDREN: POSSIBLY SAFE
when used orally by children and adolescents in amounts commonly found in foods and beverages (4912,11833).
Intake of caffeine in doses of less than 2.5 mg/kg daily is not associated with significant adverse effects in children and adolescents (11733,98806). ...when used for gargling three times daily for up to 90 days (90150).
There is insufficient reliable information available about the safety of green tea extract when used orally in children. However, taking green tea extract orally has been associated with potentially serious, albeit uncommon and unpredictable cases, of hepatotoxicity in adults. Therefore, some experts recommend that children under the age of 18 years of age do not use products containing green tea extract (94897).
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of green tea, pregnant patients should closely monitor their intake to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,11733,16014,16015,98806). In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014). This increased risk may be most likely to occur in those with genotypes that confer a slow rate of caffeine metabolism (98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, most healthy pregnant patients can safely consume doses up to 300 mg daily without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). Advise keeping caffeine consumption below 300 mg daily. This is similar to the amount of caffeine in about 6 cups of green tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Based on animal models, green tea extract catechins are also transferred to the fetus, but in amounts 50-100 times less than maternal concentrations (15010). The potential impact of these catechins on the human fetus is not known, but animal models suggest that the catechins are not teratogenic (15011).
PREGNANCY: POSSIBLY UNSAFE
when used orally in amounts providing more than 300 mg caffeine daily.
Caffeine from green tea crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Advise keeping caffeine consumption from all sources below 300 mg daily. This is similar to the amount of caffeine in about 6 cups of green tea. High maternal doses of caffeine throughout pregnancy have also resulted in symptoms of caffeine withdrawal in newborn infants (9891). High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight (2709,2711). However, some research has also found that intrauterine exposure to even modest amounts of caffeine, based on maternal blood levels during the first trimester, is associated with a shorter stature in children ages 4-8 years (109846). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
There is also concern that consuming large amounts of green tea might have antifolate activity and potentially increase the risk of folic acid deficiency-related birth defects. Catechins in green tea inhibit the enzyme dihydrofolate reductase in vitro (15012). This enzyme is responsible for converting folic acid to its active form. Preliminary evidence suggests that increasing maternal green tea consumption is associated with increased risk of spina bifida (15068). Also, evidence from epidemiological research suggests that serum folate levels in pregnant patients with high green tea intake (57.3 mL per 1000 kcal) are decreased compared to participants who consume moderate or low amounts of green tea (90171). More evidence is needed to determine the safety of using green tea during pregnancy. For now, advise pregnant patients to avoid consuming large quantities of green tea.
LACTATION: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of green tea, nursing parents should closely monitor caffeine intake. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations (9892).
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Consumption of green tea might cause irritability and increased bowel activity in nursing infants (6026). There is insufficient reliable information available about the safety of green tea extracts when applied topically during breast-feeding.
POSSIBLY SAFE ...when used orally and appropriately, short term. MSM in doses of 1.5-6 grams daily or 50 mg/kg daily has been used safely in studies lasting up to 6 months (8574,12469,14335,17127,19312,96446,96448,102555). One specific product (OptiMSM, Bergstrom Nutrition) is Generally Recognized As Safe (GRAS) by the United States Food and Drug Administration (FDA) (102555). ...when used topically. Topical cream containing MSM and silymarin, as well as topical gel containing MSM, hyaluronic acid, and tea tree oil, have been used with apparent safety for up to 20 days (19318,19319).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Pregnenolone has been used safely for up to 12 weeks, with doses titrated up to 500 mg daily (94026,94027,97923,104274). There is insufficient reliable information available about the safety of pregnenolone when used long-term.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Pregnenolone has been used safely for up to 10 weeks at doses of 200 mg daily in adolescents aged 11-17 years (104275). There is insufficient reliable information available about the safety of pregnenolone in younger children or when used orally for longer durations.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Roman chamomile has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used topically as a 2% gel for up to 4 weeks (107369). ...when the essential oil is inhaled or used topically as aromatherapy (7107). There is insufficient reliable information available about the safety of Roman chamomile when used orally in amounts greater than those found in foods.
PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts.
Roman chamomile is believed to be an abortifacient (4). Some population research has found a possible link between the use of Roman chamomile and an increased incidence of reduced birth weight, threatened miscarriage, and preterm labor (97292). There is insufficient reliable information available about the safety of the topical use of Roman chamomile during pregnancy; avoid using.
LACTATION:
Insufficient reliable information available; avoid using (4).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Rose geranium oil has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used topically and appropriately, short-term. A single application of rose geranium oil in concentrations up to 100% has been safely used in a clinical trial (16653). ...when used intranasally and appropriately, short-term. Rose geranium oil has been applied with sesame oil in the nose safely (93881). There is insufficient reliable information available about using rose geranium oil orally for medicinal purposes.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid amounts greater than those found in foods.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Sage is approved for use as a food in the United States (4912).
POSSIBLY SAFE ...when used orally in medicinal doses, short-term. Common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) have been used with apparent safety when taken orally in doses of 280 mg daily for up to 8 weeks (10334,10810,17177,105338). ...when used topically. Common sage (Salvia officinalis) has been used with apparent safety as a single agent or in combination products for up to one week (10437,72619,107023). ...when the essential oil is inhaled as aromatherapy, short-term (72658).
POSSIBLY UNSAFE ...when used orally in high doses or long-term (12,1304). Some species of sage, including common sage (Salvia officinalis), contain a thujone constituent that can be toxic if consumed in large enough quantities (12,1304).
PREGNANCY: LIKELY UNSAFE
when used orally.
The constituent thujone can have menstrual stimulant and abortifacient effects (19).
LACTATION: POSSIBLY UNSAFE
when used orally; sage is thought to reduce the supply of mother's milk (19).
LIKELY SAFE ...when used orally and appropriately. St. John's wort extracts in doses up to 900 mg daily seem to be safe when used for up to 12 weeks (3547,3550,4835,5096,6400,6434,7047,13021,13156,13157)(14417,76143,76144,89666,89669,95510). Some evidence also shows that St. John's wort can be safely used for over one year (13156,13157,76140), and may have better tolerability than selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) (4897,76153,76143,104036).
POSSIBLY SAFE ...when used topically and appropriately. St. John's wort 0.5% extract seems to be safe when used once weekly for 4 weeks (110327). St. John's wort oil has been used with apparent safely twice daily for 6 weeks (110326). However, topical use of St. John's wort can cause photodermatitis with sun exposure (110318).
POSSIBLY UNSAFE ...when used orally in large doses. St. John's wort extract can be unsafe due to the risk of severe phototoxic skin reactions. Taking 2-4 grams of St. John's wort extract (containing hypericin 5-10 mg) daily appears to increase the risk of photosensitivity (758,4631,7808).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Preliminary population research has found that taking St. John's wort while pregnant is associated with offspring that develop neural tube, urinary, and cardiovascular malformations. Subgroup analyses suggest that these risks may be higher when taking St. John's wort during the first trimester when compared with the second or third trimester. However, more research is needed to confirm these findings (106052). Animal-model research also shows that constituents of St. John's wort might have teratogenic effects (9687,15122). Until more is known, St. John's wort should not be taken during pregnancy.
LACTATION: POSSIBLY UNSAFE
when used orally.
Nursing infants of mothers who take St. John's wort have a greater chance of experiencing colic, drowsiness, and lethargy (1377,15122,22418); avoid using.
CHILDREN: POSSIBLY SAFE
when used orally, and appropriately, short-term.
St. John's wort extracts in doses up to 300 mg three times daily seem to be safe when used for up to 8 weeks in children aged 6-17 years (4538,17986,76110).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Yarrow products that are thujone-free have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912); however, products containing thujone might not be safe. Thujone is a chemical that stimulates the central nervous system and is poisonous in large doses.
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (2,12,100346). Yarrow whole plant extract has been used with apparent safety at a dose of 250-500 mg daily for 12 months (100346). ...when used intravaginally as a cream containing yarrow extract 2% daily for 7 days (105360). There is insufficient reliable information available about the safety of yarrow when applied topically.
PREGNANCY: LIKELY UNSAFE
when used orally; yarrow is believed to be an abortifacient and affect the menstrual cycle (12).
LACTATION:
Insufficient reliable information available; avoid use.
LIKELY SAFE ...when used in amounts commonly found in foods. Ylang ylang oil has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of ylang ylang oil when used orally or topically in medicinal amounts.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in food.
Ylang ylang oil has Generally Recognized as Safe (GRAS) status in the US (4912).
CHILDREN: POSSIBLY SAFE
when used topically.
Ylang ylang oil has been used with apparent safety as three applications to the scalp at 5-day intervals (13483). There is insufficient reliable information available about the safety of ylang ylang oil when used orally in medicinal amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food.
Ylang ylang oil has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of using ylang ylang oil in medicinal amounts.
Below is general information about the interactions of the known ingredients contained in the product Prenolone + (with DHEA). 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, aloe gel might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
 Details
In vitro research shows that aloe gel can inhibit platelet aggregation. This inhibition was greater than that seen with celecoxib, but less than that seen with aspirin (105501).
|
Aloe might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
|
Theoretically, aloe might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research shows that aloe extract induces CYP1A2 enzymes (111404).
|
Theoretically, aloe latex might increase the risk of adverse effects when taken with cardiac glycosides.
Details
Overuse of aloe latex can increase the risk of adverse effects from cardiac glycoside drugs, such as digoxin, due to potassium depletion. Overuse of aloe, along with cardiac glycoside drugs, can increase the risk of toxicity (19).
|
Theoretically, aloe latex might increase the risk of hypokalemia when taken with diuretic drugs.
Details
Overuse of aloe latex might compound diuretic-induced potassium loss, increasing the risk of hypokalemia (19).
|
Theoretically, aloe latex might increase the risk for fluid and electrolyte loss when taken with stimulant laxatives.
Details
|
Theoretically, aloe latex might increase the risk of bleeding when taken with warfarin.
Details
Aloe latex has stimulant laxative effects. In some people aloe latex can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of aloe vera.
|
Theoretically, taking bergamot with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Animal research suggests that bergamot juice has hypoglycemic effects (34407).
|
Theoretically, topical bergamot essential oil might increase the risk of side effects when used along with photosensitizing drugs.
Details
|
Theoretically, spirulina blue-green algae might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs. However, this is unlikely.
Details
Spirulina blue-green algae have shown antiplatelet and anticoagulant effects in vitro (18311,18312,75892,92162,92163). However, one preliminary study in 24 patients receiving spirulina blue-green algae 2.3 grams daily for 2 weeks showed no effect on platelet activation or measures of clotting time (97202).
|
Theoretically, taking blue-green algae with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Human research shows that spirulina blue-green algae can have hypoglycemic effects in patients with diabetes, at least some of whom were using antidiabetes drugs (18299). However, blue-green algae does not seem to improve glycated hemoglobin (HbA1c) levels in patients with diabetes (102689,109970). A meta-analysis of animal studies also suggests that spirulina blue-green algae have hypoglycemic effects (109970).
|
Theoretically, concurrent use of blue-green algae might interfere with immunosuppressive therapy.
Details
|
Theoretically, calendula might have additive effects when used with CNS depressants, although this appears to be unlikely.
Details
|
Theoretically, DHEA might increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
|
Theoretically, DHEA might increase the risk of psychiatric adverse events when used with antidepressants.
Details
In a human case report, the use of a selective serotonin reuptake inhibitor (SSRI) with DHEA caused a manic episode (7023). Concern for this interaction may be greater in younger individuals with higher baseline DHEA levels.
|
Theoretically, DHEA might interfere with the clinical effects of aromatase inhibitors.
Details
DHEA is a potent estrogen agonist, which may antagonize the anti-estrogen activity of aromatase inhibitors (10401).
|
Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.
Details
Some preliminary evidence shows that DHEA may inhibit CYP3A4 (1389); however, the clinical significance of this potential interaction is not known.
|
Theoretically, DHEA might increase the effects and adverse effects of estrogen therapy.
Details
DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones (6012,7614,8593,10986,12651,12564,15027,21321,21323,21324)(21325,21326,21327,21328,21330,21331,21356,21364,21389,21393)(21397,21398,21417,21419,21427,47273,47348,88375,90304). Also, in clinical research, estrogen-progestin oral contraceptives and conjugated estrogens reduce blood levels of DHEA and DHEA-S (21372,21373,21374,21437,21438). The clinical significance of these findings is unclear.
|
Theoretically, DHEA might interfere with the anti-estrogen effects of fulvestrant.
Details
|
Theoretically, DHEA might interfere with the anti-estrogen effects of tamoxifen.
Details
|
Theoretically, DHEA might increase the effects and side effects of testosterone therapy.
Details
DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones (6012,7614,8593,10986,12651,12564,15027,21321,21323,21324)(21325,21326,21327,21328,21330,21331,21356,21364,21389,21393)(21397,21398,21417,21419,21427,47273,47348,88375,90304,99924,99925,104162). The clinical significance of these findings is unclear.
|
DHEA can increase blood levels of triazolam.
Details
Administration of DHEA 200 mg daily for two weeks was shown to inhibit the cytochrome P450 3A4 (CYP3A4) metabolism of triazolam. This inhibition appears to be due to DHEA-S, rather than DHEA (1389).
|
DHEA might reduce the effectiveness of the tuberculosis vaccine.
Details
Animal research shows that high doses of DHEA can reduce the efficacy of the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine (21316).
|
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, ginkgo might decrease the levels and clinical effects of alprazolam.
Details
In clinical research, ginkgo extract (Ginkgold) 120 mg twice daily seems to decrease alprazolam levels by about 17%. However, ginkgo does not appear to decrease the elimination half-life of alprazolam. This suggests that ginkgo is more likely to decrease absorption of alprazolam rather than induce hepatic metabolism of alprazolam (11029).
|
Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.
Details
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation (6048,9760). Several case reports have documented serious bleeding events in patients taking ginkgo (244,578,579,8581,13002,13135,13179,13194,14456,87868). However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting (87732). A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time (12114). An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin (91326). It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation (14811). However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT (17179). In addition, a single dose of ginkgo plus clopidogrel (14811) or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation (17111,87846). Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time (109526).
|
Theoretically, ginkgo might reduce the effectiveness of anticonvulsants.
Details
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves (8232). Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity (11296). However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090).
|
Theoretically, taking ginkgo with antidiabetes drugs might alter the response to antidiabetes drugs.
Details
Ginkgo leaf extract seems to alter insulin secretion and metabolism, and might affect blood glucose levels in people with type 2 diabetes (5719,14448,103574). The effect of ginkgo seems to differ depending on the insulin and treatment status of the patient. In diet-controlled diabetes patients with hyperinsulinemia, taking ginkgo does not seem to significantly affect insulin or blood glucose levels. In patients with hyperinsulinemia who are treated with oral hypoglycemic agents, taking ginkgo seems to decrease insulin levels and increase blood glucose following an oral glucose tolerance test. Researchers speculate that this could be due to ginkgo-enhanced hepatic metabolism of insulin. In patients with pancreatic exhaustion, taking ginkgo seems to stimulate pancreatic beta-cells, resulting in increased insulin and C-peptide levels, but with no significant change in blood glucose levels in response to an oral glucose tolerance test (14448).
|
Theoretically, ginkgo might decrease the levels and clinical effects of atorvastatin.
Details
In humans, intake of ginkgo extract appears to increase atorvastatin clearance, reducing the area under the curve of atorvastatin by 10% to 14% and the maximum concentration by 29%. However, this interaction does not appear to affect cholesterol synthesis and absorption (89706). Further, a model in rats with hyperlipidemia suggests that administering ginkgo extract does not impact blood levels of atorvastatin and leads to lower total cholesterol, low-density lipoprotein cholesterol, and triglycerides when compared with rats given atorvastatin alone (111331).
|
Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.
Details
|
Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
Details
Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes (13108). However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19 (87824).
|
Theoretically, ginkgo might increase levels of drugs metabolized by CYP2C9.
Details
In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity (11026,12061,14337). The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.
|
Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.
Details
There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4 (1303,6423,6450,11026,87800,87805,111330). Ginkgo does not appear to affect hepatic CYP3A4 (11029). However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates (11027,87800,93578). Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity (10847). However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4) (16821,25464).
|
Theoretically, ginkgo might decrease the levels and clinical effects of efavirenz.
Details
There are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. In one case, an HIV-positive male experienced over a 50% decrease in efavirenz levels over the course of 14 months while taking ginkgo extract. HIV-1 RNA copies also increased substantially, from less than 50 to more than 1500. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4) (16821). In another case report, a patient stable on antiviral therapy including efavirenz for 10 years, had an increase in viral load from <50 copies/mL to 1350 copies/mL after 2 months of taking a combination of supplements including ginkgo. After stopping ginkgo, the viral load was again controlled with the same antiviral therapy regimen (25464).
|
Theoretically, ginkgo might increase the risk of bleeding when used with ibuprofen.
Details
Ginkgo might have antiplatelet effects and has been associated with several case reports of spontaneous bleeding. In one case, a 71-year-old male had taken a specific ginkgo extract (Gingium, Biocur) 40 mg twice daily for 2.5 years. About 4 weeks after starting ibuprofen 600 mg daily he experienced a fatal intracerebral hemorrhage (13179). However, the antiplatelet effects of ginkgo have been questioned. A meta-analysis and other studies have not found a significant antiplatelet effect with standardized ginkgo extracts, 80 mg to 480 mg taken daily for up to 32 weeks (17179).
|
Theoretically, taking ginkgo with oral, but not intravenous, nifedipine might increase levels and adverse effects of nifedipine.
Details
Animal research and some clinical evidence suggests that taking ginkgo leaf extract orally in combination with oral nifedipine might increase nifedipine levels and cause increased side effects, such as headaches, dizziness, and hot flushes (87764,87765). However, taking ginkgo orally does not seem to affect the pharmacokinetics of intravenous nifedipine (87765).
|
Theoretically, taking ginkgo with omeprazole might decrease the levels and clinical effects of omeprazole.
Details
Clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce cytochrome P450 (CYP) 2C19 enzymes and decrease levels of omeprazole by about 27% to 42% (13108).
|
Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.
Details
A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect (87830).
|
Theoretically, taking ginkgo with risperidone might increase the levels and adverse effects of risperidone.
Details
A single case of priapism has been reported for a 26-year-old male with schizophrenia who used risperidone 3 mg daily along with ginkgo extract 160 mg daily (87796). Risperidone is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4. CYP3A4 activity might be affected by ginkgo. Theoretically, ginkgo may inhibit the metabolism of risperidone and increase the risk of adverse effects.
|
Theoretically, ginkgo might decrease the levels and clinical effects of rosiglitazone.
Details
Animal research shows that ginkgo leaf extract orally 100 or 200 mg/kg daily for 10 days alters the pharmacodynamics of rosiglitazone in a dose-dependent manner. The 100 mg/kg and 200 mg/kg doses reduce the area under the concentration time curve (AUC) of rosiglitazone by 39% and 52%, respectively, and the half-life by 28% and 39%, respectively. It is hypothesized that these changes may be due to induction of cytochrome P450 2C8 by ginkgo (109525).
|
Theoretically, taking ginkgo with drugs that lower the seizure threshold might increase the risk for convulsions.
Details
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves (8232). Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity (11296). However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090,14281).
|
Theoretically, ginkgo might decrease the levels and clinical effects of simvastatin.
Details
Clinical research shows that taking ginkgo extract can reduce the area under the curve and maximum concentration of simvastatin by 32% to 39%. However, ginkgo extract does not seem to affect the cholesterol-lowering ability of simvastatin (89704).
|
Theoretically, ginkgo might increase the levels and clinical effects of sofosbuvir.
Details
Animal research in rats shows that giving a ginkgo extract 25 mg/kg orally daily for 14 days increases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 11%, increases the half-life by 60%, and increases the plasma concentration at 4 hours by 38%. This interaction appears to be related to the inhibition of intestinal P-glycoprotein by ginkgo (109524).
|
Theoretically, ginkgo might increase the blood levels of tacrolimus.
Details
In vitro evidence suggests that certain biflavonoids in ginkgo leaves (i.e. amentoflavone, ginkgetin, bilobetin) may inhibit the metabolism of tacrolimus by up to 50%. This interaction appears to be time-dependent and due to inhibition of cytochrome P450 (CYP) 3A4 by these bioflavonoids. In rats given tacrolimus 1 mg/kg orally, amentoflavone was shown to increase the area under the concentration time curve (AUC) of tacrolimus by 3.8-fold (111330).
|
Taking ginkgo with talinolol seems to increase blood levels of talinolol.
Details
There is some evidence that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of talinolol by 36% in healthy male individuals. However, single doses of ginkgo do not seem to affect talinolol pharmacokinetics (87830).
|
Theoretically, ginkgo might increase the levels and clinical effects of trazodone.
Details
In a case report, an Alzheimer patient taking trazodone 20 mg twice daily and ginkgo leaf extract 80 mg twice daily for four doses became comatose. The coma was reversed by administration of flumazenil (Romazicon). Coma might have been induced by excessive GABA-ergic activity. Ginkgo flavonoids are thought to have GABA-ergic activity and act directly on benzodiazepine receptors. Ginkgo might also increase metabolism of trazodone to active GABA-ergic metabolites, possibly by inducing cytochrome P450 3A4 (CYP3A4) metabolism (6423).
|
Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.
Details
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation (6048,9760). Several case reports have documented serious bleeding events in patients taking ginkgo (244,576,578,579,8581,13002,13135,13179,13194,14456,87868). Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38% (91326). There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels (12061). However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176,87727,87889). A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT (17179). There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR (11905).
|
Theoretically, concomitant use of goji fruit polysaccharides or goji root bark with antidiabetes drugs might have additive effects.
Details
Animal and in vitro research show that goji root bark and fruit polysaccharides might have hypoglycemic effects (7126,92118,94667). However, clinical research has only shown that taking goji fruit polysaccharides with or without antidiabetes drugs modestly reduces postprandial glucose when compared with control, with no reports of hypoglycemia (92117).
|
Theoretically, concomitant use of goji root bark, but not goji fruit, with antihypertensive drugs might have additive effects.
Details
|
Theoretically, goji berry might inhibit CYP2C19 and reduce metabolism of CYP2C19 substrates.
Details
In vitro research shows that goji berry tincture and juice inhibit CYP2C19 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP2C19 substrates. However, this has not been reported in humans.
|
Theoretically, goji berry might inhibit CYP2C9 and reduce metabolism of CYP2C9 substrates.
Details
In vitro research shows that goji berry tincture and juice inhibit CYP2C9 enzymes (105486). Additionally, multiple case reports suggest that goji berry concentrated tea and juice inhibit the metabolism of warfarin, a CYP2C9 substrate (7158,105462). Concomitant use with goji may decrease metabolism and increase levels of CYP2C9 substrates.
|
Theoretically, goji berry might inhibit CYP2D6 and reduce metabolism of CYP2D6 substrates.
Details
In vitro research shows that goji berry juice inhibits CYP2D6 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP2D6 substrates. However, this has not been reported in humans.
|
Theoretically, goji berry might inhibit CYP3A4 and reduce metabolism of CYP3A4 substrates.
Details
In vitro research shows that goji berry juice inhibits CYP3A4 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP3A4 substrates. However, this has not been reported in humans.
|
Theoretically, goji berry might increase the levels and clinical effects of flecainide.
Details
In one case report, a 75-year-old patient stable on flecainide and warfarin presented to the emergency room with fainting and pleomorphic arrhythmia caused by flecainide toxicity. Flecainide toxicity was attributed to drinking 1-2 glasses of concentrated goji tea daily for 2 weeks. Theoretically, goji may have inhibited the cytochrome P450 2D6 (CYP2D6) metabolism of flecainide (105462).
|
Goji can increase the effects of warfarin and possibly increase the risk of bleeding.
Details
There are at least 5 case reports of increased international normalized ratio (INR) in patients stabilized on warfarin who began drinking goji juice, concentrated goji tea, or goji wine (7158,16529,23896,105462,105487). Goji may inhibit the metabolism of warfarin by cytochrome P450 2C9 (CYP2C9) (7158).
|
Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
|
Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
Details
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water (53177). Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.
|
Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
Details
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2 (2539).
|
It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
Details
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes (11094,53011,53089). However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism (11094). The effects of continued grape juice consumption are unclear.
|
Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
Details
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes (53011). However, this interaction has not been reported in humans.
|
Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
Details
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes (52949). However, this interaction has not been reported in humans.
|
It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
Details
|
Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Details
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination (53011).
|
Grape juice might decrease phenacetin absorption.
Details
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2) (2539).
|
Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
Details
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425% (98424).
|
Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).
|
Theoretically, alcohol might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370).
|
Theoretically, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity (733,8028,8029,12882,100524).
|
Theoretically, taking green tea with antidiabetes drugs might interfere with blood glucose control.
Details
|
Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
Details
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected (102714). Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin (19079). It is not clear if drinking green tea alters the absorption of atorvastatin.
|
Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15).
|
Theoretically, green tea might interfere with the effects of bortezomib.
Details
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines (17212). Advise patients taking bortezomib, not to take green tea.
|
Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Details
Green tea contains caffeine. Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg (23559,23561). Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals (23562).
|
Theoretically, green tea might reduce the levels and clinical effects of celiprolol.
Details
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98% (104607). This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine (19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Details
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42% (11736).
|
Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Details
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels (90173). Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine (13741).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Details
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65% (8644).
|
Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2) (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.
|
Green tea is unlikely to produce clinically significant changes in the levels and clinical effects of CYP3A4 substrates.
Details
|
Theoretically, green tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Green tea contains caffeine. Caffeine might inhibit dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).
|
Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
Details
In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).
|
Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Details
|
Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Details
|
Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).
|
Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Details
Green tea contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide (23560). However, this effect has not been reported in humans.
|
Theoretically, green tea might reduce the effects of felbamate and increase the risk for convulsions.
Details
Green tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate (23563). However, this effect has not been reported in humans.
|
Green tea can decrease blood levels of fexofenadine.
Details
Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter (111029). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates (19079,102714,102730).
|
Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
|
Theoretically, green tea might increase the levels and adverse effects of flutamide.
Details
Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.
|
Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
|
Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Details
|
Theoretically, green tea might reduce the levels and clinical effects of imatinib.
Details
In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81% (104600). This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.
|
Theoretically, green tea might reduce the levels and clinical effects of lisinopril.
Details
Preliminary clinical research shows that a single dose of green tea extract reduces plasma concentrations of lisinopril. Compared to a control group, peak levels and area under the curve (AUC) of lisinopril were reduced by approximately 71% and 66%, respectively (104599). This may be due to inhibition of organic anion transporting polypeptides (OATP) by green tea catechins (19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).
|
Theoretically, abrupt green tea withdrawal might increase the levels and adverse effects of lithium.
Details
|
Theoretically, metformin might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571). Theoretically, concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.
|
Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Methoxsalen can reduce caffeine metabolism (23572). Concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.
|
Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260).
|
Theoretically, green tea might increase the levels and adverse effects of midazolam.
Details
Animal research suggests that green tea extract can increase the maximum plasma concentration, but not the half-life, of oral midazolam. This effect has been attributed to the inhibition of intestinal cytochrome P450 3A4 (CYP3A4) and induction of hepatic CYP3A4 enzymes by green tea constituents (20896). However, it is unlikely that this effect is clinically significant, as the dose used in animals was 50 times greater than what is commonly ingested by humans.
|
Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Details
Green tea contains caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15). In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension (91086). Hypertension was resolved after the patient switched to drinking decaffeinated coffee.
|
Green tea seems to reduce the levels and clinical effects of nadolol.
Details
Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect (19071). Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour (102721). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine (19071,19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).
|
Theoretically, green tea might increase the levels and adverse effects of nicardipine.
Details
Green tea contains EGCG. Animal research shows that EGCG increases the area under the curve (AUC) and absolute oral bioavailability of nicardipine. The mechanism of action is thought to involve inhibition of both intestinal P-glycoprotein and hepatic cytochrome P450 3A (90136). The effect of green tea itself on nicardipine is unclear.
|
Theoretically, concomitant use might increase the risk of hypertension.
Details
Green tea contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).
|
Green tea seems to reduce the levels of nintedanib.
Details
Clinical research shows that green tea can significantly decrease blood levels of nintedanib. Taking green tea extract twice daily for 7 days 30 minutes prior to a meal along with nintedanib with the meal decreased the 12-hour area under the curve (AUC) values for nintedanib by 21%. There was no effect on the maximum concentration of nintedanib (111028).
|
Theoretically, green tea might reduce the absorption of organic anion-transporting polypeptide (OATP) substrates.
Details
OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates, including lisinopril, and celiprolol (19079,102714,102730).
|
Green tea might increase the levels and adverse effects of P-glycoprotein (P-gp) substrates.
Details
In vitro research and case reports suggest that green tea inhibits drug efflux by P-gp, potentially increasing serum levels of P-gp substrates. Case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking green tea and certain P-gp substrates (111644).
|
Theoretically, green tea might decrease the effects of pentobarbital.
Details
Green tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
|
Theoretically, green tea might reduce the effects of phenobarbital and increase the risk for convulsions.
Details
|
Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
|
Theoretically, green tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
|
Theoretically, green tea might increase the levels and clinical effects of pioglitazone.
Details
Green tea contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.
|
Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Green tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).
|
Theoretically, green tea extract might alter the absorption and distribution of rosuvastatin.
Details
In animal research, giving green tea extract with rosuvastatin increased plasma levels of rosuvastatin. Rosuvastatin is a substrate of organic anion-transporting polypeptide (OATP)1B1, which is expressed in the liver. The increased plasma levels may have been related to inhibition of OATP1B1 (102717). However, in humans, taking EGCG with rosuvastatin reduced plasma levels of rosuvastatin, suggesting an inhibition of intestinal OATP (102730). It is not clear if drinking green tea alters the absorption of rosuvastatin.
|
Theoretically, concomitant use might increase stimulant adverse effects.
Details
Green tea contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).
|
Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
|
Theoretically, green tea might increase the levels and adverse effects of theophylline.
Details
Green tea contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).
|
Theoretically, green tea might increase the levels and adverse effects of tiagabine.
Details
Green tea contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).
|
Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
|
Theoretically, green tea might reduce the effects of valproate and increase the risk for convulsions.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of both verapamil and caffeine.
Details
Animal research suggests that the green tea constituent EGCG increases the area under the curve (AUC) values for verapamil by up to 111% and its metabolite norverapamil by up to 87%, likely by inhibiting P-glycoprotein (90138). Also, theoretically, concomitant use of verapamil and caffeinated beverages such as green tea might increase plasma caffeine concentrations and the risk of adverse effects, due to the caffeine contained in green tea. Verapamil increases plasma caffeine concentrations by 25% (11741).
|
Theoretically, green tea may increase the risk of bleeding if used with warfarin.
Details
Conflicting reports exist regarding the potential of green tea to antagonize the effect of warfarin; however, most evidence suggests that drinking green tea in moderation is unlikely to cause a significant interaction. Green tea contains a small amount of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects (1460,1461,1463,8028). Therefore, use of green tea in moderate amounts is unlikely to antagonize the effects of warfarin; however, very large doses should be avoided.
|
Concomitant use of pregnenolone may reduce the effects of benzodiazepines.
Details
Very preliminary clinical research shows that chronic use of pregnenolone reduces sedative effects of diazepam when compared with chronic use of placebo. This effect may be related to the activity of pregnenolone at GABAA receptors (94031).
|
Theoretically, taking pregnenolone might enhance the effects of estrogens.
Details
Pregnenolone is a precursor for several steroid hormones, including estrogens (3008).
|
Theoretically, taking pregnenolone might enhance the effects of progesterone.
Details
|
Theoretically, taking pregnenolone might enhance the effects of progestin.
Details
Pregnenolone is a precursor for several steroid hormones, including progestin (3008).
|
Theoretically, taking pregnenolone might enhance the effects of testosterone.
Details
|
Theoretically, sage might decrease the clinical effects of anticholinergic drugs.
Details
|
Theoretically, sage might interfere with the clinical effects of anticonvulsant drugs.
Details
Some species of sage can cause convulsions when consumed in large quantities (10812).
|
Theoretically, taking sage with antidiabetes drugs might increase the risk of hypoglycemia.
Details
In patients with polycystic ovary syndrome (PCOS) or inadequately controlled type 2 diabetes, common sage (Salvia officinalis) has demonstrated hypoglycemic activity (91971,103380). However, other clinical research in patients with inadequately controlled type 2 diabetes shows that common sage extract does not lower fasting blood glucose levels (105340).
|
Theoretically, sage might increase or decrease the effects of antihypertensive drugs.
Details
Animal research suggests that common sage (Salvia officinalis) can cause prolonged blood pressure reduction (4152). However, clinical research suggests that Spanish sage (Salvia lavandulaefolia) can increase blood pressure in some people with hypertension (10334). Until more is known, use with caution.
|
Theoretically, taking sage might increase the sedative and adverse effects of benzodiazepines.
Details
In vitro evidence suggests that certain components of common sage (Salvia officinalis) can bind to benzodiazepine receptors (72588). This effect has not been reported in humans.
|
Theoretically, sage might have additive effects when used with cholinergic drugs.
Details
|
Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.
Details
Some constituents of sage have CNS depressant activity (10334).
|
Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C19.
Details
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C19 (10848). So far, this interaction has not been reported in humans.
|
Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.
Details
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9 (10848). So far, this interaction has not been reported in humans.
|
Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.
Details
|
Theoretically, sage might decrease the levels and clinical effects of drugs metabolized by CYP2E1.
Details
Animal research suggests that drinking common sage (Salvia officinalis) tea increases the expression of CYP2E1 (72627). So far, this interaction has not been reported in humans.
|
Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.
Details
|
Theoretically, sage might interfere with hormone therapy.
Details
In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity (39572). The clinical significance of this effect is unclear.
|
Theoretically, sage might increase levels of drugs transported by P-glycoprotein.
Details
In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein (72641). This effect has not been reported in humans.
|
St. John's wort increases the clearance of alprazolam and decreases its effects.
Details
Alprazolam, which is used as a probe for cytochrome P450 3A4 (CYP3A4) activity, has a two-fold increase in clearance when given with St. John's wort. St. John's wort reduces the half-life of alprazolam from 12.4 hours to 6 hours (10830).
|
St. John's wort may increase the clearance of ambristentan and decrease its effects.
Details
Clinical research in healthy volunteers shows that taking St. John's wort 900 mg daily decreases the area under the concentration-time curve of ambrisentan 5 mg by 17% to 26%. Ambrisentan clearance was increased by 20% to 35% depending on CYP2C19 genotype. However, these small changes are unlikely to be clinically significant (99511).
|
St. John's wort might have additive phototoxic effects with aminolevulinic acid.
Details
Concomitant use with St. John's wort extract may cause synergistic phototoxicity. Delta-aminolevulinic acid can cause a burning erythematous rash and severe swelling of the face, neck, and hands when taken with St. John's wort (9474).
|
St. John's wort might decrease the levels and clinical effects of boceprevir.
Details
Boceprevir increases the maximum concentration and concentration at 8 hours of the St. John's wort constituent, hypericin, by approximately 30%. However, St. John's wort does not significantly change the area under the concentration-time curve or maximum plasma concentration of boceprevir 800 mg three times daily in healthy adults (95507,96552).
|
St. John's wort might reduce the levels and effects of bupropion.
Details
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort (89662).
|
St. John's wort might increase the levels and effects of clopidogrel.
Details
Taking St. John's wort with clopidogrel seems to increase the activity of clopidogrel. In clopidogrel non-responders, taking St. John's wort seems to induce metabolism of clopidogrel to its active metabolite by cytochrome P450 enzymes 3A4 and 2C19. This leads to increased antiplatelet activity (13038,89671,96552). Theoretically, this might lead to an increased risk of bleeding in clopidogrel responders.
|
St. John's wort might decrease the levels and clinical effects of clozapine.
Details
A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort (96552).
|
St. John's wort increases the clearance of contraceptive drugs and reduces their clinical effects.
Details
Females taking St. John's wort and oral contraceptives concurrently should use an additional or alternative form of birth control. St. John's wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy (11886,11887,13099). Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's wort extract (9880). St. John's wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives (1292,7809,9204).
|
St. John's wort reduces the levels and clinical effects of cyclosporine.
Details
Concomitant use can decrease plasma cyclosporine levels by 30% to 70% (1234,4826,4831,4834,7808,9596,10628,96552). Using St. John's wort with cyclosporine in patients with heart, kidney, or liver transplants can cause subtherapeutic cyclosporine levels and acute transplant rejection (1234,1293,1301,6112,6435,7808,9596). This interaction has occurred with a St. John's wort extract standardized to 0.3% hypericin and dosed at 300-600 mg per day (6435,10628). Withdrawal of St. John's wort can result in a 64% increase in cyclosporine levels (1234,4513,4826,4831,4834). St. John's wort induces cytochrome P450 3A4 (CYP3A4) and the multi-drug transporter, P-glycoprotein/MDR-1, which increases cyclosporine clearance (1293,1340,9204,9596).
|
St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.
Details
|
St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.
Details
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion, a CYP2B6 substrate, reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20% (89662).
|
St. John's wort may increase the metabolism and reduce the levels of CYP2C19 substrates.
Details
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces CYP2C19 and increases metabolism of mephenytoin (Mesantoin). In patients with wild-type 2C19 (2C19*1/*1) metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism (17405). Theoretically, St. John's wort might increase metabolism of other CYP2C19 substrates.
|
St. John's wort may increase the metabolism and reduce the levels of CYP2C9 substrates.
Details
There is contradictory research about the effect of St. John's wort on CYP2C9. Some in vitro research shows that St. John's wort induces CYP2C9, but to a lesser extent than CYP3A4 (9204,10848,11889). St. John's wort also induces metabolism of the S-warfarin isomer, which is a CYP2C9 substrate (11890). Other research shows that St. John's wort 300 mg three times daily for 21 days does not significantly affect the pharmacokinetics of a single 400 mg dose of ibuprofen, which is also a CYP2C9 substrate (15546). Until more is known, use St. John's wort cautiously in patients who are taking CYP2C9 substrates.
|
St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.
Details
|
St. John's wort reduces the levels and clinical effects of digoxin.
Details
St. John's wort can reduce the bioavailability, serum levels, and therapeutic effects of digoxin. Taking an extract of St. John's wort 900 mg, containing hyperforin 7.5 mg or more, daily for 10-14 days, can reduce serum digoxin levels by 25% in healthy people. St. John's wort is thought to affect the multidrug transporter, P-glycoprotein, which mediates the absorption and elimination of digoxin and other drugs (382,6473,7808,7810,9204,96552,97171). St. John's wort products providing less than 7.5 mg of hyperforin daily do not appear to affect digoxin levels (97171).
|
St. John's wort reduces the levels and clinical effects of docetaxel.
Details
Clinical research shows that taking a specific St. John's wort product (Hyperiplant, VSM) 300 mg three times daily for 14 days increases docetaxel clearance by about 14%, resulting in decreased plasma concentrations of docetaxel in cancer patients. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (89661).
|
Theoretically, St. John's wort may reduce the levels and clinical effects of fentanyl.
Details
Given that St. John's wort induces cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, it is possible that concomitant use of St. John's wort with fentanyl will reduce plasma levels and analgesic activity of fentanyl (96552). However, some clinical research in healthy adults shows that taking St. John's wort (LI-160, Lichtwer Pharma) 300 mg daily for 21 days does not alter the pharmacokinetics or clinical effects of intravenous fentanyl (102868). It is unclear if these findings can be generalized to oral, intranasal, or transdermal fentanyl.
|
St. John's wort may increase the levels and clinical effects of fexofenadine.
Details
A single dose of St. John's wort decreases the clearance of fexofenadine and increases its plasma levels. However, the effect of St. John's wort on plasma levels of fexofenadine seems to be lost if dosing is continued for more than 2 weeks (9685). Patients taking fexofenadine and St. John's wort concurrently should be monitored for possible fexofenadine toxicity.
|
St. John's wort may reduce the levels and clinical effects of finasteride.
Details
St. John's wort reduces plasma levels of finasteride in healthy male volunteers due to induction of finasteride metabolism via cytochrome P450 3A4 (CYP3A4). The clinical significance of this interaction is not known (96552).
|
St. John's wort may reduce the levels and clinical effects of gliclazide.
Details
Taking St. John's wort decreases the half-life and increases clearance of gliclazide in healthy people (22431).
|
St. John's wort may increase the metabolism and reduce the effectiveness of atorvastatin, lovastatin, and rosuvastatin. However, it does not seem to affect pravastatin, pitavastatin, or fluvastatin.
Details
Concomitant use of St. John's wort can reduce plasma concentrations of the active simvastatin metabolite, simvastatin hydroxy acid, by 28%. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter. This increases simvastatin clearance. It also increases the clearance of atorvastatin (Lipitor), lovastatin (Mevacor), and rosuvastatin (Crestor). St. John's wort does not seem to affect the plasma concentrations of pravastatin (Pravachol), pitavastatin (Livalo) or fluvastatin (Lescol), which are not substrates of CYP3A4 or P-glycoprotein (10627,96552,97171).
|
St. John's wort reduces the levels and clinical effects of imatinib.
Details
Taking St. John's wort 900 mg daily for 2 weeks reduces the bioavailability and half-life of a single dose of imatinib and decreases its serum levels by 30% in healthy volunteers. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, which increases clearance of imatinib (11888,96552).
|
St. John's wort may reduce the levels and clinical effects of indinavir.
Details
In healthy volunteers, taking St. John's wort concurrently with indinavir reduces plasma concentrations of indinavir by inducing metabolism via cytochrome P450 3A4 (CYP3A4) (96552). Theoretically, this could result in treatment failure and viral resistance.
|
St. John's wort reduces the levels and clinical effects of irinotecan.
Details
St. John's wort 900 mg daily for 18 days decreases serum levels of irinotecan by at least 50%. Clearance of the active metabolite of irinotecan, SN-38, is also increased, resulting in a 42% decrease in the area under the concentration-time curve (9206,97171). This is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (7092,96552).
|
St. John's wort might reduce the levels and clinical effects of ivabradine.
Details
Taking St. John's wort 900 mg containing 7.5 mg of hyperforin daily for 14 days with a single dose of ivabradine causes a 62% reduction in plasma levels of ivabradine. This interaction is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, increasing the metabolism of ivabradine (96552,97171).
|
St. John's wort reduces the levels and clinical effects of ketamine.
Details
Taking St. John's wort 300 mg three times daily for 14 days can decrease maximum serum levels of ketamine by around 66% and area under the concentration-time curve of ketamine by 58%. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort (89663).
|
St. John's wort reduces the levels and clinical effects of mephenytoin.
Details
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces cytochrome P450 2C19 (CYP2C19) and significantly increases metabolism of mephenytoin (Mesantoin). In people with wild-type 2C19, metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism (17405).
|
St. John's wort might reduce the levels and clinical effects of methadone.
Details
St. John's wort might decrease the effectiveness of methadone by reducing its blood concentrations. In one report, two out of four patients on methadone maintenance therapy for addiction experienced methadone withdrawal symptoms after taking St. John's wort 900 mg daily for a median of 31 days. There was a median decrease in blood methadone concentration of 47% (range: 19% to 60%) when compared to baseline (22419).
|
St. John's wort might reduce the levels and clinical effects of methylphenidate.
Details
St. John's wort might decrease the effectiveness of methylphenidate. In one report, an adult male, stabilized on methylphenidate for attention deficit-hyperactivity disorder (ADHD), experienced increased attention problems and ADHD symptoms after taking St. John's wort 600 mg daily for 4 months. ADHD symptoms improved when St. John's wort was discontinued (15544). The mechanism of this interaction is unknown.
|
St. John's wort decreases the levels and clinical effects of NNRTIs.
Details
St. John's wort increases the oral clearance of nevirapine (Viramune) by 35%. Subtherapeutic concentrations are associated with therapeutic failure, development of viral resistance, and development of drug class resistance. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter (1290,1340,4837,96552).
|
St. John's wort decreases the levels and clinical effects of omeprazole.
Details
Taking St. John's wort, 300 mg orally three times daily for 14 days, reduces serum concentrations of omeprazole by inducing its metabolism via cytochrome P450 (CYP) 2C19 and 3A4. The reduction of omeprazole serum levels is dependent on CYP2C19 genotype, with reductions up to 50% in extensive metabolizers and 38% in poor metabolizers (22440,96552).
|
St. John's wort decreases the levels and clinical effects of oxycodone.
Details
St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity (96552).
|
St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.
Details
St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action (382,1340,7810,11722).
|
St. John's wort decreases the levels and clinical effects of phenobarbital.
Details
St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped (9204).
|
St. John's wort decreases the levels and clinical effects of phenprocoumon.
Details
St. John's wort appears to increase the metabolism of phenprocoumon (an anticoagulant that is not available in the US) by increasing the activity of the cytochrome P450 2C9 (CYP2C9) enzyme. This may result in decreases in the anticoagulant effect and international normalized ratio (INR) (9204).
|
St. John's wort decreases the levels and clinical effects of phenytoin.
Details
St. John's wort may increase the metabolism of phenytoin. Plasma concentrations of phenytoin should be monitored closely. The dose of phenytoin may need to be increased when St. John's wort is started and decreased when it is stopped (9204).
|
Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.
Details
|
Theoretically, St. John's wort might decrease the levels and clinical effects of procainamide.
Details
Animal research shows that taking St. John's wort extract increases the bioavailability of procainamide, but does not increase its metabolism (14865). Whether this interaction is clinically significant in humans is not known.
|
St. John's wort reduces the levels and clinical effects of PIs.
Details
In healthy volunteers, St. John's wort can reduce the plasma concentrations of indinavir (Crixivan) by inducing cytochrome P450 3A4 (CYP3A4). This might result in treatment failure and viral resistance (1290,7808,96552). St. John's wort also induces P-glycoprotein, which can result in decreased intracellular protease inhibitor concentrations and increased elimination (9204).
|
Theoretically, St. John's wort might decrease the effectiveness of reserpine.
Details
Animal research shows that St. John's wort can antagonize the effects of reserpine (758).
|
St. John's wort decreases the levels and clinical effects of rivaroxaban.
Details
A small pharmacokinetic study in healthy volunteers shows that taking a single dose of rivaroxaban 20 mg after using a specific St. John's wort extract (Jarsin, Vifor SA) 450 mg orally twice daily for 14 days reduces the bioavailability of rivaroxaban by 24% and reduces rivaroxaban's therapeutic inhibition of factor Xa by 20% (104038).
|
Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.
Details
|
St. John's wort decreases the levels and clinical effects of tacrolimus.
Details
Taking a St. John's wort extract (Jarsin) 600 mg daily significantly decreases tacrolimus serum levels. Dose increases of 60% may be required to maintain therapeutic tacrolimus levels in patients taking St. John's wort. St. John's wort is thought to lower tacrolimus levels by inducing cytochrome P450 3A4 (CYP3A4) enzymes (7095,10329). A small clinical study in healthy adults also shows that taking St. John's wort 300 mg three times daily for 10 days decreases the total systemic exposure to tacrolimus by 27% and 33% after taking a single 5 mg dose of immediate-release or prolonged-release tacrolimus, respectively (113094).
|
St. John's wort might decrease the levels of theophylline, although this effect might not be clinically relevant.
Details
St. John's wort does not seem to significantly affect theophylline pharmacokinetics (11802). There is a single case report of a possible interaction with theophylline. A patient who smoked and was taking 11 other drugs experienced an increase in theophylline levels after discontinuation of St. John's wort. This increase has been attributed to a rebounding of theophylline serum levels after St. John's wort was no longer present to induce metabolism via cytochrome P450 1A2 (CYP1A2) (3556,7808,9204). However, studies in healthy volunteers show that St. John's wort is unlikely to affect theophylline to any clinically significant degree (11802).
|
St. John's wort might decrease the levels and clinical effects of tramadol.
Details
|
St. John's wort might decrease the levels and clinical effects of voriconazole.
Details
Clinical research shows that taking St. John's wort with voriconazole reduces voriconazole exposure and increases voriconazole metabolism by approximately 107%. Voriconazole is primarily metabolized by cytochrome P450 (CYP) 2C19, with CYP3A4 and CYP2C9 also involved (89660). St. John's wort induces CYP2C19, CYP3A4, and CYP2C9 (9204,10830,10847,10848,11889,11890,17405,22423,22424,22425)(22427,48603).
|
St. John's wort decreases the levels and clinical effects of warfarin.
Details
Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers (11890,15176). This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4 (11890). St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin (1292). In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption (10448).
|
St. John's wort might decrease the levels and clinical effects of zolpidem.
Details
|
Theoretically, taking yarrow with lithium might increase the levels and adverse effects of lithium.
Details
Animal research shows that yarrow has diuretic activity (106018). Theoretically, due to these potential diuretic effects, yarrow might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.
|
Below is general information about the adverse effects of the known ingredients contained in the product Prenolone + (with DHEA). 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 and topically, aloe products are generally well tolerated when used in typical doses.
However, oral aloe latex is associated with a greater risk of adverse effects, especially when used in high doses or long-term.
Most Common Adverse Effects:
Orally: Aloe latex may cause abdominal pain, cramps, and diarrhea.
Topically: Burning, erythema, and itching. Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Aloe latex is associated with serious adverse effects when taken in high doses or long-term. Cases of acute hepatitis due to a hypersensitivity reaction to aloe leaf extract has been reported.
Dermatologic ...Topically, aloe gel has occasionally been associated with burning (12164,19741,30697,30706), itching (12164,19741,30697), eczema (90122), erythema (19748,30706,90123), contact dermatitis (12163,12164,30695,30736,30737,30738,30740), popular eruption (30732), and urticaria (30712). Also, a case of generalized nummular and popular dermatitis attributed to hypersensitivity has been reported for a 47-year-old male who used aloe leaf gel, both topically and orally, for 4 years (30740).
Endocrine ...A case of severe hypokalemia has been reported for a male breast cancer patient who was undergoing chemotherapy and using aloe vera 1 liter daily orally for 2 weeks. The hypokalemia was attributed to the cathartic effects of aloe and resolved once aloe use was discontinued (30704).
Gastrointestinal
...Orally, aloe latex can cause abdominal pain and cramps.
Long-term use or abuse of aloe latex can cause diarrhea, sometimes with hypokalemia, albuminuria, hematuria, muscle weakness, weight loss, arrhythmia, and pseudomelanosis coli (pigment spots in intestinal mucosa). Pseudomelanosis coli is believed to be harmless, and usually reverses with discontinuation of aloe. It is not directly associated with an increased risk of developing colorectal adenoma or carcinoma (6138). Orally, aloe gel may cause nausea, stomach cramps, and other gastrointestinal complaints in some patients (104174,111921,111663).
Topically, applying aloe gel in the mouth may cause nausea within 5 minutes of application in some patients (90124).
Hematologic ...A case of Henoch-Schonlein purpura, characterized by abdominal pain, purpura, and severe arthralgia, has been reported in a 52-year-old male who drank aloe juice prepared from four to five leaflets for 10 days prior to symptom development (91598).
Hepatic ...Cases of acute hepatitis have been reported after ingestion of aloe leaf extracts for between 3 weeks and 5 years. This is thought to be a hypersensitivity reaction (15567,15569,16386,17419,90126,91598). A case of acute hepatitis has also been reported for a 45-year-old female who drank two ounces of Euforia juice (Nuverus International), a product containing green tea, noni, goji, and aloe, daily for one month (90125). However, one small clinical trial in healthy individuals shows that taking aloe gel 2 ounces twice daily for 60 days does not impair liver function (104174).
Renal ...Orally, aloe latex can cause hemorrhagic gastritis, nephritis, and acute kidney failure following prolonged use of high doses (1 gram daily or more) (8961).
General
...Orally or as aromatherapy, bergamot seems to be well tolerated when used short-term.
Topically, bergamot is possibly unsafe.
Most Common Adverse Effects:
Topically: Blisters, erythema, photosensitivity, pigment spots, pustules, and skin lesions.
Dermatologic
...Frequent contact with the peel or oil of bergamot can cause erythema, blisters, pustules, dermatoses leading to scab formation, and pigment spots (18).
Topically, photosensitivity can also occur, especially in fair-skinned people (11019).
Gastrointestinal ...Orally, bergamot extract has been associated with one case of heartburn in clinical research (96356).
Musculoskeletal ...Orally, muscle cramps have been reported for a patient starting one week after switching from drinking 4 liters of black tea to drinking 4 liters of Earl Grey tea daily. The muscle cramps were attributed bergapten, a constituent of bergamot essential oil in Earl Grey tea. The patient's symptoms subsided after discontinuing Earl Grey tea intake and remained absent upon re-initiation of Earl Grey tea intake 1 liter daily (34344).
General
...Orally, spirulina blue-green algae seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, bloating, diarrhea, dizziness, fatigue, flatulence, headache, nausea, and vomiting.
Dermatologic ...Orally, a severe rash has been reported in a 49-year-old woman after taking a spirulina blue-green algae supplement (species and dose unknown). After stopping the supplement, inflammatory myopathy with muscle weakness and elevated creatine kinase occurred. The condition resolved with corticosteroid and cyclophosphamide treatment (75936). In another case report, an 82 year-old woman developed a blistering skin condition over a 2-year period while taking spirulina blue-green algae (A. platensis, dose unknown). She had partly hemorrhagic bullae, secreting erosions and macerations. These symptoms resolved when the supplement was stopped and the patient was treated with oral prednisone, topical silver sulfadiazine, and topical triamcinolone / neomycin (75921).
Gastrointestinal ...Orally, gastrointestinal complaints are amongst the most common adverse effects associated with spirulina blue-green algae, including nausea, vomiting, diarrhea, and abdominal cramps (19272,75924,91713,109969). Similarly, common adverse effects associated with the blue-green algae species Aphanizomenon flos-aquae are stomach upset, flatulence, diarrhea, and bloating (14842).
Hematologic ...Orally, three cases of mild gum bleeding and one case of mild bruising have been reported in patients taking spirulina blue-green algae (Cyactiv, Cerule LLC) 2. 3 grams daily (containing approximately 1 gram of phycocanin) for 2 weeks (97202).
Hepatic ...Orally, significant elevations of liver function tests within 2 weeks of starting a spirulina blue-green algae supplement (species and dose unknown) have been reported in a 52-year-old man stabilized on amlodipine, simvastatin, and acarbose. A biopsy showed feathery degeneration and ballooning of hepatic cells. Cholestasis was present, and an ex-vivo lymphocyte stimulation test for spirulina blue-green algae was positive. All drugs and the spirulina blue-green algae supplement were stopped, with return of the LFTs to normal (9172).
Immunologic
...Orally, urticarial rashes and pruritus have occurred as part of generalized allergic reactions to blue-green algae (91706,91711,91712).
In one case report, a 14-year-old male experienced anaphylaxis with urticaria, lip edema, and asthma 6 hours after taking five tablets of spirulina blue-green algae (A. platensis, strength unknown). He had a positive skin prick test. Oral challenge to an extract of the tablets, and IgE from his serum, reacted with the beta chain of C-phycocyanin from A. platensis (91712).
In another case report, a 17-year-old male with a history of multiple allergies developed rash, pruritus, angioedema, wheezing, and dyspnea within 10 minutes of taking spirulina blue-green algae (A. platensis) 300 mg. He had a positive skin test to A. platensis but no other ingredients of the tablets (91706).
Musculoskeletal ...Orally, after a 49-year-old woman stopped taking a spirulina blue-green algae supplement (species and dose unknown), the patient experienced inflammatory myopathy with muscle weakness and elevated creatine kinase. The condition resolved with corticosteroid and cyclophosphamide treatment (75936). Another case report describes acute rhabdomyolysis that occurred after consumption of spirulina (Arthrospira platensis, Hawaiian spirulina, Solgar Inc., Leonia, NJ) 3 grams daily for 1 month. The 24-year old man presented with weakness, myalgias, elevated creatine kinase and liver function tests, and myoglobinuria (75922).
General
...Orally and topically, calendula is generally well tolerated.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions.
Dermatologic ...Topically, a preparation containing calendula powder 0. 1% resulted in inflammation around the wound to which it was applied (96647). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of calendula, licorice, and snail secretion filtrate to the face. The specific role of calendula is unclear (110322).
Immunologic ...Orally, calendula can cause allergic reactions. Topically, calendula can cause eczematous allergic reactions. Calendula-specific patch testing is recommended prior to usage to determine allergenic potential. Testing is particularly necessary in individuals sensitive to the Asteraceae/Compositae family (10691,11458,96647). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. A preparation containing calendula powder 0.1% resulted in hives in a patient with a ragweed allergy (96647). Despite the widespread use of calendula and the occurrence of allergies to other family members, there has been only one report of anaphylaxis (11152).
General ...No adverse effects reported. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally and topically, DHEA seems to be well tolerated when used in typical doses, short-term.
However, there is some concern that long-term oral use of DHEA may be linked to a greater risk for cancer.
Most Common Adverse Effects:
Orally: Acne, headache, insomnia, mood changes, and nausea. In females, masculinization symptoms including deepening of the voice, increased size of genitals, irregular menses, oily skin, reduced breast size, and unnatural hair growth. In males, aggression, breast tenderness or enlargement (gynecomastia), urinary urgency, and testicular wasting.
Serious Adverse Effects (Rare):
Orally: Possible increased risk for cardiovascular events and various types of cancer.
Cardiovascular ...Incidences of arrhythmia (21334,47540), chest pain (21332,21333), palpitations (21332,21333,88492), hypertension, and transient ischemic attacks (21353,21354,47300) have been reported. DHEA has also been found to decrease high-density lipoprotein (HDL) levels (21344,21345,21346,21347,21348,21349) and increase triglycerides (21334).
Dermatologic ...Acne has been the most commonly reported adverse effect in human research, particularly in females (2113,2114,4242,7614,7559,12561,12574,21346,21351,21354)(21355,21356,21357,21358,21360,21361,21362,21363,21364,47300)(47355,47409,90304,103185). However, it is generally mild and may be treated by reducing the dose (7559). Incidences of contact dermatitis (47402), acneiform dermatitis (2113), greasy hair and skin (17218,21351,21355,21363,21387,21389,47355), keratosis (47402), skin rash (12574,21361,21363), erythema (21334), scalp itching (17218,21357), and skin spots (21387) have also been reported. Increased hair growth and hirsutism have been noted in several clinical trials, including the development of mild mustache in females (2114,4242,12561,12574,17218,21346,21351,21354,21355,21358) (21361,21362,21363,21370,21387,21389,21415,47300). Increased perspiration and odor have also been reported in human research (17218,21354,21356,21357).
Endocrine ...In postmenopausal patients, high doses of DHEA (1600 mg daily) induced insulin resistance, reportedly due to increased androgen levels that occurred during supplementation (21324).
Gastrointestinal ...Gastrointestinal disturbances such as nausea, diarrhea, and abdominal discomfort have been noted in human research (2111,6098,7559,12574,21348,21358,21386).
Genitourinary ...In older adults, elevated and severe urinary symptoms (as evidenced by scores of more than 20, using the American Urological Association Symptom Index for Benign Prostatic Hyperplasia [International Prostate Symptom Score]) and urinary tract infection were reported (21353). Rare incidences of abnormal menses (2114) and increased discharge (21415) have been reported. DHEA has been associated with hematuria (47300).
Hepatic ...Elevated liver enzymes have been reported following DHEA supplementation (21364,47300). However, an analysis of multiple studies in varied patient populations taking DHEA supplements found no elevations in liver enzymes (107791).
Musculoskeletal ...Incidences of asthenia, arthralgia, and myalgia, including calf cramps, have been reported (12574,21354,21358,21365,47355).
Neurologic/CNS ...In humans, dizziness, fatigue, malaise, sleep disturbances, increased dreaming, night sweats, restlessness, "painful spots," and a crawling scalp sensation have been reported (3865,21354,21363,21389). There is a case of seizure associated with DHEA use in a 30 year-old female with fragile X syndrome and no history of convulsive disorder who used DHEA to try to improve ovarian production (47344).
Ocular/Otic ...In patients with Sjögren syndrome, maculae lesions, ocular pain and dryness, and painful eye exams have been reported (21358,21363,21365).
Oncologic ...Preclinical research suggests that DHEA may increase the risk of cancer, particularly prostate, liver, breast, and pancreatic cancers (2111,10370,10401,10403,12565,21332,21333,21334,47251,47256)(47366,47388,47539). High concentrations of DHEA in postmenopausal patients have been associated with an increased risk of breast cancer (2115,6445).
Psychiatric ...DHEA-induced mania has been reported (5870,6102,7023,21383). Clinical studies have also reported anxiety, nervousness, irritability, emotional change, and depression in patients receiving DHEA (2114,21358,21360,21370).
Pulmonary/Respiratory ...Increased cough and nasal congestion have been noted in human research (3865,11334). A report of acute respiratory failure was made in clinical study evaluating the use of DHEA in patients with myotonic dystrophy (type 1) (21334).
Other ...Perceived increases in weight gain have been reported with use of DHEA (2114,21361).
General ...Orally, Ecklonia cava extract and Ecklonia cava polyphenols seem to be well tolerated.
Dermatologic ...Orally, alopecia has been reported by one person in a clinical trial (106335).
Gastrointestinal ...Orally, nausea, dyspepsia, and diarrhea have been reported by one person each in a clinical trial (106335).
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, ginkgo leaf extract is generally well tolerated when used for up to 6 years.
However, the seed and crude plant contain toxic constituents and should be avoided.
Intravenously, ginkgo leaf extract seems to be well tolerated when used for up to 30 days.
Topically, no adverse effects have been reported with ginkgo as a single ingredient. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Dizziness, gastrointestinal symptoms, headache.
Serious Adverse Effects (Rare):
Orally: Arrhythmia, bleeding, Stevens-Johnson syndrome.
Cardiovascular
...Cardiac arrhythmias suspected to be related to ginkgo have been reported.
Internationally, there are at least 162 reports from 18 countries, with 34% of cases considered serious, involving five deaths and four life-threatening events. Additionally, a report from Canada found that 10 out of 15 cases of arrhythmia were considered serious. Ginkgo was the only suspect ingredient in 57% of all international reports, with symptoms generally presenting within days of initiation. The most common symptoms included palpitations, tachycardia, bradycardia, syncope, and loss of consciousness. Most cases were reported to be related to oral use of ginkgo leaf products; however, some cases were associated with oral use of the seed, and others with intravenous or intramuscular use of the leaf. Documented discontinuation of ginkgo led to recovery in approximately 84% of cases where ginkgo was the sole suspect. Despite these findings, ginkgo cannot be confirmed as the causal agent. It is possible that these reports are confounded by underlying co-morbidities. Of the reported cases, the main reason for ginkgo use was tinnitus, a symptom commonly associated with pre-existing arrhythmias (105253,105254). Despite this large number of reports, only three cases of cardiac arrhythmia have been published in the literature (105253,105254). In one case, frequent nocturnal episodes of paroxysmal atrial fibrillation were reported for a 35-year-old female taking ginkgo extract 240 mg daily orally for 2 months. Arrythmias ceased following discontinuation of ginkgo (87884).
Increases in blood pressure were commonly reported with ginkgo in a safety database analysis; however, information on the magnitude of the increase was limited, and reports included both oral and intravenous administration (115628).
In one clinical trial, the rate of ischemic stroke and transient ischemic attacks was significantly higher in patients taking ginkgo extract orally when compared with placebo (16635). It is unclear if these events were due to ginkgo, other factors, or a combination.
Dermatologic ...Topically, ginkgo fruit pulp can cause contact dermatitis, with intense itching, edema, papules, and pustules which take 7-10 days to resolve after stopping contact (112946).
Gastrointestinal
...Orally, ginkgo extract may cause mild gastrointestinal discomfort or pain (3965,8543,17112,87818,87858), nausea and vomiting (8543,17112,87728,87844,87858), diarrhea (87844), dry mouth (17112), and constipation (5719,87787).
However, post-market surveillance suggests that the incidence of these events is relatively low, occurring in less than 2% of patients (88007).
Fresh ginkgo seeds can cause stomach ache, nausea, vomiting, or diarrhea. Ingesting roasted seeds in amounts larger than the normal food amounts of 8-10 seeds per day, or long-term, can also cause these same adverse reactions (8231,8232).
Genitourinary ...Orally, ginkgo extract has been reported to cause blood in the urine (87858,115628).
Hematologic
...Spontaneous bleeding is one of the most concerning potential side effects associated with ginkgo.
There are several published case reports linking ginkgo to episodes of minor to severe bleeding; however, not all case reports clearly establish ginkgo as the cause of bleeding. In most cases, other bleeding risk factors were also present including taking other medications or natural medicines, old age, liver cirrhosis, recent surgery, and other conditions. In most cases, bleeding occurred after several weeks or months of taking ginkgo (13135). Large-scale clinical trials and a meta-analysis evaluating standardized ginkgo leaf extracts show that the incidence of bleeding in patients taking ginkgo is not significantly higher than in those taking placebo (16634,16635,17179,17402).
There are several case reports of intracerebral bleeding. Some of these cases resulted in permanent neurological damage and one case resulted in death (244,578,8581,13135,13179,14456,87868,87977).
There are at least 4 cases of ocular bleeding including spontaneous hyphema (bleeding from the iris into the anterior part of the eye) and retrobulbar hemorrhage associated with ginkgo use (579,10450,13135).
There are also cases of surgical and post-surgical complications in patients using ginkgo. Retrobulbar hemorrhage (bleeding behind the eye) during cataract surgery has been associated with ginkgo use (10450). Excessive postoperative bleeding requiring transfusion has also occurred following laparoscopic surgery in a patient who had been taking ginkgo leaf extract (887). There have also been two cases of excessive bleeding during surgery and post-surgical hematoma in patients undergoing rhytidoplasty and blepharoplasty (13002). In another case, an elderly patient taking ginkgo experienced excessive postoperative bleeding following total hip arthroplasty (13194). In another case, use of ginkgo following liver transplantation surgery was associated with subphrenic hematoma requiring evacuation by laparotomy. The patient also subsequently experienced vitreous hemorrhage (14315). In another case, an elderly patient who had taken ginkgo chronically experienced excessive post-operative bleeding following an ambulatory surgical procedure (14453).
In another case, an elderly man experienced nose bleeds and ecchymosis following use of ginkgo. One case of diffuse alveolar hemorrhage in a female taking ginkgo and ginseng for over one year has been reported (95670). These instances of bleeding stopped when ginkgo was discontinued, and recurred when the patient started taking ginkgo again (13135).
Persistent bleeding has also occurred following dental surgery (87862) and laparoscopic cholecystectomy (88000). Nosebleed has also been reported as an adverse effect in a clinical trial (87813).
Immunologic ...Orally, ginkgo leaf extract can cause allergic skin reactions in some patients (14449,15578,112946). In one case, a patient developed acute generalized exanthematous pustulosis 48 hours after taking a single-ingredient ginkgo product. The rash resolved within 10 days after discontinuing ginkgo (14449). In another case, progressive erythema of the face, neck, trunk, and extremities occurred after two 60 mg oral doses of ginkgo extract (112946). There is also a case of Stevens-Johnson syndrome following a second administration of a preparation containing ginkgo leaf extract, choline, vitamin B6, and vitamin B12 (208). In another case, systemic edema and severe arthralgia was reported after contact with a ginkgo tree nut and manifested as multifocal lymphadenopathy associated with an allergic reaction on PET/CT scan imaging (95672).
Musculoskeletal ...Edema has been reported for three patients treated with ginkgo extract 40 mg orally three times daily (87818).
Neurologic/CNS ...Orally, ginkgo extract may cause headache (6220,8543,87818), dizziness (5719,87818), increased desire to sleep (87839,115628), and sedation (10893) in some patients. In addition, although ginkgo leaf and ginkgo leaf extract contain only small amounts of ginkgotoxin, there are anecdotal reports of seizure occurring after use of ginkgo leaf preparations both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090,11296,14281).
Ocular/Otic
...Orally, ginkgo may cause tinnitus is some patients (8543,115628).
Topically, eye drops containing ginkgo extract and hyaluronic acid may cause stinging sensations in some people (87829).
Psychiatric ...Orally, ginkgo has been associated with a single case of mood dysregulation. A 50-year-old female with schizophrenia developed irritability, difficulty controlling anger, and agitation after one week of taking ginkgo 80 mg twice daily. The mood changes resolved within 2-3 days of discontinuation. When ginkgo was re-trialed at a later date, the same symptoms reappeared, and again dissipated after discontinuation of the ginkgo product. The relationship between ginkgo and mood dysregulation was considered to be "probable" based on the Naranjo adverse drug reaction probability scale (96763); however, the exact mechanism by which ginkgo may have affected mood regulation is unknown.
General
...Orally, goji fruit seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Allergic reactions including anaphylaxis.
Dermatologic ...A case of photosensitivity secondary to consumption of goji berries has been reported. The patient presented with a pruriginous eruption that had lasted for 2 weeks. The patient had been taking goji berries for 5 months and cat's claw for 3 months. Upon testing, it was revealed that the patient tested positive to goji berries in a photoprovocation test, but not to cat's claw (40263).
Hepatic ...Orally, consumption of goji berries has been associated with a single case report of autoimmune hepatitis (52541). A case of acute hepatitis has also been reported in a female who consumed 2 ounces of a specific combination product (Euforia, Nuverus International) containing goji berry, pomegranate, curcumin, green tea, noni, acai berry, aloe vera, blueberry, resveratrol, mangosteen, and black seed, daily for one month. It is unclear whether the liver injury was caused by goji berry, other ingredients, or the combination (90125).
Immunologic ...Several cases of allergic reactions secondary to consumption of goji berries have been reported. Symptoms included facial angioedema with dyspnea, pharyngeal itching, itching in the mouth, ears, and axilla, labial angioedema, and perioral skin rash (92116). Anaphylaxis has also been reported (52538).
General
...Orally, the whole fruit, as well as the seed, fruit, and leaf extracts, seem to be well tolerated.
Topically, grape seed extracts seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, dry mouth, dyspepsia, headache, joint pain, and nausea.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to grape skin has been reported.
Dermatologic ...Orally, mild hair thinning has been reported in a patient taking a specific grape leaf extract AS195 KG) (2538). Urticaria (hives) has also been reported with this same extract (53206). Cases of contact dermatitis have been reported in grape workers, including those working in California vineyards (53270,53272,53275).
Gastrointestinal ...Orally, abdominal pain and nausea have been reported with use of grape seed extract, but these effects typically occur at rates similar to placebo (9182,13162). In a case report of a 57-year-old man, intermittent nausea, vomiting, and diarrhea occurred over a 10-day period and improved once grape seed extract was stopped (96764). Gastrointestinal adverse effects have also been reported with use of a different grape seed extract (Entelon, Hanlim Pharm). However, the specific types of gastrointestinal effects were not described (100954). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused flatulence, mild constipation, gastrointestinal discomfort, diarrhea, dyspepsia, dry mouth, and retching (2538,52985,53206). Diarrhea, gastrointestinal distress, indigestion, and aversion to taste have been reported with use of Concord grape juice (52972,53166,53175,53181,53199). Loose stools have been reported in a clinical trial of grape pomace (99270). Bowel obstruction caused by intact grapes and grape seeds has been described in case reports (53241,53284,53278). Excessive consumption of grapes, dried grapes, raisins, or sultanas might cause diarrhea due to laxative effects (4201).
Hematologic ...Orally, one case of leg hematoma following a minor trauma was reported in a person using grape leaf extract (2538). Also, one case of bruising was reported in a person drinking Concord grape juice daily for 2 weeks (52972).
Immunologic ...Orally, there is one report of an anaphylactic reaction to oral grape skin extract, which included urticaria and angioedema (4073).
Musculoskeletal ...Orally, musculoskeletal disorders, including back pain, have been reported with use of a specific grape leaf extract AS195 KG) (2538,53206). Joint pain and lumbago have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (91541).
Neurologic/CNS ...Orally, headache has been reported with use of grape seed extract, but this effect occurs at rates similar to placebo (9182,91541). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused dizziness, tiredness, headache, and sleep problems (2538,53206). As a class, nervous system adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of adverse neurologic effects were not described (100954).
Ocular/Otic ...Orally, ocular adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of ocular adverse effects were not described (100954).
Pulmonary/Respiratory ...Orally, nasopharyngitis and oropharyngeal pain have been reported with use of a specific grape leaf extract AS195 KG) (53206). Sore throat, cough, allergic rhinitis, and nasopharyngitis have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (9182,91541). One case report describes a 16-year-old female who developed increased levels of immunoglobulin E (IgE) following skin-prick exposure to grape vine pollen, as well as positive test responses following bronchial and conjunctival provocation (53301). Reduced forced vital capacity has been described in California grape workers (53080,53081). Occupational eosinophilic lung was diagnosed in a grape grower with a history of asthma. Respiratory exposure to sulfites in grape was implicated as the cause of the adverse reaction (53285).
Other
...Orally, grape products can cause adverse effects due to contamination with pesticides or mycotoxins.
Some evidence has shown that pesticides used in vineyards may remain on grape surfaces post-harvesting. For example, the fungicide folpet sprayed on grapevines has been shown to remain on the grape surface. Although there was minimal penetration of the epicuticular wax, it showed high resistance to washing (52935). Carbaryl has been identified in over 58% of juice samples collected in Canada. This pesticide reportedly occurred more frequently in grape than in other juices. However, estimates of short-term intake were below proposed acute reference doses (53003).
Ochratoxin A is a mycotoxin that is suspected to be nephrotoxic, teratogenic, hepatotoxic and carcinogenic and has been identified in grape juice, frozen grape pulps, and red and white wine sold in Rio de Janeiro, Brazil. However, the highest levels identified in grape products were lower than the established virtually safe dose of 5 ng/kg of body weight daily (53010,53004). Ochratoxin A has also been identified in red, but not white, grape juice marketed in Switzerland, Canada, and the U.S. (53292,53020).
General
...Orally, green tea is generally well tolerated when consumed as a beverage in moderate amounts.
Green tea extract also seems to be well tolerated when used for up to 12 months.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, dyspepsia, flatulence, and nausea.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity, hypokalemia, and thrombotic thrombocytopenic purpura have been reported rarely.
Cardiovascular
...Acute or short-term oral administration of green tea may cause hypertension (53719,54014,54065,54076,102716).
The risk may be greater for green tea products containing more than 200 mg epigallocatechin gallate (EGCG) (90161). However, consumption of brewed green tea does not seem to increase blood pressure or pulse, even in mildly hypertensive patients (1451,1452). In fact, some evidence suggests that habitual tea consumption is associated with a reduced risk of developing hypertension (12518). Also, epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension or with cardiovascular disease mortality in patients with hypertension (13739,111027). Rarely, green tea consumption may cause hypotension (53867).
Epidemiological research suggests that regular caffeine intake of up to 400 mg per day, or approximately 8 cups of green tea, is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, and temporary loss of consciousness has been associated with the combined use of ephedra and caffeine (2729). There is also a report of ischemic stroke in an athlete who consumed ephedra 40-60 mg, creatine monohydrate 6 grams, caffeine 400-600 mg, and a variety of other supplements daily for 6 weeks (1275). In theory, combining caffeinated green tea with ephedra would have similar effects.
In a case report, the EGCG component of a specific weight loss supplement (Hydroxycut) was thought to be responsible for atrial fibrillation (54028). The patient was given two doses of intravenous diltiazem and was loaded with intravenous digoxin. Thirty-six hours after the last product dose, she spontaneously converted to normal sinus rhythm. The authors suggested that the block of the atrial-specific KCNA5 potassium channel likely played a role in this response.
A case of thrombotic thrombocytopenic purpura has been reported for a patient who consumed a weight loss product containing green tea (53978). She presented at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. Twelve procedures of plasmapheresis were performed, and corticosteroid treatment was initiated. She was discharged after 20 days.
Dermatologic ...Orally, green tea may cause skin rashes or skin irritation (53731,54038,90161,90187,102716). Topically, green tea may cause local skin reactions or skin irritation, erythema, burning, itching, edema, and erosion (53731,54018,97136,104609,111031). A green tea extract ointment applied to the cervix can cause cervical and vaginal inflammation, vaginal irritation, and vulval burning (11310,36442,36438). When applied to external genital or perianal warts, a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins can cause erythema, pruritus, local pain, discomfort and burning, ulceration, induration, edema, and vesicular rash (15067,53907).
Endocrine
...There is some concern that, due to its caffeine content, green tea may be associated with an increased risk of fibrocystic breast disease, breast cancer, and endometriosis.
However, this is controversial since findings are conflicting (8043). Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996).
A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages, such as green tea, and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
A case of hypoglycemia has been reported for a clinical trial participant with type 2 diabetes who used green tea in combination with prescribed antidiabetes medication (54035).
Gastrointestinal ...Orally, green tea beverage or supplements can cause nausea, vomiting, abdominal bloating and pain, constipation, dyspepsia, reflux, morning anorexia, increased thirst, flatulence, and diarrhea. These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,36398,53719,53867,53936,54038,54076,90139,90140)(90161,90175,90187,97131,97136,102716).
Hepatic
...There is concern that some green tea products, especially green tea extracts, can cause hepatotoxicity in some patients.
In 2017, the regulatory agency Health Canada re-issued a warning to consumers about this concern. The updated warning advises patients taking green tea extracts, especially those with liver disease, to watch for signs of liver toxicity. It also urges children to avoid taking products containing green tea extracts (94897). In 2020, the United States Pharmacopeia (USP) formed an expert panel to review concerns of green tea extract-related hepatotoxicity. Based on their findings, USP determined that any products claiming compliance with USP quality standards for green tea extract must include a specific warning on the label stating "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)" (102722).
Numerous case reports of hepatotoxicity, primarily linked to green tea extract products taken in pill form, have been published. A minimum of 29 cases have been deemed at least probably related to green tea and 38 have been deemed possibly related. In addition, elevated liver enzymes have been reported in clinical research (14136,15026,53740,53746,53775,53859,54027,90139,90162,90164)(93256,94898,94899,102716,102720,102722,107158,111020,111644). Most cases of toxicity have had an acute hepatitis-like presentation with a hepatocellular-elevation of liver enzymes and some cholestasis. Onset of hepatotoxic symptoms usually occurs within 3 months after initiation of the green tea extract supplement, and symptoms can persist from 10 days to 1 year (95439,94897,94898,107158). Some reports of hepatotoxicity have been associated with consumption of green tea-containing beverages as well (15026,53742,54016,90125,90143).
In most cases, liver function returned to normal after discontinuation of the green tea product (14136,15026,53859,93256,107158). In one case, use of a specific ethanolic green tea extract (Exolise, Arkopharma) resulted in hepatotoxicity requiring a liver transplant. Due to concerns about hepatotoxicity, this specific extract was removed from the market by the manufacturer (14310). Since then, at least 5 cases of liver toxicity necessitating liver transplantation have been reported for patients who used green tea extracts (94898,107158). In another case, use of green tea (Applied Nutrition Green Tea Fat Burner) in combination with whey protein, a nutritional supplement (GNC Mega Men Sport), and prickly pear cactus resulted in acute liver failure (90162).
Despite the numerous reports of hepatotoxicity associated with the use of green tea products, the actual number of hepatotoxicity cases is low when the prevalence of green tea use is considered. From 2006 to 2016, liver injury from green tea products was estimated have occurred in only 1 out of 2.7 million patients who used green tea products (94897,95440).
In addition to the fact that green tea hepatotoxicity is uncommon, it is also not clear which patients are most likely to experience liver injury (94897,95440). The hepatotoxicity does not appear to be an allergic reaction or an autoimmune reaction (94897). It is possible that certain extraction processes, for example, ethanolic extracts, produce hepatotoxic constituents. However, in most cases, the presence of contaminants in green tea products has not been confirmed in laboratory analyses (90162).
Although results from one analysis of 4 small clinical studies disagrees (94899), most analyses of clinical data, including one conducted by the European Food Safety Association, found that hepatotoxicity from green tea products is associated with the dose of EGCG in the green tea product. Results show that daily intake of EGCG in amounts greater than or equal to 800 mg per day is associated with a higher incidence of elevated liver enzymes such as alanine transaminase (ALT) (95440,95696,97131). However, it is still unclear what maximum daily dose of EGCG will not increase liver enzyme levels or what minimum daily dose of EGCG begins to cause liver injury. In many cases of liver injury, the dose of green tea extract and/or EGCG is not known. Therefore, a minimum level of green tea extract or EGCG that would cause liver injury in humans cannot be determined (102722). Keep in mind that daily intake of green tea infusions provides only 90-300 mg of EGCG daily. So for a majority of people, green tea infusions are likely safe and unlikely to cause liver injury (95696). Also, plasma levels of EGCG are increased when green tea catechins are taken in the fasting state, suggesting that green tea extract should be taken with food (102722).
Until more is known, advise patients that green tea products, especially those containing green tea extract, might cause liver damage. However, let them know that the risk is uncommon, and it is not clear which products are most likely to cause the adverse effect or which patients are most likely to be affected. Advise patients with liver disease to consult their healthcare provider before taking products with green tea extract and to notify their healthcare provider if they experience symptoms of liver damage, including jaundice, dark urine, sweating, or abdominal pain (102722).
Immunologic ...Orally, matcha tea has resulted in at least one case of anaphylaxis related to green tea proteins. A 9-year-old male experienced systemic redness and hives, nausea, and anaphylaxis 60 minutes after consuming matcha tea-flavored ice cream (107169). The caffeine found in green tea can also cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Orally, the ingestion of the green tea constituent epigallocatechin gallate (EGCG) or a decaffeinated green tea polyphenol mixture may cause mild muscle pain (36398).
There is some concern regarding the association between caffeinated green tea products and osteoporosis. Epidemiological evidence regarding the relationship between caffeinated beverages such as green tea and the risk for osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake of less than 400 mg per day, or about 8 cups of green tea, doesn't seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).
Neurologic/CNS
...Orally, green tea can cause central nervous system stimulation and adverse effects such as headache, anxiety, dizziness, insomnia, fatigue, agitation, tremors, restlessness, and confusion.
These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,53719,90139,102716). The green tea constituent epigallocatechin gallate (EGCG) or decaffeinated green tea may also cause mild dizziness and headache (36398).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, temporary loss of consciousness, and hospitalization requiring life support has been associated with the combined use of ephedra and caffeine (2729).
Topically, green tea extract (Polyphenon E ointment) may cause headache when applied to the genital area (36442).
Psychiatric ...Green tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, and psychological dependence (11832). The existence or clinical importance of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance (11839). Other researchers suggest symptoms such as headache; tiredness and fatigue; decreased energy, alertness, and attentiveness; drowsiness; decreased contentedness; depressed mood; difficulty concentrating; irritability; and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms such as delirium, nausea, vomiting, rhinorrhea, nervousness, restlessness, anxiety, muscle tension, muscle pains, and flushed face have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Pulmonary/Respiratory ...A case of granulomatous alveolitis with lymph follicles has been reported for a 67-year-old female who used green tea infusions to wash her nasal cavities for 15 years (54088). Her symptoms disappeared 2 months after stopping this practice and following an undetermined course of corticosteroids. In a case report, hypersensitivity pneumonitis was associated with inhalation of catechin-rich green tea extracts (54025). Occupational exposure to green tea dust can cause sensitization, which may include nasal and asthmatic symptoms (11365).
Renal ...There are two cases of hypokalemia associated with drinking approximately 8 cups daily of green tea in an elderly couple of Asian descent. The hypokalemia improved after reducing their intake by 50%. It is possible that this was related to the caffeine in the green tea (98418).
Other ...Orally, intake of a specific green tea extract product (Polyphenon E) may cause weight gain (90139).
General
...Orally, MSM is generally well tolerated.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, gastrointestinal discomfort, nausea.
Dermatologic ...In rare cases, MSM has caused pruritus when taken orally (8574).
Gastrointestinal ...Orally, MSM may cause mild gastrointestinal discomfort, nausea, bloating, and diarrhea (8574,12469).
Immunologic ...Orally, MSM may increase allergy symptoms (8574).
Neurologic/CNS ...Orally, MSM may cause headache, fatigue, insomnia, and difficulty concentrating (8574,14335).
Ocular/Otic ...In a case report, a 35-year-old female presented with bilateral acute angle closure glaucoma, which resolved 4 days after discontinuing a multi-ingredient product. Although the product contained over 35 vitamins, minerals, and other ingredients, only MSM contained sulfur, which the authors suggest acted like a sulfa-drug to cause acute angle closure glaucoma (90613).
General
...Orally, pregnenolone is generally well tolerated.
Most Common Adverse Effects:
Orally: Acne, agitation, diarrhea, drowsiness, excitement, hair loss, skin abscess, sweating, tremor.
Cardiovascular ...A case of palpitations has been reported after oral use of pregnenolone (94031).
Dermatologic ...Orally, pregnenolone has been reported to cause skin abscesses, acne, and hair loss (94027,94031). A case of skin rash accompanied by a burning sensation on the back and sides of the hands has also been reported with oral pregnenolone use, possibly related to a photosensitivity reaction. The rash cleared on its own (94031).
Gastrointestinal ...Orally, pregnenolone may cause diarrhea. Constipation has also been reported after oral use; however, it is not certain if this effect was due to pregnenolone (94026).
Musculoskeletal ...A case of muscle pain/stiffness has been reported after oral use of pregnenolone (94032).
Neurologic/CNS ...Orally, pregnenolone has been reported to cause restlessness, tiredness, sweating, and a case of cold extremities (94026,94032). Sleep problems, drowsiness, and tremor have also been reported; however, it not certain if these effects were due to pregnenolone (94026,94031).
Psychiatric ...Orally, pregnenolone has been reported to cause depressive affect and increased appetite (94026,94031). Increased excitement, agitation, increased motor activity, and anorexia have also been reported; however, it is not certain if these effects were due to pregnenolone (94026).
Pulmonary/Respiratory ...A case of sinusitis has been reported after oral use of pregnenolone (94027).
General
...Roman chamomile is generally well tolerated.
Most Common Adverse Effects:
Topically: Allergic skin reactions.
Dermatologic ...Topically, Roman chamomile can cause contact dermatitis (4,567,97292). Allergic skin reactions can occur in up to 20% of individuals exposed to Roman chamomile (19). Multiple case reports have described the development of topical allergic reactions, including eczema and rash, with the use of cleaning products and cosmetics containing chamomile oil or chamomile extract (97292). In one case report, a 55-year-old man experienced disseminated erythroderma with itchy, scaly lesions after non-contact exposure to an area containing many plant varieties. Patch testing confirmed the presence of allergenicity to Roman chamomile (97292).
Gastrointestinal ...Orally, large amounts of Roman chamomile might cause vomiting, although data are conflicting (11,12).
Immunologic ...Allergic skin reactions can occur in up to 20% of individuals exposed to Roman chamomile (19). Cross-sensitivity can occur in individuals with sensitivity to the Asteraceae/Compositae family (19,97292). Multiple case reports have described the development of topical and respiratory allergic reactions with the use of cleaning products and cosmetics containing chamomile oil or chamomile extract (97292).
Pulmonary/Respiratory ...A case report describes the development of cough and rhinitis in a 20-year-old female after exposure to chamomile-scented toilet paper. Skin prick testing confirmed the presence of allergenicity to the toilet paper product (97292).
General ...Orally, rose geranium oil is well tolerated when used in food amounts. Topically, rose geranium oil seems to be well tolerated, short-term.
Dermatologic ...Topically, rose geranium oil has been associated with reports of dermatitis in hypersensitive individuals and burning sensations when applied to the face (16653).
Gastrointestinal ...When applied with droppers in the nose, rose geranium oil has been reported to cause a bad taste (93881).
Neurologic/CNS ...Topically, rose geranium oil has been associated with reports of lightheadedness and eye irritation when applied to the face (16653).
Ocular/Otic ...Topically, rose geranium oil has been associated with reports of eye irritation when applied to the face (16653).
General
...Orally, topically, and when inhaled, sage seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, agitation, diarrhea, dizziness, nausea, and vomiting.
Topically: Burning, dermatitis, pain.
Serious Adverse Effects (Rare):
Orally: Generalized tonic-clonic seizures associated with the thujone, camphor, and/or cineol constituents.
Cardiovascular ...By inhalation, sage essential oil has been reported to increase the blood pressure of hypertensive patients (10334).
Dermatologic
...Orally, sage extract has been reported to cause acneiform skin eruptions in one patient in a clinical trial (91970).
Topically, sage leaves can cause contact dermatitis (46902,72661,72710). Sage extract can cause burning and pain (10437).
Gastrointestinal
...Orally, sage can cause nausea, vomiting, abdominal pain, and diarrhea (10810,17177).
Topically, sage extract sprayed into the mouth and throat can cause dryness or mild burning of the throat (72619).
Neurologic/CNS ...Orally, sage can cause dizziness or agitation (10810,17177). Thujone, a constituent of common sage (Salvia officinalis), is a neurotoxin and can cause seizures (10812,12868). Camphor and cineol, constituents of common sage and Spanish sage, can also cause neurotoxicity and seizures in high doses (10334,12868). Generalized tonic-clonic seizures have been reported in adults, children, and infants after ingestion of sage oil (12868,72666).
Pulmonary/Respiratory
...Orally, sage can cause wheezing (10810,17177).
Occupational exposure to sage dust can cause reduction in ventilatory capacity and chronic respiratory impairment (72672,72682,72686).
General
...Orally, St.
John's wort is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dizziness, dry mouth, gastrointestinal discomfort (mild), fatigue, headache, insomnia, restlessness, and sedation.
Topically: Skin rash and photodermatitis.
Serious Adverse Effects (Rare):
Orally: There have been rare case reports of suicidal ideation and psychosis after taking St. John's wort.
Cardiovascular
...In clinical research, palpitations have been reported for patients taking St.
John's wort orally, although the number of these events was higher for the patients taking sertraline (76070). In one case report, an adult female developed recurrent palpitations and supraventricular tachycardia (SVT) within 3 weeks of initiating St. John's wort 300 mg daily. SVT and related symptoms responded to Valsalva maneuvers and did not recur after discontinuing therapy (106051).
Edema has also been reported in clinical research for some patients treated with St. John's wort 900-1500 mg daily for 8 weeks (10843). Cardiovascular collapse following induction of anesthesia has been reported in an otherwise healthy patient who had been taking St. John's wort for 6 months (8931). A case of St. John's wort-induced hypertension has been reported for a 56-year-old patient who used St. John's wort extract 250 mg twice daily for 5 weeks. Blood pressure normalized after discontinuation of treatment (76073). A case of new-onset orthostatic hypotension and light-headedness has been reported for a 70 year-old homebound patient who was taking multiple prescription medications and herbal products, including St. John's wort (76128). When all herbal products were discontinued, these symptoms improved, and the patient experienced improvement in pain control.
Dermatologic
...Both topical and chronic oral use of St.
John's wort can cause photodermatitis (206,620,758,4628,4631,6477,13156,17986,76072,76148)(95506,110318). The average threshold dose range for an increased risk of photosensitivity appears to be 1.8-4 grams St. John's wort extract or 5-10 mg hypericin, daily. Lower doses might not cause this effect (4542,7808). For example, a single dose of St. John's wort extract 1800 mg (5.4 mg hypericin) followed by 900 mg (2.7 mg hypericin) daily does not seem to produce skin hypericin concentrations thought to be high enough to cause phototoxicity (3900,4542,76266). Females appear to have a higher risk of dose-related photosensitivity. In a dose-ranging, small clinical trial, almost all of the female participants experienced mild to moderate photosensitivity with paresthesia in sun-exposed skin areas after administration of St. John's wort (Jarsin, Casella Med) 1800 mg daily for 3-6 days. Symptoms resolved about 12-16 days after discontinuation (95506). Male participants reported no adverse effects at this dose, and both genders reported no adverse effects at lower doses. Light or fair-skinned people should employ protective measures against direct sunlight when using St. John's wort either topically or orally (628).
Total body erythroderma without exposure to sunlight, accompanied by burning sensation of the skin, has also been reported (8930). Orally, St. John's wort may cause pruritus or skin rash, although these events seem to occur infrequently (76140,76148,76245). A case of persistent scalp and eyebrow hair loss has been reported for a 24-year-old schizophrenic female who was taking olanzapine plus St. John's wort 900 mg/day orally (7811). Also, a case of surgical site irritation has been reported for a patient who applied ointment containing St. John's wort (17225).
Endocrine ...A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 67-year-old male with depression has been reported. During a 3-month period, the patient was taking St. John's wort 300 mg daily then increased to 600-900 mg daily with no adverse effects despite a low serum sodium level of 122mEq/L, elevated levels of urine sodium, and urine osmolality suggestive of SIADH. St. John's wort appeared to be the only contributing factor. The patient's sodium level normalized 3 weeks after discontinuation of St. John's wort (95508).
Gastrointestinal ...Orally, St. John's wort may cause dyspepsia, anorexia, diarrhea, nausea, vomiting, and constipation, although these events seems to occur infrequently (4897,13021,17986,76070,76071,76113,76146,76150,76271).
Genitourinary
...Orally, St.
John's wort can cause intermenstrual or abnormal menstrual bleeding (1292,76056). However, this effect has occurred in patients who were also taking an oral contraceptive. Changes in menstrual bleeding might be the result of a drug interaction (1292,76056). Also, St. John's wort has been associated with anorgasmia and frequent urination when used orally (10843,76070).
Sexual dysfunction can occur with St. John's wort, but less frequently than with SSRIs (10843). A case of erectile dysfunction and orgasmic delay has been reported for a 49-year-old male after taking St. John's wort orally for one week. Co-administration of sildenafil 25-50 mg prior to sexual activity reversed the sexual dysfunction. Previously, the patient had experienced orgasmic delay, erectile dysfunction, and inhibited sexual desire when taking a selective serotonin reuptake inhibitor (sertraline) (4836).
Hepatic ...A case of acute hepatitis with prolonged cholestasis and features of vanishing bile duct syndrome has been reported for a patient who used tibolone and St. John's wort orally for 10 weeks (76135). A case of jaundice with transaminitis and hyperbilirubinemia has been reported for a 79 year-old female who used St. John's wort and copaiba (95505). Laboratory values normalized 7 weeks after discontinuation of both products.
Musculoskeletal ...Orally, St. John's wort may cause muscle or joint stiffness, tremor, muscle spasms, or pain, although these events appear to occur rarely (76070).
Neurologic/CNS ...St. John's wort may cause headache, dizziness, fatigue, lethargy, or insomnia (5096,13021,76070,76071,76113,76132,76133,76150,89666). Isolated cases of paresthesia have been reported for patients taking St. John's wort (5073). A case of subacute toxic neuropathy has been reported for a 35-year-old female who took St. John's wort 500 mg daily orally for 4 weeks (621).
Ocular/Otic ...There is concern that taking St. John's wort might increase the risk of cataracts. The hypericin constituent of St. John's wort is photoactive and, in the presence of light, may damage lens proteins, leading to cataracts (1296,17088). In population research, people with cataracts were significantly more likely to have used St. John's wort compared to people without cataracts (17088). Ear and labyrinth disorders have been possibly attributed to use of St. John's wort in clinical research, although these events rarely occur (76120).
Psychiatric
...St.
John's wort can induce hypomania in depressed patients and mania in depressed patients with occult bipolar disorder (325,3524,3555,3568,10845,76047,76064,76137,110318). Cases of first-episode psychosis have been reported for females who used St. John's wort orally. In both cases, symptoms resolved following discontinuation of St. John's wort and treatment with antipsychotics for several weeks (13015,89664). Also, psychosis and delirium have been reported for a 76-year-old female patient who used St. John's wort for 3 weeks. The patient may have been predisposed to this effect due to undiagnosed dementia (76270). Restlessness, insomnia, panic, and anxiety have been noted for some patients taking St. John's wort orally (5073,13156,76070,76132,76268,76269,89665).
In isolated cases, St. John's wort has been associated with a syndrome consisting of extreme anxiety, confusion, nausea, hypertension, and tachycardia. These symptoms may occur within 2-3 weeks after it is started, in patients with no other predisposing factors. This syndrome has been diagnosed as the serotonin syndrome (6201,7811,110318). In one case, the symptoms began after consuming tyramine-containing foods, including aged cheese and red wine (7812). In an isolated case, a 51-year-old female reported having had suicidal and homicidal thoughts for 9 months while taking vitamin C and a St. John's wort extract. Symptoms disappeared within 3 weeks of discontinuing treatment (76111). A case of decreased libido has been reported for a 42-year-old male with mood and anxiety disorders who had taken St. John's wort orally for 9 months (7312).
St. John's wort has been associated with withdrawal effects similar to those found with conventional antidepressants. Headache, nausea, anorexia, dry mouth, thirst, cold chills, weight loss, dizziness, insomnia, paresthesia, confusion, and fatigue have been reported. Withdrawal effects are most likely to occur within two days after discontinuation but can occur one week or more after stopping treatment in some people. Occurrence of withdrawal symptoms may not be related to dose or duration of use (3569,11801).
Pulmonary/Respiratory ...Orally, St. John's wort may cause sore throat, swollen glands, laryngitis, sinus ache, sweating, and hot flashes, although the frequency of these events appears to be similar to placebo (76150).
Renal ...Orally, St. John's wort has been associated with a case report of acute kidney failure in a 46-year-old female after one dose of homemade St. John's wort tea. Three sessions of hemodialysis were required before there was full recovery (106741). However, causality is unclear since the patient had also been taking diclofenac intermittently for a month prior to developing kidney failure.
Other ...Sjogren's syndrome has been reported in a patient taking herbal supplements including St. John's wort, echinacea, and kava. Echinacea may have been the primary cause, because Sjogren's syndrome is an autoimmune disorder. The role of St. John's wort in causing this syndrome is unclear (10319).
General
...Orally and intravaginally, yarrow seems to be well tolerated.
Most Common Adverse Effects:
Topically: Dermatitis.
Dermatologic
...Topically, yarrow can cause atopic or allergic dermatitis or urticaria due to its sesquiterpene lactone content (52558,68385,77007).
Yarrow has also been reported to cause phototoxic and photo-allergic dermatitis and airborne contact dermatitis (68385).
Intravaginally, aggravated facial acne was reported by 1 of 40 patients in a clinical trial (105360).
Endocrine ...Intravaginally, an early menses was reported by 1 of 40 patients in a clinical trial (105360).
Genitourinary ...Intravaginally, aggravated vaginal pruritus and dryness were reported by 1 of 40 patients in a clinical trial (105360).
Immunologic ...Topically, yarrow can cause atopic or allergic dermatitis or urticaria due to its sesquiterpene lactone content (52558,68385,77007,96911). It has also been reported to cause phototoxic and photo-allergic dermatitis and airborne contact dermatitis (68385). In one 44-year-old female, handling yarrow flowers resulted in rhinitis and asthma (96911).
General
...There is currently a limited amount of information on the adverse effects of ylang ylang oil.
A thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Topically: Dermatitis, pruritus.
Dermatologic ...Topically, ylang ylang oil in combination with other herbs can cause localized pruritus (13483).
Immunologic ...Topically, ylang ylang oil in combination with other herbs has caused contact dermatitis in various case reports (98615).
