Ingredients | Amount Per Serving |
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(Stevia rebaudiana )
(leaf)
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7 mg |
(DHEA)
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5 mg |
(Citricidal spp. )
(Seed)
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350 mcg |
purified Water, castor oil, Polysorbate 60, Natural flavors, Benzyl Alcohol, Sorbitan Stearate, potassium sorbate Note: as preservatives, Lecithin (Form: Soy), Xanthan Gum, disodium EDTA Note: preservative
Below is general information about the effectiveness of the known ingredients contained in the product BioSom. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product BioSom. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. 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.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Grapefruit has Generally Recognized as Safe status (GRAS) in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes. A grapefruit seed extract has been safely used in clinical research (5866). In addition, capsules containing grapefruit pectin 15 grams daily have been used in clinical research for up to 16 weeks (2216).
POSSIBLY UNSAFE ...when used orally in excessive amounts. Preliminary population research shows that consuming a quarter or more of a whole grapefruit daily is associated with a 25% to 30% increased risk of postmenopausal breast cancer (14858). Grapefruit juice is thought to reduce estrogen metabolism resulting in increased endogenous estrogen levels. More evidence is needed to validate this finding.
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of using medicinal amounts of grapefruit during pregnancy and lactation; avoid using.
LIKELY SAFE ...when certain stevia constituents, including stevioside and rebaudiosides A, D, and M, are used orally as sweeteners in foods. These constituents have generally recognized as safe (GRAS) status in the US for this purpose (16699,16700,16702,16705,16706,108049). The stevia constituent stevioside has been safely used in doses of up to 1500 mg daily for 2 years (11809,11810,11811). There is insufficient reliable information available about the safety of whole stevia or stevia extracts when used orally. The European Food Safety Authority (EFSA) has determined that the acceptable intake of steviol glycosides is 4 mg/kg daily (106456); however, it is unclear how this relates to the use of whole stevia or stevia extract.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product BioSom. 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, DHEA might increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, DHEA might increase the risk of psychiatric adverse events when used with antidepressants.
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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.
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Theoretically, DHEA might interfere with the clinical effects of aromatase inhibitors.
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DHEA is a potent estrogen agonist, which may antagonize the anti-estrogen activity of aromatase inhibitors (10401).
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Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.
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Some preliminary evidence shows that DHEA may inhibit CYP3A4 (1389); however, the clinical significance of this potential interaction is not known.
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Theoretically, DHEA might increase the effects and adverse effects of estrogen therapy.
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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.
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Theoretically, DHEA might interfere with the anti-estrogen effects of fulvestrant.
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Theoretically, DHEA might interfere with the anti-estrogen effects of tamoxifen.
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Theoretically, DHEA might increase the effects and side effects of testosterone therapy.
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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.
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DHEA can increase blood levels of triazolam.
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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).
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DHEA might reduce the effectiveness of the tuberculosis vaccine.
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Animal research shows that high doses of DHEA can reduce the efficacy of the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine (21316).
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Grapefruit juice can decrease blood levels of acebutolol, potentially decreasing the clinical effects of acebutolol.
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Clinical research shows that grapefruit juice can modestly decrease acebutolol levels by 7% and reduce peak plasma concentration by 19% by inhibiting organic anion transporting polypeptide (OATP) (17603,18101). The acebutolol half-life is also extended by 1.1 hours when grapefruit juice is consumed concomitantly (18101). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction (17603,17604).
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Grapefruit juice can decrease blood levels of aliskiren, potentially decreasing the clinical effects of aliskiren.
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Clinical research shows that grapefruit juice can decrease aliskiren levels by approximately 60% by inhibiting organic anion transporting polypeptide (OATP) (91428). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction (17603,17604).
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Grapefruit juice can increase blood levels of amiodarone, potentially increasing the effects and adverse effects of amiodarone.
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Grapefruit juice might decrease blood levels of amprenavir, although this is not likely to be clinically significant.
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Some clinical research shows that grapefruit juice can slightly decrease amprenavir levels (17673); however, this is probably not clinically significant.
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Grapefruit juice can increase blood levels of oral artemether, potentially increasing the effects and adverse effects of artemether.
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Grapefruit juice might increase blood levels of some oral benzodiazepines, potentially increasing the effects and adverse effects of these drugs.
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Clinical research shows that grapefruit juice can increase plasma triazolam concentrations. Repeated consumption of grapefruit juice greatly increases triazolam concentrations and prolongs the half-life, probably due to inhibition of cytochrome P450 3A4 (CYP3A4) (7776,22118,22131,22133). Some studies show that grapefruit juice, particularly when taken in large quantities, reduces the clearance and increases the maximum blood levels, area under the plasma concentration curve (AUC), and duration of effect of midazolam. However, there is no effect on intravenous midazolam (4300,10159,11275,17601,22117,22119,16711,91427,95978). Grapefruit juice has also been shown to increase the maximum blood levels and duration of effect of diazepam, but the clinical significance of this is not known (3228). This interaction does not appear to occur with alprazolam (17674).
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Grapefruit juice can increase blood levels of blonanserin, potentially increasing the effects and adverse effects of blonanserin.
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Blonanserin is metabolized primarily by cytochrome P450 3A4 (CYP3A4). A small clinical study shows that taking grapefruit juice along with oral blonanserin increases exposure to blonanserin almost 6-fold due to inhibition of intestinal CYP3A4 by grapefruit juice and prolongs the elimination half-life of blonanserin by 2.2-fold due to inhibition of hepatic CYP3A4 by grapefruit juice (96943).
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Grapefruit juice can increase blood levels of budesonide, potentially increasing the effects and adverse effects of budesonide.
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Budesonide is metabolized by cytochrome P450 3A4 (CYP3A4). A small clinical study shows that taking grapefruit juice along with oral budesonide increases the plasma concentration of budesonide. This effect is attributed to grapefruit-induced inhibition of CYP3A4 in both the colon and small intestine (91425).
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Grapefruit juice can increase blood levels of buspirone, potentially increasing the effects and adverse effects of buspirone.
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Clinical research shows that grapefruit juice increases absorption and plasma concentrations of buspirone (3771).
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Grapefruit juice can decrease the clearance of caffeine, potentially increasing the effects and adverse effects of caffeine.
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Clinical research shows that grapefruit juice decreases caffeine clearance (4300).
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Grapefruit juice can increase blood levels of oral calcium channel blockers, potentially increasing the effects and adverse effects of these drugs.
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Clinical research shows that grapefruit juice increases absorption and plasma concentrations of amlodipine (523), nifedipine (528,22114), nisoldipine (529), verapamil (7779,8285), felodipine, nimodipine, nicardipine, diltiazem, pranidipine, nitrendipine, and manidipine (524,528,1388,4300,7780,11276,22136,53338,22138,22139) (22140,22141,22142,22143,22147,22148,22149,53367,22158),
This interaction is likely the result of the inhibition of intestinal metabolism of these drugs by CYP3A4 (7779,7780), although some research suggests grapefruit may alter plasma drug levels by reducing the rate of gastric emptying (22167). Consuming grapefruit juice 1 liter daily increases steady state concentrations of verapamil by as much as 50% (8285). However, some references dispute the clinical relevance of the interactions with amlodipine, diltiazem, and verapamil (3230,4300,22159). Other research in healthy individuals suggests plasma levels of felodipine and nifedipine are not affected when given intravenously (22144,22146). There is considerable interindividual variability in the effect of grapefruit juice on drug metabolism, which might account for inconsistent study results (7777,7779,8285). In healthy older adults, the hemodynamic response to felodipine plus grapefruit juice might be influenced by altered autonomic regulation. In older healthy adults, a single dose of grapefruit juice and felodipine enhanced the blood pressure-lowering effects of felodipine. However, after a week of grapefruit juice and felodipine (steady state), the hypotensive activity was reduced, possibly due to compensatory tachycardia (1392). Research indicates it is necessary to withhold grapefruit juice for as long as 3 days to avoid interactions with felodipine and nisoldipine (5068,5069,6453,22145).
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Grapefruit juice can increase blood levels of carbamazepine, potentially increasing the effects and adverse effects of carbamazepine.
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Clinical research shows that grapefruit juice increases absorption and plasma concentrations of carbamazepine (524).
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Grapefruit juice can increase blood levels of carvedilol, potentially increasing the effects and adverse effects of carvedilol.
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Clinical research shows that grapefruit juice increases the bioavailability of a single dose of carvedilol by 16% (5071).
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Grapefruit juice can decrease blood levels of celiprolol, potentially decreasing the clinical effects of celiprolol.
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In human research, taking grapefruit juice within two hours of celiprolol appears to decrease absorption and blood levels of celiprolol by approximately 85% (91421). This interaction is due to grapefruit-induced inhibition of organic anion transporting polypeptide (OATP) (17603,17604,22161). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction (17603,17604).
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Grapefruit juice can increase blood levels of cisapride, potentially increasing the effects and adverse effects of cisapride.
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Theoretically, grapefruit juice might increase blood levels of clomipramine, potentially increasing the effects and adverse effects of clomipramine.
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Case reports have shown that clomipramine trough levels increase significantly after the addition of grapefruit juice to the therapeutic regimen (5064).
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Grapefruit juice can decrease blood levels of the active metabolite of clopidogrel, thereby decreasing the antiplatelet effect of clopidogrel.
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Clopidogrel is an antiplatelet prodrug that is metabolized primarily by cytochrome P450 2C19 (CYP2C19) to form the active metabolite. A small clinical study shows that taking grapefruit juice with clopidogrel decreases plasma levels of the active metabolite by more than 80% and impairs the antiplatelet effect of clopidogrel. This effect is possibly due to grapefruit-induced inhibition of CYP2C19 (91419).
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Theoretically, grapefruit juice might increase blood levels of colchicine, potentially increasing the effects and adverse effects of colchicine.
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Colchicine is an alkaloid that undergoes P-glycoprotein (P-gp) mediated drug efflux in the intestines, followed by metabolism by cytochrome P450 3A4 (CYP3A4). There is concern that grapefruit juice will increase the effects and adverse effects of colchicine due to grapefruit-induced inhibition of P-gp and/or CYP3A4. In vitro evidence shows that grapefruit juice increases absorption of colchicine by inhibiting P-gp (94158). A case of acute colchicine toxicity has been reported for an 8-year-old female who drank grapefruit juice while taking high-dose colchicine, long-term (94157). However, one small clinical study in healthy adults shows that drinking grapefruit juice 240 mL twice daily for 4 days does not affect the bioavailability or adverse effects of a single dose of colchicine 0.6 mg taken on the fourth day (35762).
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Grapefruit juice can increase blood levels of oral cyclosporine, potentially increasing the effects and adverse effects of cyclosporine.
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Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP1A2.
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In vitro research suggests that grapefruit juice might inhibit CYP1A2 enzymes (12479). So far, this interaction has not been reported in humans.
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Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C19.
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In vitro research suggests that grapefruit juice might inhibit CYP2C19 enzymes (12479). Also, a small clinical study shows that taking grapefruit juice with clopidogrel, an antiplatelet prodrug that is metabolized primarily by CYP2C19, decreases plasma levels of the active metabolite and impairs the antiplatelet effect of clopidogrel. This effect is likely due to grapefruit-induced inhibition of CYP2C19 (91419).
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Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C9.
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In vitro research suggests that grapefruit juice might inhibit CYP2C9 enzymes (12479). So far, this interaction has not been reported in humans.
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Grapefruit juice can increase levels of drugs metabolized by CYP3A4.
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Clinical research shows that grapefruit juice can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects (3227,3774,8283,8285,8286,22129,91427,104190). When taken orally, effects of grapefruit juice on CYP3A4 levels appear to last at least 48 hours (91427). Grapefruit's ability to inhibit CYP3A4 has even been harnessed to intentionally increase levels of venetoclax, which is metabolized by CYP3A4, in an elderly patient with acute myeloid leukemia who could not afford full dose venetoclax. The lower dose of venetoclax in combination with grapefruit juice resulted in serum levels of venetoclax in the therapeutic reference range of full dose venetoclax and positive treatment outcomes for the patient (112287).
Professional consensus recommends the consideration of patient age, existing medical conditions, additional medications, and the potential for additive adverse effects when evaluating the risks of concomitant use of grapefruit juice with any medication metabolized by CYP3A4. While all patients are at risk for interactions with grapefruit juice consumption, patients older than 70 years of age and those taking multiple medications are at the greatest risk for a serious or fatal interaction with grapefruit juice (95970,95972). |
Grapefruit juice can increase blood levels of dapoxetine, potentially increasing the effects and adverse effects of dapoxetine.
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Pharmacokinetic research shows that drinking grapefruit juice 250 mL prior to taking dapoxetine 60 mg can increase the maximum plasma concentration of dapoxetine by 80% and prolong the elimination half-life by 43%. This effect is attributed to the inhibition of both intestinal and hepatic cytochrome P450 3A4 (CYP3A4) by grapefruit (95975).
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Grapefruit juice can increase blood levels of dextromethorphan, potentially increasing the effects and adverse effects of dextromethorphan.
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Clinical research shows that grapefruit juice can inhibit cytochrome P450 3A4 (CYP3A4) metabolism, causing increased dextromethorphan levels (11362).
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Grapefruit juice can increase blood levels of erythromycin, potentially increasing the effects and adverse effects of erythromycin.
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Clinical research shows that concomitant use of erythromycin with grapefruit can inhibit cytochrome P450 3A4 (CYP3A4) metabolism of erythromycin, increasing plasma concentrations of erythromycin by 35% (8286).
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Grapefruit juice can increase blood levels of estrogens, potentially increasing the effects and adverse effects of estrogens.
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Clinical research shows that grapefruit increases the levels of endogenous and exogenous estrogens by inhibiting cytochrome P450 3A4 (CYP3A4) enzymes (525,526,14858). Grapefruit juice increases exogenously administered 17-beta-estradiol by about 20% in females without ovaries and ethinyl-estradiol in healthy females (525,526,22160).
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Grapefruit juice can decrease blood levels of etoposide, potentially decreasing the clinical effects of etoposide.
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Clinical research shows that grapefruit juice decreases the absorption and plasma concentrations of etoposide. There is some evidence that grapefruit juice co-administered with oral etoposide can reduce levels of etoposide by about 26% (8744). Grapefruit juice seems to inhibit organic anion transporting polypeptide (OATP), which is a drug transporter in the gut, liver, and kidney (7046,17603,17604). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction (17603,17604).
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Grapefruit juice can decrease blood levels of fexofenadine, thereby decreasing the clinical effects of fexofenadine.
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Clinical research shows that grapefruit juice can significantly decrease oral absorption and blood levels of fexofenadine. In one study, consuming a drink containing grapefruit juice 25% decreased bioavailability of fexofenadine by about 24%. Consuming a full-strength grapefruit juice drink reduced bioavailability by 67% (7046). In another study, consuming grapefruit juice 300 mL decreased fexofenadine levels by 42%. Consuming 1200 mL of grapefruit juice reduced levels by 64% (17602). Similarly, drinking grapefruit juice 240 mL decreased the oral bioavailability of fexofenadine by 25% in another pharmacokinetic study (112288). Fexofenadine manufacturer data indicates that concomitant administration of grapefruit juice and fexofenadine results in larger wheal and flare sizes in research models. This suggests that grapefruit also reduces the clinical response to fexofenadine (17603).
Grapefruit juice seems to inhibit organic anion transporting polypeptide (OATP), which is a drug transporter in the gut, liver, and kidney (7046,17603,17604,22161). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction (17603,17604). |
Grapefruit juice can increase blood levels of fluvoxamine, potentially increasing the effects and adverse effects of fluvoxamine.
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Clinical research shows that grapefruit juice inhibits metabolism and increases fluvoxamine levels and peak concentration (17675).
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Grapefruit juice can increase blood levels of halofantrine, potentially increasing the effects and adverse effects of halofantrine.
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Clinical research shows that grapefruit juice inhibits cytochrome P450 3A4 (CYP3A4) metabolism, which increases halofantrine levels and peak concentration, as well as a marker of ventricular tachyarrhythmia potential (22129).
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Grapefruit juice can increase blood levels of statins that are metabolized by cytochrome P450 3A4 (CYP3A4), potentially increasing the effects and adverse effects of these statins. Additionally, grapefruit juice might interfere with the bioavailability of statins that are substrates of organic anion transporting polypeptides (OATP).
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Clinical research shows that grapefruit juice inhibits metabolism and increases absorption and plasma concentrations of statins that are metabolized by CYP3A4. These include lovastatin (527,11274), simvastatin (3774,7782,22127), and atorvastatin (3227,12179,22126). Keep in mind that there is considerable variability in the effect of grapefruit juice on drug metabolism, so individual patient response is difficult to predict (7777,7781).
Some statins, including pravastatin, fluvastatin, pitavastatin, and rosuvastatin, are not metabolized by CYP3A4. However, grapefruit juice might still affect the bioavailability of these statins. These statins are substrates of OATP. Grapefruit juice can inhibit OATP. Therefore, grapefruit juice may reduce the bioavailability or increase drug levels of these statins depending on the type of OATP. However, grapefruit juice affects OATP for only a short time. Therefore, separating drug administration by at least 4 hours is likely to avoid this interaction (3227,12179,17601,22126,91420). |
Grapefruit juice can interfere with itraconazole absorption, although the clinical significance of this interaction is unclear.
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Grapefruit juice can decrease blood levels of levothyroxine, potentially decreasing the effectiveness of levothyroxine.
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Clinical research shows that grapefruit juice modestly decreases levothyroxine levels by 11% by inhibiting organic anion transporting polypeptide (OATP) (17604,22163). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction (17603,17604).
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Grapefruit juice can decrease blood levels of the active metabolite of losartan, potentially decreasing the clinical effects of losartan.
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Losartan is an inactive prodrug which must be metabolized to its active form, E-3174, to be effective. In one human study, grapefruit juice reduced losartan metabolism, increased losartan AUC, and reduced the AUC of the major active losartan metabolite, E-3174 (1391).
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Grapefruit juice can increase blood levels of methadone, potentially increasing the effects and adverse effects of methadone.
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Clinical research shows that grapefruit juice inhibits the metabolism of methadone, increasing methadone levels and peak concentrations (17676). In one case, a 51-year-old male taking methadone 90 mg daily and no other medications was found unresponsive. The patient reported drinking grapefruit juice 500 mL daily for 3 days prior to the event. Methadone is a substrate of cytochrome P450 3A4 (CYP3A4), and grapefruit juice-induced inhibition of CYP3A4 is the likely cause of this interaction (102056).
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Grapefruit juice can increase blood levels of methylprednisolone, potentially increasing the effects and adverse effects of methylprednisolone.
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Clinical research shows that grapefruit juice can increase the plasma concentration of orally administered methylprednisolone. Grapefruit juice 200 mL three times daily given with methylprednisolone 16 mg increased methylprednisolone half-life by 35%, peak plasma concentration by 27%, and total area under the curve by 75% (3123).
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Grapefruit juice might decrease blood levels of nadolol, potentially decreasing the clinical effects of nadolol.
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Nadolol is a substrate of organic anion transporting polypeptide 1A2 (OATP1A2) (17603,17604,22161). Some research shows that grapefruit juice and its constituent naringin can inhibit organic anion transporting polypeptides (OATP), which can reduce the bioavailability of OATP substrates (17603,17604,22161,91427). However, preliminary clinical research shows that grapefruit juice containing a low amount of naringin does not significantly affect levels of nadolol (91422). It is not known if grapefruit juice containing higher amounts of naringin reduces the bioavailability of nadolol.
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Grapefruit juice can increase blood levels of nilotinib, potentially increasing the effects and adverse effects of nilotinib.
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Clinical research shows that grapefruit juice inhibits metabolism and increases absorption of nilotinib. Grapefruit juice increases nilotinib levels by 29% and peak concentration by 60% (17677).
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Grapefruit juice can decrease levels of drugs that are substrates of OATP.
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In vitro and clinical research show that consuming grapefruit juice inhibits OATP, which reduces the bioavailability of oral drugs that are substrates of OATP. Various clinical studies have shown reduced absorption of OATP substrates when taken with grapefruit, including fexofenadine, acebutolol, aliskiren, celiprolol, levothyroxine, nadolol, and pitavastatin (17603,17604,18101,22126,22134,22161,22163,91420,91427,91428,112288). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction (17603,17604).
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Grapefruit juice can increase blood levels of oxycodone, potentially increasing the effects and adverse effects of oxycodone.
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Oxycodone is metabolized by both cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6). A small clinical study shows that grapefruit juice can increase plasma levels of oral oxycodone about 1.7-fold by inhibiting CYP3A4. While the analgesic effects of oxycodone do not seem to be affected, taking grapefruit juice along with oxycodone may theoretically increase the adverse effects of oxycodone (91423).
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Grapefruit juice does not seem to affect renal P-glycoprotein (P-gp). Theoretically, it might inhibit intestinal P-gp, but evidence is conflicting.
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While most in vitro research shows that grapefruit products inhibit P-gp, (1390,11270,11278,11362,95976), research in humans is less clear. Two small clinical studies in healthy adults using digoxin as a probe substrate show that grapefruit juice does not inhibit P-gp in the kidneys (11277,11282). It is unclear whether this applies to intestinal P-gp, for which digoxin is not considered to be a sensitive probe (105568). Grapefruit juice has been shown to reduce levels of fexofenadine (7046,17602,112288), and increase levels of quinidine (5067,22121). However, as both of these drugs are also substrates of other enzymes and transporters, it is unclear what role, if any, intestinal P-gp has in these findings.
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Grapefruit juice can increase blood levels of pitavastatin, potentially increasing the effects and adverse effects of pitavastatin.
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Pharmacokinetic research shows that taking grapefruit juice with pitavastatin 2-4 mg can increase blood levels of pitavastatin by 13% to 14%. Unlike simvastatin and atorvastatin, pitavastatin is not significantly metabolized by cytochrome P450 3A4 (CYP3A4) enzymes. Grapefruit juice appears to increase levels of pitavastatin by inhibiting its uptake by organic anion transporting polypeptide 1B1 (OATP1B1) into hepatocytes for metabolism and clearance from the body (22126,91420). Grapefruit juice seems to increase levels of pitavastatin to a greater degree in patients homozygous for a specific polymorphism (388A>G) in the OATP1B1 gene compared to those heterozygous for this polymorphism (91420).
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Grapefruit juice can decrease blood levels of the active metabolite of prasugrel, thereby decreasing the antiplatelet effect of prasugrel.
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Prasugrel is a prodrug that is metabolized by cytochrome P450 3A4 (CYP3A4) into its active metabolite. A small pharmacokinetic study in healthy volunteers shows that drinking grapefruit juice 200 mL three times daily for 4 days and taking a single dose of prasugrel 10 mg with an additional 200 mL of grapefruit juice on day 3, results in a 49% lower peak plasma level and a 26% lower overall plasma exposure to the active metabolite when compared with drinking water. However, despite the reduced exposure, platelet aggregation seems to be reduced by an average of only 5% (105567). The clinical significance of this interaction is unclear.
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Grapefruit juice can increase blood levels of praziquantel, potentially increasing the effects and adverse effects of praziquantel.
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Clinical research shows that grapefruit juice can inhibit cytochrome P450 3A4 (CYP3A4) metabolism of praziquantel. Plasma concentrations of praziquantel can increase by as much as 160% when administered with 250 mL of commercially available grapefruit juice (8282).
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Grapefruit juice may increase blood levels of primaquine, potentially increasing the effects and adverse effects of primaquine.
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Clinical research shows that grapefruit juice increases the bioavailability of primaquine by approximately 20% (22130). The clinical significance of this interaction is not clear.
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Grapefruit or grapefruit juice, especially if consumed in large amounts, can cause additive QT interval prolongation when taken with QT interval-prolonging drugs, potentially increasing the risk of ventricular arrhythmias.
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Clinical research in healthy volunteers shows that drinking 6 liters of grapefruit juice over 6 hours prolonged the QTc by a peak amount of 14 milliseconds (ms). This prolongation was similar to the QT prolongation caused by the drug moxifloxacin. In individuals with long QT syndrome, a smaller dose of grapefruit juice, 1.5 liters, resulted in a greater peak QTc prolongation of about 30 ms (100249). The effect of smaller quantities of grapefruit juice on the QT interval is unclear.
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Grapefruit juice may increase blood levels of quetiapine, increasing the effects and adverse effects of quetiapine.
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Quetiapine is metabolized by cytochrome P450 3A4 (CYP3A4). Grapefruit can inhibit CYP3A4 (3227,3774,8283,8285,8286,22129,91427,104190). In one case report, a healthy 28-year-old female with bipolar disorder stabilized on quetiapine 800 mg daily presented with quetiapine toxicity considered to be related to consuming a gallon of grapefruit juice over the past 24 hours (108848).
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Grapefruit juice can alter blood levels of quinidine, potentially increasing or decreasing the clinical effects of quinidine.
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Grapefruit juice can increase blood levels of saquinavir, potentially increasing the effects and adverse effects of saquinavir.
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Grapefruit juice can increase blood levels of scopolamine, potentially increasing the effects and adverse effects of scopolamine.
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Clinical research shows that grapefruit juice can inhibit cytochrome P450 3A4 (CYP3A4) metabolism of scopolamine, increasing its absorption and plasma concentrations. Oral bioavailability of scopolamine can increase by 30% when administered with 150 mL of grapefruit juice (8284).
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Grapefruit juice can increase blood levels of sertraline, potentially increasing the effects and adverse effects of sertraline.
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Clinical research shows that grapefruit juice inhibits the cytochrome P450 3A4 (CYP3A4) metabolism of sertraline, increasing blood levels of sertraline (22122).
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Grapefruit juice can increase blood levels of sildenafil, potentially increasing the effects and adverse effects of sildenafil.
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Clinical research shows that grapefruit juice inhibits cytochrome P450 3A4 (CYP3A4) metabolism of sildenafil, increasing its absorption and plasma concentrations. Oral bioavailability of sildenafil can increase by 23% when administered with 500 mL of commercially available grapefruit juice (8283).
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Grapefruit juice may slightly increase blood levels of sunitinib, potentially increasing the effects and adverse effects of sunitinib.
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Sunitinib is metabolized by cytochrome P450 3A4 (CYP3A4). Grapefruit and grapefruit juice can inhibit CYP3A4 and increase levels of some drugs metabolized by this enzyme. One small clinical study shows that drinking 200 mL of grapefruit juice three times daily can increase the bioavailability of sunitinib by 11% (91429). While this effect is unlikely to be clinically significant, patients should use caution when using grapefruit along with sunitinib. Dose adjustments may be necessary.
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Grapefruit juice can increase blood levels of tacrolimus, potentially increasing the effects and adverse effects of tacrolimus.
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Clinical research shows that drinking grapefruit juice 200 mL daily while taking tacrolimus 3 mg daily increases the trough blood concentration of tacrolimus by approximately 3-fold in patients with connective tissue diseases (95974). A single case has also reported a 10-fold increase in tacrolimus trough levels after the ingestion of grapefruit juice over 3 days (22122). This effect is attributed to the inhibition of cytochrome P450 3A4 (CYP3A4) by grapefruit (95974).
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Theoretically, grapefruit juice might increase blood levels of tadalafil, potentially increasing the effects and adverse effects of tadalafil.
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Animal research shows that grapefruit juice increases tadalafil serum concentrations and overall exposure, likely through inhibition of cytochrome P450 3A4 enzymes (104189).
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Grapefruit juice might decrease blood levels of talinolol, potentially decreasing the clinical effects of talinolol.
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Clinical research suggests that grapefruit juice reduces talinolol bioavailability, likely by inhibiting intestinal uptake (22135). The clinical significance of this effect is unclear.
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Grapefruit juice can increase blood levels of terfenadine, potentially increasing the effects and adverse effects of terfenadine.
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Grapefruit juice can decrease blood levels of theophylline, potentially decreasing the effectiveness of theophylline.
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Clinical research shows that grapefruit juice seems to modestly decrease theophylline levels when given concurrently with sustained-release theophylline (11013). The mechanism of this interaction is unknown.
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Grapefruit juice can increase blood levels of ticagrelor, thereby increasing the effects and adverse effects of ticagrelor.
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Ticagrelor is metabolized by cytochrome P450 3A4 (CYP3A4). Grapefruit can inhibit CYP3A4. A small clinical study shows that taking grapefruit juice with ticagrelor increases blood levels of ticagrelor more than two-fold and increases the antiplatelet activity of ticagrelor (91418).
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Grapefruit juice can increase blood levels of tolvaptan, potentially increasing the effects and adverse effects of tolvaptan.
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Tolvaptan is metabolized by cytochrome P450 3A4 (CYP3A4). Grapefruit can inhibit CYP3A4. A small clinical study shows that grapefruit juice can increase the bioavailability and blood levels of tolvaptan by approximately 1.6-fold for up to 16 hours (91426).
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Theoretically, drinking large amounts of grapefruit juice might increase the effects and adverse effects of warfarin.
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In one case report, a patient experienced significantly increased international normalized ratio (INR) associated with consumption of 50 ounces of grapefruit juice daily (12061). However, smaller amounts of grapefruit juice might not be a problem. In a small clinical trial, consumption of 24 ounces of grapefruit juice daily for one week had no effect on INR in males treated with warfarin (12063).
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Theoretically, stevia might increase the risk for hypoglycemia when combined with antidiabetes drugs.
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Preliminary clinical research in patients with type 2 diabetes suggests that taking a single dose of stevia extract 1000 mg reduces postprandial blood glucose levels when taken with a meal (11812). However, other clinical research in patients with type 1 or type 2 diabetes suggests that taking stevioside 250 mg three times daily does not significantly affect blood glucose levels or glycated hemoglobin (HbA1C) after three months of treatment (16705).
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Theoretically, combining stevia or stevia constituents with antihypertensive agents might increase the risk of hypotension.
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Theoretically, stevia might decrease clearance and increase levels of lithium.
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Below is general information about the adverse effects of the known ingredients contained in the product BioSom. 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, 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, grapefruit and grapefruit juice are generally well tolerated.
Serious Adverse Effects (Rare):
Orally: Allergic reactions in sensitive individuals have been reported. When large quantities are consumed, arrhythmias, mineralocorticoid excess, QT prolongation, and pseudohyperaldosteronism have been reported. There is also some concern for increased breast cancer risk with grapefruit consumption.
Cardiovascular ...Orally, consumption of pink grapefruit juice 1000 mL can cause QT prolongation and cause arrhythmias in healthy patients and worsen arrhythmias in cardiomyopathy patients (13031,91424).
Endocrine ...Orally, high doses of grapefruit juice have been observed to cause pseudohyperaldosteronism and mineralocorticoid excess (53340,53346).
Gastrointestinal ...In a case report, grapefruit juice held against the teeth resulted in enamel and tooth surface loss (53368).
Immunologic ...Orally, grapefruit can cause allergic sensitization characterized by eosinophilic gastroenteritis, urticaria, and generalized pruritus (53351,53360).
Oncologic ...Preliminary population research shows that postmenopausal adults who consume a quarter or more of a whole grapefruit daily have a 25% to 30% increased risk of developing breast cancer (14858). Grapefruit is a potent inhibitor of cytochrome P450 3A4, which metabolizes estrogen. Consuming large amounts of grapefruit might significantly increase endogenous estrogen levels and therefore increase the risk of breast cancer. More evidence is needed to validate these findings. Until more is known, advise patients to consume grapefruit in moderation.
Renal ...In population research, consumption of 240 mL/day of grapefruit juice is associated with an increased risk of kidney stones (4216,53372).
General
...Orally, stevia and steviol glycosides appear to be well tolerated.
Most minor adverse effects seem to resolve after the first week of use.
Most Common Adverse Effects:
Abdominal bloating, dizziness, headache, myalgia, nausea, and numbness.
Serious Adverse Effects (Rare):
Allergic reactions.
Gastrointestinal ...Orally, stevia and steviol glycosides such as stevioside, can cause gastrointestinal adverse effects such as abdominal fullness and nausea. However, these generally resolve after the first week of use (11809,11810).
Immunologic ...Theoretically, stevia might cause allergic reactions in individuals sensitive to plants in the Asteraceae/Compositae family (11811). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.
Musculoskeletal ...Orally, stevia and steviol glycosides may cause myalgia, but this generally resolves after the first week of use (11809,11810).
Neurologic/CNS ...Orally, stevia and steviol glycosides may cause headache, dizziness, and numbness (11809,11810).