| Ingredients | Amount Per Serving: |
|---|---|
|
(Cholecalciferol)
(Vitamin D (Form: as Cholecalciferol) )
|
400 IU |
|
(Zn)
(Zinc Gluconate)
(Zinc (Form: from Zinc Gluconate) )
|
10 mg |
|
(from Brewer's Yeast)
(Selenium (Form: from Brewer's Yeast) )
|
200 mcg |
|
(Inositol Hexaphosphate)
|
400 mg |
|
(Serenoa repens )
(berry)
(40%)
|
320 mg |
| 200 mg | |
|
(standardized yielding)
|
120 mg |
|
pure Lycopene
(5%)
|
6 mg |
|
(Pygeum africanum )
(bark)
(2.5%)
|
20 mg |
|
(Cucurbita pepo )
(seed)
|
10 mg |
Vegetarian Capsule (Form: HPMC), Microcrystalline Cellulose (Form: Plant Fiber), Silicon Dioxide (Alt. Name: SiO2), Rice Flour, Ascorbyl Palmitate
Below is general information about the effectiveness of the known ingredients contained in the product Prosplex For Men. 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
Below is general information about the safety of the known ingredients contained in the product Prosplex For Men. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when consumed in amounts commonly found in foods (1854).
POSSIBLY SAFE ...when used orally and appropriately, short-term. IP-6 600 mg twice daily has been used with apparent safety for up to 2 weeks (102320). There is insufficient reliable information available about the safety of IP-6 when used orally in higher doses or for longer than 2 weeks or when used topically.
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (1854).
There is insufficient reliable information available about the safety of IP-6 when used in amounts greater than those found in foods; avoid using.
LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods (2406,7772,7773). ...when used orally in supplemental doses. Lycopene supplements have been used safely in doses of 15-45 mg daily for 4 to 6 months (60389,60399,60482,102180,102182,109431). Some limited evidence suggests that 120 mg daily is safe for up to one year (60372).
PREGNANCY: LIKELY SAFE
when consumed in amounts commonly found in foods.
There is insufficient reliable information available about the safety of lycopene supplements during pregnancy. Small, low-quality clinical studies have shown conflicting results about the safety of using lycopene 2-4 mg daily during pregnancy (60337,60428).
LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods.
There is insufficient reliable information available about the safety of lycopene supplements during lactation; avoid using in amounts greater than those typically found in foods.
LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods.
POSSIBLY SAFE ...when the seed or seed oil is used orally and appropriately in medicinal amounts, short-term. Pumpkin seed has been used with apparent safety in a dose of up to 10 grams daily for up to 12 months (92383). Pumpkin seed oil has been used with apparent safety in a dose of up to 400 mg daily for up to 6 months (92378). There is insufficient reliable information available about the safety of pumpkin seed oil when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.
LIKELY SAFE ...when used orally and appropriately. Pygeum 75-200 mg daily has been used safely in clinical trials for up to 12 months (3903,6368,10425,10426).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Quercetin has been used with apparent safety in doses up to 1 gram daily for up to 12 weeks (481,1998,1999,16418,16429,16430,16431,96774,96775,96782)(99237,102539,102540,102541,104229,104679,106498,106499,107450,109620)(109621). ...when used intravenously and appropriately. Quercetin has been used with apparent safety in doses less than 945 mg/m2. Higher doses have been reported to cause nephrotoxicity (9564,16418). There is insufficient reliable information available about the safety of quercetin when used topically.
POSSIBLY UNSAFE ...when used intravenously in large amounts. Doses greater than 945 mg/m2 have been reported to cause nephrotoxicity (9564,16418).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Saw palmetto has been safely used in clinical studies lasting up to 3 years (2735,6750,6752,6764,6772,6773,11354,14274,15550,17202,17306,17684,73315,73383,73384,73385,73389,89441,96410,96412,110540).
POSSIBLY SAFE ...when used rectally and appropriately. Saw palmetto has been used safely in clinical research at a dose of 640 mg once daily for 30 days (73387). However, the long-term safety of saw palmetto administered rectally is not known.
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally.
Saw palmetto has hormonal activity (6766); avoid using.
LIKELY SAFE ...when used orally and appropriately. Selenium appears to be safe when taken short-term in amounts below the tolerable upper intake level (UL) of 400 mcg daily (4844,7830,7831,7836,7841,9724,9797,14447,17510,17511)(17512,17513,17515,17516,97087,97943,109085); however, there is concern that taking selenium long-term might not be safe. Some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). Some evidence also shows that taking a selenium supplement 200 mcg daily for an average of 3-8 years increases the risk of developing type 2 diabetes (97091,99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661). ...when used intravenously. Selenium, as selenious acid, is an FDA-approved drug. Sodium selenite intravenous infusions up to 1000 mcg daily have been safely used for up to 28 days (90347,92910).
POSSIBLY UNSAFE ...when used orally in high doses or long-term. Doses above 400 mcg daily can increase the risk of developing selenium toxicity (4844,7825). Additionally, some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). There is also concern that taking a selenium supplement 200 mcg daily long-term, for an average of 3-8 years, increases the risk of developing type 2 diabetes (99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Selenium seems to be safe when used short-term in doses below the tolerable upper intake level (UL) of 45 mcg daily for infants up to age 6 months, 60 mcg daily for infants 7 to 12 months, 40-90 mcg daily for children 1 to 3 years, 100-150 mcg daily for children 4 to 8 years, 200-280 mcg daily for children 9 to 13 years, and 400 mcg daily for children age 14 years and older (4844,86095); however, there is some concern that long-term use might not be safe. ...when used via a nasogastric tube in premature infants (7835,9764).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately.
Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily (4844,17507,74419,74481,74391); however, there is concern that long-term use might not be safe.
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses above 400 mcg daily may cause significant toxicity (4844).
LACTATION: POSSIBLY SAFE
when used orally and appropriately.
Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily when taken short-term (4844,74467); however, there is concern that long-term use might not be safe.
LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses above 400 mcg daily may cause significant toxicity (4844,7838). ...when used orally in HIV-positive women. Selenium supplementation in HIV-positive women not taking highly active antiretroviral therapy may increase HIV-1 levels in breast milk (90358).
LIKELY SAFE ...when used orally or intramuscularly and appropriately. Vitamin D has been safely used in a wide range of doses (7555,16888,16891,17476,95913,98186,104619,105209,109059). When used orally long-term, doses should not exceed the tolerable upper intake level (UL) of 4000 IU (100 mcg) daily for adults (17506,99773); however, much higher doses such as 50,000 IU (1250 mcg) weekly orally for 6-12 weeks are often needed for the short-term treatment of vitamin D deficiency (16891,17476). Monthly oral doses of up to 60,000 IU (1500 mcg) have also been safely used for up to 5 years (105726). Toxicity usually does not occur until plasma levels exceed 150 ng/mL (17476).
POSSIBLY UNSAFE ...when used orally in excessive doses, long-term. Taking doses greater than the tolerable upper intake level (UL) of 4000 IU (100 mcg) daily for adults for long periods can increase the risk of hypercalcemia (17506); however, much higher doses are often needed for short-term treatment of vitamin D deficiency. Toxicity typically occurs when levels exceed 150 ng/mL (17476).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
When used long-term, doses should not exceed the tolerable upper intake level (UL) of 1000 IU (25 mcg) daily for those 0-6 months of age, 1500 IU (37.5 mcg) daily for those 6-12 months of age, 2500 IU (62.5 mcg) daily for those 1-3 years of age, 3000 IU (75 mcg) daily for those 4-8 years of age, and 4000 IU (100 mcg) daily for those 9 years and older (17506); however, much higher doses are often needed for the short-term treatment of vitamin D deficiency. Some research shows that giving vitamin D 14,000 IU (350 mcg) weekly for a year in children aged 10-17 years is safe (16875). A meta-analysis of clinical studies shows that 1000 IU (25 mcg) daily in those up to a year of age and greater than 2000 IU (50 mcg) daily in those aged 1-6 years does not increase the risk of serious adverse events (108424).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses for longer than one year.
Taking doses greater than the tolerable upper intake level (UL) long-term can increase the risk of hypercalcemia (17506).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
Vitamin D is safe when used in doses below the tolerable upper intake level (UL) of 4000 IU (100 mcg) daily (17506,95910).
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive amounts.
Tell patients not to use doses above the tolerable upper intake level (UL) of 4000 IU (100 mcg) daily. Hypercalcemia during pregnancy due to excessive vitamin D intake can lead to several fetal adverse effects, including suppression of parathyroid hormone, hypocalcemia, tetany, seizures, aortic valve stenosis, retinopathy, and mental and/or physical developmental delay (17506).
LACTATION: LIKELY SAFE
when used orally and appropriately.
Vitamin D is safe when used in doses below the tolerable upper intake level (UL) of 4000 IU (100 mcg) daily (17506).
LACTATION: POSSIBLY UNSAFE
when used orally in excessive amounts.
Tell patients not to use doses above the tolerable upper intake level (UL) of 4000 IU (100 mcg) daily (17506).
LIKELY SAFE ...when used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 40 mg daily (7135). ...when used topically and appropriately (2688,6538,6539,7135,8623,11051,111291).
POSSIBLY SAFE ...when used orally and appropriately in doses higher than the tolerable upper intake level (UL). Because the UL of zinc is based on regular daily intake, short-term excursions above 40 mg daily are not likely to be harmful. In fact, there is some evidence that doses of elemental zinc as high as 80 mg daily in combination with copper 2 mg can be used safely for approximately 6 years without significant adverse effects (7303,8622,92212). However, there is some concern that doses higher than the UL of 40 mg daily might decrease copper absorption and result in anemia (7135).
POSSIBLY UNSAFE ...when used intranasally. Case reports and animal research suggest that intranasal zinc might cause permanent anosmia or loss of sense of smell (11155,11156,11703,11704,11705,11706,11707,16800,16801,17083). Several hundred reports of anosmia have been submitted to the US Food and Drug Administration (FDA) and the manufacturer of some intranasal zinc products (Zicam) (16800,16801). Advise patients not to use intranasal zinc products.
LIKELY UNSAFE ...when taken orally in excessive amounts. Ingestion of 10-30 grams of zinc sulfate can be lethal in adults (7135). Chronic intake of 450-1600 mg daily can cause multiple forms of anemia, copper deficiency, and myeloneuropathies (7135,17092,17093,112473). This has been reported with use of zinc-containing denture adhesives in amounts exceeding the labeled directions, such as several times a day for several years (17092,17093). Advise patients to follow the label directions on denture adhesives that contain zinc.
CHILDREN: LIKELY SAFE
when used orally and appropriately (7135).
Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL). The UL for children is based on age: 4 mg daily for 0-6 months, 5 mg daily for 7-12 months, 7 mg daily for 1-3 years, 12 mg daily for 4-8 years, 23 mg daily for 9-13 years, and 34 mg daily for 14-18 years (7135,97140).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Taking amounts greater than the UL can cause sideroblastic anemia and copper deficiency (7135). ...when used topically on damaged skin. An infant treated with 10% zinc oxide ointment for severe diaper rash with perianal erosions developed hyperzincemia. Absorption seemed to occur mainly via the erosions; plasma levels dropped after the erosions healed despite continued use of the ointment (106905).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during pregnancy in those 14-18 years of age and 40 mg daily in those 19-50 years of age (7135).
PREGNANCY: LIKELY UNSAFE
when used orally in doses exceeding the UL (7135).
LACTATION: LIKELY SAFE
when used orally and appropriately.
Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during lactation in those 14-18 years of age, and 40 mg daily for those 19-50 years of age (7135).
LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL.
Higher doses can cause zinc-induced copper deficiency in nursing infants (7135).
Below is general information about the interactions of the known ingredients contained in the product Prosplex For Men. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, concomitant use of IP-6 with drugs that affect platelet aggregation may increase the risk of bleeding. In vitro IP-6 can inhibit platelet aggregation (1867). This effect has not been demonstrated in humans.
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Theoretically, taking lycopene with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
 Details
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Pumpkin might reduce excretion and increase levels of lithium.
Details
Pumpkin is thought to have diuretic properties (92383). Theoretically, this might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.
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Theoretically, concomitant use of quercetin and antidiabetes drugs might increase the risk of hypoglycemia.
Details
Clinical research suggests that a combination of quercetin, myricetin, and chlorogenic acid reduce levels of fasting glucose in patients with type 2 diabetes, including those already taking antidiabetes agents (96779). The effect of quercetin alone is unknown. |
Theoretically, taking quercetin with antihypertensive drugs might increase the risk of hypotension.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of cyclosporine.
Details
A small study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine, possibly due to inhibition of p-glycoprotein or cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporin (16434). |
Theoretically, concomitant use might increase the levels and adverse effects of CYP2C8 substrates.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of CYP2C9 substrates.
Details
A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac, a CYP2C9 substrate, increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5% (97931). Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar), a substrate of CYP2C9 (100968). Furthermore, laboratory research shows that quercetin inhibits CYP2C9 (15549,16433). |
Theoretically, concomitant use might increase the levels and adverse effects of CYP2D6 substrates.
Details
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Theoretically, concomitant use might alter the effects and adverse effects of CYP3A4 substrates.
Details
A small clinical study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine (Neoral, Sandimmune), a substrate of CYP3A4 (16434). Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) and quetiapine (Seroquel), substrates of CYP3A4 (100968,104228). Other laboratory research also shows that quercetin inhibits CYP3A4 (15549,16433,16435). However, one clinical study shows that quercetin can increase the metabolism of midazolam, a substrate of CYP3A4, and decrease serum concentrations of midazolam by about 24% in some healthy individuals, suggesting possible induction of CYP3A4 (91573).
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Theoretically, concomitant use might increase the levels and adverse effects of diclofenac.
Details
A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. This is thought to be due to inhibition of CYP2C9 by quercetin (97931). |
Theoretically, concomitant use might increase the effects and adverse effects of losartan and decrease the effects of its active metabolite.
Details
Animal research shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) while decreasing plasma levels of losartan's active metabolite. This metabolite, which is around 10-fold more potent than losartan, is the result of cytochrome P450 (CYP) 2C9- and CYP3A4-mediated transformation of losartan. Additionally, in vitro research shows that quercetin may inhibit P-glycoprotein-mediated efflux of losartan from the intestines, resulting in increased absorption of losartan (100968). These results suggest that concomitant use of quercetin and losartan might increase systemic exposure to losartan while also decreasing plasma concentrations of losartan's active and more potent metabolite. |
Theoretically, concomitant use might decrease the levels and effects of midazolam.
Details
A small clinical study in healthy volunteers shows that quercetin can increase the metabolism of midazolam, with a decrease in AUC of about 24% (91573). |
Theoretically, quercetin might increase the effects and adverse effects of mitoxantrone.
Details
In vitro research shows that quercetin increases the intracellular accumulation and cytotoxicity of mitoxantrone, possibly through inhibition of breast cancer resistance protein (BCRP), of which mitoxantrone is a substrate (107897). So far, this interaction has not been reported in humans.
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Theoretically, concomitant use might increase the effects and adverse effects of OAT1 substrates.
Details
In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT1, with half-maximal inhibitory concentration (IC50) values less than 10 mcM (104454). So far, this interaction has not been reported in humans. |
Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.
Details
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Theoretically, concomitant use might increase the effects and adverse effects of OATP substrates.
Details
In vitro evidence shows that quercetin can inhibit organic anion-transporting peptide (OATP) 1B1-mediated uptake of estrone-3-sulfate and pravastatin (91581). Furthermore, clinical research in healthy males shows that intake of quercetin along with pravastatin increases the AUC of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells (91581). |
Theoretically, concomitant use might alter the effects and adverse effects of P-glycoprotein substrates.
Details
There is preliminary evidence that quercetin inhibits the gastrointestinal P-glycoprotein efflux pump, which might increase the bioavailability and serum levels of drugs transported by the pump (16433,16434,16435,100968,104228). A small study in healthy volunteers reported that pretreatment with quercetin increased bioavailability and plasma levels after a single dose of cyclosporine (Neoral, Sandimmune) (16434). Also, two small studies have shown that quercetin might decrease the absorption of talinolol, a substrate transported by the gastrointestinal P-glycoprotein efflux pump (91579,91580). However, in another small study, several days of quercetin treatment did not significantly affect the pharmacokinetics of saquinavir (Invirase) (16433). The reason for these discrepancies is not entirely clear (91580). Until more is known, use quercetin cautiously in combination with P-glycoprotein substrates. |
Theoretically, concomitant use might increase the effects and adverse effects of pravastatin.
Details
In vitro evidence shows that quercetin can inhibit OATP 1B1-mediated uptake of pravastatin (91581). Also, preliminary clinical research in healthy males shows that intake of quercetin along with pravastatin increases the maximum concentration of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells (91581).
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Theoretically, quercetin might increase the effects and adverse effects of prazosin.
Details
In vitro research shows that quercetin inhibits the transcellular efflux of prazosin, possibly through inhibition of breast cancer resistance protein (BCRP), of which prazosin is a substrate. BCRP is an ATP-binding cassette efflux transporter in the intestines, kidneys, and liver (107897). So far, this interaction has not been reported in humans.
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Theoretically, concomitant use might increase the effects and adverse effects of quetiapine.
Details
Animal research shows that pretreatment with quercetin can increase plasma levels of quetiapine and prolong its clearance, possibly due to inhibition of cytochrome P450 3A4 (CYP3A4) by quercetin. Additionally, the brain-to-plasma ratio of quetiapine concentrations increased, possibly due to inhibition of P-glycoprotein at the blood-brain barrier (104228). This interaction has not been reported in humans.
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Theoretically, concomitant use might inhibit the effects of quinolone antibiotics.
Details
In vitro, quercetin binds to the DNA gyrase site on bacteria (481), which may interfere with the activity of quinolone antibiotics.
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Theoretically, quercetin might increase the effects and adverse effects of sulfasalazine.
Details
Animal research shows that quercetin increases the maximum serum concentration (Cmax) and area under the curve (AUC) of sulfasalazine, possibly through inhibition of breast cancer resistance protein (BCRP), of which sulfasalazine is a substrate (107897). So far, this interaction has not been reported in humans.
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Theoretically, quercetin may increase the risk of bleeding if used with warfarin.
Details
Animal and in vitro studies show that quercetin might increase serum levels of warfarin (17213,109619). Quercetin and warfarin have the same human serum albumin (HSA) binding site, and in vitro research shows that quercetin has stronger affinity for the HSA binding site and can theoretically displace warfarin, causing higher serum levels of warfarin (17213). Animal research shows that taking quercetin for 2 weeks before initiating warfarin increases the maximum serum level of warfarin by 30%, the half-life by 10%, and the overall exposure by 63% when compared with control. Concomitant administration of quercetin and warfarin, without quercetin pre-treatment, also increased these measures, but to a lesser degree. Researchers theorize that inhibition of CYP3A4 by quercetin may explain these effects (109619). So far, this interaction has not been reported in humans.
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Saw palmetto might increase the risk of bleeding with anticoagulant or antiplatelet drugs.
Details
Saw palmetto is reported to prolong bleeding time (8659). Theoretically, it might increase the risk of bleeding when used concomitantly with anticoagulant or antiplatelet drugs.
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Saw palmetto might reduce the effectiveness of contraceptive drugs.
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Saw palmetto might have antiestrogenic effects (6766). Theoretically, it might interfere with contraceptive drugs taken concomitantly.
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Saw palmetto might reduce the effectiveness of estrogens.
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Saw palmetto might have antiestrogenic effects (6766). Theoretically, it might interfere with estrogens taken concomitantly.
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Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity (14540). Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation (74406).
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Theoretically, selenium might prolong the sedating effects of barbiturates.
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Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
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Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels (14544,14545,14546,101343). It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium (14545).
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Gold salts might interfere with selenium activity in tissues.
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Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
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Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
Details
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.
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Theoretically, selenium might interfere with warfarin activity.
Details
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors (14541). Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity (14540).
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Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
Details
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption (11595,11597,22916). This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically (11529,11596,11597).
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Vitamin D might reduce absorption of atorvastatin.
Details
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change (16828). Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.
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Taking calcipotriene with vitamin D increases the risk for hypercalcemia.
Details
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia (15). Theoretically, combining calcipotriene with vitamin D supplements might increase the risk of hypercalcemia.
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Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
Details
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found (110539). A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced (16828). While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.
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Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
Details
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin (15). Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.
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Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
Details
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.
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Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Details
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently (3072,11541,69580). This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily (11539,11540).
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Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Details
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation (10574). Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.
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Amiloride can modestly reduce zinc excretion and increase zinc levels.
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Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses (830,11626,11627,11634). The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.
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Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
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Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption (93578). Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication (90216).
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Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
Details
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose (94163). To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.
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Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Details
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin (11624,11625). It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.
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Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
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Zinc might reduce the levels and clinical effects of penicillamine.
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By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated (2678,4534,11605). Advise patients to take zinc and penicillamine at least 2 hours apart.
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Zinc can decrease the levels and clinical effects of quinolones antibiotics.
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Zinc modestly reduces levels of ritonavir.
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Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption (93578). In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16% (90216). However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.
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Zinc might reduce levels of tetracycline antibiotics.
Details
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time (3046,4945). Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40% (11615). Demeclocycline and minocycline cause a similar interaction (4945). However, doxycycline does not seem to interact significantly with zinc (11615). Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.
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Below is general information about the adverse effects of the known ingredients contained in the product Prosplex For Men. 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, IP-6 is well tolerated when consumed in amounts commonly found in foods (1854). No adverse effects have been reported when IP-6 is used in medicinal amounts; however, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, lycopene is generally well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal complaints, skin rash.
Cardiovascular ...A case of chest pain has been reported in a pregnant patient who was taking a specific lycopene product (LycoRed, Jagsonpal Pharmaceuticals) 2 mg daily (60428). The role of lycopene in this event has not been determined.
Dermatologic
...Orally, lycopene supplements have been reported to cause allergic skin reactions in some clinical studies (60409,60417).
Skin rash also occurred in a pregnant patient who was taking a specific lycopene product (LycoRed, Jagsonpal Pharmaceuticals) (60428).
There is at least one case report of carotenoderma, with a yellow-orange coloration in the stratum corneum of the skin, in a 26-year-old female who consumed 20-30 cherry tomatoes and 180 mL tomato juice, as well as other carotenoid-rich foods, daily for up to 10 years. Plasma levels of carotenoids, mainly lycopene, were elevated (109774).
Gastrointestinal ...Orally, gastrointestinal side effects associated with use of lycopene supplements include diarrhea, flatulence, abdominal distension, nausea, vomiting, dyspepsia, and anorexia (60372,60384,60417,60433,60464).
General
...Orally, pumpkin products are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.
Dermatologic ...There are two case reports of adult females developing substantial transient hair loss 1-3 weeks after consumption of a meal containing either bitter-tasting pumpkin or undefined squash. This adverse effect was attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).
Gastrointestinal ...Orally, pumpkin seed oil has been reported to cause mild abdominal discomfort in clinical trials (5093,92378). There are also two case reports of adults developing severe nausea, vomiting, and diarrhea following consumption of a meal containing either bitter-tasting pumpkin or undefined squash. These adverse effects were attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).
Immunologic
...Orally, pumpkin seed oil and pumpkin pulp have been reported to cause anaphylactic reactions in children and adults.
A case review highlights 4 cases of anaphylaxis in children (3 from pumpkin pulp, 1 from pumpkin seeds), and 7 cases in adults (1 from pumpkin flesh, 6 from pumpkin seeds). Symptoms of anaphylaxis include urticaria, angioedema of the lips or face, dyspnea, dysphagia, and oropharyngeal itching and swelling. A case report describes a 2-year-old male presenting with urticaria, swollen lips, and increased dyspnea 10 minutes after ingesting pumpkin seeds. The patient was found to have elevated allergen-specific immunoglobulin E (IgE) and a positive skin-prick test for pumpkin seeds. Symptoms resolved after treatment with epinephrine, systemic glucocorticoids, salbuterol, and antihistamines (107843).
There may also be concern for allergic reaction due to inhalation or topical exposure. One case report describes an 8-year-old child developing anaphylaxis while carving a pumpkin; another highlights that inhalation of pumpkin seed flour may have potentiated anaphylaxis in 3 individuals following the ingestion of pumpkin seeds (107843). Further research is necessary to assess the relationship between anaphylaxis and route of administration.
General ...Orally and intravenously, quercetin seems to be well tolerated in appropriate doses. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Gastrointestinal ...Intravenous administration of quercetin is associated with nausea and vomiting (9564).
Neurologic/CNS ...Orally, quercetin may cause headache and tingling of the extremities (481,111500). Intravenously, quercetin may cause pain at the injection site. Injection pain can be minimized by premedicating patients with 10 mg of morphine and administering amounts greater than 945 mg/m2 over 5 minutes (9564). In addition, intravenous administration of quercetin is associated with flushing and sweating (9564).
Pulmonary/Respiratory ...Intravenous administration of quercetin at doses as high as 2000 mg/m2 is associated with dyspnea that may persist for up to 5 minutes (9564).
Renal ...Intravenously, nephrotoxicity has been reported with quercetin in amounts greater than 945 mg/m2 (9563,9564,70304).
General
...Orally, saw palmetto is well tolerated and adverse effects are mild, infrequent, and reversible.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, decreased libido, diarrhea, dizziness, fatigue, headache, nausea, rhinitis, vomiting.
Cardiovascular ...Occasionally, cases of hypertension, postural hypotension, tachycardia, angina pectoris, arrhythmia, extrasystole, angiopathy, myocardial infarction, and congestive heart failure have been reported in patients using saw palmetto orally (6424,6484,6752,6772,17684,73388,89441). One case of severe bradycardia and second degree heart block was reported in a 64 year-old male taking an unknown amount of saw palmetto for a few weeks (96413).
Dermatologic ...A case report describes a 61-year-old male who developed a fixed drug eruption with localized blisters and erosions three days after starting oral saw palmetto. The lesions resolved when saw palmetto was stopped, but recurred when it was reintroduced six months later. Topical corticosteroid treatment was necessary and the patient was left with some residual hyperpigmented patches (104805). A combination of saw palmetto and beta-sitosterol has been associated with a single report of worsening acne (15550).
Endocrine ...Two case reports involving one 11-year-old female undergoing treatment for telogen effluvium and another 10-year-old female undergoing treatment for hirsutism, describe hot flashes and the onset of menarche associated with use of saw palmetto. One of these patients was consuming saw palmetto in a food supplement; the other was taking a supplement containing saw palmetto 320 mg daily (73361,96414). In both cases, the hot flashes resolved following treatment discontinuation. In one case, a rechallenge with saw palmetto caused a recurrence of hot flashes.
Gastrointestinal ...Gastrointestinal complaints such as nausea, vomiting, constipation, diarrhea, gastralgia, and halitosis are the most frequently reported adverse effects associated with saw palmetto (6484,6752,60442,73315,73320,73348,73354,73383,73385,73388,89441). Less often, cases of duodenal ulcer, dyspepsia, or heartburn have been reported (6772,73329,73354). Meteorism (intestinal gas accumulation) has also been reported with saw palmetto, although causality was unclear (60442).
Genitourinary ...Some clinicians are concerned that saw palmetto might cause erectile dysfunction, ejaculatory disturbance, or altered libido because of its potential effects on 5-alpha-reductase. Some preliminary clinical studies have reported sexual dysfunction, particularly ejaculatory dysfunction, erectile dysfunction, and reduced libido, in patients taking saw palmetto (5093,17202,17684,73383,89441). However, most of these patients were previously diagnosed with prostate disorders, so causality is unclear. Additionally, several clinical studies indicate that the occurrence of impotence in males taking saw palmetto is similar to placebo and tamsulosin (Flomax), and significantly less than finasteride (Proscar) (2732,6424,17306,107481). Rarely, cases of testicular pain, vesical tenesmus, and urinary tract infections have been reported in patients using saw palmetto extract orally (73388).
Hematologic ...Saw palmetto might have antiplatelet effects and potentially increase the risk of bleeding in some patients. There is one report of excessive intraoperative bleeding in a patient who took saw palmetto prior to surgery. Bleeding time normalized when saw palmetto was discontinued (8659). Also, one case of cerebral hemorrhage has been reported, but details are not available to determine causality (6772,73348). A case of retroperitoneal hematoma after bilateral inguinal hernia repair is reported in a male patient taking saw palmetto. The patient was discharged after a 3-day hospitalization in stable condition (112177).
Hepatic ...A case report describes a patient who developed acute hepatitis and pancreatitis while taking saw palmetto. Symptoms resolved when saw palmetto was discontinued, and reemerged upon re-challenge (14457). Other cases of acute hepatitis and pancreatitis, with elevated alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin have been reported in patients using saw palmetto orally (14457,73350,73351).
Musculoskeletal ...Orally, saw palmetto may cause fatigue, weakness, muscle pain, and back pain, although these adverse events are rare (6424,73388,89441). A case of saw palmetto-related rhabdomyolysis was reported in an 82-year-old male presenting with kidney dysfunction, increased C-reactive protein levels, and elevated serum creatine kinase (73358).
Neurologic/CNS ...Orally, saw palmetto can cause headaches, dizziness, insomnia, and fatigue (6750,6752,6772,11354,60442,73348,73385,73388,89441).
Ocular/Otic ...A case of intraoperative floppy-iris syndrome (IFIS) has been reported in a patient using saw palmetto orally (73340). However, no statistically significant association between saw palmetto and IFIS was found in a case series of 660 patients undergoing cataract surgery (73347).
Pulmonary/Respiratory ...Rhinitis is one of the more commonly reported adverse effects of saw palmetto (73348). One patient taking saw palmetto extract 160 mg twice daily reported "breathlessness" (73388). Two cases of respiratory depression have been reported in patients using saw palmetto extract (Permixon) 320 mg (6772).
General
...Orally, selenium is generally well-tolerated when used in doses that do not exceed the tolerable upper intake level (UL) of 400 mcg daily.
Intravenously, selenium is generally well-tolerated.
Most Common Adverse Effects:
Orally: Gastric discomfort, headache, and rash. Excessive amounts can cause alopecia, dermatitis, fatigue, nail changes, nausea and vomiting, and weight loss.
Serious Adverse Effects (Rare):
Orally: Excessive ingestion has led to cases of multi-organ failure and death.
Dermatologic ...Excess selenium can produce selenosis in humans, affecting liver, skin, nails, and hair (74304,74326,74397,74495,90360,113660) as well as dermatitis (74304). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer (10687). Mild skin rash has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).
Endocrine
...Multiple clinical studies have found an association between increased intake of selenium, either in the diet or as a supplement, and the risk for type 2 diabetes (97091,99661).
One meta-analysis shows that a selenium plasma level of 90 mcg/L or 140 mcg/L is associated with a 50% or 260% increased risk for developing type 2 diabetes, respectively, when compared with plasma levels below 90 mcg/L. Additionally, consuming selenium in amounts exceeding the recommended dietary allowance (RDA) is associated with an increased risk of developing diabetes when compared with consuming less than the RDA daily. Also, taking selenium 200 mcg daily as a supplement is associated with an 11% increased risk for diabetes when compared with a placebo supplement (99661).
Hypothyroidism, secondary to iodine deficiency, has been reported as a result of selenium intravenous administration (14563,14565). One large human clinical trial suggested a possible increased risk of type 2 diabetes mellitus in the selenium group (16707).
Gastrointestinal ...In human research, nausea, vomiting, and liver dysfunction has been reported as a result of high selenium exposure (74439,74376,113660). Mild gastric discomfort has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).
Genitourinary ...The effect of selenium supplementation on semen parameters is unclear. In human research, selenium supplementation may reduce sperm motility (9729); however, follow-up research reported no effect on sperm motility or any other semen quality parameter (74441).
Musculoskeletal ...Chronic selenium exposure of 30 mg daily for up to 24 weeks may cause arthralgia, myalgia, and muscle spasms (113660).
Neurologic/CNS ...Chronic exposure to organic and inorganic selenium may cause neurotoxicity, particularly motor neuron degeneration, leading to an increased risk of amyotrophic lateral sclerosis (ALS) (74304). Headache has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months and in patients taking sodium selenate 30 mg daily for up to 24 weeks (97943,113660).
General
...Orally or intramuscularly, vitamin D is well tolerated.
Serious Adverse Effects (Rare):
Orally or intramuscularly: Excessive doses can lead to vitamin D toxicity with symptoms of hypercalcemia, and also sometimes azotemia and anemia.
Cardiovascular ...Vitamin D intoxication can occur when vitamin D supplements are taken orally in excessive doses. Rarely, people develop hypertension (10142). An analysis of clinical research suggests that, when taken orally, vitamin D might modestly increase levels of low-density lipoprotein (LDL)-cholesterol. However, it is not clear if this increase is clinically significant (84642).
Gastrointestinal ...Orally, vitamin D may cause dry mouth. In clinical research, intake of vitamin D 50,000 IU weekly for 4 weeks followed by 50,000 IU monthly for 5 months thereafter was associated with a 3.7-fold increase in reports of dry mouth compared with placebo (91348).Vitamin D intoxication can occur when vitamin D supplements are taken orally in excessive doses. Symptoms of vitamin D toxicity include pancreatitis (10142,84433). Vomiting occurred in one patient given a single dose of 200,000 IU (104624).
Genitourinary ...Vitamin D intoxication can occur when vitamin D supplements are taken orally in excessive doses. Advanced symptoms may include decreased libido (10142). Vaginal discharge and itching have been reported in a clinical trial following oral use (91348).
Hematologic
...Lab values of urinary and blood calcium, phosphate, albumin, blood urea nitrogen, serum cholesterol, aspartate aminotransferase, and alanine aminotransferase concentrations might increase with vitamin D use, especially with high doses (10142,91349,93943).
A case of elevated international normalized ration (INR) has been reported for an 84 year-old patient who took vitamin D 50,000 IU daily for 2 months. The patient's serum levels of vitamin D increased from <7 ng/mL to 100 ng/mL over 6 months. To resolve symptoms, vitamin D supplementation was discontinued (84433).
Musculoskeletal ...Vitamin D intoxication can occur when vitamin D supplements are taken in excessive doses (10142,17506). Symptoms of vitamin D toxicity include osteoporosis in adults and decreased growth in children (10142).
Ocular/Otic ...Vitamin D intoxication can occur when vitamin D supplements are taken orally in excessive doses (10142,17506). Symptoms of vitamin D toxicity include calcific conjunctivitis and photophobia (10142).
Psychiatric ...Vitamin D intoxication can occur when vitamin D supplements are taken orally in excessive doses (10142,17506). In rare cases, symptoms of vitamin D toxicity include psychosis (10142,93002).
Pulmonary/Respiratory ...Vitamin D intoxication can occur when vitamin D supplements are taken orally in excessive doses. Advanced symptoms of vitamin D toxicity may include runny nose (10142,17506,93002).
Renal ...Vitamin D intoxication can occur when vitamin D supplements are taken orally in excessive doses. Symptoms of vitamin D toxicity include azotemia. Vitamin D may also cause hypercalcemia, with advanced symptoms including kidney stones or kidney insufficiency due to precipitation of calcium phosphate in the tubules. Symptoms of renal impairment include frequency, nighttime awakening to urinate, thirst, inability to concentrate urine, and proteinuria. Renal impairment is usually reversible with discontinuation of vitamin D supplements (10142,93002,93943,110831,110833).
General
...Orally, zinc is well tolerated in doses below the tolerable upper intake level (UL), which is 40 mg daily for adults.
Topically, zinc is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, metallic taste, nausea and vomiting (dose-related).
Topically: Burning, discoloration, itching, stinging, and tingling when applied to irritated tissue.
Intranasally: Bad taste, dry mouth, headache, irritation, reduced sense of smell.
Serious Adverse Effects (Rare):
Orally: There have been cases of acute renal tubular necrosis, interstitial nephritis, neurological complications, severe vomiting, and sideroblastic anemia after zinc overdose.
Intranasally: There have been cases where intranasal zinc caused permanent loss of smell (anosmia).
Dermatologic
...Topically, zinc can cause burning, stinging, itching, and tingling when applied to inflamed tissue (6911,8623,87297).
Zinc oxide can be deposited in the submucosal tissue and cause dark discoloration of the skin. This can occur with prolonged topical application to intact skin, application to eroded or ulcerated skin, or penetrating traumatic exposure, and also parenteral administration (8618).
In rare cases, oral zinc has resulted in worsened acne (104056), skin sensitivity (6592), a leishmanial reaction with a macular rash that occurred on exposed parts of the body (86935), eczema (104055), systemic contact dermatitis (109457), and the development of severe seborrheic dermatitis (86946).
Gastrointestinal
...Orally, zinc can cause nausea (338,2663,2681,6592,6700,18216,106230,106233,106227,113661), vomiting (2663,2681,6519,6592,96069,96074), a metallic or objectionable taste in the mouth (336,338,6700,11350,18216,106902,113661), abdominal cramping (6592,96069), indigestion (87227), heartburn (96069), dry mouth (87533), and mouth irritation (336,2619).
When used orally in amounts above the tolerable upper intake level, zinc may cause irritation and corrosion of the gastrointestinal tract (331,86982,87315,106902), watery diarrhea (1352), epigastric pain (2663,2681), and severe vomiting (2663,2681).
Intranasally, zinc can cause bad taste, dry mouth, and burning and irritation of the throat (8628,8629).
When used topically as a mouth rinse, zinc may cause tooth staining (90206).
Hematologic ...There is concern that high daily doses of zinc, above the tolerable upper intake level (UL) of 40 mg per day, might increase the risk of copper deficiency, potentially leading to anemia and leukopenia (7135,112473). To prevent copper deficiency, some clinicians give a small dose of copper when zinc is used in high doses, long-term (7303).
Hepatic ...There are two cases of liver deterioration in patients with Wilson disease following initiation of treatment with zinc 50-200 mg three times daily. The mechanism of action is not understood, and the event is extremely uncommon (86927,87470).
Immunologic ...Daily doses of 300 mg of supplemental zinc for 6 weeks appear to impair immune response (7135). A case of erythematosus-like syndrome, including symptoms such as fever, leg ulcers, and rash, has been reported following intake of effervescent tablets (Solvezink) containing zinc 45 mg (87506). In another case, severe neutropenia was reported after taking supplemental zinc 900 mg daily for an unknown duration (112473).
Musculoskeletal ...Orally, zinc may cause body aches in children (113661).
Neurologic/CNS
...Zinc-containing denture adhesives can cause toxicity if used more frequently than recommended for several years.
Case reports describe hyperzincemia, low copper levels, blood dyscrasias, and neurological problems, including sensory disturbances, numbness, tingling, limb weakness, and difficulty walking in patients applying denture adhesive multiple times daily for several years (17092,17093,90205,90233). Due to reports of zinc toxicity associated with use of excessive amounts of zinc-containing denture adhesives for several years, GlaxoSmithKline has reformulated Polygrip products to remove their zinc content (17092,17093).
Intranasally (8628) and orally (87534), zinc can cause headache. When used orally in amounts above the tolerable upper intake level (UL), zinc may cause central nervous system (CNS) symptoms including lethargy, fatigue, neuropathy, dizziness, and paresthesia (2663,2681,87369,87470,87533,87534,112473).
Oncologic ...There is concern that zinc might worsen prostate disease. For example, some preliminary evidence suggests that higher dietary zinc intake increases the risk for benign prostatic hyperplasia (6908). Epidemiological evidence suggests that taking more than 100 mg of supplemental zinc daily or taking supplemental zinc for 10 or more years doubles the risk of developing prostate cancer (10306). Another large-scale population study also suggests that men who take a multivitamin more than 7 times per week and who also take a separate zinc supplement have a significantly increased risk of prostate cancer-related mortality (15607). However, a large analysis of population research suggests that there is no association between zinc intake and the risk of prostate cancer (96075).
Pulmonary/Respiratory
...There are several hundred reports of complete loss of sense of smell (anosmia) that may be permanent with use of zinc gluconate nasal gel, such as Zicam (11306,11155,11707,16800,16801,17083,86999,87535).
Loss of sense of smell is thought to be dose related but has also been reported following a single application (11306,11155,11707,16800). Patients often report having sniffed deeply when applying the gel, then experiencing an immediate burning sensation, and noticing anosmia within 48 hours (17083). On June 16, 2009, the US Food and Drug Administration (FDA) advised patients not to use a specific line of commercial zinc nasal products (Zicam) after receiving 130 reports of loss of smell (16800). The manufacturer of these products had also received several hundred reports of loss of smell related to its intranasal zinc products (16801). Zinc sulfate nasal spray was used unsuccessfully for polio prophylaxis before the polio vaccine was developed. It caused loss of smell and/or taste, which was sometimes permanent (11713). Animal studies suggest that zinc sulfate negatively affects smell, possibly by damaging the olfactory epithelium and neurons (11156,11703,11704,11705,11706). Zinc gluconate nasal spray has not been tested for safety in animals or humans. The clinical studies of intranasal zinc have not described anosmia as an adverse effect, but testing was not done to see if zinc use adversely affected sense of smell (6471,8628,8629,10247). Also, these clinical studies reported tingling or burning sensation in the nostril, dry nose, nose pain, and nosebleeds.
When used in amounts above the tolerable upper intake level (UL), zinc may cause flu-like symptoms including coughing (2663).
Renal ...In overdose, zinc can cause acute renal tubular necrosis and interstitial nephritis (331,1352,87338).
Other ...Occupational inhalation of zinc oxide fumes can cause metal fume fever with symptoms including fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, and salivation (331).
