Ingredients | Amount Per Serving |
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(Ca)
(Calcium Phosphate)
(Calcium (Form: from Calcium Phosphate) )
|
50 mg |
(Trifolium pratense )
((25:1) (providing))
(standardized Red Clover extract Genus: Trifolium Species: pratense Note: (25:1) (providing) )
|
200 mg |
Isoflavones
(Biochanin A, Daidzein, Formononetin, Genistein)
|
80 mg |
Calcium Phosphate (Alt. Name: Ca Phosphate), Microcrystalline Cellulose, Coating Solution, Silica, Croscarmellose Sodium, Magnesium Stearate, Mixed Tocopherols, Carnauba Wax
Below is general information about the effectiveness of the known ingredients contained in the product Promensil Menopause Double Strength. 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
Below is general information about the safety of the known ingredients contained in the product Promensil Menopause Double Strength. 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 used orally or intravenously and appropriately. Calcium is safe when used in appropriate doses (7555,12928,12946,95817). However, excessive doses should be avoided. The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: Age 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg; 19-50 years, 2500 mg; 51+ years, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stone, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients not to consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).
POSSIBLY UNSAFE ...when used orally in excessive doses. The National Academy of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 19-50 years, 2500 mg; 51 years and older, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients to not consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Calcium is safe when used in appropriate doses (17506).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses.
The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately (945,1586,3263,3264,17506).
The World Health Organization (WHO) recommends prescribing oral calcium supplementation 1.5-2 grams daily during pregnancy to those with low dietary calcium intake to prevent pre-eclampsia (97347).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
The Institute of Medicine sets the same daily tolerable upper intake level (UL) for calcium according to age independent of pregnancy status: 9-18 years, 3000 mg; 19-50 years, 2500 mg (17506). Doses over these amounts might increase the risk of neonatal hypocalcemia-induced seizures possibly caused by transient neonatal hypoparathyroidism in the setting of excessive calcium supplementation during pregnancy, especially during the third trimester. Neonatal hypocalcemia is a risk factor for neonatal seizures (97345).
LIKELY SAFE ...when used orally in amounts commonly used in foods. Red clover has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912,10372).
POSSIBLY SAFE ...when used orally and appropriately in supplemental amounts. Red clover extracts containing up to 80 mg isoflavones have been used with apparent safety in clinical studies lasting up to 2 years (3375,6127,8925,11089,11091,17091,19540,19556,91524,102901,102840). ...when used topically and appropriately. Red clover extracts have been used topically with apparent safety for up to 4 weeks (102839).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Red clover has estrogenic activity (19555); avoid using. There is insufficient reliable information available about the safety of the topical use of red clover during pregnancy and lactation.
Below is general information about the interactions of the known ingredients contained in the product Promensil Menopause Double Strength. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
Details
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease (21631). However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption (93006).
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Calcium reduces the absorption of bisphosphonates.
Details
Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates (12937).
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Taking calcipotriene with calcium might increase 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 (12938). Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.
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Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Details
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects (6124). But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers (12939,12947).
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Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Details
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction (15794,21632). So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.
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Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
Details
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Theoretically, calcium may reduce the therapeutic effects of diltiazem.
Details
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.
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Calcium seems to reduce levels of dolutegravir.
Details
Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation (93578).
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Calcium seems to reduce levels of elvitegravir.
Details
Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation (94166).
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Calcium seems to reduce the absorption and effectiveness of levothyroxine.
Details
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Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
Details
Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients (38953). Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.
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Calcium seems to reduce the absorption of quinolone antibiotics.
Details
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Calcium may reduce levels of raltegravir.
Details
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir (94164). However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure (94165).
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Calcium seems to reduce the absorption of sotalol.
Details
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes (10018).
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Calcium seems to reduce the absorption of tetracycline antibiotics.
Details
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut (1843).
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Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Details
Thiazides reduce calcium excretion by the kidneys (1902). Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.
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Theoretically, calcium may reduce the therapeutic effects of verapamil.
Details
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.
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Although some laboratory research suggests that red clover may have anticoagulant and antiplatelet activity, clinical research has not shown this effect.
Details
In vitro research suggests that genistein in red clover has antiplatelet effects, and historically, red clover was thought to have anticoagulant effects due to its coumarin content. However, some experts state that this is unlikely as most natural coumarins have not been shown to have anticoagulant effects, and their content in red clover is low (17091,19557,19558,19559). Additionally, some clinical research in postmenopausal patients found no effect on coagulation or prothrombin time with the use of red clover flowering tops 378 mg daily for 12 months or red clover isoflavone (Rimostil) 50 mg daily for 2 years (17091,91524).
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Theoretically, soy might reduce the clearance of caffeine; however, a small clinical study found no effect.
Details
Red clover contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females (23582). However, this effect does not seem to occur with the lower amounts of genistein found in red clover. A clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine (105693).
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Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
Details
In vitro evidence shows that red clover inhibits CYP1A2 (12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate (105693).
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Theoretically, red clover might increase the levels and clinical effects of drugs metabolized by CYP2C19.
Details
In vitro evidence suggests that red clover weakly inhibits CYP2C19 (12479). This interaction has not been reported in humans.
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Theoretically, red clover might increase levels of drugs metabolized by CYP2C9; however, a small clinical study found no effect.
Details
In vitro evidence suggests that red clover might inhibit CYP2C9 (12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of tolbutamide, a CYP2C9 probe substrate (105693).
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Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.
Details
In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes (6450,12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of alprazolam, a CYP3A4 probe substrate (105693).
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Theoretically, concomitant use of large amounts of red clover might interfere with estrogen therapy.
Details
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Theoretically, red clover might increase the risk of methotrexate toxicity.
Details
In a case report, a 52-year-old female receiving weekly methotrexate injections for psoriasis developed symptoms of methotrexate toxicity, including severe vomiting and epigastric pain, after three days of taking red clover 430 mg daily. Toxicity resolved after red clover was discontinued. However, no liver function tests or methotrexate levels were reported (91522).
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Theoretically, the phytoestrogens in red clover might interfere with tamoxifen.
Details
In vitro and animal research suggests that genistein, a constituent of red clover, might antagonize the antitumor effects of tamoxifen (8192). However, there is some evidence from an animal study that red clover does not reduce the efficacy of tamoxifen (102901). Until more is known, tell patients taking tamoxifen to avoid red clover.
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Below is general information about the adverse effects of the known ingredients contained in the product Promensil Menopause Double Strength. 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 intravenously, calcium is well-tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Belching, constipation, diarrhea, flatulence, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about calciphylaxis and kidney stones.
Cardiovascular
...There has been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI).
Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these results, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Reasons for these discrepancies are not entirely clear. It may relate to whether calcium is taken as monotherapy or in combination with vitamin D. When taken with vitamin D, which is commonly recommended, calcium supplementation does not appear to be associated with an increased risk of CVD, CHD, or MI (93533,107231). Also, the association between calcium supplementation and CVD, CHD, or MI risk may be influenced by the amount of calcium consumed as part of the diet. Supplementation with calcium may be associated with an increased risk of MI in people with dietary calcium intake above 805 mg daily, but not in those with dietary calcium intake below 805 mg daily (17482). To minimize the possible risk of CVD, CHD, or MI, advise patients not to consume more than the recommended daily intake of 1000-1200 mg and to consider total calcium intake from both dietary and supplemental sources (17484). While dietary intake of calcium is preferred over supplemental intake, advise patients who require calcium supplements to take calcium along with vitamin D, as this combination does not appear to be associated with an increased risk of MI (93533).
Rarely, calcium intake can increase the risk of calciphylaxis, which usually occurs in patients with kidney failure. Calciphylaxis is the deposition of calcium phosphate in arterioles, which causes skin ulcers and skin necrosis. In a case report, a 64-year-old female with a history of neck fracture, sepsis, and ischemic colitis presented with painful leg ulcers due to calciphylaxis. She discontinued calcium and vitamin D supplementation and was treated with sodium thiosulfate and supportive care (95816).
Gastrointestinal ...Orally, calcium can cause belching, flatulence, nausea, gastrointestinal discomfort, and diarrhea (1824,1843,12950,38803). Although constipation is frequently cited as an adverse effect of calcium, there is no scientific substantiation of this side effect (1824,1843,1844,1845,12950,38978). Calcium carbonate has been reported to cause acid rebound, but this is controversial (12935,12936).
Oncologic ...There is some concern that very high doses of calcium might increase the risk of prostate cancer. Some epidemiological evidence suggests that consuming over 2000 mg/day of dietary calcium might increase the risk for prostate cancer (4825,12949). Additional research suggests that calcium intake over 1500 mg/day might increase the risk of advanced prostate cancer and prostate cancer mortality (14132). Consumption of dairy products has also been weakly linked to a small increase in prostate cancer risk (98894). However, contradictory research suggests no association between dietary intake of calcium and overall prostate cancer risk (14131,14132,104630). More evidence is needed to determine the effect of calcium, if any, on prostate cancer risk.
Renal ...Kidney stones have been reported in individuals taking calcium carbonate 1500 mg daily in combination with vitamin D 2000 IU daily for 4 years (93943).
General
...Orally and topically, red clover seems to be well tolerated.
Most Common Adverse Effects:
Orally: Myalgia, nausea, and vaginal spotting.
Dermatologic ...Orally, a specific red clover isoflavone product (Promensil) has been associated with mild cases of psoriasis and thrush, although a direct causal link has not been established (9552).
Gastrointestinal ...Orally, red clover has been reported to cause nausea (8194).
Genitourinary ...In human research, 80 mg, but not 40 mg, of a specific red clover isoflavone product (Promensil) increased the duration of menstrual cycles in patients with mastalgia (9552). Red clover has also been reported to cause vaginal spotting (8194).
Hematologic ...In one case report, a 53-year-old female had a spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero. It is not clear if this was due to red clover, another ingredient, the combination of ingredients, or other factors (70419). In another case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis 3 days after taking a combination phytoestrogen product containing red clover 250 mg, wild yam 276 mg, dong quai 100 mg, and black cohosh 250 mg (13155). It is unclear if red clover contributed to this event.
Musculoskeletal ...Orally, red clover has been reported to cause myalgia (8194).
Neurologic/CNS ...Orally, a specific red clover isoflavone product (Medoflavon) has been associated with headache, although with a similar frequency to placebo (19545).
Oncologic ...Due to potential estrogenic effects of red clover isoflavones, there has been some concern that red clover might increase the risk of estrogen-sensitive cancers such as breast cancer or uterine cancer. A meta-analysis of 8 clinical trials suggests that increased intake of red clover- and soy-derived isoflavones may modestly increase mammographic breast density in premenopausal, but not postmenopausal, adults when compared with placebo. However, in a sub-group analysis assessing only isolated red clover isoflavones, there was no change in breast density (70428). Furthermore, a 2015 review by the European Food Safety Authority (EFSA) reported no increase in risk of breast cancer in females taking isoflavone-containing supplements (91725). Similarly, no effect was found on endometrial thickness and histopathological changes in the uterus after up to 36 months of supplementation with 40-120 mg daily of isoflavones from red clover extract (91725).