Two capsules contains: Pyridoxine Hydrochloride (Vitamin B6) 2 mg • Cyanocobalamin (Vitamin B12) 10 mcg • Cholecalciferol (Vitamin D3) 2000 IU • Proprietary Blend 1000 mg: Horny Goat Weed , Tribulus terrestris (45% Saponins), Yohimbe bark extract, Fenugreek extract (60% Fenusides).
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Alpha. 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
Below is general information about the safety of the known ingredients contained in the product Alpha. 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 in amounts commonly found in foods. Fenugreek has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when the seed is used orally in medicinal amounts. Fenugreek seed powder 5-10 grams daily has been used with apparent safety for up to 3 years. Fenugreek seed extract 1 gram daily has been used with apparent safety for up to 3 months (7389,9783,18359,18362,49868,90112,90113,90117,93419,93420)(93421,93422,93423,96065,103285,108704).
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of fenugreek when used in larger amounts. Unusual body and urine odor has been reported after consumption of fenugreek tea. Although the odor appears to be harmless, it may be misdiagnosed as maple syrup urine disease (9782,96068).
PREGNANCY: LIKELY UNSAFE
when used orally in amounts greater than those found in food.
Fenugreek has potential oxytoxic and uterine stimulant activity (12531). There are case reports of congenital malformations, including hydrocephalus, anencephaly, cleft palate, and spina bifida, after consumption of fenugreek seeds during pregnancy (96068). Consumption of fenugreek immediately prior to delivery may cause the neonate to have unusual body odor. Although this does not appear to cause long-term sequelae, it may be misdiagnosed as maple syrup urine disease (9781,96068).
LACTATION: POSSIBLY SAFE
when used orally to stimulate lactation, short-term.
Although most available clinical studies lack safety testing in the lactating parent or infant (12535,22569,22570), some evidence suggests that taking fenugreek 1725 mg three times daily orally for 21 days does not cause negative side effects in the infant (90115).
POSSIBLY SAFE ...when horny goat weed extract is used orally and appropriately, short-term. A specific extract of horny goat weed containing 60 mg icariin, 15 mg daidzein, and 3 mg genistein (Xianling Gubao; Tong Ji Tang Pharmacal Company) has been used daily with apparent safety for up to 24 months (14900,97268). Another aqueous extract of horny goat weed containing up to 25.36% icariin has been used in a dose of 300 mL daily with apparent safety for up to 6 months (55452). Another horny goat weed extract has been used with apparent safety at doses up to 1000 mg daily (providing 200 mg icariin) for up to 30 days (108311).
POSSIBLY UNSAFE ...when used orally long-term or in high doses. Long-term use, or taking high doses of some species of horny goat weed, has been linked to serious adverse effects including respiratory arrest (10346).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Horny goat weed might have androgenic activity (10346). Theoretically, it might harm a developing fetus; avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY UNSAFE ...when the spine-covered fruit is used orally. There have been reports of bilateral pneumothorax and bronchial polyp after oral consumption of the spine-covered fruit (818).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Animal research suggests that tribulus might adversely affect fetal development (12674); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally, topically, intravenously, intramuscularly, or intranasally and appropriately. Vitamin B12 is generally considered safe, even in large doses (15,1344,1345,1346,1347,1348,2909,6243,7289,7881)(9414,9416,10126,14392,15765,82832,82949,82860,82864,90386)(111334,111551).
PREGNANCY: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA for vitamin B12 during pregnancy is 2.6 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA of vitamin B12 during lactation is 2.8 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 while breastfeeding.
LIKELY SAFE ...when used orally and appropriately in doses that do not exceed the tolerable upper intake level (UL) of 100 mg daily in the form of pyridoxine for adults (15,6243). ...when used parenterally and appropriately. Injectable vitamin B6 (pyridoxine) is an FDA-approved prescription product (15).
POSSIBLY SAFE ...when used orally and appropriately in doses of 101-200 mg daily (6243,8558).
POSSIBLY UNSAFE ...when used orally in doses at or above 500 mg daily. High doses, especially those exceeding 1000 mg daily or total doses of 1000 grams or more, pose the most risk. However, neuropathy can occur with lower daily or total doses (6243,8195). ...when used intramuscularly in high doses and frequency due to potential for rhabdomyolysis (90795).
CHILDREN: LIKELY SAFE
when used orally and appropriately in doses that do not exceed the tolerable upper intake level (UL) of vitamin B6 in the form of pyridoxine 30 mg daily for children aged 1-3 years, 40 mg daily for 4-8 years, 60 mg daily for 9-13 years, and 80 mg daily for 14-18 years (6243).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately in amounts exceeding the recommended dietary allowance (5049,8579,107124,107125,107135).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses, long-term (6243).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
A special sustained-release product providing vitamin B6 (pyridoxine) 75 mg daily is FDA-approved for use in pregnancy. Vitamin B6 (pyridoxine) is also considered a first-line treatment for nausea and vomiting in pregnancy by the American College of Obstetrics and Gynecology (111601). However, it should not be used long-term or without medical supervision and close monitoring. The tolerable upper intake level (UL) refers to vitamin B6 in the form of pyridoxine and is 80 mg daily for those aged 14-18 years and 100 mg daily for 19 years and older (6243).
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses.
There is some concern that high-dose maternal vitamin B6 (pyridoxine) can cause neonatal seizures (4609,6397,8197).
LACTATION: LIKELY SAFE
when used orally in doses not exceeding the tolerable upper intake level (UL) of vitamin B6 in the form of pyridoxine 80 mg daily for those aged 14-18 years and 100 mg daily for those 19 years and older.
The recommended dietary allowance (RDA) in lactating women is 2 mg daily (6243). There is insufficient reliable information available about the safety of vitamin B6 when used in higher doses in breast-feeding women.
LIKELY SAFE ...when used orally or intramuscularly and appropriately. Vitamin D has been safely used in a wide range of doses (7555,16888,16891,17476,95913,98186,104619,105209,109040,109059)(115580,115590). 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 (16891,17476,115590). 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).
POSSIBLY UNSAFE ...when used orally. Yohimbine, a constituent of yohimbe, has been associated with serious adverse effects including cardiac arrhythmia, agitation, myocardial infarction, seizure, and others (17465). Some research shows that yohimbine can be safely used under close medical supervision for up to 10 weeks (3305,3307,3311,3313). However, due to safety concerns, yohimbe should not be used without medical supervision.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally.
Yohimbe might have uterine relaxant effects and also cause fetal toxicity (19).
Below is general information about the interactions of the known ingredients contained in the product Alpha. 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, fenugreek might have additive effects when used with anticoagulant or antiplatelet drugs.
 Details
Some of the constituents in fenugreek have antiplatelet effects in animal and in vitro research. However, common fenugreek products might not contain sufficient concentrations of these constituents for clinical effects. A clinical study in patients with coronary artery disease or diabetes shows that taking fenugreek seed powder 2.5 grams twice daily for 3 months does not affect platelet aggregation, fibrinolytic activity, or fibrinogen levels (5191,7389,49643).
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Theoretically, fenugreek seed might have additive hypoglycemic effects when used with antidiabetes drugs.
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Theoretically, fenugreek seed might alter the clinical effects of clopidogrel by inhibiting its conversion to the active form.
Details
Animal research shows that fenugreek seed 200 mg/kg daily for 14 days increases the maximum serum concentration of clopidogrel by 21%. It is unclear how this affects the pharmacokinetics of the active metabolite of clopidogrel; however, this study found that concomitant use of fenugreek seed and clopidogrel prolonged bleeding time by an additional 11% (108701).
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Theoretically, fenugreek seed might have additive hypotensive effects when used with metoprolol.
Details
Animal research shows that fenugreek seed 300 mg/kg daily for 2 weeks decreases systolic and diastolic blood pressure by 9% and 11%, respectively, when administered alone, and by 15% and 22%, respectively, when given with metoprolol 10 mg/kg (108703).
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Theoretically, fenugreek might decrease plasma levels of phenytoin.
Details
Animal research shows that taking fenugreek seeds for 1 week decreases maximum concentrations and the area under the curve of a single dose of phenytoin by 44% and 72%, respectively. This seems to be related to increased clearance (110905). So far, this interaction has not been reported in humans.
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Theoretically, concurrent use of sildenafil and fenugreek might reduce levels and therapeutic effects of sildenafil.
Details
Animal research shows that taking fenugreek seeds for 1 week reduces maximum concentrations and the area under the curve of a single dose of sildenafil by 27% and 48%, respectively (110898). So far, this interaction has not been reported in humans.
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Theoretically, fenugreek may reduce the levels and clinical effects of theophylline.
Details
Animal research shows that fenugreek 50 grams daily for 7 days reduces the maximum serum concentration (Cmax) of theophylline by 28% and the area under the plasma drug concentration-time curve (AUC) by 22% (90118).
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Theoretically, fenugreek might have additive effects with warfarin and increase the international normalized ratio (INR).
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Theoretically, horny goat weed might increase the risk of bleeding.
Details
In vitro research and animal research shows that horny goat weed can inhibit platelet aggregation and thrombus formation (105832). This effect has not been reported in humans.
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Theoretically, horny goat weed might increase the risk of hypotension.
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Laboratory research suggests that horny goat weed might have hypotensive effects (10346). This effect has not been reported in humans.
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Theoretically, horny goat weed might increase the effects and side effects of CYP1A2 substrates.
Details
In vitro, horny goat weed leaf extract inhibits CYP1A2 (97267). This effect has not been reported in humans.
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Theoretically, horny goat weed might increase the effects and side effects of CYP2B6 substrates.
Details
In vitro, horny goat weed leaf extract inhibits CYP2B6 (97267). This effect has not been reported in humans.
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Theoretically, horny goat weed might increase the effects and side effects of CYP3A4 substrates.
Details
In vitro, horny goat weed extract inhibits CYP3A4 and suppresses CYP3A4 mRNA expression (112708). This effect has not been reported in humans.
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Theoretically, concomitant use of horny goat weed with estrogens might increase their therapeutic and adverse effects.
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Taking tribulus with antidiabetes drugs might increase the risk of hypoglycemia.
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Clinical research shows that Tribulus can lower blood glucose levels in adults with type 2 diabetes who are taking antidiabetes medications (97327).
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Theoretically, taking tribulus with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, tribulus might increase the levels and clinical effects of lithium.
Details
Tribulus is thought to have diuretic properties (12681). Due to these potential diuretic effects, tribulus might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.
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Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
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Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Details
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure (30859,82959,83093). Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine (83091).
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Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Details
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people (3046).
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High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
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High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
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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.
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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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Theoretically, combining yohimbe bark with antiplatelet or anticoagulant drugs might have additive effects; however, this has not been reported in clinical research.
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Research in healthy adults shows that taking yohimbine, a constituent of yohimbe bark, in doses of 8 mg or more, seems to inhibit platelet aggregation in vitro by binding to the alpha-2 adrenoceptor (86773,86806,86835,86853). The effects of yohimbe bark itself are unclear; yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed (86862,89263).
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Theoretically, yohimbe might reduce the effects of antihypertensive drugs.
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Theoretically, yohimbe might precipitate clonidine withdrawal.
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Chronic clonidine use can downregulate alpha-2 adrenoreceptors. Animal research and one human case report suggest that concomitant administration of yohimbine, an alpha-2 adrenoceptor antagonist, may precipitate clonidine withdrawal and lead to sympathomimetic toxicity, including hypertensive crisis (111406).
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Theoretically, yohimbe might decrease the levels and clinical effects of CYP1A2 substrates.
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In vitro research shows that yohimbe extract induces CYP1A2 enzymes (111404).
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CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
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In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes (105688,105697,105698). Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine and reduces the clearance of yohimbine compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers. (114932).
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Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.
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In vitro research suggests that yohimbine, a constituent of yohimbe bark, inhibits CYP2D6 enzyme activity (23117).
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Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe bark.
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Theoretically, yohimbe might decrease the levels and clinical effects of CYP3A4 substrates.
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In vitro research shows that yohimbe extract induces CYP3A4 enzymes (111404).
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Concomitant use of MAOIs with yohimbe can result in additive effects.
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Paroxetine decreases the clearance of yohimbine and may increase its effects.
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Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine by about 350% and reduces the clearance of yohimbine by about 80% compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers. No significant changes in pharmacokinetic parameters of yohimbine were observed with coadministration of paroxetine in patients who are poor CYP2D6 metabolizers (114932).
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Theoretically, using yohimbine with phenothiazines might have additive effects.
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Yohimbine, a constituent of yohimbe, has alpha-2 adrenergic antagonist effects. Theoretically, combining it with phenothiazines can cause additive alpha-2 adrenergic antagonism (19).
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Theoretically, taking yohimbe with stimulant drugs can have additive effects.
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Theoretically, taking yohimbe with TCAs can increase adverse effects.
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A small clinical study in patients taking TCAs for at least 4 weeks shows that receiving doses of intravenous yohimbine 2.5-20 mg daily for up to 7 days precipitates severe anxiety, agitation, and tremor (105881). The effects of yohimbe bark itself are unclear; oral yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed (86862,89263).
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Below is general information about the adverse effects of the known ingredients contained in the product Alpha. 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, fenugreek seed is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, diarrhea, dyspepsia, flatulence, hypoglycemia, and nausea.
Serious Adverse Effects (Rare):
All ROA: Severe allergic reactions including angioedema, bronchospasm, and shock.
Endocrine ...Orally, large doses of fenugreek seed, 100 grams daily of defatted powder, have caused hypoglycemia (164,96068).
Gastrointestinal ...Orally, fenugreek seed can cause mild gastrointestinal symptoms, such as diarrhea, dyspepsia, abdominal distention and pain, nausea, and flatulence, especially when taken on an empty stomach (622,12534,18349,93421,96065,96068,105016).
Immunologic ...Fenugreek can cause allergic reactions when used orally and topically, and when the powder is inhaled (719,96068). Orally, fenugreek has caused bronchospasm, diarrhea, and itching, and skin reactions severe enough to require intravenous human immunoglobulin (96068). Topically, fenugreek paste has resulted in facial swelling, wheezing, and numbness around the head (719,96068). When used both orally and topically by a single individual, asthma and rhinitis occurred (96068). Inhalation of fenugreek powder has resulted in fainting, sneezing, runny nose, and eye tearing (719,96068).
Neurologic/CNS ...Orally, loss of consciousness has occurred in a 5 week-old infant drinking tea made from fenugreek (9782). Dizziness and headaches have been reported in clinical research of fenugreek extract (49551,93419). However, these events are rare.
Renal ...Orally, fenugreek aqueous see extract may increase the frequency of micturition, although this even appears to be rare (49551).
Other
...Consumption of fenugreek during pregnancy, immediately prior to delivery, may cause the neonate to have an unusual body odor, which may be confused with maple syrup urine disease.
It does not appear to cause long-term sequelae (9781). This unusual body odor may also occur in children drinking fenugreek tea. A case of a specific urine and sweat smell following oral fenugreek extract use has been reported for a patient in one clinical trial (18349).
In 2011, outbreaks of enteroaggregative hemorrhagic Escherichia coli (EATEC) O104:H4 infection occurred in Germany and Spain. Epidemiological studies linked the outbreaks to fenugreek seeds that had been imported from Africa. However, laboratory analyses were unable to isolate the causative strain of bacteria from fenugreek seed samples (49776,49777,49781,90114).
General
...Orally, horny goat weed seems to be well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Dizziness, dry mouth, nosebleed, thirst, and vomiting.
Serious Adverse Effects (Rare):
Orally: Respiratory arrest.
Cardiovascular ...A 66-year-old male with a history of cardiovascular disease developed tachyarrhythmia after taking horny goat weed for 2 weeks (13006). It is not clear if this product contained only horny goat weed or a combination of ingredients; therefore, assigning causality is not possible.
Gastrointestinal ...Orally, long-term use of horny goat weed has been associated with reports of vomiting, dry mouth, thirst, and nosebleed (10346).
Hepatic ...A case of hepatotoxicity characterized by abdominal pain, nausea, vomiting, and fever has been reported in a 40-year-old male patient with hepatitis C, after a month of taking one tablet daily of a combination product containing horny goat weed and multiple other ingredients (Enzyte, Vianda). Symptoms improved following cessation of the product, but it is not clear if they were due to horny goat weed, another ingredients, or hepatitis C (91590). An observational study over 24 years found 26 cases of drug-induced hepatoxicity associated with horny goat weed (112707).
Musculoskeletal ...Orally, large doses of horny goat weed may cause exaggeration of tendon reflexes to the point of spasm (10346).
Neurologic/CNS ...Orally, long-term use of horny goat weed has been associated with reports of dizziness (10346).
Psychiatric ...There is a case report of hypomania in a 66-year-old male who took horny goat weed for 2 weeks (13006). It is not clear if this product contained only horny goat weed or a combination of ingredients; therefore, assigning causality is not possible.
Pulmonary/Respiratory ...Orally, large doses of horny goat weed may cause respiratory arrest (10346).
General
...Orally, tribulus seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Cases of liver and kidney injury, seizures, and chronic painful erection with impaired sexual function have been reported. Pneumothorax and bronchial polyp after consuming the spine-covered tribulus fruit have been reported.
Gastrointestinal ...Orally, tribulus can cause abdominal pain, cramping, nausea, vomiting, diarrhea, and constipation (92022,92027). However, in one study, the rates of these gastrointestinal complaints were similar for patients taking tribulus and those receiving placebo (92022).
Genitourinary ...In one case report, a patient taking two tribulus tablets (unknown dose) daily for 15 days presented to the local emergency department with a painful erection lasting 72 hours. The priapism was resolved with medical management; however, post-episode sexual function was impaired (92023).
Hepatic ...In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of tribulus water (92069).
Neurologic/CNS ...Orally, tribulus has been reported to cause general excitation and insomnia. These symptoms were reversed upon discontinuation of the drug or decreasing the dose (78867). In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of tribulus water (92069).
Pulmonary/Respiratory ...In one case report, a patient developed a bilateral pneumothorax after consuming the spine-covered fruit of tribulus (818). In another case report, a patient developed a polyp in the lobar bronchus of the right interior lobe due to the presence of a tribulus fruit spine (78852).
Renal ...In one case report, a patient drinking tribulus water 2 liters daily for two days presented with lower limb weakness, seizures, hepatitis, and acute kidney injury. The patient's condition improved after hemodialysis and discontinuation of the tribulus water (92069). In another case report, a healthy male taking one tribulus tablet (unknown dose) daily for a few months for bodybuilding purposes developed hyperbilirubinemia followed by acute kidney failure 2-3 weeks later. The patient was managed with intravenous fluids and a low-salt, low-protein diet (92025).
Other ...In one case report, gynecomastia was observed in a male weightlifter taking an herbal combination product containing tribulus. However, it is not clear if this adverse effect can be attributed to tribulus alone (78859).
General
...Orally, intramuscularly, and topically, vitamin B12 is generally well-tolerated.
Most Common Adverse Effects:
Intramuscular: Injection site reactions.
Serious Adverse Effects (Rare):
Intramuscularly: Severe hypokalemia has been rarely linked with correction of megaloblastic anemia with vitamin B12.
Cardiovascular ...In human clinical research, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12, followed by daily oral administration after coronary stenting, increased restenosis rates (12150). Hypertension following intravenous administration of hydroxocobalamin has been reported in human research (82870,82864).
Dermatologic
...Orally or intramuscularly, vitamin B12 can cause allergic reactions such as rash, pruritus, erythema, and urticaria.
Theoretically, allergic reactions might be caused by the cobalt within the vitamin B12 molecule (82864,90373,90381,103974). In one case report, oral methylcobalamin resulted in contact dermatitis in a 59-year-old Japanese female with a cobalt allergy (103974). In another case report, a 69-year-old female developed a symmetrical erythematous-squamous rash for 5 years after oral vitamin B12 supplementation for 10 years. A patch test confirmed that the systemic allergic dermatitis was due to vitamin B12 supplementation, which resolved 3 months after discontinuation (114578).
Vitamin B12 (intramuscular or oral) has also been associated with at least 19 cases of acneiform eruptions which resolved upon discontinuation of vitamin B12 (90365,90369,90388). High-dose vitamin B12 (20 mcg daily) and vitamin B6 (80 mg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may last up to four months after the supplement is stopped and can be treated with systemic corticosteroids and topical therapy (10998,82870,82871).
Gastrointestinal ...Intravenously, vitamin B12 (hydroxocobalamin) 2. 5-10 grams can cause nausea and dysphagia (82864).
Genitourinary ...Intravenously, vitamin B12 (hydroxocobalamin) 5-15 grams has been associated with chromaturia in clinical research (82870,82871,112282,112264).
Hematologic ...According to case report data, the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia (82914).
Musculoskeletal ...According to case report data, correction of megaloblastic anemia with vitamin B12 has precipitated gout in susceptible individuals (82879).
Neurologic/CNS ...Treatment with vitamin B12 has been rarely associated with involuntary movements in infants with vitamin B12 deficiency (90370,90385,90397). In some cases these adverse reactions were misdiagnosed as seizures or infantile tremor syndrome (90370,90385). These adverse reactions presented 2-5 days after treatment with vitamin B12 and resolved once vitamin B12 was discontinued (90370,90385,90397).
Oncologic ...Although some epidemiological research disagrees (9454), most research has found that elevated plasma levels of vitamin B12 are associated with an increased risk of various types of cancer, including lung and prostate cancers and solid tumors (50411,102383,107743). One study found, when compared with blood levels of vitamin B12 less than 1000 ng/mL, plasma vitamin B12 levels of at least 1000 ng/mL was strongly associated with the occurrence of solid cancer (107743). It is unclear if increased intake of vitamin B12, either through the diet or supplementation, directly affects the risk of cancer. It is possible that having cancer increases the risk of vitamin B12 elevation. However, one observational study has found that the highest quintile of dietary intake of vitamin B12 is associated with a 75% increased incidence of developing esophageal cancer when compared with the lowest quintile in never drinkers, but not drinkers (107147).
Renal ...There is a case report of oxalate nephropathy in a 54-year-old male which was determined to be related to the use of intravenous hydroxocobalamin as treatment for cyanide poisoning. Intermittent hemodialysis was started 5 days after admission, along with a low-oxalate diet, oral calcium acetate, and pyridoxine 5 mg/kg daily (107148). A review of the use of intravenous hydroxocobalamin for suspected cyanide poisoning in 21 intensive care units in France between 2011 and 2017 resulted in a 60% increased odds of acute kidney injury and a 77% increased odds of severe acute kidney injury in the first week. However, biopsies were not conducted and a direct link with use of hydroxocobalamin could not be made (107139).
Other ...Several studies have found that higher vitamin B12 levels may be associated with increased mortality or decreased survival rates in hospitalized elderly patients (82889,82812,82857,82895). Human research has also found a positive correlation between vitamin B12 status and all-cause mortality in Pima Indians with diabetes (82863).
General
...Orally or by injection, vitamin B6 is well tolerated in doses less than 100 mg daily.
Most Common Adverse Effects:
Orally or by injection: Abdominal pain, allergic reactions, headache, heartburn, loss of appetite, nausea, somnolence, vomiting.
Serious Adverse Effects (Rare):
Orally or by injection: Sensory neuropathy (high doses).
Dermatologic ...Orally, vitamin B6 (pyridoxine) has been linked to reports of skin and other allergic reactions and photosensitivity (8195,9479,90375). High-dose vitamin B6 (80 mg daily as pyridoxine) and vitamin B12 (20 mcg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may persist for up to 4 months after the supplement is stopped, and may require treatment with systemic corticosteroids and topical therapy (10998).
Gastrointestinal ...Orally or by injection, vitamin B6 (pyridoxine) can cause nausea, vomiting, heartburn, abdominal pain, mild diarrhea, and loss of appetite (8195,9479,16306,83064,83103,107124,107127,107135). In a clinical trial, one patient experienced infectious gastroenteritis that was deemed possibly related to taking vitamin B6 (pyridoxine) orally up to 20 mg/kg daily (90796). One small case-control study has raised concern that long-term dietary vitamin B6 intake in amounts ranging from 3.56-6.59 mg daily can increase the risk of ulcerative colitis (3350).
Hematologic ...Orally or by injection, vitamin B6 (pyridoxine) can cause decreased serum folic acid concentrations (8195,9479). One case of persistent bleeding of unknown origin has been reported in a clinical trial for a patient who used vitamin B6 (pyridoxine) 100 mg twice daily on days 16 to 35 of the menstrual cycle (83103). It is unclear if this effect was due to vitamin B6 intake.
Musculoskeletal ...Orally or by injection, vitamin B6 (pyridoxine) can cause breast soreness or enlargement (8195).
Neurologic/CNS ...Orally or by injection, vitamin B6 (pyridoxine) can cause headache, paresthesia, and somnolence (8195,9479,16306). Vitamin B6 (pyridoxine) can also cause sensory neuropathy, which is related to daily dose and duration of intake. Doses exceeding 1000 mg daily or total doses of 1000 grams or more pose the most risk, although neuropathy can occur with lower daily or total doses as well (8195). The mechanism of the neurotoxicity is unknown, but is thought to occur when the liver's capacity to phosphorylate pyridoxine via the active coenzyme pyridoxal phosphate is exceeded (8204). Some researchers recommend taking vitamin B6 as pyridoxal phosphate to avoid pyridoxine neuropathy, but its safety is unknown (8204). Vitamin B6 (pyridoxine) neuropathy is characterized by numbness and impairment of the sense of position and vibration of the distal limbs, and a gradual progressive sensory ataxia (8196,10439). The syndrome is usually reversible with discontinuation of pyridoxine at the first appearance of neurologic symptoms. Residual symptoms have been reported in patients taking more than 2 grams daily for extended periods (8195,8196). Daily doses of 100 mg or less are unlikely to cause these problems (3094).
Oncologic ...In females, population research has found that a median intake of vitamin B6 1. 63 mg daily is associated with a 3.6-fold increased risk of rectal cancer when compared with a median intake of 1.05 mg daily (83024). A post-hoc subgroup analysis of results from clinical research in adults with a history of recent stroke or ischemic attack suggests that taking folic acid, vitamin B12, and vitamin B6 does not increase cancer risk overall, although it was associated with an increased risk of cancer in patients who also had diabetes (90378). Also, in patients with nasopharyngeal carcinoma, population research has found that consuming at least 8.6 mg daily of supplemental vitamin B6 during treatment was associated with a lower overall survival rate over 5 years, as well as a reduced progression-free survival, when compared with non-users and those with intakes of up to 8.6 mg daily (107134).
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, there is limited information available about the adverse effects of yohimbe.
Yohimbine, a constituent of yohimbe, might be unsafe; most reported adverse effects are dose-related.
Most Common Adverse Effects:
Orally: Yohimbine, a constituent of yohimbe, has been associated with anxiety, agitation, diaphoresis, diarrhea, flushing, headache, hypertension, increased urination, nausea, tachycardia, tremors, vertigo, and vomiting.
Serious Adverse Effects (Rare):
Orally: Yohimbine, a constituent of yohimbe, has been associated with atrial fibrillation, hypertensive crisis, myocardial infarction, and QT interval prolongation.
Cardiovascular ...Orally, yohimbine, a constituent of yohimbe, has been associated with hypertension, especially at higher doses (3312,17465,86801,86802,86804,86811,86820,86822,86834,86856)(86786,86896). A case of hypertensive crisis was reported in a 63-year-old male taking a yohimbine-containing herbal product once daily for one month. The patient was successfully managed with intravenous nitroprusside followed by clonidine (91521). Tachycardia, fluid retention, palpitations, and chest discomfort have also been reported (3312,17465,86786,86793,86801,86802,86804,86822,86843,86854)(86856,86866,86867,86869,86871,86874,86875). Conduction abnormalities have also been reported (86856,86786). There have been some reports of myocardial infarction, atrial fibrillation, and QT interval prolongation (17465). In theory, these effects may also occur with the use of yohimbe bark extract.
Dermatologic ...Orally, yohimbine, a constituent of yohimbe, may cause rash, erythrodermic skin eruption, and exanthema (3312,3971,86804,86896,86878).
Gastrointestinal ...Orally, yohimbine, a constituent of yohimbe, may cause nausea, vomiting, increased salivation, diarrhea, and gastrointestinal distress (3970,17465,49902,86780,86781,86786,86801,86804,86824,86827)(86828,86829,86863,86878,86882,86896).
Genitourinary ...Orally, yohimbine may cause dartos contraction or decreased libido in some patients (86786,86882). A case of severe intractable priapism has been reported for a 42-year-old male who took a supplement containing yohimbe extract the previous day for sexual enhancement. Treatment with phenylephrine 400 mcg was unsuccessful at resolving the priapism, so surgical insertion of a proximal cavernosal spongiosum shunt was needed (86804).
Hematologic ...A case of drug-induced agranulocytosis has been reported following prolonged use of oral yohimbine, a constituent of yohimbe (86877).
Immunologic ...There is one report of a hypersensitivity reaction including fever; chills; malaise; itchy, scaly skin; progressive renal failure; and lupus-like syndrome associated with ingestion of a one-day dose of yohimbine, a constituent of yohimbe (6169).
Musculoskeletal ...Orally, yohimbine, a constituent of yohimbe, may cause muscle aches (86850).
Neurologic/CNS ...Orally, yohimbine, a constituent of yohimbe, has been associated with reports of general central nervous system (CNS) and autonomic excitation, tremulousness, head twitching, seizure threshold changes, enhanced brain norepinephrine release, decreased energy, dizziness, vertigo, and headache (3312,3971,86774,86779,86786,86804,86827,86857,86870,86882)(86883). Cold feet and chills have also been reported with yohimbine (86827,86896). Other adverse reactions include flushing and diaphoresis (17465). Excessive doses of yohimbine can also cause paralysis (11,18). A case of acute neurotoxicity characterized by malaise, vomiting, loss of consciousness, and seizures has been reported for a 37-year-old bodybuilder who ingested a single dose of yohimbine 5 grams. Improvement was seen within 12 hours following treatment with furosemide, labetalol, clonidine, urapidil, and gastrointestinal decontamination (86801).
Psychiatric ...Orally, yohimbine, a constituent of yohimbe, may increase malaise, fatigue, insomnia, restlessness, agitation, and anxiety (3312,3970,3971,17465,86786,86801,86804,86822,86827,86834)(86868,86878,86882,86896). In a clinical study of healthy subjects, administration of yohimbine increased impulsivity, with larger doses increasing impulsivity more than 50% (86784,86810).
Pulmonary/Respiratory ...Orally, yohimbine, a constituent of yohimbe, may cause bronchospasm, tachypnea, cough, and rhinorrhea (17465,86825,86850). A case of sinusitis characterized by pain and discomfort above both eyes has been reported for a 59-year-old male taking yohimbine 5.4 mg three times daily to treat erectile dysfunction. Symptoms resolved within 24 hours of discontinuing yohimbine. The effect was attributed to the alpha-2 adrenergic antagonist effects of yohimbine (94112). Excessive doses of yohimbine can cause respiratory depression (1118).
Renal ...Orally, yohimbine, a constituent of yohimbe, may increase urinary frequency (3312,3970,3971,17465,86804,86827,86850,86861,86882). A case of acute renal failure has been reported for a 42-year-old male taking yohimbine. Normalization of renal function was achieved following 2 weeks of treatment with corticosteroids. The renal dysfunction was attributed to yohimbine-induced systemic lupus erythematosus (6169).
