| Ingredients | Amount Per Serving |
|---|---|
|
Ultimate Multi Mineral
|
1000 mg |
|
(Ca Carbonate, CaCO3)
|
500 mg |
|
(Mg Citrate)
|
250 mg |
|
Zinc Amino Acid Chelate
(Zn AAC)
|
17.5 mg |
|
(Mn AAC)
|
5 mg |
| 45 mg | |
| 2000 IU | |
|
(Iodine)
|
5 mg |
| 75 mg | |
|
(A.K)
|
75 mg |
|
(Iron)
(iron)
|
25 mg |
Cellulose, Glycerin, Water
Below is general information about the effectiveness of the known ingredients contained in the product Ultimate Multimineral. 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
There is insufficient reliable information available about the effectiveness of watercress.
There is insufficient reliable information available about the effectiveness of yellow dock.
Below is general information about the safety of the known ingredients contained in the product Ultimate Multimineral. 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 the fruit (nut) is consumed in amounts normally found in food.
POSSIBLY UNSAFE ...when the bark is used orally or topically, due to its juglone content (2). When applied topically, juglone-containing bark can cause skin irritation. When used orally on a daily basis, the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12). There is insufficient reliable information available about the safety of the leaf or hull when used orally as a medicine or when applied topically.
PREGNANCY AND LACTATION: LIKELY SAFE
when the fruit (nut) is consumed in amounts normally found in foods.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when the bark is used orally or topically (12); avoid using.
There is insufficient reliable information available about the safety of black walnut leaf or hull when used orally in medicinal amounts during pregnancy or lactation; avoid using.
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). Other clinical studies suggest that, when combined with vitamin D supplementation, calcium supplementation is not associated with an increased risk of CVD, CHD, or MI (93533,107231). 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, to consider total calcium intake from both dietary and supplemental sources (17484), and to combine calcium supplementation with vitamin D supplementation (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). Other clinical studies suggest that, when combined with vitamin D supplementation, calcium supplementation is not associated with an increased risk of CVD, CHD, or MI (93533,107231). 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, to consider total calcium intake from both dietary and supplemental sources (17484), and to combine calcium supplementation with vitamin D supplementation (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 and appropriately. Oral magnesium is safe when used in doses below the tolerable upper intake level (UL) of 350 mg daily (7555). ...when used parenterally and appropriately. Parenteral magnesium sulfate is an FDA-approved prescription product (96484).
POSSIBLY UNSAFE ...when used orally in excessive doses. Doses greater than the tolerable upper intake level (UL) of 350 mg daily frequently cause loose stools and diarrhea (7555).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Magnesium is safe when used in doses below the tolerable upper intake level (UL) of 65 mg daily for children 1 to 3 years, 110 mg daily for children 4 to 8 years, and 350 mg daily for children older than 8 years (7555,89396). ...when used parenterally and appropriately (96483).
CHILDREN: LIKELY UNSAFE
when used orally in excessive doses.
Tell patients not to use doses above the tolerable upper intake level (UL). Higher doses can cause diarrhea and symptomatic hypermagnesemia including hypotension, nausea, vomiting, and bradycardia (7555,8095).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Magnesium is safe for those pregnant and breast-feeding when used in doses below the tolerable upper intake level (UL) of 350 mg daily (7555).
PREGNANCY AND LACTATION: POSSIBLY SAFE
when prescription magnesium sulfate is given intramuscularly and intravenously prior to delivery for up to 5 days (12592,89397,99354,99355).
However, due to potential adverse effects associated with intravenous and intramuscular magnesium, use during pregnancy is limited to patients with specific conditions such as severe pre-eclampsia or eclampsia. There is some evidence that intravenous magnesium can increase fetal mortality and adversely affect neurological and skeletal development (12590,12593,60818,99354,99355). However, a more recent analysis of clinical research shows that increased risk of fetal mortality seems to occur only in the studies where antenatal magnesium is used for tocolysis and not for fetal neuroprotection or pre-eclampsia/eclampsia (102457). Furthermore, antenatal magnesium does not seem to be associated with increased risk of necrotizing enterocolitis in preterm infants (104396). There is also concern that magnesium increases the risk of maternal adverse events. A meta-analysis of clinical research shows that magnesium sulfate might increase the risk of maternal adverse events, especially in Hispanic mothers compared to other racial and ethnic groups (60971,99319).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Tell patients to avoid exceeding the tolerable upper intake level (UL) of 350 mg daily. Taking magnesium orally in higher doses can cause diarrhea (7555). ...when prescription magnesium sulfate is given intramuscularly and intravenously prior to delivery for longer than 5 days (12592,89397,99354,99355). Maternal exposure to magnesium for longer than 5-7 days is associated with an increase in neonatal bone abnormalities such as osteopenia and fractures. The U.S. Food and Drug Administration (FDA) recommends that magnesium injection not be given for longer than 5-7 days (12590,12593,60818,99354,99355).
LIKELY SAFE ...when used orally and appropriately. Oral manganese is safe when used in doses below the tolerable upper intake level (UL) of 11 mg daily for adults 19 years and older (1994,7135). ...when used parenterally and appropriately. Parenteral manganese chloride and manganese sulfate are FDA-approved prescription products.
POSSIBLY UNSAFE ...when used orally in high doses. Doses exceeding 11 mg daily can cause significant adverse effects (7135). ...when used parenterally in moderate or high doses, long-term. Reports of neurotoxicity and Parkinson-like symptoms have been reported with parenteral nutrition manganese doses above 60 mcg daily. It is recommended that adults on long-term parenteral nutrition receive manganese in doses of no more than 55 mcg daily (99302).
LIKELY UNSAFE ...when inhaled in moderate doses, long-term. According to the US Occupational Safety and Health Administration (OSHA), the permissible exposure limit (PEL) for manganese is 5 mg/m3. Exposure to higher amounts of manganese dust or fumes has been associated with central nervous system toxicity, Parkinson-like symptoms, and poor bone health (61296,102516).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Manganese is safe in children when used in daily doses less than the tolerable upper intake level (UL) of 2 mg in children 1-3 years, 3 mg in children 4-8 years, 6 mg in children 9-13 years, and 9 mg in children 14-18 years (7135).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses.
Daily doses greater than the UL are associated with a greater risk of toxicity (7135).
CHILDREN: LIKELY UNSAFE
when inhaled at moderate doses, long-term.
Exposure to high amounts of manganese dust has been associated with central nervous system toxicity and Parkinson-like symptoms (61296).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Manganese is safe when used in doses below the tolerable upper intake level (UL) of 11 mg daily during pregnancy or lactation in those aged 19 or older. However, those under 19 years of age should limit doses to less than 9 mg daily (7135).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses over the UL are associated with a greater risk of toxicity (7135). Additionally, observational research shows that adults with higher blood manganese levels have greater odds of delivering low birth weight or small for gestational age (SGA) male, but not female, infants (102515).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when inhaled at moderate doses, long-term.
Manganese salts can cross the placenta, and animal research suggests that large amounts of manganese may be teratogenic (61296).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Parsley has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term (12,13173).
LIKELY UNSAFE ...when used orally in very large doses e., 200 grams). Parsley oil contains significant amounts of the potentially toxic constituents, apiole and myristicin (11). Apiole can cause blood dyscrasias, kidney toxicity, and liver toxicity; myristicin can cause giddiness and hallucinations (4). ...when parsley seed oil is used topically. Applying parsley seed oil to the skin can cause photodermatitis upon sun exposure (4). There is insufficient reliable information available about the safety of the topical use of parsley leaf and root.
PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts.
Parsley has been used orally as an abortifacient and to stimulate menstrual flow (4,12,515,19104,92873). Population evidence suggests that maternal intake of An-Tai-Yin, an herbal combination product containing parsley and dong quai, during the first trimester increases the risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in doses up to 100 mEq total potassium daily, not to exceed 200 mEq in a 24-hour period (95010,107989). Oral potassium chloride and potassium citrate are FDA-approved prescription products (95010,107989). Larger doses increase the risk of hyperkalemia (15). ...when administered intravenously (IV) at appropriate infusion rates (95011). Parenteral potassium is an FDA-approved prescription product (15,95011). A tolerable upper intake level (UL) for potassium has not been established; however, potassium levels should be monitored in individuals at increased risk for hyperkalemia, such as those with kidney disease, heart failure, and adrenal insufficiency (100310,107966).
CHILDREN: LIKELY SAFE
when used orally and appropriately in dietary amounts.
A tolerable upper intake level (UL) has not been established for healthy individuals (6243,100310).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in dietary amounts of 40-80 mEq daily (15).
A tolerable upper intake level (UL) has not been established for healthy individuals (100310).
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).
LIKELY SAFE ...when consumed in amounts commonly found in foods.
POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Watercress extract 750 mg/kg daily has been used with apparent safety for up to 5 weeks (103891).
POSSIBLY UNSAFE ...when used orally in excessive amounts or long-term (8,12,19). Watercress can cause gastric mucosal irritation (8,12,85599) or damage (19).
CHILDREN: LIKELY UNSAFE
when used orally in medicinal amounts; avoid using in children younger than 4 years old (12,19).
PREGNANCY: LIKELY UNSAFE
when used in medicinal amounts.
Watercress might stimulate menstruation or have abortifacient effects (19).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when properly prepared and consumed in amounts commonly found in foods. Young leaves must be boiled to remove the oxalate content; death has occurred after consuming uncooked leaves (6,18).
POSSIBLY UNSAFE ...when the uncooked leaves are consumed. Young leaves must be boiled to remove the oxalate content; death has occurred after consuming uncooked leaves (6,18). There is insufficient reliable information available about the safety of properly prepared yellow dock when used orally in medicinal amounts.
PREGNANCY: POSSIBLY UNSAFE
when used orally; avoid using.
Yellow dock contains anthraquinone glycosides; unstandardized laxatives are not desirable during pregnancy (4).
LACTATION: POSSIBLY UNSAFE
when used orally; avoid using.
Anthraquinones are secreted into breast milk (4,5).
Below is general information about the interactions of the known ingredients contained in the product Ultimate Multimineral. 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.
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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.
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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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Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
Details
Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously (13362).
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Use of acid reducers may reduce the laxative effect of magnesium oxide.
Details
A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect (90033). This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.
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Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
Details
In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations (20304,20305). Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity (20306). However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur (60759).
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Magnesium can decrease absorption of bisphosphonates.
Details
Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours (13363).
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Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
Details
Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium (3046,20264,20265,20266), although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness (60831). High doses of magnesium could theoretically have additive effects with other calcium channel blockers.
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Magnesium salts may reduce absorption of digoxin.
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Gabapentin absorption can be decreased by magnesium.
Details
Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43% (90032). Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.
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Magnesium might precipitate ketamine toxicity.
Details
In one case report, a 62-year-old hospice patient with terminal cancer who had been stabilized on sublingual ketamine 150 mg four times daily experienced severe ketamine toxicity lasting for 2 hours after taking a maintenance dose of ketamine following an infusion of magnesium sulfate 2 grams (105078). Since both magnesium and ketamine block the NMDA receptor, magnesium is thought to have potentiated the effects of ketamine.
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Magnesium can reduce the bioavailability of levodopa/carbidopa.
Details
Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa (100265).
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Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
Details
Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics (9613,9614,9622). Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.
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Magnesium decreases absorption of quinolones.
Details
Magnesium can form insoluble complexes with quinolones and decrease their absorption (3046). Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.
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Sevelamer may increase serum magnesium levels.
Details
In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear (96486).
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Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Details
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes (3046,97492,107364). Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate (107364). A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg) (96485). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg (107364). Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time (112781,112782). It does not affect the activity of subsequently administered neostigmine (112782).
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Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Details
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone (20307). A similar interaction occurs between magnesium hydroxide and glipizide (20308). The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas (22364).
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Magnesium decreases absorption of tetracyclines.
Details
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity (12586). Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.
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Theoretically, the risk for manganese toxicity might increase when taken with antipsychotic drugs.
Details
Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients (61493).
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Theoretically, manganese might reduce the absorption of quinolone antibiotics.
Details
Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron (488).
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Theoretically, manganese might reduce the absorption of tetracycline antibiotics.
Details
Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron (488).
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Theoretically, parsley might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
Animal research suggests that parsley has antiplatelet effects (68209).
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Theoretically, parsley might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
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Theoretically, aspirin might increase the severity of allergic reactions to parsley.
Details
In one case, severe urticaria and swelling were reported after taking aspirin with parsley in an individual with a known mild parsley allergy (5054).
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Theoretically, parsley might increase serum levels of CYP1A2 substrates.
Details
Laboratory research suggests that parsley can inhibit CYP1A2 (68176).
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Theoretically, parsley might enhance or interfere with the effects of diuretic drugs.
Details
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Theoretically, parsley might increase the duration of pentobarbital effects.
Details
Animal research suggests that parsley juice prolongs the action of pentobarbital, perhaps by decreasing cytochrome P450 levels (25362). It is not known if this occurs in humans or if this applies to other barbiturates or sedatives.
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Theoretically, large quantities of parsley might increase sirolimus levels.
Details
In one case report, an adult female with a history of kidney transplant presented with elevated blood sirolimus levels, approximately 4-7 times greater than previous measures, after daily consumption of a juice containing approximately 30 grams of parsley for 7 days. Sirolimus levels returned to normal a week after the parsley juice was discontinued (106010).
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Theoretically, large amounts of parsley leaf and root might decrease the effects of warfarin.
Details
Parlsey contains vitamin K (19).
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Using ACEIs with high doses of potassium increases the risk of hyperkalemia.
Details
ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).
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Using ARBs with high doses of potassium increases the risk of hyperkalemia.
Details
ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).
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Concomitant use increases the risk of hyperkalemia.
Details
Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia (15).
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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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Watercress might reduce the metabolism of chlorzoxazone and increase its effects and side effects. Clinical research in healthy volunteers shows that a single ingestion of watercress 50 grams increases the chlorzoxazone plasma concentration-time curve by about 56% and increases its half-life by about 53% (4018).
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Watercress is thought to have diuretic properties (18). Theoretically, due to these potential diuretic effects, watercress might reduce excretion and increase levels of lithium.
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Watercress contains vitamin K. Consuming large amounts of watercress might antagonize the anticoagulant effects of warfarin (11285).
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Theoretically, yellow dock might increase the risk of digoxin toxicity when used long-term or in large amount.
Details
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Theoretically, yellow dock might increase the risk of hypokalemia when taken with diuretics.
Details
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Theoretically, the laxative effects of yellow dock might increase the effects of warfarin, including the risk of bleeding.
Details
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Below is general information about the adverse effects of the known ingredients contained in the product Ultimate Multimineral. 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, black walnut fruit (nut) is well tolerated.
However, the leaf, bark, and hull of black walnut contain high quantities of tannins, which may cause adverse effects when used orally or topically.
Most Common Adverse Effects:
Orally: The leaf, bark, and hull can cause gastrointestinal upset.
Topically: Hull preparations may cause a temporary yellow or brown discoloration at the site of application. The leaf, bark, and hull can cause skin irritation.
Serious Adverse Effects (Rare):
Orally: The bark may increase the risk for tongue cancer or lip leukoplakia when used long-term.
All routes of administration: Allergic reactions, including anaphylaxis.
Dermatologic ...Topically, black walnut leaf, bark, or hull may have an irritating effect on the skin due to tannin content. Black walnut hull preparations might cause a temporary yellow or brown discoloration of the skin at the site of application (12).
Gastrointestinal ...Orally, black walnut leaf, bark, or hull may cause gastrointestinal upset due to tannin content (12). Also, daily use of the juglone-containing bark of a related species (English walnut) is associated with increased risk of tongue cancer and lip leukoplakia (2,12).
Hepatic ...Orally, black walnut leaf, bark, or hull may cause liver damage if taken for extended periods of time due to tannin content (12).
Immunologic ...Tree nuts, which include black walnuts, can cause allergic reactions in sensitive individuals. Due to the prevalence of this allergy in the general population, tree nuts are classified as a major food allergen in the United States (105410).
Renal ...Orally, black walnut leaf, bark, or hull may cause kidney damage if taken for extended periods of time due to tannin content (12).
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
...Magnesium is generally well tolerated.
Some clinical research shows no differences in adverse effects between placebo and magnesium groups.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal irritation, nausea, and vomiting.
Intravenously: Bradycardia, dizziness, flushing sensation, hypotension, and localized pain and irritation. In pregnancy, may cause blurry vision, dizziness, lethargy, nausea, nystagmus, and perception of warmth.
Serious Adverse Effects (Rare):
All ROAs: With toxic doses, loss of reflexes and respiratory depression can occur. High doses in pregnancy can increase risk of neonatal mortality and neurological defects.
Cardiovascular
...Intravenously, magnesium can cause bradycardia, tachycardia, and hypotension (13356,60795,60838,60872,60960,60973,60982,61001,61031,114681).
Inhaled magnesium administered by nebulizer may also cause hypotension (113466). Magnesium sulfate may cause rapid heartbeat when administered antenatally (60915,114681).
In one case report, a 99-year-old male who took oral magnesium oxide 3000 mg daily for chronic constipation was hospitalized with hypermagnesemia, hypotension, bradycardia, heart failure, cardiomegaly, second-degree sinoatrial block, and complete bundle branch block. The patient recovered after discontinuing the magnesium oxide (108966).
Dermatologic ...Intravenously, magnesium may cause flushing, sweating, and problems at the injection site (including burning pain) (60960,60982,111696,114681). In a case study, two patients who received intravenous magnesium sulfate for suppression of preterm labor developed a rapid and sudden onset of an urticarial eruption (a skin eruption of itching welts). The eruption cleared when magnesium sulfate was discontinued (61045). Orally, magnesium oxide may cause allergic skin rash, but this is rare. In one case report, a patient developed a rash after taking 600 mg magnesium oxide (Maglax) (98291).
Gastrointestinal
...Orally, magnesium can cause gastrointestinal irritation, nausea, vomiting, and diarrhea (1194,4891,10661,10663,18111,60951,61016,98290).
In rare cases, taking magnesium orally might cause a bezoar, an indigestible mass of material which gets lodged in the gastrointestinal tract. In a case report, a 75-year-old female with advanced rectal cancer taking magnesium 1500 mg daily presented with nausea and anorexia from magnesium oxide bezoars in her stomach (99314). Magnesium can cause nausea, vomiting, or dry mouth when administered intravenously or by nebulization (60818,60960,60982,104400,113466,114681). Antenatal magnesium sulfate may also cause nausea and vomiting (60915,114681). Two case reports suggest that giving magnesium 50 grams orally for bowel preparation for colonoscopy in patients with colorectal cancer may lead to intestinal perforation and possibly death (90006).
Delayed meconium passage and obstruction have been reported rarely in neonates after intravenous magnesium sulfate was given to the mother during pregnancy (60818). In a retrospective study of 200 neonates born prematurely before 32 weeks of gestation, administration of prenatal IV magnesium sulfate, as a 4-gram loading dose and then 1-2 grams hourly, was not associated with the rate of meconium bowel obstruction when compared with neonates whose mothers had not received magnesium sulfate (108728).
Genitourinary ...Intravenously, magnesium sulfate may cause renal toxicity or acute urinary retention, although these events are rare (60818,61012). A case of slowed cervical dilation at delivery has been reported for a patient administered intravenous magnesium sulfate for eclampsia (12592). Intravenous magnesium might also cause solute diuresis. In a case report, a pregnant patient experienced polyuria and diuresis after having received intravenous magnesium sulfate in Ringer's lactate solution for preterm uterine contractions (98284).
Hematologic ...Intravenously, magnesium may cause increased blood loss at delivery when administered for eclampsia or pre-eclampsia (12592). However, research on the effect of intravenous magnesium on postpartum hemorrhage is mixed. Some research shows that it does not affect risk of postpartum hemorrhage (60982), while other research shows that intrapartum magnesium administration is associated with increased odds of postpartum hemorrhage, increased odds of uterine atony (a condition that increases the risk for postpartum hemorrhage) and increased need for red blood cell transfusions (97489).
Musculoskeletal
...Intravenously, magnesium may cause decreased skeletal muscle tone, muscle weakness, or hypocalcemic tetany (60818,60960,60973).
Although magnesium is important for normal bone structure and maintenance (272), there is concern that very high doses of magnesium may be detrimental. In a case series of 9 patients receiving long-term tocolysis for 11-97 days, resulting in cumulative magnesium sulfate doses of 168-3756 grams, a lower bone mass was noted in 4 cases receiving doses above 1000 grams. There was one case of pregnancy- and lactation-associated osteoporosis and one fracture (108731). The validity and clinical significance of this data is unclear.
Neurologic/CNS
...Intravenously, magnesium may cause slurred speech, dizziness, drowsiness, confusion, or headaches (60818,60960,114681).
With toxic doses, loss of reflexes, neurological defects, drowsiness, confusion, and coma can occur (8095,12589,12590).
A case report describes cerebral cortical and subcortical edema consistent with posterior reversible encephalopathy syndrome (PRES), eclampsia, somnolence, seizures, absent deep tendon reflexes, hard to control hypertension, acute renal failure and hypermagnesemia (serum level 11.5 mg/dL), after treatment with intravenous magnesium sulfate for preeclampsia in a 24-year-old primigravida at 39 weeks gestation with a previously uncomplicated pregnancy. The symptoms resolved after 4 days of symptomatic treatment in an intensive care unit, and emergency cesarian delivery of a healthy infant (112785).
Ocular/Otic ...Intravenously, magnesium may cause blurred vision (114681). Additionally, cases of visual impairment or nystagmus have been reported following magnesium supplementation, but these events are rare (18111,60818).
Psychiatric ...A case of delirium due to hypermagnesemia has been reported for a patient receiving intravenous magnesium sulfate for pre-eclampsia (60780).
Pulmonary/Respiratory ...Intravenously, magnesium may cause respiratory depression and tachypnea when used in toxic doses (12589,61028,61180).
Other ...Hypothermia from magnesium used as a tocolytic has been reported (60818).
General
...Orally and parenterally, manganese is generally well tolerated when used in appropriate doses.
High doses might be unsafe.
Serious Adverse Effects (Rare):
All routes of administration: Neurotoxicity, including Parkinson-like extrapyramidal symptoms, when used in high doses.
Cardiovascular ...Chronic occupational exposure to manganese dust or fumes can cause orthostatic hypotension, and heart rate and rhythm disturbances (61363).
Endocrine ...Chronic occupational exposure to manganese dust or fumes can cause elevations in thyrotropin-releasing hormone (TRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels (61378).
Hepatic ...Manganese intoxication may cause cirrhosis and hepatic steatosis. In one case, a 13-year-old female with manganese intoxication developed severe, life-threatening neurological symptoms, with liver biopsy indicating incomplete cirrhosis and microvesicular steatosis. Chelation therapy and multiple rounds of therapeutic plasma exchange were required before symptoms resolved. The source of manganese exposure was not identified, and it is not clear if the impaired liver function contributed to the manganese accumulation or if elevated manganese exposure led to the liver damage.
Musculoskeletal ...Chronic occupational exposure to manganese dust or fumes has been associated with lower bone quality in females, but not males, suggesting that prolonged manganese exposure might increase the risk of osteoporosis in females (102516). A meta-analysis of 11 observational studies in adults also suggests that increased environmental exposure to airborne manganese sources is associated with lower motor function scores (108537).
Neurologic/CNS
...Orally, there is concern that higher doses of manganese might increase the risk of neurotoxicity, including Parkinson-like extrapyramidal symptoms (7135,10665,10666).
One severe case of irreversible Parkinson disease possibly related to taking manganese 100 mg daily for 2-4 years has been reported (96418). In another case, a 13-year-old female with manganese intoxication (diagnosed from blood manganese levels and cranial MRI evidence) developed severe neurological symptoms including loss of consciousness, decorticate posture, clonus, increased reflexes in the extremities, isochoric pupils, and no painful stimulus response. Liver biopsy also showed incomplete cirrhosis and microvesicular steatosis. The patient was intubated, and chelation therapy and multiple rounds of therapeutic plasma exchange were required before symptoms resolved. The source of the child's manganese exposure was not identified (112137). Individuals with impaired manganese excretion can also experience these effects even with very low manganese intake. Manganese accumulation due to chronic liver disease seems to cause Parkinson-like extrapyramidal symptoms, encephalopathy, and psychosis (1992,7135). One review recommends stopping supplementation if aminotransferase or alkaline phosphatase levels rise beyond twice normal (99302).
Chronic occupational exposure to manganese dust or fumes can also cause extrapyramidal reactions (1990,7135). In 1837, Couper observed that exposure to manganese dust particles produces a neurological syndrome characterized by muscle weakness, tremor, bent posture, whispered speech, and excess salivation (61264). Additionally, observational research in children has found that elevated manganese levels detected in the hair and fingernails due to environmental exposure may be associated with impaired neurocognitive function or development (108535). A meta-analysis of 11 observational studies in adults also suggests that increased environmental exposure to airborne manganese sources is associated with lower cognitive function scores (108537).
Intravenously, manganese might increase the risk of neurotoxicity when administered at high doses or for an extended duration. Cases of Parkinson-like symptoms have been reported in patients receiving parenteral nutrition containing more than 60 mcg of manganese daily. Moderate MRI intensity uptake for manganese in the globus pallidus and basal ganglion areas of the brain has been shown in patients receiving parenteral manganese (96416,99302).
Psychiatric ...Chronic occupational exposure to manganese dust or fumes can cause mood disturbance and dementia (1990,7135). A case report describes a man who presented with confusion, psychosis, dystonic limb movements, and cognitive impairment after chronic industrial manganese exposure (99415). Symptoms of manganese toxicity from inhalational exposure develop slowly with initial fatigue and personality changes, progressing to hallucinations, delusions, hyperexcitability, Parkinson-like symptoms, dystonia, and dementia (99415). Additionally, observational research has found that chronic environmental exposure to manganese sources such as mining operations and various industrial processes may be associated with a greater risk for developing symptoms of depression (108536).
Pulmonary/Respiratory ...Chronic occupational exposure to manganese dust or fumes can cause acute chemical pneumonitis, pulmonary edema, or acute tracheobronchitis (61495).
General
...Orally, parsley seems to be well tolerated when used low to moderate doses.
Large doses may be unsafe.
Serious Adverse Effects (Rare):
Orally, Hallucinations, hemolytic anemia, hypotension, hepatic impairment, kidney impairment, nephrotic syndrome, paralysis, and thrombocytopenia purpura when taken in very high doses (200 grams parsley oil or 10 grams or more of parsley's apiole or myristicin constituents).
Cardiovascular ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with myristicin include hypotension and bradycardia (4).
Dermatologic
...Orally, parsley oil can cause contact photodermatitis with sun exposure (4).
Topically, parsley can cause contact photodermatitis (4).
Hematologic ...Parsley contains the potentially toxic constituent apiole, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hemolytic anemia and thrombocytopenia purpura (4).
Hepatic ...Parsley contains the potentially toxic constituents, apiole and myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hepatic dysfunction (4). Adverse effects specifically associated with the constituent myristicin include fatty degeneration of the liver (4).
Immunologic ...A case of anaphylaxis involving severe angioedema leading to unconsciousness has been reported in a woman who consumed parsley 45 minutes prior to symptoms. The patient responded to epinephrine, antihistamines, intravenous fluids, oxygen therapy, and 1 mg/kg methylprednisolone. The woman had consumed one cup of chopped parsley nearly every day for several years, but upon skin testing, the patient tested positive to parsley (92869). There is also a report of lip angioedema after consumption of raw parsley. The patient had anaphylaxis to raw arugula, and reported itchy red lesions after contact with the leaves of either raw parsley or arugula. The patient had positive skin prick tests to both plants. The reaction may have been due to oral allergy syndrome, as the patient could tolerate cooked arugula and parsley, but not raw (92870).
Ocular/Otic ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). An adverse effect specifically associated with the constituent myristicin includes deafness (4).
Psychiatric ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with the constituent myristicin include giddiness and hallucinations (4).
Renal ...Parsley contains the potentially toxic constituents, apiole and myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include nephrosis and kidney irritation (4). Adverse effects specifically associated with the constituent myristicin include fatty degeneration of the kidneys (4).
General
...Orally or intravenously, potassium is generally well-tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, belching, diarrhea, flatulence, nausea, and vomiting.
Serious Adverse Effects (Rare):
All ROAs: High potassium levels can cause arrhythmia, heart block, hypotension, and mental confusion.
Cardiovascular ...Orally or intravenously, high potassium levels can cause hypotension, cardiac arrhythmias, heart block, or cardiac arrest (15,16,3385,95011,95626,95630).
Gastrointestinal ...Orally or intravenously, high doses of potassium can cause, nausea, vomiting, abdominal pain, diarrhea, and flatulence (95010,95011). Bleeding duodenal ulcers have also been associated with ingestion of slow-release potassium tablets (69625,69672).
Neurologic/CNS ...Orally or intravenously, high potassium levels can cause paresthesia, generalized weakness, flaccid paralysis, listlessness, vertigo, or mental confusion (15,16,3385,95011).
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, watercress is well-tolerated when consumed in food amounts.
There is limited reliable information available about the adverse effects of watercress when used in medicinal amounts. When excessive doses are used, watercress can cause gastrointestinal irritation (85599). Consuming raw watercress has been associated with the development of fascioliasis, a parasitic fluke disease of the liver (85575,85574,85573,85567,85564,85582,85563,85562,85580,85561,85560)(85554,85558,85596,85579,85571,85569,85583,85586,85584,85588)(85585,85590,85592,85591).
Topically, watercress can cause contact dermatitis (85594,85587).
Dermatologic ...Topically, watercress can cause contact dermatitis, resulting in hives, rash, itching, or swollen skin (85594,85587).
Gastrointestinal ...Orally, large quantities of watercress may cause gastrointestinal irritation (85599).
Hepatic ...Raw, wild watercress can be contaminated with parasitic flukes which, when ingested, cause the liver disease fascioliasis. Symptoms include abdominal pain, fever, vomiting, diarrhea, urticaria, eosinophilia, and hepatomegaly (85575,85574,85573,85567,85564,85582,85563,85562,85580,85561)(85560,85554,85558,85596,85579,85571,85569,85583,85586,85584)(85588,85585,85590,85592,85591). Clinical research shows that taking a standardized extract of watercress orally 750 mg/kg daily for 5 weeks is not associated with increases in liver function enzymes (109666).
Renal ...Orally, excessive or prolonged use of watercress may theoretically cause kidney damage (85598). However, in overweight adults with physical disabilities, taking a watercress extract 750 mg/kg daily for 5 weeks does not cause any change in levels of creatinine or urea (109666).
General
...Orally, yellow dock seems to be well tolerated when properly prepared and consumed in food amounts.
Consuming raw yellow dock leaves or rhizomes may be unsafe.
Serious Adverse Effects (Rare):
Orally: Raw leaves or rhizomes can cause hypocalcemia, kidney stones, and vomiting.
Cardiovascular ...Orally, yellow dock has been linked to ventricular fibrillation and death after ingestion of 500 grams (17). Oxalic acid, a constituent of yellow dock, reacts with calcium in plasma, forming insoluble calcium oxalate, which can cause hypocalcemia; the crystals may precipitate in the blood vessels and heart (12). Older or uncooked leaves should be avoided (6).
Dermatologic ...Orally, yellow dock can cause dermatitis when consumed in large amounts (4). Topically, contact with the plant may cause dermatitis in people sensitive to yellow dock (6).
Gastrointestinal ...Orally, vomiting may occur after ingestion of fresh rhizome (18). Consuming excessive amounts can cause diarrhea and nausea (6). Excessive use can also cause abdominal cramps and intestinal atrophy (4). There is one report of a death, preceded by vomiting and diarrhea, after ingestion of 500 grams of yellow dock (17). Older or uncooked leaves should be avoided (6).
Genitourinary ...Orally, yellow dock can cause polyuria when consumed in large amounts (6).
Hematologic ...Orally, in one case report, a 38-year-old female developed immune-mediated thrombocytopenia after consuming a "cleansing" tea containing unknown amounts of yellow dock and burdock. The patient presented with bruising, mild weakness, and fatigue, which started 2-3 days after consuming the tea, and was found to have a platelet count of 5,000 per mcL. Symptoms resolved after platelet transfusion and treatment with oral dexamethasone (108971). It is unclear if these effects were caused by yellow dock, burdock, the combination, or other contributing factors.
Hepatic ...Orally, yellow dock has been linked to liver failure and death after ingestion of 500 grams (17). Oxalic acid, a constituent of yellow dock, reacts with calcium in plasma, forming insoluble calcium oxalate, which can cause hypocalcemia; the crystals may precipitate in the liver (12). Older or uncooked leaves should be avoided (6).
Neurologic/CNS ...Orally, yellow dock has been linked to coma and death after ingestion of 500 grams (17). Older or uncooked leaves should be avoided (6).
Pulmonary/Respiratory ...Orally, yellow dock has been linked to respiratory depression and death after ingestion of 500 grams (17). Oxalic acid, a constituent of yellow dock, reacts with calcium in plasma, forming insoluble calcium oxalate, which can cause hypocalcemia; the crystals may precipitate in the lungs (12). Older or uncooked leaves should be avoided (6).
Renal ...Orally, yellow dock can cause polyuria when consumed in large amounts (6). There is one report of a death, preceded by kidney failure, after ingestion of 500 grams (17). Oxalic acid, a constituent of yellow dock, reacts with calcium in plasma, forming insoluble calcium oxalate, which can cause hypocalcemia; the crystals may precipitate in the kidneys. Individuals with a history of kidney stones should use yellow dock cautiously (12). Older or uncooked leaves should be avoided (6).
Other ...Orally, yellow dock can cause hypokalemia when taken in large amounts (4). There is one report of a death, preceded by severe metabolic acidosis, after ingestion of 500 grams of yellow dock (17). Oxalic acid, a constituent of yellow dock, reacts with calcium in plasma, forming insoluble calcium oxalate, which can cause hypocalcemia; the crystals may precipitate in the kidneys, blood vessels, heart, lungs, and liver (12). Older or uncooked leaves should be avoided (6).
