| Ingredients | Amount Per Serving |
|---|---|
|
Calories
|
210 {Calories} |
|
Calories from Fat
|
50 {Calories} |
|
Total Fat
|
5 g |
|
Saturated Fat
|
2 g |
|
Cholesterol
|
85 mg |
|
Total Carbohydrates
|
9 g |
|
Dietary Fiber
|
1 g |
|
Sugar
|
2 g |
|
Protein
|
32 g |
| 156 IU | |
|
(Ca)
|
252 mg |
|
(Fe)
|
3 mg |
| 107 mg | |
|
(Na)
|
220 mg |
|
(K)
|
410 mg |
Protein Blend (Form: Calcium Caseinate, Milk Protein concentrate (Form: from Fresh Ultrafiltered Skim Milk, containing Native Micellar casein, and Whey Proteins), OhYeah! Total Protein System consisting of ultrafiltered Whey Protein concentrate, Whey Protein Isolate), dutch process Cocoa, Omega-MCT Interfusion Matrix (Form: Dipotassium Phosphate, Disodium Phosphate, Maltodextrin (Form: Potato), Medium-Chain Triglycerides, Mono{Glycerides} and Diglycerides, non-fat dry Milk, Silicon Dioxide (Alt. Name: SiO2), Sodium Caseinate, Sodium Silicoaluminate, Soy Lecithin, Sunflower Oil, Tocopherols) Note: Consisting of, Natural and Artificial flavors, Salt, Sucralose, Acesulfame Potassium
Below is general information about the effectiveness of the known ingredients contained in the product Total Protein System Chocolate Milkshake. 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
Below is general information about the safety of the known ingredients contained in the product Total Protein System Chocolate Milkshake. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally or intravenously and appropriately. Calcium is safe when used in appropriate doses (7555,12928,12946,95817). However, excessive doses should be avoided. The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: Age 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg; 19-50 years, 2500 mg; 51+ years, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stone, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). 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. For people age 14 and older with adequate iron stores, iron supplements are safe when used in doses below the tolerable upper intake level (UL) of 45 mg per day of elemental iron. The UL is not meant to apply to those who receive iron under medical supervision (7135,96621). To treat iron deficiency, most people can safely take up to 300 mg elemental iron per day (15). ...when used intravenously and appropriately. Ferric carboxymaltose 200 mg and iron sucrose 200 mg have been given intravenously for up to 10 doses with no reported serious adverse effects (91179). A meta-analysis of clinical studies of hemodialysis patients shows that administering high-dose intravenous (IV) iron does not increase the risk of hospitalization, infection, cardiovascular events, or death when compared with low-dose IV iron, oral iron, or no iron treatment (102861). A more recent meta-analysis of clinical studies of all patient populations shows that administering IV iron does not increase the risk of hospital length of stay or mortality, although the risk of infection is increased by 16% when compared with oral iron or no iron (110186). Another meta-analysis of 3 large clinical trials in patients with heart failure shows that IV ferric carboxymaltose at a dose of around 1500 mg every 6 months for a year does not increase the incidence of adverse effects when compared with placebo (113901). Despite these findings, there are rare reports of hypophosphatemia and/or osteomalacia (112603,112608,112609,112610,113905).
LIKELY UNSAFE ...when used orally in excessive doses. Doses of 30 mg/kg are associated with acute toxicity. Long-term use of high doses of iron can cause hemosiderosis and multiple organ damage. The estimated lethal dose of iron is 180-300 mg/kg; however, doses as low as 60 mg/kg have also been lethal (15).
CHILDREN: LIKELY SAFE
when used orally and appropriately (7135,91183,112601).
CHILDREN: LIKELY UNSAFE
when used orally in excessive amounts.
Tell patients who are not iron-deficient not to use doses above the tolerable upper intake level (UL) of 40 mg per day of elemental iron for infants and children aged 0-13 years and 45 mg per day for children aged 14-18 years. Higher doses frequently cause gastrointestinal side effects such as constipation and nausea (7135,20097). Iron is the most common cause of pediatric poisoning deaths. Doses as low as 60 mg/kg can be fatal (15).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Iron is safe during pregnancy and breast-feeding in patients with adequate iron stores when used in doses below the tolerable upper intake level (UL) of 45 mg daily of elemental iron (7135,96625,110180).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally in high doses.
Tell patients who are not iron deficient to avoid exceeding the tolerable upper intake level (UL) of 45 mg daily of elemental iron. Higher doses frequently cause gastrointestinal side effects such as nausea and vomiting (7135) and might increase the risk of preterm labor (100969). High hemoglobin concentrations at the time of delivery are associated with adverse pregnancy outcomes (7135,20109).
LIKELY SAFE ...when used orally and appropriately short-term (15). ...when sodium phosphate is used rectally and appropriately, no more than once every 24 hours, short-term (104471). Long-term use or high doses used orally or rectally require monitoring of serum electrolytes (2494,2495,2496,2497,2498,3092,112922). ...when used intravenously. Potassium phosphate is an FDA-approved prescription drug (15).
POSSIBLY UNSAFE ...when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL) of 4 grams daily for adults under 70 years and 3 grams daily for adults older than 70. Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur (7555). ...when used rectally more frequently than once every 24 hours, in excessive doses, with longer retention enema time, or in older patients with comorbidity or renal impairment (112922). The US Food and Drug Administration (FDA) warns that this may increase the risk of hyperphosphatemia, dehydration, and electrolyte imbalances leading to kidney and heart damage (104471).
CHILDREN: LIKELY SAFE
when used orally and appropriately at recommended dietary allowances (RDAs).
The daily RDAs are: children 1-3 years, 460 mg; children 4-8 years, 500 mg; males and females 9-18 years, 1250 mg (7555). ...when sodium phosphate is used rectally and appropriately, no more than once every 24 hours, short-term in children 2 years and older (104471). ...when used intravenously. Intravenous potassium phosphate is an FDA-approved prescription drug (15).
CHILDREN: POSSIBLY UNSAFE
when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL) of 3 grams daily for children 1-8 years of age and 4 grams daily for children 9 years and older.
Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur (7555). ...when sodium phosphate is used rectally more frequently than once every 24 hours, or in children under 2 years of age or with Hirchsprung disease (112922). The US Food and Drug Administration (FDA) warns that these uses may increase the risk of hyperphosphatemia, dehydration, and electrolyte imbalances leading to kidney and heart damage (104471).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately at the recommended dietary allowance (RDA) of 1250 mg daily for individuals 14-18 years of age and 700 mg daily for those over 18 years of age (7555).
...when sodium phosphate is used rectally and appropriately short-term (15). ...when used intravenously. Intravenous potassium phosphate is an FDA-approved prescription drug (15).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL).
Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur. The UL during pregnancy is 3.5 grams daily. During lactation, the UL is 4 grams daily (7555).
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 and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).
POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.
CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310).
Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses.
Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).
LIKELY SAFE ...when used orally or intramuscularly and appropriately. Vitamin A, as pre-formed vitamin A (retinol or retinyl ester), is safe in adults when taken in doses below the tolerable upper intake level (UL) of 10,000 IU (3000 mcg) daily (7135). Higher doses increase the risk of side effects. In an analysis of studies, taking vitamin A supplements alone or in combination with other antioxidants is associated with an increased risk of mortality from all causes (15305,90775). Vitamin A is available in two different forms: pre-formed vitamin A (retinol or retinyl ester) and provitamin A (carotenoids). The safety concerns associated with high vitamin A intake refer to pre-formed vitamin A only. Some supplements contain vitamin A in both pre-formed and provitamin A forms. For these supplements, the amount of pre-formed vitamin A should be used as the reference amount to determine safety.
POSSIBLY SAFE ...when used topically and appropriately, short-term. Retinol up to 0.5% has been used on the skin daily for up to 12 weeks with apparent safety. No serious adverse effects have been reported in clinical trials (103671,103680,114500).
POSSIBLY UNSAFE ...when used orally in high doses. Doses higher than the UL of 10,000 IU (3000 mcg) per day of pre-formed vitamin A (retinol or retinyl ester) might increase the risk of side effects (7135). While vitamin A 25,000 IU (as retinyl palmitate) daily for 6 months followed by 10,000 IU daily for 6 months has been used with apparent safety in one clinical trial (95052), prolonged use of excessive doses of vitamin A can cause hypervitaminosis A (7135). The risk for developing hypervitaminosis A is related to total cumulative dose of vitamin A rather than a specific daily dose (1467,1469). In an analysis of studies, taking vitamin A supplements alone or in combination with other antioxidants is associated with an increased risk of mortality from all causes (15305,90775). There is insufficient reliable information available about the safety of using sublingual formulations of vitamin A.
CHILDREN: LIKELY SAFE
when used orally or intramuscularly and appropriately.
The amount of pre-formed vitamin A (retinol or retinyl ester) that is safe depends on age. For children up to 3 years of age, doses less than 2000 IU (600 mcg) per day seem to be safe. For children ages 4 to 8, doses less than 3000 IU (900 mcg) per day seem to be safe. For children ages 9 to 13, doses less than 5667 IU (1700 mcg) per day seem to be safe. For children 14 to 18, doses less than 9333 IU (2800 mcg) per day seem to be safe (7135). Vitamin A is available in two different forms: pre-formed vitamin A (retinol or retinyl ester) and provitamin A (carotenoids). The safety concerns associated with high vitamin A intake occur with pre-formed vitamin A only. Some supplements contain vitamin A in both pre-formed and provitamin A forms. For these supplements, the amount of pre-formed vitamin A should be used as the reference amount for determining safety.
CHILDREN: POSSIBLY UNSAFE
when pre-formed vitamin A (retinol or retinyl ester) is used orally in excessive doses.
For children up to 3 years of age, avoid doses greater than 2000 IU (600 mcg) per day. For children ages 4 to 8, avoid doses greater than 3000 IU (900 mcg) per day. For children ages 9 to 13, avoid doses greater than 5667 IU (1700 mcg) per day. For children ages 14 to 18, avoid doses greater than 9333 IU (2800 mcg) per day (7135). Higher doses of vitamin A supplementation have been associated with increased risk of side effects such as pneumonia, bone pain, and diarrhea (319,95051). Long-term supplementation with low to moderate doses on a regular basis can cause severe, but usually reversible, liver damage (11978).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally or intramuscularly and appropriately.
Vitamin A, as pre-formed vitamin A (retinol or retinyl ester), is safe during pregnancy and lactation when used in doses less than 10,000 IU (3000 mcg) per day in adults 19 years of age and older and 2800 mcg daily in those 14-18 years of age (7135,16823,107293). Vitamin A is available in two different forms: pre-formed vitamin A (retinol or retinyl ester) and provitamin A (carotenoids). The safety concerns associated with high vitamin A intake occur with pre-formed vitamin A only. Some supplements contain vitamin A in both pre-formed and provitamin A forms. For these supplements, the amount of pre-formed vitamin A should be used as the reference amount to determine safety.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally or intramuscularly in excessive doses.
Daily intake of greater than 10,000 IU (3000 mcg) can cause fetal malformations (3066,7135). Excessive dietary intake of vitamin A has also been associated with teratogenicity (11978). The first trimester of pregnancy seems to be the critical period for susceptibility to vitamin A-associated birth defects such as craniofacial abnormalities and abnormalities of the central nervous system (7135). Pregnant patients should monitor their intake of pre-formed vitamin A (retinol or retinyl ester). This form of vitamin A is found in several foods including animal products, particularly fish and animal liver, some fortified breakfast cereals, and dietary supplements (3066).
Below is general information about the interactions of the known ingredients contained in the product Total Protein System Chocolate Milkshake. 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.
Details
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Calcium may reduce levels of raltegravir.
Details
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir (94164). However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure (94165).
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Calcium seems to reduce the absorption of sotalol.
Details
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes (10018).
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Calcium seems to reduce the absorption of tetracycline antibiotics.
Details
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut (1843).
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Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Details
Thiazides reduce calcium excretion by the kidneys (1902). Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.
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Theoretically, calcium may reduce the therapeutic effects of verapamil.
Details
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.
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Iron reduces the absorption of bisphosphonates.
Details
Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract (15).
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Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
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Administration of intravenous iron within one month of denosumab administration might increase the risk of severe hypophosphatemia and hypocalcemia.
Details
A case of severe hypocalcemia (albumin corrected calcium 6.88 mg/dL, ionized calcium 3.68 mg/dL) and hypophosphatemia (<0.5 mg/dL) with respiratory acidosis, QT interval prolongation, and nonsustained ventricular tachycardia was reported in a 76-year-old male who had received an iron polymaltose infusion within 2 weeks of a subcutaneous injection of denosumab. Serum parathyroid hormone was also elevated (348 pg/mL). Subsequent iron infusions with iron polymaltose and ferric carboxymaltose were followed by transient hypophosphatemia, but without hypocalcemia. Additionally, a literature review describes 6 additional cases of hypophosphatemia and hypocalcemia in patients 52-92 years of age who had been administered intravenous iron as either ferric carboxymaltose or iron polymaltose and subcutaneous denosumab within 1-4 weeks of each other (113905).
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Iron might decrease dolutegravir levels by reducing its absorption.
Details
Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation (93578). When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54% (94190).
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Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Details
Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation (93578). One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation (94190). Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation (93578,93579).
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Iron might decrease levodopa levels by reducing its absorption.
Details
Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50% (9567). The clinical significance of this hasn't been determined.
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Iron might decrease levothyroxine levels by reducing its absorption.
Details
Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract (9568).
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Iron might decrease methyldopa levels by reducing its absorption.
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Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
Details
Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research (3046,20152,20153,20154,20155).
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Iron might decrease penicillamine levels by reducing its absorption.
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Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine (3046,3072,20156).
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Iron might decrease levels of quinolone antibiotics by reducing their absorption.
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Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
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Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90% (15).
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Theoretically, taking phosphate salts with bisphosphonates might increase the risk of hypocalcemia.
Details
Combining bisphosphonates and phosphate can cause hypocalcemia. In one report, hypocalcemic tetany developed in a patient taking alendronate (Fosamax) who received a large dose of phosphate salts as a pre-operative laxative (14589).
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Taking erdafitinib with phosphate salts increases the risk of hyperphosphatemia.
Details
Erdafitinib increases phosphate levels. It is recommended that patients taking erdafitinib restrict phosphate intake to no more than 600-800 mg daily (104470).
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Taking futibatinib with phosphate salts increases the risk of hyperphosphatemia.
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Futibatinib can cause hyperphosphatemia, as reported in 88% of patients in clinical studies. In addition, 77% of patients in clinical studies required use of a phosphate binder to manage hyperphosphatemia. Phosphate salts should generally be avoided by people taking this medication (112912).
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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.
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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.
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Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia (15).
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Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
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Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
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Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).
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Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
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High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.
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Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
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The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.
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Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
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Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.
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Theoretically, taking high doses of vitamin A in combination with other potentially hepatotoxic drugs might increase the risk of liver disease.
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Concomitant use of retinoids with vitamin A supplements might produce supratherapeutic vitamin A levels.
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Retinoids, which are vitamin A derivatives, could have additive toxic effects when taken with vitamin A supplements (3046).
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Theoretically, taking tetracycline antibiotics with high doses of vitamin A can increase the risk of pseudotumor cerebri.
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Benign intracranial hypertension (pseudotumor cerebri) can occur with tetracyclines and with acute or chronic vitamin A toxicity. Case reports suggest that taking tetracyclines and vitamin A concurrently can increase the risk of this condition (10545,10546,10547). Avoid high doses of vitamin A in people taking tetracyclines chronically.
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Theoretically, high doses of vitamin A could increase the risk of bleeding with warfarin.
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Vitamin A toxicity is associated with hemorrhage and hypoprothrombinemia, possibly due to vitamin K antagonism (505). Advise patients taking warfarin to avoid doses of vitamin A above the tolerable upper intake level of 10,000 IU/day for adults.
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Below is general information about the adverse effects of the known ingredients contained in the product Total Protein System Chocolate Milkshake. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally and intravenously, calcium is well-tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Belching, constipation, diarrhea, flatulence, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about calciphylaxis and kidney stones.
Cardiovascular
...There has been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI).
Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these results, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Reasons for these discrepancies are not entirely clear. It may relate to whether calcium is taken as monotherapy or in combination with vitamin D. When taken with vitamin D, which is commonly recommended, calcium supplementation does not appear to be associated with an increased risk of CVD, CHD, or MI (93533,107231). Also, the association between calcium supplementation and CVD, CHD, or MI risk may be influenced by the amount of calcium consumed as part of the diet. Supplementation with calcium may be associated with an increased risk of MI in people with dietary calcium intake above 805 mg daily, but not in those with dietary calcium intake below 805 mg daily (17482). To minimize the possible risk of CVD, CHD, or MI, advise patients not to consume more than the recommended daily intake of 1000-1200 mg and to consider total calcium intake from both dietary and supplemental sources (17484). While dietary intake of calcium is preferred over supplemental intake, advise patients who require calcium supplements to take calcium along with vitamin D, as this combination does not appear to be associated with an increased risk of MI (93533).
Rarely, calcium intake can increase the risk of calciphylaxis, which usually occurs in patients with kidney failure. Calciphylaxis is the deposition of calcium phosphate in arterioles, which causes skin ulcers and skin necrosis. In a case report, a 64-year-old female with a history of neck fracture, sepsis, and ischemic colitis presented with painful leg ulcers due to calciphylaxis. She discontinued calcium and vitamin D supplementation and was treated with sodium thiosulfate and supportive care (95816).
Gastrointestinal ...Orally, calcium can cause belching, flatulence, nausea, gastrointestinal discomfort, and diarrhea (1824,1843,12950,38803). Although constipation is frequently cited as an adverse effect of calcium, there is no scientific substantiation of this side effect (1824,1843,1844,1845,12950,38978). Calcium carbonate has been reported to cause acid rebound, but this is controversial (12935,12936).
Oncologic ...There is some concern that very high doses of calcium might increase the risk of prostate cancer. Some epidemiological evidence suggests that consuming over 2000 mg/day of dietary calcium might increase the risk for prostate cancer (4825,12949). Additional research suggests that calcium intake over 1500 mg/day might increase the risk of advanced prostate cancer and prostate cancer mortality (14132). Consumption of dairy products has also been weakly linked to a small increase in prostate cancer risk (98894). However, contradictory research suggests no association between dietary intake of calcium and overall prostate cancer risk (14131,14132,104630). More evidence is needed to determine the effect of calcium, if any, on prostate cancer risk.
Renal ...Kidney stones have been reported in individuals taking calcium carbonate 1500 mg daily in combination with vitamin D 2000 IU daily for 4 years (93943).
General
...Orally or intravenously, iron is generally well tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, gastrointestinal irritation, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about oral or gastric ulcerations.
Intravenously: Case reports have raised concerns about hypophosphatemia and osteomalacia.
Cardiovascular
...There is debate regarding the association between coronary heart disease (CHD) or myocardial infarction (MI) and high iron intake or high body iron stores.
Some observational studies have reported that high body iron stores are associated with increased risk of MI and CHD (1492,9542,9544,9545,15175). Some observational studies reported that only high heme iron intake from dietary sources such as red meat are associated with increased risk of MI and CHD (1492,9546,15174,15205,15206,91180). However, the majority of research has found no association between serum iron levels and cardiovascular disease (1097,1099,9543,9547,9548,9549,9550,56469,56683).
There is one case of Kounis syndrome, also referred to as allergic angina or allergic myocardial infarction, in a 39-year-old female patient without previous coronary artery disease given intravenous ferric carboxymaltose. The patient experienced anaphylactic symptoms, including headache, abdominal pain, and breathing difficulties, 3 minutes after starting the infusion. She was further diagnosed with non-ST-elevation myocardial infarction (112607).
There is also a case of a 56-year-old female, negative for HFE mutation homozygosity, diagnosed with acquired iron overload cardiomyopathy after starting ferrous sulfate 325 mg twice daily 3 years prior for iron deficiency secondary to alcoholic cirrhosis with esophageal varices and encephalopathy. The patient had no follow-up care over the 3 years and denied any blood transfusions over that time (113906).
Dermatologic ...Cutaneous hemosiderosis, or skin staining, has been reported following intravenous (IV) iron infusion in various case reports. Most of these cases are due to extravasation following iron infusion (112605,112611). In one case, extravasation has occurred following iron derisomaltose infusion in a 41-year-old female with chronic kidney disease (112605). Rarely, diffuse cutaneous hermosiderosis has occurred. In one case, a 31-year-old female with excessive sweating developed cutaneous hemosiderosis in the armpits following an (IV) iron polymaltose infusion (112611).
Endocrine
...Population research in females shows that higher ferritin levels are associated with an approximately 1.
5-fold higher odds of developing gestational diabetes. Increased dietary intake of heme-iron, but not non-heme iron, is also associated with an increased risk for gestational diabetes. The effects of iron supplementation could not be determined from the evaluated research (96618). However, in a sub-analysis of a large clinical trial in pregnant adults, daily supplementation with iron 100 mg from 14 weeks gestation until delivery did not affect the frequency or severity of glucose intolerance or gestational weight gain (96619).
Intravenous (IV) iron may trigger hypophosphatemia in some patients (113905). A meta-analysis of clinical studies in adults with iron deficiency anemia shows that IV ferric carboxymaltose is associated with a higher risk of hypophosphatemia when compared with other IV formulations (i.e. iron dextran, iron isomaltoside, iron sucrose, and ferumoxytol) (115899). Severe hypophosphatemia requiring IV phosphate has also occurred following IV ferric carboxymaltose (112608,112610).
Additionally, cases of osteomalacia related to hypophosphatemia subsequent to parenteral iron administration have been rarely reported (112603,112609).
Gastrointestinal
...Orally, iron can cause dry mouth, gastrointestinal irritation, heartburn, abdominal pain, constipation, diarrhea, nausea, or vomiting (96621,102864,104680,104684,110179,110185,110188,110189,110192,115894).
These adverse effects are uncommon at doses below the tolerable upper intake level (UL) of 45 mg per day of elemental iron in adults with normal iron stores (7135). Higher doses can be taken safely in adults with iron deficiency, but gastrointestinal side effects may occur (1095,20118,20119,56698,102864). Taking iron supplements with food seems to reduce gastrointestinal side effects (7135). However, food can also significantly reduce iron absorption. Iron should be taken on an empty stomach, unless it cannot be tolerated.
There are several formulations of iron products such as ferrous sulfate, ferrous gluconate, ferrous fumarate, and others. Manufacturers of some formulations, such as polysaccharide-iron complex products (Niferex-150, etc), claim to be better tolerated than other formulations; however, there is no reliable evidence to support this claim. Gastrointestinal tolerability relates mostly to the elemental iron dose rather than the formulation (17500).
Enteric-coated or controlled-release iron formulations might reduce nausea for some patients, however, these products also have lower absorption rates (17500).
Liquid oral preparations can blacken and stain teeth (20118).
Iron can also cause oral ulcerations and ulcerations of the gastric mucosa (56684,91182,96622,110179). In one case report, an 87-year-old female with Alzheimer disease experienced a mucosal ulceration, possibly due to holding a crushed ferrous sulfate 80 mg tablet in the mouth for too long prior to swallowing (91182). The ulceration was resolved after discontinuing iron supplementation. In another case report, a 76-year old male suffered gastric mucosal injury after taking a ferrous sulfate tablet daily for 4 years (56684). In a third case report, a 14-year-old female developed gastritis involving symptoms of upper digestive hemorrhage, nausea, melena, and stomach pain. The hemorrhage was attributed to supplementation with ferrous sulfate 2 hours after meals for the prior 2 weeks (96622). In one case report, a 43-year old female developed atrophic gastritis with non-bleeding ulcerations five days after starting oral ferrous sulfate 325 mg twice daily (110179).
Intravenously, iron can cause gastrointestinal symptoms such as nausea and diarrhea(104684,110192,115894).
Hematologic ...Orally, iron supplements have been associated with hemochromatosis. In one case report, a 56-year-old female, negative for HFE mutation homozygosity, was diagnosed with acquired hemochromatosis after starting ferrous sulfate 325 mg twice daily 3 years prior, without follow-up care, for a previous iron deficiency secondary to alcoholic cirrhosis with esophageal varices and encephalopathy (113906).
Immunologic
...Although there is some clinical research associating iron supplementation with an increased rate of malaria infection (56796,95432), the strongest evidence to date does not support this association, at least for areas where antimalarial treatment is available (95433,96623).
In an analysis of 14 trials, iron supplementation was not associated with an increased risk of malaria (96623). In a sub-analysis of 7 preliminary clinical studies, the effect of iron supplementation was dependent upon the access to services for antimalarial treatment. In areas where anemia is common and services are available, iron supplementation is associated with a 9% reduced risk of clinical malaria. In an area where services are unavailable, iron supplementation was associated with a 16% increased risk in malaria incidence (96623). The difference in these findings is likely associated with the use of malaria prevention methods.
A meta-analysis of clinical studies of all patient populations shows that administering intravenous (IV) iron, usually iron sucrose and ferric carboxymaltose, increases the risk of infection by 16% when compared with oral iron or no iron. However, sub-analyses suggest this increased risk is limited to patients with inflammatory bowel disease (IBD) (110186). Additionally, a meta-analysis in adults with cancer-associated anemia shows that IV iron does not increase the risk of infection when compared with oral iron or no iron therapy (115892).
Intravenously, iron has rarely resulted in allergic reactions, including anaphylactoid reactions (110185,110192,112606,112607). There is one case of Kounis syndrome, also referred to as allergic angina or allergic myocardial infarction, in a 39-year-old female patient without previous coronary artery disease given IV ferric carboxymaltose. The patient experienced anaphylactic symptoms, including headache, abdominal pain, and breathing difficulties, 3 minutes after starting the infusion. She was further diagnosed with non-ST-elevation myocardial infarction (112607).
Musculoskeletal ...Intravenous (IV) iron may trigger hypophosphatemia in some patients, and cases of osteomalacia related to hypophosphatemia subsequent to parenteral iron administration have been rarely reported (112609,113905). In one case, a 70-year-old male with a genetic hemorrhagic disorder infused with ferric carboxymaltose developed lower limb pain with hypophosphatemia and diffuse bone demineralization in the feet (112609). In a second case, a 61-year-old male developed femoral neck insufficiency fractures following repeated ferric carboxymaltose transfusions for anemia related to vascular malformation in the bowel (112603).
Oncologic
...There is a debate regarding the association between high levels of iron stores and cancer.
Data are conflicting and inconclusive (1098,1099,1100,1102). Epidemiological studies suggest that increased body iron stores may increase the risk of cancer or general mortality (56703).
Occupational exposure to iron may be carcinogenic (56691). Oral exposure to iron may also be carcinogenic. Pooled analyses of population studies suggest that increasing the intake of heme iron increases the risk of colorectal cancer. For example, increasing heme iron intake by 1 mg/day is associated with an 11% increase in risk (56699,91185).
Pulmonary/Respiratory ...Orally, iron has been associated with rare reports of iron pill aspiration. This occurs when all or part of the pill is aspirated into the lungs. Once in the lungs, it can cause a chemical burn of the bronchial mucosa. Dozens of cases of iron pill aspiration have been reported in individuals ranging in age from 22 months to 92 years. Patients presented with cough, dyspnea, wheezing, and hemoptysis. The hemoptysis led to death in 2 patients due to hemorrhage. Long-term complication of fibrosis and bronchial stenosis was reported in a few of the cases. In one case, a 48-year-old female accidentally aspirated a ferrous sulfate tablet and presented to the emergency department with cough, blood-stained sputum, chest pain, dyspnea, and acute distress. Bronchoscopy was performed, parts of the pill were retrieved, and chemical burns and necrotic tissue were observed in the bronchus intermedius mucosa and throughout the middle and lower lobes. Debridement with bronchoalveolar lavage was performed. The patient was transferred to the intensive care unit, placed on mechanical ventilation for 2 days, treated with corticosteroids, and discharged on the fifth day of hospitalization. Four weeks post-discharge the patient had significantly improved but still had some reduction in lung capacity.
Other ...Intravenously, sodium ferric gluconate complex (SFGC) caused drug intolerance reactions in 0. 4% of hemodialysis patients including 2 patients with pruritus and one patient each with anaphylactoid reaction, hypotension, chills, back pain, dyspnea/chest pain, facial flushing, rash and cutaneous symptoms of porphyria (56527).
General
...Orally, intravenously, and rectally, phosphate salts are generally well tolerated when used appropriately and/or as prescribed.
Most Common Adverse Effects:
Orally: Abdominal pain, anal irritation, bloating, diarrhea, headache, gastrointestinal irritation, hyperphosphatemia, hypocalcemia, malaise, nausea, sleep disturbance, and vomiting.
Rectally: Hyperphosphatemia and hypocalcemia.
Serious Adverse Effects (Rare):
Orally: Extraskeletal calcification.
Cardiovascular ...Orally, a case of allergic acute coronary syndrome e., Kounis syndrome) is reported in a 43-year-old female after ingesting a specific sodium phosphate laxative product (Travad oral). She presented with maculopapular rash that progressed to anaphylaxis and a non-ST elevation acute coronary syndrome. The patient recovered after hospitalization for 3 days with medical management (112894).
Gastrointestinal ...Orally, phosphate salts can cause gastrointestinal irritation, nausea, abdominal pain, bloating, anal irritation, and vomiting (15,2494,2495,2496,2497,93846,93848,93850,93851,93853,107008). Sodium and potassium phosphates can cause diarrhea (15). Aluminum phosphate can cause constipation (15). A large comparative study shows that, when taken orally as a bowel preparation for colonoscopy, sodium phosphate is associated with gastric mucosal lesions in about 4% of patients (93868).
Neurologic/CNS ...Orally, phosphate salts can commonly cause malaise (93846). Headaches and sleep disturbance may also occur (93848,93851).
Renal ...Orally, use of sodium phosphate for bowel cleansing has been associated with an increased risk of acute kidney injury in some patients (93863). However, a pooled analysis of clinical research suggests that results are not consistent for all patients (93864). Some evidence suggests that female gender, probably due to lower body weight, iron-deficiency anemia, dehydration, and chronic kidney disease are all associated with an increased risk of sodium phosphate-induced kidney dysfunction (93865).
Other
...Orally, phosphate salts can cause fluid and electrolyte disturbances including hyperphosphatemia and hypocalcemia, and extraskeletal calcification.
Potassium phosphates can cause hyperkalemia. Sodium phosphates can cause hypernatremia and hypokalemia (15,2494,2495,2496,2497,107008).
Rectally, phosphate salts can cause fluid and electrolyte disturbances including hyperphosphatemia and hypocalcemia (15,112922).
Deaths related to intake of oral or rectal phosphate salts are rare and most have occurred in infants and are related to overdose (93866). However, death has also been reported in elderly patients using sodium phosphate enemas, mainly at standard doses of 250 mL (93867).
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, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level.
Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.
Cardiovascular
...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263).
A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).
Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).
Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).
Musculoskeletal
...Observational research has found that low sodium levels can increase the risk for osteoporosis.
One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).
Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).
Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).
Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).
General
...Orally, vitamin A is generally well-tolerated at doses below the tolerable upper intake level (UL).
Serious Adverse Effects (Rare):
Orally: In very high doses, vitamin A can cause pseudotumor cerebri, pain, liver toxicity, coma, and even death.
Dermatologic ...Chronic oral use of large amounts of vitamin A causes symptoms of vitamin A toxicity including dry skin and lips; cracking, scaling, and itchy skin; skin redness and rash; hyperpigmentation; shiny skin, and massive skin peeling (7135,95051). Hypervitaminosis A can cause brittle nails, cheilitis, gingivitis, and hair loss (15,95051). Adverse effects from a single ingestion of a large dose of vitamin A is more common in young children than adults (15). In children, approximately 25,000 IU/kg can cause skin redness and generalized peeling of the skin a few days later and may last for several weeks (15).
Gastrointestinal ...There is some evidence that oral vitamin A supplementation might increase the risk of diarrhea in children. Although vitamin A can prevent diarrhea and reduce mortality in malnourished children, doses as low as 10,000 IU weekly for 40 weeks have been associated with diarrhea in well-nourished children (319). Diarrhea (82326,82389), nausea (7135,100329), abdominal pain (95051), abdominal fullness (100329), and vomiting (7135,82559,95051,109755) have been reported following use of large doses of oral vitamin A. Adverse effects from a single ingestion of a large dose of vitamin A is more common in young children than adults (15). In children, approximately 25,000 IU/kg can cause vomiting and diarrhea (15). Chronic use of large amounts of vitamin A causes symptoms of vitamin A toxicity including anorexia, abdominal discomfort, and nausea and vomiting (7135).
Genitourinary ...Hypervitaminosis A can cause reduced menstrual flow (15). Intravaginally, all-trans retinoic acid can cause vaginal discharge, itching, irritation, and burning (9199).
Hematologic ...Hypervitaminosis A can cause spider angiomas, anemia, leukopenia, leukocytosis, and thrombocytopenia (15,95051).
Hepatic ...Since the liver is the main storage site for vitamin A, hypervitaminosis A can cause hepatotoxicity, with elevated liver enzymes such as alanine aminotransferase (ALT, formerly SGPT) and aspartate aminotransferase (AST, formerly SGOT), as well as fibrosis, cirrhosis, hepatomegaly, portal hypertension, and death (6377,7135,95051).
Musculoskeletal
...Vitamin A can increase the risk for osteoporosis and fractures.
Observational research has found that chronic, high intake of vitamin A 10,000 IU or more per day is associated with an increased risk of osteoporosis and hip fracture in postmenopausal adults, as well as overall risk of fracture in middle-aged males (7712,7713,9190). A meta-analysis of these and other large observational studies shows that high dietary intake of vitamin A or retinol is associated with a 23% to 29% greater risk of hip fracture when compared with low dietary intake (107294). High serum levels of vitamin A as retinol also increase the risk of fracture in males. Males with high serum retinol levels are seven times more likely to fracture a hip than those with lower serum retinol levels (9190). Vitamin A damage to bone can occur subclinically, without signs or symptoms of hypervitaminosis A. Some researchers are concerned that consumption of vitamin A fortified foods such as margarine and low-fat dairy products in addition to vitamin A or multivitamin supplements might cause excessive serum retinol levels. Older people have higher levels of vitamin A and might be at increased risk for vitamin A-induced osteoporosis.
Vitamin A's effects on bone resorption could lead to hypercalcemia (95051).
Hypervitaminosis can cause slow growth, premature epiphyseal closure, painful hyperostosis of the long bones, general joint pain, osteosclerosis, muscle pain, and calcium loss from the bones (15,95051). One child experienced severe bone pain after taking vitamin A 600,000 IU daily for more than 3 months (95051). Vitamin A was discontinued and symptoms lessened over a period of 2 weeks. The patient made a full recovery 2 months later.
Neurologic/CNS
...Orally, adverse effects from a single large dose of vitamin A are more common in young children than adults (15).
Headache, increased cerebrospinal fluid pressure, vertigo, and blurred vision have been reported following an acute oral dose of vitamin A 500,000 IU (7135). In children, approximately 25,000 IU/kg can cause headache, irritability, drowsiness, dizziness, delirium, and coma (15). Chronic use of large amounts of vitamin A causes symptoms of vitamin A toxicity including fatigue, malaise, lethargy, and irritability (7135).
There are reports of bulging of the anterior fontanelle associated with an acute high oral dose of vitamin A in infants (7135,90784,95053,95054). In children, approximately 25,000 IU/kg can cause increased intracranial pressure with bulging fontanelles in infants (15). Also, muscular incoordination has been reported following short-term high doses of vitamin A (7135).
A case of intracranial hypertension involving diffuse headaches and brief loss of vision has been reported secondary to topical use of vitamin A. The patient was using over-the-counter vitamin A preparations twice daily including Avotin 0.05% cream, Retin-A gel 0.01%, and Isotrexin gel containing isotretinoin 0.05% and erythromycin 2%, for treatment of facial acne. Upon exam, the patient was noted to have bilateral optic disc edema. The patient discontinued use of topical vitamin A products. Two months later, the patient reported decreased headaches and an improvement in bilateral optic disc edema was seen (95056).
Ocular/Otic ...In children, oral vitamin A approximately 25,000 IU/kg can cause swelling of the optic disk, bulging eyeballs, and visual disturbances (15). Adverse effects from a single ingestion of a large dose of vitamin A are more common in young children than adults (15).
Oncologic ...There is concern that high intake of vitamin A might increase some forms of cancer. Population research suggests high vitamin A intake might increase the risk of gastric carcinoma (9194).
Psychiatric ...Chronic oral use of large amounts of vitamin A causes symptoms of vitamin A toxicity, which can include symptoms that mimic severe depression or schizophrenic disorder (7135).
Pulmonary/Respiratory ...There is some evidence that oral vitamin A supplementation might increase the risk of pneumonia and diarrhea in children. Although vitamin A can prevent diarrhea and reduce mortality in malnourished children, doses as low as 10,000 IU weekly for 40 weeks have been associated with pneumonia and diarrhea in well-nourished children (319). In preschool children, high-dose vitamin A also increases the risk of respiratory infection (82288).
Other ...Chronic use of large amounts of vitamin A (>25,000 IU daily for more than 6 years or 100,000 IU daily for more than 6 months) can cause symptoms of vitamin A toxicity including mild fever and excessive sweating (7135). High intakes of vitamin A may result in a failure to gain weight normally in children and weight loss in adults (15).
