| Ingredients | Amount Per Serving |
|---|---|
|
Calories
|
20 Calorie(s) |
|
Total Carbohydrates
|
1 Gram(s) |
|
Total Sugars
|
1 Gram(s) |
|
(Niacinamide)
|
30 mg |
|
(Pyridoxal 5-Phosphate)
|
35 mg |
|
(Methylcobalamin)
|
1000 mcg |
|
(Mg)
(Magnesium Citrate)
|
65 mg |
|
(Na)
(Pink Himalayan Salt)
|
280 mg |
|
(Coconut Fruit Water, Powder, Dipotassium Phosphate, Potassium Citrate)
|
250 mg |
|
Pump & Performance
|
|
| 10000 mg | |
|
(Beta-Alanine)
|
3200 mg |
|
Creatine Matrix
|
|
|
(Creatine Monohydrate)
|
3000 mg |
|
NO3-T
(Creatine Nitrate)
|
2000 mg |
|
Power & Burn
|
|
|
BetaPower
(Betaine Anhydrous)
|
2500 mg |
|
(L-Carnitine Tartrate)
|
1500 mg |
|
Cellular Hydration & ATP Amplifier
|
|
| 2000 mg | |
|
(fruit)
|
500 mg |
|
elevATP
(Ancient Peat extract, Apple fruit extract)
|
150 mg |
|
Energy & Focus
|
|
| 2500 mg | |
| 388 mg | |
|
PurCaf
(Caffeine)
(organic green coffee)
|
|
|
AmaTea
(Guayusa Leaf Extract)
|
|
|
(Alpha-Glycerylphosphorylcholine)
(Alpha-Glycerylphosphorylcholine 50%)
|
300 mg |
|
AmaTea
(Guayusa Leaf Extract)
|
100 mg |
|
(Huperzia serrata )
(whole herb)
(Huperzine A)
(1% Huperzine A)
|
10 mg |
Citric Acid, Malic Acid, Natural Flavors, Silicon Dioxide (Alt. Name: SiO2), Calcium Silicate (Alt. Name: Ca Silicate), Steviol Glycosides, Sucralose, Beta-Carotene
Below is general information about the effectiveness of the known ingredients contained in the product Pre-Kaged Elite Orange Mango. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
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 toothed clubmoss.
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 Pre-Kaged Elite Orange Mango. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately. Alpha-GPC has been used with apparent safety at doses of 400 mg three times daily (1200 mg/day) for up to 6 months (12102,12176). ...when used intramuscularly and appropriately. Alpha-GPC has been administered intramuscularly with apparent safety at doses of 1000-1200 mg/day for 28 to 90 days (12100,12102).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral beta-alanine, including a specific commercial product (CarnoSyn, Natural Alternatives International), has been used with apparent safety in doses up to 6.4 grams daily for 12 weeks in younger adults (14611,16025,16439,16441,18227,94357,97972,101028,101029,104144,106717), and up to 3.2 grams daily for 12 weeks in adults aged 55 years and older (16442,97955,97961,97965).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in medicinal amounts.
LIKELY SAFE ...when used orally, parenterally, or rectally and appropriately. Caffeine has Generally Recognized As Safe (GRAS) status in the US (4912,98806). Caffeine is also an FDA-approved product and a component of several over-the-counter and prescription products (4912,11832). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of caffeine up to 400 mg daily are not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806). This amount of caffeine is similar to the amount of caffeine found in approximately 4 cups of coffee. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
POSSIBLY UNSAFE ...when used orally, long-term or in high doses (91063). Chronic use, especially in large amounts, can produce tolerance, habituation, psychological dependence, and other adverse effects (3719). Acute use of high doses, typically above 400 mg daily, has been associated with significant adverse effects such as tachyarrhythmia and sleep disturbances (11832). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
LIKELY UNSAFE ...when used orally in very high doses. The fatal acute oral dose of caffeine is estimated to be 10-14 grams (150-200 mg/kg). Serious toxicity can occur at lower doses depending on variables in caffeine sensitivity such as smoking, age, or prior caffeine use (11832,95700,97454,104573). Caffeine products sold to consumers in highly concentrated or pure formulations are considered to a serious health concern because these products have a risk of being used in very high doses. Concentrated liquid caffeine can contain about 2 grams of caffeine in a half cup. Powdered pure caffeine can contain about 3.2 grams of caffeine in one teaspoon. Powdered pure caffeine can be fatal in adults when used in doses of 2 tablespoons or less. As of 2018, these products are considered by the FDA to be unlawful when sold to consumers in bulk quantities (95700).
CHILDREN: POSSIBLY SAFE
when used orally or intravenously and appropriately in neonates under the guidance of a healthcare professional (6371,38340,38344,91084,91087,97452).
...when used orally in amounts commonly found in foods and beverages in children and adolescents (4912,11833,36555). Daily intake of caffeine in doses of less than 2.5 mg/kg daily are not associated with significant adverse effects in children and adolescents (11733,98806). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
PREGNANCY: POSSIBLY SAFE
when used orally in amounts commonly found in foods.
Intakes of caffeine should be monitored during pregnancy. Caffeine crosses the human placenta, but is not considered a teratogen (38048,38252,91032). Fetal blood and tissue levels are similar to maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,16014,16015,98806,108814). In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014,37960). This increased risk seems to occur in those with genotypes that confer a slow rate of caffeine metabolism (98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). However, observational research in a Norwegian cohort found that caffeine consumption is associated with a 16% increased odds of the baby being born small for gestational age when compared with no consumption (100369,103707). The same Norwegian cohort found that low to moderate caffeine consumption during pregnancy is not associated with changes in neurodevelopment in children up to 8 years of age (103699). Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea.
PREGNANCY: POSSIBLY UNSAFE
when used orally in amounts over 300 mg daily.
Caffeine crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260,98806). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea. Additionally, high doses of caffeine throughout pregnancy have resulted in symptoms of caffeine withdrawal in newborn infants (9891). High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight (2709,2711,91033,91048,95949). In a cohort of mother/infant pairs with a median maternal plasma caffeine level of 168.5 ng/mL (range 29.5-650.5 ng/mL) during pregnancy, birth weights and lengths were lower in the 4th quartile of caffeine intake compared with the 1st. By age 7, heights and weights were lower by 1.5 cm and 1.1 kg respectively. In another cohort of mother/infant pairs with higher maternal pregnancy plasma caffeine levels, median 625.5 ng/mL (range 86.2 to 1994.7 ng/mL), heights at age 8 were 2.2 cm lower, but there was no difference in weights (109846).
LACTATION: POSSIBLY SAFE
when used orally in amounts commonly found in foods.
Caffeine intake should be closely monitored while breast-feeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations and caffeine peaks in breastmilk approximately 1-2 hours after consumption (23590).
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine is excreted slowly in infants and may accumulate. Caffeine can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants exposed to caffeine (2708,6026).
LIKELY SAFE ...when used orally and appropriately. Several studies show that drinking coconut water is safe (17666,17669,17678,17679,17680,95126,95136). Coconut water is commonly consumed as a beverage. There is insufficient reliable information available about the safety of intravenous use of coconut water.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Drinking coconut water appears to be safe when used in children (17666). Coconut water is commonly consumed as a beverage.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
In one case report, a neonate developed severe hyponatremia (113 mEq/L) with seizures shortly after delivery, which was attributed to the mother's consumption of 3 liters of coconut water at the onset of labor (115939).
LIKELY SAFE ...when used orally and appropriately, short-term. Creatine supplementation appears to be safe when used at loading doses of up to 25 grams daily or 0.3 grams/kg daily for up to 14 days in healthy adults (1367,2100,2101,3996,4569,10064,15354,15520,46570,46587)(46673,46688,46719,46753,46801,103278,103279,108336). Creatine supplementation also appears to be safe when used at maintenance doses of 4-5 grams daily for up to 18 months (2101,4578,15353,15354,15520,46587,46673,46690,46753,46838,102164,103278,108336).
POSSIBLY SAFE ...when used orally and appropriately, long-term. Creatine supplementation has been safely used at doses of up to 10 grams daily for up to 5 years in some preliminary clinical research (1367,3996). There is insufficient reliable information available about the safety of creatine when used topically.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Creatine supplementation appears to be safe when used in appropriate doses in infants and children. Creatine 3-5 grams daily for 2-6 months has been safely used in children 5-18 years of age (6182,46596,46739,46841). Creatine 2 grams daily for 6 months has been safely used in children 2-5 years of age (46841). Additionally, weight-based dosing of creatine 0.1-0.4 grams/kg daily in infants and children or 4.69 grams/m2 in children weighing over 40 kg has been used safely for up to 6 months (46623,46629,46694,46759,104672).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. L-carnitine has been safely used in clinical trials lasting up to 12 months (1947,3620,3621,3623,3624,3625,3626,3627,3628,3629) (3630,3639,4949,8047,9790,12352,16104,16105,16106,16107) (16109,16110,23437,26496,26499,58150,58156,58161,58169,58182) (58189,58204,58207,58209,58213,58294,58523,58554,58556,58647) (58679,58715,58778,58793,58830,58831,58882,59023,59029,59043) (90624,90633,104177,111872,111876,111883,111884,111891,111898). ...when used parenterally as an FDA-approved prescription medicine. Avoid using D-carnitine and DL-carnitine. These forms of carnitine can act as competitive inhibitors of L-carnitine and may cause symptoms of L-carnitine deficiency (1946).
CHILDREN: POSSIBLY SAFE
when used orally or intravenously and appropriately.
L-carnitine has been safely used orally in children for up to 6 months (1433,3622,58166,58502,58981,59188,111887,111900,115351). It has also been safely used orally and intravenously in preterm infants (3633,3634,3635,3636,3637,58163,58190,58800,58902,59097)(59161).
PREGNANCY:
Insufficient reliable information available; avoid using.
LACTATION: POSSIBLY SAFE
when used orally.
Supplemental doses of L-carnitine have been given to infants in breast milk and formula with no reported adverse effects. The effects of large doses used while nursing are unknown, but L-carnitine is secreted in the breast milk (3616).
POSSIBLY SAFE ...when used orally and appropriately. In clinical trials, L-citrulline has been used with apparent safety for up to 2 months at doses of 1.5-6 grams daily (94954,94956,94961,94962,100974). Doses of up to 15 grams have also been used as single doses or within a 24 hour period (16470,16473).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
L-citrulline has been used with apparent safety in infants at a dose of 0.17 grams/kg daily (16472). It has also been used in children 6.5-10 years of age at a dose of 7.5 grams daily for 26 weeks (100976). ...when used intravenously and appropriately. An intravenous bolus dose of L-citrulline 150 mg/kg followed by 9 mg/kg/hour for 48 hours has been used safely in children under 6 years of age (16469).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
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 prescription products are used orally and appropriately (12033). ...when niacinamide supplements are taken orally in doses below the tolerable upper intake level (UL) set by the Institute of Medicine (IOM). The UL of niacinamide is 30 mg daily for adults 18 years of age and 35 mg daily for adults 19 years and older (6243).
POSSIBLY SAFE ...when used orally in doses greater than 30 mg but less than 900 mg daily. The European Food Safety Authority has set the tolerable upper intake level (UL) of niacinamide at 900 mg daily (104937). However, oral niacinamide has been safely used in doses up to 1500 mg daily for 12 weeks in some clinical trials (25561,94188,98940,107709,110502) and up to 1000 mg daily for 12 months in other trials (93362,113559,113560). ...when used topically and appropriately for up to 16 weeks (5940,93360,110497,110498,110501,113681,113683,113684).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Niacinamide has been safely used in children for up to 7 years in doses below the tolerable upper intake level (UL) (4874,9957). The UL of niacinamide for children by age is: 1-3 years, 10 mg daily; 4-8 years, 15 mg daily; 9-13 years, 20 mg daily; 14-18 years, 30 mg daily (6243).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the tolerable upper intake level (UL) for niacinamide.
The UL of niacinamide during pregnancy and lactation is 30 mg daily for those 14-18 years of age and 35 mg daily for those 19 years and older (6243). There is insufficient reliable information available about the safety of larger oral doses of niacinamide or topical niacinamide; 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 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 in amounts found in foods. Typical daily intakes for adults range from 40-400 mg (101471).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Taurine 2-4 grams daily in two or three divided doses has been used safely in studies lasting up to 3 months (5248,5271,8217,8221,10454,77147,95612,98337,104165,104167). Higher doses of taurine 6 grams daily have been used safely in studies lasting up to 4 weeks (98336,98337). A risk assessment of orally administered taurine has identified an Observed Safe Level (OSL) of up to 3 grams daily for healthy adults (31996).
CHILDREN: LIKELY SAFE
when used in amounts found in foods.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts.
Taurine 2.4-4.8 grams daily in three divided doses has been safely used in children 6-16 years of age for up to 12 weeks (103210).
PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts found in foods.
There is insufficient reliable information available about the safety of taurine when used in medicinal amounts during pregnancy and lactation; avoid using.
There is insufficient reliable information available about the safety of toothed clubmoss.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Tyrosine has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Tyrosine has been used safely in doses up to 150 mg/kg daily for up to 3 months (7210,7211,7215). ...when used topically and appropriately (6155).
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of tyrosine during pregnancy and lactation when used in medicinal amounts.
Some pharmacokinetic research shows that taking a single dose of tyrosine 2-10 grams orally can modestly increase levels of free tyrosine in breast milk. However, total levels are not affected, and levels remain within the range found in infant formulas. Therefore, it is not clear if the increase in free tyrosine is a concern (91467).
LIKELY SAFE ...when used orally, topically, intravenously, intramuscularly, or intranasally and appropriately. Vitamin B12 is generally considered safe, even in large doses (15,1344,1345,1346,1347,1348,2909,6243,7289,7881)(9414,9416,10126,14392,15765,82832,82949,82860,82864,90386)(111334,111551).
PREGNANCY: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA for vitamin B12 during pregnancy is 2.6 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA of vitamin B12 during lactation is 2.8 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 while breastfeeding.
LIKELY SAFE ...when used orally and appropriately in doses that do not exceed the tolerable upper intake level (UL) of 100 mg daily in the form of pyridoxine for adults (15,6243). ...when used parenterally and appropriately. Injectable vitamin B6 (pyridoxine) is an FDA-approved prescription product (15).
POSSIBLY SAFE ...when used orally and appropriately in doses of 101-200 mg daily (6243,8558).
POSSIBLY UNSAFE ...when used orally in doses at or above 500 mg daily. High doses, especially those exceeding 1000 mg daily or total doses of 1000 grams or more, pose the most risk. However, neuropathy can occur with lower daily or total doses (6243,8195). ...when used intramuscularly in high doses and frequency due to potential for rhabdomyolysis (90795).
CHILDREN: LIKELY SAFE
when used orally and appropriately in doses that do not exceed the tolerable upper intake level (UL) of vitamin B6 in the form of pyridoxine 30 mg daily for children aged 1-3 years, 40 mg daily for 4-8 years, 60 mg daily for 9-13 years, and 80 mg daily for 14-18 years (6243).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately in amounts exceeding the recommended dietary allowance (5049,8579,107124,107125,107135).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses, long-term (6243).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
A special sustained-release product providing vitamin B6 (pyridoxine) 75 mg daily is FDA-approved for use in pregnancy. Vitamin B6 (pyridoxine) is also considered a first-line treatment for nausea and vomiting in pregnancy by the American College of Obstetrics and Gynecology (111601). However, it should not be used long-term or without medical supervision and close monitoring. The tolerable upper intake level (UL) refers to vitamin B6 in the form of pyridoxine and is 80 mg daily for those aged 14-18 years and 100 mg daily for 19 years and older (6243).
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses.
There is some concern that high-dose maternal vitamin B6 (pyridoxine) can cause neonatal seizures (4609,6397,8197).
LACTATION: LIKELY SAFE
when used orally in doses not exceeding the tolerable upper intake level (UL) of vitamin B6 in the form of pyridoxine 80 mg daily for those aged 14-18 years and 100 mg daily for those 19 years and older.
The recommended dietary allowance (RDA) in lactating women is 2 mg daily (6243). There is insufficient reliable information available about the safety of vitamin B6 when used in higher doses in breast-feeding women.
Below is general information about the interactions of the known ingredients contained in the product Pre-Kaged Elite Orange Mango. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, alpha-GPC might decrease the effects of scopolamine.
 Details
A small clinical study shows that alpha-GPC can partially counteract the attention and memory impairment effects caused by scopolamine given intramuscularly (12103). Whether alpha-GPC can decrease the beneficial anti-motion sickness effects of the scopolamine patch (Transderm Scop) is unclear.
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Theoretically, caffeine might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Some evidence shows that caffeine is a competitive inhibitor of adenosine and can reduce the vasodilatory effects of adenosine in humans (38172). However, other research shows that caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).
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Theoretically, concomitant use might increase levels and adverse effects of caffeine.
Details
Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects (6370).
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Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
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Theoretically, taking caffeine with antidiabetes drugs might interfere with blood glucose control.
Details
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Theoretically, large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists (15).
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Theoretically, caffeine might reduce the effects of carbamazepine and increase the risk for convulsions.
Details
Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg (23559,23561). Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals (23562).
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Theoretically, cimetidine might increase the levels and adverse effects of caffeine.
Details
Cimetidine decreases the rate of caffeine clearance by 31% to 42% (11736).
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Caffeine might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Details
Caffeine might increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Although researchers speculate that caffeine might inhibit CYP1A2, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine (13741). In one case report, severe, life-threatening clozapine toxicity and multiorgan system failure occurred in a patient with schizophrenia stabilized on clozapine who consumed caffeine 600 mg daily (108817).
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Theoretically, contraceptive drugs might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Theoretically, caffeine might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Caffeine inhibits dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).
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Theoretically, disulfiram use might increase the levels and adverse effects of caffeine.
Details
Disulfiram decreases the rate of caffeine clearance (11840).
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Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
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Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (1275,6486,10307).
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
Details
Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide (23560). However, this effect has not been reported in humans.
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Theoretically, caffeine might reduce the effects of felbamate and increase the risk for convulsions.
Details
Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate (23563). However, this effect has not been reported in humans.
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Details
Fluconazole decreases caffeine clearance by approximately 25% (11022).
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Theoretically, caffeine might increase the levels and adverse effects of flutamide.
Details
In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). However, this effect has not been reported in humans.
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
Fluvoxamine reduces caffeine metabolism (6370).
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Abrupt caffeine withdrawal might increase the levels and adverse effects of lithium.
Details
Caffeine has diuretic activity. When abruptly discontinued, caffeine may alter the clearance of lithium (609). There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal (610) and 6 case reports of elevated serum lithium levels after reducing or eliminating caffeine intake (114665). In one case, a male with schizoaffective disorder stabilized on lithium had an elevated lithium level after reducing his caffeine intake by 87%. At a later date, he increased his caffeine intake by 6-fold, resulting in a subtherapeutic lithium level and a recurrence of psychiatric symptoms (114665).
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Theoretically, metformin might increase the levels and adverse effects of caffeine.
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Animal research suggests that metformin can reduce caffeine metabolism (23571). However, this effect has not been reported in humans.
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Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
Details
Methoxsalen reduces caffeine metabolism (23572).
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Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the risk of a hypertensive crisis.
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Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15). In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension (91086). Hypertension was resolved after the patient switched to drinking decaffeinated coffee.
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Theoretically, concomitant use might increase the risk of hypertension.
Details
Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).
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Theoretically, caffeine might decrease the effects of pentobarbital.
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Caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, caffeine might reduce the effects of phenobarbital and increase the risk for convulsions.
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
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Theoretically, caffeine might reduce the effects of phenytoin and increase the risk for convulsions.
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Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
Details
Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.
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Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce the metabolism of one or both agents (11739).
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Theoretically, concomitant use might increase stimulant adverse effects.
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Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
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Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
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Theoretically, caffeine might increase the levels and adverse effects of theophylline.
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Large amounts of caffeine might inhibit theophylline metabolism (11741).
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Theoretically, caffeine might increase the levels and adverse effects of tiagabine.
Details
Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).
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Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
Details
In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
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Theoretically, caffeine might reduce the effects of valproate and increase the risk for convulsions.
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Theoretically, verapamil might increase the levels and adverse effects of caffeine.
Details
Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, taking coconut water with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking coconut water with antihypertensive drugs might increase the risk of hypotension.
Details
Preliminary clinical research shows that drinking coconut water might lower systolic and diastolic blood pressure in patients with hypertension (17680).
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Theoretically, L-carnitine might increase the anticoagulant effects of acenocoumarol.
Details
L-carnitine might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation with concomitant use. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165).
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Theoretically, L-carnitine might decrease the effectiveness of thyroid hormone replacement.
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Theoretically, L-carnitine might increase the anticoagulant effects of warfarin.
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Theoretically, concomitant use of L-citrulline with antihypertensive drugs might have additive effects and increase the chance of hypotension.
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Theoretically, concurrent use of phosphodiesterase-5 (PDE-5) inhibitors and L-citrulline might result in additive vasodilation.
Details
L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation (7822,16460,16461). Theoretically, taking L-arginine with PDE-5 inhibitors might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported (105065).
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Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
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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.
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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.
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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.
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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, niacinamide may have additive effects when used with anticoagulant or antiplatelet drugs, especially in patients on hemodialysis.
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Niacinamide might increase the levels and adverse effects of carbamazepine.
Details
Plasma levels of carbamazepine were increased in two children given high-dose niacinamide, 60-80 mg/kg/day. This might be due to inhibition of the cytochrome P450 enzymes involved in carbamazepine metabolism (14506). There is not enough data to determine the clinical significance of this interaction.
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Niacinamide might increase the levels and adverse effects of primidone.
Details
Case reports in children suggest niacinamide 60-100 mg/kg/day reduces hepatic metabolism of primidone to phenobarbital, and reduces the overall clearance rate of primidone (14506); however, there is not enough data to determine the clinical significance of this potential interaction.
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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.
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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.
Details
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.
Details
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.
Details
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.
Details
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, taurine might increase the risk of hypotension when taken with antihypertensive drugs.
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Theoretically, taurine might reduce excretion and increase plasma levels of lithium.
Details
Taurine is thought to have diuretic properties (3647), which might reduce the excretion of lithium.
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In animal models, toothed clubmoss and huperzine A, an active constituent of toothed clubmoss, reversed cognitive deficits induced by scopolamine (3135, 103325). Theoretically, concurrent use of anticholinergic drugs and toothed clubmoss might decrease the effectiveness of toothed clubmoss or the anticholinergic drug.
Details
Some anticholinergic drugs include atropine, benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and trihexyphenidyl (Artane).
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Huperzine A, a constituent of toothed clubmoss, has demonstrated acetylcholinesterase inhibitory properties (3082,103325). Theoretically, concurrent use of toothed clubmoss with cholinergic drugs might have additive effects and increase the risk of cholinergic side effects.
Details
Cholinergic drugs include bethanechol (Urecholine), donepezil (Aricept), echothiophate (Phospholine Iodide), edrophonium (Enlon, Reversol, Tensilon), neostigmine (Prostigmin), physostigmine (Antilirium), pyridostigmine (Mestinon, Regonol), succinylcholine (Anectine, Quelicin), and tacrine (Cognex).
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Theoretically, tyrosine might decrease the effectiveness of levodopa.
Details
Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system (2719). Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.
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Theoretically, tyrosine might have additive effects with thyroid hormone medications.
Details
Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones (7212).
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Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
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Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Details
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure (30859,82959,83093). Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine (83091).
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Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Details
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people (3046).
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High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
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High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
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Below is general information about the adverse effects of the known ingredients contained in the product Pre-Kaged Elite Orange Mango. 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, alpha-GPC seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Stroke.
Dermatologic ...Orally, some patients can experience skin rash (12102). Intramuscularly, alpha-GPC can cause erythema at the injection site (12101).
Gastrointestinal
...Orally, alpha-GPC has been rarely associated with diarrhea, heartburn, nausea, and vomiting (12102).
Intramuscularly, alpha-GPC has been rarely associated with diarrhea, heartburn, nausea, and vomiting (12102).
Neurologic/CNS
...Orally, alpha-GPC has been rarely associated with dizziness, excitation, headache, and insomnia (12102).
Alpha-GPC use for at least 2 months has also been associated with an elevated risk of stroke when compared with non-users or those who used alpha-GPC for less than 2 months (108883).
Intramuscularly, alpha-GPC has been rarely associated with confusion, excitation, fainting, headache, and insomnia (12102).
General
...Orally, beta-alanine seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Flushing, paresthesia.
Gastrointestinal ...While rare, digestion problems have been reported with oral beta-alanine use (94341).
Neurologic/CNS ...Orally, beta-alanine can cause a dose-dependent feeling of pins and needles (paresthesias) along with skin flushing (16438,94333,94335,94338,94341,94342,94349,101028,101029,106711). This generally starts on the scalp within 20 minutes of the dose, spreading to most of the body, and lasting for about an hour. This was described as severe at a dose of 40 mg/kg, tolerable at a dose of 20 mg/kg, and very mild at a dose of 10 mg/kg. At the lowest dose it only occurred in 25% of subjects (16438). In some studies, beta-alanine has been given as frequently as 8 times per day so that each dose can be kept below 10 mg/kg (16438,16439). Other clinical research shows that taking beta-alanine in a tablet formulation eliminates the presence of parasthesias at a dose of 1.6 grams when compared with a solution made from powdered beta-alanine. This effect may be due to delayed absorption (97974,97975). Although paresthesias still occur with sustained-release formulations, their presence is less frequent when compared with immediate-release formulations (101029).
General
...Caffeine in moderate doses is typically well tolerated.
Most Common Adverse Effects:
Orally: Anxiety, dependence with chronic use, diarrhea, diuresis, gastric irritation, headache, insomnia, muscular tremors, nausea, and restlessness.
Serious Adverse Effects (Rare):
Orally: Stroke has been reported rarely.
Cardiovascular
...Caffeine can temporarily increase blood pressure.
Usually, blood pressure increases 30 minutes after ingestion, peaks in 1-2 hours, and remains elevated for over 4 hours (36539,37732,37989,38000,38300).
Although acute administration of caffeine can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722,38335). However, the form of caffeine may play a role in blood pressure increase after a more sustained caffeine use. In a pooled analysis of clinical trials, coffee intake was not associated with an increase in blood pressure, while ingesting caffeine 410 mg daily for at least 7 days modestly increased blood pressure by an average of 4.16/2.41 mmHg (37657). Another meta-analysis of clinical research shows that taking caffeine increases systolic and diastolic blood pressure by approximately 2 mmHg when compared with control. Preliminary subgroup analyses suggest that caffeine may increase blood pressure more in males or at doses over 400 mg (112738).
When used prior to intensive exercise, caffeine can increase systolic blood pressure by 7-8 mmHg (38308). The blood pressure-raising effects of caffeine are greater during stress (36479,38334) and after caffeine-abstinence of at least 24 hours (38241).
Epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension (38190). Habitual coffee consumption also doesn't seem to be related to hypertension, but habitual consumption of sugared or diet cola is associated with development of hypertension (13739).
Epidemiological research has found that regular caffeine intake of up to 400 mg daily is not associated with increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453,103708), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806). One clinical trial shows that in adults with diagnosed heart failure, consumption of 500 mg of coffee does not result in an increased risk for arrhythmia during exercise (95950). However, caffeine intake may pose a greater cardiovascular risk to subjects that are not regular users of caffeine. For example, in one population study, caffeinated coffee consumption was associated with an increased risk of ischemic stroke in subjects that don't regularly drink coffee (38102). In a population study in Japanese subjects, caffeine-containing medication use was modestly associated with hemorrhagic stroke in adults that do not consume caffeine regularly (91059).
The most common side effect of caffeine in neonates receiving caffeine for apnea is tachycardia (98807,114658).
Dermatologic ...There are several case reports of urticaria after caffeine ingestion (36546,36448,36475).
Endocrine
...Some evidence shows caffeine is associated with fibrocystic breast disease or breast cancer in females; however, this is controversial since findings are conflicting (8043,108806).
Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
Clinical research in healthy adults shows that an increase consumption of caffeine results in increased insulin resistance (91023).
Gastrointestinal ...Gastrointestinal upset, nausea, diarrhea, abdominal pain, and fecal incontinence may occur with caffeine intake (36466,37755,37806,37789,37830,38138,38136,38223,95956,95963). Also, caffeine may cause feeding intolerance and gastrointestinal irritation in infants (6023). Perioperative caffeine during cardiopulmonary bypass surgery seems to increase the rate of postoperative nausea and vomiting (97451). Caffeine and coffee consumption have been associated with an increase in the incidence of heartburn (37545,37575,38251,38259,38267) and gastrointestinal esophageal reflux disease (GERD) (38329,37633,37631,37603).
Genitourinary ...Caffeine, a known diuretic, may increase voiding, give a sense of urgency, and irritate the bladder (37874,37961,104580). In men with lower urinary tract symptoms, caffeine intake increased the risk of interstitial cystitis/painful bladder syndrome (38115). Excessive caffeine consumption may worsen premenstrual syndrome. Consumption of up to 10 cups of caffeinated drinks daily was associated with increased severity of premenstrual syndrome (38177). Finally, population research shows that exposure to caffeine was not associated with an increased risk of endometriosis (91035).
Immunologic ...Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Caffeine can induce or exacerbate muscular tremors (38136,37673,38161).
There has also been a report of severe rhabdomyolysis in a healthy 40-year-old patient who consumed an energy drink containing 400 mg of caffeine (4 mg/kg) and then participated in strenuous weightlifting exercise (108818).
Epidemiological evidence regarding the relationship between caffeine use and the risk for osteoporosis is contradictory. Caffeine can release calcium from storage sites and increase its urinary excretion (2669,10202,11317,111489). Females with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake, less than 300 mg daily, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317). Premature infants treated with intravenous caffeine for apnea of prematurity, have a lower bone mineral content compared with infants who are not treated with caffeine, especially when treatment extends beyond 14 days (111489).
Neurologic/CNS ...Caffeine can cause headaches, anxiety, jitteriness, restlessness, and nervousness (36466,37694,37755,37806,37865,37830,37889,38223,95952). In adolescents, there is an inverse correlation between the consumption of caffeine and various measurements of cognitive function (104579). Insomnia is a frequent adverse effect in children (10755). Caffeine may result in insomnia and sleep disturbances in adults as well (36445,36483,36512,36531,37598,37795,37819,37862,37864,37890)(37968,37971,38091,38242,91022,92952). Additionally, caffeine may exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204). Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, temporary loss of consciousness, and hospitalization requiring life support has been associated with the combined use of ephedra and caffeine (2729). Finally, epidemiological research suggests that consuming more than 190 mg of caffeine daily is associated with an earlier onset of Huntington disease by 3.6 years (91078).
Ocular/Otic
...In individuals with glaucoma, coffee consumption and caffeine intake has been found to increase intraocular pressure (8540,36464,36465,37670).
The magnitude of this effect seems to depend on individual tolerance to caffeine. Some research in healthy young adults shows that caffeine increases intraocular pressure to a greater degree in low-consumers of caffeine (i.e., 1 cup of coffee or less daily) when compared to high-consumers (i.e., those consuming 2 cups of coffee or more daily) (100371). The peak increase of intraocular pressure seems to occur at about 1.5 hours after caffeine ingestion, and there is no notable effect 4 hours after ingestion (36462,100371).
Oncologic ...Most human studies which have examined caffeine or methylxanthine intake have found that they do not play a role in the development of various cancers, including breast, ovarian, brain, colon, rectal, or bladder cancer (37641,37737,37775,37900,38050,38169,38220,91054,91076,108806).
Psychiatric
...Caffeine may lead to habituation and physical dependence (36355,36453,36512,36599), with amounts as low as 100 mg daily (36355,36453).
An estimated 9% to 30% of caffeine consumers could be considered addicted to caffeine (36355). Higher doses of caffeine have caused nervousness, agitation, anxiety, irritability, delirium, depression, sleep disturbances, impaired attention, manic behavior, psychosis and panic attacks (36505,37717,37818,37839,37857,37982,38004,38017,38028,38072)(38079,38138,38306,38325,38331,38332,97464). Similar symptoms have been reported in a caffeine-naïve individual experiencing fatigue and dehydration after a dose of only 200 mg, with resolution of symptoms occurring within 2 hours (95952).
Withdrawal: The existence or clinical importance of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance (11839). Headache is the most common symptom, due to cerebral vasodilation and increased blood flow (37769,37991,37998). Other researchers suggest symptoms such as tiredness and fatigue, decreased energy, alertness and attentiveness, drowsiness, decreased contentedness, depressed mood, difficulty concentration, irritability, and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms typically occur 12-24 hours after the last dose of caffeine and peak around 48 hours (37769,36600). Symptoms may persist for 2-9 days. Withdrawal symptoms such as delirium, nausea, vomiting, rhinorrhea, nervousness, restlessness, anxiety, muscle tension, muscle pains, and flushed face have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839). In a case report, caffeine consumption of 560 mg daily was associated with increased suicidality (91082).
Renal ...Data on the relationship between caffeine intake and kidney stones are conflicting. Some clinical research shows that caffeine consumption may increase the risk of stone formation (37634,111498), while other research shows a reduced risk with increasing caffeine intakes (111498). A meta-analysis of 7 studies found that overall, there is an inverse relationship, with a 32% decrease in the risk of kidney stones between the lowest and highest daily intakes of caffeine (111498).
Other ...People with voice disorders, singers, and other voice professionals are often advised against the use of caffeine; however, this recommendation has been based on anecdotal evidence. One small exploratory study suggests that caffeine ingestion may adversely affect subjective voice quality, although there appears to be significant intra-individual variability. Further study is necessary to confirm these preliminary findings (2724).
General ...Orally, coconut water is well tolerated.
Endocrine ...In one case report, a 35-year-old female consumed 3 liters of coconut water at the onset of labor. After delivery, the full-term neonate experienced seizures, and severe hyponatremia (113 mEq/L) was identified. The infant required treatment with infusions of 3% hypertonic sodium chloride along with 10% dextrose in normal saline (115939).
Gastrointestinal ...When consumed as a rehydration beverage following exercise, some people experience fullness or stomach upset (17678,95126). However, gastrointestinal distress is not reported in all studies (95139). Also, in some cases it appears to occur at a lower rate when compared with drinking plain water or drinking a carbohydrate-electrolyte rehydration fluid (17678).
Neurologic/CNS ...In one case report, a 69-year-old male died within approximately 30 hours of consuming a small amount of coconut water that was found to contain 3-nitropropionic acid due to spoilage with Arthrinium saccharicola. About 3 hours after consumption, the patient developed sweating, nausea, and vomiting, and was in a state of reduced consciousness when presenting to the hospital about 1.5 hours later. Other symptoms included confusion, dystonia, and poor balance, as well as metabolic acidosis. The coconut was pre-shaved and although refrigeration was recommended, it had been stored at room temperature for approximately one month after purchase (107670).
General
...Orally, creatine is generally well-tolerated.
Topically, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Dehydration, diarrhea, gastrointestinal upset, muscle cramps, and water retention.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about interstitial nephritis, renal insufficiency, rhabdomyolysis, and venous thrombosis.
Cardiovascular
...Some research suggests that creatine supplementation can cause edema.
In a randomized controlled trial, 26% of patients with amyotrophic lateral sclerosis (ALS) receiving creatine 10 grams daily reported edema after 2 months of treatment compared to 9% with placebo. The difference between groups was statistically significant at 2 months but not at month 4 and beyond. Creatine is believed to cause slight water retention, which may have been more apparent in patients who were immobilized due to ALS (46647). While this adverse drug reaction did not lead to worsening cardiac function in these patients, theoretically, creatine-related water retention could worsen congestive heart failure or hypertension.
There is one case report of lone atrial fibrillation in a 30-year-old male vegetarian. He started powdered creatine 20 grams daily for 5 days, followed by 2.5 grams daily for a month. However, he discontinued powdered creatine due to severe cramping and diarrhea, and reinitiated creatine supplementation a month later with an encapsulated formulation. Aside from gelatin in the capsule, creatine was the only ingredient listed in both formulations. During the loading dose phase, the patient developed dyspnea and palpitations and was diagnosed with lone atrial fibrillation in the emergency department. Symptoms resolved with treatment and supplement discontinuation (13187). Theoretically, alterations in electrolyte balance due to dehydration or diarrhea could lead to conduction abnormalities and arrhythmia; however, in this case, the patient had normal electrolyte levels. Contaminants in dietary supplements might also be responsible for adverse reactions; this specific creatine product was not tested for contaminants. It remains unclear whether creatine was associated with this event.
Theoretically, taking creatine nitrate might reduce blood pressure and heart rate due to its nitrate component. However, clinical research shows that creatine nitrate 12 grams daily for 7 days followed by 3 grams daily for 21 days does not lower blood pressure or heart rate acutely or chronically when compared to creatine monohydrate or placebo (95959).
Dermatologic
...In a small clinical trial of older, healthy males, one subject out of the 10 receiving creatine 5 grams four times daily for 10 days followed by 4 grams daily for 20 days reported a skin rash during the study.
The type and severity of rash and whether it resolved after creatine was discontinued were not discussed (4572). Also, skin rash has been reported by patients taking celecoxib and creatine; however, whether this effect was due to creatine or celecoxib is unclear (46706).
Topically, burning, itching, redness, irritation, and perception of changes in skin temperature have been reported (104669).
Endocrine ...Creatine may influence insulin production (11330). In human research, insulin levels increased 120 and 240 minutes after creatine supplementation (46760); however, there was no effect in another trial (46732). In a clinical study, 0.3 grams/kg of creatine daily for one week significantly increased cortisol levels by 29%. However, the levels returned to baseline at week 2 (46615).
Gastrointestinal
...Some small clinical studies have reported diarrhea and vomiting with oral creatine supplementation (4584,11332,46562,46684,46698,46704,104673).
Also, gastrointestinal distress, transient abdominal discomfort, constipation, heartburn, and nausea have been reported by a small number of individuals in randomized, controlled clinical trials (4572,11332,46527,46528,46573,46589,46622,46668,46684,46695), (46704,46771,95964,104668,104669,104673,108316). However, most high-quality clinical research shows that creatine does not increase the incidence of gastrointestinal upset (103102,103278,103279).
Undissolved creatine powder may cause gastroenteritis (1368). Additionally, simultaneous intake of creatine and caffeine powder may increase the occurrence of gastrointestinal distress (95964).
Hematologic ...There are two case reports of creatine-related venous thrombosis in otherwise healthy adults. In the first case, an active 18-year-old male who had been taking an unspecified dose of creatine daily for 3 months was diagnosed with venous thrombosis via MRI. The patient reported increased thirst and fluid consumption when taking creatine. In the second case, an active 31-year-old male who had recently taken a 5-hour flight was diagnosed with deep vein thrombosis. He had been taking an unspecified dose of creatine. After stopping creatine and receiving anticoagulation therapy for 6 months, both patients' thromboses were resolved and did not recur. Researchers speculate that dehydration might be to blame for these adverse events, as dehydration increases the risk of thrombosis. In both cases, thrombophilic conditions were ruled out, and a temporal relationship between creatine consumption and thrombosis was established (90301). However, it remains unclear if creatine was responsible for these thrombotic events.
Hepatic
...Despite two case reports describing hepatic injury in patients taking creatine (46701,90319), meta-analyses and clinical studies specifically evaluating the safety of creatine have not identified an increased risk for hepatic injury (103278,103279).
In addition, population research suggests that there is not an association between creatine intake and liver fibrosis, cirrhosis, or hepatic steatosis. However, this study largely included subjects consuming less than 4 grams daily (112208).
One preliminary clinical trial specifically evaluated the effect of creatine loading and maintenance doses on hepatic function indices in healthy adults. No clinically significant changes in hepatic indices were reported in patients taking creatine loading doses of 20 grams daily for 5 days followed by maintenance doses of 3 grams daily for 8 weeks (46521). Another clinical study evaluated the impact of creatine monohydrate and creatine nitrate on liver function enzymes, showing no change in levels within 5 hours after the first dose of 12 grams or after continued consumption of 12 grams daily for 7 days followed by 3 grams daily for 21 days (95959). The patients that experienced hepatic injury in the available case reports were also taking other exercise supplements. Whether the reported adverse hepatic effects were due to creatine or the other supplements patients were taking is unclear. Also, neither of these case reports addressed whether the supplements were tested for contamination (46701,90319).
Musculoskeletal ...Creatine-associated increase in body mass is well documented in randomized, controlled clinical trials and is often as large as 1-2 kg during the five-day loading period of creatine (2101,4569,4589,4591,4600,4605,46504,46561,46815,46827)(46830,46843,95962,103279,112201). This may be considered an unwanted adverse reaction in some individuals and a desired effect of supplementation in others. This weight gain may interfere with mass-dependent activities such as running and swimming (46504,46823). Muscle cramping due to creatine supplementation has been reported in controlled clinical trials and may result from water retention in skeletal muscle (2104,4572,4584,30915,46562,46695,46826,46827,104673). However, most high quality clinical research shows that creatine does not increase the incidence of musculoskeletal injuries or muscle cramping (103102). In one case report, rhabdomyolysis in a weight lifter using creatine 25 grams daily over a one-year period has been reported (12820). Another case report describes an adult male who developed acute compartment syndrome of the leg after regular consumption of an unspecified amount of creatine and cocaine (112210).
Neurologic/CNS ...In clinical research, thirst, sleepiness, mild headache, and syncope have been reported for patients taking creatine, although the events were uncommon (46578,46615,46820). More serious adverse events have been reported for patients taking creatine in combination with other ingredients. A case of ischemic stroke has been reported for an athlete who consumed creatine monohydrate 6 grams, caffeine 400-600 mg, ephedra 40-60 mg, and a variety of other supplements daily for 6 weeks (1275). In another case, a 26 year old male reported with a hemorrhagic stroke linked to taking the supplement Jack3d, which contains creatine, DMAA, schizandrol A, caffeine, beta-alanine, and L-arginine alpha-ketoglutarate (90318). It is likely that these adverse events were due to other ingredients, such as caffeine, ephedra, and DMAA, which are known to have stimulant and vasoconstrictive properties.
Oncologic ...Population research shows that use of muscle building supplements such as creatine, protein, and androstenedione is associated with an increased odds of testicular germ cell cancer. This risk appears to be more apparent in early users, those using two or more muscle building supplements, and those with long-term use of the supplements. The odds of testicular germ cell cancer may be increased by up to 155% in males taking both creatine and protein supplements (90329). The risk of testicular germ cell cancer from creatine alone is unclear from this study.
Psychiatric ...Anxiety, irritability, depression, aggression, and nervousness have been reported in clinical research for patients taking creatine, although the effects are not common (46518). A case of acute organic psychosis was reported in a 32-year-old soldier in Iraq who was consuming excessive amounts of caffeine coupled with use of creatine (Creatamax, MaxiNutrition) one tablet twice daily for 3 weeks plus a specific stimulant containing bitter orange, guarana seed extract, and St. John's wort extract (Ripped Fuel Ephedra Free, Twinlabs) two tablets three times daily for 2 days prior to admission. The psychosis was considered likely due to caffeine consumption in combination with the stimulant supplement rather than creatine (37982).
Renal
...Isolated cases of renal dysfunction in patients taking creatine have been reported, including a case of interstitial nephritis in a healthy male (184) and a case of renal insufficiency in a football player (46828).
In contrast to these cases, several clinical studies and case reports have shown that creatine does not affect markers of renal function in healthy adults (2120,3996,4573,16535,46735,46749,46758,46779,46813,95959,103279). Doses studied included 5- to 7-day loading regimens of 12 to 21 grams daily (2120,46813), or maintenance doses of 3-10 grams daily for up to 2 years (16535,46712,46758,95959). In two additional studies, creatine supplementation 15.75 grams for 5 days followed by 4.25 grams daily for 20 days with carbohydrate and protein ingestion led to no change of renal stress markers (46844). Other clinical research has shown that ingestion of creatine up to 30 grams daily for 5 years is not associated with an increased incidence of renal dysfunction (103102).
Other case reports involve patients with pre-existing renal dysfunction. For example, in one case, a patient with a history of recurrent renal failure developed relapsing steroid-responsive nephritis syndrome after taking creatine (1368,2118). In another case, a patient with diabetic nephropathy who was taking creatine and metformin developed severe metabolic acidosis and acute renal failure. It is unclear if creatine contributed to this event, as metformin alone is known to cause metabolic acidosis (46738). These case reports have raised concern that individuals with pre-existing renal dysfunction may be at increased risk for renal injury with creatine supplementation. However, no prospective clinical trials have been conducted in this population to clarify this concern.
In addition, two cases of acute kidney injury and hypercalcemia have been reported in 16 year old males that took 1-4 servings of creatine for less than 4 weeks; however, the creatine product contained unlabeled, very high doses of vitamin D, which is the likely cause of these symptoms (109739).
In one survey, 13% of male collegiate athletes taking creatine reported dehydration (4584). The Association of Professional Team Physicians has warned that creatine may cause dehydration, heat-related illnesses, and electrolyte imbalances, and reduce blood volume. Mild transient dehydration resulting in an elevated serum creatinine was also reported in a single person in a clinical trial (104672). However, a study found that creatine supplementation during preseason football training had no effect on fluid or electrolyte status (46845). Additionally, most high quality clinical research shows that creatine does not increase dehydration (103102). A theoretical increase in risk of dehydration due to intracellular fluid shifts has led most creatine manufacturers to caution about adequate hydration with creatine supplementation (4576).
Other
...There have been reports of heat intolerance with oral creatine supplementation (46505).
Increases in formaldehyde production have been reported with creatine use. A-24 year-old man taking supratherapeutic doses of creatine monophosphate in combination with an energy supplement developed malignant hyperthermia after undergoing anesthesia. His symptoms included tachycardia, hypertension, hypercarbia, and hyperthermia. Environmental factors are suspected to have played a role in the development of malignant hyperthermia, so whether this adverse event was due to creatine at all is unclear (46717).
In 1997, three collegiate wrestlers died after engaging in a rapid weight-loss program in order to qualify for competition (93628). Initially creatine supplementation was considered to have contributed to or caused these deaths (12820,93629); however, investigations by the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) did not confirm this belief (12820,93630). It appears that only one of the three wrestlers had been using creatine. Instead, the deaths were related to drastic, short-term weight loss in which the wrestlers wore rubber suits, avoided hydration, and performed workouts in rooms with temperatures up to 33 °C (1368,93631).
General
...Orally and intravenously, L-carnitine is generally well tolerated.
Most Common Adverse Effects:
All routes of administration: Abdominal cramps, abdominal pain, diarrhea, gastritis, heartburn, nausea, reduced appetite, and vomiting. A fish-like body odor has also been reported.
Serious Adverse Effects (Rare):
All routes of administration: Seizures.
Cardiovascular ...According to population research, plasma L-carnitine levels are associated with increased risk of cardiovascular disease and major cardiac events (90635). However, oral supplementation with L-carnitine does not appear to be associated with an increased risk of cardiovascular disease. In fact, a meta-analysis of clinical research shows that L-carnitine supplementation is associated with a reduction in all-cause mortality, as well as ventricular arrhythmias and the development of angina and does not increase the development of heart failure or myocardial reinfarction (59037). Also, another meta-analysis suggests that L-carnitine does not affect mortality or cardiovascular outcomes in patients with a previous myocardial infarction (90630).
Dermatologic ...Orally, L-carnitine has been reported to cause skin rash in a small number of cases (16105,91724). Two patients in a hair growth study using topical carnitine reported mild itching and increased dandruff, while a third reported strong itching with reddish bumps and a burning sensation (58390). When a specific formulation containing L-carnitine, licochalcone, and 1,2-decanediol was applied to the face, mild skin dryness and tightness was reported by 12% of volunteers, compared with 4% to 8% of those in the vehicle-only control group (26493).
Gastrointestinal ...Orally and intravenously, L-carnitine has been associated with nausea, epigastric discomfort, vomiting, abdominal cramps, heartburn, gastritis, anorexia, and diarrhea (3616,3624,59030,95069,95070,101562,107410,111870,111887,111891). Orally, diarrhea or colitis symptoms (1433,3630,16105,16107,16111,23437,58523,58554,59020,90623), nausea and abdominal pain (16105,16106,26499,58169,58392,58554,90623,90634), indigestion (26703), and constipation (58523) have been reported in various clinical trials.
Hematologic ...In one case report, L-carnitine 990 mg twice daily was started in a female presenting to hospital with valproic acid toxicity. Blood phosphorous levels subsequently fell from 2.3 mg/dL to 1.3 mg/dL over 4 days. After discontinuation of L-carnitine, blood phosphorus levels increased to 1.8 mg/dL. The authors suggested that the role of L-carnitine in improved protein metabolism may play a role in the declining levels of phosphorous in the blood and increased risk of hypophosphatemia (90628).
Neurologic/CNS ...Orally or intravenously, L-carnitine has been associated with seizures (3616). Orally, use of L-carnitine in clinical trials has resulted in headache, although this event is rare (58554,95070,111891). L-carnitine may also cause agitation (95070).
Other ...Orally or intravenously, L-carnitine has been associated with a fish-like body odor (1433,3616,58166,59854,90623). One of its metabolites, trimethylamine N-oxide, can cause the urine, breath, and sweat to have a fishy odor (12756,58664).
General
...Orally, L-citrulline seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, heartburn.
Gastrointestinal ...Orally, gastrointestinal intolerance, stomach discomfort, and heartburn have been reported with L-citrulline use (94955,94963,94966).
Genitourinary ...Orally, 2 of 25 patients with pulmonary hypertension reported increased urinary frequency and edema while taking 1 gram of powdered L-citrulline in water daily (94963).
Pulmonary/Respiratory ...Orally, 2 of 25 patients with pulmonary hypertension reported cough while taking 1 gram of powdered L-citrulline in water daily (94963).
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, niacinamide is well tolerated in amounts typically found in food.
When used topically and orally in higher doses, niacinamide seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, drowsiness, itching, gastrointestinal disturbances, headache, and rash.
Topically: Burning sensation, itching, and mild dermatitis.
Dermatologic ...Orally, large doses of niacinamide are associated with occasional reports of rashes, itching, and acanthosis nigricans (4880,11695,11697,14504,107709), though a meta-analysis of 19 clinical studies suggests that dermatological adverse event rates are similar between niacinamide and control (110497). Topically, application of niacinamide in a cream has been reported to cause a burning sensation, itching and pruritus, crusting, and mild dermatitis (93357,93360,110501,110498).
Endocrine ...Orally, niacinamide in high doses, 50 mg/kg daily, has been associated with modestly higher insulin requirements in patients with type 1 diabetes, when compared with taking niacinamide 25 mg/kg daily. Theoretically, high-dose niacinamide might increase insulin resistance, although to a lesser extent than niacin (4881,14512).
Gastrointestinal ...Orally, large doses of niacinamide can cause gastrointestinal disturbances including nausea, vomiting, heartburn, anorexia, epigastric pain, flatulence, and diarrhea (6243,11694,11695,11696,11697,107709,110497,113682).
Hematologic ...Orally, niacinamide supplementation might increase the risk for thrombocytopenia in patients undergoing hemodialysis (98940,107709). A meta-analysis of small clinical studies shows that taking niacinamide during hemodialysis to reduce phosphate levels is associated with a 2.8-fold increased risk for thrombocytopenia when compared with placebo. In one of the included studies, platelet levels returned to normal within 20 days after niacinamide discontinuation (98940).
Hepatic ...Orally, older reports of elevated liver function tests with high doses of niacinamide (3 grams or more daily) have raised concerns about liver toxicity. However, newer studies have not reported this concern; it is possible that some of these cases were due to contamination with niacin (4880,11694,11695,14503).
Neurologic/CNS ...Orally, large doses of niacinamide can cause dizziness, drowsiness, and headaches (11694,11695,11696,11697,107709).
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, taurine is generally well-tolerated when used in typical doses for up to one year.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, and dyspepsia.
Serious Adverse Effects (Rare):
Orally: Hypersensitivity reactions in sensitive individuals. Case reports raise concerns for serious cardiovascular adverse effects, but these reports have involved energy drinks containing taurine and other ingredients. It is unclear if these adverse effects are due to taurine, other ingredients, or the combination.
Cardiovascular ...Changes in heart rate and increased blood pressure have been reported following the co-administration of taurine and caffeine, although the effects of taurine alone are unclear (77088). In healthy individuals, consumption of energy drinks containing taurine increased platelet aggregation and decreased endothelial function (77151,112268,112741). A case of cardiac arrest following strenuous exercise and an excessive intake of energy drinks containing caffeine and taurine has been reported (77136). In another case report, a 28-year-old male without cardiovascular risk factors presented to the hospital with radiating chest pain, shortness of breath, and diaphoresis after excessive intake of an energy drink containing taurine, caffeine, sugar, and glucuronolactone. Electrocardiogram findings confirmed myocardial infarction, and subsequent catheterization confirmed thrombotic occlusion (112741).
Endocrine ...Orally, taurine has been reported to cause hypoglycemia (77153).
Gastrointestinal ...Orally, constipation has been reported following the administration of taurine (77231). Dyspepsia has also been reported after oral taurine use (104165).
Hematologic ...In clinical research, taurine reduced platelet aggregation (77245). A case of massive intravascular hemolysis, presenting with confusion, dark urine, dyspnea, emesis, and fever, has been reported following the administration of a naturopathic vitamin infusion containing taurine, free amino acids, magnesium, and a vitamin B and D complex (77177). However, the effects of taurine alone are unclear.
Immunologic ...A case report describes a hypersensitivity reaction in a female patient with a history of allergies to sulfonamides, sulfites, and various foods, after ingestion of taurine and other sulfur-containing supplements. The amount of taurine in the products ranged from 50-500 mg per dose. The allergic reaction recurred upon rechallenge with taurine 250-300 mg (91514).
Neurologic/CNS
...In a case study, encephalopathy occurred in a body-builder who took approximately 14 grams of taurine in combination with insulin and anabolic steroids.
It is not known if this was due to the taurine or the other drugs taken (15536).
Cases of seizures following the consumption of energy drinks containing taurine have been reported (77105,77196). In clinical research, taurine has been reported to cause drowsiness and ataxia in epileptic children (77241).
Psychiatric ...In a case report, a 36-year-old male with adequately controlled bipolar disorder was hospitalized with symptoms of mania after consuming several cans of an energy drink containing taurine, caffeine, glucuronolactone, B vitamins, and other ingredients (Red Bull Energy Drink) over a period of four days (14302). It is unknown if this effect was related to taurine.
Pulmonary/Respiratory ...In human research, an exacerbation of pulmonary symptoms of cystic fibrosis has been associated with taurine supplementation, although this could also be caused by progression of the disease (77231).
Renal ...A case of acute kidney failure has been reported following the concomitant intake of 1 liter of vodka and 3 liters of an energy drink providing taurine 4. 6 grams, caffeine 780 mg, and alcohol 380 grams (77185).
General
...No adverse effects have been reported.
However, a thorough evaluation of safety outcomes has not been conducted.
Orally, huperzine A, a constituent of toothed clubmoss, can cause dizziness, nausea, and sweating (3140).
Gastrointestinal ...Orally, huperzine A, a constituent of toothed clubmoss, can cause nausea (3140).
Neurologic/CNS ...Orally, huperzine A, a constituent of toothed clubmoss, can cause dizziness and sweating (3140).
General
...Orally, tyrosine seems to be well tolerated.
No serious adverse effects have been documented; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Fatigue, headache, heartburn, and nausea.
Gastrointestinal ...Orally, tyrosine can cause nausea and heartburn when taken at a dose of 150 mg/kg (7211). Taking tyrosine 4 grams daily in combination with 5-hydroxytryptophan 800 mg and carbidopa 100 mg can cause diarrhea, nausea, and vomiting. These effects can be mitigated by lowering the dosage (918).
Musculoskeletal ...Orally, larger doses of tyrosine (150 mg/kg) can cause arthralgia, but this is uncommon (7211).
Neurologic/CNS ...Orally, larger doses of tyrosine (150 mg/kg) can cause headache and fatigue (7211). Taking a combination of tyrosine 4 grams, 5-hydroxytryptophan 800 mg, and carbidopa 100 mg can cause drowsiness and agitation. These effects can be mitigated by lowering the dosage (918).
General
...Orally, intramuscularly, and topically, vitamin B12 is generally well-tolerated.
Most Common Adverse Effects:
Intramuscular: Injection site reactions.
Serious Adverse Effects (Rare):
Intramuscularly: Severe hypokalemia has been rarely linked with correction of megaloblastic anemia with vitamin B12.
Cardiovascular ...In human clinical research, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12, followed by daily oral administration after coronary stenting, increased restenosis rates (12150). Hypertension following intravenous administration of hydroxocobalamin has been reported in human research (82870,82864).
Dermatologic
...Orally or intramuscularly, vitamin B12 can cause allergic reactions such as rash, pruritus, erythema, and urticaria.
Theoretically, allergic reactions might be caused by the cobalt within the vitamin B12 molecule (82864,90373,90381,103974). In one case report, oral methylcobalamin resulted in contact dermatitis in a 59-year-old Japanese female with a cobalt allergy (103974). In another case report, a 69-year-old female developed a symmetrical erythematous-squamous rash for 5 years after oral vitamin B12 supplementation for 10 years. A patch test confirmed that the systemic allergic dermatitis was due to vitamin B12 supplementation, which resolved 3 months after discontinuation (114578).
Vitamin B12 (intramuscular or oral) has also been associated with at least 19 cases of acneiform eruptions which resolved upon discontinuation of vitamin B12 (90365,90369,90388). High-dose vitamin B12 (20 mcg daily) and vitamin B6 (80 mg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may last up to four months after the supplement is stopped and can be treated with systemic corticosteroids and topical therapy (10998,82870,82871).
Gastrointestinal ...Intravenously, vitamin B12 (hydroxocobalamin) 2. 5-10 grams can cause nausea and dysphagia (82864).
Genitourinary ...Intravenously, vitamin B12 (hydroxocobalamin) 5-15 grams has been associated with chromaturia in clinical research (82870,82871,112282,112264).
Hematologic ...According to case report data, the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia (82914).
Musculoskeletal ...According to case report data, correction of megaloblastic anemia with vitamin B12 has precipitated gout in susceptible individuals (82879).
Neurologic/CNS ...Treatment with vitamin B12 has been rarely associated with involuntary movements in infants with vitamin B12 deficiency (90370,90385,90397). In some cases these adverse reactions were misdiagnosed as seizures or infantile tremor syndrome (90370,90385). These adverse reactions presented 2-5 days after treatment with vitamin B12 and resolved once vitamin B12 was discontinued (90370,90385,90397).
Oncologic ...Although some epidemiological research disagrees (9454), most research has found that elevated plasma levels of vitamin B12 are associated with an increased risk of various types of cancer, including lung and prostate cancers and solid tumors (50411,102383,107743). One study found, when compared with blood levels of vitamin B12 less than 1000 ng/mL, plasma vitamin B12 levels of at least 1000 ng/mL was strongly associated with the occurrence of solid cancer (107743). It is unclear if increased intake of vitamin B12, either through the diet or supplementation, directly affects the risk of cancer. It is possible that having cancer increases the risk of vitamin B12 elevation. However, one observational study has found that the highest quintile of dietary intake of vitamin B12 is associated with a 75% increased incidence of developing esophageal cancer when compared with the lowest quintile in never drinkers, but not drinkers (107147).
Renal ...There is a case report of oxalate nephropathy in a 54-year-old male which was determined to be related to the use of intravenous hydroxocobalamin as treatment for cyanide poisoning. Intermittent hemodialysis was started 5 days after admission, along with a low-oxalate diet, oral calcium acetate, and pyridoxine 5 mg/kg daily (107148). A review of the use of intravenous hydroxocobalamin for suspected cyanide poisoning in 21 intensive care units in France between 2011 and 2017 resulted in a 60% increased odds of acute kidney injury and a 77% increased odds of severe acute kidney injury in the first week. However, biopsies were not conducted and a direct link with use of hydroxocobalamin could not be made (107139).
Other ...Several studies have found that higher vitamin B12 levels may be associated with increased mortality or decreased survival rates in hospitalized elderly patients (82889,82812,82857,82895). Human research has also found a positive correlation between vitamin B12 status and all-cause mortality in Pima Indians with diabetes (82863).
General
...Orally or by injection, vitamin B6 is well tolerated in doses less than 100 mg daily.
Most Common Adverse Effects:
Orally or by injection: Abdominal pain, allergic reactions, headache, heartburn, loss of appetite, nausea, somnolence, vomiting.
Serious Adverse Effects (Rare):
Orally or by injection: Sensory neuropathy (high doses).
Dermatologic ...Orally, vitamin B6 (pyridoxine) has been linked to reports of skin and other allergic reactions and photosensitivity (8195,9479,90375). High-dose vitamin B6 (80 mg daily as pyridoxine) and vitamin B12 (20 mcg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may persist for up to 4 months after the supplement is stopped, and may require treatment with systemic corticosteroids and topical therapy (10998).
Gastrointestinal ...Orally or by injection, vitamin B6 (pyridoxine) can cause nausea, vomiting, heartburn, abdominal pain, mild diarrhea, and loss of appetite (8195,9479,16306,83064,83103,107124,107127,107135). In a clinical trial, one patient experienced infectious gastroenteritis that was deemed possibly related to taking vitamin B6 (pyridoxine) orally up to 20 mg/kg daily (90796). One small case-control study has raised concern that long-term dietary vitamin B6 intake in amounts ranging from 3.56-6.59 mg daily can increase the risk of ulcerative colitis (3350).
Hematologic ...Orally or by injection, vitamin B6 (pyridoxine) can cause decreased serum folic acid concentrations (8195,9479). One case of persistent bleeding of unknown origin has been reported in a clinical trial for a patient who used vitamin B6 (pyridoxine) 100 mg twice daily on days 16 to 35 of the menstrual cycle (83103). It is unclear if this effect was due to vitamin B6 intake.
Musculoskeletal ...Orally or by injection, vitamin B6 (pyridoxine) can cause breast soreness or enlargement (8195).
Neurologic/CNS ...Orally or by injection, vitamin B6 (pyridoxine) can cause headache, paresthesia, and somnolence (8195,9479,16306). Vitamin B6 (pyridoxine) can also cause sensory neuropathy, which is related to daily dose and duration of intake. Doses exceeding 1000 mg daily or total doses of 1000 grams or more pose the most risk, although neuropathy can occur with lower daily or total doses as well (8195). The mechanism of the neurotoxicity is unknown, but is thought to occur when the liver's capacity to phosphorylate pyridoxine via the active coenzyme pyridoxal phosphate is exceeded (8204). Some researchers recommend taking vitamin B6 as pyridoxal phosphate to avoid pyridoxine neuropathy, but its safety is unknown (8204). Vitamin B6 (pyridoxine) neuropathy is characterized by numbness and impairment of the sense of position and vibration of the distal limbs, and a gradual progressive sensory ataxia (8196,10439). The syndrome is usually reversible with discontinuation of pyridoxine at the first appearance of neurologic symptoms. Residual symptoms have been reported in patients taking more than 2 grams daily for extended periods (8195,8196). Daily doses of 100 mg or less are unlikely to cause these problems (3094).
Oncologic ...In females, population research has found that a median intake of vitamin B6 1. 63 mg daily is associated with a 3.6-fold increased risk of rectal cancer when compared with a median intake of 1.05 mg daily (83024). A post-hoc subgroup analysis of results from clinical research in adults with a history of recent stroke or ischemic attack suggests that taking folic acid, vitamin B12, and vitamin B6 does not increase cancer risk overall, although it was associated with an increased risk of cancer in patients who also had diabetes (90378). Also, in patients with nasopharyngeal carcinoma, population research has found that consuming at least 8.6 mg daily of supplemental vitamin B6 during treatment was associated with a lower overall survival rate over 5 years, as well as a reduced progression-free survival, when compared with non-users and those with intakes of up to 8.6 mg daily (107134).
