| Ingredients | Amount Per Serving 1 Scoop (10 g) |
|---|---|
|
Calories
|
35 Calorie(s) |
|
Total Carbohydrates
|
5 Gram(s) |
|
(Thiamine Hydrochloride)
(Thiamin (Form: as Thiamin HCl) )
|
1.2 mg |
| 1.3 mg | |
|
(Niacinamide)
(Niacin (Form: as Niacinamide) )
|
16 mg |
|
(Pyridoxine Hydrochloride)
(Vitamin B6 (Form: as Pyridoxine HCl) )
|
1.7 mg |
|
(Cyanocobalamin)
(Vitamin B12 (Form: as Cyanocobalamin) )
|
2.4 mcg |
|
(Na)
|
5 mg |
|
Anabolic Strength Blend
|
3.95 Gram(s) |
| 2 Gram(s) | |
|
(Beta-Alanine)
|
1.2 Gram(s) |
| 750 mg | |
|
Metabolic Ignition Blend
|
650 mg |
|
(Camellia sinensis )
(leaf)
|
250 mg |
| 250 mg | |
| 150 mg |
Maltodextrin, Citric Acid, Natural flavors, Silica, Sucralose, Acesulfame Potassium, Red Beet powder Note: color
| Ingredients | Amount Per Serving 2 Scoop (20 g) |
|---|---|
|
Calories
|
70 Calorie(s) |
|
Total Carbohydrates
|
9 Gram(s) |
|
(Thiamine Hydrochloride)
(Thiamin (Form: as Thiamin HCl) )
|
2.4 mg |
| 2.6 mg | |
|
(Niacinamide)
(Niacin (Form: as Niacinamide) )
|
32 mg |
|
(Pyridoxine Hydrochloride)
(Vitamin B6 (Form: as Pyridoxine HCl) )
|
3.4 mg |
|
(Cyanocobalamin)
(Vitamin B12 (Form: as Cyanocobalamin) )
|
4.8 mcg |
|
(Na)
|
10 mg |
|
Anabolic Strength Blend
|
7.9 Gram(s) |
| 4 Gram(s) | |
|
(Beta-Alanine)
|
2.4 Gram(s) |
| 1.5 Gram(s) | |
|
Metabolic Ignition Blend
|
1300 mg |
|
(Camellia sinensis )
(leaf)
|
500 mg |
| 500 mg | |
| 300 mg |
Maltodextrin, Citric Acid, Natural flavors, Silica, Sucralose, Acesulfame Potassium, Red Beet powder Note: color
Below is general information about the effectiveness of the known ingredients contained in the product Super Advanced Shred Igniter Raspberry Lemonade. 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
Below is general information about the safety of the known ingredients contained in the product Super Advanced Shred Igniter Raspberry Lemonade. 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, 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 and appropriately. BCAAs 12 grams daily have not been associated with significant adverse effects in studies lasting for up to 2 years (68,72,73,74,10117,10146,10147,37120,92643,97531,103351,103352). ...when used intravenously and appropriately. BCAAs are an FDA-approved injectable product (13309).
CHILDREN: LIKELY SAFE
when used orally in dietary amounts of 71-134 mg/kg daily (11120,13308).
CHILDREN: POSSIBLY SAFE
when larger, supplemental doses are used orally and appropriately for up to 6 months (13307,13308,37127).
PREGNANCY:
Insufficient reliable information available; avoid using amounts greater than those found in food.
Although adverse effects have not been reported in humans, some animal research suggests that consumption of supplemental isoleucine, a BCAA, during the first half of pregnancy may have variable effects on birth weight, possibly due to abnormal placental development (103350).
LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.
Although the safety of increased BCAA consumption during lactation is unclear, some clinical research suggests that a higher concentration of isoleucine and leucine in breastmilk during the first 6 months postpartum is not associated with infant growth or body composition at 2 weeks, 2 months, or 6 months (108466).
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 green tea is consumed as a beverage in moderate amounts (733,6031,9222,9223,9225,9226,9227,9228,14136,90156)(90159,90168,90174,90184,95696). Green tea contains caffeine. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 8 cups of green tea daily, or approximately 400 mg of caffeine, is 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). ...when green tea extract cream or ointment is used topically and appropriately, short-term. A green tea extract 3% cream, applied twice daily, has been used with apparent safety for up to 8 weeks, and a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins has been safely used for up to 16 weeks (15067). The safety of treatment for longer durations or multiple treatment courses is not known.
POSSIBLY SAFE ...when green tea extract is used orally. Green tea extract containing 7% to 12% caffeine has been used safely for up to 2 years (8117,37725). Also decaffeinated green tea extract up to 1.3 grams daily enriched in EGCG has been used safely for up to 12 months (90158,97131). In addition, green tea extract has been safely used as part of an herbal mixture also containing garcinia, coffee, and banaba extracts for 12 weeks (90137). ...when used topically and appropriately as a cream or mouthwash (6065,11310,90141,90150,90151).
POSSIBLY UNSAFE ...when consumed as a beverage in large quantities. Green tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, psychological dependence, and other significant adverse effects. Doses of caffeine greater than 600 mg per day, or approximately 12 cups of green tea, have been associated with significant adverse effects such as tachyarrhythmias and sleep disturbances (11832). These effects would not be expected to occur with the consumption of decaffeinated green tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. There is also some speculation that green tea products containing higher amounts of the catechin epigallocatechin gallate (EGCG) might have increased risk of adverse events. Some research has found that taking green tea products containing EGCG levels greater than 200 mg is associated with increased risk of mild adverse effects such as constipation, increased blood pressure, and rash (90161). Other research has found that doses of EGCG equal to or above 800 mg daily may be associated with increased risk of liver injury in humans (95440,95696,97131).
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 per kilogram). Serious toxicity can occur at lower doses depending on variables in caffeine sensitivity such as smoking, age, and prior caffeine use (11832).
CHILDREN: POSSIBLY SAFE
when used orally by children and adolescents in amounts commonly found in foods and beverages (4912,11833).
Intake of caffeine in doses of less than 2.5 mg/kg daily is not associated with significant adverse effects in children and adolescents (11733,98806). ...when used for gargling three times daily for up to 90 days (90150).
There is insufficient reliable information available about the safety of green tea extract when used orally in children. However, taking green tea extract orally has been associated with potentially serious, albeit uncommon and unpredictable cases, of hepatotoxicity in adults. Therefore, some experts recommend that children under the age of 18 years of age do not use products containing green tea extract (94897).
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of green tea, pregnant patients should closely monitor their intake to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,11733,16014,16015,98806). In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014). This increased risk may be most likely 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, most healthy pregnant patients can safely consume doses up to 300 mg daily without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). Advise keeping caffeine consumption below 300 mg daily. This is similar to the amount of caffeine in about 6 cups of green tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Based on animal models, green tea extract catechins are also transferred to the fetus, but in amounts 50-100 times less than maternal concentrations (15010). The potential impact of these catechins on the human fetus is not known, but animal models suggest that the catechins are not teratogenic (15011).
PREGNANCY: POSSIBLY UNSAFE
when used orally in amounts providing more than 300 mg caffeine daily.
Caffeine from green tea crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Advise keeping caffeine consumption from all sources below 300 mg daily. This is similar to the amount of caffeine in about 6 cups of green tea. High maternal doses of caffeine throughout pregnancy have also 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). However, some research has also found that intrauterine exposure to even modest amounts of caffeine, based on maternal blood levels during the first trimester, is associated with a shorter stature in children ages 4-8 years (109846). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
There is also concern that consuming large amounts of green tea might have antifolate activity and potentially increase the risk of folic acid deficiency-related birth defects. Catechins in green tea inhibit the enzyme dihydrofolate reductase in vitro (15012). This enzyme is responsible for converting folic acid to its active form. Preliminary evidence suggests that increasing maternal green tea consumption is associated with increased risk of spina bifida (15068). Also, evidence from epidemiological research suggests that serum folate levels in pregnant patients with high green tea intake (57.3 mL per 1000 kcal) are decreased compared to participants who consume moderate or low amounts of green tea (90171). More evidence is needed to determine the safety of using green tea during pregnancy. For now, advise pregnant patients to avoid consuming large quantities of green tea.
LACTATION: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of green tea, nursing parents should closely monitor caffeine intake. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations (9892).
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Consumption of green tea might cause irritability and increased bowel activity in nursing infants (6026). There is insufficient reliable information available about the safety of green tea extracts when applied topically during breast-feeding.
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).
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 and appropriately. Riboflavin 400 mg daily has been taken for up to 3 months, and 10 mg daily has been taken safely for up to 6 months (4912,91752,105480). A tolerable upper intake level (UL) has not been established (3094,91752,94089).
CHILDREN: LIKELY SAFE
when used orally and appropriately in dietary amounts.
A tolerable upper intake level (UL) has not been established (3094,94089). ...when used orally in higher doses for up to 1 year. Doses of 100-200 mg daily have been used safely for 4-12 months in children ages 9-13 years (71483,105484).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately in dietary amounts.
A tolerable upper intake level (UL) has not been established (3094,94089).
LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).
POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.
CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310).
Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses.
Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).
LIKELY SAFE ...when used orally and appropriately. A tolerable upper intake level (UL) has not been established for thiamine, and doses up to 50 mg daily have been used without adverse effects (15,6243). ...when used intravenously or intramuscularly and appropriately. Injectable thiamine is an FDA-approved prescription product (15,105445).
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).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in dietary amounts of 1.
4 mg daily. A tolerable upper intake level (UL) has not been established for healthy individuals (3094,6243).
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 Super Advanced Shred Igniter Raspberry Lemonade. 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, BCAAs might alter the effects of antidiabetes medications.
 Details
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BCAAs in large doses can reduce the effects of levodopa.
Details
BCAAs may compete with levodopa for transport systems in the intestine and brain and decrease the effectiveness of levodopa (66,2719). Small clinical studies how that concomitant ingestion of protein or high doses of leucine or isoleucine (100 mg/kg) and levodopa can exacerbate tremor, rigidity, and the "on-off" syndrome in patients with Parkinson disease (3291,3292,3293,3294).
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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.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
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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.
Details
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Details
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.
Details
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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.
Details
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.
Details
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Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Details
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.
Details
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.
Details
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Details
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
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Theoretically, caffeine might reduce the effects of phenytoin and increase the risk for convulsions.
Details
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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.
Details
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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.
Details
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.
Details
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.
Details
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.
Details
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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, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
Details
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425% (98424).
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Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't 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, alcohol might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370).
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Theoretically, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity (733,8028,8029,12882,100524).
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Theoretically, taking green tea with antidiabetes drugs might interfere with blood glucose control.
Details
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Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
Details
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected (102714). Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin (19079). It is not clear if drinking green tea alters the absorption of atorvastatin.
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Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15).
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Theoretically, green tea might interfere with the effects of bortezomib.
Details
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines (17212). Advise patients taking bortezomib, not to take green tea.
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Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Details
Green tea contains caffeine. 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, green tea might reduce the levels and clinical effects of celiprolol.
Details
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98% (104607). This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine (19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Details
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42% (11736).
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Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Details
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels (90173). Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine (13741).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Details
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65% (8644).
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2) (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.
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Green tea is unlikely to produce clinically significant changes in the levels and clinical effects of CYP3A4 substrates.
Details
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Theoretically, green tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Green tea contains caffeine. Caffeine might inhibit 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 might increase the risk of adverse effects from caffeine.
Details
In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).
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Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Details
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Details
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).
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Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Details
Green tea contains caffeine. 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, green tea might reduce the effects of felbamate and increase the risk for convulsions.
Details
Green tea contains caffeine. 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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Green tea can decrease blood levels of fexofenadine.
Details
Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter (111029). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates (19079,102714,102730).
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
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Theoretically, green tea might increase the levels and adverse effects of flutamide.
Details
Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
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Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Details
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Theoretically, green tea might reduce the levels and clinical effects of imatinib.
Details
In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81% (104600). This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.
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Theoretically, green tea might reduce the levels and clinical effects of lisinopril.
Details
Preliminary clinical research shows that a single dose of green tea extract reduces plasma concentrations of lisinopril. Compared to a control group, peak levels and area under the curve (AUC) of lisinopril were reduced by approximately 71% and 66%, respectively (104599). This may be due to inhibition of organic anion transporting polypeptides (OATP) by green tea catechins (19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).
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Theoretically, abrupt green tea withdrawal might increase the levels and adverse effects of lithium.
Details
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Theoretically, metformin might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571). Theoretically, concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.
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Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Methoxsalen can reduce caffeine metabolism (23572). Concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.
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Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260).
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Theoretically, green tea might increase the levels and adverse effects of midazolam.
Details
Animal research suggests that green tea extract can increase the maximum plasma concentration, but not the half-life, of oral midazolam. This effect has been attributed to the inhibition of intestinal cytochrome P450 3A4 (CYP3A4) and induction of hepatic CYP3A4 enzymes by green tea constituents (20896). However, it is unlikely that this effect is clinically significant, as the dose used in animals was 50 times greater than what is commonly ingested by humans.
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Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Details
Green tea contains caffeine. 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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Green tea seems to reduce the levels and clinical effects of nadolol.
Details
Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect (19071). Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour (102721). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine (19071,19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).
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Theoretically, green tea might increase the levels and adverse effects of nicardipine.
Details
Green tea contains EGCG. Animal research shows that EGCG increases the area under the curve (AUC) and absolute oral bioavailability of nicardipine. The mechanism of action is thought to involve inhibition of both intestinal P-glycoprotein and hepatic cytochrome P450 3A (90136). The effect of green tea itself on nicardipine is unclear.
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Theoretically, concomitant use might increase the risk of hypertension.
Details
Green tea contains caffeine. 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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Green tea seems to reduce the levels of nintedanib.
Details
Clinical research shows that green tea can significantly decrease blood levels of nintedanib. Taking green tea extract twice daily for 7 days 30 minutes prior to a meal along with nintedanib with the meal decreased the 12-hour area under the curve (AUC) values for nintedanib by 21%. There was no effect on the maximum concentration of nintedanib (111028).
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Theoretically, green tea might reduce the absorption of organic anion-transporting polypeptide (OATP) substrates.
Details
OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates, including lisinopril, and celiprolol (19079,102714,102730).
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Green tea might increase the levels and adverse effects of P-glycoprotein (P-gp) substrates.
Details
In vitro research and case reports suggest that green tea inhibits drug efflux by P-gp, potentially increasing serum levels of P-gp substrates. Case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking green tea and certain P-gp substrates (111644).
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Theoretically, green tea might decrease the effects of pentobarbital.
Details
Green tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, green tea might reduce the effects of phenobarbital and increase the risk for convulsions.
Details
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Details
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
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Theoretically, green tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
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Theoretically, green tea might increase the levels and clinical effects of pioglitazone.
Details
Green tea contains caffeine. 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.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Green tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).
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Theoretically, green tea extract might alter the absorption and distribution of rosuvastatin.
Details
In animal research, giving green tea extract with rosuvastatin increased plasma levels of rosuvastatin. Rosuvastatin is a substrate of organic anion-transporting polypeptide (OATP)1B1, which is expressed in the liver. The increased plasma levels may have been related to inhibition of OATP1B1 (102717). However, in humans, taking EGCG with rosuvastatin reduced plasma levels of rosuvastatin, suggesting an inhibition of intestinal OATP (102730). It is not clear if drinking green tea alters the absorption of rosuvastatin.
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Theoretically, concomitant use might increase stimulant adverse effects.
Details
Green tea contains caffeine. 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.
Details
Green tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
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Theoretically, green tea might increase the levels and adverse effects of theophylline.
Details
Green tea contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).
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Theoretically, green tea might increase the levels and adverse effects of tiagabine.
Details
Green tea contains caffeine. 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
Green tea contains caffeine. 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, green tea might reduce the effects of valproate and increase the risk for convulsions.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of both verapamil and caffeine.
Details
Animal research suggests that the green tea constituent EGCG increases the area under the curve (AUC) values for verapamil by up to 111% and its metabolite norverapamil by up to 87%, likely by inhibiting P-glycoprotein (90138). Also, theoretically, concomitant use of verapamil and caffeinated beverages such as green tea might increase plasma caffeine concentrations and the risk of adverse effects, due to the caffeine contained in green tea. Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, green tea may increase the risk of bleeding if used with warfarin.
Details
Conflicting reports exist regarding the potential of green tea to antagonize the effect of warfarin; however, most evidence suggests that drinking green tea in moderation is unlikely to cause a significant interaction. Green tea contains a small amount of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects (1460,1461,1463,8028). Therefore, use of green tea in moderate amounts is unlikely to antagonize the effects of warfarin; however, very large doses should be avoided.
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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.
Details
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Theoretically, L-carnitine might increase the anticoagulant effects of warfarin.
Details
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Theoretically, niacinamide may have additive effects when used with anticoagulant or antiplatelet drugs, especially in patients on hemodialysis.
Details
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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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Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.
Details
In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics (23372). It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.
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Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
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Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
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Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).
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Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
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High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.
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Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
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The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.
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Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
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Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.
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Trimethoprim might increase blood levels of thiamine.
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In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations (111678).
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Theoretically, tyrosine might decrease the effectiveness of levodopa.
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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.
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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.
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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.
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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 Super Advanced Shred Igniter Raspberry Lemonade. 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, 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
...Orally or intravenously, BCAAs are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, diarrhea, nausea, vomiting.
All routes of administration: High doses can lead to fatigue and loss of motor coordination.
Cardiovascular ...Orally, a single case of hypertension following the use of BCAAs has been reported (37143).
Dermatologic ...Orally, a single case of skin blanching following the use of BCAAs has been reported (681). It is not known if this effect was due to use of BCAAs or other factors.
Gastrointestinal ...Orally, BCAAs can cause nausea, vomiting, diarrhea, and abdominal distension. Nausea and diarrhea has been reported to occur in about 10% of people taking BCAAs (10117,37143,92643,97531).
Neurologic/CNS ...Orally and intravenously, BCAAs can cause fatigue and loss of motor coordination due to increased plasma ammonia levels (693,694,10117). Short-term use of 60 grams of BCAAs containing leucine, isoleucine, and valine for 7 days in patients with normal metabolic function seems to increase levels of ammonia, but not to toxic plasma levels (10117). However, liver function should be monitored with high doses or long-term use (10117). Due to the potential of increased plasma levels of ammonia and subsequent fatigue and loss of motor coordination, BCAAs should be used cautiously before or during activities where performance depends on motor coordination (75). Orally, BCAAs may also cause headache, but this has only been reported in one clinical trial (681).
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, green tea is generally well tolerated when consumed as a beverage in moderate amounts.
Green tea extract also seems to be well tolerated when used for up to 12 months.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, dyspepsia, flatulence, and nausea.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity, hypokalemia, and thrombotic thrombocytopenic purpura have been reported rarely.
Cardiovascular
...Acute or short-term oral administration of green tea may cause hypertension (53719,54014,54065,54076,102716).
The risk may be greater for green tea products containing more than 200 mg epigallocatechin gallate (EGCG) (90161). However, consumption of brewed green tea does not seem to increase blood pressure or pulse, even in mildly hypertensive patients (1451,1452). In fact, some evidence suggests that habitual tea consumption is associated with a reduced risk of developing hypertension (12518). Also, epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension or with cardiovascular disease mortality in patients with hypertension (13739,111027). Rarely, green tea consumption may cause hypotension (53867).
Epidemiological research suggests that regular caffeine intake of up to 400 mg per day, or approximately 8 cups of green tea, is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, and temporary loss of consciousness has been associated with the combined use of ephedra and caffeine (2729). There is also a report of ischemic stroke in an athlete who consumed ephedra 40-60 mg, creatine monohydrate 6 grams, caffeine 400-600 mg, and a variety of other supplements daily for 6 weeks (1275). In theory, combining caffeinated green tea with ephedra would have similar effects.
In a case report, the EGCG component of a specific weight loss supplement (Hydroxycut) was thought to be responsible for atrial fibrillation (54028). The patient was given two doses of intravenous diltiazem and was loaded with intravenous digoxin. Thirty-six hours after the last product dose, she spontaneously converted to normal sinus rhythm. The authors suggested that the block of the atrial-specific KCNA5 potassium channel likely played a role in this response.
A case of thrombotic thrombocytopenic purpura has been reported for a patient who consumed a weight loss product containing green tea (53978). She presented at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. Twelve procedures of plasmapheresis were performed, and corticosteroid treatment was initiated. She was discharged after 20 days.
Dermatologic ...Orally, green tea may cause skin rashes or skin irritation (53731,54038,90161,90187,102716). Topically, green tea may cause local skin reactions or skin irritation, erythema, burning, itching, edema, and erosion (53731,54018,97136,104609,111031). A green tea extract ointment applied to the cervix can cause cervical and vaginal inflammation, vaginal irritation, and vulval burning (11310,36442,36438). When applied to external genital or perianal warts, a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins can cause erythema, pruritus, local pain, discomfort and burning, ulceration, induration, edema, and vesicular rash (15067,53907).
Endocrine
...There is some concern that, due to its caffeine content, green tea may be associated with an increased risk of fibrocystic breast disease, breast cancer, and endometriosis.
However, this is controversial since findings are conflicting (8043). 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, such as green tea, 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).
A case of hypoglycemia has been reported for a clinical trial participant with type 2 diabetes who used green tea in combination with prescribed antidiabetes medication (54035).
Gastrointestinal ...Orally, green tea beverage or supplements can cause nausea, vomiting, abdominal bloating and pain, constipation, dyspepsia, reflux, morning anorexia, increased thirst, flatulence, and diarrhea. These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,36398,53719,53867,53936,54038,54076,90139,90140)(90161,90175,90187,97131,97136,102716).
Hepatic
...There is concern that some green tea products, especially green tea extracts, can cause hepatotoxicity in some patients.
In 2017, the regulatory agency Health Canada re-issued a warning to consumers about this concern. The updated warning advises patients taking green tea extracts, especially those with liver disease, to watch for signs of liver toxicity. It also urges children to avoid taking products containing green tea extracts (94897). In 2020, the United States Pharmacopeia (USP) formed an expert panel to review concerns of green tea extract-related hepatotoxicity. Based on their findings, USP determined that any products claiming compliance with USP quality standards for green tea extract must include a specific warning on the label stating "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)" (102722).
Numerous case reports of hepatotoxicity, primarily linked to green tea extract products taken in pill form, have been published. A minimum of 29 cases have been deemed at least probably related to green tea and 38 have been deemed possibly related. In addition, elevated liver enzymes have been reported in clinical research (14136,15026,53740,53746,53775,53859,54027,90139,90162,90164)(93256,94898,94899,102716,102720,102722,107158,111020,111644). Most cases of toxicity have had an acute hepatitis-like presentation with a hepatocellular-elevation of liver enzymes and some cholestasis. Onset of hepatotoxic symptoms usually occurs within 3 months after initiation of the green tea extract supplement, and symptoms can persist from 10 days to 1 year (95439,94897,94898,107158). Some reports of hepatotoxicity have been associated with consumption of green tea-containing beverages as well (15026,53742,54016,90125,90143).
In most cases, liver function returned to normal after discontinuation of the green tea product (14136,15026,53859,93256,107158). In one case, use of a specific ethanolic green tea extract (Exolise, Arkopharma) resulted in hepatotoxicity requiring a liver transplant. Due to concerns about hepatotoxicity, this specific extract was removed from the market by the manufacturer (14310). Since then, at least 5 cases of liver toxicity necessitating liver transplantation have been reported for patients who used green tea extracts (94898,107158). In another case, use of green tea (Applied Nutrition Green Tea Fat Burner) in combination with whey protein, a nutritional supplement (GNC Mega Men Sport), and prickly pear cactus resulted in acute liver failure (90162).
Despite the numerous reports of hepatotoxicity associated with the use of green tea products, the actual number of hepatotoxicity cases is low when the prevalence of green tea use is considered. From 2006 to 2016, liver injury from green tea products was estimated have occurred in only 1 out of 2.7 million patients who used green tea products (94897,95440).
In addition to the fact that green tea hepatotoxicity is uncommon, it is also not clear which patients are most likely to experience liver injury (94897,95440). The hepatotoxicity does not appear to be an allergic reaction or an autoimmune reaction (94897). It is possible that certain extraction processes, for example, ethanolic extracts, produce hepatotoxic constituents. However, in most cases, the presence of contaminants in green tea products has not been confirmed in laboratory analyses (90162).
Although results from one analysis of 4 small clinical studies disagrees (94899), most analyses of clinical data, including one conducted by the European Food Safety Association, found that hepatotoxicity from green tea products is associated with the dose of EGCG in the green tea product. Results show that daily intake of EGCG in amounts greater than or equal to 800 mg per day is associated with a higher incidence of elevated liver enzymes such as alanine transaminase (ALT) (95440,95696,97131). However, it is still unclear what maximum daily dose of EGCG will not increase liver enzyme levels or what minimum daily dose of EGCG begins to cause liver injury. In many cases of liver injury, the dose of green tea extract and/or EGCG is not known. Therefore, a minimum level of green tea extract or EGCG that would cause liver injury in humans cannot be determined (102722). Keep in mind that daily intake of green tea infusions provides only 90-300 mg of EGCG daily. So for a majority of people, green tea infusions are likely safe and unlikely to cause liver injury (95696). Also, plasma levels of EGCG are increased when green tea catechins are taken in the fasting state, suggesting that green tea extract should be taken with food (102722).
Until more is known, advise patients that green tea products, especially those containing green tea extract, might cause liver damage. However, let them know that the risk is uncommon, and it is not clear which products are most likely to cause the adverse effect or which patients are most likely to be affected. Advise patients with liver disease to consult their healthcare provider before taking products with green tea extract and to notify their healthcare provider if they experience symptoms of liver damage, including jaundice, dark urine, sweating, or abdominal pain (102722).
Immunologic ...Orally, matcha tea has resulted in at least one case of anaphylaxis related to green tea proteins. A 9-year-old male experienced systemic redness and hives, nausea, and anaphylaxis 60 minutes after consuming matcha tea-flavored ice cream (107169). The caffeine found in green tea can also cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Orally, the ingestion of the green tea constituent epigallocatechin gallate (EGCG) or a decaffeinated green tea polyphenol mixture may cause mild muscle pain (36398).
There is some concern regarding the association between caffeinated green tea products and osteoporosis. Epidemiological evidence regarding the relationship between caffeinated beverages such as green tea and the risk for osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). 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 of less than 400 mg per day, or about 8 cups of green tea, doesn't seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).
Neurologic/CNS
...Orally, green tea can cause central nervous system stimulation and adverse effects such as headache, anxiety, dizziness, insomnia, fatigue, agitation, tremors, restlessness, and confusion.
These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,53719,90139,102716). The green tea constituent epigallocatechin gallate (EGCG) or decaffeinated green tea may also cause mild dizziness and headache (36398).
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).
Topically, green tea extract (Polyphenon E ointment) may cause headache when applied to the genital area (36442).
Psychiatric ...Green tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, and psychological dependence (11832). 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). Other researchers suggest symptoms such as headache; tiredness and fatigue; decreased energy, alertness, and attentiveness; drowsiness; decreased contentedness; depressed mood; difficulty concentrating; irritability; and lack of clear-headedness are typical of caffeine withdrawal (13738). 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).
Pulmonary/Respiratory ...A case of granulomatous alveolitis with lymph follicles has been reported for a 67-year-old female who used green tea infusions to wash her nasal cavities for 15 years (54088). Her symptoms disappeared 2 months after stopping this practice and following an undetermined course of corticosteroids. In a case report, hypersensitivity pneumonitis was associated with inhalation of catechin-rich green tea extracts (54025). Occupational exposure to green tea dust can cause sensitization, which may include nasal and asthmatic symptoms (11365).
Renal ...There are two cases of hypokalemia associated with drinking approximately 8 cups daily of green tea in an elderly couple of Asian descent. The hypokalemia improved after reducing their intake by 50%. It is possible that this was related to the caffeine in the green tea (98418).
Other ...Orally, intake of a specific green tea extract product (Polyphenon E) may cause weight gain (90139).
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, 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, riboflavin is generally well tolerated.
Most Common Adverse Effects:
Orally: Dose-related nausea and urine discoloration.
Gastrointestinal ...Orally, riboflavin has been associated with rare diarrhea and dose-related nausea (1398,71483). In one clinical study, one subject out of 28 reported having diarrhea two weeks after starting riboflavin 400 mg daily (1398).
Genitourinary ...Orally, high doses of riboflavin can cause bright yellow urine. Furthermore, in one clinical study, one subject out of 28 reported polyuria two weeks after starting riboflavin 400 mg daily (1398,3094).
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 and parenterally, thiamine is generally well tolerated.
Serious Adverse Effects (Rare):
Parenterally: Hypersensitivity reactions including angioedema and anaphylaxis.
Immunologic
...Orally, thiamine might rarely cause dermatitis and other allergic reactions.
Parenterally, thiamine can cause anaphylactoid and hypersensitivity reactions, but this is also rare (<0.1%). Reported symptoms and events include feelings of warmth, tingling, pruritus, urticaria, tightness of the throat, cyanosis, respiratory distress, gastrointestinal bleeding, pulmonary edema, angioedema, hypotension, and death (15,35585,105445).
In one case report, a 46-year-old female presented with systemic allergic dermatitis after applying a specific product (Inzitan, containing lidocaine, dexamethasone, cyanocobalamin and thiamine) topically by iontophoresis; the allergic reaction was attributed to thiamine (91170).
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).
