Each capsule contains: Niacin (as inositol niacinate) 20 mg • Chromium (as chromium niacinate) 100 mcg • Gymnema leaf (gymnema sylvestre, containing 75% gymnemic acid) 150 mg • Bitter Melon fruit 40:1 extract (momordica charantia) 50 mg • Jambolan seed 16:1 extract (syzgium cumini) 50 mg • Vanadium (as vanadyl sulfate) 950 mcg. Other Ingredients: Rice Flour, Vegetable Polysaccharide Capsule.
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Below is general information about the effectiveness of the known ingredients contained in the product Chromium Forte. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Chromium Forte. 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 the fruit is used orally and appropriately, short-term. Powdered bitter melon fruit 0.5-12 grams daily for up to 4 months has been used (92126,100631,100632,109583). Extracts of bitter melon fruit have also been used safely for up to 3 months (36,15566,106408). There is insufficient reliable information available about long-term use of bitter melon or the safety of bitter melon when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Animal research shows that two proteins isolated from the raw fruit of bitter melon possess abortifacient properties (3724,35719,35722,35728). Also, one animal study shows that bitter melon juice significantly reduces the fertility rate of mice (35728). However, these effects of bitter melon have not been assessed in humans.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Chromium has been safely used in doses up to 1000 mcg daily for up to 6 months (1934,5039,5040,6858,6859,6860,6861,6862,6867,6868)(7135,7137,10309,13053,14325,14440,17224,90057,90061)(90063,94234,95095,95096,95097,98687); however, most of these studies have used chromium doses in a range of 150-600 mcg. The Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, long-term. Chromium has been safely used in a small number of studies at doses of 200-1000 mcg daily for up to 2 years (7060,7135,42618,42628,42666,110605,110607,110609). However, the Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts not exceeding the daily adequate intake (AI) levels by age: 0-6 months, 0.
2 mcg; 7-12 months, 5.5 mcg; 1-3 years, 11 mcg; 4-8 years, 15 mcg; males 9-13 years, 25 mcg; males 14-18 years, 35 mcg; females 9-13 years, 21 mcg; females 14-18 years, 24 mcg (7135). POSSIBLY SAFE...when used orally and appropriately in amounts exceeding AI levels. Chromium 400 mcg daily has been used safely for up to 6 weeks (42680).
PREGNANCY: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for pregnancy is 28 mcg daily for those 14-18 years of age and 30 mcg daily for those 19-50 years of age (7135).
PREGNANCY: POSSIBLY SAFE
when used orally in amounts exceeding the adequate intake (AI) levels.
There is some evidence that patients with gestational diabetes can safely use chromium in doses of 4-8 mcg/kg (1953); however, patients should not take chromium supplements during pregnancy without medical supervision.
LACTATION: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for lactation is 44 mcg daily for those 14-18 years of age and 45 mcg daily for those 19-50 years of age (7135). Chromium supplements do not seem to increase normal chromium concentration in human breast milk (1937). There is insufficient reliable information available about the safety of chromium when used in higher amounts while breast-feeding.
POSSIBLY SAFE ...when used orally and appropriately. Gymnema leaf extract has been used safely in doses of 200 mg twice daily for up to 20 months or 300 mg twice daily for 12 weeks (45,46,42604,105346).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Jambolan tea prepared from 2 grams of jambolan leaves per liter of water has been consumed in place of water with apparent safety in clinical research (13092).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when niacin is taken in food or as a supplement in amounts below the tolerable upper intake level (UL) of 30 mg daily for adults 18 years of age and 35 mg daily for adults 19 years and older (6243). ...when prescription products are used orally and appropriately in doses of up to 2 grams daily (12033). CHILDREN:
LIKELY SAFE ...when used orally in amounts that do not exceed the tolerable upper intake level (UL). The ULs of niacin for children are: 1-3 years of age, 10 mg daily; 4-8 years of age, 15 mg daily; 9-13 years of age, 20 mg daily; 14-18 years of age, 30 mg daily (6243).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the tolerable upper intake level (UL).
The UL of niacin during pregnancy and lactation is 30 mg daily for 14-18 years of age and 35 mg daily for 19 years and older (6243).
There is insufficient reliable information available about the safety of larger oral doses of niacin during pregnancy or lactation; avoid using.
LIKELY SAFE ...when used orally and appropriately. Vanadium is safe when taken in amounts below the tolerable upper intake level (UL) of 1.8 mg daily (7135).
POSSIBLY UNSAFE ...when used orally in high doses. Taking more than the tolerable upper intake level (UL) of 1.8 mg daily can increase the risk of gastrointestinal side effects and theoretically, kidney toxicity (7135). In some cases, patients with diabetes have used very high doses (100 mg daily) safely for up to 4 weeks (3055,3056,3057). However, there is concern that prolonged use of high doses might cause serious side effects including kidney damage (7135). Doses of 22.5 mg daily for five months can cause cramps and diarrhea (3012).
CHILDREN: LIKELY SAFE
when used orally in amounts found in foods (7135).
There is insufficient reliable information available about the safety of vanadium when used in amounts greater than those typically found in foods.
PREGNANCY: LIKELY SAFE
when used orally in amounts found in foods (7135).
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Epidemiological research has found that increased urinary levels of vanadium are associated with an increased risk of both term and preterm premature rupture of membranes (PROM). When comparing tertiles of urinary vanadium levels, patients in the middle tertile had 1.66 times the risk of term PROM when compared with the lowest tertile, and those in the highest tertile had 3.75 times the risk. For preterm PROM (rupture prior to 37 weeks' gestation), those in the highest tertile had an 8.14 times increased risk when compared with those in the lowest tertile (99052). Epidemiological research has also found that higher prenatal serum levels of vanadium are associated with impaired fetal growth, particularly in male newborns. The risk appears greatest with vanadium exposure in the second trimester (102096).
LACTATION: LIKELY SAFE
when used orally in amounts found in foods (7135).
There is insufficient reliable information available about the safety of vanadium when used in amounts greater than those typically found in foods; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Chromium Forte. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Taking bitter melon with antidiabetes drugs might increase the risk of hypoglycemia.
 Details
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Theoretically, bitter melon might increase levels of P-glycoprotein substrates.
Details
Bitter melon might inhibit the p-glycoprotein (P-gp) intestinal pump and increase intracellular levels of P-gp substrates. In vitro research in intestinal cells shows that 1-monopalmitin, a constituent of bitter melon, increases levels of daunomycin, a P-gp substrate (97509). Additionally, drinking bitter melon juice has been associated with a case of acute pancreatitis in a patient who had been taking pazopanib, a P-gp substrate, for 8 years. Researchers theorize that inhibition of P-gp led to increased levels of pazopanib, resulting in pazopanib-induced pancreatitis (109581).
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Theoretically, bitter melon might increase levels of pazopanib, potentially increasing the risk of adverse effects.
Details
In one case, a 65-year-old patient taking pazopanib for 8 years for renal cell carcinoma experienced signs and symptoms consistent with acute pancreatitis 4 days after drinking bitter melon juice at a dose of 100-150 mL daily. The patient's symptoms, amylase levels, and lipase levels improved upon discontinuation of bitter melon and pazopanib. Pazopanib treatment was re-initiated with no further evidence of pancreatitis. Researchers theorize that inhibition of P-glycoprotein by bitter melon led to increased levels of pazopanib, a P-glycoprotein substrate, resulting in pazopanib-induced pancreatitis (109581).
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Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
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Theoretically, aspirin might increase chromium absorption.
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Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood (21055).
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Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
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Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
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Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone (16012). Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.
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NSAIDs might increase chromium levels in the body.
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Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention (7135).
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Theoretically, taking gymnema with antidiabetes drugs might increase the risk of hypoglycemia.
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Gymnema reduces blood glucose levels in some human and animal research. In human studies, it has been shown to enhance the blood glucose lowering effects of hypoglycemic drugs (45,46,92119,92121,92123). However, other research in adults with prediabetes or metabolic syndrome suggests that gymnema does not reduce fasting levels of blood glucose (96235,105346). Until more is known, monitor blood glucose levels closely.
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Theoretically, gymnema might increase levels of drugs metabolized by CYP1A2.
Details
Animal and in vitro research shows that gymnema can inhibit the CYP1A2 enzyme (96236,96237,96238). In one animal study, oral administration of gymnema for 7 days increased the plasma concentrations of phenacetin, a CYP1A2 substrate, by about 1.4-fold and reduced the clearance of phenacetin by about 29% (96237).
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Theoretically, gymnema might increase or decrease levels of drugs metabolized by CYP2C9.
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Theoretically, gymnema might increase levels of drugs metabolized by CYP3A4.
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One in vitro study using rat liver microsomes shows that gymnema can modestly inhibit the CYP3A4 enzyme (96238). However, other in vitro research using human liver microsomes shows that gymnema does not affect CYP3A4 activity (96236). Animal research also shows that gymnema does not alter the function of CYP3A4. In one study in rats, oral administration of gymnema for 7 days did not alter the clearance of amlodipine, a CYP3A4 substrate (96237).
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Theoretically, taking gymnema with phenacetin might increase the levels of phenacetin.
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Theoretically, taking gymnema with tolbutamide might the decrease levels of tolbutamide.
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Animal research shows that gymnema, administered orally for 7 days, increases the clearance of tolbutamide by 2.4-fold when compared to control (96237).
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Animal research shows that jambolan seed and bark extracts can lower blood glucose levels (13599,13600,13601,104282). Theoretically, jambolan might have additive effects when used with antidiabetes drugs. This might increase the risk of hypoglycemia in some patients. Monitor blood glucose levels closely.
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There is some in vitro evidence that jambolan can inhibit CYP2C9 (99067). Theoretically, concomitant use of jambolan with CYP2C9 substrates may increase levels of drugs metabolized by CYP2C9.
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Animal research shows that jambolan seed extract reduces the sitagliptin maximum plasma concentration and area under the curve by 39% and 22%, respectively. However, blood glucose levels were actually reduced to a greater extent in mice taking jambolan and sitagliptin in combination when compared with either product taken alone (104282). Theoretically, jambolan seed extract might alter the clearance of sitagliptin, although this may not alter the clinical effects of sitagliptin.
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Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.
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Alcohol can exacerbate the flushing and pruritus associated with niacin (4458,11689). Large doses of niacin might also exacerbate liver dysfunction associated with chronic alcohol use. A case report describes delirium and lactic acidosis in a patient taking niacin 3 grams daily who ingested 1 liter of wine (14510). Advise patients to avoid large amounts of alcohol while taking niacin.
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Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol.
Details
Large doses of niacin can reduce urinary excretion of uric acid, potentially resulting in hyperuricemia (4860,4863,12033). Doses of uricosurics such as allopurinol might need to be increased to maintain control of gout in patients who start taking niacin (4458). People who have frequent attacks of gout despite uricosuric therapy should avoid niacin (4863).
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Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.
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Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs.
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Niacin impairs glucose tolerance in a dose-dependent manner, probably by causing or aggravating insulin resistance and increasing hepatic production of glucose (4860,4863,11692,11693). In diabetes patients, niacin 4.5 grams daily for 5 weeks can increase plasma glucose by an average of 16% and glycated hemoglobin (HbA1c) by 21% (4860). However, lower doses of 1.5 grams daily or less appear to have minimal effects on blood glucose (12033). In some patients, glucose levels increase when niacin is started, but then return to baseline when a stable dose is reached (12033,93344). Up to 35% of patients with diabetes may need adjustments in hypoglycemic therapy when niacin is added (4458,4860,4863,11689,12033).
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Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs.
Details
The vasodilating effects of niacin can cause hypotension (4863,12033,93341). Furthermore, some clinical evidence suggests that a one-hour infusion of niacin can reduce systolic, diastolic, and mean blood pressure in hypertensive patients. This effect is not observed in normotensive patients (25917).
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Large doses of aspirin might alter the clearance of niacin.
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Aspirin is often used with niacin to reduce niacin-induced flushing (4458,11689). Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal (4458,4852,4853,11689). Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45% (14524). This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg (11689,14524).
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Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction.
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In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30% (14511).
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Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients.
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Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
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Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses (4863,11689,11691,25929,25930,25931,113553). Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin (11691,25930,25931,93342,113553).
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Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients.
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Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins (14508,25918). However, a significantly increased risk of myopathy has not been demonstrated in clinical trials, including those using an FDA-approved combination of lovastatin and niacin (Advicor) (7388,11689,12033,14509).
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Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid.
Details
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia (4863,12033). Doses of uricosurics such as probenecid might need to be increased to maintain control of gout in patients who start taking niacin (4458). People who have frequent attacks of gout despite uricosuric therapy should avoid niacin (4863).
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Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone.
Details
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia (4863,12033). Doses of uricosurics such as sulfinpyrazone might need to be increased to maintain control of gout in patients who start taking niacin (4458). People who have frequent attacks of gout despite uricosuric therapy should avoid niacin (4863).
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Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones.
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Clinical research and case reports suggests that taking niacin can reduce serum levels of thyroxine-binding globulin by up to 25% and moderately reduce levels of thyroxine (T4) (25916,25925,25926,25928). Patients taking thyroid hormone for hypothyroidism might need dose adjustments when using niacin.
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Theoretically, concomitant use of niacin and transdermal nicotine might increase the risk of flushing and dizziness.
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Theoretically, vanadium might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
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In vitro research shows that the sodium orthovanadate form of vanadium prolongs clotting time, likely through inhibition of thrombin and factor Xa (3054).
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Theoretically, vanadium might increase the risk of hypoglycemia when taken with antidiabetes drugs.
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Below is general information about the adverse effects of the known ingredients contained in the product Chromium Forte. 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, bitter melon is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, constipation, diarrhea, dizziness, fatigue, flatulence, headache, heartburn, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Hypoglycemic coma and seizures (in children).
Dermatologic ...In one clinical study, two out of 31 patients taking bitter melon 4 grams daily experienced skin rash. Reports of skin rashes did not occur for patients taking bitter melon 2 grams daily (92126).
Endocrine ...Two cases of hypoglycemic coma have occurred in children after administration of a bitter melon tea (15568).
Gastrointestinal ...The most common adverse effects associated with bitter melon in clinical studies are gastrointestinal, such as heartburn, anorexia, nausea, vomiting, diarrhea, constipation, flatulence, and abdominal discomfort (92126,100632,100633,106408). In one study, these events occurred in about 3% to 16% of patients taking bitter melon (92126).
Neurologic/CNS ...Headaches, dizziness, and fatigue have been reported after the ingestion of bitter melon (15568,92126,100633,112372). In one clinical study, about 5% of patients taking bitter melon 2-4 grams daily reported dizziness (92126). Two cases of seizures have occurred in children after administration of a bitter melon tea (15568).
Renal ...In one case report, a 60-year-old female was diagnosed with acute interstitial nephritis after a gradual decline in renal function over 9 months. The patient later admitted to taking bitter melon extract 600 mg daily for 3 months followed by 1200 mg daily for 4 months for diabetes. Upon discontinuation of bitter melon and treatment with prednisolone, serum creatinine levels returned to baseline within 3 months (109582).
General
...Orally, chromium is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal irritation, headaches, insomnia, irritability, mood changes.
Serious Adverse Effects (Rare):
Orally: Rare cases of kidney and liver damage, rhabdomyolysis, and thrombocytopenia have been reported.
Dermatologic
...Orally, chromium-containing supplements may cause acute generalized exanthematous pustulosis (42561), skin rashes (42679), and urticaria (17224).
Also, chromium picolinate or chromium chloride may cause systemic contact dermatitis when taken orally, especially in patients with contact allergy to chromium (6624,90058). In one clinical study, a patient taking chromium nicotinate 50 mcg daily reported itchy palms that improved after the intervention was discontinued. It is unclear of this effect was due to the chromium or another factor (95096).
Topically, hexavalent chromium, which can be present in some cement, leather products, or contaminated soil, may cause allergic contact dermatitis (42645,42789,90060,90064,110606).
A case of lichen planus has been reported for a patient following long-term occupational exposure to chromium (42688).
Endocrine ...Orally, cases of hypoglycemia have been reported for patients taking chromium picolinate 200-1000 mcg daily alone or 200-300 mcg two or three times weekly in combination with insulin (42672,42783). Chromium picolinate has also been associated with weight gain in young females who do not exercise and in those following a weight-lifting program (1938).
Gastrointestinal
...Orally, chromium in the form of chromium picolinate, chromium polynicotinate, chromium-containing brewer's yeast, or chromium-containing milk powder may cause nausea, vomiting, diarrhea, decreased appetite, constipation, flatulence, or gastrointestinal upset (14325,42594,42607,42622,42643,42679).
Long-term exposure to heavy metals, including chromium, has been associated with increased risk of gallbladder disease and cancer (42682,42704).
Genitourinary ...Orally, chromium polynicotinate has been associated with disrupted menstrual cycles in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Hematologic ...Anemia, hemolysis, and thrombocytopenia were reported in a 33 year-old female taking chromium picolinate 1200-2400 mcg daily for 4-5 months (554). The patient received supportive care, blood product transfusions, and hemodialysis and was stabilized and discharged a few days later. Lab values were normal at a one-year follow-up.
Hepatic ...Liver damage has been reported for a 33-year-old female taking chromium picolinate 1200 mcg daily for 4-5 months (554). Also, acute hepatitis has been reported in a patient taking chromium polynicotinate 200 mcg daily for 5 months (9141). Symptoms resolved when the product was discontinued. Two cases of hepatotoxicity have been reported in patients who took a specific combination product (Hydroxycut), which also contained chromium polynicotinate in addition to several herbs (13037).
Musculoskeletal ...Acute rhabdomyolysis has been reported for a previously healthy 24-year-old female who ingested chromium picolinate 1200 mcg over a 48-hour time period (42786). Also, chromium polynicotinate has been associated with leg pain and paresthesia in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Neurologic/CNS ...Orally, chromium picolinate may cause headache, paresthesia, insomnia, dizziness, and vertigo (6860,10309,14325,42594). Vague cognitive symptoms, slowed thought processes, and difficulty driving occurred on three separate occasions in a healthy 35-year-old male after oral intake of chromium picolinate 200-400 mcg (42751). Transient increases in dreaming have been reported in three patients with dysthymia treated with chromium picolinate in combination with sertraline (2659). A specific combination product (Hydroxycut) containing chromium, caffeine, and ephedra has been associated with seizures (10307). But the most likely causative agent in this case is ephedra.
Psychiatric ...Orally, chromium picolinate has been associated with irritability and mood changes in patients taking the supplement to lose weight, while chromium polynicotinate has been associated with agitation and mood changes in patients taking the supplement to prevent weight gain during smoking cessation (6860,42643).
Renal
...Orally, chromium picolinate has been associated with at least one report of chronic interstitial nephritis and two reports of acute tubular necrosis (554,1951,14312).
Laboratory evidence suggests that chromium does not cause kidney tissue damage even after long-term, high-dose exposure (7135); however, patient- or product-specific factors could potentially increase the risk of chromium-related kidney damage. More evidence is needed to determine what role, if any, chromium has in potentially causing kidney damage.
Intravenously, chromium is associated with decreased glomerular filtration rate (GFR) in children who receive long-term chromium-containing total parenteral nutrition - TPN (11787).
Topically, burns caused by chromic acid, a hexavalent form of chromium, have been associated with acute chromium poisoning with acute renal failure (42699). Early excision of affected skin and dialysis are performed to prevent systemic toxicity.
Other ...Another form of chromium, called hexavalent chromium, is unsafe. This type of chromium is a by-product of some manufacturing processes. Chronic exposure can cause liver, kidney, or cardiac failure, pulmonary complications, anemia, and hemolysis (9141,11786,42572,42573,42699). Occupational inhalation of hexavalent chromium can cause ulceration of the nasal mucosa and perforation of the nasal septum, and has been associated with pneumoconiosis, allergic asthma, cough, shortness of breath, wheezing, and increased susceptibility to respiratory tract cancer and even stomach and germ cell cancers (42572,42573,42601,42610,42636,42667,42648,42601,42788,90056,90066). Although rare, cases of interstitial pneumonia associated with chromium inhalation have been reported. Symptoms resolved with corticosteroid treatment (42614).
General ...Orally, gymnema seems to be well tolerated.
Hepatic ...A case of drug-induced hepatitis characterized by weakness, fatigue, jaundice, and elevated liver enzymes, has been reported for a patient who consumed gymnema tea three times daily for 10 days. The patient was administered prednisone 60 mg once daily and was eventually tapered off prednisone and discharged. Laboratory values normalized after 6 months (95005). A case of hepatitis-associated aplastic anemia characterized by jaundice, elevated liver function tests, and pancytopenia has been reported for a patient who consumed gymnema 2 grams twice daily for at least a month. Treatment with ursodeoxycholic acid for 8 weeks led to resolution of cholestatic hepatitis; however, the pancytopenia was not responsive to treatment with immunosuppressive drugs and the patient died 5 months after presentation (110021). The exact reason for these adverse effects is not clear; they may have been idiosyncratic.
General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, niacin is well tolerated in the amounts found in foods.
It is also generally well tolerated in prescription doses when monitored by a healthcare provider.
Most Common Adverse Effects:
Orally: Flushing, gastrointestinal complaints (abdominal pain, constipation, diarrhea, heartburn, nausea, vomiting), and elevated liver enzymes.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity, myopathy, thrombocytopenia, and vision changes.
Cardiovascular
...Orally, flushing is a common dose-related adverse reaction to niacin.
A large meta-analysis of clinical studies shows that up to 70% of patients may experience flushing (96211). Although flushing can occur with doses of niacin as low as 30 mg daily, it is more common with the larger doses used for treatment of dyslipidemia. The flushing reaction is due to prostaglandin-induced blood vessel dilation and can also include symptoms of burning, tingling, urticaria, erythema, pain, and itching of the face, arms, and chest. There may also be increased intracranial blood flow and headache (4889,26089,93341,104933). Onset is highly variable and ranges from within 30 minutes to as long as 6 weeks after the initial dose (6243). Flushing can be minimized via various strategies, including taking doses with meals, slow dose titration, using extended release formulations, pretreating with non-steroidal anti-inflammatory drugs, taking regular-release niacin with meals, or taking the sustained-release product at bedtime (4852,4853,4854,4857,4858,25922,26073,26084). Flushing often diminishes with continued use but can recur when niacin is restarted after missed doses (4863,6243,26081). The vasodilating effects of niacin can also cause hypotension, dizziness, tachycardia, arrhythmias, syncope, and vasovagal attacks, especially in patients who are already taking antihypertensive drugs (4863,12033,93341,110494).
High doses of niacin can raise homocysteine levels. A 17% increase has been reported with 1 gram daily and a 55% increased has been reported with 3 grams daily. Elevated homocysteine levels are an independent risk factor for cardiovascular disease (490); however, the clinical significance of this effect is unknown. A large-scale study (AIM-HIGH) found that patients receiving extended-release niacin (Niaspan) 1500-2000 mg daily with a statin had an over two-fold increased risk of ischemic stroke (1.6%) when compared with those receiving only simvastatin (0.7%). However, when the risk was adjusted for confounding factors, niacin was not found to be associated with increased stroke risk (17627,93354). A meta-analysis of three clinical trials conducted in approximately 29,000 patients showed a higher risk of mortality in patients taking niacin in addition to a statin when compared with a statin alone. However, with a p-value of 0.05 and confidence interval including 1, the validity of this finding remains unclear (97308).
Endocrine
...Orally, niacin can impair glucose tolerance in a dose-dependent manner.
Dosages of 3-4 grams daily appear to increase blood glucose in patients with or without diabetes, while dosages of 1.5 grams daily or less have minimal effects (12033). Niacin is thought to impair glucose tolerance by increasing insulin resistance or increasing hepatic output of glucose (4863,11692,11693). In patients with diabetes, niacin 4.5 grams daily for 5 weeks has been associated with an average 16% increase in plasma glucose and 21% increase in glycated hemoglobin (HbA1C) (4860). Up to 35% of patients with diabetes may need to increase the dose or number of hypoglycemic agents when niacin is started (4458,4860,4863,11689,12033). Occasionally, severe hyperglycemia requiring hospitalization can occur (11693). In patients with impaired fasting glucose levels, niacin may also increase fasting blood glucose, and adding colesevelam might attenuate this effect (93343).
Although patients without diabetes seem to only experience small and clinically insignificant increases in glucose (4458), niacin might increase their risk of developing diabetes. A meta-analysis of clinical research involving over 26,000 patients shows that using niacin over 5 years is associated with increased prevalence of new onset type 2 diabetes at a rate of 1 additional case of diabetes for every 43 patients treated with niacin (96207). This finding is limited because the individual trials were not designed to assess diabetes risk and the analysis could not be adjusted for confounding factors like obesity. One small clinical study shows that taking extended-release niacin with ezetimibe/simvastatin does not increase the risk of a new diagnosis of diabetes or need for antidiabetic medication when compared with ezetimibe/simvastatin alone after 16 months (93344). This may indicate that the increased risk of developing diabetes is associated with niacin use for more than 16 months.
Niacin therapy has also been linked with hypothyroidism and its associated alterations in thyroid hormone and binding globulin tests (such as decreased total serum thyroxine, increased triiodothyronine, decreased thyroxine-binding globulin levels, and increased triiodothyronine uptake) (25916,25925,25926,25928).
Gastrointestinal ...Orally, large doses of niacin can cause gastrointestinal disturbances including nausea, vomiting, bloating, heartburn, abdominal pain, anorexia, diarrhea, constipation, and activation of peptic ulcers (4458,4863,12033,26083,93341,96211). These effects may be reduced by taking the drug with meals or antacid, and usually disappear within two weeks of continued therapy (4851,26094). Gastrointestinal effects may be more common with time-release preparations of niacin (11691).
Hematologic ...Orally, sustained-release niacin has been associated with cases of reversible coagulopathy, mild eosinophilia, and decreased platelet counts (4818,25915,26097,93340). Also, there have been reports of patients who developed leukopenia while taking niacin for the treatment of hypercholesterolemia (25916).
Hepatic ...Orally, niacin is associated with elevated liver function tests and jaundice, especially with doses of 3 grams/day or more, and when doses are rapidly increased (4458,4863,6243). The risk of hepatotoxicity appears to be higher with slow-release and extended-release products (4855,4856,4863,6243,11691,12026,12033,93342). Niacin should be discontinued if liver function tests rise to three times the upper limit of normal (4863). There are rare cases of severe hepatotoxicity with fulminant hepatitis and encephalopathy due to niacin (4863,6243,11691). In one case, a patient taking extended-release niacin 2500 mg daily for 15 years developed decompensating cirrhosis and was diagnosed with chronic, toxic, metabolic liver injury. Despite medical intervention, the patient died (113553). Also, there is at least one case of niacin-induced coagulopathy resulting from liver injury without liver enzyme changes (93340).
Musculoskeletal ...Orally, niacin has been associated with elevated creatine kinase levels (4818,4888). Also, several cases of niacin-induced myopathy have been reported (26100,26111). Concomitant administration of niacin and HMG-CoA reductase inhibitors may increase the risk of myopathy and rhabdomyolysis (14508,25918,26111); patients should be monitored closely.
Neurologic/CNS ...Orally, high-dose niacin has been associated with cases of neuropsychiatric adverse events such as extreme pain and psychosis. Two 65-year-old males taking niacin orally for 5 months for the treatment of dyslipidemias developed severe dental and gingival pain. The pain was relieved by the discontinuation of niacin. The pain was thought to be due to inflammation and pain referral to the teeth (4862). In one case report, a 52-year-old male with no history of psychiatric illness who initially complained of hot flushes when taking niacin 500 mg daily, presented with an acute psychotic episode involving mania after niacin was increased to 1000 mg daily (93350).
Ocular/Otic ...Orally, chronic use of large amounts of niacin has been associated with dry eyes, toxic amblyopia, blurred vision, eyelid swelling, eyelid discoloration, loss of eyebrows and eyelashes, proptosis, keratitis, macular edema, and cystic maculopathy, which appear to be dose-dependent and reversible (4863,6243,26112).
General
...Orally, vanadium is well tolerated when taken in amounts below the tolerable upper intake level (UL) of 1.
8 mg daily. Higher doses may cause adverse effects.
Most Common Adverse Effects:
Orally: Gastrointestinal adverse effects, including abdominal discomfort, diarrhea, flatulence, and nausea, when taken at doses above the UL.
Serious Adverse Effects (Rare):
Orally: Kidney damage, when taken long-term at high doses.
Topically: Contact dermatitis and other allergic reactions in sensitive individuals.
Cardiovascular ...Higher levels of vanadium in the body have been associated with a greater risk for hypertension (107923). However, it is unclear if oral supplementation with vanadium causes elevated blood pressure.
Dermatologic ...Allergic reactions to vanadium metal have been reported (99051,102095). A 68-year-old female developed an itchy, erythematous rash, ocular pruritus, and a positive skin test to vanadium after implantation of a vanadium-containing knee prosthesis (99051). Contact dermatitis, presenting as pruritic eczema of the hand, and a positive skin patch test to vanadium was reported in a 39-year-old male who worked with vanadium-containing tools (102095).
Endocrine ...In some cases, patients with diabetes have used very high doses (100 mg daily) safely for up to 4 weeks (3055,3056,3057). However, high body levels of vanadium have been associated with an increased incidence malnutrition-related diabetes mellitus (3020).
Gastrointestinal ...Orally, vanadium most commonly causes mild gastrointestinal upset (7135). There is concern that taking doses exceeding the tolerable upper intake level (UL) of 1.8 mg per day can increase the risk of gastrointestinal side effects and possibly lead to more severe toxicity. At higher doses, vanadium frequently causes gastrointestinal effects including abdominal discomfort, diarrhea, nausea, and flatulence (3012,3055,3056,3057,12557,12558). Doses of 22.5 mg daily can also cause cramps (3012). Vanadium has also been associated with green discoloration of the tongue, which is unrelated to dose (7135).
Immunologic
...Allergic reactions to vanadium metal have been reported (99051,102095).
A 68-year-old female developed an itchy, erythematous rash, ocular pruritus, and a positive skin test to vanadium after implantation of a vanadium-containing knee prosthesis (99051). Contact dermatitis, presenting as pruritic eczema of the hand, and a positive skin patch test to vanadium was reported in a 39-year-old male who worked with vanadium-containing tools (102095).
Higher levels of vanadium in the body have been associated with a weakened immune system in children, as measured by reductions in CD3+ and CD4+ cell counts (107924). However, it is unclear if oral supplementation with vanadium causes a weakened immune system or increases the risk of infection.
Neurologic/CNS ...Orally, vanadium has been rarely associated with fatigue, lethargy, and focal neurological lesions, which are unrelated to dose (7135).
Pulmonary/Respiratory ...Severe and chronic respiratory tract disorders have been reported from occupational exposure to vanadium dusts (17).
Renal ...In some cases, patients with diabetes have used very high doses (100 mg daily) of vanadium safely for up to 4 weeks (3055,3056,3057). However, there is concern based on animal research that prolonged use of high doses might cause serious side effects including kidney damage (7135). High body levels of vanadium have also been associated with an increased incidence of kidney stones, distal renal tubular acidosis, hypokalemic periodic paralysis, and sudden unexplained nocturnal death (3020).
