Four tablets contain: Niacin (as Nicotinic Acid ) 100 mg • Evodia Rutaecarpa fruit extract 100 mg • Gynostemma leaf, stem extract 100 mg • Bioperine brand Black Pepper fruit extract 5 mg • Gypentoside 98 mg • Ornithine Blend: Ornithine Alpha Ketoglutarate 550 mg • Arginine Blend 3000 mg: L-Arginine Hydrochloride , Arginine Alpha Ketoglutarate . Other Ingredients: Dicalcium Phosphate, Microcrystalline Cellulose, Hydroxypropyl Cellulose, Croscarmellose Sodium, Stearic Acid, Silicon Dioxide.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Nitric Oxide Booster. 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
There is insufficient reliable information available about the effectiveness of evodia.
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 Nitric Oxide Booster. 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 for up to 3 years (5311,18113,30784,30785,30778). When used topically for up to 8 weeks (111125). ...when used intravenously and appropriately (5308,5309,5310,5311,5312,5313).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Black pepper has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when black pepper oil is applied topically. Black pepper oil is nonirritating to the skin and is generally well tolerated (11). ...when black pepper oil is inhaled through the nose or as a vapor through the mouth, short-term. Black pepper oil as a vapor or as an olfactory stimulant has been used with apparent safety in clinical studies for up to 3 days and 30 days, respectively (29159,29160,29161,90502). There is insufficient reliable information available about the safety of black pepper when used orally in medicinal amounts.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
CHILDREN: POSSIBLY UNSAFE
when used orally in large amounts.
Fatal cases of pepper aspiration have been reported in some patients (5619,5620). There is insufficient reliable information available about the safety of topical pepper oil when used in children.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
PREGNANCY: LIKELY UNSAFE
when used orally in large amounts.
Black pepper might have abortifacient effects (11,19); contraindicated. There is insufficient reliable information available about the safety of topical pepper when used during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
There is insufficient reliable information available about the safety of black pepper when used in medicinal amounts during breast-feeding.
There is insufficient reliable information available about the safety of evodia when used orally. In animal studies, evodia has induced QT interval prolongation and Torsade de pointes (97035). It is not clear what dose, if any, is required to produce a similar effect in humans.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Active constituents in evodia have uterine stimulant activity in animal models. Evodia might also decrease litter size in animal models (15229). Theoretically, taking evodia during pregnancy might adversely affect pregnancy outcome.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Tea containing jiaogulan 3 grams has been taken twice daily with apparent safety for up to 3 months (94054,95519,95520). Jiaogulan extract has been used with apparent safety at a dose of up to 450 mg daily for up to 4 months (7069,7070,57056,94058,100961,106651). An in vitro study suggests that low, medium, and high doses of jiaogulan polysaccharides are safe in a model of the human intestinal epithelial barrier (110700).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Ginsenoside Rb1, which is identical to the jiaogulan constituent gypenoside 3, has teratogenic effects in animal models; avoid using (10447).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. L-arginine has been used safely in clinical studies at doses of up to 24 grams daily for up to 18 months (3331,3460,3595,3596,5531,5532,5533,6028,7815,7816)(8014,8473,13709,31943,91195,91196,91963,99264,99267,110380)(110387). A tolerable upper intake level (UL) for arginine has not been established, but the observed safe level (OSL) of arginine intake established in clinical research is 20 grams (31996). ...when used intravenously and appropriately. Parenteral L-arginine is an FDA-approved prescription product (15). ...when used topically and appropriately. L-arginine appears to be safe when 5 grams is applied as a topical cream twice daily for 2 weeks or when a dentifrice is used at a dose of 1.5% w/w for up to 2 years (14913,96806). ...when inhaled, short-term. L-arginine appears to be safe when inhaled twice daily at a dose of 500 mg for up to 2 weeks (96807).
CHILDREN: POSSIBLY SAFE
when used orally in premature infants and children (8474,32286,96803,97392,110391).
...when used intravenously and appropriately (97392). Parenteral L-arginine is an FDA-approved prescription product (15). ...when used topically, short-term. A dentifrice containing L-arginine appears to be safe when used at a dose of 1.5% w/w for up to 2 years in children at least 3.7 years of age (96806). ...when inhaled, short-term. L-arginine appears to be safe when inhaled twice daily at a dose of 500 mg for up to 2 weeks in children at least 13 years of age (96807).
CHILDREN: POSSIBLY UNSAFE
when used intravenously in high doses.
Parenteral L-arginine is an FDA-approved prescription product (15). However, when higher than recommended doses are used, injection site reactions, hypersensitivity reactions, hematuria, and death have occurred in children (16817).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
L-arginine 12 grams daily for 2 days has been used with apparent safety in pregnancy during the third trimester (11828). L-arginine 3 grams daily has been taken safely during the second and/or third trimesters (31938,110379,110382). ...when used intravenously and appropriately, short-term. Intravenous L-arginine 20-30 grams daily has been used safely in pregnancy for up to 5 days (31847,31933,31961,31978).
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.
POSSIBLY SAFE ...when used orally and appropriately. Ornithine ketoglutarate has been used with apparent safety at a dose of 10-30 grams daily for 3 weeks (2443,67446,67447,67449,67456). ...when used intravenously and appropriately. Ornithine ketoglutarate 350 mg/kg daily, added to total parenteral nutrition, has been used with apparent safety (2445,2446).
CHILDREN: POSSIBLY SAFE
when used intravenously and appropriately.
Ornithine ketoglutarate 15 grams daily, added to total parenteral nutrition, has been used with apparent safety for 5 months (2444).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Nitric Oxide Booster. 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, black pepper might increase the effects and side effects of amoxicillin.
 Details
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin (29269). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
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In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation (29206). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.
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Theoretically, black pepper might increase blood levels of atorvastatin.
Details
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold (104188). This has not been reported in humans.
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Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
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One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects (16833). In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner (103819).
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Theoretically, black pepper might increase the effects and side effects of cyclosporine.
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In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine (29282). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP1A1.
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In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP1A1 (29213). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2B1.
Details
In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP2B1 (29332). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
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Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
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Black pepper is thought to have diuretic properties (11).
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Black pepper might increase blood levels of nevirapine.
Details
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study (29209).
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Theoretically, black pepper might increase levels of P-glycoprotein substrates.
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Theoretically, black pepper might increase the sedative effects of pentobarbital.
Details
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time (29214).
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Black pepper might increase blood levels of phenytoin.
Details
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin (537,14442). Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin (14375). Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper (14442).
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Black pepper might increase blood levels of propranolol.
Details
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol (538).
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Black pepper might increase blood levels of rifampin.
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Black pepper might increase blood levels of theophylline.
Details
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline (538).
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Theoretically, taking evodia with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.
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Theoretically, evodia might decrease the levels and clinical effects of caffeine.
Details
In animal models, evodia extract decreases caffeine levels by up to 71%. Evodia extract induces hepatic cytochrome P450 1A2 (CYP1A2) enzyme, of which caffeine is a substrate (15241).
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Theoretically, evodia might decrease the levels and clinical effects of chlorzoxazone.
Details
Animal research shows that administration of rutaecarpine, a constituent of evodia, with chlorzoxazone reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646%. This interaction is likely due to induction of cytochrome P450 2E1 (CYP2E1) by rutaecarpine (107913).
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Theoretically, drugs that inhibit CYP1A2 might increase the levels and clinical effects of evodia.
Details
The evodia constituent rutaecarpine is metabolized by CYP1A2 (15253).
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Evodia might reduce the levels and clinical effects of CYP1A2 substrates through induction of CYP1A2.
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Theoretically, evodia might reduce the levels and clinical effects of CYP2E1 substrates through induction of CYP2E1.
Details
Animal research suggests that rutaecarpine, a constituent of evodia, induces CYP2E1 activity. In rats, rutaecarpine increases markers of CYP2E1 activity, and administration of rutaecarpine with chlorzoxazone, a known CYP2E1 substrate, reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646% (107913).
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Theoretically, taking CYP3A4 inducers might decrease the levels and clinical effects of evodia.
Details
Animal research shows that concomitant administration of dexamethasone, a known CYP3A4 inducer, with the alkaloid constituents of evodia significantly reduces the area under the curve (AUC), maximum concentration (Cmax), and half-life of these constituents (107911).
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Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of evodia.
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Animal research shows that concomitant administration of ketoconazole, a known CYP3A4 inhibitor, with the alkaloid constituents of evodia significantly increases the area under the curve (AUC), maximum concentration (Cmax), and half-life of these constituents (107911).
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Theoretically, evodia might increase the levels and clinical effects of CYP3A4 substrates.
Details
In vitro research shows that evodia extract inhibits hepatic CYP3A4 (15236). This effect has not been reported in humans.
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Theoretically, evodia might have an additive effect with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
Details
Evodia has demonstrated dose-dependent activity as a proarrhythmic agent in animal and in vitro studies. Evodia infusion in animals extends the action duration potential and induces prolongation of the QT interval and Torsade de pointes (97035).
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Theoretically, evodia might decrease the levels and clinical effects of theophylline.
Details
The evodia constituent rutaecarpine decreases theophylline levels and half-life by about 70% in animal models (15227). This constituent appears to induce hepatic cytochrome P450 1A2 (CYP1A2) enzyme activity, of which theophylline is a substrate (15227,15230). Rutaecarpine is the primary active constituent of evodia; however, it is not known if the whole crude extract of evodia also causes this interaction.
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Theoretically, jiaogulan might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
In vitro research suggests that jiaogulan has antiplatelet effects (7071).
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Theoretically, jiaogulan might increase the risk of hypoglycemia when taken with antidiabetes drugs.
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Theoretically, jiaogulan might decrease the effectiveness of immunosuppressive therapy.
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Theoretically, concomitant use of L-arginine and ACE inhibitors may increase the risk for hypotension and hyperkalemia.
Details
Combining L-arginine with some antihypertensive drugs, especially ACE inhibitors, seems to have additive vasodilating and blood pressure-lowering effects (7822,20192,31854,31916). Furthermore, ACE inhibitors can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients (32213,32218). Theoretically, concomitant use of ACE inhibitors with L-arginine may increases the risk of hyperkalemia.
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Theoretically, concomitant use of L-arginine and ARBs may increase the risk of hypotension and hyperkalemia.
Details
L-arginine increases nitric oxide, which causes vasodilation (7822). Combining L-arginine with ARBs seems to increase L-arginine-induced vasodilation (31854). Furthermore, ARBs can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients (32213,32218). Theoretically, concomitant use of ARBs with L-arginine may increases the risk of hyperkalemia.
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Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.
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Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.
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Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.
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L-arginine increases nitric oxide, which causes vasodilation (7822). Clinical evidence shows that L-arginine can reduce blood pressure in some individuals with hypertension (7818,10636,31871,32201,32167,32225,31923,32232,110383,110384). Furthermore, combining L-arginine with some antihypertensive drugs seems to have additive vasodilating and blood pressure-lowering effects (7822,20192,31854,31916).
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Theoretically, concurrent use of isoproterenol and L-arginine might result in additive effects and hypotension.
Details
Preliminary clinical evidence suggests that L-arginine enhances isoproterenol-induced vasodilation in patients with essential hypertension or a family history of essential hypertension (31932).
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Theoretically concomitant use of potassium-sparing diuretics with L-arginine may increases the risk of hyperkalemia.
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Theoretically, concurrent use of sildenafil and L-arginine might increase the risk for hypotension.
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In vivo, concurrent use of L-arginine and sildenafil has resulted in increased vasodilation (7822,8015,10636). Theoretically, concurrent use might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported (105065).
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Theoretically, concomitant use of L-arginine and testosterone might have additive effects.
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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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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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Below is general information about the adverse effects of the known ingredients contained in the product Nitric Oxide Booster. 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, topically, and intravenously, alpha-ketoglutarate seems to be well tolerated.
General
...Orally, black pepper seems to be well tolerated when used in the amounts found in food or when taken as a medicine as a single dose.
Topically and as aromatherapy, black pepper oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Burning aftertaste, dyspepsia, and reduced taste perception.
Inhalation: Cough.
Serious Adverse Effects (Rare):
Orally: Allergic reaction in sensitive individuals.
Gastrointestinal ...Orally, black pepper can cause a burning aftertaste (5619) and dyspepsia (38061). Single and repeated application of piperine, the active constituent in black pepper, to the tongue and oral cavity can decrease taste perception (29267). By intragastric route, black pepper 1.5 grams has been reported to cause gastrointestinal microbleeds (29164). It is not clear if such an effect would occur with oral administration.
Immunologic ...In one case report, a 17-month-old male developed hives, red eyes, facial swelling, and a severe cough following consumption of a sauce containing multiple ingredients. Allergen skin tests were positive to both black pepper and cayenne, which were found in the sauce (93947).
Ocular/Otic ...Topically, ground black pepper can cause redness of the eyes and swelling of the eyelids (5619).
Pulmonary/Respiratory ...When inhaled through the nose as an olfactory stimulant, black pepper oil has been reported to cause cough in one clinical trial (29162).
General ...There is no reliable evidence regarding the safety of evodia from clinical trials. In animal studies, evodia has induced QT prolongation and Torsade de pointes (97035).
Cardiovascular ...In animal studies, evodia acts as a proarrhythmic agent with a dose-dependent effect. Evodia infusion has resulted in QT prolongation and Torsade de pointes (97035). It is not clear what dose of evodia, if any, is required to produce a similar effect in humans.
General
...Orally, jiaogulan seems to be well tolerated when used for up to 4 months.
Most Common Adverse Effects:
Orally: Diarrhea and nausea.
Gastrointestinal ...Orally, jiaogulan may cause diarrhea and nausea (6,106651). Dry mouth has also been reported with oral jiaogulan use (106651).
Neurologic/CNS ...Orally, jiaogulan may cause dizziness and insomnia (106651).
General
...Oral, intravenous, and topical L-arginine are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, nausea, diarrhea, headache, insomnia, flushing.
Intravenously: Excessively rapid infusion can cause flushing, headache, nausea and vomiting, numbness, and venous irritation.
Cardiovascular ...L-arginine taken orally by pregnant patients in a nutrition bar containing other antioxidants was associated with a 36% greater risk of palpitations when compared with a placebo bar (91197). It is unclear if this effect was due to L-arginine, other ingredients, or other factors.
Dermatologic ...Orally, arginine can cause flushing, rash, and hives (3460,32138,102587,104223). The skin reactions were likely of allergic etiology as oral L-arginine has been associated with eosinophilia (32138). In one case report, intravenous administration caused allergic reactions including urticaria, periorbital edema, and pruritus (11830). Excessively rapid infusion of L-arginine has caused flushing, local venous irritation, numbness. Extravasation has caused necrosis and superficial phlebitis (3330,16817).
Gastrointestinal
...Orally, L-arginine has been reported to cause nausea, diarrhea, vomiting, dyspepsia, gastrointestinal discomfort, and bloating (1363,31855,31871,31972,31978,32261,90198,91197,96811,99243)(102587,102592).
Orally, L-arginine has been reported to cause esophagitis in at least six adolescents. Symptoms, which included pain and dysphagia, occurred within 1-3 months of treatment in most cases (102588). There are at least two cases of acute pancreatitis possibly associated with oral L-arginine. In one case, a 28-year-old male developed pancreatitis after consuming a shake containing 1.2 grams of L-arginine daily as arginine alpha-ketoglutarate. The shake also contained plant extracts, caffeine, vitamins, and other amino acids. Although there is a known relationship between L-arginine and pancreatitis in animal models, it is not clear if L-arginine was directly responsible for the occurrence of pancreatitis in this case (99266).
Intravenously, excessively rapid infusion of L-arginine has been reported to cause nausea and vomiting (3330,16817).
Musculoskeletal ...Intravenous L-arginine has been associated with lower back pain and leg restlessness (32273). Orally, L-arginine has been associated with asthenia (32138).
Neurologic/CNS ...Orally, L-arginine has been associated with headache (31855,31955,32261,91197,102587,102592), insomnia, fatigue (102587,102592), and vertigo (32150,102592).
Oncologic ...In breast cancer patients, L-arginine stimulated tumor protein synthesis, which suggests stimulated tumor growth (31917).
Pulmonary/Respiratory ...When inhaled, L-arginine can cause airway inflammation and exacerbation of airway inflammation in asthma (121). However, two studies assessing oral L-arginine in patients with asthma did not detect any adverse airway effects (31849,104223).
Renal ...Intravenously, L-arginine has been associated with natriuresis, kaliuresis, chloruresis, and systemic acidosis (32225). Orally, L-arginine can cause gout (3331,3595).
Other ...Orally, L-arginine has been associated with delayed menses, night sweats, and flushing (31855).
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). 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, ornithine ketoglutarate seems to be well -tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, diarrhea, nausea, and vomiting.
Dermatologic ...Orally, pruritus has occurred rarely (67466).
Gastrointestinal ...Orally, the most common adverse effects are gastrointestinal in nature, including abdominal pain, bloating, diarrhea, nausea, and vomiting (67449,67453,67466).
