Clinical C 100t

Orthoplex

Orthoplex Clinical C provides targeted, specialised nutrients to regenerate Vitamin C and provide longer lasting therapeutic benefits.

Gluten Free
Egg Free
Dairy Free
Vegan
Vegetarian
    Product Details

    Pack Size
    63 Tablet

    Adult Dose
    Take 1-2 tablets once or twice daily, or as recommended by your healthcare practitioner

    BIO

    Storage
    Store below 25°C in a cool, dry place away from direct sunlight.

    Indications

      • Contains synergistic ingredients that support the optimal health and function of the immune system.
      • Contains ingredients that play a role in glutathione peroxidase and glutathione regeneration, and therefore help reduce oxidative stress.
      • Contains ingredients that are involved in the production of energy in the body.
      • Contains sustainably derived mixed tocotrienols and tocopherols, representing the complete eight isomer forms of Vitamin E.

      Contraindications

      • No contraindications
      • Pregnancy and lactation: not advised due to insufficient safety data

      Contraindications are taken from Natural Medicines database and are correct as of March 2019.

    Excipients
    Microcrystalline cellulose, calcium hydrogen phosphate dihydrate, croscarmellose sodium, macrogol 400, EvNolMax, colloidal anhydrous silica, ascorbyl palmitate, Hypromellose, Carnauba Wax.

    Warning
    Vitamin and mineral supplements should not replace a balanced diet. This medicine contains selenium which is toxic in high doses. A daily dose of 150μg for adults of selenium from dietary supplements should not be exceeded. Adults only. Not recommended for use by pregnant and lactating women. The maximum recommended dose (4 tablets) contains 210mg sodium.

    Ingredients

    Each tablet contains

    Calcium ascorbate dihydrate 726.0mg
    Sodium ascorbate 452.0mg
    Glutathione 10.0mg
    Rutoside 25.0mg
    Hesperidin 25.0mg
    Alpha lipoic acid 20.0mg
    Selenomethionine 38.0mcg
    equiv. Selenium 15.0mcg
    Nicotinamide 5.0mg
    Pyridoxal 5-phosphate monohydrate 2.19mg
    equiv. Pyridoxine 1.5mg
    Palm tocotrienols complex (EVNolMax™) 2.0mg
    Drug Interactions
    Significance
    Ingredient
    Interaction Descriptions
    Moderate
    VITAMIN B6
    (Pyridoxal 5-phosphate, Pyridoxine hydrochloride, Pyridoxal 5-phosphate monohydrate, Pyridoxine)
    Be cautious with this combination.
    View Interactions:
    Moderate

    PHENYTOIN (Dilantin)

    Be cautious with this combination.

    Moderate

    PHENYTOIN (Dilantin)

    Be cautious with this combination.

    Moderate

    PHENYTOIN (Dilantin)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.<br> Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6 (3046,10801).

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    10801

    Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: B

    Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.<br> Clinical research shows that vitamin B6 can decrease systolic blood pressure in hypertensive patients (30859,82959,83093).

    References

    30859

    Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639.

    82959

    Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.

    83093

    Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363.

    Moderate

    AMIODARONE (Cordarone)

    Be cautious with this combination.

    Moderate

    AMIODARONE (Cordarone)

    Be cautious with this combination.

    Moderate

    AMIODARONE (Cordarone)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: B

    Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.<br> Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect (8892,8893).

    References

    8892

    Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2.

    8893

    Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9.

    Moderate

    PHENOBARBITAL (Luminal)

    Be cautious with this combination.

    Moderate

    PHENOBARBITAL (Luminal)

    Be cautious with this combination.

    Moderate

    PHENOBARBITAL (Luminal)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.<br> Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6 (3046,10801).

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    10801

    Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256.

    Minor

    LEVODOPA

    Be watchful with this combination.

    Minor

    LEVODOPA

    Be watchful with this combination.

    Minor

    LEVODOPA

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: D

    Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.<br> 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).

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    Moderate
    NIACIN
    (Nicotinamide, Nicotinic acid, Vitamin B3)
    Be cautious with this combination.
    View Interactions:
    Moderate

    HEPATOTOXIC DRUGS

    Be cautious with this combination.

    Moderate

    HEPATOTOXIC DRUGS

    Be cautious with this combination.

    Moderate

    HEPATOTOXIC DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity. <br> Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses (4863,11689,11691,25929,25930,25931). Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin (11691,25930,25931,93342).

    References

    4863

    American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9.

    11689

    Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71.

    11691

    Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81.

    25929

    Etchason JA, Miller TD, Squires RW, et al. Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin. Mayo Clin Proc. 1991;66(1):23-8.

    25930

    Henkin Y, Johnson KC, Segrest JP. Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin. JAMA. 1990;264(2):241-3.

    25931

    Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med. 1991;91(3):239-46.

    93342

    Bassan M. A case for immediate-release niacin. Heart Lung. 2012 Jan-Feb;41(1):95-8.

    Moderate

    HMG-CoA REDUCTASE INHIBITORS ("Statins")

    Be cautious with this combination.

    Moderate

    HMG-CoA REDUCTASE INHIBITORS ("Statins")

    Be cautious with this combination.

    Moderate

    HMG-CoA REDUCTASE INHIBITORS ("Statins")

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients. <br> 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).

    References

    7388

    Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93.

    12033

    McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.

    14508

    Reaven P, Witztum JL. Lovastatin, nicotinic acid and rhabdomyolysis (letter). Ann Int Med 1988;109:597-8.

    11689

    Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71.

    14509

    Ito MK. Advances in the understanding and management of dyslipidemia: using niacin-based therapies. Am J Health-Syst Pharm 2003;60(suppl 2):s15-21.

    25918

    Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health Syst Pharm. 1995;52(15):1639-45.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: B

    Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs. <br> 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).

    References

    12033

    McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.

    4863

    American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9.

    25917

    Gadegbeku CA, Dhandayuthapani A, Shrayyef MZ, Egan BM. Hemodynamic effects of nicotinic acid infusion in normotensive and hypertensive subjects. Am J Hypertens. 2003;16(1):67-71.

    93341

    Aramwit P, Srisawadwong R, Supasyndh O. Effectiveness and safety of extended-release nicotinic acid for reducing serum phosphorus in hemodialysis patients. J Nephrol. 2012 May-Jun;25(3):354-62.

    Moderate

    ALLOPURINOL (Zyloprim)

    Be cautious with this combination.

    Moderate

    ALLOPURINOL (Zyloprim)

    Be cautious with this combination.

    Moderate

    ALLOPURINOL (Zyloprim)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: C

    Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol. <br> 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).

    References

    4860

    Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 1990;264:723-6.

    12033

    McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.

    4458

    Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32.

    4863

    American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs. <br> 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).

    References

    4860

    Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 1990;264:723-6.

    12033

    McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.

    4458

    Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32.

    4863

    American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9.

    11689

    Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71.

    11692

    Kahn SE, Beard JC, Schwartz MW, et al. Increased B-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. Diabetes 1989;38:562-8.

    11693

    Schwartz ML. Severe reversible hyperglycemia as a consequence of niacin therapy. Arch Int Med 1993;153:2050-2.

    93344

    Guyton JR, Fazio S, Adewale AJ, Jensen E, Tomassini JE, Shah A, Tershakovec AM. Effect of extended-release niacin on new-onset diabetes among hyperlipidemic patients treated with ezetimibe/simvastatin in a randomized controlled trial. Diabetes Care. 2012 Apr;35(4):857-60.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs. <br> Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin (25915). Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin (25916).

    References

    25915

    Dearing BD, Lavie CJ, Lohmann TP, Genton E. Niacin-induced clotting factor synthesis deficiency with coagulopathy. Arch Intern Med. 1992;152(4):861-3.

    25916

    O'Brien T, Silverberg JD, Nguyen TT. Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin. Mayo Clin Proc. 1992;67(5):465-8.

    Moderate

    BILE ACID SEQUESTRANTS

    Be cautious with this combination.

    Moderate

    BILE ACID SEQUESTRANTS

    Be cautious with this combination.

    Moderate

    BILE ACID SEQUESTRANTS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction. <br> In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30% (14511).

    References

    14511

    Product information: Niaspan. Kos Pharmaceuticals. Cranbury, NJ. 2005. Available at www.niaspan.com/professional/content/pdfs/productinfo.pdf. (Accessed 3 March 2006).

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones. <br> 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.

    References

    25916

    O'Brien T, Silverberg JD, Nguyen TT. Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin. Mayo Clin Proc. 1992;67(5):465-8.

    25925

    Cashin-Hemphill L, Spencer CA, Nicoloff JT, et al. Alterations in serum thyroid hormonal indices with colestipol-niacin therapy. Ann Intern Med. 1987;107(3):324-9.

    25926

    Drinka PJ. Alterations in thyroid and hepatic function tests associated with preparations of sustained-release niacin. Mayo Clin Proc. 1992;67(12):1206.

    25928

    Shakir KM, Kroll S, Aprill BS, Drake AJ 3rd, Eisold JF. Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. Mayo Clin Proc. 1995;70(6):556-8.

    Moderate

    PROBENECID (Benemid)

    Be cautious with this combination.

    Moderate

    PROBENECID (Benemid)

    Be cautious with this combination.

    Moderate

    PROBENECID (Benemid)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: C

    Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid. <br> 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).

    References

    12033

    McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.

    4458

    Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32.

    4863

    American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9.

    Moderate

    ALCOHOL (Ethanol)

    Be cautious with this combination.

    Moderate

    ALCOHOL (Ethanol)

    Be cautious with this combination.

    Moderate

    ALCOHOL (Ethanol)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: D

    Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.<br> 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.

    References

    4458

    Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32.

    11689

    Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71.

    14510

    Schwab RA, Bachhuber BH. Delirium and lactic acidosis caused by ethanol and niacin coingestion. Am J Emerg Med 1991;9:363-5.

    Moderate

    SULFINPYRAZONE (Anturane)

    Be cautious with this combination.

    Moderate

    SULFINPYRAZONE (Anturane)

    Be cautious with this combination.

    Moderate

    SULFINPYRAZONE (Anturane)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: C

    Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone. <br> 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).

    References

    12033

    McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004;164:697-705.

    4458

    Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32.

    4863

    American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9.

    Moderate

    GEMFIBROZIL (Lopid)

    Be cautious with this combination.

    Moderate

    GEMFIBROZIL (Lopid)

    Be cautious with this combination.

    Moderate

    GEMFIBROZIL (Lopid)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients. <br> A case of myopathy from concomitant use of niacin and gemfibrozil has been reported (25920). Niacin alone has also been associated with cases of myopathy (26100,26111). Using gemfibrozil with niacin might further increase the risk of developing myopathy.

    References

    25920

    Litin SC, Anderson CF. Nicotinic acid-associated myopathy: a report of three cases. Am J Med. 1989;86(4):481-3.

    26100

    Gharavi AG, Diamond JA, Smith DA, Phillips RA. Niacin-induced myopathy. Am J Cardiol. 1994;74(8):841-2.

    26111

    Litin SC, Anderson CF. Nicotinic acid-associated myopathy: a report of three cases. Am J Med. 1989;86(4):481-3.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: likely
    Level of Evidence: B

    Large doses of aspirin might alter the clearance of niacin.<br> 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).

    References

    4458

    Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32.

    11689

    Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71.

    4852

    Whelan AM, Price SO, Fowler SF, Hainer BL. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract 1992;34:165-8.

    4853

    Jungnickel PW, Maloley PA, Vander Tuin EL, et al. Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions. J Gen Intern Med 1997;12:591-6.

    14524

    Ding RW, Kolbe K, Merz B, et al. Pharmacokinetics of nicotinic acid-salicylic acid interaction. Clin Pharmacol Ther 1989;46:642-7.

    Moderate
    SELENIUM
    (Sodium selenite, Selenium, Selenomethionine)
    Be cautious with this combination.
    View Interactions:
    Moderate

    BARBITURATES

    Be cautious with this combination.

    Moderate

    BARBITURATES

    Be cautious with this combination.

    Moderate

    BARBITURATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, selenium might prolong the sedating effects of barbiturates.<br> Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates (14601,14602). Selenium seems to prolong the sedative effect of pentobarbital in animal models (14601).

    References

    14601

    Debski B, Milner JA. Dietary selenium supplementation prolongs pentobarbital induced hypnosis. J Nutr Biochem 2004;15:548-53.

    14602

    Ishikawa M, Sasaki M, Koiwai K, et al. Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. J Pharmacobiodyn 1992;15:377-85.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, selenium might interfere with warfarin activity. <br> Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors (14541). Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity (14540).

    References

    14540

    Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96.

    14541

    Davila JC, Edds GT, Osuna O, Simpson CF. Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium. Am J Vet Res 1983;44:1877-83.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.<br> Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity (14540). Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation (74406).

    References

    14540

    Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96.

    74406

    Salonen, J. T., Salonen, R., Seppanen, K., Rinta-Kiikka, S., Kuukka, M., Korpela, H., Alfthan, G., Kantola, M., and Schalch, W. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status. Am.J Clin.Nutr. 1991;53(5):1222-1229.

    Moderate

    IMMUNOSUPPRESSANTS

    Be cautious with this combination.

    Moderate

    IMMUNOSUPPRESSANTS

    Be cautious with this combination.

    Moderate

    IMMUNOSUPPRESSANTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy. <br> In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system (74483,74445).

    References

    74445

    Peretz, A., Neve, J., Desmedt, J., Duchateau, J., Dramaix, M., and Famaey, J. P. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am.J Clin.Nutr. 1991;53(5):1323-1328.

    74483

    Kiremidjian-Schumacher, L., Roy, M., Wishe, H. I., Cohen, M. W., and Stotzky, G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol.Trace Elem.Res. 1994;41(1-2):115-127.

    Minor

    NIACIN

    Be watchful with this combination.

    Minor

    NIACIN

    Be watchful with this combination.

    Minor

    NIACIN

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: A

    Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels. <br> A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.

    References

    7388

    Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93.

    11537

    Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6.

    Minor

    CONTRACEPTIVE DRUGS

    Be watchful with this combination.

    Minor

    CONTRACEPTIVE DRUGS

    Be watchful with this combination.

    Minor

    CONTRACEPTIVE DRUGS

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.<br> Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels (14544,14545,14546,101343). It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium (14545).

    References

    14544

    Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988;73:163-5.

    14545

    Lloyd B, Lloyd RS, Clayton BE. Effect of smoking, alcohol and other factors on the selenium status of a healthy population. J Epidemiol Commun Health 1983;37:213-7.

    14546

    Capel ID, Jenner M, Williams DC, et al. The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity. J Steroid Biochem 1981;14:729-32.

    101343

    Fallah S, Sani FV, Firoozrai M. Effect of contraceptive pill on the selenium and zinc status of healthy subjects. Contraception. 2009;80(1):40-3.

    Moderate
    ALPHA-LIPOIC ACID
    (Alpha lipoic acid)
    Be cautious with this combination.
    View Interactions:
    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents. <br> The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.

    References

    391

    Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.

    14012

    Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S.

    14013

    Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Moderate

    THYROID HORMONE

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.<br> Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form (8946).

    References

    8946

    Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittelforschung 1991;41:1294-8.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.<br> The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.

    References

    391

    Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.

    14012

    Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S.

    14013

    Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.<br> In vitro, alpha-lipoic acid inhibits platelet aggregation (98682).

    References

    98682

    Karkabounas S, Papadopoulos N, Anastasiadou C, et al. Effects of a-lipoic Acid, carnosine, and thiamine supplementation in obese patients with type 2 diabetes mellitus: A randomized, double-blind study. J Med Food. 2018;21(12):1197-1203.

    Minor

    ANTIDIABETES DRUGS

    Be watchful with this combination.

    Minor

    ANTIDIABETES DRUGS

    Be watchful with this combination.

    Minor

    ANTIDIABETES DRUGS

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: B

    Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.<br> Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels (3545,3874,3875,3876,20490,20493,104650), larger clinical studies in patients with diabetes have shown no effect (20494,20495,20496,20498,90443,90445,103326). Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers (3870).

    References

    3545

    Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with Type 2 diabetes. Diabetes Care 1999;22:280-7.

    3870

    Gleiter CH, Schreeb KH, Freudenthaler S, et al. Lack of interaction between thioctic acid, glibenclamide and acarbose. Br J Clin Pharmacol 1999;48:819-25.

    3874

    Jacob S, Henriksen EJ, Tritschler HJ, et al. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabet 1996;104:284-8.

    3875

    Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45:872-4.

    3876

    Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled, pilot trial. Free Rad Biol Med 1999;27:309-14.

    20490

    Porasuphatana S., Suddee S., Nartnampong A., Konsil J., Harnwong B., Santaweesuk A. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study. Asia Pac J Clin Nutr 2012;21(1):12-21.

    20493

    Ansar H., Mazloom Z., Kazemi F., Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J 2011;32(6):584-588.

    20494

    de Oliveira A. M., Rondó P. H., Luzia L. A., D'Abronzo F. H., Illison V. K. The effects of lipoic acid and a-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Diabetes Res Clin Pract 2011;92(2):253-260.

    20495

    Mazloom Z., Ansar H. The Effect of Alpha-Lipoic Acid on Blood Pressure in Type 2 Diabetics. Iranian Journal of Endocrinology and Metabolism 2009;11(3):245-250.

    20496

    Volchegorskii I. A., Rassokhina L. M., Koliadich M. I., Alekseev M. I. [Comparative study of alpha-lipoic acid and mexidol effects on affective status, cognitive functions and quality of life in diabetes mellitus patients]. Eksp Klin Farmakol 2011;74(11):17-23.

    20498

    Du X., Edelstein D., Brownlee M. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. Diabetologia 2008;51(10):1930-1932.

    90443

    Hegazy SK, Tolba OA, Mostafa TM, Eid MA, El-Afify DR. Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Rev Diabet Stud 2013;10(1):58-67.

    90445

    Huang Z, Wan X, Liu J, et al. Short-term continuous subcutaneous insulin infusion combined with insulin sensitizers rosiglitazone, metformin, or antioxidant a-lipoic acid in patients with newly diagnosed type 2 diabetes mellitus. Diabetes Technol Ther 2013;15(10):859-69.

    103326

    Ebada MA, Fayed N, Fayed L, et al. Efficacy of alpha-lipoic acid in the management of diabetes mellitus: A systematic review and meta-analysis. Iran J Pharm Res. 2019;18(4):2144-2156.

    104650

    Derosa G, D'Angelo A, Preti P, Maffioli P. Safety and efficacy of alpha lipoic acid during 4 years of observation: A retrospective, clinical trial in healthy subjects in primary prevention. Drug Des Devel Ther. 2020;14:5367-5374.

    Moderate
    HESPERIDIN
    (Citrus bioflavonoid extract, Hesperidin)
    Be cautious with this combination.
    View Interactions:
    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension. <br> Some clinical and animal research shows that hesperidin can decrease blood pressure (54851,94543,98697,105278). However, other clinical research shows that hesperidin does not affect blood pressure (102315).

    References

    54851

    Yamamoto, M., Suzuki, A., Jokura, H., Yamamoto, N., and Hase, T. Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition 2008;24(5):470-476.

    94543

    Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. Am J Clin Nutr 2011;93(1):73-80.

    98697

    Homayouni F, Haidari F, Hedayati M, Zakerkish M, Ahmadi K. Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial. Phytother Res. 2018;32(6):1073-1079.

    102315

    Mohammadi M, Ramezani-Jolfaie N, Lorzadeh E, Khoshbakht Y, Salehi-Abargouei A. Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled clinical trials. Phytother Res. 2019 Mar;33(3):534-545.

    105278

    Valls RM, Pedret A, Calderón-Pérez L, et al. Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study). Eur J Nutr. 2021;60(3):1277-1288.

    Moderate

    DILTIAZEM (Cardizem, others)

    Be cautious with this combination.

    Moderate

    DILTIAZEM (Cardizem, others)

    Be cautious with this combination.

    Moderate

    DILTIAZEM (Cardizem, others)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hesperidin may increase the levels and clinical effects of diltiazem.<br> Animal research suggests that hesperidin may enhance the bioavailability of diltiazem, increasing the plasma area under the curve of diltiazem by up to 65.3% (91761). This effect has not been reported in humans.

    References

    91761

    Cho, YA, Choi, DH, and Choi, JS. Effect of hesperidin on the oral pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. J Pharm Pharmacol. 2009;61(6):825-829.

    Moderate

    P-GLYCOPROTEIN SUBSTRATES

    Be cautious with this combination.

    Moderate

    P-GLYCOPROTEIN SUBSTRATES

    Be cautious with this combination.

    Moderate

    P-GLYCOPROTEIN SUBSTRATES

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hesperidin might inhibit P-glycoprotein-mediated drug efflux and potentially increase levels of drugs that are substrates of P-glycoprotein. <br> In vitro research shows that hesperidin can inhibit P-glycoprotein efflux (54908). This effect has not been reported in humans.

    References

    54908

    El-Readi, M. Z., Hamdan, D., Farrag, N., El-Shazly, A., and Wink, M. Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines. Eur.J.Pharmacol. 1-25-2010;626(2-3):139-145.

    Moderate

    VERAPAMIL (Calan, others)

    Be cautious with this combination.

    Moderate

    VERAPAMIL (Calan, others)

    Be cautious with this combination.

    Moderate

    VERAPAMIL (Calan, others)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hesperidin might increase the levels and clinical effects of verapamil.<br> Animal research suggests that hesperidin may enhance the bioavailability of verapamil, increasing the plasma area under the curve of verapamil by 96.8% (91762). This effect has not been reported in humans

    References

    91762

    Piao, YJ and Choi, JS. Enhanced bioavailability of verapamil after oral administration with hesperidin in rats. Arch Pharm Res. 2008;31(4):518-522.

    Moderate

    CNS DEPRESSANTS

    Be cautious with this combination.

    Moderate

    CNS DEPRESSANTS

    Be cautious with this combination.

    Moderate

    CNS DEPRESSANTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, concomitant use with CNS depressants may cause additive sedative effects. <br> Animal studies show that hesperidin has sedative effects, due to opioid receptor activity (54841) and can increase sedation when used with diazepam (54789). This effect has not been reported in humans.

    References

    54789

    Fernandez, S. P., Wasowski, C., Paladini, A. C., and Marder, M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur.J.Pharmacol. 4-11-2005;512(2-3):189-198.

    54841

    Loscalzo, L. M., Wasowski, C., Paladini, A. C., and Marder, M. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur.J.Pharmacol. 2-12-2008;580(3):306-313.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hesperidin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. <br> Animal research suggests that hesperetin, a bioflavonoid aglycone derivative of hesperidin, may have antiplatelet activity (54822).

    References

    54822

    Jin, Y. R., Han, X. H., Zhang, Y. H., Lee, J. J., Lim, Y., Chung, J. H., and Yun, Y. P. Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity. Atherosclerosis 2007;194(1):144-152.

    Moderate

    CELIPROLOL (Celicard)

    Be cautious with this combination.

    Moderate

    CELIPROLOL (Celicard)

    Be cautious with this combination.

    Moderate

    CELIPROLOL (Celicard)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, hesperidin may decrease the levels and clinical effects of celiprolol.<br> Animal research shows that concomitant use of hesperidin may reduce the plasma area under the curve of celiprolol by up to 75% (91760). This effect has not been reported in humans.

    References

    91760

    Uesawa, Y. and Mohri, K. Hesperidin in orange juice reduces the absorption of celiprolol in rats. Biopharm Drug Dispos. 2008;29(3):185-188.

    Moderate
    VITAMIN C
    (Calcium ascorbate, Magnesium ascorbate, Magnesium ascorbate monohydrate, Sodium ascorbate, Ascorbic acid, Calcium ascorbate dihydrate, Ascorbic acid (in liposomal form) ZEAL® )
    Be cautious with this combination.
    View Interactions:
    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Moderate

    ALKYLATING AGENTS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.<br> The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

    References

    391

    Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.

    14012

    Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S.

    14013

    Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Moderate

    LEVOTHYROXINE (Synthroid, others)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Vitamin C can increase levothyroxine absorption. <br> Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH (102978).

    References

    102978

    Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403.

    Moderate

    ALUMINUM

    Be cautious with this combination.

    Moderate

    ALUMINUM

    Be cautious with this combination.

    Moderate

    ALUMINUM

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.<br> Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption (10549,10550,10551,21556). In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely (10549). Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

    References

    10549

    Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.

    10550

    Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601.

    10551

    Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7.

    21556

    Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Moderate

    WARFARIN (Coumadin)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    High-dose vitamin C might reduce the levels and effectiveness of warfarin.<br> Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption (11566). There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time (9804,9806). Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant (9805,9806,11566,11567). However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR) (90942). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

    References

    9804

    Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671.

    9805

    Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479.

    9806

    Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166.

    11566

    Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7.

    11567

    Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6.

    90942

    Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Moderate

    ESTROGENS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Vitamin C might increase blood levels of estrogens. <br> Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products (129,130,11161). It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall (129,11161). When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when women who are deficient in vitamin C take supplements (11161). Monitor these patients for estrogen-related side effects.

    References

    129

    Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.

    130

    Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.

    11161

    Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35.

    Moderate

    INDINAVIR (Crixivan)

    Be cautious with this combination.

    Moderate

    INDINAVIR (Crixivan)

    Be cautious with this combination.

    Moderate

    INDINAVIR (Crixivan)

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Vitamin C can modestly reduce indinavir levels. <br> One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown (11300,93578).

    References

    93578

    Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15.

    11300

    Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70.

    Moderate

    FLUPHENAZINE (Prolixin)

    Be cautious with this combination.

    Moderate

    FLUPHENAZINE (Prolixin)

    Be cautious with this combination.

    Moderate

    FLUPHENAZINE (Prolixin)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, vitamin C might decrease levels of fluphenazine. <br> In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started (11017). The mechanism is not known, and there is no further data to confirm this interaction.

    References

    11017

    Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Moderate

    ANTITUMOR ANTIBIOTICS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.<br> The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

    References

    391

    Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.

    14012

    Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S.

    14013

    Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Minor

    ACETAMINOPHEN (Tylenol, others)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: probable
    Level of Evidence: B

    High dose vitamin C might slightly prolong the clearance of acetaminophen.<br> A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases (6451). This effect is not likely to be clinically significant.

    References

    6451

    Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21.

    Minor

    NIACIN

    Be watchful with this combination.

    Minor

    NIACIN

    Be watchful with this combination.

    Minor

    NIACIN

    Be watchful with this combination.

    Severity: mild
    Occurrence: possible
    Level of Evidence: A

    Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.<br> A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

    References

    7388

    Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93.

    11537

    Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Minor

    ASPIRIN

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Acidification of the urine by vitamin C might increase aspirin levels.<br> It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction is not clinically significant.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    10588

    Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413.

    10589

    Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31.

    Minor

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be watchful with this combination.

    Minor

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be watchful with this combination.

    Minor

    CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.<br> It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046,4531). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    4531

    Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.

    10588

    Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413.

    10589

    Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31.

    Minor

    SALSALATE (Disalcid)

    Be watchful with this combination.

    Minor

    SALSALATE (Disalcid)

    Be watchful with this combination.

    Minor

    SALSALATE (Disalcid)

    Be watchful with this combination.

    Severity: insignificant
    Occurrence: possible
    Level of Evidence: B

    Acidification of the urine by vitamin C might increase salsalate levels. <br> It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.

    References

    3046

    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.

    10588

    Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413.

    10589

    Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31.

    Minor
    TOCOTRIENOLS
    (Tocotrienols complex - palm (sustainably sourced), Palm tocotrienols complex, Palm tocotrienols complex (EVNolMax™))
    Be watchful with this combination.
    View Interactions:
    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: B

    Concomitant use of tocotrienols with anticoagulant or antiplatelet agents might increase the risk of bleeding. However, this has not been reported in humans. <br> Taking tocotrienols orally inhibits experimentally-induced platelet aggregation in humans (3237,104429). Theoretically tocotrienols might increase the risk of bleeding if taken with antiplatelet or anticoagulant drugs. However, tocotrienols 400-800 mg daily have been used with aspirin and/or clopidogrel for 1 year with no clear cumulative antiplatelet effects and no reports of bleeding (104429).

    References

    3237

    Mensink RP, van Houwelingen AC, Kromhout D, Hornstra G. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr 1999;69:213-9.

    104429

    Slivka A, Rink C, Paoletto D, Sen CK. Platelet function in stroke/transient ischemic attack patients treated with tocotrienol. FASEB J. 2020;34(9):11838-11843.


    Full Reference List

    3046
    Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
    10588
    Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413.
    10589
    Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31.
    4531
    Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
    391
    Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
    14012
    Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S.
    14013
    Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S.
    11017
    Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008.
    93578
    Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15.
    11300
    Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70.
    129
    Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
    130
    Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
    11161
    Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35.
    7388
    Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93.
    11537
    Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6.
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    90942
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    10549
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    10551
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    21556
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    102978
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    6451
    Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21.
    91760
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    54822
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    54841
    Loscalzo, L. M., Wasowski, C., Paladini, A. C., and Marder, M. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur.J.Pharmacol. 2-12-2008;580(3):306-313.
    91762
    Piao, YJ and Choi, JS. Enhanced bioavailability of verapamil after oral administration with hesperidin in rats. Arch Pharm Res. 2008;31(4):518-522.
    54908
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    91761
    Cho, YA, Choi, DH, and Choi, JS. Effect of hesperidin on the oral pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. J Pharm Pharmacol. 2009;61(6):825-829.
    54851
    Yamamoto, M., Suzuki, A., Jokura, H., Yamamoto, N., and Hase, T. Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition 2008;24(5):470-476.
    94543
    Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. Am J Clin Nutr 2011;93(1):73-80.
    98697
    Homayouni F, Haidari F, Hedayati M, Zakerkish M, Ahmadi K. Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial. Phytother Res. 2018;32(6):1073-1079.
    102315
    Mohammadi M, Ramezani-Jolfaie N, Lorzadeh E, Khoshbakht Y, Salehi-Abargouei A. Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled clinical trials. Phytother Res. 2019 Mar;33(3):534-545.
    105278
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    98682
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    3545
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    3870
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    3874
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    3875
    Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45:872-4.
    3876
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    Rating System Description

    Level of Significance: Stop‑Light Rating System Occurrence/Severity
    Major

    Do not use combination; contraindicated; strongly discourage patients from using this combination; a serious adverse outcome could occur.

    Moderate

    Use cautiously or avoid combination; warn patients that a significant interaticon or adverse outcome could occur.

    Minor

    Be aware that there is a chance of an interaction; advise patients to watch for warning signs of a potential interaction.

    Likelihood of Occurrence

    Likely: Well‑controlled human studies have demonstrated existence of this interaction.

    Probable: Interaction has not been documented in well‑controlled studies, however interaction has been demonstrated in human studies or in controlled animal studies plus multiple case reports.

    Possible: Interaction has been documented in animal or in vitro research, or interaction has been documented in humans but is limited to case reports or conflicting clinical research.

    Unlikely: Interaction has been demonstrated in animal or in vitro research but has been shown not to occur in humans.

    Severity

    High: Life threatening or requires medical intervention to prevent a serious adverse event.

    Moderate: Worsened clinical status and/or requires medication adjustment.

    Mild: May cause minor clinical side effects. Unlikely to require medication adjustment.

    Insignificant: Drug or supplement levels may be affected but will not cause clinical effects.

    Level of Evidence

    A: High-quality randomized controlled trial(RCT).

    A: High-quality meta-analysis (quantitative systematic review)

    B: Nonrandomized clinical trial

    B: Nonquantitative systematic review

    B: Lower quality RCT

    B: Clinical cohort study

    B: Case-control study

    B: Historical control

    B: Epidemoilogic study

    C: Consensus

    C: Expert opinion

    D: Acecdotal evidence

    D: In vitro or animal study

    D: Theoretical based on pharmacology


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    Disclaimer: This information on interactions is licensed from the TRC Natural Medicines Database. Neither Bio Concepts nor TRC are providing medical, clinical or other advice and nothing should be interpreted as constituting such advice. Currently this does not check for drug-drug or supplementsupplement interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgement is necessary.