Vitamin E Synergy 60c

Orthoplex

Vitamin E Synergy combines the eight isomers of mixed tocopherols and mixed tocotrienols with a specific synergistic blend of antioxidants including Glutathione, Alpha Lipoic Acid and Vitamin C to support the regeneration of Vitamin E.

Gluten Free
Egg Free
Dairy Free
Vegetarian
    Product Details

    Pack Size
    60 Capsule

    Adult Dose
    Take 1 soft gel capsule daily or as recommended by your registered healthcare practitioner.

    BIO

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

    Indications

      • Contains Vitamin E which protects polyunsaturated fatty acids in cell membranes from lipid peroxidation
      • Contains Vitamin E, part of an antioxidant network that protects cells from oxidative stress
      • Contains Vitamin C, which can regenerate oxidised Vitamin E
      • Contains Alpha lipoic acid, an antioxidant that can regenerate other antioxidants

    Excipients
    Purified water, caprylic/capric triglyceride, glycerol, gelatin, yellow beeswax, chlorophyllin-copper complex, coconut oil, lecithin.

    Warning
    Vitamin supplements should not replace a balanced diet. Not recommended for use by pregnant and lactating women. Only suitable for adults.

    Ingredients

    Each capsule contains

    Mixed (low-alpha type) tocopherols concentrate 150.0mg
    Tocotrienols complex - palm (sustainably sourced) 80.0mg
    Ascorbic acid 100.0mg
    Glutathione (Setria®) 5.0mg
    Alpha lipoic acid 50.0mg
    Drug Interactions
    Significance
    Ingredient
    Interaction Descriptions
    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
    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.

    Moderate
    VITAMIN E
    (Beta tocopherol, d-alpha-Tocopheryl acid succinate, Alpha tocopherol, Vitamin E, Alpha tocotrienol, Tocopherols concentrated - mixed, Mixed (low-alpha type) tocopherols concentrate, d-alpha-Tocopheryl acetate, d-alpha Tocopheryl succinate , d-alpha-Tocopherol )
    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 E might reduce the effectiveness of alkylating agents.<br> There's concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa (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 vitamin E have on chemotherapy. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

    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: high
    Occurrence: possible
    Level of Evidence: B

    Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding. <br> Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors (4733,4844,11580,11582,11583,11584,11586). These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily (11582,11585). Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol (10364). RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors (11999). Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.

    References

    10364

    Liu M, Wallmon A, Olsson-Mortlock C, et al. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr 2003;77:700-6.

    4733

    Liede KE, Haukka JK, Saxen LM, Heinonen OP. Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid. Ann Med 1998;30:542-6.

    4844

    Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.

    11580

    Schrogie JJ. Coagulopathy and fat-soluble vitamins (letter). JAMA 1975;232:19.

    11582

    Celestini A, Pulcinelli FM, Pignatelli P, et al. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica 2002;87:420-6.

    11583

    Stampfer MJ, Jakubowski JA, Faigel D, et al. Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels. Am J Clin Nutr 1988;47:700-6.

    11584

    Jandak J, Steiner M, Richardson PD. Alpha-tocopherol, an effective inhibitor of platelet adhesion. Blood 1989;73:141-9.

    11585

    Freedman JE, Farhat JH, Loscalzo J, Keaney JF. Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 1996;94:2434-40.

    11586

    Steiner M. Vitamin E, a modifier of platelet function: rationale and use in cardiovascular and cerebrovascular disease. Nutr Rev 1999;57:306-9.

    11999

    Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr 2004;80:143-8.

    Moderate

    SELUMETINIB (Koselugo)

    Be cautious with this combination.

    Moderate

    SELUMETINIB (Koselugo)

    Be cautious with this combination.

    Moderate

    SELUMETINIB (Koselugo)

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: D

    Taking selumetinib with vitamin E can result in a total daily dose of vitamin E that exceeds safe limits and therefore might increase the risk of bleeding.<br> Selumetinib contains 48-54 IU vitamin E per capsule (102971). The increased risk of bleeding with vitamin E appears to be dose-dependent (11582,11585,34577). Be cautious when using selumetinib in combination with supplemental vitamin E, especially in patients at higher risk of bleed, such as those with chronic conditions and those taking antiplatelet drugs (102971).

    References

    11582

    Celestini A, Pulcinelli FM, Pignatelli P, et al. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica 2002;87:420-6.

    11585

    Freedman JE, Farhat JH, Loscalzo J, Keaney JF. Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 1996;94:2434-40.

    34577

    Sesso, H. D., Buring, J. E., Christen, W. G., Kurth, T., Belanger, C., MacFadyen, J., Bubes, V., Manson, J. E., Glynn, R. J., and Gaziano, J. M. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA 11-12-2008;300(18):2123-2133.

    102971

    Prescribing information: KOSELUGO (selumetinib) capsules. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf.

    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, antioxidant effects of vitamin E might reduce the effectiveness of antitumor antibiotics.<br> There's concern that antioxidants could reduce the activity of antitumor antibiotic drugs such as doxorubicin, which 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 vitamin E have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

    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

    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: B

    Using vitamin E with warfarin might increase the risk of bleeding.<br> Due to interference with production of vitamin K-dependent clotting factors, use of more than 400 IU of vitamin E daily with warfarin might increase prothrombin time (PT), INR, and the risk of bleeding, (91,92,93). At a dose of 1000 IU per day, vitamin E can antagonize vitamin K-dependent clotting factors even in people not taking warfarin (11999). Limited clinical evidence suggests that doses up to 1200 IU daily may be used safely by patients taking warfarin, but this may not be applicable in all patient populations (90).

    References

    90

    Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol 1996;77:545-6.

    91

    Corrigan JJ Jr. The effect of vitamin E on warfarin-induced vitamin K deficiency. Ann N Y Acad Sci 1982;393:361-8.

    92

    Corrigan JJ Jr. Coagulation problems relating to vitamin E. Am J Pediatr Hematol Oncol 1979;1:169-73.

    93

    Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA 1974;230:1300-1.

    11999

    Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr 2004;80:143-8.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Moderate

    CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: D

    Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates. <br> Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4 (13499,13500). Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.

    References

    13499

    Landes N, Pfluger P, Kluth D, et al. Vitamin E activates gene expression via the pregnane X receptor. Biochem Pharmacol 2003;65:269-73. .

    13500

    Brigelius-Flohe R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737-40.

    Moderate

    CYCLOSPORINE (Neoral, Sandimmune)

    Be cautious with this combination.

    Moderate

    CYCLOSPORINE (Neoral, Sandimmune)

    Be cautious with this combination.

    Moderate

    CYCLOSPORINE (Neoral, Sandimmune)

    Be cautious with this combination.

    Severity: high
    Occurrence: unlikely
    Level of Evidence: B

    A specific form of vitamin E might increase absorption and levels of cyclosporine. <br> There is some evidence that one specific formulation of vitamin E (D-alpha-tocopheryl-polyethylene glycol-1000 succinate, TPGS, tocophersolan, Liqui-E) might increase absorption of cyclosporine. This vitamin E formulation forms micelles which seems to increase absorption of cyclosporine by 40% to 72% in some patients (624,625,10368). However, this interaction is unlikely to occur with the usual forms of vitamin E.

    References

    624

    Chang T, Benet LZ, Hebert MF. The effect of water-soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther 1996;59:297-303.

    625

    Pan SH, Lopez RR Jr, Sher LS, et al. Enhanced oral cyclosporine absorption with water-soluble vitamin E early after liver transplantation. Pharmacother 1996;16:59-65.

    10368

    Sokol RJ, Johnson KE, Karrer FM, et al. Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E. Lancet 1991;338:212-4..

    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 E might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.<br> A combination of niacin and simvastatin (Zocor) effectively raises high-density lipoprotein (HDL) cholesterol levels in people 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% (7388,11537). Vitamin E alone combined with a statin does not seem to decrease HDL levels (11286,11287). It is not known whether the adverse effect on HDL is due to one of the other antioxidants 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.

    11286

    Stein JH, Carlsson CM, Papcke-Benson K, et al. The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. J Am Coll Cardiol 2001;38:1806-13..

    11287

    Carlsson CM, Papcke-Benson K, Carnes M, et al. Health-related quality of life and long-term therapy with pravastatin and tocopherol (vitamin E) in older adults. Drugs Aging 2002;19:793-805. .

    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

    624
    Chang T, Benet LZ, Hebert MF. The effect of water-soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther 1996;59:297-303.
    625
    Pan SH, Lopez RR Jr, Sher LS, et al. Enhanced oral cyclosporine absorption with water-soluble vitamin E early after liver transplantation. Pharmacother 1996;16:59-65.
    10368
    Sokol RJ, Johnson KE, Karrer FM, et al. Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E. Lancet 1991;338:212-4..
    13499
    Landes N, Pfluger P, Kluth D, et al. Vitamin E activates gene expression via the pregnane X receptor. Biochem Pharmacol 2003;65:269-73. .
    13500
    Brigelius-Flohe R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737-40.
    90
    Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol 1996;77:545-6.
    91
    Corrigan JJ Jr. The effect of vitamin E on warfarin-induced vitamin K deficiency. Ann N Y Acad Sci 1982;393:361-8.
    92
    Corrigan JJ Jr. Coagulation problems relating to vitamin E. Am J Pediatr Hematol Oncol 1979;1:169-73.
    93
    Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA 1974;230:1300-1.
    11999
    Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr 2004;80:143-8.
    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.
    11582
    Celestini A, Pulcinelli FM, Pignatelli P, et al. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica 2002;87:420-6.
    11585
    Freedman JE, Farhat JH, Loscalzo J, Keaney JF. Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 1996;94:2434-40.
    34577
    Sesso, H. D., Buring, J. E., Christen, W. G., Kurth, T., Belanger, C., MacFadyen, J., Bubes, V., Manson, J. E., Glynn, R. J., and Gaziano, J. M. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA 11-12-2008;300(18):2123-2133.
    102971
    Prescribing information: KOSELUGO (selumetinib) capsules. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf.
    10364
    Liu M, Wallmon A, Olsson-Mortlock C, et al. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr 2003;77:700-6.
    4733
    Liede KE, Haukka JK, Saxen LM, Heinonen OP. Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid. Ann Med 1998;30:542-6.
    4844
    Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
    11580
    Schrogie JJ. Coagulopathy and fat-soluble vitamins (letter). JAMA 1975;232:19.
    11583
    Stampfer MJ, Jakubowski JA, Faigel D, et al. Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels. Am J Clin Nutr 1988;47:700-6.
    11584
    Jandak J, Steiner M, Richardson PD. Alpha-tocopherol, an effective inhibitor of platelet adhesion. Blood 1989;73:141-9.
    11586
    Steiner M. Vitamin E, a modifier of platelet function: rationale and use in cardiovascular and cerebrovascular disease. Nutr Rev 1999;57:306-9.
    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.
    11286
    Stein JH, Carlsson CM, Papcke-Benson K, et al. The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. J Am Coll Cardiol 2001;38:1806-13..
    11287
    Carlsson CM, Papcke-Benson K, Carnes M, et al. Health-related quality of life and long-term therapy with pravastatin and tocopherol (vitamin E) in older adults. Drugs Aging 2002;19:793-805. .
    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.
    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.
    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.
    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.
    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.
    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.
    6451
    Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21.
    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.
    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.
    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.

    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.