Oral administration of vitamin C (3 gm po) 90 minutes after acetaminophen dosing has been shown to cause a rapid and pronounced decrease in the excretion rate of acetaminophen sulfate (Houston and Levy 1976).

In a double-blind, randomized, crossover study designed to evaluate the effects of aspirin on gastroduodenal injury, 14 healthy volunteers received aspirin (900 mg bid) and either allopurinol (100 mg bid), sulphasalazine (1 g bid), vitamin C (1 g bid), or placebo (McAlindon et al. 1996). Vitamin C reduced aspirin-induced duodenal injury. Renal clearance of aspirin and other acidic medications may also be reduced by high doses of vitamin C (500 mg/day or more), especially in older patients (Schumann 1999).

In dogs, the combination of furosemide (20 mg IV or 40 mg po) and ascorbic acid (150 mg or 500 mg po) increased both urinary output and excretion of unchanged furosemide (Lee and Chiou 1998). Similar results were observed in rats treated with both furosemide (6 mg po) and ascorbic acid (up to 100 mg po).

Administration of vitamin C during long-term nonintermittent administration of glycerolnitrate eliminated vascular tolerance in healthy subjects (Bassenge et al. 1998). In a double-blind, placebo-controlled study with 24 healthy volunteers and 24 patients with ischemic heart disease, coadministration of vitamin C (2 g tid) and nitroglycerin prevented nitrate tolerance (Watanabe et al. 1998a). Concomitant administration of intravenous vitamin C and nitroglycerin also prevented nitrate tolerance in patients with congestive heart failure (Watanabe et al. 1998b).

Vitamin C (1 g bid) protects against aspirin-induced duodenal injury; it may also protect against gastroduodenal injury induced by other NSAIDs such as ibuprofen (McAlindon et al. 1996).

Ascorbic acid (1 g) can interfere with oral contraceptive metabolism, leading to higher blood levels of estradiol (Stockley 1999). However, daily use of ascorbic acid and a combination oral contraceptive (30 µg ethinyl estradiol and 150 µg levonorgestrel) in 37 women for two consecutive cycles did not affect Cmax and AUC values for ethinyl estradiol (Zamah et al. 1993). A similar study also found that vitamin C did not affect Cmax and AUC values for levonorgestrel (Kuhnz et al. 1995). In addition, vitamin C exhibited antioxidant effects when supplied with 17beta-estradiol close to physiological levels (Huang et al. 1999). It protected LDL from oxidation in vitro; 17beta-estradiol monotherapy had no antioxidant effect.

Administration of propranolol (80 mg po) to five healthy volunteers pretreated with ascorbic acid (2 g) affected the absorption and metabolism of the drug (Gonzalez et al. 1995). This combination decreased maximum plasma concentrations and urinary excretion of the drug, and increased the time to reach Cmax.

In one study, the bioavailability of tetracycline hydrochloride was increased by concomitant administration of vitamin C (100 mg/day) in healthy subjects (Omray 1981). More research is needed to confirm these effects.

There are case reports of decreased prothrombin in patients taking vitamin C and warfarin (Harris 1995; Smith 1972). In one case, the patient was taking high doses of vitamin C (16 g/day) (Smith 1972). In follow-up studies, no association was found between vitamin C (1 g/day) and warfarin in humans (Harris 1995). Patients taking warfarin should not exceed the recommended dietary allowance for vitamin C (60 mg/day for adults).

Bassenge E, Fink N, Skatchkov M, Fink B. Dietary supplement with vitamin C prevents nitrate tolerance. J Clin Invest. 1998;102(1):67-71.

Gonzalez J, Valdivieso A, Calvo R, Rodriguez-Sasiain J, et al. Influence of vitamin C on the absorption and first pass metabolism of propranolol. Eur J Clin Pharmacol. 1995;48:295-297.

Harris JE. Interaction of dietary factors with oral anticoagulants: review and applications. J Am Diet Assoc. 1995;95(5):580-584.

Houston JB, Levy G. Drug Biotransformation interactions in man VI: acetaminophen and ascorbic acid. J Pharm Sci. 1976;65(8):1218-1221.

Huang M, Li J, Teoh H, Man RY. Low concentrations of 17beta-estradiol reduce oxidative modification of low-density lipoproteins in the presence of vitamin C and vitamin E. Free Radic Biol Med. 1999; 27(3-4):438-441.

Kuhnz W, Olouton T, Humpel M, Back D, Zamah N. Influence of high doses of vitamin on the bioavailability and the serum protein binding of levonorgestrel in women using a combination oral contraceptive. Contraception. 1995;51:111-116.

Lee M, Chiou W. Mechanism of ascorbic acid enhancement of the bioavailability and diuretic effect of furosemide. Drug Metab Dispos. 1998;26:401-407.

McAlindon M, Muller A, Filipowicz B, Hawkey C. Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers. Gut. 1996;38:518-524.

Omray A. Evaluation of pharmacokinetic parameters of tetracylcine hydrochloride upon oral administration with vitamin C and vitamin B complex. Hindustan Antibiot Bull. 1981;23(VI):33-37.

Schumann K. Interactions between drugs and vitamins at advanced age. Int J Vitam Nutr Res. 1999;69:3173-178.

Smith EC. Interaction of ascorbic acid and warfarin [letter]. JAMA. 1972;221(10):1166.

Stockley IH. Drug Interactions. London: Pharmaceutical Press, 1999; 432.

Watanabe H, Kakihana M, Ohtsuka S, Sugishita Y. Randomized, double-blind, placebo-controlled study of ascorbate on the preventive effect of nitrate tolerance in patients with congestive heart failure. Circ. 1998b;97(9):886-891.

Watanabe H, Kakihana M, Ohtsuka S, Sugishita Y. Randomized, double-blind, placebo-controlled study of the preventive effect of supplemental oral vitamin C on attenuation of development of nitrate tolerance. J Am Coll Cardiol. 1998a;31:1323-1329.

Zamah N, Humpel M, Kuhnz W, Louton T, et al. Absence of an effect of high vitamin C dosage on the systemic availability of ethinyl estradiol in women using a combination oral contraceptive. Contraception. 1993;48:377-391.