• Class: antioxidant.
• Mechanism of action: superoxide dismutase catalyzes the conversion of superoxide to oxygen and hydrogen peroxide, reducing damage from radical oxygen species.
° Osteoarthritis: 16 mg as an intra-articular injection every two weeks.54
=> Rheumatoid arthritis: 4 mg intra-articular injection once weekly for up to 6 weeks.55
° Osteoarthritis: vitamin C in the form of calcium ascorbate 1 gram daily for 2 weeks has been used.57
° Postoperative pain: a single prophylactic dose of 2 grams of vitamin C by mouth, 1 hour prior to anesthesia has been used in patients (tested in patients receiving cholecystectomy).58
• Adverse effects: dose-related adverse effects, most common including nausea, vomiting, esophagitis, heartburn, abdominal cramps, gastrointestinal obstruction, fatigue, flushing, headache, insomnia, sleepiness, and diarrhea.59
° Doses greater than the tolerable upper limit of 2 g per day can increase the risk of severe adverse effects such as osmotic diarrhea.
° Acetaminophen: high doses of vitamin C (3 grams) competitively inhibit the sulfate conjugation of acetaminophen, resulting in an increase in the fractions of the dose of acetaminophen excreted as acetaminophen glucuronide and a decrease in the fraction excreted as acetaminophen sulfate. May not be clinically significant.60
° Alkylating agents: use of vitamin C during chemotherapy may reduce the activity of chemotherapy and generate free radicals.61
=> Aluminum: vitamin C can increase the amount of aluminum absorbed from aluminum compounds.62
=> Aspirin/salicylates: acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules and increase plasma salicylate levels.63
=> Estrogen: vitamin C may increase plasma estrogen levels up to 47% when vitamin C is taken with oral contraceptives or hormone replacement therapy, including topical products.64
° Fluphenazine: vitamin C may decrease fluphenazine levels when used concurrently with vitamin C 500 mg twice daily.65
=> Protease inhibitors: taking vitamin C orally along with indinavir may modestly reduce indinavir levels.66 Vitamin C may modestly reduce levels of other protease inhibitors as well.
=> Dihydropyridine calcium channel blockers: these medications (e.g., nicardipine) inhibit uptake of vitamin C by intestinal cells. It is unknown if this is clinically significant.67
=> Warfarin: high doses of vitamin C may reduce the response to warfarin, possibly causing diarrhea and reduced w'arfarin absorption, and it was concluded that it was not clinically significant.68
• Cautions: do not exceed tolerable upper limit of 2g per day.
• Class: antioxidant.
• Mechanism of action: mechanism in relation to pain reduction is not known and further research is needed.
<= Rheumatoid arthritis/osteoarthritis: 600 mg orally twice daily.69
<= Alkylating agents: the use of antioxidants such as vitamin E during chemotherapy can interfere with chemotherapy activity and may generate free radicals.61
<= Anticoagulant/antiplatelet drugs: concomitant use of vitamin E and anticoagulant or antiplatelet drugs might increase the risk of bleeding by inhibition of platelet aggregation and antagonization of the effects of vitamin К-dependent clotting factors.71
<> Cytochrome P450 3A4 substrates: vitamin E may increase the metabolism of drugs metabolized by CYP3A4. Vitamin E appears to bind with the nuclear receptor (pregnane X receptor [PXR]), which may result in increased expression of CYP4A4.72
° Warfarin: taking chondroitin in combination with glucosamine might increase the anticoagulation effects of warfarin and increase risk of bruising and bleeding. May increase INR.76
• Cautions: allergy to shark and bovine.