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Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been associated with the damage to the gastrointestinal tract. One proposed mechanism of injury to the gastrointestinal mucosa by NSAIDs is oxygen radical-dependent microvascular injury. There is reasonable evidence to support the benefit of the addition of ascorbic acid, an ingredient with antioxidant properties, to moderate the adverse gastrointestinal (GI) effects of aspirin. Pharmacokinetic data have demonstrated that aspirin and ascorbic acid combination therapy can assist in mitigating the decrease in levels of ascorbic acid secondary to aspirin monotherapy. Endoscopic evaluation has demonstrated that the addition of ascorbic acid to aspirin significantly improves Lanza scores and rates of blood loss when compared to aspirin administration alone. When taken with ascorbic acid, the patient-reported tolerability of aspirin has been shown to be comparable to paracetamol and placebo. The existing body of evidence is relevant to short-term therapy with analgesic aspirin doses, and extrapolation to long-term therapy with low-dose aspirin is not appropriate. The purported benefit of an aspirin and ascorbic acid combination is a local observance and is not suspected to influence the adverse GI effects experienced as a result of systemic prostaglandin inhibition. Nevertheless, ascorbic acid may be a viable addition to the strategies employed to improve the gastrointestinal tolerability of aspirin.