Impact of antioxidant supplementation on chemotherapeutic toxicity: A systematic review of the evidence from randomized controlled trials

Abstract

Much debate has focused on whether antioxidants interfere with the efficacy of cancer chemotherapy. The objective of this study is to systematically review the randomized, controlled clinical trial evidence evaluating the effects of concurrent use of antioxidants with chemotherapy on toxic side effects. We performed a search of literature from 1966‐October 2007 using MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch and EMBASE databases. Randomized, controlled clinical trials reporting antioxidant‐based mitigation of chemotherapy toxicity were included in the final tally. Searches were performed following a standardized protocol for systematic reviews. Only 33 of 965 articles considered, including 2,446 subjects, met the inclusion criteria. Antioxidants evaluated were: glutathione (11), melatonin (7), vitamin A (1), an antioxidant mixture (2), N‐acetylcysteine (2), vitamin E (5), selenium (2), L‐carnitine (1), Co‐Q10 (1) and ellagic acid (1). The majority (24) of the 33 studies included reported evidence of decreased toxicities from the concurrent use of antioxidants with chemotherapy. Nine studies reported no difference in toxicities between the 2 groups. Only 1 study (vitamin A) reported a significant increase in toxicity in the antioxidant group. Five studies reported the antioxidant group completed more full doses of chemotherapy or had less‐dose reduction than control groups. Statistical power and poor study quality were concerns with some studies. This review provides the first systematically reviewed evidence that antioxidant supplementation during chemotherapy holds potential for reducing dose‐limiting toxicities. However, well‐designed studies evaluating larger populations of patients given specific antioxidants defined by dose and schedule relative to chemotherapy are warranted. © 2008 Wiley‐Liss, Inc.

Adverse effects of antioxidative vitamins

“…The chronic poisoning symptoms include: feeling of chronic fatigue, irritability, double vision, nystagmus, sleep disturbances, cracking and bleeding lips and gums, shedding of hair, rashes and ulceration of the skin, muscular coordination disturbances, renal dysfunction (haematuria), and even oedema of the optic disc and other symptoms that could suggest a brain tumor. Hypervitaminosis A can also lead to auditory sensations which are not caused by any sound stimulus (parestesia) [22,23,28,29]. The excessive intake of vitamin A affects harmfully the haematopoietic system, leading to aplastic anemia.…”

“…Toxic effects appear when the ability of plasma RBP (retinol binding proteinthe carrier for vitamin A in blood) to bind retinol and to conjugate its excess with glucuronate is exceeded, which leads to harmful exposure of the cells to free vitamin A [14,22,23]. Patients with hepatic and renal diseases and children are especially susceptible to the adverse effects of this vitamin.…”

Sıçanlarda Bortezomib İndüklü Karaciğer Hasarında B-1,3-(D)-Glukan’ın Hepatoprotektif Etkileri

“…Many studies, though, have demonstrated that oxidative stress is responsiple for chemotherapeutic druginduced liver toxicology [11] . In mitigation of chemotherapy side effects, some antioxidant drugs or agents with anticancer effects have been determined helpful depending on the reducing effect on oxidative stress [12] . Many studies have shown that beta-1,3-D-glucan, an antioxidant and anti-cancer agent, has protective antioxidant activity against chemotherapy-induced liver toxicity [13] .…”

Nutrition in oncology: the case of micronutrients (Review)

“…Against this background it is evident that a supportive nutrition therapy should be an integral part of cancer care (44)(45)(46). In addition to a sufficient supply of energy substrates, vitamins and minerals as well as long-chain ˆ-3 fatty acids are becoming more and more interesting (31, [47][48][49][50][51][52][53][54][55][56], although the therapeutic benefit of such supplements is the subject of a controversial discussion, especially in respect ONCOLOGY REPORTS 24: 815-828, 2010 of supplements with high concentrations of antioxidants like the vitamins C and E and the trace element selenium (57)(58)(59)(60)(61)(62)(63)(64)(65)(66).…”