*4.1.3. Clinical trials*

In 1990, Philipov et al. carried out a limited clinical study with 15 patients with malignant brain tumors. There was no significant survival prolongation with selenium addition on patients' diet [28].

In 1996, Lissoni et al. evaluated the effects of melatonin using with radiotherapy on 30 patients with glioblastoma multiforme. They showed that the melatonin addition in normal therapy provided prolonged survival time, decreased side-effects. Based on these results they suggested that concomitant therapy may be more effective for glioblastoma patients [27].

In 2010, Delorenze et al. exhibited that the relationship between daily intake of antioxidants and survival rate was variable depends on tumor grade. They also showed that the supplementation of higher dose vitamin E has increased the survival in grade III gliomas; otherwise, vitamin C and genistein were decreased the survival rate [26].

In 2010, the side-effects welding from radiotherapy were decreased with lycopene supplementation in patients with high-grade glioma [54].

In 2015, Mulpur et al. carried out a study to check complementary therapy options among glioblastoma multiforme patients. They found that multivitamins or omega-3-fatty acids did not affect survival, but for Vitamin D and E further investigations are necessity [55].
