DISCUSSION
The main aim of this study was to determine the feasibility of obtaining specific micronutrient values at set intervals during chemotherapy and documenting side effects. The secondary aim was to advocate for significantly more clinical and basic research to establish the role of micronutrients in pediatric cancer diagnosis and outcomes.
Cancer survival is affected by micronutrient deficiency in several reports.4,5,6 Mucositis has been linked to vitamin A and D deficiency.6,7. Vitamin D is the most frequently documented micronutrient associated with a poorer outcome4-6,9-11. Zn deficiency has been linked to increased viral infections and poorer outcomes.12 Cardiomyopathy does occur in Se deficiency.13 Whether low Se adds to anthracycline cardiomyopathy is unknown. Poorer overall survival and increased toxicity has been documented in Se deficiency.14 Vitamin E or Cu effect on outcomes is less clear but they may play a role15,16,17
Folate may potentially aid leukemia proliferation as originally documented by Farber18,19 However, other reports demonstrated that low folate levels at diagnosis is a poor prognostic factor in leukemia 3,4 Depleted antioxidant levels have been reported in the treatment of leukemia and solid tumor patients.20 Any supplementation that has antioxidant potential is currently not recommended21 Though theoretically valid, these concerns are unproven in any pediatric randomized trial.
Micronutrient evaluation is not routinely undertaken in pediatric oncology units. It is generally considered unnecessary unless there are clinical manifestations. Research has suggested that micronutrients or other bioactive food supplementation may interfere with the effectiveness of chemotherapy. It has been shown that reduced micronutrients may increase carcinogenesis in adults and may play a role for cancer prevention.22,23,24 In pediatrics, a meta-analysis of folate substitution or a high folic acid diet during pregnancy does reduce pediatric cancers such as leukemia, neuroblastoma, and retinoblastoma.25 This is likely due to an epigenetic role in DNA methylation.23,24 There is an increasing understanding of nutrigenomics, nutrigenetics, and other relevant ”omics” in which micronutrients and other bioactive foods may have a role in gene expression.26 The microbiome may also be linked to treatment toxicity and micronutrient status27
Micronutrient research should be embedded in large Phase III co-operative group studies. There is an urgent need to understand the relevance of micronutrients to the biology of pediatric cancer and the treatment thereof.28,29