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