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Antioxidant intake in paediatric oncology patients
Clinical Nutrition xxx (2014) 1e5
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Original article
Antioxidant intake in paediatric oncology patients Sonja Slegtenhorst a, b, *, Janicke Visser b, Amos Burke a, Rosan Meyer c a
Dept of Paediatric Haematology and Oncology, Box 181, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Hills Road, Cambridge, Cambridgeshire CB2 0QQ, United Kingdom b Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University, PO BOX 19063, Tygerberg 7505, South Africa c Dept. Gastroenterology, Great Ormond Street Hospital Foundation Trust, London WC1N 3JH, United Kingdom
a r t i c l e i n f o
s u m m a r y
Article history: Received 7 May 2014 Accepted 13 December 2014
Background & aims: Antioxidant intake can affect both free radical and the nutritional status of children receiving cancer treatment. The aim of this study was to investigate whether children with cancer met their antioxidant requirements. Methods: A prospective observational study was performed at a single hospital in England from June 2008 to February 2010. Children with a solid tumour, lymphoma or leukaemia were included. Dietary intakes including 3 modes of feeding (‘diet alone’, ‘diet þ tube’ feeding or ‘diet þ vitamin-mineral supplementation’ (VMS)) were collected with an estimated food record (EFR) 1 and 3 month post-diagnosis. Four and 24-hr food recalls were performed to validate the food records. Results: Forty two children were included: 57% leukaemia or lymphoma and 43% solid tumours. Sixty seven percent underwent chemotherapy and 33% a combination of therapies. In months 1 and 3, greater numbers of children achieved 100% of requirements for ‘diet þ VMS’ (p < 0.05) than for other feeding modes. However, considerable proportions of all feeding groups did not achieve 100% of the Recommended Nutrient Intake (RNI) for vitamin A, C, E, selenium and zinc. This was most marked in the ‘diet alone’ group. Significant proportions did not achieve the Lower Recommended Nutrient Intake (LRNI) for some antioxidants. The ‘diet alone’ group had the highest proportion not meeting LRNI for vitamin A (p << 0.001; 1st month) and zinc (p < 0.02; 3rd month). Conclusion: Inadequate antioxidant intake was observed in a significant proportion of cancer patients when feeding was not augmented in any way. More research is required to determine the clinical implications of these findings. © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Keywords: Antioxidant intake Paediatric Oncology patients
1. Introduction The primary outcomes of nutritional support for children undergoing cancer treatment is to ensure continued age appropriate growth and development throughout treatment, hence preventing malnutrition [1]. Cancer, notwithstanding its treatment, is renowned for its high incidence of malnutrition in children (6%e 50%) and is highly dependent on the type, stage and location of the tumour [2,3]. Malnourished children are at higher risk of infections, worse outcomes, impaired tolerance to chemotherapy, impaired immune function and the need for more frequent chemotherapy
* Corresponding author. Nutrition and Dietetic Department, BOX 119, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Hills Road, Cambridge, Cambridgeshire CB2 0QQ, United Kingdom. Tel.: þ44 (0)1223 216655. E-mail address: [email protected] (S. Slegtenhorst).
dose adjustments. [3e7] An important component of cancer treatment is the nutritional management which ensures adequate antioxidant intake. Considerable benefits are seen in well nourished patients during cancer treatment [6,8e10]. On the other hand, antioxidants also have the potential to reduce the production of free radicals from anti-cancer therapies which may lead to reduced killing of cancer cells [11]. Oncologists have expressed concerns that the protective mechanism of antioxidants may not differentiate between healthy and cancerous cells and additional supplementation could interfere with the anti-cancer activity of conventional therapies [12]. We therefore are presented with a dilemma; adequate antioxidant intake which is essential for normal cellular homeostasis versus a potential theoretical risk of reducing the effectiveness of anti-cancer therapy with antioxidant supplementation. There is paucity of data in antioxidants treatment and requirements during cancer treatment for children.
http://dx.doi.org/10.1016/j.clnu.2014.12.010 0261-5614/© 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Please cite this article in press as: Slegtenhorst S, et al., Antioxidant intake in paediatric oncology patients, Clinical Nutrition (2014), http:// dx.doi.org/10.1016/j.clnu.2014.12.010
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S. Slegtenhorst et al. / Clinical Nutrition xxx (2014) 1e5
We therefore set out to establish the actual dietary intake of antioxidants (vitamin A, E, C, selenium and zinc) in a paediatric oncology population and compared them to the United Kingdom Department of Health's (DOH UK) antioxidant requirements for healthy children [13]. 2. Materials and methods A prospective observational study was performed at Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, England from June 2008 to February 2010. Ethical approval was obtained for this study and informed consent was obtained from all participants prior to enrolment in the study. All newly diagnosed children between 1 and 16 years with solid tumours, lymphomas or leukaemia were eligible to be included in the study. Children on home parenteral nutrition receiving breastmilk, and those less than 1 year of age were excluded from the study. Patients were recruited to the study within 1 month post diagnosis. In this same period, patients were assessed by a paediatric oncology dietitian. All the children received the same dietetic assessment and care. Data was collected by means of two dietary tools; a 4-day estimated food record (EFR) over consecutive days (Wednesday to Saturday) and 4 repeated non-consecutive 24-hr recalls in the 1st and 3rd month post diagnosis [14]. As no validated 4-day EFR existed which aimed at establishing antioxidant intake in paediatrics in the United Kingdom (UK), the researcher adapted an existing food record currently used in the Nutrition and Dietetic Department (Cambridge University Hospitals NHS Foundation Trust, UK) to suit the study's requirement. The 24-hr recall method was performed as a secondary dietary intake measurement (test method) to ensure accuracy and reliability of the EFR. EFR's and 24hr recalls were analysed using the Standard Manual on Food Portions from the Fish and Food Ministry of Agriculture [15]. Anthropometric measurements including weight e [Seca 701 Electronic Personal Scales (GMBH & Co)] and height e Harpenden Stadeometer (Holtain Ltd) and demographic parameters were collected. The weight-for-age z-scores were then assessed against the World Health Organization (WHO) Global Database on Child Growth and Malnutrition [16]. Antioxidant intake (vitamin A, E, C, selenium and zinc) was compared to the RNI, LRNI and Safe Upper Intake commonly used in the UK. As children with cancer treatment are often reliant on a variety of supplements and often require enteral feeding, nutrition intake was categorised for the purpose of analysis into ‘diet alone’, diet and tube feeds (‘diet þ tube’) or diet and vitamin-mineral supplementation (‘diet þ VMS’). 3. Statistics Statistical evaluation was undertaken using SPSS 16 statistical software (SPSS Science, Apache Software Foundation, Chicago, IL, USA) and dietary intake of antioxidants determined using Diet Plan 6.3 programme (Forrestfield Software Limited, Horsham, UK). Nonparametric tests i.e Fishers Exact, and ShapiroeWilk, bivariate correlation and t - tests were used. A p-value 0.05 was considered significant. Both the ShapiroeWilk and Fishers Exact Test was used due to the smaller analysis categories. 4. Results 4.1. Subjects Fifty two children were recruited into the study, however 10 were excluded due to the following reasons: 4 (8%) withdrew from
study; 1 (2%) was not discharged from hospital during treatment; 1 (2%) transferred to an out of area hospital; 4 (8%) consented to study, but did not respond to requests for data. Of the remaining 42 children, 20 were boys (48%) and 22 were girls (52%). The median age was 6 years and 9 months (SD 4.8). Their diagnoses included haematological malignancies (leukaemia; 14 (33%), lymphomas; 10 (24%)) and others (solid tumours; 18 (43%)). Twenty eight (67%) underwent chemotherapy and 14 (33%) a combination of therapies. Two (5%) and 6 (15%) respectively of children in the 1st and 3rd month were found to be malnourished based on z-scores. In the 1st month, 2 (5%) of children achieved a z-score of <-2 and in the 3rd month, 4 (10%) achieved this score. The mean z-score for the study population calculated at the 1st and 3rd month was 0.22 and 0.34 respectively, indicated that the weight of the population remained relatively the same over this period. There was no statistical difference between the three feeding modes for energy and protein intake. 4.2. Vitamin and/or mineral supplement use In the 1st month, 8 (27%) of the children consumed vitamin and/ or mineral supplements and 4 (18%) in the 3rd month. These supplements were either VS or VMS used in approximately equal proportion at each time point. For the purposes of analysis all were analysed in the ‘diet þ VMS’ group. 4.3. Dietary method correlation Of the 42 children's data analysed, 30 (71%) returned their EFR's in the 1st month's collection of data, however the return rate in the 3rd month was less (n ¼ 22; 52%). The validity of the EFR was established through correlation with the 24-hr recalls for both the 1st and 3rd months (Table 1). There was a strong correlation between the EFR and 24-hr recall at both time points for ‘diet alone’ (p << 0.001); the exception being for selenium and zinc at time point 2. For other feeding modes the majority of dietary intakes correlated, however greater day to day variation was seen, in particular in the more complex patients receiving dietary intake and tube feeding. The overall trend however, showed that the children receiving nutritional support showed a higher percentage of RNI antioxidant intake as measured by the EFR method. Underreporting or missing foods is a common limitation of 24-hr recalls, which is related to it's reliance on memory and omissions such as beverages, sauces and supplements are common [17,18]. Several studies in children have found a benefit with using a food diary/
Table 1 Correlation of the Estimated Food Record and 24-hr recall antioxidant intake values for diet alone and antioxidants (1st and 3rd month). r e value
p- value
recall 1 recall 2
0.70 0.70
<<0.001 <<0.001
recall 1 recall 2
0.56 0.72
<<0.001 <<0.001
recall 1 recall 2
0.54 0.45
<<0.001 0.05
recall 1 recall 2
0.64 0.50
<<0.001 0.67
recall 1 recall 2
0.81 0.38
<<0.001 0.10
Antioxidants Vitamin A EFR 1a & 24-hr EFR 2a & 24-hr Vitamin C EFR 1a & 24-hr EFR 2a & 24-hr Vitamin E EFR 1a & 24-hr EFR 2a & 24-hr Selenium EFR 1a & 24-hr EFR 2a & 24-hr Zinc EFR 1a & 24-hr EFR 2a & 24-hr a
EFR ¼ estimated food record.
Please cite this article in press as: Slegtenhorst S, et al., Antioxidant intake in paediatric oncology patients, Clinical Nutrition (2014), http:// dx.doi.org/10.1016/j.clnu.2014.12.010
S. Slegtenhorst et al. / Clinical Nutrition xxx (2014) 1e5
history in comparison to 24-hr recalls; for the reason that it does not rely on memory, provides more reliable and detailed intakes (i.e. less missing or phantom foods) [18,19]. A decision was therefore made to use the EFR in preference to the 24-hr recall method. 4.4. Antioxidant intake compared to dietary reference values In all feeding modes there was a proportion of children not achieving 100% of the RNI for vitamin A, C, E, selenium and zinc (Table 2). However, the ‘diet alone’ group was consistently the group receiving inadequate amounts of antioxidants (Table 2); with the intake improved with children on ‘diet þ tube’ and the most replete those on ‘diet þ VMS’. In particular, Vitamin A, selenium and zinc intake were low in the ‘diet alone’ group with the least number of children meeting the LRNI for vitamin A (p << 0.001, 1st month) and zinc (p < 0.02, 3rd month) in comparison to the other feeding modes. Inadequate intakes of zinc and selenium was seen at 1 month in both the ‘diet alone’ group and in a proportion of those who received ‘diet þ VMS’. However the inadequate intake in the ‘diet þ VMS’ group was confined to those children who took supplements containing vitamins only without minerals. At the 3 month time-point the ‘diet alone’ group still had children receiving inadequate (
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leukaemia receiving chemotherapy and/or radiotherapy. Our findings showed a large proportion of children displayed inadequate intakes of antioxidants. The ‘diet alone’ feeding mode was highlighted as the most nutritionally depleted. In contrast more children achieved their RNI receiving tube feeds but the most replete antioxidant intake was found in the group having ‘diet þ VMS’. The adequate intake of antioxidants remains undisputed, however excessive intake is a source of controversy [8,20]. It is therefore likely that in order to achieve optimal age appropriate nutritional requirements, that a combination of feeding modes will be required. This combination will ultimately be dictated by the cancer type, stage of disease and treatment. To our knowledge this is the first study establishing antioxidant intake in this population solely using dietary intake assessment tools. The ‘diet alone’ group (without any tube feeding or supplements) had the greatest number of children not meeting their normal antioxidant requirements, with a significant proportion not achieving even the LRNI. It is not clear what the effect of such inadequate dietary antioxidant intake is on tolerance of chemotherapy or on treatment outcome. We did not observe any significant improvement or change in the antioxidant intake of the ‘diet alone’ group between the assessments at the first and third months. This is consistent with findings from Kennedy et al. [21] whereby the percentage of children (on diet alone) achieving below standard nutrient values did not change appreciably over time. In the ‘diet alone’ group, the majority of the inadequate antioxidant intake was for vitamin A and zinc at both time-points; it is uncertain what additional negative impact this would have had on growth which would already have been affected by illness and cancer therapy. It is well reported that growth failure in children with cancer is multifactorial and in prolonged periods could lead to height growth cessation [7,8]. The aforementioned micronutrients play a key role in growth, by functioning as essential micronutrients in cell differentiation, development and linear growth [22e24]. It has been suggested that a contributing factor to the poor growth is zinc dyshomeostasis and redistribution in cachexic children and that zinc could have deleterious consequences on growth [25]. The weight-for-age scores were suggestive of a nourished population, however this data did not reflect long-term nutrition
Table 2 Percentage of children achieving less than the Lower Recommended Nutrient Intake and 100% of Recommended Nutrient Intake for Antioxidants. EFR 1a 1st month
EFR 2a 3rd month
Diet Diet þ tube Diet þ tube Diet þ VMSb Diet þ VMSb Diet Diet Diet þ tube Diet þ tube Diet þ VMSb Diet þ VMSb Diet 100% RNIc LRNI%d 100% RNIc LRNI%d 100% RNIc LRNI%d 100% RNIc LRNI%d 100%RNIIc LRNI%d 100% RNIc LRNI%d Vitamin A
45%* (5/11) Vitamin C 9% (1/11) Vitamin E~ e Selenium Zinc
9% (1/11) 45%* (5/11)
9% (1/11) 82% (9/11) 55% (6/11) 36% (4/11) 36% (4/11)
0% (0/13) 0% (0/13) e 0% (0/13) 0% (0/13)
46% (6/13) 77% (10/13) 77% (10/13) 69% (9/13) 77% (10/13)
0% (0/8) 0% (0/8) e 29% (2/7) 29% (2/7)
100%* (8/8) 100% (8/8) 88% (7/8) 43% (3/7) 43% (3/7)
50% (5/10) 0%* (0/10) e 30% (3/10) 50%* (5/10)
0% (0/10) 70% (7/10) 50% (5/10) 20% (2/10) 20% (2/10)
25% (2/8) 0%* (0/8) e 0% (0/8) 0% (0/8)
50% (4/8) 88% (7/8) 88% (7/8) 63% (5/8) 63% (5/8)
0% (0/4) 0%* (0/4) e 0% (0/2) 0% (0/2)
75% (3/4) 100% (4/4) 100% (4/4) 50% (1/2) 50% (1/2)
(n) ¼ patient numbers. * Significance at p < 0.05. ( ) Brackets show number of children in that particular mode of feeding achieving less than the Lower Recommended Nutrient Intake or 100% Recommended Nutrient Intake. ~ Vitamin E is measured as a safe intake, no Recommended Nutrient Intake available. *This particular feeding mode had a statistically greater number of children achieving less than the Lower Recommended Nutrient Intake or 100% Recommended Nutrient Intake compared to the other feeding modes in that month. a EFR ¼ estimated food record. b VMS ¼ multi e vitamin-mineral supplementation. c RNI ¼ Recommended Nutrient Intake. d LRNI ¼ Lower Recommended Nutrient Intake.
Please cite this article in press as: Slegtenhorst S, et al., Antioxidant intake in paediatric oncology patients, Clinical Nutrition (2014), http:// dx.doi.org/10.1016/j.clnu.2014.12.010
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which may have been more indicative with weightefor-height scores. In addition without biochemical markers we were unable to pursue this further. The lower intakes of selenium and zinc for the ‘diet þ VMS’ group was due to the greater number of children using vitamin supplements which do not contain these minerals. The greater appeal for a vitamin supplement over a vitamin-mineral supplement was likely due to palatability. Similar percentages of children using vitamins were found in studies by Bussieres et al. [26] and Mottonen and Uhari [27] showing vitamin intakes of 20% and 40% respectively. Tube fed children consistently obtained good intakes for most of the antioxidants with the exception of vitamin A. This low vitamin A intake may be attributed to the poor oral intake than from the tube feed in itself. Overall, ‘diet þ tube’ feeding provided good intakes of antioxidants. The findings above support the delivery of antioxidants via tube feeding; however tube feeding cannot be advocated on antioxidants alone and therefore the child would need a dietary and growth assessment to determine if tube feeding appropriate. One of the vitamins that did consistently achieve good intakes across all the feeding groups was vitamin C. This was seen with values of greater than 200% of the RNI and in some instances up to seven times the RNI. The higher vitamin C results were likely due to the predominant higher intake of fruit juice, squash, tube feeds and vitamin supplements from observation of the dietary analysis. This did raise the concern as to whether the intakes of these children could pose an interference with certain chemotherapy/radiotherapy and/or toxicity. However, the children did not exceed the recommended UK Safe Upper limits of grams per day (unspecified grams) [13]. Although there is limited evidence available on serum vitamin C levels in children and adolescents with cancer [28] Kennedy et al.'s [21] study showed that greater vitamin C intakes at 6 months were associated with fewer therapy delays, less toxicity, and fewer days spent in the hospital [21]. The effect of vitamin A and vitamin E supplementation in relation to different cancers and treatments are very variable and most of the available data relates to adult cancers.[29] Scope for further studies in the paediatric population is required. Fluctuations in daily dietary intake was seen, particularly in the more complex patients requiring nutritional support. These complex patients are usually at higher nutritional risk due to their cancer type, staging and treatment regimes, hence greater variability would be expected. Upon closer inspection the variability in the ‘diet þ tube’ group was compounded by parents' frequent adjustments in feed amounts given to the child during and post treatment sessions. Dietary assessment tools based on recording or recall are clearly limited in this setting and direct measurement of biochemical markers are preferable for future studies. The advantage of biochemical markers, is that in comparison to estimated dietary intakes, they provide accurate measures and correlate better with dietary intake, due to less errors.[30] Estimated dietary intake measurement errors are attributable to the variability in nutrients and food components (ie related to where foods have grown, been processed and cooked (seen with vitamin E and selenium)), subjective data collection, inaccurate completion of dietary tools, poor availability of comprehensive food tables and reliance on memory recall. Limitations include a low sample size which may have influenced the study's results; as this required that generalized feeding modes needed to be created (i.e tube and sip feed group combined). A larger study population would have allowed for specific feeding categories i.e. tube feeds or sips feeds and specific vitamin and mineral supplements. The 24hr recall deemed limiting due to its tendency to underreport in comparison to the EFR, however its main purpose in this study was to perform as a second dietary
intake measurement (test method). Comparative dietary method studies in children showed that 3-day food records showed the greatest agreement between observed and reported intakes in comparison to the 24hr recall and food frequency questionnaire [18], hence the EFR was used as the main dietary tool. A proportion of children had inadequate or excessive reported intakes of antioxidants however without blood/biochemical markers we were unable to verify this; future studies should include these markers. Further studies are required to investigate the clinical significance of such inadequate intakes. 6. Conclusion In this study a large proportion of the children undergoing treatment for leukaemia, lymphoma and solid tumours displayed inadequate intakes of antioxidants. The ‘diet alone’ feeding mode was highlighted as the most nutritionally depleted in antioxidants. This was a consistent trend seen both at diagnosis and 3 months into treatment. The consequences of malnutrition are well documented and are multiple in children who are undernourished compared to those well-nourished during cancer treatment. Vitamin A and zinc were highlighted as especially depleted in the diet alone mode. On the other hand vitamin C consistently achieved good intakes in comparison to the recommended intake. This was found specifically with the children on diet plus vitamins and/or mineral supplements. Further paediatric randomized control studies are required to determine the effect of antioxidant supplementation in cancer treatment and exact guidance on dosage. Based on this study it would seem reasonable to suggest that a vitamin-mineral supplement could be recommended for children who are not receiving any other form of dietary supplementation to ensure that they achieve adequate intake of vitamins A and E; selenium and zinc. It is also important to recognise the pivotal role that parents/carers play in ensuring that children and young people with cancer meet their nutritional requirements. Further studies should validate the EFR dietary tool in assessing antioxidant adequacy in children with cancer by correlation between serum antioxidant levels and the dietary tool assessments. In the future, studies should investigate whether optimal nutritional adequacy (multimodal) is associated with better tolerance of cancer therapies and the effect (if any) of supplementation on the efficacy of cancer treatment. Statement of authorship Sonja Slegtenhorst e developed original concept, wrote the protocol, conducted the study and analysis and prepared the manuscript. Dr Rosan Meyer e facilitated the development of the protocol, analysed the data and contributed to the writing and review of the manuscript. Dr Janicke Visser e facilitated the development of the protocol and reviewed the manuscript. Dr Amos Burke e developed original study concept, participated in study design, interpreted the data and contributed to the writing and review of the manuscript. All authors read and approved the final manuscript. Funding sources No sponsors were used to fund or formulate this study. Conflict of interest The authors have no conflicts of interest.
Please cite this article in press as: Slegtenhorst S, et al., Antioxidant intake in paediatric oncology patients, Clinical Nutrition (2014), http:// dx.doi.org/10.1016/j.clnu.2014.12.010
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Acknowledgements This research project would not have been possible without the support of many people. I wish to express my gratitude to Laura Mcgeeney, Jane, Emerton, Dr Ken Ong, Isla Kuhn, John and Christine Forster for their invaluable support and guidance. Further thanks are extended to the Department of Paediatric Haematology and Oncology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust. The material for this paper was presented for my MSc in Nutrition in December 2011 (Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University). References [1] Rickard KA, Kirksey A, Baehner RL. Effectiveness of enteral and parenteral nutrition in the management of children with Wilm's tumour. Am J Clin Nutr 1980 Dec;56:2881e7. [2] Donaldson SS, Wesley MN, DeWys WK, Suskind RM, Jaffe N, van Eys J. A study of the nutritional status of paediatric cancer patients. Am J Dis Child 1981 Dec;135(12):1107e12. [3] van Eys J. Malnutrition in children with cancer: incidence and consequence. Cancer 1979 May;43(5 Suppl):2030e5. [4] van Eys J. Nutrition in the treatment of cancer in children. J Am Coll Nutr 1984;3(2):159e68. [5] Kibirige MS, Morris-Jones PH, Stevens RF, Rayner C. Nutrition, infection and morbidity in leukaemia. Ped Haem Oncol 1988;5(3):179e85. [6] Andrassy RJ, Chwals WJ. Nutritional support of the pediatric oncology patient. Nutrition 1998 Jan;14(1):124e9. [7] Schmitt F, Caldari D, Corradini N, Gicquel P, Lutz P, Leclair MD, et al. Tolerance and efficacy of preventive gastrostomy feeding in pediatric oncology. Pediatri Blood Cancer 2012 Nov;5:874e80. [8] Ward E. Childhood cancers. In: Shaw V, Lawson M, editors. Clinical paediatric dietetics. Oxford: Blackwell Publishing; 2007. p. 461e72. [9] Sala A, Penchaz P, Barr RD. Children, cancer, and nutrition e a dynamic triangle in review. Cancer 2004 Feb 15;100(4):677e87. [10] Bauer J, Jürgens H, Frühwald MC. Important aspects of nutrition in children with cancer. Adv Nutr 2011 Mar;2:67e77. [11] Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr 2001 Oct;5(5 Suppl):464Se72S. [12] Ladas E, Kelly KM. The antioxidant debate. Explore Ny 2010;6(2):75e85.
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[13] Department of Health. Dietary reference values for food energy and nutrients for the United Kingdom. London: HMSO; 1999. [14] Gibson RS. Principles of nutritional assessment. 2nd ed. Oxford: Oxford University Press; 2005. [15] Fish and food ministry of agriculture. Standard manual on food portions and household measures in the United Kingdom. [England]. [16] de Onis M. Child growth and development. In: Semba RD, Bloem MW, editors. Nutrition and health in developing countries. 2nd ed. Totowa: Humana Press; 2008. p. 113e7. [17] Lee RD, Nieman DC. Nutritional assessment. London: McGraw-Hill; 2003. [18] Crawford PB, Obarzanek E, Morrison J, Sabry ZI. Comparative advantage of 3-day food records over 24-hour recall and 5-day food frequency validated by observation of 9- and 10-year old girls. J Am Dent Assoc 1994;94: 626e30. [19] Persson LA, Carlgren G. Measuring children's diet: evaluation of dietary assessment techniques in infancy and childhood. Int J Epidemiol 1984 Dec;13(4):506e17. [20] Lawenda B, Kelly K, Ladas E, Sagar S, Vickers A, Blumberg J. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 2008 Jun;100:773e83. [21] Kennedy DD, Tucker KL, Ladas ED, Rheingold SR, Blumberg J, Kelly KM. Low antioxidant vitamin intakes are associated with increases of adverse effects of chemotherapy in children with acute lymphoblastic leukaemia. Am J Clin Nutr 2004 Jun;79:1029e36. [22] Wolbach SB. Vitamin A deficiency and excess in relation to skeletal growth. J Bone Jt Surg Am 1947 Jan;29:171e92. [23] Macdonald RS. The role of zinc in growth and cell proliferation. J Nutr 2000 May;130(5S suppl):1500Se8S. [24] Nish Y. Zinc and growth. J Am Coll Nutr 1996 Aug;15(4):340e4. [25] Siren PM, Siren MJ. Systemic zinc redistribution and dyshomeostasis in cancer cachexia. J Cachexia Sarcopenia Muscle 2010 Sep;1(1):23e33. res JF, The ore ^t Y, Lebel D, Kish S, Moghrabi A, et al. Use of [26] Martel D, Bussie complementary therapies in children with cancer. Paed Blood Cancer 2005 Jun;44:660e8. € tto €nen M, Uhari M. Use of micronutrients and alternative drugs by children [27] Mo with acute lymphoblastic leukemia. Med Pediatr Oncol 1997 Mar;28(3): 205e8. [28] Lima de Araújo L, Maciel Barbosa J, Gomes Ribeiro AP, Oliveira dos Santos AC, Pedrosa F. Nutritional status, dietary intake and serum levels of vitamin C upon diagnosis of cancer in children and adolescents. Nutr Hosp 2012 MareApr;27(2):496e503. [29] Ladas EJ, Jacobson JS, Kennedy DD, Teel K, Fleischauer A, Kelly KM. Antioxidants and cancer therapy: a systematic review. J Clin Oncol 2004;22(3): 517e28. [30] Potischman N, Freudenheim JL. Biomarkers of nutritional exposure and nutritional status: an overview. J Nutr 2003;133(3):873Se4S.
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Contents lists available at ScienceDirect
Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu
Original article
Antioxidant intake in paediatric oncology patients Sonja Slegtenhorst a, b, *, Janicke Visser b, Amos Burke a, Rosan Meyer c a
Dept of Paediatric Haematology and Oncology, Box 181, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Hills Road, Cambridge, Cambridgeshire CB2 0QQ, United Kingdom b Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University, PO BOX 19063, Tygerberg 7505, South Africa c Dept. Gastroenterology, Great Ormond Street Hospital Foundation Trust, London WC1N 3JH, United Kingdom
a r t i c l e i n f o
s u m m a r y
Article history: Received 7 May 2014 Accepted 13 December 2014
Background & aims: Antioxidant intake can affect both free radical and the nutritional status of children receiving cancer treatment. The aim of this study was to investigate whether children with cancer met their antioxidant requirements. Methods: A prospective observational study was performed at a single hospital in England from June 2008 to February 2010. Children with a solid tumour, lymphoma or leukaemia were included. Dietary intakes including 3 modes of feeding (‘diet alone’, ‘diet þ tube’ feeding or ‘diet þ vitamin-mineral supplementation’ (VMS)) were collected with an estimated food record (EFR) 1 and 3 month post-diagnosis. Four and 24-hr food recalls were performed to validate the food records. Results: Forty two children were included: 57% leukaemia or lymphoma and 43% solid tumours. Sixty seven percent underwent chemotherapy and 33% a combination of therapies. In months 1 and 3, greater numbers of children achieved 100% of requirements for ‘diet þ VMS’ (p < 0.05) than for other feeding modes. However, considerable proportions of all feeding groups did not achieve 100% of the Recommended Nutrient Intake (RNI) for vitamin A, C, E, selenium and zinc. This was most marked in the ‘diet alone’ group. Significant proportions did not achieve the Lower Recommended Nutrient Intake (LRNI) for some antioxidants. The ‘diet alone’ group had the highest proportion not meeting LRNI for vitamin A (p << 0.001; 1st month) and zinc (p < 0.02; 3rd month). Conclusion: Inadequate antioxidant intake was observed in a significant proportion of cancer patients when feeding was not augmented in any way. More research is required to determine the clinical implications of these findings. © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Keywords: Antioxidant intake Paediatric Oncology patients
1. Introduction The primary outcomes of nutritional support for children undergoing cancer treatment is to ensure continued age appropriate growth and development throughout treatment, hence preventing malnutrition [1]. Cancer, notwithstanding its treatment, is renowned for its high incidence of malnutrition in children (6%e 50%) and is highly dependent on the type, stage and location of the tumour [2,3]. Malnourished children are at higher risk of infections, worse outcomes, impaired tolerance to chemotherapy, impaired immune function and the need for more frequent chemotherapy
* Corresponding author. Nutrition and Dietetic Department, BOX 119, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Hills Road, Cambridge, Cambridgeshire CB2 0QQ, United Kingdom. Tel.: þ44 (0)1223 216655. E-mail address: [email protected] (S. Slegtenhorst).
dose adjustments. [3e7] An important component of cancer treatment is the nutritional management which ensures adequate antioxidant intake. Considerable benefits are seen in well nourished patients during cancer treatment [6,8e10]. On the other hand, antioxidants also have the potential to reduce the production of free radicals from anti-cancer therapies which may lead to reduced killing of cancer cells [11]. Oncologists have expressed concerns that the protective mechanism of antioxidants may not differentiate between healthy and cancerous cells and additional supplementation could interfere with the anti-cancer activity of conventional therapies [12]. We therefore are presented with a dilemma; adequate antioxidant intake which is essential for normal cellular homeostasis versus a potential theoretical risk of reducing the effectiveness of anti-cancer therapy with antioxidant supplementation. There is paucity of data in antioxidants treatment and requirements during cancer treatment for children.
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We therefore set out to establish the actual dietary intake of antioxidants (vitamin A, E, C, selenium and zinc) in a paediatric oncology population and compared them to the United Kingdom Department of Health's (DOH UK) antioxidant requirements for healthy children [13]. 2. Materials and methods A prospective observational study was performed at Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, England from June 2008 to February 2010. Ethical approval was obtained for this study and informed consent was obtained from all participants prior to enrolment in the study. All newly diagnosed children between 1 and 16 years with solid tumours, lymphomas or leukaemia were eligible to be included in the study. Children on home parenteral nutrition receiving breastmilk, and those less than 1 year of age were excluded from the study. Patients were recruited to the study within 1 month post diagnosis. In this same period, patients were assessed by a paediatric oncology dietitian. All the children received the same dietetic assessment and care. Data was collected by means of two dietary tools; a 4-day estimated food record (EFR) over consecutive days (Wednesday to Saturday) and 4 repeated non-consecutive 24-hr recalls in the 1st and 3rd month post diagnosis [14]. As no validated 4-day EFR existed which aimed at establishing antioxidant intake in paediatrics in the United Kingdom (UK), the researcher adapted an existing food record currently used in the Nutrition and Dietetic Department (Cambridge University Hospitals NHS Foundation Trust, UK) to suit the study's requirement. The 24-hr recall method was performed as a secondary dietary intake measurement (test method) to ensure accuracy and reliability of the EFR. EFR's and 24hr recalls were analysed using the Standard Manual on Food Portions from the Fish and Food Ministry of Agriculture [15]. Anthropometric measurements including weight e [Seca 701 Electronic Personal Scales (GMBH & Co)] and height e Harpenden Stadeometer (Holtain Ltd) and demographic parameters were collected. The weight-for-age z-scores were then assessed against the World Health Organization (WHO) Global Database on Child Growth and Malnutrition [16]. Antioxidant intake (vitamin A, E, C, selenium and zinc) was compared to the RNI, LRNI and Safe Upper Intake commonly used in the UK. As children with cancer treatment are often reliant on a variety of supplements and often require enteral feeding, nutrition intake was categorised for the purpose of analysis into ‘diet alone’, diet and tube feeds (‘diet þ tube’) or diet and vitamin-mineral supplementation (‘diet þ VMS’). 3. Statistics Statistical evaluation was undertaken using SPSS 16 statistical software (SPSS Science, Apache Software Foundation, Chicago, IL, USA) and dietary intake of antioxidants determined using Diet Plan 6.3 programme (Forrestfield Software Limited, Horsham, UK). Nonparametric tests i.e Fishers Exact, and ShapiroeWilk, bivariate correlation and t - tests were used. A p-value 0.05 was considered significant. Both the ShapiroeWilk and Fishers Exact Test was used due to the smaller analysis categories. 4. Results 4.1. Subjects Fifty two children were recruited into the study, however 10 were excluded due to the following reasons: 4 (8%) withdrew from
study; 1 (2%) was not discharged from hospital during treatment; 1 (2%) transferred to an out of area hospital; 4 (8%) consented to study, but did not respond to requests for data. Of the remaining 42 children, 20 were boys (48%) and 22 were girls (52%). The median age was 6 years and 9 months (SD 4.8). Their diagnoses included haematological malignancies (leukaemia; 14 (33%), lymphomas; 10 (24%)) and others (solid tumours; 18 (43%)). Twenty eight (67%) underwent chemotherapy and 14 (33%) a combination of therapies. Two (5%) and 6 (15%) respectively of children in the 1st and 3rd month were found to be malnourished based on z-scores. In the 1st month, 2 (5%) of children achieved a z-score of <-2 and in the 3rd month, 4 (10%) achieved this score. The mean z-score for the study population calculated at the 1st and 3rd month was 0.22 and 0.34 respectively, indicated that the weight of the population remained relatively the same over this period. There was no statistical difference between the three feeding modes for energy and protein intake. 4.2. Vitamin and/or mineral supplement use In the 1st month, 8 (27%) of the children consumed vitamin and/ or mineral supplements and 4 (18%) in the 3rd month. These supplements were either VS or VMS used in approximately equal proportion at each time point. For the purposes of analysis all were analysed in the ‘diet þ VMS’ group. 4.3. Dietary method correlation Of the 42 children's data analysed, 30 (71%) returned their EFR's in the 1st month's collection of data, however the return rate in the 3rd month was less (n ¼ 22; 52%). The validity of the EFR was established through correlation with the 24-hr recalls for both the 1st and 3rd months (Table 1). There was a strong correlation between the EFR and 24-hr recall at both time points for ‘diet alone’ (p << 0.001); the exception being for selenium and zinc at time point 2. For other feeding modes the majority of dietary intakes correlated, however greater day to day variation was seen, in particular in the more complex patients receiving dietary intake and tube feeding. The overall trend however, showed that the children receiving nutritional support showed a higher percentage of RNI antioxidant intake as measured by the EFR method. Underreporting or missing foods is a common limitation of 24-hr recalls, which is related to it's reliance on memory and omissions such as beverages, sauces and supplements are common [17,18]. Several studies in children have found a benefit with using a food diary/
Table 1 Correlation of the Estimated Food Record and 24-hr recall antioxidant intake values for diet alone and antioxidants (1st and 3rd month). r e value
p- value
recall 1 recall 2
0.70 0.70
<<0.001 <<0.001
recall 1 recall 2
0.56 0.72
<<0.001 <<0.001
recall 1 recall 2
0.54 0.45
<<0.001 0.05
recall 1 recall 2
0.64 0.50
<<0.001 0.67
recall 1 recall 2
0.81 0.38
<<0.001 0.10
Antioxidants Vitamin A EFR 1a & 24-hr EFR 2a & 24-hr Vitamin C EFR 1a & 24-hr EFR 2a & 24-hr Vitamin E EFR 1a & 24-hr EFR 2a & 24-hr Selenium EFR 1a & 24-hr EFR 2a & 24-hr Zinc EFR 1a & 24-hr EFR 2a & 24-hr a
EFR ¼ estimated food record.
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history in comparison to 24-hr recalls; for the reason that it does not rely on memory, provides more reliable and detailed intakes (i.e. less missing or phantom foods) [18,19]. A decision was therefore made to use the EFR in preference to the 24-hr recall method. 4.4. Antioxidant intake compared to dietary reference values In all feeding modes there was a proportion of children not achieving 100% of the RNI for vitamin A, C, E, selenium and zinc (Table 2). However, the ‘diet alone’ group was consistently the group receiving inadequate amounts of antioxidants (Table 2); with the intake improved with children on ‘diet þ tube’ and the most replete those on ‘diet þ VMS’. In particular, Vitamin A, selenium and zinc intake were low in the ‘diet alone’ group with the least number of children meeting the LRNI for vitamin A (p << 0.001, 1st month) and zinc (p < 0.02, 3rd month) in comparison to the other feeding modes. Inadequate intakes of zinc and selenium was seen at 1 month in both the ‘diet alone’ group and in a proportion of those who received ‘diet þ VMS’. However the inadequate intake in the ‘diet þ VMS’ group was confined to those children who took supplements containing vitamins only without minerals. At the 3 month time-point the ‘diet alone’ group still had children receiving inadequate (
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leukaemia receiving chemotherapy and/or radiotherapy. Our findings showed a large proportion of children displayed inadequate intakes of antioxidants. The ‘diet alone’ feeding mode was highlighted as the most nutritionally depleted. In contrast more children achieved their RNI receiving tube feeds but the most replete antioxidant intake was found in the group having ‘diet þ VMS’. The adequate intake of antioxidants remains undisputed, however excessive intake is a source of controversy [8,20]. It is therefore likely that in order to achieve optimal age appropriate nutritional requirements, that a combination of feeding modes will be required. This combination will ultimately be dictated by the cancer type, stage of disease and treatment. To our knowledge this is the first study establishing antioxidant intake in this population solely using dietary intake assessment tools. The ‘diet alone’ group (without any tube feeding or supplements) had the greatest number of children not meeting their normal antioxidant requirements, with a significant proportion not achieving even the LRNI. It is not clear what the effect of such inadequate dietary antioxidant intake is on tolerance of chemotherapy or on treatment outcome. We did not observe any significant improvement or change in the antioxidant intake of the ‘diet alone’ group between the assessments at the first and third months. This is consistent with findings from Kennedy et al. [21] whereby the percentage of children (on diet alone) achieving below standard nutrient values did not change appreciably over time. In the ‘diet alone’ group, the majority of the inadequate antioxidant intake was for vitamin A and zinc at both time-points; it is uncertain what additional negative impact this would have had on growth which would already have been affected by illness and cancer therapy. It is well reported that growth failure in children with cancer is multifactorial and in prolonged periods could lead to height growth cessation [7,8]. The aforementioned micronutrients play a key role in growth, by functioning as essential micronutrients in cell differentiation, development and linear growth [22e24]. It has been suggested that a contributing factor to the poor growth is zinc dyshomeostasis and redistribution in cachexic children and that zinc could have deleterious consequences on growth [25]. The weight-for-age scores were suggestive of a nourished population, however this data did not reflect long-term nutrition
Table 2 Percentage of children achieving less than the Lower Recommended Nutrient Intake and 100% of Recommended Nutrient Intake for Antioxidants. EFR 1a 1st month
EFR 2a 3rd month
Diet Diet þ tube Diet þ tube Diet þ VMSb Diet þ VMSb Diet Diet Diet þ tube Diet þ tube Diet þ VMSb Diet þ VMSb Diet 100% RNIc LRNI%d 100% RNIc LRNI%d 100% RNIc LRNI%d 100% RNIc LRNI%d 100%RNIIc LRNI%d 100% RNIc LRNI%d Vitamin A
45%* (5/11) Vitamin C 9% (1/11) Vitamin E~ e Selenium Zinc
9% (1/11) 45%* (5/11)
9% (1/11) 82% (9/11) 55% (6/11) 36% (4/11) 36% (4/11)
0% (0/13) 0% (0/13) e 0% (0/13) 0% (0/13)
46% (6/13) 77% (10/13) 77% (10/13) 69% (9/13) 77% (10/13)
0% (0/8) 0% (0/8) e 29% (2/7) 29% (2/7)
100%* (8/8) 100% (8/8) 88% (7/8) 43% (3/7) 43% (3/7)
50% (5/10) 0%* (0/10) e 30% (3/10) 50%* (5/10)
0% (0/10) 70% (7/10) 50% (5/10) 20% (2/10) 20% (2/10)
25% (2/8) 0%* (0/8) e 0% (0/8) 0% (0/8)
50% (4/8) 88% (7/8) 88% (7/8) 63% (5/8) 63% (5/8)
0% (0/4) 0%* (0/4) e 0% (0/2) 0% (0/2)
75% (3/4) 100% (4/4) 100% (4/4) 50% (1/2) 50% (1/2)
(n) ¼ patient numbers. * Significance at p < 0.05. ( ) Brackets show number of children in that particular mode of feeding achieving less than the Lower Recommended Nutrient Intake or 100% Recommended Nutrient Intake. ~ Vitamin E is measured as a safe intake, no Recommended Nutrient Intake available. *This particular feeding mode had a statistically greater number of children achieving less than the Lower Recommended Nutrient Intake or 100% Recommended Nutrient Intake compared to the other feeding modes in that month. a EFR ¼ estimated food record. b VMS ¼ multi e vitamin-mineral supplementation. c RNI ¼ Recommended Nutrient Intake. d LRNI ¼ Lower Recommended Nutrient Intake.
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which may have been more indicative with weightefor-height scores. In addition without biochemical markers we were unable to pursue this further. The lower intakes of selenium and zinc for the ‘diet þ VMS’ group was due to the greater number of children using vitamin supplements which do not contain these minerals. The greater appeal for a vitamin supplement over a vitamin-mineral supplement was likely due to palatability. Similar percentages of children using vitamins were found in studies by Bussieres et al. [26] and Mottonen and Uhari [27] showing vitamin intakes of 20% and 40% respectively. Tube fed children consistently obtained good intakes for most of the antioxidants with the exception of vitamin A. This low vitamin A intake may be attributed to the poor oral intake than from the tube feed in itself. Overall, ‘diet þ tube’ feeding provided good intakes of antioxidants. The findings above support the delivery of antioxidants via tube feeding; however tube feeding cannot be advocated on antioxidants alone and therefore the child would need a dietary and growth assessment to determine if tube feeding appropriate. One of the vitamins that did consistently achieve good intakes across all the feeding groups was vitamin C. This was seen with values of greater than 200% of the RNI and in some instances up to seven times the RNI. The higher vitamin C results were likely due to the predominant higher intake of fruit juice, squash, tube feeds and vitamin supplements from observation of the dietary analysis. This did raise the concern as to whether the intakes of these children could pose an interference with certain chemotherapy/radiotherapy and/or toxicity. However, the children did not exceed the recommended UK Safe Upper limits of grams per day (unspecified grams) [13]. Although there is limited evidence available on serum vitamin C levels in children and adolescents with cancer [28] Kennedy et al.'s [21] study showed that greater vitamin C intakes at 6 months were associated with fewer therapy delays, less toxicity, and fewer days spent in the hospital [21]. The effect of vitamin A and vitamin E supplementation in relation to different cancers and treatments are very variable and most of the available data relates to adult cancers.[29] Scope for further studies in the paediatric population is required. Fluctuations in daily dietary intake was seen, particularly in the more complex patients requiring nutritional support. These complex patients are usually at higher nutritional risk due to their cancer type, staging and treatment regimes, hence greater variability would be expected. Upon closer inspection the variability in the ‘diet þ tube’ group was compounded by parents' frequent adjustments in feed amounts given to the child during and post treatment sessions. Dietary assessment tools based on recording or recall are clearly limited in this setting and direct measurement of biochemical markers are preferable for future studies. The advantage of biochemical markers, is that in comparison to estimated dietary intakes, they provide accurate measures and correlate better with dietary intake, due to less errors.[30] Estimated dietary intake measurement errors are attributable to the variability in nutrients and food components (ie related to where foods have grown, been processed and cooked (seen with vitamin E and selenium)), subjective data collection, inaccurate completion of dietary tools, poor availability of comprehensive food tables and reliance on memory recall. Limitations include a low sample size which may have influenced the study's results; as this required that generalized feeding modes needed to be created (i.e tube and sip feed group combined). A larger study population would have allowed for specific feeding categories i.e. tube feeds or sips feeds and specific vitamin and mineral supplements. The 24hr recall deemed limiting due to its tendency to underreport in comparison to the EFR, however its main purpose in this study was to perform as a second dietary
intake measurement (test method). Comparative dietary method studies in children showed that 3-day food records showed the greatest agreement between observed and reported intakes in comparison to the 24hr recall and food frequency questionnaire [18], hence the EFR was used as the main dietary tool. A proportion of children had inadequate or excessive reported intakes of antioxidants however without blood/biochemical markers we were unable to verify this; future studies should include these markers. Further studies are required to investigate the clinical significance of such inadequate intakes. 6. Conclusion In this study a large proportion of the children undergoing treatment for leukaemia, lymphoma and solid tumours displayed inadequate intakes of antioxidants. The ‘diet alone’ feeding mode was highlighted as the most nutritionally depleted in antioxidants. This was a consistent trend seen both at diagnosis and 3 months into treatment. The consequences of malnutrition are well documented and are multiple in children who are undernourished compared to those well-nourished during cancer treatment. Vitamin A and zinc were highlighted as especially depleted in the diet alone mode. On the other hand vitamin C consistently achieved good intakes in comparison to the recommended intake. This was found specifically with the children on diet plus vitamins and/or mineral supplements. Further paediatric randomized control studies are required to determine the effect of antioxidant supplementation in cancer treatment and exact guidance on dosage. Based on this study it would seem reasonable to suggest that a vitamin-mineral supplement could be recommended for children who are not receiving any other form of dietary supplementation to ensure that they achieve adequate intake of vitamins A and E; selenium and zinc. It is also important to recognise the pivotal role that parents/carers play in ensuring that children and young people with cancer meet their nutritional requirements. Further studies should validate the EFR dietary tool in assessing antioxidant adequacy in children with cancer by correlation between serum antioxidant levels and the dietary tool assessments. In the future, studies should investigate whether optimal nutritional adequacy (multimodal) is associated with better tolerance of cancer therapies and the effect (if any) of supplementation on the efficacy of cancer treatment. Statement of authorship Sonja Slegtenhorst e developed original concept, wrote the protocol, conducted the study and analysis and prepared the manuscript. Dr Rosan Meyer e facilitated the development of the protocol, analysed the data and contributed to the writing and review of the manuscript. Dr Janicke Visser e facilitated the development of the protocol and reviewed the manuscript. Dr Amos Burke e developed original study concept, participated in study design, interpreted the data and contributed to the writing and review of the manuscript. All authors read and approved the final manuscript. Funding sources No sponsors were used to fund or formulate this study. Conflict of interest The authors have no conflicts of interest.
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Acknowledgements This research project would not have been possible without the support of many people. I wish to express my gratitude to Laura Mcgeeney, Jane, Emerton, Dr Ken Ong, Isla Kuhn, John and Christine Forster for their invaluable support and guidance. Further thanks are extended to the Department of Paediatric Haematology and Oncology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust. The material for this paper was presented for my MSc in Nutrition in December 2011 (Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University). References [1] Rickard KA, Kirksey A, Baehner RL. Effectiveness of enteral and parenteral nutrition in the management of children with Wilm's tumour. Am J Clin Nutr 1980 Dec;56:2881e7. [2] Donaldson SS, Wesley MN, DeWys WK, Suskind RM, Jaffe N, van Eys J. A study of the nutritional status of paediatric cancer patients. Am J Dis Child 1981 Dec;135(12):1107e12. [3] van Eys J. Malnutrition in children with cancer: incidence and consequence. Cancer 1979 May;43(5 Suppl):2030e5. [4] van Eys J. Nutrition in the treatment of cancer in children. J Am Coll Nutr 1984;3(2):159e68. [5] Kibirige MS, Morris-Jones PH, Stevens RF, Rayner C. Nutrition, infection and morbidity in leukaemia. Ped Haem Oncol 1988;5(3):179e85. [6] Andrassy RJ, Chwals WJ. Nutritional support of the pediatric oncology patient. Nutrition 1998 Jan;14(1):124e9. [7] Schmitt F, Caldari D, Corradini N, Gicquel P, Lutz P, Leclair MD, et al. Tolerance and efficacy of preventive gastrostomy feeding in pediatric oncology. Pediatri Blood Cancer 2012 Nov;5:874e80. [8] Ward E. Childhood cancers. In: Shaw V, Lawson M, editors. Clinical paediatric dietetics. Oxford: Blackwell Publishing; 2007. p. 461e72. [9] Sala A, Penchaz P, Barr RD. Children, cancer, and nutrition e a dynamic triangle in review. Cancer 2004 Feb 15;100(4):677e87. [10] Bauer J, Jürgens H, Frühwald MC. Important aspects of nutrition in children with cancer. Adv Nutr 2011 Mar;2:67e77. [11] Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr 2001 Oct;5(5 Suppl):464Se72S. [12] Ladas E, Kelly KM. The antioxidant debate. Explore Ny 2010;6(2):75e85.
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[13] Department of Health. Dietary reference values for food energy and nutrients for the United Kingdom. London: HMSO; 1999. [14] Gibson RS. Principles of nutritional assessment. 2nd ed. Oxford: Oxford University Press; 2005. [15] Fish and food ministry of agriculture. Standard manual on food portions and household measures in the United Kingdom. [England]. [16] de Onis M. Child growth and development. In: Semba RD, Bloem MW, editors. Nutrition and health in developing countries. 2nd ed. Totowa: Humana Press; 2008. p. 113e7. [17] Lee RD, Nieman DC. Nutritional assessment. London: McGraw-Hill; 2003. [18] Crawford PB, Obarzanek E, Morrison J, Sabry ZI. Comparative advantage of 3-day food records over 24-hour recall and 5-day food frequency validated by observation of 9- and 10-year old girls. J Am Dent Assoc 1994;94: 626e30. [19] Persson LA, Carlgren G. Measuring children's diet: evaluation of dietary assessment techniques in infancy and childhood. Int J Epidemiol 1984 Dec;13(4):506e17. [20] Lawenda B, Kelly K, Ladas E, Sagar S, Vickers A, Blumberg J. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 2008 Jun;100:773e83. [21] Kennedy DD, Tucker KL, Ladas ED, Rheingold SR, Blumberg J, Kelly KM. Low antioxidant vitamin intakes are associated with increases of adverse effects of chemotherapy in children with acute lymphoblastic leukaemia. Am J Clin Nutr 2004 Jun;79:1029e36. [22] Wolbach SB. Vitamin A deficiency and excess in relation to skeletal growth. J Bone Jt Surg Am 1947 Jan;29:171e92. [23] Macdonald RS. The role of zinc in growth and cell proliferation. J Nutr 2000 May;130(5S suppl):1500Se8S. [24] Nish Y. Zinc and growth. J Am Coll Nutr 1996 Aug;15(4):340e4. [25] Siren PM, Siren MJ. Systemic zinc redistribution and dyshomeostasis in cancer cachexia. J Cachexia Sarcopenia Muscle 2010 Sep;1(1):23e33. res JF, The ore ^t Y, Lebel D, Kish S, Moghrabi A, et al. Use of [26] Martel D, Bussie complementary therapies in children with cancer. Paed Blood Cancer 2005 Jun;44:660e8. € tto €nen M, Uhari M. Use of micronutrients and alternative drugs by children [27] Mo with acute lymphoblastic leukemia. Med Pediatr Oncol 1997 Mar;28(3): 205e8. [28] Lima de Araújo L, Maciel Barbosa J, Gomes Ribeiro AP, Oliveira dos Santos AC, Pedrosa F. Nutritional status, dietary intake and serum levels of vitamin C upon diagnosis of cancer in children and adolescents. Nutr Hosp 2012 MareApr;27(2):496e503. [29] Ladas EJ, Jacobson JS, Kennedy DD, Teel K, Fleischauer A, Kelly KM. Antioxidants and cancer therapy: a systematic review. J Clin Oncol 2004;22(3): 517e28. [30] Potischman N, Freudenheim JL. Biomarkers of nutritional exposure and nutritional status: an overview. J Nutr 2003;133(3):873Se4S.
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