Association of Brain Derived Neurotrophic Factor with Iron as well as Vitamin D, Folate and Cobalamin in Pediatric Metabolic Syndrome
The impact of metabolic syndrome (MetS) on cognition and functions of the brain is being investigated. Iron deficiency and deficiencies of B9 (folate) as well as B12 (cobalamin) vitamins are best-known nutritional anemias. They are associated with cognitive disorders and learning difficulties. The antidepressant effects of vitamin D are known and the deficiency state affects mental functions negatively. The aim of this study is to investigate possible correlations of MetS with serum brain-derived neurotrophic factor (BDNF), iron, folate, cobalamin and vitamin D in pediatric patients. 30 children, whose age- and sex-dependent body mass index (BMI) percentiles vary between 85 and 15, 60 morbid obese children with above 99th percentiles constituted the study population. Anthropometric measurements were taken. BMI values were calculated. Age- and sex-dependent BMI percentile values were obtained using the appropriate tables prepared by the World Health Organization (WHO). Obesity classification was performed according to WHO criteria. Those with MetS were evaluated according to MetS criteria. Serum BDNF was determined by enzyme-linked immunosorbent assay. Serum folate was analyzed by an immunoassay analyzer. Serum cobalamin concentrations were measured using electrochemiluminescence immunoassay. Vitamin D status was determined by the measurement of 25-hydroxycholecalciferol [25-hydroxy vitamin D3, 25(OH)D] using high performance liquid chromatography. Statistical evaluations were performed using SPSS for Windows, version 16. The p values less than 0.05 were accepted as statistically significant. Although statistically insignificant, lower folate and cobalamin values were found in MO children compared to those observed for children with normal BMI. For iron and BDNF values, no alterations were detected among the groups. Significantly decreased vitamin D concentrations were noted in MO children with MetS in comparison with those in children with normal BMI (p ≤ 0.05). The positive correlation observed between iron and BDNF in normal-BMI group was not found in two MO groups. In THE MetS group, the partial correlation among iron, BDNF, folate, cobalamin, vitamin D controlling for waist circumference and BMI was r = -0.501; p ≤ 0.05. None was calculated in MO and normal BMI groups. In conclusion, vitamin D should also be considered during the assessment of pediatric MetS. Waist circumference and BMI should collectively be evaluated during the evaluation of MetS in children. Within this context, BDNF appears to be a key biochemical parameter during the examination of obesity degree in terms of mental functions, cognition and learning capacity. The association observed between iron and BDNF in children with normal BMI was not detected in MO groups possibly due to development of inflammation and other obesity-related pathologies. It was suggested that this finding may contribute to mental function impairments commonly observed among obese children.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.3669291Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 85
 A. A. Nikonorov, M. G. Skalnaya, A. A. Tinkov, and A. V. Skalny, “Mutual interaction between iron homeostasis and obesity pathogenesis,” J Tr El Med Biol, vol. 30, pp. 207-214, Apr. 2015.
 C. A. Hutchinson, “A review of iron studies in overweight and obese children and adolescents: a double burden in the young?” Eur. J. Nutr., vol. 55, pp. 2179–2197, 2016
 M. Citelli, T. Faria, V. Silva, M. Martins, R. Silva, A. Luna et.al., “Obesity promotes alterations in iron recycling,” Nutrients, vol. 7, pp. 335-348, 2015.
 S. A. Ritchie, and J. M. C. Connell, “The link between abdominal obesity, metabolic syndrome and cardiovascular disease,” Nutr. Metab. Cardiovasc. Dis., vol. 17, pp. 319-326, 2007.
 A. Del Parigi, F. Panza, C. Capurso, and V. Solfrizzi, “Nutritional factors, cognitive decline and dementia,” Brain. Res. Bull., vol 69, no. 1, pp.1-19, Mar. 2006.
 R. Green, and A. D. Mitra, “Megaloblastic anemias: Nutritional and other causes,” Med. Clin. North Am., vol 101, no. 2, pp. 297-317, Mar. 2017.
 M. M. Donma and O. Donma, “Cobalamin, folate and metabolic syndrome parameters in pediatric morbid obesity and metabolic syndrome,” Int J Med Health Sci, vol.12, no.5, pp.249-252, May 2018.
 M. S. Boulkrane, J. Fedotova , V. Kolodyaznaya, V. Micale, F. Drago, A. J. M. V. den Tol et. al., “Vitamin D and depression in women: a mini-review,” Curr. Neuropharmacol., Nov. 2019, (E-pub ahead of print).
 J. Zugic-Soares, R. Pettersen, J. Saltyte Benth, A. B. Knapskog, G. Selbaek, and N. Bogdanovic, “Higher vitamin D levels are associated with better attentional functions: Data from the NorCog Register,” J. Nutr. Health Aging, vol. 23, no.8, pp. 725-731, 2019.
 O. Donma and M. M. Donma, “Evaluation of vitamin D levels in obese and morbid obese children,” Int J Med Health Sci, vol.12, no.5, pp.245-248, May 2018.
 R. A. H. Adan, E. M. van der Beek, J. K. Buitelaar, J. F. Cryan, J. Hebebrand, S. Higgs et. al., “Nutritional psychiatry: Towards improving mental health by what you eat,” Eur. Neuropsychopharmacol., Nov. 2019, (E-pub ahead of print
 S. Araki, Y. Yamamoto, K. Dobashi, K. Asayama, and K. Kusuhara, “Decreased plasma levels of brain-derived neurotrophic factor and its relationship with obesity and birth weight in obese Japanese children,” Obes. Res. Clin. Pract., vol.8, no.1, pp. e63-e69, Jan.-Feb. 2014.
 J. D. Martínez-Ezquerro, M. E. Rendón-Macías, G. Zamora-Mendoza, J. Serrano-Meneses, B. Rosales-Rodriguez, D. Escalante-Bautista et al., “Association between the brain-derived neurotrophic factor val66met polymorphism and overweight/obesity in pediatric population,” Arch. Med. Res., vol. 48, no. 7, pp. 599-608, Oct. 2017.
 L. Lughetti, E. Casarosa, B. Predieri, V. Patianna, and S. Luisi, “Plasma brain-derived neurotrophic factor concentrations in children and adolescents,” Neuropeptides, vol. 45, no. 3, pp.205-211, Jun. 2011.
 A. H. El-Gharbawy, D. C. Adler-Wailes, M. C. Mirch, K. R. Theim, L. Ranzenhofer, M. Tanofsky-Kraff et al., “Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents,” J. Clin. Endocrinol. Metab., vol. 91, no. 9, pp. 3548-3552, Sep. 2006.
 C. C. Lin, C. T. Lee, Y. T. Lo, T. L. Huang, “Brain-derived neurotrophic factor protein and mRNA levels in patients with bipolar mania-A preliminary study,” Biomed. J., vol. 39, no. 4, pp. 272-276, Aug. 2016.
 S. Mehrpouya, A. Nahavandi, F. Khojasteh, M. Soleimani, M. Ahmadi, and M. Barati, “Iron administration prevents BDNF decrease and depressive-like behavior following chronic stress,” Brain Res., vol. 1596, pp. 79-87, Jan. 2015.
 J. A. Estrada, I. Contreras, F. B. Pliego-Rivero, and G. A. Otero, “Molecular mechanisms of cognitive impairment in iron deficiency: alterations in brain-derived neurotrophic factor and insulin-like growth factor expression and function in the central nervous system,” Nutr. Neurosci., vol. 17, no. 5, pp. 193-206, 2014.
 S. Motamedi, I. Karimi, and F. Jafari, “The interrelationship of metabolic syndrome and neurodegenerative diseases with focus on brain-derived neurotrophic factor (BDNF): Kill two birds with one stone,” Metab. Brain Dis., vol 32, no. 3, pp. 651-665, Jun. 2017.
 World Health Organization (WHO). The WHO Child Growth Standards. Available at: http://www.who.int/childgrowth/en/ Accessed on June 10, 2016.
 P. Zimmet, K. G. Alberti, F. Kaufman, N. Tajima, M. Silink, S. Arslanian, G. Wong, P. Bennett, J. Shaw, S. Caprio, and IDF consensus group, “The metabolic syndrome in children and adolescents- an IDF consensus report”, Pediatr. Diabetes, vol. 8, no. 5, pp. 299 - 306, Oct. 2007.
 F. P. N. Arcanjo, C. P. C Arcanjo, and P. R. Santos, “School children with learning difficulties have low iron status and high anemia prevalence,” J. Nutr. Metab., vol. 2016, Article ID. 73571, 2016.
 R. Haussman, C. Sauer, S. Neumann, A. Zweiniger, J. Lange, and M. Donix, “Folic acid and vitamin B12 determination in the assessment of cognitive disorders,” Nervenarzt, vol.90, no. 11, pp. 1162-1169, Nov. 2019.
 J. I. B. Botella-Carretero, F. Alvarez-Blasco, JJ Villafruela, J. A. Balsa, C. Vazquez, and H. F. Escobar-Morreale, “Vitamin D deficiency is associated with the metabolic syndrome in morbid obesity,” Clin. Nutr., vol.26, no.5, pp.573-580, Nov. 2007.
 J. M. Ordonez-Mena, B. Schottker, V. Fedirko, M. Jenab, A. Olsen, J. Halkjaer, et al., “Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an analysis of cohorts participating in the CHANCES consortium,” Eur. J. Epidemiol., vol. 31, no.3, pp. 311-323, Mar. 2016
 M. Matejcic, J. de Batlle, C. Ricci, C. Biessy, F. Perrier, I, Huybrechts et al, “Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort,” Int. J. Cancer, vol. 140, no. 6, pp. 1246-1259, Mar. 2017.
 B. Krusinska, L. Wadolowska, M. Biernacki, M. A. Slowinska, and M. Drozdowski, “Serum “vitamin-mineral” profiles. Associations with postmenaupausal breast cancer risk including dietary patterns and supplementation. A case-control study,” Nutrients, vol.11, pp.2244, 2019.