Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral/neurodevelopmental disorder. Some early studies indicated that increased intake of added sugars might have a role in ADHD. In the present study, we tested this possibility by evaluating the urinary excretion of oligosaccharides and glycosaminoglycans (GAGs) in ADHD and control subjects. Forty ADHD subjects matched with 34 controls were enrolled in the study. The subjects underwent a standardized dietary regimen. The urine levels of oligosaccharides and GAGs were quantified biochemically, and their covariance and association were evaluated statistically. Fructose (21/40, 52.5%), maltose (26/40, 65%), galactose (30/40, 75%), and lactose (38/40, 95%) excretions were frequently found in the urine of ADHD subjects (p < 0.05), an excretion which does not occur normally. Furthermore, these subjects showed a pathologic tGAG (glycosaminoglycan) excretion (40/40, 100%). The present study supports the thesis that carbohydrate metabolism differs in ADHD subjects compared with control subjects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albayrak Ö, Pütter C, Volckmar AL, Cichon S, Hoffmann P, Nöthen MM, Jöckel KH, Schreiber S, Wichmann HE, Faraone SV, Neale BM, Herpertz-Dahlmann B, Lehmkuhl G, Sinzig J, Renner TJ, Romanos M, Warnke A, Lesch KP, Reif A, Schimmelmann BG, Scherag A, Hebebrand J, Hinney A, Psychiatric GWAS Consortium: ADHD Subgroup (2013) Common obesity risk alleles in childhood attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 162B:295–305. https://doi.org/10.1002/ajmg.b.32144
American Academy of Pediatrics (2000) Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics 105:1158–1170. https://doi.org/10.1542/peds.105.5.1158
Banaschewski T, Becker K, Scherag S, Franke B, Coghill D (2010) Molecular genetics of attention-deficit/hyperactivity disorder: an overview. Eur Child Adolesc Psychiatry 19:237–257. https://doi.org/10.1007/s00787-010-0090-z
Banaschewski T, Becker K, Dopfner M, Holtmann M, Rosler M, Romanos M (2017) Attention-deficit/hyperactivity disorder. Dtsch Arztebl Int 114:149–159. https://doi.org/10.3238/arztebl.2017.0149
Breggin PR (2000) The NIMH multimodal study of treatment for attention-deficit/hyperactivity disorder: a critical analysis. Int J Risk Saf Med 13:15–22
Endreffy I, Dicso F (1988) Glycosaminoglycan excretion in connective tissue diseases. Clin Biochem 21:135–138. https://doi.org/10.1016/s0009-9120(88)80103-6
Endreffy I, Bjørklund G, Dicso F, Urbina MA, Endreffy E (2016) Acid glycosaminoglycan (aGAG) excretion is increased in children with autism spectrum disorder, and it can be controlled by diet. Metab Brain Dis 31:273–278. https://doi.org/10.1007/s11011-015-9745-2
Ernst M, Cohen RM, Liebenauer LL, Jons PH, Zametkin AJ (1997) Cerebral glucose metabolism in adolescent girls with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 36:1399–1406. https://doi.org/10.1097/00004583-199710000-00022
Felt JM, Castaneda R, Tiemensma J, Depaoli S (2017) Using person fit statistics to detect outliers in survey research. Front Psychol 8:863. https://doi.org/10.3389/fpsyg.2017.00863
Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP (2017) Educational and health outcomes of children treated for attention-deficit/hyperactivity disorder. JAMA Pediatr 171:e170691. https://doi.org/10.1001/jamapediatrics.2017.0691
Fukuzawa T, Fukazawa M, Ueda O, Shimada H, Kito A, Kakefuda M, Kawase Y, Wada NA, Goto C, Fukushima N, Jishage K, Honda K, King GL, Kawabe Y (2013) SGLT5 reabsorbs fructose in the kidney but its deficiency paradoxically exacerbates hepatic steatosis induced by fructose. PLoS One 8:e56681. https://doi.org/10.1371/journal.pone.0056681
Gowd V, Gurukar A, Chilkunda ND (2016) Glycosaminoglycan remodeling during diabetes and the role of dietary factors in their modulation. World J Diabetes 7:67–73. https://doi.org/10.4239/wjd.v7.i4.67
Hendriksz CJ, Muenzer J, Vanderver A, Davis JM, Burton BK, Mendelsohn NJ, Wang N, Pan L, Pano A, Barbier AJ (2015) Levels of glycosaminoglycans in the cerebrospinal fluid of healthy young adults, surrogate-normal children, and hunter syndrome patients with and without cognitive impairment. Mol Genet Metab Rep 5:103–106. https://doi.org/10.1016/j.ymgmr.2015.11.001
Herrerias CT, Perrin JM, Stein MT (2001) The child with ADHD: using the AAP clinical practice guideline. American Academy of Pediatrics. Am Fam Physician 63:1803–1810
Herska M, Moscovich DG, Kalian M, Gottlieb D, Bach G (1987) Aryl sulfatase a deficiency in psychiatric and neurologic patients. Am J Med Genet 26:629–635. https://doi.org/10.1002/ajmg.1320260318
Hiebert LM (2017) Proteoglycans and diabetes. Curr Pharm Des 23:1500–1509. https://doi.org/10.2174/1381612823666170125154915
Hiebert LM, Han J, Mandal AK (2014) Glycosaminoglycans, hyperglycemia, and disease. Antioxid Redox Signal 21:1032–1043. https://doi.org/10.1089/ars.2013.5695
Highsmith S, Garvin JH Jr, Chipman DM (1975) Mechanism of action of bovine testicular hyaluronidase mapping of the active site. J Biol Chem 250:7473–7480
Johnson RJ, Gold MS, Johnson DR, Ishimoto T, Lanaspa MA, Zahniser NR, Avena NM (2011) Attention-deficit/hyperactivity disorder: is it time to reappraise the role of sugar consumption? Postgrad Med 123:39–49. https://doi.org/10.3810/pgm.2011.09.2458
Kaplan G, Newcorn JH (2011) Pharmacotherapy for child and adolescent attention-deficit hyperactivity disorder. Pediatr Clin N Am 58(99–120):xi. https://doi.org/10.1016/j.pcl.2010.10.009
Koekkoek LL, Mul JD, la Fleur SE (2017) Glucose-sensing in the reward system. Front Neurosci 11:716. https://doi.org/10.3389/fnins.2017.00716
Lepedda AJ, De Muro P, Capobianco G, Formato M (2017) Significance of urinary glycosaminoglycans/proteoglycans in the evaluation of type 1 and type 2 diabetes complications. J Diabetes Complicat 31:149–155. https://doi.org/10.1016/j.jdiacomp.2016.10.013
Lindblad F, Eickhoff M, Forslund AH, Isaksson J, Gustafsson J (2015) Fasting blood glucose and HbA1c in children with ADHD. Psychiatry Res 226:515–516. https://doi.org/10.1016/j.psychres.2015.01.028
Lloyd G, Stead J, Cohen D (2006) Critical new perspectives on ADHD. Routledge Eds, Oxford
Matochik JA, Liebenauer LL, King AC, Szymanski HV, Cohen RM, Zametkin AJ (1994) Cerebral glucose metabolism in adults with attention deficit hyperactivity disorder after chronic stimulant treatment. Am J Psychiatry 151:658–664. https://doi.org/10.1176/ajp.151.5.658
Olsson U, Egnell AC, Lee MR, Lundén GO, Lorentzon M, Salmivirta M, Bondjers G, Camejo G (2001) Changes in matrix proteoglycans induced by insulin and fatty acids in hepatic cells may contribute to dyslipidemia of insulin resistance. Diabetes 50:2126–2132. https://doi.org/10.2337/diabetes.50.9.2126
Peres GB, Juliano MA, Simoes MJ, Michelacci YM (2013) Lysosomal enzymes are decreased in the kidney of diabetic rats. Biochim Biophys Acta 1832:85–95. https://doi.org/10.1016/j.bbadis.2012.09.011
Rafalovich A (2005) Exploring clinician uncertainty in the diagnosis and treatment of attention deficit hyperactivity disorder. Sociol Health Illn 27:305–323. https://doi.org/10.1111/j.1467-9566.2005.00444.x
Reed MO, Jakubovski E, Johnson JA, Bloch MH (2017) Predictors of long-term school-based behavioral outcomes in the multimodal treatment study of children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 27:296–309. https://doi.org/10.1089/cap.2015.0168
Schäfer N, Friedrich M, Jørgensen ME, Kollert S, Koepsell H, Wischmeyer E, Lesch KP, Geiger D, Döring F (2018) Functional analysis of a triplet deletion in the gene encoding the sodium glucose transporter 3, a potential risk factor for ADHD. PLoS One 13:e0205109. https://doi.org/10.1371/journal.pone.0205109
Selekman J (2002) Attention-deficit/hyperactivity disorder. J Sch Nurs 18:270–276. https://doi.org/10.1177/10598405020180050601
Thapar A, Cooper M (2016) Attention deficit hyperactivity disorder. Lancet 387:1240–1250. https://doi.org/10.1016/S0140-6736(15)00238-X
Visser J, Jehan Z (2009) ADHD: a scientific fact or a factual opinion? A critique of the veracity of attention deficit hyperactivity disorder. Emot Behav Diffic 14:127–140
Voss AA, Diez-Sampedro A, Hirayama BA, Loo DD, Wright EM (2007) Imino sugars are potent agonists of the human glucose sensor SGLT3. Mol Pharmacol 71:628–634. https://doi.org/10.1124/mol.106.030288
Wasserman T, Wasserman LD (2015) The misnomer of attention-deficit hyperactivity disorder. Appl Neuropsychol Child 4:116–122. https://doi.org/10.1080/21622965.2015.1005487
Wu W, Yang D, Tiselius HG, Ou L, Mai Z, Chen K, Zhu H, Xu S, Zhao Z, Zeng G (2015) Collection and storage of urine specimens for measurement of urolithiasis risk factors. Urology 85:299–303. https://doi.org/10.1016/j.urology.2014.10.030
Yousefi Chaijan P, Sharafkhah M, Salehi B, Rafiei M (2015) Attention deficit hyperactivity disorder in children with early stages of chronic kidney disease. Med J Islam Repub Iran 29:181
Yu CJ, Du JC, Chiou HC, Feng CC, Chung MY, Yang W, Chen YS, Chien LC, Hwang B, Chen ML (2016) Sugar-sweetened beverage consumption is adversely associated with childhood attention deficit/hyperactivity disorder. Int J Environ Res Public Health 13(7). https://doi.org/10.3390/ijerph13070678
Zendarski N, Sciberras E, Mensah F, Hiscock H (2017) Early high school engagement in students with attention/deficit hyperactivity disorder. Br J Educ Psychol 87:127–145. https://doi.org/10.1111/bjep.12140
Acknowledgments
The authors thank Dénes Kövendi M.D. and Éva Sátorhegyi M.D. for the assistance of diagnosis.
Author information
Authors and Affiliations
Contributions
All authors confirmed they have contributed to the intellectual content of this paper and have met the following three requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Corresponding authors
Ethics declarations
Conflict of Interest
The authors declare that they have no conflicts of interest.
Ethical Approval
All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Endreffy, I., Bjørklund, G., Urbina, M.A. et al. High Levels of Glycosaminoglycans in the Urines of Children with Attention-Deficit/Hyperactivity Disorder (ADHD). J Mol Neurosci 70, 1018–1025 (2020). https://doi.org/10.1007/s12031-020-01496-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-020-01496-w