An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders

Clinical Therapeutics

Volumn 35, Issue 5, 2013, Pages 592-602

  Taliou, Anilia ^a   Zintzaras, Elias ^b   Lykouras, Lefteris ^a   Francis, Kostantinos ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b UNIVERSITY OF THESSALY   (Greece)

Author keywords

ASD; Brain; Flavonoids; Inflammation; Luteolin

Indexed keywords

LUTEOLIN; QUERCETIN; RUTOSIDE;

ABDOMINAL PAIN; ARTICLE; AUTISM; CHILD; CHILD BEHAVIOR; CLINICAL ARTICLE; CLINICAL TRIAL; DAILY LIFE ACTIVITY; DIET SUPPLEMENTATION; DISORIENTATION; DRUG ABSORPTION; DRUG EFFICACY; DRUG FORMULATION; DRUG TOLERABILITY; FEMALE; GASTROENTERITIS; HUMAN; INCREASED APPETITE; IRRITABILITY; MALE; OPEN STUDY; PILOT STUDY; PRESCHOOL CHILD; PROSPECTIVE STUDY; SCHOOL CHILD; SIDE EFFECT; SLEEP DISORDER; SPEECH DISORDER; TIC;

ADMINISTRATION, ORAL; ANTI-INFLAMMATORY AGENTS; CHILD; CHILD DEVELOPMENT DISORDERS, PERVASIVE; CHILD, PRESCHOOL; DIETARY SUPPLEMENTS; DRUG COMBINATIONS; FEMALE; GREECE; HUMANS; LUTEOLIN; MALE; PILOT PROJECTS; PROSPECTIVE STUDIES; QUERCETIN; RUTIN; TREATMENT OUTCOME;

EID: 84877905373     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2013.04.006     Document Type: Article

References (50)

1. McPartland J., Volkmar F.R. Autism and related disorders. Handb Clin Neurol 2012, 106:407-418.
2. Johnson C.P., Myers S.M. American Academy of Pediatrics Council on Children With Disabilities. Identification and evaluation of children with autism spectrum disorders. Pediatrics 2007, 120:1183-1215.
3. Autism, Developmental Disabilities Monitoring Network Surveillance Year Principal I, Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 2012, 61:1-19.
4. Kim Y.S., Leventhal B.L., Koh Y.J., et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry 2011, 168:904-912.
5. Broadstock M., Doughty C., Eggleston M. Systematic review of the effectiveness of pharmacological treatments for adolescents and adults with autism spectrum disorder. Autism 2007, 11:335-348.
6. Rogers S.J., Vismara L.A. Evidence-based comprehensive treatments for early autism. J Clin Child Adolesc Psychol 2008, 37:8-38.
7. King B.H., Hollander E., Sikich L., et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry 2009, 66:583-590.
8. McPheeters M.L., Warren Z., Sathe N., et al. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics 2011, 127:e1312-e1321.
9. Canitano R. Novel treatments in autism spectrum disorders: from synaptic dysfunction to experimental therapeutics. Behav Brain Res 2012 Nov 29, [E-pub ahead of print].
10. Smile S., Anagnostou E. New models for considering the role of medication in the treatment and elucidation of the etiology of autism. Curr Psychiatry Rep 2012, 14:726-731.
11. Theoharides T.C., Doyle R., Francis K., et al. Novel therapeutic targets for autism. Trends Pharmacol Sci 2008, 29:375-382.
12. Theoharides T.C., Zhang B., Conti P. Decreased mitochondrial function and increased brain inflammation in bipolar disorder and other neuropsychiatric diseases. J Clin Psychopharmacol 2011, 31:685-687.
13. Hagberg H., Gressens P., Mallard C. Inflammation during fetal and neonatal life: implications for neurologic and neuropsychiatric disease in children and adults. Ann Neurol 2012, 71:444-457.
14. El-Ansary A., Al-Ayadhi L. Neuroinflammation in autism spectrum disorders. J Neuroinflammation 2012, 9:265.
15. Pardo C.A., Vargas D.L., Zimmerman A.W. Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry 2005, 17:485-495.
16. Ashwood P., Wills S., Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol 2006, 80:1-15.
17. Gurney J.G., McPheeters M.L., Davis M.M. Parental report of health conditions and health care use among children with and without autism: National Survey of Children's Health. Arch Pediatr Adolesc Med 2006, 160:825-830.
18. Magalhaes E.S., Pinto-Mariz F., Bastos-Pinto S., et al. Immune allergic response in Asperger syndrome. J Neuroimmunol 2009, 216:108-112.
19. Angelidou A., Alysandratos K.D., Asadi S., et al. Brief report: "allergic symptoms" in children with autism spectrum disorders. More than meets the eye?. J Autism Dev Disord 2011, 41:1579-1585.
20. Jyonouchi H. Autism spectrum disorders and allergy: observation from a pediatric allergy/immunology clinic. Expert Rev Clin Immunol 2010, 6:397-411.
21. Theoharides T.C., Angelidou A., Alysandratos K.D., et al. Mast cell activation and autism. Biochim Biophys Acta 2012, 1822:34-41.
22. Theoharides T.C. Autism spectrum disorders and mastocytosis. Int J Immunopathol Pharmacol 2009, 22:859-865.
23. Middleton E., Kandaswami C., Theoharides T.C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000, 52:673-751.
24. Kempuraj D., Madhappan B., Christodoulou S., et al. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol 2005, 145:934-944.
25. Parker-Athill E., Luo D., Bailey A., et al. Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism. J Neuroimmunol 2009, 217:20-27.
26. Theoharides T.C., Asadi S., Panagiotidou S. A case series of a luteolin formulation (NeuroProtek(R)) in children with autism spectrum disorders. Int J Immunopathol Pharmacol 2012, 25:317-323.
27. Diagnostic Criteria from DSM-IV-TR 2000, American Psychiatric Association, American Psychiatric Association, Washington, DC.
28. Lord C., Risi S., Lambrecht L., et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 2000, 30:205-223.
29. Shimoi K., Okada H., Furugori M., et al. Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans. FEBS Lett 1998, 438:220-224.
30. Subiza J., Subiza J.L., Hinojosa M., et al. Anaphylactic reaction after the ingestion of chamomile tea: a study of cross-reactivity with other composite pollens. J Allergy Clin Immunol 1989, 84:353-358.
31. Sparrow S.S., Balla D., Cicchetti D.V. Vineland Adaptive Behavior Scales-Survey Edition 1984, American Guidance Service, Circle Pines, Minn.
32. Scahill L., Lord C. Subject selection and characterization in clinical trials in children with autism. CNS Spectr 2004, 9:22-32.
33. Aman M.G., Singh N.N., Stewart A.W., Field C.J. Psychometric characteristics of the aberrant behavior checklist. Am J Ment Defic 1985, 89:492-502.
34. Rimland B., Edelson M. Autism Treatment Evaluation Checklist: Statistical Analyses 2000, Autism Research Institute, San Diego, CA.
35. Berk M., Ng F., Dodd S., et al. The validity of the CGI severity and improvement scales as measures of clinical effectiveness suitable for routine clinical use. J Eval Clin Pract 2008, 14:979-983.
36. Carter A.S., Volkmar F.R., Sparrow S.S., et al. The Vineland Adaptive Behavior Scales: supplementary norms for individuals with autism. J Autism Dev Disord 1998, 28:287-302.
37. Williams S.K., Scahill L., Vitiello B., et al. Risperidone and adaptive behavior in children with autism. J Am Acad Child Adolesc Psychiatry 2006, 45:431-439.
38. Rothman K.J. No adjustments are needed for multiple comparisons. Epidemiology 1990, 1:43-46.
39. Anderson D., Oti R., Lord C., Welch K. Patterns of growth in adaptive social abilities among children with autism spectrum disorders. J Abnorm Child Psychol 2009, 37:1019-1034.
40. Freeman B., Del'Homme M., Guthrie D., Zhang F. Vineland Adaptive Behavior Scale scores as a function of age and initial IQ in 210 autistic children. J Autism Dev Disord 1999, 29:379-384.
41. Harris S.L., Handleman J.S., Belchic J., Glasberg B. The Vineland Adaptive Behavior Scales for young children with autism. Spec Serv Schools 1995, 10:45-54.
42. Fisch G.S., Simensen R.J., Schroer R.J. Longitudinal changes in cognitive and adaptive behavior scores in children and adolescents with the fragile X mutation or autism. J Autism Dev Disord 2002, 32:107-114.
43. Charman T., Howlin P., Berry B., Prince E. Measuring developmental progress of children with autism spectrum disorder on school entry using parent report. Autism 2004, 8:89-100.
44. McCracken J.T., McGough J., Shah B., et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002, 347:314-321.
45. Magiati I., Moss J., Yates R., et al. Is the Autism Treatment Evaluation Checklist a useful tool for monitoring progress in children with autism spectrum disorders?. J Intellect Disabil Res 2011, 55:302-312.
46. Kadouri A., Corruble E., Falissard B. The improved Clinical Global Impression Scale (iCGI): development and validation in depression. BMC Psychiatry 2007, 7:7.
47. Forkmann T., Scherer A., Boecker M., et al. The Clinical Global Impression Scale and the influence of patient or staff perspective on outcome. BMC Psychiatry 2011, 11:83.
48. Kraemer H.C., Wilson G.T., Fairburn C.G., Agras W.S. Mediators and moderators of treatment effects in randomized clinical trials. Arch Gen Psychiatry 2002, 59:877-883.
49. Harwood M., Danielewska-Nikiel B., Borzelleca J.F., et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 2007, 45:2179-2205.
50. Kawanishi S., Oikawa S., Murata M. Evaluation for safety of antioxidant chemopreventive agents. Antioxid Redox Signal 2005, 7:1728-1739.