21 research outputs found
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
Background: Accumulating evidence suggests an association between autism
spectrum disorders (ASD) and inflammation in brain regions related to
cognitive function. The natural flavonoid luteolin has antioxidant,
anti-inflammatory, mast cell blocking, and neuroprotective effects. It
was shown to improve cognitive performance in a mouse model of ASD, but
its effect in humans has not been adequately studied.
Objectives: The goal of this study was to assess the effectiveness and
tolerability in white children with ASD of a dietary supplement
containing 2 flavonoids (>95% pure), luteolin (100 mg/capsule, from
chamomile) and quercetin (70 mg/capsule), and the quercetin glycoside
rutin (30 mg/capsule) from the Sophora japonica leaf, formulated in
olive kernel oil to increase oral absorption.
Methods: Fifty children (4-10 years old; 42 boys and 8 girls) with ASD
were enrolled in a 26-week, prospective, open-label trial at the 2nd
University Department of Psychiatry at “Attikon” General Hospital,
Athens, Greece. Children were referred for the study by their respective
physicians or came from the practice of the senior author. ASD diagnosis
by clinical assessment was based on the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition, Text Revision, symptom list
and corroborated by using the Autism Diagnostic Observation Schedule.
The dose of the study formulation used was 1 capsule per 10 kg weight
per day with food. The primary outcome measures were the age-equivalent
scores in the Vineland Adaptive Behavior Scales domains. Secondary
outcomes included the Aberrant Behavior Checklist, the Autism Treatment
Evaluation Checklist, and the Clinical Global Impression Improvement
score. Data were measured at baseline, week 18, and week 26. Parents
were interviewed for any possible improvements they noticed and
instructed to report any unusual adverse events.
Results: A total of 40 children completed the protocol. There was a
significant improvement in adaptive functioning as measured by using the
VABS age-equivalent scores (8.43 months in the communication domain,
7.17 months in daily living skills, and 8 months in the social domain; P
< 0.005), as well as in overall behavior as indicated by the reduction
(26.6%-34.8%) in Aberrant Behavior Checklist subscale scores. Age,
sex, and history of allergies had no effect on the results, whereas the
initial level of functioning or difficulty did predict the final outcome
in most of the measures used. There was a transient (1-8 weeks)
increased irritability in 27 of the 50 participants.
Conclusions: These results are encouraging in that the combination of
the flavonoids luteolin and quercetin seemed to be effective in reducing
ASD symptoms, with no major adverse effects. (c) 2013 Elsevier HS
Journals, Inc. All rights reserved
Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6
Autism spectrum disorders (ASDs) have been associated with brain inflammation as indicated by microglia activation, as well as brain expression and increased plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF). Here we report that serum levels of IL-6 and TNF were elevated (61.95±94.76 pg ml-1 313.8 ±444.3 pg ml-1, respectively) in the same cohort of patients with elevated serum levels of corticotropin-releasing hormone (CRH) and neurotensin (NT), while IL-9, IL-31 and IL-33 were not different from controls. The elevated CRH and NT levels did not change after treatment with a luteolin-containing dietary formulation. However, the mean serum IL-6 and TNF levels decreased significantly (P=0.036 and P=0.015, respectively) at the end of the treatment period (26 weeks) as compared with levels at the beginning; these decreases were strongly associated with children whose behavior improved the most after luteolin formulation treatment. Our results indicate that there are distinct subgroups of children within the ASDs that may be identifiable through serum levels of IL-6 and TNF and that these cytokines may constitute distinct prognostic markers for at least the beneficial effect of luteolin formulation