Epigallocatechin-3-Gallate Plus Omega-3 Restores the Mitochondrial Complex I and F0F1-ATP Synthase Activities in PBMCs of Young Children with Down Syndrome: A Pilot Study of Safety and Efficacy

Abstract

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21. Epigallocatechin-3-gallate (EGCG) is a multimodal nutraceutical with antioxidant properties. EGCG inhibits DYRK1A overexpression and corrects DS mitochondrial dysfunction in vitro. The present study explores safety profiles in DS children aged 1–8 years treated with EGCG (10 mg/kg/die, suspended in omega-3, per os, in fasting conditions, for 6 months) and EGCG efficacy in restoring mitochondrial complex I and F0F1-ATP synthase (complex V) deficiency, assessed on PBMCs. The Griffiths Mental Developmental Scales—Extended Revised (GMDS-ER) was used for developmental profiling. Results show that decaffeinated EGCG (>90%) plus omega-3 is safe in DS children and effective in reverting the deficit of mitochondrial complex I and V activities. Decline of plasma folates was observed in 21% of EGCG-treated patients and should be carefully monitored. GMDS-ER scores did not show differences between the treated group compared to the DS control group. In conclusion, EGCG plus omega-3 can be safely administered under medical supervision in DS children aged 1–8 years to normalize mitochondria respiratory chain complex activities, while results on the improvement of developmental performance are still inconclusive.

Catechins as a Potential Dietary Supplementation in Prevention of Comorbidities Linked with Down Syndrome

“…When the mitochondrial respiratory chain is not operative, it is the main producer of ROS. It has consequences in biogenesis, structure, dynamics, and metabolism of the mitochondrial of T21, which subsequently is associated with neurogenesis and neuroplasticity impairment [ 85 ]. In experiments using EGCG in cultured fibroblasts and lymphoblasts from DS patients, Valenti and his colleagues have been able to show a protective effect on mitochondrial energy deficit and oxidative stress by lessening mitochondrial energy damage.…”

“…These in vitro findings can also be related to another in vivo study, Scala and coworkers have shown that in DS children aged between 1 and 8 years, a treatment of decaffeinated EGCG enriched by omega-3 for 6 months ensues the repairing of the deficit of mitochondrial complex I and ATP synthase. Moreover, they give evidence about the safety of EGCG in children without side effects in hepatic, renal, and thyroid function [ 85 ].…”

Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes

“…It has also been demonstrated that EGCG exerts a positive effect on cognitive function by promoting ROS scavenging ( Schroeder et al, 2009 ) and counteracting the Aβ-induced mitochondrial apoptotic processes ( Fukutomi et al, 2021 ). Importantly, it has recently been reported that EGCG treatment ameliorates mitochondrial respiration deficits in children affected by Down syndrome ( Scala et al, 2021 ). A recent meta-analysis of 17 studies performed on animal models of AD has demonstrated that EGCG can rescue cognitive impairment and Aβ pathology through the combination of its anti-inflammatory, antioxidant, and antiaggregating activities ( Zhang et al, 2020 ).…”

Dietary supplements for children with Down syndrome: exploration of current use and scientific evidence : Fieldwork and literature study

“…Furthermore, Vacca & Valenti letter describe a trial in their letter, consisting of only two participants; one child with DS as a treatment group, whereas the younger brother served as a control. In a more recent publication the same group looked into the safety of EGCG and omega-3 in a pilot study with 20 DS children of 0-8 years old and they concluded it can be safely administered under medical supervision in DS children [115].…”