{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:51:48Z","timestamp":1776372708470,"version":"3.51.2"},"reference-count":53,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Brain Foundation"},{"name":"XEL Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is associated with mitochondrial dysfunction, but studies demonstrating the efficacy of treatments are scarce. We sought to determine whether a mitochondrial-targeted dietary supplement designed for children with ASD improved mitochondrial function and ASD symptomatology using a double-blind placebo-controlled cross-over design. Sixteen children [mean age 9 years 4 months; 88% male] with non-syndromic ASD and mitochondrial enzyme abnormalities, as measured by MitoSwab (Religen, Plymouth Meeting, PA, USA), received weight-adjusted SpectrumNeeds\u00ae (NeuroNeeds, Old Lyme, CT, USA) and QNeeds\u00ae (NeuroNeeds, Old Lyme, CT, USA) and placebos matched on taste, texture and appearance during two separate 12-week blocks. Which product was received first was randomized. The treatment significantly normalized citrate synthase and complex IV activity as measured by the MitoSwab. Mitochondrial respiration of peripheral blood mononuclear cell respiration, as measured by the Seahorse XFe96 (Agilent, Santa Clara, CA, USA) with the mitochondrial oxidative stress test, became more resilient to oxidative stress after the treatment, particularly in children with poor neurodevelopment. The mitochondrial supplement demonstrated significant improvement in standardized parent-rated scales in neurodevelopment, social withdrawal, and hyperactivity with large effect sizes (Cohen\u2019s d\u2019 = 0.77\u20131.25), while changes measured by the clinical and psychometric instruments were not significantly different. Adverse effects were minimal. This small study on children with ASD and mitochondrial abnormalities demonstrates that a simple, well-tolerated mitochondrial-targeted dietary supplement can improve mitochondrial physiology and ASD symptoms. Further larger controlled studies need to verify and extend these findings. These findings are significant as children with ASD have few other effective treatments.<\/jats:p>","DOI":"10.3390\/ijms26062479","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T06:52:30Z","timestamp":1741675950000},"page":"2479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Mitochondrial Supplement Improves Function and Mitochondrial Activity in Autism: A Double-Blind Placebo-Controlled Cross-Over Trial"],"prefix":"10.3390","volume":"26","author":[{"given":"Zo\u00eb","family":"Hill","sequence":"first","affiliation":[{"name":"Autism Discovery and Treatment Foundation, Phoenix, AZ 85050, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7111-9576","authenticated-orcid":false,"given":"Patrick J.","family":"McCarty","sequence":"additional","affiliation":[{"name":"Tulane Medical School, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard G.","family":"Boles","sequence":"additional","affiliation":[{"name":"Mitochondrial and Molecular Medicine, Pasadena, CA 91105, USA"},{"name":"NeuroNeeds, Old Lyme, CT 06371, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-2937","authenticated-orcid":false,"given":"Richard E.","family":"Frye","sequence":"additional","affiliation":[{"name":"Autism Discovery and Treatment Foundation, Phoenix, AZ 85050, USA"},{"name":"Rossignol Medical Center, Phoenix, AZ 85050, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Estimated Prevalence of Autism and Other Developmental Disabilities Following Questionnaire Changes in the 2014 National Health Interview Survey","volume":"87","author":"Zablotsky","year":"2015","journal-title":"Natl. 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