Richard E. Frye MD, PhD

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Hill, Z.; McCarty, P.J.; Boles, R.G.; Frye, R.E. A Mitochondrial Supplement Improves Function and Mitochondrial Activity in Autism: A Double-Blind Placebo-Controlled Cross-Over Trial. Int. J. Mol. Sci. 2025, 26, 2479.

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Frye RE, Rincon N, Mccarty PJ, Brister D, Scheck AC, Rossignol DA. Neurobiology of Disease. 3 May 2024. https://doi.org/10.1016/j.nbd.2024.106520

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Frye RE, Mccarty PJ, Werner BA, Rose S, Scheck A. Front. Physiol. Sec. Mitochondrial Research. Vol 15 -2024. doi: 10.3389/fphys.2024.1306038

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Omri Bar , Elizabeth Vahey , Mark Mintz , Richard E. Frye , Richard G. Boles. International Journal of Molecular Sciences. 18 Jan 2024.

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Omri Bar , Elizabeth Vahey , Mark Mintz , Richard E. Frye , Richard G. Boles. Preprints.org. 14 Aug 2023.

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Poling, J. S., Frye, R. E., Shoffner, J., & Zimmerman, A. W. (2006). Developmental regression and mitochondrial dysfunction in a child with autism. Journal of child neurology, 21(2), 170–172. https://doi.org/10.1177/08830738060210021401

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Frye, R., Rossignol, D. Mitochondrial Dysfunction Can Connect the Diverse Medical Symptoms Associated With Autism Spectrum Disorders. Pediatr Res 69, 41–47 (2011).

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Rossignol, D.A., Frye, R.E. Substantial Problems with Measuring Brain Mitochondrial Dysfunction in Autism Spectrum Disorder Using Magnetic Resonance Spectroscopy. J Autism Dev Disord 42, 640–642 (2012). https://doi.org/10.1007/s10803-011-1276-z

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Frye RE. Mitochondrial disease in 22q13 duplication syndrome. J Child Neurol. 2012 Jul;27(7):942-9. doi: 10.1177/0883073811429858. Epub 2012 Feb 28. PMID: 22378673.

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Rossignol, D., Frye, R. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 17, 290–314 (2012). https://doi.org/10.1038/mp.2010.136

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Frye, R., Melnyk, S. & MacFabe, D. Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Transl Psychiatry 3, e220 (2013). https://doi.org/10.1038/tp.2012.143

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Frye, R., DeLaTorre, R., Taylor, H. et al. Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl Psychiatry 3, e273 (2013). https://doi.org/10.1038/tp.2013.51

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Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, Melnyk S, James SJ. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One. 2014 Jan 8;9(1):e85436. doi: 10.1371/journal.pone.0085436. PMID: 24416410; PMCID: PMC3885720.

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Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, Melnyk S, James SJ. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One. 2014 Jan 8;9(1):e85436. doi: 10.1371/journal.pone.0085436. PMID: 24416410; PMCID: PMC3885720.

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Rossignol DA, Frye RE. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol. 2014 Apr 22;5:150. doi: 10.3389/fphys.2014.00150. PMID: 24795645; PMCID: PMC4001006.

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Richard E. Frye, Shannon Rose, John Slattery & Derrick F. MacFabe (2015) Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome, Microbial Ecology in Health and Disease, 26:1, DOI: 10.3402/mehd.v26.27458

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Frye RE. Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder. Epilepsy Behav. 2015 Jun;47:147-57. doi: 10.1016/j.yebeh.2014.08.134. Epub 2014 Nov 4. PMID: 25440829.

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Frye, R., Cox, D., Slattery, J. et al. Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome. Sci Rep 6, 19544 (2016). https://doi.org/10.1038/srep19544

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Niyazov DM, Kahler SG, Frye RE. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment. Mol Syndromol. 2016 Jul;7(3):122-37. doi: 10.1159/000446586. Epub 2016 Jun 3. PMID: 27587988; PMCID: PMC4988248.

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Rose S, Bennuri SC, Wynne R, Melnyk S, James SJ, Frye RE. Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study. FASEB J. 2017 Mar;31(3):904-909. doi: 10.1096/fj.201601004R. Epub 2016 Nov 18. PMID: 27864377; PMCID: PMC5354548.

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Frye RE, Rose S, Chacko J, Wynne R, Bennuri SC, Slattery JC, Tippett M, Delhey L, Melnyk S, Kahler SG, MacFabe DF. Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines. Transl Psychiatry. 2016 Oct 25;6(10):e927. doi: 10.1038/tp.2016.189. PMID: 27779624; PMCID: PMC5290345.

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Rose S, Bennuri SC, Wynne R, Melnyk S, James SJ, Frye RE. Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study. FASEB J. 2017 Mar;31(3):904-909. doi: 10.1096/fj.201601004R. Epub 2016 Nov 18. PMID: 27864377; PMCID: PMC5354548.

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Delhey, L.M.; Nur Kilinc, E.; Yin, L.; Slattery, J.C.; Tippett, M.L.; Rose, S.; Bennuri, S.C.; Kahler, S.G.; Damle, S.; Legido, A.; Goldenthal, M.J.; Frye, R.E. The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. J. Clin. Med. 2017, 6, 18. https://doi.org/10.3390/jcm6020018

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Frye, R.E., Rose, S., Wynne, R. et al. Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines. Sci Rep 7, 4478 (2017). https://doi.org/10.1038/s41598-017-04821-3

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Frye, R.E., Rose, S., Wynne, R. et al. Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines. Sci Rep 7, 4478 (2017). https://doi.org/10.1038/s41598-017-04821-3

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Khemakhem, A.M., Frye, R.E., El-Ansary, A. et al. Novel biomarkers of metabolic dysfunction is autism spectrum disorder: potential for biological diagnostic markers. Metab Brain Dis 32, 1983–1997 (2017). https://doi.org/10.1007/s11011-017-0085-2

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Delhey L, Kilinc EN, Yin L, Slattery J, Tippett M, Wynne R, Rose S, Kahler S, Damle S, Legido A, Goldenthal MJ, Frye RE. Bioenergetic variation is related to autism symptomatology. Metab Brain Dis. 2017 Dec;32(6):2021-2031. doi: 10.1007/s11011-017-0087-0. Epub 2017 Aug 29. PMID: 28852932; PMCID: PMC5681971.

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Burger BJ, Rose S, Bennuri SC, et al. Autistic Siblings with Novel Mutations in Two Different Genes: Insight for Genetic Workups of Autistic Siblings and Connection to Mitochondrial Dysfunction. Frontiers in Pediatrics. 2017 ;5:219. DOI: 10.3389/fped.2017.00219. PMID: 29075622; PMCID: PMC5643424.

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Rose S, Bennuri SC, Murray KF, Buie T, Winter H, Frye RE. Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study. PLoS One. 2017 Oct 13;12(10):e0186377. doi: 10.1371/journal.pone.0186377. PMID: 29028817; PMCID: PMC5640251.

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Parikh S, Goldstein A, Karaa A, Koenig MK, Anselm I, Brunel-Guitton C, Christodoulou J, Cohen BH, Dimmock D, Enns GM, Falk MJ, Feigenbaum A, Frye RE, Ganesh J, Griesemer D, Haas R, Horvath R, Korson M, Kruer MC, Mancuso M, McCormack S, Raboisson MJ, Reimschisel T, Salvarinova R, Saneto RP, Scaglia F, Shoffner J, Stacpoole PW, Sue CM, Tarnopolsky M, Van Karnebeek C, Wolfe LA, Cunningham ZZ, Rahman S, Chinnery PF. Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2017 Dec;19(12):10.1038/gim.2017.107. doi: 10.1038/gim.2017.107. Epub 2017 Jul 27. PMID: 28749475; PMCID: PMC7804217.

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Frye RE, Nankova B, Bhattacharyya S, Rose S, Bennuri SC, MacFabe DF. Front Immunol. 2017 Dec 22;8:1670. doi: 10.3389/fimmu.2017.01670. PMID: 29312285; PMCID: PMC5744079.

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Rose S, Bennuri SC, Davis JE, Wynne R, Slattery JC, Tippett M, Delhey L, Melnyk S, Kahler SG, MacFabe DF, Frye RE. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism. Transl Psychiatry. 2018 Feb 2;8(1):42. doi: 10.1038/s41398-017-0089-z. PMID: 29391397; PMCID: PMC5804031.

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Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder. Mol Diagn Ther. 2018 Oct;22(5):571-593. doi: 10.1007/s40291-018-0352-x. PMID: 30039193; PMCID: PMC6132446.

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Barone R, Alaimo S, Messina M, Pulvirenti A, Bastin J; MIMIC-Autism Group; Ferro A, Frye RE, Rizzo R. A Subset of Patients With Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses. Front Psychiatry. 2018 Dec 7;9:636. doi: 10.3389/fpsyt.2018.00636. PMID: 30581393; PMCID: PMC6292950.

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Bennuri SC, Rose S, Frye RE. Mitochondrial Dysfunction Is Inducible in Lymphoblastoid Cell Lines From Children With Autism and May Involve the TORC1 Pathway. Front Psychiatry. 2019 May 7;10:269. doi: 10.3389/fpsyt.2019.00269. PMID: 31133888; PMCID: PMC6514096.

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Rose S, Carvalho E, Diaz EC, Cotter M, Bennuri SC, Azhar G, Frye RE, Adams SH, Børsheim E. A comparative study of mitochondrial respiration in circulating blood cells and skeletal muscle fibers in women. Am J Physiol Endocrinol Metab. 2019 Sep 1;317(3):E503-E512. doi: 10.1152/ajpendo.00084.2019. Epub 2019 Jun 18. PMID: 31211617.

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Jyonouchi H, Geng L, Toruner GA, Rose S, Bennuri SC, Frye RE. Serum microRNAs in ASD: Association With Monocyte Cytokine Profiles and Mitochondrial Respiration. Front Psychiatry. 2019 Sep 10;10:614. doi: 10.3389/fpsyt.2019.00614. PMID: 31551826; PMCID: PMC6748029.

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Singh K, Singh IN, Diggins E, Connors SL, Karim MA, Lee D, Zimmerman AW, Frye RE. Ann Clin Transl Neurol. 2020 May;7(5):683-694. doi: 10.1002/acn3.51034. Epub 2020 Apr 28. PMID: 32343046; PMCID: PMC7261756.

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Frye RE. Mitochondrial Dysfunction in Autism Spectrum Disorder: Unique Abnormalities and Targeted Treatments. Semin Pediatr Neurol. 2020 Oct;35:100829. doi: 10.1016/j.spen.2020.100829. Epub 2020 Jun 23. PMID: 32892956.

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Frye RE, Cakir J, Rose S, Delhey L, Bennuri SC, Tippett M, Palmer RF, Austin C, Curtin P, Arora M. Early life metal exposure dysregulates cellular bioenergetics in children with regressive autism spectrum disorder. Transl Psychiatry. 2020 Jul 7;10(1):223. doi: 10.1038/s41398-020-00905-3. PMID: 32636364; PMCID: PMC7341836.

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Frye RE, Cakir J, Rose S, Delhey L, Bennuri SC, Tippett M, Melnyk S, James SJ, Palmer RF, Austin C, Curtin P, Arora M. Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology. Mol Psychiatry. 2021 May;26(5):1561-1577. doi: 10.1038/s41380-020-00885-2. Epub 2020 Sep 22. PMID: 32963337; PMCID: PMC8159748.

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Frye RE, Cakir J, Rose S, Palmer RF, Austin C, Curtin P, Arora M. Mitochondria May Mediate Prenatal Environmental Influences in Autism Spectrum Disorder. J Pers Med. 2021 Mar 18;11(3):218. doi: 10.3390/jpm11030218. PMID: 33803789; PMCID: PMC8003154.

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Frye RE, Lionnard L, Singh I, Karim MA, Chajra H, Frechet M, Kissa K, Racine V, Ammanamanchi A, McCarty PJ, Delhey L, Tippett M, Rose S, Aouacheria A. Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder. Transl Psychiatry. 2021 Oct 13;11(1):527. doi: 10.1038/s41398-021-01647-6. PMID: 34645790; PMCID: PMC8514530.

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Frye RE. A Personalized Multidisciplinary Approach to Evaluating and Treating Autism Spectrum Disorder. J Pers Med. 2022 Mar 14;12(3):464. doi: 10.3390/jpm12030464. PMID: 35330464; PMCID: PMC8949394.

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Werner BA, McCarty PJ, Lane AL, Singh I, Karim MA, Rose S, Frye RE. Time dependent changes in the bioenergetics of peripheral blood mononuclear cells: processing time, collection tubes and cryopreservation effects. Am J Transl Res. 2022 Mar 15;14(3):1628-1639. PMID: 35422946; PMCID: PMC8991115.

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Brister D, Werner BA, Gideon G, McCarty PJ, Lane A, Burrows BT, McLees S, Adelson PD, Arango JI, Marsh W, Flores A, Pankratz MT, Ly NH, Flood M, Brown D, Carpentieri D, Jin Y, Gu H, Frye RE. Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis. Metabolites. 2022 Apr 20;12(5):371. doi: 10.3390/metabo12050371. PMID: 35629876; PMCID: PMC9148155.

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Jensen AR, Lane AL, Werner BA, McLees SE, Fletcher TS, Frye RE. Modern Biomarkers for Autism Spectrum Disorder: Future Directions. Mol Diagn Ther. 2022 Sep;26(5):483-495. doi: 10.1007/s40291-022-00600-7. Epub 2022 Jun 27. PMID: 35759118; PMCID: PMC9411091.

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Brister D, Rose S, Delhey L, Tippett M, Jin Y, Gu H, Frye RE. Metabolomic Signatures of Autism Spectrum Disorder. J Pers Med. 2022 Oct 17;12(10):1727. doi: 10.3390/jpm12101727. PMID: 36294866; PMCID: PMC9604590.

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Frye RE, Lane A, Worner A, Werner BA, McCarty PJ, Scheck AC, Collins HL, Adelman SJ, Quadros EV, Rossignol DA. The Soluble Folate Receptor in Autism Spectrum Disorder: Relation to Autism Severity and Leucovorin Treatment. J Pers Med. 2022 Dec 8;12(12):2033. doi: 10.3390/jpm12122033. PMID: 36556254; PMCID: PMC9786140.

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Frye, R.E.; Nanda, H.; Pleasure, S.J.; Casanova, M.F.; Boles, R.G.; Lewine, J.; Gaitanis, J.; Adams, J.B. Synchrony 2022: Epilepsy and Seizures in Autism Spectrum Disorder Roundtable. J. Pers. Med. 2023, 13, 557. https://doi.org/10.3390/jpm13030557

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Frye, RE. The Autism File: Biomedical Update. 2015. pp. 28-34.

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Rossignol, DA, Frye, RE. Autism Science Digest: The Journal of Autismone. 2011. pp. 21-27.

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