Nutritional interventions in primary mitochondrial disorders: Developing an evidence base

• Published in: Molecular genetics and metabolism Vol. 119; no. 3; pp. 187 - 206
• Main Authors: Camp, Kathryn M., Krotoski, Danuta, Parisi, Melissa A., Gwinn, Katrina A., Cohen, Bruce H., Cox, Christine S., Enns, Gregory M., Falk, Marni J., Goldstein, Amy C., Gopal-Srivastava, Rashmi, Gorman, Gráinne S., Hersh, Stephen P., Hirano, Michio, Hoffman, Freddie Ann, Karaa, Amel, MacLeod, Erin L., McFarland, Robert, Mohan, Charles, Mulberg, Andrew E., Odenkirchen, Joanne C., Parikh, Sumit, Rutherford, Patricia J., Suggs-Anderson, Shawne K., Tang, W.H. Wilson, Vockley, Jerry, Wolfe, Lynne A., Yannicelli, Steven, Yeske, Philip E., Coates, Paul M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016
• Subjects: Dietary Supplements; Humans; Medical foods; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial disease; Mitochondrial Diseases - diet therapy; Mitochondrial Diseases - metabolism; Nutritional interventions; Nutritional Status; OXPHOS; Primary mitochondrial disorders; Vitamins - therapeutic use; TMAO; NCATS; FDA; CDE; mtDNA; MSeqDR; CoQ10; CPEO; cGMP; CNS; NICHD; OXPHOS; GMDI; SIMD; ODA; Mitochondrial disease; Primary mitochondrial disorders; DSHEA; NAMDC; ORDR; FFDCA; ODS; ACMG; PMD; Dietary supplements; MitoGlobal; NHGRI; NIH; Medical foods; IMP; RDCRN; NINDS; IEM; NAD; RC; MMS; RCTs; IRB; NMDAS; nDNA; Nutritional interventions; MELAS; ATP; UMDF; FSDU; MRC
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2016.09.002

In December 2014, a workshop entitled “Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base” was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD. •NIH convened a workshop to address the evidence base for nutritional interventions in primary mitochondrial disease (PMD).•Dietary supplements are commonly used as management modalities for PMD despite limited evidence of safety and efficacy.•PMD are rare, clinically, phenotypically, and genetically heterogeneous, a challenge to conducting clinical trials.•Resources to support clinical trials include patient registries and biorepositories, and common data elements.•Future research is needed to define the diseases; identify biomarkers, outcome measures, and endpoints.