Nutritional interventions in primary mitochondrial disorders: Developing an evidence base

Kathryn M Camp; Danuta Krotoski; Melissa A Parisi; Katrina A Gwinn; Bruce H Cohen; Christine S Cox; Gregory M Enns; Marni J Falk; Amy C Goldstein; Rashmi Gopal-Srivastava; Gráinne S Gorman; Stephen P Hersh; Michio Hirano; Freddie Ann Hoffman; Amel Karaa; Erin L MacLeod; Robert McFarland; Charles Mohan; Andrew E Mulberg; Joanne C Odenkirchen; Sumit Parikh; Patricia J Rutherford; Shawne K Suggs-Anderson; W H Wilson Tang; Jerry Vockley; Lynne A Wolfe; Steven Yannicelli; Philip E Yeske; Paul M Coates

doi:10.1016/j.ymgme.2016.09.002

Nutritional interventions in primary mitochondrial disorders: Developing an evidence base

Mol Genet Metab. 2016 Nov;119(3):187-206. doi: 10.1016/j.ymgme.2016.09.002. Epub 2016 Sep 20.

Authors

Kathryn M Camp¹, Danuta Krotoski², Melissa A Parisi³, Katrina A Gwinn⁴, Bruce H Cohen⁵, Christine S Cox⁶, Gregory M Enns⁷, Marni J Falk⁸, Amy C Goldstein⁹, Rashmi Gopal-Srivastava¹⁰, Gráinne S Gorman¹¹, Stephen P Hersh¹², Michio Hirano¹³, Freddie Ann Hoffman¹⁴, Amel Karaa¹⁵, Erin L MacLeod¹⁶, Robert McFarland¹⁷, Charles Mohan¹⁸, Andrew E Mulberg¹⁹, Joanne C Odenkirchen²⁰, Sumit Parikh²¹, Patricia J Rutherford²², Shawne K Suggs-Anderson²³, W H Wilson Tang²⁴, Jerry Vockley²⁵, Lynne A Wolfe²⁶, Steven Yannicelli²⁷, Philip E Yeske²⁸, Paul M Coates²⁹

Affiliations

¹ Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
² Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
³ Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
⁴ National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
⁵ Department of Pediatrics, Akron Children's Hospital, Akron, OH 44308, USA. Electronic address: [email protected].
⁶ MitoAction, Boston, MA 02205, USA. Electronic address: [email protected].
⁷ Division of Medical Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: [email protected].
⁸ The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: [email protected].
⁹ Division of Child Neurology, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA. Electronic address: [email protected].
¹⁰ National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
¹¹ Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: [email protected].
¹² J. Willard & Alice S. Marriott Foundation, Bethesda, MD 20817, USA. Electronic address: [email protected].
¹³ Columbia University Medical Center, New York, NY 10032, USA. Electronic address: [email protected].
¹⁴ HeteroGeneity, LLC, Washington, DC 20011, USA. Electronic address: [email protected].
¹⁵ Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: [email protected].
¹⁶ Division of Genetics and Metabolism, Children's National Health System, Washington, DC 20010, USA. Electronic address: [email protected].
¹⁷ Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: [email protected].
¹⁸ United Mitochondrial Disease Foundation, Pittsburgh, PA 15239, USA. Electronic address: [email protected].
¹⁹ Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20903, USA. Electronic address: [email protected].
²⁰ National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
²¹ Neurosciences, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: [email protected].
²² Vitaflo International Ltd, Liverpool L34BQ, UK. Electronic address: [email protected].
²³ Office of Nutrition and Food Labeling, Food and Drug Administration, College Park, MD 20740, USA. Electronic address: [email protected].
²⁴ Center for Clinical Genomics, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: [email protected].
²⁵ University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA. Electronic address: [email protected].
²⁶ National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
²⁷ Medical and Scientific Affairs, Nutricia North America, Rockville, MD 20850, USA. Electronic address: [email protected].
²⁸ United Mitochondrial Disease Foundation, Pittsburgh, PA 15239, USA. Electronic address: [email protected].
²⁹ Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].

Abstract

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.

Keywords: Dietary supplements; Medical foods; Mitochondrial disease; Nutritional interventions; OXPHOS; Primary mitochondrial disorders.

Publication types

Review

MeSH terms

Dietary Supplements*
Humans
Mitochondria / drug effects
Mitochondria / metabolism
Mitochondrial Diseases / diet therapy*
Mitochondrial Diseases / metabolism
Nutritional Status*
Vitamins / therapeutic use*

Substances

Vitamins

Abstract

Publication types

MeSH terms

Substances

Grants and funding