Nutritional interventions in primary mitochondrial disorders: Developing an evidence base.
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.
Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: campkm@od.nih.gov.
Kathryn M
KM
Camp
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: krotoskd@mail.nih.gov.
Danuta
D
Krotoski
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: parisima@mail.nih.gov.
Melissa A
MA
Parisi
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gwinnk@ninds.nih.gov.
Katrina A
KA
Gwinn
Department of Pediatrics, Akron Children's Hospital, Akron, OH 44308, USA. Electronic address: bcohen@chmca.org.
Bruce H
BH
Cohen
MitoAction, Boston, MA 02205, USA. Electronic address: outreach@mitoaction.org.
Christine S
CS
Cox
Division of Medical Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: genns@stanford.edu.
Gregory M
GM
Enns
The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: falkm@email.chop.edu.
Marni J
MJ
Falk
Division of Child Neurology, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA. Electronic address: amy.goldstein@chp.edu.
Amy C
AC
Goldstein
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rashmi.gopal-srivastava@nih.gov.
Rashmi
R
Gopal-Srivastava
Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: grainne.gorman@newcastle.ac.uk.
Gráinne S
GS
Gorman
J. Willard & Alice S. Marriott Foundation, Bethesda, MD 20817, USA. Electronic address: hershs@starpower.net.
Stephen P
SP
Hersh
Columbia University Medical Center, New York, NY 10032, USA. Electronic address: mh29@cumc.columbia.edu.
Michio
M
Hirano
HeteroGeneity, LLC, Washington, DC 20011, USA. Electronic address: fhoffman@heterogeneity-LLC.com.
Freddie Ann
FA
Hoffman
Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: akaraa@mgh.harvard.edu.
Amel
A
Karaa
Division of Genetics and Metabolism, Children's National Health System, Washington, DC 20010, USA. Electronic address: emacleod@childrensnational.org.
Erin L
EL
MacLeod
Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: robert.mcfarland@newcastle.ac.uk.
Robert
R
McFarland
United Mitochondrial Disease Foundation, Pittsburgh, PA 15239, USA. Electronic address: chuckm@umdf.org.
Charles
C
Mohan
Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20903, USA. Electronic address: amulberg@amicusrx.com.
Andrew E
AE
Mulberg
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jo21x@nih.gov.
Joanne C
JC
Odenkirchen
Neurosciences, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: parikhs@ccf.org.
Sumit
S
Parikh
Vitaflo International Ltd, Liverpool L34BQ, UK. Electronic address: triciarutherford@vitaflo.co.uk.
Patricia J
PJ
Rutherford
Office of Nutrition and Food Labeling, Food and Drug Administration, College Park, MD 20740, USA. Electronic address: shawne.suggs-anderson@fda.hhs.gov.
Shawne K
SK
Suggs-Anderson
Center for Clinical Genomics, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: tangw@ccf.org.
W H Wilson
WH
Tang
University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA. Electronic address: gerard.vockley@chp.edu.
Jerry
J
Vockley
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lynne.wolfe@nih.gov.
Lynne A
LA
Wolfe
Medical and Scientific Affairs, Nutricia North America, Rockville, MD 20850, USA. Electronic address: steven.yannicelli@nutricia.com.
Steven
S
Yannicelli
United Mitochondrial Disease Foundation, Pittsburgh, PA 15239, USA. Electronic address: philip.yeske@umdf.org.
Philip E
PE
Yeske
Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: coatesp@od.nih.gov.
Paul M
PM
Coates
D019587:Dietary Supplements; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000178:diet therapy* / Q000378:metabolism; D009752:Nutritional Status; D014815:Vitamins / Q000627:therapeutic use*
D014815:Vitamins
Dietary supplements; Medical foods; Mitochondrial disease; Nutritional interventions; OXPHOS; Primary mitochondrial disorders
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