Nutritional Supplements for Mitochondrial Diseases Need Scientific Validation, Experts Contend

The use of vitamins and other nutritional supplements to treat mitochondrial diseases needs to be scientifically validated, a study contends.

The research, “Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems,” appeared in the journal Annual Review of Pathology: Mechanisms of Disease.

Defects in mitochondria, the cells’ power plants, can cause complex disorders that are potentially life-threatening. Patients can have a variety of symptoms, including developmental delays, chronic fatigue, muscle weakness, nerve pain, and inability to tolerate exercise. Scientists have identified approximately 300 genes in which inherited mutations lead to mitochondrial disease.

Given the lack of proven therapies for these conditions, mitochondrial disease patients frequently take various vitamins and supplements. However, the substances are largely unregulated, with no scientific studies backing up their reported effects.

“Our major objectives were to review the basic scientific evidence for compounds already being used in mitochondrial disease patients and to advocate a framework for rigorously evaluating their safety and efficacy in this population,” Marni J. Falk, one of the study’s authors, said in a press release. Falk is executive director of the Mitochondrial Medicine Frontier Program at Children’s Hospital of Philadelphia (CHOP).

The study involved experts from eight centers. “There’s a large gap between the compounds that patients are routinely using and the degree to which those compounds have been scientifically tested,” Zarazuela Zolkipli-Cunningham, a neuromuscular specialist and one of the study’s co-authors, said.

An example is coenzyme Q₁₀ (CoQ₁₀), a compound that is involved in energy production in mitochondria. CoQ₁₀ is an antioxidant, but there is no scientific evidence of its reported health benefits and no standardized formulations. Furthermore, the effects of CoQ₁₀ may be significantly different in healthy people and in patients with a mitochondrial disease, because alterations in mitochondria affect any organ and system.

“Unlike prescription medications, which are closely regulated and standardized by the U.S. Food and Drug Administration, vitamins, dietary supplements, and medical foods are considered in our country to be in a separate regulatory category with much less stringent requirements,” Falk said. He added that not only is the regulation of nutritional products less stringent, but also “their claims are limited to optimizing general public health, not to treating specific diseases. So we know a lot less about their safety and efficacy in patients.”

The experts reviewed the primary nutritional substances used in mitochondrial disease, including vitamins and related substances (such as thiamine, folic acid, riboflavin, and nicotinic acid), metabolic-modifying substances (CoQ₁₀, creatine, L-arginine), modulators of cell signaling (resveratrol), and a ketogenic diet.

 They called for all nutritional therapies to be rigorously tested using a variety of experimental models, including mice that model human mitochondrial disorders.

CHOP is evaluating possible therapies in cells, worms and zebrafish, aiming to discover therapies tailored to the specific mitochondrial disease of each patient. In collaboration with external partners, researchers plan to start four Phase 2 or Phase 3 studies soon. The program now has a dietitian in order to use nutrition for the benefit of mitochondrial disease patients.

“Our toolbox is so much better than what was available 20 years ago,” Falk said. However, a long road lies ahead until proven, effective nutritional therapies are available for mitochondrial disorders, she cautioned.