Table 2. Mitochondrial medications and supplements^*.

Medication	Dosage (pediatric)	Dosage (adult)	Monitoring	Adverse effects	Comments
CoQ10 as ubiquinol (preferred)	2–8 mg/kgpo daily divided in two doses	50–600 mg po daily	May obtain pretherapy level and monitor CoQ1 level in leukocytes or plasma	Wakefulness, sleep disruption; may reduce warfarin concentration	Solubilized bioavailable formulation preferred. Absorption may be improved when taken with meals
CoQI0as ubiquinone	10–30 mg/kg po daily divided in 2 doses	300–2400 mg po daily divided 2–3 times a day	May obtain pretherapy level and monitor CoQ10evel in leukocytes or plasma	Wakefulness, sleep disruption; may reduce warfarin concentration	Less potent than ubiquinol and less well absorbed; solubilized bio available formulation preferred. Absorption may be improved when taken with meals
Riboflavin (B2)	50–400 mg po daily	50–400 mg po daily	Not usually done	High doses may cause anorexia and nausea	Changes urine color and smell; effects may be minimized by giving at bedtime
L-Creatine	0.1 g/kg po daily; maximum 10 g/d	5 g po daily, given 1–2 times per day	Renal function	GI upset	Primarily used in myopathy patients, though evidence exists for routine use in all mitochondrial disease patients; converted to creatinine in the gut
L-Arginine	Acute stroke: 500 mg/kg IV per day for 1 –3 days; Maintenance: 150–300 mg/kgpo or IV daily divided 2–3 times a day	Acute stroke: 500 mg/kg IV per day for 1–3 days; Maintenance: 150–300 mg/kg po or IV daily divided 2–3 times a day	Plasma arginine in amino acid profile	Hypotension (with IV loading), hyponatremia, headache, nausea, diarrhea. Myelinolysis reported with high dose in single case	Used with metabolic strokes, especially in MELAS or in those with low-normal plasma arginine; citrulline is used in urea cycle defects as an alternative to arginine
L-Carnitine	10–100 mg/kg per day IV or po divided 3 times a day	100–1000 mg per dose, given IV or po 2–3 times a day	Pretherapy free and total plasma carnitine levels	GI upset, fishy odor (due to bacterial degradation; may be improved with antibiotic). Reports of cardiac rhythm disturbances in long-chain fatty acid oxidation defects	FDA-approved for metabolic diseases; available as prescription generic and brand. Only 10%–20% absorbed. Acetyl-carnitine is an alternative
B50or B100 (B vitamin complexes)	1 tab po given 1–2 times a day	1 tab po given 1–2 times a day	Not usually done	Toxic neuropathy may occur with chronic use of larger doses than recommended	Poorly palatable
Vitamin E	1–2 IU/kg po daily	100–200 IU po daily	Not usually done	Possible adverse cardiac risks at doses > 400 IU/d	Absorption may be improved when taken with meals
Vitamin C	5 mg/kg po daily	50–200 mg po daily	Not usually done	Increases iron absorption; high doses may cause renal insufficiency (single case report)	Easily absorbed water-soluble vitamin
Alpha-lipoic acid	50–200 mg/d	50–200 mg/d	Not usually done	None known	None
Folinic acid as leucovorin, containing both D and L isomers	0.5–1.5 mg/kg po daily, given 1–2 times per day (higher doses are used in folinic acid-responsive epilepsy)	2.5–25 mg po daily given 1–2 times per day	May assess spinal fluid folate and plasma/urine pipecolic acid	Rash and pruritus	Cerebral folate can also be replenished with Isovorin (L-isomer, active form) or 5-methyl-tetrahydrofolate (Deplin), the natural transport form of folate across the blood-brain barrier. Consider for patients with symptom worsening or with proven cerebral folate deficiency

^*CoQ10 and a B vitamin are the most commonly used medications in a starting “mitochondrial treatment cocktail.”

CoQ10—coenzyme Q10; FDA—US Food and Drug Administration; GI—gastrointestinal; IV—intravenous; MELAS—mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes; po—by mouth.