Published research studies of idebenone (for Friedreich's Ataxia, Alzheimer's disease) have used a standard dose of no more than 5mg/kg/day, in divided doses. E.g., a person weighing 50 lb., or about 23 kg, would  take a total of 115 mg of idebenone per day.  The heart disease seems to improve with the 5mg/kg/day dose, but the ataxia doesn't appear to be responding and might require a higher dose.   The Phase One trial of idebenone, recently completed at the NIH, has studied doses of idebenone up to 75 mg/kg/day (1725 mg of idebenone per day in a 50 lb. person), showing only mild gastrointestinal side-effects (primarily nausea) in just a few participants.  The higher doses were absorbed well by the body and might succeed in getting enough idebenone across the blood-brain barrier to affect neurologic symptoms.   The Phase Two trial at the NIH, due to begin in Fall 2005, will look at placebo, low, medium, and high doses of idebenone, to test for improvement in heart and ataxic symptoms.  Idebenone can be obtained as a 45 mg capsule and as a 150 mg capsule.  One of the suppliers has prepared a website that summarizes idebenone research studies completed in all neurologic diseases to date (www.idebenone.org).

Coenzyme Q10 has also had published studies in FRDA at doses of 400mg per day, taken with 2100 IU of vitamin E, showing benefits for the heart disease (Raffaele Lodi et al. 2001, Annals of Neurology 49:590-596).  In other genetic diseases where the mitochondrion is involved, doses up to 600mg per day have been studied.  Some of my ataxia patients trying to take 600mg per day complained of side-effects (dizziness, weakness) that forced them to reduce the dose.  Coenzyme Q10 can also cause bruising and bleeding. The patients recently reported by Dr. DiMauro (O. Musumeci et al. 2001, Neurology 56:849-855), who had ataxia with coenzyme Q10 deficiency (their bodies were only making 1/3 of the normal amount), took 600mg per day without a problem.  Three of them (all adults) took doses up to 3000mg per day.  When coenzyme Q10 is recommended for regular heart disease patients or 'anti-aging' benefits, the dose is usually 60-200mg per day.

The one published study of adult FRDA patients and vitamin E (R. Lodi, 2001, above) used a standard dose of 2100 IU per day.  Vitamin E is usually taken at doses of 400mg per day, as an "anti-aging" supplement, and at 800-1000mg per day in diseases where an "anti-oxidant" "might" help (e.g., Parkinson's disease, cancer).  In diseases with vitamin E deficiency (e.g., ataxia with vitamin E deficiency, abetalipoproteinemia or hypobetalipoproteinemia, or gastrointestinal diseases with poor vitamin E absorption), the dose recommended is up to 100 IU/kg/day. So our hypothetical 50lb. (23kg) vitamin E-deficient person would take 2300 IU per day (someone weighing 150lb., or 70kg, would take 7000 IU per day!).  The problem with high doses of vitamin E is that it does act as a blood thinner and can cause bruising and bleeding.   It also crystalizes out in the muscle.  For FRDA, doses between 400 and 2100 IU are probably safe (lower dose for children, higher for adults). 

The other vitamin E issue is "natural vitamin E" vs. "synthetic vitamin E." Vitamin E is a mixture of chemicals called "tocopherols" (alpha, beta, gamma, and delta).  The d-form of the alpha-tocopherol is the most biologically active and probably the best form to take.   It comes as an "unesterified" or "natural" preparation (plain old d-alpha tocopherol) and as an esterifed or "synthetic" preparation (d-alpha tocopherol acetate or succinate).  The esterified forms are water soluble and better absorbed (d-alpha tocopherol succinate is supposed to be the best).  For someone not making enough bile (liver or gall bladder disease), a water soluble preparation is required.  One has to read the labels on any vitamin E supplement to see exactly what one is getting.  Two popular "natural" brands are actually quite different--one has mixed unesterified forms (the active alpha form probably getting diluted out by the beta, gamma, delta forms and the whole mix not being well absorbed because it is not water soluble).  The other, which bills itself as "natural" has d-alpha tocopherol succinate only.  Caveat emptor.

Information provided by Dr. Susan Perlman, UCLA Ataxia Clinic and published to FAPG with permission 12/2001