What is Idebenone?
Idebenone (2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)1,4-benzoquinone) is a synthesized organic compound that belongs to the benzoquinone family. It is structurally similar to coenzyme Q-10 (CoQ10) and was originally developed by Takeda Pharmaceutical Company (trademark name Sovrima). It may also be known as Avan, Catena, Cerestebon, CV-2619, and Noben.
How does it work?
Like CoQ10, idebenone is believed to act as a powerful antioxidant that protects cells from damaging free radicals. It is incorporated into the lipid membranes that surround cells and their organelles. This is especially true for mitochondria, the organelles that produce energy substrates for all cellular activity. If taken regularly, idebenone resides in cellular membranes and is available to protect the brain against free radicals that are produced when there is a reduction in blood flow caused by stroke, trauma, or chronic cerebrovascular insufficiency (poor circulation to the brain). This is what makes it different from CoQ10, which actually produces free radicals in low-oxygen environments.
Its presence in the mitochondrial membrane also allows it to participate in the electron-transport chain (ETC), the process by which mitochondria generate adenosine triphosphate (ATP), which is the primary energy substrate in the body. Therefore, the mechanism of idebenone is 2-fold; it protects against harmful oxidation while simultaneously boosting energy levels.
Idebenone is considered a cerebral stimulant that increases the level of energy available to the brain. It is touted as anti-aging, energy and cognition enhancing, and neuroprotective. People who have used it report improved mood, better mental clarity and focus, and higher energy levels.
Some companies sell it in transdermal creams (containing 1% idebenone) that are advertised as topical wrinkle treatments, but this claim is supported by limited clinical research. In fact, one study found that certain forms of idebenone may cause irritation and toxicity in skin cells; idebenone esters (e.g., idebenone linoleate) are safer than idebenone in this particular application. Therefore, be sure to read the labels of these creams!
It is a potential therapy for Alzheimer’s disease patients, who seem to show slight improvements in short- and long-term memory and attention on an idebenone regimen. However, FDA-approved clinical studies in the U.S. were discontinued due to lack of efficacy. It is currently approved to treat cardiac hypertrophy (enlarged heart) in patients with Friedreich’s ataxia, and is currently under clinical investigation for treating Leber hereditary optic neuropathy (LHON), mitochondrial diseases, and neuromuscular disorders. It entered Phase III clinical trials for Duchenne’s muscular Dystrophy in 2009.
Idebenone Side Effects
Idebenone is well-tolerated, but mild side effects including upset stomach, dizziness, anxiety, headache, and restlessness have been reported. A small study of 14 healthy male adults found that 6 of volunteers developed at least one of these mild to moderate symptoms when taking 2.25 g/day.
Although one study found that idebenone could induce neuronal death, the protocol those researchers used employed an excessively high dose of the compound that was applied directly to cultured cells. Therefore, their results are not likely to be reflective of an appropriate idebenone regimen.
Idebenone undergoes extensive first-pass metabolism in the liver and does not accumulate in the body, even when taken chronically at high doses. Pharmacokinetic studies have demonstrated that there is a dose-dependent response up to ~2.25 g per day. Patients with Alzheimer’s disease are instructed to take 90-120 mg of idebenone 3 times a day. Clinical trials in people suffering from Friedreich’s ataxia have used doses of 5, 15, and 45 mg/kg (corresponding to daily intakes of 700 mg, 1.05 g, and 3.15 g in an average-sized adult, respectively). Even the higher doses were well tolerated (up to 2.25 g), with a similar number of side effects in each group.
Vendors that sell idebenone to healthy populations recommend taking 30 mg tablets 2-3 times/day. Idebenone is fat-soluble and should not be taken on an empty stomach; plasma (blood) concentrations increase approximately 5-fold when the compound is taken with food.
Becker, Claudia, Katharine Bray-French, and Juergen Drewe. “Pharmacokinetic Evaluation of Idebenone.” Expert Opinion on Drug Metabolism & Toxicology 6.11 (2010): 1437-444. Print.
Bodmer, Michael, Pierre Vankan, Manfred Dreier, Klaus W. Kutz, and Jürgen Drewe. “Pharmacokinetics and Metabolism of Idebenone in Healthy Male Subjects.” European Journal of Clinical Pharmacology 65.5 (2009): 493-501. Print.
Di Prospero, Nicholas A., Angela Baker, Neal Jeffries, and Kenneth H. Fischbeck. “Neurological Effects of High-dose Idebenone in Patients with Friedreich’s Ataxia: A Randomised, Placebo-controlled Trial.” The Lancet Neurology 6.10 (2007): 878-86. Print.
Giorgio, V., V. Petronilli, A. Ghelli, V. Carelli, M. Rugolo, G. Lenaz, and P. Bernardi. “The Effects of Idebenone on Mitochondrial Bioenergetics.” Biochimica Et Biophysica Acta – Bioenergetics 1817.2 (2012): 363-69. Print.
Hausse, A. O., Y. Aggoun, D. Bonnet, D. Sidi, A. Munnich, A. Rötig, and P. Rustin. “30 Idebenone and Reduced Cardiac Hypertrophy in Friedreich’s Ataxia.” Heart 87.4 (2002): 346-49. Print.
Kutz, Klaus, Jürgen Drewe, and Pierre Vankan. “Pharmacokinetic Properties and Metabolism of Idebenone.” Journal of Neurology 256.S1 (2009): 31-35. Print.
Natkunarajah, J., and L. Ostlere. “Allergic Contact Dermatitis to Idebenone in an Over-the-counter Anti-ageing Cream.” Contact Dermatitis 58.4 (2008): 239. Print.
Tai, Kwok-Keung, L. Pham, and D. D. Truong. “Idebenone Induces Apoptotic Cell Death in the Human Dopaminergic Neuroblastoma SHSY-5Y Cells.” Neurotoxicity Research 20.4 (2011): 321-28. Print.
Voronkova, K. V., and M. N. Meleshkov. “Use of Noben (idebenone) in the Treatment of Dementia and Memory Impairments without Dementia.” Neuroscience and Behavioral Physiology 39.5 (2009): 501-06. Print.
Wempe, M. F., J. W. Lightner, E. L. Zoeller, and P. J. Rice. “Investigating Idebenone and Idebenone Linoleate Metabolism: In Vitro Pig Ear and Mouse Melanocyte Studies.” Journal of Cosmetic Dermatology 8.1 (2009): 63-73. Print.
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