5 replies to this topic

[Rags847]

This Wikipedia entry makes CoQ10 seem dangerous (if one experiences a low oxygen condition).
Is Idebenone the better choice?

http://en.wikipedia.org/wiki/Idebenone

Idebenone (pronounced eye-deb-eh-known) is an organic compound of the quinone family and promoted commercially as a synthetic analog of Coenzyme Q₁₀ (CoQ₁₀).

Idebenone is claimed to have properties similar to CoQ₁₀ in its antioxidant properties.^[specify]

Idebenone is different from Coenzyme Q₁₀ in one very important way. During a hypoxic (low oxygen) condition, CoQ₁₀ can switch function from an anti-oxidizing to an auto-oxidizing process. This auto-oxidation rapidly produces free radicals which damage the tissues of the body.^{[verification needed]}

Idebenone is said to perform the same functions as CoQ₁₀ without the risk of an auto-oxidation reaction.^{[verification needed]}

Idebenone is said to promote NGF (nerve growth factor) in the brain.^{[verification needed]} It appears to reduce tinnitus (ringing in the ears).^{[verification needed]} Idebenone has also been used in topical applications to treat wrinkles.

Takeda Pharmaceuticals studied Idebenone which it got approved for Alzheimer's disease and Stroke.

Idebenone has reduced the rate of deterioration of cardiac function in patients with Friedreich's ataxia (http://www.ncbi.nlm....ov/sites/entrez

Edited by Rags847, 10 February 2008 - 04:20 PM.

[Athanasios]

One side note is that many more people are allergic to Idebenone than CoQ10.

[Rags847]

One side note is that many more people are allergic to Idebenone than CoQ10.

What kind of allergic symptoms do they suffer?
Skin rash?

[Athanasios]

What kind of allergic symptoms do they suffer?
Skin rash?

Yes, I know this is the consequence where topical application is concerned.

[krillin]

Ann N Y Acad Sci. 2002 Apr;959:199-213.
Role of mitochondria in oxidative stress and aging.
Lenaz G, Bovina C, D'Aurelio M, Fato R, Formiggini G, Genova ML, Giuliano G, Merlo Pich M, Paolucci U, Parenti Castelli G, Ventura B.
Dipartimento di Biochimica G. Moruzzi, Università di Bologna, Via Irnerio 48, 40126 Bologna, Italy. lenaz@biocfarm.unibo.it

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and of aging. We have investigated the role of Complex I in superoxide radical production and found by combined use of specific inhibitors of Complex I that the one-electron donor in the Complex to oxygen is a redox center located prior to the sites where three different types of coenzyme Q (CoQ) competitors bind, to be identified with an Fe-S cluster, most probably N2, or possibly an ubisemiquinone intermediate insensitive to all the above inhibitors. Short-chain coenzyme Q analogues enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analogue idebenone is particularly effective, raising doubts about its safety as a drug. The mitochondrial theory of aging considers somatic mutations of mitochondrial DNA induced by ROS as the primary cause of energy decline; in rat liver mitochondria, Complex I appears to be most affected by aging and to become strongly rate limiting for electron transfer. Mitochondrial energetics is also deranged in human platelets upon aging, as demonstrated by the decreased Pasteur effect (enhancement of lactate production by respiratory inhibitors). Cells counteract oxidative stress by antioxidants: CoQ is the only lipophilic antioxidant to be biosynthesized. Exogenous CoQ, however, protects cells from oxidative stress by conversion into its reduced antioxidant form by cellular reductases. The plasma membrane oxidoreductase and DT-diaphorase are two such systems: likewise, they are overexpressed under oxidative stress conditions.

PMID: 11976197

[abelard lindsay]

Short-chain coenzyme Q analogues enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analogue idebenone is particularly effective, raising doubts about its safety as a drug.

PMID: 11976197

Regarding the safety of Idebenone, the study below tested up to 75mg/kg and found no dose limiting toxicity. Most people think 150mg is a big dose!

Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia.
Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP.

Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-3705, USA. diprospern@ninds.nih.gov

BACKGROUND: Friedreich ataxia (FA) is a progressive, multisystem degenerative disorder in which oxidative stress is believed to have a role. Recent clinical studies indicate that the antioxidant idebenone, administered at 5 mg/kg per day, reduces the cardiac hypertrophy that occurs in FA, but improvement in neurologic measures is unclear. Some studies suggest that higher doses of idebenone may be more effective, but pharmacology and toxicology at higher doses have not been investigated in human beings. OBJECTIVE: To determine the safety, tolerability, and pharmacokinetics of increasing doses of idebenone in subjects with FA. DESIGN: Open-label, phase 1A dose-escalation trial followed by an open-label, 1-month phase 1B trial. SETTING: National Institutes of Health Clinical Center, Bethesda, Md. PATIENTS: Phase 1A included 78 subjects with FA (24 adults, 27 adolescents, and 27 children), and phase 1B included 15 subjects with FA (5 adults, 5 adolescents, and 5 children). INTERVENTIONS: Oral idebenone was administered to groups of 3 subjects in each age cohort during day 1. In phase 1A, the dose was increased in 10-mg/kg increments in each successive dose group to a maximum of 75 mg/kg. In phase 1B, oral idebenone was administered at 60 mg/kg divided in 3 doses per day for 1 month. MAIN OUTCOME MEASURES: We studied the type, number, and frequency of adverse events, and pharmacokinetic parameters including maximum drug concentration, time to maximum drug concentration, area under the curve, and half-life. RESULTS: In the first phase of the study, no dose-limiting toxicity was observed and the maximum allowed dose of 75 mg/kg was achieved in all cohorts. Plasma levels of total idebenone were found to increase proportional to drug dose up to 55 mg/kg. Variability in absorption of the drug was observed, but drug half-life was relatively consistent across dose levels. In the second phase of the study, 14 of 15 subjects with FA tolerated idebenone at a dose of 60 mg/kg per day for 1 month. All adverse events were mild, and pharmacokinetic parameters including maximum drug concentration, time to maximum drug concentration, and half-life did not differ significantly across age cohorts. CONCLUSIONS: These findings indicate that higher doses of idebenone lead to a proportional increase in plasma levels up to 55 mg/kg per day and that high-dose idebenone is well-tolerated in patients with FA. These findings are essential to planning efficacy trials of high-dose idebenone in FA and other degenerative diseases in which oxidative damage has been implicated.

PMID: 17562928 [PubMed - indexed for MEDLINE]