When Coenzyme Q10 was found to produce heart and energy improvement, it soon became apparent that it was a most important supplement

Now there is also a synthetic variant available called idebenone, it has all the qualities of CoQ10 but with an even greater range and depth of protection. It protects the precious tiny mitochondria (the energy producing cells) and even has brain-enhancing qualities.

It is, if you like, the “ultimate” CoQ10 and as such qualifies as an important anti-aging supplement.

Mitochondria, Oxygen and Energy Production

There are literally thousands of mitochondria in every cell of our body. Their primary role is to produce pregnenolone (see the same)- the precursor to the steroids and to produce ATP (adenosine triphosphate)- the “raw energy” that powers virtually every activity of our bodies.

In the process of producing ATP, the mitochondria utilize oxygen and CoQ10 in a process of energy production called the “electron transport chain” or ETC.

Unfortunately oxygen can also be a potent free radical (unstable- out of control- molecules). As a result of the amount of oxygen used inside the mitochondria (in fact most of the oxygen we breathe is used inside the electron transport chain to produce ATP), a lot of free-radical damage can occur.

Free radicals therefore have to be “mopped up” by free radical scavengers and protected from occurring by anti-oxidants. If left “unchecked” free radical damage inside the mitochondria will eventually lead to its malfunction and eventually cessation. As cells cannot “borrow” energy from one another, in the end, the organ they ” provide” for becomes damaged and ultimately this will lead to organ failure and possibly death.

Whilst under “normal” circumstances CoQ10 provides protection and free radical scavenging, this can change under the condition of ischemia (poor blood flow).

This can take happen during a heart attack, stroke, trauma or shock, it can even be affected by general poor blood supply due to “aging” affecting the condition of the heart’s pumping capabilities. As a result of poor blood supply the oxygen levels drop and this causes CoQ10 to oxidize itself, effectively turning itself into another free radical! Under more extreme conditions a large presence of free radicals can cease ATP production and therefore create a life threatening condition.

This is one key-area where idebenone has been shown to be much more effective than CoQ10. Under the same hypoxic (low oxygen) conditions that cause CoQ10 to become oxidized- idebenone prevents free radical damage and maintains relatively normal ATP production.

Idebenone should therefore be the supplement of choice for those concerned with stroke, heart conditions, shock, trauma and mitochondrial failure/ conditions.

Slowing Aging

The mitochondria are key life-preserving cells producing over 90% of ATP bio-energy. As we’ve seen their vast use of oxygen exposes them to free radicals and therefore over a lifetime they become ever more damaged and therefore inefficient.

The mitochondria most at risk from aging- free radical damage are those in the heart, brain and skeletal muscles. Therefore a key aspect of current anti-aging thinking is to slow down/ prevent damage from occurring to mitochondrial function. According to the research, idebenone is the current- most effective drug capable of performing this task.

Dementia, Memory and Cognition

Nerve Growth Factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central nervous system (CNS).

In dementia’s such as Alzheimer’s, it is known that learning and memory are impaired by the loss of neurons in an area of the brain called the magnocellular cholinergic neuronal system.

Nerve Growth Factor cannot cross the blood brain barrier and in scientific experiments, it has only been able to be utilized when it is injected directly into the brain. However, animal experiments have shown that oral use of idebenone tablets induce an increase in NGF and improve choline- acetyltransferase activity.

One rat study demonstrated that idebenone stimulated NGF synthesis and recovered reduced NGF content in aged rat brains. After 21 days of successive idebenone supplementation the NGF brain quantity of aged rats was increased to an amount similar to young rats.

As a result of these studies, idebenone is being used in the treatment of senile dementias, particularly Alzheimer’s disease. In a German clinical study, 90mg of idebenone was administered for 6 months; Alzheimer patients thereafter showed statistically significant improvement.

Treatment with idebenone was found effective on memory, attention and orientation. Perhaps most importantly of all, idebenone slowed down the natural progression of the disease.

Furthermore, there were so few (and minor) side effects that the study ended with “… results demonstrate the efficacy and safety of idebenone in the treatment of Alzheimer’s disease patients.”

Once again, as with most nootropics, clinical trials indicate that patients with mild dementia seem more likely to respond, than those with greater functional decline.

It’s the old story, catch it and treat it early before it becomes a major problem.

Comparing CoQ10 and Idebenone

1. Idebenone is so much more potent than CoQ10 in its anti-oxidant abilities. In fact, studies indicate that idebenone is 30-100 times more effective than vitamin E or vinpocetine as a free radical quencher.

2. Idebenone protects under hypoxic conditions, a situation where CoQ10 can become quite the reverse.

3. Idebenone (unlike CoQ10) has been shown to increase Nerve Growth Factor and enhance cholinergic activity, thereby showing it to have cognitive enhancement abilities.

4. Idebenone is a superb anti-oxidant for protecting the all important mitochondria, by both “mopping up” free radical activity and protecting the unique mitochondrial DNA (mtDNA)- unique because it is only derived from our mother’s genes.

In fact when organs are “harvested” for transplant to another patient, very often it is idebenone that is used to protect it from damage. That is the level of free radical protection offered by idebenone.

However, rather than switching from CoQ10 to idebenone, some studies have suggested that adding idebenone to a CoQ10 supplement is the best way to “cover all the bases.”

Side Effects and Contraindications

Side effects have been rare and usually of mild intensity when they do occur. Those noted have been insomnia, gastralgia, nausea and anxiety. There are no known contraindications, but it is known that concurrent use of anti-convulsants will affect/ impede its pharmacokinetics.

Doses and Uses

Idebenone may be useful in the treatment and prevention of all the following,

Stroke.
Alzheimer’s disease.
Liver, kidneys, heart or brain disturbances.
Multiple Sclerosis.
Chronic fatigue.
Persons in need of “high-energy” quotas.
Anti-aging protection.

Normal anti-aging doses may be considered at 45mg to 90mg daily, (normally one or two tablets). For specific treatment purposes dosages of 45-90mg three times a day may be required. It is suggested that late evening use by avoided in order to help prevent insomnia.

CoQ10 was one of the “earth-shattering” discoveries in recent years and as such has become a well-known and demanded supplement. Idebenone with its even greater and broader range of uses is (we feel), also likely to impact onto the general public’s attention. This is going to occur as soon as the word spreads and the momentum has reached a certain point.

Note: Idebenone cream will be available in 2004 from Allergan, the company that introduced Botox.

References:                                       http://www.idebenone.info/

1. Parnetti L, Senin U, Mecocci P, “Cognitive enhancement therapy for Alzheimer’s disease. The way forward.” Drugs 1997 May; 53(5):752-768.

2. Weyer G, Babeji-Dolle RM, Hadler D, Hofmann S, Herrmann WM, “A controlled study of 2 doses of idebenone in the treatment of Alzheimer’s disease.” Neuropsychobiology 1997; 36(2):73-82

3. Ranen NG and colleagues, “A controlled trial of idebenone in Huntington’s disease” Mov Disord 1996 Sep; 11(5):549-554

4. Ikejiri Y, Mori E, Ishii K, Nishimoto K, Yasuda M, Sasaki M, “Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS” Neurology 1996; Aug 47(2); 583-585.

5. Pisano P and colleagues, “Plasma concentrations and pharmacokinetics of idebenone and its metabolites following single and repeated doses in young patients with mitochondrial encephalomyopathy.” Eur J Pharmacol 1996; 51(2):167-169.

6. Gillis JC, Benefield P, McTavish D, “Idebenone, a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders.” Drugs Aging 1994; Aug;5(2): 133-152.

7. Bergamasco B, Scarzella L, LaCommare P, “Idebenone, a new drug in the treatment of cognitive impariment in patinets with dementia of the Alzheimer type.” Funct Neurol 1994; May;9(3):161-168

8. Nitta A and colleagues “Oral administration of idebenone induces nerve growth factor in the brain and improves learning and memory in basal forebrain-lesioned rats.” Dept of Neuropsychopharmacology, Nagoya University, Japan.

9. Nitta A, Hasegawa T, Nabeshima T, “Oral administration of idebenone, a stimulator of NGF synthesis recovers reduced NGF content in aged rat brain.” Neuosci Lett 1993 Dec 12; 163(2):219-222.

10. Kakihana M, Yamazaki N, Nagaoka A, “Effects of idebenone on the levels of acetylcholine, choline, free fatty acids and energy metabolites in the brains of rats with cerebral ischaemia.” Arch Gerontol Geriatr 1989 May 8(3);247-256

11. Ihara Y, Namba S, Sato T, Shiraba T, “Mitochondrial encephalomyopathy (MELAS), pathological study and successful therapy with coenzyme Q10 and idebenone.” J Neurol Sci 1989 May; 90(3):263-271.

12. Suno M, Nagaoka A, “Inhibition of brain mitochondrial swelling by idebenone.” Arch Gerontol Geriatr 1989 May; 8(3):299-305.

13. Ihara Y, Namba S, Shiraba T, “Mitochondrial encephalomyopathy (MELAS), pathological study and successful therapy with coenzyme Q10 and idebenone.” J Neurol Sci 1989 May; 90(3):263-271.

14. Lerman-Sagie T, Rustin P, Lev D, “Dramatic improvement in mitochondrial cardiomyopathy following treatment with idebenone.” J Inherit Metab Dis 2001 Feb;24(1):28-34.

15. Gutzmann H, Hadler D., “Sustained efficacy and safety of idebenone in the treatment of Alzheimer’s disease: update on a 2-year double-blind multicentre study.” J Neural Transm Suppl 1998;54:301-10.

16. Yamada K, Nitta A, Hasegawa T, “Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer’s disease.” Behav Brain Res 1997 Feb;83(1-2):117-22.

DISCLAIMER; ALL INFORMATION IS EDUCATIONAL AND SHOULD NOT REPLACE THE ADVICE OF YOUR PHYSICIAN.

The above article is copyrighted and may not be copied without the written permission of International Antiaging Systems, Les Autelets Suite A, Sark GY9 0SF, Channel Islands, UK.

Gillis JC, Benefield P, McTavish D.

Adis International Limited,
Auckland, New Zealand.
Drugs Aging 1994 Aug;5(2):133-52

ABSTRACT

Idebenone is a benzoquinone compound which has been investigated in elderly patients with dementia. Its precise mechanism(s) of action remains unknown, but in vitro and in vivo studies suggest the drug may diminish nerve cell damage due to ischaemia, correct neurotransmitter defects and/or cerebral metabolism and facilitate memory and learning. In the small number of studies available for evaluation, idebenone was generally superior to placebo and comparable with bifemelane, oxiracetam and nebracetam on the basis of a number of objective and subjective tests and rating scales in patients with mild to moderate cognitive decline. Clinical trial results indicate that patients with mild dementia seem more likely to respond than those with greater functional decline. The degree of benefit conferred by idebenone is often difficult to determine, but in those who respond, improvement is generally mild to moderate. Therapy with idebenone appears well tolerated for up to 2 years, and no changes in vital signs or laboratory values have been seen in clinical trials. In view of the lack of a proven agent to limit or halt the progression of dementia in the elderly, idebenone may warrant consideration in patients with mild cognitive dysfunction on the basis of preliminary evidence of predominantly mild improvement of functional status in some patients and good tolerability. However, further well designed studies, including comparisons with newer and commonly used agents, such as tacrine, are required to better define the role of idebenone in this complex area of treatment.

Hirai K, Hayako H, Kato K, Miyamoto M.

Pharmaceutical Research Division,
Takeda Chemical Industries Ltd., Osaka, Japan
Naunyn Schmiedebergs Arch Pharmacol 1998 Nov;358(5):582-5

ABSTRACT

The application of amyloid beta-peptide (Abeta) 1-40 (10 microM) caused neurodegeneration of hippocampal neuronal cells, as indicated by the release of lactate dehydrogenase (LDH) into the culture medium. Treatment with idebenone (10-1000 nM), a potent antioxidant in mitochondria, protected the hippocampal neurons against the Abeta1-40(10 microM)-induced neurotoxicity. To determine the morphological change in neurons during the Abeta1-40-induced cytotoxicity, the cells were immunostained with anti-MAP2 antibodies. After 4-day exposure to 10 microM Abeta1-40, the number of neurons was reduced, and the surviving neurons had an apparently reduced number of neurites which were shorter than those of control neurons. When idebenone was added to the culture medium with Abeta1-40, the number of surviving neurons was significantly increased, and their neurites were as long as seen in control culture. These results suggest that reactive oxygen species mediate neurotoxicity of Abeta1-40, and idebenone protects neurons against the Abeta1-40-induced neurotoxicity.

Shivaram KN, Winklhofer-Roob BM, Straka MS,
Devereaux MW, Everson G, Mierau GW, Sokol RJ.

Department of Pediatrics,
University of Colorado School of Medicine,
Denver, CO USA

ABSTRACT

Oxidant stress induced by hydrophobic bile acids has been implicated in the pathogenesis of liver injury in cholestatic liver disorders. We evaluated the effect of idebenone, a coenzyme Q analogue, on taurochenodeoxycholic acid (TCDC)-induced cell injury and oxidant stress in isolated rat hepatocytes and on glycochenodeoxycholic acid (GCDC)-induced generation of hydroperoxides in fresh hepatic mitochondria. Isolated rat hepatocytes in suspension under 9% oxygen atmosphere were preincubated with 0, 50, and 100 micromol/l idebenone for 30 min and then exposed to 1000 micromol/l TCDC for 4 h. LDH release (cell injury) and thiobarbituric acid reactive substances (measure of lipid peroxidation) increased after TCDC exposure but were markedly suppressed by idebenone pretreatment. In a second set of experiments, the addition of 100 micromol/l idebenone up to 3 h after hepatocytes were exposed to 1000 micromol/l TCDC resulted in abrogation of subsequent cell injury and markedly reduced oxidant damage to hepatocytes. Chenodeoxycholic acid concentrations increased to 5.15 nmol/10(6) cells after 2 h and to 7.05 after 4 h of incubation of hepatocytes with 1000 micromol/l TCDC, and did not differ in the presence of idebenone. In freshly isolated rat hepatic mitochondria, when respiration was stimulated by succinate, 10 micromol/l idebenone abrogated the generation of hydroperoxides during a 90-minute exposure to 400 micromol/l GCDC. These data demonstrate that idebenone functions as a potent protective hepatocyte antioxidant during hydrophobic bile acid toxicity, perhaps by reducing generation of oxygen free radicals in mitochondria.

Mordente A, Martorana GE, Minotti G, Giardina B.

Institute of Biological Chemistry,
Catholic University School of Medicine, Rome, Italy.

Chem Res Toxicol 1998 Jan;11(1):54-63

Abstract

Idebenone is a synthetic analogue of coenzyme Q that is currently employed in the treatment of vascular and degenerative diseases of the central nervous system. There is some evidence to suggest that idebenone might function as an antioxidant; however, it has not been demonstrated whether this function pertains to the quinone or hydroquinone form of idebenone. Here we demonstrate that idebenone can scavenge a variety of free radical species, including organic radicals such as 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and diphenylpicrylhydrazyl, peroxyl and tyrosyl radicals, and peroxynitrite. Idebenone can also redox couple with hypervalent species of Mb or Hb, thus preventing lipid peroxidation promoted by these species. Likewise, idebenone inhibits microsomal lipid peroxidation induced by ADP-iron complexes or organic hydroperoxides. In so doing, idebenone prevents the destruction of cytochrome P450, which otherwise would accompany lipid peroxidation. Irrespective of the experimental system under investigation, idebenone functions by virtue of the electron-donating properties of the hydroquinone form. Redox coupling of this hydroquinone with free radicals generates the quinone compound, which per se lacks antioxidant activity. In many experiments, the antioxidant effects of idebenone become appreciable at approximately 2 microM, which is well in the range of plasma levels attainable in patients given oral doses of this drug. Moreover, comparative experiments have shown that the antioxidant efficiency of idebenone varies from no less than 50% to slightly more than 100% of that of vitamin E or Trolox. We would therefore propose that the neuroprotective effects of idebenone can be attributed, at least in part, to its ability to function as an antioxidant, involving redox cycling between hydroquinone and quinone.

Suno M, Nagaoka A.

Central Research Division,
Takeda Chemical Industries, Ltd., Osaka, Japan
Arch Gerontol Geriatr 1989 May;8(3):299-305

ABSTRACT

The effects of idebenone on the swelling of rat brain mitochondria were studied. When FeCl3 was added to a mitochondrial suspension, a pronounced mitochondrial swelling occurred accompanied by the production of lipid peroxide; the two phenomena were closely correlated (r = 0.96, p less than 0.01). idebenone inhibited the mitochondrial swelling and lipid peroxidation in a concentration-dependent manner; the concentration giving 50% inhibition was 37 microM for swelling and 53 microM for lipid peroxidation. Metabolites of idebenone also inhibited the lipid peroxidation. These results suggest that idebenone stabilizes the mitochondrial membrane by inhibiting lipid peroxidation in brain mitochondria.

Schutz E, Wieland E, Hensel A, Niedmann PD,
Dreiss A, Armstrong VW, Schuff-Werner P, Oellerich M.

Abteilung Klinische Chemie,
Georg-August-Universitat, Gottingen, Germany. eschuetz@med.uni-goettingen.de
Clin Biochem 1997 Dec;30(8):619-24

ABSTRACT

OBJECTIVE: Despite the large body of evidence for a major role of neutrophils and oxidant stress, the exact pathogenesis of the early ischemia/reperfusion injury after cold preservation of the liver is not well understood. The potential benefit of an antioxidant on metabolic liver function during reperfusion has been demonstrated in several studies.

MATERIALS AND METHODS: We describe a cold storage/reperfusion damage model with isolated perfused pig livers, where the effects of neutrophils and idebenone, a recently developed benzoquinone antioxidant, were studied. The integrity of sinusoidal endothelial cells (SEC) was estimated by hyaluronic acid concentration in perfusate and the expression of endothelial constitutive nitric oxide synthase (ecNOS) after reperfusion and compared to lipid peroxidation and antioxidant content.

RESULTS: Hyaluronic acid displayed the highest levels and ecNOS mRNA was most depressed in livers reperfused with neutrophils after 20 h cold storage; this was accompanied by an increase in lipid peroxidation (TBARS) and a breakdown of endogenous lipophilic antioxidants (alpha-tocopherol and coenzyme Q-10). These effects were attenuated, when neutrophils were excluded from reperfusion and almost completely abolished by the addition of 200 mumol/L idebenone.

CONCLUSIONS: These data suggest that a leukocyte-mediated damage based on reactive oxygen species markedly contributes to the reperfusion injury of SEC after cold preservation of the liver. Therefore, the presence of effective antioxidants in the early reperfusion phase may be beneficial for liver graft integrity.

Yokoyama H, Tsuchihashi N, Ogata T, Hiramatsu M, Mori N.

Institute for Life Support Technology,
Yamagata Technopolis Foundation, Japan.
MAGMA 1996 Sep-Dec;4(3-4):247-50

ABSTRACT

Electron spin resonance (ESR) measurements after intracerebroventricular injection of a nitroxide radical were carried out in rats (n = 6) that received oral idebenone for 2 weeks and in control rats (n = 5), using an in vivo rapid scan ESR spectrometer. The half-life of nitroxide, which was estimated from the change in the peak height (delta M = +1) of the ESR signals from the head, was used as a marker for the elimination of the nitroxide radical. The half-life in the rats treated with idebenone was significantly shorter than it was in the controls (p < 0.05). This finding indicates that the treatment with idebenone can enhance the intracerebral-eliminating ability of the nitroxide radical.

Esposti MD, Ngo A, Ghelli A, Benelli B,
Carelli V, McLennan H, Linnane AW.

Centre for Molecular Biology and Medicine,
Monash University, Melbourne, Victoria, Australia.
Arch Biochem Biophys 1996 Jun 15;330(2):395-400

ABSTRACT

We have studied the interaction of idebenone with the energy-conserving complexes of the respiratory chain in beef heart mitochondria and compared its energetic efficiency with that of other analogs of coenzyme Q. idebenone is a very effective substrate for succinate:Q reductase and ubiquinol:cytochrome c reductase, but it is clearly a poor substrate for NADH:Q reductase (complex I). Indeed, idebenone is a strong inhibitor of both the redox and proton pumping activity of complex I, showing effects in part similar to those of coenzyme Q-2. However, the mechanism of idebenone interaction with complex I may be different from that of Q-2 because of its different sensitivity to inhibitors. The possible relevance of the present findings to the therapeutic use of idebenone is discussed.

Scavini C, Rozza A, Lanza E,
Favalli L, Racagni G, Brunello N.

Institute of Pharmacology,
University of Pavia, Italy.
Eur Neuropsychopharmacol 1996 May;6(2):95-102

ABSTRACT

The effect of idebenone on the serotonergic system was evaluated in the aging rat by measuring the kinetic constants of 3H-5HT and 3H-ketanserin binding sites in the cerebral cortex of rats at 3, 15 and 24 months of age following acute and subchronic administration of the drug. Idebenone displayed no in vitro affinity toward any population of serotonin receptors and did not modify their kinetic parameters after a single dose of 100 mg/kg, at any age tested. A subchronic treatment with the drug for 21 days at the dose of 30 mg/kg did not induce any relevant change in 3- and 15-month-old rats, whereas it significantly increased the density of both 3H-5HT and 3H-ketanserin binding sites in 24-month-old rats, where a lower number of receptors is detected as a consequence of aging. This effect was rather specific, since under the same experimental conditions no changes were detected in the density of cortical beta-adrenergic receptors in aged animals. In microdialysis studies, acute administration with idebenone did not affect 5HT and 5HIAA release at any age. Conversely, the pattern of serotonin metabolism was significantly modified in aged rats following repeated treatment with idebenone and was partially restored to a value similar to the one observed in young animals. These results suggest that idebenone, a putative neuroprotective agent which has been shown to improve brain metabolism in ischemic conditions, might also attenuate age-associated neuronal damage, acting probably on several neurotransmitter systems which undergo selective modification during aging.