Idebenone seems to be a potent antioxidant than its natural analog coenzyme Q10 and may be useful as an anti-aging ingredient and photoprotectant. It is however also a strong contact allergen.


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments




Showed strong photoprotection against sunburn cell formation in human skin and inhibition of DNA damage in keratinocytes in vitro, but effects seem to vary widely depending on the formulation.




Appears to be a more powerful antioxidant than vitamin E, vitamin C, kinetin, coenzyme Q10 and alpha lipoic acid.


Increased skin hydration


0.5% idebenone lotions improved skin surface hydration by 23% after 6 weeks, but this may be due to the effect of the cosmetic base.


Smoother skin


Patients who used a 0.5% idebenone lotion twice daily for 6 weeks recorded a 26% improvement in skin roughness.


Wrinkle treatment


Led to visible improvements in wrinkles around the eyes as well as an overall reduction in fine lines and wrinkles, possibly attributable to idebenone's ability to increase collagen expression and limit its degradation.

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Table of contents:

1. Sources

Idebenone is a synthetic analog of coenzyme Q10[1][2] that was originally developed for treating Alzheimer's disease and other cognitive disturbances. Like coenzyme Q10, it is lipophilic despite having a shorter side chain that increases its solubility in water.[3]

2. Bioavailability

Idebenone has a low molecular weight of 338.44 daltons, a pKa of 15.19 and a log P of 3.49. These physicochemical properties mean that it may be able to penetrate the skin passively.[4] Indeed, a small amount (0.02% of the applied dose) of idebenone has been shown to permeate across pig ear skin.[5]

However, it is not very stable under conditions of moderately high temperature and humidity, with 58% of free idebenone lost after 45 days' storage at 40°C and a relative humidity of 75%.[6] To overcome this limitation, idebenone can be encapsulated within nanoparticles and nanostructured lipid carriers designed to enhance its chemical stability.[6][4]

Such formulations have the added advantage that they can also increase the penetration of idebenone into the skin. Idebenone incorporated into nanostructured lipid carriers passed through the epidermis and dermis of guinea pig skin more easily than idebenone in an oil solution or in nanoemulsions,[4] as well as diffused through rat skin more effectively than an idebenone gel.[7] Idebenone-loaded solid lipid nanoparticles may be useful for targeting idebenone to the upper skin layers.[8]

Idebenone was partly metabolized to idebenone acid during its passage through pig ear skin, with the biotransformation presumably proceeding via the intermediate idebenone aldehyde which was further oxidized.[5]

3. Effects on the skin

The clinical efficacies of 2 commercial idebenone formulations were assessed in a clinical trial. 41 women were randomized to apply either of the 0.5% or 1% idebenone lotions to the entire face twice daily for 6 weeks. At the end of the study, the women who had used the 1% idebenone product had achieved a 26% reduction in skin roughness/dryness, a 29% reduction in fine lines/wrinkles, a 37% increase in skin hydration and an overall 33% improvement of photodamaged skin. The women who had used the 0.5% idebenone formulation, too, saw a 23% reduction in skin roughness/dryness, a 27% reduction in fine lines/wrinkles, a 37% increase in skin hydration, and an overall 30% improvement in photodamaged skin. In addition, the digital photographs recorded visible improvements in periorbital rhytides and pigment dyschromia for both sets of subjects, and histological analysis revealed an increase in collagen I as well as a decrease in matrix metalloproteinase-1. The moisturization effect was thought to be associated more with the base rather than with idebenone itself and the decrease in skin roughness/dryness was thought to be a combination of the two, but this could not be confirmed as a placebo was not employed in the study. The improvement in pigmentation may be due to idebenone's structural similarities to hydroquinone, which is known to inhibit increased melanin production by melanocytes, there is no evidence as of yet to support this notion.[9]

In 2013, an independent study conducted by the University of Michigan conducted a meta-analysis of 5 commercial products in an attempt to identify factors that could predict responsiveness to antiaging cosmeceuticals. 1 of the products tested was Prevage MD, a 1% idebenone cream, which was applied twice daily for 10 days by 16 subjects. All 5 products including the idebenone cream were found to be effective at raising procollagen I levels only in a subset of treated individuals that had hypo-collagenesis at baseline, but it is conceivable that a longer treatment period would have allowed for an increase to be seen in the individuals with normo-collagenesis.[10]

3.2 Antioxidant effect

Idebenone can scavenge a variety of free radicals and reactive oxygen species, including peroxyl radicals and superoxide anions.[11][12] It is also known to inhibit lipid peroxidation.[13]

Comparative experiments indicate that idebenone is more effective at protecting against oxidative stress overall than α-tocopherol (vitamin E), kinetin, coenzyme Q10, ascorbic acid (vitamin C) and alpha lipoic acid,[14] but that its antioxidant potency is less than that of ergothioneine.[15] A 3% antioxidant complex containing botanical extracts rich in ferulic acid, caffeic acid and other polyphenols also possessed an antioxidative capacity that was 2.5 times greater than 1% idebenone, as measured by the quenching of superoxide anion radicals.[16]

Entrapment of idebenone within nanocapsules enhanced its antioxidant effect in one study,[17] but loading of idebenone onto nanostructured carriers did not alter its lipid peroxidation activity in another.[7] Incorporation of idebenone into nanocapsules or nanoparticles has however been shown to preserve or prolong its antioxidant efficacy, perhaps by stabilizing idebenone or protecting it from degradation.[6][18]

3.3 Photoprotection

The results of a human sunburn cell assay suggest that idebenone may afford substantial photoprotection to the skin. 0.5% idebenone led to a 38% reduction in sunburn cell formation, higher than the same concentration of vitamin E (30%), kinetin (20%), coenzyme Q10 (11%), alpha lipoic acid (9%) and vitamin C (0%). Furthermore, it provided the greatest inhibition of nuclear thymine dimer photoproducts (45%) in irradiated keratinocyte cultures, compared to ascorbic acid (36%), kinetin (36%), vitamin E (34%), ubiquinone (4%) and alpha lipoic acid (0%).[14]

Experiments on albino mice indicated that a plain idebenone gel had an SPF of about 10, calculated as the ratio of the minimal erythemal dose (MED) with respect to time for protected skin and the MED with respect to time for unprotected skin, while another formulation containing 1% idebenone loaded onto nanostructured lipid carriers had an SPF of 23. These values compared favourably with a reference sunscreen product, which was found to have an SPF of about 15.[7]

However, in another study a 1.0% idebenone solution, a commercial 1% idebenone cream (Prevage), and a 0.5% idebenone cream (TRUE Youth Revealing Complex) were all ineffective in reducing erythema generated by 5x MED of solar-simulated UV light after application to patches of pig skin daily for 4 days. The 0.5% idebenone cream did decrease sunburn cell formation to a significant extent at 4-5x MED, but this may have been due to the sunscreen in the formulation.[19]

4. Side Effects

4.1 Contact dermatitis

Idebenone appears to be a strong contact allergen, a role it was attributed in 4 case reports in 2007 and 2008. The first case was of a 47-year-old woman who developed an edematous vesicular dermatitis of the face, ears and neck within 24 hours of having an anti-aging cream (Prevage by Elizabeth Arden) applied at a salon.[20] The second patient was a 43-year-old women who developed an itchy eruption at the sites where an anti-aging cream had been applied 2 days previously.[21] The third case, a 50-year-old woman, had a more acute onset of symptoms, with heat and tightness after 4 hours followed by erythema and perioribtal swelling the day after.[22] In all 3 cases, patch testing yielded a positive reaction to 0.5% idebenone, which is the same concentration found in the Prevage cream.[20][21][22] The last patient was a 38-year-old actress who had a burning, swollen face after applying Prevage MD, a more concentrated formulation with 1% idebenone.[23]

Likewise, an independent study of Prevage MD, which contains 1% idebenone, reported that 5 out of 16 (31%) subjects experienced irritation with the cream.[10]

Because idebenone displayed delayed in vitro toxicity in melanocytes and it is known to be metabolized in both pig ear tissue and mouse melanocytes, this metabolism of idebenone to idebenone acid is thought to be responsible for activating skin irritation during in vivo usage.[24]

Scientific References

  1. Jung YS, et. al. Synthesis of idebenone; a synthetic analog of coenzyme Q. Synth Commun. (2001)
  2. Tsoukala A, Bjørsvik H. Synthetic Route Discovery and Introductory Optimization of a Novel Process to Idebenone. Org Process Res Dev. (2011)
  3. Wieland E, et. al. Idebenone protects hepatic microsomes against oxygen radical-mediated damage in organ preservation solutions. Transplantation. (1995)
  4. Li B, Ge ZQ. Nanostructured lipid carriers improve skin permeation and chemical stability of idebenone. AAPS PharmSciTech. (2012)
  5. Wempe MF, et. al. Investigating idebenone and idebenone linoleate metabolism - in vitro pig ear and mouse melanocyte studies. J Cosmet Dermatol. (2009)
  6. Amorim Cde M, et. al. Antioxidant idebenone-loaded nanoparticles based on chitosan and N-carboxymethylchitosan. Nanomedicine. (2010)
  7. Salunkhe SS, et. al. Topical delivery of Idebenone using nanostructured lipid carriers: evaluations of sun-protection and anti-oxidant effects. J Pharm Investig. (2013)
  8. Montenegro L, et. al. Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in vitro evaluation. Int J Pharm. (2012)
  9. McDaniel DH, et. al. Clinical efficacy assessment in photodamaged skin of 0.5% and 1.0% idebenone. J Cosmet Dermatol. (2005)
  10. Sachs DL, et. al. Hypo-collagenesis in photoaged skin predicts response to anti-aging cosmeceuticals. J Cosmet Dermatol. (2013)
  11. Mordente A, et. al. Antioxidant properties of 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (idebenone). Chem Res Toxicol. (1998)
  12. Murakami M, Zs -Nagy I. Superoxide radical scavenging activity of idebenone in vitro studied by ESR spin trapping method and direct ESR measurement at liquid nitrogen temperature. Arch Gerontol Geriatr. (1990)
  13. Suno M, Nagaoka A. Inhibition of lipid peroxidation by a novel compound, idebenone (CV-2619). Jpn J Pharmacol. (1984)
  14. McDaniel DH, et. al. Idebenone: a new antioxidant - Part I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants. J Cosmet Dermatol. (2005)
  15. Dong KK, et. al. A comparison of the relative antioxidant potency of L-ergothioneine and idebenone. J Cosmet Dermatol. (2007)
  16. Zhai H, et. al. Determination of the antioxidative capacity of an antioxidant complex and idebenone: an in vitro rapid and sensitive method. J Cosmet Dermatol. (2008)
  17. Palumbo M, et. al. Improved antioxidant effect of idebenone-loaded polyethyl-2-cyanoacrylate nanocapsules tested on human fibroblasts. Pharm Res. (2002)
  18. Leonardi A, et. al. Antioxidant activity of idebenone-loaded neutral and cationic solid-lipid nanoparticles. Pharm Dev Technol. (2014)
  19. Oresajo C, et. al. Ubiquinone, idebenone, and kinetin provide ineffective photoprotection to skin when compared to a topical antioxidant combination of vitamins C and E with ferulic acid. J Cosmet Dermatol. (2008)
  20. Sasseville D, Moreau L, Al-Sowaidi M. Allergic contact dermatitis to idebenone used as an antioxidant in an anti-wrinkle cream. Contact Dermatitis. (2007)
  21. Natkunarajah J, Ostlere L. Allergic contact dermatitis to idebenone in an over-the-counter anti-ageing cream. Contact Dermatitis. (2008)
  22. Fleming JD, White JM, White IR. Allergic contact dermatitis to hydroxydecyl ubiquinone: a newly described contact allergen in cosmetics. Contact Dermatitis. (2008)
  23. Mc Aleer MA, Collins P. Allergic contact dermatitis to hydroxydecyl ubiquinone (idebenone) following application of anti-ageing cosmetic cream. Contact Dermatitis. (2008)
  24. Wempe MF, et. al. Investigating idebenone and idebenone linoleate metabolism: in vitro pig ear and mouse melanocyte studies. J Cosmet Dermatol. (2009)