Coenzyme Q10

Coenzyme Q₁₀ is a naturally occurring skin antioxidant and energizer that can help combat many of the detrimental signs of aging such as wrinkles, rough skin and reduced skin elasticity.

Effects


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

C

Antioxidant

Strong

Lowers skin oxidative stress by scavenging free radicals, preventing membrane lipid peroxidation and oxidative DNA damage.

C

Wrinkle treatment

Strong

Makes wrinkles shallower, possibly by increasing the production of type IV and VII collagens while at the same time inhibiting the induction of collagen-degrading enzymes.

C

Increased skin elasticity

Strong

Increases the expression of elastin in fibroblasts, thereby raising skin elasticity. The effect is particularly strong for creams in which CoQ10 is encapsulated within solid lipid nanoparticles.

C

Increased skin hydration

Strong

A simple cream with 0.3% CoQ10 improved skin hydration by 40% after only 1 month. The solid lipid nanoparticle cream had a more pronounced increase, perhaps due to an occlusive effect.

C

Smoother skin

Strong

A 0.3% CoQ10 cream used over 6 months led to a 26% improvement in skin smoothness as measured by microtopography.

D

Skin lightening

Mild

Brightens the skin by Inhibiting the activity of tyrosinase, an enzyme involved in melanin synthesis.

D

Healing

Mild

May improve collagen production and inhibit inflammation caused by skin injuries via its antioxidative effects.

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Scientific Research


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Table of contents:

1. Sources

Coenzyme Q₁₀ (CoQ₁₀) or ubiquinone-10 is a fat-soluble compound that exists as a yellow or orange powder in its natural form.[1][2] Chemically, it consists of a benzoquinone head attached to a side chain of 10 isoprene units. The quinone head can alternately assume 3 different redox states that are vital for its various functions: ubiquinone, the fully oxidized form, semiquinone, the partially reduced form that is also a free radical, and ubiquinol, the fully reduced form.[3]

CoQ₁₀ is present in the inner mitochondrial membrane of every cell in the human body,[4] where it is a crucial component of the electron transport chain and plays a pivotal role in cellular energy generation.[5] The fully reduced form, ubiquinol-10, is also an important physiological lipophilic antioxidant.[6]

Although intracellular synthesis is the major source of CoQ₁₀ in the human body, CoQ₁₀ can also be obtained from the diet. Meat, fish, nuts and some oils have the highest levels, while lower levels can be found in dairy products, fruits, vegetables and cereals.[7][8] The average dietary intake of CoQ₁₀ is about 3-6 mg/day.[9][10]

In humans, CoQ₁₀ is present in the highest concentrations in the heart, kidney and liver,[11] but it also exists in the skin as part of the skin surface lipids.[12] The concentration of CoQ₁₀ is 10-fold higher in the epidermis than in the dermis.[13]

The levels of CoQ₁₀ in human tissues such as the heart and the brain have been reported to decline with age.[14][15] Because the levels of CoQ₁₀ in the epidermis also decreases in a linear fashion from age 30 onwards, the skin may be another tissue that potentially benefits from exogenously supplied CoQ₁₀.[16]

2. Bioavailability

2.1 Topical administration

CoQ₁₀ has a relatively large molecular weight of 863 daltons and is highly lipophilic as a consequence of the 10 isoprene units in its chemical structure.[17] Delivering CoQ₁₀ to the deeper layers of the skin is challenging due to its low aqueous solubility.[18] Moreover, it labile to heat, deteriorating at temperatures of about 46°C,[1] and degrades under UV irradiation.[19] These factors combine to limit the topical bioavailability of CoQ₁₀.

As a result, different formulations for encapsulating CoQ₁₀ for topical applications have been developed. These include liposomes,[18][20] nanoemulsions,[21] nanocapsules,[2][22] solid lipid nanoparticles[23][24] and nanostructured lipid carriers.[25][26][27][28]

CoQ₁₀ suspended in olive oil or encapsulated in solid lipid nanoparticles, lecithin-based lipid nanoparticles or liposomes have been shown to penetrate rat skin.[2][20][23][29] Similarly, topical application of CoQ₁₀ in ethanol to pig skin, which closely resembles human skin in terms of permeability, led to penetration of CoQ₁₀ into the stratum corneum, with approximately 20% penetrating further into the viable layers of the epidermis and 2% into the dermis.[16]

2 forms of CoQ₁₀, pure CoQ₁₀ and yeast CoQ₁₀ (8% CoQ₁₀ by weight in a glycoprotein matrix) have been investigated for their absorption in human skin. Between 2-6% of CoQ₁₀ was absorbed in the stratum corneum 1 hour after topical application. The yeast form was better absorbed, with 34% more absorption over the pure form in young subjects and 23% more absorption over the pure form in middle-aged subjects. Older subjects were also found to absorb over twice as much CoQ₁₀ as the younger subjects regardless of the form applied, which was thought to be due to the smaller corneocytes and lower hydration level of the stratum corneum in the older subjects. In addition, CoQ₁₀ appeared to move from the stratum corneum to the epidermis and dermis overnight, as no CoQ₁₀ was detected in the stratum corneum 12 hours after the last application.[3]

Another study in which a cream containing 0.05% CoQ₁₀ was applied daily to the faces and backs of 25 volunteers found that the level of CoQ₁₀ in the sebum was raised without significantly affecting the stratum corneum or plasma concentrations of the redox couple ubiquinol/ubiquinone.[30]

2.2 Oral administration

The uptake and distribution of CoQ₁₀ appears to involve incorporation into chylomicrons for transport to the lymph and peripheral blood.[31] However the bioavailability of oral CoQ₁₀ is at best only moderate, perhaps due to its poor water solubility.[32][33]

Several advancements have been made to enhance the bioavailability of CoQ₁₀ supplements using approaches like size reduction, solubility enhancement and novel drug carriers such as liposomes, microspheres, nanoparticles, nanoemulsions and self-emulsifiying systems.[34]

In one study, supplementation with 30 mg CoQ₁₀ raised the average blood CoQ₁₀ concentration from 1 mg/l to 2 mg/l after 3 months,[35] and a correlation between the ingested dose and the increase in plasma CoQ₁₀ level has been observed.[33][36][37] The extent of the increase in plasma CoQ₁₀ concentration also seems to depend on the pre-existing CoQ₁₀ status, as a single dose of 30 mg had only a marginal elevating effect on in subjects that were not CoQ₁₀-deficient.[38]

Importantly, there is evidence that oral supplementation of CoQ₁₀ can raise skin levels of CoQ₁₀. CoQ₁₀ intake elevated the epidermal (but not the dermal) CoQ₁₀ level of hairless male mice.[39] Moreover, in human volunteers daily oral administration of 50 mg CoQ₁₀ plus topical treatment with a 0.05% CoQ₁₀ cream raised the levels of CoQ₁₀ in the stratum corneum and in the sebum, in contrast with topical treatment alone which only increased the sebum levels of CoQ₁₀.[30]

3. Effects on the skin

3.1 Antioxidant effect

Ubiquinol-10, the fully reduced form of CoQ₁₀, is an effective lipid-soluble antioxidant at physiological concentrations. It efficiently scavenged free radicals generated chemically within liposomal membranes and was about as effective in preventing lipid peroxidation as α-tocopherol, which is regarded as the best lipid-soluble antioxidant in humans.[6]

CoQ₁₀ has also shown that it is capable of protecting keratinocytes against UV radiation. It suppressed the depletion of gluthathione and markedly decreased the oxidative DNA damage caused when keratinocytes were irradiated with UV light.[16][40] CoQ₁₀ treatment also mitigated the increase in cellular levels of reactive oxygen species (ROS) when cultures of primary fibroblasts were irradiated with UVB.[41]

More importantly, when 0.3% CoQ₁₀ was applied to the forearm of volunteers twice daily for 7 days, the treated skin sites had significantly lower levels of ultra weak photon emission, a measure of oxidative stress, following UVA exposure. This indicates that CoQ₁₀ does exert an antioxidant effect on human skin in vivo.[16]

In 1999, the first in vivo study on the effects of CoQ₁₀ on aged skin was published. A 0.3% CoQ₁₀ cream or vehicle control was applied once daily around the eyes of 20 elderly volunteers. After 6 months of treatment, the depth of deep wrinkles, which are characteristic of photoaging, were visibly reduced. Microtopography revealed a 27% reduction in the mean peak to valley depth of the skin, plus a 26% improvement in the variation of the microtopography from a flat surface, indicative of increased skin smoothness, compared to vehicle-treated controls.[16] Another clinical trial had similar results, finding that the use of a 1% CoQ₁₀ cream for 5 months reduced the wrinkle score grade in the active group, unlike the control group which had no improvement.[42]

This anti-wrinkle effect is understandable, as CoQ₁₀ is known to exert a positive influence on the dermal matrix. It significantly increased the levels of glycosaminoglycans in human fibroblasts that had been cultured for a prolonged period to mimic chronological aging, and suppressed the expression of matrix-eroding collagenase produced by such fibroblasts in response to UV irradiation.[16] The latter result has been reproduced elsewhere, with CoQ₁₀ blocking the induction of matrix metalloproteinase-1 in separate cultures of human fibroblasts.[41][42][43]

Interestingly, creatine, another important component of the cellular energy system, appears to synergize with CoQ₁₀ in topical formulations. In a double-blind, vehicle-controlled trial, a topical preparation containing CoQ₁₀ + stabilized creatine led to stronger improvements in wrinkle reduction than a similar preparation containing CoQ₁₀ alone after 2 months of product application.[44]

As a result, it has been proposed that the bioenergetic role of CoQ₁₀ may be involved in its antiaging effects. Significant age-dependent differences are known to exist in the mitochondrial function of keratinocytes isolated from skin biopsies of young and old donors, and it has been postulated that reactive oxygen species (ROS) are generated in aging skin as byproducts of an impaired mitochondrial respiration. The enhanced production of ROS is associated with changes in protein structure and function, changes in gene expression, DNA damage and further impairment of mitochondrial protein complexes and enzymes, which in turn may accelerate the aging process. It is therefore possible that CoQ₁₀ helps combat the signs of aging by reinforcing the endogenous mitochondrial energy capacity of skin cells.[45][46]

A double-blinded study compared the antiaging effects of a simple CoQ₁₀ cream with those of a CoQ₁₀-loaded solid lipid nanoparticle (SLN) cream. 25 women applied one of the creams every night, and measurements of skin hydration and skin elasticity were taken using a corneometer and a cutometer on days 0, 30 and 60. After 1 month, women who had used the simple cream had a 40% increase in skin humidity and a 5% increase in skin elasticity, whereas those using the SLN cream had a 65% increase in skin humidity and a 120% increase in skin elasticity. These improvements persisted and became even more profound at the end of the second month, with the simple cream raising skin humidity and skin elasticity by 40% and 20%, and the SLN cream leading to a 120% and 125% rise in skin humidity and skin elasticity, respectively.[24]

The superior effect of the SLN cream on skin hydration may be due to the occlusive effect of lipid nanoparticles.[47] CoQ₁₀ has also been demonstrated to increase the gene expression of elastin in human dermal fibroblasts in a dose-dependent manner, which may account for its effectiveness in improving skin elasticity.[41]

Another study had 50 female volunteers with mild-to-moderate photodamage apply a cream containing 0.05% CoQ₁₀, 0.1% vitamin E and 1% squalene to their faces, upper backs and forearms daily for 2 months, with half also receiving oral administration of 25 mg of CoQ₁₀ + 25 mg of vitamin E acetate + 25 μg of selenium aspartate twice a day after meals during this period. At the end of the treatments, all 25 volunteers who had received both oral and topical treatment noted subjective improvements in the condition of their skin (softness, smoothness and brightness), which in 10 cases were highly improved. Of the 25 volunteers who received topical treatment, there were 4 cases of high improvement, 20 case of improvement and 1 case with no change. Moreover, profilometry revealed statistically significant differences in the deepness of wrinkling in both groups between the baseline and final visit.[30]

The increased softness was attributed to the sebum-like fractions of the cream acting as an emollient.[30] CoQ₁₀ has also been shown to inhibit tyrosinase activity, resulting in a lower melanin content in a mouse melanoma cell line,[41] which explains why it has been observed to brighten the skin.[30]

CoQ₁₀ has also been shown to accelerate the production of basement membrane components in vitro, namely laminin 332 and type IV and VII collagens in keratinocytes and fibroblasts respectively, though it had no effect on type I collagen production in fibroblasts. The increased production of laminin 332 is especially significant as laminin 332 promotes basement membrane repair. The basement membrane functions to tightly link the epidermis to the dermis at the dermal epidermal junction, and impairment of its structure may facilitate aging processes by damaging the dermal extracellular matrices and inducing keratinocyte abnormality.[41][48]

In addition, CoQ₁₀ decreased the size of the corneocytes in aged skin. Since the area of the corneocytes is proportional to the time taken for keratinocytes to differentiate and move from the basal layer to the stratum corneum, this is thought to be an indicator of a higher rate of epithelium turnover, which is known to be lower in aged skin.[16]

3.3 Improved wound healing

The process of wound repair may be adversely affected by the presence of reactive oxygen species, which are produced in response to cutaneous injury[49] and may cause cellular damage by membrane lipid peroxidation.[50] Hence, improving local antioxidant activity may be beneficial to wound healing.

Experiments on mice with skin incisions found that the group treated with 100 mg/kg CoQ₁₀ had a higher level of a collagen-like polymer as well as lower levels of myeloperoxidase and phospholipase A2, 2 biomarkers of inflammation, compared to the control group that received no treatment, indicating a cutaneous healing effect.[51] Furthermore, the combination of CoQ₁₀, α-tocopherol, soy phospholipids and L-methionine was advantageous for skin healing, trophism and accelerated re-epithelization in rats on which the effects of laser resurfacing and chemical peeling had been reproduced.[52]

3.4 Ineffective photoprotection

CoQ₁₀ is not an effective photoprotectant. A 1% CoQ₁₀ solution did not decrease erythema or sunburn cell formation in pig skin irradiated with UV light compared to a positive control,[53] and did not exhibit any photoprotective effect in an experiment on human skin fibroblasts despite its radical scavenging ability.[54] However, CoQ₁₀ may increase the photoprotective effect of the flavonoid luteolin, as the combination of luteolin, tocopherol and CoQ₁₀ in a 4:4:1 ratio and at a concentration of 2 µg/mL showed complete photoprotection of human skin fibroblasts irradiated with solar simulated light.[54]

4. Side Effects

CoQ₁₀ is not cytotoxic to cultured keratinocytes even at a concentration of 200 μg/mL, which is the limit of solubility. Occlusive patch tests conducted on volunteers found no irritancy potential for 0.3% CoQ₁₀, and CoQ₁₀ can be tolerated even by people with sensitive skin.[16][55]

CoQ₁₀ is highly safe for use as a dietary supplement; published reports of safety studies have not identified any serious adverse effects causally related to its ingestion.[56] There is strong evidence of safety at intakes up to 1200 mg/day for adults.[57]

Scientific References


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