Vitamin E: what are the beneficial combinations of active ingredients?

Also known as ascorbic acid, vitamin C is a well-known active ingredient valued for its antioxidant properties. Indeed, by donating an electron, this molecule can neutralize free radicals generated by UV exposure, pollution, or tobacco before they damage cellular components and DNA. However, note that this photoprotection does not make vitamin C a sunscreen per se. Vitamin E, found primarily in the stratum corneum of the skin, has similar properties. It acts differently, though: its chemical structure allows it to donate a hydrogen atom, which stabilizes free radicals. It then becomes a free radical itself, but is relatively stable due to its aromatic nature. Vitamin E, however, can no longer act.

Several studies have investigated the potential synergy between vitamin E and vitamin C, and the results show that their combination allows for enhancing antioxidant protection provided by these molecules. Indeed, vitamin C, whose redox potential is lower than that of vitamin E, can reduce the latter to regenerate its activity. Moreover, it has been shown that daily application for four days of a solution containing 15% vitamin C and 1% vitamin E enabled doubling the protection against actinic erythema compared to the application of either vitamin alone. It should be noted, however, that the referenced study was conducted on pigs. It would be valuable for clinical trials in humans to confirm these findings.

From a mechanistic standpoint, vitamins E and C work in tandem in the skin through a chain antioxidant mechanism.

Vitamin E, located in lipid membranes, is the first to neutralize free radicals generated notably by UV radiation. In the process, it becomes oxidized and is converted into a less active radical form called the tocopheryl radical. This is where vitamin C comes into play: present in the aqueous phase, it donates an electron to the tocopheryl radical, regenerating vitamin E to its active form while itself being oxidized to dehydroascorbic acid. This recycling enables vitamin E to continue protecting membrane lipids, while vitamin C can in turn be regenerated by other cellular reducing systems such as glutathione. Together, they form a complementary antioxidant system: vitamin E acts in the lipid phase and vitamin C in the aqueous phase, while extending vitamin E’s effectiveness and reactivating it.

More commonly known as retinol, one of its derivatives, vitamin A is considered one of the most effective cosmetic actives for stimulating cellular turnover and offsetting the natural breakdown of collagen and elastin. It is therefore especially used in products designed to combat skin aging and loss of firmness. However, vitamin A has two major drawbacks: it can be irritating and is therefore not recommended for sensitive skin, and it is subject to oxidation by sunlight. Thus, following sun exposure, vitamin A can convert into various reactive intermediates that can cause skin damage.

Vitamin E, due to its antioxidant activity, could serve as a cofactor to stabilize vitamin A and protect it from oxidation.

Another potential benefit of combining vitamin E and vitamin A: an enhanced anti-inflammatory effect. Indeed, one study suggests this by evaluating the topical co-administration of α-tocopherol (0.1%) and retinol (0.05%) in a microemulsion. Tested in vivo on skin rendered inflamed by the application of TPA, an irritating compound, the vitamin E-loaded microemulsion led to a significant decrease in TNF-α expression, a marker of inflammation. The simultaneous addition of retinol further enhanced this effect: TNF-α expression was reduced to a greater extent than in the group receiving vitamin E alone, demonstrating a synergistic effect between the two molecules. These results suggest that the topical combination of vitamin A and vitamin E may be beneficial for alleviating skin inflammation.

Although it is incorrect to label vitamin E as a preservative, it nonetheless plays a significant role in oil-based cosmetic formulations. Indeed, most vegetable oils are rich in omega-3 fatty acids, compounds whose chemical structure contains numerous double bonds. This characteristic makes them susceptible to oxidative degradation triggered particularly by atmospheric oxygen and UV radiation. Oxidation of these oil constituents negatively affects their cosmetic and organoleptic properties. When rancid, they can become harmful to the skin and even comedogenic.

Thanks to its antioxidant properties, vitamin E can counteract this phenomenon and help to preserve the quality of vegetable oils. Vitamin E is thus relevant to use with vegetable oils rich in omega-3, such as alpha-linoleic acid. It also works similarly with sebum by preventing the lipid peroxidation of squalene, one of its major components. By doing so, it inhibits its conversion to squalene peroxide, a comedogenic molecule. The vitamin E is thus an ally for oily skin.

Note: For the same reasons, it is interesting to combine vitamin E and aloe vera, an ingredient with moisturizing properties. Indeed, aloe vera gel can become slightly yellow over time, due to its oxidation in contact with air. Vitamin E can help prevent this phenomenon thanks to its antioxidant action.

Selenium is an essential trace element for the body. Primarily localized in the kidneys and liver, studies have shown that it stimulates immune system activity and protects cardiovascular function. It is also a potent anti-inflammatory and antioxidant. Mainly found in raw vegetables, selenium can also be found in dietary supplements.

A study examined the vitamin E/selenium combination and its effects on acne. Twenty-nine patients suffering from this skin condition were asked to take a tablet containing 0.2 mg of selenium and 10 mg of tocopherols twice a day for 12 weeks. At the end of the trial, scientists observed a significant reduction in the number and severity of acne lesions in the patients, particularly among those with inflammatory acne. However, the chemical mechanisms underlying the synergy between vitamin E and selenium remain unknown.

A daily intake of selenium exceeding 900 μg can be toxic and result in gastrointestinal disturbances, hair loss, and bad breath.

Coenzyme Q10, also known as ubiquinone, is a naturally occurring antioxidant in the body. Primarily found in mitochondria where it helps activate cellular energy production, it is also present in sebum where it acts synergistically with vitamin E to protect its components from oxidation. A study involving 100 volunteers also showed that exposing sebum to UV irradiation equivalent to four times the minimal erythemal dose (MED), i.e. the minimum amount of light capable of causing sunburn, decreased vitamin E levels by 84.2%, coenzyme Q10 by 70%, and squalene by only 13%. The same UV dose applied in the absence of vitamin E and CoQ10 led to a 90% reduction in squalene, clearly demonstrating the protective role these two molecules normally play.

In addition to its protective effect on sebum, the vitamin E/coenzyme Q10 combination has shown some potential to improve the quality of life of individuals suffering from psoriasis. In one study, 58 patients were divided into two groups: the first received a corticosteroid-based treatment combined with a daily supplementation of coenzyme Q10 (50 mg), vitamin E (50 mg), and selenium (48 μg), while the second group received only corticosteroids. After 35 days, a more significant improvement in the condition of the patients in the first group was observed. It appears that the tested combination of active compounds may provide real support in the daily management of psoriasis symptoms.

Zinc is a crucial element for the proper functioning of the body and the maintenance of skin health. It is naturally present in small amounts in the body, and zinc intake is primarily achieved through diet and sometimes dietary supplements. In addition to contributing to the development of bodily tissues, this element is involved in the metabolism of certain proteins, lipids, and carbohydrates. The zinc is also one of the most recommended active agents for those with combination to oily skin, and it can help combat acne issues. A lesser-known protein, lactoferrin is one component of the immune system, and it possesses antimicrobial and antifungal activity.

In a recent study, 82 patients with acne received twice-daily capsules containing lactoferrin (100 mg), vitamin E (7.3 mg), and zinc (5 mg). After 12 weeks, the researchers observed a significant improvement in the patients’ skin condition, coupled with a reduction in sebum secretion rates. Supplementation with vitamin E, zinc, and lactoferrin was therefore relatively effective, although the patients’ acne was not completely eradicated.

The association between vitamin E and vitamin D is based on the complementarity of their biological mechanisms, notably in the management of oxidative stress, inflammation, and immunity. Vitamin D primarily acts by activating the VDR receptor, thereby regulating the expression of genes involved in cell differentiation, inflammation control, energy metabolism, and immune modulation. Vitamin E, for its part, provides direct protection to cell membranes thanks to its antioxidant capacity, thereby limiting damage caused by free radicals implicated in numerous chronic diseases. Combining these two vitamins could lead to improved oxidative stress management and more effective cellular protection.

The combination of vitamins D and E is common in dietary supplements, but less so in cosmetics.

The collagen is an essential structural protein that ensures the firmness, strength, and cohesion of skin tissues. When applied topically, its effect on fibroblasts, the cells responsible for synthesizing collagen, remains limited due to its large molecular size impeding penetration; nevertheless, it still contributes to improved skin hydration. On the other hand, if they are peptides of collagen, molecules with a lower molecular weight, studies have shown that they can stimulate fibroblast activity.

Although no study has investigated the combination of vitamin E and topical collagen, their respective mechanisms suggest potential benefits.

Indeed, the antioxidant properties of vitamin E help protect the skin’s collagen fibers. A recent rat study also demonstrated that topical application of alpha-tocopherol, the active form of vitamin E, increased collagen density during the early phase of wound healing. Researchers observed a significant rise in fibroblast numbers and an improved collagen density score in treated animals compared to placebo. While these findings derive from an animal model, they nonetheless support the idea that vitamin E can modulate collagen dynamics and suggest that combining it with collagen-based treatments could be relevant.

The hyaluronic acid is a molecule naturally present in the skin, capable of holding up to 1,000 times its weight in water. When applied topically, it helps to maintain skin hydration, improves skin suppleness, and contributes to smoothing wrinkles and fine lines. Combining hyaluronic acid with vitamin E can therefore be beneficial, as one targets hydration while the other protects the skin against oxidative stress.

This potential synergy could also be promising in the context of skin wound healing. A study evaluated a formulation containing hyaluronic acid, vitamin E, and raspberry and green tea extracts to assess its impact on tissue repair. In a test in vitro performed on human fibroblasts, the preparation significantly outperformed the control formula, which lacked the active ingredients. These results suggest that the hyaluronic acid, particularly in its low-molecular-weight form, capable of penetrating the stratum corneum, combines its hydrating effect with that of vitamin E and other antioxidants to accelerate re-epithelialization, stimulate keratinocyte migration, and contribute to collagen remodeling, thereby improving the process of wound healing.

The association between vitamin E and vitamin K is extensively studied due to their shared metabolic pathways and potential interactions, particularly regarding vitamin K’s role in blood coagulation. Vitamin E can interfere with vitamin K function by competing for enzymes that convert phylloquinone (vitamin K1) into menaquinone-4 (MK-4), the active form in tissues. They also share similar metabolic mechanisms, and both can activate the pregnane X receptor (PXR), which regulates their metabolism and elimination. This is why high vitamin E intakes can sometimes reduce vitamin K availability and increase bleeding risk, highlighting the benefit of combining them during supplementation.

Since February 4, 2009, the use of pure vitamin K1 has been prohibited in cosmetics due to reported cases of contact dermatitis. It is now used in its oxidized form, which is more stable and better tolerated, and is sometimes combined with vitamin E, even though this topical pairing has not yet been evaluated in independent clinical studies.

Some people assume that associating vitamin E with glycerin could help reduce hyperpigmentation. However, if studies in vitro suggest that vitamin E can interfere with melanogenesis, while glycerin itself shows no effect on pigmentation. In formulations, glycerin improves the stability of vitamin E by modulating the physical structure of emulsions. For example, research shows that high glycerin concentrations (40–50%) produce smaller, more stable vitamin E acetate nanoemulsions, which optimize antioxidant protection and extend product shelf life.

The combination of vitamin E and glycerin is therefore fully compatible and beneficial for boosting the skin’s hydration and antioxidant protection.

The combination of vitamin E and niacinamide is highly relevant, as both active ingredients act on complementary dimensions of skin health. Vitamin E supports antioxidant defenses, while niacinamide strengthens the skin barrier, improves hydration, and reduces inflammation. It is therefore common to find them in skincare formulations targeting a dull complexion or a compromised skin barrier, often alongside other ingredients such as hyaluronic acid.

A study clearly illustrates this synergy in a formula containing 4% niacinamide, 0.2% vitamin E, 0.4% hyaluronic acid, 5% lysed extract of Vitreoscilla filiformis, a probiotic, and 80% thermal spring water. Tested in different models ex vivo and in vivo, this treatment improved barrier function after various challenges: abrupt temperature fluctuations, irritation, or sleep deprivation. In a study of 22 women, it significantly accelerated skin barrier recovery, reducing water loss to 20.3% compared to 31.7% in the untreated area after five days. When participants were sleep-deprived, a single application enhanced the skin’s natural recovery by 69.5% after one hour.

These results support the value of combining niacinamide with vitamin E to fortify the skin barrier and help the skin withstand daily environmental stressors.

The combination of vitamin E and panthenol, also known as provitamin B5, is commonly used in skincare because their actions are complementary. As noted earlier, vitamin E provides antioxidant protection, while panthenol acts as a humectant, enhances barrier function, and soothes the skin. A clinical study involving 246 women with hyperpigmentation offers additional insights into the benefits of panthenol paired with vitamin E. For 10 weeks, participants applied daily a lotion containing niacinamide, panthenol, and tocopheryl acetate, compared to a control lotion. Image analyses demonstrated that the test lotion significantly reduced the appearance of hyperpigmentation and improved skin tone uniformity, with observable results as early as 6 weeks.

Note : It is likely that niacinamide, owing to its depigmenting properties, contributed to the favorable results observed.

Note : Several forms of vitamin E exist, including four tocopherols and four tocotrienols. Therefore, it is possible to formulate a blend of tocopherols and tocotrienols, combining different forms of vitamin E for more comprehensive antioxidant protection.

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