Which active ingredients can be combined with vitamin C?

The association between vitamin C and hyaluronic acid is among the most prevalent combinations in cosmetics, and for good reason. These two actives, among the most extensively documented in the scientific literature, complement each other perfectly without any risk of interaction or instability. Combining hyaluronic acid and vitamin C allows you to simultaneously boost the skin’s antioxidant defense, radiance, hydration, reduce wrinkles, dark spots, and redness. This combination is therefore very beneficial for the skin.

A study in vitro published in 2017 highlighted the benefit of combining hyaluronic acid with vitamin C to counteract the effects of oxidative stress and inflammation on human chondrocytes, cells essential for proper cartilage function. In this research, normal chondrocytes and chondrocytes stimulated with interleukin-1β (IL-1β), a pro-inflammatory cytokine heavily implicated in osteoarthritis, were exposed to different media enriched with hyaluronic acid (100 µg/mL), ascorbic acid (50 µg/mL), or a combination of both.

In stimulated cells, the combination of these two actives led to a marked improvement in their morphology and viability, as well as a significant reduction in IL-1β-induced cytotoxicity. The study also revealed a substantial decrease in the expression of several pro-inflammatory mediators that degrade the extracellular matrix, such as the metalloproteinases MMP-3 and MMP-9, particularly in the group treated with the hyaluronic acid and ascorbic acid combination. Similarly, the antioxidant protection provided by the enzyme SOD increased significantly.

The ferulic acid is a polyphenol naturally present in the cell walls of numerous plants, notably in rice bran, corn, or oats. It is particularly recognized for its powerful antioxidant properties. These properties are linked to its ability to neutralize free radicals through its phenolic structure. Ferulic acid also inhibits certain pro-oxidant enzymes, such as lipoxygenase, and limits lipid peroxidation of cellular membranes. Moreover, studies have shown that ferulic acid could regulate the expression of genes involved in the inflammatory response by reducing the production of pro-inflammatory mediators, such as the cytokines IL-6 and TNF-α.

A study evaluated the photoprotective effect of a topical formulation containing 10% ascorbic acid, 0.5% ferulic acid, and 2% phloretin, another antioxidant. Ten volunteers applied this antioxidant mixture or a placebo to their lower back for four consecutive days. From the third day on, the treated areas were exposed to UV irradiation ranging from 1 to 5 times the minimal erythema dose (MED). On the fifth day, skin biopsies were performed. The results showed that UV exposure induced, in a dose-dependent manner, visible inflammation, an increase in the number of sunburned cells, and the formation of thymine dimers, indicating DNA damage, as well as overexpression of the metalloproteinase MMP-9 and the p53 protein, which are involved in collagen degradation and the cellular stress response. Treatment with the antioxidant mixture significantly attenuated all of these markers,

In addition to strict sun protection, the combination of vitamin C and ferulic acid can help protect the skin from UV rays.

The tranexamic acid, initially used in medicine for its antifibrinolytic properties, has gained increasing interest in dermatology in recent years, particularly in the management of brown spots. Its primary mechanism of action relies on tyrosinase inhibition, thereby reducing melanin synthesis. Furthermore, tranexamic acid limits inflammation that promotes hyperpigmentation. The combination of tranexamic acid with vitamin C, also known for its tyrosinase-inhibitory role and its skin-brightening capacity, would strengthen the depigmenting effects of these two active ingredients.

A study explored the potential benefit of this combination in ten women aged 18 to 55 with treatment-resistant melasma. Over eight weeks, participants applied each evening a topical formulation containing 2% tranexamic acid and 2% vitamin C. Changes in their hyperpigmentation were evaluated using the Melasma Area and Severity Index (MASI) and the melasma-specific quality of life scale (MelasQoL). The results, summarized in the table below, showed a progressive and significant improvement in the MASI score and quality of life. Furthermore, no adverse reactions were reported.

The association between vitamin C and vitamin E is based on a well-established biological complementarity. Both have antioxidant properties, but their mechanisms of action differ and reinforce each other. Vitamin C acts in the skin’s hydrophilic compartments, where it neutralizes free radicals by donating an electron, thereby protecting cellular components—particularly DNA—from oxidative stress. Vitamin E, by contrast, acts mainly in lipophilic environments, notably within the stratum corneum. It stabilizes free radicals by donating a hydrogen atom but thereby becomes a radical itself. This is where synergy comes into play: thanks to its lower redox potential, vitamin C can recycle oxidized vitamin E, restoring its antioxidant capacity.

This synergy was illustrated in an experimental study conducted in pigs, a model frequently used for its similarity to human skin. The researchers evaluated the protective effect of a topical solution containing 15% vitamin C and 1% vitamin E against UV rays. After daily application for four days, it was observed that this combination allowed to double photoprotection against actinic erythema compared to the isolated use of each vitamin. Although these findings are promising, they would need to be confirmed by clinical trials in human volunteers.

Combining vitamin C with retinol enables the targeting of multiple mechanisms involved in skin aging. Retinol, a form of vitamin A, is recognized for its ability to stimulate keratinocyte proliferation, cellular regeneration, and the synthesis of type I and III collagen. These effects help improve skin firmness and reduce the depth of wrinkles. Meanwhile, vitamin C reinforces this action by stabilizing newly synthesized collagen fibers. This duo thus acts synergistically to even out skin tone and prevent photoaging. The combination of retinol and vitamin C may help diminish imperfections. This is what a study conducted by NATAKANKITKUL and their team suggests.

This study compared three formulations: one containing 0.2% retinol, another containing 5% sodium ascorbyl phosphate, a vitamin C derivative, and a third combining both active compounds. Forty-five participants with acne were divided into three groups of fifteen, each applying one of the formulations daily for eight weeks. At the end of the protocol, a significant reduction in the number of acne lesions was observed in all three groups, but the most pronounced results were recorded in subjects who used the retinol + vitamin C combination.

The bakuchiol is a plant-derived compound extracted from the seeds of Psoralea corylifolia, often presented as a natural alternative to retinol. Unlike the latter, bakuchiol generally does not cause irritation or photosensitization, making it an appealing active for sensitive skin. Biologically, it acts notably by modulating the expression of genes involved in collagen synthesis, inflammation, and pigment regulation, thereby providing firming, depigmenting, and anti-inflammatory effects. The combination of bakuchiol with vitamin C poses no specific compatibility issues: they can be used together to benefit from their complementary effects on radiance, firmness, and skin-tone uniformity.

However, to date, no study has demonstrated any synergy between vitamin C and bakuchiol. Their combination is therefore based on a rationale of complementarity.

The glycolic acid is an alpha-hydroxy acid (AHA) naturally found in certain fruits, known for its exfoliating effectiveness. Thanks to its low molecular weight, it easily penetrates the stratum corneum, where it acts by weakening the junctions between corneocytes, thereby promoting their shedding. This action stimulates cell renewal, improves skin texture, reduces pigment irregularities, and allows better absorption of subsequently applied actives. Glycolic acid can, in particular, be combined with vitamin C or its derivatives to reduce dark spots.

A clinical study was conducted in 2021 to compare the efficacy of combining a 40% glycolic acid peel with a vitamin C cream versus a standard treatment of 4% hydroquinone, tretinoin, and topical corticosteroids in the management of melasma. The trial enrolled 178 patients with a MASI score above 10. Participants were randomly divided into two groups: group A received the glycolic acid peel every two weeks along with a daily application of vitamin C cream, while group B used only the hydroquinone cream. After six weeks, results showed a significantly greater improvement in group A, with a reduction in hyperpigmentation of 94.38%, compared to 79.77% in group B. This study thus suggests that combining a glycolic acid peel with a vitamin C–based skincare regimen may be effective in reducing the visibility of pigmented spots.

Caution : The combined use of glycolic acid and pure vitamin C may irritate sensitive skin.

The combination of vitamin C and salicylic acid may be beneficial for enhancing skin radiance and evening out skin tone, particularly in individuals exhibiting pigmentary irregularities or blemishes. Salicylic acid is a BHA that primarily works by exfoliating the outermost layers of the epidermis and clearing clogged pores. Its lipophilic nature enables it to penetrate deeply into pores to break down debris. Pairing it with vitamin C could simultaneously target two skin concerns: blemishes and dull skin tone, even hyperpigmentation.

A clinical study demonstrated the benefit of this synergy in the management of melasma. Fifty female patients were divided into two groups to receive a 30% salicylic acid peel every two weeks for two months. One group additionally received vitamin C–based mesotherapy, with the vitamin C injected directly into the pigmented lesions. Clinical evaluations conducted up to six months after the start of the protocol revealed a significant reduction in the MASI score in the peel + vitamin C group, indicating a more pronounced improvement in hyperpigmentation. The protocol was generally well tolerated, with only a mild, transient burning sensation reported as a side effect.

Naturally present in coffee, tea, or guarana, the caffeine is also a widely used active ingredient in cosmetics for its ability to stimulate blood circulation. It is particularly valued for eye‐contour care because, by improving blood flow to this area, it helps prevent fluid buildup under the eyes, thereby lessening the dark appearance of under‐eye circles and the puffiness of bags. It is entirely possible to combine caffeine with vitamin C to benefit from their respective actions in reducing signs of fatigue.

It would be interesting to evaluate the combination of vitamin C and caffeine in future clinical studies.

The vitamin B12, or cobalamin, is a water-soluble vitamin essential for proper cellular function, including DNA synthesis, cell division, and fatty acid metabolism. In cosmetics, its use remains limited, but some studies have shown that it can help to soothe skin inflammation by inhibiting nitric oxide production in keratinocytes. The combination of vitamin B12 and vitamin C shows no known incompatibility in topical application and could enable the combined benefits of these two molecules: the former for its soothing potential, the latter for its antioxidant and unifying action.

This association between vitamin C and vitamin B12 would also be interesting to investigate.

The hydroquinone is a depigmenting agent considered a reference standard in the management of hyperpigmentation. It acts by competitively inhibiting the tyrosinase enzyme, which is essential for melanin synthesis in melanocytes, resulting in a gradual reduction of skin pigmentation. However, although effective, hydroquinone is banned for over-the-counter use in Europe, notably because of lingering doubts remain regarding its safety of use. Since hydroquinone is strictly a professional treatment, we recommend following the prescribing professional’s advice and not combining it with vitamin C without first asking their opinion.

In addition to its topical use in cosmetics, vitamin C can be taken orally to support overall health. There are numerous dietary supplements containing vitamin C, and some combine this active ingredient with other nutrients to enhance its absorption or bolster its physiological effects. Among the most commonly encountered combinations are:

• Vitamin C and iron : This is one of the most well-established combinations. Vitamin C enhances intestinal iron absorption by reducing ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), a form more easily assimilated by the body. This mechanism is particularly beneficial for individuals with iron deficiency, especially those following a vegetarian diet.

• Vitamin C and magnesium : Magnesium can also be taken with vitamin C without any interference between the two molecules. Although no clearly established synergistic effect exists, this combination is commonly used to support nervous system balance and reduce fatigue.

• Vitamin C and zinc : The combination of zinc and vitamin C is widely used to reinforce immune defenses. Zinc exhibits anti-inflammatory properties, and its association with vitamin C has been explored in various studies, although the underlying interaction mechanisms remain only partially elucidated.

• Vitamin C and vitamin D : The combination of vitamin C and vitamin D is also popular in dietary supplements. Although their mechanisms of action are distinct—vitamin D modulates innate and adaptive immunity, and vitamin C serves an antioxidant role—their pairing poses no contraindications and may provide broader coverage of immune requirements.

• Vitamin C and glutathione : In another context, glutathione, an intracellular antioxidant, has its stability and effectiveness enhanced by the presence of vitamin C. The latter contributes to the regeneration of reduced glutathione (GSH) from its oxidized form (GSSG), thereby supporting the body’s overall antioxidant defenses.

• Vitamin C and copper : This association is more delicate. Indeed, although vitamin C and copper do not directly oppose each other, vitamin C can reduce cupric copper (Cu²⁺) to cuprous copper (Cu⁺), which in theory may interfere with its transport or metabolism. That said, there are now many dietary supplements combining copper and vitamin C with the aim of strengthening the immune system.

• Vitamin C and probiotics : To support the skin microbiota or prevent digestive inflammatory responses, certain capsules combine vitamin C with probiotics. Some studies have shown that this can indeed be beneficial, although further research on the subject is still needed.

• Vitamin C and quercetin : Finally, quercetin, a flavonoid naturally found in plants, is often combined with vitamin C for its immunomodulatory and antioxidant effects. Vitamin C may indeed stabilize quercetin and improve its bioavailability.

Before considering supplementation, it is advisable to seek the advice of a healthcare professional. While certain supplements may prove useful in cases of deficiency, their use without a clear indication is not always appropriate and can sometimes be counterproductive.