With which active ingredients can vitamin C be combined?

The silk tree extract, derived from Albizia julibrissin, is a plant‐based ingredient still little known, yet one that has protective and antioxidant properties. Native to Asia, this tree is nicknamed the ‘tree of serenity’ due to its historical use in combating stress. The silk tree extract works by targeting protein glycation, a harmful process for the body that accelerates its ageing. Glycation corresponds to the binding of sugars to the fibres of collagen and elastin, stiffening them and reducing their functionality. The silk tree extract slows this process by inhibiting the formation of advanced glycation end products (AGEs). It thus protects the extracellular matrix and helps prevent skin tissue sagging.

Combining silk tree extract with vitamin C allows simultaneous targeting of oxidative stress and glycation, two key mechanisms of skin ageing, to enhance skin radiance.

One of the key properties of vitamin C is its ability to stimulate collagen synthesis in the skin. In vitro studies in vitro have shown that it acts as a cofactor for prolyl-hydroxylase and lysyl-hydroxylase, two enzymes involved in the stabilisation and cross-linking of collagen fibres. Vitamin C may also upregulate the genes associated with the production of type I and III collagen, the most abundant in the skin. These various effects of the vitamin C would enable it to strengthen the firmness and resilience of the skin.

This ability of vitamin C to support collagen biosynthesis explains why these two actives are often combined in skincare products or routines. However, it is important to note that, in most cases, the collagen applied has a primarily hydrating effect, as its high molecular weight limits its penetration into the skin. However, hydrolysed collagen derivatives, consisting of low-molecular-weight peptides, are better absorbed by the skin and may stimulate the production of endogenous collagen fibres, according to certain studies in vitro. The combination of vitamin C and hydrolysed collagen peptides appears thus promising for firming the skin and preventing the appearance of wrinkles and fine lines.

Aloe vera and vitamin C are both water-soluble, which facilitates their incorporation into aqueous formulations, such as serums or gels. Aloe vera, particularly in its pure gel form, is recognised for its richness in polysaccharides, amino acids and vitamins, including trace amounts of naturally occurring vitamin C and minerals. It exerts an immediate soothing effect on irritated skin, for example following exposure to the sun, while boosting epidermal hydration through its ability to retain water in the skin’s superficial layers. Aloe vera also contributes to skin regeneration, as evidenced by its nickname the “natural bandage”.

When combined with vitamin C, aloe vera enhances formulation tolerance while optimising their efficacy. While vitamin C stimulates collagen synthesis and protects the skin from oxidative stress, aloe vera contributes to epidermal hydration and soothes the skin. This complementary action allows them to adapt to a wide range of skin types and to address various concerns: dull complexion, dehydrated skin, redness...

The aloe vera and vitamin C form a gentle and complementary combination.

While niacinamide and vitamin C are sometimes considered incompatible, they actually exhibit an interesting synergy.

The myth that they could not be used simultaneously stems from early studies in which chemical reactions between pure vitamin C and niacinamide were observed at very high temperatures, producing nicotinic acid—a molecule capable of causing redness and irritation. However, these conditions do not reflect the environment of modern cosmetic formulations. vitamin C, such as sodium ascorbyl phosphate or ascorbyl glucoside, which are entirely compatible with niacinamide.

The combination of vitamin C and niacinamide is particularly interesting for targeting pigmentation spots or photoageing. While vitamin C acts upstream in melanin synthesis by inhibiting the enzyme tyrosinase, niacinamide acts downstream, blocking the transfer of melanosomes to keratinocytes. Their combination thus acts at different levels of melanogenesis, increasing the likelihood of visible improvements in brown spots. Several studies have shown that the concurrent use of niacinamide and vitamin C significantly reduces UV-induced pigmentation while bolstering the skin’s resilience to oxidative stress.

The combination of vitamin C and hyaluronic acid is one of the most widely used combinations in cosmetics, and for good reason. These two active ingredients, 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 enables simultaneous action on the skin’s antioxidant defence, complexion radiance, hydration, wrinkles, brown spots and redness. This combination is therefore highly beneficial for the skin.

A study in vitro published in 2017 highlighted the benefits 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 strongly implicated in osteoarthritis, were exposed to various media enriched with hyaluronic acid (100 µg/mL), ascorbic acid (50 µg/mL), or a combination of both.

In stimulated cells, the association between these two active compounds resulted in 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 degrading 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. Likewise, the antioxidant protection afforded by the enzyme SOD increased significantly.

The ferulic acid is a polyphenol naturally found in the cell walls of many plants, notably in rice bran, maize or oats. It is particularly recognised for its potent antioxidant properties. These are linked to its ability to neutralise free radicals thanks to its phenolic structure. Ferulic acid also acts by inhibiting certain pro-oxidant enzymes, such as lipoxygenase, and by limiting lipid peroxidation of cellular membranes. Furthermore, studies have shown that the 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 assessed the photoprotective effect of a skin care formulation containing 10% ascorbic acid, 0.5% ferulic acid and 2% phloretin, another antioxidant. Ten volunteers applied this antioxidant blend or a placebo to the lower part of their backs for four consecutive days. From the third day onwards, the treated areas were exposed to UV radiation at doses ranging from one to five times the minimal erythemal 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 sunburn cells, the formation of thymine dimers, indicating DNA damage, as well as the overexpression of the matrix metalloproteinase MMP-9 and the p53 protein, which are involved in collagen breakdown and the cellular stress response. Treatment with the antioxidant blend 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 radiation.

The tranexamic acid, originally used in medicine for its antifibrinolytic properties, has in recent years attracted growing interest in dermatology, particularly in the management of brown spots. Its primary mechanism of action depends on the inhibition of tyrosinase, thereby suppressing melanin production. Furthermore, tranexamic acid limits inflammation that stimulates hyperpigmentation. The combination of tranexamic acid with vitamin C, also recognised for its tyrosinase-inhibitory effect and its capacity to brighten the complexion, is thought to enhance the depigmenting effects of these two actives respectively.

A study explored the therapeutic potential of this combination in ten women aged 18 to 55 years with treatment-resistant melasma. Over eight weeks, participants applied each evening a topical formulation containing 2% tranexamic acid and 2% vitamin C. Their hyperpigmentation was monitored using the Melasma Area and Severity Index (MASI) and the Melasma Quality of Life (MelasQoL) scale. The results, summarised in the table below, demonstrated a progressive and significant improvement in both the MASI score and quality of life. Moreover, no adverse reactions were reported.

The association between vitamin C and vitamin E is based on a well-established biological complementarity. Both possess antioxidant properties, but their mechanisms of action differ and mutually reinforce one another. Vitamin C acts in the hydrophilic compartments of the skin, where it neutralises free radicals by donating an electron. In doing so, it protects cellular components, particularly DNA, from oxidative stress. Vitamin E, on the other hand, functions primarily in lipophilic environments, notably within the stratum corneum. It stabilises free radicals by donating a hydrogen atom, but in doing so becomes a radical itself. This is where the synergy comes in: thanks to its lower redox potential, vitamin C can recycle oxidised vitamin E, enabling it to regain its antioxidant power.

This synergy was demonstrated in an experimental pig study, a model frequently used for its resemblance to human skin. The researchers evaluated the protective effect of a topical solution containing 15% vitamin C and 1% vitamin E against UV radiation. After daily application for four days, it was observed that this combination allowed doubling of photoprotection against actinic erythema compared with the isolated use of each vitamin. Although these findings are promising, they would warrant confirmation by clinical trials conducted on human volunteers.

Combining vitamin C with retinol targets multiple mechanisms involved in skin ageing. Retinol, a form of vitamin A, is known for its ability to stimulate keratinocyte proliferation, cellular regeneration and the synthesis of type I and III collagen. These effects help to improve skin firmness and reduce the depth of wrinkles. Meanwhile, vitamin C enhances this action by stabilising newly synthesised collagen fibres. This duo therefore acts synergistically to even out skin tone and prevent photoageing. The combination of retinol and vitamin C may also help to mitigate blemishes, as suggested by a study conducted by NATAKANKITKUL and colleagues.

This study compared three formulations: one containing 0.2% retinol, another containing 5% sodium ascorbyl phosphate, a derivative of vitamin C, and a third combining both actives. 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 marked results were recorded in subjects who used the retinol + vitamin C combination.

Retinol and pure vitamin C can be irritating, so we advise against their combined use on sensitive skin.

The bakuchiol is a plant-derived compound extracted from the seeds of Psoralea corylifolia, often described as a natural alternative to retinol. Unlike retinol, bakuchiol generally does not cause irritation or photosensitisation, making it a valuable ingredient for sensitive skin. Biologically, it acts by modulating the expression of genes involved in collagen synthesis, inflammation and pigment regulation, which confers firming, depigmenting and anti-inflammatory effects. Combining bakuchiol with vitamin C presents no particular compatibility issues: they can be used together to benefit from their complementary effects on radiance, firmness and evening out skin tone.

However, as yet, no study has demonstrated any synergy between vitamin C and bakuchiol. Their combination is therefore based on a complementary rationale.

The glycolic acid is an alpha-hydroxy acid (AHA) naturally present in certain fruits, known for its exfoliating efficacy. Thanks to its low molecular weight, it easily penetrates the stratum corneum where it acts by weakening the junctions between corneocytes, thus promoting their desquamation. This action stimulates cell renewal, improves skin texture, attenuates pigmentary irregularities and allows better absorption of subsequently applied active ingredients. Glycolic acid can notably be combined with vitamin C or its derivatives to reduce brown spots.

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

Caution The simultaneous application of glycolic acid and pure vitamin C may irritate sensitive skin.

The combination of vitamin C and salicylic acid may be beneficial in enhancing skin radiance and evening out the complexion, especially in those with pigmentary irregularities or blemishes. Salicylic acid is a BHA that functions primarily by exfoliating the superficial layers of the epidermis and clearing blocked pores. Its lipophilic nature enables it to penetrate deeply into the pores to dislodge debris. Combining it with vitamin C could simultaneously address two skin concerns: blemishes and a dull or even hyperpigmented complexion.

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

Naturally present in coffee, tea and guarana, the caffeine is also a highly utilised cosmetic active ingredient due to its capacity to stimulate blood circulation. It is particularly valued for eye-contour care because, by improving blood flow in this area, it prevents fluid accumulation beneath the eyes, thus diminishing the dark appearance of circles and the puffiness of under-eye bags. It is entirely feasible to combine caffeine with vitamin C in order to benefit from their respective actions to reduce signs of fatigue.

It would be of scientific interest to evaluate the combination of vitamin C and caffeine in future clinical trials.

The vitamin B12, or cobalamin, is a water-soluble vitamin essential for proper cellular function, particularly in DNA synthesis, cell division and fatty acid metabolism. In cosmetics, its use remains limited, but some studies have shown that it can help soothe skin inflammation by inhibiting nitric oxide production in keratinocytes. The combination of vitamin B12 and vitamin C presents no known incompatibility in topical application, and could allow the respective benefits of these two molecules to be combined: the first for its soothing potential, the second 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 operates by competitively inhibiting the tyrosinase enzyme, essential to melanin synthesis in melanocytes, resulting in a progressive reduction of skin pigmentation. However, although effective, hydroquinone is prohibited in Europe for domestic use, notably as concerns remain regarding its safety of use. As hydroquinone is solely a professional treatment, we advise you to follow the recommendations of the practitioner who prescribed it and not to combine it with vitamin C without consulting them.

In addition to its topical application in cosmetics, vitamin C can be taken orally to support one’s health. There are numerous vitamin C dietary supplements, 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 nutrient interactions. Vitamin C enhances the intestinal absorption of iron by reducing ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), a form more readily assimilated by the body. This feature 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 interference between the two molecules. Although there is no clearly established synergistic effect, 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 strengthen immune defences. Zinc exhibits anti-inflammatory properties, and its pairing with vitamin C has been explored in various studies, although the mechanisms underlying their interaction 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, while vitamin C acts as an antioxidant — their co-administration poses no contraindications and may allow for broader coverage of immunological requirements.

• Vitamin C and glutathione : In another context, glutathione, an intracellular antioxidant, sees its stability and efficacy enhanced by the presence of vitamin C. The latter contributes to the regeneration of reduced glutathione (GSH) from its oxidised form (GSSG), which supports the body’s overall antioxidant defences.

• Vitamin C and copper : This combination is somewhat more delicate. Indeed, although vitamin C and copper do not directly antagonise one another, vitamin C can reduce cupric copper (Cu²⁺) to cuprous copper (Cu⁺), which, in theory, could interfere with its transport or metabolism. Nevertheless, there are now numerous nutritional 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 inflammatory responses in the digestive system, certain capsules combine vitamin C with probiotics. Some studies have shown that this can indeed be beneficial, although further research is still required.

• Vitamin C and quercetin : Finally, quercetin, a flavonoid naturally present in plants, is often associated with vitamin C for its immunomodulatory and antioxidant effects. Vitamin C may indeed stabilise quercetin and enhance 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, using them without a clear indication is not always appropriate and can sometimes be counterproductive.

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