Which active ingredients should be combined with ferulic acid?

It is first possible to combine ferulic acid with Ashitaba extract, a medicinal plant symbolizing longevity in Japan. This combination could be particularly relevant for protecting the skin from oxidative stress and preventing skin aging. Indeed, ferulic acid is a well-established antioxidant known for its ability to neutralize free radicals and stabilize other antioxidants, such as vitamin C or vitamin E. Rich in flavonoids, the Ashitaba extract is renowned for activating certain cellular repair pathways, notably by inducing autophagy, an intracellular protection and recycling mechanism that removes waste, dysfunctional cells, and dead cells to prevent their accumulation. Ashitaba extract can also scavenge free radicals.

The ferulic acid and Ashitaba extract thus possess complementary mechanisms of action that could be relevant for slowing the onset of aging signs. However, it remains difficult to assert that they act synergistically. Indeed, to date, no clinical trial has yet assessed the efficacy of this combination. Only work carried out separately on each of these active ingredients has highlighted their benefits, without permitting any conclusions on the potential advantage of combining them.

The combination of ferulic acid and resveratrol is often considered to enhance the skin’s antioxidant defenses. Resveratrol, a polyphenol notably found in grape skin, is recognized for its ability to activate the sirtuin pathway, particularly SIRT1, which is involved in regulating cellular aging. In contrast to ferulic acid, which acts mainly by neutralizing free radicals and stabilizing other antioxidants, resveratrol works more indirectly by stimulating endogenous cellular defense mechanisms. The interest in combining them therefore lies in pairing an immediate antioxidant effect with the activation of deeper cellular protective mechanisms, especially to shield the skin from oxidative stress caused by repeated UV exposure or pollution.

A study in vitro explored the antioxidant effects of various combinations of resveratrol and ferulic acid to determine the most effective proportions. To do this, researchers used aqueous resveratrol solutions combined with a hydroalcoholic resveratrol solution. Several ratios were tested. The antioxidant activity of these mixtures was measured using the DPPH and ABTS methods, two standard assays for evaluating the capacity to neutralize free radicals. The greatest antioxidant activity was achieved with the solution containing 3% resveratrol and 0.5% ferulic acid. Although these are preclinical data, the results suggest that the combination of ferulic acid and resveratrol could be relevant for protecting the skin from oxidative stress.

The combination of vitamin C and vitamin E with ferulic acid is based on a well-documented complementarity among these three antioxidants. Vitamin C, being water-soluble, primarily acts in the aqueous phase of tissues, while vitamin E, being lipid-soluble, protects lipid structures from oxidation, especially cell membranes. Ferulic acid, in turn, plays a stabilizing and synergistic role: it enhances the efficacy of both vitamins while limiting their degradation, particularly that of vitamin C, which is known for its instability in aqueous solution. Combining these three compounds allows achieving a broader antioxidant coverage and a more stable formulation, for example to prevent photoaging.

A study in vivo particularly interesting was conducted to assess the photoprotective efficacy of a complex combining 15% L-ascorbic acid (vitamin C), 1% alpha-tocopherol (vitamin E), and 0.5% ferulic acid, referred to as CEFer in the study. After topical application of this formulation or the vehicle to human skin sites for four days, the researchers exposed these areas to UV radiation simulating sunlight, at doses ranging from 2 to 10 times the MED. As a reminder, the MED is the minimal erythema dose, that is, the minimal UV dose causing sunburn.

The results showed significant protection against UV-induced damage, in contrast to the vehicle control. CEFer markedly reduced both erythema and the occurrence of so-called “sunburn” cells, decreasing from 31.5 ± 14.3 with the vehicle to 8.4 ± 7 with CEFer. “Sunburn” cells are UV-damaged keratinocytes that undergo apoptosis to prevent the transmission of DNA mutations. Cytokine analysis also revealed a decrease in the expression of proinflammatory mediators such as interleukins IL-1α, IL-6, IL-8, IL-10, and TNF-α. This study illustrates the strong synergy among the three antioxidants—ferulic acid, vitamin C, and vitamin E—enabling not only formulation stabilization but also the delivery of multifactorial protection against UV-induced oxidative stress.

It is also possible to combine ferulic acid with retinol. This combination is particularly useful for preventing or targeting skin laxity. Indeed, the retinol is well known for its effects on cellular renewal and its ability to stimulate collagen synthesis, which makes it indispensable for mature skin. It may be relevant to pair it with ferulic acid, whose powerful antioxidant properties can complement retinol’s action to slow the onset of signs of aging. Moreover, ferulic acid is suggested to help stabilize retinoids in formulations, limiting their oxidation and degradation from light or air.

A recent study conducted on human HaCaT keratinocytes highlighted the synergistic effects of retinol and ferulic acid. The keratinocytes were first exposed to UVB (54 mJ/cm²) to induce cellular damage. They were then treated for 24 h with various concentrations of retinol and ferulic acid, alone or in combination. Retinol exhibited significant toxicity starting at 90 nM, whereas ferulic acid did not affect cell viability, even at high doses. Different retinol:ferulic acid ratios were tested (1:0, 1:1, 1:2, etc), and the optimal synergistic effect was observed at 100 μM retinol and 120 nM ferulic acid.

At these concentrations, the retinol/ferulic acid combination effectively protected cells against oxidative stress. Compared with the control group, MDA levels, a lipid peroxidation product, dropped markedly (from 40.07 to 17.95 U/mg protein), while the levels of the antioxidant enzymes SOD, GSH, and CAT increased significantly, as shown in the table below. Production of reactive oxygen species was also reduced, as was the expression of the COX-2 enzyme, which catalyzes the conversion of arachidonic acid to prostaglandin H2.

Ferulic acid can also be combined with niacinamide, which can be likened to a cosmetic Swiss Army knife due to its great versatility. Niacinamide indeed exhibits antioxidant, anti-inflammatory, and depigmenting properties, as well as the ability to strengthen the skin barrier. When paired with ferulic acid, this molecule may gain improved stability and provide the skin with better protection against oxidative stress.

An investigation assessed the effect of a combination containing 5% niacinamide and 0.5% ferulic acid in an emulsion applied daily by 13 volunteers. Although the protocol involved a small cohort, it included a comparison with a placebo, allowing for a clearer evaluation of the formula’s impact. Skin tone uniformity, cutaneous hydration, and skin elasticity were measured using instruments: a mexameter for pigmentation, a corneometer for hydration, and an elastometer for elasticity. The results demonstrated a significant improvement in these parameters compared to the placebo. It is nonetheless unfortunate that no group tested niacinamide or ferulic acid alone. This omission makes it difficult to determine whether the observed effects result from synergy between the two actives or are primarily attributable to one of them.

It might also be relevant to combine ferulic acid with hyaluronic acid. Widely used in cosmetics, it is particularly recognized for its ability to attract water into skin tissues. In fact, depending on its molecular weight, the hyaluronic acid can hold up to 1,000 times its weight in water, which contributes to reinforcing the barrier function. Associating it with ferulic acid would theoretically allow for targeting two skin concerns: dehydration and oxidative stress. This combination would also be compatible from a formulation standpoint, as both hyaluronic acid and ferulic acid are preferentially used in aqueous solutions. However, it has not yet been tested to date, unlike the individual effects of ferulic acid and hyaluronic acid.

In the absence of clinical data, we can simply assume that these active ingredients might act synergistically.

Ferulic acid could also be combined with the salicylic acid. Widely used in cosmetics and dermatology, the latter is a lipophilic beta-hydroxy acid (BHA) capable of penetrating deep into pores to unclog them. The salicylic acid is particularly renowned for its ability to eliminate blackheads. By pairing it with ferulic acid, one could theoretically target two complementary mechanisms: one aimed at reducing blemishes and the other at protecting the skin from oxidative stress. This approach is even more coherent since oxidative stress can itself worsen blemishes. Indeed, free radicals can oxidize sebum squalene into squalene peroxide, a comedogenic compound. Note that low levels of vitamin E, a naturally occurring lipophilic antioxidant present in sebum, have been linked to acne, to the point that some scientists consider the vitamin E as a marker of the severity of this skin disease.

Once again, this synergy remains theoretical, as no studies have yet evaluated the combined effects of ferulic acid and salicylic acid.

Finally, ferulic acid could potentially be combined with glycolic acid, a low-molecular-weight alpha-hydroxy acid (AHA) known for its exfoliating properties due to its ability to break intercorneocyte bonds. In doing so, glycolic acid helps restore a more radiant complexion. Combining it with ferulic acid could therefore be interesting for dull skin or skin with pigmentation spots. Indeed, oxidative stress plays an important role in the appearance of brown spots by activating tyrosinase, an enzyme essential for proper melanogenesis. By neutralizing free radicals, ferulic acid could slow hyperpigmentation at its source, while glycolic acid would accelerate its fading by promoting cellular turnover.

To date, no clinical study has evaluated the potential synergy between ferulic acid and glycolic acid. Therefore, this remains a hypothesis at this time.

• PINNELL S. R. & al. A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. Journal of the American Academy of Dermatology (2008).

• SHARAD J. Glycolic acid peel therapy – A current review. Clinical, Cosmetic and Investigational Dermatology (2013).

• ARIF T. Salicylic acid as a peeling agent: A comprehensive review. Clinical, Cosmetic and Investigational Dermatology (2015).

• CAESAR L. K. & al. A review of the medicinal uses and pharmacology of Ashitaba. Planta Medica (2016)

• YANG J.-H. & al. Topical application of glycolic acid suppresses the UVB induced IL-6, IL-8, MCP-1 and COX-2 inflammation by modulating NF-κB signaling pathway in keratinocytes and mice skin. Journal of Dermatological Science (2017).

• ZENG N. & al. Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives. Life Sciences (2021).

• SUTEU D. & al. Physico-chemical characterization of the antioxidant mixture resveratrol-ferulic acid for applications in dermato-cosmetic products. Farmacia (2022).

• AHMAD A. & al. Development of niacinamide/ferulic acid-loaded multiple emulsion and its in vitro/in vivo investigation as a cosmeceutical product. BioMed Research International (2022).

• KEROB D. & al. Benefits of topical hyaluronic acid for skin quality and signs of skin aging: From literature review to clinical evidence. Dermatologic Therapy (2022).

• DU Z. & al. Ferulic acid in synergy with retinol alleviates oxidative injury of HaCaT cells during UVB-induced photoaging. Aging (2024).