Which active ingredients should be combined with ferulic acid?

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

The ferulic acid and Ashitaba extract thus exhibit complementary modes of action that may be relevant in delaying the onset of signs of ageing. However, it remains challenging to assert that they act synergistically. Indeed, to date, no clinical trial has yet evaluated the efficacy of this combination. Only studies conducted separately on each of these active ingredients have highlighted their benefits, without permitting any conclusion on the value of combining them.

The combination of ferulic acid and resveratrol is often considered for strengthening the skin’s antioxidant defences. Resveratrol, a polyphenol notably present in grape skin, is recognised for its ability to activate the sirtuin pathway, particularly SIRT1, which is involved in regulating cellular ageing. Unlike ferulic acid, which primarily acts by neutralising free radicals and stabilising other antioxidants, resveratrol exerts a more indirect effect by stimulating endogenous cellular defence mechanisms. The benefit of combining them therefore lies in pairing immediate antioxidant action with the activation of deeper cellular protective mechanisms, notably to shield the skin from oxidative stress induced by repeated exposure to UV radiation or pollution.

A study in vitro explored the antioxidant effects of various combinations of resveratrol and ferulic acid, with the aim of determining the most effective proportions. To this end, the researchers employed aqueous resveratrol solutions alongside a hydroalcoholic resveratrol solution. Several ratios were tested. The antioxidant activity of these mixtures was measured using the DPPH and ABTS assays, two standard tests used to evaluate the capacity to neutralise free radicals. The highest antioxidant activity was observed in 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 against 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, water-soluble, acts primarily in the aqueous phase of tissues, while vitamin E, fat-soluble, protects lipid structures from oxidation, notably cell membranes. Ferulic acid, for its part, plays a stabilising and synergistic role: it enhances the efficacy of both vitamins while limiting their degradation, particularly that of vitamin C, known for its instability in aqueous solution. Combining these three compounds allows for a broader antioxidant coverage and a more stable formulation, for instance to prevent the photoageing.

A study in vivo that was particularly interesting was carried out to evaluate the photoprotective efficacy of a complex comprising 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 for four days to areas of human skin, 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 erythemal dose, that is, the minimal UV dose inducing sunburn.

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

It is also possible to combine ferulic acid with retinol. This combination is particularly interesting for preventing or targeting skin laxity. Indeed, the retinol is well known for its effects on cell turnover and its ability to stimulate collagen synthesis, which makes it essential for mature skin. It can be beneficial to pair it with ferulic acid, whose potent antioxidant properties can complement retinol’s action to slow the onset of ageing signs. Furthermore, it has been suggested that ferulic acid could help stabilise retinoids in formulations, limiting their oxidation and degradation when exposed to light or air.

A recent study on human HaCaT keratinocytes demonstrated the synergistic effects of retinol and ferulic acid. The keratinocytes were first exposed to UVB irradiation (54 mJ/cm²) to induce cellular damage. The cells were then treated for 24 hours with varying concentrations of retinol and ferulic acid, either alone or in combination. Retinol showed significant toxicity from 90 nM onwards, 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 with 120 nM ferulic acid.

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

Ferulic acid can also be combined with niacinamide, which can be likened to a Swiss Army knife in cosmetics due to its considerable versatility. Niacinamide possesses antioxidant, anti-inflammatory and depigmenting properties, as well as the ability to strengthen the skin barrier. When combined with ferulic acid, this molecule could benefit from improved stability and provide the skin with enhanced protection against oxidative stress.

A study evaluated the effect of a formulation combining 5% niacinamide and 0.5% ferulic acid in an emulsion applied daily by 13 volunteers. Although conducted on a small cohort, the protocol included a comparison with a placebo, enabling a clearer understanding of the formula’s impact. The uniformity of complexion, skin hydration and skin elasticity were measured using instruments: the Mexameter for pigmentation, the Corneometer for hydration and the Elastometer for elasticity. The results demonstrated a significant improvement in these various parameters compared with the placebo. It is nevertheless unfortunate that no group received niacinamide or ferulic acid alone. This makes it difficult to determine whether the observed effects arise from a 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 primarily known for its ability to attract water into cutaneous tissues. Indeed, depending on its molecular weight, the hyaluronic acid can retain up to 1,000 times its weight in water, which helps reinforce the barrier function. Pairing it with ferulic acid would theoretically enable the targeting of two skin concerns: dehydration and oxidative stress. This combination would also be advantageous from a formulation perspective, as both hyaluronic acid and ferulic acid are preferentially used in aqueous solutions. However, it has not 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 compounds could act synergistically.

Ferulic acid could also be associated with the salicylic acid. Widely used in cosmetics and dermatology, the latter is a lipophilic beta-hydroxy acid (BHA) capable of penetrating deeply into pores to unclog them. The salicylic acid is particularly renowned for its ability to eliminate blackheads. By combining it with ferulic acid, one could theoretically target two complementary mechanisms: one aiming to reduce blemishes and the other to protect the skin from oxidative stress. This approach is all the more coherent as oxidative stress itself can exacerbate blemishes. Free radicals are indeed capable of oxidising sebum squalene into squalene peroxide, a comedogenic compound. It is worth noting that low levels of vitamin E, a naturally occurring lipophilic antioxidant in sebum, have been linked to acne, to the extent that some scientists regard vitamin E as a marker of the severity of this skin condition.

Once again, this synergy remains theoretical, as no study to date has 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) recognised for its exfoliating properties through its ability to disrupt intercorneocyte bonds. In doing so, glycolic acid helps restore a more radiant complexion. Therefore, pairing it with ferulic acid could be beneficial for dull skin or those with pigmentation spots. Indeed, oxidative stress plays a significant role in the emergence of brown spots by activating tyrosinase, a key enzyme in the proper course of the melanogenesis. By neutralising free radicals, ferulic acid could slow hyperpigmentation at the source, while glycolic acid would accelerate its fading by promoting cellular turnover.

To date, no clinical study has assessed the potential synergy between ferulic acid and glycolic acid; thus, it remains, for the time being, a hypothesis.

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