⚠️ Auto-extracted by Claude on 2026-05-19. Verify quantitative claims and source attributions against primary sources. Canonical-DB IDs (PubChem CID 445858, ChEMBL CHEMBL32749) confirmed via REST API 2026-05-19. Lin 2005 claims are PDF-verified via lin-2005-ce-ferulic-photoprotection; all other citations are abstract-only or secondary-source.
Ferulic Acid
A naturally occurring hydroxycinnamic acid polyphenol found in the cell walls of most plants, most abundantly in rice bran, wheat bran, and oat bran. Best known in dermatology as the stabilizing and potentiating additive in the C+E+Ferulic combination (15% L-ascorbic acid + 1% α-tocopherol + 0.5% ferulic acid, pH 3.2), which provides approximately 8-fold greater photoprotection than vehicle — roughly double the C+E-only formulation — in a validated porcine skin model 1. The formulation is the biochemical basis for the SkinCeuticals C E Ferulic product archetype and numerous imitators. Ferulic acid’s stabilization mechanism is explicitly unknown per the foundational primary source 1. Isolated ferulic-acid evidence (without co-formulated vitamins C and E) is sparse; almost all clinical evidence for ferulic acid comes from combination-formulation trials that cannot isolate its individual contribution.
Identity
| Field | Value |
|---|---|
| PubChem CID | 445858 (confirmed via REST API 2026-05-19) |
| InChIKey | KSEBMYQBYZTDHS-HWKANZROSA-N |
| ChEMBL ID | CHEMBL32749 (pref_name: FERULATE; confirmed via InChIKey lookup 2026-05-19) |
| CAS | 1135-24-6 |
| Molecular formula | C10H10O4 (MW 194.18 Da) |
| IUPAC name | (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid |
| Class | Hydroxycinnamic acid; phenylpropanoid; polyphenol |
| Canonical SMILES | COC1=C(C=CC(=C1)/C=C/C(=O)O)O |
Note on ChEMBL ID: The training-knowledge value CHEMBL66653 was confirmed via REST API to be an unrelated nitro-containing synthetic pharmaceutical (C14H13N3O7). The correct ChEMBL entry for ferulic acid is CHEMBL32749 (FERULATE). Per the “Canonical-DB memory unreliable” protocol note, the provided ChEMBL ID was not trusted; ID was resolved fresh by InChIKey lookup.
Natural sources and commercial supply
Ferulic acid is a universal cell-wall constituent in plants, esterified to arabinoxylan and other hemicellulosic polysaccharides via feruloyl-CoA transferases. Rich dietary sources include:
- Grain brans: wheat bran (~0.5–2 g/kg), rice bran (~1–4 g/kg), oat bran — the dominant commercial extraction substrate
- Coffee: chlorogenic acid hydrolysis releases ferulic acid; brewed coffee contributes ~50–100 mg ferulic acid equivalents per cup
- Citrus peel: esterified to pectin fractions
- Tomatoes, sweet corn, beetroot: free + bound forms
Commercial extraction for cosmetic and pharmaceutical use is primarily from rice bran oil deodorizer distillate (a byproduct of the physical refining process), where ferulic acid accumulates as a free-form after saponification of the ester bonds. Purity of commercial cosmetic-grade material is typically ≥99% (HPLC).
Chemistry
Structural basis for UV absorption
Ferulic acid is a phenylpropanoid: a trans-cinnamic acid backbone bearing a 4-hydroxyl group and a 3-methoxy substituent on the benzene ring. The extended conjugated π system — phenyl ring → vinyl bridge (C=C, E-configuration) → carboxylic acid — produces a UV absorption band centred at approximately 310–330 nm (UVB/UVA-II boundary), with extinction coefficient in the range of ~15,000–18,000 L·mol⁻¹·cm⁻¹. This makes ferulic acid a minor UV chromophore capable of absorbing and dissipating UV photons, contributing (modestly) to photoprotection as a direct UV filter in addition to its radical-scavenging activity.
pKa and ionisation state
The carboxylic acid pKa of ferulic acid is approximately 4.4–4.7. At the physiological dermal pH of ~7.4, ferulic acid is essentially fully ionised (the ferulate anion). At the formulation pH of 3.0–3.5 typically used for C+E+Ferulic topical products, the neutral form predominates, which may influence skin penetration dynamics.
Stability
Ferulic acid itself is susceptible to oxidative degradation under alkaline conditions, heat, and light — forming vanillin, protocatechuic acid, and other degradation products. Commercial C+E+Ferulic formulations must therefore be maintained at:
- pH 3.0–3.5 (protonated, more stable form; also required for vitamin C activity)
- Low water activity where possible
- Protected from light and heat during storage
Yellowing or darkening of a C+E+Ferulic product indicates oxidation of the vitamin C component; significantly oxidised products should be discarded.
Mechanism of action
1. Direct radical scavenging (antioxidant)
The phenolic 4-OH group donates a hydrogen atom (H•) to reactive oxygen and nitrogen species (ROS/RNS), including hydroxyl radical, lipid peroxyl radicals, and superoxide-derived species. The resulting ferulic acid phenoxyl radical is stabilised by resonance delocalisation across the extended conjugated π system (phenyl → vinyl → carbonyl) and by the electron-donating 3-methoxy group. This resonance stability reduces the reactivity of the phenoxyl radical, making ferulic acid an efficient chain-breaking antioxidant.
In the context of UV-irradiated skin, the primary substrate for radical scavenging is UV-generated singlet oxygen, hydroxyl radical (from Fenton-type iron chemistry), and lipid peroxyl radicals from membrane oxidation. Ferulic acid’s antioxidant activity contributes to the total antioxidant capacity of a C+E+Ferulic formulation alongside ascorbate and α-tocopherol, though the relative contribution of each component is difficult to partition experimentally.
2. UV chromophore (photoaging-prevention)
As described in Chemistry, ferulic acid absorbs in the UVB/UVA-II range and contributes a minor UV-filtering effect additive to the antioxidant protection. The Lin 2005 study included a ferulic-acid-alone arm, which showed measurable but substantially smaller photoprotection than the C+E+F combination, confirming that UV absorption contributes to the overall effect but is not the primary mechanism of the formulation’s potency 1.
3. Formulation stabilisation of vitamins C and E — mechanism unknown
Adding ferulic acid at 0.5% to a solution of 15% L-ascorbic acid + 1% α-tocopherol at pH 3.2 prevents the spontaneous oxidation of both vitamins that otherwise occurs in aqueous solution, as demonstrated by colorimetric stability assays and by the enhanced photoprotective potency retained in the formulation 1. This stabilisation effect roughly doubles the photoprotective potency of the C+E base (from ~4-fold to ~8-fold protection vs vehicle by erythema and sunburn-cell endpoints in porcine skin).
The mechanism of this stabilisation effect is explicitly unknown per the primary source. Lin 2005 (p. 829, Discussion) states: “the mechanism of ferulic acid’s stabilizing effect on vitamins C and E is unknown.” The paper proposes three speculative non-exclusive mechanisms without experimental evidence for any:
- Additive antioxidant contribution (ferulic acid scavenges ROS that would otherwise oxidise vitamins C and E)
- UV-chromophore contribution (minor UV filtering attenuates photodegradation of the vitamins)
- Direct formulation stabilisation chemistry (ferulic acid slows oxidative degradation in the vehicle)
Metal-ion chelation is frequently cited in secondary sources and marketing materials as the mechanism. This claim is NOT supported by Lin 2005 — the metal-chelation mechanism is absent from the paper entirely. See lin-2005-ce-ferulic-photoprotection for the primary-source verification that confirmed this fabrication in earlier secondary literature.
no-mechanism — the stabilisation mechanism remains unresolved 20 years after the foundational paper.
4. Anti-inflammatory activity
Ferulic acid has been shown in cell-culture and rodent models to suppress NF-κB activation, reduce IL-6 and TNFα secretion, and attenuate COX-2-mediated prostaglandin E2 production. The anti-inflammatory activity likely contributes to acute UV-erythema reduction observed in formulation studies, though isolating ferulic acid’s anti-inflammatory contribution from that of co-formulated ascorbate and tocopherol is not possible from published data. dose-response-unclear
The C+E+Ferulic combination — foundational evidence
The biochemical basis for this formulation class rests primarily on a single pivotal study:
Lin FH et al. 2005 (J Invest Dermatol 125:826–832; PMID 16185284; PDF-verified 2026-05-19) 1:
| Formulation arm | UV protection vs vehicle (erythema) | Sunburn cells | Thymine dimers | Caspase-3 / caspase-7 |
|---|---|---|---|---|
| Vehicle | 1× (reference) | Baseline | Baseline | Baseline |
| C+E (15% L-AA + 1% α-toc) | ~4-fold | Reduced | Reduced | Reduced |
| C+E+F (+0.5% ferulic acid) | ~8-fold | Further reduced | Further reduced | Further reduced |
| Ferulic acid alone (0.5%) | Minor (substantially less than combination) | N/A | N/A | N/A |
Model: weanling white Yorkshire pigs (Sus scrofa domesticus); n=6/group (erythema + histology), n=3/group (Western blot). Porcine skin is the strongest available non-human proxy for human photoprotection studies due to epidermal-thickness, follicular-density, and UV-response similarity.
Key gap for translation: No large powered human RCT has directly replicated the ~8-fold protection figure from porcine skin at these concentrations (see lin-2005-ce-ferulic-photoprotection § Extrapolation to Humans). The combination is commercially dominant (SkinCeuticals C E Ferulic and imitators), and the human mechanistic basis (antioxidant synergy, UV-induced CPD reduction) is conserved, but the specific fold-protection number derives from porcine experiments.
Recent clinical evidence (2021–2026)
All three recent RCTs with ferulic acid test the C+E+Ferulic combination, not isolated ferulic acid. The individual contribution of ferulic acid cannot be separated from these designs.
Qin et al. 2025 — post-laser photoaging (PMID 40414817; doi:10.1111/jocd.70251) 2: Randomised investigator-blinded split-face trial (n=50, 45 female, mean age 31.6 yr; Chinese population). CE Ferulic serum applied to one side after nonablative fractional Fraxel laser, normal saline to the other side, for 7 days. Erythema score at Day 7 significantly lower on CEF side (0.04 ± 0.40 vs 0.18 ± 0.48; p=0.011); improved skin hydration and higher patient satisfaction on the treated side. Limitation: 7-day follow-up only; L’Oréal/SkinCeuticals funding; cannot isolate ferulic acid contribution. Abstract-only verification 2026-05-19.
Kim et al. 2025 — neck skin rejuvenation with microneedle RF (PMID 40464749; doi:10.1080/09546634.2025.2504655) 3: Prospective randomised double-blind split-neck placebo-controlled trial (n=31, ages 30–65); antioxidant serum (C+E+ferulic acid) applied after fractional microneedle radiofrequency × 2 sessions, placebo to contralateral neck. At week 12: wrinkle severity reduction 29.9% vs 18.0% (p<0.001); elasticity increased 12.9% vs 2.3%; 87.5% improved global aesthetic rating. FWCI 26.15 (citation percentile 100%) — unusually high citation velocity for a small trial. Limitation: small n; SkinCeuticals involvement; combination product. Abstract-only verification 2026-05-19.
Shi et al. 2026 — post-ablative CO2 laser wound healing (PMID 41521693; doi:10.1111/jocd.70634) 4: Randomised investigator-blinded split-face trial (n=64, ages 18–50) assessing CEF serum applied immediately and for 14 days after ablative fractional CO2 laser for atrophic acne scars. Day 7 complete scab detachment: 60.9% (CEF) vs 34.4% (control; p=0.0026); improved erythema and melanin indices. L’Oréal/SkinCeuticals funding. This is a wound-healing / post-procedure application rather than pure photoaging; the endpoint (scab detachment) reflects acute reparative healing kinetics, not long-term structural photoaging. Abstract-only verification 2026-05-19.
Critical interpretive note: All three recent RCTs test the combination formulation and are partly or fully sponsored by SkinCeuticals / L’Oréal. The evidence supports the C+E+F combination for post-procedure skin recovery and photodamage reduction. None of these trials isolates ferulic acid’s individual contribution, and ferulic acid’s dose-response as a single agent remains uncharacterised in controlled human studies.
Oral supplementation — brief overview
Ferulic acid is sold as an oral supplement (common dose: 100–250 mg/day), positioned as a systemic antioxidant. Evidence for oral ferulic acid in human aging outcomes is extremely sparse — essentially preclinical. Key considerations:
- Oral bioavailability: free ferulic acid is moderately well-absorbed from the small intestine (~20–35% of dose); ester-bound ferulic acid from grain brans requires colonic fermentation or gastric hydrolysis before absorption. Peak plasma concentrations after 50–100 mg oral dose are in the low micromolar range.
- Rapid conjugation: ferulic acid is rapidly sulfated and glucuronidated in the intestinal wall and liver; most circulating ferulic acid post-absorption is conjugated (ferulate sulfate, glucuronide). Whether conjugated forms retain biological activity is unclear. dose-response-unclear
- Systemic antioxidant clinical evidence: a small number of short-duration trials (mostly < 8 weeks, n < 50) report improvements in oxidative stress biomarkers (MDA, 8-OHdG, FRAP) with oral ferulic acid, but no aging-endpoint or hard-outcome RCT exists. needs-replication
- The topical administration route, with its direct target-tissue concentration advantage and avoidance of first-pass metabolism, is far better-supported by evidence than oral supplementation for skin-aging endpoints.
Effects on aging hallmarks
| Hallmark | Effect | Mechanism | Evidence basis |
|---|---|---|---|
| genomic-instability | Reduces UV-induced thymine dimer (CPD) formation in epidermis | Antioxidant scavenging of indirect UV-induced ROS → less oxidative DNA strand damage; minor UV chromophore (direct UV filtering) | 1 — C+E+F combination; porcine model |
| chronic-inflammation | Reduces UV-induced erythema, sunburn-cell formation, caspase-3/7 activation | Antioxidant attenuation of UV-induced oxidative stress; NF-κB suppression (preclinical) | 1 — C+E+F combination; porcine model |
| loss-of-proteostasis | Indirect: formulation stabilisation preserves vitamin C bioavailability → supports prolyl-hydroxylase-dependent collagen synthesis | Ferulic acid stabilises L-ascorbic acid in the formulation; L-ascorbic acid is the cofactor for collagen-synthesising hydroxylases — see ascorbic-acid | 1 — formulation stability; mechanistic link via ascorbic acid cofactor role |
Pharmacokinetics and formulation
- Topical penetration: ferulic acid penetrates human epidermis and dermis when formulated at appropriate pH and vehicle. Penetration is enhanced at acidic pH (neutral form). Exact Cmax and tissue distribution data for topical ferulic acid are not well-characterised as isolated compound; most PK data are from the C+E+F combination context.
- Formulation pH requirement: 3.0–3.5 (required to maintain L-ascorbic acid stability; also promotes ferulic acid in neutral form for penetration)
- Light and heat stability: protect from direct sunlight; store <25°C
ClinicalTrials.gov status (as of 2026-05-19)
2 active studies (RECRUITING + ACTIVE_NOT_RECRUITING) matching “ferulic acid” per ClinicalTrials.gov v2 API:
| NCT | Title | Status | Condition |
|---|---|---|---|
| NCT07173166 | Non-pharmacological Interventions for Neurotoxicity in CAR-T patients | RECRUITING | Hematologic cancer |
| NCT07404072 | Ferulic acid as adjunct to mechanical debridement in periodontitis | ACTIVE_NOT_RECRUITING | Periodontitis |
Neither trial targets aging endpoints. The clinical-trial evidence base for ferulic acid in aging or dermatologic aging is currently absent — all aging-context evidence is from the published RCT literature (not registered trials).
Cross-references
- lin-2005-ce-ferulic-photoprotection — the foundational C+E+Ferulic photoprotection study; PDF-verified 2026-05-19; source of all Lin 2005 claims on this page
- ascorbic-acid — vitamin C component; regenerates α-tocopherol; prolyl-hydroxylase cofactor; ferulic acid stabilises L-ascorbic acid in the C+E+F formulation
- alpha-tocopherol — vitamin E component; lipid-phase chain-breaking antioxidant; regenerated by vitamin C; co-stabilised by ferulic acid
- genomic-instability — UV-induced thymine dimers (CPDs) as primary genomic instability endpoint in skin
- chronic-inflammation — UV erythema, SASP, and cytokine-driven photoaging
- loss-of-proteostasis — collagen ECM degradation as the dominant photoaging phenotype
- skin-aging — photoaging as the clinical phenotype most studied with this compound
- uv-protection — UV avoidance as the primary photoprotection intervention; C+E+F as an adjunct
- keratinocytes — sunburn cells (apoptotic keratinocytes); CPD formation in keratinocyte nuclei stub
Extrapolation table
| Dimension | Status |
|---|---|
| Radical-scavenging pathway conserved in humans? | Yes — UV-induced ROS chemistry and phenolic H-atom donation are universal |
| UV-induced CPD / erythema phenotype conserved in humans? | Yes / partial — porcine skin is the strongest non-human proxy; underlying UV photobiology is conserved |
| Formulation stabilisation mechanism replicated in humans? | Not applicable — mechanism unknown; formulation stability tested in vitro |
| C+E+F combination photoprotection replicated in humans? | Partial — multiple human clinical studies confirm combination benefit post-procedure and for photoaging; no large standalone RCT of C+E+F vs vehicle in naive photoaged skin matching Lin 2005 porcine design |
Limitations and gaps
| Gap | Tag | Notes |
|---|---|---|
| Mechanism of ferulic acid’s stabilising effect on vitamins C and E unknown per Lin 2005 | no-mechanism | Metal-chelation claim in secondary sources is NOT supported by primary source; flag any such attribution |
| Isolated ferulic acid efficacy not separable from C+E+F combination | dose-response-unclear | All clinical trials use combination formulations; ferulic acid alone has no powered human RCT |
| No aging-endpoint RCT for ferulic acid (alone or in combination) with structural endpoints (biopsy collagen, wrinkle depth, CPD density) as co-primary outcomes | needs-replication | Post-procedure and erythema-endpoint trials exist; photoaging-reversal trials do not |
| Oral supplementation evidence is preclinical-level | needs-human-replication | Bioavailability, effective systemic dose, and human anti-aging efficacy entirely uncharacterised by powered RCTs |
| ChEMBL ID CHEMBL66653 (initial seeder brief) resolves to an unrelated synthetic pharmaceutical; correct ID is CHEMBL32749 | — | Confirmed via InChIKey lookup 2026-05-19; CHEMBL66653 should not be cited for ferulic acid |
| All three 2024–2026 RCTs have industry funding (SkinCeuticals / L’Oréal) | needs-replication | Independent replication with non-industry funding needed |
R16 intervention matrix note
This compound page links to chronic-inflammation, genomic-instability, and loss-of-proteostasis — all three hallmark pages exist in hallmarks/. The mechanisms: values (antioxidant, anti-inflammatory, photoaging-prevention) all correspond to defined classes in intervention-classes. The mechanism formulation-stabilization (mentioned in the seeder brief) does not target an aging hallmark and is not a defined intervention class — it is documented in the body only, per R16 rules. This compound will appear in the Dataview blocks for antioxidant and anti-inflammatory classes in interventions-by-hallmark.md.
Footnotes
Footnotes
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lin-2005-ce-ferulic-photoprotection · PMID 16185284 · doi:10.1111/j.0022-202X.2005.23768.x · Lin FH, Lin JY, Gupta RD, Tournas JA, Burch JA, Selim MA, Monteiro-Riviere NA, Grichnik JM, Zielinski J, Pinnell SR · J Invest Dermatol 2005 Oct;125(4):826–32 · n=6/group (erythema + sunburn cells); n=3/group (caspase Western blots) · in-vivo porcine skin model (weanling white Yorkshire pigs) · C+E+F (0.5% ferulic acid + 15% L-AA + 1% α-tocopherol) provides ~8-fold photoprotection vs vehicle (double the ~4-fold from C+E alone); ferulic acid stabilises the formulation; mechanism of stabilisation explicitly stated as unknown; reduced caspase-3 + caspase-7 + thymine dimers · PDF-verified 2026-05-19 · in archive (citation_percentile 100%; 340 citations; FWCI 13.6) ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8
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doi:10.1111/jocd.70251 · PMID 40414817 · Qin X, Zhai J, Zhou C, Wang Y, Chen M, Zhu L, Shi Q, Chen W, Zhang L, Luo X, Li K · J Cosmet Dermatol 2025 · rct · n=50 (45 female; mean age 31.6 yr; Chinese population) · split-face controlled trial; CE Ferulic serum vs saline for 7 days after nonablative fractional Fraxel laser · erythema score Day 7: 0.04 ± 0.40 (CEF) vs 0.18 ± 0.48 (control); p=0.011 · L’Oréal/SkinCeuticals funding · combination product; cannot isolate ferulic acid contribution · abstract-only verification 2026-05-19 · in archive (FWCI 8.72; citation_percentile 100%; download pending) ↩
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doi:10.1080/09546634.2025.2504655 · PMID 40464749 · Kim J, Lee SG, Boo J, Kim H, Hwang S, Liu C, Yan X, Brieva P, Kim J · J Dermatolog Treat 2025 · rct · n=31 (ages 30–65) · prospective randomised double-blind split-neck placebo-controlled; C+E+ferulic serum vs placebo after fractional microneedle RF × 2 sessions · wrinkle severity reduction 29.9% vs 18.0% (p<0.001); elasticity +12.9% vs +2.3% at 12 weeks · SkinCeuticals involvement · combination product; cannot isolate ferulic acid contribution · abstract-only verification 2026-05-19 · in archive (FWCI 26.15; citation_percentile 100%; diamond OA; download pending) ↩
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doi:10.1111/jocd.70634 · PMID 41521693 · Shi Y, Xu S, Zhang W · J Cosmet Dermatol 2026 · rct · n=64 (ages 18–50) · randomised investigator-blinded split-face; CE Ferulic serum vs saline immediately and for 14 days after ablative fractional CO2 laser for atrophic acne scars · complete scab detachment Day 7: 60.9% (CEF) vs 34.4% (control); p=0.0026 · L’Oréal/SkinCeuticals funding · wound-healing endpoint; combination product; cannot isolate ferulic acid contribution · abstract-only verification 2026-05-19 · in archive (download pending; citation_percentile null) ↩