Naringenin
Naringenin — evidence, uses & status

Class: small_molecule
Synonyms: 4′,5,7-trihydroxyflavanone
flavanone
grapefruit polyphenol
biotech-fermented naringenin (Debut / Deinde)
INCI: Naringenin
Function tags: skin appearance (cosmetic)
antioxidant
anti-inflammaging (mechanism-level)
barrier support
Overall evidence grade: B
WADA prohibited: no
Last updated: 2026-07-20

In brief: Naringenin is a flavanone polyphenol naturally present in citrus fruits (concentrated in grapefruit peel). Independent laboratory research (2016–2024) consistently shows it has meaningful biological activity on skin cells: anti-inflammatory, anti-oxidative, MMP-suppressing, UV- protective — and, uniquely among four common polyphenols in a 2024 comparison, superior anti-lipoperoxidation in stratum corneum. However, every one of these independent studies is either in-vitro (cells, reconstructed skin models) or on animals. The only human clinical trial is an in-house study by Debut Biotech / Deinde (n=30, 8 weeks, 0.45% naringenin), which is a promising signal but not independent proof of visible anti-aging effect. The claim "15× more effective than niacinamide" is a cell-culture single-biomarker comparison, not a head-to-head clinical trial. Naringenin is a plausible barrier-protective, gentle anti-oxidative ingredient — appropriate for sensitive and perimenopausal skin — but the strong marketing framing outruns the current independent evidence base.

## Identity

a **flavanone** — specifically 4′,5,7-trihydroxyflavanone — a subclass of flavonoid polyphenols. Naturally present in citrus fruits, most concentrated in the peel and pith of grapefruit and other citrus. Bitter taste characteristic (naringin, the glycoside form, is responsible for grapefruit bitterness; naringenin is the aglycone). Also produced by biotech fermentation using engineered microorganisms — Debut Biotech's process yields ~99% pure naringenin used exclusively in their Deinde brand at 0.45% concentration.

## Development & history

- Isolated and characterised as a citrus flavonoid in the mid-20th century.
- Extensive study since the 1990s as a dietary polyphenol with anti-oxidative, anti-inflammatory, and metabolic activity.
- Topical skin research began in the 2010s: **Martinez 2016** (topical cream in mouse UVB model), **Yin 2016** (ERK2/MMP-1 mechanism), **Kim 2018** (SIRT1/NF-κB in human fibroblasts) — all published before any consumer brand licensed the ingredient.
- **Debut Biotech** developed a biotech-fermented naringenin, obtained patents, and launched it as the flagship active in their DTC brand **Deinde** in January 2024, positioning it around the concept of "[inflammaging](/learn/what-is-inflammaging-naringenin)" (a 25-year-old immunology term coined by Franceschi in 2000).
- **Ruscinc 2024** (Frontiers in Chemistry) — most rigorous independent comparative study to date — found naringenin uniquely superior among four polyphenols for stratum corneum anti-lipoperoxidation.
- Consumer awareness rose sharply through 2024–2025; ingredient remains almost exclusively associated with the Deinde brand in the DTC market.

## Mechanism (as proposed)

a flavonoid that acts through multiple documented pathways in skin cells. It binds directly to **ERK2**, blocking UVB-induced MMP-1 expression (mechanism suppressing collagen degradation, per Yin 2016). It activates **SIRT1** and blocks **NF-κB** inflammatory signalling in dermal fibroblasts (mechanism reducing senescence-associated cytokines, per Kim 2018). It shows **anti-oxidative** activity — uniquely among common cosmetic polyphenols, it protects rather than damages stratum corneum lipids under UV stress (Ruscinc 2024). In pigmented reconstructed epidermis it reduces melanogenesis gene expression (Martinez 2023). The biotech marketing framing translates these mechanisms as "interrupting inflammaging" and "15× more effective than niacinamide" — these translations require caution: the cell-culture and animal evidence is real, but the extrapolation to visible anti-aging results on human faces currently rests on one in-house 30-person clinical study by the brand selling the product.

Evidence grades by outcome:
outcome: Topical: anti-oxidative barrier protection
grade: B
base: Ruscinc et al. 2024 (Frontiers in Chemistry) — comparative study of 4 polyphenols in 0.1% gels; naringenin the only one showing significant anti-lipoperoxidation in stratum corneum (others were pro-oxidant under UV stress)
effect: Reduction of UV-induced lipid peroxidation in stratum corneum; superior to chlorogenic acid, apigenin, kaempferol
caveat: In vitro / ex vivo skin model; not a visible-outcome human RCT; independent replication with clinical endpoints still lacking
outcome: Topical: MMP-1 suppression / anti-photoaging (mechanism)
grade: B
base: Yin 2016 (J Cell Mol Med) — naringenin binds ERK2 and suppresses UVB-induced MMP-1 in cells and mice; Martinez 2016 (PLOS ONE) — topical naringenin cream reduced UVB-induced skin inflammation and oxidative damage in hairless mice; Martinez 2023 (Cosmetics MDPI) — UVB and pollution protection in human skin cells
effect: Consistent anti-inflammatory, anti-oxidative, MMP-suppressing activity across independent labs
caveat: All independent evidence is in-vitro (cells, reconstructed epidermis) or animal (mice); no independent human RCT with visible endpoints
outcome: Anti-inflammatory (skin senescence / inflammaging mechanism)
grade: B
base: Kim 2018 (Biomedical Dermatology) — human dermal fibroblasts; naringenin activates SIRT1, blocks NF-κB, reduces MMP expression. Published 6 years before Deinde launch, no brand affiliation.
effect: Reduction of inflammatory cytokines and MMPs in fibroblast cell models
caveat: In vitro; effect in living skin harder to demonstrate; brand-affiliated claims of "15× more effective than niacinamide" derive from cell-culture single-biomarker comparison at unmatched concentrations — not head-to-head clinical
outcome: Visible anti-aging / inflammaging (finished product)
grade: C
base: Deinde in-house RCT — 8 weeks, placebo-controlled, double-blind, n=30, 0.45% naringenin serum; 100% moisture/elasticity, 97% fine-line reduction reported
effect: Improvement in subject-assessed and instrumental endpoints
caveat: Small sample size; in-house / brand-run; no independent replication; "% of participants improved" does not report magnitude of change
outcome: Pigmentation / melanogenesis (in-vitro)
grade: C
base: Martinez 2023 — pigmented reconstructed epidermis; naringenin reduced pigmentation-related gene expression and melanin content
effect: In-vitro pigmentation reduction
caveat: Not translated to clinical endpoints; other polyphenols show similar in-vitro effects that do not translate to visible in vivo results
outcome: "15x more effective than niacinamide" superiority
grade: F
base: Marketing claim
caveat: No human study compares this compound to niacinamide. The only human trial ran against a vehicle control, not against niacinamide, and measured moisture, elasticity and fine lines. The multiplier comes from a single inflammatory marker in cell culture at concentrations that were not matched between the two ingredients. A ratio between two ingredients requires both of them in one study; that study has never been run.
outcome: "Interrupts the root cause of skin aging" causal claim
grade: D
base: Marketing claim
caveat: The one human trial — 8 weeks, placebo-controlled, double-blind, n=30 — measured moisture, elasticity and the appearance of fine lines. It did not measure inflammaging or any causal driver of aging, and the inflammaging mechanism itself rests on cultured human dermal fibroblasts. Two things remain unshown: that inflammaging is a settled single root cause of skin aging, and that this compound interrupts it in living skin. The trial measured appearance; the promise asserts cause.
outcome: Safety (topical)
base: Ruscinc 2024 HET-CAM assay — non-irritating; decades of dietary exposure (citrus consumption); no significant topical safety signals
effect: Well tolerated
caveat: Photostability of the molecule under UV requires appropriate formulation; grapefruit-derived versus biotech-fermented forms are chemically identical

Legal status:
region: INT
status: Lawful cosmetic ingredient
note: Topical Naringenin is a lawful cosmetic ingredient in the EU (Regulation (EC) 1223/2009), UK, US, and Asia. CosIng-listed. Biotech- fermented naringenin (produced by Debut Biotech and used exclusively in the Deinde brand) is chemically identical to plant-extracted naringenin and follows the same regulatory pathway. Not restricted.

Cosmetic claims:
allowed: for the appearance of calm, healthy-looking skin
supports the look of a resilient skin barrier
antioxidant
helps skin look protected from environmental stress
forbidden: reverses aging
interrupts the root cause of skin aging
15 times more effective than niacinamide
reduces inflammation
anti-inflammatory
stops inflammaging
inhibits MMP
protects collagen (as a stand-alone claim)

Note: Naringenin is a lawful cosmetic ingredient globally. Vallydia does not currently sell a naringenin product — the biotech-fermented form is exclusively formulated into the Deinde brand by Debut Biotech, and plant- extracted forms of varying purity are used by other brands. This registry entry provides independent evidence-grading as a reference; the reference science below spans both cell/animal mechanism studies and one in-house brand clinical trial.

Sources:
Martinez RM, et al. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice. PLOS ONE. 2016.
Jung SK, Ha SJ, Jung CH, et al. Naringenin targets ERK2 and suppresses UVB-induced photoaging. J Cell Mol Med. 2016.
Kim HK, et al. Inhibitory effect of naringenin on LPS-induced skin senescence by SIRT1 regulation in HDFs. Biomedical Dermatology. 2018.
Martinez RM, et al. Protective Effects of Naringenin against UVB Irradiation and Air Pollution-Induced Skin Aging and Pigmentation. Cosmetics MDPI. 2023; 10(3):88.
Ruscinc N, et al. Comparative study of four polyphenols (chlorogenic acid, apigenin, kaempferol, naringenin) on stratum corneum lipid peroxidation. Frontiers in Chemistry. 2024.
Franceschi C, et al. Inflammaging: an evolutionary perspective on immunosenescence. Ann NY Acad Sci. 2000. (context — the concept naringenin marketing is built around)