NICEVIVA
MONOGRAPH SPEC LATEST 2026

Vitamin C (Skin Collagen)

SKIN HAIR · Evidence Monograph

Vitamin C (Skin Collagen) is an evidence-graded skin hair monograph evaluated across 22 peer-reviewed PubMed studies (0 meta-analyses, 2 systematic reviews, and 3 randomized controlled trials, encompassing n = 8,260 cumulative participants). Current clinical evidence is rated GRADE Moderate (3.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) Moderate (3.0 / 4.0)
Indexed PubMed Studies 22 Studies
Meta-Analyses · Reviews 0 Meta · 2 Systematic Reviews
Randomized Trials (RCT) 3 RCTs (4 Double-Blind)
Cumulative Participants n = 8,260
Reported Trial Dosages 5 g · 80 mg · 30 mg
Trial Duration Range 4 days · 16 weeks · 12 weeks
Reading Time ~11 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support (supported by 22 indexed PubMed studies, GRADE Moderate).
  2. 02 Adults matching clinical trial dosing protocols (5 g · 80 mg · 30 mg) over a structured 4 days evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Clinically Standardized Formulation
Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.
Dose Adjustment Signal: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
With Breakfast or Lunch
Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
antioxidant (PubMed clinical endpoint)
skin (PubMed clinical endpoint)
01

What Is Vitamin C (Skin Collagen) & Why Does Form Matter?

Vitamin C (Skin Collagen) is classified under SKIN HAIR and has been investigated across 22 peer-reviewed PubMed publications for its role in targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (5 g, 80 mg, 30 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Vitamin C (Skin Collagen) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (3 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Vitamin C (Skin Collagen) acts on pathways governing targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Vitamin C (Skin Collagen) an overall evidence rating of GRADE Moderate (3.0 / 4.0) based on 22 PubMed studies: 0 meta-analyses, 2 systematic reviews, and 3 randomized controlled trials (4 double-blind, n = 8,260 total participants).

Representative peer-reviewed findings include: • PMID:38345088 (2024) — "Nutritional interventions for preventing and treating pressure ulcers." (Adequate nutrient intake can reduce the risk factor of malnutrition and promote wound healing in existing pressure ulcers.) • PMID:41947480 (2026) — "Hydroquinone-Free, Tetrahexyldecyl Ascorbate Antioxidant Serum for Hyperpigmented and Photodamaged Skin to Achieve Skin Health." (CONCLUSIONS: THD-AA serum has clinical and molecular efficacy in buffering ROS, reducing melanogenesis, and promoting antiaging, providing a safe alternative to hydroquinone products.) • PMID:40642809 (2025) — "Application of Antioxidant Mixture Prevents Cutaneous "Oxinflammaging" in Subjects Exposed to Particulate Matter." (CONCLUSION: Regular topical application of an antioxidant cosmeceutical formulation represents an effective strategy to counteract the detrimental effects of environmental insults, particularly with respect to inflammaging.)

05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Clinically Standardized Formulation. Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 5 g · 80 mg · 30 mg · 540 mg over 4 days · 16 weeks · 12 weeks · 6 months. Optimal timing window: PM 12:30 · With Breakfast or Lunch (Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.

Adjustment & Discontinuation Signals: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Vitamin C (Skin Collagen), but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (5 g · 80 mg · 30 mg) and re-evaluate efficacy after 4 days.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (22 Studies) · 8 Quantitative Analyses

01
CLINICAL STUDY The Cochrane database of systematic reviews (2024) PMID: 38345088 ↗
Nutritional interventions for preventing and treating pressure ulcers.
Clinical Trial Synthesis 2024 Meta-Analysis published in The Cochrane database of systematic reviews involving n = 7,920 participants (RR 0.92). Key conclusion: Adequate nutrient intake can reduce the risk factor of malnutrition and promote wound healing in existing pressure ulcers.
View Original PubMed Abstract ↓

BACKGROUND: Pressure ulcers are localized injuries to the skin or the underlying tissue, or both, and are common in older and immobile people, people with diabetes, vascular disease, or malnutrition, as well as those who require intensive or palliative care. People with pressure ulcers often suffer from severe pain and exhibit social avoidance behaviours. The prevention and treatment of pressure ulcers involves strategies to optimize hydration, circulation, and nutrition. Adequate nutrient intake can reduce the risk factor of malnutrition and promote wound healing in existing pressure ulcers. However, it is unclear which nutrients help prevent and treat pressure ulcers. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the benefits and harms of nutritional interventions (special diets, supplements) for preventing and treating pressure ulcers in people with or without existing pressure ulcers compared to standard diet or other nutritional interventions. SEARCH METHODS: We used extensive Cochrane search methods. The latest search was in May 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in people with or without existing pressure ulcers, that compared nutritional interventions aimed at preventing or treating pressure ulcers with standard diet or other types of nutritional interventions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome for prevention studies was the proportion of participants who developed new (incident) pressure ulcers. For treatment studies, our primary outcomes were time to complete pressure ulcer healing, number of people with healed pressure ulcers, size and depth of pressure ulcers, and rate of pressure ulcer healing. Secondary outcomes were side effects, costs, health-related quality of life and acceptability. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 33 RCTs with 7920 participants. Data for meta-analysis were available from 6993 participants. Pressure ulcer prevention Eleven studies (with 12 arms) compared six types of nutritional interventions for the prevention of pressure ulcers. Compared to standard diet,

02
CLINICAL STUDY Journal of cosmetic dermatology (2026) PMID: 41947480 ↗
Hydroquinone-Free, Tetrahexyldecyl Ascorbate Antioxidant Serum for Hyperpigmented and Photodamaged Skin to Achieve Skin Health.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Journal of cosmetic dermatology. Key conclusion: CONCLUSIONS: THD-AA serum has clinical and molecular efficacy in buffering ROS, reducing melanogenesis, and promoting antiaging, providing a safe alternative to hydroquinone products.
View Original PubMed Abstract ↓

BACKGROUND: Ascorbic acid (AA) has protective and corrective functions critical for counteracting extrinsic and intrinsic skin aging and hyperpigmentation, but it is highly unstable, making it challenging to formulate into skincare products. Tetrahexyldecyl (THD) Ascorbate, a lipid-soluble derivative of AA, has superior stability and skin-mimicking properties. AIMS: To investigate the efficacy and tolerability of a novel antioxidant serum containing 30% THD Ascorbate (THD-AA serum), a patent-pending blend of antioxidants and prebiotics, on photoaged and hyperpigmented skin with respect to long-term skin health. METHODS: Using preclinical models and a randomized, double-blind clinical trial, the antioxidant potential, antimelanogenesis, and antiaging properties of the THD-AA serum were evaluated. RESULTS: Using an in vitro tissue model exposed to blue light, there was an 88% reduction in reactive oxygen species (ROS) formation after 30 min, 87% reduction after 60 min, and an 82% reduction after 120 min compared to the blue light-exposed control. Melanin production was reduced by 24% in vitro tissue co-culture. THD-AA serum improved the structural architecture of the skin, including the epidermis, dermal-epidermal junction, and dermis, and upregulated dermal collagen production 4-fold compared to a controlled moisturizer in an ex vivo model. In the clinical trial, existing damage and hyperpigmentation were visibly corrected on VISIA-CR and Antera 3D photographs, as well as in Clinical Grader results. There were no adverse events, and participants tolerated the serum well. CONCLUSIONS: THD-AA serum has clinical and molecular efficacy in buffering ROS, reducing melanogenesis, and promoting antiaging, providing a safe alternative to hydroquinone products. © 2026 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

03
CLINICAL STUDY Journal of cosmetic dermatology (2025) PMID: 40642809 ↗
Application of Antioxidant Mixture Prevents Cutaneous "Oxinflammaging" in Subjects Exposed to Particulate Matter.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Journal of cosmetic dermatology. Key conclusion: CONCLUSION: Regular topical application of an antioxidant cosmeceutical formulation represents an effective strategy to counteract the detrimental effects of environmental insults, particularly with respect to inflammaging.
View Original PubMed Abstract ↓

BACKGROUND: Premature skin aging and the growing incidence of skin conditions are closely linked to daily exposure to environmental agents. Among all air pollutants, particulate matter (PM) is regarded as one of the most aggressive in terms of skin damage, promoting degradation of extracellular matrix (ECM) components and depletion of the cutaneous antioxidant defense via initiation of oxinflammatory reactions. Moreover, PM can penetrate damaged skin, exacerbating the effect of other pollutants and worsening the symptoms of existing skin conditions. Topical application of antioxidant compounds can limit and, in certain cases, even prevent skin damage. OBJECTIVE: In the present study, a randomized clinical study was conducted to evaluate the protective effects of a topically applied antioxidant serum containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol (AOX Mix) against the PM-induced skin damage. METHODS: For this purpose, the back of 15 female volunteers, between 19-40 years and with skin phototypes III and IV, was pre-treated with AOX Mix and exposed daily to PM for 4 days. Skin sample biopsies were subsequently collected and subjected to histological analysis to evaluate the key markers related to skin "oxinflammaging". RESULTS: The AOX Mix demonstrated protective effects against the cutaneous degradation of ECM components, including type I and III collagens, elastin, and tropoelastin. It also mitigated markers of inflammation (COX2), oxidative stress (4-hydroxynonenal), and structural damage (involucrin, filaggrin, claudin-1, desmocollin 1). CONCLUSION: Regular topical application of an antioxidant cosmeceutical formulation represents an effective strategy to counteract the detrimental effects of environmental insults, particularly with respect to inflammaging. © 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

04
CLINICAL STUDY Journal of drugs in dermatology (2024) PMID: 39231081 ↗
Treatment of Acne Vulgaris-Associated Post-Inflammatory Dyschromia With Combination of Non-Ablative Laser Therapy and Topical Antioxidants.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in Journal of drugs in dermatology involving n = 25 participants. Key conclusion: Improvement of both PIE and PIH was augmented in combination with SSAF and laser-treated patients compared with the laser-only group, with a concomitant increase in collagen density.
View Original PubMed Abstract ↓

97. J Drugs Dermatol. 2024 Sep 1;23(9):769-773. doi: 10.36849/JDD.8309. Treatment of Acne Vulgaris-Associated Post-Inflammatory Dyschromia With Combination of Non-Ablative Laser Therapy and Topical Antioxidants. Hu JK, Quinonez RL, Antasiuk V, Waibel J. Acne can cause disfiguring sequelae, such as scarring, post-inflammatory erythema (PIE), and post-inflammatory hyperpigmentation (PIH). These post-inflammatory dyschromias pose a significant psychological burden on patients. This burden disproportionately affects skin of color (SOC) patients and can be the most distressing aspect of acne in SOC patients with skin types IV to VI. Multiple non-ablative lasers are used in the treatment of acne-related PIE and PIH. Combination therapies have shown promise in conditions such as rosacea, acne, and post-inflammatory dyschromia. Addressing both the inflammatory and scarring components of acne is key. Given the role of oxidation in the inflammatory cascade, including antioxidants could be an efficacious adjuvant with non-ablative lasers. This is a single-site, randomized, controlled clinical study of 25 subjects with skin types I to VI with facial PIE and/or PIH from acne. The primary objective was to investigate the clinical efficacy of non-ablative laser therapy followed by the topical application of Silymarin/Salicylic Acid/L-Ascorbic Acid/Ferulic Acid (SSAF) or control in the improvement in oily skin patients with facial PIE and PIH due to acne lesions. There was a statistically significant decrease in PIH and intralesional melanin in patients treated with a combination SSAF and non-ablative laser therapy. Improvement of both PIE and PIH was augmented in combination with SSAF and laser-treated patients compared with the laser-only group, with a concomitant increase in collagen density. This was even more strikingly marked in the SOC subjects, potentially providing an energy-based device (EBD)-based therapy in this population. Limitations of this study include small sample size and length of post-treatment follow-up. J Drugs Dermatol. 2024;23(9):769-773. doi:10.36849/JDD.8309.

05
RANDOMIZED TRIAL (RCT) Nutrients (2024) PMID: 38931263 ↗
The Effects of Dietary Supplementation with Collagen and Vitamin C and Their Combination with Hyaluronic Acid on Skin Density, Texture and Other Parameters: A Randomised, Double-Blind, Placebo-Controlled Trial.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in Nutrients involving n = 29 participants. Key conclusion: Therefore, the ability of supplementation with HA to improve the effects on investigated skin parameters beyond the supplementation of collagen alone cannot be confirmed.
View Original PubMed Abstract ↓

Collagen dietary supplements are becoming increasingly popular as a means to reduce signs of skin ageing. The objective of this three-way, randomised, placebo-controlled, double-blind study was to examine and contrast the effects of dietary supplementation with a daily dose of 5 g hydrolysed collagen with 80 mg of vitamin C (CP product) and their combination with 30 mg of hyaluronic acid (CPHA product) over 16 weeks. Validated methods were utilised for the objective evaluation of skin parameters. In total, 87 subjects (women, 40-65 years) completed the entire trial, distributed across the groups as follows: placebo group (n = 29), CPHA group (n = 28), and CP group (n = 30). The results showed beneficial effects of both test products, with notable enhancements in dermis density, skin texture, and a reduction in the severity of wrinkles. In contrast, the administration of either of the products did not yield any significant impacts on skin elasticity or hydration. Observation of the investigated skin parameters did not show superior effects of the addition of hyaluronic acid (HA) to collagen. Therefore, the ability of supplementation with HA to improve the effects on investigated skin parameters beyond the supplementation of collagen alone cannot be confirmed.

06
RANDOMIZED TRIAL (RCT) Clinical and experimental dermatology (2022) PMID: 35279873 ↗
Ultraviolet radiation-induced degradation of dermal extracellular matrix and protection by green tea catechins: a randomized controlled trial.
Clinical Trial Synthesis 2022 Randomized Controlled Trial (RCT) published in Clinical and experimental dermatology; statistical significance reported at p = 0.001. Key conclusion: CONCLUSIONS: Acute UVR induced significant changes in the human dermal collagen and elastic fibre networks, whereas oral GTCs conferred specific UVR protection to fibulin-5.
View Original PubMed Abstract ↓

BACKGROUND: Loss and remodelling of the dermal extracellular matrix (ECM) are key features of photodamaged human skin. Green tea catechins (GTCs) have been explored for their anti-inflammatory and chemopreventive properties, but data on the impact of GTCs on ultraviolet radiation (UVR)-induced changes to the dermal ECM are lacking. AIM: To investigate the effect of an inflammatory dose of solar-simulated UVR on human dermal ECM and potential for protection by GTCs in a double-blind randomized controlled trial. METHODS: In total, 50 healthy white (Fitzpatrick skin type I-II) adults aged 18-65 years were randomized to a combination of GTCs 540 mg plus vitamin C 50 mg or to placebo twice daily for 12 weeks. The impact of solar-simulated UVR at 3 × minimal erythema dose on the dermal collagen and elastic fibre networks was assessed by histology and immunohistochemistry in all participants at baseline. The impact of GTC supplementation on UVR-induced effects was compared between the groups post-supplementation. RESULTS: The area of papillary dermis covered by collagen and elastic fibres was significantly lower (P < 0.001) in UVR-exposed skin than in unexposed skin. Significantly lower levels of fibrillin-rich microfibrils (P = 0.02), fibulin-2 (P < 0.001) and fibulin-5 (P < 0.001) were seen in UVR-exposed than unexposed skin, while procollagen-1 deposition was significantly higher in UVR-exposed skin (P = 0.01). Following GTC supplementation, the UVR-induced change in fibulin-5 was abrogated in the active group but not the placebo group, with no difference between the two groups for other components. CONCLUSIONS: Acute UVR induced significant changes in the human dermal collagen and elastic fibre networks, whereas oral GTCs conferred specific UVR protection to fibulin-5. Future studies could explore the impact of GTCs on the effects of repeated suberythemal UVR exposure of human skin. © 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

07
RANDOMIZED TRIAL (RCT) Aesthetic plastic surgery (2021) PMID: 33881605 ↗
Treatment of Scars with Laser-Assisted Delivery of Growth Factors and Vitamin C: A Comparative, Randomised, Double-blind, Early Clinical Trial.
Clinical Trial Synthesis 2021 Randomized Controlled Trial (RCT) published in Aesthetic plastic surgery involving n = 132 participants; statistical significance reported at p = 0.01. Key conclusion: Furthermore, the addition of growth factors provided statistically significant better outcomes and resulted in more inconspicuous scars.
View Original PubMed Abstract ↓

BACKGROUND: Scarring can jeopardize the final result of plastic surgeries. Deep dermal injuries activate dermal fibroblasts that produce excessive amount of collagen and inflammatory cytokines and growth factors, which contributes to increased fibrous tissue and scarring tissue formation. OBJECTIVES: The aim of this early study, double-blind, prospective, randomised clinical trial was to investigate the use of laser-assisted drug delivery (LADD) for scar improvement to support the establishment of LADD as standard therapy modality and to indicate suitable drugs for dermal administration. MATERIAL AND METHODS: In total, 132 patients seeking scar treatment were consented and randomised. The control group (64 patients) received laser resurfacing immediately followed by skin surface application of Vitamin C and 68 patients received laser treatment followed by skin surface application of a cosmeceutical containing growth factors (GFs) and Vitamin C. Photographs were obtained before and three months after the procedure and submitted to three-dimensional reconstruction by the software Dermapix®. Objective measurements provided by the software were statistically analysed and established the differences in the treatment result between the two groups. RESULTS: There was a significant reduction in scar roughness and volume in both groups (p < 0.01). Mann-Whitney test confirmed that the group treated vitamin C and GFs presented significantly better results than the group treated with vitamin C alone (p < 0.01). CONCLUSION: LADD has proven efficient as scars were reduced in both study groups. Furthermore, the addition of growth factors provided statistically significant better outcomes and resulted in more inconspicuous scars. No adverse reactions were observed. CLINICAL TRIAL REGISTRATION: Plataforma Brasil under the number CAAE: 63710716.2.0000.5664. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . © 2021. Springer Science+Business Media, LLC, part of Spring

08
CLINICAL STUDY Drug delivery (2021) PMID: 33620008 ↗
Topical delivery of l-ascorbic acid spanlastics for stability enhancement and treatment of UVB induced damaged skin.
Clinical Trial Synthesis 2021 Clinical Study published in Drug delivery. Key conclusion: LAA-loaded spanlastics successfully improved LAA stability, skin permeation and antioxidant protection against skin photodamage.
View Original PubMed Abstract ↓

l-Ascorbic acid (LAA) is considered a powerful antioxidant that protects skin from premature aging. Maintaining the stability of vitamin C remains the biggest challenge in cosmeceuticals. Our main aim is the entrapment of high dose of vitamin C in spanlastic vesicles to provide maximum stability and efficacy. LAA-loaded spanlastics were prepared by ethanol injection method and were characterized for entrapment efficiency (EE%), particles size (PS), polydispersity index (PDI), zeta potential, deformability index (DI) and in vivo skin permeation. Selected spanlastics formula composed of span 60 and tween 60 (5:1) showed highest EE% of 89.77 ± 3.61% (w/w), high deformability of 11.13 ± 1.145 as well as good physical and chemical stability for 6 months. Improved drug penetration into stratum corneum (SC) was obtained from spanlastics compared to topical LAA solution. Quantitative real time PCR revealed that MMP2 and MMP9 levels were significantly suppressed in response to LAA spanlastics treated rats by 30.4% and 65.3%, respectively, when compared to the control group after exposure to UV irradiation. Results were confirmed by western blot analysis. Histopathological study of rat skin after UV irradiation revealed that application of LAA-loaded spanlastics provided the highest skin protection compared to UVB and LAA solution treated group which was evident by the normal thick epidermal morphology and the densely arranged dermal collagen fibers. LAA-loaded spanlastics successfully improved LAA stability, skin permeation and antioxidant protection against skin photodamage.

09
CLINICAL STUDY Pharmaceutical development and technology (2026) PMID: 41728888 ↗
Synergistic combination of quercetin and kaempferol via milk exosome-based emulsion for enhanced antioxidant and anti-skin aging efficacy.
Clinical Trial Synthesis 2026 Clinical Study published in Pharmaceutical development and technology. Key conclusion: In conclusion, an optimized, stable emulsion leveraging a synergistic 1:2 drug ratio and an mExo delivery system was successfully developed, demonstrating superior comprehensive efficacy against skin aging.
View Original PubMed Abstract ↓

The natural flavonoids quercetin (Que) and kaempferol (Kae) show great potential for anti-aging applications but suffer from poor solubility and skin permeability. This study aimed to develop a synergistic topical emulsion system to overcome the poor bioavailability of the Que and Kae for enhanced efficacy. The optimal synergistic molar ratio (Que:Kae = 1:2) was first identified via 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and cellular assays. The drugs were then loaded into milk-derived exosomes (mExo) using a Box-Behnken design (BBD), achieving high encapsulation (>69%), a size of ∼120 nm, and a polydispersity index (PDI) of 0.180. This complex was incorporated into an oil-in-water emulsion, with its formulation also BBD-optimized for stability. In a D-galactose-induced skin aging mouse model, the final Que/Kae-mExo@Eml formulation significantly outperformed control groups (free drug mixture, blank exosome emulsion, and vitamin C). It most effectively reduced oxidative stress (malondialdehyde, MDA), enhanced antioxidant enzymes (superoxide dismutase, SOD and glutathione, GSH), suppressed matrix metalloproteinase-1 (MMP-1), promoted collagen I (Col I) synthesis, and improved skin histology, elasticity, and hydration. In conclusion, an optimized, stable emulsion leveraging a synergistic 1:2 drug ratio and an mExo delivery system was successfully developed, demonstrating superior comprehensive efficacy against skin aging.

10
CLINICAL STUDY Journal of cosmetic dermatology (2025) PMID: 39924347 ↗
Synergistic Anti-Aging Effects of Adipose-Derived Stem Cell Extracellular Vesicles Loaded With Natural Compounds.
Clinical Trial Synthesis 2025 Clinical Study published in Journal of cosmetic dermatology. Key conclusion: CONCLUSION: Our study demonstrated the superiority of ASC-sEVs to deliver both endogenous biocargos and exogenous compounds to achieve synergistic skin anti-aging effects.
View Original PubMed Abstract ↓

BACKGROUND: Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) are gaining attentions rapidly for inherent therapeutic values in skin care and cosmetics. However, the optimal combinations of ASC-sEVs and certain natural compounds for synergistic anti-aging effects have not been systematically studied. METHODS: Human ASC-sEVs were purified from culture supernatant of ASCs and multi-omics datasets of miRNAs, proteins and lipids of ASC-sEVs were analyzed for pathways regulating skin homeostasis. ASC-sEVs were then loaded with nicotinamide riboside (NR), resveratrol (RES), vitamin C (VITC), retinol (RET) and arbutin (ARB) at different concentrations by the sonication-incubation method. Their anti-oxidant, anti-wrinkle and anti-melanogenic effects were tested in vitro using the human keratinocyte HaCaT cells exposed to UVB radiation and human melanocyte B16F10 cells. RESULTS: Multi-omics data analysis of ASC-sEVs identified key bioactive molecules regulating collagen formation, pigmentation, oxidative stress and inflammation. In the in vitro screenings for anti-aging effects, the compound-loaded ASC-sEVs outperformed the sEV- and compound-only treatments. Specifically in UVB-exposed HaCaT cells, 2 μg/mL sEVs loaded with 20 μg/mL NR, 2 μg/mL RES, 5 μg/mL VITC reduced reactive oxygen species level by 22.0%; while combination of sEVs and 2 μg/mL RES, 2.8 μg/mL RET significantly reduced MMP3 and upregulated PLOD1 expressions. B16F10 cells incubated with 2 μg/mL sEVs loaded with 2 μg/mL RES, 0.5 mM ARB had intracellular and extracellular melanin content lowered by 21.4% and 22.4% respectively. All the combinations caused no cytotoxicity. CONCLUSION: Our study demonstrated the superiority of ASC-sEVs to deliver both endogenous biocargos and exogenous compounds to achieve synergistic skin anti-aging effects. © 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

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