Effects of a Dietary Supplement on Collagen Production and Evaluation of Its Regenerative and Anti-Ageing Propertiess (REGEN-C)

This study evaluates the effects of a dietary supplement containing natural bioactive compounds on biological processes associated with skin ageing and extracellular matrix integrity. Ageing is characterized by a progressive decline in the function of dermal fibroblasts, the primary cells responsible for collagen production and maintenance of skin structure. Over time, these cells exhibit reduced proliferative capacity, decreased collagen synthesis, and increased accumulation of oxidative and glycative damage, leading to deterioration of skin elasticity and overall tissue homeostasis.

The study integrates in vitro and clinical approaches to investigate the potential benefits of the formulation. In the clinical component, healthy adult participants received either the nutraceutical formulation or a matched placebo daily for a period of six weeks. Blood samples were collected at baseline and at the end of the intervention to assess changes in systemic biomarkers associated with collagen metabolism, oxidative stress, and glycation.

Specifically, the study measured circulating levels of Pro-Collagen I Alpha as an indicator of collagen biosynthesis, protein carbonyls as markers of oxidative protein damage, and Advanced Glycation End Products as markers of glycation-related molecular damage. These biomarkers collectively reflect key biological mechanisms underlying skin ageing and broader ageing processes.

The objective of the study is to determine whether supplementation with the formulation can support extracellular matrix homeostasis, enhance collagen production, and reduce molecular damage associated with oxidative stress and glycation, thereby contributing to healthy ageing.

Study Overview

• Status: Completed
• Conditions: Oxidative Stress; Healthy Ageing; Skin Ageing
• Intervention / Treatment: Dietary supplement: Collagen-Supporting Nutraceutical Formulation; Dietary supplement: Placebo

Detailed Description

Ageing of the skin is a multifactorial biological process characterized by progressive structural and functional decline of the dermis. Dermal fibroblasts are the principal cells responsible for the synthesis and maintenance of the extracellular matrix (ECM), including type I and type III collagen, which are essential for maintaining skin integrity, elasticity, and mechanical strength. During ageing, fibroblasts progressively lose proliferative capacity and enter a state of replicative senescence associated with irreversible cell-cycle arrest and altered cellular function. This transition is driven by mechanisms such as telomere shortening, oxidative stress, mitochondrial dysfunction, and persistent DNA damage responses, ultimately leading to reduced collagen synthesis and impaired tissue repair.

In parallel, ageing is accompanied by increased oxidative and glycative stress, which contribute to cumulative molecular damage. Oxidative modification of proteins results in the formation of protein carbonyls, widely recognized as stable markers of oxidative protein damage. Glycation reactions lead to the formation of Advanced Glycation End Products (AGEs), which accumulate in long-lived proteins such as collagen, promoting crosslinking, reduced tissue elasticity, and impaired extracellular matrix remodeling. These processes are further amplified by the accumulation of senescent fibroblasts, which secrete pro-inflammatory and matrix-remodeling factors, contributing to chronic low-grade inflammation and progressive tissue deterioration.

Targeting these interconnected mechanisms, including extracellular matrix metabolism, oxidative stress, glycation, and proteostasis, represents a promising strategy for supporting healthy ageing. Nutraceutical formulations containing natural bioactive compounds have emerged as potential modulators of these pathways, with evidence suggesting their ability to enhance antioxidant defenses, reduce protein damage, and support collagen biosynthesis.

The present study applies a translational framework to evaluate the biological effects of a collagen-supporting nutraceutical formulation. The investigation included an initial in vitro component using human fibroblasts to assess cellular responses related to ageing dynamics, followed by a randomized, placebo-controlled clinical intervention in healthy adults to determine systemic effects.

In the clinical study, participants received either the nutraceutical formulation or a matched placebo administered orally for six consecutive weeks. The formulation consisted of a combination of structural components of collagen, amino acids involved in collagen biosynthesis, antioxidants, enzymatic cofactors, and micronutrients supporting skin and cellular homeostasis. Specifically, each tablet contained hydrolyzed marine collagen peptides (200 mg) and hyaluronic acid (100 mg) to support extracellular matrix structure and hydration. It also included key amino acids required for collagen synthesis, namely glycine (120 mg), proline (60 mg), and hydroxyproline (60 mg), which contribute to collagen formation, stabilization, and maturation.

To address oxidative stress and molecular damage, the formulation incorporated antioxidant compounds including quercetin (50 mg), reduced glutathione (50 mg), and astaxanthin (0.1 mg), aiming to enhance cellular redox balance and protect proteins and membranes from oxidative modification. In addition, vitamin C (80 mg) and zinc (10 mg) were included as essential cofactors for enzymatic processes involved in collagen biosynthesis. The formulation was further supplemented with vitamin D3 (30 μg, 1200 IU) and biotin (100 μg) to support cellular homeostasis, skin health, and metabolic regulation. Excipients were included to ensure stability and appropriate tablet formulation.

Blood samples were collected at baseline and at the end of the intervention period to evaluate changes in circulating biomarkers associated with key biological processes relevant to ageing. The selected biomarkers included Pro-Collagen I Alpha as an indicator of collagen biosynthesis and extracellular matrix turnover, protein carbonyls as markers of oxidative protein damage, and Advanced Glycation End Products as markers of glycation burden. Together, these biomarkers provide complementary information on collagen metabolism, oxidative stress, and protein modification, allowing for an integrated assessment of biological ageing processes.

The study is designed to determine whether supplementation with the formulation can modulate these biomarkers in a manner consistent with improved extracellular matrix homeostasis and reduced molecular damage. By focusing on measurable systemic endpoints linked to fundamental mechanisms of ageing, the study aims to provide evidence for the potential role of targeted nutraceutical interventions in supporting skin health and broader healthy ageing trajectories.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 11521
      • Hellenic Pasteur Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Adults aged 29 to 82 years Individuals with Fitzpatrick skin types I-VI Presence of mild to moderate fine lines and wrinkles Presence of mild to moderate photoaging consistent with chronological ageing Generally healthy individuals without known medical conditions that, in the opinion of the investigator, could interfere with study participation Ability to understand the study procedures and provide written informed consent

Exclusion Criteria:

1. Body mass index (BMI) greater than 28 kg/m² Current diagnosis of cancer and/or undergoing chemotherapy or radiotherapy Use of dietary supplements during the study period Ongoing long-term treatment for autoimmune or chronic diseases Pregnancy, breastfeeding, or intention to become pregnant during the study period Severe photoaging beyond mild to moderate classification History of cosmetic procedures or dermatological conditions that, in the opinion of the investigator, could interfere with accurate skin assessment, including but not limited to rosacea, acne, or excessively oily or dry skin Known hypersensitivity or allergic reaction to any component of the study product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nutraceutical Formulation; Participants receive an oral nutraceutical formulation containing collagen peptides, amino acids, antioxidants, vitamins, and trace elements designed to support collagen biosynthesis, extracellular matrix homeostasis, and reduction of oxidative and glycative stress. The formulation is administered daily for six weeks.	Dietary supplement: Collagen-Supporting Nutraceutical Formulation; The intervention consists of an oral dietary supplement formulated to support collagen biosynthesis and extracellular matrix homeostasis. Each tablet contains hydrolyzed marine collagen peptides, hyaluronic acid, and amino acids (glycine, proline, hydroxyproline) involved in collagen formation and stabilization. The formulation also includes antioxidant compounds (quercetin, reduced glutathione, astaxanthin) to support redox balance, as well as vitamin C and zinc as cofactors in collagen synthesis. Additional components include vitamin D3 and biotin to support cellular and skin health. The supplement is administered daily for six weeks.
Placebo Comparator: Placebo Comparator; Participants receive a matched placebo formulation administered orally on a daily basis for six weeks. The placebo is similar in appearance and dosing schedule to the active intervention but does not contain bioactive ingredients.	Dietary supplement: Placebo; The placebo consists of an inert oral formulation matched in appearance and administration schedule to the active dietary supplement. It contains excipients without active bioactive ingredients and is administered daily for six weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma Pro-Collagen I Alpha levels	Change in circulating Pro-Collagen I Alpha concentrations as a biomarker of collagen biosynthesis and extracellular matrix turnover.	Baseline (Day 0) and Week 6
Change in plasma protein carbonyl levels	Change in plasma protein carbonyl concentrations as a measure of oxidative protein damage.	Baseline (Day 0) and Week 6
Change in plasma Advanced Glycation End Products (AGEs) levels	Change in plasma AGEs concentrations as a measure of glycation-related molecular damage.	Baseline (Day 0) and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant-reported self-assessment of skin-related effects and tolerability	Self-administered participant questionnaire evaluating perceived effects of the intervention on skin appearance and condition, including elasticity, hydration, wrinkle appearance, pigmentation-related changes, and overall skin quality, together with general well-being and any self-reported adverse effects.	Week 6

Collaborators and Investigators

• Sponsor: Marianna Kapetanou

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Actual): February 1, 2026
• Study Completion (Actual): March 1, 2026

Study Registration Dates

• First Submitted: April 3, 2026
• First Submitted That Met QC Criteria: April 3, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Antioxidants; Oxidative Stress; Nutraceutical; Dietary Supplement; Extracellular Matrix; Healthy Ageing; Advanced Glycation End Products; Skin Ageing; Collagen Biosynthesis; Protein Carbonyls; Proteostasis; Collagen Metabolism
• Other Study ID Numbers: 3 8 1 3 / 1 7 - 0 6 - 2 0 2 4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data (IPD) will not be shared due to privacy and data protection considerations, including compliance with applicable regulations such as the General Data Protection Regulation (GDPR). Data will be reported and made available in aggregate form to ensure participant confidentiality.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No