Effect of Collagen and MSM Supplementation on Advanced Glycation End Products in Skin: Part B of the TO-COSKIN4 Study

• Caucasian female volunteers aged 40 to 65 years at the time of signing the Informed Consent Form (ICF).
• Signed ICF.
• Fitzpatrick skin phototypes I-IV.
• Presence of visible facial telangiectasias, primarily on the cheeks.
• Presence of facial erythema with a baseline score of 3 or less on the 5-point Clinician's Erythema Assessment (CEA) scale.
• Stable erythema-prone facial skin for at least 3 months prior to inclusion, without clinical signs of active rosacea.
• In good general health, as determined by medical history.
• Body mass index (BMI) below 35.
• Willingness and ability to comply with all study procedures and complete a subject diary; maintain usual lifestyle habits; not initiate or modify oestrogen or progesterone therapies; maintain the same cosmetic and skincare routine and comply with sun protection guidelines; avoid rejuvenation treatments; refrain from food supplements containing collagen or other protein-based supplements, MSM, or anti-inflammatory and/or antioxidant compounds with a known or potential impact on skin inflammation or vascular response; and refrain from shaving, waxing, epilating or otherwise removing hair from the forearms for the duration of the study.

Exclusion Criteria:

• Pregnancy or breastfeeding.
• Vegan diet.
• Following a weight-loss diet or another special or restrictive diet (e.g. very-low-calorie, ketogenic or intermittent fasting), or planning to start one during the study.
• Heavy smoking (more than 20 cigarettes per day) or frequent alcohol-induced flushing.
• Occupational or hobby-related excessive heat exposure (e.g. chefs, sauna workers).
• Anticipated sunbathing or solarium use, or major planned changes in sun exposure before or during the study.
• Planned major changes during the study in skincare routine or hormonal therapy (contraception or hormone replacement therapy).
• Significant changes in dietary habits or dietary supplementation within 3 months prior to inclusion.
• Regular use within 3 months prior to inclusion of food supplements containing MSM, collagen or other protein-based supplements, or anti-inflammatory (e.g. bioflavonoids/rutin, curcumin, EPA) and/or antioxidant supplements with a known or potential impact on skin inflammation or vascular response.
• Any diagnosed, uncontrolled, untreated or unstable medical condition.
• Clinically significant history of metabolic, gastrointestinal, hepatic, renal or haematological disease.
• Diagnosed diabetes mellitus (type 1 or type 2), or current use of glucose-lowering medication.
• Current use, or use within 12 months prior to study entry, of medicines for weight reduction, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, or planned use during the study.
• Mental incapacity or psychiatric condition that may impair understanding of the study or compliance with study requirements.
• Any clinically significant acute or chronic inflammatory skin disease (e.g. acne, perioral dermatitis, psoriasis, atopic dermatitis, lupus).
• Skin pigmentation disorders at the assessment sites.
• Active rosacea within 3 months prior to study entry (papules/pustules, frequent flushing episodes typical of rosacea, or ocular involvement).
• Frequent vasomotor hot flushes (e.g. perimenopausal or menopausal).
• Use of medications affecting skin or vascular reactivity (e.g. systemic corticosteroids, anticoagulants, vasodilators, antibiotics known to affect vascular response, immunomodulators, regular or long-term use of NSAIDs).
• Use of systemic retinoids within 3 months prior to study entry.
• Changes of skincare routine within 4 weeks prior to study entry.
• Use of highly concentrated topical products affecting inflammatory or vascular facial responses (e.g. more than 15% azelaic acid, 10% vitamin C) within 4 weeks prior to study entry.
• Invasive rejuvenation treatments (e.g. medium or deep chemical peels, ablative or vascular laser therapies) within 6 months prior to study entry.
• Non-invasive or minimally invasive rejuvenation treatments (e.g. microneedling, mesotherapy, superficial chemical peels, radiofrequency, electrotherapy, ultrasound, IPL) within 3 months prior to study entry.
• Tattoos, scars, birthmarks, pronounced hyperpigmentation, visible vessels, or an active skin lesion or skin disease at the volar forearm of both forearms.
• Self-tanning products applied to the forearms, or deliberate UV exposure of the forearms (sunbathing, solarium), within 4 weeks before the first visit.
• Known or suspected allergy to any ingredient of the investigational products.