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

This nested substudy (Part B) of the VIST TO-COSKIN4 study (NCT07345195) evaluates whether 16 weeks of daily dietary supplementation with two investigational products containing collagen, methylsulfonylmethane (MSM) and vitamin C affects advanced glycation end products (AGEs) in the skin, compared with placebo. AGEs are compounds formed when sugars bind to proteins such as collagen, and they accumulate in the skin with age. They are assessed non-invasively by skin autofluorescence on the forearm. Part B includes the same participants (healthy women aged 40 to 65 years), randomisation and visits as the main study. The primary objective is to evaluate the effect of each investigational product, compared with placebo, on skin autofluorescence after 16 weeks; the secondary objective is to evaluate the effect after 8 weeks.

Inclusion Criteria: * 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.