Cite as: Archiv EuroMedica. 2026. 16; 4. DOI 10.35630/2026/16/Iss.4.27
Collagen is the principal structural protein of connective tissues, including the skin, cartilage, tendons, bone, and blood vessels. Ageing is associated with changes in collagen synthesis, organisation, cross-linking, and degradation, which contribute to reduced tissue integrity and function. Collagen supplementation has therefore been investigated as a nutritional strategy to support tissue health in middle-aged and older adults.
This narrative review aimed to summarise current evidence on the physiological role of collagen, age-related changes in collagen metabolism, and the effects and safety of collagen supplementation in middle-aged and older adults.
PubMed, MEDLINE, and Google Scholar were searched for English-language publications published primarily between January 2010 and May 2026. Selected earlier studies were included to provide relevant mechanistic background. Systematic reviews, randomised controlled trials, cohort studies, observational studies, case series, and experimental studies supporting biological plausibility were considered.
The most consistent clinical findings concerned selected skin outcomes, including modest improvements in hydration, elasticity, dermal density, and wrinkle appearance. Collagen supplementation was also associated with improvements in some musculoskeletal outcomes, particularly osteoarthritis-related pain, although several studies evaluated collagen together with exercise or other nutritional interventions. Evidence regarding obesity, glucose and lipid metabolism, arterial stiffness, and other cardiovascular outcomes was limited and inconsistent. Collagen supplementation was generally well tolerated, but most studies were short-term and long-term safety was rarely assessed.
Collagen supplementation may provide modest benefits for selected skin and musculoskeletal outcomes, but the magnitude, consistency, durability, and clinical relevance of these effects remain uncertain. Current evidence does not support specific clinical recommendations for metabolic or cardiovascular conditions. Large-scale, long-term randomised controlled trials using well-characterised collagen preparations and clinically relevant outcomes are required.
Keywords: collagen supplementation, hydrolysed collagen, collagen peptides, skin ageing, joint health, cardiovascular health, metabolic syndrome.
Collagen is a structural protein and the main component of connective tissues [1]. It is a component of skin, tendons, cartilage and blood vessels in mammals [1]. Collagen not only forms a structural support but also regulates proliferation, migration, differentiation, and apoptosis of cells. This occurs through interactions with cell surface receptors and integrins [2].
Collagen is a diverse family of structural glycoproteins that constitute the main component of the extracellular matrix and provide mechanical support to various tissues [3]. Its characteristic triple-helical structure, formed by three α-chains containing repeating Gly–X–Y sequences, contributes to its high tensile strength and stability [3,4]. Variations in amino acid composition, chain organisation, and molecular structure among collagen types determine their tissue distribution and biological functions [3,4].
Humans produce at least 28 collagen types with distinct structural and functional properties [5]. Fibrillar collagens, particularly types I, II, and III, are the predominant forms in connective tissues and provide mechanical strength and structural integrity to tissues such as skin, bone, cartilage, tendons, and blood vessels [5–7]. Type I collagen is the most abundant collagen type in the human body, whereas type II is a major component of cartilage and type III contributes to the flexibility and organisation of vascular and other soft tissues [5–7]. Other collagen types, including network-forming and fibril-associated collagens, support extracellular matrix organisation and regulate interactions between structural components [5,8].
Collagen undergoes progressive structural and functional alterations with ageing. Age-related collagen decline manifests clinically across multiple organ systems, with the most prominent effects seen in dermatologic, musculoskeletal, cardiovascular, and wound healing domains.
Skin changes represent the most visible clinical manifestations of collagen loss. Progressive collagen fragmentation and decline lead to structurally weakened and thin skin with characteristic features including wrinkles, laxity, and increased fragility [9]. Elderly skin shows increased vulnerability to injury, resulting in more frequent lacerations and bruising, particularly manifesting as senile purpura [10, 11]. Age-related collagen alterations create a tissue microenvironment that promotes delayed wound healing [12]. The disrupted collagen matrix impairs fibroblast adhesion and migration, reducing the mechanical signals necessary for proper wound repair [13]. This creates a self-perpetuating cycle where weakened collagen organisation further limits the ability to generate new collagen during the healing process [14].
Additionally, research indicates that the ageing process significantly compromises the integrity of the musculoskeletal system through the progressive loss and biochemical alteration of collagen. In bone tissue, collagen synthesis in aged osteoblasts declines which shows an inverse correlation with collagen production in age-related osteoporosis [15]. Beyond a decrease in tissue mass, the structural quality of bone is affected by changes in collagen cross-linking; while enzymatic cross-links provide strength, there is a significant increase in non-enzymatic cross-links with age, which makes the bone matrix more brittle and prone to fractures [16]. Similar degenerative patterns are observed in articular cartilage, where chondrocytes exhibit a decreased capacity for proliferation and synthesis of essential matrix components [17]. Specifically, ageing leads to reduced synthesis of type II collagen and aggrecan [18]. Ageing is also associated with increased production of matrix-degrading enzymes (such as matrix metalloproteinases), pro-inflammatory mediators, and elevated levels of reactive oxygen species (ROS), all of which contribute to matrix degradation [17,18]. These cumulative changes result in progressive cartilage matrix loss, explaining the heightened predisposition to osteoarthritis observed in ageing populations [17,19].
Another important manifestation of age-related collagen remodelling is vascular ageing. It is characterised by increased arterial stiffness due to collagen accumulation and elastin degradation in vessel walls [20]. Paradoxically, compared with other tissues, collagen turnover is reduced in ageing arteries. The accumulation of collagen modified by advanced glycation end-products (AGEs) causes it to become resistant to enzymatic degradation, thereby impairing collagenolysis and contributing to decreased arterial compliance [21, 22]. This structural change results in increased pulse wave velocity, which correlates with cardiovascular disease risk and all-cause mortality [21]. Arterial stiffening creates a positive feedback loop with hypertension, where each condition accelerates the other [21].
These age-related alterations in collagen structure and function have led to increasing interest in collagen supplementation as a potential strategy to support connective tissue integrity in ageing populations.
Collagen supplements are derived from animal and marine sources, including bovine, porcine, fish, and poultry tissues [23]. Due to safety concerns, religious and dietary restrictions, and sustainability considerations, additional sources such as marine by-products, plant-based alternatives, and recombinant collagen are increasingly being explored [23, 24].
Commercial collagen products are typically obtained through enzymatic hydrolysis of native collagen, resulting in hydrolysed collagen peptides with lower molecular weight and increased solubility [25]. This process enhances gastrointestinal digestibility and facilitates absorption compared with native collagen [26].
Collagen supplements are widely available in various formulations, including powders, capsules, tablets, liquids, and gummies, allowing individuals to select products based on convenience and preference [27]. Regardless of the formulation, orally administered hydrolysed collagen is digested in the gastrointestinal tract into small peptides and amino acids, including hydroxyproline-containing di- and tripeptides [28]. These peptides have been detected in systemic circulation following oral administration. Nevertheless, their tissue distribution and in vivo biological activity remain incompletely understood [28].
Experimental and preclinical evidence suggests that collagen-derived peptides may exert biological activity beyond their role as amino acid precursors. Proposed mechanisms include stimulation of collagen and elastin synthesis, inhibition of collagen-degrading enzymes, and modulation of inflammatory pathways. However, most of these findings are derived from in vitro or animal studies, and their clinical relevance in humans remains to be fully elucidated [29, 30, 31].
This provides evidence of bioavailability beyond simple amino acid absorption. Preclinical studies further suggest that these peptides may reach the skin and interact with dermal fibroblasts, potentially stimulating extracellular matrix synthesis, including collagen, elastin, and hyaluronic acid. Additional experimental evidence implicates modulation of signalling pathways associated with tissue remodelling and oxidative stress regulation [32]. However, most mechanistic data originate from in vitro or animal models, and their relevance to clinically observed effects in humans remains unclear [28].
The aim of this narrative review was to summarise current evidence on the physiological role of collagen, age-related changes in collagen metabolism, and the effects and safety of collagen supplementation in middle-aged and older adults.
The objectives were:
A literature search was conducted using the following electronic databases: PubMed (MEDLINE), and Google Scholar. Additional relevant publications were identified through manual screening of reference lists of included studies and relevant reviews.
The literature search included publications published primarily between January 2010 and May 2026. Six earlier studies published between 1998 and 2009 were additionally included because they provided fundamental mechanistic information relevant to collagen metabolism and the biological rationale for collagen supplementation. The final literature search was conducted in May 2026.
The search strategy was developed using combinations of keywords related to collagen supplementation, connective tissue health, and age-related conditions. Boolean operators (AND/OR) were applied to combine search terms. The following search string was used:
(collagen supplementation OR hydrolysed collagen OR collagen peptides) AND (joint health OR musculoskeletal system OR osteoarthritis OR cardiovascular health OR metabolic syndrome OR obesity OR skin ageing OR skin health).
The search strategy was adapted according to the requirements of each database.
Studies were eligible for inclusion if they fulfilled the following criteria:
Inclusion criteria:
Exclusion criteria:
This narrative review included evidence from systematic reviews, randomised controlled trials (RCTs), cohort studies, observational studies, and case series. Experimental and mechanistic studies were considered only to support the biological rationale and proposed mechanisms of action of collagen supplementation.
The initial literature search identified 1724 records. After removal of duplicate publications and screening of titles and abstracts according to predefined eligibility criteria, 1662 records were excluded due to irrelevance, lack of full-text availability, non-English language, or overlapping study populations. Following full-text assessment, a total of 62 publications were included in the final qualitative synthesis.
Titles and abstracts were independently screened according to predefined inclusion and exclusion criteria. Full texts of potentially eligible publications were subsequently assessed for final inclusion. Any disagreements regarding study eligibility were resolved through discussion and consensus among the reviewers.
Collagen supplementation has gained increasing attention as a nutritional strategy with potential benefits across multiple physiological systems, including the musculoskeletal, metabolic, cardiovascular, and integumentary systems. Although preclinical studies frequently demonstrate broad biological activity, clinical evidence remains heterogeneous, with effects that appear most consistent for structural and connective tissue-related outcomes rather than for systemic metabolic disease endpoints.
Osteoarthritis (OA) is one of the most common age-related musculoskeletal disorders and represents a major area of interest in collagen supplementation research. Available evidence suggests that collagen derivatives may be associated with modest improvements in pain and selected aspects of physical function in individuals with OA [33, 34]. A 2024 meta-analysis of 35 randomised controlled trials involving more than 3,000 participants reported small-to-moderate beneficial effects of collagen supplementation on OA symptoms [33]. Earlier meta-analyses published in 2019 suggested that collagen supplementation may reduce pain intensity assessed using the Visual Analogue Scale (VAS), although improvements in functional outcomes measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were not consistently demonstrated [34]. A reduction in pain among individuals with osteoarthritis was also reported in a clinical study published in 2023 [35].
In contrast, a randomised controlled trial from 2025 evaluating combined undenatured type II collagen and hydrolysed collagen supplementation over 12 weeks did not demonstrate significant differences compared with placebo in pain intensity, functional outcomes, or rescue medication use [36].
A substantial proportion of clinical research has evaluated collagen supplementation as part of multimodal interventions, particularly in combination with resistance exercise or other nutritional components. In individuals with knee OA, a 2025 pilot study suggested that a combination of type II collagen, glucosamine, and chondroitin may improve patient-reported symptoms and quality of life, although objective functional outcomes showed limited changes [37]. Similarly, collagen peptides combined with calcium and vitamin D over 12 months were associated with improvements in selected bone parameters, including trabecular and cortical bone characteristics, as well as reductions in bone turnover markers in postmenopausal women with osteopenia [38].
Several studies have investigated collagen supplementation together with resistance training. In middle-aged untrained men, supplementation with specific bioactive collagen peptides combined with a 12-week resistance training program was associated with improvements in body composition and muscle strength compared with placebo [39]. Furthermore, clinical studies investigating collagen supplementation alongside resistance exercise suggest that this combination may promote tendon adaptations, including increases in patellar tendon cross-sectional area and improvements in the rate of force development [40, 41].
Similarly, in older men with sarcopenia, collagen peptide supplementation combined with resistance training was associated with greater increases in fat-free mass and muscle strength, as well as reductions in fat mass, compared with placebo [42].
Additional evidence from preclinical studies suggests that collagen peptides may influence connective tissue remodelling. In animal models, low-molecular-weight collagen peptides were associated with increased collagen deposition, angiogenesis, improved collagen fibre organisation, and modulation of inflammatory and degenerative processes following tendon and ligament injury [43]. However, these findings should be interpreted primarily as evidence supporting biological plausibility rather than direct confirmation of clinical efficacy in humans.
Another rapidly expanding area of research concerns the potential role of collagen supplementation in metabolic health and obesity-related outcomes. While preclinical studies frequently demonstrate broad multi-targeted metabolic effects, evidence from clinical studies in middle-aged and older adults remains limited and heterogeneous, highlighting a persistent gap between experimental findings and clinical outcomes.
Several mechanisms have been proposed to explain the potential metabolic effects of collagen-derived peptides. Experimental evidence suggests that collagen peptides may modulate appetite regulation, fatty acid oxidation, glucose metabolism, and gut microbiota composition [44–51]. However, these mechanistic findings have not yet been consistently translated into clinically meaningful effects in middle-aged and older adults.
Current evidence regarding the metabolic effects of collagen supplementation in middle-aged and older adults remains limited and inconclusive. One study reported potential improvements in selected metabolic parameters, including glycaemic control, insulin-related markers, and some cardiovascular risk indicators, following marine collagen peptide supplementation [52]. Conversely, a randomised controlled trial in adults with overweight or obesity using continuous glucose monitoring reported slight unfavorable changes in glycaemic variability, postprandial glucose exposure, fasting insulin concentrations, and insulin resistance after short-term collagen hydrolysate supplementation [53].
Overall, evidence regarding the metabolic effects of collagen supplementation in middle-aged and older adults remains limited and inconsistent. While preclinical studies suggest potential metabolic benefits, clinical trials are constrained by small sample sizes, short intervention periods, and study heterogeneity. Further long-term randomised controlled trials are needed to clarify the clinical relevance, optimal dosing, and potential mechanisms of action of collagen supplementation.
Collagen supplementation has been associated with modest beneficial effects on several cardiovascular risk markers. However, the available evidence remains heterogeneous, and the clinical significance of these findings has yet to be fully established.
Particularly promising findings have been reported in relation to vascular function and arterial stiffness [54-56]. Several clinical studies indicate that collagen supplementation may improve markers of arterial elasticity, including the cardio-ankle vascular index (CAVI) and pulse wave velocity (PWV). In individuals at elevated cardiovascular risk, collagen tripeptide supplementation reduced both the LDL/HDL ratio and CAVI values [54].
Similarly, supplementation with chicken-derived collagen hydrolysate and porcine collagen peptides significantly reduced PWV in subjects with mild hypertension and in older adults, respectively [55, 56]. These findings suggest that collagen peptides may play a supportive role in vascular health.
The mechanisms underlying these effects are not yet fully understood. Experimental studies in vitro and in animal models suggest that bioactive collagen-derived peptides may inhibit angiotensin-converting enzyme (ACE), thereby reducing angiotensin II production and promoting vasodilation [57].
Despite these encouraging findings, not all clinical studies have demonstrated beneficial cardiovascular effects. A recent randomised controlled trial published in 2025 found no significant changes in blood pressure, lipid profiles, markers of endothelial dysfunction, or inflammatory biomarkers following four weeks of collagen hydrolysate supplementation in adults with overweight or obesity. These findings suggest that the cardiovascular effects of collagen peptides may depend on factors such as intervention duration, collagen source, peptide composition, dosage, and population characteristics [58].
Collectively, current evidence suggests that collagen supplementation may be associated with changes in selected cardiovascular risk factors; however, the available data are insufficient to determine the clinical significance of these findings. Further research is needed to clarify the potential role of collagen peptides in cardiovascular health.
Skin ageing is associated with progressive changes in the dermal extracellular matrix, including reduced collagen content, decreased elasticity, wrinkle formation, and impaired hydration. Several randomised controlled trials have investigated the effects of collagen supplementation on skin-related outcomes in middle-aged and older adults. A placebo-controlled trial in middle-aged women reported that 12-week supplementation with hydrolysed marine collagen (1 g/day) improved selected skin parameters, including elasticity, hydration, and wrinkle-related measures [59]. Similar beneficial effects on skin quality have been observed in other randomised placebo-controlled trials involving middle-aged and older women following 8–12 weeks of collagen peptide supplementation [60, 61].
Preclinical studies have suggested that collagen-derived peptides, particularly hydroxyproline-containing dipeptides and tripeptides, may influence dermal fibroblast activity and are associated with increased expression of collagen, elastin, and hyaluronic acid, as well as modulation of inflammatory and oxidative stress pathways involved in skin ageing [62].
Collectively, the current body of evidence is derived primarily from short-term randomised controlled trials and preclinical studies, which are characterised by methodological heterogeneity and a lack of long-term follow-up. Across the evaluated outcomes, the evidence appears more consistent for connective tissues, including the skin, tendons, and articular cartilage, than for systemic metabolic outcomes, suggesting tissue-specific responsiveness to collagen-derived peptides. However, further well-designed studies are needed to establish the optimal peptide composition, dosing strategies, and long-term effects on skin health. Table 1 summarises the characteristics, main findings, and limitations of the studies included in this review.
Table 1. Characteristics, main findings, and limitations of studies investigating the effects of oral collagen supplementation on musculoskeletal, metabolic, cardiovascular, and skin health outcomes.
| Authors (Year) | Study design | Population | Sample size (patients/participants) | Collagen type and dose | Duration | Control | Main findings | Main limitations |
| Liang et al. (2024) [33] | Trial sequential meta-analysis of 35 RCTs | Patients with osteoarthritis (mean age 50-60) | 3,165 | Various collagen derivatives and doses | Variable; follow-up duration < 6 months | Placebo/active controls | Small-to-moderate improvements in osteoarthritis symptoms. | Considerable heterogeneity in collagen formulation, dose and study duration; potential risk of industry-related bias |
| García-Coronado et al. (2019) [34] | Meta-analysis of 5 RCTs | Patients with osteoarthritis, (mean age >50 years) | 519 | Various oral collagen supplements; dose 40 mg – 10 g per day | 10-48 weeks | Placebo | Significant reduction in VAS pain; no significant improvement in WOMAC functional score | Small number of studies; methodological heterogeneity |
| Chen et al. (2023) [35] | Randomised, double-blind, pilot trial | Adults with knee OA (45–75 years) | 160 | EC (5.81 g)+HC-II (2.0 g/d) / HC-II (2.0 g/d) + resistance training | 24 weeks | Placebo | Significant reduction in pain in both EC+HC-II and HC-II groups compared with placebo | Short intervention; small sample size; potential risk of industry-related bias |
| Yuenyongviwat et al. (2025) [36] | Randomised controlled trial | Patients with osteoarthritis (50–80 years) | 68 | Undenatured type II collagen (20 mg/d) + hydrolysed collagen (480 mg/d) | 12 weeks | Placebo | No significant improvements in pain, function or rescue medication use | Combined collagen formulation |
| Fladerer-Grollitsch et al. (2025) [37] | Randomised, double-blind, placebo-controlled pilot trial | Patients with osteoarthritis (mean age ~60 years) | 52 | Type II collagen + glucosamine + chondroitin (dose not reported) | 12 weeks | Placebo | Improved symptoms and quality of life; little effect on objective functional outcomes | Multicomponent intervention; potential risk of industry-related bias |
| Lampropoulou-Adamidou et al. (2022) [38] | Randomised controlled trial | Postmenopausal women with osteopenia | 51 | Collagen peptides (5 g/d) + calcium lactate (500 mg/d) + vitamin D (400 IU/d) | 12 months | Calcium + vitamin D | Improved bone microarchitecture and reduced bone turnover | Multicomponent intervention; risk of industry-related bias |
| Zdzieblik et al. (2021) [39] | Randomised controlled trial | Middle-aged untrained men | 97 | Bioactive collagen peptides (15 g/d) + resistance training | 12 weeks | Placebo (primary control); whey protein (active control) | Increased fat-free mass and muscle strength | Exercise may have contributed to observed effects; risk of industry-related bias |
| Nulty, Phelan & Erskine (2025) [40] | Randomised controlled trial | Middle-aged men | 41 | Hydrolysed collagen (30 g/d) + resistance training | 12 weeks | Placebo + resistance training | Greater increases in patellar tendon cross-sectional area and improved tendon mechanical properties following resistance training compared with placebo. | Male-only population; effects cannot be extrapolated to sedentary individuals or clinical populations. |
| Kuwaba et al. (2023) [41] | Randomised, double-blind crossover trial | Healthy middle-aged men | 19 | fish-derived CPs (5 g/d) | Collagen peptides; 33 days supplementation, 23-day washout, followed by another 33 days supplementation | Placebo | Reduced exercise-induced muscle soreness | Short-term outcomes only; Potential industry bias. |
| Zdzieblik et al. (2015) [42] | Randomised, double-blind, placebo-controlled trial | Elderly sarcopenic men (72.2 ± 4.7 years) | 53 | Specific bioactive collagen peptides (15 g/d) | 12 weeks + resistance training (3 sessions/week) | Placebo (silica) | CP supplementation combined with resistance training increased fat-free mass and muscle strength and reduced fat mass compared with placebo | Small sample size; elderly men with sarcopenia only; resistance training contributed to effects; collagen product-related industry involvement |
| Zhu et al. (2010) [52] | Randomised, double-blind, placebo-controlled trial | Older adults with type 2 diabetes mellitus and primary hypertension (mean age >60 years) | 150 | Marine collagen peptides (13g/d) | 3 months | Placebo | Marine collagen peptides were associated with improvements in glycaemic control, insulin-related parameters, and selected blood pressure measures | Short duration; limited information on collagen dose/formulation; specific population with metabolic diseases limits generalizability |
| Chavez-Alfaro et al. (2025) [53] | Randomised controlled trial | Adults with overweight/obesity (40-65 years) | 56 | Porcine collagen hydrolysate (10 g/d) | 4 weeks | Placebo | No improvement in glucose metabolism; slight deterioration in glycaemic variability | Short intervention |
| Tomosugi et al. (2017) [54] | Clinical trial | Adults at increased cardiovascular risk (aged 44-64 years) | 32 | Collagen tripeptides (16 g/d) | 6 months | None | Reduced LDL/HDL ratio and cardio-ankle vascular index | Industry-related author affiliations; lack of placebo control; small sample size. |
| Kouguchi et al. (2013) [55] | Randomised, placebo-controlled trial | Mild hypertension/high-normal blood pressure | 58 | Chicken collagen hydrolysate (2.8 g/d) | 2 weeks for pre-treatment observation, 12 weeks for treatment, 4 weeks for post-treatment observation | Placebo | CCH supplementation was associated with lower changes in brachial-ankle pulse wave velocity (baPWV), reduced blood pressure, and increased serum nitric oxide (NOx), suggesting potential beneficial effects on vascular function | Short intervention duration; relatively small sample size; population with elevated blood pressure limits generalizability; Potential industry bias, limited information on long-term clinical outcomes |
| Igase et al. (2018) [56] | Double-blind randomised trial | Healthy older adults (66-80 years) | 70 | Porcine collagen peptides (2.5 g/d) | 12 weeks | Placebo | Pork collagen peptide supplementation significantly reduced brachial-ankle pulse wave velocity (baPWV) compared with placebo, suggesting a potential improvement in arterial stiffness and possible vascular benefits | Short intervention period; relatively small sample size; one author affiliated with collagen peptide manufacturer |
| Chavez-Alfaro et al. (2025) [58] | Randomised controlled trial | Adults with overweight/obesity (40-75 years) | 56 | Porcine collagen hydrolysate (10 g/d) | 4 weeks | Placebo | No significant effects on blood pressure, endothelial function or inflammation | Short duration |
| Evans et al. (2021) [59] | Randomised, triple-blind, placebo-controlled, parallel-group trial | Healthy women aged 45–60 years with visible signs of skin ageing | 100 | Hydrolysed freshwater marine collagen (1 g/d) | 12 weeks | Placebo | improvements in skin elasticity, wrinkle parameters, hydration, and skin appearance compared with placebo | Short intervention period; only women included |
| Vleminckx et al. (2024) [60] | Randomised, double-blind, placebo-controlled trial | East Asian adults 40-65 years | 90 | Hydrolysed collagen (5 g/d) + vitamin C (80 mg/d) (CP); hydrolysed collagen (5 g/d) + vitamin C (80 mg/d) + hyaluronic acid (30 mg/d) (CPHA) | 16 weeks | Placebo (without collagen, vitamin C, or hyaluronic acid) | Collagen + vitamin C supplementation, with or without hyaluronic acid, was associated with improvements in dermis density, skin texture, and wrinkle severity. | Short intervention period; only women included; |
| Žmitek et al. (2024) [61] | Randomised, double-blind trial | Healthy middle-aged women 40 – 65 years | 90 | Collagen (5 g/d) + vitamin C (80 mg /d) ± hyaluronic acid (30 mg/d) | 16 weeks | Placebo | Improved skin density and texture | Multimodal intervention, Short intervention period; only women included, partial industry support. |
Abbreviations: baPWV, brachial–ankle pulse wave velocity; CCH, chicken collagen hydrolysate; CP, collagen peptides; CPHA, collagen peptides with vitamin C and hyaluronic acid; EC, essence of chicken; HC-II, hydrolysed type II collagen; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NOx, nitric oxide metabolites; OA, osteoarthritis; RCT, randomised controlled trial; VAS, Visual Analogue Scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.
Collagen is a fundamental structural component of the extracellular matrix, contributing to the mechanical integrity and biological function of multiple tissues, including skin, cartilage, bone, tendons, and blood vessels [5–7]. Ageing is associated with progressive alterations in collagen synthesis, organisation, cross-linking, and degradation, which contribute to functional decline across several organ systems [10–22]. These age-related changes provide the biological rationale for investigating collagen supplementation as a potential nutritional strategy to support connective tissue maintenance.
The findings of the present review suggest that the effects of collagen supplementation are not uniform across physiological systems. The most consistent findings have been reported for outcomes directly related to extracellular matrix function, including skin health, selected symptoms of osteoarthritis, and adaptations of musculoskeletal tissues, whereas evidence supporting systemic metabolic and cardiovascular benefits remains limited and heterogeneous.
A major challenge in interpreting the current literature is the considerable heterogeneity of collagen preparations investigated in clinical studies. Collagen supplements should therefore not be considered a uniform intervention, as they differ substantially in collagen type, source, manufacturing process, peptide composition, and molecular characteristics. Clinical trials have evaluated hydrolysed collagen peptides, collagen tripeptides, and undenatured type II collagen derived from marine, bovine, porcine, or chicken sources.
These preparations may differ substantially in their biological mechanisms of action. Hydrolysed collagen peptides may provide bioactive peptide fragments that modulate fibroblast activity and extracellular matrix-related processes, although these mechanisms are supported primarily by experimental studies [25, 32]. Undenatured type II collagen and hydrolysed collagen peptides should therefore be considered distinct interventions.
Consequently, pooling different collagen formulations into a single category may contribute to the variability observed between studies and limit the identification of the most effective preparation.
The source and molecular characteristics of collagen may further influence its biological activity. Experimental and mechanistic studies suggest that peptide size, molecular weight distribution, and bioavailability may affect peptide absorption and subsequent biological responses, although the clinical relevance of these differences remains insufficiently established [23–25]. However, relatively few clinical trials provide detailed characterisation of peptide composition or directly compare different collagen formulations. Therefore, it remains unclear whether differences in clinical outcomes reflect true differences between collagen products or rather differences in study populations, intervention protocols, and outcome measures.
Variation in supplementation protocols represents another important source of heterogeneity and may contribute to differences in reported effects. Clinical trials have used a wide range of collagen doses and intervention durations depending on the investigated outcome, collagen formulation, and study population. Intervention duration has varied substantially, ranging from several weeks [53, 58] to twelve months [38], which may be particularly relevant given that connective tissues differ in their remodelling rates and may require longer periods to demonstrate structural adaptations.
Dosing regimens have also varied considerably across studies. Trials evaluating skin-related outcomes have generally used lower doses, commonly around 1–5 g/day [59, 60 ,61], whereas studies investigating musculoskeletal outcomes, particularly in combination with resistance training, have frequently used higher doses ranging from approximately 5 to 30 g/day [39-42].
However, direct dose–response comparisons remain limited, and current evidence is insufficient to establish optimal dosing strategies for specific clinical applications. Dosage should therefore be interpreted together with collagen type, source, peptide composition, molecular weight distribution, and bioavailability.
Differences between study populations also complicate interpretation of the available evidence. Clinical trials have included healthy adults [41, 56, 59, 61], individuals with osteoarthritis [33–37], patients with sarcopenia [42], postmenopausal women with osteopenia [38], adults with overweight or obesity [53, 58], and patients with diabetes mellitus and/or hypertension [52, 54]. These populations differ in nutritional status, physical activity, inflammatory status, disease burden, and baseline tissue metabolism, which may influence the response to collagen supplementation. Future studies should therefore identify the populations most likely to benefit rather than assume uniform effects across all individuals.
The overall strength of evidence is additionally limited by methodological differences between studies. Many trials include relatively small sample sizes, short intervention periods, and heterogeneous outcome measures, which limits direct comparison between studies and contributes to inconsistent conclusions. In addition, relatively few investigations have evaluated long-term outcomes or clinically meaningful endpoints such as disease progression, functional independence, or quality of life. Another relevant consideration is transparency regarding commercial involvement. Several collagen supplementation studies included in this review reported commercial support, provision of study products by manufacturers, or involvement of industry-affiliated researchers [33, 35, 37-39, 41, 42, 54, 56, 61]. Although commercial support does not necessarily invalidate study findings, disclosure of funding sources and potential conflicts of interest remains essential when interpreting the available evidence.
From a clinical perspective, collagen supplementation should currently be considered a supportive nutritional intervention rather than an independent treatment for age-related diseases. Its potential value appears to depend on the specific population, collagen formulation, and treatment context. Current data provide the strongest support for potential benefits in connective tissue-related outcomes, whereas findings regarding broader metabolic and cardiovascular effects remain insufficient to justify clinical recommendations beyond established preventive strategies.
This review and the available evidence have several limitations. The literature search was limited to PubMed, MEDLINE, and Google Scholar and included only publications available in English; therefore, relevant studies indexed in other databases or published in other languages may have been missed.
The included studies differed substantially in design, sample size, population characteristics, collagen formulations, doses, intervention durations, control groups, and outcome measures. Many trials included relatively small samples and short intervention periods, while long-term clinical outcomes and long-term safety were rarely assessed.
Collagen supplementation was frequently evaluated as part of multimodal interventions, including resistance training [35, 39, 40, 42], calcium and vitamin D [38], glucosamine and chondroitin [37], and vitamin C with or without hyaluronic acid [60, 61]. Consequently, the independent contribution of collagen could not always be determined.
Several studies also reported commercial support, provision of study products by manufacturers, or involvement of industry-affiliated researchers [33, 35, 37–39, 41, 42, 54, 56, 61]. This should be considered when interpreting the findings.
These limitations restrict direct comparison between studies and limit the ability to determine the efficacy of specific collagen preparations, establish optimal dosing regimens, or formulate clinical recommendations for particular populations or conditions.
Ageing is associated with progressive changes in collagen synthesis, degradation, and tissue integrity across multiple tissues. The available evidence suggests that collagen supplementation may be associated with modest improvements in selected skin and musculoskeletal outcomes, particularly skin hydration and elasticity and osteoarthritis-related pain. However, the magnitude, consistency, durability, and clinical relevance of these effects remain uncertain. Evidence regarding metabolic and cardiovascular outcomes is limited and heterogeneous and does not support specific clinical recommendations. Collagen supplementation was generally well tolerated in the included studies, but most interventions were short-term and long-term safety remains insufficiently established. Further large-scale, long-term randomised controlled trials using well-characterised collagen preparations and clinically relevant outcome measures are required.
Conceptualization: Aleksandra Błoch, Natalia Rządzińska. Methodology: Aleksandra Pakulska, Kornelia Fimiarz. Formal analysis: Aleksandra Błoch, Natalia Rządzińska. Data collection: Aleksandra Kłosowicz, Maria Miller, Aleksandra Kamińska. Writing, original draft preparation: Aleksandra Pakulska, Aleksandra Kamińska, Maria Miller. Writing, review and editing: Kornelia Fimiarz, Aleksandra Kłosowicz. Supervision: Natalia Rządzińska, Aleksandra Błoch.
All authors have read and approved the final version of the manuscript.
This research received no external funding.
The authors declare no conflicts of interest.
Artificial intelligence tools were used for language editing and stylistic correction. The authors reviewed and approved the final text and remain responsible for its content.