Introduction
This is a clinical study review of
PMC10102402 (Collagen supplementation in skin and orthopedic diseases).
In recent decades, advancements in science, healthcare, and nutrition have significantly increased human life expectancy. However, this extended longevity is often accompanied by age-related conditions, particularly affecting the skin and musculoskeletal system. Collagen, a primary structural protein in the body, plays a pivotal role in maintaining the integrity and functionality of skin, bones, and joints. This review aims to elucidate the benefits of collagen supplementation in managing and potentially mitigating various skin and orthopedic diseases.
Understanding Collagen
Structure and Function
Collagen is a fundamental component of the extracellular matrix (ECM) in the dermis and articular cartilage. It influences the body's mechanical, organizational, and tissue formation properties. Approximately 25%–35% of the total protein mass in mammals is collagen, with over 29 types identified to date. In humans, types I, II, and III comprise 80%–90% of the total collagen content. Type I is predominant in the skin, contributing about 80%, while type II is mainly found in cartilage.
The collagen molecule is characterized by a triple-helix structure formed by three polypeptide alpha chains. This unique structure is crucial for the protein's stability and functionality. The repetitive [Gly – X–Y]n sequence, where X and Y are often proline and hydroxyproline, respectively, is a hallmark of collagen, providing it with remarkable tensile strength and resilience.
Sources and Production
Collagen used in supplements is primarily extracted from industrial by-products such as bones, cartilage, tendons, and skin of cattle, pigs, chickens, fish, or other marine organisms. These sources undergo hydrolysis to produce bioactive peptides with varying molecular weights, typically ranging from 0.3 to 8 kDa. Hydrolyzed collagen is favored for its high digestibility and bioavailability, making it a potent nutraceutical product.
Digestion and Absorption
Once ingested, collagen is broken down in the gastrointestinal tract into dipeptides, tripeptides, and free amino acids, which are absorbed in the small intestine. The presence of proline and hydroxyproline enhances the bioactivity of these peptides, as they resist proteolytic degradation, ensuring their availability for various metabolic processes.
Collagen and Skin Health
The Aging Process and Skin
The skin is the largest organ in the human body, acting as a barrier against external environmental factors. Collagen, elastin, and hyaluronic acid are critical in maintaining skin structure and hydration. However, intrinsic aging and exposure to external factors like solar radiation, pollution, and poor nutrition lead to a decline in collagen synthesis, resulting in reduced skin elasticity, increased wrinkle formation, and skin dryness.
Clinical Evidence on Collagen Supplementation
Numerous clinical studies have investigated the impact of collagen supplementation on skin health. Table 1 summarizes key studies demonstrating hydrolyzed collagen's effectiveness in improving skin attributes such as elasticity, hydration, and wrinkle reduction.
Collagen Source |
Design |
Population |
Duration |
Dose/Day |
Result |
Fish (Pangasius hypophthalmus) |
T-RCT |
Women, 45–60 years (45) |
12 weeks |
10 g |
Decrease in face wrinkle score; Increase in skin elasticity, hydration, shine, and firmness |
Dipeptides (Pro-Hyp, Hyp-Gly) |
D-RCT |
Chinese healthy women, 37–48 years (56) |
8 weeks |
2.5 g |
Increase in skin hydration and facial skin elasticity; Decrease in facial skin roughness |
Low-CP and High-CP |
D-RCT |
Chinese women, 35–55 years (85) |
8 weeks |
5 g |
Increase in skin moisture; Decrease in wrinkles area and roughness; High-CP also decreased number and depth of wrinkles |
Tripeptide form |
S-RCT |
Korean women and men, 30–48 years (32) |
12 weeks |
3 g |
Increase in stratum corneum hydration and skin elasticity; No change in TEWL and skin erythema |
Fish (Peptan F) and Porcine (Peptan P) |
D-RCT |
Japanese women, 40–59 years (33) |
8 weeks |
10 g |
Increase in skin hydration |
Swine-origin (VERISOL®) |
D-RCT |
Women, 35–55 years (69) |
8 weeks |
2.5–5 g |
Increase in skin elasticity; No significant difference in skin moisture, water evaporation, and smoothness between dosages |
Tripeptides (Gly-Pro-Hyp) |
D-RCT |
Women, 40–60 years (53) |
12 weeks |
1 g |
Increase in hydration, skin elasticity, and decrease in wrinkle depth |
Fish scales (Nitta Gelatin Inc., India) |
D-RCT |
Healthy women, 40–51 years (71) |
12 weeks |
3 g |
Increase in skin moisture and elasticity; Decrease in roughness |
Mechanisms of Action
The beneficial effects of hydrolyzed collagen on the skin are attributed to its dual-action mechanism. Firstly, the amino acids provided by collagen supplementation support the synthesis of endogenous collagen and elastin fibers. Secondly, bioactive peptides bind to fibroblast membrane receptors, stimulating the production of new collagen, elastin, and hyaluronic acid.
Histological studies support these findings, showing improved skin structure, reduced solar elastosis, and better-organized collagen fibers following collagen supplementation. For instance, Czakja et al. demonstrated enhancements in skin histology with hydrolyzed fish collagen. At the same time, Evans et al. observed significant improvements in skin elasticity, hydration, and wrinkle reduction in a randomized clinical trial involving women aged 45–60.
Systematic Reviews and Meta-Analyses
Systematic reviews and meta-analyses further corroborate the positive effects of collagen supplementation on skin health. Choi et al. and Barati et al. independently reviewed multiple randomized clinical trials, concluding that collagen supplements increase skin elasticity, hydration, and density while enhancing wound healing and protective functions against aging. However, these reviews also highlight the need for more extensive, standardized studies to confirm these benefits.
Collagen and Orthopedic Health
The Role of Collagen in Bone and Joint Health
Collagen is a key component of the ECM in bones and cartilage, contributing to the structural integrity and function of the skeletal system. Type II collagen is predominant in cartilage, forming a fibrillar network essential for joint mobility and resilience. Aging, strenuous physical activity and other factors such as trauma and hormonal changes can lead to collagen degradation, resulting in conditions like osteoarthritis and osteoporosis.
Clinical Evidence on Collagen Supplementation
Clinical studies have shown that collagen supplementation can improve various aspects of bone and joint health. Collagen peptides have been found to increase bone strength, density, and mass and improve joint stiffness, mobility, and functionality. Table 2 provides an overview of relevant animal model studies assessing the effects of hydrolyzed collagen on orthopedic health.
Collagen Source |
Animal Model |
Duration |
Dose/Day |
Result |
Type I-H |
Male C57BL/6J mice (OA) |
12 weeks |
Standard feed plus Type I–H bovine (200 Da), 3.8 mg or 38 mg |
Increase in cartilage area, chondrocytes, proteoglycan matrix; Decrease in apoptosis |
Mechanisms of Action
The orthopedic benefits of hydrolyzed collagen are primarily due to its bioactive peptides, which stimulate chondrocytes and osteoblasts, enhancing the synthesis of ECM components. Furthermore, collagen peptides can modulate inflammatory responses, reducing joint pain and improving mobility.
Systematic Reviews and Meta-Analyses
Recent reviews and meta-analyses have consistently reported favorable outcomes with collagen supplementation in managing orthopedic conditions. These studies emphasize collagen's role in improving bone density and joint functionality and reducing pain, particularly in individuals with age-related bone loss or high physical stress on joints.
Practical Considerations and Future Directions
Dosage and Duration
The optimal dosage and duration of collagen supplementation for skin and orthopedic benefits vary across studies. Most clinical trials have used doses ranging from 1 to 10 grams per day over 8 to 12 weeks. While these studies demonstrate significant improvements, long-term effects and the sustainability of these benefits post-supplementation remain active research areas.
Safety and Efficacy
Collagen supplements are generally considered safe, and no severe adverse effects have been reported in clinical trials. However, individuals with allergies to specific animal sources should exercise caution. Additionally, the variability in collagen processing methods and peptide profiles underscores the need for standardized products to ensure consistent therapeutic outcomes.
Conclusion
Collagen supplementation is a promising intervention for managing skin and orthopedic diseases. It significantly improves skin elasticity, hydration, wrinkle reduction, bone density, and joint functionality. Despite the encouraging evidence, further large-scale, long-term studies are essential to establish standardized guidelines for collagen use in clinical practice.
By understanding the multifaceted roles of collagen in the human body, healthcare professionals and patients can better appreciate its potential as a nutraceutical product for promoting skin and musculoskeletal health. As research continues to evolve, collagen supplementation may become a cornerstone in managing age-related conditions, enhancing the quality of life for individuals worldwide.