Biovailability of Collagen

Collagen Science Update – June 2024 Edition

Bioavailability is the absorption of bioactive compounds, such as amino acids or bioactive peptides, into the body’s systematic circulation to exert their beneficial action (Larder et al., 2023). Collagen is the most abundant protein in humans, and its production is commonly known to decrease with age. Native collagen cannot be directly absorbed by the body in its original form. Orally ingested collagen is hydrolysed in the body’s intestinal tract prior to its absorption, and post-prandial absorption rates, bioavailability, and bioactivity are dependent on the molecular weight of the collagen being consumed (Steele, 2022). Topically applied collagen does not reach the deeper layers of the skin to effectively and lastingly restore collagen synthesis; therefore, the development of highly bioavailable nutritional collagen peptides (CPs) is essential for restoring the collagen biomatrix (Bolke et al., 2019). 

Research has demonstrated that CPs, produced via the hydrolysis of collagen, are broken down into amino acids and smaller peptides (i.e., dipeptides and tripeptides) and can reach the bloodstream and tissues, enhancing the bioavailability of collagen (Bolke et al., 2019; Steele, 2022; Devasia et al., 2024). Different forms of supplemental collagen can be utilized to target specific areas within the body based on the bioavailability of the type of collagen used and collagen supplement types may differ depending on their source materials and methods of preparation. Collagen hydrolysates (CHs) or specific collagen peptides (SCPs) are derived from cow, pig, or fish gelatin via a mixture of thermal treatment and enzymatic hydrolysis. Further purification results in collagen tripeptide (CTP) which mainly consists of types I and III collagen. Unhydrolyzed or undenatured collagen mainly contains type II collagen (Steele, 2022). CPs/CHs have low molecular weights (3 to 6 kDa) and are the product of industrially processed collagen. CPs/CHs have high bioactive peptide content and are therefore, highly bioavailable. Due to this, CPs/CHs are the choice collagen ingredient for the treatment of osteoarthritis (OA) in adults (Larder et al., 2023). 

Applications

Orally administered collagen is considered safe and highly biocompatible with positive therapeutic effects on pain management in OA, balancing blood sugars in type II diabetes, wound healing, skin aging, and post-exercise body composition and strength. Additional applications of collagen include its support in managing osteoporosis, hypertension, rheumatoid arthritis, tendinopathy, cellulite, atopic dermatitis, sarcopenia, and brittle nail syndrome (Steele, 2022). 

This edition highlights three recent publications that provide new insights on the influence of bioavailable collagen in skin and joint health, the use of bioavailable CPs in managing knee joint OA, as well as a thorough review on alternative bioavailable marine collagen sources.     

The Influence of Available Oral Collagen Supplementation on the Function of Joints and Skin

This comprehensive review article examined the role of oral collagen supplementation and its impact on skin and joint health. It assessed different sources of collagen, and the effects of the degree of hydrolysis on absorbability. The authors conducted a thorough literature search on Google Scholar and PubMed to explore various types of oral collagen supplements and their influence on health. Hydrolyzed collagen from bovine tissues was found to exhibit antihypertensive, antioxidant and antimicrobial properties. A plant-based supplement containing anthocyanin-rich rice bran and husk extract from purple glutinous rice (Oryza sativa L.) was found to significantly reduce collagen degradation through collagen-stimulating effects via matrix mellaproteinases-2 inhibition. Hydrolyzed collagen from porcine skin was observed to have lower molecular weight and therefore high bioavailability, antioxidant capabilities, anti-aging effects and Angiotensin-Converting Enzyme (ACE)-inhibitory potency. Collagen sourced from fish scale showed moisture absorption ability which can counteract skin aging and melanogenesis. From the scientific literature, it was noted that higher degrees of collagen hydrolysis resulted in lower molecular weights, increased water solubility, and increased bioavailability in the body. The results from these studies suggest that CPs can improve skin hydration, elasticity, barrier function and reduce wrinkles, with multiple clinical trials finding significant improvements in wrinkle measures and skin whitening with low-molecular-weight CPs. Many studies also reported improvements in pain relief, joint function and cartilage protection with native type II collagen and hydrolyzed collagen compounds in OA patients. The authors of this review conclude that oral collagen supplementation shows potential for improving skin and joint health by promoting collagen synthesis, but more investigation is required to guide clinical use.

Access to the study: https://apcz.umk.pl/JEHS/article/view/48419 

Reference: Kościołek, D., Urbaś, M., Kępczyk, M., Kościołek, A., Surowiecka, K., Misiak, J., Ojdana, M., Szalbot, K., Tokarski, M., & Marczak, N. (2024). The influence of available oral collagen supplementation on the function of joints and skin. Journal of Education, Health and Sport, 61:214–229. https://doi.org/10.12775/JEHS.2024.61.014 

Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability

This randomized, double-blind, active and placebo-controlled, five-arm clinical trial investigated the efficacy, safety, and tolerability of a high-functional bovine CP called “Type J” or “Wellnex” in managing knee joint OA in adults. Type J CP was developed with enhanced levels of active dipeptides, with a 30-fold increase in the active molecule content compared to existing conventional CPs, to exhibit a highly functional effect in managing joint health. The average molecular weight of Type J CP is < 1 kDa compared to the average molecular weight of < 5 kDa in conventional CPs. The active dipeptide content of Type J CPs is > 3,000 ppm, whereas the active dipeptide content in conventional CPs is < 100 ppm. The high content of the active dipeptides, proline-hydroxyproline and hydroxyproline-glycine, in Type J CP contributes to its enhanced efficacy compared to conventional CPs. A total of 115 adult participants between the ages of 30 and 65 years, diagnosed with OA, and with a moderately active lifestyle were enrolled. Participants were randomized to receive 2.5 g, 5 g, or 10 g of Type J CP, 10 g of a conventional CP or a placebo for three months. It was observed that 2.5 g of Type J CP showed significant improvements that were equivalent to 10 g of conventional CP based on Western Ontario McMaster Universities Arthritis Index (WOMAC) scores, Quality of Life (QoL), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels, and Magnetic Resonance Imaging Osteoarthritis Knee (MOAKs) scores in comparison to the placebo. Type J CP at 5 g and 10 g doses also showed significant improvements across all outcomes versus the placebo. Any adverse events reported during this study were ruled as not related to the investigational product by the investigator. These results suggest that Type J CP is an effective and safe nutraceutical therapy for managing knee OA symptoms and slowing cartilage degradation.

Access to the study: https://pubmed.ncbi.nlm.nih.gov/38235711/ 

Reference: Devasia, S., Joseph, J.T., P S, S., Koizumi, S., Clarke, L., V T, S., Kailas, A.P., & Madhavan, S. (2024). Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability. Cartilage, 19476035231221211. https://doi.org/10.1177/19476035231221211

A Review on Marine Collagen: Sources, Extraction Methods, Colloids Properties, and Food Applications

This review article explored alternative marine collagen sources and summarized the emerging trends in collagen production from sources such as fish, jellyfish, sea cucumbers, crustaceans, and sponges, as well as examined the significant variations in their physicochemical properties. From the literature, it was cited that fish collagen from skin, bone, cartilage, and scales surpasses collagen sourced from bovine or porcine sources in bioavailability, demonstrating greater absorption efficiency and quicker bloodstream circulation due to its low molecular weight. Traditional collagen extraction techniques using acetic acid and pepsin, as well as environmentally friendly methods such as ultrasonication, result in higher yields and stronger helical structures. The colloidal structure-forming properties of marine collagens includes their ability to form foam, film, gel, and emulsion, which are beneficial functions for formulating food products. Potential applications of marine collagen in the food and nutraceutical industry include its use as biodegradable film-forming materials, colloid stabilizers, foaming agents, and micro-encapsulating agents. The authors emphasize a growing interest in utilizing industrial by-products and optimizing collagen extraction from marine sources due to their environmentally friendly methods and applications in various food and nutraceutical products.

Access to the study: https://jlse.springeropen.com/articles/10.1186/s42825-024-00152-y 

Reference: Farooq, S., Ahmad, M.I., Zheng, S. Ali, U., Li, Y., Shixiu, C., & Zhang, H. (2024). A review on marine collagen: sources, extraction methods, colloids properties, and food applications. Collagen & Leather, 6(11). https://doi.org/10.1186/s42825-024-00152-y 

Bottom Line 

The importance of bioavailable collagen and its various benefits for human health have been highlighted. CPs and hydrolyzed collagen compounds have been shown to have high bioavailability due to their low molecular weights, allowing absorption into the bloodstream to reach targeted areas. The available research has demonstrated that bioavailable collagen supplementation can provide therapeutic effects for managing OA and improving skin health. However, additional research would help to further elucidate optimal sources, production methods, and clinical usage of bioavailable collagen products to fully leverage their effect.

References 

Bolke, L., Schlippe, G., Gerß, J., & Voss, W. (2019). A Collagen Supplement Improves Skin Hydration, Elasticity, Roughness, and Density: Results of a Randomized, Placebo-Controlled, Blind Study. Nutrients, 11(10):2494. https://doi.org/10.3390/nu11102494 

Devasia, S., Joseph, J.T., P S, S., Koizumi, S., Clarke, L., V T, S., Kailas, A.P., & Madhavan, S. (2024). Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability. Cartilage, 19476035231221211. https://doi.org/10.1177/19476035231221211

Larder, C.E., Iskandar, M.M., & Kubow, S. (2023). Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis. Medicines (Basel, Switzerland), 10(9):50. https://doi.org/10.3390/medicines10090050 

Steele, C. (2022). Collagen: a review of clinical use and efficacy. Nutritional Medicine Journal, 1(2):12–36.