Collagen constitutes one-third of the total protein in humans and is the most abundant form of structural protein in the body. Collagen has a structure that is similar to a rope. The collagen triple helix is made up of three chains that spiral around one another. These constituent parts combine to form collagen fibrils, which are incredibly strong and tensile. The primary role of collagen is to maintain connective tissue health and mechanical properties of the skin. As collagen is the principal component of the extracellular matrix, it is essential for the strength, regulation, and regeneration of this tissue [1, 2].
Three amino acids, glycine, proline, and hydroxyproline, are found in high concentrations in collagen, giving it its distinctive triple-helix shape. Because of this, collagen is hydrolyzed enzymatically, breaking down into smaller bioactive peptides (the main supplement form of collagen) that are easily absorbed in the digestive system before entering circulation. Due to hydrolysis, collagen peptides do not possess the gelling properties of gelatine and are soluble in cold water. Bovine, porcine, marine, and poultry hydrolyzed collagen are currently the sources of collagen peptides .
Health Benefits of Collagen
A lifetime of permanent adaptation and acclimatization of an organism is made possible by healthy skin, which acts as an active interface between the internal and exterior surroundings of the body. Intrinsic aging, irradiation, intake of an unbalanced diet, and stress-related micronutrient deficiencies are the variables that accelerate the aging process of the skin, which results in an age-dependent loss of collagen in the skin .
The physiological aging of the skin caused by a decrease in collagen synthesis is influenced by both internal and external factors. It has been established that the collagen content of young and healthy skin exceeds 75%. Collagen fibers are synthesized primarily by the fibroblasts in the deeper layers of the skin. As such, rejuvenation of the biomatrix can be effectively improved only through a supply of sufficient nutrients via the blood stream. In mature skin, collagen production decreases and the biomatrix of the skin begins to collapse when the collagen scaffold loses its strength and stability. This process can be accelerated by factors like sunlight, smoking, pollution, excessive alcohol usage, and nutrient insufficiency. After that, the elasticity is reduced, and lines and wrinkles start to appear. The skin becomes thinner and drier as a result of the loss of collagen . Aging-related decreases in stratum corneum hydration, impairment of sebaceous and sweat glands, and increases in transepidermal water loss (TEWL) have also been reported. Such changes impair skin’s barrier function and result in dry skin, and dry, thin skin is prone to damage caused by friction .
Collagen is a constituent protein of the epidermis, ligaments, tendons, bones, and cartilage and is the main component of the extracellular matrix. The extracellular matrix retains water and supports a smooth, firm, and strong skin. Collagen fibers in the epidermis are implicated in skin elasticity. With aging, the skin’s collagen metabolism is noticeably diminished [1, 3]. Consuming collagen peptides can increase collagen synthesis, however their molecular sizes and amino acid composition vary greatly. The bovine collagen peptides are characterized by a high homogeneity of the amino acid profile with the human collagen protein . When oral collagen peptides are ingested, dipeptides (e.g., prolyl-hydroxyproline and hydroxyprolyl-glycine) and tripeptides move into the blood, and free amino acids are absorbed. Peptides containing hydroxyproline move into the blood particularly easily and remain in the blood for a long time. Such hydroxyproline-containing peptides stimulate the growth of skin fibroblasts and increase the production of hyaluronic acid, suggesting that these peptides are the active ingredients of the supplements that improve stratum corneum hydration and skin elasticity. The actions of these peptides are characteristic of collagen peptides because prolyl-hydroxyproline and hydroxyprolyl-glycine are not produced from commonly consumed proteins . A high bioavailability as assured by the specific digestion of the oligopeptides to the even shorter bioactive di- and tripeptides formed in the gastrointestinal tract provides the skin with the specific collagen I and III protein amino acid pattern required to sustain a sufficient synthesis of the decisive component of the skin biomatrix. The collagen structure also requires specific cofactors such as vitamin C which is necessary for collagen synthesis as well as antioxidants that protect the protein from oxidation .
Collagen supplements can improve skin hydration, elasticity, and dermal collagen density, according to a systematic review of the dermatological uses of oral collagen supplementation. Eleven studies with a total of 805 patients suggest that administration of collagen peptides can positively impact various skin conditions and skin aging. Supplementing with collagen was safe with no reported adverse effects .
Proksch et al. found that after taking 2.5 g of collagen per day for 56 days, there was a substantial decrease in eye wrinkle volume along with an increase of procollagen type I and elastin. Furthermore, it was demonstrated by Schunck et al. the intake of 2.5 g collagen peptides over a period of 180 days resulted in a statistically significant reduction in the amount of cellulite and skin waviness on the thighs .
Joint Pain Relief
Collagen contributes ~ 65–80% dry weight of tendons, with collagen crosslinks aiding the tendon structure to endure resistance from high-impact stresses and shear forces. Collagen is therefore essential for preserving tendon health and reducing the risk of injury in sports . Collagen hydrolyzates, which are processed and pre-digested collagen compounds, are offered as collagen capsules at pharmacies and health food stores. Different processing and manufacturing methods to make collagen hydrolyzate can yield different products, with differences in amino acid content and peptide sequences that vary in molecular weight. The possibility of transport to other parts of the body, such joints, may be higher for lower molecular weight peptides because they may be more readily absorbed in the small intestine .
The most prevalent protein in intervertebral discs and articular cartilage is type II collagen. There have been suggestions that oral collagen supplementation may enhance cartilage regeneration since type II collagen is the major protein in cartilage. Unfortunately, there is still no definitive evidence to support this. Based on the level of hydrolysis, various collagen formulations have been created, with undenatured collagen and hydrolyzed collagen being the most popular .
Hydrolyzed collagen is a form of collagen that is also referred to as collagen hydrolyzate. Collagen hydrolyzate and gelatin may be the same in terms of amino acid composition, but they possess different chemical properties. Collagen is a natural protein with a molecular weight of about 300 kDa. To improve absorption, collagen hydrolyzates are processed intensively to fragment the large collagen molecules into smaller ones. In order to create hydrolyzed collagen, native collagen undergoes denaturation followed by a hydrolysis process, resulting in very low molecular mass (3–6 kDa) collagen peptides, compared to native collagen size (285–300 kDa). Collagen hydrolyzates can be produced using a variety of processing and post-processing techniques, resulting in a variety of products with various collagen peptide sequences and molecular weights. These differences can potentially impact biological function in terms of regulating joint inflammation and effect on subchondral bone. Furthermore, lower molecular weight collagen peptides may be more easily absorbed in the small intestine, theoretically increasing the possibility that they will reach other parts of the body, such as joints .
In all five investigations, collagen peptide supplementation (COL) was shown to have positive benefits on joint pain, joint function, length of pain-free intense activity, and need for alternative therapies, particularly when combined with an exercise rehabilitation program. Both Clark and colleagues (2008) (10 g/day COL) and Zdzieblik et al. (2017) (5 g/day COL) observed that COL led to a decrease in activity-related joint discomfort and use of alternative therapies to manage pain. Interestingly, even though Zdzieblik et al. (2017) supplemented for 12 weeks, it was still effective in alleviating joint symptoms. Contrarily, Clark and colleagues (2008) found no statistically significant improvement until the final visit at 24 weeks, suggesting that it might take around 3 months for the advantages of COL to be felt. These results also suggest that 5 g/day COL may be as effective as 10 g/day COL in alleviating pain during activity for athletes, in the absence of a degenerative joint disease .
Collagen hydrolyzates were used as a dietary supplement in 147 healthy athletes with activity-related joint discomfort who were physically fit, active, and free of signs of joint disease during a 24-week clinical research conducted by Clark and colleagues. The experimental group (n = 73) received 25 mL of a liquid formulation of 10 g of collagen hydrolyzates. The placebo group (n = 74) received 25 mL of liquid xanthan. The primary measured outcome was a change in the visual analog scales (assessed by a physician) from baseline during the study phase in relation to pain, mobility, and inflammation. The team investigated joint pain at rest and when walking, standing, carrying objects, and lifting. The healthy population utilized in this clinical trial exhibited improvement in joint pain and discomfort when given an oral supplement containing collagen hydrolyzates. Despite the small sample size and limitations of the study, the findings revealed that athletes perceived a benefit from taking collagen hydrolyzates .
Another clinical trial used a randomized double-blind, controlled study design and recruited 250 subjects with primary knee osteoarthritis (OA) to assess the efficacy of a collagen hydrolyzate supplementation on OA pain and function. For six months, the patients received 10 g of collagen hydrolyzate every day. According to visual analog scales and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscales, the authors found a significant improvement in knee joint function and pain. The subjects who consumed the least meat protein in their diets and had the worst joint degeneration appeared to benefit the most. The study concluded that collagen hydrolyzates are safe and effective and warrant further consideration as a functional food ingredient .
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