When people exhaust the possibilities of exercise, physical therapies, and over-the-counter medications to support they often turn to nutritional supplements.
Glucosamine sulfate, chondroitin sulfate, hyaluronic acid, and methylsulfonylmethane (MSM) have been very popular supplement options. But there’s another important dietary supplement ingredient that has been shown in a variety of studies to support joint health.
Collagen II (aka chicken-sternal cartilage) was discovered in 1969 and has a long history of use in veterinary medicine for supporting joint health in animals. It finally attracted the attention of researchers and clinicians in recent years looking for new ways to support joint health over time. One of several different subtypes of present in the human body, collagen II is a major component of joint tissue, where it interacts with other molecules to form the structural scaffold for the extracellular matrix of joint cartilage.
The following up-to-date review of the literature related to joint cartilage physiology and collagen II supplementation shows how this unique molecule might be the key to supporting greater freedom and movement for many of your patients.
JOINT CARTILAGE STRUCTURE
Joint cartilage is a specialized form of connective tissue. Unlike most tissues in the body, joint cartilage contains no nerves, blood vessels, or lymphatics. It’s composed of a single type of specialized cells known as chondrocytes.
Chondrocytes are metabolically active cells that are influenced by growth factors, mechanical forces, hydrostatic pressure, and other signals. These forces affect the ability of chondrocytes to create and repair the extracellular matrix that surrounds them. But despite being the only type of cell in joint cartilage, chondrocytes make up only 1 percent to 3 percent of the joint cartilage volume—the remainder is the extensive extracellular matrix.
Chondrocytes have a limited capacity to replicate, which compromises the ability of cartilage to heal in response to injury. The survival of chondrocytes and the health of joint cartilage rely on an optimal microenvironment from the extracellular matrix.
This extracellular matrix is a vast network of fibrils, proteoglycans, other non-collagenous proteins, lipids, phospholipids, and hyaluronic acid. As much as 80 percent of the extracellular matrix consists of water, which is bound by large glycosaminoglycan molecules called aggrecans.
COLLAGEN II STRUCTURE
The structural backbone of the extracellular matrix consists of collagen fibrils—which are composed mainly of collagen II. Consequently, collagen II is the primary type of collagen in joint cartilage.
Collagen II consists of three polypeptide chains that are identical to one another. Known as alpha chains, these polypeptides twist into a triple helix. The helical structure is stabilized by cross-links between glycine, proline, hydroxyproline, lysine, and aspartate along the polypeptide chains.
CARTILAGE REMODELING
Collagen II and other collagen molecules are in a dynamic state of flux, participating in the ongoing turnover of the entire extracellular matrix. Whereas chondrocytes coordinate collagen synthesis, other forces coordinate its breakdown.
Under physiologic conditions, matrix metalloproteinases (MMPs) degrade , releasing cartilage degradation products into circulation. One of those degradation products, which can be detected in the urine, is C-terminal cross-linking telopeptide of type II collagen (CTX-II).
Cytokines such as interleukin I and TNF-alpha have been found to stimulate the activity of MMPs, accelerate collagen degradation, and increase urinary CTX-II levels. Other molecules that influence the health of cartilage include advanced glycation end products (AGEs). Collagens are long-lived proteins that can be modified by the process of glycation. When AGEs cross-link collagen molecules, the joint cartilage becomes increasingly stiff.
COLLAGEN II AS A DIETARY SUPPLEMENT
There are two broad categories of collagen II in dietary supplements: undenatured and hydrolyzed. Both of these forms of oral collagen II are likely to support joint health, but possibly by different mechanisms.
Undenatured type II collagen (UC-II) has the most scientific research. It’s been extensively studied for joint health support in both animals and humans. UC-II is derived from sternal chicken cartilage and is prepared by a proprietary process to maintain its bioactivity.
The supplement label for a product containing UC-II might list standardized chicken cartilage, standardized chicken collagen, standardized type II collagen complex, or natural collagen concentrate. The label will also state how much UC-II the product provides. Most supplements contain 40 mg of standardized collagen II (providing 10 mg of UC-II) per serving.
Hydrolyzed type II collagen is a form of collagen that has been reduced to small peptides. It’s not standardized and can be derived from beef, chicken, or marine cartilage. Hydrolyzed collagen can be found in dietary supplements and functional foods. The label might list bovine collagen, marine collagen, hydrolyzed chicken cartilage, hydrolyzed collagen type II, or BioCell collagen. Hydrolyzed collagen is often provided in amounts of 400 mg or more per serving.
MECHANISMS OF ORAL COLLAGEN II
One theory why oral collagen II (including both UC-II and hydrolyzed collagen II) supports joint health is that it provides the perfect complement of amino acids and peptides needed for cartilage remodeling.
Another theory is that oral collagen II supports a healthy immune response. Researchers have found that undenatured collagen II interacts with gut-associated lymphoid tissue to influence signaling that supports the healthy activity of killer T cells and regulatory T cells. This mechanism has been found to support healthy in people who experience joint problems associated with changes in immune function.
However, the interaction between collagen II and has only been demonstrated with the standardized form of UC-II—not with hydrolyzed collagen II. It has also been suggested that lower daily intakes of UC-II may be more effective at supporting healthy immune function than higher intakes.
COLLAGEN II STUDIES IN ANIMALS
Collagen II supplementation’s ability to support has been studied in humans, dogs, and horses—all of whom experience changes in joint function with age.
In dogs, collagen II (taken at 40 mg per day for 90 days) reduced discomfort upon limb manipulation and decreased lameness after physical exertion. However, the effect of collagen II was only maintained during the trial period and waned when supplementation was discontinued.
In horses, collagen II supplementation was compared with glucosamine and chondroitin supplementation, as well as placebo. Collagen II (taken at 480 mg or 640 mg per day) was found to be more useful for supporting joint health than the combination of glucosamine and chondroitin.
COLLAGEN II STUDIES IN HUMANS
In humans, collagen II supplementation has been evaluated in the context of joint health changes associated with exercise, aging, and immune function. Studies conducted in the 1990s explored the role of collagen II supplementation in joint health associated with immune function. Four randomized, controlled trials showed tendencies toward improvement with collagen II supplementation, but only one study reported statistically significant results. The intake of collagen II in these studies was low (in the range of 250 mcg per day).
Studies in more recent years have shifted attention to the effect of collagen II on joint discomfort associated with exercise and activity. These studies utilized higher daily intakes of collagen II than the previous studies. Participants took 40 mg of collagen II per day (providing varying amounts of UC-II) on an empty stomach each evening. One study that followed the 40-mg-per day protocol found that UC-II improved joint discomfort associated with strenuous exercise. Two other trials found that UC-II supported healthy physical function and flexibility of joints, and was more effective than a combination of glucosamine and chondroitin.
SAFETY OF COLLAGEN II
Although most studies in animals and humans have found that collagen II is well tolerated, without adverse effects, there may be a subset of people in which this is not the case.
Anecdotal reports suggest that UC-II might worsen joint health in a small percentage of people who experience joint discomfort associated with changes in immune function.
In these few reported cases, discontinuing UC-II supplementation resolved the problem and didn’t result in any long-term adverse effects. Further research is needed to determine whether hydrolyzed collagen II is a better option in this subset of people.
SUGGESTED USE
As the studies mentioned above show, undenatured collagen II is most commonly recommended at an intake of 40 mg of standardized chicken collagen per day, providing 10 mg of UC-II. It’s best taken on an empty stomach, and most study protocols recommend taking it before bed.
In contrast to undenatured collagen II, hydrolyzed collagen II can be taken in larger quantities, ranging from 400 mg to 1,000 mg per day. Because it provides small peptides and amino acids, it’s best taken with food.
Both forms of collagen II can be taken alone or in combination with other dietary supplement ingredients. Synergistic formulas might combine collagen II with hyaluronic acid, methylsulfonylmethane (MSM), glucosamine, chondroitin, natural eggshell membrane, vitamin C, turmeric, or other natural compounds that support joint health.