Research

Joint Health

There are currently seven human studies regarding undenatured Type II Collagen and undenatured Proteoglycan and their efficacy in decreasing knee pain and improving mobility.

Main Study:

The figure below is from a randomized, double-blind, placebo-controlled study conducted in 2016 with 60 healthy subjects experiencing pain or rigidity in the knee. It shows a statistically significant improvement in knee pain in the test group that was given SCP-II compared to the placebo group. The test group that took SCP-II also showed a statistically greater improvement than the control group that took glucosamine.

In a reanalysis of this study done in 2020, the data was differentiated by “knee with stronger pain” and “contralateral knee” rather than right knee and left knee. This reanalysis would show more accurate results because it was identified that the results of the previous study were greatly influenced by the right and left knee condition at baseline, which were substantially different between the three groups (placebo, glucosamine, SCP-II). While the previous study showed only improvement in VAS pain score in the left knee for the SCP-II group, the reanalysis showed that at 6 weeks, the VAS pain score for both the knee with stronger pain and the contralateral knee significantly decreased. At 6 weeks, the glucosamine group and placebo group showed no significant differences.

Additional Studies:

• In a 16 week study with healthy subjects experiencing knee discomfort (25 in the test group, 25 in the placebo group), those that were given 10mg of Salmon Proteoglycan showed significant improvement in pain levels when walking compared to the placebo group. Subjects that were 50 years and older also experienced significant improvement in knee pain when doing exercises that required bending and extending the knee. (Kuriyama et al. 2021).

• In a 16 week study with healthy subjects experiencing knee discomfort (25 in the test group, 25 in the placebo group), those that were given 10mg of Salmon Undenatured Collagen showed significant improvement in pain levels when walking compared to the placebo group. Subjects that were 50 years and older also experienced significant improvement in knee pain when doing exercises that required bending and extending the knee. (Kuriyama et al. 2023).

• In a 12 week study with 36 healthy subjects experiencing knee discomfort, those that were given 10mg Salmon Proteoglycan showed significant improvement in pain levels when going up and down stairs starting at 8 weeks, as well as an improvement in knee extension as early as 4 weeks when compared to the placebo (Najima et al. 2016).

• In a 12 week study with 66 healthy subjects experiencing knee discomfort, those that were given 5mg Salmon Proteoglycan showed significant decrease in knee discomfort at 4 weeks of intake compared to the Placebo. CRP levels also showed a declining trend that corresponded to the changes in discomfort levels measure by VAS score (Kuriyama et al. 2017).

• In a 16 week study, 55 healthy subjects with knee discomfort were given either 10mg Salmon Proteoglycan or a Placebo and biomarkers for cartilage metabolism was measured. In subjects experiencing high levels of pain and constant pain in the knee, the biomarker for Type II Collagen degradation significantly decreased in the test group compared to the placebo group. Therefore, proteoglycan may have a protective effect on cartilage metabolism in subjects with severe or constant knee pain by decreasing the amount of Type II Collagen degradation (Tomonaga et al. 2017).

• Undenatured Type II Collagen from chicken cartilage given to 55 healthy volunteers showed significant improvement in range of bend and stretch of joints at 120 days of treatment (Lugo et al. 2013).

• Undenatured Type II Collagen from chicken cartilage significantly reduced knee pain in 191 individuals with osteoarthritis when compared to the placebo group. Type II Collagen also had a greater effect than individuals taking glucosamine + chondroitin at 180 days of treatment. Glucosamine + chondroitin supplementation failed to have a statistically significant improvement when compared to the placebo group (Lugo et al 2016).

• Non-human studies have shown the mechanism of action of undenatured Type II Collagen can be attributed to its ability to initiate the production of two important anti-inflammatory factors (IL-10 and TGF-β).

• Non-human studies have shown Proteoglycan reduces the production of matrix metalloproteinase (an enzyme that contributes to the degradation of cartilage), as well as have immunomodulatory, anti-inflammatory, and wound healing effects.

Mechanism of Action

One of the most common forms of arthritis is Rheumatoid arthritis (RA), which is an autoimmune disease that causes chronic inflammation in the joints. Animal studies have shown that oral administration of undenatured Type II Collagen and undenatured Proteoglycan are able to reduce the amount of inflammatory cytokines released in mice with collagen-induced arthritis.

The mechanism of action is believed to be the active site on undenatured Type II Collagen, which is an epitope, and the active site on undenatured Proteoglycan, which is its terminal C-site. These active sites are recognized by the body when ingested, and work on regulatory T-cells and Th17 cells to inhibit an exaggerated immune response by the body that causes the release of inflammatory cytokines and chemokines in the joints.

It is important to note that denatured Type II Collagen and denatured Proteoglycan will not have this same effect because the active sites will not be intact in the denatured form.

Skin Health

Main Study:

In a randomized, double-blind, placebo-controlled study with 19 subjects, a dose of 5mg/day of proteoglycan was administered for 2 weeks. The results of the study showed a significant decrease in wrinkles, pores, blotches, and improvement in skin elasticity and looseness in the test group.

The results below from the study show that those who took salmon proteoglycan had a significant reduction in the number of wrinkles underneath the eyes compared to the placebo group (4A) and the number of conspicuous pores and darkened pores were also significantly reduced from baseline (4B). In the group that ingested salmon proteoglycan, the number of blotches in the skin showed significant change in contrast to the placebo group (4C).

In the same study, analysis of skin looseness confirmed that salmon proteoglycan improved the elasticity of skin. The smaller the gap between the red circle (drawn when face is turned to the front) and the blue circle (drawn when lying on their face) showed a greater improvement in skin looseness.