May 2025 Issue

CPE Monthly: Potential Therapeutic Benefits of Collagen Supplements
By Danielle VenHuizen, RDN
Today’s Dietitian
Vol. 27 No. 5 P. 36

Take this course and earn 2 CEUs on our Continuing Education Learning Library

Collagen has become increasingly popular as a dietary supplement. Often sold as a cream-colored, slightly granular powder, collagen’s uses range from purely cosmetic to therapeutic. Many studies have sought to investigate its potential role in areas such as joint pain, bone mineralization, wound healing, and skin elasticity. It’s even been studied for its potential benefit in type 2 diabetes and CVD.

In response to many favorable studies, the supplement market is booming; Americans spent an estimated $122 million on collagen supplements in 2018.1 The global collagen market was estimated at $3.71 billion in 2016, with expected growth to $6.63 billion by 2025.2 Due to its growing popularity, it’s important that RDs understand collagen’s role in human health and under what circumstances its use might be warranted in a therapeutic nutrition plan.

This continuing education course examines the use of collagen as a supplement in the treatment of various health conditions and discusses how RDs can educate patients on its therapeutic benefits.

Functions of Collagen
Collagen is the most abundant structural protein in the human body. It makes up roughly one-third of the total protein in mammals and is found in fibrous tissues such as the skin, bones, tendons, ligaments, cartilage, and blood vessels. It has a triple-helix structure comprising three repeating amino acids. Most common among these are glycine, proline, and hydroxyproline.3

Collagen peptides can be synthesized in the human body from free amino acids, but there’s also evidence that collagen peptides can be absorbed intact when ingested from animal sources.3 The main sources of exogenous collagen peptides include bovine, porcine, marine, and chicken, typically in concentrated, commercial supplement powders; however, they also can be prepared as broths.

In addition, plant-based collagen products are available on the market.4,5 These don’t contain actual collagen but instead provide an assortment of antioxidants, amino acids, and micronutrients that may support the body’s own collagen production. These collagen “builders” or “boosters,” as they’re often called, aren’t included in this discussion because they’re not collagen and there’s no research to support their claims of benefit.

There are four main types of collagen, each providing different structural capacities in the body. Type I is the most plentiful, making up more than 90% of bone and 80% of skin, and conferring structure to tendons and ligaments. Type II is found in cartilage, while type III makes up the rest of skin collagen and is also involved in the structure of blood vessels and organ tissues. Type IV is involved with lungs, bones, hair, and fetal membranes.6

Collagen is a vital structural compound in the body. Unfortunately, it tends to degenerate with age. This gradual breakdown is normal; however, it can be accelerated by oxidative exposures such as pollution, smoking, sedentary lifestyle, poor nutrition, and concomitant diseases.7 This degeneration poses cosmetic and functional problems in the body. Skin, for example, begins to lose its elasticity and hydration. Joints and tendons weaken and degrade over time, furthering the likelihood of pain and injury. The risk of progression to osteoarthritis (OA) increases. The collagen matrix that forms the framework of bones breaks down, resulting in decreased bone density and strength.

This raises the question of whether administering oral collagen might help ward off these chronic, progressive ailments and even promote regeneration of collagen tissues. Supplement industries are already touting these claims as true, but it’s important to evaluate the current evidence before making the same assertions to patients and clients.

The Research on Collagen’s Effects
Many recent trials have attempted to evaluate the effects of oral collagen supplementation on various health conditions. Studies have looked at its potential role in strengthening tendons and ligaments, reducing joint pain and OA, improving bone density, supporting better regulation of blood glucose and blood lipid levels, enhancing wound healing, improving sarcopenia, and even enhancing skin appearance from a cosmetic standpoint.

It should be noted that animal studies are predominant, so much of the current information available isn’t directly applicable to humans. More studies, particularly human interventions, need to be conducted. Even so, there may be some conclusions to be drawn from the current evidence available. Each of these health concerns and related collagen claims will be evaluated against the empirical evidence that’s available.

Tendon and Ligament Health
Roughly 30% of all medical consultations are for musculoskeletal complaints. The majority of those are related to tendon and ligament injuries.8,9 Tendon injuries are notoriously hard to treat and take a long time to heal. Standard treatments typically include rest, ice, and, possibly, anti-inflammatory medications. Surgery and physical therapy may be indicated in some instances. New and novel approaches to treatment are needed to speed healing and promote complete recovery.10

Because tendons are ligaments composed of dense collagen fibers, it’s been theorized that supplemental collagen may aid in their repair, but there are few studies from which to draw any conclusions.
When rabbits were given daily, oral collagen peptides in doses ranging from 0.2 g/kg up to 1 g/kg body weight over a 56-day period, the size of the collagen fibrils and the amount of glycosaminoglycans (an important structural element of tendons) increased in the Achilles tendon.11

Another study looking at a combined supplement involving collagen, vitamin C, and mucopolysaccharides failed to find any significant benefit from oral administration on rats in repair of the Achilles tendon.10 In this case, the study duration was short, only three weeks. The researchers did notice an increase in markers for cell proliferation; hence, it’s possible more changes would have been observed with a longer trial.

At this time, there aren’t enough supportive studies to recommend collagen as an aid to tendon repair. More studies are needed to shed light on its potential role in musculoskeletal healing.

Joint Pain and OA
OA is an inflammatory degenerative joint disease and the leading cause of joint pain. Often leading to disability, it produces a huge burden on the economy and the health care system. So far, there are no effective treatment options apart from pain-reducing medications and, in some cases, joint replacement. For this reason, many seek out alternative therapies. It’s estimated that expenditures on alternative treatments for OA nearly equal those spent on drugs.12

Collagen has been targeted and marketed as a potential nutraceutical that might stimulate collagen biosynthesis and reduce inflammatory destruction. Studies have shown that hydrolyzed collagen exerts anti-inflammatory effects.13,14 This may explain in part the reduction in joint pain that’s been reported by participants in many studies of collagen use.2,15-17

Not all researchers agree on the role of collagen in stimulating cartilage growth and repair. Earlier studies have reported the ability of collagen to stimulate the synthesis of proteoglycans and collagen in vitro.18 There has been evidence of cell proliferation and protection of cartilage.19 More recently, researchers have found that this isn’t always the case. The use of different types of collagen produces varying results, and in some cases no collagen growth was observed, leading one group of researchers to conclude that collagen doesn’t stimulate the growth of collagen in human cartilage.20 Others report similar findings.17

It remains unclear whether collagen is supportive for OA. There are many published cases of improvement in pain parameters and reduction in inflammatory markers; however, there is no clear data to show that there’s actually any repair or growth of cartilage, which is the key target for those seeking to find permanent relief for OA. That said, studies on humans are limited, so more research is needed.

Osteoporosis
Significant research has gone into ways to increase bone mineral density in osteoporosis patients. Current drug therapies have shown some effectiveness, but compliance tends to be poor and there are often serious side effects.19 Nonpharmacological therapies, including healthful diet, exercise, smoking cessation, and vitamin supplementation, have been shown to be useful as well, but these usually only prevent further bone degradation, not restore what was lost.21

While calcium and other minerals are often thought of as the building blocks of bones, 30% of a bone’s weight is its organic matrix, and most of that comprises collagen. Without this strong framework in place, there would be no place for minerals to attach.22 For this reason, collagen supplements have been marketed as aids for increasing bone density and strength.

The literature seems to suggest evidence for collagen’s use. In vitro, collagen can stimulate osteoblast metabolism and activity, leading to increases in bone mineralization.23 Trials on ovariectomized rats found that hydrolyzed collagen significantly reduced bone loss and was as efficient as the drug raloxifene.24 Also, a collagen derived from silver carp skin increased bone density in aged mice.22

In humans, a trial involving menopausal women with osteopenia found that supplementation over six months with a calcium/vitamin D/collagen chelate reduced bone loss more than did using a combination of calcium and vitamin D.25 A more recent study showed that 5 g of hydrolyzed collagen per day over a 12-month period significantly increased bone mineral density in the spine and the femoral neck of postmenopausal women. There was no significant increase in the placebo group.21

Overall, the results appear positive for the role of collagen in bone preservation and remineralization. More studies are needed, particularly in humans, to better understand the mechanisms and appropriate dosage recommendations.

Type 2 Diabetes
Supplement use is quite common among patients with type 2 diabetes. It’s estimated that up to 40% of individuals with blood glucose dysregulation use complementary and integrative medicine as part of their treatment.26 Part of that effort is in targeting inflammation, which has been given more attention in research as a potential treatment strategy; various supplements, including collagen, have been shown to exhibit anti-inflammatory properties.8,13,14,27

Increased effort has gone into evaluating whether collagen might have any impact on blood glucose status in subjects with diabetes. The results appear promising. Rat studies have confirmed anti-inflammatory benefits and have demonstrated improvements in diabetic markers. Supplementation led to significant reductions in C-reactive protein, increases in serum superoxide dismutase, and decreases in fasting blood glucose and HbA1c numbers.28,29

One study noted that GLUT4 was upregulated in supplemented rats, hinting at the role collagen may play in insulin sensitivity and glucose uptake.30 The doses in these studies ranged from moderate to high, running from 0.225 g/kg bodyweight to 9 g/kg bodyweight; however, ingestion at any of these levels showed improvement over the control groups. Two in-vitro studies suggested that collagen has an inhibitory effect on dipeptidylpeptidase-IV (DPP-IV) activity. DPP-IV counteracts glucagonlike peptide-1, a hormone that helps slow gastric emptying, balance blood glucose levels, and increase satiety.31,32

There is far less data on humans. A 2010 study evaluated the effect of marine collagen on subjects with diabetes. Dosing at 13 g per day brought about significant reductions in fasting blood glucose, HbA1c, and high-sensitivity C-reactive protein. The researchers concluded that collagen treatment improved glucose metabolism.33 These researchers also found that the same dosage of collagen may hold blood pressure–lowering benefits as well as improved glucose management in people with both hypertension and type 2 diabetes.34

While more studies are clearly needed to elucidate the direct role collagen may play in type 2 diabetes, the research indicates collagen may be a useful supplement for reducing inflammation and improving glucose sensitivity, particularly for clients with diabetes for whom standard treatments can’t be used or who aren’t achieving the desired effects.

CVD
Collagen may be useful for the treatment of hypertension and lipid management, both strongly linked to CVD.

Again, there is limited data, but that which exists shows some benefit. A chicken collagen supplement showed reductions in blood pressure in subjects with hypertension at 2.9 g collagen per day.35 Marine-derived collagen also demonstrated antihypertensive effects in human and rat trials.34,36,37 All studies reported that collagen provided angiotensin-converting enzyme–inhibiting activity that may have resulted in lowered blood pressure.

Collagen may also improve blood lipid levels. Several earlier studies showed lipid-lowering effects with collagen supplementation, but a recent study showed mixed results.14,33,38,39 Researchers found a significant increase in HDL cholesterol and decrease in the LDL:HDL ratio but a slight increase in LDL cholesterol and triglycerides.40

Most authors agreed that supplemental collagen may be helpful in the treatment or prevention of CVD. While benefits for lipid management are less clear, the use of collagen for blood pressure may be helpful. More studies would be valuable for determining its usefulness.

Wound Healing
There’s some evidence to suggest that oral collagen might help speed wound healing. While there are no human trials to assess this, rat studies indicate that oral collagen, in this case derived from chum salmon skin, may speed wound closure and regeneration of tissue at the wound site.41 Another study utilizing marine collagen peptides from chum salmon, this time looking at speed of healing in rats post cesarean section, again found that wound healing was accelerated. There was improved wound closure, increased collagen deposition, and angiogenesis, leading the authors to conclude that collagen would be therapeutically beneficial for wound healing in clinical practice.42 A third study, using skin gelatin from chum salmon, showed promise that oral collagen may help enhance wound healing in patients with diabetes.43

Wound healing is of great clinical importance and warrants further investigation if oral collagen could reduce patient health care spending, improve quality of life, and even save lives by speeding recovery.

Sarcopenia
Collagen may also aid in the treatment of sarcopenia, a condition that often leads to increased risks of falls, frailty, and reduced quality of life.1

Exercise is known to reduce the progression of this process, but it’s been postulated that the addition of certain proteins might enhance muscle growth and increases in strength.

Data in this area is relatively limited, but one recent randomized controlled trial found a positive correlation between the addition of collagen peptides along with exercise on muscle growth over exercise alone. The participants ingested 15 g hydrolyzed collagen following each training session for 12 weeks. The supplemented group showed a more significant increase in fat-free mass and muscle strength than the placebo group.44 This area warrants more research; however, preliminary results hint that collagen supplementation, along with existing standard exercise recommendations, might prevent or reverse the progression of sarcopenia.

Skin/Cosmetic Applications
The largest driver of oral collagen supplementation use has been the desire to improve physical appearance. The cosmetics industry has touted collagen for years as a way to improve skin elasticity and condition.45

Collagen has been widely marketed in the form of pills, powders, portable sachets, and combination treatments with other nutraceuticals such as probiotics, fiber blends, and antioxidants. It’s likely that clients have encountered these products and the purported beauty and antiaging claims. RDs should be aware of this research, as many likely work with clients who are already using these products and may have questions as to their effectiveness and safety on aging and skin health.

There are quite a few studies pertaining to collagen use and appearance. A 2015 review found numerous results showing increases in skin hydration, reduced fine lines/wrinkles, and improved skin elasticity in both rat and human trials.6 Recent studies have supported these conclusions.

Bovine collagen hydrolysate was associated with skin laxity, repaired collagen fibers, and increased collagen content in aged mice.46 Collagen also reduced cytokine production and repaired aged collagen fibers in mice, suggesting an antiaging effect.47 A group of photoaged women aged 40 to 60 years old experienced a significant improvement in skin wrinkling and skin elasticity after 12 weeks of supplementation.48 A 2019 review concluded that oral collagen may increase skin elasticity, reduce wrinkling, increase collagen density, and improve hydration in the skin.45

Thus, there seems to be significant evidence that collagen reduces the effects of aging in the skin. Dosages from 2.5 g per day to 10 g per day appear to confer measurable benefits. However, it should be noted that some of these studies have industry funding, which may skew results, and any findings to the contrary may not have been published.

Considerations With Collagen Use
Overall, it appears that collagen likely confers some beneficial effects in the health areas outlined. Questions remain, however, as to what type of over-the-counter supplements are effective for the average consumer and in what amounts, given the fact that almost all of the studies used different forms of collagen and varied dosages. Concerns have been raised about the actual absorption of collagen in the human digestive tract, as well as the safety of collagen consumption and risks of toxicity.

Supplemental Collagen
While studies on collagen have been promising in many areas, the practicalities of supplementation are complicated. First, the collagen used in the various studies was derived from different sources. Most collagen is derived from bovine, porcine, marine, or chicken sources. Of the marine type, the choices vary from fish skins to jellyfish. It remains unclear whether these collagen types are interchangeable and provide the same results. There are few studies that measure one type of collagen against another.

In one such study, researchers found different concentrations of peptides based on the source. They concluded that due to the inability to maintain a consistent and reproducible peptide mixture between different collagen preparations, it’s not possible to say that one collagen mixture can produce the same results as another. Effectively, they aren’t interchangeable.20

Ideally, it would be advisable to utilize the same collagen used in research; however, those preparations often aren’t commercially available. Some were specifically designed for a study or were products available only in another country, hence not a choice for the average US consumer. While utilized in many of the studies, particularly those on skin aging, marine collagen isn’t as plentiful in supplement form as is bovine, nor is it as affordable.3 Consumers may not realize that the forms they purchase are different from those used in the studies, which may influence their results.

In addition, homemade and commercially prepared bone broth are rich in collagen and have been touted as a natural food source of these peptides. A recent paper, however, noted some concerns with bone broth and the actual amount of collagen in the final preparations. Researchers found that different recipes and methods of preparation yielded differing amounts of collagen peptides in the final products. While getting to therapeutic levels was feasible in some of the preparations, producing this consistently in the home would be difficult and hard to measure.49 If taking collagen for therapeutic benefit, using supplements with portion information would be preferable to ensure the desired dosage.

Dosage
There’s no scientific consensus on the appropriate dosage of collagen for treating any condition. The research has shown benefits from dosages of 2.5 to 5 g per day for skin health.50 Between 8 and 12 g per day may be beneficial for OA, with upwards of 40 g per day showing benefit in some cases.19,51 A dose of 5 g per day has been associated with lessened joint pain.15

Clearly, doses vary and benefits are found in various amounts in varying health conditions. Standard dosing often recommended on product packages is 10 to 20 g per day, which seems appropriate given the research.

Absorption
Some researchers have argued that the results seen in the research aren’t due to the collagen itself but from an increase in consumption of amino acids that assist with repair and growth.52 Collagen isn’t absorbed intact, they argue, but instead is broken down into individual amino acids in the digestive tract and then absorbed into the bloodstream. While this makes sense on the surface, research has shown that many of these intact peptides are actually absorbed whole into the bloodstream, which is how they then provide therapeutic benefit.3,6

Safety and Toxicity
As with any supplement, safety and toxicity have been studied around collagen use. So far, very few adverse effects from oral collagen have been noted.49,53 Collagen tends to be easily digested and rarely produces any gastrointestinal side effects.6 Toxicity tends to be rare, and no concerns with heavy metals or contaminants have been reported.54,55

Immunogenicity may be a problem for some, however. Due to the fact that the proteins in collagen can change shape and even misfold at times, there’s a possibility of developing a sensitivity or allergic reaction to collagen, especially when it’s taken long term. Interestingly, marine-sourced collagens tend to result in a lower inflammatory response than do other types of animal-derived collagen.55

One final concern pertains to bovine spongiform encephalopathy (BSE) with bovine-derived collagen use. BSE is a degenerative disease caused by abnormal proteins (prions) that affect the nervous system of cattle. Although extremely rare, it can be transmitted to humans via food products that are contaminated with these prions. The US government has taken steps to minimize these risks, putting into place stringent regulations around processing procedures of cow-derived materials.56 It also has banned the import of cattle from areas where BSE exists in higher frequency, further reducing the risk of contamination.57

For the highest assurance of safety, care should be taken to determine supplements’ origin to ensure they are sourced and produced in the United States by reputable companies.

Putting It Into Practice
It appears that, overall, collagen supplementation may have benefits for human health, but there isn’t enough empirical evidence from human studies to establish clear recommendations. From support in bone and joint health to anti-inflammatory benefits and improved skin, collagen peptides seem to exhibit several health-promoting properties with little risk of adverse effects. The type and dosage of collagen that would confer the most benefit, however, remain unclear, and much more research is needed. In addition, a concern with these studies is industry funding, which may bias findings and deemphasize unfavorable trials.

According to the evidence, most of which comprises animal trials, marine collagen appears to have the largest number of favorable studies and a lower risk of side effects. Unfortunately, it’s not as abundant on the market as bovine collagen and is often more expensive. Collagen in the form of bone broth may be another way to safely consume collagen peptides, but there is no reliable way for the average consumer to know how much collagen is in the final product.

It may seem safe and potentially beneficial to recommend collagen in the areas outlined, but, again, there are no clear guidelines as to appropriate product choice or dosage. Patients should be advised to consult with their physicians before initiating any new supplementation.

— Danielle VenHuizen, RDN, is a Seattle-based dietitian and owner of Food/Sense Nutrition.

 

Learning Objectives
After completing this continuing education course, nutrition professionals should be better able to:

1. Define the role of collagen in the human body.
2. Identify how collagen use might be beneficial for various health conditions.
3. Discuss safety and toxicity considerations with the use of collagen supplementation.
4. List the types of collagen supplements on the market and approximate dosage recommendations.
5. Cite three ways to educate patients on the pros and cons of collagen use.

 

Examination

1. Collagen makes up roughly how much of the total protein in mammals?
a. One-quarter
b. One-third
c. One-half
d. Two-thirds

2. Which three amino acids are most abundant in collagen peptides?
a. Glycine, leucine, and hydroxyproline
b. Proline, arginine, and threonine
c. Proline, glycine, and hydroxyproline
d. Glycine, glutamine, and valine

3. What percentage of bone is made up of an organic matrix comprising mostly collagen?
a. 10%
b. 25%
c. 30%
d. 45%

4. Collagen appears to exert which of the following beneficial characteristics?
a. Anti-inflammatory properties
b. An anabolic effect
c. A catabolic effect
d. An effect on cartilage growth

5. Studies have shown that oral collagen intake may help which of the following?
a. Bone mineralization
b. Cartilage growth
c. Energy level
d. Eyesight

6. While collagen appears to reduce pain in osteoarthritis, it’s unclear whether it promotes the growth of which of the following?
a. Bone
b. Connective tissue
c. Inflammation
d. Cartilage

7. There’s insufficient evidence to recommend collagen as supportive for which of the following conditions?
a. Osteoporosis
b. Tendon repair
c. Skin elasticity
d. CVD

8. It is postulated that collagen may help those with type 2 diabetes by doing which of the following?
a. Enhancing weight loss
b. Reducing inflammation and increasing glucose uptake by GLUT4 transporters
c. Increasing the patient’s ability to stick to a low-carb diet
d. None of the above

9. What’s the scientific consensus for collagen supplement dosage?
a. 5 g/day
b. 10 g/day
c. It depends on the type of collagen being used.
d. There’s no scientific consensus.

10. Which of the following is a challenge of consuming collagen though homemade bone broth?
a. It’s difficult to know how much collagen is in the final product.
b. It’s difficult to prepare.
c. There are too many concerns with toxicity.
d. There are high levels of collagen in bone broth products.

 

References
1. Collagen market size, share and trends analysis report by source, by product (gelatin, hydrolyzed, native, synthetic), by application (food & beverage, healthcare, cosmetics), by region, and segment forecasts, 2020-2027. Grand View Research website. https://www.grandviewresearch.com/industry-analysis/collagen-market. Updated February 20, 2020. Accessed December 4, 2020.

2. Puigdellivol J, Berenger CC, Pérez Fernández MÁ, et al. Effectiveness of a dietary supplement containing hydrolyzed collagen, chondroitin sulfate, and glucosamine in pain reduction and functional capacity in osteoarthritis patients. J Diet Suppl. 2019;16(4):379-389.

3. Yazaki M, Ito Y, Yamada M, et al. Oral ingestion of collagen hydrolysate leads to the transportation of highly concentrated gly-pro-hyp and its hydrolyzed form of pro-hyp in the bloodstream and skin. J Agric Food Chem. 2017;65(11):2315-2322.

4. Helm J. Can collagen reverse aging? U.S. News & World Report. March 23, 2020. https://health.usnews.com/health-news/blogs/eat-run/articles/what-is-collagen-good-for. Accessed December 4, 2020.

5. Collagen — Chapter 11. USDA Animal and Plant Health Inspection Service website. https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/export/iregs-for-animal-product-exports/eu-animal-products-not-for-human-consumption/ct_product_eu_collagen_11_other. Accessed December 4, 2020.

6. Sibilla S, Godfrey M, Brewer S, Budh-Raja A, Genovese L. An overview of the beneficial effects of hydrolysed collagen as a nutraceutical on skin properties: scientific background and clinical studies. Open Nutraceuticals J. 2015;8:29-42.

7. Addor FAS, Vieira JC, Melo CSA. Improvement of dermal parameters in aged skin after oral use of a nutrient supplement. Clin Cosmet Investig Dermatol. 2018;11:195-201.

8. Fusini F, Bisicchia S, Bottegoni C, Gigante A, Zanchini F, Busilacchi A. Nutraceutical supplement in the management of tendinopathies: a systematic review. Muscles Ligaments Tendons J. 2016;6(1):48-57.

9. Snedeker JG, Foolen J. Tendon injury and repair – a perspective on the basic mechanisms of tendon disease and future clinical therapy. Acta Biomater. 2017;63;18-36.

10. Gemalmaz HC, Sariyilmaz K, Ozkunt O, Gurgen SG, Silay S. Role of a combination dietary supplement containing mucopolysaccharides, vitamin C, and collagen on tendon healing in rats. Acta Orthop Traumatol Turc. 2018;52(6):452-458.

11. Minaguchi J, Koyama Y, Meguri N, et al. Effects of ingestion of collagen peptide on collagen fibrils and glycosaminoglycans in Achilles tendon. J Nutr Sci Vitaminol (Tokyo). 2005;51(3):169-174.

12. Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52(3):167-175.

13. Dar QA, Schott EM, Catheline SE, et al. Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis. PLoS One. 2017;12(4):e0174705.

14. Wang JB, Xie Y, Pei XR, Yang RY, Zhang ZF, Li Y. The lipid-lowering and antioxidative effects of marine collagen peptides. Zhonghua Yu Fang Yi Xue Za Zhi. 2008;42(4):226-230.

15. Oesser S, Schulze CH, Zdzieblik D, Konig D. Efficacy of specific bioactive collagen peptides in the treatment of joint pain. Osteoarthritis Cartilage. 2016;24(1):S189.

16. Trč T, Bohmová J. Efficacy and tolerance of enzymatic hydrolysed collagen (EHC) vs. glucosamine sulphate (GS) in the treatment of knee osteoarthritis (KOA). Int Orthop. 2011;35(3):341-348.

17. Schadow S, Siebert HC, Lochnit G, Kordelle J, Rickert M, Steinmeyer J. Collagen metabolism of human osteoarthritic articular cartilage as modulated by bovine collagen hydrolysates. PLoS One. 2013;8(1):e53955.

18. Benito-Ruiz P, Camacho-Zambrano MM, Carrillo-Arcentales JN, et al. A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. Int J Food Sci Nutr. 2009;60 Suppl 2:99-113.

19. Porfirio, E, Bernardes Fanaro G. Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: a systematic review. Rev Bras Geriatr Gerontol. 2016;19(1):153-164.

20. Schadow S, Simons VS, Lochnit G, et al. Metabolic response of human osteoarthritic cartilage to biochemically characterized collagen hydrolysates. Int J Mol Sci. 2017;18(1):207.

21. König D, Oesser S, Scharla S, Zdzieblik D, Gollhofer A. Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women-a randomized controlled study. Nutrients. 2018;10(1):97.

22. Zhang L, Zhang S, Song H, Li B. Effect of collagen hydrolysates from silver carp skin (Hypophthalmichthys molitrix) on osteoporosis in chronologically aged mice: increasing bone remodeling. Nutrients. 2018;10(10):1434.

23. Daneault A, Prawitt J, Fabien-Soulé V, Coxam V, Wittrant Y. Biological effect of hydrolyzed collagen on bone metabolism. Crit Rev Food Sci Nutr. 2017;57(9):1922-1937.

24. Guillerminet F, Fabien-Soulé V, Even PC, et al. Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice. Osteoporos Int. 2012;23(7):1909-1919.

25. Elam ML, Johnson SA, Hooshmand S, et al. A calcium-collagen chelate dietary supplement attenuates bone loss in postmenopausal women with osteopenia: a randomized controlled trial. J Med Food. 2015;18(3):324-331.

26. Birdee GS, Yeh G. Complementary and alternative medicine therapies for diabetes: a clinical review. Clin Diabetes. 2010;28(4):147-155.

27. Agrawal NK, Kant S. Targeting inflammation in diabetes: newer therapeutic options. World J Diabetes. 2014;15:5(5):697-710.

28. Wang J, Zhang Z, Pei X, Yang R, Li Y. Effects of marine collagen peptides on blood glucose and lipid metabolism in hyperinsulinemic rats. Wei Sheng Yan Jiu. 2010;39(2):143-146.

29. Zhu C, Zhang W, Liu J, et al. Marine collagen peptides reduce endothelial cell injury in diabetic rats by inhibiting apoptosis and the expression of coupling factor 6 and microparticles. Mol Med Rep. 2017;16(4):3947-3957.

30. Zhu C, Zhang W, Mu B, et al. Effects of marine collagen peptides on glucose metabolism and insulin resistance in type 2 diabetic rats. J Food Sci Technol. 2017;54(8):2260-2269.

31. Hatanaka T, Kawakami K, Uraji M. Inhibitory effect of collagen-derived tripeptides on dipeptydylpeptidase-IV activity. J Enzyme Inhib Med Chem. 2014;29(6):823-828.

32. Hsu KC, Tung YS, Huang SL, Jao CL. Dipeptidyl peptidase-IV inhibitory activity of peptides in porcine skin gelatin hydrolysates. In: Hernández-Ledesma B, Hsieh CC, eds. Bioactive Food Peptides in Health and Disease. Rijeka, Croatia: Intech Open Access Publisher; 2013:205-218.

33. Zhu CF, Li GZ, Peng HB, Zhang F, Chen Y, Li Y. Treatment with marine collagen peptides modulates glucose and lipid metabolism in Chinese patients with type 2 diabetes mellitus. Appl Physiol Nutr Metab. 2010;35(6):797-804.

34. Zhu CF, Li GZ, Peng HB, Zhang F, Chen Y, Li Y. Therapeutic effects of marine collagen peptides on Chinese patients with type 2 diabetes and primary hypertension. Am J Med Sci. 2010;340(5):360-366.

35. Kouguchi T, Ohmori T, Shimizu M, et al. Effects of a chicken collagen hydrolysate on the circulation system in subjects with mild hypertension or high-normal blood pressure. Biosci Biotechnol Biochem. 2013;77(4):691-697.

36. Zhuang Y, Sun L, Zhang Y, Liu G. Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides on renovascular hypertension. Mar Drugs. 2012;10(2):417-426.

37. Lin L, Lv S, Li B. Angiotensin-I-converting enzyme (ACE)-inhibitory and antihypertensive properties of squid skin gelatin hydrolysates. Food Chem. 2012;131(1):225-230.

38. Tang L, Sakai Y, Ueda Y, Katsuda S. Effects of oral administration of tripeptides derived from type I collagen (collage tripeptide) on atherosclerosis development in hypercholesterolemic rabbits. J Biosci Bioeng. 2015;119(5):558-563.

39. Koyama Y, Kusubata M. Effects of collagen peptide ingestion on blood lipids in rats fed a high-lipid and high-sucrose diet. Food Sci Technol Res. 2013;19(6):1149-1153.

40. Tomosugi N, Yamamoto S, Takeuchi M, et al. Effect of collagen tripeptide on atherosclerosis in healthy humans. J Atheroscler Thromb. 2017;24(5):530-538.

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