Studies musculosceletal system-joints


Scientific studies/data: Collagen hydrolysate (CH)

Study: Journal: Researchers Type of study Conclusion
Resorption and distribution of collagen hydrolysate:
Oral administration of C-labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice.
Journal of Nutrition 129. January 1999
p. 1891-1895
Oesser et al.
Surgical Research of the Department of General Surgery and Thoracic Surgery of the University of Kiel
Absorption of 14C labeled gelatin hydrolysate was
compared to control mice administered 14C labeled proline following intragastric application. Plasma and tissue
radioactivity was measured over 192 h.
Ninety-five percent of enterally applied
gelatin hydrolysate was absorbed within the first 12 h. The distribution of the labeled gelatin in the various tissues was similar to that of labeled proline with the exception of cartilage, where a pronounced and long-lasting accumulation of gelatin hydrolysate was observed. In cartilage, measured radioactivity was more than twice as high
following gelatin administration compared to the control group. These results demonstrate
intestinal absorption and cartilage tissue accumulation of gelatin hydrolysate and suggest a potential mechanism for previously observed clinical benefits of orally administered gelatin.
Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen Cell & Tissue Research 311
p. 393-39
Oesser et al. The effect of  collagen hydrolysate on the formation of type II collagen by mature bovine chondrocytes in a cell culture model. The presence of extracellular collagen hydrolysate (CH) led to a dose-dependent increase in type II collagen secretion. However, native collagens as well as a collagen-free hydrolysate of wheat proteins failed to stimulate the production of type II collagen in chondrocytes. These results clearly indicate a stimulatory effect of collagen hydrolysate on the type II collagen biosynthesis of chondrocytes and suggest a possible feedback mechanism for the regulation of collagen turnover in cartilage tissue.


Scientific studies/data: Collagen hydrolysate (CH)

Study: Journal: Researchers Type of study Conclusion
Therapy of osteoarthritis: What effect have gelatine products? Therapiewoche 41
Heft 38.
Pp 2456-2461
Adam M Randomized, double-blind Cross-Over-Study over four months, 81 patients Patients with osteoarthritis in knee or hip received 10g of collagen hydrolysate  over a period of two months (plus 2 months wash-out period). CH showed a significant reduction of pain in the patient population.
Absorption and effectiveness of orally administered low molecular weight collagen hydrolysate in rats Journal of Agric Food Chem
2010 Jan 27; 58(2): 835-41
Watanabe-Kamiyama et al. Radioactive  low molecular weight collagen hydrolysate (LMW-CH) administered to rats Findings show that LMW-CH exerts a beneficial effect on osteoporosis by increasing the organic substance content of bone. LMW-CH was absorbed into the blood of rats in the peptide form. Glycyl-prolyl-hydroxyproline tripeptide remained in the plasma and was increased in the femur.
Role of collagen hydrolysate in bone and joint disease. Seminars in arthritis and rheumatism
Vol 30, No 2 (Oct)
Moskowitz RW et al. Multicenttered (USA, UK, Deutschland), randomised, double blind,  placebo controlled study.
389 Patients with Gonarthrosis,
10g CH daily intake during 24 weeks and 8 weeks wash-out)
Collagen hydrolysate is of interest as a therapeutic agent of potential utility in the treatment of osteoarthritis and osteoporosis. Its high level of safety makes it attractive as an agent for long-term use in these chronic disorders.
The German study showed significant results on pain reduction and improved function over placebo. In the USA and UK no significant difference was reported, however they experienced a much higher drop-out  rates: USA 42%, UK 37% compared to Germany 7%. The authors explains this due to different habits in taking pain killers, study condition,s and nutrional habits. CH has a unpleasant taste.


Scientific studies/data: Collagen hydrolysate (CH)

Study: Journal: Researchers Type of study Conclusion
8-Week study on the use of collagen hydrolysate as dietary supplement for skin anti-aging purposes Rousselot Studies, May 2009 Rousselot Placebo controlled, double-blind  study with 40 women aged 40 to 59 years. Results:
-26% reduction in micro-furrows
+28% skin hydratation
+ 19% skin suppleness
-23% reduction in the depth
-40% width of the wrinkles
Effect of collagen hydrolysate in articular pain Complementary Therapies in Medicine, Volume 20, Issue 3, June 2012, 124130 O. Bruyère, B. Zegels, L. Leonori, V. Rabenda, A. Janssen, C. Bourges, J.-Y. Reginster Randomized, double-blind, placebo controlled, 6 months
200 patients
Study results suggest that collagen hydrolysate 1200 mg/day could increase the number of clinical responders (i.e. improvement of at least 20% on the VAS) compared to placebo.
Aenderung der Gewebeeigenschaften durch CH-Einnahme . Eine biomechanische in-vivo Pilotstudie Extracta orthopaedica 4
Pp 12-15
Weh L, Petau C Biomechanische Charakteristika der Fingerkapseln (computergesteuer-tes Fingerhyper-extensometer. 24 Personen nahmen über 6 Monaten jeweils 10g KH. Die Resultate zeigen eine verminderte Integralfläche der Kraft/Winkel-Regressionskurve (p˂0,001), was auf eine erhöhte Gewebefestigkeit zurückzuführen ist.
24-Week study on the use of collagen hydrolysate as dietary supplement in athletes with activity-related joint pain. Current Medical Research and Opinion. 2008 May;24(5):1485-96. Clark KL et al. Randomized, placebo-controlled, double-blind study
147 patients
The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study’s size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance.


Scientific studies/data: Collagen hydrolysate type II (CH II)

Study: Journal: Researchers Study type Conclusion
Effect of oral administration  of type II collagen on rheumatoid arthritis (RA) Science,
Vol. 261,
pp 1727-1730
David E. Trentham, Roselynn A. Dynesius-Trentham, E. John Orav, Daniel Combitchi, Carlos Lorenzo, Kathryn Lea Sewell, David A. Hafler and Howard L. Weiner Randomized, double-blind, placebo controlled trial involving 60 patients with severe active RA. Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis.
The trial shows a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.


Scientific studies/data: Collagen hydrolysate type II (CH II)

Study: Journal: Researchers Study type Conclusion
Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 1998 May;41(5):938. Barnett ML, Kremer JM 274 patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA).
Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent. Further controlled studies are required to assess the efficacy of this treatment approach.
The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells.


Scientific studies/data: Collagen hydrolysate type II (CH II)

Study: Journal: Researchers Study type Conclusion
Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial International Journal of Medical Sciences
Int J Med Sci 2009; 6(6):312-321.
David C. Crowley1, Francis C. Lau2, Prachi Sharma1, Malkanthi Evans1, Najla Guthrie1, Manashi Bagchi2, Debasis Bagchi2,3, Dipak K. Dey4, Siba P. Raychaudhuri 5,6, Randomized, double-blind trail, 52 patients.
40mg CH type II (4 capsules) a day vs 1500mg/1200mg CS/GS (4 capsules) a day.
Previous studies have shown that undenatured type II collagen (UC-II) is effective in the treatment of rheumatoid arthritis, and preliminary human and animal trials have shown it to be effective in treating osteoarthritis (OA). The present clinical trial evaluated the safety and efficacy of UC-II as compared to a combination of glucosamine and chondroitin (G+C) in the treatment of OA of the knee. The results indicate that UC-II treatment was more efficacious resulting in a significant reduction in all assessments from the baseline at 90 days.
Although both treatments reduced the Western Ontario McMaster Osteoarthritis Index (WOMAC) score, treatment with UC-II reduced the WOMAC score by 33% as compared to 14% in G+C treated group after 90 days. Similar results were obtained for visual analog scale (VAS) scores. Although both the treatments reduced the VAS score, UC-II treatment decreased VAS score by 40% after 90 days as compared to 15.4% in G+C treated group. The Lequesne’s functional index was used to determine the effect of different treatments on pain during daily activities. Treatment with UC-II reduced Lequesne’s functional index score by 20% as compared to 6% in G+C treated group at the end of 90-day treatment.


Scientific studies/data: chondroïtin- and glucosamine sulfate

Study: Journal: Researchers Study type Conclusion
GAIT study New England Journal of Medicine 354/8, pp. 795-808, Feb/2006. Clegg et al multicenter, double-blind, placebo- and celecoxib-controlled osteoarthritis.
1583 patients
Analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the  subgroup of patients with moderate to severe knee pain.
Combined chondroitin sulfate and glucosamine for painful knee OA Annals Rheum. Disease 2015 0:8 Hochberg MC et al. Multicenter, randomised, double-blind, non-inferiority trial versus celecoxib CS+GS has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitaltion and joint swelling/effusion after 6 months in patients with painful knee OA, with a good safety profile.
Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause. 2004 Mar-Apr;11(2):138-43. Bruyere O at al. Preplanned combination of two three-year, randomized, placebo-controlled,  studies evaluating the effect of glucosamine sulfate on symptoms and structure modification in OA.
318 women
This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.


Scientific studies/data: Rose hip (RHP)

Study: Journal: Researchers Study type Conclusion
A Novel Rose Hip Preparation with Enhanced
Anti-Inflammatory and Chondroprotective Effects
Mediators of Inflammation
Volume 2014, Article ID 105710, 10 pages
Joseph Schwager, Nathalie Richard, Rotraut Schoop, and SwenWolfram In vitro cell cultures with RHP extracts. Rose hip powder (RHP) alleviates osteoarthritis (OA) due to its anti-inflammatory and cartilage-protective properties. Substances
contained in RHP might contribute to its clinical efficacy. The activity of two RHP (i.e., RH-A, from the whole fruit, RH-B,
from fruits without seeds) was investigated in human peripheral blood leukocytes (PBL) and primary chondrocytes (NHAC-kn).
RH-A and RH-B diminished the secretion of chemokines and cytokines in LPS/IFN-


Scientific studies/data: Rose hip (RHP)

Study: Journal: Researchers Study type Conclusion
Rose hip and its constituent galactolipids confer cartilage protection by modulating cytokine, and chemokine expression. BMC Complement Altern. Med.
2011 Nov 3;11:105. doi: 10.1186/1472-6882-11-105
Schwager J. Cellular systems (macrophages, peripheral blood leukocytes and chondrocytes), which respond to inflammatory and OA-inducing stimuli, are used as in vitro surrogates to evaluate the possible pain-relief and disease-modifying effects of RHP. Clinical studies have shown that rose hip powder (RHP) alleviates osteoarthritis (OA). This might be due to anti-inflammatory and cartilage-protective properties of the complete RHP or specific constituents of RHP.
RHP and GLGPG (Galakto-Lipids) attenuate inflammatory responses in different cellular systems (macrophages, PBLs and chondrocytes). The effects on cytokine production and MMP expression indicate that RHP and its constituent GLGPG down-regulate catabolic processes associated with osteoarthritis (OA) or rheumatoid arthritis (RA). These data provide a molecular and biochemical basis for cartilage protection provided by RHP.
A powder made from seeds and shells of a rose‐hip subspecies (Rosa canina-cynorrhodon) reduces symptoms of knee and hip osteoarthritis Osteoarthritis and Cartilage (2008), 16, Supplement 1, S8–S9 K. Winther et al. Randomized, double-blind, placebo-controlled,
94 patients with OA
The data suggest that the present herbal remedy can alleviate symptoms of osteoarthritis and reduce the consumption of ‘rescue medication’.


Scientific studies/data: Natural eggshell membrane (NEM)

Study: Journal: Researchers Study type Conclusion
Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled clinical study. Clinical Rheumatology
05/2009; 28(8):907-14
Kevin J. Ruff randomized, multicenter, double-blind, placebo-controlled Osteoarthritis Pain
Sixty-seven patients were randomly assigned to receive either oral NEM(R) 500 mg (n = 34) or placebo (n = 33) daily for 8 weeks.
Natural Eggshell Membrane (NEM(R)) is a new novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy articular cartilage and the surrounding synovium.
Supplementation with NEM(R) produced an absolute rate of response that was statistically significant (up to 26.6%) versus placebo at all time points for both pain and stiffness.
Supplementation with NEM(R), 500 mg taken once daily, significantly reduced both joint pain and stiffness compared to placebo at 10, 30, and 60 days.
Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies Clin Interv Aging. 2009; 4: 235–240., 2009 Kevin J. Ruff Eleven (single-arm trial) and 28 (double-arm trial) patients received oral NEM® 500 mg once daily for four weeks Supplementation with NEM®, 500 mg taken once daily, significantly reduced pain, both rapidly (seven days) and continuously (30 days).


Scientific studies/data: Chondroitinesulfate (CS)

Study: Journal: Researchers Study type Conclusion
Osteoarthritis Progression Prevention.
Chondroïtine sulphate (CS)
Arthritis & Rheumatism
Vol. 60 No 2, Feb 2009
pp 524-533
André Kahan, Daniel Uebelhart, Florent de Vathaire, Pierre D. Delmas, Jean-Yves Reginster International, randomized, double-blind, placebo controlled
622 patients
2 years
The long-term combined structure modifying and symptom modifying effects of CS suggest that  it could be a disease-modifying agent in patients with OA.
Chondroïtine sulphate (CS) reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients. Annals of Rheumatic Disease  (BMJ group)
2011 June 1; 70 (6)
p. 982-989
Lukas Martin Wildi,  Jean-Pierre Raynaud, Johannes Martel-Pelletier, André Beaulieu Randomised, double-blind
Placebo controlled
70 patients
6 months + 6 months
Controlled pilot  study
using MRI
CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment, and BML, at 12 months. These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA.
Cochrane Summaries
Review of 43 studies with 9110 people
    Review of 43 studies and 9110 people

In people with OA:

  • CS may improve pain
  • CS improves pain by 20%
  • CS may improve quality of life measured by Lequesne’s index (pain-function-disability)
  • CS slightly slows down narrowing of knee space

Some efficacy and low risk


Scientific studies/data: Glucosamine sulfate (GS)

Study: Journal: Researchers Study type Conclusion
Glucosamine Sulfate Prevents Total Joint Replacement In The Long-Term Follow-Up Of Knee Osteoarthritis Patients Arthritis Rheum. 2004: 50, 9 (suppl): 251 Karel Pavelka et al To assess the incidence of joint replacement after a further long-term follow-up. Patients of two recent randomised, placebo controlled, double-blind, 3-year clinical trials in knee osteoarthritis (OA) , with GS. 136 patients

Treatment for up to 3 years with glucosamine sulphate in knee OA prevented total joint replacement during a further follow-up of 5 years after drug withdrawal, probably because of the effect on joint structure achieved during treatment.

14 out of 136 had knee replacement:
11/67 who had been on placebo (16.4%)
3/69 who had been on GS (4.3%)

Glucosamine sulfate in the treatment of knee osteoarthritis symptoms Arthritis & Rheumatism Volume 56, Issue 2, pages 555–567, February 2007 Gabriel Herrero-Beaumont et al. 318 patients randomized, placebo controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of OA, was used as a side comparator. To date, no studies have demonstrated any other pharmacologic treatment to have the same efficacy as glucosamine sulfate for the long-term treatment of OA symptoms. The efficacy results obtained with glucosamine sulfate were significant and clinically relevant in the present study in which acetaminophen, the currently recommended preferred medication (2, 3), was used as a side comparator.


Scientific studies/data: Antioxidants gentian, edelweiss, extramel®

Study: Journal: Researchers Study type Conclusion
Free radical scavenging activities of yellow gentian (Gentiana lutea L.) measured by electron spin resonance Department of Agronomy, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, Ljubljana, Slovenia. A Kusšar et al. Electron spin resonance (ESR) spectrometry This study proves that yellow gentian leaves and roots exhibit considerable antioxidant properties, expressed either by their capability to scavenge DPPH or superoxide radicals.
In vivo efficacy of different extracts of Edelweiss (Leontopodium alpinum Cass.) in animal models Journal of Ethnopharmacology Ester Speroni et al Extracts of the aerial parts and roots of Edelweiss were investigated for their anti-inflammatory and analgesic effects after oral administration. Histological evaluation of the treated paws showed a significant reduction of the inflammatory response in the pre-treated specimens.
Effect of an oral supplementation with a proprietary melon juice concentrate (Extramel®) on stress and fatigue in healthy people Nutrition Journal Marie-Anne Milesi et al. Double-blind. Placebo controlled
70 healthy participants
This pilot  study showed that an oral supplementation with a proprietary melon juice concentrate rich in SOD may have a positive effect on several signs and symptoms of perceived stress and fatigue
Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthritis Rheum. 1996 Apr; 39(4):648-56. McAlindon TE et al. Participants in the Framingham Osteoarthritis Cohort Study underwent knee evaluations by radiography.
640 patients.
High intake of antioxidant micronutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with OA.


Scientific studies/data: amino acids, vitamines, minerals

Molecule Effets
L-lysine L-Lysine is a necessary building block for all protein in the body. L-Lysine plays a major role in calcium absorption; building muscle protein; recovering from surgery or sports injuries; and the body’s production of hormones, enzymes, and antibodies. L-Lysine is a main amino acid for elastine and collagen.
L-méthionine Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids.
L-thréonine L-threonine is a key component of collagen, elastin and enamel proteins
Vit C Ascorbic acid or vitamin C is a common enzymatic cofactor in mammals used in the synthesis of collagen. Ascorbate is a powerful reducing agent capable of rapidly scavenging a number of reactive oxygen species (ROS).
Moderately higher blood levels of vitamin C measured in healthy persons have been found to be prospectively correlated with decreased risk of cardiovascular disease and ischaemic heart disease, and an increase life expectancy.
Vit D Vitamin D is a group of fat-soluble secosteroids responsible for intestinal absorption of calcium and phosphate
Vit E As a fat-soluble antioxidant, it stops the production of reactive oxygen species formed when fat undergoes oxidation