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Collagen hydrolysate in joint health.

This article will explain the aetiology of osteoarthritis and outline the disadvantages of current conventional therapy and the need for new treatments that positively affect the disease state without unwanted side-effects. Collagen hydrolysate is one of a class of new nutraceuticals that addresses these issues. Its mode of action is explained, which involves the regeneration of collagen tissue. Data from animal studies show no analgesic or anti-inflammatory activity and, although limited clinical data are available, results show a reduction in pain in osteoarthritis sufferers and some functional improvement. Reported side-effects are minor.

Current pharmaceutical treatments for osteoarthritis (OA) concentrate on removing the pain experienced by patients and, in some cases, reducing the inflammation of their joints. There is no current therapy that can cure the disease because the treatments are symptomatic. Many patients are prescribed non-steroidal anti-inflammatory drugs (NSAIDs) that work by inhibiting cyclo-oxgenase enzymes and, therefore, interfere with prostaglandin production. As the condition has limited anti-inflammatory indications, it is thought that NSAIDS are given as analgesics rather than for their anti-inflammatory properties. (1)

This pharmacological treatment, which simply provides pain relief, is not enough for some patients and the prolonged administration of NSAIDs can have a detrimental effect on the patient by causing gastrointestinal problems, such as peptic and stomach ulcers. These problems occur because of the inhibition of prostaglandin production. NSAIDs can also lead to renal toxicity, which is especially problematic in seniors who may already have impaired renal function. (2) In additon, NSAIDs often have to be co-administered to the elderly with proton pump inhibitors to reduce the associated side-effects. This can lead to further problems resulting from poor compliance. There is also evidence to suggest that prolonged use may inhibit synthesis of the collagen matrix, which is obviously an issue for sufferers of the disease, who already have a reduced amount of collagen in their affected joints. (2) The currently available therapies on the market are unsatisfactory for treating the disease because of their inadequate efficacy and unwanted side-effects. (3) As a result, alternative treatments need to be found that will offer greater or equal pain relief, and provide the anti-inflammatory benefits of the extant pharmacological interventions, but with the added bonus of reduced toxic effects. (3)

The Collagen Solution

Collagen hydroysate, a pharmaceutical-grade collagen with a molecular weight (MW) range of 1000-6000 Daltons, is derived from pharmacological gelatin, by hydrolysis, with approved enzymes to give a mixture of collagen peptides. (4) Gelatin is derived from animal sources (hides and bones) and has been used for many years as a staple part of our diets; as such, it is generally regarded as safe by the US Food and Drug Administration (FDA). It was thought that gelatin would be digested upon oral administration by protease enzymes and, therefore, be of no use as a pharmaceutical product. However, it was found that the gelatin proteins are only digested to a certain extent and that the required high molecular weight proteins are actually absorbed intestinally. (4-6) Following intestinal absorption, it appears that the required proteins accumulate in the cartilage where they remain active. At this site of action in the cartilage, collagen hydrolysate stimulates collagen biosynthesis in the chondrocytes. (4)


In osteoarthritis, a pathophysiological effect causes imbalances in cartilage tissue that lead to its degeneration. Cartilage is made up of chondrocytes and an extracellular matrix, of which 60-80% is water. It is thought that collagen hydrolysate has no analgesic or anti-inflammatory properties and that its mode of action is directed towards regeneration within these chondrocytes. (4,5) It was found that the excess amino acids, contained within collagen, could help in the synthesis of cartilage, and it is believed that supplementation with a daily dose of 10g of collagen hydrolysate, would have a direct effect on cartilage of patients within their affected joints. (6) This could aid in actually reversing the disease, rather than being just a symptomatic treatment. It could help to prevent cartilage degeneration and possibly assist the body in repairing the already damaged cartilage. This would mean that the cartilage would return to its specialized phenotypic appearance--a low friction coefficient, flexibility and smoothness--thereby reducing pain in the joints of sufferers and increase their weight bearing ability. This results in increased freedom of movement; the upshot being an improvement in the patients' quality of life. (5)

Trials and Studies

In vitro studies have been done using collagen hydrolysate with cell cultures. The cells treated with collagen hydrosylate, at a dose of 0.5 mg/mL during an 11 day period, showed a significant increase in the synthesis of type II collagen by the chondrocytes compared with the untreated cells. (5) Animal studies have also been done wherein mice were given radio-labelled collagen hydrolysate, or proline, as a comparative test. This animal study showed that, when given orally, the collagen reached sufficient plasma concentrations because it is easily absorbed by the intestines and reaches maximal plasma concentration after six hours. (4,5) In the cartilage of mice receiving collagen hydrolysate, there was a higher concentration of radioactivity in their cartilage when compared with the mice receiving the proline alternative. (4) The collagen hydrosylate absorbed was in high molecular weight form (1000-10,000 Daltons). (5) The amino acid and protein make-up of the gelatin may be responsible for the accumulation in the cartilage and the clinical effect of regeneration. (4) In vitro, it is seen that type I or II collagen hydrolysate increases collagen type II synthesis by chondrocytes. In mice studies, it was seen that the collagen preferably accumulated in the articular cartilage. (7) These findings show that collagen hydrolysate is suitable for oral administration to humans and early findings show it could have a positive result on cartilage regeneration.

A randomized, double blind, placebo-controlled trial, using 81 patients, looked at collagen hydrolysate and two other gelatin-based products, and compared them with egg albumin. (4,5) Only 52 patients completed the trial and it was found that, overall, the three gelatin products were superior to albumin at decreasing pain from the baseline level, but there was also a reduced need for conventional analgesics with the gelatin products. (4) This was thought to be a result of the regenerative effects of collagen hydrolysate, as it is not thought to have analgesic properties. This study showed an overall reduction in pain in patients suffering from OA of the knee or hip. These trials provide evidence for a possible therapeutic use for collagen hydrolysate as a treatment in OA. (4) A multinational study, done by Moskowitz and colleges, looked at 20 different clinical trial centres in three countries using 398 patients, all receiving either 10 g of collagen hydrolysate daily or the placebo alternative. During a 24 week period, the WOMAC (Western Ontario MacMaster) pain score was used to assess the results. (4,5) In the test centres, overall, there was no significant benefit of collagen hydrolysate compared with the placebo. However, at the German site, there was a significant improvement in pain reduction and functional improvement. Also, in patients with increased severity of symptoms at the start of the trial and a baseline WOMAC score of greater than 220 mm, collagen was favoured over the placebo. (4) The results from this trial do not show any advantage of giving collagen hydrolysate, as there was no pain reduction in the overall group of patients. These trials lack any evidence to suggest that collagen hydrolysate is an efficient treatment for OA. (7) However, some patients did benefit from being administered with collagen. As a result of the evidence of safety, its ability to accumulate in the cartilage where it is required, and its ability to synthesize collagen from chondrocytes, which could lead to regeneration, further studies into the long-term effects of collagen hydroslate should be performed. The studies need to concentrate on which populations of OA sufferers would benefit most from the use of collagen and, also, if long-term administration would lead to improvement.

Any side-effects reported in studies were mainly gastrointestinal, such as heaviness in the stomach. (4) Another reason why patients did not complete the study was because of improved symptoms; some patients refused to cross over as they believed their symptoms were greatly improved. We can see from this that collagen hydrolysate is comparatively safe; therefore, further long-term trials in patients with varying degrees of symptoms should be done over longer study periods to see if there is more cartilage regeneration and a greater improvement in symptoms.

For more information

Georgina Ell and Brian Lockwood

School of Pharmacy & Pharmaceutical Sciences

University of Manchester

Manchester M13 9PT, UK.

Tel. +44 161 275 2399


(1.) J. Wood, "Osteoarthritis and its Management," Pharm. J. 262, 744-746 (1999).

(2.) W.J. Kraemer, et al., "Effect of a Cetylated Fatty Acid Topical Cream on Functional Mobility and Quality of Life of Patients with Osteoarthritis," J. Rheumatol. 31, 767-774 (2004).

(3.) M.L. Barnett, et al., "Treatment of Rheumatoid Arthritis with Oral Type II Collagen: Results of a Multicenter, Double-Blind, Placebo-Controlled Trial," Arthritis Rheum. 41, 290-297 (1998).

(4.) R.W. Moskowitz, "Role of Collagen Hydrolysate in Bone and Joint Disease," Semin. Arthritis Rheum. 30, 87-99 (2000).

(5.) A.E. Bello and S. Oesser, "Collagen Hydrolysate for the Treatment of Osteoarthritis and Other Joint Disorders: A Review of the Literature," Curr. Med. Res. Opin. 22, 2221-2232 (2006).

(6.) C.L. Deal and R.W. Moskowitz, "Nutraceuticals as Therapeutic Agents in Osteoarthritis. The Role of Glucosamine, Chondroitin Sulfate and Collagen Hydrolysate," Rheum. Dis. Clin. North Am. 25, 379-395 (1999).

(7.) L.G. Ameye and W.S.S. Chee, "Osteoarthritis and Nutrition. From Nutraceuticals to Functional Foods: A Systematic Review of the Scientific Evidence," Arthritis Res. Ther. 8, R127 (2006).

EFAs and Bone Health

An estimated seven million people in the UK have osteoporosis and suffer from weakened bones that may be prone to breakage. The disease often remains undetected until the first break occurs.

The statistics show that one in two women and one in five men over the age of 50 in the UK will experience a bone fracture that will be associated with osteoporosis.

Bone health is mainly inherited ... but there are a number of things we can do to build bone health for the future. Exercise is certainly key to maintaining the health of your bones; in particular, research has shown that weight-bearing exercise helps to boost your skeleton. So activities such as walking, jogging, dancing, tennis and weight lifting will all help. Obviously, the above activities are all preventive measures but, if you already have osteoporosis, it's more sensible to stick to more gentle exercise such as swimming, walking and tai chi.

Many people are aware that calcium is good for our bones but, rather than taking calcium supplements, it's far more important to ensure that we eat a balanced diet and maintain a healthy weight. However, Essential Fatty Acids (EFAs) also play a role in the prevention of osteoporosis. There has been more and more research pointing towards the benefits of EFAs and their help in reducing joint stiffness and pain, maintaining brain function, protecting against heart disease, improving skin condition, raising energy levels and strengthening the immune system. Omega-3 fatty acids help to increase levels of calcium in the body, deposit calcium in the bones and improve bone strength. A deficiency in certain Essential Fatty Acids, can cause bone loss. EFAs have been shown to increase calcium absorption from the gut. They do this by enhancing the effects of vitamin D. The best sources of EFAs are flaxseeds and flaxseed oil. Other sources are oily fish such as mackerel and wild salmon.


Rosie Hayward is a great example of someone who has greatly benefited from including EFAs in their diet. When Rosie was in her 20s, she was an environmental worker and her days would consist of making fences, pruning trees and clearing paths. She loved it; so, when she started experiencing health problems in 1992 at the age of 27, she was concerned. It started with severe pain in her lower back, something she initially put down to the physical strain of the job. But it didn't improve, resulting in her having to take more time off work. By 1995, the pain had got worse and had extended to her toe and finger joints and the whole of her back. Rosie also had iritis, inflammation in the back of her eye that meant she was in pain even if she wore sunglasses and sat in the pitch black. Finally, after years of pain, she was diagnosed with Reiter's Syndrome, a form of arthritis that produces pain, swelling, redness, and heat in the joints. She also had ankylosing spondylitis, inflammation of the spine, which compounded the pain.

Rosie had to give up work because, at times, she couldn't even walk. She ended up in hospital in total agony several times. But the drugs weren't working so she began to read up on healthy living and eating in a bid to find some answers. The thing that interested her most was reading about the benefits of seed oils. Rosie started including more EFAs in her diet using them in salad dressings, spooning seed oil onto meals and 'hiding' it in smoothies. Within weeks her inflammation started going down and her joints started to feel flexible again. She hasn't had a bad flare-up since 2001.

She was so bowled over by the results that she began to think that more people should be using it--and what better way than if she produced a seed oil herself. She wanted to create a product that would appeal to as many people as possible and the result was Cool Oil--a nutty tasting oil containing flaxseed, pumpkinseed and hempseed oils in the right proportions for optimum health. Cool Oil is a blend of organic seed oils that gives the optimum ratio of Omega 3, 6 and 9 EFAs that our bodies require. Cool Oil is available from The Groovy Food Company and is also sold in Boots, TESCO, Holland & Barrett, Sainsbury's, Harvey Nicholls, Selfridges and Fresh and Wild. For further information, visit
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Article Details
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Title Annotation:bone and joint health
Author:Ell, Georgina; Lockwood, Brian
Publication:Nutraceutical Business & Technology
Article Type:Cover story
Geographic Code:4EUUK
Date:Mar 1, 2008
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