Collagen supplements benefit and side effects, dosage and type, by Ray Sahelian, M.D.
July 11 2014

Collagen is a fibrous protein found in vertebrates, the major element of skin, bone, tendon, cartilage, blood vessels and teeth. It forms insoluble fibers of high tensile strength and which contains the unusual amino acids hyroxyproline and hydroxylysine. It is rich in glycine but lacks cysteine and tryptophan, and has an unusually regular amino-acid domain.

The collagen superfamily is highly complex and shows a remarkable diversity in molecular and supramolecular organization, tissue distribution and function. However, all its members share a common structural feature, the presence of at least one triple-helical domain, which corresponds to a number of (Gly-X-Y)n repeats (X being frequently proline and Y hydroxyproline) in the amino acid sequence.

Collagen supplement oral pill
In the past few years several companies have started selling collagen supplements. There's limited human research evaluating the role of collagen supplements in treating medical conditions, and hence, at this time, claims made regarding collagen capsules need to have further collaboration. Chicken Collagen II (Unhydrolyzed) is being promoted by raw material supply companies.
   For those who do not have a medical background, it may make sense that If collagen loss leads to skin sagging and wrinkles, then replenishing collagen either orally or through creams should restore elasticity and health of aging skin. But, I need to see scientific proof that collagen, applied topically, can penetrate the epidermis. The collagen molecules are very complex and large and would not penetrate, and even if collagen did penetrate, it would not be able to incorporate itself within the complex collagen structure in the skin. Here I report some early studies.

Effect on skin
Clin Interv Aging. 2012. Ingestion of BioCell Collagen, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs. Daily supplementation with 1 g of BCC for 12 weeks led to a significant reduction of skin dryness/scaling and global lines / wrinkles as measured by visual/tactile score. Additionally, a significant increase in the content of hemoglobin and collagenin the skin dermis was observed after 6 weeks of supplementation. This study provides preliminary data suggesting that dietary supplementation with BCC elicits several physiological events which can be harnessed to counteract natural photoaging processes to reduce visible aging signs in the human face. HOWEVER, a controlled study is necessary to verify these observations.

Q. For what purpose would one use collagen supplements?
   A. Very little human research is available with collagen supplements to know for certain what conditions they would benefit. I will make further comments when several more studies have been published. One study has looked at its role in rheumatoid arthritis and another for osteoarthritis.

Email
I have been taking (NeoCell - super collagen +c Type 1 & 3) and I have experienced hair dryness and skin dryness could this be a side effect is this a normal reaction to it?

   A. I have not heard of these side effects before but a good way to find out is to stop the NeoCell to see if the dryness goes away and was related to its use.

Arthritis and osteoarthritis
J Agric Food Chem. 2012. Effect of the novel low molecular weight hydrolyzed chicken sternal cartilage extract, BioCell Collagen, on improving osteoarthritis-related symptoms: a randomized, double-blind, placebo-controlled trial. Schauss AG, Stenehjem J, Park J, Endres JR, Clewell A. AIBMR Life Sciences, Inc., Puyallup, Washington, United States. The aim of this randomized, double-blind, placebo-controlled trial was to investigate the tolerability and efficacy of BioCell Collagen (BCC), a low molecular weight dietary supplement consisting of hydrolyzed chicken sternal cartilage extract, in the treatment of OA symptoms. Subjects were divided into two groups and administered either 2 g of BCC or placebo for 70 days. Other outcome measurements included visual analogue scale (VAS) for pain and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores taken on days 1, 35, and 70. The tolerability profile of the treatment group was comparable to that of the placebo. Intent-to-treat analysis showed that the treatment group, as compared to placebo, had a significant reduction of VAS pain on day 70 and of WOMAC scores on both days 35 and 70. The BCC group experienced a significant improvement in physical activities compared to the placebo group on days 35 and 70. BCC was well tolerated and found to be effective in managing OA-associated symptoms over the study period, thereby improving patient's activities of daily living.

Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial.
Int J Med Sci. 2009; Crowley DC, Lau FC, Sharma P, Evans M, Guthrie N, Bagchi M, Bagchi D. KGK Synergize Incorporated, London, ON, Canada.
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; whereas, this effect was not observed in G+C treatment group. Specifically, 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% in G+C treated group. UC-II treated subjects showed significant enhancement in daily activities suggesting an improvement in their quality of life.

Chicken collagen and rheumatoid arthritis
Dr. Wei Wei at Anhui Medical University in Hefei and colleagues conducted a randomized 24-week trial comparing chicken collagen (0.1 milligrams daily in pill form) and methotrexate (10 milligrams per week) in 236 patients with rheumatoid arthritis. Other "second-line" drugs for rheumatoid arthritis had been discontinued, but patients were allowed to continue use of nonsteroidal antiinflammatory drugs. Patients in both groups saw a decrease in pain, morning stiffness, number of tender and swollen joints, and improvement in their health-related quality of life. At the end of the trial, 41 percent of patients treated with chicken collagen and 58 percent of those treated with methotrexate had improved. Arthritis & Rheumatism, 2008.

A randomized, double-blind, multicenter, controlled clinical trial of chicken type II collagen in patients with rheumatoid arthritis.
Arthritis Rheum. 2008. Anhui Medical University, Key Laboratory of Antiinflammatory and Immunopharmacology in Anhui Province, Hefei, China.
To assess the efficacy and safety of chicken type II collagen in rheumatoid arthritis compared with methotrexate. We conducted a prospective, 24-week, followup, multicenter, double-blind, controlled study of chicken type II collagen (0.1 mg/day) versus methotrexate (10 mg/week) in patients with active rheumatoid arthritis. In both groups there was a decrease in pain, morning stiffness, tender joint count, swollen joint count. In the methotrexate group, erythrocyte sedimentation rate and C-reactive protein level decreased. Rheumatoid factor did not change in either group. At 24 weeks, 68% of patients in the chicken type II collagen group and 83% in the methotrexate group met the American College of Rheumatology 20% improvement criteria. chicken type II collagen is effective in the treatment of rheumatoid arthritis. chicken type II collagen is well tolerated, and the incidence of adverse events of chicken type II collagen is lower than that of methotrexate.

Weight loss
There is no evidence at this time that collagen supplements lead to weight loss.

Wound Healing
Collagen plays a major role in wound healing. Its presence is important in all stages of the healing process. However, this does not mean that ingesting a collagen supplement leads to better wound healing.

Collagen and the Heart
Collagen fibers are the most abundant components of the extracellular matrix in arteries and myocardium. Disturbances in the collagen turnover (synthesis and degradation) have been linked to inflammatory diseases including cardiovascular pathological syndromes. In the myocardium, changes in collagen turnover may result in ventricle dilatation and subsequent contractile dysfunction. In arteries, collagen synthesis and degradation are associated with the progression of atherosclerotic disease and intimal hyperplasia following injury. Collagen synthesis is tightly regulated at several levels: synthesis of procollagens, suitable folding of polypeptides, secretion and cross-linking of mature fibers. On the other hand, degradation of newly synthesised procollagen and mature collagen fibers depends on the action of Matrix-Metalloproteinases (MMPs).

Collagen i antibody
Anti-type II collagen autoantibodies are present in rheumatoid arthritis.

Collagen disease
Glucocorticoids are irreplaceable for the treatment of connective tissue diseases due to their strong and rapid anti-inflammatory and immuno-modulatory effects. Its use and their dosage depend on the activity of the disease and organ manifestations. There is no alternative to high doses, often even as intravenous pulse therapy, in life-threatening situations with imminent organ failure. Despite an additional immuno- suppressive medication, glucocorticosteroids are mandatory for long-term treatment in most cases. In special situations like high age, gravity or comorbidities like renal failure or hepatosis, glucocorticosteroids are the option with the least possible potential for complications. In the future, new corticosteroids and steroid sparing immuno-suppressants like biologics will be able to reduce the spectrum and the severity of corticoid-induced side effects. Modern state-of-the-art therapeutic regimens for patients with connective tissue diseases should not only be able to sufficiently control the disease activity but also include the prophylaxis of associated comorbidities like arteriosclerosis, osteoporosis or infections.

Collagen cream use
Collagen cream concentrate is promoted for dry skin.

Catrix Collagen
Catrix is a new collagen wound-healing powder that has been shown to be effective in the treatment of wounds healing by secondary intent such as pressure ulcers, venous stasis ulcers and diabetic ulcers as well as second-degree burns and post-radiation dermatitis. Catrix has also been shown to be effective in the treatment of wounds unresponsive to conventional treatments. It promotes the growth of fibroblasts and keratinocytes in the wound, prevents loss of fluid from the wound and protects the wound from bacterial infections and other agents. Catrix is biodegradable and therefore does not require removal from the wound bed before re-application.

Research review
Increase in bone mineral density through oral administration of shark gelatin to ovariectomized rats.
Nutrition. 2005.
The incidence of bovine spongiform encephalopathy has resulted in marine collagen hydrolysate (low-molecular-weight gelatin) being sold as supplements and cosmetics in Japan. Shark skin collagen is one of the important sources of marine collagen. We examined the effect of shark skin gelatin in an osteoporosis model animal. Shark skin gelatin was orally administered to ovariectomized rats with a low-protein diet. Bone mineral density of the right femur was measured. Collagen and glycosaminoglycan in the tibial end were extracted and analyzed by western blotting and cellulose acetate membrane electrophoresis, respectively. Administering collagen to the ovariectomized rats resulted in the bone mineral density of the femur epiphysis being higher than that in the sham-operated rats. The contents of type I collagen and glycosaminoglycan in the epiphysis were increased by administering shark skin gelatin. These results indicated that shark skin gelatin would be useful as a dietary supplement for treating osteoporosis.

Results from a new study with adult athletes at the German Olympic Center in Essen, Germany find that during a 12-week study period, 79 percent of the study's participants had statistically significant improvement in joint mobility and flexibility after a course of CH-Alpha.  The postmarketing surveillance study was conducted to determine whether CH-Alpha, a nutritional supplement containing collagen hydrolysate, could ease restricted mobility and pain in athletes' knees or hips when walking or climbing stairs, or pain in the shoulder when lifting and manipulating objects above the head. The objective of this postmarketing surveillance study was to determine whether oral use of Collagen Hydrolysate CH-Alpha in athletically active individuals suffering from arthralgia induced by high-intensity athletic activity confers benefit in terms of improvement in pain, functional limitations, or inflammatory activity. This study aimed to determine whether participating athletes' subjective well-being and objective findings, as assessed by the treating physician, change when taking collagen hydrolysate and, if so, whether these changes can be quantified by selected outcome measures. Subjects took 10g of Collagen Hydrolysate CH-Alpha per day for 12 weeks. Subjects were interviewed and assessed before starting to take collagen hydrolysate (baseline visit), during treatment (interim visit at 4 to 6 weeks after the start of therapy), and at the end of therapy (final visit at 12 weeks). The results showed that during the 12-week study, most participants had marked improvement in most of the metrics employed, with significant improvements in mobility, hip or knee pain related to exertion and when walking up stairs, and in shoulder pain when lifting and manipulating objects above the head. Pain on movement was eased in 78 percent of the 86 subjects whose study results were fully evaluated. In athletes with hip or knee pain and those with shoulder pain, 79 percent had reduced pain when climbing stairs or lifting heavy objects respectively. CH-Alpha is a liquid in a vial providing 10 grams of collagen hydrolysate, a collection of proteins and amino acids (the building blocks necessary for joint health). CH-Alpha is a natural product with an amino acid composition nearly identical to the collagen found in the extracellular matrix in joints. CH-Alpha(TM) may increase the concentration of type II collagen and proteoglycans through the stimulation of chondrocytes. The CH-Alpha used in the Olympic Center study was developed and is marketed by GELITA Health Products, which has supported scientific research on collagen hydrolysate since the late 1970s.
1. Oral administration of 14-C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice. (C57/BL) Am. J. Nutrition, 1999.
2. Oesser S, Seifert J. Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen. Cell Tiss. Res. 311: 393-399, 2003.
3. Role of collagen hydrolysate in bone and joint disease. Semin. Arthritis Rheum, 2000.

Questions
Q. I've been told recently that vitamin C plays an integral role in the formation of collagen for soft tissues such as ligaments and tendons of my joints, and I was recommended to possibly take supplemental vitamin C since I lift weights and need to ensure good repair and strengthening of my collagen and soft tissues. Do you agree with this viewpoint on vitamin C for ligament and tendon health, especially in athletes, etc.? Are there any other nutrients you would recommend for collagen health in addition or instead?
     A. Vitamin C is certainly helpful for collagen health, but it is unclear whether additional Vitamin C will make much of a difference if someone already has a healthy diet with plenty of fresh vegetables and fruits. There are many different nutrients involved in overall tendon, ligament, collagen, and joint health. You could consider Joint Power Rx for overall joint and collagen health.

Q. I just read your article about collagen supplements. Very informative, especially for the layman. I am 48 years old and in pretty good shape. I work out regularly and am in good health except for osteoarthritis. I have worked at physical labor most of my life and have also had 2 spinal laminectomies, one cervical and the other lumbar. My question is, would collagen supplements help with the arthritis and would it aid in rebuilding of the muscle from heavy work-outs and also help keep skin tone?  I take protein supplements, only 30 - 60 grams a day. I eat well, pasta, veg's, 2% milk and breads. Not much on fruit though. I also take one B-12 and a B Complex with C daily. The only med's I take is one 325 mg. buffered aspirin a day.
   A. Collagen supplements have not been studied adequately in osteoarthritis. You may wish to read the web site on osteoarthritis and also on diet for suggestions.

Q. I refer to your website quite often. I have recently started taking a product with chicken collagen type II. Researching it on the web has produced a lot of varying claims as to what form is best, hydrolyzed or not, pill powder or liquid, etc. I was hoping to find out more from you regarding chicken collagen supplements.
   A. I will form an opinion when good human research is published.

Q. I am 36 years old and suffered a distended bladder 2 years ago, due to fluid retention when nurses forgot to fit a catheter after the birth of my baby, I consequently suffer from a cystocele (2nd degree bladder prolapse) and was wondering whether taking collagen supplements would help in the strengthening of my pelvic floor muscles and repair of tissue damage. I practice Kegel exercises daily, but avoid citrus juices due to recurring UTIís and an allergy to citrus, I am therefore also concerned I am not getting enough vitamin C. If collagen supplement would help should I be taking types 1 and 3 or type 2 collagen supplement?
   A. I have not seen human studies with collagen supplement use.

Q, What about facial creams and masks that contain collagen? Do they work?
   A. We have not studied the area of facial creams with collagen to have an opinion, as of January 2008.

Q. I tried GNC Taut Collagen drinks for a month and felt quite good. However, I read reports that it's useless since the collagen will only be broken down into amino acids in the stomach. What then is the usefulness of collagen drinks or capsules at all? I am thinking about Nature Farm's Collagen Matrix or Fancl Collagen Drink (with Q10) too. Some say that eating fruits and vegetables help. I have been doing that but I believe that since collagen production slows down as we grow older, we may need an extra help if we want our skin to stay firm and bone health.
   A. We have not seen any good human studies regarding ingesting collagen for skin health. For the time being we are skeptical that collagen ingested internally will have much of an effect on skin health.

Q. I have been advised to use a good quality collagen supplement to help enhance the vitality of radiated tissue in my palate and throat (recovering form throat cancer and anticipating further surgery to my soft palate). In addition high dose vitamin C, in the region of 2-4 grams a day, may also be useful as it assists collagen in its functioning. Anti-oxidant nutrients such as vitamin A, E, selenium, zinc and others would help to protect tissues against damage and assist the immune system. I would suggest a good multivitamin and mineral formulation and also an additional anti-oxidant complex. However, from reading your site you are not so sure about the above advice. Can you confirm your position on collagen supplements to enhance tissue damaged by radium treatment?
   A. I have not seen any human research that using a collagen supplement has health benefits. Some of the other nutrients you mention may be helpful. But overall health improvement with diet, exercise, and deep sleep will also be of benefit. General health improvement will allow the body to heal itself better. MultiVit Rx is an excellent multivitamin.

Q. I came across an ad that said, "BioCell Collagen II TF is a fine powder with improved solubility and reduced bitter tones for ready to drink formulations, chewables, and functional foods. BioCell Collagen II TF provides the same composition of absorbable hydrolyzed collagen type II, chondroitin sulfate, and hyaluronic acid, but without the bitterness. " Is this supplement effective?
   A. I have not come across any human studies with this product.

Q. I would like your opinion on vegetable collagen supplement. Can it improve the elasticity of the skin? Does it have nutritional benefits for vegetarian women ?
   A. I have not come across any human studies with vegetable collagen supplements. I tend to doubt that ingesting collagen orally would have any effect on skin health.

Q. I was used to have excellent, resistant healthy nails before I have my 3 kids! after pregnancies and hard working as a busy mom, my nails turn to broken, chipped dull nails for many years. Recently one of my friends told me about her experience with collagen tablets from Costco. she was amazed with the result and recomended it to me. Now this is about one month I am taking this tablet 3 a day. I cannot believe it. after about 10 years of dealing with broken, short ugly nails, my nails are as beautiful as they used to be. I am so happy. after so many years I could have my nails long again! That was like my wishes came true. Now I am recomending it to all my friends. I hope this letter have a useful benefit in your research.
   A. What is the name of the collagen supplement product you are using?
      Q.  The name of the collagen supplement product is Collagen + C from NeoCell Company. As I told you my friend has the same experience with this Collagen + C from NeoCell Company product and her nails. I hope it helps your research.
          Q. I am the one who is taking the collagen tablet everyday, and I have seen so much different in growing my nails. I am so happy for that, but one of my friends recently told me about links between collagen and cancer. I am so shocked and considering to stop taking the collagen tablets.
             A. As of October 2008, we are not aware of any human studies in terms of collagen supplement use and an increased risk for cancer.

Q. I'm emailing you to inquire whether your research team have come across any new research information on oral collagen supplements affecting cholesterol levels as there appears to be little data on this subject.
   A. As of 2012, we have not seen such studies.

If one is on 6 grams of pure MSM per day, does one still need collagen pills?
    We are still awaiting studies to determine the role of collagen supplements in the treatment of medical conditions. The use of MSM depends on what is being treated, and whether there are alternative supplements that have been studied more thoroughly. it is too general a question to answer.

Do you think it would be safe and/or effective to pop open a collagen capsule, mix with distilled water into a paste, and apply to the under-eye area as a remedy for dark circles? Could a paste of pure whey protein do any good?
    I doubt these methods would be effective, but it does not seem that it would harmful to try.

First, I want to thank you for compiling this information. I have found it very useful. I want to comment on your section on that page labeled "collagen supplement oral pill." The answer to that question talks about how topical collagen cannot be absorbed by the body, which is a bit misleading since you are talking about an oral supplement. You correctly state later that not much research has been done on oral collagen supplements, but later you list a type II collagen study that supports oral collagen supplements for rheumatoid arthritis. I have a collagen deficiency (Type I) and have had success with a Type I & III collagen supplement (bovine). I am trying to get researchers to take a look at oral supplements, if only to rule them out, but I am having no luck. Thanks again for your work.
    One study is not enough to come to conclusions about the benefit of a supplement. Different academic centers need to do several studies to confirm results and benefits. We wish you well.
        I certainly agree that one study is not enough. I have had many people tell me without any evidence that collagen supplements do not work (oral or topical) and that study was all I could find to try to encourage them to do more studies. I don't understand why so many researchers have ignored collagen supplements for the disorder that I have, which is a collagen deficiency, or the resistance I encounter when I ask if they plan to study it. I have been taking NeoCell SuperCollagen + C. It is the only supplement I have found that uses collagen types I and III instead of the more common type 2. My disorder (Osteogenesis Imperfecta) is a type I collagen deficiency, so I thought I'd give it a try. The only therapies available for OI are for increasing bone mass, but I have much more of a problem with joint laxity due to faulty connective tissue. Going up and down stairs has been agony for years. It's a certain angle of the knee that is the killer; the knee will pop out (extremely painful and embarrassing when I yelp) if I am not careful of the angle. My other joints have issues too. I don't lift weights because of the strain on the joints, etc, etc. But the knees are my main weakness. Anyway, the supplement had me going down stairs comfortably in a week. Going down the stairs took seconds, not minutes. I take between 9 and 12 tablets a day and I notice when I forget to take it. I recently decided that I felt ok and did not need to keep taking it (it does add up, and I'm currently unemployed), and quit and for the 5 days I managed to go without, I got painful twinges in areas around my joints. I started taking it again yesterday, and the twinges have eased off, though I'm still taking stairs a bit slower than I was. I understand it's anecdotal, but the NeoCell site has a testimonial from another person with a collagen disorder (Ehlers Danlos Syndrome). Thank you for taking an interest. If I can add anything, please let me know. 36 yo OI patient in Michigan.

Collagen supplement press release received December 2008
Adding BioCell Collagen II TF to your functional foods, beverages, chewables and liquid formulations provides the same composition of absorbable hydrolyzed collagen type II, chondroitin sulfate, and hyaluronic acid without affecting the taste profile of your products. The 100% natural BioCell Collagen II Taste-Free (TF) provides the same joint and skin health-promoting benefits as BioCell Collagen II in a highly soluble, palatable and odorless form. This makes it an ideal choice for new product development formulators of vitamin waters, cosmeceuticals, beauty supplement drinks, fortified foods and juices, liquid joint support beverages, chewable dietary supplements and additional products. BioCell Collagen IIģ is widely used by our marketing partners in products providing nutritional support and promoting: Healthy Active Joints, Healthy Young Looking Skin, Healthy Strong Connective Tissue. BioCell Collagen II is available in four different grades for various formulation applications:
BioCell Collagen II Standard powder for two piece capsules and soft gel applications.
BioCell Collagen II TG (Tablet Grade) Increased particle size for tablet compression applications.
   Comments: I will await to see actual human research with this product or other similar collagen supplement products beforre determining their benefits and side effects.

Do you have an opinion on the effectiveness in drinking Jusuru liquid bio cellcollagen product? I have heard that it is supposed to erase the wrinkles on your face and make the skin more firm.
   As of March 2012 I have not seen studies with Jusuru.