My Requested Review on Stem cell Supplement Cyplexinol…

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cyplexinol review

I was asked yesterday on twitter by @BrandingJane to review Cyplexinol, a “stem cell activator”. I had some comments I posted on twitter, but here’s the full review. This is a timely request, as it seems like many supplements have begun to brand themselves as stem cell activators.

First, what is Cyplexinol? It’s a partial hydrolyzed collagen complex. Collagen is a common dietary supplement that’s derived directly from animals or fish. This is then broken down further via various means (usually a type of fermentation with alkali). This type of partially digested collagen is quite commonly sold, as a search for hydrolyzed collagen turns up many hits on Amazon.

First, looking through the Cyplexinol website, there’s at least one focus on it’s use in osteoarthritis. So what evidence exists that hydrolyzed collagen helps osteoarthritis? When I ran a search at the U.S. National Library of Medicine this morning I came up with 9 hits. One of these is for a specific type of hydrolyzed collagen called BioCell (from chickens). This small randomized controlled trial seemed to show that BioCell was effective in reducing pain and function in knee and hip arthritis patients. That’s pretty much it other than a few reviews on how it may work that contain some very small pilot studies of under 10 people.

The company that makes Cyplexinol seems to have also published a small study similar to the BioCell study in that it uses the same metrics and has about the same number of knee and hip arthritis patients. This also seemed to show efficacy for pain and function. While I applaud both of these companies for pulling the trigger on small studies, it’s important to put that in context. For example, if I search a more commonly used arthritis supplement like Glucosamine this morning, the U.S. National Library of Medicine web-site returns 823 studies! Suffice it to say that the amount of data that we have that common supplements like Glucosamine are likely effective is massive while the amount of data we have that hydrolyzed collagen helps arthritis is small.

So to summarize at the mid-point of the review, we have a collagen supplement that’s commonly sold under the moniker hydrolyzed collagen (a.k.a. collagen hydrolysate) with it’s own small study to show that it’s version of hydrolyzed collagen could be effective in arthritis. We also have one other study on a different version of the supplement that seems to show the same thing. From a personal experience standpoint, we used the BioCell collagen in our office for many years and after observing hundreds of patients that took it, I would say that it did seem to have some moderate effects on our arthritis patients. However, the next part of the Cyplexinol web-site (the part that their branding agent wanted me to review) is where this story goes off the tracks.

The “Research” page at the Cyplexinol site is a master piece of deception with regard to stem cells. Let me explain. To support that Cyplexinol is helpful for stem cells the page contains many links concerning Bone Morphogenic Protiens (BMPs). This little family of molecules are pretty cool, in that there are thousands of studies that show that BMPs can help direct stem cells to become everything from bone to cartilage. Now to do this using a stem cell culture where you can observe the effects takes incredibly specific doses of BMPs (the two most common are BMP-2 and BMP-7). Adjust that dose slightly or introduce the BMP at a different time, and you will or won’t cause stem cells to become bone or cartilage. In addition, many times to get BMPs into cells, a researcher will use a virus to carry instructions for making the protein into the cell.

What does all of this have to do with Cyplexinol? Nothing, which is where this gets very disturbing. There is nothing about a patient taking an oral supplement that might or might not contain BMPs and the research performed using very specific doses of recominanant BMPs exposed directly to cells in tissue culture. More disturbing still is that after each study where the effects of BMP’s are mentioned, the manufacturers of this dietary supplement have artificially inserted the word Cyplexinol. The message seems to be that Cyplexinol was used in the study. Here are some of the more interesting examples:

A good example is this study, which looks at the growth factor IGF-2 and how it interacts with BMP-9 to promote bone formation. However, no where in the reseearch is cyplexinol mentioned. In fact, the source of these growth factors was in fact virus inserted into cells that expressed mRNA that then produced these growth factors. Despite this the text of the “Research” on the cyplexinol web-site reads, “Insulin-like growth factor 2 (IGF-2) potentiates BMP-9 (Cyplexinol®) induced osteogenic differentiation and bone formation.” This paper has nothing to do with an oral supplement called cyplexinol.

How about this one?”…BMPs  (Cyplexinol®) clearly play a central role in both bone cartilage formation and repair. Recent research into the regulation of the BMP pathway has led to the discovery of a number of small molecular weight compounds as candidate bone anabolic agents.” This is a book chapter that summarizes many studies on BMPs, none of which have anything to do with Cyplexinol.

Or this study? …BMP-7 (Cyplexinol®) may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the injury.” This study tests Stryker’s BMP-7 recombinant protein by injecting it at a very specific dose into sheep joints. Cyplexinol is mentioned nowhere in the paper and again, this experiment had nothing to do with taking an oral supplement containing hydrolyzed collagen.

I’m almost surprised that the manufacturers haven’t used a study I’m on with CSU that used BMPs and stem cells. I’m sure that like the university authors of these studies, I had never heard of Cyplexinol before being contacted by the branding agent, despite being very familiar with the research on BMPs and stem cells. Maybe there’s some body of research that shows that hydrolyzed collagen contains BMPs? I had to show this search screen (below), as it sort of sums up the issues nicely:

cyplexinol research

There’s nothing listed in the U.S. National Library of Medicine showing that either Cyplexinol or hydrolyzed collagen contain BMPs. There’s also nothing listed on the Wikipedia page for hydrolyzed collagen about BMPs. A web search turns up a bunch of hits from the manufacturer, but I’m unable to find the study on Cyplexinol containing BMPs on that site. That web search did contain a bit of a research study on collagen from pig skins that showed that this type of preparation helped bones heal by stimulating BMPs in the bone (which is a foregone conclusion if anything helps bones heal). Even if the manufacturer could produce a study showing that Cyplexinol contained some BMPs, this would still have nothing to do with the research listed on the web-site as proof that Cyplexinol activates stem cells. This would be an apples to oranges comparison.

This issue is becoming quite prevalent in the supplement world. A manufacturer lists a bunch or unrelated studies as proof that the supplement is effective. To the casual lay observer, the research looks impressive. However, once an expert digs in, it becomes quickly apparent that the supplement being sold has little to with the research being quoted.

The upshot? Hydrolyzed collagen might help arthritis pain. Having said that, the body of evidence to this end is dwarfed by more common supplements like Glucosamine or Chondroitin. So if you’re looking for a joint supplement and the more common supplements with better data don’t work or you can’t tolerate them, consider trying an inexpensive form of hydrolyzed collagen (there are more than 20 on Amazon right now). The concept that Cyplexinol helps stem cells is deceiving. Despite listing many credible research studies on BMPs and stem cells and artificially inserting it’s brand name after every mention of the protein, none of the listed studies have anything to do with Cyplexinol. In addition, I can’t even find where hydrolyzed collagen in any form contains BMPs! In conclusion, there’s no evidence presented that shows that Cyplexinol will help your stem cells. While the company could have performed it’s own in-vitro research testing the supplement with real human stem cells, I don’t see any evidence that this study was ever performed.

Chris Centeno, MD

Regenexx Founder

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications.
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