Cyplexinol Review 2: More of the BMP Shuffle…

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Last year I was contacted by a marketing agent on Twitter about the “research” supporting a new supplement called Cyplexinol. When I dug into this supplement, what I found was very disturbing. Yesterday a physician who uses stem cells sent me a copy of the company’s most recent e-mail ad campaign which looks as factually inaccurate as everything I reviewed last year in my first Cyplexinol review.

In summary, Cyplexinol is a nutritional supplement that claims to help stem cells and plays a game that I call the BMP shuffle. What are BMPs? Bone Morphogenic Proteins, or BMPs, are found in your body and are sold commercially for research with a few used as drugs. They are very well studied proteins that can help stem cells differentiate into other cells such as cartilage and bone. The big issue is that Cyplexinol is marketed as a supplement rich in BMPs (which appears to be based on nothing more than blind faith) and as a result borrows the entire several decade body of BMP research as it’s own. In my post last year, I noted that every time that the term Bone Morphogenic Protein or BMP appeared in a random lab study which had nothing to do with the supplement Cyplexinol, the marketing team for the supplement company inserted the brand name (Cyplexinol). This is despite no evidence that I was able to find that this supplement, which is simple hydrolyzed collagen, has anything to do with BMPs.

What is hydrolyzed collagen? Here’s what Wikipedia says: “hides are put in a lime slurry pit for up to 3 months, loosening collagen bonds; the hides are then washed to remove lime, and the collagen extracted in boiling water. The extracted collagen is evaporator concentrated, desiccated with drum driers, and pulverized”. So Cyplexinol is the “goo” that you get after you leave cow hides in a slurry pit with alkali for a few months. The company that makes the supplement has been busy, as the cow hide “goo” is found in other private labelled brands such as “Ortho-Stemulate”, “Super Smart Bone Morphogenic Protein Caps”, “Ostinol”, “Flexibility TRF-150”, “Chondrinol”, “Stem Cell Activator”, and others. So what can this “goo” do?

First, given that the main thrust of marketing for the supplement is that it’s a natural source of BMPs, where’s the beef? Did the manufacturers conduct a lab experiment using ELISAs for BMPs? Nope. Did they expose Cyplexinol to human MSCs and observed what happened in the lab? Nope. Is there research performed by other parties on these topics? I searched the three published works found on the Cyplexinol web-site for any information that might reference back to a paper or other data that shows that the supplement is rich in BMPs. I found nothing. Even more bizarre is that most of the company sponsored papers on the web-site claim that this has been previously reported. I again looked at the National Library of Medicine to see if someone else had published that hydrolyzed collagen was rich in BMPs:

cyplexinol 2

Regrettably, nobody has published a thing on hydrolyzed collagen containing BMPs.

I looked at the Cyplexinol web-site to see if any new patient research had been posted. I found one case study (a single patient) who seemed to have improved bone density on DEXA scans. I also found a 2012 study which is the experience of 28 patients treated at 4 different clinics with Cyplexinol. However, regrettably the patients were also treated with Glucosamine and Chondoitin, supplements that we know have a pretty good research track record of helping arthritis symptoms, so it’s unclear if the Cyplexinol did anything to help these hip and knee arthritis patients. The 2013 study listed is a little more convincing, in that about 80 patients were treated with either Cyplexinol or a placebo. The issue is that the Cyplexinol group’s response, while statistically significant, wasn’t clinically meaningful. The MCID (the least change in the functional score that is believed to ensure that the patient improved) is bigger than the small score changes seen in this study on the WOMAC functional questionnaire. Hence, the paper didn’t show that the Cyplexinol patients had a significant clinical improvement.

Still on the company’s web-site is the same bizarre insertion of the brand name “Cyplexinol” into the titles of many research studies on BMPs that have nothing to do with Cyplexinol. In this case, the company inserts it’s brand name into the titles of random legitimate research studies on the use of BMPs with stem cells or cartilage/bone. This is despite the fact that the terms Cyplexinol nor “hydrolyzed collagen” never appear in the paper and the supplement wasn’t used in the study cited.

So let’s look at the marketing statements in the e-mail:


The last time I looked there was no research on Cyplexinol and “stem cells”, so I ran that search again at the US National Library of Medicine, which turned up:

cyplexinol 1

Huh? The term, “Cyplexinol” isn’t in the US National Library of Medicine! Perhaps the generic version, which is “hydrolyzed collagen”? The only research I can find is one paper discussing that the substance actually reduced the ability of stem cells to turn into cartilage, one of the purported uses of Cyplexinol. Hence, this seems to be the same bait and switch as the last time I looked at this issue, the company is claiming it’s hydrolyzed collagen has BMPs and ripping off the BMP scientific literature showing that these proteins can help stem cells. Score at round 1: Cyplexinol 0-Reality 1

Statement 2: “…first biologically active nutritional supplement that addresses bone and joint conditions based on 40 years of research.”

Wow! 40 years of research! The problem is that the only “research” that I was able to find were the small studies noted above. These studies listed on the manufacturer’s web-site were published in 2012 and 2013, so where does the 40 years come from? Without a single paper demonstrating that Cyplexiol contains BMPs, the makers of the supplement use the discovery of BMPs in 1983 to make the statement that the supplement has 40 years of research support! They might as well claim that since cow hides containing collagen were used by the founding fathers that Cyplexinol story is really 250 years old! Score at round 2: Cyplexinol 0-Reality 2

Statement 3: “Bone and joint supplements on the market may ease unpleasant symptoms, but they don’t solve the problem of degenerating tissue. Bone morphogenetic proteins (BMPs) activate stem cells to grow new bone and cartilage tissue through a process called osteoinduction. ZyCal Bioceuticals uses a patented process to produce Cyplexinol®, a BMP-complex clinically proven to differentiate mesenchymal stem cells into osteoblasts to grow new bone tissue, and chondrocytes to build new cartilage tissue.”

While it’s true that there is copious research on BMPs and bone and cartilage growth, there is no evidence that cyplexinol contains BMPs or that it is “proven to differentiate mesenchymal stem cells into osteoblasts to grow new bone tissue, and chondrocytes to build new cartilage tissue.” Score at round 3: Cyplexinol 0-Reality 3

Statement 4: Cyplexinol® is a BMP-complex that activates stems cells to grown bone and cartilage tissue via osteoinduction. See discussion above. Score at round 4: Cyplexinol 0-Reality 4

The upshot? I don’t use the word “Fraud” lightly, as often there are degrees of B.S. found in the medicine and the supplement industry. However, when the deception is intentional and blatant and pervasive, it’s likely the best fit descriptor. Cyplexinol has nothing to do with stem cells, BMPs, cartilage, nor bone, so it’s likely best to set your e-mail junk filter to include the term!

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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. View Profile

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