Placebo effect & “the fade” after stem cell clinic shots

placebo effect, expectations from hype
Placebo effect, expectations from hype, public domain image

Sometimes when I talk about possible placebo effects with fans of stem cell clinics I feel like placebo becomes akin to a bad word in the discussion. However, any kind of medical procedure can cause placebo effects in people. We’re all susceptible to it.

placebo effect, expectations from hype
Placebo effect, expectations from hype, public domain image

I believe that many perceived positive outcomes at stem cell clinics are really placebo effects.


For one thing, many patients have told me about a phenomenon I’ll call “the fade”. Stem cell clinics themselves know exactly what I mean by “the fade.” It’s a big reason I think there isn’t a genuine positive benefit of the stem cell clinic offerings.

A typical patient going to a stem cell clinic (even patients who become big fans of clinics and of less FDA oversight) who thinks they benefited does not have a lasting positive outcome, but instead has only a temporary sense that they feel better. This improvement generally fades within days, weeks, or at most a few months.

Admittedly, it’s possible that “the fade” is sometimes not due to placebo effect and instead could be due to the body taking some time to eliminate the injected stem cells, but I bet it’s mostly placebo-related. Either way it means patients don’t get what they have come to expect. Another thing that supports the idea of placebo effects being common at clinics is that both some patients and clinics will sometimes say that they either instantly feel better or feel better within just minutes. No, stem cells aren’t magic that works so fast like that.

What happens next for patients with quickly fading perceived results?

After one injection and “the fade” kicking in, the clinics will frequently tell the patient they need another stem cell injection and in fact they can get a somewhat discounted price on injection 2, which then becomes injection 3, and so on. Clinics make big bucks off of repeat customers, while usually neglecting to tell new patients that the typical customer does not just get one $5,000 or $10,000 injection (or more), but many such shots.

Some stem cell clinic customers fully acknowledge that they might have had a placebo effect from clinic injections, but others get offended at the idea. The effect may also be related to expectations and clinics often do hard sells on the supposed miraculous power of their stem cells (see image above).

In a 2013 article on Texas stem cell clinic Celltex, Dr. Arnold Caplan, often called the godfather of mesenchymal stem cells, the type used at most stem cell clinics, had this mind-blowing quote on expensive placebo effects (note that “Jones” mentioned is a Celltex leader who himself got stem cells):

“Jones found he needed another stem cell infusion four months later (he has had them every four months since) to keep his symptoms under control. “I’m afraid to be without stem cells,” he says. So far he’s received 3 billion stem cells by infusion and injection and spent more than $100,000. Plenty of people, including medical colleagues, have suggested he’s experiencing a placebo effect. Jones is convinced he’s not. “My therapy was real, it was effective, and it made me better.” The most rigorous trials—double-blind, randomized, placebo-controlled—are designed to prove any benefits are due solely to the treatment. “There’s no question that with therapies like this there is a very high placebo effect,” says Caplan of Case Western. “The FDA will shudder, but I say, if you want to pay $25,000 and get pain relief for four months as a placebo, go do it.”

Caplan is right about the big potential for placebo effects, but I don’t agree with him on the idea of it being OK that patients may often be getting just placebo effects. Also, from what I’ve heard “the fade” usually kicks in earlier than four months. This quote further doesn’t really seem to appreciate the economic hardship that many patients go through, sometimes through online fundraising that exposes their private health info, to pay that price tag. I also doubt that the average patient thinks the benefit will only be for a month or a few months at best.

Finally, placebo is actually a good word overall as it is used to describe a component of a properly controlled, blinded clinical trial, one that is actually able to really tell if stem cells really work and are safe.


  1. Dear Paul,

    Myself and others that have used my counterpart’s technologies do experience a placebo effect. Usually it lasts for about 24-48 hours immediately after transplant. During that period one experiences what I would call “Superman Syndrome”. During that time period one feels like anything and everything is possible, especially things you could not currently do, but loved to do in a previous life. After about 48 hours, after the placebo effect wears off, then it boils down to did it help or not? I have found that some areas I wanted treated were not the ones that were actually treated by the stem cells. The body seems to know what is the most serious areas and treats those first. For me, objective measurable effects last for 2-4 months, and then I need another transplant. But remember, my disease is trying to kill me on a daily basis.

    Take care,
    Edward Young

  2. Paul-

    I talked yesterday with a group of lifelong learners, and in spite of not working on arthritis treatments, I got a lot of questions about stem cell therapy for arthritis. They confirmed that they are told that they have to come back every three to six months.
    Since stem cells do not regenerate cartilage, there’s no wonder that there needs to be another injection every few months. I have arthritis in my right thumb, and every 6 months or so, I have a talk with my hand specialist. He is doing some work with a local scientist to test the effects of stem cell injections. He told me that the steroid injections seem to last longer! I’m sure that I’m not experiencing a placebo effect because my insurance paid for the steroid injection!

  3. All stakeholders interested in stem cells should be careful stating things as fact when they are anecdotal. Using terms like “they” and “scientist” with no additional data is dangerous although if the format is social media hopefully people understand that sources are not vetted and are in fact opinions. I have never told any patient they need to return for treatments every 3-6 months for any orthobiologic including stem cells and I consider myself a thoughtful publicly available orthopedic surgeon and regenerative medicine doctor with 19 years experience. The wealth of level 1 RCT data for PRP use in knee OA suggests that PRP (not even a stem cell treatment) is better than placebo, steroids, and viscosupplementation not only in pain relief but also in length of benefit. There is growing data on mesenchymal stem cell treatment for arthritis but clearly not the same volume as what we already have in the literature for PRP. There are quantitative differences between the two orthobiologics that make using bone marrow and mesenchymal stem cells an attractive option for treating arthritis. There are studies showing MSCs can promote and stimulate cartilage growth….google Alberto Gobbi, MD and review his recent two publications out of Italy. Please go to and actually review published data in reputable journals….or even google scholar. I treat many people who have tried NSAIDs, rehab, bracing, steroid injections, and sometimes even viscosupplementation and it is only after the Orthobiologic injection that they report the most relief…..could that still be placebo? Of course….but they had potential for placebo with every other treatment tried also….so for that patient at the the “placebo” effect was greatest for the orthobiologic. I respect Arnold Caplan, PhD but he has never been a clinician or been responsible for takin care of patients or making surgical decisions…. and his own opinions have changed over the years based on his lectures at meetings. I know of no actual doctor (MD/DO) reputable in this field who would inject stem cells every two months in a patient for an orthopedic condition. Many many of us are trying hard to be ethical and thoughtful and evidence based in this space…..we are seeing patients daily and use orthobiologics not as magic bullets but as a tool that is effective for some patients…often when other therapies have failed or when the surgical alternative carries risks and recovery time that is best delayed or avoided if possible. is where our position statements are presented in a multidisciplinary format.

  4. Regarding fade, has there been any distinction made between the effects of SVF and Wharton’s Jelly allograft, since age of progenitor cells is important?

    Can temporary benefit be an effect of growth factors residing in the PRP used along with the SVF? As growth factors are not being renewed, the beneficial effect fades over time.

    • The sale of allograft amniotic fluid and umbilical cord blood and Wharton’s jelly “stem cells” has caused much confusion and fraud in this young medical specialty. Here is the clinical problem….. A shock thaw (ie,.30 minute room temperature thaw) of a 1cc frozen vial of any allograft product in the USA is problematic for several clinical and regulatory reasons. #1 There are no functional living stem cells after a 3 minute to 30 minute thaw from a product frozen that was frozen at -20C or lower. #2 If there were living stem cells in the allograft product….then the product is not correctly registered with the FDA….all of these products on the market have taken the cheaper, online, “scout’s honor” route to getting their product on the market without safety or efficacy studies that would be required if they did indeed have living stem cells. In effect, their registration with the FDA under Section 361 tells the FDA that the product has no living stem cells (which I agree with). BUT their clinical marketing trumpets
      “millions of living stem cells” in a 1cc frozen vial….simply not true and many other than myself have tested the product as the bedside post thaw. I urge all clinicians selling these products to people to test them under a microscope at least to verify living stem cells.

        • Yep, just as a simple bench test in the office tryphan blue is enough to show the lack of living cells. More involved testing for trilineage differentiation and plastic adherence and the flow cytometry markers accepted as showing MSCs…can also be done…but in my experience….a simple living or dead stain or test is sufficient to disprove the marketing claims. Believe me, a s a orthopedic surgeon and regen med doctor, would love to have an off the shelf stem cell treatment with 2-30 million stem cells per cc. I just can’t find one yet that delivers that after thawing in the office OR that is appropriately FDA registered.

    • At least in the USA, making SVF from adipose is not allowed…..The Justice Department has currently stopped to large clinic networks from doing just the….Cell Surgical Network and US Stem Cell…..both actions have been discussed on this Blog!

      • Hi Don,
        Just a bit of a clarification. My understanding is that the FDA is trying to halt what those firms are doing, but without a temporary injunction or voluntary stop by the companies on the apparent noncompliant activities, any stop via DOJ has to await a trial that could take anywhere from 18-24 months. Meantime a court decision or some other step by FDA, it seems business at usual at these firms.

  5. Paul I think you are right, here is the link to the Department of Justice action against the two mentioned companies:
    The cases are currently working their way thru court.

    My own opinion is that the Department of Justice will prevail in both cases..

    The US Department of Justice is seeking permanent injunction against Cell Surgical and US Stem Cell.
    I do know of at least two former Cell Surgical affiliates that have switched to using bone marrow derived stem cells but I am not sure if that was on recommendation from the Cell Surgical Network or an individual clinic decision.
    It would seem prudent to stop a treatment (making SVF from adipose) that the FDA deemed a biologic drug making procedure years ago and for which they are now seeking permanent injunction…..I am sure there is the potential for additional patient liability for clinics delivering a product not appropriately cleared by the FDA.

  6. This University of Miami conducted clinical trial is randomzed, double-blind, and placebo-controlled. It seems to provide a different perspective.

    Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, PlaceboControlled Clinical Trial

    Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty

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