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.

Why?

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.

18 Comments


  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 pubmed.com 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.
    http://www.orthobioethics.com 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.
        Paul


  5. Paul I think you are right, here is the link to the Department of Justice action against the two mentioned companies:
    https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm607257.htm
    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
    https://academic.oup.com/biomedgerontology/article/72/11/1513/3977809
    https://www.ncbi.nlm.nih.gov/pubmed/28977399

    Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty
    https://academic.oup.com/biomedgerontology/article/72/11/1505/3746183
    https://www.ncbi.nlm.nih.gov/pubmed/28444181


  7. I got adipose stem cells 18 months ago and I was able to drop my 900mg of Gabapentin 11 days after the procedure. I am sure the initial pain relief could not have been due to actual healing, but must have been due to the powerful, well-documented, anti-inflammatory effect of stem cells. I’m also sure that pain relief it lasts over a year must involve some degree of healing or changes to how the immune system works to cause pain. I have a spinal cord injury due to a lumbar puncture that apparently is inflamed so I need to watch my activity or I still get horrific flare ups. My life is nothing like before the day of that LP. But it is far better than post injury thanks to ny own stem cells. Based on the two years before that I believe I would be in far worse shape due to progression. Had I not been discouraged from stem cell therapy for 2 years by my doctor and articles like this one, I would be considerably better off than I am today.

    I suppose until one experiences the miracle of neuropathic pain relief through adipose derived stem cells or bone marrow stem cells for that matter one will be inclined to deem it a placebo effect.

    That is understandable.

    What is a bit harder for me to understand is the passionate desire expressed by so many here to ban a procedure that many patients claim to have benefited from.

    Where is there a better example of the freedom in the pursuit of happiness than seeking to improve one’s health?

    someday we will have a data-driven outcomes-based medical system. The path there is a long and difficult one, and it is not helped by heavy-handed regulation in the form of outright bans but rather by intelligent guidelines and very strict marketing rules. And my patients sharing their outcomes broadly, whether they be good or bad.

    I appreciate efforts to expose and communicate the dangers and the lies of stem cell therapy or any other medical procedure. It’s a fine line between a genuine desire to protect people from scams and harm and an arrogant impulse 2 prevent people from . havin access to the help that they desperately need.

    When I share my story I always mention many others have been to the same doctor and been deeply disappointed by the results. That they are the minority doesn’t matter, each one needs to accept the possibility of disappointment or injury or infection or whatever.

    I would suggest a similar humility is in order for those who are attempting to assert their influence over others’ access to healthcare.


    • Nice post and finished with the key aspect that binds it all together – access to healthcare – and paying the costs. For most people in industrialized nations, are covered by the state e.g. through Medicaid, Medicare (US), NHS (UK), AOK (Germany), KKH (Japan), etc. What these national health services cover and what they don´t is determined through approval of medicines by regulators (FDA, EMA, etc) and then negotiations between suppliers (usually Pharma companies) and the health service. It may be that a new drug is approved and then not covered because the health service determines that the price is too high for the benefit gained (measured in quality-adjusted life years (QALY)).

      Now the question – how can a health service determine the QALY without rigorous, controlled clinical trials that regulators can analyze and determine whether there is a benefit or not? They cannot, and all the single voices that, as you said, “claim to have benefited” cannot easily be put together to form a group that can be compared to another group without treatment. On top of this is the problem of the actual measured benefit – patients claiming “to have benefited” is not a metric that regulators and health services can use to determine a significant benefit. These are the strict marketing rules that save lives.

      The passionate desire you are seeing on this blog is, in my opinion, based on a knowledge and understanding of what is involved and essential to provide safe and effective therapies for patients and avoid them being taken for an expensive and potentially dangerous ride. Of course this sober viewpoint results in patients feeling that hope is being stolen from them. For those with life-threatening illnesses, that cannot wait for pharma companies to do the clinical trials and regulators and health services to approve drugs, hope costs a a few thousand dollars and in most cases it is nothing more than that. Those that say they had a great improvement that later subsided later may be getting the effects from the stem cells or just the effects of their own bodies reaction to them (and any placebo can have this effect).

      You say that your neuropathy is much improved thanks to your stem cells – that´s great but as a regulator it is meaningless and may (in theory) be due to any number of other things, which were not “controlled” by having a comparitor, and without this they cannot approve autologous adipose stem cells for anything.

      In my opinion there will be many stem cell based therapies in the next decade – and from being an MSC skeptic – I have seen cord blood MSCs used to prevent Graft-versus-Host disease at statistically significant rates in our transplant clinic, so I am now hopeful for such new therapies. But I will also passionately defend the silent majority of patients from the loud claims of others that stem cells cure multiple sclerosis, Parkinson´s disease, etc., when there simply is no credible clinical evidence that regulators can work with.


    • Don’t try to protect me from my decisions. I have a brain and can do my own research. It is my money and my life. It works and you know nothing about it. It is not dangerous but now it will be because I will have to go to a different country to have it done. Please go enjoy your life and leave the rest of us to ours.


      • Rose, some see you as a desperate patient who needs to be protected from your ill-founded hope in therapies that have not met the official regulatory criteria. I see you as a fellow warrior who is seeking to maximize her quality of life in the face of repression by those who, rather than SERVE, and CAUTION patients, would rather CONTROL and RESTRICT access to health care.

        I pray your journey is a safe and productive one with results that exceed your expectations.

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