What is Prolotherapy? How does it compare to PRP & other Regenerative Medicine?

What is Prolotherapy?

We asked Neurosurgeon Dr. Joseph Shehadi from Phenicell Regenerative Institute and Neurosurgery Associates what he thinks about Prolotherapy.

Here is what he had to say on the topic:

Hello, I’m Dr. Joseph Shehadi a neurosurgeon.


And today I’d like to go over Prolotherapy.

Prolotherapy has a long history that dates back to Roman times when soldiers were given hot needles into their injured shoulders in order to try to help them. However, in 1956 Prolotherapy was made Popular by a general surgeon named George Hackett. It has been 60 years and Prolotherapy is still not yet FDA-approved.

However, it is much cheaper and more affordable than PRP or stem cells and there is some Merit. Prolotherapy is also called proliferation therapy.


It’s an injection of an irritant that causes the body to react. Hoping for proliferation and then remodeling. It is considered by some a type of regenerative tissue injection usually is Sugar’s concentrated dextrose that is injected or salt hypertonic saline such as 25% saline or 50% saline, but keep in mind there are actually no biological agents and no genetic materials like exosomes which have messenger RNA and DNA and there’s actually no live cells that are injected like a true stem cell injection would contain.

Prolotherapy is controversial. Like PRP and stem cell injections Prolotherapy is also not yet FDA-approved despite being around us so much longer. Patients sometimes get confused about these various types of therapies.

Doctors need to educate patients a little better. Indications for Prolotherapy are similar to the indications for PRP. Most common are knee pain and shoulder pain. However, there’s a difference in indications when it comes to stem cells or more complex therapies. Stem cells and Exosomes are indicated and used for more complex disorders: Such as Lyme disease, Strokes multiple sclerosis, spinal cord injury, lupus, dementia, and other disorders.

Prolotherapy, in recent literature, has been compared to normal saline and has been compared to PRP and other similar treatments. Here in 2018, a Hong Kong group study the efficacy of intra-articular hypertonic dextrose Prolotherapy compared it to essentially some normal saline or control for knee osteoarthritis in a randomized triple blinded study. They used to 25% dextrose Prolotherapy and had 76 patients involved They realized that intra-articular dextrose Prolotherapy was better than nothing, and was better than simple normal saline.


This slide is a comparison of Prolotherapy vs. PRP
On the left-hand side, we have Prolotherapy. And on the right-hand side of the slide is PRP.
Prolotherapy is essentially hypertonic saltwater or concentrated dextrose which is sugar. No stem cells or proteins injected.
However, PRP contains multiple growth factors, which you will see on the next slide.
It’s also not yet FDA-approved but it’s only been 30 years not 60 years. Some insurances are considering paying for PRP and amniotic fluid for simple joints such as the knee. PRP is also been used recently by famous professional athletes like Tiger Woods and Kobe Bryant.

What are the differences between Prolotherapy and PRP? Explained by Neurosurgeon Joseph Shehadi from the Neurosurgery Associates Team and Phenicell Regenerative Institute.
Prolotherapy Vs. PRP

This slide illustrates the various useful content found in platelet-rich plasma in particular platelet growth factors such as VEGF and IGF and platelet-derived growth factors as well as interleukins, like il-1 and granulocytes monocytes and lymphocytes that all work together to help promote healing.


Prolotherapy is not quite as good as PRP for plantar fasciitis as Illustrated in this 2014 research article. However, they both have some good but the PRP was slightly better. This study only included 21 patients. Prolotherapy is not quite as good as PRP for knees either.

This more recent study in 2019 comparing Prolotherapy with dextrose vs. A variety of interventional treatments. This is a pretty good study because it contained a lot of patients or 328 patients that were treated with hypertonic dextrose vs. Another 348 patients treated with various treatments such as PRP, hyaluronic acid, etcetera. Prolotherapy was better than lidocaine alone And as good as hyaluronic acid in general but was not quite as good as PRP patients.


Prolotherapy is not as strong or as long-lasting as exosomes or stem cells since as I mentioned, they do not contain any specific biological agents. Recent research and interest in Prolotherapy pales in comparison to the interest in research of PRP or stem cells, which I like to illustrate in the next few slides. According to pubmed.gov which you can see for yourself on the internet. Prolotherapy was only seen 254 times as illustrated in this slide. Which is far less than the over 12000 research articles on the platelet-rich plasma in recent times and those both pale in comparison to the number of research articles on stem cells, which is 363000 research studies and a subset of stem cells in general which are particularly popular are Mesenchymal stem cells. And if you look at the PubMed research for just Mesenchymal stem cells alone. It is over 67,000 research articles.


For more information about Prolotherapy or PRP or stem cells or any regenerative medicine topic. Please feel free to contact our office or stay tuned for more videos.