Dr. Dobri Kiprov: The Science Behind Plasma Exchange for Longevity

By | February 5th, 2025

Heralded as a longevity treatment for bio-hacking enthusiasts and tech CEOs, therapeutic plasma exchange also has applications for people concerned about inflammatory diseases like Alzheimer’s. Is it safe? Effective? Backed by science? Global Apheresis founder Dr. Dobri Kiprov explains.

Therapeutic plasma exchange is a medical procedure that works like a “blood filter.” When someone undergoes therapeutic plasma exchange, their blood is passed through an apheresis machine, and their filtered plasma is removed and discarded. They then get a re-infusion of red blood cells and replacement fluid — essentially, replacing their old blood plasma with new blood plasma.

It’s pricy, and it’s experimental, but it’s trending in longevity spaces, hailed by biohacking enthusiasts and tech CEOs as a fountain of youth. Advocates say it has the potential to help people living with autoimmune diseases and neurodegenerative diseases, too.  But how does it work, and what is the science behind it?

For Global Apheresis founder and plasmapheresis pioneer Dr. Dobri Kiprov, understanding this treatment starts with a mouse study from 2005. This study involved parabiosis, where an older mouse and a younger mouse’s circulatory systems were connected. The older mouse, which received blood from the younger mouse, became younger, and the younger mouse, receiving the older blood, became older. 

So, what was it in the blood that made these opposite reactions in the mice to swapping out their blood? For many scientists, this pointed to plasma, particularly young plasma.   

“People decided that human plasma from young people is the fountain of life. This is much more complicated than that,” Kiprov explained. “However, in the meantime, we found quite a few factors in the old blood that caused the inflammation and the aging of the young mouse.” 

The procedure made headlines when the CEO of tech company Kernel Bryan Johnson famously got actual human plasma from his teenage son — but this kind of “plasma infusion” isn’t standard TPE. And it carries higher risks, like immune reactions or infections. Johnson later switched to real TPE using albumin, similar to what Global Apheresis offers, likely because it’s safer, more scientifically backed, and doesn’t rely on direct plasma donation.

In Global Apheresis’s TPE procedures, experts take blood, separate out the plasma (the liquid part of one’s blood that can carry toxins or antibodies), and replace it with something healthier. Instead of using actual human plasma, Global Apheresis uses a purified solution made of 5 percent albumin (a key protein in human plasma, derived from donated human plasma) mixed with saline. This method avoids risks tied to using fresh frozen plasma from donors while still offering the benefits of TPE.

In particular, in his research, Kiprov has focused on how proteins from inflammation can accumulate in the blood and in plasma. he has pioneered the use of TPE to mitigate the effects of aging and has conducted several controlled and uncontrolled studies. In addition to the other conditions they treat, Global Apheresis does offer TPE for people living with Alzheimer’s or those worried about their risk. In particular, Kiprov has studied how this treatment can work as an intervention for the disease, such as the AMBAR study, in which mild-to-moderate Alzheimer’s disease patients received this treatment. 

In this conversation with Being Patient founder Deborah Kan, Kiprov discusses in greater detail the mouse study that inspired his work and the specifics of the AMBAR study. He breaks down what TPE is and what people concerned about Alzheimer’s disease should know about treatment. 

Read or watch the conversation below. 

Being Patient: It seems quite normal to live into your 90s today. Are people living healthier lives, or are they not?

Dr. Dobri Kiprov: Unfortunately, they’re not. People are living longer, but the later part of their lives are usually miserable. They suffer from a variety of diseases. Almost all of these diseases are related to chronic inflammation. Alzheimer’s is one of those diseases, but it’s not limited to that. 

It involves the cardiovascular system. People suffer from heart attacks, strokes, diabetes, and so forth. The last 10 or 20 years of most people are spent with many physicians, on many medications, in hospitals, on wheelchairs, and that’s not a life that one wants.

Being Patient: Tell us about inflammation. Alzheimer’s pathology has beta-amyloid plaques, tau tangles, and then inflammation. I have been told that when you reach an inflammatory state, you usually see symptoms. What does inflammation look like in the brain?

Kiprov: Most of these diseases are due to chronic inflammation, and attacking chronic inflammation in our medical approach to aging and these diseases is essential. There are two kinds of inflammation: one one is good, [and] the other one is bad. Inflammation is a defense mechanism by the body to [protect] us from infections, cancer, and a variety of other things. 

Everything that the body recognizes as foreign will be attacked by the immune system, and usually, this happens through acute inflammation. If you get infected with the flu virus, there is a curve that you get— you start sneezing and coughing and all that. It reaches a nadir, and then, over several days, it goes away, and you forget about it. This is acute inflammation, a normal response that cures us of infections and so forth. 

The chronic inflammation can be triggered by acute inflammation, which does not go away because of some sort of a defect or disease of the immune system that does not allow us to get back to normal. From acute inflammation to normal, which is no inflammation, but there is always some remnant of inflammation. 

We call this chronic inflammation. Chronic inflammation can be induced by acute inflammation that gets a little awry. Also it can be caused by trauma, cancer, or some other disease that causes inflammation continuously, and the body is not capable of getting back to normal. 

The inflammation continues as we age. All these components of the immune system that circulate in the blood get somewhat overwhelmed over time, so we accumulate a lot of inflammatory factors [and] proteins, usually that circulate in the blood, and the body is not capable anymore [of getting] rid of them. Older people suffer from chronic inflammation much more frequently than younger people.

Being Patient: There was a mouse study involving the circulatory systems of an older mouse and a younger mouse that inspired your research. Tell us about that.

Kiprov: The original experiment was called parabiosis. It is an animal model that combines the circulation of two genetically identical animals. In this case, it was mice. This was done by the team of Irina and Michael Conboy and their colleagues at Stanford University at that time. 

What they did to study aging: They combined the circulation of two mice. One of the mice was young and the other one was old. They observed that the younger mouse became older, and the older mouse became younger. 

Most people forget the fact that the young mouse became older. They were interested in the older mouse becoming younger. The natural assumption right away was that there was something in the blood that was rejuvenating, some molecule. We [are] always looking for a silver bullet, the fountain of life. 

“The natural assumption right away was
that there was something in the blood
that was rejuvenating, some molecule.
We [are] always looking for a silver
bullet, the fountain of life.”

People decided that human plasma from young people is the fountain of life. This is much more complicated than that. To tell you the truth, this was 2005 now, so 20 years later, there have been millions and millions and millions of dollars spent to find out the silver bullet in the young plasma. 

Despite the fact that many very accomplished scientists have been involved in this field, nothing has been found. It is not that easy [to find] an answer to that. However, in the meantime, we found quite a few factors in the old blood that caused the inflammation and the aging of the young mouse.

Being Patient: When you say that the younger mouse became older and the older mouse became young, did one of them suddenly become diseased, and the other one was healthier with disease? What did that look like in the mouse study?

Kiprov: Interestingly enough, in animals, we are able to do autopsies and find out exactly what happened in different organs, and the Conboys did morphologic studies, which I have seen. They documented morphologic changes in different organs. In the liver, for example, they documented an increase in fibrosis [in the younger mouse] and a decrease in fibrosis in the older mouse. 

“People decided that human plasma
from young people is the fountain of
life. This is much more
complicated than that.”

In the brain, they found that it is their neurologic changes, morphologic, that happened in both the younger and the older mice. They were able to document that. and also did physiologic studies in the blood that showed significant changes. 

Basically, what happened, according to them — and I agree with that assessment — is that they were able, by combining the two circulations, to change the environment in the body where all the other cells live, from stem cells to neurons. 

All cells live in the environment of the blood, predominantly the plasma, because that’s where the proteins are and so forth. Changing the environment from old to young, we call that the milieu. It is essential for rejuvenation and continuation of normal cell proliferation. 

Being Patient: Tell us about the research you’ve conducted using TPE with people who have had Alzheimer’s disease.

Kiprov: This study was initiated by a group of scientists in Barcelona. There is a very famous Alzheimer’s scientific community in Barcelona. Barcelona is also the home of a company called Grifols, which is a family-owned company. It’s a biomedical company. They are involved in the production of albumin and other medications made from human plasma. 

The idea behind the study was that, as you and your audience probably know, the [theoretical] cause of Alzheimer’s disease is amyloid. Amyloid is a protein that circulates in the blood, gets deposited in the brain, and causes damage. There are arguments against that, but so far, that’s the predominant theory for Alzheimer’s disease. 

I’ll show you in a little bit that that’s not exactly true, but to a certain extent it is true. The Grifols people said, “Well, we make albumin,” which is a very important part of the plasma. It is the most significant protein in the plasma. In the molecule, albumin has multiple receptors on its side, and it has been shown in vitro that these receptors attract amyloid. 

Their idea was [that] if we overwhelm the blood system with albumin, it will prevent it from accumulating in the blood, in the brain. There was an idea behind there. To do that, they had to do plasma exchange because otherwise ,they would overwhelm the body with fluid. So, they [were going to] remove the old plasma and substitute it with the human albumin that they make. 

Everything today, and probably in the past as well, is done because of money. They want to sell their product. They decided that their products are gonna predominate here. To their credit, they funded, generously, a very serious clinical experiment that involved placebo-controlled clinical trials, [with] 400 people divided into different groups. [They] performed plasma exchange in Barcelona, as well as in different places in the United States. 

My staff and I were in charge of the procedures in the United States, so the results were pretty good. We were able to arrest the progression of the disease in moderately severe Alzheimer’s disease in 67 percent of patients. At that time, this was unheard of. It was great. In the mild Alzheimer’s disease, we saw significant improvement in cognitive function, memory, and everyday life. 

The study was pretty successful, and it was published. Unfortunately, it was published in 2021, right in the midst of the pandemic. It didn’t get as much attention as it deserved because the attention was someplace else. 

Being Patient: You compared the results of cognitive tests in the AMBAR study to monoclonal antibody drugs. What did you find in the study?

Kiprov: The AMBAR study outperformed all of those. In addition to that, the monoclonal antibodies attack the amyloid plaques in the brain. If they’re successful with killing them, this causes a dramatic change in the brain, including edema, infarct, and so forth, and causes horrible side effects. Some people have developed suicidal thoughts, some people have died, some people have had strokes, and so forth. 

These events are pretty common: 40 percent in the two of the monoclonal antibodies. The newest one has a little less. Just the fact that these serious side effects do exist pretty much limits their use, because people are afraid to take them. In our case, we had zero side effects of this nature. 

The pathophysiology of Alzheimer’s disease is not only related to amyloid, but it’s related to other systems as well. One is genetic and the other one is the immune system. It is inflammation and infection. P-tau is another protein that is deposited in the brain abnormally. It’s related to infection, nutrition, and so forth. 

“Just the fact that these serious side
effects do exist pretty much limits
their use, because people are afraid to
take them. In our case, we had
zero side effects of this nature.”

The etiology of Alzheimer’s disease is very complex. Monoclonal antibodies were designed to attack a single molecule or a part of a molecule in the body. Attacking a part of a molecule in the body is highly unlikely to affect all these different things involved in the cause of the disease.

Being Patient: Did TPE impact the plaque in the brain? What happened in the brain with this treatment?

The MRI studies have not been published yet. I know it’s been several years, but it takes time to do the evaluation. I don’t have the answer to the plaques, per se. It is very difficult to evaluate the number of plaques and the volume of plaques and then calculate how this was diminished. There are new tests now that are much more accurate and better for diagnosis and research than the tests that were available to us at that time, five or six years ago. 

“This data … is still being evaluated.
The amount of amyloid in the
blood was calculated. It was
definitely diminished.”

This data is not available, not to me, not to anybody yet. It is still being evaluated. The amount of amyloid in the blood was calculated. It was definitely diminished. The idea was that if you diminish the amyloid in the blood, you will reduce the accumulation of plaques. Whether we remove the plaques from the brain, we don’t know that yet.

Being Patient: Are you following up on these participants who received the treatment? Is getting TPE continuous?

The initial study involved six treatments within a short period of time, and when I say a short period of time, it was about a month. [There were] six treatments, almost once a week. We perform six procedures within a month, and then follow that with monthly procedures for another six treatments. Overall, they got 12 procedures. 

Is that enough? The answer is no because Alzheimer’s disease is a chronic disease. The treatments available today, both ours and others, are going to be chronic treatments. They are not curative. We don’t cure anybody with whatever we do so far. 

“It’s in the economy of scale; the more
procedures we do, the less expensive
it’s going to get. Slowly, we’re going
to get there, but we’re not there yet.”

The other thing that is very important is that what we do is not only curative, but it is also preventive. Today, we have the test to identify the population that is at high risk for Alzheimer’s disease through genetic testing and through other parameters that are available to us now. 

These are just over the last several years. We can identify people with genetic predisposition, or just the beginning of the disease, at an early stage because people with genetic predisposition will develop the disease much earlier than usual. 

The usual Alzheimer’s patient is 80 years old, and these people get the disease very early, in their 40s and in their 50s, which is very unusual for typical Alzheimer’s disease. I’m treating two sisters who lost their parents at age 50— they’re at a very high risk for developing the disease, so we treat them periodically to prevent them from developing the disease.

Being Patient: Is therapeutic plasma exchange FDA-approved?

Kiprov: Yes. Therapeutic Plasma Exchange is FDA-approved. The FDA basically approves the machines that we use, and we, as physicians, can use the procedure for whatever reason we need to. 

Being Patient: What risk is associated with therapeutic plasma exchange?

This is a study I did that evaluates the adverse reactions of therapeutic plasma exchange published in the literature from major hospitals around the world, from France to Sweden to Japan to the United States and so forth. The blue lines indicate the percentage of side effects that people see. These [names] are the authors of the articles. 

As you can see, it varies dramatically. These guys have very high adverse reactions. These have less, and Dr. Kaplan and myself give much less. The AMBAR study has about 10 percent. The red ones are the ones where people used fresh frozen plasma rather than the albumin that we use. 

Fresh frozen plasma is much more dangerous in terms of side effects and even death. [It] very much depends where the procedures are performed and who is doing them. 

People who are well trained and know what they’re doing will have a very, very small amount of side effects. Actually, in our experience, in the last study we did, we had less than one percent. We had only one side effect in more than 300 procedures. If the procedure is performed by experienced people in a correct environment, the side effects will be minimal.

Being Patient: What are the side effects of this treatment?

Kiprov: The side effects can vary. They are usually related to the vascular axis. There is the unpleasant experience of starting IVs. The IVs can leak. They can cause hematoma [and] they can cause some bleeding. They can cause infection in some people. 

We don’t use that in outpatient facilities, but some people use central lines because the peripheral veins are inadequate, and the central lines are associated with infections pneumothorax, which isthe  accumulation of air in the lungs and stuff like that. 

Yes, some of the side effects can be serious. Minor side effects include tingling of the fingers and around the mouth, and hypotension, a drop in blood pressure. These are more common, but we, in our experience, do not allow any side effects to happen; we prevent them. The key to good medicine is prevention rather than treatment. 

Being Patient: Would you think of this more as an effective preventative treatment for people concerned about Alzheimer’s disease or other inflammatory chronic diseases? Is it better to start earlier rather than later?

Kiprov: The answer is yes. In any medical situation, the earlier you start, the better your chances of succeeding. If you start early, you are 100 times better than if you start late. This can be the flu. This can be cancer. 

Being Patient: What about the cost of therapeutic plasma exchange? Does insurance cover it?

Kiprov: For certain diseases, it is covered, but it has to be done in a hospital setting at the moment. What we do is we treat patients in an outpatient setting for a variety of reasons. First of all, they don’t have to wait in line to get to the hospital. It’s considerably less expensive to get to the hospital. 

Just your first step in the hospital is 10 grand before you start getting treatments. We can offer the treatment considerably less expensive. It is still expensive for most people, but we can offer it much less than the hospital can offer it and in a much more pleasant environment that is more acceptable to patients. 

They feel good coming here. They want to come but unfortunately, it is not readily reimbursable by insurance companies. We are working on a solution for that. It’s going to take time. Everything with insurance companies takes time. Also, the number of procedures. It’s in the economy of scale; the more procedures we do, the less expensive it’s going to get. Slowly, we’re going to get there, but we’re not there yet. 

Katy Koop is a writer and theater artist based in Raleigh, NC.

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One thought on “Dr. Dobri Kiprov: The Science Behind Plasma Exchange for Longevity

  1. Your video on TPE said you would leave a YouTube link and Kiprov website link.
    Please send these to me or show where they are listed. Thanks.

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