Why Bryan Johnson Stopped Taking Rapamycin, a Drug He Hoped Would Slow His Aging
Bryan Johnson
For about four years, Bryan Johnson has worked with a team of medical professionals to build what he calls "the world's best health protocol." One part of that effort was rapamycin, which he describes as one of the world's most promising experimental drugs for slowing the speed of aging. In this video, he explains why he stopped taking it. He reports that the drug caused side effects that went away once he quit, and that a study published afterward suggested rapamycin may have been accelerating the biological speed of aging in humans. His position is that the result is uncertain but worth taking seriously, and that failed experiments should be shared as openly as successful ones.
From Easter Island Soil to Transplant Medicine
Johnson starts with the drug's history. According to his account, rapamycin was discovered in the 1960s in a soil sample that scientists collected from a cave on Easter Island. The sample contained a bacterium with powerful antifungal properties, and the compound was named rapamycin. Researchers first thought it could become a cure for fungal problems such as athlete's foot. Before that work went further, they found that the compound was also a powerful immunosuppressant.
Johnson describes this property as cutting both ways. Immunosuppressants can save lives in some cases, but for large portions of the population, suppressing the immune system "can be a death sentence." In 1999, the FDA approved rapamycin for organ transplant patients. High doses were meant to stop the immune system from attacking a newly transplanted organ. Johnson notes that rejection is still a major problem and says more than a third of transplants are rejected by the body.
The Longevity Connection
Johnson says that despite plenty of research on the drug, nobody linked rapamycin to longevity until 2009. As he tells it, a study that year gave rapamycin to older mice and found that it extended lifespan by 14% in females and 9% in males. When researchers repeated the study in younger mice, rapamycin extended longevity further. When they combined it with other drugs such as acarbose, the reported gains were larger still: 28% in females and 34% in males. Johnson says these findings were replicated in other animals, which gave researchers hope for the final test in humans.
Researchers were cautious about giving it to people, he explains, because of the serious side effects seen in transplant patients. Those included metabolic disruptions such as high cholesterol, tissue swelling, soft tissue infections, and impaired wound healing. Johnson says more recent studies suggested that lower doses or intermittent dosing reduced these side effects. His reasoning at the time was that if the side effects could be managed, the potential upside was "just too great to ignore."
How Rapamycin Is Supposed to Work, and Its Costs
Johnson explains that rapamycin's longevity potential rests on its ability to inhibit mTORC1, a growth pathway whose overactivation he says plays a role in many age-related diseases. He lists several natural ways to inhibit mTORC1: caloric restriction, fasting, exercise, and "activators." Rapamycin does it directly.
The benefits his team hoped for were a lower biological age, a slower speed of aging, better organ-specific biological age markers, and possible rejuvenation of the immune system and skin.
He is clear that these benefits come at a price. Rapamycin also inhibits mTORC2, which he links to the metabolic side effects mentioned earlier. It suppresses the immune system as well, including natural killer (NK) cells, which he calls "your cancer killing cells." He calls this a double-edged sword, which is why the dosing protocol matters so much. Other risks he lists are disruptions to cholesterol, insulin, and blood glucose, and possibly smaller gains from exercise and muscle growth. Johnson says he knew about all of this before he started.
Trying to Find the Right Dose
Johnson shows the pill, which is triangle-shaped, and describes the team's attempts to get enough rapamycin for the benefits without suppressing his immune system too much. They tried several protocols:
- five pills per week
- six pills one week, then 13 pills the next
- 13 pills two weeks in a row
To see how the drug behaved in his body, the team drew blood 90 minutes after he took the pills and again at 24, 48, 72, and 96 hours. The goal was to measure how much rapamycin was in his blood and how quickly it fell back to zero. With that data, they hoped to find a dose high enough to produce the intended effects but low enough to avoid the side effects.
No Noticeable Benefits, Several Side Effects
Johnson says he never noticed any benefit. "Everything seemed to be the same." He did notice side effects. He got canker sores in his mouth, and wounds sometimes healed more slowly than they should. His blood reports showed cholesterol disruptions, and his blood glucose rose somewhat.
The side effect that bothered him most was a higher resting heart rate. He calls resting heart rate the most important biomarker he tracks every day, because he considers it the biggest influence on his sleep quality. These side effects continued for several years. Johnson says he accepted that trade-off for the potential longevity benefits.
Testing Whether Rapamycin Was the Cause
Blueprint involves many interventions at the same time, so Johnson says it is always hard to tell which one is causing a particular effect. His team suspected rapamycin because the side effects matched what they had read in the literature, and they decided to test that suspicion by stopping the drug. According to the video and its description, he stopped on September 28.
He reports that once he was off rapamycin, his blood glucose dropped, his cholesterol corrected, and the soft tissue infections went away. He concludes that the side effects did come from rapamycin. The team also had a longer-term worry about cancer. Because the drug suppresses the immune system, including NK cells, they were concerned that years of that suppression might raise his long-term cancer risk.
The Preprint That Pointed the Other Way
On October 27, about a month after he stopped, a preprint came out that evaluated several longevity interventions, including rapamycin. Johnson says it found that rapamycin accelerated the biological speed of aging in humans across 16 epigenetic clocks. He calls this "huge news."
He finds the outcome funny. "Irony hunts me," he says, and he calls it the most humorous possible result: a drug he took for longevity may have been speeding up his aging. He adds that "you got to give it to irony."
He does not treat the preprint as settled. Rapamycin may still have all the benefits people have imagined, he says, and the study could be flawed in some way. He calls that "entirely a possibility" and says this is how science works. For now, his team is taking a cautious step by paying attention to the data while waiting to see whether new evidence refutes it. He says it is important to stay cautious as new evidence comes in.
Risk, Damage, and the "Game"
Asked whether he did lasting damage to himself, Johnson answers: "Maybe. I don't know." He acknowledges that many people think he takes excessive risks. His response is that everyone takes risks. Eating fast food or going to bed late has known effects, he argues, including faster aging and metabolic disruption. He describes his project as a game: using science and data to figure out which things truly slow aging and which speed it up. He considers the rapamycin result part of that game and part of the scientific method, and says he is fine with how it turned out.
He closes by saying he is laughing along with viewers who find the story funny, and calls irony "the love language of the universe." He says the lesson is not to stop trying new things. It is to share results whether or not they work, "that way we all learn."
For the past four years, I have been working with a team of medical professionals trying to build the world's best health protocol. Now, in doing this, we were trying one of the world's most promising experimental drugs for slowing down my speed of aging. Turns out I was actually accelerating my speed of aging. The name of the drug, rapamycin. Here's what happened.
Rapamycin was first discovered in the 1960s by scientists gathering a soil sample in a cave on Easter Island. In that soil sample, they found a bacterium that had powerful antifungal properties. They named that compound rapamycin. Researchers thought it might be the ultimate cure for many fungal problems such as athlete's foot. But before they could develop that further, they also discovered rapamycin was a powerful immunosuppressant. In some cases, immunosuppressants can save someone's life. But for large portions of the population, suppressing the immune system can be a death sentence.
In 1999, the FDA approved rapamycin's usage for organ transplant patients because of its immunosuppressant properties. The idea was that high doses of rapamycin would stop the body's immune system from attacking the organ that was just transplanted. Even now, this is a major problem with over a third of transplants being rejected by the body. And while there's been plenty of research, nobody made the connection of rapamycin and longevity until 2009.
In 2009, a study in older mice showed that dosing rapamycin increased lifespan for females 14% and males 9%. When they repeated the study in younger mice, they showed that rapamycin further increased longevity. Now, when they combined rapamycin with other drugs such as acarbose, they showed even further longevity benefits. In females, it was 28%, in males, it was 34%. The findings were replicated in other animals which gave researchers hope for the final test which was in humans.
Now in dosing humans with rapamycin, researchers were cautious because of the significant side effects they'd seen in organ transplant patients. These include metabolic disruptions like high cholesterol, tissue swelling, soft tissue infections, impaired wound healing. But more recent studies showed that intermittent dosing or lower doses reduce these side effects. Now, if they could mitigate the side effects, the positives were just too great to ignore.
So, let's get into the science. How does rapamycin work? Rapamycin's potential in longevity centers around its ability to inhibit something called mTORC1. This is a growth pathway whose overactivation plays a role in many age-related diseases. Now, if you want to naturally inhibit mTORC1, you can do things such as caloric restriction, fasting, exercise, and activators. Inhibiting mTORC1 is what rapamycin is doing directly.
So, what were the benefits? We were looking at reduction of my biological age, my speed of aging, and organ-specific biological age markers, as well as potential benefits for rejuvenation of the immune system and skin. But it's not free. Rapamycin also inhibits mTORC2, which has been linked to the side effects that we discussed before, the metabolic dysfunctions. Rapamycin also suppresses the immune system and specifically NK cells, your cancer killing cells. So it has a double-edged sword, making the dosing protocol very important. Other risks include disruptions in cholesterol, insulin and blood glucose, and finally potentially reduced gains in both exercise and muscle growth.
So, I knew all of this going in. So, what happened? First, this is what rapamycin looks like. It's a triangle-shaped pill. Now, knowing the risks of having too much rapamycin in my body to suppress my immune system, but also wanting just enough for the benefits, we tried many things. We tried protocols including five of these pills per week. We tried a protocol of six pills one week and 13 pills the next week. We tried 13 and 13, and then 90 minutes after taking the pills, we would take my blood and measure the level of rapamycin in my blood and then measure 24 hours later, 48, 72, 96. We were trying to assess how much rapamycin was in my blood, how fast did it decay back to zero. Now knowing that information, we then could figure out: is the dose appropriate for the effects, then also narrow enough to avoid the side effects.
Now, in doing this, I didn't notice any benefits. Everything seemed to be the same. I did, however, notice side effects. For example, I'd have cankers in my mouth, or maybe a wound wouldn't heal fast enough. My blood report showed that I had cholesterol disruptions. My blood glucose spiked a little bit. And then perhaps the thing that was most painful for me, it increased my resting heart rate, which as you know from watching my videos, is the most important biomarker I track every single day because it's the most influential thing determining my sleep quality. Now, these side effects continued for several years, but again, I was willing to make the trade-off for the potential longevity benefits.
Now, of course, in Blueprint, we are doing many things. So, it's always trying to isolate: is this thing causing that thing? Now, we suspected rapamycin would be the cause of these side effects because we'd read the literature. So, we wanted to put it to the test. So, with that in mind, we decided to test discontinuing rapamycin. And sure enough, without it, my blood glucose dropped, my cholesterol corrected, soft tissue infections went away. The side effects were in fact from rapamycin. Now, we also had some concerns about cancer. Remember, rapamycin suppresses the immune system including NK cells, which are your cancer fighting cells, and we were worried it might have some kind of long-term increased risk with this suppression.
Now, on October 27th, a month after we discontinued rapamycin, a preprint came out, which is a paper that they were evaluating several longevity interventions, including rapamycin. It showed that rapamycin accelerated the biological speed of aging in humans across 16 epigenetic clocks. This was huge news. Now, of course, what this means is irony hunts me. We talk about this on the channel a lot, which is it's kind of the funniest, most humorous outcome that could happen: a drug that I was taking for longevity actually was accelerating my speed of aging. So, you got to give it to irony. It's pretty funny.
Now, in saying all of this, we have to keep in mind rapamycin may in fact have all the benefits we've imagined, and that study was simply flawed for some reason. That's entirely a possibility. That is the way science works. We are taking a cautious step at this point though and observing that data, and want to see more data that comes out that could refute that. It's always important to be cautious as you see new evidence emerge.
Now did I cause myself lasting damage by taking rapamycin? Maybe. I don't know. A lot of people think that I take excessive risk in doing these things. And I always remind them they too are taking risks. When you eat that fast food meal or you go to bed late, those effects are known. You are accelerating your speed of aging. You're causing metabolic disruption in your body. So, this is a game we're playing: we're trying to figure out using science and data which things legitimately slow down the speed of aging and which things accelerate it. I consider it to be part of the game. I'm fine with the whole outcome. It's just part of the scientific method.
For those of you who are laughing at home, I'm with you, laughing with you. Irony is the love language of the universe. The conclusion here is not to try new things. The conclusion here is to share things, whether they work or whether they don't. That way we all learn.
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