I’m a PRACTICING board-certified neurosurgeon with a dedicated health and wellness practice, and I’ve been in this space for a decades. I want to offer a perspective you won’t often hear from the influencer ecosystem.
The internet has done real damage to the practice of medicine. There’s an entire industry built around health content — podcasts, substacks, supplement lines — populated by people who have never examined a patient, written a prescription, or sat with someone at the end of their life. Some are physicians who have traded clinical rigor for revenue. Others aren’t physicians at all. What they share is a business model that depends on your continued engagement and purchasing, not your outcomes.
Peptides are a good example. Most have limited efficacy data, and several carry mechanisms of action that should give thoughtful clinicians pause. Structurally, peptides are amino acid chains — the same basic chemistry as the misfolded proteins responsible for prion diseases like CJD. I’ve cared for patients with that disease. They die within weeks. In that context, I’ll just say this: be careful what you put into your body based on the advice of someone whose income depends on your doing so (and by proxy, even your viewership).
There are excellent, experienced physicians out there — people who stay current, think critically, and don’t have a supplement line. Seek them out before changing your protocols. And BTW, Attia is NOT one of them. Were it not for Tim Ferris and Oprah, he would be a destitute flunky. And there are many more like him…
One of the main postulates of quantum physics says that information is never lost. None. It means that all our dirty jokes, dubious acquaintances and stupid comments have been recorded. Bits of this information is scrambled and not accessible to us, but imagine that it was. Imagine that this global database has been released just as
Epstein files. Would all of us, Peter’s critics, look clean?
You may argue that PA is a social media influencer and we’re not. Maybe not. At least at his scale. But aren’t we influencing people in our proximity? Our children, family, friends, colleagues, teammates? The size of scale is not an excuse. Besides, he has never pretended to be a moral authority.
Ask yourself how much were you really harmed by his bad personal decisions? And how much did you benefit from the insights of Peter and his guests? Are you ready to erase it along with Peter?
I am not.
"“In the armory of thought man forges the weapons by which he destroys himself; he also fashions the tools with which he builds himself heavenly mansions of joy and strength and peace…between these two extremes are all grades of character, and man is the maker and master…and shaper of condition, environment and destiny…All that a man achieves and all that he fails to achieve is the direct result of his own thoughts.”
~ From James Allen, As a Man Thinketh.
I agree that association with a person convicted with what Epstein has been convicted at the time of correspondence is not the same as spreading dumb jokes around. It’s another league. But… just curious, how many people knew that PA is communicating with Epstein? It’s not a spy thriller, some of those with whom he was fairly close, and who is actively erasing him now, must have been aware. Also, it’s not possible to undo good things that he has done to many of us. Here is the hard one: would you deny the help of a good doctor if you knew about him what you knew about PA, and if your health was at stake? Say, oncologist.
Yes and a hint of the prevalent anti-science crowd who freely exploit the work of scientists (up to and including the mere fact that they are alive to decry science) using the latest scientific advancements and derivatives thereof.
As a younger man, I found it easier to find footing on moral high ground. Today, nearsightedness has revealed that I have little such purchase. I do not respect what Attia did in the past nor do I respect his less than full throated repudiation of it, but I have only my hope that I would have done better in the same situation and, frankly, I doubt that I would have.
I don’t suppose I had in mind all of the accusations leveled at Attia when I made my comment. I was focused on his failing to disassociate with JE at the point that he likely knew better, as evidenced in at least one of his emails. None of us can understand the nuanced issues in the development of the relationship. We do know that after the fact logical reconstructions are, like memories, partially reconstructed and virtually always inaccurate to some degree. I allow that our full understanding of the nuance might change our views, at least slightly.
I tend to agree about Peter. Most people can’t relate to how things work among the extremely wealthy party set. Look up the Jimmy Saville scandal for another example. There are several more Epstein and Saville types out there whose names we don’t know. Meanwhile, Matt Karberlein has stepped up with an excellent podcast on brain health. I hope Peter comes back with good guests again because he excels as an interviewer.
If my life depended on it and the best oncologist happened to be a mass murderer, I’d still choose him every day and twice on Sundays.
That said, respectfully, I don’t think those two things are really connected.
I’m not trying to compare PA to an actual criminal, but I don’t think that talent, money, nor the good someone has done should affect whether or not they’re held accountable.
I haven’t seen anyone suggest people undo the good they’ve received from PA. I’m still on rapa and I’ll continue to check my ApoB, just as Pulp Fiction will remain my favorite movie, all while hoping Weinstein remains in jail.
My personal goal is to never give the rich and famous any more leeway than I’d give a janitor. In fact, I’d rather reserve my sympathy for a janitor who actually shows contrition.
Certainly poor judgement on Peter’s point, not sure that reduces his expertise or his guests. Although there is no evidence that he did anything illegal. If we are going to place guilt by association with Epstein, the we need to be consistent. Bill Clinton, Bill Gates, Steve Bannon, Ehud Barak, Sergey Brin, Deepak Chopra, David Copperfield, Stephen Hawking to name a few.
Following some peoples logic on this post about PA being medically discredited due to a link with Epstein, I guess nobody should listen to Bill Gates about any health or vaccine related opinions. Hell, Gates has 0 medical or health education and many think he walks on water on vaccines and virius’s. (some in Africa might have a different opinion).
I listened to his previous podcast on metabolic clocks while hiking the other day. It was a little strange to hear him carry the whole show sans guests but he pulled it off with precision and a without the off-point rambling common to other gero podcasters.
While I was familiar with perhaps 80% of the content, I admired his precision and concision. Anyone who doubts his understanding or his teaching skills is not paying attention.
Is anyone still paying to hear Peter’s AMA podcasts? Im curious what he had to say about SS-31. He times those “free” previews perfectly to cut off when he is about to start talking about the relevant stuff.
It is actually the shortest peptide Peter is aware of—it’s a synthetic 4 amino acid peptide
Peter points out, “It’s synthetic, meaning this peptide does not exist by itself in nature, it was synthesized for a very important purpose, and it is popularly used for mitochondrial health.”
Peter has seen many ads for this on Instagram, and it’s promoted all over the place for mitochondrial health, longevity, improved exercise performance, better cognitive function, cardiometabolic benefits
He gets patients pinging him about this constantly
What do we know about it?
It actually is an FDA-approved peptide
It has an FDA-approved indication, it’s sold under the brand name Forzinity
SS-31 is the name that it is sold under on the gray market
And it is used for treating a very rare and severe X-linked mitochondrial disease known as Barth syndrome
X-linked just means that the gene travels on the X chromosome (it’s a genetic condition)
It is a disease that presents in very early life with cardiomyopathy, skeletal muscle weakness, growth delay, chronically low white blood cell counts, that leads to significant infections
It’s actually a pretty dramatic disease
Historically, Barth syndrome was almost always fatal during childhood
And even today with all the medical advances we have, people really struggle with this condition to live beyond their 40s or maybe their 50s
Childhood mortality is very substantial with this
This is one of those diseases that’s referred to as an orphan disease, meaning it’s very rare, but obviously has significant morbidity and mortality associated with it
Back to the mechanism of action
SS-31 is kind of interesting ‒ virtually every drug out there, whether it be a small molecule or a peptide, they usually bind to specific receptors
That’s actually NOT the case with SS-31—instead, it selectively binds something called cardiolipin
Now, this is a phospholipid that’s found in the mitochondria, specifically on the inner mitochondrial membrane
And cardiolipin helps maintain the structure of the membrane and support the folds where the electron transport chain is located
This in turn, of course, is responsible for producing the vast majority of energy in the cell in the form of ATP
Listeners will remember this was discussed in detail in the podcast with Nav Chandel when we talked about mitochondria
So, this mechanism makes sense for treating somebody with Barth syndrome, which is caused by defective cardiolipin remodeling—which leads to mitochondrial dysfunction in high energy tissues, like the heart and skeletal muscle
This is why they present with cardiomyopathy and profound skeletal muscle weakness
But then the question is, so if we just stop there, you might say, “Well, should we be using this if we don’t have Barth syndrome?” Well, let’s think about that.
If you bind cardiolipin, SS-31 does appear to stabilize the intermitochondrial membrane, which can improve electron transport chain efficiency, again, reducing the generation of excess reactive oxygen species
In preclinical and early human work, this translates to better mitochondrial function and ATP [production]
So it is a viable mechanism, at least if we just want to leave it at that first question
Does the mechanistic rationale for SS-31 translate into measurable benefits? [22:15]
If it is a viable mechanism, do we have any evidence that it has the intended downstream effects in humans?
For those with Barth syndrome, the answer is yes
There was a very small study—which is understandable given how rare this disease is
The study was called the TAZPOWER trial that had 12 males with genetically confirmed Barth syndrome, and they received 40 mg of the equivalent of SS-31 subcutaneously once daily in a randomized double-blinded placebo-controlled crossover design
A crossover designs allows you to give 6 people a treatment, the other 6 would get the placebo, you would run them out, and then you would do a washout and then flip it
So, it’s more statistically powerful
It was followed by an open-label extension that ran for almost 4 years
What were they measuring in these people, and what were the results?
Remember, these people are severely, severely limited
So, it’s not like you’re testing their VO2 max, this was done based on a 6-minute walk test
⇒ The improvement, based on the use of the drug, was going from about 400 meters (so walking a quarter mile in 6 minutes), adding somewhere between 60-90 meters to that, over 6 to 24 weeks
They also tested quad strength with leg extensions
⇒ People on this drug experienced a 40 to 50% improvement in leg extension strength
The other thing that Peter thinks is really exciting (in the sense that it’s really nice when you see biochemistry at work), is the ratio of pathological to mature cardiolipin fell by roughly 40-50%, which aligned with the functional improvement
So, again, you’re very confident that what you were seeing was due to the intended consequence of the drug
Now, the bigger question is: If you go outside of Barth syndrome, do we have any evidence that this is going to work?
Here Peter would say the evidence is pretty thin when we’re talking about enhancement of a generally healthy individual (which is what this is about)
Peter has yet to see a single Instagram ad talking about cardiolipin, SS-31, for people with Barth syndrome
Everything he’s seeing is “longevity health influencer space,” and so that’s what he will focus on
There were a handful of other small RCTs that assessed SS-31 for patients with heart failure (so these people don’t have Barth syndrome)—they’ve arrived at heart failure, almost always through to atherosclerosis with reduced ejection fraction
Even some age-related macular degeneration studies
But they didn’t show any significant improvement on their primary endpoints
Even a trial that investigated SS-31 for mitochondrial myopathies (that were different from Barth syndrome) haven’t been promising
There was a phase III study called the MMPOWER-3 trial in primary mitochondrial myopathy patients, and it didn’t show a difference in the primary endpoint
Which was the 6-minute walk test
Although the patients subjectively reported lower fatigue
This suggests to Peter that unless you have a defect, a cardiolipin stabilizer like SS-31 isn’t going to do anything
The upshot here is Peter doesn’t think we can assume that anybody, absent somebody with Barth syndrome, is really going to experience a benefit associated with using SS-31, shy of a placebo effect
SS-31 continued: safety considerations, gray market risks, the balance of risk versus reward, and why it belongs in bucket #3 [26:00]
What do we know about if we have any safety data or even data to inform potential usage protocols for SS-31?
The evidence for safety is there in Barth syndrome because it is an FDA-approved drug
But again, that’s a pretty extreme phenotype
Across all the trials we’ve discussed, the safety profile was definitely fair
Peter didn’t see anything that was of concern
The main side effect was injection site reactions
That’s incredibly common and nothing to be concerned with
Peter’s takeaway is that safety was not an issue
Also, these things are cleared pretty quickly
As it true for many peptides
So within 48 hours, it’s mostly gone
Now everything Peter just said is based on the FDA-approved product
Nobody can make those claims for these gray market products
Where you don’t have any idea what the purity is
You have no sense of anything from contamination risks to lack of sterility
Again, you’re giving up the good manufacturing processes that are typically done in drugs
Based on all of that, when looking at SS-31, how are you thinking about the balance of potential risk versus reward?
Mechanistically, SS-31 is very strong and it makes sense as a mitochondrial target
It targets cardiolipin, it stabilizes the inner membrane, it improves ATP production, etc.
But it appears that it only does this in people that have a very, very serious genetic condition that is compromised by everything we just discussed
Again, we see that it can improve by 20-25% the 6-minute walk test, and 40-50% in leg extension
So if you have Barth syndrome, Peter thinks this drug is a godsend
But when you go beyond that very, very niche orphan application, the story is remarkably unimpressive
“The claims that SS-31 slows aging or boosts energy or enhances performance are completely speculative.”‒ Peter Attia
Peter is not going to doubt that there are people out there who are claiming that this drug has helped them
But when you’re dealing with the power of the placebo effect, you have to rely on clinical data, randomized blinded clinical data
And when we’ve looked at those, the answer is not there for even other populations such as these primary mitochondrial myopathies
Putting this all together, Peter would say SS-31 looks useful in a very specific orphan condition, and otherwise he thinks it’s mostly a bunch of marketing
For people thinking about this, are there any other legitimate approved alternatives available?
Yes, but it’s ridiculous—the FDA version sells for $800,000 a year
It’s an infuriating reality of these orphan drugs
Although in fairness to the companies that develop them, when they’re developing a drug for so few people, they have to recoup their costs (although Peter is not sure that that cost is fully justifiable)
Obviously, the gray market versions are incredibly cheap relative to this, but even using a pretty low theoretical dose like 4 mg per day (which is a dose that was studied, but was ineffective in the heart failure trial), you’re still spending $10,000 a year
And there you’re buying something that is unregulated and you don’t know your purity and stuff like that
A legitimate version exists, it’s just not economical for anybody; and the gray market version isn’t cheap—Peter doesn’t think it’s justifiable
Wrapping up SS-31, what bucket do you put it in from the framework earlier?
Peter puts it in bucket #3
It has a viable mechanism via the cardiolipin binding
It’s approved for use in this very rare, severe mitochondrial defect
We have safety and efficacy data for that group, but it’s not approved beyond it
Peter’s recommendation would be to probably pass on this
He doesn’t think it makes sense to do either the approved version of the drug for $800,000 a year or the non-approved version at $10,000 a year
This is one reason why certain types of memory work as they do. Forgetting and constructive re-remembering are essential to the construction of a character-driven self-image. More often called our “better angels,” we imbue ourselves with aspirational character based on selective recall and reconstruction.