No Biological Free Lunches

“When we try to pick out anything by itself, we find it hitched to everything else in the Universe.”
— John Muir

“The light that burns twice as bright burns half as long, and you have burned so very, very brightly, Roy.”
— Blade Runner

There are few or no biological free lunches. 

This short post will cover the essentials of how this principle applies to performance-enhancing drugs.

But before we dive in, let’s watch some entertainment that drives the point home…

Growth agents have a place in medicine¹, and some sports effectively require them at higher levels. That said, there are risks when you turn the volume to 11 within complex hormonal cascades with equally complex feedback loops. I have some personal experience here. When I long ago had my shoulder completely reconstructed (video here; viewer discretion is advised), a portfolio of anabolic drugs was part of the recovery plan. This wasn’t advised by my surgeon. I found gray-area longevity doctors recommended by world-class athletes, and the cocktail was incredibly effective for regaining full range of motion.

Physical optimization is fundamentally about trade-offs.

And if you ask “Is this risky?,” the follow-up question is sometimes relative: “Risky as compared to what?” In this case, I decided that using these powerful drugs with supervision was an acceptable risk relative to the likelihood of otherwise never regaining full function of my left shoulder.

I did a ton of homework, I budgeted for possible problems, and I didn’t take it lightly.

It’s alarming how many folks now treat “T” or “TRT” (testosterone replacement therapy) as something akin to taking a multivitamin, when they never would have considered taking androgenic-anabolic steroids (AAS) a few years earlier. Like Patagonian toothfish has become Chilean sea bass on fashionable menus worldwide, it’s quite the rebrand story, but that doesn’t change the underlying biology.

It also doesn’t change the underlying “replacement” part of TRT, which applies to many drugs.

If you take something exogenously (originating from outside an organism; think “exo” of exoskeleton) that your body produces endogenously (originating from inside an organism), your body—in its infinite wisdom—will reduce or stop producing said something. Endocrinology abhors waste. This is why many men’s testicles will shrink down to Raisinets when they take supplemental testosterone, and for a decent percentage of those men, the deflated balloons will not return to baseline function without post-cycle therapy (PCT) drugs like Clomid/clomifene and/or hCG. Side note: just as with testosterone, you shouldn’t casually take hCG. Faustian bargains abound if you don’t have a basic grasp of the systems you’re tinkering with.

This also applies to supplements and food. The more technical FDA definition of “drug” highlights a legal distinction, not a pharmacological one. If something’s intended to produce a change in your body, consider it a drug and you’ll make fewer mistakes. This is helpful reframing, whether the input is a prescription drug, illicit drug, peptide, mineral, supplement, or banana.

Separately, many growth agents aren’t hyper-selective (e.g., human growth hormone [HGH], IGF-1), meaning that they don’t just affect one tissue type. If, like some enhanced Major League Baseball players, your head jumps a few helmet sizes, that enlarged cranium won’t shrink when your muscles atrophy after getting off the sauce. Ditto if you unknowingly supersize your liver and spleen. It’s hard to hit undo on Dolph Lundgren jawlines if you’re a woman, it can be tricky to unwind drug-induced breast tissue growth (gynecomastia) if you’re a male, and it’s hard to whisper your organs down a size if you’re a human.

Think very carefully about which doors are two-way doors—reversible—and which are one-way doors. Best to measure twice and cut once.

This is not to say there isn’t a place for TRT. There is. But the use case matters, and the dose makes the poison. If I were 50+ years old and had chronically low testosterone plus symptoms of low testosterone plus I’d been evaluated for possible reversible causes of low T, I might consider TRT to bring me within physiologically normal levels. This is fundamentally different from someone taking supraphysiological doses—amounts greater than normally found in the body—for getting swole like a kangaroo.

This all might seem complicated, but most of what I’m saying boils down to basic logic and a few guidelines. 

I’m not a doctor, and I don’t play one on the Internet, but the below heuristics have helped me avoid a lot of problems with performance-enhancing “drugs,” as broadly defined earlier:

1. Assume there is no biological free lunch.
   
   
2. Assume that the larger the amplitude of positive effect of *anything*, the larger the amplitude of side effects, whether they are known or unknown. This could apply to modafinil or a high-octane macchiato.
   
   
3. Don’t ask a barber if you need a haircut. If someone is selling the thing you’re considering, or its use has become their identity, expect biased advice.
   
   
4. Replicate before you escalate. This comes back to “measure twice, cut once.” I’ve seen many friends take dramatic steps before replicating their tests. If you booze over the weekend, sleep like garbage, and then do a blood draw later AM on Monday, you might find that—gasp!—you have low testosterone. Before you pull out the big guns, perhaps you should repeat the test on two Wednesdays and do so earlier in the morning, when T will typically be higher. Some evidence also suggests predictable seasonal variations in T levels. Last but not least, labs make mistakes. I recall one well-respected lab for allergy testing returning 100% positive results for black bean allergy to all of their clients for a two-week period. It was a lab error. Before any intervention with possible side effects, replicate.
   
   
5. I routinely cycle off of drugs and supplements I can safely cycle off of for short periods of time. This might be one week every two months and one entire month a year. These are basically intermittent wash-out periods, intended to allow my body to reestablish some homeostasis and feedback loops without a bunch of confounding variables. Put another way, we don’t know what we don’t know, and some medically supervised form of pharma-fasting is an insurance policy. I think about cheap insurance in life a lot. THIS DOES NOT APPLY TO CRITICAL MEDICATIONS, AND YOU SHOULD SPEAK WITH YOUR DOCTOR BEFORE MAKING ANY CHANGES TO YOUR HEALTHCARE REGIMEN. Please don’t win any Darwin Awards.
   
   
6. Know how you could get off of any substance before you get on it. Our understanding of biology is incomplete, so as with any form of gambling, no matter how informed, know your exit plan before you sit down at the table.
   
   
7. Biceps are temporary, baseball helmet sizes are forever.

Choose wisely and play the long game, my friends.

– T

P.S. Sincere thanks to AS, PA, SG, KS, and MN for reading drafts and providing feedback. Of course, any screwups are mine. In timely news, the following came out in Forbes, just as I was about to hit publish: “Billionaire Peter Thiel Backs Doping-Friendly Olympics Rival — What To Know About The ‘Enhanced Games.’” I’ll certainly watch this competition, but truth be told, the doping Olympics already exists, and it’s called the Olympics. Athletes and coaches just have to be champions in two categories simultaneously: their sport and cat-and-mouse drug testing. I suggest the podcasts, documentaries, and books below for a taste of how sophisticated this has become.

Additional resources:

Use of Growth Hormone, IGF-I, and Insulin for Anabolic Purpose: Pharmacological Basis, Methods of Detection, and Adverse Effects

All things testosterone and testosterone replacement therapy by Dr. Peter Attia. (Exclusively for my audience, Peter kindly made this podcast episode—a 2-hour deep dive on testosterone and TRT—available for free. It is normally behind a paywall and part of Dr. Peter Attia’s membership, which offers extensive show notes for every podcast episode, member-only “Ask Me Anything” episodes, premium articles produced by Peter and his dedicated team of world-class research analysts, and much more. Click here to learn more about becoming a member.)

Bigger, Stronger, Faster (Documentary)  

Icarus (Documentary)

Anabolics, 11th Edition by William Llewellyn

Game of Shadows: Barry Bonds, BALCO, and the Steroids Scandal that Rocked Professional Sports by Mark Fainaru-Wada and Lance Williams

“The World’s Most Famous Performance-Enhancement Chemist” (Podcast episode on The Tim Ferriss Show with Patrick Arnold.)

Patrick Arnold, widely considered “the father of prohormones,” is an organic chemist known for introducing androstenedione (remember Mark McGwire?), 1-Androstenediol (marketed as “1-AD”), and methylhexanamine into the dietary supplement market.

He also created the designer steroid tetrahydrogestrinone, best known as THG and “the clear.” THG, along with two other anabolic steroids that Patrick manufactured (best known: norboletone), were not banned at the time of their creation. They were hard-to-detect drugs at the heart of the BALCO professional sports doping scandal, which thrust Barry Bonds and others into the spotlight. BALCO distributed these worldwide to world-class athletes in a wide variety of sports, ranging from track and field to professional baseball and football.

1. Some types of hypopituitarism, wasting syndromes/diseases, surgical care, etc. ↩︎

The Tim Ferriss Show is one of the most popular podcasts in the world with more than one billion downloads. It has been selected for "Best of Apple Podcasts" three times, it is often the #1 interview podcast across all of Apple Podcasts, and it's been ranked #1 out of 400,000+ podcasts on many occasions. To listen to any of the past episodes for free, check out this page.