Longevity influencer Bryan Johnson stirred up a ton of interest when he started a microdosing experiment about a year ago [1].
His experiment had some unexpected results — as we’ll see in a minute. And it helped fuel the exploding microdosing trend. So let’s take a look at the logic behind microdosing GLP-1 and GIP meds (the combination found in Tirzepatide), and then address the crucial question: Is this even a good idea?
Table of Contents
- Why Microdosing?
- Anti-Inflammatory and Anti-Aging Potential
- Calorie Restriction Mimicry
- Risks
- So what happened to Bryan Johnson?
- References
Why Microdosing?
The story of the discovery of glucagon-like peptide 1 (GLP-1) is a fascinating one.
For decades, researchers knew the gut signaled the pancreas to release insulin in response to food. But they didn’t know exactly how. So they were on the hunt for the hormone involved.
After exhaustive research efforts, GLP-1 was finally identified in 1986 [2]. This hormone turned out to have a powerful range of effects. Most significantly, it stimulates insulin production, slows the emptying of food from the stomach, and increases feelings of satiety [3].
Initially, the excitement was about creating a medicine that would mimic GLP-1 to treat type 2 diabetes. By 2005, the first GLP-1 medication gained FDA approval in the U.S. [4].
But it soon became apparent GLP-1 medications had another incredibly important effect: they were helping people shed massive amounts of weight. That led to the approval in 2021 of the GLP-1 med semaglutide under the name Wegovy for weight loss [4].
And new studies are constantly emerging that reveal additional possible benefits for this class of medication.
That’s why Bryan Johnson set out to test the effects of GLP-1 meds on himself in late 2024. He used a medication called Tirzepatide, which mimics the action of GLP-1 plus another hormone called GIP [1].
So what was his reasoning? He’s neither overweight nor diabetic. Instead, he wanted to test their potential to combat aging and extend lifespan [1].
Anti-Inflammatory and Anti-Aging Potential
One effect he had in mind is the anti-inflammatory action of GLP-1s.
Numerous studies are uncovering this and clarifying the mechanisms. GLP-1 receptor agonists (GLP-1RAs) have emerged as promising therapeutic agents with potent anti-inflammatory properties and diverse clinical implications [5].
Chronic inflammation is associated with aging, and it’s a risk factor for chronic disease and mortality [6]. It’s also a driver of the world’s top killer — heart disease.
Calorie Restriction Mimicry
Another mechanism Johnson pointed to was caloric restriction mimicry.
Researchers have found that reducing calorie intake — without malnutrition — extends healthy lifespan in numerous organisms. It improves risk factors related to type 2 diabetes, heart disease, cancer, and diseases like dementia affecting the brain [7].
But why would cutting back our calorie intake have this effect?
There are several mechanisms involved. One key player is the mTOR pathway. You can think of it like a switch with a “build” setting and a “repair” setting. When there are plenty of resources — that is, when we’re eating normally and especially getting adequate protein — the switch is set to “build.” This tells cells to grow, multiply, and produce proteins.
But when calorie intake is reduced, resources are limited. The mTOR pathway flips to the “repair” setting, activating cellular repair processes [8].
Multiple studies link the mTOR pathway to aging. Interventions like calorie restriction that nudge mTOR into the “repair” mode have been shown to extend lifespan in yeast, worms, flies, and mice [8].
The CALERIE study tested a 25% calorie restriction diet in humans for 2 years. It looked at metrics like blood pressure, lipids, insulin response, and other cardiometabolic risk factors. The results were positive, with significant reductions in multiple risk markers related to heart disease and type 2 diabetes [9].
Participants did lose weight — about 7.5 kg (roughly 16 pounds) — but researchers found the benefits remained even after controlling for weight loss. That means calorie restriction itself drove the improvements, not just the drop in body weight [9].
So where do GLP-1s come in?
Johnson cites their ability to mimic the effects of calorie restriction.
A recent study tested this in mice using a low dose of GLP-1 medication — small enough to have negligible effects on body weight and food consumption [10]. This allowed researchers to isolate benefits unrelated to weight loss.
Researchers administered a daily intraperitoneal dose of exenatide (5 nmol/kg body weight) to 11-month-old mice, continuing the treatment for 30 weeks [10].
The results were impressive: GLP-1 medication counteracted age-related decline across multiple body systems, including the circulatory system and tissues throughout the body [10].
The effects were similar to those of calorie restriction and rapamycin, both of which work by flipping the mTOR switch into repair mode. Researchers found substantial overlap between the effects of GLP-1 and rapamycin in terms of how they influenced biological pathways [10].
Johnson also pointed to potential benefits of GLP-1 medications in reducing the risk of heart disease, Alzheimer’s, and cancer — all of which have been supported by recent research [4].
With this impressive — albeit still hypothetical — set of benefits, Johnson’s experiment makes sense.
But why microdosing?
He used just 1/5 of the typical dose of Tirzepatide. The idea was to harness the potential benefits we’ve discussed — without causing weight loss, which wasn’t his goal [1].
Risks
So how did Johnson’s experiment turn out?
We’ll return to that in a moment. But first, let’s address the risks — because his experiment helped drive the accelerating trend of microdosing GLP-1s in pursuit of longevity.
One major risk is muscle loss. With any weight loss strategy — including GLP-1s — lean mass loss can range from 25–40% of the total weight lost [11].
While we’re talking about microdosing here (with the goal of avoiding significant weight loss), the truth is that we don’t know what dose is small enough to avoid weight loss while still delivering health benefits. Even a so-called “micro” dose might lead to unintended weight and muscle loss.
This is a big concern because muscle mass naturally declines with age — about 1% per year starting at age 40 [12]. Over time, this loss contributes to frailty, immobility, and loss of independence.
So the real risk is this: Healthy older adults could be experimenting with GLP-1s and unintentionally shedding muscle mass at a time when they can least afford it — possibly undermining any longevity benefits.
Then there are the known side effects of GLP-1s. The most common are gastrointestinal symptoms like nausea, vomiting, diarrhea, constipation, and cramps [13].
More serious — though rare — adverse effects include pancreatitis, kidney or gallbladder injury, and vision problems [13].
There have also been concerns about thyroid cancer, but a recent large study across multiple cohorts found no increased short-term risk [14].
Again, the hope with microdosing is to avoid these side effects.
But — and this is critical — that’s just a hope. There are no studies yet that examine the effects of small doses of GLP-1s in non-obese, non-diabetic, healthy adults.
Intriguingly, a clinical trial is currently underway to do just that. It’s expected to be completed by the end of this year [15].
Until then, we lack long-term safety data, and we don’t know whether microdosing GLP-1s is effective or safe.
So what happened to Bryan Johnson?
His story becomes something of a cautionary tale.
He quit his microdosing experiment after just 3 weeks. Why? His resting heart rate increased by 7% — a known side effect of Tirzepatide, even at normal doses. Johnson hadn’t expected that effect at such a small dose [16].
And even if Tirzepatide hadn’t caused any side effects for Johnson, we still wouldn’t be able to draw clinical conclusions. Just because something works (or doesn’t) for one person doesn’t mean it will for others — especially in Johnson’s case, where he’s taking numerous other supplements and medications.
This highlights just how much we don’t know right now. The benefits of microdosing GLP-1s are still completely hypothetical.
The risks, on the other hand, are known.
For people who are overweight or have type 2 diabetes, GLP-1s are a game changer. They deliver significant improvements in risk metrics for serious chronic diseases. And in most cases, the benefits outweigh the costs.
But for my patients who aren’t overweight or aren’t managing diabetes, I don’t recommend microdosing GLP-1s — just like I don’t recommend metformin to those same patients, and for very similar reasons.
References
1. https://x.com/bryan_johnson/status/1869779170945126850
2. https://www.pnas.org/doi/10.1073/pnas.2415550121
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC6812410/
4. https://www.nature.com/articles/s41392-024-01931-z
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC10823863/
6. https://pubmed.ncbi.nlm.nih.gov/37501048/
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC9036399/
8. https://www.mdpi.com/2308-3417/5/4/95
9. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30151-2/abstract
10. https://www.biorxiv.org/content/10.1101/2024.05.06.592653v1
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC12322565/
12. https://pmc.ncbi.nlm.nih.gov/articles/PMC5772850/
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC11790292/
14. https://www.liebertpub.com/doi/10.1089/thy.2024.0387
15. https://clinicaltrials.gov/study/NCT07092605
16. https://x.com/bryan_johnson/status/1885024727095529895?lang=en
