The Popular Longevity Supplement That Can Physically "Break" Your Heart, or Even Potentially Kill You

(And What I Recommend to Stay Safe AND Improve Longevity Instead)

By Brenden Henry

Most people have no idea how close they are to hurting themselves with the supplements they take.

Over the years I have witnessed countless people thinking they were about to partake in something that would be good for them.

But the wild part of it all is, that:

It’s usually not your average, mostly sedentary, junk-food eating person who's about to get into serious trouble (though they will eventually if they keep that up).

It’s the researchers and biohackers who:

• Listen to every podcast

• Read studies all day

• Optimize their stack every few months

• Combine various “longevity” compounds because some influencer said it was good.

These are the people who walk straight into biological landmines.

Not because they’re stupid. They at least usually understand “this does that”.

But because nobody ever taught them how all of the pathways that a single supplement affects can potentially interact with other pathways including other supplements.

That’s the embarrassing truth about the current longevity space too:

Most of the people recommending supplement stacks have no idea what they’re doing to the core control systems of biology.

They see a study saying berberine is good for diabetics (which is true)...

But without realizing that it also effects:

• mitochondrial Complex I

• cardiac electrophysiology

And that combining it with other supplements that affect these pathways could result in damage.

Sometimes permanent damage.

This is the story of one man who found that out the hard way.
A smart, highly informed biohacker who now lives with a pacemaker.

Because he started taking 2 "highly recommended" supplements together, which many people still recommend to this day.

The Guy Who Did “Everything Right”

Earlier this year I was taking the history from an older gentleman who became a client.

He wasn’t your average client. He was:

• Highly intelligent

• Deep into health research

• Listened to podcasts

• Followed the big biohacking channels

• Actually read primary literature and even conducted some studies of his own.

Exactly the kind of person who should, in theory, be safer than average.

His main focus a few years earlier was on optimizing insulin sensitivity and reducing his long term cardiovascular risk. 

You know, the usual list of metabolic syndrome stuff:

• Central fat gain

• High triglycerides

• Low HDL

• High blood pressure

• Insulin resistance

So he started taking metformin, one of the most common glucose-lowering drugs on the planet.

Whether metformin is the “best” choice for glucose lowering is neither here nor there. There are strong arguments for SGLT2 inhibitors or even other agents, including natural supplements in specific contexts. But that wasn’t his real mistake.

The problem came later.

Because he didn’t just stay on metformin. He did what every “motivated” person does: He started stacking.

And there's nothing inherently wrong with stacking, it's one of the most foundational and biggest moves you can make to get a greater biological optimization.

But it can cause harm if done wrong.

The Stack That Broke His Heart

At some point, after hearing the same advice repeated by enough influencers, blogs, and “evidence-based” supplement companies, he added berberine.

Metformin + Berberine.

You have probably heard about berberine, as it's often referred to as:

• “Metformin mimetic”

• “Powerful AMPK activator”

• “As effective as metformin for glucose control”

• “Great for longevity stacks”

And to be clear:
Berberine does work for glucose and lipids in many people.
That’s why it’s so popular.

But here’s the problem:

Both of these compounds converge on the same upstream system:

Mitochondrial Complex I, with both of them acting as an inhibitor of this electron transport chain ¹ ².

In fact, it's partly how either of them result in glucose lowering, by reducing ATP production within the mitochondria leading to a higher ratio of AMP/ADP in various tissues. (But it's not the only mechanism).

What you’re actually doing is:

• reducing oxidative phosphorylation capacity

• forcing cells into a lower-energy operating mode

For some tissues, intermittently, or slightly, that can be fine or even beneficial in certain contexts like glucose lowering.

For others?

It’s a massive problem.

Especially the tissues that never get to rest.

Like the heart.

Why the Heart Got Hit First

Cardiac conduction tissue runs on a very small margin of energy. Once you start inhibiting that, here’s what can and DID happen to this gentleman over time:

• He stayed on metformin.

• He added berberine.

• He kept both going, long-term, because his markers looked “great.”

• Eventually he began feeling fatigued, light-headed, occasionally close to passing out.

By the time he landed in the ER, his heart rate was dropping into dangerous territory. He had symptomatic bradyarrhythmias.

You see, what happens if you inhibit mitochondrial complex 1 too far is, quite literally, death. 

We have seen this with potent inhibitors like rotenone³.

But as it turns out, Berberine has an additional mechanism of action: 

It is an agonist of the M2 muscarinic receptor, with an affinity that is similar to the classic agonist carbachol.  

In neonatal rodent cardiomyocytes, berberine causes the contraction rate of the heart to drop ⁴.

At the hospital, Cardiology ran an EKG and Echo and diagnosed him with:

A conduction disease, which led to him ultimately getting a pacemaker later on.

Could you prove that the metformin + berberine combo was the only cause? No. But mechanistically, the stack created the perfect storm for a vulnerable conduction system as he was effectively reducing ATP in the very cells responsible for generating and propagating his heartbeat.

Which is risky in of itself, but the muscarinic m2 agonism was putting the brakes on his heart beat. 

Could a younger person with resilient conduction tissue tolerate that for a while? Maybe.

An older person with subclinical conduction weakness?

You’ve just pushed them over the edge.

And this is not the only case of this happening. This clients friend, a renown longevity influencer, had a similar scare, though did not end up with a pacemaker because he caught the problem soon enough. Unfortunately he didn’t want to share that story with anyone because he was worried it might turn people away from biohacking.

I think you deserve to know the truth.

We need to talk openly about the risks in biohacking, not just the wins. These things happen when people are stacking supplements without understanding the full impact on the body’s control systems.

“But Everyone Recommends Metformin or Berberine…”

Exactly.

That’s the problem.

People are recommending supplements that they don't understand. And then some people, including those who do their own research, often miss something. 

Sometimes something very important. 

And the result is potentially deadly.

That’s why I Built CEL and the Biological Recode System

The entire purpose behind the Biological Recode System is to give people a map of the control architecture so they’re not guessing. 

Provide them with a tool, “The Biorecode Engine”, that takes individual biomarkers, symptoms, and advanced “stacking” principles into consideration before providing you a program to follow. 

And if you don’t want to risk biohacking yourself, I’d highly recommend you check that out here

To Rewriting Your Biology,
Brenden Henry
Former Biomedical Engineer
Founder of Peptide Science Institute &
CuttingEdgeLongevity