Metformin as an Electroceutical

These days, one of the most exciting fields with implications in regenerative medicine, cancer biology, and longevity is bioelectricity.

If this is your first foray into bioelectricity, the first thing to know is that, despite it being a relatively recently recognized branch of science, researchers have been making observations related to bioelectricity for decades.

In May 2021 I read an article that forever changed my perspective on medicine and health research. The article was called “Persuading the Body to Regenerate Its Limbs” and was published in the New Yorker. It was essentially an overview of the discoveries made by a scientist called Michael Levin (who I suggest you follow on Twitter) and all the breadcrumbs he followed in his path to becoming one of the pioneers of bioelectricity.

At the time, I had no idea who Michael Levin was and I knew nothing of bioelectricity but I had heard of (and was very interested in) the work of Robert O. Becker—an orthopedic surgeon who experimented with salamanders and electricity in the 1970s and 80s. When the New Yorker article referenced Becker’s book, I knew I was learning about something very important.

Today, myself and others realize the immense potential and incredible promise of bioelectricity. While most of the scientific community is still unaware, the increasing number of YouTube videos and podcast episodes indicates a growing awareness of the field.

In a nutshell, much like neurons use electrical impulses to communicate, all cells in our body (and in other organisms) use electricity to make collective decisions about target morphology.

Cells in our bodies use bioelectricity to communicate and to make decisions among themselves about what they will become

~Hutson, M. Persuading the Body to Regenerate Its Limbs

This makes it obvious that, if you learn the bioelectric language of how cells communicate, you can intercept and change the “messages” to influence health outcomes.

Where bioelectricity might apply is, for instance, in correcting birth defects. Imagine if you could simply give a baby a drug cocktail that results in a specific bioelectrical pattern that corrects the birth defect that the baby would have had. Powerful?

Now, imagine that you’ve got a car accident resulting in a severed limb. What if you could “persuade” the body’s own cells to regrow the missing limb?

And what if, in a person with metastatic cancer, you can simply induce a specific bioelectric pattern that forces the cancer cells to become normal cells once again, without you having to try to target and destroy them?

And perhaps the ultimate: what if, when the body starts breaking down with signs of aging, you can simply specify a bioelectrical pattern of youthful cells—and the body will automatically readjust itself so that your cells are young again?

This is the potential power of bioelectricity, and it is perhaps one of the most exhilarating times of this century.

Since bioelectricity has been in the limelight, many drugs have emerged as potential so-called electroceuticals—molecules that have the potential of changing the communication between cells.

Such drugs are mostly ion channel modulators.

It is estimated that ~10-20% of all existing approved drugs target either voltage- or ligand-gated ion channels.

The challenge of bioelectricity is finding the right electroceuticals to induce a particular outcome in a given model organism.

Metformin is an anti-diabetic drug with pleiotropic effects. If you’ve heard about it, chances are the recent hype around its potential benefits in longevity is the reason.

Whenever a drug exerts such pleiotropic effects, it would be reasonable to assume bioelectricity might be a potential explanation.

Early evidence suggesting metformin might be an electroceutical consists of observational studies that showed an association between metformin and a lower risk of cardiac arrhythmias (Study 1 , Study 2 , Study 3 , Study 4 ).

Mechanistically, metformin has been known for a while to modulate small conductance calcium-activated potassium channels (SK channels). While these are voltage-independent ion channels, it would be correct to label metformin as an ion channel modulator.

More importantly, a recent 2021 paper showed that metformin also regulates voltage-gated sodium (Na⁺) channel Na_v1.7. This suggests that metformin does indeed have the potential of influencing cell-to-cell communications.

Even more telling is a recent study published in March 2022, showing that children of men taking metformin pre-conception had an increased risk of birth defects. Seeing as ion channel modulators can often be teratogenic, this is yet another clue.

Another study, conducted in rat retinal Müller cell line (rMC-1) cells, showed that metformin corrected the levels of the voltage-gated potassium channel Kir4.1.

Given that metformin impacts at least three different ion channels, of which two are voltage-gated, it would be reasonable to assume that it would make for a potentially interesting electroceutical.

My previous article on metformin titled “Metformin Anti-Aging Therapy: Latest Research on the Longevity Benefits of Taking Metformin” goes into great detail on metformin’s potential benefits to lifespan extension. As of today, scientists still cannot agree on which of metformin’s mechanisms of action is the one most relevant to its anti-hyperglycemic effects or its purported longevity-promoting effects. The reason is metformin seems to “attack” many cellular pathways and has therefore been implicated not only in Type 2 Diabetes treatment (which is its main indication) but also in cancer, polycystic ovarian syndrome, NAFLD, inflammation, etc.

The possibility that metformin exerts bioelectrical signaling activities, which is a higher level of control over cell morphology and therefore cell fate, is real and should be investigated.

The TAME clinical trial is testing whether individuals taking metformin can delay the development or progression of age-related chronic diseases. If, when completed, the study shows metformin slows down the process of aging, exploring its effects as an electroceutical should be prioritized.

If you liked this article or found it useful, please give it a like, share, pin it — whatever it is that you do, I’d really appreciate it.