For years, metformin was thought to be a potential longevity drug, with early studies suggesting diabetics on the medication lived longer than healthy individuals. This sparked interest in the biohacking community, with many healthy people starting to take it in hopes of extending their lifespan. However, more recent research has cast doubt on these initial findings, leading to a re-evaluation of metformin’s role in anti-aging. (This article is based on the expertise of Dr. Annette Bosworth and Dr. Ralph Defrono)
The Metformin Longevity Debate: A Look Back
The idea that metformin could be a longevity drug really took off in 2014 after a study by Banister suggested that diabetics on metformin lived longer than non-diabetics. This was a big deal because you’d expect diabetics, at best, to live as long as healthy people if their blood sugar was well-controlled. The idea that they might live longer implied metformin could actually boost life expectancy, even for those without diabetes.
This got a lot of attention in the longevity world. You know, those super-healthy people who track every calorie and avoid sugar like the plague? Some of them started taking metformin, hoping it would help them live longer. But then, in 2022, a study tried to repeat those findings and it didn’t work out.
Key Takeaways from the Re-evaluation:
- Initial Study Flaws: The original 2014 study had some significant issues.
- Exclusion Criteria: People in the metformin group were kicked out if they needed other diabetes medications. This meant only the healthiest metformin users stayed in the study, ignoring those whose diabetes worsened.
- Control Group Bias: The non-metformin group was removed if they developed diabetes. Since diabetes is more common as people age, this unfairly favored the control group by removing older individuals who might have developed the condition.
- Replicated Findings: After correcting for these biases, studies found what most people expected: non-diabetics generally live longer than diabetics.
- Disappointment and Truth: While it was disappointing that metformin wasn’t a magic longevity pill, getting to the truth is what really matters.
How Metformin Actually Works
So, if metformin isn’t a longevity drug, how does it actually help lower blood sugar? The way it works is by helping to move glucose from your blood into your cells. It does this by partially blocking something called complex one in your mitochondria. Think of mitochondria as the powerhouses of your cells. Metformin also increases the conversion of glucose to lactic acid within your cells.
For a long time, I used a diagram to explain this, often using a muscle cell. The key player here is a receptor called GLUT4. This receptor’s activity depends on concentration. As long as there’s more glucose outside the cell than inside, glucose will move into the cell through this receptor. We keep this process going by quickly turning glucose into lactate. Metformin helps this by slowing down the energy flow after lactate is made.
We can actually measure this. If you’re taking metformin and I prick your finger, your resting lactate levels will be higher. It’s even dose-dependent – the more metformin you take, the higher your lactate goes. I used to tell patients that metformin reduced the power inside their muscle cells, but I thought it was worth it for the potential of longevity and lower blood sugar. Turns out, that wasn’t quite right.
The Big Misconception: Where Metformin Doesn’t Go
This is where many people, including myself, Peter Attia, and most doctors, got it wrong. We thought metformin actually entered muscle cells. But Dr. Ralph Defrono has pointed out something very important: metformin doesn’t actually enter muscle cells.
The reason for this is that muscle cells lack a specific transporter, called an organic cation transporter, which is needed for metformin to get inside. This transporter is found on liver cells, which is why metformin is most effective in the liver.
I knew metformin’s main action was in the liver, but I was mistaken to think it was also working inside muscle cells in the way I had warned patients about for years. It simply doesn’t have the ‘permission’ to enter those cells, and therefore, it can’t lower the power output of a muscle cell.
Metformin accumulates in the liver and, among other things, lowers blood sugar by stopping the liver from making glucose (a process called gluconeogenesis). The drug is then filtered out by your kidneys. It can’t raise lactic acid in your muscle cells because it can’t get into them. The higher lactate levels we see in your blood when you’re on metformin come from increased glucose turnover into lactate only within your liver cells.
Metformin for Anti-Aging: Is It Still a Good Idea?
So, while metformin is a good idea if your blood sugar is too high, is it still a good idea for anti-aging if your blood sugar is already under control? Not necessarily.
There are still people who choose to take metformin purely for longevity. Brian Johnson, the billionaire biohacker, is one of them. However, based on the current evidence, I don’t have enough confidence to recommend taking it for anti-aging if your blood sugar is already well-managed.
If your blood sugar isn’t controlled, metformin remains one of the cheapest and safest options to help with that. It works well alongside lifestyle changes like diet and exercise. If you’re struggling with stubborn blood sugar, there are specific strategies that can help. You can find more information on how to lower blood sugar by clicking here.
Source: Dr. Annette Bosworth