Anti-aging science is no longer science fiction, it’s just science! Hearing this a few years ago would have sounded crazy! But now there’s plenty of evidence to show we all age at different rates (see my previous post biological age and why it matters) and that we can influence the rate at which we age, by targeting specific factors.

Metformin – a prescription medicine mostly known for its use in the treatment of type 2 diabetes – has gained a reputation as one of the possible ways to target aging.

In this post I explore the evidence and the science behind metformin and its potential effect on longevity.

A brief history of metformin

Let’s start with some history! Metformin  goes back to the 17th century. Galega officinalis, also known as French Lilac or Goat’s rue, was used as a traditional medicine in Europe to treat plague, fever, snake bites and other illness. The plant is a natural source of metformin-like compounds and was first reported for use in the treatment of diabetes symptoms in 1772.

In 1957, the French doctor Jean Stern managed to get metformin approved to treat diabetes in France under the brand Glucophage. The following year, the drug was introduced to treat diabetes in the UK and other European countries. It took a lot longer for metformin to be used in the US. 1995 to be more precise!

And now you’re more clued up about the origins of metformin!

Metformin for longevity?

Emerging evidence suggests that metformin has health benefits which go beyond its sugar-lowering effects, namely improving lifespan and healthspan. These are the two keywords in the longevity world. I guess lifespan is self-explanatory. A common definition of healthspan is “the period of life spent in good health, free from the chronic diseases and disabilities of aging”. In more simple words, the period of your life when you’re healthy. Ideally your lifespan would be equal to your healthspan. Let me take you through some of the science behind metformin and its potential anti-aging effect.

Metformin in animal studies

In the early 2000s, several studies showed that metformin extends the lifespan and healthspan in lab mice. A 2008 study by a Russian team showed that treating female mice with metformin extends their mean lifespan by nearly 40%, whilst slowing down the age-related switch-off of their reproductive function. Another study  showed that adding metformin to the mice’s diet increased their lifespan by almost 6% and resulted in benefits like lower cholesterol and better physical performance.

Work  on one of the prominent models for longevity research – the roundworm C. elegans – demonstrated that metformin extended their lifespan by up to 50%, as well as increased their healthspan. Impressive!

Metformin and longevity in humans

Although no one has studied the effects of taking metformin in healthy humans yet (a bit more on this later), the evidence that metformin may have longevity benefits in humans is mounting. There’s a lot we can learn from observational studies on people with diabetes taking metformin. A UK study  found that metformin lowered mortality in people with type 2 diabetes compared to those without diabetes. There were almost 180,000 people in the study. The 78000 put on metformin had the lowest death rates -by nearly 15%. These are people with type 2 diabetes who tend to be more obese and have other medical conditions and they still had a lower mortality compared to people who didn’t have diabetes (and weren’t taking metformin). Mind-blowing!

A major systematic review which looked at 53 studies, has shown that metformin can reduce the death rate of people with diabetes from all causes, compared to people who didn’t have the condition (and weren’t taking metformin) or those who did have diabetes but were taking other medicines. Other benefits included less heart disease and a lower risk of developing cancer.  Metformin also appeared to increase the health and life spans of people with diabetes, independent of its effect on diabetes control.

What we still don’t know is whether healthy people will have the same benefits on aging and aging-related diseases, in the same way that people with diabetes do. The now famous trial Targeting Aging with Metformin  (TAME) led by Nir Barzilai of the Albert Einstein College of Medicine aims to study just that. The trial will test if those taking metformin will experience a delay in the development of age-related diseases- like heart disease, cancer and dementia – compared to those who take a placebo. The study will run over six years and plans to recruit 3000 people aged between 65 and 79 years.

It would be a major scientific breakthrough if the TAME study can demonstrate that we can target the biology of aging. This means we would be able to prevent a wide range of diseases at the same time, rather than treating each age-related condition separately.

So how does metformin work for longevity?

It is thought that metformin mimics some of the positive effects of fasting. It appears to do this by targeting several aging-related mechanisms . Some of them are more complex than others. I’ll briefly go through these giving you a few keywords in case you want to research this further.

The primary target of metformin is what’s called complex I in the mitochondria – these are the powerhouses of our cells which produce most of our energy. This triggers a whole host of other reactions, like increasing AMPK (the energy sensor in our cells) and decreasing mTOR (our cells’ nutrient sensor). This in turn translates into benefits like reducing inflammation and inducing autophagy (this promotes cells clean up and renewal).

So, tweaking the right knobs in our cells can activate our bodies’ defences against aging

Are there any downsides to taking metformin?

The wide use of metformin as an antidiabetic drug for more than 60 years by hundreds of millions of people worldwide gives confidence that the drug is quite safe. But like all drugs it’s not side-effects free.

The most common side effects involve the digestive system and include diarrhoea, stomach cramps and passing wind. These are generally mild and go away with time. You can reduce those effects by taking metformin with meals. A more serious possible side effect is lactic acidosis. When this happens, ketones (these are chemicals the liver produces when it breaks down fats) build up in the body and this can be life-threatening if not treated quickly. Cases of lactic acidosis linked to metformin use are rare  but what we don’t know is whether we’ll see more cases if the drug is used more widely.

Long-term use of metformin can cause vitamin B12 deficiency . So, if you’re taking metformin you may want to think about testing your vitamin B12 levels regularly.

The effect on exercise is something else to consider. A recent study  has suggested that metformin may counteract the benefits of exercise on cardio-respiratory fitness (heart and lungs performance), insulin sensitivity and the mitochondrial respiration in the muscle cells (a higher respiration means a more efficient energy production). In a nutshell, metformin seems to cancel some of the benefits of exercise, but we need more research in this area.

Can I take metformin for aging?

Metformin is a prescription only medicine in most countries and now is only licensed to treat type 2 diabetes. The drug is used off label for conditions like polycystic ovary syndrome (PCOS) and pre-diabetes, but you’re likely to struggle to find a doctor who would be happy to prescribe it off label for aging or to prevent aging-related diseases.

The evidence from animal studies and the retrospective studies are clearly promising enough to get scientists like David Sinclair and Nir Barzilai excited about metformin and take it. Although, those studies are not as strong as powered studies like the TAME study which has been specifically designed to test metformin’s effect in healthy individuals. The TAME clinical trial is still in the process of getting approved by the Food and Drug Administration (FDA).

So, while waiting for the results of such studies, the drug remains unlicensed for aging and you shouldn’t take it without speaking to your doctor first.

_{Disclaimer: The author is not a clinician and does not give medical advice. Always speak to your doctor for personal medical advice.}

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