Metformin. It’s the most popular drug for treating type-2 diabetes.
But recent research suggests that it might be useful in improving longevity.
Should you include it in your regimen of anti-aging therapies?
In today’s video, we’ll be taking a look at the pros and cons of taking metformin to turn back the clock on aging,
and hopefully, get a little closer to answering that question.
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Metformin is one of the most widely studied and well understood medications on the market today.
It was discovered in 1922, introduced in France in 1957, and in the US in 1995.
It’s a first line medication for the treatment of type-2 diabetes, particularly in people who are overweight.
It’s the most commonly used oral medication for diabetes
and, according to the World Health Organization,
it’s the safest and most effective medicine needed in a health system.
It’s risks are well known, and they consist primarily of digestive upset.
It cheap, costing between $5 and $25 a month
and it’s the fourth-most prescribed medication in the United States.
But recent research has shown metformin to be a potentially powerful tool
in the fight to defeat aging and extend longevity.
Taking a look at what it does and how it works
might provide a clue to why this drug that’s almost a century old
might be useful in slowing down, or even reversing, the aging process.
Metformin works in several different ways,
most of them having to do with insulin sensitivity and blood sugar levels,
but it also activates the AMPK pathway.
Let’s start by taking a look at how it helps to control blood sugar levels.
First, it blocks the absorption of glucose in the intestine.
Next, metformin decreases gluconeogenesis, which is the production of glucose in the liver,
by reducing the amount of glucose that the liver releases into the blood.
Finally, metformin goes into the bloodstream and supports the absorption of glucose into the muscles.
When you have sugar in the bloodstream, your body has 3 options available.
First, store it as fat or adipose tissue.
Second, store it in the muscles for a quick, backup source of energy.
And third, use it for fuel.
Metformin improves the uptake of glucose into the muscles, for either storage as glucogen or as fuel.
It also improves blood sugar levels by increasing insulin sensitivity,
and it does this by improving insulin binding to insulin receptors.
But insulin can also suppress fatty acid oxidation, the actual breaking down of fatty acids in the mitochondria.
Metformin decreases the suppression of fatty acid oxidation by insulin.
In addition to all this good stuff, metformin also activates the AMPK pathway,
a master metabolic regulator that favors both fat- and sugar-burning.
The classic molecular target for metformin is Complex I of the mitochondrial respiratory chain.
Metformin causes an increase in the ratio of cellular ADP to ATP in the mitochondrial matrix,
leading to activation of the AMPK pathway.
This in turn leads to a couple of things.
First, AMPK activation is required for the inhibition of liver glucose production, or gluconeogenesis.
Second, it probably plays a role in increased insulin sensitivity.
It might also help in treating or preventing cancer.
Studies in 2015 and in 2018 suggest that people who are taking metformin might have a lower risk of cancer.
Some studies are suggesting that this lowered risk might be as much as 30 - 50%.
And some researchers have suggested that it may slow, or even halt, tumor cell growth.
But what about longevity?
There’s a considerable list of longevity researchers, scientists and doctors
who regularly take metformin for it’s beneficial effects in staving off the ravages of aging.
People like David Sinclair, Aubrey de Grey, Bill Anderson and Bill Fallon.
Why are these guys taking metformin?
Well, let’s take a look at that.
And to do that, we need to look at some of the effects and mechanisms of metformin
that have nothing to do with diabetes.
So, first off, metformin inhibits the mTOR pathway, which is one of the nutritional sensing pathways,
and this pathway needs to be inhibited for extended lifespans.
The other is the Insulin-like Growth Factor 1 pathway and the Insulin/Insulin-like Growth Factor1 Signaling pathway .
And guess what? Metformin also inhibits those pathways.
It also restores youthful methylation.
Methylation of the DNA is when a methyl group attaches itself to the DNA,
and it’s an epigenetic factor that contributes to aging.
Measuring DNA methylation is a way of determining biological age.
For example, the Horvath Clock measures DNA methylation.
Metformin may also reduce the amount of damage that accumulates from chronic inflammation and oxidative stress.
two factors which also contribute to aging in a big way.
And a study done by the Veteran’s Adminstration has suggested that metformin may reduce the incidence of dementia.
In fact, it looks so promising that there are currently a number of studies going on
that are looking directly at metformin’s effects on aging.
There’s a study called Targeting Aging with Metformin (TAME) that plans to recruit 3,000 adults without diabetes,
aged 65-79 and that study will continue for 4 years.
Another study is being done by the University of Texas Health Sciences Center in San Antonio
and sponsored by the National Institute on Aging.
This study includes 120 elderly people and plans to conclude in October of 2022.
Then there’s the Metformin in Longevity Study which was done by the same team doing the TAME study.
The MILES study has already been completed and they’re now in the process of analyzing the results.
And finally, there was a study called theThymic Regeneration, Immunorestoration and
Insulin Mitigation trial that was lead by Dr. Greg Fahy.
This 12 month study was able to reverse the epigenetic clock in nine men aged 51 to 65 by an average of 2.5 years.
And metformin was one of the drugs used in this study.
However, there are some caveats.
For one thing, the study of metformin as an anti-aging drug is just getting started,
and meaningful results aren’t expected for several years.
Now, for someone like me who’s just turned 70,
I don’t feel like waiting for several years to find out whether or not
this will turn out to be a medication that can produce significant results in defeating aging.
Then there’s a new study that came out in the February, 2019 edition of Aging Cell.
This study was done by the Oklahoma Medical Research Foundation, Colorado State University and the University of Illinois,
and it suggests that exercising while taking metformin might not be such a good idea.
Working on the idea that many of the anti-aging therapies are additive,
they took a look at doing exercise combined with taking metformin.
It’s generally well-known that both exercise and metformin benefit longevity.
Exercise can improve levels of fitness as well as blood sugar levels and insulin sensitivity.
It can also enhance mitochondrial health by boosting the efficiency of individual mitochondrion
and by increasing the number of mitochondria through mitochondrial biogenesis.
Metformin seems to work on the same pathways and has been shown to have similar effects.
So, it was thought that combining exercise with taking metformin might possible amplify the effects of both.
But that’s not what happened.
In fact, it seems that exercise and metformin kind of cancel each other out.
People who were doing both had about half the gains in fitness
that the people had who were taking a placebo with their exercise.
They had negligible improvement in insulin sensitivity.
Finally, the people on the placebo had about a 25% rise in mitochondria respiration,
while those on metformin saw little if any improvement.
Now, there have been some criticisms of this study.
It was done on a small group of people over a short period of time.
It was done with everyone taking the same dose.
And it was done with a group of elderly people who were not previously doing any exercise.
So the researchers cautioned that the results do not mean people should stop taking metformin,
even if they’re taking it to slow aging.
The point that I’m trying to make, I guess, is that it’s way to early in the research
to draw any conclusions about the efficacy of taking metformin to slow aging.
So, if you’re an older person, like I am, you’ll just have to draw your own conclusions.
However, if you do decide to biohack your own system and take metformin off label,
there’s some things that you might want to know.
Although it’s been found to be a very safe drug to take over almost a century of investigation,
it does have a few side effects.
Most of them have to do with digestive issues,
such as upset stomach, nausea, diarrhea, constipation, gas, heartburn and bloating.
This seems to be exacerbated by eating excess carbs.
It can also cause muscle weakness, low blood sugar, and chills.
But there’s a couple of side effects that need to be taken seriously,
although they’re both pretty rare and completely avoidable.
Metformin gets cleared from the body through the kidneys,
and if you have kidney disease, metformin can build up in the system, causing lactic acidosis,
which can be life threatening.
Also, metformin can interfere with the absorption of vitamin B12, leading to anemia and an iron deficiency.
If you do decide to start taking metformin off-label, you can take it up to twice a day,
but be sure to take it with a meal…otherwise the chances of digestive upset go up.
Don’t take it if you have kidney disease or suspect that your kidneys might be dysfunctional.
And supplement with vitamin B12 when taking metformin.
Now, with regards to dosage…that’s a bit more difficult, especially if you’re not diabetic.
I’ve heard of people taking metformin doses of as little as 125 mg. to prevent aging.
The participants of the study on metformin and exercise started out taking 2,000 mg. per day.
Both the TAME study and the MILES study uses a dosage of 1,700 mg.
And the TRIIM study used a dose of 500 mg.
So, the effective dosage of metformin to prevent or slow aging seems to be unclear at this time.
Regardless of whether or not you decide to add metformin to your arsenal of weapons in the fight to defeat aging,
having an understanding of the pathways that metformin affect
and how they function can only improve our base of knowledge and help us to turn back the clock on aging.
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