Anti-diabetes drug Metformin may also be an anti-aging drug

[Pointedstick]

http://www.nzherald.co.nz/lifestyle/new ... d=11553026

Scientists think the best candidate for an anti-ageing drug is metformin, the world's most widely used diabetes drug which costs just 10 cents a day.

Metformin increases the number of oxygen molecules released into a cell, which appears to boost robustness and longevity.

When Belgian researchers tested metformin on the tiny roundworm C. elegans the worms not only aged slower, but they also stayed healthier longer. Last year Cardiff University found anecdotal evidence that when patients with diabetes were given the drug metformin they lived longer than others without the condition, even though they should have died eight years earlier on average.

The new clinical trial called Targeting Aging with Metformin, or TAME, is scheduled to begin in the US next winter. Scientists from a range of institutions are currently raising funds and recruiting 3,000 70 to 80-year-olds who have, or are at risk of, cancer, heart disease and dementia.

[Libertarian666]

What are the side effects? If it doesn't cause anything too terrible, maybe it's worth trying...

[ochotona]

Speaking as someone who may have to take metformin in the future, I find this news a bit cheering. Though, I'd rather not take one more prescription drug.

[MachineGhost]

What are the side effects? If it doesn't cause anything too terrible, maybe it's worth trying...

Depletes Vitamin B12 which is easy enough to fix.  There's also a lot of fear mongering and hand wringing about lactic acidosis, but it's never been observed in those free of kidney dysfunction.  And I think there's only one actual observation in the literature.

[MachineGhost]

Speaking as someone who may have to take metformin in the future, I find this news a bit cheering. Though, I'd rather not take one more prescription drug.

If it helps, metformin is a synthetic derivative from the goat's rue plant but with the toxin removed.  Very few drugs are that close to "natural" anymore, if at all.  https://en.wikipedia.org/wiki/Galega_officinalis

Still, you can probably get most of the same effect with other AMPK activators.  What metformin does is essentially mimick the calorie restriction state.

If you've got Type II diabetes, you need to learn about intermittent fasting.  Search the forum.

[Pointedstick]

…On the other hand, maybe it can increase the risk of Alzheimer's: http://www.eurekalert.org/pub_releases/ ... 040513.php

Ya can't win.

[MachineGhost]

…On the other hand, maybe it can increase the risk of Alzheimer's: http://www.eurekalert.org/pub_releases/ ... 040513.php

Ehhh, I say that's isolationist reductionist rubbish!  It's a huge leap to assume that metformin causes Alzheimer's or that there is even a mechanism between activating AMPK in the body vs the brain or that AMPK is actually the cause of Alzheimer's.  As Mark Leavy says, correlation is not causation.  Alzheimer's is Diabetes Type III so if you know anything about diabetes you should be more concerned about the snowballing insulin resistance in the brain than possible resolution via AMPK activation.  Metformin actually breaks down and deactivates the proteins that contribute to the neurofibrillary tangles characteristic of neurons affected by Alzheimer’s.  Gwarsh!!!

<rant about fat old lazy people eating horribly nutritionally devoid diets omitted>

[Fred]

Ageing is not an inevitable part of life because all cells contain a DNA blueprint which could keep a body functioning correctly for ever. Some marine creatures do not age - or grow weaker as time passes - at all.

The Christians among us can have a field day with that since they believe that Adam and Eve were created perfect and not subject to death in the beginning. Death came from eating the forbidden fruit of the knowledge of good and evil - in scientific terms there must have been an altering of the DNA blueprint at that moment.

If the Bible story holds true then it must be futile to correct the mutation because God does not want man to live forever. After driving Adam and Eve out of the garden He set a cherubim with a flaming sword to guard the way to the tree of life lest they eat of it and live forever.

Interesting stuff.

[MachineGhost]

The Christians among us can have a field day with that since they believe that Adam and Eve were created perfect and not subject to death in the beginning. Death came from eating the forbidden fruit of the knowledge of good and evil - in scientific terms there must have been an altering of the DNA blueprint at that moment.

Yeah, we went from a gorilla to homo sapiens. :-p

[Reub]

I've actually been taking a small dose of metformin but have recently stopped. It saps all of my energy for some reason. This is my third attempt at using it and cannot recommend it. Depletes B12, raises homocysteine,  reduces testosterone levels, and may very well effect muscles and ability to exercise. I am done with it. Be leery about the hype.

[MachineGhost]

I've actually been taking a small dose of metformin but have recently stopped. It saps all of my energy for some reason. This is my third attempt at using it and cannot recommend it. Depletes B12, raises homocysteine,  reduces testosterone levels, and may very well effect muscles and ability to exercise. I am done with it. Be leery about the hype.

Since you have the MTHFR mutation, maybe you deplete B12 at a faster rate than normal concomittant with metformin.  Have you tried doubling the Activated B's or homocysteine formula?

[Pointedstick]

All kinds of interesting information here: http://www.gwern.net/Longevity#metformin

This person is pretty positive on Metformin. Thoughts, MG or those in the medical field?

[Reub]

"Blood glucose levels were well controlled in all three groups. When the groups were
compared without separating men and women, no differences were seen in heart
metabolism. But when the participants were separated by gender, it became clear that the
medicines had different, and sometimes opposite, effects on cardiac function.
The biggest difference between men and women was seen in the group taking metformin
alone. The drug appeared to improve heart function in women, but it caused the hearts of
men to burn less sugar and more fat — a shift that can eventually cause changes in heart
muscle, leading to heart failure.
“Instead of making heart metabolism more normal in men, metformin alone made it worse,
looking even more like a diabetic heart. But in women, metformin had the desired effect —
lowering fat metabolism and increasing glucose uptake by the heart,” said senior author"
Robert J. Gropler, MD.

[Benko]

PS,

It is worth reading about AMPK: what activating it does, and what lifestyle and supplements can activate it.  MTOR as well.

MG probably has better references, but here is one relevant link to AMPK:

http://selfhacked.com/2014/11/21/natura ... ctivators/

A lot of the things you've heard about relating to health/weight loss relate to AMPK:  exercise, fasting, metformin, berberine, green tea, fish oil, cinnamon, and the tcm herb Danshen/Salvia Miltiorrhiza.  Reading along those lines and the research reviews on examine.com can give you the background you need to make an informed decision.


Though I've gone through phases of taking zillions of supps as well as some smart drugs, my current personal bias is to get as much possible from diet e.g. blueberries rather than Pterostilbene supplementation, fish over fish oil (see recent kresser comments) and only take things in pill form that I cannot get in other ways.  Taking metformin/berberine for therapeutic purposes eg weight loss/lowering blood sugar for a period of time is one thing, taking something like that as a healthy person given its wide ranging actions forever is another.

Oh and apparently metformin gives a number of people diarrhea, so if you try it, only buy a small amount to try it in case you are one of those people.

[Reub]

PS, if I were going to go down this path I would utilize berberine over metformin. The berberine did not effect me in this negative way and has much less side effects but probably the same positive aspects as metformin.

https://examine.com/supplements/berberine/

[Pointedstick]

Thanks for the recommendation, Reub. Can you get it in any foods, or is it always going to be found in supplement form?

[Reub]

As far as I know you would get it through supplementation. Here is a good, inexpensive source:

http://www.swansonvitamins.com/swanson- ... mg-60-caps

Btw, it is much more readily absorbed if you take it with coconut oil, which is also very healthy by itself and will raise your good Hdl.

I would recommend occasional blood workups so that you can see the effects on your fasting blood glucose, inflammation (Crp) and cholesterol levels.

[Benko]

PS,

Berberine is a reasonable choice, buT BE SURE TO READ THE EXAMINE.com section on it as it interacts significantly with certain drugs including antibiotics.

e.g. Berberine may interact with microlide antibiotics such as azithromycin and clarithromycin at hERG channels on the heart, leading to serious cardiotoxicity

also

High doses of berberine taken acutely, due to their poor intestinal uptake rate, may cause cramping and diarhhea; for this reason, berberine should be taken in multiple doses throughout the day

[Reub]

Yes, do not use with those 2 antibiotics.  Also I never have GI symptoms taking it.

The warnings and side effects for metformin are much, much worse!

[Reub]

http://www.faim.org/diabetes/avoid-the- ... wagon.html

[D1984]

http://www.faim.org/diabetes/avoid-the- ... wagon.html

Reub (Benko, or MG, or any of the other supplement experts please feel free to chime in as well),

What do you make of the following:

http://diabetesupdate.blogspot.com/2013 ... ll-be.html

Anything to be concerned about regarding berberine's DPP-4 inhibitory effects (which can turn off a mechanism the immune system uses to kill cells that have become cancerous), its downregulation of the cytochrome P450 enzymes (which should only be a problem if you are taking drugs that are metabolized by these enzymes....although that's most pharmaceutical drugs, isn't it...then again white grapefruit juice does the same thing to the P450 enzymes and it never killed anybody), and most importantly its potential for upregulation of GLP-1 (which to be fair diabetes drugs like Januvia and Exenatide do as well) and the potential long-term side of effects of said upregulation which include the growth of abnormal cells in the pancreas and potentially could lead to pancreatitis or precancerous tumors or even pancreatic cancer?

Anything to be seriously concerned about or is the person who wrote that post just pulling up spurious correlations and hypothetical maybes about effects and using it to try and incite people not to use berberine?

[Benko]

D1984,

There are 3 different possible contexts for this discussion:

1. treating diabetes (or polycystic ovaries I suppose)
2. short term use for e.g. obesity
3. use by healthy people for anti-aging.

Many choices in life come down to risk vs benefit.  If you are diabetic that is very different discussion from the one we were having about situation 3 above. 

What is the context for your inquiry?

[Benko]

Ran across this this morning:

Diabetes Drug Improves Gut Bacteria - WebMD, 12/4/15 - "taking metformin had positive effects on the intestinal bacteria of people with type 2 diabetes. Specifically, the drug improved the ability of the bacteria to produce certain types of short-chain fatty acids that reduce blood sugar levels in different ways"
http://qualitycounts.com/newsletter15/151209.htm

which is not meant as an endorsement of metformin, but a reminder of the importance of gut flora (including for weight) and that everything effects everything.

[Reub]

If a person is relatively healthy I wouldn't recommend metformin or berberine, but rather, more exercise of various types including resistance training, cardio, and interval work. Additionally an increase in dietary fiber is very important for optimum cholesterol, weight control, and blood sugar regulation, preferably before eating. I am using a soluble fiber called PHGG, partially hydrolyzed guar gum, prior to meals. And obviously cut back on carbs and refined foods as much as possible. Getting enough sleep too.

Oh yes, some kind of caloric restrictions seem to help wrt longevity as well according to the studies. I try to only eat within an 8 hour daily window (usually for me between 11AM and 7PM and don't eat anything for a few hours before bedtime).

[D1984]

D1984,

There are 3 different possible contexts for this discussion:

1. treating diabetes (or polycystic ovaries I suppose)
2. short term use for e.g. obesity
3. use by healthy people for anti-aging.

Many choices in life come down to risk vs benefit.  If you are diabetic that is very different discussion from the one we were having about situation 3 above. 

What is the context for your inquiry?

Benko,

I am having labs done in late January for HgA1c and FBG, among others (I have not had any lab work or blood testing done for over a decade and a half at the moment). If they come back showing me as diabetic or pre-diabetic then I am wondering which I should start taking and which would have the least long-run bad effects. I am considering any of the following: berberine, metfomin, mulberry leaf extract containing at least 6 mg 1-DNJ per dose, or bitter melon.

As to why I think i might risk being diabetic or pre-diabetic - my diet wasn't the greatest until about two months ago when I switched from mostly SAD (with one to three sodas a day typically, to boot) to a moderately low carb diet with a target of from 1425 to 1480 calories per day (for a 31 year old male, 6 ft 2, fairly sedentary but do get occasional exercise) with less than 15% of those calories coming from carbs, ideally, and none coming from liquid carbs like sodas or juices. I don't know how it will effect the blood work but I am down roughly 21 lbs (from 185.9 to 164. since I started this diet (on 12-6-2015) and no longer have to take antacids much at all...think I have taken two since I started the diet (was previously taking them almost every day for heartburn...sometimes two a day).

If I do end up with test results showing diabetic or pre-diabetic A1c levels then I want to try and control it by diet as much as possible but if that's not possible then I want to take the least damaging drugs that are currently available.