Metformin Reduces Diabetic Risk by Improving Gut Health

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MarkM

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"Since 1995, Life Extension® has recommended metformin to nondiabetics as a possible way to slow biological aging.

Metformin’s primary beneficial mechanism is to increase cellular AMPK. As people age, AMPK activity declines and sets the stage for a host of degenerative illnesses.

New studies have uncovered another benefit to metformin: It boosts a beneficial intestinal bacterium called Akkermansia muciniphila. Studies show that this bacterium has specific actions that combat diabetes and obesity.
This study from Johns Hopkins sheds new light on metformin’s role as a microbiome-modifying, anti-diabetic drug."


Metformin Reduces Diabetic Risk by Improving Gut Health

September 2018

By Stacy Grant

The gut microbiome consists of trillions of microorganisms that inhabit the human gastrointestinal tract.
Having an imbalanced gut microbiome is associated with cancer, vascular disease, allergies, neurodegenerative disorders, and depression.

In 2017, researchers at Johns Hopkins Bloomberg School of Public Health announced a series of discoveries linking disturbances in the microbiome to diabetes. Fortunately, they also found a solution.

Metformin is the most widely prescribed drug to treat type II diabetes.

Since 1995, Life Extension® has recommended metformin to nondiabetics as a possible way to slow biological aging.

Metformin’s primary beneficial mechanism is to increase cellular AMPK.

As people age, AMPK activity declines and sets the stage for a host of degenerative illnesses.

New studies have uncovered another benefit to metformin: It boosts a beneficial intestinal bacterium called Akkermansia muciniphila.

Studies show that this bacterium has specific actions that combat diabetes and obesity.

This study from Johns Hopkins sheds new light on metformin’s role as a microbiome-modifying, anti-diabetic drug.

Akkermansia Improves Metabolic Health
Gut health hinges on having a healthy balance of the right kinds of bacteria.
Akkermansia muciniphila is one of the good guys, and its specialty seems to lie in beneficially affecting metabolic health.

Until 2016, little was known about the organism’s role in human metabolism.5-9 That changed with publication of a French study.

In a 12-week dietary intervention, the Sorbonne’s researchers studied 49 overweight and obese adults. Subjects undertook six weeks of a calorie-restricted diet followed by six weeks of a diet aimed at weight stabilization.
The study showed that subjects with the highest baseline abundance of Akkermansia muciniphila in their stool had the best parameters associated with metabolic health, including:
  • The lowest fasting glucose,
  • The lowest waist-to-hip ratios (a measure of central obesity),
  • The lowest mean diameter of fat cells, and
  • The best metabolic status, as indicated by lower plasma-triglyceride levels and better body-fat distribution.5
Having an abundance of Akkermansia also predicted greater improvements following the calorie-restriction phase of the study. For example, the subjects with higher baseline Akkermansia levels had greater improvements in markers of insulin resistance, blood lipids, and body fat composition after the intervention, compared with those having lower abundance of the organism.They also showed less liver-cell damage, a common outcome of excessive liver fat associated with non-alcoholic fatty liver disease (NAFLD).

As an added benefit, having plenty of Akkermansia muciniphila was associated with having an abundance of other microbial species with known benefits to metabolic health.

In addition to confirming Akkermansia muciniphila’s role in metabolic health, this study also suggests that interventions that boost Akkermansia are likely to be useful in counteracting obesity, diabetes, and their deadly cardiovascular consequences.

And it turns out that an unanticipated yet potent way to boost Akkermansia is a drug that’s already well-known for its glucose-lowering, anti-diabetic benefits: metformin.

Metformin’s Akkermansia-Boosting Effects
Metformin is a derivative of the French lilac (Galega officinalis) with an ever-expanding list of benefits and an excellent safety record.

It has been used for more than 50 years to treat type II diabetes.

More recently, reports have indicated that metformin’s metabolic benefits might involve alterations to the gut microbiome. Intrigued, researchers at the Johns Hopkins Bloomberg School of Public Health teamed up with colleagues in Colombia to develop a deeper understanding of metformin’s impact on the microbiome.

The study involved 28 individuals with diabetes and 84 others without diabetes that were matched to the diabetic subjects by sex, age, and body mass index (BMI). Half of the diabetic subjects were taking metformin, while the other half were not.

What the researchers found was remarkable. Compared with subjects who did not have diabetes, the diabetic subjects taking metformin had higher abundance of Akkermansia muciniphila, while diabetics not taking metformin lacked this increase.

There may be no citizen of the gut microbiome community better suited to protecting us against diabesity—the combination of diabetes and obesity—than Akkermansia because of its ability to improve insulin resistance, blood lipids, and body-fat composition.

As an added benefit, the diabetics given metformin also had higher levels of bacteria known for their ability to produce essential short-chain fatty acids (such as butyrate).Short chain fatty acids are increasingly being recognized for their anti-inflammatory properties in the intestine and elsewhere in the body.

In sharp contrast, diabetics not taking metformin showed a higher abundance of bacteria in the Clostridiaceae family, which have been associated with higher levels of gut and system-wide inflammation.

These beneficial shifts in the diabetic gut microbiome are precisely what one would desire in an antidiabetic therapy: reduction in bacteria associated with inflammation (which promotes insulin resistance and therefore diabetes), and increases in bacteria known to protect gut integrity and soothe inflammation.

Metformin’s Metabolic Effects

Another study out in late 2016 vividly demonstrates the important health benefits of metformin as a gut microbiome-modulating drug.

It found that metformin’s ability to improve the gut microbiome can reverse a condition known to cause everything from digestive issues and hormone imbalances, to skin issues and food allergies, to autoimmune diseases and depression.

The condition is called leaky gut, and it occurs when the otherwise-tight intestinal wall becomes permeable, allowing things like toxins, bacteria, and undigested food to “leak” out of the intestines and travel throughout the body through the bloodstream. The immune system targets them as imposters and attacks them. This leads not only to the effects listed above, but to a body-wide state of low-grade inflammation.

Two primary underlying causes of a leaky gut include a high-fat diet and an unbalanced (dysbiotic) gut microbiome, and it can lead to a cascade of events that have a harmful impact on blood sugar and insulin resistance.

The chief culprit in this scenario is a ubiquitous, highly-toxic family of compounds called lipopolysaccharides, or endotoxins. When lipopolysaccharides are released into the circulation, they cause a profound inflammatory response, even when present in amounts as miniscule as one-trillionth of a gram.

One of the most devastating results of lipopolysaccharide-induced chronic inflammation is the development of insulin resistance. This occurs when damaged cells lose the ability to respond to insulin signaling, leading to high blood-sugar levels that damage tissues.

While it is virtually impossible to avoid these dangerous endotoxins, studies have shown that modulating the composition of the gut microbiome can limit how much of them are absorbed into the circulation—which has beneficial effects on metabolic health.

Metformin Reverses Leaky Gut

Another 2016 study found that metformin’s ability to modulate a dysbiotic gut microbiome has a profound impact on leaky gut and its consequences.

For this study, scientists fed mice a high-fat diet for 18 weeks to induce insulin resistance.18 They then treated the mice with either metformin alone, or metformin following injections of lipopolysaccharides to produce high-grade inflammation.

The results showed that metformin treatment:
  • Reversed gut leakiness induced by a high-fat diet,
  • Lowered the resulting elevated circulating lipopolysaccharide levels, and
  • Increased the abundance of beneficial Lactobacillus and Akkermansia in the gut microbiome.
This study shows that metformin exerts favorable changes on a dysbiotic gut microbiome—a benefit that results in a sharp decrease in pro-inflammatory compounds associated with diabetes and obesity. It also offers additional insights into why metformin is such a potent actor in fighting these disorders.

This study highlights the importance of microbiome composition in metabolic health and strengthens the case for Akkermansia muciniphila as a chief guardian of gut balance.

Summary

Metformin is a multitargeted drug with broad-spectrum metabolic benefits in diabesity, the deadly combination of diabetes and obesity.

New studies show that some of metformin’s metabolic benefits stem from its impact on the gut microbiome.
These studies show that metformin boosts the amount of Akkermansia muciniphila. People with higher levels of Akkermansia have better metabolic health, lower blood sugar, and healthier body-fat distributions than those with lower levels.

By inducing these beneficial gut microbiome changes, metformin reduces gut leakiness and lowers levels of circulating toxins that induce inflammation throughout the body—effects that help to reduce inflammation-related insulin resistance and elevated blood-sugar levels.

Probiotics are one important means of supporting good gut microbiome balance and overall health. Metformin may be considered along with probiotics as a beneficial, gut microbiome-modulating intervention that can promote intestinal as well as metabolic health.

http://www.lifeextension.com/Magazine/2018/9/Metformin-Improves-Gut-Health/Page-01
 
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Vince

Super Moderator
I've been on Metformin SR two 1500mg since 2010. Along with my low carb diet I've been able to keep my A1c steady at 5.2
 
M

MarkM

Guest
I read a tremendous amount of positive things about it and its potential anti-aging benefit and is supposed to be beneficial to those that are non-diabetic.
 

Vince

Super Moderator
Yeah I've read about metformin benefits for a number of years. My first preventive cardiologist recommended it for me and I've been taking it every since.

Metformin did lower my B12 levels so I do supplement with B12 now.
 
M

MarkM

Guest

Leesto

Active Member
I've been on Metformin SR two 1500mg since 2010. Along with my low carb diet I've been able to keep my A1c steady at 5.2

That's fabulous Vince!

Just a data point: 2.5 years ago my HBa1C was 13.0. I started taking 2000 mg of Metformin per day and also 40 mg. of Glipizide. After 6 months my HBa1C went down to 10.5. Doctor wanted me to start insulin but I balked. I went on the ketogenic diet and my HBa1C came down to 6.4. Now I just take Metformin not Glipizide. If I stop the Metformin for several months my A1C goes up to about 7.5. Clearly Metformin has an effect on the A1C (not to mention the other benefits it offers). But in my 63 YO diabetic body the ketogenic diet has a far greater impact than oral meds.
 

Vince

Super Moderator
That's fabulous Vince!

Just a data point: 2.5 years ago my HBa1C was 13.0. I started taking 2000 mg of Metformin per day and also 40 mg. of Glipizide. After 6 months my HBa1C went down to 10.5. Doctor wanted me to start insulin but I balked. I went on the ketogenic diet and my HBa1C came down to 6.4. Now I just take Metformin not Glipizide. If I stop the Metformin for several months my A1C goes up to about 7.5. Clearly Metformin has an effect on the A1C (not to mention the other benefits it offers). But in my 63 YO diabetic body the ketogenic diet has a far greater impact than oral meds.
Congratulations your hard work has definitely paid off for you.
 

DragonBits

Well-Known Member
I've been on Metformin SR two 1500mg since 2010. Along with my low carb diet I've been able to keep my A1c steady at 5.2

Vince, at it's highest point, how high had your A1C gotten before you focussed on getting it down? And or fasting BG.

Just curious to see what can be done.

Btw, Congrats
 

Vince

Super Moderator
Vince, at it's highest point, how high had your A1C gotten before you focussed on getting it down? And or fasting BG.

Just curious to see what can be done.

Btw, Congrats
It's been almost 10 years now since I first saw (the Wheat Belly Doctor) Dr. William R Davis. He used to have a practice in Milwaukee and it was only 10 minutes from my house. He started me on the no grain low carb diet, I thought he was a nut but I gave it a try. It definitely changed my life forever, I was diagnosed as insulin resistant. I have no idea what my A1C was at that time but after he retired. I met Tara Dall one of the leading lipidologist in the United States. She was a little further away, good half an hour. I credit them two people with giving me the knowledge to control my blood sugar and all the damage that it does to a person's body.
 

Nelson Vergel

Founder, ExcelMale.com
My gut got so much better with Metformin (some people report the opposite). But after taking it for 3-4 weeks my fatigue gets worse. It really slows down ATP production in the mitochondria.
 

DragonBits

Well-Known Member
Vince, I saw
In people with Type 2 diabetes who take metformin therapy, serum folic acid levelsdecrease 7 percent and vitamin B12 levelsdecrease by 14 percent. (17) B12 and folic acid depletion also increases homocysteine levels. In addition, metformin may deplete CoQ10, thereby increasing heart disease risk.Dec 11, 2016
A Practical Guide to Avoiding Drug-Induced Nutrient Depletion ...
Nutrition Review | A blog about health science, human physiology, and nutrition, with a focus on alternative medicine and life extension. › 2016/12 › p...

I am now taking metformin, I only take 500 ER twice a say.

I saw in one post where you supplement with 5000 mcg of B12, was that right?

Only ask because it seems really high.

Seems a lot higher than you would need, the "high potency" b complex I was taking has 100 mcg of b12 and says that is 4000% of DV. The min recommended is 2.4 mcg.

So was it really 5000 mcg of B12?

And Cq10, I currently take 300 mg, do you think that is enough to more than compensate for any loss due to metformin?

My Cq!0 levels before taking this supplement was 1.39 (.37-2.20) , not at all low much not high either. I think early next year I will retest Cq!0 levels.
 

Vince

Super Moderator
Vince, I saw


I am now taking metformin, I only take 500 ER twice a say.

I saw in one post where you supplement with 5000 mcg of B12, was that right?

Only ask because it seems really high.

Seems a lot higher than you would need, the "high potency" b complex I was taking has 100 mcg of b12 and says that is 4000% of DV. The min recommended is 2.4 mcg.

So was it really 5000 mcg of B12?

And Cq10, I currently take 300 mg, do you think that is enough to more than compensate for any loss due to metformin?

My Cq!0 levels before taking this supplement was 1.39 (.37-2.20) , not at all low much not high either. I think early next year I will retest Cq!0 levels.
Yes, that is a level that I was taking for many years. 5000 MCG of vitamin B12, I recently reduced the level to 2500 MCG. When I had my B12 levels checked (5000mcg) they were about two-time the maximum level. I was told it was completely safe to have that high of level.
 

DragonBits

Well-Known Member
My gut got so much better with Metformin (some people report the opposite). But after taking it for 3-4 weeks my fatigue gets worse. It really slows down ATP production in the mitochondria.

Nelson, that is a very specific answer as a source of your fatigue.

Makes me wonder, is there a test for ATP production in the mitochondria?

I read a little about an organic acid test, it seems similar to the dutch test, are either of those involved?
 
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