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Tuesday, February 8, 2011

Metformin and Dementia - The Good, The Bad, and The Ugly

Metformin ...a commonly prescribed drug to control blood sugar might increase the risk of Alzheimer’s disease.

Metformin ...a common diabetic drug may help in fighting brain disorders like Alzheimer's or dementia

This is creepy, but says it all!
Late last year a friend and reader of this blog suggested I look into the drug Metformin as possibly being beneficial in treating FTD. It was published all over the place that Metformin was a possible cure for Alzheimer's - even Time Magazine picked up the story. Well, it made for nice headlines, but after a couple months of digging more deeply into the actual research I am left a little confused, and very skeptical. To be sure you really have to dig deep to get a clear picture. If you were to Google "Metformin + Dementia" the results returned are overwhelmingly positive. If you Google "Metformin+increased amyloid" they are overwhelmingly negative.

The way I see it, in my own demented mind, is that the research needs to be interpreted very conservatively when it comes to pointing a finger at Metformin as either a cause or a cure. It is probably neither. When I delved into the actual chemistry it appears that it is Insulin, rather than Metformin, that is causing the actual beneficial effects observed. Metformin serves to manipulate the uptake and activity of Insulin in the brain, and influences the utilization of glucose in the process. It all comes back to the original hypothesis that Amyloid and Tau overproduction and phosphorylization is a byproduct of brain cells being starved for nutrition, and overproducing those substances in a last-gasp effort at survival. That is just my oversimplified summary-interpretation of what is going on based on the result that Metformin alone causes an increase in amyloid, and Metformin along with Insulin reduces amyloid.

More likely to be of benefit than Metformin, is another class of related drugs used to treat diabetes. A research study suggested that a certain class of diabetes drug, commonly called a glitazone, might lower the risk of Alzheimer’s in people with diabetes. Pilot studies in small groups of patients have hinted that the drugs may be of some help, and the National Institute on Aging is sponsoring research in this area

In the study, researchers used the records of 142,328 patients in the Veterans Affairs system who did not have dementia but were just starting to take a glitazone or insulin. They tracked the patients for six years. Compared with those using insulin, among the patients who took pioglitazone (Actos) or rosiglitazone (Avandia), there were nearly 20 percent fewer cases of Alzheimer’s. The glitazones had a similar advantage over another diabetes drug, metformin.

Glitazones lower blood sugar by helping the body to use insulin more efficiently, so that less insulin is needed. The drugs may also lower inflammation. It is interesting that the study directly compares against Metformin, and as far as I can tell was never widely reported. It makes me wonder if there is a money trail to follow somewhere in all of this. That is a lot of people, but it is just looking at data not actually manipulating any variables or comparing drugs in a double-blind study which would be more conclusive, so again, a conservative approach is my course.

So, here is an interesting question. I took Metformin without Insulin for several years. I developed FTD. Could that be the cause? Did Metformin cause my condition? It is as good of a working hypotheses as any for me right now. At least as good as blaming it on Albino Brain-Chiggers!

There are many, many interesting articles both pro and con on the subject of Metformin and FTD and Alzheimer's, but below is the one I found most readable, and even-handed. Though this mentions Alzheimer's, there are also studies out there makinbg similar links to FTD due to the similar brain chemistry.  I have copied the article in it's entirety, even the video, as well as provided the link to the original article at the end.

Here it is:
Research published today is suggesting that a commonly prescribed drug to control blood sugar might increase the risk of Alzheimer’s disease. But, as this ScienCentral News video explains, it also suggests that using the drug in combination with insulin might reduce the risk.





Interviewees: Francesca Fang-Liao,University of Tennessee School of Medicine and Huaxi Xu, Burnham Institute for Medical Research and Gregory Brewer, Southern Illinois University School of Medicine
Produced by Joyce Gramza– Edited by James Eagan
Copyright © ScienCentral, Inc
Clinical Implications?
Besides well-known complications like nerve damage, people with type 2 diabetes also have twice the normal risk of Alzheimer’s disease. In fact, some researchers even describe Alzheimer’s as a "type 3" diabetes.
So Alzheimer’s researchers at San Diego’s Burnham Institute for Medical Research tested the effects of diabetes treatments on brain cells. They found that metformin, a drug commonly-prescribed to diabetics and prediabetics (those at risk of becoming diabetic), can more than double the production of amyloid-beta, or a-beta, the protein that forms toxic brain plaques in Alzheimer’s.

Francesca Fang-Liao, Huaxi Xu and their team saw this increase in a-beta after treating brain cells in the lab with metformin. However, the effect was reversed when they added insulin. As they wrote in the Proceedings of the National Academy of Sciences, they also confirmed both findings in the brains of mice given metformin, or metformin plus insulin.

"Based on the chemical structure of metformin, it doesn’t look to be able to cross the blood brain barrier," says Liao, who is now at the University of Tennessee School of Medicine. "However… when we gave metformin in the drinking water [of mice] we found that after one or two days it reached to the brain, accumulating there in significant concentrations.



"We found that (for the metformin-only mice) the a-beta level had been greatly increased in the brain, particularly in both the cortical area and the hippocampal area. Those are the regions that are mostly affected in the Alzheimer’s disease patient," she explains.
"We believe that this work has probably significant implications in the current medication prescribed to the diabetic patient," says Liao.

Adds Xu, "If you are a patient with diabetes, you already have a higher chances of getting Alzheimer’s disease than normal people. If you take metformin alone, you further increase the chance of getting Alzheimer’s disease."

Xu says the protective role of insulin against Alzheimer’s was suggested by his previous work in collaboration with 2000 Nobel laureate Paul Greengard.

Memory Effects?
But other Alzheimer’s experts are more cautious. Southern Illinois University School of Medicine’s Gregory Brewer says the study is "intriguing and raises a red flag of caution about metformin. But on the other hand, the missing link in the paper is the fact that their studies did not show any problems or measure any problems with memory."

Brewer, who holds an endowed Chair in Alzheimer’s disease research, points out that a-beta is produced in very tiny amounts in our cells throughout our lifetime, and that some researchers think small amounts of a-beta may actually be required for learning and memory.

"What we don’t know is whether those levels were toxic to the brain cells that they were studying," Brewer says. He says that if further research does reveal memory problems in mice that get metformin alone, it’s good news that combination therapy appears to be a solution.

But in the meantime, "the complications from diabetes are more severe than from Alzheimer’s disease… if you don’t treat the diabetes, you’ll die much sooner." Brewer adds that a healthy diet and exercise are known to be beneficial in both diabetes and Alzheimer’s disease.

Liao and Xu say they are now working on behavioral and memory testing in the mice, but point out that other research is already hinting that insulin may reduce diabetics’ risk of Alzheimer’s.

They point to a human study published in December 2008 in which researchers led by Michal Beeri at Mount Sinai School of Medicine compared brain autopsy findings of diabetic patients against the patients’ treatment records.

"They found that the patients’ brain from the single therapy has shown much more dramatic Alzheimer’s disease pathology than the patient that had taken combination drugs," explains Liao. "So that’s kind of supporting our observation. However, they haven’t collected enough patients which have been taking metformin specifically… as a single agent."

Liao says collecting and comparing that information in large numbers of patients would take major effort and funding, and hopes one of the outcomes of their work will be to call attention to the need for such a study.

Add Insulin?
Liao says that thanks to previous research by Xu and others, more doctors are already prescribing insulin along with metformin for treating diabetes.

"Indeed, in the clinical setting, insulin has been brought into the treatment more and more frequently nowadays, even in the prediabetic setting, in addition to metformin," she says. "I would say that would be a good trend."

The researchers agree with Brewer that a-beta itself remains a subject of controversy among Alzheimer’s researchers.

"Whether the human body or human cell needs a certain level of a-beta protein for normal function is still under great debate in the Alzheimer’s field," says Xu. But, he says, researchers in the field do agree that "over-production of this a-beta protein, by any abnormal process associated with genetic reasons or environmental factors, is bad for the human being."

This research was published in the Proceedings of the National Academy of Sciences early online edition the week of February 23, 2009, and was funded by the National Institutes of Health and the Alzheimer’s Association.

Here is the link to the original article: Diabetes Drug Linked To Alzheimer’s


The Good: Metformin may help dementia
The Bad: Metformin may cause dementia
The Ugly: I took Metformin, and have been diagnosed with dementia. Maybe I have Albino Brain-Chiggers.

So... for now I am only going to take Metformin when and if my blood sugar goes awry, and then only for a short duration. Until more research is done to prove if Metformin is a cause or cure I must place it into the category of interesting, informative, and investigative.

I would like to give a special 'Thank you!" to Kevin for starting me down this path of research, which led me to something which I do think will be of help, and that is the substitution of some ketones for glucose to circumvent the insulin resistance causing an energy utilization deficiency in the brain. I found that while researching this ...and so it goes. There will be more on that in a later post.

Everything here is my account of what happened to me, or my interpretation of stuff, except what I copied from somewhere else. Every case of FTD is different. Keep in mind as you read this that the person who wrote this has dementia. That would be ME.
Medical Disclaimer.

Comments are welcome.


9 comments:

  1. check the following recent article:
    "Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer's-like changes" by Gupta A, Bisht B, Dey CS,published in Neuropharmacology journal (2011;60(6):910-20.
    It is a interesting study!!!!!

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  2. I just stumbled across your post while googling about metformin and dimentia. I've been taking metformin alone (w/o insulin) for years, and I've developed memory problems and bouts of dimentia so bad that it is beginning to affect my daily life. It is both scary and embarrassing! I am only 33. I'm actually scheduled to see a neurologist tomorrow because my GP did not find anything 'abnormal' (i.e. vitamin deficiency, etc) in some labwork. Apparently she must not know anything about this link between metformin and AD!

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  3. I too had a negative experience with Metformin. I awoke one morning after initially suffering from severe muscle aches, and memory loss/fogginess to find that my vision had suffered. I could not read the morning paper! I was lucky my doctor had discovered research that uncovered a link btw alzheimer's and metformin and she took me off this dreadful drug. 2 weeks later my vision returned to normal and all other symptoms disappeared. I also discovered that whilst taking met. I had more symptoms of diabetes than I did BEFORE. NOW the clincher. A friend who also took metformin whilst I had WARNED him and his family of the risks, has now died from the effects of dementia after only 2 years on metformin.
    Only yesterday another friend told me of vision problems,memory loss and muscle cramps after only 2 weeks on metformin.
    There IS a money trail and while there IS an increasing number of diabetics who develop alzheimers,there is also a relative number of those who are takig METFORMIN!!!! DO the MATH people!!!

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  4. I have not been able to access the original research report cited on your blog, only an abstract, which doesn't tell much. Diabetics are more likely to develop Altzheimer's than the general population. But the questions are, how well controlled were these diabetics who developed Altzheimer's? Did they eat a low carb diet or did they eat the standard ADA American Death Association diet? How high were their A1cs? Many diabetics need to be on insulin to control their blood sugars. Unfortunately, doctors are more worried about being sued if patients go hypo than they are if they are sued for damage caused by high blood sugars --ie brain damage from high blood sugars and degenerating brains.

    Here's another article that raises concerns about this research report you cited here.
    http://www.sciencentral.com/video/2009/02/23/diabetes-drug/

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  5. My doctor first put me on Metformin for the diabetes in the late 1990's, immediately I had memory problems. I couldn't spell, I couldn't drive to our local hospital (which I had been to many, many times for my wife) suddenly I didn't know how to get there. So I quit taking it and my memory returned. Then about 4 years later my doctor said I had to get back on something so he gave me Actos, same problem. Then he tried another brand with the same result, memory loss. After trying several different brands I quit taking it completely. This time though,,,the memory loss/problems never went away, The damage is permanent. Numerous people comment on my memory when things/I go weird. I used to read books alot, now I can't. I also used to write stories and they were good but now I can't. The worst thing though is,,,all the time I was on the medication my blood sugar levels always stayed the same, there was never any improvement.
    With all the people having this problem and brain damage (some at very young ages,,,I'm 57) why hasn't there ever been any class action suits filed against the producers? I would rather be able to think and have elevated blood sugar then to take the medicine and become an idiot that can't think, spell, or remember anything.
    The least they could do is say, "This may cause memory loss or thinking problems and if that happens, quit taking the medicine and come back and see us"

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  6. Husband had diagnosis of Alzheimers and mild cognitive impairment. I started him on 1T coconut oil 3x a day and raised to 2T 3 x a day plus followed insulin resistant diet, high in Omega 3s, no white carbs, force him to walk with me and the dog daily, and he basically went back to how he was 20 years ago. Look at research done by Dr. Newport and read Stop Alzheimers Now, has great great information in it. Country with lowest rate of Alzheimers is Japan, which probably has highest consumption of fish, good fats! Thanks for your post!

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  7. Hi everyone

    Further to my post Jan 21 2012, I have been doing considerable research regarding diabetes and metformin. Disregard anything you read about its benefits. Doctors put me on insulin alone and the effects were disastrous. I became tired just climbing the stairs, constantly felt weak, had considerable "hypos", brain became foggy due to LACK of glucose.

    I STOPPED taking everything. NO DRUGS. I am now taking only natural substances and exercising. My= sugar levels are not yet consistent but I believe it to be improving.

    I have discovered further evidence re metformin. ANOTHER friend has recently been diagnosed with early stage dimentia. Guess what...metformin. As I said before..do the math.

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  8. having metformin 500 mg SR every day and was having memory loss every day that it affected my work.I often used to forget names of persons, missed appointments, misplaced keys. After reading the side effects about memory loss due to metformin I have stopped now. I also strongly beleive the cognitive ability of a person comes down drastically.

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  9. Very nice post here thanks for it .I always like and such a super contents of these post.Excellent and very cool idea and great content of different kinds of the valuable information's.
    metformin side effects

    ReplyDelete