Metformin ...a common diabetic drug may help in fighting brain disorders like Alzheimer's or dementia
|This is creepy, but says it all!|
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:
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
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 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.
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.
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.
Comments are welcome.