THE MOST EFFECTIVE AND UNDER-APPRECIATED LIFE EXTENSION
DRUG
By Ward Dean M.D.
Metformin, an anti-diabetic biguanide drug, has recently been introduced in
the United States for the treatment of non-insulin dependent diabetes (type II
diabetes). In addition to its promise in treating diabetes, metformin may prove
to be one of the most promising anti-aging; life extending drugs available!
Metformin is chemically very similar to phenformin, an anti-diabetic drug
that was discontinued in the United States by the FDA in 1976. The reason for
phenformin’s removal from the market was because of a number of excess deaths in
diabetic patients, caused by lactic acidosis.
These deaths were invariably due to its continued use in diabetic patients
who had compromised kidney or liver function. No deaths were ever reported in
patients who had normal kidney and liver function.
Phenformin’s removal from the market was greatly lamented by most
diabetologists, one of who once told me “phenformin did everything! It lowered
insulin, reduced blood cholesterol and triglycerides, stimulated immunity and
even resulted in weight loss!”
He blamed the excess deaths with phenformin’s use on the “stupid docs” who
continued to use it in the face of abnormal liver or kidney function. Metformin
is similar to phenformin in its beneficial metabolic effects, but it is much
safer, in that it has even fewer propensities to cause lactic acidosis than
phenformin.
One of the most universal changes with age, is a progressive loss of glucose
tolerance. When this loss of glucose tolerance becomes pronounced, it is
diagnosed as diabetes.
Indeed the diagnostic criteria for older people are much less strict than the
criteria for younger people; otherwise, nearly every senior citizen would be
diagnosed as diabetic.
In parallel (or perhaps, the cause) of this loss of glucose tolerance with
age, is a progressive loss of insulin sensitivity, i.e. a loss of response to
insulin by peripheral tissues.
Metformin’s mechanism of action is unlike other anti-diabetic drugs, like the
sulfonylureas (e.g. Glyburide, Diabinase). The sulfonylueas act by increasing
the output of insulin from the pancreas, kind of like putting the pancreas on
the dining room table and going over it with a rolling pin, squeezing out
whatever insulin remains in the already over worked pancreas. After a period of
time, this often results in pancreatic failure, transforming a type II
(non-insulin dependant) diabetic into a type 1 (insulin dependant) diabetic.
Metformin, to the contrary, acts by increasing the sensitivity of peripheral
tissues (like muscles) to the effects of insulin. In effect, it rejuvenates this
response, restoring the effects of glucose and insulin too much younger
physiological levels. Although metformin is approved only for use in type II
(non insulin dependant) diabetics, I use it with a great deal of success on my
type 1 (insulin dependant) diabetic patients as well.
When used with insulin dependant patients, I find that they are able to
dramatically reduce their doses of insulin, and more easily maintain stable
levels of blood glucose. Metformin acts in a much more physiologic manner than
either the sulfonylureas, or even exogensously administered (i.e. injected)
insulin itself.
Consequently, if rarely, if ever, causes hypoglycemia, which may often result
from the use of insulin or the sulfonylureas.
One potential side effect in long term users of metformin, is that it may
cause malabsorption of vitamin B12, consequently, I recommend that anyone taking
metformin also supplement their diet liberally with vitamin B12.
Diabetes is believed by many gerontologists to be an example of accelerated
or premature aging.
Since nearly everyone suffers from “subclinical” diabetes (i.e. a loss of
glucose tolerance with age), I recommend metformin to all my life extension
patients who are over 40.
I believe metformin has a profound and truly “rejuvenating effect” on glucose
and insulin metabolism. Among other benefits, this results in a reduced rate of
pro-aging cross linkages in collagen. Dilman (1992) lists the following benefits
of phenformin, which are shared by metformin;
1) Lowers blood cholesterol, triglycerides and beta
lipo-proteins.
2) Reduces development of atherosclerosis
.
3) Reduces insulin levels.
4) Increases hypothalamo-pituitary
sensitivity (which declines with age).
5) Improves cellular
immunity.
6) Reduces incidence of chemically induced cancer in
rats.
7) Enhances activity of anti-cancer drugs.
8) Suppresses
the growth of some tumors.
Finally phenformin (and presumably metformin) increased the maximum lifespan
of experimental animals.
Consequently, in view of its record of safety and paucity of side effects,
its physiological mode of action, and broad range of beneficial effects, I
strongly encourage all of my patients over the age of 40 to take 500mg of
metformin twice a day.
Copyright 2003. This article may not be reproduced for public
broadcast in any form, without the written permission of: International Antiaging Systems