This column last specifically reviewed the topic of metformin benefit on cancer reduction two months ago. We know that stress and bad diet -dysnutrition and lack of exercise – promote the risks of fatigue, insulin resistance, lipidemia, diabetes, obesity, cancer, infection..
To put diabetes in perspective, we need to read the classic articles by
A J Hodgson of 1912 of his experience with diabetes over 20 years in Canada, in which he posed as the “chief cause in the growing epidemic of diabetes that past half century the rapid increase of intake of glucose or ‘corn syrup’, the astounding amounts being eaten at speed; and the nervous stress and strain of American life”. Nothing seems to have changed in the endless Western preference for exposure to stress and lunatic gluttony; and lunatic Regulatory blindness the past century in doing nothing to enforce improvement in the food chain, while cigarette smoking and cannabis have been drastically regulated. So much of what Hodgson wrote about the chief cause of epidemic ie type 2 diabetes remains true today- personal hygiene, the unwillingness to eat and exercise sensibly;
Banting Macleod Best & Collip ( Toronto 1921) on the first extraction and use of insulin,
Werner and Bell (Dublin 1922) on the first synthesis of dimethylguanidine- metformin.
DIABETES AND CANCER INCIDENCE:
*The Finnish ATBC study 2006 showed that the worst obesity and metabolic syndrome associated with 40% increase in bowel especially rectal cancer.
*In older obese women in Italy 1999, type 2 diabetes tripled the incidence of endometrial cancer.
*In a 10year study in Jena, Germany (2005), insulin-treated diabetics showed a 10 fold increase in cancer (mostly rectum and colon) compared to the control population.
*In a study of pancreas cancer in Italy 2004, pancreas cancer was three times more common in those with type 2 DM than in non-diabetics.
*We have previously reviewed the evidence that lowering lipidemia – hypolipidemia– with statins may increase cancer risk, without reducing insulin resistance or diabetes risk.
A new trial from the Univ Connecticut last month , and two new reviews last week- from the European Institute of Oncology and the University California, strengthen the case that meformin is a crucial cancer preventive and therapy, that by promoting AMPK at the cellular level, it switches off cancer cell proliferation ie immortality, while promoting anti-aging in all healthy tissues.
METHODS: Pubmed and Google search for English abstracts under “metformin AND CANCER”
There are now at least 12 studies and trials of metformin and cancer available on Pubmed and through the internet;
too disparate to do a metanalysis, but certainly a review offering nothing but good news:
Metformin has been reported in studies to produce less cancers and cancer-related deaths than occur without it ie with insulin or sulphonylureas or without any antidiabetic drugs:
metformin and cancers in human :
* 29% fewer cancer deaths (non significant) in diabetics after mean 13.6yrs –UKPDS 1998;
* reverse endometrial hyperplasia in a woman- 2003 Mayo clinic ;
*perhaps 21% fewer cancers in diabetics on metformin Tayside UK 2005
*metformin benefit on cancer in human cancer cell cultures:
Prostate cancer in vitro France 2008
lung cancer in vitro Univ Arizona 2005;
colon cancer in vitro Pennsylvania 2007;
ovarian cancer McGill 2008;
and in hamsters: pancreas cancer Nebraska 2001;
and in mice lung cancer McGill 2008 ..
YET USA Industry and regulators – owing to obvious commercial vested interests- take the indefensible stance that eg human estriol is an unregistered new drug that must be proven in trials. It is said that no new drug can be registered there before an average of $600million has been spent on research and trials. So no sane for-profit company is going to fund trials on an unpatentible natural molecule – especially a sex hormone that has evolved in humans for millions of years , without a single reported case of natural or use-related adversity.
The same goes for metformin- a natural plant derivative first isolated 87 years ago, the only drug ever tested in a 20year RCT- and proven in numerous trials and controlled studies to have zero serious adverse effects, and proven to be a panacea- the only drug effective against virtually every major chronic degenerative disease of aging.
Yet threatening regulatory concern is hypocritically expressed – without the slightest evidence against it – when metformin is used as the only evidence-based drug to prevent and reverse the epidemic complications of overweight BEFORE obesity, PCOS, hypertension, arthritis, diabetes, CVD, stroke, visual / renal impairment, neuropathy, or cancer present.
It is well shown in studies that waiting for obesity let alone diabetes increases major disease let alone premature death by 2 to 5 fold; and that used in prevention it reduces the incidence of new diabetes by 30% to 90% in a dose-dependent fashion up to reasonable dose tolerance; and in type 2 diabetes halves the incidence of premature death.
So since metformin is associated with reduction of even cancer, it should (except in terminal or wasted non-diabetic patients, or temporarily in unstable renal or respiratory-metabolic function) be added cautiously and titrated up to moderate dose short of intolerance in any patient presenting at any age after 12yrs if not younger with rising overweight ie BMI much > 25kg/sqm or waist girth much >80cm, unresponsive to diet and lifestyle attempts
Dedicated to (mal)nutrition- metabolic syndrome – PCOS – diabetes – cancer and metformin sufferers, and researchers: Werner and Bell (Dublin); Sirs Harold Himsworth and Stanley Davidson (UK); Professors Jack Brock, Stewart Truswell and WPU Jackson at University of Cape Town UCT; Frank Maudsley Parsons (Univ Leeds); Rick Turner and Rury Holman(UKPDS); Gilbert Forbes, Tim Lohman, Gerald Reaven, Fred Naftolin, Charles Glueck (USA); and the DPPRG trialists on all continents.