Study: Reduction of colon cancer risk with metformin
Study: Reduction of colon cancer risk with metformin
Note: This is the second part of a two -part series about whether metformin has a place in naturopathy. You can find the first part here.
Reference
t. Higurashi, K. Hosono, H. Takahashi et al. Metformin for chemo prevention of metachronous colorectal adenomes or polyps in post-polypectomy patients without diabetes: a multicenter, double-blind, placebo-controlled, randomized phase 3 study. lancet oncol . 2016; 17 (4): 475-483.
Design
A 1-year-old multicenter, double-blind, placebo-controlled, randomized clinical study of phase 3 was carried out in order to review the security and chemoforming effects of metformin in sporadic colon cancer (evaluated by adenomal and polyp-recurrence) in patients with a high risk of adenom.
participant
One hundred and fifty -one non -diabetic adult patients, in whom individual or several colorectal adenomas or polyps were previously removed by endoscopy, the study from 5 hospitals in Japan were included. 79 were assigned to the metformin group and 72 of the placebo group. After 1 year, 71 patients in the metformin group and 62 underwent a 1-year follow-up colonoscopy in the placebo group.
medication and dosage study
metformin 250 mg per day
target parameter
Number and prevalence of adenomes or polyps
important knowledge
The prevalence of both adenomes and total polyps (hyperplastic polyps plus adenome) was significantly lower in the metforming group than in the placebo group. In the metformin group, 27 polyps (38.0 %) occurred in 71 patients. In the placebo group, 35 polyps (56.5 %) occurred in 62 patients (risk ratio [RR]: 0.67; p = 0.034). The metformin group had 22 adenomas in 71 patients (30.6 %) and the placebo group had 32 out of 62 patients (51.6 %; rr: 0.60; p = 0.016). In 15 (11 %) patients, side effects were observed who were all degrees 1. Low -dosed metformin reduced the prevalence and number of metachronous adenomes or polyps according to polypectomy.
practice implications
These results indicate that metformin in patients in whom a polyp or adenoma has been removed during routine colonoscopy can be of considerable use. The findings are noticeable for two reasons: firstly, it was non-diabetics; Second, these patients received relatively low doses metformin. Diabetics are typically prescribed 1,000 mg or more metformin per day.
intestinal cancer (CRC) arises from a accumulation of DNA mutations within normal cells that lead to cancer via polyps. The mechanisms of metformin seem to block this process. Therefore, metformin should be included in the list of active ingredients that prevent polyps and thus colon cancer.
Several earlier works by Higurashi and colleagues (authors of this present study) were preceded by this clinical study with metformin for CRC prevention. These showed the chemofeating effect of metformin in 2 rodent models and 1 human study on colorectal carcinogenesis. In a study from 2008, they showed that Metformin suppressed the development of intestinal polyps in a mouse model of family adenomatous polyposis. 1 In 2010, they reported that metformin reported azoxymethane-induced formation of colorectal aberrant crypt stoves (ACF) by activating adenosine monophosphate-activated activated Protein kinase (AMPK) suppressed. 2
In order to reduce the burden of colon cancer, the authors of a study from 2007 propose a paradigm shift - a departure from the current focus on the early detection of cancer towards efforts to actually reduce the incidence of cancer (ie). They emphasize: “Several large epidemiological and/or clinical studies have evaluated the possible preventive effects of more than 200 active ingredients, including fiber, calcium and non-steroidal anti-inflammatory drugs (NSAIDS), including aspirin and selective cyclooxygenase-2 (COX- 2) inhibitors to protect it CRC development. ” 3 The NSAIDS and COX-2 inhibitors have proven to be the most promising, although the latter are associated with an increased risk of cardiovascular events.
curcumin was on our list of nutritional supplements that should be considered to prevent CRC, since it effectively inhibited the polyp formation in mice that were fed with a high -fat diet. 5 While curcumin as well as metformin AMPK, it does not have the human data to support its use. Since the authors of the present study believe that the mechanism of action of metformin is activated by activating AMPK, we could think about whether other AMPK activators could have a similar preventive effect.
These results are noticed for two reasons: firstly, it was non -diabetics; Second, these patients received relatively low doses of metformin.
Berberin is often proposed as a botanical replacement for metformin in the treatment of type 2 diabetes mellitus. 6 Berber also activates ampk and inhibits the formation of colon tumors in mouse models.
metformin has a significant impact on the digestive tract, a fact that patients will inform you if you take too much dose. The regular intake of metformin changes the intestinal microbioma. These shifts explain part of the effect of metformin on the glucose high -homöostasis. 8 It has been shown that Berberin promotes similar changes in the intestinal microbioma.
Regardless of whether the drug Metformin falls into your scope or not, or whether your patients do not use it for philosophical reasons that the information in this current study is of interest. We can translate the results of this Metformin study to the fact that other means that have similar chemical effects on AMPK or the intestinal native could bring similar, albeit unproven.
note of the editorial office
Is Metformin Natural Canteen?
Our practice in the magazine for naturopathy is to emphasize the use of natural and complementary medicines so that our primary readership, naturopathic doctors, remains informed about current research results that influence their clinical practice. The provision of information about the prescription drug metformin can appear as a deviation from this practice. After careful consideration, we decided to review two research work on metformin, since the information is of clinical relevance for many of our patients. Some would argue that metformin is not a natural medicine as a prescription drug. Others would argue that it is a synthetic imitation of chemical galega officinalis , it falls into a less defined category. The prescription of metformin now falls within the area of responsibility of many of our colleagues, so that this distinction may be important. Even for those of us who cannot prescribe metformin, his new potential benefit in the prevention and treatment of cancer is still relevant, since many natural substances and lifestyle practices that we routinely prescribe patients can have similar effects on physiology.
In June 2016 there were almost 2000 articles to which PubMed (according to Mesh terms) was referred to, which refers to metformin and cancer. In this issue, two publications from 2016 will be presented. The mechanisms of action of metformin lead to a list of advantages against cancer, including the blocking of the MTOR signal path, the stimulation of the apoptosis of cancer stem cells, the inhibition of angiogenesis, the oppression of Her2 (human epidermal growth factor receptor 2, a protein that is sometimes associated with breast cancer), the increase in the advantage of more Chemotherapy and improvement in the killing of radiation cells. There are indications that Berberin can cause some of these effects, and while this idea creates great enthusiasm among our colleagues in relation to the use of Berber in similar situations, there are far more published evidence of metformin. There is no recognizable structural similarity between metformin and berberin molecules and the two substances do not always create the same effects. Although some speak of Berber as a botanical replacement for metformin, one should be careful with such assumptions, especially when it has been shown that metformin causes something that has not yet been shown for Berber.
Jakob Schor
editor, abstracts & comment
Journal of Naturopathy
- Tomimoto A, Endo H, Sugiyama M, et al. Metformin suppresses the growth of intestinal polyps in APCMIN/+mice. cancer science . 2008; 99 (11): 2136-2141.
- k. Hosono, H. Endo, H. Takahashi et al. Metformin suppresses azoxymethane-induced colorectal aberrant crypt stoves by activating the amp-activated protein kinase. mol carcinog . 2010; 49 (7): 662-671.