The 12+ Benefits of Metformin

Beyond Diabetes: Fight Cancer, Aging, Dysbiosis

Metformin is a standard anti-diabetic drug, taken by millions since 1957. It is currently being prescribed to over 150 million individuals worldwide. R R 

 
https://www.ncbi.nlm.nih.gov/pubmed/27939359

https://www.ncbi.nlm.nih.gov/pubmed/27939359

 

Basics

 
 

Metformin was discovered in 1922. R

It is one of the few miracle drugs that has ever been created. 

Many of the benefits metformin seems to have is through increasing production of butyrate and HDAC inhibition, in butyrate deprived diabetes patients. 

Metformin is a biguanide derived from the plant Galega officinalisR

G. officinalis is rich in guanidine, which has helped create other biguanides. R

Other biguanides have been used for diabetes, such as phenformin and buformin, but they are commonly associated with lactic acidosis. R

Benefits

1. Improves Metabolic Function

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613459/figure/F1/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613459/figure/F1/

 

Metformin is notorious for the treatment of pre-diabetes, type 1 and type 2 diabetes. R 

It lowers blood sugar/suppress glucose production in liver. R 

It can lower hemoglobin A1c levels. R

It doesn’t help diabetic retinopathy. R

It increases cortisol regeneration (by 11-beta-HSD1). R

Metformin also inhibits oxLDL-increased LOX-1 expression and oxLDL-collapsed AKT/eNOS levels (probably via SIRT1 and AMPK). R

2. Protects The Heart and Lungs

Metformin can lower the risk of heart disease. R

It helps chronic heart failure (by improving VE/VCO2 slope). R

It also attenuates lung fibrosis development (suppressing NOX4). R

Metformin can increase the bioavailability of nitric oxide, decrease the formation of AGEs, intercellular cell adhesion molecules (ICAMs) & vascular cell adhesion molecules (VCAMs). R

3. Improves The Gut Microbiome

 
 

Metformin improves gut microbiota. R

It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations, serotonin, and histamine and increases the bile acid pool within the intestine, and alters the microbiome. R

Metformin can increase the production of butyrate and helps dysbiosis. R

It shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota. R

Animal and human studies have shown that metformin can increase the diversity and composition of diabetic patient's gut microbiota. R

4. Is Anti-Microbial

 
 

Metformin also acts as a anti-microbial, since it can inhibit the growth of certain bacteria. R

For example, it can alter folate metabolism in bacteria, without changing the host folate levels (by inhibiting DHFR). R

It inhibits bacterial methionine synthase, thus preventing "methyl trapping". R

It inhibits NDH-1, leading to increased reactive oxygen species (ROS), leading to accelerated bacterial death. R

Metformin can decrease dihydroxyacetone phosphate (DHAP) and increase the nicotinamide adenine dinucleotide hydrogenase - nicotinamide adenine dinucleotide (NADH-NAD) ratio in bacteria. R

This decreases the amount of energy bacteria have. R

Most of metformin's anti-microbial activity has been shown to mostly effect:

  • E. Coli R
  • Pseudomonas species R
  • Bacillus subtilis. R
  • Mycobacterium tuberculosis R
  • Listeria monocytogene R
  • Salmonella R
  • Rickettsia spp. R
  • Legionella pneumophilia R
  • Coxiella burnetti R
  • Shigella flexneri R
  • Francisella tularensis R
  • Burkholderia pseudomallei R

5. May Increase Longevity

Metformin may be anti-aging.R

It increased the lifespan of worms and mice. R

It increases insulin sensitivity, reduces LDL and cholesterol, helps with physical performance. R

It also is a metabolic stressor (propagated by the peroxiredoxin PRDX-2, oxidative stress via SKN-1/Nrf2, regulated by AMPK). R R R

Metformin can decrease IGF-1. R

It is currently being investigated for treatment and prevention of "type 3 diabetes"/Alzheimers. R

Through butyrate production, metformin can downregulate the expression of transforming growth factor beta (TGF-b) a pro-fibrotic cytokine. R

6. Regulates Hormones

In women, metformin may help polycystic ovary syndrome (increasing FOXO1, ATG3, and UV radiation resistance-associated gene). R

It also acts on gonadotropin-releasing hormone (GnRH) since it acts to inhibits follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion. R

It inhibits FSH action on ovarian granulosa cells. R

In men, it regulates male hormones. R

Metformin administration was associated with a reduction in total testosterone, free testosterone, and 17-hydroxyprogesterone and an increase in sex hormone binding globulin and dehydroepiandrosterone sulphate in normal males. R

In diabetic patients, metformin decreases the levels of thyroid stimulating hormone (TSH) by enhancing the effects of thyroid hormones in the pituitary and activating the AMPK). R

7. Fights Cancer

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613459/figure/F2/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613459/figure/F2/

 

Metformin both suppresses cancer cell growth and promotes organismal longevity through a key transcriptional target that is induced through inhibition of mitochondrial respiration and modulation of mTOR signaling. R

Metformin is a HDAC inhibitor. R

In diabetic patients, metformin decreases the risk of cancer. R R

It increases survival from rectal cancer. R

Metformin induced cell growth inhibition in renal cells (upregulating miRNA34a). R

It is insignificant to Prostate Stimulating Antigen (PSA). R

Combined with pifithrin-α, metformin helped with Parkin-mediated mitophagyR

Metformin may help with breast cancer. R

It helps drenocortical carcinoma (via inhibition of H295R cell growth in vivo). R

It also helps gynecologic cancers. R

In vitro, metformin has shown to help with bladder cancer. R

The ongoing GLINT Trial will give us more results in the future. 

8. Protects Against Stroke and Injury

In rats, metformin protects against stroke injury. R

In humans, it inhibits glutamate induced excitotoxicity in neurons. R

Metformin may also help with recovery from spinal cord injury. R

9. Helps With Weight and Obesity

 
belly-2473_960_720.jpg
 

In bipolar patients taking lithium, metformin helped fight weight gain. R

It decreased fat while increasing tolerance to hypoxia (via AMPK). R R

Metformin may help limit exposure of abdominal fat to glucose, and consequently, prevent a further increase in abdominal fat. R

It may be anti-obesity by affecting appetite suppression, improving leptin resistance, suppressing neuropeptide Y gene expression, regulating ghrelin, and increasing GLP-1 levels. R

Metformin also increases irisin, which increases the browning of white fat. R

10. Improves Liver Function

Metformin improves liver function, as it is able to lower blood sugar/suppress glucose production in liver. R R

It has been shown to be helpful in the treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) (by stimulating PPAR-α, which in turn activates fibroblast growth factor 21 (FGF 21)). R

Also, metformin was able to alleviates hepatosteatosis (via AMPK SIRT1). R

11. Improves Skin Quality

 
 

Metformin has been suggested for treatment of psoriasis. R

It has also been shown to be beneficial for hormonal acne, hidradenitis suppurativa and acanthosis nigricans.  R

12. Protects The Brain From Certain Toxins

Metformin can attenuate morphine antinociceptive tolerance decreasing neuroinflammation. R

It is also neuroprotective against the short- and long-lasting dopaminergic neurodegeneration induced by MDMA. R

Alternatives To Metformin

 
 

Berberine is a great alternative as it can improve metabolic functions, reduce inflammaiton, help the gut microbiome, and activate AMPK. R R

Caveats

Metformin is only by prescription in the United States.

Metformin may cause a vitamin B12 deficiency. R

Metformin may also cause lactic acidosis. R

Metformin blocks DAO production and so may contribute to/make histamine intolerance worse. R

Metformin has also been reported to decrease the blood levels of thyroid-stimulating hormone in people with hypothyroidism. R

Metformin is synergistic with ashwaganda helping hypothyroidism. R

Metformin is generally well tolerated. R

It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. R

Common side effects include diarrhea, nausea and abdominal pain. R

The use of metformin during all parts of pregnancy is controversial. R

It interacts with cimetidine and cephalexin. R R

Survival following intentional overdoses with up to 63,000 mg (63 g) of metformin have been reported, although fatalities have been rare. R

In old aged mice, it impaired visual acuity and spatial memory. R

Mechanism Of Action

Metformin:

  • Chronic intake reduces NRF2 R
  • Increases serum IL-10 (in T2D) R
  • Inhibits mTOR and activates AMPK R
  • Inhibits NF-kB R
  • Inhibits PPAR-gamma R
  • Inhibits Th17 upregulation R
  • Reduces TNF-a in blood R
  • Reduces MPC1 in urine R
  • Suppresses TGFB1 binding to receptor R
  • Upregulates AMPK and FOXO1 R
  • Works on GLUT4 R

More Research

  • The increase in insulin binding after metformin treatment has also been demonstrated in patients with NIDDM. R