Metformin & Simvastatin

New Finnish cell study [1] below.

I have used Metformin & Simvastatin for quite some time - perhaps on flimsy evidence, at the beginning.

The problem with most of the Metformin-PCa studies is that they involve only diabetics. However the 2014 Swiss study [2] that convinced Dr. Myers to recommend it, did not involve men who were already using Metformin. I'm assuming that none of the 44 CRPC men were diabetic.

"Thirty-six percent of patients were progression-free at 12 wk, 9.1% were progression-free at 24 wk, and in two patients a confirmed ≥ 50% prostate-specific antigen (PSA) decline was demonstrated. In 23 patients (52.3%) we observed a prolongation of PSA DT after starting metformin."

"1000 mg twice daily" is a bit higher than my 500 mg thrice daily.

A number of human studies have shown a benefit for statin use in PCa, and there are good reasons why this might be so: (i) excessive accumulation of cholesterol in cancer cells, (ii) the ability of PCa cells to create androgens from cholesterol, & (iii) the ability of PCa cells to manufacture cholesterol.

I don't want to cherry-pick Simvastatin studies, & the name is only important in the context of the new study. The researchers were looking for possible synergy of statins with Metformin, & Simvastatin was the selected statin.

Why, given the human studies, should we be interested in cell studies at this point? Well, it's nice to know what might be going on in the body, & why each may be beneficial, & the degree to which the combination might be synergistic.

Turns out that we already have two cell/mouse studies that looked at the combination:

[3] (2014 - Ohio) "Here, we report that combination of simvastatin and metformin acts synergistically, within the pharmacologic range, to inhibit C4-2B3/B4 mCRPC cell viability, with minimal adverse effect on PrEC normal prostate epithelial cells, prevents invasion, migration, and colony formation, and inhibits primary tumor formation, cachexia, bone metastasis, and biochemical failure in a C4-2B4 orthotopic mouse model, through amelioration of CRPC metabolic aberrations."

[4] (Same team - 2014): "Because normal cells do not possess the same metabolic aberrations as metastatic CRPC cells, SIM+MET treatment had only a minimal effect on normal prostate epithelial cell viability, ~5% decrease in viability at the top-end of the pharmacological range.10 In stark contrast, SIM+MET treatment significantly inhibits metastatic CRPC cell viability and metastatic properties, ameliorates CRPC metabolic aberrations, and induces cell cycle arrest and necrotic cell death in CRPC cells. Although C4-2B cells are resistant to cell death by extrinsic apoptosis, they are not resistant to necrotic cell death, making SIM+MET an excellent novel potential chemotherapeutic option for apoptosis- and chemotherapy-resistant metastatic CRPC cells."

In the new study, which used PCa "(LNCaP) and normal (RWPE-1) prostate epithelial cell lines":

"Metformin decreased the relative cell number of LNCaP cells by inducing G1 cell cycle block, autophagy ... whereas RWPE-1 cells were resistant to metformin."

"However, RWPE-1 cells were sensitive to simvastatin, which induced G2 cell cycle block, autophagy and apoptosis ... in these cells."

"Combination of metformin and simvastatin ... increased autophagy and instead of apoptosis, induced necrosis in LNCaP cells. Synergistic effects were not observed in RWPE-1 cells."

"These results suggest, that prostate cancer cells may be more vulnerable to combined growth-inhibiting effects of metformin and simvastatin compared to normal cells. The data presented here provide evidence for the potency of combined metformin and statin, also at pharmacologic concentrations, as a chemotherapeutic option for prostate cancer."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/273...

[2] ncbi.nlm.nih.gov/pubmed/244...

[3] mct.aacrjournals.org/conten...

[4] ncbi.nlm.nih.gov/pmc/articl...

3 Replies

oldestnewest
  • Thanks for the update! I take 850mg metformin 3x per day (max dose) and 40mg simvastatin with coq10 100mg at night. Undetectable PSA <0.02.

  • How long <.02 ?

  • I have been taking metformin and atorvastatin for years and was diagnosed April 2015 with PC and at times was taking 1000mg of morning and 1000mg in the evening of metformin and was taking simvastatin before was changed to atorvastatin. Just saying............

You may also like...