how statins slow growth of prostate

[shortPSADT]

Cedars-Sinai Cancer investigators have found that lowering blood cholesterol enhances the action of immune cells, slowing the growth of prostate cancer. (Clinical Cancer Research: doi.org/10.1158/1078-Q434.c.... It provides a rationale for large-scale clinical testing of using cholesterol lowering therapy to prevent prostate cancer progression.

They established that lowering cholesterol acts through the immune system and not just directly on cancer cells.

My personal experience is that by taking Repatha, a relatively new drug that lowers cholesterol dramatically --more than statins -- has increased my PSA doubling time to 18.8 months, from an initial 1 month! Never before in my 23 year history of recurring bouts of oligometastic disease have I ever seen such a remarkable improvement. Usually I just play "whack a mole" with SBRT ever couple of years and get a year or two remission. Now I'm hoping for a relative long period without any kind of treatments except diet and Repatha. My total cholesterol in now 119, my LDL is 43, triglycerides 84 and HDL 60.

Here is my recent PSA history: 0.484 on 6/26/23, 0.400 on 7/24/23, 0.541 on 8/24/23, and finally 0.483 on 9/14/23. Another relevant fact is that I went on a plant based diet starting about 6 months ago and it is know that for some people this stabilizes or even reduces PSA.

[Hidden]

This is good to know.

[Mike1971]

Hi shortPSADT,

Thank you, this is very interesting.

It seems the link you provided does not work - any chance you can fix that? Thanks a bunch!

[Derf4223 in reply to Mike1971]

Dr. Google to the rescue cedars-sinai.edu/research/n....

[Mike1971 in reply to Derf4223]

Thx!

[shortPSADT in reply to Mike1971]

Seems like Derf4223 response my have the correct link. Sorry, I am not very good at this.

[Papillon2]

Fantastic! Keep it up and you will have to change your "nom de guerre".

healthunlocked.com/advanced...

[Medline]

Repatha (evolocumab) is a PCSK9 inhibitor, while several studies have shown that statins (HMG-CoA reductase inhibitors) increase PCSK9 levels [pubmed.ncbi.nlm.nih.gov/180..., pubmed.ncbi.nlm.nih.gov/235...]. PCSK9 inhibition, but not HMG-CoA reductase inhibition, is also associated with a lower risk of prostate cancer [pubmed.ncbi.nlm.nih.gov/365..., pubmed.ncbi.nlm.nih.gov/351...].

PCSK9 expression is regulated by SREBP2 (sterol regulatory element-binding protein 2). When intracellular cholesterol levels are low (as in statin therapy), SREBP2 is activated, which promotes PCSK9 transcription and reduces the anticancer effect of statins. Dipyridamole or metformin may prevent statin-induced SREBP2 activation and sensitize prostate cancer cells to statins [pubmed.ncbi.nlm.nih.gov/310..., pubmed.ncbi.nlm.nih.gov/305...].

[SViking in reply to Medline]

Thank you for your post. But that’s too much information for me to digest. So should we take a statin or not? I just started Lipitor a few months ago. What would be the best statin to take if they are in fact good for slowing progression?

[shortPSADT in reply to SViking]

I have no ideas as to the best statin. I couldn't tolerate any of them and that is how I got on Repatha.

[lokibear0803 in reply to Medline]

OK so here’s my paraphrase and a question:

— statins inhibit HMG-CoA reductase, but that’s not shown to help with PCa

— evolocumab has a different action: it inhibits PCSK9, which is shown to help with PCa

— lowered cholesterol levels activate SREBP2, which counters evolocumab’s effect

— taking metformin or dipyridamole may prevent that SREBP2 activation, thus allowing evolocumab to work against PSCK9; these two drugs may also sensitize PCa to regular statins (i.e. the HMG-CoA reductase inhibitors)

So I’m currently in the process of finding the best statin to take (i.e. well tolerated), and perhaps evolocumab (a non-statin) could be better — as per OP’s experience, reduced ASE‘s and impressive PCa action (and I do realize, this is n = 1).

So I might consider starting with evolocumab alone unless/until any PCa benefit tapers off (due theoretically to SREBP2 activation), at which point I could try adding metformin.

Am I interpreting correctly? I’m not asking for medical advice here; I will be meeting with my PCP and MO in the coming month, and this could nicely inform those discussions. TIA for any feedback.

[shortPSADT in reply to Medline]

Over my head -- I don't know much about biochemistry.

[TuffNuttoCrack]

My secondary cardiologist that specializes in men having APC immediately put me on Crestor 5mg and said men taking statins do better. Every statin I had tried previously, complications were too bad and we stopped.

[BB_1 in reply to TuffNuttoCrack]

I am taking Atorvastatin 1o mg daily.

[shortPSADT in reply to TuffNuttoCrack]

I failed mevacor, pravastatin and zocor. All three sent my liver enzymes over the top! That's how I eventually got on Reptha -- it doesn't have the same issues. But the downside is that it is expensive.

[BB_1]

I take Atorvastatin 10 mg daily

[pd63 in reply to BB_1]

I take 40mg daily, 10mg seems a baby dose

[BB_1 in reply to pd63]

still experimenting and I take other repurposed drugs

[Benkaymel in reply to BB_1]

I've been taking 20mg atorvastatin since way before I was diagnosed with PCa. It may have kept my PSA low but didn't prevent the tumours from growing.

[BB_1 in reply to Benkaymel]

I also take Metformin 500 mg to reduce insulin levels and I am not diabetic.

[Don_1213 in reply to BB_1]

Same here - twice daily.

[Don_1213 in reply to pd63]

I think I'm at 80mg daily.. 40mg seems wimpy (used to be at that, but wasn't doing enough, and apparently I can tolerate 80..)

[Jewelrylady in reply to pd63]

My husband was taking 20mg, but after starting Lupron, Zytiga and prednisone his lipid lab tests shot up so he’s increased to 40mg now. His liver labs went up, too, but doctor says they should go down by next test so he’s not changing hormone dosage yet.

[Rfs1975]

How about Berberine instead of Statins? ncbi.nlm.nih.gov/pmc/articl...

[BB_1 in reply to Rfs1975]

I take both

[MateoBeach]

wonderful response! Good potential tool for others to explore. You may have to change your HU name. 😆

[SpencerBoy11]

Been on statins for at least 25 years. Maybe it would be worse than it is?

[awb1]

Good to hear a discussion on statins . . . the alphabet soup of biochemstry is over my head, but I've been taking low dose rosuvastatin for several years, plus metformin . . . both off label, my A1c is 5.7 and cholesterol around 120.

[caysary]

I tried many stains but they all gave me severe muscle problems until I was on 10 mg crestor the brand name. Fantastic hi tech drug

[j-o-h-n]

From the Google Bugle:

Statins are drugs that can lower your cholesterol. They work by blocking a substance your body needs to make cholesterol. Lowering cholesterol isn't the only benefit associated with statins. These medications have also been linked to a lower risk of heart disease and stroke.

From me:

Statins give us the opportunity to periodically debate/discuss as to whether statins are good, bad or indifferent for your health. (Thank you Mr. Statin).......

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 09/18/2023 1:28 PM DST

[binati]

The central point for each of us is to know whether PSA level is correctly giving us the status of our PCa. Otherwise we are treating the PSA and not the disease!!

[PhilipSZacarias]

Good discussion. I will review the papers referenced. By the way, the first link did not work. I surmised that it was: pubmed.ncbi.nlm.nih.gov/347...

[ElemanJ]

Is it the statin that helps or the lower cholesterol level? If it’s the cholesterol level then even natural remedies such as Pektin, beta-glucans etc. to lower cholesterol could help.