Based on these studies, do you think it's best to use simvastatin as your choice of statins? I'm using Crestor 5 mg plus 5mg Zetia and my ldl has gone down to a level, which puts me at risk of infection. Plus, my brain isnt functioning nearly as well as it used to. My current ldl is 27. This probably was caused by the Nubeqa causing a buildup of Crestor in my system (one of the potential, negative interactions). I'm not sure if I'll try Simvastatin again or just go with 2.5mg of crestor and 2.5 of zetia per day, to see if that can raise the ldl closer to 70-90.
3.1. Differential Effects of 3 Different Hydrophilic and Lipophilic Statins with or without Enzalutamide on Prostate Cancer Cells
We first investigated the short-term effects of three different statins on various PCa cell lines, representing different stages of the disease: androgen-sensitive LNCaP cells, androgen-insensitive PC-3 cells and two cell lines mimicking castration resistance (LNCaPabl, 22Rv1). We selected three widely prescribed statins (simvastatin, atorvastatin and rosuvastatin) because of their different pharmaceutical characteristics as reviewed by Althanoon [18]. Simvastatin and atorvastatin are lipophilic pro drugs, which are metabolized through cytochrome P450 CYP4A5, whereas rosuvastatin is hydrophilic and does not need an additional activation step. In addition, atorvastatin and rosuvastatin both use the organic anion transporting polypeptide OATP1P1 for cellular uptake [18].
Cell viability was determined after treatment of cells with rising concentrations of each statin ranging from 0.1 to 5 µM over 3 days. We tested these concentrations as they were commonly used in preclinical trials on statins in PCa [23,24]. Of note, a previous pharmacological study showed that even high doses of lovastatin that are required to reach plasma bioactivity levels in this µM range are well-tolerated [25].
Simvastatin demonstrated the strongest growth inhibitory effect of all three statins, followed by atorvastatin and rosuvastatin, which in fact did not express any significant inhibition on the investigated cell lines (Figure 1A). At a concentration of 1 µM, simvastatin accomplished a >50% reduction of cell growth representing the IC50, whereas atorvastatin reached the IC50 mark at a concentration of 3 µM in the same cell lines. Responsiveness to the three statins also strongly differed among the cell lines. Simvastatin and atorvastatin had the strongest growth-inhibitory effect in androgen-insensitive PC-3 cells, followed by LNCaP cells, which mimic hormone-sensitive PCa. The two castration-resistant cell lines, LNCaPabl and 22Rv1, on the other hand, were clearly less sensitive to statin treatment. Representative images of each cell line after treatment with the most effective dose of 5 µM are shown in Figure 1B.
Biomedicines 11 00029 g001a 550Biomedicines 11 00029 g001b 550Figure 1. Growth-inhibitory effects of statins on different PCa cell lines. (A) Four different PCa cell lines (LNCaP, LNCaPabl, 22Rv1, PC-3) were treated with increasing concentrations of simvastatin (sim), atorvastatin (ato), and rosuvastatin (rosu) in the absence or presence of 5 µM enzalutamide (enza) over 72 h. Cell viability was assessed with a colorimetric CellTiter 96® Aqueous one solution cell proliferation assay and expressed as percentage of mock control (DMSO) that was set 100%. (B) Representative images were taken after 72 h of treatment with 5 µM of the indicated statin (100× magnification). (C) Induction of apoptosis was assessed after treatment of cells with 5 µM of each statin through a caspase 3/7 assay. Caspase 3/7 activity was expressed as percentage of mock control that was set 100%. Data are represented as mean ± SEM. (** p < 0.01, *** p < 0.001).
Corresponding with the effect obtained on cell viability, simvastatin significantly induced apoptosis in LNCaP and PC-3 cells and to a much lesser extend in LNCaPabl and 22Rv1 cells (Figure 1C). Atorvastatin, by contrast, only induced apoptosis in PC-3 cells whereas rosuvastatin did not induce apoptosis in any of the cell lines (Figure 1A,B).
In combination with 5 µM of the anti-androgen enzalutamide, there was a weak increase in growth inhibition of androgen-sensitive LNCaP cells compared to statins alone, particularly at lower concentrations between 2 and 4 µM (Figure 1A), whereas there was no apparent additive effect of statins and enzalutamide in PC-3 cells. In castration-resistant LNCaPabl cells, enzalutamide combined with atorvastatin resulted in the most prominent growth inhibition. Notably, simvastatin and also rosuvastatin were able to increase the effect of enzalutamide in 22Rv1 cells. These data suggest that statins may in fact be able to enhance the tumor growth inhibitory effect of enzalutamide, however, depending on the type of statin and the tumor cell line.
3.2. Differential Effects of Statins on the Expression of HMGCR
One of the possible explanations for the differential effects of statins observed in PCa cells is the transcriptional upregulation of enzymes of the mevalonate pathway by sterol regulatory element binding protein 2 (SREBP2), a feedback mechanism that is activated by statin treatment. Previous studies have demonstrated that AR-negative PC-3 cells lack SREBP2 expression and are therefore highly responsive to statins [26]. Therefore, we next investigated changes in HMGCR expression after treatment of our 4 PCa cell lines with the three different statins through qPCR. As depicted in Figure 2A, simvastatin treatment induced an upregulation of HMGCR in AR-positive LNCaP, LNCaPabl and 22Rv1 cells but not in AR-negative PC-3 cells, confirming previously published results [26]. Similarly, HMGCS1 was significantly upregulated by simvastatin in LNCaP, LNCaPabl and 22Rv1 cells but did not affect the expression in PC-3 cells (Figure 2B). Treatment with atorvastatin and rosuvastatin, by contrast, increased the expression of HMGCR and HMGCS1 in all 4 cell lines, including PC-3 cells, indicating that a lack of response to the different statins cannot solely be explained by the SREBP2 mediated feedback mechanism.
Biomedicines 11 00029 g002 550Figure 2. Expression of HMGCR (A) and HMGCS1 (B) after treatment with statins (5 µM) was determined via real-time qPCR and normalized to the housekeeping gene hydroxybilane synthase (HMBS). Data are represented as mean ± SEM. (* p < 0.05, ** p < 0.01, *** p < 0.001).
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I’ve been on Crestor (rosuvastatin) for 8+ years now per Snuffy Myers. He liked Crestor because he said it doesn’t interfere with some of the ADT drugs used . At one point my dosage I think was 20 mg which dropped LDL cholesterol too low and caused a lot of brain fog, more than usual. He said a certain level is needed for brain function so we reduced the dosage to 5 mg and things improved. Been on that dose ever since.
yes, Crestor interacts with nubeqa. It’s on the side effect label. Dr ekberg and others cite quality study statistics showing that very low ldl levels increase all cause mortality by 300%, due to infection, heart attack stroke etc. I’d like to use the simvastatin for its cancer fighting superiority but it causes me muscle aches and pains that are every-present.
Simvastatin horribly aggravated my GERD/heartburn for which I take omeprazole. It was like it completely neutralized the omeprazole. I am on atorvastatin instead.
i will never take oneprozle or any ppi again. They will cause permanent damage to the gut, and possibly the heart, as well as potentially cause cancer.
Horrible, intractable heartburn caused by a hiatal hernia you could drive a truck through leaves me no choice. Been taking omeprazole for over a decade with no harm.
I'm taking usually 40mg of Crestor against cancer, however now on short course of Nubeqa for5.5 weeks and reduced Crestor to 10mg, when stop Nubeqa will go back to 40mg
"...At a concentration of 1 µM (micromolar), simvastatin accomplished a >50% reduction of cell growth..."
The mean concentration of simvastatin in human serum is 4.3 nM (nanomolar) after a 40 mg dose [ncbi.nlm.nih.gov/pmc/articl...]. Therefore, 1 μM simvastatin is equivalent to 9302 mg!
So the effective cancer fighting dose is way more then a person can take?
But in some studies, they shoes that statins increase longevity for apc patients, do something in the statins is causing the extra longevity, and it appears to be more than just lipid level lowering.
I think you need to try different statins and experiment with them monitoring your blood values and how your body feels.
Example when I tried atorvastatin, in one month I drop it because all my muscles was in crazy pain.
Creator I started from 20 mg, increased to 40 mg. I tappered now to 10 mg because of Nubeqa , when stop Nubeqa, will increase Crestor to 40 mg. I go off statins and metformin for around 20 days -30 days approximately every 4 months, as I go to spiritual plant medicine retreats (Aya, Iboga, Kambo) and drop all meds before, during and after the retreats except Orgovyx or Lupron. As one should stop all possible medicine when in such retreats. So body get a brake from metformin and statins and don’t forget how to function without them😅
And preempting your question, no this my behavior is not based on any medical paper or research… just how I and my body feels about it.
Hi Do you know if any papers or studies similarly to this have been done for Metformin? My husband takes 500mg XR every day. I have looked but I haven’t found anything.
George - Based on an HU patient's report of good results and Consumer Lab tests showing that the Red Yeast Rice based supplement Cholestene was an "or equal" to pharma product lovastatin, I started using the supplement a little over 2 years ago - primarily due to below normal HDL. In just 3 months of use I got my lipids into a near-perfect range and with excellent total Cholestrol (147), LDL/HDL ratio (2.4), Tri/HDL ratio (1.0), an d a 68% increase in HDL (from 37 to 62). I do lipids labs once a year and with continued use of Cholestene, maintained similar results over the next year.
With that in mind, below is a link to what our fine regulators have to say about Red Yeast Rice supplements. It should be noted that the active ingredient of lovastatin, monacolin K, is produced by Red Yeast Rice, but came to market first as a pharma product. That has resulted in the following statement from the linked NIH document:
How does the U.S. Food and Drug Administration (FDA) regulate red yeast rice products?
According to the FDA, red yeast rice products that have enhanced or added lovastatin—which is structurally identical to monacolin K—cannot be marketed as a dietary supplement in the United States. This regulation is based on the FDA’s approval of lovastatin as a new drug before it was ever marketed as a food or dietary supplement. (emphasis added.)
On several occasions, the FDA sent warning letters to companies selling red yeast rice products that had enhanced or added lovastatin, telling the companies to correct their violations.
So, draw your own conclusions, but note that some RYR products tested by Consumer Lab apparently had little to none monacolin K - thanks, of course, to FDA intimidation.
Ciao, Kaptin K9
PS. Here is a excerpt from a Feb 2023 People's Pharmacy Q&A in The Winston-Salem Journal (NC) specifically about Cholestene:
Q. I am a naturopathic physician and find the info in your column quite useful. This week in your column, you recommended HPF Cholestene brand red yeast rice. Unless its position has changed recently, the Food and Drug Administration recommends people NOT buy this brand because lovastatin is one of the ingredients.
A. You are correct. The FDA “is advising consumers not to purchase or use Cholestene, a product promoted and sold for cholesterol management ... FDA laboratory analysis confirmed Cholestene contains lovastatin, the active ingredient in the FDA-approved prescription drug Mevacor, used to treat patients with high blood cholesterol levels.”
We have always found the FDA’s position puzzling. It’s OK for people to take lovastatin as a prescription drug, but the same ingredient is inappropriate in a dietary supplement. A meta-analysis and systematic review of 30 studies of red yeast rice preparations concluded that this natural product can reduce risk factors associated with heart disease (Frontiers in Pharmacology, Feb. 21, 2022). People taking RYR were less likely to die during the studies. (emphasis added.)
We're the government and we're here to help? (help whom?) . . .Stay S&W, K9)
I just found some study results on RYR. Based on these study findings, it seems that you may have had a great HDL response that is atypical, based on what was mentioned after the 2006 study:
"There was an increase of HDL-C levels between 15% and 22% by Zhibituo. However, the findings for Xuezhikang were not consistent ranging from a 2% to 17% increase and 15% decrease in four trials. Cholestin did not change the HDL-C levels after the treatment [7].A beneficial effect of increasing HDL-C levels was shown when Xuezhikang was compared with placebo (WMD 0.11 mmol/L; 95%CI 0.05 to 0.17; 4 trials, n = 323) [8,24-26], and when Zhibituo was compared with no treatment (WMD 0.21 mmol/L; 95% CI 0.04 to 0.38; 1 trial, n = 62) [22] and with placebo (WMD 0.21 mmol/L; 95% CI 0.15 to 0.27; 3 trials, n = 291) [27-29] (Table (Table6).6). Different treatment durations showed that of RYR preparations increased HDL-C levels compared with placebo by 6 weeks (WMD 0.27; 95% CI 0.17 to 0.38; 2 trials, n = 86) [27,28] and 8 weeks (WMD 0.11; 95% CI 0.05 to 0.16; 5 trials, n = 406) [7,8,24-26]. There was no significant difference between RYR and placebo at 4 weeks and at 12 weeks for HDL-C levels [7,25,26]."
thanks Cujoe, good info, as usual. I also subscribe to consumerlab. I'm going to look into this deeper. I have a couple questions for ya:
1. Had you ever tried raising HDL with anything else, before taking the RYR? That includes statins. If statins, did they raise your HDL at all?
2. what were the numbers for your ldl and triglycerides, when your HDL was 62?
3. Has anyone on this website cited what slows cancer growth, is it the lower level of the triglycerides and ldl, or does it have something to do with the statin or ryr, directly attacking the cancer?
4. Is there any difference in cancer fighting between lovastatin and red yeast rice? Is the side effect profile the same?
5. Also, I can't find Cholestene on Amazon. Did consumer labs say any other brands have accurate dose amounts and quality ingredients?
1. Naicin is known to increase HDL, but is subject to serious flushing in most people. It requires a rather large dose to be effective and I had enough flushing on a tiny trial dosage (made lupron look like a cold shower) to cause me to abandoned that idea after a couple of weeks. Excercise is also said to raise it.
Peter Attia has a wealth of information on lipids and thinks we are focused on the wrong indicators. Many podcasts at his website and he now has a world-class cardio doc on his staff.
2. Just multiply out the ratios I quoted.
3. Cholesterol: An important actor on the cancer immune scene, Frontiers in Immunology, 21 November 2022.
4. I'm not qualified to answer that question. You can search posts here and at APC. I know Patrick has several posts that deal with the differences between hydrophilic & lipophilic statins.There is also a new category of stains that some think is superior. Here is link for info on that:
5. Cholestene is still widely available through online supplement companies, like Vitacost, iHerb, AllStarHealth, etc. I also seem to remember when traveling being able to get it at The Vitamin Shoppe. (A quick check indicates they still carry it - at about 50% more than at online suppliers, of course.)
My guess on why it does not show up on Amazon has to do with the FDA breathing down the comapny's neck. I also think the ownership of the brand has recently changed. As I remember it, the HPC logo was always on the label, but as indicated in the Vitacost product page the sponsoring company was Healthy Origins. I'm a bit suspicious that HO might have spun the product off to an LLC in order to buffer themselves from any possible actions by the FDA. The People's Pharmacy comment in my reply sums up my view on the matter.
I’m just back from a 4 day BMW motorcycle rally in eastern Oregon with my brother from California. Next week hiking 9 miles into a backcountry luxury resort for 3 days with my wife and dog Mateo. But in the meantime I have 3 days of hand surgery for my Dupuytrens contracture (claw hand). So very busy summer so far! Want to come visit? Pablo
I seem to remember a motoring trip in Western Canada in there somewhere this spring or summer? Would love to make a trip out West for some backcounrty hiking, but am occupied with things here local for rest of summer. Big annual family gatherings around the 4th, so I'll be headed to the beach and then to Raleigh next week. Routine MO appointment to follow mid-month.
As you know Ms. M is planning to make a fall visit around time of my NH reunion event. We will need to do some cordination with your VT bike trip. All contigent, of course, on how things go for her over the next month or so.
I didn't realize you had a biker bro'. Having lost my older brother to cancer 10 years ago, I am envious of your opportunity for the rally event. While I doubt that you need reminding, don't pass on those sorts of opportunities, as time just keeps flying by at our ages. Enjoy the backcountry hike and best of luck for a perfect result from the hand surgey. I'll expect to see you+ somewhere in NE this fall. (With a restored ambidextrous handshake.)
So for clarity sake, the levels below are what is noted in my general physical labs as indicating normal levels or thresholds/targets:
Cholesterol <=199 mg/dL
HDL Cholesterol >=41 mg/dL
Triglycerides <=149 mg/dL
LDL Cholesterol (Calc) <=99 mg/dL
Non-HDL Cholesterol <=129 mg/dL
As PCa Patients, are there optimal levels we should be targeting, not just normal levels? With Lipids having an associated interaction with PCa than Blood Sugars, I believe it is a valid question to try and determine if there are... but how, who or what doctor follows this bread crumbs trail? Certainly not our oncology team...
The metabolic action/reaction in our bodies has to be related? No? Does the PCa cause some sort of cell signaling to create a more hospitable environment for it's progression, existence? I know my personal history and family history is high blood Lipids, and I too was high Triglycerides when younger but not too high, close to 200. But when I was diagnosed, my lipids were through the roof at almost 700... Now my numbers I think are better:
Cholesterol 98 mg/dL
HDL Cholesterol 35 mg/dL
Triglycerides 172 mg/dL
LDL Cholesterol (Calc) 29 mg/dL
Non-HDL Cholesterol 63 mg/dL
Or are the LDL's too low?
Glucose has been a battle, average 145 +/-, and now slightly anemic blood draws due to Lynparza being added to Degarelix and Darolutamide...
It's a crazy battle to try and balance all these numbers and effects.
CO, Im riding an ex. bike right now so i'll keep it short: Triglicerides to HDL is probably most important. Get the hdl as high as you can, and get the tri's down so that they are at least 2 to 1 ratio with hdl. 1:1 ratio is even better. Based on your numbers, try lowering tri's to 80 and getting HDL above 40-45. Your ldl is ultra low, like mine. What drug do you think caused your ldl to drop that low? You can use vascepa to lower triglcerides. Vascepa is jusy fish oil EPA.
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