I am taking Rosuvastatin, 20mg/day for sllghtly high cholestrol. I currently read that low-dose statin therapy may promote angiogenesis (the growth of new blood vessels) via multiple mechanisms, including enhanced NO ( nitric oxide) production, augmented VEGF release, and activation of the Akt signaling pathway. I understand that CLL is aggravated by VEGF ( vascular endothelial growth factor) and by the activation of the Akt signaling pathway. I am considering contacting my primary care physician and asking whether it may be appropriate to change my cholestrol prescription to a non-statin drug . I have not done any research on this concern yet, but plan to very shortly.
Does anyone have any comments to the above ?
Thanks, Mark
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markjeep51
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Mark, I'm glad you have a call into your PCP. I'd just add that it's fairly rare for CLL to form solid tumours, where angiogenesis is required for tumour growth to provide oxygen and food to the cancer . It's nearly always restricted to the lymphatic system, where it accumulates in the nodes, spleen (a specialised node) and the bone marrow. These automatically grow and with treatment, automatically shrink, as the CLL cells are destroyed.
There's epidemiological work done suggesting lipophilic statin use is associated with fewer cases of CLL than expected across large populations. But it's unclear what, if any, survival benefit statin use may confer.
Researchers are interested in how CLL interacts with lipids and are recommending further research. It seems CLL can "hijack" some of the lipid pathways. I developed lipid metabolism disorders starting after my diagnosis.
Structure Activity Relationship software indicated simvastatin (the original lipophilic statin) should be synergystic when used with venetoclax. I don't have the links where I read about this, but it generated a study using pitavistatin and venetoclax:
I am taking simvastatin in an attempt to simulate, somewhat, the aforementioned study. If you need a statin, IMO you should switch to a lipophilic one. Or a drug with another mechanism. The one you are on (hydrophilic) remains mostly in the liver, instead of permeating various body tissues. The downside to tissue permeation is a higher potential for side effects. Since the major side effects of statin use are related to depletion of Coenzyme Q 10, it is recommended to supplement with CoQ10 when taking lipophilic statins. I take a (quality tested) brand of CoQ10 supplement around lunch, and my simvastatin at bedtime, since most cholesterol production occurs overnight.
As AussieNeil mentioned, the metabolic pathways for solid tumors differ compared to CLL.
Thank you very much for the great summary ! But I am still a little confused. My main original question was that it appears that statin lowering cholesterol drugs might increase ones VEGF and the activation of the Akt signaling pathways, which is apparently, not good for CLL patients, as I understand it. Meaning that VEGF and Akt activation will further inhibit B-cell apoptosis. If this is indeed true, then it would appear to make sense that I continue with taking Rosuvastatin ( which is a hydrophilic statins ) which as you say, mainly stays in one's liver, which seems to be what I should strive for, in particular case ( I am still on w&w but will be starting IgG infusions tomorrow). If it is the lipophic statins which permeate the entire body, this is something I do not want because such, as I understant it, will increase my VEGF and activate my Akt signaling pathways resulting in a decrease in B-cell apoptosis. Therefore, I must be missing something very fundamental because you are suggesting that I might want to switch over to a lipophic type static or something different than my current hydrophilic statin medication. Please help me understand where I am going wrong. Thanks Mark
Statins apparently do not do this in *CLL* cells. What are your sources indicating these pathways are affected in CLL or any normal tissue?
I am seeing some studies indication this VEGF/ATK activation only occurs in vivo as a response to injury or inflammation. VEGF in relatively healthy subjects is decreased with statin use:
The most current article discussing statin side effects, on mesenchymal stem cells, I could find is behind a paywall so I am unaware of what it says. But those are bone precursors and likely not relevant to CLL stem cells.
So I am replying to my post instead of editing, because I don't want to lose the links;I am having that software issue where the links gets changed. Anyway Markjeep51, I wasn't sure if I indicated I am really, really interested in seeing any links to information you have regarding negative effects of statins. I never liked that these meds were being "pushed" onto so many without, IMO, adequate study. And as we can see by the recent stuff coming out where statins seem to be detrimental for ocular surgeries, even though they are helping bone surgeries, it makes me kind of double down on my belief drugs should be thoroughly studied before being recommended en masse. So I am super interested in any data showing potential harm; if these are mouse or other animal things, or what.
And apologies for confusing you; I totally missed "answering your question" before launching into my spiel. To answer the second one, barring evidence to the contrary, I would indeed recommend that *if* you had to be on a statin, then it seems only the ones that permeate body tissues (lipophilic ones) seem to confer some benefit re:CLL, specifically.
Great reply and thank you very much for all the time you have spent with me! I'll get back to you in a few days with the references which indicated that VEGF is not good for CLL people. Too much going on at home at the moment; retirement life is much more busy than I expected. I think I have documented on my computer all such references. But I suspect they may be based on limited test tube experiments only.
What I have are a few medical articles on why it is good to try and down regulate VEGF.
1. See " Drink your prevention: Beverages with cancer preventive phytochemicals" ( 2014). This talks about the down regulation of VEGF.
2. See ' The role of oxidative stress and the effects of antioxidants on the incidence of infections complications of CLL" (2014)
3. See " A combination with probiotic complex, zinc, and Coemzyme Q10 attenuates autoimmune arthritis by regulation of the Th17/Treg balance " (2018)
This article states " The combination of probiotic complex, zinc and CoQ10 reduce collagen-induced arthritis (CIA) severity by down regulating the levels of IgG, IgG1 and IgG2a in serum". Since I have collagen induced arthritis in both knees, then this statement is positive news to me. But from a CLL perspective, and since I have a significantly degrated immune (IgG) system, this ( the down regulations of IgG) is not what I want to happen. I just had my first Igg infusion yesterday; everything went fine.
All the above articles I think can be found on Pubmed database.
4. What frustrates me is that I have the following statement and I can not figure out where I got it from. " Bcl-2 is known to have proangiogenic activities. This may be of value inasmuch as (i) CLL-cells constitutively secrets the angiogenic factor VEGF and b FGF and (ii) neo angiogenesis is an important problem in CLL". Does this make any sense ? As I stated, I don't know where I found this statement; sorry.
I have no articles on the effects of cholestrol statis drugs on CLL patients. And I have not had a chance to read all the references to posted.
My main interest is to clarify whether I should stay on the Rosuvastatin ( which is a hydrophilic statins - staying mainly in my liver ) or go on a lipophic statins (which permeate the entire body), or ome other cholestrol lower medication, relative to my CLL. You are suggesting that I go on a lipophic statin. My oncologist has no clue about such matters but will bring up with topic with my primary care physician( PCP) shortly but I am not holding my breath about what my PCP can contribute to this discussion.
I just don't remember where I came up with the thought that cholestrol statin drugs increase one VEGF levels, which may be bad for CLL patients; must have been some general statements on the internet I saw somewhere. But I will contact my PCP now and see what i come up with. I'll let you know. Thanks Mark
If so, this article talks about pathways more relevant to *solid tumors*. As AussieNeil had commented, the pathways for CLL aren't the same for solid tumors. If all cancers had the same metabolic pathways, we wouldn't need to find various different targeted treatments for the different cancers, one drug would work all. Have you seen some of the breast cancer drug ads in the US referring to "HR+, HER2-" subset of breast cancer patients? Even within solid tumors, the markers can differ and treatment in patients other than those containing certain markers mat not work.
IMO the takeaway is, blood cancers are entirely different than solid tumors, and what may be helpful or harmful in one, doesn't automatically translate across the board.
I don't know why I started at the bottom of your list, but I will review the others shortly.
Other articles containing the aforementioned sentence in 4 refer to how CLL cell contain both VEGF stimulating as well as VEGF suppressing proteins, and that CLL cells can express VEGF intrinsically. So I can see where various articles of this type raise questions regarding compounds that potentially stimulate VEGF. However, what is theoretically possible does not always happen *in vivo*.
A recent example demonstrating this would be how hydroxychloroquine, based on chemical structure, has anti viral activity against Covid-19. But testing shows that for the majority of people, the doses needed to achieve this effect, cause unacceptable toxicity. So just because certain compounds can stimulate VEGF, and have done so in animal models or in cell culture or other tests, doesn't automatically mean we can extrapolate to say it will occur in our body.
As I look at the articles that come up when I search those sentences, many of them relate to how BCL2 is important in CLL pathogenesis, because the cell pathways involve VEGF and angiogenesis, but it looks like the takeaway was more like "blocking BCL2 will give us therapeutic benefit" as opposed to "not stimulating VEGF is important/will give therapeutic benefit". And there are a number of these proteins, IDK if one or another is "more important" in CLL.
Statins are bad for everyone not only CLL patients. Trying to lower serum cholesterol levels with the help of statins is nonsense. Serum cholesterol levels are not a problem as long as the composition of the cholesterol molecules is in order. It's all about particle size. About which the serum cholesterol test says nothing. And about glycation. Read the "Straight Dope on Cholesterol" series by Dr. Peter Attia before you harm your health needlessly.
Well, I wouldn't say it's nonsense. I would instead argue that unless the composition (size and ratios) of the cholesterol subparticles are abnormal, one doesn't automatically need to treat with a statin. And that "family history" needs to look at *reasons* for dyslipedemias. Plus patients being informed that they should fast before drawing lipid levels and possibly being diagnosed with dyslipedemia. I know I had a new doc do a lipid panel when I moved to New York; I wasn't expecting bloodwork on my initial visit because I was otherwise healthy, just establishing a new relationship after moving there. At that time I ate eggs frequently for breakfast and had done so that day. My cholesterol levels of course were elevated and with my father having a single fatal heart attack at a young age (mmm 45-46?) this doc wanted me on a statin. Repeat bloodwork and my discussion regarding my dad's rheumatic fever infection (causes cardiac damage) at an early age topped with him being a 2+ pack a day smoker and overweight, had me denying the statin. Repeat fasting tests showed, of course, that things were normal. Everything was fine except total cholesterol (slightly elevated) for decades. I refused treatment for decades because I agree, the total cholesterol number isn't necessarily the trigger to treat. It wasn't until my particle sizes and ratios slowly skewed abnormal starting after the CLL diagnosis, topped off with the potential synergistic effect with Venclexta, did I agree to treat. And I am on a low dose; standard starting one is 20mg and I take 10mg. My cholesterol dropped so much on the 20mg, IMO the red blood cell dyscrasia that developed afterwards were related to "too low" of a cholesterol lever (135? really low). Dropping the dose saw RBC parameters return to normal, as well as the cholesterol ones.
And with the studies being done around how statins help the tissue around bone implants regrow better, I wouldn't say they are bad "across the board". IMO from what I am reading there probably *is* activation of VEGF/ATK pathways, else this beneficial effect in hip and knee implants wouldn't be seen. I am seeing data for positive results in traumatized or ischemic or otherwise abnormal tissues. But with studies around ocular surgery showing poorer outcomes, I agree that statins aren't necessarily "always good." Instead, like most things in medicine, I would argue that each patient be assessed and monitored for benefit.
It is nonsense because bringing down the serum cholesterol level artificially with pills does not fix the underlying root cause of why it was up in the first place. If it was up due to a low carb diet and the composition of the cholesterol molecules is okay then the serum cholesterol level figure can be safely ignored. If it was up because of a crappy diet and the composition of the cholesterol molecules is disastrous then bringing down the serum cholesterol levels artificially with pills doesn't fix the problem. And statins are known to cause cancer too. The paleo indicator of health says this: if your triglycerides are low and your HDL is high, you can safely ignore your total serum cholesterol number. If your triglycerides are high and your HDL is low, you are in trouble irrespective of statins bringing down your serum cholesterol level or not. Cholesterol is like the bullet in the machine gun that is the immune system. No bullets you can't fight. One of the first signs of liver cancer is a huge drop in cholesterol levels without any apparent course. That's what I read somewhere.
May I have some links of where you read statins cause cancer? And are you saying that lowering cholesterol with statins induces liver cancer? You can't make bald health claims without references, y'know. There should be documentation of some sort indicating this, even if rigorous studies haven't yet been done.
I agree that drugs like statins "just given" without addressing the underlying cause would be "bad medicine" overall. But many patients won't or can't change their diet, or exercise, or whatever, so we do what we can. Do we only give statins to people who have a "known" reason for dyslipidemia? Since my dyslipedemia seems to be caused by my CLL, does that mean I can't have the drug to prevent a heart attack or other cardiovascular event? I must live with increased probability of an incident? I would get at/correct the underlying cause, if I could.
"Prolonged (more than 4 years) use of statins was associated with a significantly increased risk of colorectal cancer (odds ratio 1.23, 95%CI 1.10 to 1.38), bladder cancer (odds ratio 1.29, 95%CI 1.08 to 1.54) and lung cancer (odds ratio 1.18, 95%CI 1.05 to 1.34). There were no significant associations with any other cancers."
No, I'm not saying lowering serum cholesterol with statins will cause liver cancer. The point in case was that cholesterol is a very important part of the immune system and trying to lower serum cholesterol levels is pointless because it fixes nothing and can cause harm. What needs to be fixed is the composition of the cholesterol molecules and statins won't do that. Only diet can. If the only thing going for statins was that they don't cause cancer, then what's the point taking them?
There is one exception that I know of, and that's familial hypercholesterolemia where statins can be life savers because those who have it won't live long otherwise, it's such a grave condition it kills people quickly.
Those who WON'T change their diet, have a problem and better take responsibility for what they WON'T do. Those who CAN'T, are kidding themselves at least in the affluent western societies. It's like those who won't quit or can't quit smoking. Nearly all of them can and will, but only when it's too late and they get a lung cancer diagnosis. They just don't take the matter seriously enough prior to that. Such are humans.
With blood cancer looks like statins are a good thing. Looks like, but who knows. Maybe it's good for the blood cancer but not the possible secondary cancers? I wish I knew.
BTW I suspect that most statin research is funded by the statin makers. No proof, but there could be conflicts of interest hidden in plain sight.
LeoPa, *associations* aren't causes. Studies talking about associations aren't the same thing as saying they are "proof" that "statins cause cancer". Cholesterol being the bad guy in heart disease is a prime example, remember? Elevated cholesterol was *associated* with heart disease; it wasn't until people drilled down and did studies did cholesterol (sort of) recover from getting the reputation for automatically being the cause. As you yourself pointed out, a high cholesterol by itself isn't automatically a problem. Same thing with statins. Based on how most all of my patients who asked about "can't I get off of this pill" were more willing to "just take a pill" than change their diet and exercise; from what they told me they had unhealthy life choices, I would bet you money that the statins themselves per se aren't 100% the bad guys here. With all your dietary knowledge, can you not see that people who choose to eat junk will be more than likely to have internal organ problems? Were these studies adjusted for other risk factors like smoking? My father in law, who himself was an opthalmologic surgeon, eats crap, wants to *just take pills* which I simply can't understand, being a former MD. He wonders why he has inflammatory skin disease. (He also won't clean his house, which on top of the food choices added to this IMO) He blames his kidney problems all on "genetics" and NSAIDS instead of his personal habits of rarely drinking water, instead drinking root beer and cola and highly sugared coffee/teas all day in a high altitude environment! He resisted changing his diet until this last bout that had him bedridden for over a year.
Anyway, getting back on topic, some research is showing that statins may be beneficial in at least some cancers.
Thank you, you're right. Then what's the reason people with no blood cancer are put en masse on statins? That they may be beneficial for some cancers? Or are they told that statins prevent heart disease? Or is it because it is a billion dollar business for the manufacturers? With this raging inflation a billion is not what it used to be but it is still serious money 😁.
Oh, I agree that mass generalizations aren't always optimal. I totally am against statements like "every adult should be on baby aspirin" or "every adult should be on a statin". Like vaccinations, even if there is an overall great increase in health benefits for a population as a whole, it still should be assessed at *the patient* level, whether or not to do it.
Hi Mark. You might be interested to know that in the Uk a dose of rosuvastatin 20 mg is considered a high dose statin. Even a 10 mg dose of rosuvastatin is considered high intensity here. Rosuvastatin is 4 times stronger than atorvastatin (ie 80mg) and eight times stronger than simvastatin. My understanding is that here, generally, 20mg atorvastatin dose would be considered for prevention in people at high risk, and 80mg atorvastatin for known heart disease. The dose varies in people who don’t respond, or who have familial hypercholesteraemia (a specific disease). I’m not an expert but thought you might be interested.
Good point. I made a mistake in reporting my medication. I am taking only 10 mg of Rosuvastatin, not 20mg. The bottle says 20mg but I am to cut the pills in half. My mistake.
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