Fluvastatin lowers viral load...

I'm told that Fluvastatin, a cholesterol-lowering drug, also reduces viral load.  Anyone know about this?

[meki]

Nada... Sorry man.

[Trish77]

Apparently, that is the case.  Being inherently curious, I googled, "fluvastatin HCV" and came up with some interesting hits.  There is currently a Phase II study going on with Fluvastatin along with regular SOC treatment and because Fluvastatin, like Alinia, is already an approved drug, it would be available sooner and more easily than the PI drugs, for example, currently in trial.  

http://www.hepatitis-central.com/mt/archives/2008/04/fluvastatin_low.html

These links really made me sit up and take notice.  It suggests that Fluvastatin is the most effective out of all the statins and may even replace ribavirin as the drug to be used with interferon in SOC therapy:

http://www.hivandhepatitis.com/hep_c/news/2008/042208_a.html

http://www.hivandhepatitis.com/hep_c/news/2006/071106_a.html

Have I missed discussion of this on these boards?  We talk about Alinia but haven't heard much about Fluvastatin.  Seems something to be rather excited about.  Am I missing something?

Trish

[copyman]

nothing has been proven with this. i think they are doing some trials with statins and may hear more about it in the future

[jmjm530]

The news has been around for a couple of years and potentially very exciting, both for pre-dosing and treatment, esp the replacing riba part. Funny, because I held off taking statins prior to treatment because I thought I'd have a better chance with a liver that was taxed less, as statins can tax the liver somewhat. If I knew about the study then, I would have taken statins prior to treatment, both for my original intent -- lower cholesterol -- as well as the potential to make tx more effective. Currently I'm on a statin (lipitor) and it has  dramatically lowered my cholesterol levels. FWIW my liver specialists gave me the green light for statins prior, during and post treatment, but the discussion was in the context of lowering cholesterol.

-- Jim

[Trish77]

That is rather exciting, as it makes statins safe to take during SOC.  If one is able to get a doc to prescribe fluvastatin on top of SOC..makes sense to me that that also increases one's chances.  

As well, if one is wanting to lower viral load prior to treatment, seems fluvastatin is a good option.

I really want to know more about this.  Gawd, I need more hours in a day.  

[geterdone]

What does statins do such as Fluvastatin for the reduction of the Virus and virions?

jasper

[ClippedWings]

Here's an article from the HCV advocate in 2006.  My doc put me on statins as I started treatment despite my having normal cholesterol.  Just another weapon in the armory.


The publication this summer of a study showing that statin drugs inhibited hepatitis C virus (HCV) replication in laboratory studies generated considerable excitement among HCV positive individuals and their providers. What are statins, and do they represent a new hope for people with HCV?

What are Statins?
Statins, also known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are approved for the treatment of elevated cholesterol. Low-density lipoprotein (LDL) cholesterol contributes to atherosclerosis (hardening of the arteries), and elevated LDL is associated with an increased risk of cardiovascular disease. A different type of cholesterol, high-density lipoprotein (HDL), exerts a protective effect by transporting fats out of the body.

Statins work by inhibiting an enzyme needed for the production of cholesterol in the liver. In addition to decreasing LDL cholesterol, the drugs also modestly reduce triglyceride levels and raise HDL cholesterol.

The currently marketed statin drugs are:

• atorvastatin (Lipitor)
• fluvastatin (Lescol)
• lovastatin (Mevacor)
• pravastatin (Pravachol)
• simvastatin (Zocor)

With increasing rates of obesity and associated metabolic conditions – both in HCV positive individuals and in the population as a whole – the statins have become one of the most widely prescribed classes of drugs

Statins and HCV
In the July 2006 issue of Hepatology, M. Ikeda and colleagues reported on a study showing that certain statins were active against HCV in laboratory cell cultures. Because it is difficult to maintain HCV in vitro, the authors developed an HCV RNA replication system, or “replicon,” to evaluate the anti-HCV activity of these drugs.

The researchers found that fluvastatin demonstrated the strongest activity against HCV. Atorvastatin and simvastatin showed intermediate anti-HCV inhibitory activity, while lovastatin demonstrated only weak activity against the virus. One statin, pravastatin, demonstrated no anti-HCV activity in the laboratory.

The authors also found that when statins were administered with interferon alpha, all except pravastatin exerted an even stronger inhibitory effect on HCV. In the case of fluvastatin, the effect appeared to be synergistic, meaning that the combined effect was greater than the sum of the two drugs considered separately.

The researchers concluded that statins “could be potentially useful as new anti-HCV reagents in combination with interferon.” They noted that fluvastatin plus interferon appeared more effective against HCV than the current standard regimen of pegylated interferon plus ribavirin.

How Do Statins Inhibit HCV?
The reasons for the inhibitory effect of statins on HCV are not well understood. Because all statins work as HMG-CoA reductase inhibitors, the fact that some had minimal or no activity against HCV suggests the antiviral effect occurs by some other mechanism.

In addition, statins did not kill host liver cells, indicating that the anti-HCV activity was not due to cytotoxicity. The researchers suggested that “statins possess the ability to inhibit the replication of HCV RNA via a specific antiviral mechanism.”

Because the antiviral activity of statins was reversed by adding them to the cell cultures mevalonate or geranylgeraniol (two compounds that play a role in the HMG-CoA reductase biosynthesis pathway), the authors suggested that inhibition of these proteins might somehow interfere with HCV replication.

Statin Safety
Though statins are widely prescribed, they are not free of side effects and risks. One of these is the potential for liver toxicity (hepatotoxicity). Though statins have not been extensively studied in people with hepatitis C, it is often the case that drugs that have the potential to cause hepatotoxicity are more likely to do so in patients with pre-existing liver disease.

One recent study, however, found that statins did not appear to increase the risk for hepatotoxicity in patients with hepatitis C.

S. Khorashadi and colleagues assessed the incidence of liver toxicity in 166 HCV positive patients treated with statins, 332 HCV positive people not receiving statins, and 332 HCV negative individuals taking the drugs. They found that among HCV positive individuals, use of statins was associated with a higher rate of mild-to-moderate liver biochemistry elevations compared with those not on statins (23% vs 13%, respectively), but a lower incidence of severe liver enzyme elevations (1% vs 7%).

Among patients started on statins, the rates of mild-to-moderate elevations were similar in subjects with and without HCV (23% vs 16%, respectively). HCV positive and negative patients also had similar rates of severe elevations and statin discontinuation due to hepatotoxicity. The authors concluded that “[s]tatin therapy was not associated with a higher risk of severe hepatotoxicity in patients with chronic hepatitis C and appeared safe.”

For HIV/HCV coinfected individuals, an additional concern is the potential for interactions between statins and antiretroviral drugs, particularly protease inhibitors, which could alter drug levels in the body.

Looking to the Future
HCV positive people have already begun asking whether statins might play a role in hepatitis C treatment. Research on this class of drugs as antiviral therapy is still in the preclinical stage, and it will be some time before human clinical trials show whether statins are effective for this indication. In the United States, however, clinicians may prescribe medications “off-label” for indications other than that for which the drugs were approved.

The latest data suggests that statins may one day become a component of combination therapy for chronic hepatitis C, and that the drugs appear to have an acceptably low level of hepatotoxicity in people with HCV. While we await the results of further research, HCV positive individuals who are already taking statins to reduce their cholesterol may be deriving an additional, unexpected benefit.

[merryBe]

the question becomes does one need to be on statins as they do carry risks.

also, each stage of liver disease lowers ones ability to make chlolesterol, ergo making statins further contraindicated; and changes to thyroid function, also common in HCV patients especially treaters further effects lipid levels, as do changes to blood sugar levels common in treatment as well.

It follows one needs to do some serious homework before adding any drug to ones regime.

[Trish77]

While your point is well-taken that one should take care to add drugs to one's regime without full knowledge of the impact, in THIS case further study has shown that while active liver disease is a contraindication for taking a statin, the use of statins for persons with HCV has actually resulted in an improvement in ALT levels for those with abnormal levels and a maintenance in ALT levels for those with normal levels AND, most importantly, a marked increase in SVR rates.  

The suggestion here is that statins are not not only for persons with cholesterol issues.  The suggestion is that statins can safely be taken regardless of cholesterol levels as it helps in both cases, which is a great bonus.  This does not make the statin contraindicated if no cholesterol issues are present.  It simply makes the use of the statin for other than it's usual application, no different than Alinia.  Plenty of people are taking Alinia, regardless if they have "Montezuma's Revenge", because it aids with SOC in treating HCV.  

Fluvastatin has been shown to be the most effective of the statins so far.

Here is a link to a study that shows that statins not only did no harm to liver functions of persons with HCV but actually helped:

http://www.medicalnewstoday.com/articles/71550.php

This article does indicate that there is a process that must be followed to introduce a statin as part of a treatment regimen for someone with an active liver disease such as HCV, but that it CAN be done.  

[eureka254]

"The researchers found that fluvastatin demonstrated the strongest activity against HCV. Atorvastatin and simvastatin showed intermediate anti-HCV inhibitory activity, while lovastatin demonstrated only weak activity against the virus."
---------------
My husband is currently on simvastatin due to a cardiac condition, and it was OK'd as appropriate even with his HCV and cirrhosis.  Although, with this new information, I'll be asking his cardiologist if he should be taking fluvastation instead?!?  

It's also interesting to note that prior to being prescribed simvastatin he had elevated liver enzymes, but since taking it regularly, they've been on the high end of normal rather than elevated.  Could be coincidence, but very thought-provoking considering the new statin information.  Thanks to everyone for the great links.

[merryBe]

ALT level is not the end all of whether on adds a med onto the regime.

I respect your opinion here, but think about how most people take meds....not in a vacumn...they eat, drink thigs, and take meds...

I'm more sensitive since I now believe definitively some meds I was on in combo have had the effect of escalating my fibrosis.

Alinia hasn't given anyone I know Montezuma's revenge...in fact, it's been well tolerated by all in here, with perhaps a little day or two of adjustment. (which eating food with it can allieviate.

Statins have a huge down side, much more so than Alinia, they have some major issues as you know, just go read the sides and rates of strokes etc. so this is not just something you throw into the mix.

At stage 3 or 4 you won't make enough cholesterol...so adding statins could be deadly.
For early stages I'd suggest the more benficial PCC/diet/momounsatuates/oatmeal/whole grains/no animal fat/etc that one can do to create a more healthy profile.

Maybe we should think in terms of WHY statins would lower VL. Maybe it's because of just what HR has discusses regarding the lipid shell on each virion. Ergo any way one could create a more healthy lipid profile might simultaneously weaken this virus.
However, remember too little cholesterol is as deadly as too much, so just a cautionary that this drug would require regular monitoring in order to assure it "do no harm".
maryB

[eureka254]

Thought this abstract to a recent article pertinent to this thread:

Title:     Safety of statin therapy in patients with preexisting liver disease
Author:   Onofrei, MD
Add.Author /Butler, KL
Editor:   Fuke, DC
     Miller, HB
Citation:   PHARMACOTHERAPY 28 (4): 522-529 APR 2008
Year:   2008

"Cardiovascular disease is the leading cause of mortality in the United States. In high-risk patients, statin therapy has become the standard of care. In fact, statins are the most efficacious drugs for decreasing low-density lipoprotein cholesterol levels; they reduce both primary and secondary cardiovascular risk in the general population. However, less is known about the safety of statin use in patients with liver disease. Results from studies of statin therapy in patients with elevated liver enzyme levels, nonalcoholic fatty liver disease, hepatitis C, cirrhosis, liver transplants, and hepatocellular carcinoma show benefit without increased risk of adverse effects. Thus, based on available evidence, statin therapy should not be withheld in this patient population; however more robust prospective clinical trials are needed to confirm the safety and efficacy."

[eureka254]

And as I keep researching, more good news:

Incidence of adverse events with HMG-CoA reductase inhibitors in liver transplant patients
Author:   Martin, JE
Add.Author / Cavanaugh, TM
Editor:   Trumbull, L
     Bass, M
     Weber, F
     Aranda-Michel, J
     Hanaway, M
     Rudich, S
Citation:   CLINICAL TRANSPLANTATION 22 (1): 113-119 JAN-FEB 2008
Year:   2008
"Transplant patients are at increased risk of developing dyslipidemia, which contributes to coronary artery disease and cardiovascular events. The purpose of this study was to explore documented adverse effects of liver transplant recipients receiving lipid-lowering therapies.
Methods: A retrospective chart review of 69 liver transplant patients was conducted to evaluate the incidence of adverse effects, especially rhabdomyolysis and liver function abnormalities, in liver transplant patients treated with a lipid lowering agent (LLA). Data were collected from the time of initiation of LLA to 12 months later, looking at the type, dose, and duration of LLA, concurrent cytochrome P450 inhibitors, immunosuppression used, and laboratory parameters.
Results: For HMG-CoA reductase inhibitor therapy, simvistatin was used in five (7.8%) patients, pravastatin in 40 (62.5%), fluvastatin in one (1.6%), atorvastatin in five (7.8%), and lovastatin in three (4.7%). Gemfibrozil, a fibric acid derivative, was employed as monotherapy in 10 (15.6%) of patients. There were five patients who received combination therapy with a fibric acid derivative, four (80%) with gemfibrozil + pravastatin, and one (20%) with gemfibrozil + simvastatin. Six patients studied had adverse effects, five (7.2%) with myalgia and one (1.4%) with myopathy. LLA monotherapy with either pravastatin or atorvastatin was used in these patients. The five patients with myalgia were on concurrent therapy with cyclosporin, and the patient with myopathy was on concurrent cyclosporin + diltiazem therapy, both of which are P450 inhibitors. One out of 23 patients on a non-immunosuppressant P450 inhibitor developed adverse effects. No significant elevation of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase was noted in any patient.
Conclusions: Overall, there was a general tolerability with a low incidence of adverse events, no incidence of severe complications, and no alterations in liver function tests in the study population with the use of LLA."

[jmjm530]

I don't think anyone is saying that people should rush out and start taking statins, but it's certainly a potentially exciting development, and anyone (like in a position I was once in) holding off from statins because of the perceived risk/reward ratio might revisit the idea with their doctor. And for those that don't need statins, still something to discuss with their doctors as well as keeping an eye on future studies/developments. A few points you made.

MB: At stage 3 or 4 you won't make enough cholesterol...so adding statins could be deadly.
-------------
Do you have any support for this statement? I was stage 3 and was making too much cholesterol, but even if I wasn't, not sure adding statins would be "deadly".

MB: Maybe we should think in terms of WHY statins would lower VL. Maybe it's because of just what HR has discusses regarding the lipid shell on each virion. Ergo any way one could create a more healthy lipid profile might simultaneously weaken this virus.
-----------------------------
Before the human trial, Fluvastatin had demonstrated potent antiviral activity in vitro (in the test tube). This suggests that there is an independent mechanism at work as opposed to simply creating "a more healthy lipid profile" as one might accomplish, for example via diet.

[Trish77]

merryBe: ALT level is not the end all of whether on adds a med onto the regime.
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I am not saying, nor would I say, that lowering of ALT is the "end all" of determining whether one uses a statin or not.  It is simply one indication of a positive output of application of a statin - along with lowering of viral load and increased rates of SVR.  I've cited studies on this, not just a personal opinion.

merryBe:  I respect your opinion here, but think about how most people take meds....not in a vacumn...they eat, drink thigs, and take meds...

I'm more sensitive since I now believe definitively some meds I was on in combo have had the effect of escalating my fibrosis.
----------------------------------------------------------------------------------------------------
I'm well aware of how people take meds.  I'm in a clinical drug trial and I think about it all the time.  I would never recommend that anyone take a med in a vacuum and that is WHY I included studies with my posts.  I can appreciate your caution.  Again, that is why I have included links on studies that have measured the impact of studies.  It's good to have concerns, however, when it comes to meds that could benefit other people, it's responsible to back up those concerns with hard data.  By all means, if you have data that shows that statins are an issue for persons with HCV, that would be of great interest to ALL of us, including me.  We all want what is best for each other.  I'm not posting in an effort to be right.  From what I have read so far, including from the information and experiences of others who are posting and the various studies already undertaken and presented,  we can afford to be cautiously optimistic about statins and pay them some attention as they continue to be studied.

merryBe:  Alinia hasn't given anyone I know Montezuma's revenge...in fact, it's been well tolerated by all in here, with perhaps a little day or two of adjustment. (which eating food with it can allieviate.
---------------------------------------------------------------------------------------------------
I never said that Alinia has given people Montezuma's Revenge, caused by gastrointestinal parasites.  What I said was that people with HCV take it for something OTHER than that.  My point was to cite another example of persons with HCV taking a medicine that is usually applied for another medical condition because it has been found to produce positive outcomes in persons with HCV.  Just as fluvastatin is generally applied to lower cholesterol but has also been found to produce positive results in persons with HCV.

Maybe we should think in terms of WHY statins would lower VL. Maybe it's because of just what HR has discusses regarding the lipid shell on each virion. Ergo any way one could create a more healthy lipid profile might simultaneously weaken this virus.
However, remember too little cholesterol is as deadly as too much, so just a cautionary that this drug would require regular monitoring in order to assure it "do no harm".
--------------------------------------------------------------------------------------------------------
I have never, nor would I ever, suggest that a drug simply be thrown into the mix without considering the implications or careful monitoring.  If I was suggesting such a thing, I wouldn't have bothered to read up on it to make sure my information was reasonably sound nor to include links to more information that people can read up on to draw their own conclusions.  I would have simply posted my opinion with no backing data for it.  

Trish

[Trish77]

I think this bears repeating from earlier in this thread so that it's not missed:

http://www.medicalnewstoday.com/articles/71550.php

This article does indicate that there is a process that must be followed to introduce a statin as part of a treatment regimen for someone with an active liver disease such as HCV, but that it CAN be done.  
---------------------------------------------------------------------------------------------------------

Just to put some minds at ease, you can't just add a statin like you can a herbal supplement OR Alinia for that matter.  It has a special approval process via the FDA that must be followed to add a statin to one's drug regimen for persons with active liver disease.  There IS a careful monitoring process in place before one can add a statin for persons with liver disease, which exceeds that of a doctor prescribing it.  He has to put it through an approval process as well.  

And I'm not bashing Alinia - I was actively pursuing Alinia until I landed in a clinical drug trial and I've been keeping on eye on the outcomes there as well.  I bring it up as it's simply a good comparator of a drug who's prime use is other than HCV but is a benefit nonetheless.  I think these are interesting times for persons with HCV in that we have various possibilities we can look at that may help us in our quest for a cure.

When statins are talked about as possible replacements for ribavirin, that's something worth keeping an eye on.

Trish

[Trish77]

I'm wondering what side effects, if any, come with the statins you / your husband are taking?  Thanks.

Trish

[jmjm530]

First, thanks for posting the additional studies and commentary. A couple of points.

You said: "you can't just add a statin like you can a herbal supplement OR Alinia for that matter.  It has a special approval process via the FDA that must be followed to add a statin to one's drug regimen for persons with active liver disease..."  
-------------------
I think the reference is to researchers using statins in the context of Hep C research.

As far as I know, any physician can prescribe a statin to someone with Hepatitis C using the same standards/criteria as someone without Hepatitis C, although the kmowlegeable physician would tend to monitor liver enymes more agressively, at least in the beginning.  The criteria itself, be it high cholesterol, other cardio risk factors, or even broader -- not really sure here. Remember, Alinia also has certain criteria as I understand it, although people seem to be taking it for reasons outside of that criteria.

As far as the side effects you asked about, I did a lot of research prior to taking statins myself. What you end up with range from a statistically very safe drug to web sites entirely devoted to the evils of statins. In my case, given my cholesterol levels and family history, I weighed the risks versus rewards as best I saw them, and started taking statins. I may (or may not) be feeling some additional fatigue from the statins, but very hard to tell with so many other variables going on. Other than that, nothing to report.

No doubt statins are powerful drugs and should not be thrown into any sort of mix without much thought and discussion with your doctor.

-- Jim

[eureka254]

I had major concerns initially when my husband was prescribed simvastatin (which he's been taking for over a year now), but all his docs (PCP, cardiologist, hepatologist, and surgeon) all concurred that it was a good (and in his case, a necessary) move.  All the same, I have to admit I always had some lingering doubts with all the 'liver-damage' warnings we've all known about, especially because my husband has cirrhosis and active HCV.  (This thread has done a lot to ease my mind!)

To date, my husband seems to have suffered no ill effects from a 20mg/dose per day, and he doesn't appear to have any side effects other than the desired lowered cholesterol.  (I must add here, though, his last scan showed 'TRACE' acites (ascites), and when I pressed the docs to discuss it with us, his docs attributed it to too much salt/fluid intake.  I sincerely hope that they are right and that statins are not contributing to it.)

Hope that helps.

[Trish77]

"No doubt statins are powerful drugs and should not be thrown into any sort of mix without much thought and discussion with your doctor. "

No argument with that whatsoever.  Have not suggested otherwise.

You said: "you can't just add a statin like you can a herbal supplement OR Alinia for that matter.  It has a special approval process via the FDA that must be followed to add a statin to one's drug regimen for persons with active liver disease..."  
-------------------
I think the reference is to researchers using statins in the context of Hep C research.

Jim:  As far as I know, any physician can prescribe a statin to someone with Hepatitis C using the same standards/criteria as someone without Hepatitis C, although the kmowlegeable physician would tend to monitor liver enymes more agressively, at least in the beginning.  The criteria itself, be it high cholesterol, other cardio risk factors, or even broader -- not really sure here. Remember, Alinia also has certain criteria as I understand it, although people seem to be taking it for reasons outside of that criteria.
------------------------------------------------------------------------------------------------------------------
Hm.  Okay.  My misunderstanding.  From the excerpt I quoted (twice) I took it that while a doctor could prescribe it to someone with active liver disease, which is what I'm referring to, they would have to justify the use of it, it seemed like an extra layer of approval and therefore an extra measure of safety control on the application of it.  Perhaps I misunderstood the meaning of that.  Did you understand that differently or is that information incorrect as written?

Thanks Jim.

Regards,

Trish

[jmjm530]

Trish,

I understood it referring to researchers and not to patients. There are no additional approvals in the U.S. for prescribing statins to those with HCV versus those without. BTW my first statement was to define my position, not to contradict yours.

Be well,

-- Jim

[Trish77]

Perhaps I missed that context, as I took it to mean any doctor prescribing a statin to someone with active liver disease.  I'll go back and give it another read.  Thanks for the perspective, Jim.

I suppose I was simply further defining my own position with that statement, not feeling contraindication from you. :)

Regards,

Trish

[susan400]

I have near perfect cholesterol.  My internal medicine doctor commented on it.  However, I exercise nearly every day and I have started taking Fish Oil.   It hasn't really lowered my LFT's any, but they haven't jumped up any higher either.  I've been doing the fish oil now for about 6 mon + ?     My triglycerides are still in the safe zone.   Blood sugar although not in diabetes range is being monitored because it's just a couple of 2-3 points over normal, but I've added in 1 cinnamon pill a day for that and my Internal Medicine doctor gave me the okay on that.

Susan

[merryBe]

Hi, I stumbled on the May Clinic discussion regarding statins, about midway there is some stuff regarding liver function as it relates to statins.....

just an interesting primer is all.
this guy says myalgia is the number one side effect s with those with pain or neuropathy it would also be rules out.

note the bit about grapefruit....it's amazing how much it interferes with  so many other things!!

Welcome to Mayo Clinic's podcast. This month's topic is controlling cholesterol with statin medications. I'm your host, Rich Dietman.

We may not know exactly what it does, but most of us have heard of cholesterol, and most of us know that too much of one type of cholesterol — LDL, or low-density lipoprotein — can be bad for us. Indeed, too much LDL can lead to a buildup of deposits called plaques on the inner walls of our arteries, making them hard and narrow. That can lead to things like high blood pressure, and when plaques tear or rupture, blood clots can form and these clots can block blood flow to the heart muscle, leading to a heart attack.

In recent years, a class of drugs called statins has made it easier for doctors to control high cholesterol. Also called cholesterol-lowering drugs, statins block a substance your liver needs for the natural production of cholesterol. This, in turn, depletes cholesterol in your liver, which causes your liver to remove cholesterol that's circulating in your blood. Statins are effective in lowering cholesterol, but there can be side effects, including, in rare cases, serious muscle damage.

Here to talk about cholesterol-lowering drugs is Mayo Clinic cardiologist, Dr. Gerald Gau. Dr. Gau is a consultant in the division of cardiology and vascular medicine at Mayo Clinic. He's also a professor of medicine at Mayo Clinic College of Medicine. Dr. Gau has served on the National Cholesterol Education Program Committee, and he's a medical editor with MayoClinic.com. Dr. Gau, thanks for being with us today.

Dr. Gau: Thank you for asking me.

Rich Dietman: Before we get started talking about statins, give us a brief definition of what cholesterol or cholesterols are.

Dr. Gau: Cholesterol is a very important component of our body. We're made of cholesterol. All of our cells are cholesterol based. The membranes that surround every cell of our body are made from cholesterol. You need them. We have to have cholesterol. We take it in by what we eat. We also produce it in our body. And if everything is in good balance, we produce enough cholesterol that's needed — our cells all function normally. Our endocrine system, which is dependent on this, also functions normally, and we don't have disease. It's management of this that becomes a problem — because of lifestyles, by what we eat and what happens to this cholesterol, because too much of it can cause disease. And when it builds up in the tissues, that's what leads to heart disease, vascular disease and the problems that we're talking about, which is what led up to the evolution of drugs to help lower cholesterol. In actual fact, if we would all eat better, watch what we eat, eat less calories, keep our weight ideal and exercise, we probably wouldn't need all these drugs that we're using here today.

Rich Dietman: But for most of us, that just doesn't work out that way.

Dr. Gau: It doesn't work. In the American population, we run high cholesterols on average. The median cholesterol in our country right now is an LDL cholesterol of about 130. We do know that a cholesterol that's down below 60 is ideal. We're a long ways away from that. And since we eat this way, and we're heavier in this country, a lot of people want the quick fix. And the quick fix is we can lower your cholesterol with these drugs effectively. It's just that, until we change our lifestyle here, we're not really going to turn things around to a great degree.

Rich Dietman: And statins do something with what goes on in the liver as far as managing cholesterol.

Dr. Gau: Statins work directly in the liver. There is a system in our liver that produces cholesterol. Cholesterol is necessary in our body, and the statin mechanism, it creates bile — it's one of the mechanisms of bile creation — and bile is necessary in our digestion and absorption. So the liver makes cholesterol to make this happen. It can also remove cholesterol from the blood for this purpose. Statins work by attacking in the liver the enzyme system that produces cholesterol in the liver. And that forces the liver cells to pull it from the blood and thereby lowers your cholesterol. And so our cholesterol comes down because we stop the production in the liver.

Rich Dietman: Statins, as you said, very, very effective. If not a wonder drug, then certainly a class of drugs, that's been, it sounds like, has either prolonged lives or saved lives, but there are side effects, as you say. Talk a little bit more about those. What are some of the more prominent side effects in taking statins?

Dr. Gau: The side effect of statins, primarily in the office practice is myalgia.

Rich Dietman: Which is?

Dr. Gau: Which is an aching in our muscles, where the muscles just hurt when you walk. If the myalgia gets more severe, when you squeeze your muscles with your hands, it hurts. A lot of people find they can't climb stairs, they feel they've lost their energy, and they do a little exercise and their muscles keep on hurting after they finish. It's an effect on the muscle that is producing this by the statin. This is probably in the range, by the literature from the trials, of 1 to 5 percent. The clinic in my office, I would guess, it's closer to 10 percent to 15 percent of patients, maybe more. Other side effects are less common. It can cause nausea, stomach upset, some people get bowel disturbance, either constipation or diarrhea, you can get different drug reactions that occur. These are enhanced with increasing age. If you have a smaller body mass, a small frame, you tend to have more of these side effects as well.

Rich Dietman: What about memory loss? Is that an issue?

Dr. Gau: Memory loss is an interesting one. It's been looked at in several different ways. In case-control studies, when they followed these studies, they found that there appeared to be less progression of dementia, or cognitive loss of function, in people that were on statins vs. not on statins. However, when it was looked at in two big clinical trials — the heart protection study done in England, which is 20,000 patients, and the PROSPER study done in this country, in older patients — they found when they looked at the older patients in these two studies, that there was no difference between cognitive loss or dementia.

[merryBe]

Rich Dietman: Well, I was also going to say, as I get older, my muscles naturally seem to be achier and I forget things more and all that sort of thing, so how do you sort that out?

Dr. Gau: It is hard. What I tell patients that come in that tell me that they are finding it difficult when they walk, that their muscles start hurting, and they sit down and it goes away after a while, and they get up and do it again and it's back, I say "Take a holiday from the statin drug." You stop this drug for 10 days, two weeks in time, and these symptoms all go away. You can then reintroduce the drug and produce it again and they know what they're looking for. It isn't that they're getting older, and it's usually a nice surprise for them when they find, "Oh my God, I feel normal again."

Rich Dietman: So what do you do then for them?

Dr. Gau: You can try other agents. Some statins will do it where another statin might not, although there generally is a lot of crossover. If one does it, the next one will do it too.

Rich Dietman: How about alcohol use? Can I have a beer or two and not worry about its effect if I'm taking statins?

Dr. Gau: The answer is generally yes. Alcohol is related to liver disease. If you consume a lot of alcohol — generous amounts of alcohol — on a daily basis, your underlying liver disease changes, your liver function changes. And when you get an abnormal liver and then you give it an agent that is denatured in the liver, like statins, because that's how it is eliminated from the body, and you have already abnormal liver function going on, all of a sudden your liver says "No, we can't do this." You can also get myalgia because your statin dose is going to be higher because it's not being denatured in the liver. But more likely your liver is going to cause problems for you, and we get acute onset of liver problems. Generally, what we say if somebody's drinking alcohol in a little bit more than moderation, or they have a history of prior liver disease, we start statins with great caution. We do it slowly, we follow their liver function. Statins themselves, just using them in somebody who's not a drinker, really don't seem to cause any liver problems, although we check a liver enzyme, we rarely, if ever, seen any changes.

Rich Dietman: If I'm taking statins, you talked about liver enzyme tests, would I expect to have a routine set of blood tests?

Dr. Gau: It is recommended that before you start, we do get a baseline liver test. An AST is usually the one that is used, and this test is a simple liver test and a blood test that tells you whether your liver's having a problem or not. After you start a statin, we usually check that again at the first blood draw, six weeks to three months out. And if that remains normal, there's really not an indication you have to keep on measuring this. If I go up on the dose, I will recheck it again just to make sure that the new dose is not doing this.

Rich Dietman: If you're treating me with statins, and I know you've told me that there could be side effects, what are the side effects that you'd want me to get in touch with you right away on and others that could wait?

Dr. Gau: Every patient that we see, we tell them about the myalgia. I tell them that if they notice in doing routine, everyday activities, if their muscles start aching or they're aware that they're losing function in terms of being unable to climb stairs or be physically active or with their exercise, because I want everybody I'm treating here to be exercising. If they're aware that their muscles hurt longer after they exercise, then they should call me and let me know. I tell them, actually, to stop the statin and then call me. When you stop the statin, it takes about a week to 10 days for these symptoms to dissipate and usually the patient by that time will tell me, "I couldn't believe how much better I feel." And then we talk about what else we can do here, whether we're going to try another statin. If they're at a high dose, sometimes they'll tolerate a lower dose in combination with another agent, and there are several other agents that can be used.

Rich Dietman: Can I get rid of my side effects, if I have them, by taking coenzyme Q10?

Dr. Gau: That is a very popular belief. Remember I said in the liver where it attacks this enzyme, HMG-CoA reductase, the enzyme that leads to production of cholesterol, with our desired effect at lowering cholesterol. One of the other things that is dropped is coenzyme Q10, called ubiquinol. So they have a name for it, it's down there with the cholesterol, on another pathway that is also blocked by statins. When you start a statin, your coenzyme Q10 level in your blood drops by 50 percent. We've tried, in terms of replacing coenzyme Q10, limited studies are done on this, not a lot, no big trials, but we find that even though we give it back, this ratio sometimes does not change. It doesn't seem to have any effect on the myalgia. It is being recommended across the country over-the-counter, because coenzyme Q10 is not a prescription drug. Because of that, people take it over-the-counter and they use it, and it's being heavily marketed that if you're on a statin you should be on this, but there's no good trials, and there's no evidence that coenzyme Q10 changes the myalgia effect. So, in answer to your question, should you take it, I don't have any problem with a patient taking it, but they need to understand that coenzyme Q10 is not regulated by anybody.

Rich Dietman: Anything else that you can think of that we didn't cover that's important that we should talk about?

Dr. Gau: Well, one of the things that I get asked by my patients all the time is this thing about grapefruit juice. Statins are denatured in the liver by a system called the cytochrome P450 system. It's an enzyme system that breaks the statin down and eliminates it. In our liver, that same enzyme system is used for denaturing a whole lot of other things, and one of them is grapefruit. And so when you have a pathway that you take a lot of grapefruit juice and that pathway's busy breaking it down, you take a statin, the statin doesn't get broken down, your dose stays high in the blood. You get a bigger effect for the dose you're taking, maybe even twice, and therefore you can have more likely problems with myalgia and other symptoms because the dose is up. In the study that was done, you had to take a whole quart of grapefruit juice to get this effect.

Rich Dietman: A day?

Dr. Gau: Yeah, at once. And the statin was taken at the same time that you took the grapefruit. If you have a half a grapefruit in the morning and take your statin at night, it's not going to cause any problem for you; our liver's able to handle that without any trouble. I tell people that, yes this was done, it's in the literature, it's actually in the drug information when you read it, says avoid grapefruit juice, and then studies showed 1 quart of grapefruit juice. I have never met anybody that drinks a quart of grapefruit juice. But I tell people if they want to use grapefruit, they should know that they shouldn't take it at the same time as their statin because it will increase the dose effect. So I tell people, don't get concerned about the grapefruit, just don't drink a quart of it. And don't take it when you take your statin. Take your grapefruit in the morning and statin at night. If you do that, it's not a problem. But that's a common question asked by patients.

Rich Dietman: Well, thanks very much, Dr. Gau.

We've been talking with Dr. Gerald Gau, cardiologist and an expert in cholesterol management at Mayo Clinic. Dr. Gau is also medical editor at Mayo Clinic.com. I'm your host, Rich Dietman.

[Trish77]

merryBe, thanks for posting that.  That's good information and further illuminates the subject, answers some of my questions about side effects and the answer to that is "not that many" except in the case of myalgia for some people and it's good to be aware of it.  It's good to know that if you DO get it, that stopping the statin stops the myalgia.  The grapefruit connection is interesting and also good to know for people on statins.

Good post and thanks.

Trish

[Trish77]

Eureka, I've appreciated your posts and your input on this, particularly yours and your husband's personal experience with this.  That has also helped to understand this better.  I've read your other posts on his journey....he's a lucky man to have you in his corner.  I wish you both the best.

Trish

[Mr Liver]

Statins have shown anti-viral activity. They are being studied right now in this role. Statins which lower cholsterol are involved in an interesting paradox. Those who commence tx with high LDL levels has a significantly higher chance at SVR. A connection exists as convulted as it seems now between the two.

Statins are safe in the majority of those with impaired livers, according to my liver doc and cardio doc. Ironically, they both attended a large symposium in D.C. on this very subject right before my hear attack. Anyway, I'm on a TP wait list and I take a statin. My LDL is now 50, HDL 30. I had to go in for monthly blood labs to monitor liver function after starting statins. My ALT/AST over the 6 months didn't budge out of medium-low range.
ML

[geterdone]

Then would it not also hold true that after treatment and SVR had been established and one starts stains to lower their cholesterol and the agents of the stains eat away at the plaque build up in the arties and as the layers of plaque dissolves it would unearth imbedded virus cells that have attached to plaque in the build up stage over years (dormant cells) isolated from any T cell attacks, and in doing so be release back into the blood stream and then find their way back to the liver to re-infect new pads? If this is how stains remove plaque from the arteries and tissue I would be very leery of taking stains if this were to be proven true.

jasper

[geterdone]

Unless, as studies are now coming to the forefront that the stains do reduce the viral load when used before the start of treatment and also during treatment if all started at once, in some cases.

jasper

[geterdone]

Opps should proof read, stains should be Statins

jasper

[merryBe]

Hi, just saw your question...it was HR that clued me in on the diminushed capacity to produce as stages advance...back in some PPC discussion I think...

it also is regulated by both kidneys and thyroid...so if your are hypo you are more likely to be low...hyper and you could get quite high.

since while on tx the thyroid can really get out of balance that means adding statins could have, not will have, but could have rather deliterious results in short order...
(assuming maybe the thyroid goes belly up hypo at the same time statins are on board..and with some doc not doing regular draws....)

just saying...this would require regular monitoring, which INS may not want to pick up since it's not SOC, yet regular profiles to make sure one did not go too low would be essential...because extremely low cholesterol is life threatening

I think that puts statins into a differnt ball park than say Alinia,  which has a much safer trackk record and no additional monitoring required.

Certainly for those with high numbers it might be worth trying...but people need to know the risks vs. benefit and the biology of   the drugs.

Because of my stage and thyroid my cholesterol hovers around 100 total....so obviously stains are not for everyone.
I would eat a ton of eggs or such to build that up...but unfortunately, everything high in cholesterol is also high in iron..just about, and I'm high in iron...so catch 22.

[merryBe]

thanks for that info...I am already pushing the envelope by adding PPC for it's anti-fibrotics knowing it lowers cholesterol but may help me to form some new healthy liver able to make cholesterol.

HR and I discussed this in a PPC thread a while back..obviously the HGH may also help with new liver cells also...

I do remember from when I taught anatomy that the liver always makes it's own cholesterol whenever it get's too low. it will make it out of other things, disolving fat and muscle to come up with enough......but as HR pointed out,that is assuming there is enough healthy liver tissue tissue left to make that process, sorry I don't have that research....with HR I tend to take assume he knows of what he speaks.

Of course if anyone wants to use statins and their blood indicates they can stand some lowering...then hey....salute''...I'm all for that and have my own version.....but let's just all be aware of the contraindications and things to watch for before proceeding with any and all treatment adjuncts.
MB.
.