Some Statins May Disrupt Sleep

By Crystal Phend, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
November 08, 2007
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ORLANDO, Nov. 8 -- If patients taking simvastatin (Zocor) develop sleep disturbances, changing statins may be a good idea, researchers suggested here.

Simvastatin modestly but significantly reduced sleep quality and increased sleep problems compared with pravastatin (Pravachol), according to a large study of subjective sleep measures reported at the American Heart Association meeting.

"This provides tentative corroboration for long-standing concerns that lipophilic statins may affect sleep in some individuals," said Beatrice Golomb, M.D., Ph.D., of the University of California at San Diego, who reported the findings of a study of 1,016 patients.

Simvastatin is the most lipophilic of the statins, she noted. This may allow the drug to more readily cross the blood-brain barrier and impact serotonin or other sleep-related factors compared with statins such as pravastatin, which is the most hydrophilic.

Among other statins, lovastatin is lipophilic, rosuvastatin (Crestor) may be hydrophilic, and atorvastatin (Lipitor) is considered intermediate.

For patients who develop sleep problems after starting on a statin, "it might be prudent to switch to a different statin," Dr. Golomb said.

Sleep has not generally been reported as an adverse event in large efficacy trials, although case series and smaller trials have indicated insomnia, nightmares and other sleep disturbances may be more common with some statins.

To test sleep outcomes prospectively, the researchers conducted a double-blind trial in which 1,000 men and postmenopausal women were randomized to placebo or equivalent, or modest doses of pravastatin (40 mg) or simvastatin (20 mg).

At baseline, participants had LDL cholesterol in the 115 to 190 mg/dl range, for which statin treatment was considered optional at the time. None had known cardiovascular disease, diabetes, or a fasting blood glucose of 140 mg/dl or higher. None was on statin therapy before enrollment in the study.

Sleep quality and sleep problems were similar between treatment groups at baseline. At six months, sleep quality dropped in all three groups, but there were significant differences between them.

On-treatment sleep quality remained above average with pravastatin and placebo (mean score 15.79 and 15.50 on a 30-point visual analog Leeds scale), whereas it was below average with simvastatin (mean 14.67, P=0.003 versus pravastatin and P=0.026 versus placebo).

Sleep problems worsened during treatment to a greater degree with simvastatin than with pravastatin or placebo (0.21 versus 0.098 and 0.074 on a two-point scale from zero change to much worse). After adjustment for baseline problems with sleep, the differences were significant (P=0.038 versus pravastatin and P=0.007 versus placebo).

Sleep quality was significantly linked to tiredness and irritability, whereas sleep problems were correlated with tiredness, irritability, and cognition (all P<0.001).

More patients taking simvastatin reported sleep as much worse than at baseline than did patients on placebo (P=0.015), and a similar trend was seen compared with pravastatin (P=0.093).

However, the researchers could not pin down what specific sleep changes were occurring.

In an exploratory analysis, there were no differences in unrestful sleep or other characteristics measured. However, nightmares and sleep-disordered breathing were possibilities not measured in the study that have been seen in previous, smaller studies.

Further study is also needed to look prospectively at sleep with other statins, as well as to look at higher doses since other statin-related adverse events are dose dependent, Dr. Golomb said.

The researchers reported no relevant conflicts of interest.

Complete AHA Coverage

Primary source: American Heart Association Meeting
Source reference:
Golomb BA, et al "Simvastatin but Not Pravastatin Affects Sleep: Findings from the UCSD Statin Study" AHA Meeting 2007; Abstract 3725.

Here's my story: I was put on Zocor at a high dose about 5 years ago. I had horrible side effects, some of them psychological, like a total personality change from a relatively even-tempered to a crazy person yelling at people at work, which I'd never done in my life and I'm near retirement age. Then I was tried on different doses and other statins. I think the Zocor was worst, but none of them were good. All kinds of other symptoms that were just weird.

Of course, at that time statins were seen as wonder drugs, so my doctors cast a skeptical eye at me. I was then tried on Zetia a non-statin cholesterol drug when it first came out. I became disoriented and got lost going home from work at a job that I've held for years. I was so dizzy it seemed like I was drunk at work, just staggering around. I tried to hang in there to get past the side effects, but they actually got worse. I've seen seen hints that people on zetia can have cerebellar attaxia that may not reverse and they end up in a wheel chair because they cannot walk. This was supposed to be very safe.

The only place I found any comfort was Golumb's UCSD study. I took that into my doctor and said "no more!"

Later I went to a consulting pharmacist since I was on multiple meds. She was great, BTW! She made suggestions to my doc about them and they were followed.

She did one other thing. When she did my history and found out about the statin reactions she had a med student follow up with me and file an official report. It took a WHOLE LOT of time, like 1/2 an hour or more to complete this report. I can't see very many doctors taking the time to do this when a patient has a bad reaction. So, the vast majority of these reactions never get reported.

I've had other averse reactions to medications, but never had another medical professional file an official report (not sure if it was with the FDA or the CDC or what, but something like that).

My cholesterol is in the ok range though not fantastic range, but I have to work very hard to keep it there. It's interesting to read that these drugs disrupt sleep. If I remember right, this was one of the side effects I had that they pooh-poohed.

Bless Golumb and her studies. I'm pretty sure that she's not funded by big pharma but is an independent voice,

Rosemary, I know I should know, but do you just do the usual things to keep your cholesterol down - low saturated fat diet, fish oil supplements, daily exercise?

My doc has sent a "see me" message re my last cholesterol result. I really don't want to go on the meds. I have been trying to "be good" since last Christmas, but she obviously isn't too impressed with the results.


I appreciate all your help in other areas, and hope it's ok to ask more of you.

thanks

Di

Moby wrote:Rosemary, I know I should know, but do you just do the usual things to keep your cholesterol down - low saturated fat diet, fish oil supplements, daily exercise?

My doc has sent a "see me" message re my last cholesterol result. I really don't want to go on the meds. I have been trying to "be good" since last Christmas, but she obviously isn't too impressed with the results.


I appreciate all your help in other areas, and hope it's ok to ask more of you.

thanks

Di

You left out increased fiber (cholesterol adsorbant) intake and avoid refined carbs, especially processed sugars and syrups (forces liver to generate cholesterol).

My doc took me off those drugs last year after I began treating my OSA and my lipid panel went back to normal.

Hi Moby, here are all the things I can think of just now.

1. I use a fiber product called "Profibe" http://www.profibe.com It brings cholesterol way down, but is fairly inconvenient given my lifestyle (work too many hours and forget to take it a lot. If I took this regularly 3x a day it would work as well as a statin. It consist of soy protein bonded to citrus fiber. I'm gradually figuring out how to fit it in. When I've done this consistently for 3 or more months my cholesterol has gone down from 260 to 180. This was the only change I made at that time. I am trying to get back to this, but it's a difficult regimen. Part of the problem is that I take various meds and you must take the fiber 2 hours away from the fiber so it doesn't sweep the meds out of your system.

You have to build up fiber intake slowly due to gas. I didn't take the fiber after starting cpap for about four months because I thought the combo of aerophagia and fiber might cause me to explode .Surprisingly it does not seem to make a difference at this point. I have some aerophagia in the morning from cpap and some gas from the fiber later in the day, but my body is adjusting to it.

2. I do aerobic exercise nearly every morning for at least 30 minutes. This helps raise HDL and makes me feel good. I'm not a natural exerciser, and was never an athletic kid. I purchased an eliptical machine at the urging of my doctor. It was so expensive, I don't dare not use it .

3. I eat whole vegetables and whole fruits like crazy. At least 10 servings a day. Probably more. These are fresh or cooked from fresh by me. In winter I do use frozen ones, too. I eat as many veggie and fruit carbs as I like, but very few grain products. Since I'm gluten sensitive this is, in a way, easy.

4. I take a lot of supplements, including cod liver oil every day. I only rarely take herbs, though, and I don't use red rice yeast or policosanol because these are like statins.

5. I try to avoid refined sweets because of the effects of inflammation on the cardio system. This is a WHOLE lot easier now that I'm sleeping w/cpap. Those cravings have largely subsided.

6. I use my xpap nightly. I was hoping that this might make a difference, so it's good to hear your account, Dreamstalker.

Luckily, many of the things I do are helpful in many areas of health, not just one.

_________________

CPAPopedia Keywords Contained In This Post (Click For Definition): CPAP, aerophagia

Wow Rosemary, thanks. I've printed that out and will start on the work directly. I do belong to a gym with cross trainers, I could use them there. I just use the swimming pool really.

Thanks too DreamStalker. Good point.

Di

Moby wrote:Wow Rosemary, thanks. I've printed that out and will start on the work directly. I do belong to a gym with cross trainers, I could use them there. I just use the swimming pool really.

Thanks too DreamStalker. Good point.

Di

One more detail. I monitor my heart rate while I do aerobics. The watch/chestband devices are affordable these days. I've had mine for years and all it's ever needed is a new battery. I don't want to go too high or too low but stay in the aerobic range. If I didn't have the Polar heartrate monitor it would be hard to do this. I try to do something fun when I exercise, like listening to books on tape. Lately, I've been doing work-related reading, though.

I heard some docs on C-Span testifying before a congressional panel. They said that only 10% of people with untreated "bad" cholesterol profiles will ever develop heart disease.

In the US, $20 billion is spent every year on cholesterol-lowering prescription drugs ($15 billion statins and $5 billion other). These docs' view is that $18 billion is spent on people who would never develop heart disease even if their high cholesterol is left untreated.

So that is $18 billion wasted every year plus all the side effects these people suffer through. The dream is to find in the mapping of the human genome a key to identify which people are at risk for heart disease due to high cholesterol. Then of course, you could spend only $2 billion on medications targeted to the at risk population. There would be a cost to do the genetic profiling.

Personally, if my docs ever prescribe statins, I will take the 90% odds that heart disease is not in my profile. No statins for me.

On the other hand, if I don't get my apnea under control, I won't be around to worry about it.

I have recently seen the before and after blood lipid panel of an 88 year old woman who had been on statins, bp lowering meds, and pain medication for Osteoarthritis. A small, thin woman, by the way.

She had read about low carb diets and decided to try them. Her previous diet was very low fat, and very high in complex carbohydrates. Being rather headstrong and daring (and intelligent and with medical knowledge) she did this without talking to her doctor.

After three months on a diet full of saturated fats and no carbohyedrates. her total cholestrol and LDL admitedly rose, however:

Her HDL - the good cholesterol went up from 37 to 60 - which means weant from below the norm to what the AHA defines as a level that will "protect you from a heart attack".

Her high triglicerides (sorry, dont' remember the number) were cosiderably lower.
She had stopped all BP med and her BP is now 120 over something normal, and she no longer has osteorathritic pains because apparently our joints need some of that fat that had been cut out of her previous diet. And she's sleeping better.

So that sent me looking of info. This is from The American Journal of Clinical Nutrition, Aug 2007. Use it a starting point for further search.

Added emphasis mine

http://www.ajcn.org/cgi/content/full/86/2/276

Use this a starting point for further search.

Abstract
The persistence of an epidemic of obesity and type 2 diabetes suggests that new nutritional strategies are needed if the epidemic is to be overcome. A promising nutritional approach suggested by this thematic review is carbohydrate restriction. Recent studies show that, under conditions of carbohydrate restriction, fuel sources shift from glucose and fatty acids to fatty acids and ketones, and that ad libitum–fed carbohydrate-restricted diets lead to appetite reduction, weight loss, and improvement in surrogate markers of cardiovascular disease.

Introduction
The persistence of an epidemic of obesity and type 2 diabetes suggests that new nutritional strategies are needed if the epidemic is to be overcome. A historical perspective and recent research point to some form of carbohydrate restriction as a likely candidate for a new nutritional approach, and we present a thematic review regarding carbohydrate restriction.

The examination of diets before modernization can remind us of the remarkable ability of humans to adapt to their environment and can provide a context within which to view current diets. In contrast to current Western diets, the traditional diets of many preagricultural peoples were relatively low in carbohydrate (1, 2). In North America, for example, the traditional diet of many First Nations peoples of Canada before European migration comprised fish, meat, wild plants, and berries. The change in lifestyle of several North American aboriginal populations occurred as recently as the late 1800s, and the numerous ensuing health problems were extensively documented (3-5). Whereas many aspects of lifestyle were altered with modernization, these researchers suspected that the health problems came from the change in nutrition—specifically, the introduction of sugar and flour.

In a similar manner, before the discovery of insulin, the removal of high-glycemic carbohydrates such as sugar and flour from the diets of diabetics was found to be a successful method of controlling glycosuria. An analysis of the pattern of food consumption during the more recent obesity and diabetes epidemic found that the increase in calories was almost entirely due to an increase in carbohydrate (6). Given this context, it is reasonable to postulate that diets low in carbohydrate may be as healthy as, or even healthier than, the higher-carbohydrate diets introduced into modern society only recently.

O.

But Mr. Rooster, that's corporate capitalism ... is there any harm in making $18 billion more profit than is neccessary? Think of all the trickle-down jobs ... a handful of CEOs, few tens of scientists, several hundred marketing/media folks, thousands of outsourced manufacturing jobs in India and China ... and we can't' forget world travel perks for the regulatory leaders and campaign funding for the politicians. The masses (republicans & democrats) are all just stupid voters (if they even vote) that will never figure anything out ... give 'em vouchers and they will be just fine with anything fed to them (food, drugs, autos, reality TV shows or whatever).

Feed the corporate monster!

ozij wrote:I have recently seen the before and after blood lipid panel of an 88 year old woman ...

So that sent me looking of info. This is from The American Journal of Clinical Nutrition, Aug 2007. Use it a starting point for further search.

...

O.

Though outside my field of profession, I agree that bad carbs can be more damaging than bad fats ... at least based on my research into nutritional guidelines.

Sugar is truely an evil drug on par with nicotine, cocaine, and opiates ... but hey people gotta have jobs and the rich guys gotta make money

Do some research on strokes - causes & effects or long term deficits. We'll talk, right now I gotta run. But I enjoyed this article, right on time.

[quote="DreamStalker"]But Mr. Rooster, that's corporate capitalism ... is there any harm in making $18 billion more profit than is neccessary? Think of all the trickle-down jobs ... a handful of CEOs, few tens of scientists, several hundred marketing/media folks, thousands of outsourced manufacturing jobs in India and China ... ........

rooster wrote:Your mindset is obvious this morning.

*By "we", I mean each individual spending his own money on what he freely chooses.

Yea ... sorry. I had a tough time last night with one of the monsters while trying to "freely" spend my money to book my bro-in-law a flight for the holidays.

DreamStalker wrote: I had a tough time last night with one of the monsters while trying to "freely" spend my money to book my bro-in-law a flight for the holidays.

Pricing flights! Now that's a tangled web that reminds me of your current avatar. The airlines, for years now, have strived to charge according to the value the buyer gets. For example, the business traveler who needs/wants to travel at peak times has to pay high prices. The "casual" traveler who can take a trip or not, is enticed to take the trip with lower prices.

I think it is an appropriate strategy, but the way it is implemented by imperfect humans can drive me crazy sometimes. Fortunately, my wife is a good economist and is very persistent to negotiate good deals. So it has worked to our advantage.

My university student son just took a trip using my frequent flier points. He would not admit it, but I believe he learned a lot from his mother and me. He negotiated rock bottom prices for the rental car and hotel.

Now when he went to pick up the car, they would not let him have the price. He had the confirmation printed out in his hands and they still just refused, offering him one that was double in price. Talking to the manager was of no avail. National Car Rental sucks!

But no regulation please. Let the market decide how National fares.

I just realized I have taken this thread from statins to car rentals. Isn't one of my pet peeves people who get threads off track? Pooh on me.