Most statin problems caused by mysterious 'nocebo effect', study suggests | Hacker News Reader

Most statin problems caused by mysterious 'nocebo effect', study suggests

bbc.co.uk

48 pointscmsefton52 comments

According to Wikipedia:

> The most important adverse side effects are muscle problems, an increased risk of diabetes mellitus, and increased liver enzymes in the blood due to liver damage.

I can understand the nocebo effect giving you a headache, or even preventing the rug from reaching it full potential somehow, but diabetes? Liver damage? That's a hard pill to swallow. How does that work?

I personally know three people who experienced side effects and had no idea that it could have been linked to the statins. One had liver damage that tooks months to recover from. Another had colitis symptoms and they went away after stopping statins. A third became very weak, to the point of having trouble getting out of bed. He stopped the statins and was back to normal about a week later. All three of these people were extremely skeptical that the statins could be the problem and were astonished at the improvement.

It's hard to say how mindset affected the symptoms and recovery. They all believed the statins would help them and were also skeptical that stopping them would help.

The study was for a group of 60. That number feels unnecessarily small given how often statins are prescribed, to your point.

It is interesting, but keep in mind there may also be 100 others in your social circle taking statins without any side effects whatsoever. I don't typically talk with my friends about the lack of side effects of medications I'm on.

It's possible too that liver damage could have been caused by taking acetominophen with heavy alcohol use (e.g.), which the person might have been embarrassed to admit. I don't know. I don't know your friend. I'm also not accusing your friend of lying, but it wouldn't surprise me given human behavior.

"...keep in mind there may also be 100 others in your social circle taking statins without any side effects..."

Not 100 (I don't have that many friends), but true. I'm not saying there's tons of side effects or that they are common. I was just saying that I know of 3 examples that make me question some things related to the study. For example, if I know 3 people with seemingly true side effects and they are part of the 10% of people with side effects, so that should mean I should know 30 people with side effects. And then I should know how many people taking statins? Even if 50% have side effects, then I'd need to know 60 people taking them in my fairly small (and young) group of family and friends. Maybe my group is too small to have a valid sample size, the study could be questionable (like the one on statins and longevity that recommended prescribing statins to basically every elderly person), or there is some other issue I'm missing.

It would be nearly impossible to tell if someone was lying. I don't know that person very well, but from what they said it shouldnt be an issue. I would guess his flight surgeon investigated that as a possible cause since they are pretty strict about what medications you are allowed to take (the statin was prescribed by a different doctor and that caused some drama).

Keep in mind about 35 million people in the US take statins, and liver damage is caused by a lot of things including hepatitis.

That said, one of the best medical stories to come out of the last century was the doctor who discovered that phen-fen caused heart valve issues in a handful of patients he was treating. It wasn't the FDA, it was a doctor who saw it in his patients and discovered that was the only thing that was common in all of his patients.

It's easy how it works. Liver damage isn't the cardiologists problem. Very similar to dermatologists telling people to avoid the sun and use heavy sun screen. And now public health nurses are seeing kids in wealthy communities with rickets.

elric wants to know how a placebo/nocebo effect can cause liver damage.

Actual hepatic damage in the absence of drug interactions is quite rare, and the increase in diabetes is over years. This study didn't look at those outcomes.

My recollection from being prescribed a statin is that the doctor wanted me to see how I would "tolerate" it, and to let him know if I had any "muscle aches".

Hell, once I got past the age of 40 my muscles ache quite a bit some days. Is it coincidence or is it caused by the statin? This could be true with tiredness as well.

As far as liver damage, yeah, that's got to be either a drug interaction or by bad behaviors (heavy drinking, etc).

I find this to be highly unlikely. I took statins for about two weeks and started getting weird muscle pains and aches which resolved within 2-3 days after ending treatment. I didn't even know that muscle pains were a potential side effect until I brought it up with my doctor. I take several drugs, and statins are the only one which have brought on notable physical symptoms; so I find it unlikely that this is "all in my head", because I'm not mentally paying attention to what individual drugs are doing to my body. I find this reporting to be so irresponsible that it is borderline unethical in my opinion.

I don’t doubt what you say is true, but basing science off of self reported anecdotes is actually unethical. If you want to critique this at least attack the methodology, authors or something.

This study demonstrates only that the 60 participants in it are suggestible.

1. All participants in the study had previously been on statins and had stopped taking statins because they experienced side effects. Any results obtained from this study are not generalizable.

2. They did not separate the participants into groups. There was no control. A better design might be to have 1/3 of the group take actual statins for 12 months, 1/3 take a placebo, and 1/3 take nothing.

The participants are their own control. It's a blinded crossover study. Actually one of the best kind.

Yes I agree with that. I should have prefaced this with n=1.

I find research into the placebo/nocebo effect very interesting, and from what I understand it has been shown, that

* the effect results in real physical change,

* the effect is independent of whether you believe in it.

E.g. there is a number of RCT studies on acupuncture where needles are placed randomly, still people experience amelioration of symptoms.

So I'm wondering you are thinking that nocebo is equivalent with "in your head"?

I absolutely subscribe to the fact that placebo/nocebo can be as (or even more) powerful than the intervention that a candidate believes that they are receiving. When I read anecdotes that fall out of line with our scientific understanding of the facts (such as the one I posed above), my default assumption is that we're witnessing placebo at play. From the outside, I definitely would not trust my anecdote. After my experience though, and now knowing what I know about the drug, I still wouldn't chalk my experience up to placebo. I guess that's the catch-22 of the phenomenon, eh?

However, they most assuredly can negatively affect Vitamin D production in some people, to the point of extreme fatigue, arthritic-like joint pains severe enough to prevent walking etc. I spent a year with such pains visiting specialists with no diagnosis till I mentioned it to my heart doctor on a routine visit, who seemed to be the only one to do a blood test for Vitamin D levels, and viola, a pill a week cleaned it (mostly) up.

I’ve had terrible reactions to statins. The best way to describe it was that it felt, mentally, like my consciousness was fading and that I was dying. Closest sensations I’ve experienced to it would be fainting or moments of low blood pressure. Sort of like getting dizzy after standing up too fast, but for hours and hours. Not pleasant.

My doctors have no idea what caused these symptoms, but in both cases going off the statin (first Crestor, then Lipitor) got me back to normal.

Statins are also linked to serious personality changes: https://www.bbc.com/future/article/20200108-the-medications-...

Wasn't there a literal mechanism described by the statin side effects - namely COQ10 depletion? Yeah okay. Let's get rid of this garbage reporting. This literally serves to help pharmaceuticals at the expense of the people's health. Bad actors and malicious intent.

Every few years the industry does a push to get statins into the water supply. It's psychopathic, and because we live in a terrible world, they will eventually win. And ultimately when the health consequences are being felt and we find out that they knew about them the entire time, everybody involved will be dead and their children will be our bosses.

And some statins cross the blood brain barrier. Cholesterol is important to your brain.

There are a few mechanisms by which statins could cause side effects. This talk discusses some of them. https://www.youtube.com/watch?v=o_QdNX9etCg

20 years ago my doc suggested I start taking statins but I always said no because "I'll improve my diet" etc which never happened. Now I finally started and its not a big deal, no side effects and cholesterol is down to top end of normal for the first time ever.

I started taking statin 2 years ago. My family has a history of cholesterol disease. Within the first year my LDH and HDH level was at the optimal range. Doc cut the disease by half and the second year was within normal range but a bit higher than the first one. I honestly don’t feel any different. Doc said mostly it could be that the negative news is the worthy ones to publish. I don’t think changing diet would make a lot of difference in my case. Without statin my LDL and HDL would be off the charge. I know those two numbers alone are not determining how I could die but what else I should believe in?

There are some people for whom statins are a necessity, e.g., a bodybuilder/triathloner friend whose cholesterol is above 300 w/o statins and whose father died at 46 from a heart attack. He has little choice but to workout like crazy and take statins and is OK with that.

But I have only borderline high cholesterol. My experience has been different:

After starting 10 mg pravastatin daily, I drop things, my energy level is down, my legs feel weak (although they are not), gym workouts are miserable and I feel so extraordinarily heavy when I collapse into bed at night.

Maybe for me it is "better to burn out than to rust" (though there's not much "burn" left in the rocket).

Yeah if you have side effects you should look to switch meds or maybe stop. I was just pointing out I was afraid of side effects but never saw any.

Family history can be a good indicator of risk too. Some societies have higher levels of cholesterol and still live long lives (that 1980s swimmer of Icelandic descent comes to mind). Also keep in mind that the cutoff for high cholesterol has been lowered over time. So if I were in your shoes, I wouldn't be too worried about borderline-high cholesterol. And you can always eat natural statins too which can be found in things like walnuts and oyster mushrooms.

I'm trying to find the actual study and having some difficulty. From this descripiton:

https://medicalxpress.com/news/2020-11-patients-statins-simi...

"The study, funded by the British Heart Foundation, is published in the New England Journal of Medicine and will be presented at the American Heart Association Conference today."

The only thing I could find at the NEJM right now is this correspondence:

https://www.nejm.org/doi/full/10.1056/NEJMc2031173

Via Sci-Hub:

https://sci-hub.do/downloads/2020-11-15/03/10.1056@NEJMc2031...

This has a figure with monthly average score per patient; that seems like a bad way to look at symptom severity IMO. They also mention funding:

Supported by a grant (PG/15/7/31235) from the British Heart Foundation; a grant (212183/Z/18/Z, to Dr. Howard) from the Wellcome Trust; a grant (MR/S021108/1, to Dr. Rajkumar) from the Medical Research Council; the National Institute for Health Research Imperial Biomedical Research Centre; and the Imperial Clinical Trials Unit.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

https://www.nejm.org/doi/suppl/10.1056/NEJMc2031173/suppl_fi...

---

I'm not sure why this is correspondence, but I'd guess the main paper is to be part of the conference proceedings. IMO, the discussion would be better if we wait for the actual study to be available.

I also found this similar study:

https://academic.oup.com/ehjcvp/advance-article/doi/10.1093/...

I haven't looked at that in detail yet.

My understanding has been that the need for statins has been over-stated. The gist being, Big Sugar paid (off) a couple Harvard researchers to implicate fat and cholestoral; given sugar a free pass.

Yes, absolutely, high risk individuals can benefit from statins. But higher counts are not necessarily synonymous with risk. Family history is often a better signal than simply _a_ person's counts via a given blood test.

https://www.statnews.com/2016/09/12/sugar-industry-harvard-r...

Yeah, no. I didn't even know there _were_ side effects until I started to get serious "mental fog", memory loss, and morning muscle stiffness so bad it was difficult to descend down the stairs. I think it's harmful to suggest that it's "in the head", because these things are sometimes real, and they can often be resolved partially or fully by taking a different statin (e.g. rosuvastatin instead of atorvastatin). At best, you can ethically suggest they are _sometimes_ in the head.

Chiming in as someone else who started experiencing severe muscle aches after starting statins and which resolved a couple weeks after I ceased taking them. Prior to experiencing them I hadn't known it was a possible side effect of the drug at all.

I need to go back on them (familial hypercholesterolemia, total cholesterol > 300), but I'm dreading it.

Did you try CoQ10 supplements? I added some after the first bout of muscle pain and it tempered it (not completely).

I second this. It helped me as well.

My doctor insisted on CoQ10 - Ubiquinol, not Ubiquinon if possible.

This article is rather insulting. I've known too many people who have been bedridden due to these side effects. They take it knowing their cholesterol is high, so they great desire to see it work. Attributing it to nocebo effect is just plain obnoxious. Or maybe they are just shilling for pharmaceutical companies?

All the comments here are slagging this off. Here’s the methodology:

> The statin study, which took place at Hammersmith Hospital, focused on 60 patients who had all come off the drugs in the past due to severe side effects. They were given 12 bottles - four contained a month's worth of statins, four a month's worth of dummy pills and four were empty. Every day for a year they would score, from zero to 100, how bad their symptoms were. The study showed an average score of: 8 in those taking no tablets 15.4 while taking dummy pills 16.3 while taking statins

> The Imperial researchers said 90% of the severity of their symptoms was present when the volunteers were taking dummy pills they thought could be a statin.

Why is this “utter bullshit”? Looks like a reasonable conclusion to me?

Not OP, and I don't think it's utter bullshit, but I can see 2 serious problems:

1. small sample, 60 people is not enough to draw great conclusions. 2. they should have included people who had never taken statins before. It's quite possible that the brain was re-generating the side-effects because it was used to before by association. They can't even have a control group for that.

Problem is that adding those who have never had statins would be unethical. You don't give medication to those who don't need it, and you don't withhold it from those who don't. This was done on those who needed it but found the side effects too bad, which makes it ethical to study.

It's bullshit because they experienced it and there's no way they could fall for something like the placebo effect.

This just seems to be the mindset of most people, and though there has been a bit of research suggesting some people are more susceptible to the placebo effect I've never seen something showing people are commonly immune to it.

Isn't that description completely incomprehensible? It seems to be saying (in a roundabout way) that each participant was part of all 3 groups, with them taking the drug, placebo and nothing for a third of the year. There's a reason studies don't do this, it adds a great deal of complexity and room for error.

It's also not at all clear what symptoms the participants are rating. Are they symptoms of their underlying condition, common side effects of the drug, or side effects they had experienced previously?

>It's also not at all clear what symptoms the participants are rating

I don't see how this matters? If the symptoms were the cause of the underlying condition, they would show up roughly as often between "no pill" and "placebo."

This is utter bullshit. I was told repeatedly to get on Statins for high cholesterol. Finally the company nurse said: look, you need this but first I'll let you try red yeast. WTF? OK. It's a natural source of the same thing. It dramatically reduced my cholesterol and triglycerides -great. I was kind of excited to have such great results while giving the finger to big pharma (who isolated lovastatin from red yeast and patented it). Then the muscle aches started. I was completely unaware of that side effect, but reducing my dose helped - which I did only after being informed that it's a common side effect. You can also reduce it by taking CoQ10.

You can't have a psychological side effect if you're not even aware of it.

They didn’t say all side effects were attributable to nocebo effects.

>You can't have a psychological side effect if you're not even aware of it.

You can just by chance, though you also can consciously forget you were told or read something like one of the common side effects.

edit You mention being told to take statins several times before a nurse offered you a second choice. Why had you been so reluctant if you didn't know of the common side effects?

Stop blaming the patient for the drugs problem. I don't like taking medications in general. I had heard that statins do lower cholesterol, but that studies (right or wrong) showed no decrease in mortality so why bother. That's it. I was actually pleased with the red yeast results - the lower cholesterol would get doctors off my back and the reduced triglycerides was IMHO a very good thing! But yeah speculate about chance, or my subconscious remembering something I didn't care about if I ever did hear it.

This is straight up some jackass trying to use a cute term - nocebo - to deflect blame for side effects onto patients. That's a thing too.

So basically you don't think the placebo/noncebo effect exists and you don't think doctors are suggesting things based on a concern for your well being. Instead they're making up over a century of studies so they can blame patients for side effects.

This all seems much less likely than you heard something about cholesterol medicine causing muscle pain.

From the article:

"They were given 12 bottles - four contained a month's worth of statins, four a month's worth of dummy pills and four were empty.

Every day for a year they would score, from zero to 100, how bad their symptoms were.

The study showed an average score of:

8 in those taking no tablets

15.4 while taking dummy pills

16.3 while taking statins"

One could draw the conclusion that statins perform as well as placebos, or are at least their effectiveness is within the margin of error.

Typical doctor bullshit. They don't understand what caused a physical problem, so they blame it on the patients: "it's in your mind".

In this case, I find extremely hard to believe that liver damage, neuropathy, and diabetes can all be caused by any mental effect. Nope, it's something they just don't understand yet.

It would be interesting to know who funded this research.

As always: who funded the study

Twelve people is not a large sample size.

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