Another Big Fat Fail For The Lipid Hypothesis

Bacterial pneumonia, once a leading killer of the old and the very young, is caused by (duh) bacteria.  If you kill the bacteria, the pneumonia goes away.  It doesn’t really matter how you kill the bacteria, either.  If a patient is allergic to one drug that kills the bacteria, a doctor can prescribe a different drug that kills the bacteria and – bingo! – the pneumonia goes away. Why?


And how do we know that?


Okay, but let’s suppose we kill the bacteria we believe causes the pneumonia, but the pneumonia remains and the patient dies.  And let’s suppose this happens with multiple patients.  Then what would we conclude?


No, I’m just pointing out some basic logic here.  If we kill the bacteria but the pneumonia remains, we have to conclude that while a bacterial infection may be associated with pneumonia, it isn’t the cause.  That’s what we’d expect any honest scientist to say.

But strangely, this basic logic seems to escape researchers when a cholesterol-lowering drug fails to prevent heart attacks. Here are some quotes from a New York Times article:

It is a drug that reduces levels of LDL cholesterol, the dangerous kind, as much as statins do. And it more than doubles levels of HDL cholesterol, the good kind, which is linked to protection from heart disease.

That’s the Lipid Hypothesis in a nutshell: LDL is dangerous.  It causes heart disease — just like that nasty bacteria causes bacterial pneumonia.  HDL, meanwhile, protects against heart disease.

As a result, heart experts had high hopes for it as an alternative for the many patients who cannot or will not take statins.

Everybody sing: “Oh, we’ve got hiiiigh hopes.  Yes, we’ve got hiiiigh hopes …”

But these specialists were stunned by the results of a study of 12,000 patients, announced on Sunday at the American College of Cardiology’s annual meeting: There was no benefit from taking the drug, evacetrapib.

No benefit?  But LDL causes heart disease!  Did the drug fail to lower the LDL that causes heart disease?

Participants taking the drug saw their LDL levels fall to an average of 55 milligrams per deciliter from 84. Their HDL levels rose to an average of 104 milligram per deciliter from 46.

Well now, that is an amazing improvement in lipids.  The American Heart Association would be delighted with those numbers … although strangely, I can’t find recommended LDL levels on the AHA site anymore.  Perhaps they hired the former KGB artists who used to make people disappear from official photos once they became an embarrassment to the Kremlin.  Anyway …

Yet 256 participants had heart attacks, compared with 255 patients in the group who were taking a placebo.

In other words, no difference.  A total fail.

“We had an agent that seemed to do all the right things,” said Dr. Stephen J. Nicholls, the study’s principal investigator and the deputy director of the South Australian Health and Medical Research Institute in Adelaide.

Yup.  If high cholesterol – and specifically high LDL – causes heart disease, then you did indeed have an agent that seemed to do all the right things.

“It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?” he said, referring to the 37 percent drop in LDL levels with the drug.

Boy, that’s a real head-scratcher.  Let me think for a minute … uh … uh … perhaps the fact that two things are associated doesn’t mean one is causing the other?  I seem to recall a good scientist or two saying as much.

“All of us would have put money on it,” said Dr. Peter Libby, a Harvard cardiologist. The drug, he said, “was the great hope.”

And how are those Enron shares working for ya?

Researchers have hypotheses, but no one is certain what went wrong. “It may be that the LDL level is less important than how it gets changed,” said Dr. Paul Thompson, a cardiologist at Hartford Hospital.

Ah, yes, that must be it.  LDL causes heart disease, ya see, but lowering LDL only works if you do it exactly the right way.  And if you have bacterial pneumonia, it’s not wiping out the bacteria that cures you; it’s how you kill them.  Kill them the wrong way, and you’ll still have pneumonia … even though bacteria cause the pneumonia.

Here’s an alternate hypothesis about why the latest study was a big, fat fail:


That would be the most logical conclusion:  we beat people’s LDL levels down, but they didn’t have fewer heart attacks.  So LDL doesn’t cause heart disease.  But beating cholesterol levels down is a $36 billion per year (and climbing) business.  So we’re getting the illogical conclusion instead:

Cardiologists still have high hopes for a new class of cholesterol drugs, known as PCSK-9 inhibitors, that cause LDL to plummet to levels never seen in drug treatments.

Try to wrap your head around that one:  in a multi-year study of 12,000 people, dramatically lowering LDL levels didn’t prevent heart disease.  But cardiologists have high hopes for a new class of drugs that lower LDL levels EVEN MORE!

Everybody sing: “Oh, we’ve got hiiiigh hopes.  Yes, we’ve got hiiiigh hopes …”

And here’s the reason for those high hopes:

The PCSK-9 inhibitors can cost more than $14,000 a year …

Fourteen grand per patient, per year, year in and year out.  Yeah, that would generate a lot of hope.

… while statins can cost just pennies a day, so determining what portion of patients are truly statin intolerant has become an important question.

Yeah, about that “statin intolerant” problem: funny how research funded by drug companies is starting to demonstrate a real problem with statins isn’t it?  In one of his many great posts, Dr. Malcolm Kendrick predicted this would happen:

For years the experts have informed us that this is utter rubbish, statins are wonder-drugs, and adverse effect free. All of a sudden, now that the pharmaceutical industry is about to launch new cholesterol lowering agents, we are suddenly going to find that, why, after all, statins do cause a whole range of nasty adverse effects.

I watch this stuff with a kind of morbid fascination. The marketing game is on, billions are about to be spent pushing PCSK9-inhibitors. The Key Opinion Leaders who tirelessly promoted the wonders of statins, and who told us that they were virtually side-effect free, are now singing a completely different tune.

Sure enough, a big ol’ study just concluded that lots and lots of people have real problems with statins.  The study was led by Dr. Steve Nissen, one of the long-time pimps for — er, promoters of statins.  Returning to the New York Times article:

A second study presented at the cardiology meeting on Sunday and published online in JAMA, the Journal of the American Medical Association revealed just how vexing the issue is.

The study, directed by Dr. Nissen and paid for by Amgen, a pharmaceutical company, included more than 500 people with extremely high levels of LDL cholesterol who had tried two or more statins and had reported aching or weak muscles so severe that they said they absolutely could not continue taking the drugs.

[The result] indicated that 57 percent of patients actually could tolerate statins. Researchers then randomly assigned the remaining 43 percent to take either Amgen’s PCSK-9 inhibitor, evolocumab, or another cholesterol-lowering drug, ezetimibe, which is often taken by statin intolerant patients but has never been shown to reduce heart disease risk when taken without an accompanying statin. The patients tolerated both drugs.

My, my, my … statins go off patent (thus reducing the cost to just pennies per day), and through sheer coincidence, we get a major new study showing that nearly half of all people can’t tolerate statins – but they can tolerate the new drug that costs $14,000 per year.

And of course, we know this new and very expensive drug will prevent heart attacks because it lowers LDL.  High LDL cholesterol causes heart disease, ya see.  We’ll just continue believing that even when a drug that dramatically lowers LDL fails to prevent heart attacks.

Perhaps someday, after yet another LDL-lowering drug fails to prevent heart attacks, researchers will respond by going before the cameras and announcing that it’s time to bury the Lipid Hypothesis once and for all.

But I don’t have high hopes.


71 thoughts on “Another Big Fat Fail For The Lipid Hypothesis

  1. George Henderson (@puddleg)

    “It may be that the LDL level is less important than how it gets changed,” said Dr. Paul Thompson, a cardiologist at Hartford Hospital.

    Absolutely true. Maybe if LDL gets changed by the right thing, it doesn’t matter whether the change is up, down, or sideways.

    Like, say, if LDL is changed (or not) by a healthy diet, some exercise, sunlight, sleep, and weight loss if necessary.

    1. Thomas E.

      “That there is funny”

      Of course, whose definition of “healthy diet”, I am sure mine (likely yours as well) would cause them to have chest pains 😀

      1. Walter Bushell

        Sure! I just examined the menu of a restaurant that advertised healthy eating.

        I’d rather eat at Mickey Ds. “Turkey Bacon(!??)” But it is they type of restaurant
        that is legally allowed to make health claims.

  2. Bob Niland

    Evacetrapib is a CETP inhibitor. My understanding is that all are considered failures.

    Don’t forget the recent HOPE-3 trial results on a statin (rosuvastatin, Crestor), which had 690 people die to prove, once again, that statins make no significant difference in long-term (7 year) outcomes. The imaginary LDL-C was driven down by an impressive 30%. All-cause mortality went down by ¼ of 1% (and I’d like to know what the placebo was in those arms). These appalling results are already being used to push for wider prophylactic use of statins.

    There is no all-cause outcome data for PCSK9 inhibitors yet, but they do impressively distort the imaginary LDL-C number.

    Phrenology is still being practiced, folks, and this is what it looks like.

    1. Tom Naughton Post author

      Someday, doctors will look back on statins and other cholesterol-lowering drugs and wonder how their professional forebears could have been so stupid. Meanwhile, they’ll be prescribing their generation’s worthless/harmful drug.

  3. Tom Welsh

    Sometimes it actually hurts, deep down, to be a member of the species homo sapiens. (Although I am thinking of starting a movement to rename it “home insipiens”).

    I suppose the best way to survive the pain is to do what you help us do, Tom – laugh. But while we’re laughing, we mustn’t forget the sheer immensity of the evil that some people are trying to perpetrate. Even though their efforts do tend to demonstrate what Hannah Arendt called “the banality of evil”. Those people aren’t evil in an expansive, dramatic way like Jabba the Hutt or Pol Pot. They’re just quiet, busy, hard-working, reasonable people like Adolf Eichmann.

  4. Tom Welsh

    Oh, and before anyone rips into me for making such an inappropriate and politically incorrect comparison, let me add that it’s quite feasible those people in the medical establishment, Big Pharma and government have caused more premature death and suffering than Eichmann did.

          1. Bob Weaver

            Draft Jabba for President!!
            There, I’ve said it. If the Hutt-man runs, I may actually vote this year…

            1. Tom Naughton Post author

              I’m pretty sure his negative ratings are lower than Trump’s and Hillary’s.

          1. Walter Bushell

            Yes, the sheer stupidity, hypnotic conditioning, greed, cultic behavior etcetera of the conventional nutrition establishment hurts to much to cry.

    1. Thomas E.

      I would imagine without a doubt. I would suggest more people have been killed by doctors ties over the last 20 years than Eichmann.

      There is a private hospital in Oklahoma, that has something close to no, or 1 case of MSRA per year. And they do it simply by having an easy dress protocol, clean scrubs/clothes and shoe covers when ever a doctor or nurse enters the building and frequent hand washing and other simple protocols.

      The right thing to do is easy to spot in many cases, the hard thing is to do it.

      But when you add in all the medication interaction issues, over diagnosis and so on, 100,000’s are killed every year. Heck, in the last 2 or 3 years the fine doctors in Ontario have tried to kill my dad twice with contradictory medications. I can’t imagine the horror in my Dad mind when a doctor rushes into the room, looks at his chart and proclaimed what where they thinking ( i think harsher language was used). He had gained over 20 lbs of water weight in under 3 months and was on the verge of congestive heart failure.

      But I blather on.

  5. Jerome Burne

    Brilliant piece. Great minds and all – I did a similar post – not so witty but more details – which filled in some of the background on the route PCSK9 took to being licenced and the magic fairies that helped it along the way.

    The comforting conclusion from the Amgen study was that it might well be worth taking Rapatha (the Amgen product) along with ezetimibe (details in the post ). Interesting since while Rapatha has a trial currently underway that should (if they have got the protocol and the statistics right) show that it cuts risk of heart disease, ezetimibe even though it has been on the market for about 15 years has never, despite repeated trials, been shown to reduce your risk of heart disease. Actually I lie – a key study linked to the Rapatha story did show that it cut the risk – by 2%!!
    Still maybe it is better to have two drugs that don’t work than one.

      1. Walter Bushell

        You can make more money selling two drugs that don’t work than one, obviously.

        In fact that is a key to the American economy. If you can sell a product that doesn’t work it’s golden. The low fat Weight Watcher’s diet worked for years and is still selling, *BECAUSE* it doesn’t work. People come back time after time, because they have short term results, but every time through the cycle their is muscle loss and more metabolic damage so the victims end up worse and worse. Like the “treatment” for type II diabetes which makes the diabetes progressively worse.

          1. Walter Bushell

            But unlike planned obsolescence you don’t have to come up with new products, nor convince them the new widgets or services are better.

  6. Scott Burgess

    I’m surprised Tom, no head banging on desk?

    It’s stuff like this that makes me want to knock a few head together, how can supposedly logical, scientific minds hold so strongly onto a HYPOTHESIS, hell, not even THEORY, so strongly in the face of overwhelming evidence to the contrary?

    How many times do these puppies have to have their noses rubbed in the FACT that lowering cholesterol with DRUGS doesn’t prevent heart disease and DOES cause all kinds of other problems?

    Back to your pneumonia point here. You know what else you get with pneumonia? Antibodies! The whole lipid hypothesis is like blaming pneumonia on the antibodies rather than the bacteria.

    Patient has pneumonia, we see a whole bunch of antibodies suddenly appear in the bloodstream, ooh, they’re causing pneumonia! Let’s make a drug to lower the antibodies, that will cure pneumonia!

    Oh my! The patient dies anyway? We must not have lowered the antibodies enough.

    That is exactly what they’re doing with cholesterol lowering drugs. It’s no wonder that people are getting sicker, the very immune system that is trying to fight off cardiovascular disease is being attacked by the physicians with these drugs. Add to that, the drugs have a whole host of really nasty side effects.

    I don’t like to believe that doctors as a whole are so money driven. It’s getting really difficult not to think that though.

    Evidence shows that the absolute best way of preventing heart disease is a change in diet. All markers improve dramatically, blood pressure, cholesterol (yes, I do believe it’s a marker, but it’s like the antibodies and pneumonia, the body’s natural response to correct a problem, not the CAUSE), tooth decay, etc.

    So, what’s wrong with treating with diet? It’s not a drug. There’s no money in it.

    See, the problem is, I don’t want to be so cynical. I do not want to believe that doctors are only in it for the money. I want to believe that the vast majority of doctors became doctors because they truly want to help people.

    Sigh, maybe it’s time for me to give up that failed hypothesis and change my belief to doctors are only in it for the money.

    1. Tom Naughton Post author

      I’m cynical, but I still believe most doctors truly want to help their patients. Trouble is, they’re educated to prescribe drugs as the answer.

      1. Walter Bushell

        But most docs these days work for the insurance company, government agency, or a (usually) corporate practice and
        must follow the protocols their employer mandates.

    2. Thomas E.

      There are several issues in life where I simply can not come to a satisfactory conclusion.

      It is funny, I know many people who basically have the attitude of “How dare you condemn doctors”, and they include those at drug companies, medical schools, the whole lot.

      But the evidence seems to be clear, there is significant, by my definition, malpractice. As I mentioned earlier, the clothes many doctors wear still cause thousands of deaths a year by spreading, yup, bacteria.

      I think we should all go back and look at the story of Ignaz Semmelweis

      The story that repeats itself to this day when professionals attempt to blow the whistle.

      But to my point, as I am sure I have said before, I do believe there are many doctors who are going to massive moments of conscience when they take that step back and realize how much harm they have caused.

    3. Mike T

      The issue is that these are not really practicing doctors, but rather researchers who are being paid to ensure that the spigot on this particular revenue stream remains open and free of obstacles. Whether or not it actually improves patient health is a secondary concern.

      1. Brandon

        The funny thing is there is a branch of philosophy that believes reason trumps reality (I think it’s platoism or rationalism).

  7. Judy B

    On another blog, the doctor/author wrote that he is wondering if the lipid hypothesis should be challenged but he still likes statins….

  8. The Older Brother

    ““All of us would have put money on it,” said Dr. Peter Libby, a Harvard cardiologist…”

    HA! HA! HA! HA! HA! HA! HA! HA !HA! HA! HA! HA! HA! HA! HA! HA! eh — SNORK!!

    Damn. Just spit up a little bacon.

    These turds HAVE put money on it. Billions. Not to mention the prestige.

    The results must’ve been amazingly bad for even a Harvard cardiologist to have to admit it. I think at some point all of these highly credentialed, highly compensated lipid sycophants are going to start having to grapple with the realization that they’ve tied their careers and reputations to the 8-track, betamax bandwagon.


      1. Firebird

        They’ll die before the hypothesis does…and from a heart attack due to the stress they’re under to come up with a drug that supports the hypothesis.

      2. Mark

        Or you’ll see a complete, overnight reversal. “Oh, no, we’ve been saying for years that cholesterol doesn’t CAUSE heart disease. Statins work by reducing inflammation AND lowering cholesterol”. You only have to look at the Diabetes (profit generating) Associations and their subtley changing advice to realize their dirty underhanded tactics.

        1. Tom Naughton Post author

          I don’t expect the overnight reversal. I expect them to tiptoe backwards while hoping we don’t notice the movement.

        2. Thomas E.

          Ahhh, arggg, I really dislike this. For some reason it strike against my soul. But, it might be one of those things where we have to allow them to save face?

          A colleague of mine told me a story of were he had to give a wide company apology for a failing, that he had nothing to do with.

          It drives me nuts, but until the “experts” change their tune, many people I care about are not going to drop the low fat high carb treatment for diabetes, cancer and CVD.

    1. Walter Bushell

      Bet money on it. They bet *ALL* of our lives on it. The bet,my life, your life, our parents lives, our friends lives, our enemies lives, lives all over the world almost everyone’s life, except for a damn few hunter gather’s lives.

      No doubt they bet their own lives, but about their lives I’m not particularly concerned.

      It was and remains genocide. Legally it is merely grossly negligent homicide.

  9. Bonnie Hyderman

    So a few weeks ago I posted on the Fat Head f/b page that my doctor was shocked and horrified by my cholesterol numbers when three month prior they were nigh on perfect. I tried to explain that going carb free is likely the answer. My liver was dumping a s$*t load of gunk and that I will NOT under any circumstances take a statin. (I did many, many years ago and I am one of those intolerant the statins I mean..:) Anyways, to placate her I agreed to echo caridiograms and a 3 day EKG. 🙂 SMILING LARGE here..the office called to tell me that my heart and arteries are perfect. I tried not to laugh..but hey..I’m a 60 year old couch potato. It’s my new body and I’ll laugh if I wanna! 🙂 I’ve thanked you before, Tom. Your Fat Head movie very likely saved my life. 🙂

  10. Mike (another one)

    If the bacteria produce toxins that kill you, then killing the bacteria might not be sufficient. This can happen with some kinds of food poisoning. If you were to expose contaminated food to hard radiation after the bacteria have a chance to work, you could have sterile, yet poisonous food.

    As I recall, science got interested in statins in the first place because the previous class of cholesterol lowering drugs did have some patient benefit.

    Peter Attia has an elaborate Youtube video about the mechanism of atherosclerosis and he does describe it as being aggravated by the portion of LDL with the lowest diameters. So a drug that lowers LDL might or might not be of benefit, depending on how it affects that particular component of LDL. He also points out that eating fat and restricting carbs is how you shift the size distribution of LDL to a friendlier size. Didn’t one of your Fathead onscreen interviews allude to something very similar?

    Gary Taubes has suggested that the reason that calorie counting diets work for many people is because when you restrict calories, you tend to restrict carbs, because that is what you have been eating in the first place. This can give the appearance that calories are the most important part.

    It’s entirely possible that various LDL lowering drugs might have varying efficacy. So it could be the case that LDL does cause heart disease, and yet an LDL-lowering drug won’t prevent it.

    1. Tom Naughton Post author

      Any way you slice it, studies like this one are a poke in the eye for the Lipid Hypothesis, which simply defines LDL as the “bad” cholesterol that causes heart disease.

      1. Walter Bushell

        A steak [sic] through the heart.

        Meanwhile the NYT just published a report of a rediscovered study that fed prisoner’s a diet based on corn oil vs. animal fat. The prisoners on the animal fat diet won, of course.


      1. Annlee

        Discussed in the latest from Dr. Malcolm Kendrick (this one a sidebar to his What Causes Heart Disease?” series – which is VERY interesting, including all the comments).

    1. Stipetic

      Being on the wrong side of science, yet again, will give Willett a coronary. After all, replacing saturated fats with corn oil and its ilk is his magnum opus.

  11. Paul Miller

    Tom, your blunt (honest) take-downs of the establishment’s wrong (nutty) propaganda is badly needed and I wish you had a larger national platform. Maybe your upcoming book will help. Good luck and keep up the good work. Thanks!

  12. tony

    In order to increase profits, Big Pharma enlists a bunch of corrupt doctors to create a non-existent disease – the cholesterol paradigm – and all of a sudden millions of healthy people become sick overnight and are bamboozled into buying the dangerous and deadly statins.

    If this is free enterprise capitalism we have big problems.

    1. Tom Naughton Post author

      It’s not quite free enterprise capitalism. The federal government promoted the cholesterol paradigm, rewarded researchers who provided cover with grants, punished the researchers who questioned it by denying grants, etc.

  13. Desmond

    “‘Yet 256 participants had heart attacks, compared with 255 patients in the group who were taking a placebo.’ In other words, no difference.”

    Given the lengths that drug companies have gone to in order to stack the deck in their favor before drug trials even begin (such as cherry picking participants) I would not be surprised if PCSK-9 inhibitors are in reality far more harmful than placebos.

    1. Tom Naughton Post author

      I had the same thought. This study wasn’t of a PCSK9 inhibitor. It was a different LDL-smashing drug. That’s why researchers still have hiiigh hopes for PCSK9 inhibitors.

  14. Alex

    Did they just test overall LDL or did they both to take a look at the LDL particle count and see which were small and dense or big and fluffy ?

    1. Bob Niland

      Whenever you see “LDL”, with no mention of how arrived at, you may presume that it is “LDL-C”. The “C” stands for Calculated, and is based on the circa 1970 Friedewald equation. It is not a “test” or measure of anything. It’s an astonishingly crude approximation. Here’s a cardiologist on it:

      It is possible to actually measure various LDL particles, via advanced lipoprotein panels such as NMR, VAP and electrophoresis, which report a variety of actual “LDL-P” measures. But this is almost never done in lipid dogma trials. Asking the alleged researchers why might be impolite.

  15. Sky King

    “Oh, we’ve got hiiiigh hopes. Yes, we’ve got hiiiigh hopes …”

    Ooops there goes, yet another drug fail, and
    Ooops there goes, yet another drug fail, and
    Ooops there goes, yet another drug fail…AGAIN!


  16. Ulfric Douglas

    I never thought of Jabba the Hut as evil … his little muppet henchman was diefinitely evil though : they probably put Leia on statins to cunfuse her into wearing that outfit.

    1. Tom Naughton Post author

      As someone who first saw Star Wars as a hormone-addled teen, I’m glad they confused her.


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