Once upon a time, before the advent of statins, the dividing line between normal and high cholesterol was 280 mg/dl. That limit is in accord with this 2019 study, entitled Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults, from which the above chart is taken. Full text is available here.
*What is a hazard ratio?
The hazard ratio is equivalent to the odds that an individual in the group with the higher hazard reaches the endpoint first
The chart shown at top is an aggregate of all participants, but optimal levels vary a bit depending on age. When we look at the more detailed charts shown in figure 4, we see that 190 mg per deciliter is around the optimum for men under age 35 and women under age 45, whereas 220 is optimum for those 45 and up:
What about all of the many studies to the contrary? Here is one — another 2019 study, titled Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality, that shows risk of cardiovascular disease and mortality increases with increasing cholesterol and egg consumption, regardless of whether cholesterol was above or below 240 mg/dl (see figure 5 in study). Because of such studies, nowadays the high limit for “normal” cholesterol is set at 200 mg/dl. Why this apparent contradiction?
To answer this question we must understand that these are observational studies, and observational studies do not prove causation. There may be confounders associated with cholesterol levels. In the egg study that is exactly what happened. In the US, bacon consumption is highly correlated with egg consumption. High temperature cooking, like frying of fatty meat, creates advanced glycation end products - AGEs - that cause vascular damage. The body patches damaged arteries with plaques that contain a high concentration of cholesterol, and so cholesterol gets the blame. A large study in China found that egg consumption was associated with improved cardiovascular health.
Why the difference? Bacon is a rarity in China. Chinese in the US who have adopted American dietary habits have worse cardiovascular health than the average American, so this difference was not due to genetics. It arose solely from diet. AGEs, not cholesterol or eggs in moderation, are the bad actors. This is discussed in detail, with references, in my prior work, A Tale Of Two Studies Leads To A Deeper Understanding Of Cardiovascular Disease. High blood sugar is another bad actor that is associated with increased cardiovascular disease risk.
Because observational studies do not prove causality, we would not want to raise an otherwise healthy person's low cholesterol, based upon the large study presented above, without proof it would lower cardiovascular risk. The same consideration applies to lowering cholesterol...
The global campaign to lower cholesterol by diet and drugs has failed to thwart the developing pandemic of coronary heart disease around the world. Some experts believe this failure is due to the explosive rise in obesity and diabetes, but it is equally plausible that the cholesterol hypothesis, which posits that lowering cholesterol prevents cardiovascular disease, is incorrect. The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of [trial drug] evacetrapib despite dramatically lowering low-density lipoprotein cholesterol and raising high density lipoprotein cholesterol in high-risk patients with coronary disease. This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic.
If statins were benign medications this would not be too big a deal, but that is not so. According to this 2022 review:
Although data based on observational studies and registries indicated an incidence of SAMS [statin-associated muscle symptoms] that can reach 30%, RCTs [randomized controlled trials] suggest a much lower rate (roughly 5%)
Why the difference? Randomized controlled trials of statins generally require a run-in period wherein those who are intolerant of the medication are removed from the study without reporting them as having experienced adverse effects. For more on this see Dr. Maryanne Demasi comments below.
According to this review there is also a .5% - 1% chance of acquiring (type II) diabetes as result of statin usage over a period of 5 years.
Are people with low cholesterol truly healthy? Not according to this PhD in Biochemistry, specializing in cholesterol. He discusses the 12 million participant study:
Transcript Excerpts:
All right let's talk about cholesterol, my favorite topic. This topic is so perverted in scientific circles especially medical circles it's really frustrating. By the way I did a five year PhD on the topic of cholesterol and sex hormones. ... Now earlier this week I had a client from the country of Greece. He's a vegan and he had some blood work he sent me his total cholesterol is 110. That's very common with vegans and vegetarians. Their total cholesterol is 110, 120. And the doctor will come into the office he'll give you a high five. And he'll say, "you are the model of good health I'm so proud of you"... And you'll say - “yeah but I have depression, I have brain fog, and I have low testosterone, and I have no sex drive”. And they'll say “yeah but at least your blood test looks really good”.
That's what we're dealing with in our modern medical system - they think the lower the better in terms of cholesterol. There's plenty of people out there that will say that it's complete nonsense. First of all a big reason for that is a large portion of your brain is made of cholesterol. Secondly your sex hormones are made from cholesterol. Testosterone, estrogen, progesterone - they're made from cholesterol. If you want low testosterone give yourself low cholesterol. How do you do that? Eat super low fat you'll feel like garbage after a couple years...You've got a lot of cholesterol stored up in your brain and stored up in your cells. You have quite a good reserve of it but eventually you deplete that reserve...
My total cholesterol is usually about 240 maybe even 260 sometimes. And again I did my PhD on this topic that doesn't scare me the least. .. But what happens when I go to the doctors, the conventional doctors in America? Happens all the time ... they'll say “I'm sorry to inform you you're gonna die any minute of a heart attack unless we get you on some drugs, some statins”. Right? ... Your total cholesterol is 240 you're gonna die that's very scary for people especially if you've never studied this you just assume the doctor knows best. ... But they really haven't taken much more than like a week of classes on the topic of cholesterol. So the optimal range I mean look at the actual data the optimal range is between 180 and 280 and if you're in that range I'm as happy as could be ...
A scientist and investigative journalist:
Transcript Excerpts:
In the 1980s when former President Ronald Reagan was in power he significantly slashed public funding to the National Institutes of Health and this left a gaping hole for private industry to come in and start sponsoring their own clinical trials. And this is essentially what happened with the statin trials - the vast majority of statin trials are funded by manufacturers. So when you have drug companies sponsoring their own trials and publishing their own peer-reviewed results Cochrane has established well and truly that this favors the benefits of the drug and underestimates the risks…
Another way that you can influence public opinion and doctors opinions about the efficacy of statin medications is to design a trial to minimize the harms. And this is essentially what happened in the heart protection study. They design a trial with what they call a run-in period. So they gather say thousands of participants and they put all the participants on the drug for a period of four to six weeks. Then at the end of this run-in period there's a high dropout rate. People stop taking the medication they don't tolerate it mostly due to side effects. In the heart protection study 36% of the participants dropped out in this first phase of the trial. So with this freshly culled population of participants that's when they begin the clinical trial and they separate them between placebo and statins. So at the end the side effect rates between the statin group and the placebo group are fairly similar. So we know that cutting out all of those people that had side effects from the medication before the trial began grossly underestimates the percentage of people that will experience side effects at the end of the trial. And this is probably why we see that the side effect rate in the statin trials is wildly different to the rates that we see in real world populations. So when you ask doctors what the complication and side-effect rates are as statins they usually say around 20 to 30 percent of their patients feel muscle pain and brain fog.
Another way that a drug company can market the medication and exaggerate the benefits is to exaggerate the statistics. Now most of you have heard doctors and public health authorities say that statins reduce your risk of developing heart disease by over 30%. Now in Australia direct-to-consumer advertising is illegal but it's not illegal to advertise direct to doctors. And this is the kind of advertisement that you'll see in a doctor magazine this is an Australian doctor publication: it says lipitor reduces the risk of heart attack by 36 percent. And they have a picture of an imminent and trustworthy doctor and why wouldn't you relay that to your patients. I'd be impressed with a medication that would reduce my risk by 36 percent. But when you look closer at the study this is the study it came from statin wars exaggerating statistics from 2008 it was published in the European heart journal and again Rory Collins appears on this publication. And on table 4 it actually shows that if you take placebo your risk of having a heart attack is about 3.1% it so this is taking the sugar pill. However if you take the statin your risk drops to two percent so from 3.1% down to 2% is about a 36% reduction, but the absolute risk reduction was only 1.1%. And that sounds much less impressive especially to a patient when they're talking to their doctor about whether they want to take statins.
Now the reason this is really important for patients is because they have the fear of god put in them that you're going to die if you stop taking your statins. But these kind of statistics will just help the patient make more informed choices. Informed choices about whether or not they want to take a medication. Because if they're suffering really badly from side effects they have severe muscle pain and they can't exercise, they have brain fog, they have memory lapses, they can't function properly at work, then maybe some of them are willing to take the risk of this absolute reduction of 1.1%. So it's important to give patients honest and transparent information.
The foregoing should not be taken as personal medical advice. Please consult with your doctor before making any changes in your medication.
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