Let´s remember that cholesterol is a normal molecule in our organism. And in terms of evolution appears relatively late. As someone said before is involved in a variety of physiological processes such as vitamin D, steroid hormones, cell membranes, myelin sheath and bile acids.
Surely there is a U shaped curve, without any doubt. The thing is at what level? The paradigm lower is better is a huge simplification...If we believe that the correlation between lower events and lower cholesterol concentration is linear, then cholesterol is not very different from tobacco consumption or lead or asbestos.
Dr M's byzantine explanations to dismiss this study is unconvincing. The much simpler explanation is that cholesterol reduction is greatly oversold. Given pharma's hand in most of the pro-statin studies, it is not a surprise.
I speculate that were cholesterol 'discovered' now, it's be hailed as a miracle molecule. The Vitamin D fad has been going on for at least couple of decades. And its substrate is... cholesterol. Ditto for all the sex hormones and adrenocorticoids. As mentioned in the article, it is a crucial element of all cell membranes, cell ion transport, and is key in nerve stability. Your liver knows this and manufactures massive amounts of cholesterol, especially when dietary sources are low.
To medicalize healthy people with the made-up 'hypercholesterolemia' diagnosis is just plain wrong.
We’ve long been told to base our medical decisions on “experimental evidence,” even when such evidence shows only marginal benefits with questionable cost–risk–benefit ratios. What is truly astonishing is how such often-flawed evidence dismisses robust observational data pointing in the opposite direction.
The cholesterol–heart disease hypothesis is a prime example. It was built on a veil of vested interests and the pseudoscience popularized by Ancel Keys (Echeverry-Raad, 2024) and, fueled by pharmaceutical enthusiasm, evolved into a global obsession: lowering at all costs the very molecule that sustains human life. Cholesterol participates in more than 60 biological processes and constitutes a large part of our anatomy, especially the immune–endocrine system and the brain.
At the same time, a profitable industry replaced natural saturated fats with highly processed seed oils—polyunsaturated fatty acids (PUFAs)—produced through heat and petrochemical processing. These oils, once used as industrial lubricants in the 1930s, became “foods.” Ironically, they may have caused more deaths than all infectious pandemics combined (Echeverry-Raad, 2025).
After more than two decades of clinical trials, statins have shown only modest benefits. In primary prevention, the number needed to treat (NNT) is 217 to prevent one nonfatal myocardial infarction, 313 for a nonfatal stroke, and about 250 to prevent one death. In contrast, the number needed to harm (NNH) is 21 for myopathy and 204 for new-onset diabetes (Chou et al., 2016). Even in secondary prevention, results remain modest (4S, HPS).
In contrast, Ravnskov et al. (2016) systematically reviewed 19 cohort studies including more than 68,000 adults aged 60 and older. In 92% of these cohorts, higher LDL levels were associated with lower all-cause mortality. Cardiovascular mortality showed either no association or even a paradoxical increase with low LDL.
Disagreeing with Dr. Mandrola, I believe the findings from the large South Korean study by Sang-Wook Yi et al. (2019) are actually consistent with Ravnskov’s results—particularly in the steepest portion of the curve, where lower cholesterol levels are linked to higher mortality, especially among adults over 60 in the context of so-called “primary prevention.”
Although observational designs can never fully control for confounding variables, such consistency across diverse populations compels us to ask: should LDL-C still be viewed as a universal enemy?
In most older adults, lowering cholesterol does not extend life and may even be harmful. The discussion should therefore shift from how much lower to in whom cholesterol reduction truly makes sense—considering each individual’s genetic, metabolic, and cardiovascular risk profiles.
To summarize: higher LDL levels in people over 60 are linked to lower mortality risk. Rather than a direct protective effect, this may represent biological resilience—a powerful reason to reconsider the indiscriminate use of statins in those of us already losing some youth and vitality.
⸻
References
• Chou, R., Dana, T., Blazina, I., Daeges, M., & Jeanne, T. L. (2016). Statins for prevention of cardiovascular disease in adults: Evidence report and systematic review for the US Preventive Services Task Force. JAMA, 316(19), 2008–2024.
• Echeverry-Raad, J. (2024). A falsehood that has been repeated many times becomes true: The origin of the diabesity pandemic, the most lethal of the 21st century? J Diabetes Metab Disord Control, 11(1), 39–50. DOI: 10.15406/jdmdc.2024.11.00276
• Echeverry-Raad, J. (2025). El hombre, víctima de su civilización: hacia una Zona Sana en nutrición, movimiento y estilos de vida. In: Medina A., Gómez A. (Eds.), Zona Sana III (3rd ed.). Fedicor, Bogotá.
• Heart Protection Study Collaborative Group. (2002). MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. The Lancet, 360(9326), 7–22.
• Ravnskov, U., Diamond, D. M., Hama, R., Hamazaki, T., Hammarskjöld, B., Hynes, N., … & Sundberg, R. (2016). Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open, 6(6), e010401.
• Scandinavian Simvastatin Survival Study Group. (1994). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). The Lancet, 344(8934), 1383–1389.
• Yi, S.-W., Yi, J.-J., & Ohrr, H. (2019). Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults. Scientific Reports, 9, 1596. https://doi.org/10.1038/s41598-018-38461-y
Thank you for your article. The cholesterol misinformation continues. The trust at a large scale in the medical establishment is really an issue. Not being complotist at all I keep wondering if there is any manipulation in social medias to keep blowing on the embers to fuel fake news and fake narrative to harm people on a big scale. I am personnaly very convinced by the evidence that lowering LDL-C lessen the burden of atherosclerosis and as a MD I walk the talk for myself having seen my family history... But anyway, it's Brandolinis law, it's very hard to fight misinfoirmation. Thank you for doing this still.
Statins will take 20 Years off your life , possibly give you dementia and other unpleasant health issues .There is no such thing as bad Cholesterol ,eat Butter ,Lard ,Tallow, Olive Oil ,Coconut Oil, Avocado Oil ,stop eating killer Seed Oils ,control inflammation. Statins are a Trillion Dollar Business for big Pharma ,scandalous.
You should listen to Dr Aseem Malhotra British Cardiologist, Dr Suneel Dhand and Dr Leonard Coldwell about Cholesterol and Statins. Cholesterol is not the enemy, inflammation of the Blood Vessels is . Research was done on the benefits of Statins, it found you gained an extra of 4 days of life if that .
The clot thickens, from Malcolm Kendricks for an encompassing and solid hypothesis on the cause of atheroslerosis. The cholesterol hypothesis does not make any sense from a mechanistic and physiological point of view. The sooner it is discarded, the better it will be for patients and public health systems (statins make up a huge part of the drug reimbursement programs in western countries)
The ARR and NNT for statins is miserable: For primary preventoin, 1% ARR. NNT generally around 100 or higher. For secondary prevention, ARR is approx. 3% in the best of the studies. NNT is 33. Miserable numbers. Mortality from MI started declining in the early 1970s--well before statins. Statins had no impact on the mortlaity decline from MIs when they were introduced. Insanity is doing the same thing over and over and expecting a different result. Why we settle for lousy drugs with miserable ARR and NNT is beyond me.
Excellent read. Do you think you might be addressing the findings of the REBOOT trial as it relates to women on beta blockers following a cardiac event?
If the NNT for statins, which seems to range from 20 to several hundred, is correct, then no more than 5% of the "hundreds of thousands of patients in the statin trials would have benefited from the drug.
There are many studies demonstrating that cholesterol levels have virtually nothing to do with health or disease. No need to trot out a turkey like this one. It has long been known that consumptive diseases (mostly cancers) cause a dramatic lowering of the cholesterol level. Attributing differences in longevity due to low cholesterol is as scientifically absurd as the widely accepted belief that lowering one's cholesterol will provide a benefit.
I fear this is back to the future. My post below reminds people that the old days we used to put Swan-Ganz catheters in to get a wedge of 17 and use morphine, nitrates and aspirin and that's how we treated these massive myocardial infarctions. There would be several a night I remember one night in the CCU my wife and I were working seven bed unit. There were two people dead EKG paper strewn all over the CCU and the Colonel Nurse came in. This is the largest hospital in the Air Force. The Colonel Nurse was more concerned about my wife's appearance. She was frazzled and her hair touched the uniform- then she seemed to be about the obvious level of work we did the night before. I don't think the CCU looks like that anymore and the patients certainly are not in their 50s and 60s.
This is another example of an observational study, where the “observations” are what they are…but the interpretation esp among the chattering class on social media is what leads to the facepalms.
U-shaped associations are nothing new. Same exists for BMI (https://pubmed.ncbi.nlm.nih.gov/27146380/) because obviously, if you have an underlying condition that results in you wasting away….that’s not going to bode well for your survival. Doesn’t impugn the observation itself. But it does behoove you to understand what you’re observing, and also what you’re NOT observing.
Just as a person who, with intervention, goes from high BMI to low BMI is NOT comparable to someone who already starts with low BMI, so too that a person who goes from high cholesterol to low cholesterol with therapy is not the same as someone who starts with low cholesterol (for whatever reason).
Sadly, social media rewards the rage (and idiotic) takes. Just as there are flat-earthers and QAnon enthusiasts, there will be folks who eat up this and assorted other insanities.
Interesting trial and comment. But...
Let´s remember that cholesterol is a normal molecule in our organism. And in terms of evolution appears relatively late. As someone said before is involved in a variety of physiological processes such as vitamin D, steroid hormones, cell membranes, myelin sheath and bile acids.
Surely there is a U shaped curve, without any doubt. The thing is at what level? The paradigm lower is better is a huge simplification...If we believe that the correlation between lower events and lower cholesterol concentration is linear, then cholesterol is not very different from tobacco consumption or lead or asbestos.
Very long subect to discuss...
Just my point of view.
Dr M's byzantine explanations to dismiss this study is unconvincing. The much simpler explanation is that cholesterol reduction is greatly oversold. Given pharma's hand in most of the pro-statin studies, it is not a surprise.
I speculate that were cholesterol 'discovered' now, it's be hailed as a miracle molecule. The Vitamin D fad has been going on for at least couple of decades. And its substrate is... cholesterol. Ditto for all the sex hormones and adrenocorticoids. As mentioned in the article, it is a crucial element of all cell membranes, cell ion transport, and is key in nerve stability. Your liver knows this and manufactures massive amounts of cholesterol, especially when dietary sources are low.
To medicalize healthy people with the made-up 'hypercholesterolemia' diagnosis is just plain wrong.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10153768/
Learn from this little gem!
Also statins in primary prevention have been (accurately) found to add 4 days of life. 4!!
The cult around statins is just that - ignores REAL science, real data for spin.
Okay, Dr M, you’re “all in” on statins. That tells me everything I need to know about you.
https://www.midwesterndoctor.com/p/why-are-statins-so-dangerous
Dear colleagues,
We’ve long been told to base our medical decisions on “experimental evidence,” even when such evidence shows only marginal benefits with questionable cost–risk–benefit ratios. What is truly astonishing is how such often-flawed evidence dismisses robust observational data pointing in the opposite direction.
The cholesterol–heart disease hypothesis is a prime example. It was built on a veil of vested interests and the pseudoscience popularized by Ancel Keys (Echeverry-Raad, 2024) and, fueled by pharmaceutical enthusiasm, evolved into a global obsession: lowering at all costs the very molecule that sustains human life. Cholesterol participates in more than 60 biological processes and constitutes a large part of our anatomy, especially the immune–endocrine system and the brain.
At the same time, a profitable industry replaced natural saturated fats with highly processed seed oils—polyunsaturated fatty acids (PUFAs)—produced through heat and petrochemical processing. These oils, once used as industrial lubricants in the 1930s, became “foods.” Ironically, they may have caused more deaths than all infectious pandemics combined (Echeverry-Raad, 2025).
After more than two decades of clinical trials, statins have shown only modest benefits. In primary prevention, the number needed to treat (NNT) is 217 to prevent one nonfatal myocardial infarction, 313 for a nonfatal stroke, and about 250 to prevent one death. In contrast, the number needed to harm (NNH) is 21 for myopathy and 204 for new-onset diabetes (Chou et al., 2016). Even in secondary prevention, results remain modest (4S, HPS).
In contrast, Ravnskov et al. (2016) systematically reviewed 19 cohort studies including more than 68,000 adults aged 60 and older. In 92% of these cohorts, higher LDL levels were associated with lower all-cause mortality. Cardiovascular mortality showed either no association or even a paradoxical increase with low LDL.
Disagreeing with Dr. Mandrola, I believe the findings from the large South Korean study by Sang-Wook Yi et al. (2019) are actually consistent with Ravnskov’s results—particularly in the steepest portion of the curve, where lower cholesterol levels are linked to higher mortality, especially among adults over 60 in the context of so-called “primary prevention.”
Although observational designs can never fully control for confounding variables, such consistency across diverse populations compels us to ask: should LDL-C still be viewed as a universal enemy?
In most older adults, lowering cholesterol does not extend life and may even be harmful. The discussion should therefore shift from how much lower to in whom cholesterol reduction truly makes sense—considering each individual’s genetic, metabolic, and cardiovascular risk profiles.
To summarize: higher LDL levels in people over 60 are linked to lower mortality risk. Rather than a direct protective effect, this may represent biological resilience—a powerful reason to reconsider the indiscriminate use of statins in those of us already losing some youth and vitality.
⸻
References
• Chou, R., Dana, T., Blazina, I., Daeges, M., & Jeanne, T. L. (2016). Statins for prevention of cardiovascular disease in adults: Evidence report and systematic review for the US Preventive Services Task Force. JAMA, 316(19), 2008–2024.
• Echeverry-Raad, J. (2024). A falsehood that has been repeated many times becomes true: The origin of the diabesity pandemic, the most lethal of the 21st century? J Diabetes Metab Disord Control, 11(1), 39–50. DOI: 10.15406/jdmdc.2024.11.00276
• Echeverry-Raad, J. (2025). El hombre, víctima de su civilización: hacia una Zona Sana en nutrición, movimiento y estilos de vida. In: Medina A., Gómez A. (Eds.), Zona Sana III (3rd ed.). Fedicor, Bogotá.
• Heart Protection Study Collaborative Group. (2002). MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. The Lancet, 360(9326), 7–22.
• Ravnskov, U., Diamond, D. M., Hama, R., Hamazaki, T., Hammarskjöld, B., Hynes, N., … & Sundberg, R. (2016). Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open, 6(6), e010401.
• Scandinavian Simvastatin Survival Study Group. (1994). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). The Lancet, 344(8934), 1383–1389.
• Yi, S.-W., Yi, J.-J., & Ohrr, H. (2019). Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults. Scientific Reports, 9, 1596. https://doi.org/10.1038/s41598-018-38461-y
Thank you for your article. The cholesterol misinformation continues. The trust at a large scale in the medical establishment is really an issue. Not being complotist at all I keep wondering if there is any manipulation in social medias to keep blowing on the embers to fuel fake news and fake narrative to harm people on a big scale. I am personnaly very convinced by the evidence that lowering LDL-C lessen the burden of atherosclerosis and as a MD I walk the talk for myself having seen my family history... But anyway, it's Brandolinis law, it's very hard to fight misinfoirmation. Thank you for doing this still.
Statins will take 20 Years off your life , possibly give you dementia and other unpleasant health issues .There is no such thing as bad Cholesterol ,eat Butter ,Lard ,Tallow, Olive Oil ,Coconut Oil, Avocado Oil ,stop eating killer Seed Oils ,control inflammation. Statins are a Trillion Dollar Business for big Pharma ,scandalous.
we always here this information narrative... always... sure it's part of the problem, like LDL particles !
You should listen to Dr Aseem Malhotra British Cardiologist, Dr Suneel Dhand and Dr Leonard Coldwell about Cholesterol and Statins. Cholesterol is not the enemy, inflammation of the Blood Vessels is . Research was done on the benefits of Statins, it found you gained an extra of 4 days of life if that .
Sorry but I pass. Dr Malhotra... #sigh
The clot thickens, from Malcolm Kendricks for an encompassing and solid hypothesis on the cause of atheroslerosis. The cholesterol hypothesis does not make any sense from a mechanistic and physiological point of view. The sooner it is discarded, the better it will be for patients and public health systems (statins make up a huge part of the drug reimbursement programs in western countries)
Yes I ditto a fascinating (and witty) book and his blogs are very informative also.
Nice piece, John. Also love the use of the word dodgy 😆 in this context
The ARR and NNT for statins is miserable: For primary preventoin, 1% ARR. NNT generally around 100 or higher. For secondary prevention, ARR is approx. 3% in the best of the studies. NNT is 33. Miserable numbers. Mortality from MI started declining in the early 1970s--well before statins. Statins had no impact on the mortlaity decline from MIs when they were introduced. Insanity is doing the same thing over and over and expecting a different result. Why we settle for lousy drugs with miserable ARR and NNT is beyond me.
I believe one of the Hill criteria is a dosage response which obviously does not hold in this case.
Excellent read. Do you think you might be addressing the findings of the REBOOT trial as it relates to women on beta blockers following a cardiac event?
If the NNT for statins, which seems to range from 20 to several hundred, is correct, then no more than 5% of the "hundreds of thousands of patients in the statin trials would have benefited from the drug.
There are many studies demonstrating that cholesterol levels have virtually nothing to do with health or disease. No need to trot out a turkey like this one. It has long been known that consumptive diseases (mostly cancers) cause a dramatic lowering of the cholesterol level. Attributing differences in longevity due to low cholesterol is as scientifically absurd as the widely accepted belief that lowering one's cholesterol will provide a benefit.
I fear this is back to the future. My post below reminds people that the old days we used to put Swan-Ganz catheters in to get a wedge of 17 and use morphine, nitrates and aspirin and that's how we treated these massive myocardial infarctions. There would be several a night I remember one night in the CCU my wife and I were working seven bed unit. There were two people dead EKG paper strewn all over the CCU and the Colonel Nurse came in. This is the largest hospital in the Air Force. The Colonel Nurse was more concerned about my wife's appearance. She was frazzled and her hair touched the uniform- then she seemed to be about the obvious level of work we did the night before. I don't think the CCU looks like that anymore and the patients certainly are not in their 50s and 60s.
This is another example of an observational study, where the “observations” are what they are…but the interpretation esp among the chattering class on social media is what leads to the facepalms.
U-shaped associations are nothing new. Same exists for BMI (https://pubmed.ncbi.nlm.nih.gov/27146380/) because obviously, if you have an underlying condition that results in you wasting away….that’s not going to bode well for your survival. Doesn’t impugn the observation itself. But it does behoove you to understand what you’re observing, and also what you’re NOT observing.
Just as a person who, with intervention, goes from high BMI to low BMI is NOT comparable to someone who already starts with low BMI, so too that a person who goes from high cholesterol to low cholesterol with therapy is not the same as someone who starts with low cholesterol (for whatever reason).
Sadly, social media rewards the rage (and idiotic) takes. Just as there are flat-earthers and QAnon enthusiasts, there will be folks who eat up this and assorted other insanities.