I entirely agree with your assessment. As a biomedical scientist I measured thousands of serum cholesterol levels, and the low levels were very often in very sick people, often elderly and malnourished. I'm reminded of those claiming that excess acidity is the cause of all illness, whereas the truth is that acidosis, like a very low cholesterol, is the RESULT of illness, not the CAUSE.
I'm so delighted that you posted this. I've been so confused by people talking about acidifying and alkalinizing foods. The only good grain is millet. Etc. This has made no sense to me. I get it now, because of your clarity. Thank you.
You are more optimistic than me. We've got an anti science kook running for President in the USA who's polling in double figures and getting applauded by people like Musk, Maher, an ex Twitter CEO, ..etc
It is frightening that it is so easy to restore your faith. He used association of other U-curve graphs to disprove the association in an other u-curve graph. & had one half-baked argument that the reason why lower cholesterol has a high hazard is because people with disease have lower cholesterol by coincidence of being sick. So unfortunate that they have this really great and healthy cholesterol score, but still are dying from cancer and such. When dismissing the U-curve. What should the graph look like then? linear? Would you argue that it is best to have 0 cholesterol?
@@Joop3000 I think you miss the point, if certain diseases naturally drop your cholesterol then this becomes a symptom and the lower cholesterol shouldn’t be read as a cause. To have the correct correlation then those cofounders would need to be filtered out for it to be truly representative of whether or not the cholesterol level of a certain individual represents their risk of getting sick and not related to them already being sick
@@888jucu That is exactly what I got out of it. So, let me ask you then, if we ''filter'' (I don't think this is realistic and based in logic and evidence, but just for the sake of argument) those confounding factors out, what do we end up with then? A linear line going back to 0 cholesterol which is healthiest?
@@Joop3000 I don’t believe zero is realistic nor advisable for the general populace but probably a number significantly less than 230. That said for people with real advanced ASCVD then lowering cholesterol either with lifestyle, drugs or both has proven to be the best for their immediate health outcomes. For the general population what is the best cholesterol target seems to still be of some debate but high cholesterol certainly is well documented to be problematic regardless what certain carnivore advocates may preach. True carnivores in nature do not develop ASCVD so humans being “omnivore” means we are not fully developed to handle large quantities of saturated fats as can been seen by the fact our species develops ASCVD the more we are exposed to saturated fat be it through direct diet or internally produced by “excessive” carb intake etc
Sir, I am a soul who would get behind that except that your thought experiment is entirely invalid. You would not be arguing for people being overweight, hypertensive or pre-diabetic, you would be correcting what the normal healthy range for weight, blood pressure and blood sugar/a1c actually is based on promoting lowest mortality, taking the lowest part of U curves from massive data sets including some amount of rise on both sides to include most healthy people and variation. Based on U curves using the graphs in your video I might assign normal healthy cholesterol as 170-280, healthy BMI as 22-32, healthy blood pressure as 120-160, healthy A1C as 5.6-9. You wouldn't start trying to lower those values unless you were passing the upper end of that normal range and if you were on the lower end you might try to raise them. Cholesterol was frequently in the low to mid 200s in the 1970s and earlier when people had dramatically less diabetes, obesity, chronic inflammatory diseases, exactly where you would expect them naturally to be based on lowest mortality in the data you presented here. Cholesterol is a precursor of many hormones and LDL is a critical component of the immune system in neutralizing bacterial/fungal/viral toxins such as LPS; not having enough LDL can make smaller amounts of toxins fatal.
I see what you mean. we didn't have time to go through it all in this short video but there´s reams of randomized trial data showing a BMI in the obese range or very high BP or HbA1c raise risk of disease and death (same for high cholesterol). that's the trick, our scientific model has to reconcile all existing data
It is not the logic that gets us in trouble, it is the low probability premises. Doing the expensive research and data analysis for accurate premises is the hard work.
This is a good explanation and a reminder that correlation is not the same as causation. My 84 YO father died 3 months ago and we had just seen his lung doctor 4 days earlier. His weight was the lowest it had ever been as an adult and his blood pressure was also very low and his cholesterol thanks to taking vytorin was around 150 and frankly, better than mine. An uneducated person (ie. people who listen to "Bro" podcasts) might then conclude that low cholesterol, losing weight, and having low BP is unhealthy but in his case, when he WAS "healthy", he had very high blood pressure. He was in denial about it and I didn't find out about it until 15 years ago when he cut his finger and it would not stop bleeding and the urgent care center saw that his BP was 215 and they had to put him on an IV med to bring it down before letting us leave. After that, I became active in his care and got him a primary care doctor who managed his BP, cholesterol but the damage was done as 6 years later he needed a stent put in and 6 years after that, he had heart failure that thanks in part due to all the COVID lockdowns and in part due to the cardiologist not being aggressive with the water pills and/or wanting to do a valve replacement surgery, he had so much fluid build up in his lungs that by the time they admitted him to the hospital, the damage was done to his lungs and so at that point, surgery was completely off the table and he pretty much had to suffer for 2 1/2 years with home oxygen and being homebound and mostly just getting comfort care which led to him losing weight and his heart getting weaker. If I had a time machine, I would have made sure he got to his doctor sooner.
Interesting point in your video is that if your cholesterol is lower than expected, while you never tried to actively lower it,.... it means you probably have a disease you may not even be aware of. I know some people like that, though they are aware of the diseases. But their doctors tell them it's great. They don't tell them that their cholesterol is low because of their other diseases.
Many people for genetic reasons have low cholesterol and that is a healthy marker. It's when your cholesterol declines over time without a reason that it is cause for concern.
Great video! You see the same sort of curve for level of alcohol use and mortality, where it appears that people who don't drink at all have higher mortality. However, when you control for why a significant proportion of those people aren't drinking (due to health problems), the relationship becomes linear, with healthy people who don't drink having the lowest risk of mortality.
Excellently presented and very interesting! All I can do is repeat the famous words of Dr. John McDougall that "People Love to hear good things about their bad habits", and the internet hugely rewards those claims with tons of hits. Keep doing what you are doing!
McDougall?? rofl, A diet of white rice, fruit, fruit juice and table sugar -- cures diabetes, heart disease, arthritis, obesity, and just about everything, is the claim of Mcdougall
Unfortunately true. I've taken away some decent advice from them, but the total lack of regard for the data made me unsub from both about a year ago. I despise statins and refuse to touch one ever again, but the claims about how they "help no one and only cause harm" are too extreme. It's also absurd to claim a carnivore diet is healthier than a vegan one when fiber intake is directly associated with mortality. (And I friggin love meat.)
@@heathensein6582 layne norton has a doctorate in biochemistry the cattlemens association paid for his degree, he eats meat and has no hangups about it he clears says that the mandellian randomized trials showed high cholesterol is a independent marker for heart disease, even when low triglycerides were accounted for and high hdl it didn't matter so whose ignoring who
@@heathensein6582well, if you have followed Gil you know what he says: it is a marker, but not always associated with higher risk. It often correlates with ApoB which is much much better associated with risk.
@@BasedChadmanGo volunteer at an animal sanctuary and get to know some pigs, chickens and cows. Hang out with them and pet them. You won't love meat anymore.
Thank you for what you do. There’s so much misinformation about nutrition floating around on RUclips. It’s a shame cause people are trying to better their health but getting misinformed by non experts or outright grifters. We need more professionals to do this kind of thing. 👍
The issue I have with this is that is doesn’t seem to count the biggest killer, coronary heart disease, which is ‘typically’ associated with high cholesterol. Surely that should have had a huge impact on the the mortality rate but this doesn’t seem to generate even a blip on that data? That also should have a much higher impact in the data as the death from heart disease would generally be sudden and therefore the cholesterol state would be at its peak.
I saw this mentioned recently by a couple of other youtube "doctors" as a reason why you don't need to worry about cholesterol ... glad you made this video to clear that up, thank you!
I admit i was sucked in by dr berg and his chiropractic cronies for a while too, until the likes of gil, brad stanfield, and lately physionic, brought me back from the dark side. Watching dr berg et al now is almost cringeworthy.
@@James-zr1lu Right, especially considering the vast amount of evidence showing the positive effects of lowering LDL. One can't claim to be scientific and just ignore dozens/hundreds of other quality studies.
Thank you so much for empowering your audience and letting us decide on what to do based on the science. It's such a refreshing change from RUclipsrs that use click bait, criticise a persons character that they don't agree with and let their emotions get involved in their efforts to ultimately deliver an otherwise well intentioned message. Great work and thank you again.
This video would be helped by showing graphs from some of the better, double-blind studies that factor out the people with illness and show the curves where they "should" be. I'm skeptical without seeing those graphs. No dog in this fight, just want to actually see the better evidence.
I can't point to the exact video, but I think he shows one where he puts dot plots of all the studies on a graph and it shows pretty clearly the affect of LDL cholesterol on mortality. If you have time to check out some of his older videos on cholesterol, you will run into it.
The links to the studies are all in the description. The Korean cholestrol study is exceptionally thorough and HUGE. Read the details of it and see. (first link I believe)
People love good news about their bad habits. Probably the most generally accurate statement I've heard in the health space. I imagine it could be credited for the "cholesterol skeptic" movement.
Look at the level of cholesterol and mental illness and suicide. Under 160 seems to be a problem on this side. Despite these reasonable suppositions, many studies over decades have (for the most part) consistently linked low total serum cholesterol with suicide, violence, and depression. Total cholesterol levels below 160, and especially below 130, correlate with a higher risk of mental problems.
The curves would seem to suggest that cholesterol of 240 is just fine... as long as it's not an upward trend. And BMI of 28 is just fine, even if it's considered overweight. And systolic blood pressure of 140 is just fine. And even that an A1C of 7 is just fine! And that the danger is when these values trend upward over time, which unfortunately they tend to do, into the frank danger zones. I appreciate Dr. Gil's point that the lower end values correspond with chronic disease, and that's different from "higher is healthier;" yet it does seem to me that if strictly following the data, a *little* bit higher is actually, truly healthier! Also, some of these things are not like the others. I've got low (healthy range) blood pressure, 21 BMI, low (healthy range) blood glucose from my low carb, high fat way of eating. I don't have inflammation problems, aches and pains, energy deficits like so many other 50 year olds do, and I'm simply not concerned about my cholesterol. I've got a low resting pulse rate, even, when I tested it at the pharmacy kiosk along with my blood pressure recently. I searched it up and it suggested it could be because a person is old, or an elite athlete. I'm not quite either, so who knows! I feel great and I don't think worrying is going to improve my health OR my disposition.
For those that are worried about high cholesterol, it might be good to get a CAC score to see if there's any blockages. There is also Life Line screening that will do the same thing if you don't want to go to the doctors to get a referral for CAC. I will be doing the Life Line screening since I have high cholesterol.
A CAC score won't tell you about blockages caused by soft plaque. It will only reveal old, calcified plaque. Your arteries can be nearly fully clogged with a low CAC score.
CAC only detects calcium. Not all of the build up will be calcified, may work in very old people or people who have been developing cholesterol build-up from a young age and gave it years to calcify
Great video! Statins helped me but I stopped after 3 months. From there, diet and walking. Not so much diet as a lifestyle change. Meat was causing belly pain where my gallbladder area is and in my colon. Screw anymore surgeries, I went vegetarian 🥗. Best decision of my life.
I've watched this video three times and read a lot of the comments, and I"m still not persuaded that optimums on cholesterol aren't actually the high levels. Remove the people with cancers and other non-cardiovascular diseases, and we should see a linear effect, with those at relatively high levels still near the optimum. The comparison to the BMI, BP, and HbA1c are not persuasive as two of them are not quadratic, and the other shows a tiny risk change across a wide range of BMIs.
If you have untreated hyperlipidemia, you can have all of those markers (total cholesterol, LDL-C, triglyceride) dropping to nice levels during an acute infection, things like tooth infection, kidney infection etc.
"I wanted to take a moment to express my appreciation for this fantastic RUclips channel and the informative content that it provides. This topic is incredibly insightful and well-presented. Thank you for taking the time to share this valuable information with your viewers."
Oh boy does this answer a question I formed yesterday after watching one of the "Doctors" vids, where he put up a chart that shocked me! It showed cholesterol number ranges and associated them with good, ok, and bad, colored in Green, Yellow, and Red. This was a very odd chart to me because the "good" range was in fact from about 200-260, ok from 260 to about 340, and over 340 RED. He said however even 350 could be ok for some people! More surprising was the ranges below 200. That started yellow, and when it dropped to under about 100, there was a BIG RED. And yes, he emphasized that was the major risk of death area. I've just stopped watching any of these vids now, but now I know where their data is coming from. Thanks.
Wow, Gil, this was absolutely fantastic. You really put my mind at ease. Thank you so much for this clear, concise, reasonable, rational, scientifically correct explanation. You are doing so much good in this world, and you can tell your mother I said so. (I'm a mom, too, so my guess is she is super proud of you.)
Just to confuse matters,I remember reading that a small number of people have an extremely negative reaction,in terms of greatly increased risk of suicide,to having their cholesterol lowered.I think I read it in 'Genome,' by Matt Ridley.
Makes a video with such bold claims and fails to mention the study's limitations: "First, the use of lipid-lowering medication was unaccounted for. The risk associated with high cholesterol might have been underestimated. Additionally, this study could not determine whether statin-induced low cholesterol increases mortality." "Second, other lipid measures, such as low-density lipoprotein and high-density lipoprotein cholesterol levels, were unavailable. Recent dyslipidemia management guidelines are more closely focused on these sub-fractions of cholesterol, so the direct application of our findings to individual patient care might be somewhat limited."
Gil, Can you please expound on your understanding of the physiologic mechanism by which the cholesterol molecule gets itself positioned beneath the endothelial layer of the systemic artery? In other words, is the endothelial cell actively, or passively, transporting it from the LDL in the bloodstream, through the cell and then expelling it on the other side, or is the cholesterol molecule somehow disrupting the tight junctions between the endothelium and working their way back behind them? If so, how? And if so, why does this never happen in veins and almost never happen in the pulmonary arteries?
In order to impact the curve in such a manner, the group of sick people must be really large. The real question is whether excluding the sick people will result in a different curve.
That's the issue I have. If low cholesterol reduces the risk of death, then the healthy people with low cholesterol should go some way to balance out this curve. Maybe there are next to no healthy people with low cholesterol!?
This U curve reminds me of the J curve long associated with alcohol consumption. I.e. that one or two drinks per day was associated with lower cause of death than total abstinence from alcohol. Until further research revealed that many studies had included people who abstained from alcohol because they were taking drugs that could not be used with alcohol. Drugs to control serious, often fatal diseases. And the studies also included former alcoholics who, due to liver damage, also have a lower life expectancy. Newer studies that only included people who didn’t drink alcohol because they didn’t want to, e.g. religious or dietary reasons, showed the straight line adverse side effects response to dose levels in alcohol consumption that one would expect from any drug.
_"A recent article published in The Lancet which is the largest meta analysis to date has a very comprehensive overview of risks associated with moderate to high-level drinking. The J-curve only exists for very few hand-picked risks"_ The J curve studies are heavily biased to defend their consumption of alcohol. Either way, that completely ignores the fact that usually the moderate drinkers are wealthier ( aka better health care ) and alcohol gives addiction which leads to heavy drinking ( no, you are not immune, especially if something bad happens to you, it will be easier for you to drown in alcohol if you already drunk some before ).
The reason why those curves are welcome on social media and why people call themselves cholesterol skeptic is that it gives them license to finally do what they want to do. Most people wand to eat pizza, with a ton of cheese, dairy ice cream, a lot of sugar, bacon and all kind of meat, so if they encounter some "information" that tells them a low cholesterol is dangerous this is the good news they were looking for about their bad habits and will feel validated. People are addicted to various combinations of fat, sugar and animal protein and are on the look out for excuses to keep eating them.
Interesting ... I am wondering about the size of the risk increase at the lower end. Your argument is interesting, but is it enough to explain the size of the effect. In your opinion does this mean that a) there is a lot more undiagnosed illness than people are aware of, and that is sitting there as a large pool of potential problems representing a large proportion of the population . This is the moderate risk, high population option. b) That the risks of those in this position are very high, so that a limited number of cases are going to be driving the curve up steeply because the risk of mortality is very high. This is the high risk, moderate population option. Or c) something else ?
You nailed it. There is no way it would be that steep... also... what if you have low cholesterol and then get that disease? etc. etc. This assosication to other graphs doesn't prove anything.
Look up the latest on preserving the mevalonate pathway when glucose is restricted by compartmentalization of the HMG-CoA reductase. This is why ketosis increases cholesterol and LDL but without the glucose oxidation ROS.
Just when I was about to raise the honest question, "But aren't epidemiological studies usually conducted at large enough population sizes that people with unsuspected diseases should not bias the results?", the video goes on to explain that studies with larger populations do tend to wash these anomalies out
Do we have any idea if this graph has been normalised for those underlying disease cofounders? If its not normalised then its poorly designed or atleast not designed well for cholesterol levels vs health risk. If those cofounders have been removed then the results would require further scrutiny as the answers given in this talk wouldn’t hold
If you're wondering why so many people have difficulties with the idea that cholesterol should be as low as possible,... you have to look at the people that promote lowering cholesterol. You can't really have a conversation with them. If you ask questions, you're either ignored or told you're stupid. You don't do that much, but some others do. And it's a red flag if someone doesn't even want to answer questions.
When it comes to weight, one of the reasons, the death rate is higher with lower, BMIs is because smokers tend to be leaner, and they tend to die sooner. Also, people who are overweight, sometimes are able to live longer with diseases that cause weight loss.
I had very high cholesterol at one time along with the whole lousy package of type 2 diabetes and very high triglycerides etc. I was diagnosed in 1998 as a result of a required pre-employment physical. I'm coming up on my 25 year diaversary and haven't spent a night in the hospital yet. I certainly get frustrated with all the different gurus telling people completely different things about what is and isn't worth focusing on. The first doctor I saw in 1998 committed suicide about 4 years later. He was my age, married with young kids and went to Catholic high school. Very sad. I still think about it/him. His daughter is now a nurse.
Thanks for making this. A friend of mine recently sent me an article arguing that people with high cholesterol live longer 🤦🏻♂️. I read the article and it referred to the u-curve and the study was specifically looking at people over 60 which I think would skew these numbers even more. I shared the link to this video with him 💕
Thank you! I'm so glad I found you, because you are able to explain to lay people. And you illustrate how important it is to be discerning about nutrition/health info that comes out, and not just swallow everyone/everything blindly. I appreciate you!
"Reverse causality has been suggested as an explanation of higher mortality associated with low cholesterol levels. However, a long term follow-up study in a Japanese-American population showed that individuals with low cholesterol levels maintained over a 20-year period had the worst all-cause mortality, and concluded that reverse causality was unlikely to account for the higher mortality associated with low cholesterol entirely"
right, that's referring to the Honolulu cohort, their effect lost significance when adjusted for frailty measures (so its consistent with a disease-caused cholesterol lowering) cancer can reduce cholesterol level many years before it's diagnosed, so the best way to tease apart these effects is to look at randomized designs
How much of this data was done on populations of those practicing low carb diets or those that remained in ketosis for a considerable length of time? The problem is that when I follow a anything but high fat, red meat heavy diet, I am practically bedridden and can not hold down a job. If I eat high fat/low carb/lots of red meat I have my life back. I have to choose between preventing a heart attack and have no quality of life, or have a true quality of life and risk a heart attack. I take these studies and cholesterol seriously, but it seems like diet of the test population isn’t a recorded factor.
hi. obviously there's some severe intolerance issue (unrelated to cholesterol or the topic of this video). this is something that has to be investigated. are the symptoms GI-centered? have your doctors ruled out things like IBD, IBS? celiac? those are just some initial ideas, it will depend on the symptoms. clearly there's an underlying condition and/or imbalance that needs to be identified/diagnosed
I think the U curve is pretty real, but it is shifted to the right in small studies, and the larger and better the study, this U curve is shifted to the left, and the valley begins to conform to the values we expect.
@@Dan16673 no link, thats why i said "i think". I could be wrong, but it is kinda obvious. If you have zero cholesterol, you're also 💀. Too much or too less of something is not great. There will aways be a balance point. Except for toxins of course, in that case the lower the better.
You nailed it, Dr Carvalho! Thanks for going the extra mile to dig into the data and explain it so clearly. I wonder if the numbers of people with a given level of a blood marker factors into it those graphs, as well. For example: fewer people have an A1c under 5 (than 5.5) so perhaps a larger proportion have subclinical disease?
A bit like the French paradox. The French eat more saturated fat than any other country in Europe, they also smoke more than most, yet they have the lowest incidence of heart disease.
Have you seen their portion sizes? they eat less total fat than us, despite some of their food being quite fatty. They also don't snack as much, eat processed food as much and most live in cities and do a lot of walking.
Great explanation, thanks! I've seen people saying on social media that you need to eat plenty of dietary cholesterol to maintain high testosterone levels, even recommending pure butter for gains. Others say pretty much the opposite, that fatty foods are associated with lower testosterone. Could you please clarify?
All sexual hormones in both male and female are made from cholesterol, taken it from food is essential for a normal level. Just look at statistics on the age women get to menopause, 30 years ago it was 50+, today when we eat a lot less cholesterol together with other factors of course, many women see signs of menopause at early '40. It's that just a coincidence?
Wow, thank you for this explanation. I'm particularly and continually confused by diet guidelines these days and health guidelines which are contradictory at best over the last 20 years. I don't know what to eat. I don't know what to think about recent research. It's very difficult to navigate the healthy lifestyle and get it right.
Very true! They contradict each other daily almost . I think eating healthy fruit and veg and occasional meat and fish is the way forward. Moderation like our ancestors ate .
excellent - I was also wondering the correct interpretation of the cholesterol U-curve presented in other vidéos. As a layman, I am not equipped with the knowledge to put this information in the right context. What's amazes me is that epidemiologist did not put the correct interpretation either. Thank you for this information.
Dr. Walter Willett was recently on Simon Hill's podcast and said there's substantial evidence (including mendelian randomization) that extremely low blood cholesterol is associated with increased risk of hemorrhagic stroke. Are you familiar with any of that evidence?
Joel Fuhrman mentioned a study where high hemorrhagic stroke with vegans is linked to higher sodium intake. Apparently, meat and dairy has protective effect against hemorrhagic stroke even though those increase the risk of ischemic stroke. So as long as sodium content is low, it should be fine.
Excellent explanation, thank you. I've heard this applied to alcohol consumption. People who don't drink are more likely to die than people who drink moderately. Turns out a large number of the teetotalers gave up drinking because they were already sick, very elderly or alcoholics with liver damage.
I considered myself a moderate drinker, and then I started to experience A-fib episodes. Then, one day, I had 2 glasses of wine, which put me into A-fib for a week. I later learned from a cardiologist that alcohol can kill the hearts electrical pathways and eventually causing A-fib to be permanent. I have stopped drinking 🍸 I am on a low dose of Metropolol 25mg and have not experienced any further episodes, while I have begun reversing my heart disease based on my CAC going from 660 to 458.
I remember reading a journal article some 15 or so years ago, wherein a hospital-based physician remarked upon the phenomenon that in older people all the standard measures of good health - weight, blood pressure, cholesterol etc - were reversed. In younger people, low cholesterol, weight etc predicted future good health but in older people they tended to predict increased mortality and morbidity risk. darned if I can find it now though.
More to do with decreased grelin, so weight loss happens, and falls becomes the biggest killer of old people, because they don't have the fat as a buffer for their organs.
Did it control for cancer deaths? Because blood pressure will improve along with the weight loss while their health rapidly declines. My bad. I hadn't watched the video fully when I wrote the comment.
Weight is a poor metric. A lean person with a decent amount of muscle mass can be labeled as obese on a BMI chart. It's not that the elderly are better off being fat, they need that muscle as they age. Not only does that muscle support their bones but bone is also 50% protein, so if they've managed to maintain muscle density they're more likely to have maintained bone density as well.
@@Engrave.Danger True but things like cancer, malnutrition, poor dentition, heart failure and diabetes etc cause weight loss.and those things are more common in the elderly. Since it is now 'normal' to be overweight, it may be that in the elderly low weight is a marker for various diseases and thus for mortality risk.
I have a PCSK-9 mutation that gives me extremely low blood cholesterol. My TOTAL cholesterol has never been higher than about 131, and it's usually around 100. (I am on a statin now, but ironically, the day I went to the hospital with what turned out to be a heart attack, my total cholesterol was 91, and that was before I started the statin.)
Highly active 56yo, 6ft, 158 lbs. BP is 109/72, resting HR, 54. My 14 day avg. glucose is 83mg/ml and total Chol 557, Trigs 104, HDL 52, LDL 461. Should I be concerned about my high cholesterol or LDL?
You should ask your primary care provider. Mine is half that but my primary care provider told me that it wasn't worrisome because my BP was excellent. But if it had been over 500 I'm not sure what he would've said. Just ask them on your next visit.
Same can be said for alcohol use; once the people who are abstainers due to negative health conditions, including alcoholism are excluded, and lifelong patterns of alcohol abstinence are segregated, the u in the u-shape goes away, and the relationship between alcohol use and mortality/morbidity is linear--the more you drink, the worse it is for you.
@@chuckleezodiac24 yes, but if we stay healthy for longer, that mortality can be postponed. At least that's the theory. The art is to actually achieve that.
This is the 3rd year of me binge watching RUclips health videos. Frankly, other than staying away from processed food, alcohol, sugar, and avoid overeating, nothing else is close to being certain. Diet wise, it appears that an omnivore diet is the best hedge against all this uncertainty.
can't agree more. i'd throw though in this decent and well thought mixture some daily vigorous walking and that almighty master of all pills out there, a restful 7h sleep. life is good and tasty!
Ok I understand the explanation of the left side of the curve, thanks. What is causing the bottom of the curve to show higher numbers related to lower mortality? ie 250 versus 200 as the lowest mortality point? Also could there be a point where very low cholesterol does negatively impact the body since the body does need some to function?
The body makes its own. If your levels are too low to properly function then something else is likely the issue. Studies are showing links between low cholesterol and a few diseases but it appears as the diseases that caused the low cholesterol rather than low cholesterol causing the disease. Trials where they have artificially lowered cholesterol to extremely low levels have not shown any negative effects though these trials have been short so may or may not be lomg term issues with it. So far the evidence points to low cholesterol not being an issue itself and is just a marker for other issues but more long term study is needed to confirm absolutely.
Same question about the bottom of the curve. After watching the video I can now explain/understand the left side of the curve, but still puzzled about explanation of the bottom. Also remember these tests are measuring blood cholesterol. Every cell in our body also has the ability to make its own cholesterol.
People with the higher cholesterols are probably dying to a vascular type disease like stroke or heart disease, while the lower ones may be dying to the cholesterol lowering one like cancer and what not.
I wouldn't dismiss you at all. On October 2018 I suffered heart failure at 44 years of age. Shortly after returning home my PCP sent my latest lab results. My cholesterol was 10, yes I said 10. She said she never seen anybody that Low. I was given a Statin a year before heart failure because they said I was a type 2 diabetic. More on the diabeties part another time.
This is interesting. I've always wondered if there is a cholesterol level that is too low. My husband is on atorvastatin and his level is 122. When he started it years ago his cholesterol was in the 240 range. I'm thinking of cutting his atorvastatin dosage because that level seems quite low to me.
That level seems healthy to me. For one thing, there is no evidence that intensive cholesterol lowering is dangerous. Quite the opposite ... studies show that achieving very low levels reduces the rate of major adverse cardiovascular events. Brown and Goldstein won a Nobel Prize for their work on cholesterol. They conclude that "plasma levels of LDL-cholesterol in the range of 25-60 mg/dl (total plasma cholesterol of 110 to 150 mg/dl) might indeed be physiologic for human beings. First, in other mammalian species that do not develop atherosclerosis, the plasma LDL-cholesterol level is generally less than 80 mg/dl (Fig. 16 and ref. 120). In these animals the affinity of the LDL receptor for their own LDL is roughly the same as the affinity of the human LDL receptor for human LDL, implying that these species are designed by evolution to have similar plasma LDL levels (9,119). Second, the LDL level in newborn humans is approximately 30 mg/dl (121), well within the range that seems to be appropriate for receptor binding (Fig. 16). Third, when humans are raised on a low fat diet, the plasma LDL-cholesterol tends to stay in the range of 50 to 80 mg/dl. " www.science.org/doi/10.1126/science.3513311?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
It not all about one number on one test. Must look at big picture and must review his age, race, activity levels, diet and about 19 other blood markers to establish present status. Plus helps to know CAC score or CT scan.
@@DrAJ_LatinAmerica Thank you for your reply. My husband is high risk. Balloon angioplasty 20 years ago, heart attack with stent 6 years ago. One artery still has blockage, but I think his mind/memory has been affected (normal scan for age) and he is bursting out with fast growing skin cancers. He's also a sugar addict. He is 84 years old, though and very stubborn. He totally ignores his health. I need to make him a cardiology appointment soon.
@@jjbud3124 definitely some serious issues. At his age, he needs to do what make him happy. Definitely need to be working very closely with your doctor(s). Always Keep in mind the internet is just very rough broad strokes of information. Not medical advice regarding your husband specifically. All things are case by case, person by person. No one set diet or set of rules applies to everyone. Millions will say people don't need to take a statin medication. However millions are not your husband. Again your doctor has to look at all evidence AND has to base the treatment on the specific wishes of your husband and an agreement to follow treatment. I'm always surprised, but there are many (millions) who refuse to stop drinking, smoking, over eating, eating junk foods,..... Freedom is a double edge sword. But of luck, keep trying and God bless 🙏💪
I would have thought the rise in mortality with lower cholesterol would be partially due to more elderly people taking cholesterol lowering medications but dying from other age-related deaths.
I thought that the association between low cholesterol and increased mortality in older people was first observed long before statin drugs were available.
Yes, in a previous video he mentioned that as well. Good point. I think it could be part of the reason. My Mom was so frail when she passed and she hardly would eat anything so I bet her cholesterol was very low as a result.
Not sure these other partgicular U curves make great examples though. Because yes you CAN weigh too little. You CAN have an A1C thats too low if you have too little glucose, etc.
Great explanation as to why low cholesterol does not increase risk of death. However, what I don’t understand is why on the u curves eg blood pressure, blood glucose etc the death risk appears to at lease be a constant as higher levels than the medically advised levels eg 5.7 blood glucose and 120/80 BP. Is there a good explanation for this as well?
Thanks for that! Just what I needed. Here's me worrying about a 142 blood pressure reading and 244 total cholesterol. I'll be getting a full medical check up next Friday. Fascinating video and it's given me a new way how to view my current health.
Yes, i understand why it's a u-curve with higher mortality at lower values. But i'm still puzzled that the minimum (lowest mortality) of all those curves are at unexpected high values (of cholesterol, bloodpressure, hba1c, BMI, etc.). I would expect the minimum of these curves to be a little further to the left, at levels closer to the optimal (lower) healthy values of these parameters.
It reflects more where the population is. If you're outside of the norm you are sick ... or you have a healthier lifestyle. And being sick is a strong negative effect. So it rises the mortality more even if there were as many people with a healthier lifestyle (sickness has more influence on mortality better than healthy lifestyle). And on top of that (at least around the region where I live), it does not seem to be the case that people with a healthier lifestyle outnumber sick people.
@@tofu-munchingCoalition.ofChaos Yes, something like "it reflects more where the populaton is" was my first guess as well. But based on the "Cholesterol Facts" of the CDC (Center for Desease Control and Prevention) : [...] Percent of adults aged 20 and over with high serum total cholesterol (greater than or equal to 240 mg/dL): 11.5% (2015-2018) Mean serum total cholesterol level for adults aged 20 and over: 191 m.g/dL (2015-2018) [...] So 88,5% of the US population is below(!) 240 mg/dL with an overall average of 191 mg/dL. But the Minimum of the Mortality on the Cholesterol Chart is around 230 mg/dL. And those numbers doesn't really fit with the first guess "it reflects more where the populaton is" and "If you're outside of the norm you are sick".
@@cruisebaer This is data from South Korea. But essentially your argument seems to hold. The average TC is ≈200 [mg/dl] and the empirical SD is ≈50. For simplicity (to get a feeling where the argument is and so that I don't have to look up many numbers from the paper) let's just assume TC is normally distributed for not sick people. Their normal TC for people is ≈20% of the people is 250 or higher. If they get sick and their TC drops let's say 20%, then they overlap with the mode of TC ≈200. So sick people's abnormal range and healthy people's normal range overlap. In general if you follow the "if you're outside the norm you're sick", you still expect at the mean to have a lot of sick people with abnormal values (abnormal to their natural value). This is true as long as the SD of the marker is not drastically below the typical deviation of the marker for sick people.
Had a 220 reading and the health professionals advised me I should eat more fruits and vegetables. I told her that if I ate more fruits and vegetables I would need an import/export license. BTW, the rest of my family, who eat the standard American diet have cholesterol readings of between 300 and 400 (unmedicated).
at those levels, I´d suspect a genetic susceptibility. FH or maybe cholesterol hyperabsorption. one idea is to try a diet with vs without eggs for a couple weeks and see how it affects lipids. see our video on dietary cholesterol for more detail
The cholesterol paradox refers to a phenomenon observed in certain studies that challenges the traditional understanding of the relationship between cholesterol and cardiovascular disease (CVD). Historically, high levels of low-density lipoprotein cholesterol (LDL-C) have been considered a major risk factor for CVD, while high levels of high-density lipoprotein cholesterol (HDL-C) have been seen as protective. However, the cholesterol paradox arises when researchers observe that some individuals with low LDL-C levels still develop CVD, while others with high LDL-C levels do not. Similarly, some individuals with high HDL-C levels still experience CVD events, while those with low HDL-C levels remain unaffected. The cholesterol paradox suggests that there may be other factors beyond just cholesterol levels that contribute to CVD. These factors could include inflammation, oxidative stress, genetic predisposition, the size and density of cholesterol particles, and the overall balance of different lipoprotein subclasses. Several hypotheses have been proposed to explain the cholesterol paradox. One theory is that LDL particle size and density play a significant role. Smaller, denser LDL particles are thought to be more atherogenic (contributing to the development of atherosclerosis) than larger, more buoyant particles, even at similar cholesterol levels. Other factors such as inflammation and oxidative stress can influence the progression of atherosclerosis and CVD independently of cholesterol levels. These factors can damage blood vessels and promote plaque formation, leading to CVD events. The cholesterol paradox highlights the complexity of the relationship between cholesterol and CVD. While cholesterol levels remain an essential consideration in assessing cardiovascular risk, they are not the sole determinant. Other factors, including lifestyle, genetics, and inflammation, contribute significantly to an individual's overall risk profile for CVD.
![Niacin (Vitamin B3): Flushing Away Heart Disease. [4 Studies]](http://i.ytimg.com/vi/N17cmKCVxcw/mqdefault.jpg)
I entirely agree with your assessment. As a biomedical scientist I measured thousands of serum cholesterol levels, and the low levels were very often in very sick people, often elderly and malnourished. I'm reminded of those claiming that excess acidity is the cause of all illness, whereas the truth is that acidosis, like a very low cholesterol, is the RESULT of illness, not the CAUSE.
It can be both just like high cholesterol can be due to diet/genetics or disease
I'm so delighted that you posted this. I've been so confused by people talking about acidifying and alkalinizing foods. The only good grain is millet. Etc. This has made no sense to me. I get it now, because of your clarity. Thank you.
Dr. Atkins had a heart attack and a history of heart disease and he was overweight.
Epic Gil. Because of science communicators like you, faith is being restored in the clinical guidelines and your viewers are leading healthier lives
You are more optimistic than me. We've got an anti science kook running for President in the USA who's polling in double figures and getting applauded by people like Musk, Maher, an ex Twitter CEO, ..etc
It is frightening that it is so easy to restore your faith. He used association of other U-curve graphs to disprove the association in an other u-curve graph. & had one half-baked argument that the reason why lower cholesterol has a high hazard is because people with disease have lower cholesterol by coincidence of being sick. So unfortunate that they have this really great and healthy cholesterol score, but still are dying from cancer and such.
When dismissing the U-curve. What should the graph look like then? linear? Would you argue that it is best to have 0 cholesterol?
@@Joop3000 I think you miss the point, if certain diseases naturally drop your cholesterol then this becomes a symptom and the lower cholesterol shouldn’t be read as a cause. To have the correct correlation then those cofounders would need to be filtered out for it to be truly representative of whether or not the cholesterol level of a certain individual represents their risk of getting sick and not related to them already being sick
@@888jucu That is exactly what I got out of it. So, let me ask you then, if we ''filter'' (I don't think this is realistic and based in logic and evidence, but just for the sake of argument) those confounding factors out, what do we end up with then? A linear line going back to 0 cholesterol which is healthiest?
@@Joop3000 I don’t believe zero is realistic nor advisable for the general populace but probably a number significantly less than 230. That said for people with real advanced ASCVD then lowering cholesterol either with lifestyle, drugs or both has proven to be the best for their immediate health outcomes. For the general population what is the best cholesterol target seems to still be of some debate but high cholesterol certainly is well documented to be problematic regardless what certain carnivore advocates may preach. True carnivores in nature do not develop ASCVD so humans being “omnivore” means we are not fully developed to handle large quantities of saturated fats as can been seen by the fact our species develops ASCVD the more we are exposed to saturated fat be it through direct diet or internally produced by “excessive” carb intake etc
I find it chilling knowing that your videos NOW will probably wind up saving my life when I turn 60.
Sir, I am a soul who would get behind that except that your thought experiment is entirely invalid. You would not be arguing for people being overweight, hypertensive or pre-diabetic, you would be correcting what the normal healthy range for weight, blood pressure and blood sugar/a1c actually is based on promoting lowest mortality, taking the lowest part of U curves from massive data sets including some amount of rise on both sides to include most healthy people and variation.
Based on U curves using the graphs in your video I might assign normal healthy cholesterol as 170-280, healthy BMI as 22-32, healthy blood pressure as 120-160, healthy A1C as 5.6-9. You wouldn't start trying to lower those values unless you were passing the upper end of that normal range and if you were on the lower end you might try to raise them.
Cholesterol was frequently in the low to mid 200s in the 1970s and earlier when people had dramatically less diabetes, obesity, chronic inflammatory diseases, exactly where you would expect them naturally to be based on lowest mortality in the data you presented here. Cholesterol is a precursor of many hormones and LDL is a critical component of the immune system in neutralizing bacterial/fungal/viral toxins such as LPS; not having enough LDL can make smaller amounts of toxins fatal.
I see what you mean. we didn't have time to go through it all in this short video but there´s reams of randomized trial data showing a BMI in the obese range or very high BP or HbA1c raise risk of disease and death (same for high cholesterol). that's the trick, our scientific model has to reconcile all existing data
I just came across your channel. This is cool. Your logic is flawless
He must be Vulcan 😂.
It is not the logic that gets us in trouble, it is the low probability premises. Doing the expensive research and data analysis for accurate premises is the hard work.
As a physician for 35 years, this presentation is eye opening. Medical disease prevention criteria now seem backwards!
This is a good explanation and a reminder that correlation is not the same as causation. My 84 YO father died 3 months ago and we had just seen his lung doctor 4 days earlier. His weight was the lowest it had ever been as an adult and his blood pressure was also very low and his cholesterol thanks to taking vytorin was around 150 and frankly, better than mine. An uneducated person (ie. people who listen to "Bro" podcasts) might then conclude that low cholesterol, losing weight, and having low BP is unhealthy but in his case, when he WAS "healthy", he had very high blood pressure. He was in denial about it and I didn't find out about it until 15 years ago when he cut his finger and it would not stop bleeding and the urgent care center saw that his BP was 215 and they had to put him on an IV med to bring it down before letting us leave. After that, I became active in his care and got him a primary care doctor who managed his BP, cholesterol but the damage was done as 6 years later he needed a stent put in and 6 years after that, he had heart failure that thanks in part due to all the COVID lockdowns and in part due to the cardiologist not being aggressive with the water pills and/or wanting to do a valve replacement surgery, he had so much fluid build up in his lungs that by the time they admitted him to the hospital, the damage was done to his lungs and so at that point, surgery was completely off the table and he pretty much had to suffer for 2 1/2 years with home oxygen and being homebound and mostly just getting comfort care which led to him losing weight and his heart getting weaker. If I had a time machine, I would have made sure he got to his doctor sooner.
Probably ate many carbs
Interesting point in your video is that if your cholesterol is lower than expected, while you never tried to actively lower it,.... it means you probably have a disease you may not even be aware of.
I know some people like that, though they are aware of the diseases. But their doctors tell them it's great. They don't tell them that their cholesterol is low because of their other diseases.
Many people for genetic reasons have low cholesterol and that is a healthy marker. It's when your cholesterol declines over time without a reason that it is cause for concern.
Great video! You see the same sort of curve for level of alcohol use and mortality, where it appears that people who don't drink at all have higher mortality. However, when you control for why a significant proportion of those people aren't drinking (due to health problems), the relationship becomes linear, with healthy people who don't drink having the lowest risk of mortality.
That's good information to share thank you
Excellently presented and very interesting! All I can do is repeat the famous words of Dr. John McDougall that "People Love to hear good things about their bad habits", and the internet hugely rewards those claims with tons of hits. Keep doing what you are doing!
McDougall?? rofl, A diet of white rice, fruit, fruit juice and table sugar -- cures diabetes, heart disease, arthritis, obesity, and just about everything, is the claim of Mcdougall
Berg and Ekberg and consorts will completely ignore and discard this explanation.
Just as you people do with high cholesterol
Unfortunately true. I've taken away some decent advice from them, but the total lack of regard for the data made me unsub from both about a year ago.
I despise statins and refuse to touch one ever again, but the claims about how they "help no one and only cause harm" are too extreme.
It's also absurd to claim a carnivore diet is healthier than a vegan one when fiber intake is directly associated with mortality. (And I friggin love meat.)
@@heathensein6582 layne norton has a doctorate in biochemistry the cattlemens association paid for his degree, he eats meat and has no hangups about it he clears says that the mandellian randomized trials showed high cholesterol is a independent marker for heart disease, even when low triglycerides were accounted for and high hdl it didn't matter so whose ignoring who
@@heathensein6582well, if you have followed Gil you know what he says: it is a marker, but not always associated with higher risk. It often correlates with ApoB which is much much better associated with risk.
@@BasedChadmanGo volunteer at an animal sanctuary and get to know some pigs, chickens and cows. Hang out with them and pet them. You won't love meat anymore.
Thank you for what you do. There’s so much misinformation about nutrition floating around on RUclips. It’s a shame cause people are trying to better their health but getting misinformed by non experts or outright grifters. We need more professionals to do this kind of thing. 👍
Outright grifters is very accurate. Won't mention any names though!
The issue I have with this is that is doesn’t seem to count the biggest killer, coronary heart disease, which is ‘typically’ associated with high cholesterol. Surely that should have had a huge impact on the the mortality rate but this doesn’t seem to generate even a blip on that data? That also should have a much higher impact in the data as the death from heart disease would generally be sudden and therefore the cholesterol state would be at its peak.
So these u curves can be read as an indication of how uncommon being healthy actually is.
excellent realization
That's exactly what I thought. The paradox might be caused by a lack of healthy people!
@@bobbenoit8470 wouldn’t have to be unhealthy. It’s all dependent on when these measurements are taken: at death, 1 year out, and so on.
I saw this mentioned recently by a couple of other youtube "doctors" as a reason why you don't need to worry about cholesterol ... glad you made this video to clear that up, thank you!
chiropractic "doctors" no doubt
It's always painful to listen to professionals speak on things they don't have a clear grasp.
I admit i was sucked in by dr berg and his chiropractic cronies for a while too, until the likes of gil, brad stanfield, and lately physionic, brought me back from the dark side. Watching dr berg et al now is almost cringeworthy.
@@James-zr1lu Right, especially considering the vast amount of evidence showing the positive effects of lowering LDL. One can't claim to be scientific and just ignore dozens/hundreds of other quality studies.
@@DrummerDucky Even more painful when you have to heal yourself...
Thank you so much for empowering your audience and letting us decide on what to do based on the science. It's such a refreshing change from RUclipsrs that use click bait, criticise a persons character that they don't agree with and let their emotions get involved in their efforts to ultimately deliver an otherwise well intentioned message. Great work and thank you again.
This video would be helped by showing graphs from some of the better, double-blind studies that factor out the people with illness and show the curves where they "should" be. I'm skeptical without seeing those graphs. No dog in this fight, just want to actually see the better evidence.
I can't point to the exact video, but I think he shows one where he puts dot plots of all the studies on a graph and it shows pretty clearly the affect of LDL cholesterol on mortality. If you have time to check out some of his older videos on cholesterol, you will run into it.
You are correct. He needs to do better. My friend was even more confused. I think your suggestion would make it clearer.
The links to the studies are all in the description. The Korean cholestrol study is exceptionally thorough and HUGE. Read the details of it and see. (first link I believe)
People love good news about their bad habits. Probably the most generally accurate statement I've heard in the health space. I imagine it could be credited for the "cholesterol skeptic" movement.
"People love good news about their bad habits." -- great point and well said.
@@JonathanBennett84 credit to John A. McDougall
Look at the level of cholesterol and mental illness and suicide. Under 160 seems to be a problem on this side.
Despite these reasonable suppositions, many studies over decades have (for the most part) consistently linked low total serum cholesterol with suicide, violence, and depression. Total cholesterol levels below 160, and especially below 130, correlate with a higher risk of mental problems.
"correlate". Is there any evidence that points to causation?
The curves would seem to suggest that cholesterol of 240 is just fine... as long as it's not an upward trend. And BMI of 28 is just fine, even if it's considered overweight. And systolic blood pressure of 140 is just fine. And even that an A1C of 7 is just fine! And that the danger is when these values trend upward over time, which unfortunately they tend to do, into the frank danger zones. I appreciate Dr. Gil's point that the lower end values correspond with chronic disease, and that's different from "higher is healthier;" yet it does seem to me that if strictly following the data, a *little* bit higher is actually, truly healthier! Also, some of these things are not like the others. I've got low (healthy range) blood pressure, 21 BMI, low (healthy range) blood glucose from my low carb, high fat way of eating. I don't have inflammation problems, aches and pains, energy deficits like so many other 50 year olds do, and I'm simply not concerned about my cholesterol.
I've got a low resting pulse rate, even, when I tested it at the pharmacy kiosk along with my blood pressure recently. I searched it up and it suggested it could be because a person is old, or an elite athlete. I'm not quite either, so who knows! I feel great and I don't think worrying is going to improve my health OR my disposition.
It's so funny watching you grasping at straws
For those that are worried about high cholesterol, it might be good to get a CAC score to see if there's any blockages. There is also Life Line screening that will do the same thing if you don't want to go to the doctors to get a referral for CAC. I will be doing the Life Line screening since I have high cholesterol.
In Wales this will cost around £700. This is too much for many people.
A CAC score won't tell you about blockages caused by soft plaque. It will only reveal old, calcified plaque. Your arteries can be nearly fully clogged with a low CAC score.
@@amyntas97jones29 I live in Southern California and it costs $159.
About one-fourth to one-third of the total incident cardiovascular disease events occur in those with a CAC of zero. - AHA
CAC only detects calcium. Not all of the build up will be calcified, may work in very old people or people who have been developing cholesterol build-up from a young age and gave it years to calcify
It's like losing weight. That happening for no reason (diet, exercise) is usually mentioned as a cancer symptom.
Excellent video. Very helpful in understanding so many RUclips channels that state there's little wrong with high cholesterol. Thank you.
Great video! Statins helped me but I stopped after 3 months. From there, diet and walking. Not so much diet as a lifestyle change. Meat was causing belly pain where my gallbladder area is and in my colon. Screw anymore surgeries, I went vegetarian 🥗. Best decision of my life.
You and Dr. Seheult are the only MDs on RUclips I trust.
Dr. Gil, Thanks again for your easy to understand explanation of such a heated topic. Your dedication is truly appreciated and has taught me so much.
I understand low BMI (you could be wasting away). I don't understand an A1c under 6. What fatal disease is associated with low A1c?
@@rubygreta1 plug the question into google
@@rubygreta1 Just taking a guess here, but I wonder if it could be a side effect of lack of appetite.
Association does not equate to correlation, which does not equate to causation. Should be a fundamental scientific mantra.
I've watched this video three times and read a lot of the comments, and I"m still not persuaded that optimums on cholesterol aren't actually the high levels.
Remove the people with cancers and other non-cardiovascular diseases, and we should see a linear effect, with those at relatively high levels still near the optimum.
The comparison to the BMI, BP, and HbA1c are not persuasive as two of them are not quadratic, and the other shows a tiny risk change across a wide range of BMIs.
If you have untreated hyperlipidemia, you can have all of those markers (total cholesterol, LDL-C, triglyceride) dropping to nice levels during an acute infection, things like tooth infection, kidney infection etc.
Can you please start writing a book on nutrition and these related topics…
We need a voice like yours out there.
"I wanted to take a moment to express my appreciation for this fantastic RUclips channel and the informative content that it provides. This topic is incredibly insightful and well-presented. Thank you for taking the time to share this valuable information with your viewers."
Oh boy does this answer a question I formed yesterday after watching one of the "Doctors" vids, where he put up a chart that shocked me! It showed cholesterol number ranges and associated them with good, ok, and bad, colored in Green, Yellow, and Red. This was a very odd chart to me because the "good" range was in fact from about 200-260, ok from 260 to about 340, and over 340 RED. He said however even 350 could be ok for some people! More surprising was the ranges below 200. That started yellow, and when it dropped to under about 100, there was a BIG RED. And yes, he emphasized that was the major risk of death area. I've just stopped watching any of these vids now, but now I know where their data is coming from. Thanks.
Wow, Gil, this was absolutely fantastic. You really put my mind at ease. Thank you so much for this clear, concise, reasonable, rational, scientifically correct explanation. You are doing so much good in this world, and you can tell your mother I said so. (I'm a mom, too, so my guess is she is super proud of you.)
Helpful as always. Well presented.
Just to confuse matters,I remember reading that a small number of people have an extremely negative reaction,in terms of greatly increased risk of suicide,to having their cholesterol lowered.I think I read it in 'Genome,' by Matt Ridley.
Maybe it lowered testosterone levels?
@@beemrmem3 I bet that's right
Hi Gil.I just came across your channel.I am very impressed.We need more people like you to cut through the confusion.We should connect.
Makes a video with such bold claims and fails to mention the study's limitations:
"First, the use of lipid-lowering medication was unaccounted for. The risk associated with high cholesterol might have been underestimated. Additionally, this study could not determine whether statin-induced low cholesterol increases mortality."
"Second, other lipid measures, such as low-density lipoprotein and high-density lipoprotein cholesterol levels, were unavailable. Recent dyslipidemia management guidelines are more closely focused on these sub-fractions of cholesterol, so the direct application of our findings to individual patient care might be somewhat limited."
Gil,
Can you please expound on your understanding of the physiologic mechanism by which the cholesterol molecule gets itself positioned beneath the endothelial layer of the systemic artery? In other words, is the endothelial cell actively, or passively, transporting it from the LDL in the bloodstream, through the cell and then expelling it on the other side, or is the cholesterol molecule somehow disrupting the tight junctions between the endothelium and working their way back behind them? If so, how? And if so, why does this never happen in veins and almost never happen in the pulmonary arteries?
In order to impact the curve in such a manner, the group of sick people must be really large. The real question is whether excluding the sick people will result in a different curve.
That's the issue I have. If low cholesterol reduces the risk of death, then the healthy people with low cholesterol should go some way to balance out this curve. Maybe there are next to no healthy people with low cholesterol!?
This U curve reminds me of the J curve long associated with alcohol consumption. I.e. that one or two drinks per day was associated with lower cause of death than total abstinence from alcohol. Until further research revealed that many studies had included people who abstained from alcohol because they were taking drugs that could not be used with alcohol. Drugs to control serious, often fatal diseases. And the studies also included former alcoholics who, due to liver damage, also have a lower life expectancy. Newer studies that only included people who didn’t drink alcohol because they didn’t want to, e.g. religious or dietary reasons, showed the straight line adverse side effects response to dose levels in alcohol consumption that one would expect from any drug.
_"A recent article published in The Lancet which is the largest meta analysis to date has a very comprehensive overview of risks associated with moderate to high-level drinking. The J-curve only exists for very few hand-picked risks"_
The J curve studies are heavily biased to defend their consumption of alcohol. Either way, that completely ignores the fact that usually the moderate drinkers are wealthier ( aka better health care ) and alcohol gives addiction which leads to heavy drinking ( no, you are not immune, especially if something bad happens to you, it will be easier for you to drown in alcohol if you already drunk some before ).
The reason why those curves are welcome on social media and why people call themselves cholesterol skeptic is that it gives them license to finally do what they want to do. Most people wand to eat pizza, with a ton of cheese, dairy ice cream, a lot of sugar, bacon and all kind of meat, so if they encounter some "information" that tells them a low cholesterol is dangerous this is the good news they were looking for about their bad habits and will feel validated. People are addicted to various combinations of fat, sugar and animal protein and are on the look out for excuses to keep eating them.
Interesting ... I am wondering about the size of the risk increase at the lower end. Your argument is interesting, but is it enough to explain the size of the effect. In your opinion does this mean that a) there is a lot more undiagnosed illness than people are aware of, and that is sitting there as a large pool of potential problems representing a large proportion of the population . This is the moderate risk, high population option. b) That the risks of those in this position are very high, so that a limited number of cases are going to be driving the curve up steeply because the risk of mortality is very high. This is the high risk, moderate population option. Or c) something else ?
You nailed it. There is no way it would be that steep... also... what if you have low cholesterol and then get that disease? etc. etc. This assosication to other graphs doesn't prove anything.
Look up the latest on preserving the mevalonate pathway when glucose is restricted by compartmentalization of the HMG-CoA reductase. This is why ketosis increases cholesterol and LDL but without the glucose oxidation ROS.
Just when I was about to raise the honest question, "But aren't epidemiological studies usually conducted at large enough population sizes that people with unsuspected diseases should not bias the results?", the video goes on to explain that studies with larger populations do tend to wash these anomalies out
You are right. And while there are people with "unsuspected diseases", the good studies normalize for confounding factors eg. known diseases.
Do we have any idea if this graph has been normalised for those underlying disease cofounders? If its not normalised then its poorly designed or atleast not designed well for cholesterol levels vs health risk. If those cofounders have been removed then the results would require further scrutiny as the answers given in this talk wouldn’t hold
@@888jucu Yes, they are normalized. You can check the studies themselves!
@@PETROS_GGGAre you saying you have checked and can confirm potential illness cofounders have been removed/normalised for?
Thank u Sir. In depth understanding leaves no confusiom.
If you're wondering why so many people have difficulties with the idea that cholesterol should be as low as possible,... you have to look at the people that promote lowering cholesterol.
You can't really have a conversation with them. If you ask questions, you're either ignored or told you're stupid.
You don't do that much, but some others do. And it's a red flag if someone doesn't even want to answer questions.
Most of our cholesterol does NOT come from the foods we eat.
@@residentjess Yes, but what does that have to do with what I wrote?
When it comes to weight, one of the reasons, the death rate is higher with lower, BMIs is because smokers tend to be leaner, and they tend to die sooner. Also, people who are overweight, sometimes are able to live longer with diseases that cause weight loss.
Pretty much all studies consider smoking and alcohol usage, those stats are probably ( don't quote me on that ) adjusted with that in mind.
Excellent explanation! 🎉 thank you!
I had very high cholesterol at one time along with the whole lousy package of type 2 diabetes and very high triglycerides etc. I was diagnosed in 1998 as a result of a required pre-employment physical. I'm coming up on my 25 year diaversary and haven't spent a night in the hospital yet. I certainly get frustrated with all the different gurus telling people completely different things about what is and isn't worth focusing on. The first doctor I saw in 1998 committed suicide about 4 years later. He was my age, married with young kids and went to Catholic high school. Very sad. I still think about it/him. His daughter is now a nurse.
Thanks for making this. A friend of mine recently sent me an article arguing that people with high cholesterol live longer 🤦🏻♂️.
I read the article and it referred to the u-curve and the study was specifically looking at people over 60 which I think would skew these numbers even more.
I shared the link to this video with him 💕
The question remains, why do we see good mortality numbers at the beginning of the bad range?
Thank you! I'm so glad I found you, because you are able to explain to lay people. And you illustrate how important it is to be discerning about nutrition/health info that comes out, and not just swallow everyone/everything blindly. I appreciate you!
Even if I believe what you’re saying about the low end “paradox”, the graph still shows the least hazard at the 210 to 250 range.
"Reverse causality has been suggested as an explanation of higher mortality associated with low cholesterol levels. However, a long term follow-up study in a Japanese-American population showed that individuals with low cholesterol levels maintained over a 20-year period had the worst all-cause mortality, and concluded that reverse causality was unlikely to account for the higher mortality associated with low cholesterol entirely"
right, that's referring to the Honolulu cohort, their effect lost significance when adjusted for frailty measures (so its consistent with a disease-caused cholesterol lowering)
cancer can reduce cholesterol level many years before it's diagnosed, so the best way to tease apart these effects is to look at randomized designs
How much of this data was done on populations of those practicing low carb diets or those that remained in ketosis for a considerable length of time?
The problem is that when I follow a anything but high fat, red meat heavy diet, I am practically bedridden and can not hold down a job. If I eat high fat/low carb/lots of red meat I have my life back. I have to choose between preventing a heart attack and have no quality of life, or have a true quality of life and risk a heart attack.
I take these studies and cholesterol seriously, but it seems like diet of the test population isn’t a recorded factor.
hi. obviously there's some severe intolerance issue (unrelated to cholesterol or the topic of this video). this is something that has to be investigated. are the symptoms GI-centered? have your doctors ruled out things like IBD, IBS? celiac? those are just some initial ideas, it will depend on the symptoms. clearly there's an underlying condition and/or imbalance that needs to be identified/diagnosed
I think the U curve is pretty real, but it is shifted to the right in small studies, and the larger and better the study, this U curve is shifted to the left, and the valley begins to conform to the values we expect.
no sh8t? link?
@@Dan16673 no link, thats why i said "i think". I could be wrong, but it is kinda obvious. If you have zero cholesterol, you're also 💀. Too much or too less of something is not great. There will aways be a balance point. Except for toxins of course, in that case the lower the better.
You nailed it, Dr Carvalho! Thanks for going the extra mile to dig into the data and explain it so clearly.
I wonder if the numbers of people with a given level of a blood marker factors into it those graphs, as well. For example: fewer people have an A1c under 5 (than 5.5) so perhaps a larger proportion have subclinical disease?
A bit like the French paradox. The French eat more saturated fat than any other country in Europe, they also smoke more than most, yet they have the lowest incidence of heart disease.
Have you seen their portion sizes? they eat less total fat than us, despite some of their food being quite fatty. They also don't snack as much, eat processed food as much and most live in cities and do a lot of walking.
Amazing scientific insight, I am wondering if the "U shaped" curve is also what explains the benefits for alcohol and coffee.
An oversimplification of opposing viewpoints which is your attempt at making yourself as the one who really knows the truth.
Great explanation, thanks! I've seen people saying on social media that you need to eat plenty of dietary cholesterol to maintain high testosterone levels, even recommending pure butter for gains. Others say pretty much the opposite, that fatty foods are associated with lower testosterone. Could you please clarify?
All sexual hormones in both male and female are made from cholesterol, taken it from food is essential for a normal level. Just look at statistics on the age women get to menopause, 30 years ago it was 50+, today when we eat a lot less cholesterol together with other factors of course, many women see signs of menopause at early '40. It's that just a coincidence?
Wow, thank you for this explanation. I'm particularly and continually confused by diet guidelines these days and health guidelines which are contradictory at best over the last 20 years. I don't know what to eat. I don't know what to think about recent research. It's very difficult to navigate the healthy lifestyle and get it right.
Very true! They contradict each other daily almost . I think eating healthy fruit and veg and occasional meat and fish is the way forward. Moderation like our ancestors ate .
As is often said, people like hearing good things about their bad habits. Thx for clearing this up.
Your videos are superb. Sadly, there are medical doctors who are not delivering accurate messaging according to real science.
Thank you! This video is useful
excellent - I was also wondering the correct interpretation of the cholesterol U-curve presented in other vidéos. As a layman, I am not equipped with the knowledge to put this information in the right context. What's amazes me is that epidemiologist did not put the correct interpretation either. Thank you for this information.
Dr. Walter Willett was recently on Simon Hill's podcast and said there's substantial evidence (including mendelian randomization) that extremely low blood cholesterol is associated with increased risk of hemorrhagic stroke. Are you familiar with any of that evidence?
Joel Fuhrman mentioned a study where high hemorrhagic stroke with vegans is linked to higher sodium intake.
Apparently, meat and dairy has protective effect against hemorrhagic stroke even though those increase the risk of ischemic stroke.
So as long as sodium content is low, it should be fine.
@@jys365teresting. I hope one of these more reliable YT/Podcasters does a deeper dive soon.
Ok, I get your point. But why is the LOWEST risk at higher cholestrol values (210-240mg/l). Shouldn't that be at 200 or slightly below?
Excellent explanation, thank you. I've heard this applied to alcohol consumption. People who don't drink are more likely to die than people who drink moderately. Turns out a large number of the teetotalers gave up drinking because they were already sick, very elderly or alcoholics with liver damage.
I considered myself a moderate drinker, and then I started to experience A-fib episodes. Then, one day, I had 2 glasses of wine, which put me into A-fib for a week. I later learned from a cardiologist that alcohol can kill the hearts electrical pathways and eventually causing A-fib to be permanent. I have stopped drinking 🍸 I am on a low dose of Metropolol 25mg and have not experienced any further episodes, while I have begun reversing my heart disease based on my CAC going from 660 to 458.
The graphs are very interesting and stir up many questions, like the "why factor" .. why did it change? AIC, Cholesterol, BMI ... causation!
Wow, yet another wonderful video!
Please also use mmol/L for cholesterol levels so we Canadians can get more out of your video.
Great explanation of a complicated issue. Thank you!!
Corpses have very low blood pressure. This makes lots of sense.
I remember reading a journal article some 15 or so years ago, wherein a hospital-based physician remarked upon the phenomenon that in older people all the standard measures of good health - weight, blood pressure, cholesterol etc - were reversed. In younger people, low cholesterol, weight etc predicted future good health but in older people they tended to predict increased mortality and morbidity risk. darned if I can find it now though.
More to do with decreased grelin, so weight loss happens, and falls becomes the biggest killer of old people, because they don't have the fat as a buffer for their organs.
@@brucejensen3081 Falls are a problem to elderly because their bones brake like chalk. Ortopedic medicin for old people is death sentence.
Did it control for cancer deaths? Because blood pressure will improve along with the weight loss while their health rapidly declines. My bad. I hadn't watched the video fully when I wrote the comment.
Weight is a poor metric. A lean person with a decent amount of muscle mass can be labeled as obese on a BMI chart. It's not that the elderly are better off being fat, they need that muscle as they age. Not only does that muscle support their bones but bone is also 50% protein, so if they've managed to maintain muscle density they're more likely to have maintained bone density as well.
@@Engrave.Danger True but things like cancer, malnutrition, poor dentition, heart failure and diabetes etc cause weight loss.and those things are more common in the elderly. Since it is now 'normal' to be overweight, it may be that in the elderly low weight is a marker for various diseases and thus for mortality risk.
I have a PCSK-9 mutation that gives me extremely low blood cholesterol. My TOTAL cholesterol has never been higher than about 131, and it's usually around 100. (I am on a statin now, but ironically, the day I went to the hospital with what turned out to be a heart attack, my total cholesterol was 91, and that was before I started the statin.)
Highly active 56yo, 6ft, 158 lbs. BP is 109/72, resting HR, 54. My 14 day avg. glucose is 83mg/ml and total Chol 557, Trigs 104, HDL 52, LDL 461. Should I be concerned about my high cholesterol or LDL?
You should ask your primary care provider. Mine is half that but my primary care provider told me that it wasn't worrisome because my BP was excellent. But if it had been over 500 I'm not sure what he would've said. Just ask them on your next visit.
I'm on the same boat, my mother is at age 74 with the same problem with cholesterol. Perfectly healthy otherwise. All the way!
Same can be said for alcohol use; once the people who are abstainers due to negative health conditions, including alcoholism are excluded, and lifelong patterns of alcohol abstinence are segregated, the u in the u-shape goes away, and the relationship between alcohol use and mortality/morbidity is linear--the more you drink, the worse it is for you.
that was very informative and easy to understand. Thank you!
It means that if you are sick then you are at higher risk of dying.
@@chuckleezodiac24 yes, but if we stay healthy for longer, that mortality can be postponed. At least that's the theory. The art is to actually achieve that.
if 150 blood pressure is optimal and 120 is considered normal, but life expectancy decreases , why cut of is 120?
This channel is perfect for science understanding!
Great video ! Thank you!
This is the 3rd year of me binge watching RUclips health videos. Frankly, other than staying away from processed food, alcohol, sugar, and avoid overeating, nothing else is close to being certain. Diet wise, it appears that an omnivore diet is the best hedge against all this uncertainty.
Well said. My 5th year. Same conclusion
Moderation
can't agree more. i'd throw though in this decent and well thought mixture some daily vigorous walking and that almighty master of all pills out there, a restful 7h sleep. life is good and tasty!
@@kidoscopic Yeah, the crazy thing is that the only certain things are things we already know without watching all those health videos. 😄
Brilliant science uncovering the reasons for the U curve
Ok I understand the explanation of the left side of the curve, thanks. What is causing the bottom of the curve to show higher numbers related to lower mortality? ie 250 versus 200 as the lowest mortality point? Also could there be a point where very low cholesterol does negatively impact the body since the body does need some to function?
The body makes its own. If your levels are too low to properly function then something else is likely the issue. Studies are showing links between low cholesterol and a few diseases but it appears as the diseases that caused the low cholesterol rather than low cholesterol causing the disease. Trials where they have artificially lowered cholesterol to extremely low levels have not shown any negative effects though these trials have been short so may or may not be lomg term issues with it. So far the evidence points to low cholesterol not being an issue itself and is just a marker for other issues but more long term study is needed to confirm absolutely.
Same question about the bottom of the curve. After watching the video I can now explain/understand the left side of the curve, but still puzzled about explanation of the bottom. Also remember these tests are measuring blood cholesterol. Every cell in our body also has the ability to make its own cholesterol.
People with the higher cholesterols are probably dying to a vascular type disease like stroke or heart disease, while the lower ones may be dying to the cholesterol lowering one like cancer and what not.
I love information. And your study of studies (meta-analysis) is the cream of the crop. Thank you for helping me on my health journey.
Yeah, but can you bench like Dr. BAKER?
In all seriousness, thank you for the content, sir. I learn a lot here.
Great video.
Hats off to you for showing what a great dr with common sense is.
Excellent presentation. Thank you.
I wouldn't dismiss you at all. On October 2018 I suffered heart failure at 44 years of age. Shortly after returning home my PCP sent my latest lab results. My cholesterol was 10, yes I said 10. She said she never seen anybody that Low. I was given a Statin a year before heart failure because they said I was a type 2 diabetic. More on the diabeties part another time.
This is interesting. I've always wondered if there is a cholesterol level that is too low. My husband is on atorvastatin and his level is 122. When he started it years ago his cholesterol was in the 240 range. I'm thinking of cutting his atorvastatin dosage because that level seems quite low to me.
That level seems healthy to me. For one thing, there is no evidence that intensive cholesterol lowering is dangerous. Quite the opposite ... studies show that achieving very low levels reduces the rate of major adverse cardiovascular events. Brown and Goldstein won a Nobel Prize for their work on cholesterol. They conclude that "plasma levels of LDL-cholesterol in the range of 25-60 mg/dl (total plasma cholesterol of 110 to 150 mg/dl) might indeed be physiologic for human beings. First, in other mammalian species that do not develop atherosclerosis, the plasma LDL-cholesterol level is generally less than 80 mg/dl (Fig. 16 and ref. 120). In these animals the affinity of the LDL receptor for their own LDL is roughly the same as the affinity of the human LDL receptor for human LDL, implying that these species are designed by evolution to have similar plasma LDL levels (9,119). Second, the LDL level in newborn humans is approximately 30 mg/dl (121), well within the range that seems to be appropriate for receptor binding (Fig. 16). Third, when humans are raised on a low fat diet, the plasma LDL-cholesterol tends to stay in the range of 50 to 80 mg/dl. " www.science.org/doi/10.1126/science.3513311?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
It not all about one number on one test. Must look at big picture and must review his age, race, activity levels, diet and about 19 other blood markers to establish present status. Plus helps to know CAC score or CT scan.
@@DrAJ_LatinAmerica Thank you for your reply. My husband is high risk. Balloon angioplasty 20 years ago, heart attack with stent 6 years ago. One artery still has blockage, but I think his mind/memory has been affected (normal scan for age) and he is bursting out with fast growing skin cancers. He's also a sugar addict. He is 84 years old, though and very stubborn. He totally ignores his health. I need to make him a cardiology appointment soon.
@@jjbud3124 definitely some serious issues. At his age, he needs to do what make him happy. Definitely need to be working very closely with your doctor(s). Always Keep in mind the internet is just very rough broad strokes of information. Not medical advice regarding your husband specifically. All things are case by case, person by person. No one set diet or set of rules applies to everyone. Millions will say people don't need to take a statin medication. However millions are not your husband. Again your doctor has to look at all evidence AND has to base the treatment on the specific wishes of your husband and an agreement to follow treatment. I'm always surprised, but there are many (millions) who refuse to stop drinking, smoking, over eating, eating junk foods,..... Freedom is a double edge sword. But of luck, keep trying and God bless 🙏💪
Hello Sir :) Which cholesterol levels are you discussing here ? The HDL ( the good one ) or the LDL ( the bad one ) ??
I would have thought the rise in mortality with lower cholesterol would be partially due to more elderly people taking cholesterol lowering medications but dying from other age-related deaths.
That’s a distinct possibility.
I thought that the association between low cholesterol and increased mortality in older people was first observed long before statin drugs were available.
Yes, in a previous video he mentioned that as well. Good point. I think it could be part of the reason. My Mom was so frail when she passed and she hardly would eat anything so I bet her cholesterol was very low as a result.
@@tomgoff7887 Yes. Framingham study
@@ioodyssey3740 Thank you. Yes.
Not sure these other partgicular U curves make great examples though. Because yes you CAN weigh too little. You CAN have an A1C thats too low if you have too little glucose, etc.
Great explanation as to why low cholesterol does not increase risk of death. However, what I don’t understand is why on the u curves eg blood pressure, blood glucose etc the death risk appears to at lease be a constant as higher levels than the medically advised levels eg 5.7 blood glucose and 120/80 BP. Is there a good explanation for this as well?
Thanks for that! Just what I needed. Here's me worrying about a 142 blood pressure reading and 244 total cholesterol. I'll be getting a full medical check up next Friday. Fascinating video and it's given me a new way how to view my current health.
Congratulations for being at the peak lifespan values!
Yes, i understand why it's a u-curve with higher mortality at lower values. But i'm still puzzled that the minimum (lowest mortality) of all those curves are at unexpected high values (of cholesterol, bloodpressure, hba1c, BMI, etc.). I would expect the minimum of these curves to be a little further to the left, at levels closer to the optimal (lower) healthy values of these parameters.
Maybe it means you've been brainwashed by those doctors
@@heathensein6582 "Brainwashed" is not really a good argument. It's a claim that needs evidence.
It reflects more where the population is.
If you're outside of the norm you are sick ... or you have a healthier lifestyle. And being sick is a strong negative effect. So it rises the mortality more even if there were as many people with a healthier lifestyle (sickness has more influence on mortality better than healthy lifestyle).
And on top of that (at least around the region where I live), it does not seem to be the case that people with a healthier lifestyle outnumber sick people.
@@tofu-munchingCoalition.ofChaos Yes, something like "it reflects more where the populaton is" was my first guess as well.
But based on the "Cholesterol Facts" of the CDC (Center for Desease Control and Prevention) :
[...]
Percent of adults aged 20 and over with high serum total cholesterol (greater than or equal to 240 mg/dL): 11.5% (2015-2018)
Mean serum total cholesterol level for adults aged 20 and over: 191 m.g/dL (2015-2018)
[...]
So 88,5% of the US population is below(!) 240 mg/dL with an overall average of 191 mg/dL.
But the Minimum of the Mortality on the Cholesterol Chart is around 230 mg/dL.
And those numbers doesn't really fit with the first guess "it reflects more where the populaton is" and "If you're outside of the norm you are sick".
@@cruisebaer This is data from South Korea. But essentially your argument seems to hold. The average TC is ≈200 [mg/dl] and the empirical SD is ≈50.
For simplicity (to get a feeling where the argument is and so that I don't have to look up many numbers from the paper) let's just assume TC is normally distributed for not sick people.
Their normal TC for people is ≈20% of the people is 250 or higher. If they get sick and their TC drops let's say 20%, then they overlap with the mode of TC ≈200.
So sick people's abnormal range and healthy people's normal range overlap.
In general if you follow the "if you're outside the norm you're sick", you still expect at the mean to have a lot of sick people with abnormal values (abnormal to their natural value). This is true as long as the SD of the marker is not drastically below the typical deviation of the marker for sick people.
Had a 220 reading and the health professionals advised me I should eat more fruits and vegetables. I told her that if I ate more fruits and vegetables I would need an import/export license. BTW, the rest of my family, who eat the standard American diet have cholesterol readings of between 300 and 400 (unmedicated).
at those levels, I´d suspect a genetic susceptibility. FH or maybe cholesterol hyperabsorption. one idea is to try a diet with vs without eggs for a couple weeks and see how it affects lipids. see our video on dietary cholesterol for more detail
The cholesterol paradox refers to a phenomenon observed in certain studies that challenges the traditional understanding of the relationship between cholesterol and cardiovascular disease (CVD). Historically, high levels of low-density lipoprotein cholesterol (LDL-C) have been considered a major risk factor for CVD, while high levels of high-density lipoprotein cholesterol (HDL-C) have been seen as protective.
However, the cholesterol paradox arises when researchers observe that some individuals with low LDL-C levels still develop CVD, while others with high LDL-C levels do not. Similarly, some individuals with high HDL-C levels still experience CVD events, while those with low HDL-C levels remain unaffected.
The cholesterol paradox suggests that there may be other factors beyond just cholesterol levels that contribute to CVD. These factors could include inflammation, oxidative stress, genetic predisposition, the size and density of cholesterol particles, and the overall balance of different lipoprotein subclasses.
Several hypotheses have been proposed to explain the cholesterol paradox. One theory is that LDL particle size and density play a significant role. Smaller, denser LDL particles are thought to be more atherogenic (contributing to the development of atherosclerosis) than larger, more buoyant particles, even at similar cholesterol levels.
Other factors such as inflammation and oxidative stress can influence the progression of atherosclerosis and CVD independently of cholesterol levels. These factors can damage blood vessels and promote plaque formation, leading to CVD events.
The cholesterol paradox highlights the complexity of the relationship between cholesterol and CVD. While cholesterol levels remain an essential consideration in assessing cardiovascular risk, they are not the sole determinant. Other factors, including lifestyle, genetics, and inflammation, contribute significantly to an individual's overall risk profile for CVD.