Is it Safe to Greatly Reduce LDL Cholesterol, Far Below Normal Levels?

The dominant approach to slowing atherosclerosis remains a mix of pharmaceuticals that can, separately, reduce blood pressure and LDL cholesterol (LDL-C) in the bloodstream. In the latter case, new therapies such as PCSK9 inhibitors and improved combinations of statins are capable of doing far more than just return raised LDL-C to normal levels. It is in fact possible to reduce blood cholesterol to something like a half or quarter of normal levels, and this produces incrementally greater benefits in reduction of atherosclerosis risk. But is it safe over the long term? And if it is, why did we evolve to have the observed normal levels of cholesterol in blood?

Atherosclerosis is the build up of fatty plaques that narrow and weaken blood vessels, ultimately leading to a fatal rupture of some form. Raised blood pressure accelerates this process through mechanisms that are incompletely explored - but it is obviously the case that, at later stages, more pressure and weaker blood vessels combines to increase the risk of fatal structural failure. Cholesterol is another input, arriving from the bloodstream. The final input is the activity of the immune system, and local inflammatory signaling, as the immune cells called macrophages attempts to clean up cholesterol from blood vessel tissues and return it to the liver to be disposed of.

Atherosclerotic plaques start and grow due to the presence of damaged, oxidized cholesterol more than overall cholesterol, but the more cholesterol in total, the more oxidized cholesterol is mixed in. That proportion increases with age, as rising levels of oxidative molecules throughout the body lead to ever more oxidative damage to molecules. Macrophages respond to the presence of cholesterol, arrive, become overwhelmed by oxidized cholesterol, and become inflammatory foam cells or die. In either case they produce signaling that leads to a further influx of macrophages, a feedback loop that only worsens with time. The bulk of atherosclerotic deposits is made up of the debris of dead cells and the cholesterol they failed to clear away, a significant fraction of it oxidized cholesterol.

Thus lower blood cholesterol is good in the sense that it will slow down this process by reducing one of the inputs. Unfortunately it doesn't appear to significantly reverse atherosclerosis. Established atherosclerotic plaques remain, and the fatal end result is only put off to some degree, even for the very dramatic reductions in blood cholesterol discussed here. Better approaches are needed, such as ways to destroy oxidized cholesterol, or make macrophages resistant to oxidized cholesterol, or otherwise improve the process by which macrophages mine cholesterol from plaques and export it back to the liver. The past twenty years has seen a fair amount of innovation on the latter option, but sad to say that it has failed in human trials, even while producing as much as a 50% reversion of plaque in mice.

Is very low LDL-C harmful?

LDL-C is deposited in the arterial wall and promotes the inflammation process through the attraction of monocytes and macrophages at the site of cholesterol deposition, thus resulting in the development of atherosclerotic plaques and overt cardiovascular (CV) disease. An abundance of evidence has shown a linear relationship of LDL-C levels with the risk for CV events. Several lipid-lowering treatments such as statins, ezetimibe and the novel proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors were found to offer significant benefits in the reduction in LDL-C and importantly in the amelioration of the overall CV risk of patients with hyperlipidemia with or without CV disease.

Towards this direction, the European Society of Cardiology and the European Society of Atherosclerosis recommend the reduction in LDL-C to lower than 70 mg/dl or a reduction of at least 50% if the baseline values are between 70 and 135 mg/dl in very high-risk patients, to lower than 100 mg/dl or a reduction of at least 50% from baseline values between 100 and 200 mg/dl in high-risk patients, and to less than 115 mg/dl in low to moderate risk patients. The 2017 American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease suggest even lower LDL-C targets of <100 mg/dl, <70 mg/dl, and <55 mg/dl, in high, very high, or extreme risk diabetic patients.

The necessity for the reduction in LDL-C levels to provide significant CV beneficial effects has been shown and is recommended by all international guidelines. However, there are concerns for the optimal lower limit in which LDL-C can be reduced to achieve optimal CV benefit without causing potential adverse events. The purpose of this review is to present available data for the safety of reducing LDL-C to low or very low levels as it comes from studies of lipid-lowering drugs that achieved such levels.

In general, intensive lipid-lowering studies with statins showed that there is no increased risk of adverse events with reducing LDL-C to levels of approximately 40-50 mg/dl. The most important data for reducing LDL-C to such levels are provided from PCSK9 inhibitors studies where remarkable reductions in LDL-C levels were achieved and no increased rates of adverse events were noted with evolocumab. The slightly concerning findings with alirocumab in the ODYSSEY LONG TERM trial were not verified in the ODYSSEY OUTCOMES study. More importantly, the potential neurocognitive decline with low LDL-C was not observed in several post-hoc analyses and in the EBBINHAUS trial that was specifically designed to evaluate such events. However, it has to be noted that in most trials, the follow-up period and the exposure of the patients in low LDL-C was rather short and trials with longer study periods are needed to unveil potential harms.

Last, higher incidences of hemorrhagic stroke and cancer were not observed in these studies, even at very low LDL-C levels. In conclusion, reduction of LDL-C to less than 50 mg/dl seems safe and provides greater CV benefits compared with higher levels. Data for achieved LDL-C lower than 20-25 mg/dl is limited, although findings from the above mentioned studies are encouraging. However, further evaluation is needed for future studies and post-hoc analyses.


"It is in fact possible to reduce blood cholesterol to something like a half or quarter of normal levels, and this produces incrementally greater benefits in reduction of atherosclerosis risk. But is it safe over the long term? And if it is, why did we evolve to have the observed normal levels of cholesterol in blood?"

Why not? The same answer for most accumulating forms of damage - because most prehistoric humans were dead from infection long before atherosclerosis could exert evolutionary pressure on humans with higher levels of LDL.

Posted by: Jim at January 9th, 2019 5:26 PM

In any case this is only lightly postpone inevitable . Why so many researchers work on compensatory approach like statins while so little on regenerative approach like 7KC breaking ensyme?

Posted by: Ariel at January 9th, 2019 6:48 PM

@Ariel - "In any case this is only lightly postpone inevitable . Why so many researchers work on compensatory approach like statins while so little on regenerative approach like 7KC breaking ensyme?"

A couple of guesses, 7KC breaking enzymes have never been tried in human trials, and to boot they are a gene therapy, so there is a lot of extra risk of failure in development compared to small molecule drugs.

Also small molecule drugs have to be taken regularly, so can extract regular payments from customers. 7KC breaking enzymes might be a one off fix, or something that only needs to be taken every couple of years.

Posted by: Jim at January 9th, 2019 7:37 PM

In one medical paper the researcher described the artery plaque as like acne. How the pimple pushes out the skin. In the artery this pimple can keep getting bigger until it cuts off the blood flow, or even just reducing the blood flow causes problems.

An interesting treatment is biodegradable stents. They actually remodel the artery back to the original size. And then the stent dissolves over the course of a year or two. The plaque is still there, it just has been pushed out from clogging the blood flow.

I can imagine some gel like substance that could go into peoples arteries, and gradually dissolve that plaque. The problem I see with many ideas, is how is the drug going to get inside the artery wall to where the plaque is building up.

Posted by: aa3 at January 9th, 2019 8:08 PM

I honestly don't understand why any serious amount of research dollars are spent on the atherosclerosis problem when a cure for most is readily available in unfiltered apple cider vinegar with the "monther". The unfortunate reality that most people are, to put it politely, adverse to drinking it needs to be fixed with a culture change regarding hedonism. Ask yourselves why NIH has not done a study comparing 6 months of daily apple cider vinegar to the most used statins out there.

Posted by: Tom Schaefer at January 10th, 2019 7:15 AM

The problem is defining "normal" LDL.

Normal for persons consuming a modern Western diet is actually abnormal. Way too much fat and meat.

You can hit a LDL of 70 eating vegan relatively easily but few have the willpower.

CVD is mainly a lifestyle disease.

"Vegetarian diet and cholesterol and triglycerides levels"

"LDL values for omnivores and vegans were respectively: 123.43 ± 42.67 mg/dl and 69.28 ± 29.53 mg/dl (p < 0.001). As for TG, those values were 155.68 ± 119.84 mg/dl and 81.67 ± 81.90 mg/dl (p < 0.01)."

Posted by: Lee at January 10th, 2019 7:25 AM

My thought is that most people have platelet counts that are way too high. You only need a count of 100 for adequate clotting activity, but many people have a platelet count of 300-500. The platelets are the source of amyloid beta which is deposited in the developing plaques through out the blood vessel system, and contributes to CAD, CVD and MI's. Why don't we concentrate more on lowering platelet counts to control atherosclerosis?

Posted by: Biotechy Marcks at January 10th, 2019 7:53 AM

@Jim, why gene therapy? Enzyme therapy can work as well.

Posted by: Ariel at January 10th, 2019 11:12 AM

Jim: "Also small molecule drugs have to be taken regularly, so can extract regular payments from customers."
^^^ This ^^^
Like Chris Rock says, the money's in the comeback.

Tom Schaefer: "The unfortunate reality that most people are, to put it politely, adverse to drinking it needs to be fixed with a culture change regarding hedonism."
What color is the sky in your world? I'm imagining it is a lovely iridescent purple swirled with pink and teal. There are almost 5,000 reviews on Amazon for Bragg's ACV. I like my ACV with San Pellegrino and stevia - it's soooo taaasty, ummm... (and diluted, it won't burn my esophagus and dissolve my tooth enamel).

I've got ACV and Robitussin, I'm gonna live forever.

Posted by: CD at January 10th, 2019 11:49 AM

Hi there! Just a 2 cents.

Apple cider vinegar was definitely something I looked into at my worst, but it was not enough; it is a powerful fat burner in the form of its acetic acid and 'the mother' enzymes; plus it changes the intestinal bacterial composition towards SFA production by more of these friendly-bacterias in the gut flora. But, it's not really enough; I took (serratio)peptidases, fibrosis lowering agents, bifidobacteria supplements (like from lab made yogurt bacterial culture that contains trillions of these bacterias); in the case of the high amount of them it was worse, I knew it helped improving the cholesterol reduction but it was Dire in terms of its effect on the body; think like doing 85% CR or fasting everyday, when you are about to die. Too strong on already weak frail thin body, this bring dangerous frailty, bordering on anorexia level. I noticed that it also increased fast burning, a good thing, - a bad thing, if you are thin alraedy. It made me lose More, when there is not much 'skin/fat' in the first place (I was 150lbs at my 'heaviest' (in those pre-days, of eating whatever, and I was more 'round' in the face, slighty more 'padded' and chubbier; now I'm 130, my cheekbones protude and bones appear but I'm at my 'supposed healthy' weight and do feel much healthier - just I have to be careful to not overdo exercice or strain my body because of the disease; when I was at the worst, I dropped to 100-110lbs, there I was beginning to be skeleton anorexic for my size (5'10', 1m77). My atherosclerosis made me go down to 110lbs, don't think atherosclerosis is just a product of very fat people eating too much cholesterol-ladden food; it isn't. Your body controls/regulates cholesterol levels are 'laser-fashion', and it has such, very regulated. Many thin people have cholesterol dysfunction and as such, have cholesterol levels of 'very fat people' in thin bodies. Theirs is brought, mostly, by genetic defects in cholesterol uptake; in thin people. I am a twin, and my twin sister, also suffers from hypercholesteremia, and she weighs 115-120lbs; and is 5'8. Thus, we both suffer from genetic defect of such. Now, for most people, it's the inverse; they are obese and this greatly contributes the problem; intake of excess of cholesterol, as said in the study, ends up as build up if the liver removal rate is exceeded. But, not just that, it ends up - straight in your arteries. Like it happenede to me, and it caused the disease; I had a pulmonary embolism the first time and that one nearly killed me. The most important point when a clot will happen it to reduce fibrotic/plaque/immune activity (since it is macrophage invasion initiated by LDL signal from excess pockets of LDL in atherosclerotic lesions), then restore the redox in the artery, because ischemia is first thing that happens and then affected arterial endothelial tissue dies; and you can die if the oxygen is reduced too much at the clot point because of sudden ATP loss at that tissue from blood restriction cut from the clot jammed there after a plaque ruptured. Not only that, other organs will fail and enter ischemic state, because of lack of blood reach from clot; thus your level of O2 drops and ROS is massively produced at the ischemia tissues. LDL-ox will contribue to this as it goes into a vicious circle of more oxidized LDL, vLDL and 7-KC production. When your consume products that restore ketosis/fat burning, be careful with this (I did CR, ketosis, bifidobacteria, apple cider vinegar, etc...) because now you switch the body from cholesterol synthesis/glucose uptake towards lipid-burning for energy; which is, what you want - but not in thin state; if overly fat yes; you stand good to lose some pounds; but if you have 'no pounds' on you, no. It will accentuate the frailty and the disease too. Because when you have atherosclerosis, it is a very tricky thing; your body is trying to use glucose as its main energy because it enters - far more - into ischemia levels than regular people; glucose is the most protective thing for ischemia tissues, because it activates HSF-1/heat shock factor 1/HEME-1 (heme oygenase 1; an extremely protective element that alters iron levels to reduce iron fenton ROS reaction from heme/iron exposure causing ROS and restor O2/ATP energy balance in low O2), which it, activates Hypoxia Inducible Factor-1 HIF-1 and Phase II detox stress enzymes (GST glutathione s transferase and selenotransferase); the master regulator of ischemia response under low O2 (such as lack of blood from clot causing ischemic tissues). This regulator Reduces ROS under severe O2, because it alters ATP and makes mitochondria 'feed' on glucose rather than lipid source; you could say your body is mimicking 'cancer cells' whom feed on glucose and strive in hypoxic/anoxic env. In fact, Hypoxic factor is a contributor to cancer formation (and why oxygen kills cancers via oxygen oxidation power, while HIF-1 'protect' cancer cells from oxidation-caused by O2/peroxidation from oxygen exposure to one oxide/per-oxide of oxygen). So, it's a double-edged sword, it's good for protection under low O2 but it creates a haven for 'mutation/rogue cells' formation. As such, when you have atherosclerosis, your body needs Instant energy, much more of it to supplement the ischemic tissues aroudn arteries, and glucose provides taht, likewise for lactate production, far more than lipid burning. It's why the body chooses this as a way to combat excess fat and cholesterol. I have to be careful because too little carbs makes me go CR/ketotic, too much carbs accelerates atherosclerosis from excess blood glucoses (causing diabetes/AGEs), while enough carbs makes sure that body is capable of activating HIF-1 at the important moments.

Now, for the question of does lowering too much LDL, cause problems - yes. Like anything, too much of anything is bad. The point is, you have to reduce LDL to a very low level - but not extinction either. LDL is a part of your cells and cholestereol is present in all mitochondrial membranes for fluidity/speed kinetic. Now, HDL, is more favorable because of its signaling is the cascade you want. HDL is capable of restoring the proper liver LDL uptake via liver stearoyl receptor X (liver receptor X), and restoring proper immune reaction so that the first thing that happens is macrophage invasion is stopped so that there is no more plaque destabilizing, your atherosclerotic plaques stabilizes themselves as the levels of fibrosis element drops (thrombin (causing thrombus formation, thrombosis), and then the body can take care of reducing such plaques, disolvung the clot, reducing LDL-ox, LDL levels and increasing your HDL:LDL ratio. Your liver will produce HDL Over LDL species, and that is the single most crucial important element to reverse atherosclerosis; you need HDL cholesterol to rever it because it alters the genetic/epigenetic landscape to how it is when you don't have atherosclerosis. The plaques will shrink and, indeed, atherolsceorsis is then reversed; as it happened to me, as I stabilized my LDL levels, they drop tremendously and my HDL did not just stay put, it Raised - just as the LDL lowered itself, increasing favorable high HDL:LDL ratio; that's because the liver was producing HDL species over LDL, that's important. The bottom line is the body is made up of cholesterol, it has signaling function and mitochondrial improving function/for mito signaling. Our brains are cholesterol-fat ladden, we need it to think, that's because neurons rely of mitochondrial function, and cholesterol packed inside their membranes allow that, via fluidizing effect instead of viscous effect (slows kinetic, such as compact saturated fat and trans-saturated fat slow membrane kinetic fluidity : the membranes become rigid rather than fluid; which means low ATP and (s)low signal kinetic, and keep create mitochondrial apoptosis of neuron; and it's also why mitochondria take in first Cholesterol, Oleic acid 18:1/Palmitoleic acid 16:1 (monos/MUFA), and Linoic acid 18:2 (polys/PUFA); that's because these fatty acids have the least amount of kinks/least amount of carbon chains and highest fluidity despite having a single or two 'double-bonds' in their chain - which cause ROS/FA perodixation susceptibility (16:1, 18:1, 18:2). But, it is still not enough, and why our brains are DHA/EPA (20:5, 22:6 PUFA) membrane filled, that because they are the most fluidizing of all and allow fast neuron activity from fast mitochondrial ATP. The downshoot is that they are Highly Peroxidizable by increased carbon chain and double-bonds number length (20:5, 22:6); that means more points where ROS can attack it and create volatile peroxidation lipid-end products (ALEs, not AGEs, Advanced Lipoxidation End Products, the cause of protein carbonyls and destruction of mitochondrial membrane upon PUFA oxidiation (Causing these cataclysmic chain of lipid peroxixation)).

To end, I would say, be sure to reduce your LDL above all, but do not remove your Total cholesterol to such low levels that it is dangerous - too low IS dangerous; you need cholesterol, HDL, mostly but some LDL too; the least you can is best but too low is just a bad. The main culprit is LDL being too much and HDL is not high enoughm this completely wacks your immune system towards inflammation and macrophage activation (and platelet clotting hyperactivation too). You want to obtain a favorable HDL:LDL ratio : High HDL, low LDL. This way cholesterol signaling is kept intact by both being still around.

Wishing good luck to anyone who has my disease.

Just a 2 cents.

Posted by: CANanonymity at January 10th, 2019 2:20 PM

I was looking for ways to increase the quercetin and fisetin's bioavailability. One of moderately good solvents for quercetin is alcohol. About 1mg per ml... Then did the numbers of using 3000mg (3 grams) ... that would require about 300ml of pure ethanol... about 750 ml of vodka. This is the most common bottle size of vodka... coincidence, anybody ?

On a more serious note, it would be more important to find a regiment to reduce the pre-existing plaque. Then it could be applied/adhered to periodically. If reducing LDL doesn't reduce the existing plaque then it is just a marginal solution with probably nasty side effects and a diet that is hard to adhere to...

Posted by: cuberat at January 10th, 2019 5:37 PM

Peter Attia, an MD that is something of an expert on the subject and has a recent five hour pod cast on Cholesterol on his site, says ideally you want to be at 20th percentile on the critical metrics. I believe that would be 100mg/dl LDL, 78 APO B, 1100 LDL-P, for adult men. I can not recall details as to why going lower is problematic, but think it is just based on all cause mortality data. Aside, I am planning to start taking low dose Ezitimide as a test.

Posted by: JohnD at January 10th, 2019 10:38 PM

Hi cuberat! Just a 2 cents.

Quercetin, Trans-Resveratrol, Resveratrol and other (trans)stilbenes are good to reduce plaque, found in red wine/red grapes for example. Only low dose alcohol is beneficial and increase bioavailability/ bioabsorption. Alcohol in large doses causes hepatic steatosis, cirhosis, fat accumulation (fatty liver), and, especially, cholesterol accumulation; so, while the health preserving effect of polyphenols of red wine would be helpful, too much alcohol will mess up the cell redox and activate cholesterol synthesis, total cholesterol LDL HDL wouldi ncrease, but the ratio would be worse as LDL specie would overtake HDL; this means the alcohol has negative effect on liver x receptor and makes cholesterases increase by increasing the bad LDL; which, you guessed it, is promoting atherosclerosis. People that have eaten cholesterol rich foods and keep low cholesterol while drining red wine, is because of the tannins/phenols fractions, if removed that wine is poison, due to being pure alcohol. In fact, white wine is less healthy, per say, because the phenol concentration is weak, it's white/transparent lacking pigment/phenols (red phenolic content of red grape-pressed (in red wine)). Wine is 15% alcohol, much too high, 1 glass and it's done. As for beer, 5%, but most people consume way too many beers, and the phenolic content of it is weak, so just 'getting alcohol'. My grand-father died of liver cirosis because he drank so many beers in those days (1940s-50s) by always visiting the overactive bars back then alcohol-filled and smoke-filled, my father would hide the beers as a teenager from my grand-dad. He died at 56 years old of such when my dad was 14.

I would say the best you can do to reduce existing plaques, is controlling your diet, by cutting the largest element; cholesterol intake. That, saved my life, but it was not enough. For existing plaque, cutting cholesterol helps to stabilize them, but, as said, you need more than that. I tried many things, and not many things worked to reduce levels; antioxidants did help, but clearly, no matter how many antioxidants/polyphenols from vegetables/fruits I ate it was not enough to revert, it only slightly slows things; you need more than that to stop it. A few thingss I tried, magnesium, peptidases, melatonin, apple cider vinegar, green tea, doing more exercice (I could not, it would kill me, as it was way too hard and body about to let go anytime), only much later did I very slowly reenter exercising, I played so much with food to find the miracle one, I foud that vegetarian diet was my saviour but I had to make sure to obtain protein/a slight bit of fat too, but cholesterol was cut, completely; which, itself is not good as said - you need it; But, when you are atherosclerosed - no, you don't need it. What you need is for the body to make the Good cholesterol (HDL). So I search some more, I tried b vitamins, d3, vit e, ginseng, gingko, every fricckin spice possible, yeah I tried a shiton of stuff to reduce my disease, but most of it was veryyy slow to do anything, if anything. People forget that Reversing atherosclerosis and the plaques - is a very Long process, it could 1 2 3 years easy, and you will still be frail after; in total could take 10 years to be somewhat back to normal; I am on my year 4 and improving, but I saw new problems, because of epigenetic memory of that event, so most likely my arteries are epigenetically older than my other tissues because of that massive life trauma, sadly, so they could kill me Later (in decades, if I am still alive that is). I noticed I may suffer ischemia, which I Never had before; that's what happens has the 'lingering' effects of life altering event, later can weaken you.

Because of this I might die of a 'stroke' to the brain or some other tissue dying due to lack of O2/blood later on in my frail vasculature. I would say the most powerful things were getting Sleep, 7 hours all the time each night, being very well rested, cutting cholesterol 100% completely gone (I have not consumed 1mg of cholesterol in 4 years, that means a sh*ton of foods that I have not eaten on purpose (to keep alive)), my body took care of the cholesterol and gave the correct HDL I wish, not the LDL. I also would say, magnesium was the most saving mineral of all, that's because it is a powerful antioxidant activator, chromosome repacker, it activates GSH production to restore redox in mitochondrias/ATP (mitochondrial magnesium is a determinant of cell fate, where calcium-load causes mPTP opening loss of its cytochromeC, while magnesium ions antagonize that and protect the cell from its illfated death), also, b12 and D3, melatonin but especially b12 and d3; that's because b12 improves homocysteine levels towards reduction (high homocysteine causes redox imbalance and accelreates plaque formation), b12 is also, like folate, a methyl donor and improves dnmt methylation levels which means epigenetic improvement by improved transcription/reduction of transcriptional drifting. B12 also increase SAMe (s-adenosylmethionine levels, which protect against demethylation and imrpoves atheroscleorsis), While D3, is a ver powerful vitamin, that will completely alter the chain of HDL LDL species, d3 is necessary for cholesterol control and is a life saviour (cholacalciferol, you noticed CHOLA-calciferol, it's not a surprise whiy named so, it has definite cholesterol control in the liver itself and brain, because both have Vitamin D3 receptors, and these receptors activate liver X receptors for cholesterol disposal and inhibition of cholesterol synthesis, or rather, LDL synthesis switched to HDL synthesis). One more thing, studies demonstrated that B12 levels are correlative of LDL/HDL, meaning high b12 is correlative of high HDL:LDL ratio, while low b12 is prevalent in low HDL:LDL ratio (high LDL for HDL molecule).

But, to finsih, only All of these things together do they bring true benefit, over the Years, not a couple of months, it takes yaers to reverse atherosclerosis; stabilize happend quick enough but 'reversal'/plaque shrinking is long...eating vegetarian diet helps greatly and all the polyphenols block hepatic cholesterol synthesis or reverse LDL, for HDL instead. I know that I still have some plaque, and I'm 4 years later, so no, this not overnight thing despite doing basically everthing (except statins or do stents or other 'invasive' operations, statins are good but certainly not better than anything I've done and they have complications, but are good enough for usage, my uncle takes statin and controls his cholesterol, be prepared for life, to combat this once it happens to you. But you Can control it to live a normal life, you Can survive this. Another thing I learned that helped, is a study I read that they did with mice fed Linolenic acid (18:3) in flax seed oil, in this reversed the atherosclerotic lesions/plaques (both) in mice arteries...but don't jump to conclusion too quick; I took flax seed oikl For A Long Time, and it contributed to cholesterol/triglycerides formation in me, it did very little to stop mine as I was taking a Lot of It (and also olive oil, I tried tons of oils...all of them ended up Accelerating fat cholesterol synthesis altogether and not helping), Fatty acids composition of oils is what can revert atherosclerosis: saturated fats, 16:0 (palmitic acid, from palm oil/palm trees), 18:0 (stearic acid, found in cocoa butter - I ate tons of Dark Chocolate, and Still had Atherosclerosis, that means the polyphenols of cocoa are not all that incredible on some people and cocoa/caffeine both activate SIR/inhibit mTOR just like rapamycin, but that's not enough while the polyphenols just like red wine are not enough in dark cocoa), saturated fats increase atherosclerosis (so many studies would say 'no, saturated fats do nothing...', well many atherosclerosed rabbits and monkeys say differently,

and Did Die when they were fed saturated fatty rich diets; now, for Monos/Mono Unsaturated Fatty Aacids (MUFA), 18:1 (oleic acid, named/found from olives but in all other MUFA-rich oils), 16:1 (palmitoleic acid), MUFAs improve mitochondrial membrane fluidity and is why you Can see improvement on MUFA...but, like I said, I consumed Tons of Olive Oil Omega-9 (Extra Virgin with Polyphenol Content intact, not Oxidized Olive Oil), and I still Got Atherosclerosis. Why ? Because one study showed taht MUFAs are also Atherogenic', meaning they Can contribute to atherosclerosis and Do, in certain cases. In my case, that was the case. MUFAs were fed to monkeys again, and you know what ? They died. Extravirgin olive oil, the best, made not difference. That's because fat intake = large chance of cholesterol and triglyceride increase synthesis; and that'S exactly what they saw in these dead animals. Meaning, plaques grew even so, from improved fluidity by MUFAs or theri polyphenolic content. While, lastly, we have the PUFAs (Poly Unsaturated Fatty Acids, Omega-6 and Omega-3), we consume too much high-chain Omega-6 (arichidonic acid, 20:4, found from arachides/peanuts fatty acids; 20:4 activates immune system and creates inflammation signals), while 18:2 linoleic acid improves membrane fluidity but is more peroxidizable than 18:1 (oleic acid, more protected by 1 kink, 18:2, has 2 kinks (double bonds in the chain). It was shown that cardiolipin is special lipid foudn in the heart that is rich in 18:2 and is necessary for it, while it atherosclerosis, 18:2 seemed to restore normal function and did stabilize things. Being 2 kinks offers more fluidity and being short it is relatively resistant (by only 2 kinks). While then, we have 18:2 (linolenic acid, not to confused with linoleic acid (LinoLEIC acid 18:2, LinoLENIC acid 18:3), 18:2 is omega-6, 18:3 is a omega-3. That is the one they say improvement in mice, when they said 18:3 contained in flax seed oil, the mice saw dramatic reduction in plaque size and slowing and reversal of atherosclerosis.

My take is that 18:3 contributes to formation of Higher Chain PUFAs Omega-3, namely, DHA (22:6) and EPA (20:5), both of these are Crucial for fluidity and function, omega 3 DHA EPA imrpoved somewhat atherosclerosis; In my case, when I took Omega 3 is was more bad than good, oxidation by DHA EPA is Very Strong by 5 or 6 kinks in their carbon chain length. And, yes, I took Tons of Omega 3 + Olive Oil + Flax Seed Oil...all Before having atherosclerosis. and none of that stopped anything. So, I want to end by saying, only you can know how you body reacts and how your plaques react; you could be taking statins, warfarins, or other blood thinners to clear your blood, reduce platelet (immune system is important but it is hyperactivated in atherosclerosis, platelets and macrophages are the responsible element at the athersoclerotic lesions that cause ROS formation in vicious cycle, of more plaque formation, more LDL depot, more oxidation, etc), and if you Eat are not helping your cause, it goes right in your arteries. I have noticed that by improving my epigenetic proflie (via b12, folate, cholate, methionine, betain methyl donors) I have gained much more rejuvenating effect because I am slowing the process tremendously in my epigenetically 'aged arteries' ...Just a 2 cents.

PS: Another one is Trans-fats, they are deadly avoid them; except one specific ones, CLA, from cows. It has a lipid lowering effect, I took some to somewhat ok results but I ditched it later when I felt that I lost so much weight and began being frail (which I aggravated the artery stability).

Posted by: CANanonymity at January 11th, 2019 12:11 AM

I eat a vegan diet of only whole foods, NO oils, no added sugar, minimised saturated fat completely, down to 8-12% fat - as advised by cardiologist Dr. Esselstyn.

Beans/legumes, potato/sweet potato, broccoli, green vegetables, 1 brazil nut per day, rye bread -- calorie counted to 2000 calories per day, with liberal amounts of spices to season.

After 6 months, my LDL-C became 60mg/dl, more than halved from when I was eating a balanced diet of meat, oil, and vegetables. No drugs were required. I only spent $7 on a B12 supplement to take weekly based on blood tests showing sufficiency.

It's great that I have reduced my atherosclerosis risk, but I still have to deal wth aging at the end of the day. For the majority of the population, some kind of culture shift may be required to eliminate atherosclerosis without drug intervention.

Posted by: John at January 11th, 2019 4:19 AM

I have had carotid artery and abdominal ultrascans, with the result being that I have no noticeable plaque in my blood vessels and arteries despite being 78. I attribute much of my lack of atherosclerotic plaque to a high HDL level of 80 to 85, and a low platelet count of about 105. I think a drink of one small glass of wine helps with a high HDL level, and the alcohol and polyphenols in the wine help cleanse my vessel walls of any LDL plague.

Posted by: Biotechy Marcks at January 11th, 2019 10:32 AM

PS: I also have a moderately high bilirubin level of 1.8 on account of my genetic Gilbert's Syndrome. The high bilirubin levels in the blood vessels is highly protective of atherosclerosis because it is a strong antioxidant that cleanses the vessel endothelium of ROS particles. Also, I run/walk 12K steps/day or about 6 miles which is very good for my cardiovascular system.

Posted by: Biotechy Marcks at January 11th, 2019 1:51 PM

Hi John and Biotechy! Thanks for that.

''NO oils,'', exactly, this demonstrates that one of the large cause of atherosclerosis is just too fat intake in the form of oils or whatnot. By cutting out these oils, there was dramatic reductiong in LDL cholesterol production. I did the same, I consumed no oils in 4 years and I corroborate with you, the same happened, LDL goes down. Most foods have some small content of fat, which is good as long as teh saturated fat content is nearly nothing; but getting small amounts of PUFA is ok, since your body burns fat for energy, it needs some fuel to provide it energy, glucose is that main one but fats are not alll bad, just we have to be careful of the amount and the type; cholesterol-rich food intake is important culprit in Western diet. And, exactly, a high/increased HDL reverts the plaque process; thus high HDL:LDL ratio (the HDL rises (not just stay still, it must rise also as the body switches to HDL production over LDL), while the LDL lowers (again, it must not stay still, it must lower itself, not just a better ratio by More HDL or Less LDL; you need More HDL, and, Less LDL (by both going inversely up and down, and neither remaining frozen amount). I 100% agree with you that there needs to be more conscientization/awareness to the fact that these diseases are serious stuff and I mean we are not forcing anyone; eat what you wish/whatever diet...but we need to be mor responsable of our eating, I know it soudns dumb to say 'responsable eating' (lol). But, we have to own to it and accept the dangers of eating crap or putting our lives at risk by our 'carefree junkfood culture'; consequences should be more understood shown so people change sooner than later (too late, die).

Biotechy, ItMs incredible because of your age (in a good way) you are a true force of nature (and 12K steps 6miles...oh my I'm half your age and just get tired reading this; it shows that we can be weak in our 40s, 50s, and then it can improve if we 'survive'this long, because I'm not even sure I will reach your great age. many people don't reach 78 or even soon, 80); it's incredible that this syndrome is actually helping and by liver bilirubin overproduction you are better protected; this syndrome greatly mimics what is happening in birds. Like for example, in parrots, they have higher bilirubin/biliverdin/biles production than other animals, most long-lived birds have (parrots, pigeon, crow, albatros, etc), showing that bilirubin is a powerful metal chelator and ROS iron quencher. I guess you could say your 'curse' is your 'cure'.

Thanks it's very informing and heart warming to know, there are people who go through this, and give up a certain hope to push ourselves to fight it, live/survive. Just a 2 cents.

Posted by: CANanonymity at January 11th, 2019 6:00 PM

Wow. As is so often the case, you did not even answer your own question. If you review all the major studies of statins using absolute and not relative statistics, you will find there was no advantage to the use of statins. None on a population basis. No major decrease in all case mortality or decrease in cancer rates. Relative versus absolute statistics is essential to understanding all scientific studies

What is the absolute and not the relative gain in lowering LDL-c to lower and lower levels? What long term study or algorithm validates lowering cholesterol <80? <60? Or even <50? We know that cholesterol is absolutely essential for cell wall membrane stability.

We know from the Framingham study, the longest of any medical study, the cholesterol is a bad "predictor" of heart disease.

The side effect profile of statins is underestimated. Muscle aches, liver enzyme rise, cognitive decline, temporary amnesia.

Atherosclerosis is an inflammatory disease. LDL has been typed as Pattern A and Pattern B. Pattern B is possibly more atherogenic. Pattern A is far less atherogenic.

Finally, imaging. Imaging will show that patients with familial high LDL-c concentrations may actually have zero plaque in the carotid arteries. Whereas other patients with "normal" LDL-c may have considerable plaque.

You did not answer the seminal question. Who is pushing this trend? Who determined that lowering LDL-c to such ridiculous levels is truly beneficial? Dig much deeper. There is more marketing than science here.

Posted by: bodywise at January 13th, 2019 10:54 AM

Hi bodywise! Thank you for that. Just a 2 cents.

I apologize for not answering fully the question (Sometimes I go on tangent)
I meant, that there is not (more) advantage of taking statins, as there are complications to them as you said; but you could take them and see reduction in cholesterol (as did my uncle, he is alive and well, controlled it; my brother-in-law, same thing, taking statins and keeping cholesterol in check), I did not take them because I heard of some those side effects and was quite worried (but, I guess for some people with high cholesterol, their doctors tell them : 'statins' and that'S about it, they take it no questions or they judge the side effects are not enough to overweigh the benefits provided by them, so they take them anyhow because the dangers of atherosclerosis death far outweigh side effects of statins). But, trust me, I'm like you, I do not wish to take statins and am not taking any. And, doing ok, without them.

I am not the one pushing this trend, it is what it is, studies, overall, demonstrate that HDL:LDL ratio is determinant in many of longevity and atherosclerosis risks. People that may have high LDL-c but no plaque
is an another category; I'm not saying that LDL is all bad for you need both but there is more than enough literature showing that LDL is oftenly the culprit or it's a too low HDL, either one - outside of people protected from atherosclerosis whom show high LDL (most likely they have high HDL though). I'm not trying to dictate how you control your cholesterol, eat what you wish and if your LDL is high and you are plaque free; all the best. (For me, it's the inverse that happened). LDL, being low-density, can signal a different 'signal' than HDL during atherosclerotic lesions, which can lead to macrophage invasion/platelet activation/immune activation and cause inflammation enzymes/genes/cytokines (IL-6, TNF, thrombin, C-Reactive, INF, etc). Possibly there is more to the story, such as in certain people high total cholesterol, they can have little or no plaques; which is quite miraculous; there are genetic determinants that may render High LDL and HDL, or low, to not be enough to trigger atherosclerotic plaque formation. Or, like in diabetes, AGEs/glycation, can contribute to glycoxidation and ROS, death of endothelial cells, which can cause ischemia and then plaque instability (glucose is cholesterol synthesis promoter), it's complicated. That much is true, I am trying to dig as deep as possible. What is sure is we need cholesetrol for function but there are many shades of grey still (like why do long-lived centenarians show such high HDL, it means in certain people, this is contribute to long lifespan and atherosclerosis-free; but, probably not everyone because of different genetic signatures and SNPs). And it's true, marketing hype can twist things for sure. Thanks. Just a 2 cents.

Posted by: CANanonymity at January 13th, 2019 8:52 PM

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