"Abnormally low" cholesterol. Should I be worried?

[toasty7718]

These are the results from my blood work done a little less than a year ago

The vegans I talk to say I'm "infarction proof" and "abnormally based" for this. Just curious what your thoughts on this are (I'm a vegan of 3+ years)

Edited June 2 by toasty7718

[undeather]

Pretty sure you have some sort of genetic thing going on since your HDL is also very low.
But yeah, with a LDL-C of 52 you barely going to develop any significant cardiovascular issues until very, very old age. (at least the chanes are high!)

[Michael569]

Beautiful lipid profile  

You know this is the sort of the stuff people should be putting on their dating profile  

Plant based diet doing wonders for your cardiovascular system when done right. You can't make that up, well done! 

Edited June 3 by Michael569

[undeather]

Quote

You know this is the sort of the stuff people should be putting on their dating profile  

"21 years old, computer-engineer, loves to travel and outdoor activitives - 10/10 genotype: PCSK9-mutation carrier (LDL below 5th percentile)"

Edited June 3 by undeather

[Michael569]

12 minutes ago, undeather said:

"21 years old, computer-engineer, loves to travel and outdoor activitives - 10/10 genotype: PCSK9-mutation carrier (LDL below 5th percentile)"

Looking to match with a wealthy ApoE4 homozygous carrier. PCSK9 hyper function - of benefit. 

Note: only respond if older than 60

[toasty7718]

 

[Jason Actualization]

Could someone kindly articulate how ApoB, a mere transport protein, itself causes plaque formation?

[undeather]

1 hour ago, Jason Actualization said:

Could someone kindly articulate how ApoB, a mere transport protein, itself causes plaque formation?

All ApoB-containing lipoproteins <70 nm in diameter can cross the endothelial barrier, especially in the presence of endothelial dysfunction. In the early stages of atherosclerosis, negatively charged proteoglycans (structural components ) in the arterial wall trap apoB-lipoproteins. This happens because of electrostatic interactions with specific positively charged amino acid residues on the ApoB-proteins. 

After that happens, the process of atherosclerosis continues as usual! The trapped lipoproteins will go through oxidiation which creates a inflammatory response, macrophages will enter the arterial wall and start sucking up that delicious cholesterol (which came in through the lipoproteins). Since those macrophages are hungry little scamps and can't stop eating, they will turn into foam cells. This is when you can macroscopicly observe so called "fatty streaks" in the artery. From then on, the plaque continues to grow through various mechanisms until it ruptures and creates in infarct. Voilà - that's how plaque formation works!

[Jason Actualization]

2 hours ago, undeather said:

The trapped lipoproteins will go through oxidiation which creates a inflammatory response, macrophages will enter the arterial wall and start sucking up that delicious cholesterol (which came in through the lipoproteins).

Thanks for explaining, I really want to better understand your position/paradigm. So you would submit that unoxidized Apo-B-containing lipoproteins can accumulate in the endothelium at a sufficient rate to cause plaque formation in and of themselves, and that the primary driver of that is the amount in circulation?

Are you under the impression that the oxidation of these Apo-B-containing lipoproteins is inevitable, and that they truly are trapped in some inescapable sense?

Do you see the atherogenic process as unidirectional, i.e., merely plaque deposition, or do you see it bidirectionally as being a certain rate of deposition, and a certain rate of removal, the net of these two processes, being what we macroscopically appreciate?

Edited June 4 by Jason Actualization
Spelling

[undeather]

1 hour ago, Jason Actualization said:

Thanks for explaining, I really want to better understand your position/paradigm. So you would submit that unoxidized Apo-B-containing lipoproteins can accumulate in the endothelium at a sufficient rate to cause plaque formation in and of themselves, and that the primary driver of that is the amount in circulation?

Are you under the impression that the oxidation of these Apo-B-containing lipoproteins is inevitable, and that they truly are trapped in some inescapable sense?

Do you see the atherogenic process as unidirectional, i.e., merely plaque deposition, or do you see it bidirectionally as being a certain rate of deposition, and a certain rate of removal, the net of these two processes, being what we macroscopically appreciate?

It's not really "my" position - it's what 170 years of atherosclerosis research and discoveries have led us to conclude about humanities biggest killer, cardiovascular diseases. The lipid model of atherosclerosis fits like a glove onto a wide array of observations. Our understanding is, as almost anything in science, incomplete - but the basics are incredibly consistent with reality. 

Yes, Apo-B particle number is the best predictor of plaque progression on a population level. For individuals, we look at a complex spectrum of pathophysiological circumstences - meaning that for some people, ApoB is less of a concern than it is for others. 2 patients with the exact same ApoB exposure can develop different degrees of atherosclerosis - one might have a different phenotype for a specific receptor that allows the ApoB to get into the arterial wall even easier, while the other has an inherited enzyme defficiency which leads to lower rates of oxidation. There are thousands of controlling elements, and also other risk factors that would go into that equation. But one thing they all have in common - if you lower ApoB-particles with drugs, lifestyle, genetic mutations (like PCSK9-mutations) or even apheresis, people slow down - stop - or even reverse some of their atherosclerotic progression. This is ultra consistent across various models and also works the other way around (like in people with familial hypercholesterolemia or a progression of plaque when drugs are stopped)

No, the oxidation of Apo-B is not inevitable - many factors influence the rate of oxidation. The problem is that most antioxidants mainly deal with oxidative processes in the lumen but not necessarily in the arterial wall. This is a bit of a grey area and more reserach needs to be done - but so far, levels of antioxidants don't correlate with plaque reversal to the degree they should if there was something to the oxidation hypothesis.

We know that Reverse Cholesterol Transport happens in every human - HDL particles are able to fish  cholesterol particles out of the lesions -however, this is only possible in earlier stages of atherosclerosis. That's why, in general, higher HDL particle numbers are associated with lower cardiovascular risk. 

No, atherogenesis is not unidirectional - there is a constant build up and removal. But the body can't really keep up with all the supraphysiological levels of Apo-B particles that are present in our blood streams. Once LDL-C (which is a great proxy for ApoB) goes below 70mg/dL (maybe even below 55mg/dL) - we kinda observe a equilibrium where atherosclorosis just doesn't happen in it's usual magnitude.

 

Edited June 4 by undeather

[Scholar]

I have similar results as a vegan, the nurses usually are shocked about it. I'm not aware there are any negative consequences of having low cholesterol.

[Jason Actualization]

I'll just preface by offering you my appreciation. As a fellow healthcare worker, I appreciate you man, and I hope the following expression of a number of different points of concern and contention that I offer, are well-received.

At the end of the day, my hope is that someday soon we will all arrive at a satisfactory understanding of the cardiovascular disease underpinnings, so that we can best inform our, and our patients', daily actions to never need to deal with its consequences.

14 hours ago, undeather said:

It's not really "my" position - it's what 170 years of atherosclerosis research and discoveries have led us to conclude about humanities biggest killer, cardiovascular diseases.

Fair enough, I was just curious if you had any ideas of your own that may diverge from the mainstream understanding.

Nevertheless, given the non-trivial number of times that the target LDL-C has been modified, (as depicted below) i.e., systematically lowered,

my skepticism grows.

In my paradigm however, it's unsurprising that said target has needed to be lowered, because as we lead lives that increasingly facilitate oxidation, most notably high PUFA intake by way of increased "vegetable" oil consumption, the percent of circulation Apo-B-containing lipoproteins that becomes oxidized, also increases. Metabolic disorders also factor into this, because uncontrolled blood glucose levels facilitate glycation, the products of which undergo oxidative modification.

The paradigm I'm operating within would explain why both diabetics and those who smoke (and thus introduce themselves to oxidative stress) cigarettes are both at a much greater risk of heart disease, independent of Apo-B-containing lipoprotein concentrations.

How does the lipid hypothesis reconcile these two observations, i.e., that those who smoke and have poorly controlled blood sugar have a greater ASCVD risk?

13 hours ago, undeather said:

Yes, Apo-B particle number is the best predictor of plaque progression on a population level.

What do you predict would happen if you fed human beings (with the lowest Apo-B on the entire planet) oxidized cholesterol that was devoid of any Apo-B-containing lipoproteins, i.e., just pure cholesterol that had been pre-oxidized prior to consumption?

13 hours ago, undeather said:

But one thing they all have in common - if you lower ApoB-particles with drugs, lifestyle, genetic mutations (like PCSK9-mutations) or even apheresis, people slow down - stop - or even reverse some of their atherosclerotic progression. This is ultra consistent across various models and also works the other way around (like in people with familial hypercholesterolemia or a progression of plaque when drugs are stopped)

My concern is that this, to me, still illustrates a misunderstanding of the root cause of heart disease, and results in us combatting such with a bazooka which invariably introduces adjacent consequences, not least the deprivation of cholesterol cerebrally and the cerebrovascular diseases that could give rise to.

I would rather enter the scene with a sniper rifle and address the root cause here, which I would submit is the oxidative modification of Apo-B-containing lipoproteins, and other things in actual circulation (i.e., in the luminal space) such as phytosterols and red blood cells.

I believe Apo-B is simply a proxy for the amount of oxidizable lipoproteins, but that the rate-limiting step remains oxidative modification. Would you, rather submit that the rate-limiting step is the migration of Apo-B-containing lipoproteins into the endothelium?

13 hours ago, undeather said:

The problem is that most antioxidants mainly deal with oxidative processes in the lumen but not necessarily in the arterial wall.

Once a plaque has formed and continues to grow, how are Apo-B-containing lipoproteins still able to traverse the endothelium?

13 hours ago, undeather said:

We know that Reverse Cholesterol Transport happens in every human - HDL particles are able to fish  cholesterol particles out of the lesions -however, this is only possible in earlier stages of atherosclerosis. That's why, in general, higher HDL particle numbers are associated with lower cardiovascular risk.

Gotcha. When you said "trapped lipoproteins" my concern was that you were unaware of reverse cholesterol transport. HDL is an important piece of the puzzle, I would agree.

13 hours ago, undeather said:

No, atherogenesis is not unidirectional - there is a constant build up and removal. But the body can't really keep up with all the supraphysiological levels of Apo-B particles that are present in our blood streams. Once LDL-C (which is a great proxy for ApoB) goes below 70mg/dL (maybe even below 55mg/dL) - we kinda observe a equilibrium where atherosclorosis just doesn't happen in it's usual magnitude.

So painting with broad strokes, you would agree that net plaque deposition occurs when the rate of build up exceeds that of removal?

Are you of the mindset that Apo-B is necessary (but necessarily sufficient) for atherosclerosis to ensue, and that if, hypothetically, we had none in circulation, plaque formation would be an impossibility?

Lastly, I'm not sure that I understand your notion of "supraphysiological levels of Apo-B particles" as that would seem to suggest that modern humans are behaving in a way that renders higher Apo-B-containing particles in circulation than would otherwise be physiologically plausible. If so, could you please detail what that/those specific behavior(s) is/are, and if possible, what a physiologic amount of Apo-B in circulation would be?

Thank you.

[MarkKol]

Nice, I’m not sure how you deal with eating only vegan foods. I wouldn’t be able to tolerate it. Or consuming less than 2000 calories.

[undeather]

2 hours ago, Jason Actualization said:

I'll just preface by offering you my appreciation. As a fellow healthcare worker, I appreciate you man, and I hope the following expression of a number of different points of concern and contention that I offer, are well-received.

At the end of the day, my hope is that someday soon we will all arrive at a satisfactory understanding of the cardiovascular disease underpinnings, so that we can best inform our, and our patients', daily actions to never need to deal with its consequences.

Fair enough, I was just curious if you had any ideas of your own that may diverge from the mainstream understanding.

Nevertheless, given the non-trivial number of times that the target LDL-C has been modified, (as depicted below) i.e., systematically lowered,

my skepticism grows.

In my paradigm however, it's unsurprising that said target has needed to be lowered, because as we lead lives that increasingly facilitate oxidation, most notably high PUFA intake by way of increased "vegetable" oil consumption, the percent of circulation Apo-B-containing lipoproteins that becomes oxidized, also increases. Metabolic disorders also factor into this, because uncontrolled blood glucose levels facilitate glycation, the products of which undergo oxidative modification.

The paradigm I'm operating within would explain why both diabetics and those who smoke (and thus introduce themselves to oxidative stress) cigarettes are both at a much greater risk of heart disease, independent of Apo-B-containing lipoprotein concentrations.

How does the lipid hypothesis reconcile these two observations, i.e., that those who smoke and have poorly controlled blood sugar have a greater ASCVD risk?

What do you predict would happen if you fed human beings (with the lowest Apo-B on the entire planet) oxidized cholesterol that was devoid of any Apo-B-containing lipoproteins, i.e., just pure cholesterol that had been pre-oxidized prior to consumption?

My concern is that this, to me, still illustrates a misunderstanding of the root cause of heart disease, and results in us combatting such with a bazooka which invariably introduces adjacent consequences, not least the deprivation of cholesterol cerebrally and the cerebrovascular diseases that could give rise to.

I would rather enter the scene with a sniper rifle and address the root cause here, which I would submit is the oxidative modification of Apo-B-containing lipoproteins, and other things in actual circulation (i.e., in the luminal space) such as phytosterols and red blood cells.

I believe Apo-B is simply a proxy for the amount of oxidizable lipoproteins, but that the rate-limiting step remains oxidative modification. Would you, rather submit that the rate-limiting step is the migration of Apo-B-containing lipoproteins into the endothelium?

Once a plaque has formed and continues to grow, how are Apo-B-containing lipoproteins still able to traverse the endothelium?

Gotcha. When you said "trapped lipoproteins" my concern was that you were unaware of reverse cholesterol transport. HDL is an important piece of the puzzle, I would agree.

So painting with broad strokes, you would agree that net plaque deposition occurs when the rate of build up exceeds that of removal?

Are you of the mindset that Apo-B is necessary (but necessarily sufficient) for atherosclerosis to ensue, and that if, hypothetically, we had none in circulation, plaque formation would be an impossibility?

Lastly, I'm not sure that I understand your notion of "supraphysiological levels of Apo-B particles" as that would seem to suggest that modern humans are behaving in a way that renders higher Apo-B-containing particles in circulation than would otherwise be physiologically plausible. If so, could you please detail what that/those specific behavior(s) is/are, and if possible, what a physiologic amount of Apo-B in circulation would be?

Thank you.

Jason, we already had a lengthy exchange about this topic like 6 months ago - so I will keep it short! 

1) The reason the LDL-C targets are constantly lowered is because of the mounting evidence that lower is better. Trial after trial show additional benefits of more aggressive lipid lowering - the feared J-curve or U-curve effect just does not appear. Blood pressure recommendations show a similar pattern, which also makes sense.

2) Smoking, diabetes and hypertension are 3 huge risk factors of atherosclerosis - mainly because of their propensity to cause endothelial activation. Chemical modification (aka oxidation or glycolisation) of lipoproteins is an important part of atherogenesis and especially smoking strongly increases the proportion of ox-LDL - which makes them enter the arterial even easier. There are multiple risks factors that can modify ASCVD-risk through various mechanisms. Of course there are! But one thing that still stands above all of them - if you take away the ApoB-particles - even in presence of smoking or diabetes - then plaque burden reduces DRASTICALLY! - Far more than what quitting the cigarettes would have done on it's own. People with lifelong low ApoB (through genetic mutations) just don't develop the same quantity/quality of atheroclerosis, even in context of other risk factors like diabetes, smoking, hypertension etc. This has been shown again and agian in mendellian randomization studies. Of course, the aim for me as a doctor is to improve all risk factors - first through lifestyle intervention whenever possible - but lipids are just such a major player in this whole game. Observations just fit the model perfectly.

3) I don't know if feeding someone ox-Cholesterol would do something - especially because much of the dietary cholesterol doesn't really get absorbed - not sure how the NPC1L1-transporter in the intestines would deal with ox-Cholesterol. But I get your hypothetical: Of course, if you would increase ox-LDL in the blood, then yeah, you would  see an increased tendency of those particles to enter the arterial wall - which would likely end up with more atherogenesis. I am not saying oxidation is not important!  If you want to reduce the general oxidative bruden (through diet, movement, stress reduction...)- then Iam with you. But the problem with that hypothesis  (the true culprit being oxidation) is that histopathological/biochemical observations (mechanisms of plaque build-up/oxidation happening mainly in the arterial wall), mendellian randomziation data, and many, many intervention trials (increasing antioxidative potentials) just don't show the effect sizes if said hypothesis was true. On the other side we have a SHITTON of evidence - propably one of the most studied areas in the field of medical sciences - that reducing Apo-B particles is causally correlated with a highly reduced ASCVD-risk. 

4) Net plaque deposition occurs when the rate of build up exceeds that of removal! Yes! 
Yes, hypotheically, if we had zero ApoB in our system - atherosclerosis propably wouldn't occur. Without ApoB- there wouldn't be any lipoproteins left, except HDL.
Supraphysiolgoical, meaning "more than our body can handle". Our lipid-profile is, to a large degree, genetically determined - someone with a very, very bad lifestyle can improve their Apo-B around 30-40% (on average). Yet if everyone would live a healthy lifestyle, we would still see Apo-B concentrations above the atherogenic-threshhold. Antagonistic pleitropy (in the evolutionary sense) can explain this pretty well imo. 

Anyway, I will be on vacation for the next week - so not gonna respond any further!
Cheers

[Jason Actualization]

To anyone reading this, I would just honestly ask you to explore the possibility that the mainstream medical establishment has committed a cognitive blunder with ramifications spanning far and wide.

Ask yourself if it really makes sense that we are artificially lowering our cholesterol below physiologic levels via the addition of a drug, which will almost certainly stifle the amount of cholesterol your brain needs to thrive, and your body needs to be hormonally optimized.

Consider the oddity of the fact that our LDL target is continually decreasing, and the possibility that the oxidative modification of such, is perhaps the necessary, rate-limiting step for atherosclerotic development and progression, which we should be targeting.

Consider the migration from a sole fixation on LDL, to now ApoB, as opposed to starting over from scratch, and building back our model from the ground up.

We need a model that reconciles the fact that atherosclerosis rapidly progresses in rabbits who are fed pure, oxidized cholesterol, null and void of ApoB, LDL, or any lipoprotein for that matter.

I recognize that this would be inhumane, but I often genuinely wonder how folks would interpret a study like this, replicated in humans, assuming it did indeed elicit rapid atherosclerotic activity as I predict it would. Could they finally relinquish their ties to the prevailing LDL/ApoB paradigm?

Honestly, what is it going to take to see the truth?

Take care friends.

[Jason Actualization]

On 6/3/2024 at 6:10 AM, toasty7718 said:

These are the results from my blood work done a little less than a year ago

The vegans I talk to say I'm "infarction proof" and "abnormally based" for this. Just curious what your thoughts on this are (I'm a vegan of 3+ years)

Has your TG:HDL ratio been that high historically?

At ~3 it is certainly fair, but lower would be even better (2 or  even below 1 for example).

[Carl-Richard]

On 4.6.2024 at 3:52 PM, Scholar said:

I'm not aware there are any negative consequences of having low cholesterol.

 

Quote

Although the risks are rare, very low levels of LDL cholesterol may be associated with an increased risk of:

• Cancer
• Hemorrhagic stroke
• Depression
• Anxiety
• Preterm birth and low birth weight if your cholesterol is low while you're pregnant

https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/expert-answers/cholesterol-level/faq-20057952

I don't know anything about this by the way  

Edited June 9 by Carl-Richard

[Jason Actualization]

2 hours ago, Carl-Richard said:

 

https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/expert-answers/cholesterol-level/faq-20057952

I don't know anything about this by the way  

The most appropriate response to which, would seem to be "YIKES" and yet nobody is ringing the alarm bell amidst the rampant use of drugs that indiscriminately lower such.

Once you appreciate the necessity and sufficiency of oxidative stress in promoting heart disease, it becomes apparent that targeting a lower cholesterol is profoundly inadequate and introduces adjacent consequences approximating the drool dribbling down to the lip and chin of a demented resident in an aged care facility.

Here are the keys to the kingdom my friends, (if you never want to develop heart disease, dementia, or any of the thousands of so-called "diseases" that are downstream of the upstream oxidative stress) listed in descending order of importance, at least in my estimation, although I personally go out of my way to satisfy each of the following:

1. AVOID AT ALL COSTS notable pro oxidants such as: industrial seed oils, (corn, canola, cottonseed, soybean, sunflower, safflower, ricebran and grapeseed) smoking of any sort but most notably cigarettes, alcohol ingestion, exposure to air pollution, toxic heavy metals, pesticides/herbicides, excess UV exposure and radiation, for example emitted via medical procedures such as X-rays.

2. Get more antioxidants in your system (you may prefer nuts, seeds, and leafy greens, but I prefer pomegranate juice or wild blueberries in concert with vitamin C and E supplementation). If you do opt for supplementation, please just ensure your formulation offers not merely alpha-tocopherol, but too, gamma-tocopherol in your vitamin E supplement. 500mg of Vitamin C in supplement form is all you need to take at a time, twice a day if possible.

3. Be metabolically healthy (assess your fasting insulin and/or A1c in concert with your HDL and triglycerides to put your finger on the pulse of this). The reason that poor glucose control so greatly correlates with the modern diseases of civilization is that advanced glycation end products (AGEs) often undergo further oxidative modification. Excess iron can also introduce undesired amounts of oxidation, so ensuring that your ferritin does not creep too high is furthermore prudent, as is offloading such via whole blood donations as deemed appropriate.

4. Consume, if possible, 9x more (combined) saturated and monounsaturated fat relative to polyunsaturated fat (PUFA). Given that most folks here tend to lean plant-based, I would recommend prioritizing monounsaturated fat sources that are low in PUFA, such as macadamia nuts, to accomplish this.

Now, as you read this, if you found yourself nodding in agreement while reading the first three points, but cringing your nose at the prospect of prioritizing saturated and monounsaturated fats relative to polyunsaturated fats, I leave with the following to ponder:

Consider that the chemistry doesn't lie, is infallibly reproducible, valid, and more fundamental than are human outcome trials.

Consider that a higher saturated and mono fat to poly fat ratio has the same outcome as the first three points that you were nodding to, in that it reduces overall oxidative stress.

When the chemistry asserts that 2+2 = 4, question the pharma-funded human outcome data that says it "should" equal 5.

Do not outsource the arithmetic, plug and chug the numbers for yourself and see if it makes sense what we've been told about saturated fat and cholesterol.

I hope this reasoning resonates with you my friend.

[toasty7718]

11 hours ago, Jason Actualization said:

1. AVOID AT ALL COSTS notable pro oxidants such as: industrial seed oils, (corn, canola, cottonseed, soybean, sunflower, safflower, ricebran and grapeseed) smoking of any sort but most notably cigarettes, alcohol ingestion, exposure to air pollution, toxic heavy metals, pesticides/herbicides, excess UV exposure and radiation, for example emitted via medical procedures such as X-rays.

lmao

[Jason Actualization]

11 hours ago, toasty7718 said:

lmao

I hope you develop an appetite for a slice of humble pie over the next decade, because that's what's on the menu.

You will one day be thoroughly disgusted by the depth and breadth of human havoc downstream of these industrial oils increasingly inundating the modern food supply chain, and this moment in history will be seen for the clown act that it effectively is (i.e., the mainstream misunderstanding of cholesterol, the widespread dispensation of cholesterol-lowering medications, the demonization of saturated fat and the abominable advocacy of "heart-healthy" "vegetable" oils.

Hold on to your hat my friend.

Edited June 10 by Jason Actualization
Punctuation.