> med > lipidologie > lipoproteins > ldl-size-and-heart-disease-small-dense-vs-large-fluffy-dr-william-cromwell-nutrition-made-simple

LDL size and Heart Disease (small dense vs large "fluffy") | Dr. William Cromwell

Nutrition Made Simple! - 2023-12-11

Is it safe to have high LDL as long as it's large and "fluffy"? Is LDL size a key determinant of risk? 

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References:
1-https://jamanetwork.com/journals/jama/article-abstract/374290
2-https://pubmed.ncbi.nlm.nih.gov/15296705/
3-https://www.ahajournals.org/doi/epdf/10.1161/CIRCULATIONAHA.108.819359
4-https://europepmc.org/article/med/10499189
5-https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.111.073684
6-https://academic.oup.com/jcem/article/88/10/4525/2845681
7-https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.105.565135
8-https://www.sciencedirect.com/science/article/pii/S0021915006002590
9-https://www.lipidjournal.com/article/S1933-2874(21)00248-8/fulltext

Disclaimer: The contents of this video are for informational purposes only and are not intended to be medical advice, diagnosis, or treatment, nor to replace medical care. The information presented herein is accurate and conforms to the available scientific evidence to the best of the author's knowledge as of the time of posting. Always seek the advice of your physician or other qualified health provider with any questions regarding any medical condition. Never disregard professional medical advice or delay seeking it because of information contained in Nutrition Made Simple!.

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0:00 Intro
1:40 Small LDL is associated with risk
3:48 LDL size vs number
7:09 ApoB, lipoproteins and risk
9:16 Eliminating confounders
11:22 Genetic lessons
14:25 Small LDL keeps bad company
15:25 Summary & Takeaways

@georgehornsby2075 - 2023-12-11

Incredibly clear communication by him without oversimplifying. You may have competition...

@MindVersusMisery - 2024-02-02

I know that you were just joking, but I'd like to say that in pursuit for truth, there shouldn't be competition, but cooperation. 🙂

@Firebuck - 2023-12-11

Dr Cromwell is amazing at breaking down this complex topic! I'm not a clinician nor a statistician but even I could follow his nuanced explanation.

@alfonso365 - 2023-12-11

Best nutrition channel in the world

@HakuCell - 2023-12-11

7:32 over 90% of ApoB particles are LDL [however in a previous video, the same expert said that in most people LDL-C doesn't track well with ApoB, unless your LDL-C is very high or very low, so i'm left a little confused as to which one i should test, also considering that idk the ideal ApoB ranges.].
7:41 here are the more atherogenic ApoB particles (the bigger ones are less atherogenic).
11:08 small and large LDL particles are equally atherogenic [this seems to contradict what i wrote in the line above].
11:20 the LDL in familial hypercholesterolemia is large [and not oxLDL, i might add], yet the people with such condition have early events and cardiovascular disease.
11:59 we used to think that small was worse than large.
12:31 large and small are equally associated with heart attack, stroke, and events.

@nichtsistkostenlos6565 - 2023-12-11

Regarding your first question, I could not find when he said the LDL-C doesn't track well with ApoB for most people, can you give me the timestamp from the other video? The only reference I remember and could find was him explaining that if you have a high amount of Triglyceride Rich Remnants, that this was the cause for the discrepancy between ApoB and LDL-C as it relates to risk, but this was not typical.

@demonfedor3748 - 2023-12-11

LDL and LDL-c are two different things. LDL is the number of LDL particles,LDL-c is the amount of cholesterol inside these LDL particles. If you want the most accurate one-measure apoB and the lab usually has the intervals for that. Quick google search says less than 100 mg/dL( some other sources say 40-120 mg/dL) is good. The lower the better.

@HakuCell - 2023-12-11

@@nichtsistkostenlos6565 the video is titled "What causes heart disease? | Dr. William Cromwell" and the part on the discordance between LDL-C and ApoB starts at 10:05.

@HakuCell - 2023-12-11

@@nichtsistkostenlos6565 i have found the part of the video you're looking for but for some reason my comment reply isn't publicly visible :( oh, this one reply is visible! let me edit it real quick: the information you're looking for starts at 10:05 (in that other video by Gil with the same expert).

@junyuanchia6388 - 2023-12-12

LDL-C refers to the cholesterol content carried by the apolipoproteins, whereas LDL-P refers to the number of LDL particles.

In most people, apob tracks well with ldl-p

@fayem4091 - 2023-12-11

I am super early!
Love from an other (soon to be) dietitian from Greece!
Keep up the great work mate for both the public and us scientists all around the world!

@SM_RD - 2023-12-11

So many people are still attached to the belief that you don't have to be concerned with LDL as long as they are large particles. It's definitely gonna take some time to change this common misconception.

@Godfryd23 - 2023-12-11

Most people have no idea that there is difference type of LDL particles. 😂

@AZ89231 - 2023-12-11

It’s not a misconception. An interaction term for the LDL size phenotype must be added to the multivariate adjustment model with both subtractions which gives a clear picture that lbLDL are not associated with ASCVD in the absence of genetic perturbations.

Just bc Cromwell and Gil say it, doesn’t mean it’s gospel.

doi:10.1097/MOL.0000000000000824.

@jackbuaer3828 - 2023-12-11

@@AZ89231 Cromwell said size is not irrelevant, and it's a factor, so that seems consistent with what you're saying. Cromwell also said a high number of large particle size is not good. It does not appear to me that you're refuting that. As far as I can tell, the abstract of the reference you provided does not refute that in any manner. I did not read the full paper though.

@vadimesharak726 - 2023-12-11

Plus, it is very sad to hear the word "significant" in the matter of total less than 2% in overall.

@volos_olympus - 2023-12-12

@@AZ89231One study does not invalidate all meta-analysis.

@stellasternchen - 2023-12-11

This is a video everybody eating low carb/keto/carnivore needs to see. Influencers in that area only showing people half of the information, despite it is nothing incredibly new, comming to dangerous conclusions. There has been boycotting of statins, mistrust in primary care providers and their advice, self interpretation of blood test results if you look at the comments of such videos. Difficult to see, yet ineffective discussing with those people. Half truths are extremly dangerous. Thank you for this video, an honour to hear from such an expert that my understanding of the topic is not wrong.
I have a question though that has not been answered in this interview. In what cases does the determination of particle size sense in order to not overlook elevated risk, when you have somebody witout risk factors? As Dr. Cromwell was explaining the idea to look at particle size was given by the fact that there are individuals without otherwise detectible risk factors having myocardial infarctions.
Family history would come to my mind. In diabetics and insulin resistance you would have elevated TG, so that would give a hint at small particle size, thus not needing advanced lipid testing? Or am I wrong in that regard?

@markotrieste - 2023-12-11

Sorry but I don't see anything disproving low carb diets. Listen carefully at 14:34. If you focus on the problem of metabolic syndrome (in other words, talk about the obesity epidemics rather than familial hypercholesterolemia), then indeed what happens is a huge amount of small dense LDL. And if the problem is insulin resistance, then fasting and low carb are proven ways to solve it.

@stellasternchen - 2023-12-12

@@ChappySinclair
You misunderstand me. Not saying it is a gimmick. I did low carb myself for a time.
I‘m against spreading medical misinformation. Every diet has a downside. You need to know what it is to counter balance it and to estimate the risk vs benefit going on such diets.

You can adjust the fats in low carb if you find your LDL-C rising to much.
It also might not be the diet that is causing high LDL-C, a big part is genetics. But with the misinformation out you simply might dismiss it as harmless not listening to your doctor about it.

We are also talking about long term consequences of high LDL-C, not short term, arteriosclerosis develops over decades. Short time elevated LDL-C is not that tragic, long term is. If you read about the critique on low carb you will find exactly that, the worry about long term effects.

It is also an option to do a diet long term + taking medication to counteract the negative effects of high LDL-C.

The worst thing to do is ignoring a problem by just talking it away as if it does not exist.

@pomberry3591 - 2023-12-12

@@ChappySinclair people improve when they stop overeating, stop eating ultra processed foods, and stop drinking alcohol. If low carb is the best way for someone to stick to these things, that's great! But at the end of the day, regardless of your diet, if your healthcare provider flags something in your blood work you should probably do something about it (including getting a second opinion if needed).

@dudea3378 - 2024-03-07

​@@markotriesteThe entire country of Switzerland is proof against low carb 😂. They eat bread 5 meals a day and give zero F's. Low rate of obesity and diabeetus. Difference is they have real bread. Low carb is an American thing. We don't have real bread here, it's more like an industrial foam 😢

@krh7150 - 2024-10-11

@@dudea3378Even the home baked bread with simplest and best ingredient still spikes my blood sugar. Life style is another important factor. Europeans move much more on regular basis

@douglasharrington687 - 2023-12-11

One of the best clear and concise summaries of particle size, particle number, and interactions as it relates to CVD risk. Thanks.

@AlwaysSeekingTruth13 - 2023-12-11

Thank you for covering this important and misunderstood topic, Gil.

@DenisMacDougall-hu5ep - 2023-12-11

A clear concise explanation of a very complex topic. Reinforces the importance of lowering Ldl and Apo B.

@dekyor9547 - 2023-12-11

Covering every excuse from their book! Good job!

@scienceislove2014 - 2024-08-08

You're a breath of fresh air..
My mum just sent me an article dr. William davis (he claimed to be a cardiologist) saying how bad grains are.. and how eating pork and bacon is not what causes cvd..
And how small size ldl is the real problem..
I knew I couldn't me misled ...so headed over to your channel..

He literally lacked basic understanding of established science..
Some supposedly educated commenters who claimed to be mds themselves even said "high ldl is a result of bad metabolism.. it's a symptom like fever".. and that "plaque is there to heal after the clotting.."..

@xthechar - 2023-12-11

Pairing with a creator with a very good ability to explain complex statistical topics (like 3Blue1Brown or Stand-up Maths, for example) to explain the suppressor variable effect would be fantastic. There wasn't enough time in this conversation to dive into it but I think presenting the exact way that that it affected the particle size analysis would be fascinating and help people really come to a personal and complete understanding of this subject. Some might wave this explanation off as that the extra analysis isn't honest and just serves to let the researchers arrive at the conclusion they wanted to arrive at. That's not the case, but bringing the viewers to a place where they can really internalize why that extra analysis is necessary would really solidify the point and the message. Also, math is awesome!

@tarunleft123 - 2024-04-04

Gill, I appreciate the scientific rigour in all your videos and your passion to improve scientific communication. I strongly feel it would be much better if you use a professional camera to shoot your videos and also change the display picture of the youtube channel which is very over exposed and you are not at all visible.

@hannesforster1845 - 2024-10-15

Excellent as always. Thanks to both of you!

@mybjj9643 - 2023-12-12

That was very good, thank you. Although baffling not even a mention of Lp(a), even when discussing the most concerning ApoB containing particles. Lp(a) certainly should have been included.

@paulelkins425 - 2023-12-12

Fantastic explanation of a very confusing subject. Sure wish he would have also addressed the added risk of the dreaded Lp(a) particles. Maybe a great follow up topic?

@JamesCrockart - 2023-12-12

I got the impression that you wanted to say that LDL is not that significant unless you are insulin resistant, suffering from metabolic syndrome or are diabetic. You kind of hinted at that but maybe I'm reading to much into it. Enjoying your videos. Thanks.

@MultiKoliber - 2024-02-26

14:15 he just says that a lot of ldl is bad no matter the size. And about metabolic issues was that some of them are associated with high LDL. You misstated the point

@dsg3213 - 2023-12-11

Excellent presentation. My doctor is one who still believes large particles are less concerning than small. I've been reading several studies on cholesterol, but most seem to concentrate on cardiovascular outcomes. I would love to have you address overall mortality in relation to cholesterol levels.

@olyav5819 - 2023-12-11

Thanks for explaining this topic.

@azdhan - 2023-12-11

Great video! Many thanks for this Dr Carvalho

@johntousseau9380 - 2023-12-11

Excellent video! This was very interesting.

@drderrickchua - 2023-12-25

Why did people start differentiating between different LDLs if typical laboratory blood exams don't separate such in the first place?

@georgeelgin3903 - 2023-12-12

it's a question of ""Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to ... " and how particle sizes pro[de]mote this trigger mechanics,"

TriGlycerides are just as good a proxy for metabolic [insulin] disease as any other.. This idea of confounders [supressor variables] obscuring causation might mean something to him, but to me it is only the cross correlation that is confounding his hand waving argument. Mathematically these are the eigenvalues of the co-variance matrix of paramenters [ this is distinct from Factor Analysis yet more multivariate calculus]

@georgeyoung2123 - 2023-12-11

Can you get Dr. Cromwell to comment on how he currently treats elevated Lp(a) levels as there is no approved drug to lower that LDL type . Thank you.

@ladagspa2008 - 2024-01-07

High lp(a) risk (above 100mg/dl) is addressed by crushing ApoB via diet and statin even in absence of other risk factors as per European Heart assoc consensus statement

@superfinevids - 2023-12-11

Its not the size that matters, its how you use it. Thanks doc for the reassurance. 😂

@Battery-kf4vu - 2023-12-12

I'd have liked to have his opinion on the cholesterol paradox, ie the fact that low ldl is associated with higher mortality, especially in older people. Is it really fully explained by the fact that diseases that lead to death tend to lower cholesterol? (reverse causation )

@robertusga - 2023-12-17

Yes, unless you have outcome data to the contrary

@shauna996 - 2024-04-22

Yes, and why do most heart attack and stroke victims have normal or low ldl levels.

@marcjacobson757 - 2023-12-11

Definitely the most concise and understandable explanation I’ve heard of why risk tracks with number versus size, as well as how the confusion over particle size got started in the first place.

@nickf2170 - 2024-08-13

So what is a max number of pattern B small dense LDL that would be considered a real concern?

@zinebtlaiha9573 - 2023-12-12

Thank you for covering this topic in great detail 😊

@realfoodcures - 2023-12-16

LDL is an opsonin, meaning it prepares a bacterium to be eaten by a phagocyte. LDL is part of the immune system and goes up during infection. Once you input this missing factor, infection, then everything makes sense.

@robertusga - 2023-12-17

Now go learn the difference between LDL and LDL-c ;-)

@Suree.Lifestyle - 2023-12-11

Is there a partially empty bottle of whiskey on the desk behind Cromwell?

@esotericsolitaire - 2023-12-12

Looks that way. Moderate drinking helps the heart. The brain is a different story (cerebral hemorrhage).

@bendeguzacs6700 - 2024-06-05

Yes, but the whole background is computer-generated, like a filter

@paulmaxwell8851 - 2023-12-17

We already know that our LDL lab results really measure LDL-cholesterol: the cholesterol within the particles. It's used as a sort of proxy, to guess at particle numbers. It doesn't measure particle numbers. Is this really a useful number, when particle count is what truly matters? Is ApoB the only useful number available, and why isn't it used routinely? By the way, the latest research has clearly shown that LDL-cholesterol does NOT directly cause cardiovascular disease. I believe Dr. Carvalho has a video on this.

- 2023-12-11

Thank you for the amazing content Gil! The part about FH is really interesting too.

@Joseph1NJ - 2023-12-11

So, all LDL particles are atherogenic, but some more than others, and the fewer of both, the better?

@nanduthalange7736 - 2023-12-11

No - all LDLs are equally atherogenic

@Joseph1NJ - 2023-12-11

​​@@nanduthalange77367:40, is VLDL not LDL? "VLDL not so much." I'm still sticking with what I said unless someone clarifies this. Also I did not say "equally."

@rsalehi6568 - 2023-12-11

It appears that he is saying the small particles seem to be worse because there are too many of them, and the bigger ones seem worse because they are equivalent to a few small particles.

I think until they don't explain the mechanism of action of how these particles interact with and enter the artery walls, it is all a mathematical model.

@paulmaxwell8851 - 2023-12-17

No we do not know that. All are dangerous, but we have yet to understand exactly how relatively dangerous each is. @@nanduthalange7736

@Joseph1NJ - 2023-12-21

@@rsalehi6568 He said the larger ones, VLDL and chylomicrons "not so much because they're so large they don't get into the artery wall."

@anathardayaldar - 2023-12-11

Sounds like yet another blood test that adds to the medical bill.
Can the patient let it wait until they are referred to a lipidologist?
So not part of the screening panel?

@littlemswolf - 2023-12-11

Thanks for a great video!

@jmca_power - 2023-12-18

Great video Gil, thanks

@lindalarue1722 - 2023-12-11

Is testing for particle size useful if you have a low LDL level? Mine is calculated to be 39 mg/DL. Total cholesterol is 120 mg/DL, and HDL is 61 mg/DL.

@veganfortheanimals6994 - 2023-12-11

Good info, Doc and Doc

@adriansrfr - 2023-12-14

Small dense (damaged) ldls are typically damaged via glycation and/or oxidation. It cannot bind to receptor so stays in body with nowhere to go. Typically seen with high triglycerides.


Sdldl is a Hallmark of metabolic syndrome

@drott150 - 2023-12-11

Labcorp offers LDL particle (LDL-P) tests. But what numerical ranges in particle size and number are we supposed to refer to when interpreting our results and assessing possible risk? Dr Cromwell seems to have numerical sizes and ranges in mind associated with risk…how can we learn what those ranges are? (or appear to be at this point in time based on the current state of research?)

When Dr Cromwell talks about one particle blocking another, is he referring to a testing error or a data analysis error? He seems to say it's a data analysis error. I thought the test LDL-P results are very straightforward: a direct count and size measurement is provided with no ambiguity and that's it. What am I missing here?

@jp7357 - 2023-12-11

Haven’t you posted this before ? The bottle of,scotch is still on his desk.

@sophiekarnak3936 - 2023-12-12

That's a digital background, there are a few places in the video where the effect breaks up around the left side of his body (looking at the screen, so his right arm). Watch between the 12-13 minute marks.

@vo6888 - 2023-12-18

I heard Niacin (B3) can lower LDL. Is it True? Then why we still need Statin?

@jp7357 - 2023-12-11

Mine are small, friendly, smoochy and bouncy … friendly ldl particles are not atherogenic as it would be considered rude.

@BB-jn4dh - 2023-12-18

Hello. I understand cholesterol goes up in those with Hashimoto's diease mainly due to non diet related issues; apparently mechanism for which is not clear(?). I would really like it if discussions/ another video could be made addressing heart health and other symptoms like brain fog, fatigue etc be addressed even whilst being on thyroxine and having correct lab test results. Thank you.

@jedinxf7 - 2024-05-25

so why do lipid panels universally prioritize LDL-C over LDL-P in how they report results?

@renus6015 - 2023-12-18

my trig - 41mg/dl, ldl - 96mg/dl, hdl- 69mg/dl, small dense ldl - 49mg/dl. Am doing low carb diet.....can low saturated fat diet help to reduce small dense ldl?

@izackvail - 2023-12-11

Dr Cromwell and Gil talk about APOB in terms of particle number but my understanding is that APOB is expressed in mg/dl which is a measure of weight and not a measure of particle number. Where as LDL particle is measured in terms of nmol/L which is a true particle count. Am I understanding that correctly? So I have seen blood results where particle count is high but APOB is low. This seems to be indicative of a large concentration of small particles. i/e weight is low (APOB) but particle number is high (LDL particle count). So I am still a bit confused when he says the important factor is particle count and the important value is APOB. When APOB is not measure in these terms (from what I understand).

@PhoenixTTD - 2023-12-12

From his examples, it seemed the risk from large LDL came from genetic conditions. Are there differences in the causes and remedies of large LDL as opposed to small particles? And if I am understanding correctly, we are still concerned with particle numbers, not total cholesterol, so if the cholesterol is a little higher but in fewer particles because they are large, it is lower risk than the same amount of cholesterol in a larger number of small particles?