Tuesday, February 16, 2010

Large LDL and small HDL particles: The best combination

This post has been revised and re-published. The original comments are preserved below.

21 comments:

water said...

cool! Thank you for an interesting post

Ned Kock said...

You are welcome; thanks for dropping a note.

I am still trying to figure out why we have so many LDL particles in circulation, given that chylomicrons are cleared much faster. I hope I will get there some day.

Venkat said...

Thanks for this post Ned. I used to see your comment in Stephan's blog but was not aware that you are also blogging. Nice to know.

Your style is easy to understand, please continue your service.

Thanks

Venkat

Anonymous said...

Hmm, so are you suggesting that there are three seperate molecules involved:

a) chylomicrons
b) VLDL/IDL/LDL
c) HDL

and that the only difference between VLDL/IDL/LDL is the size of their current payload? Or do you mean that as the payload shrinks and the lipoprotein progresses from VLDL->IDL->LDL it also undergoes a change such that it is a seperate molecule?

(It has been 25 years since I did A-level chemistry)

Ned Kock said...

Venkat:

Thanks.

Anonymous:

Yes, I meant to say that, as the payload decreases, VLDL -> IDL -> LDL. The payload is primarily fat for VLDL, and cholesterol for LDL. LDL particles are then largely reabsorbed by the liver. IDL are transient particles, with a short half-life.

Anonymous said...

Thanks,

OK, so it appears you maintain that VLDL, IDL, and LDL have different molecular formulae, sorry if I'm being a bit think - I can find ambiguity in odd places.

It does raise a question in my mind about when people refer to small dense LDL vs large fluffy LDL.

i.e. what is the order of magnitude in the size of the 'small dense' vs 'large fluffy'. It would seem the small dense have to be around this 25nm diameter (or smaller), but what about large fluffy?
Are they significantly bigger than that, or around about the size of the VLDL 100nm?

Also is the transition reversible, i.e. as a LDL increases through 'fluffy' dimensions, could it transform back through LDL->IDL->VLDL?
Or is that somehow precluded?

I guess what I'm asking is if it is somehow the change in size that triggers the change in molecule (seems unlikely to me), or is it the loss of the payload (possibly carrying off some component of the lipoprotein) that triggers/effects this change.

Ned Kock said...

I wouldn’t refer to lipoprotein particles as molecules, because they are made up of different substances (fat, protein, cholesterol), which themselves are made up of molecules.

By the way, the article below has a nice illustration (hopefully blogger will not cut off part of the URL):

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=stryer&part=A3628&rendertype=figure&id=A3637

Small-dense LDL is significantly smaller than 25 nm in diameter, which is the intermediate LDL size.

LDL particles of diameter greater than 26 nm cannot pass through the gaps in the endothelium, and thus cannot contribute to the formation of plaque.

Fasting triglycerides are strongly and negatively correlated with LDL particle size. The lower the fasting triglyceride levels are, the larger the LDL particle size is, on average.

Jack C said...

Ned, your post with the pictures of the different lipids is very informative. While the actual particle size may have some influence on the atherogenicity of LDL, it appears that the small dense LDL particles get small and dense in part as a result of oxidation according the the following link:

http://www.ncbi.nlm.nih.gov/pubmed/9012647

The study found that small dense LDL particles have a higher ratio of reduced to oxidized CoQ10 indicating that oxidation of LDL has already occurred and that antioxidant defense has been impaired. The reduced antioxidant defense results in LDL particles that are more readily oxidized.

One aspect of the atherogenic character of small dense LDL that seems unrelated to particle size is the displacement of eNOS from caveolae that results in reduced NO production and consequent endothelial dysfunction. This displacement is caused by oxidized LDL, not native LDL. Caveolae are 50 to 100 nm in size so particle size would not be a factor.

Somewhere I read that the ratio of TG/LDL is a good proxy for particle size, but I seem to have misplaced the reference. After going from the traditional low fat diet to a diet high in saturated fat, my HDL increased from 55 to 110 and my TG decreased from 130 to 50 which should result in a strong pattern A LDL particle size distribution.

Ned Kock said...
This comment has been removed by the author.
Ned Kock said...

Hi Jack C, thanks.

Yes, in the article they conclude the sdLDL had already undergone some oxidation, but an sdLDL pattern causes increased oxidation.

There is also evidence that sdLDL is more prone to glycation.

A better ratio is the TG/HDL ratio.

I am writing a post about TG and LDL particle size patterns; I am still trying to find a nice sample VAP test report to link to the post.

With your TG you are very unlikely to have what is often called the sdLDL pattern (Pattern B, in VAP tests). You are likely to fall into Pattern A, which is the least atherogenic.

Moreover, your high HDL is very protective. By the way, HDL and TG are strongly and negatively correlated.

I don't think people should worry much about LDL cholesterol levels, for reasons that I spell out here:

http://healthcorrelator.blogspot.com/2010/03/bbcs-advice-replace-saturated-with.html

Ned Kock said...

Jack C:

One more thing. I think that the study you linked is really about increased risk in people suffering from familial hypercholesteromia, which seems to be linked to increased sdLDL oxidation.

Jack C said...

Hi Ned,

I was aware of the fact that the study was related to familial hypercholesteremia, but the finding that small, dense LDL has reduced antioxidant defenses would seem to explain the reason that the pattern B LDL is susceptible to oxidation, and would likely be applicable to all.

My wife had a VAP test recently that might suit your purpose. Her TC was 311, LDL 182, HDL 86 and TG 97. Her LDL particle distribution was strongly pattern A, large, bouyant LDL. I will e-mail the total test result if you could use it.

Ned Kock said...

Hi Jack C.

I found a nice one here:

http://www.atherotech.com/content/files/pdfs/vap_report_sample.pdf

Sharing your own experience is an extremely valuable thing for readers.

If you would like to prepare a guest post with your wife, based on the results of her test, I will be happy to post it.

Otherwise, I can also create a post with a link to the test, perhaps with any identifying information removed.

You can use this email if you want (it is in a figure to avoid spam):

http://www.tamiu.edu/~nedkock/#Address

Let me know.

Jack C said...

Hi Ned,

Thanks for the post of the sample VAP report as the line item descriptions for each lipid are very helpful. No such descriptions are provided on the LabCorp report.

The LabCorp report did have a graphic of sorts, not included on the sample report, showing the LDL density pattern.

I will give some thought to posting my wife's VAP Cholesterol Profile at a later time.

Ned Kock said...

Hi Jack C.

You may want to check if LabCorp was the company that actually did the VAP test.

I have seen one case recently in which LabCorp outsourced the VAP test to Atherotech, and then gave the client a summarized report.

If yours was done by Atherotech, you can even call them up and ask questions about the report.

Maybe LabCorp will also provide this service, if they are the ones doing the VAP test.

By the way, I like both companies. LabCorp has very good service. I just don't know if they do the VAP test themselves.

Sam said...

Now I'm a little more confused, but maybe in a good way! ;-)

I recently got my NMR Lipoprofile results back and it was a mixed bag (and unexpected given my diet, at least when compared to others).

If you're interested, I started a topic on it over at PaNu:

http://www.paleonu.com/panu-forum/post/1073010

My HDL size (while being a little lower than I'd like) was tagged as low. At first I thought this was on the bad side but your post has made me think. Perhaps my small HDL size (9nm) is low because there simply isn't that much cholesterol in the arterial walls to pick up?

At least that's the optimistic interpretation...

Ned Kock said...

Hi Sam.

I checked the numbers you posted at Panu. In my opinion, they are very good.

An HDL above 55 is close to the convergence point on the exponential-like decay curve of coronary event risk against HDL cholesterol:

http://healthcorrelator.blogspot.com/2010/02/what-should-be-my-hdl-cholesterol.html

In fact, for a low-risk person, the curve above suggests little need for a higher HDL than 55.

A healthy body tends to be efficient. It is not the elevated LDL-derived cholesterol that causes CVD, but other factors (chronic inflammation), in combination with that elevated cholesterol.

In the absence of those other factors, it seems reasonable to me that HDL cholesterol would not have to be that high, because the HDL particles do not have that much cholesterol to collect. I am with you in that respect. Ornish was mocked for putting forth this idea a while ago; I don't see why.

You wondered why not all LDL is large. Well, you need cholesterol for various purposes, one of them is to produce various hormones, and metabolize vitamin D3 (which is the precursor to the real thing:

http://healthcorrelator.blogspot.com/2010/02/vitamin-d-levels-sunlight-age-and.html

I think this varies from person to person, and some of the underlying processes are still a mistery.

Most people probably need a certain number of LDL particles that will be small enough to actually penetrate the endothelium for repair.

Otherwise why would all those particles be around the size of the gaps in the endothelium!?

Finally, your trigs., LDL, and total cholesterol numbers. They are consistent with those of followers of the Optimal Diet:

http://healthcorrelator.blogspot.com/2010/04/long-term-adherence-to-dr-kwasniewskis.html

In summary, I think you've got a good lipid profile overall. I too, would have expected the trigs. to be lower (although they are very close to the average OD'er, see post above).

If I were you, I would continue doing what you are doing, and keeping in touch with your doctor.

Finally, as you bring your BMI a bit lower (unless you are very muscular), you will probably see additional improvements in the numbers. One of the reasons is that you will be supplementing for adiponectin:

http://healthcorrelator.blogspot.com/2010/03/adiponectin-supplementation-body-fat.html

Sam said...

Ned, thanks for the feedback.

My last remaining 10-15 lbs of adipose tissue is (apparently) all subcutaneous fat that is amazingly and infuriatingly insulin sensitive. I think I will devote far more attention to losing it with the expectation that my lipid profile will improve even more.

Thanks to you and others I'm coming to some plausible explanations for what I thought were anomalies. My lowering carbs to <20g/day (a level I'm quite experienced and comfortable with) should help drop the fat and trigs - hopefully.

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