Why (LDL particle) size matters.

Having gone through the math(s) with several people, I thought I'd stick it in a blog post for posterity.

I know that this is a diagram of a chylomicron, but bear with me!

Cholesterol synthesised in the liver is exported in LDL particles. The more cholesterol that's synthesised, the more particles there need to be to carry it.

∴ LDL-P (particle number) ∝ LDL-C (total amount of cholesterol)

The particles are roughly spherical with a very thin wall (consisting of a phospholipid mono-layer, the yellow wiggly lines with a green end bit in the above diagram).

Volume of a sphere = 4/3 * π * r³, where r = half the diameter.

If there's a 10% reduction in LDL particle size, the volume reduces to 0.729, relative to the original size. Therefore, to carry the same amount of cholesterol requires 1/0.729 = 1.37 times more particles, which is a 37% increase in the number of LDL particles, relative to the original size.

∴ LDL-P (particle number) ∝ 1/LDLsize³

As it's LDL particle number that determines the infiltration of LDL cholesterol into the media of artery walls, it's advisable to keep cholesterol synthesis to a minimum by keeping fat intake to a reasonable level * (i.e. not Nutritional Ketosis level) and keeping LDL particle size to a maximum by keeping sugars & fast starches intake to a reasonable level*.

Before someone asks, what I mean by a reasonable level is a level that is burned by the body without having a chronic excess. An acute excess can be stored, provided that mean intake is less than mean burning.

How COULD I write a post about LDL-P and forget to include THIS?

Historical perspectives on the impact of n-3 and n-6 nutrients on health, by Bill Lands.

Here's Fig. 1. from http://www.sciencedirect.com/science/article/pii/S0163782714000253

Relating tissue HUFA balance with blood cholesterol and heart attacks. Results from the 25-year follow-up in the Seven Countries Study [35] were discussed in an earlier review [10] which noted that “Food energy imbalances which elevate blood cholesterol may be fatal only to the degree that omega-6 (n-6) exceeds omega-3 (n-3) in tissue HUFA. Such evidence raises questions about the hypothesis that blood cholesterol levels cause CHD.” Northern Europe and Southern Europe have abbreviations “No.” and “So.”, respectively. The Figure is reprinted with permission of the publisher.

Hat-tip to Dr. Thomas Dayspring for Tweeting this review.

Fig. 1 is interesting, as it shows a significant association between 25-year CHD mortality and Serum Total Cholesterol for every region except Japan. What's different about Japan, compared to Northern Europe, USA, Serbia, Southern Europe & Crete?

According to Measuring Blood Fatty Acids as a Surrogate Indicator for Coronary Heart Disease Risk in Population Studies , Philippines & Iceland have lower % linoleic acid than Japan. Where's the CHD vs TC data?

Could another difference be that the Japanese eat rice, a relatively intact grain, instead of foods made from wheat grain dust (i.e. flour) as their main source of dietary carbohydrates?

See also Using 3–6 differences in essential fatty acids rather than 3/6 ratios gives useful food balance scores , and Omega 3-6 Balance Score.

Another tasty analogy.

Here's a tasty analogy.

From http://grannychoe.com/recipe3_Soup.php

In Ultra-high-fat (~80%) diets: Fat storage, and a delicious analogy, I analogised the effect of carbohydrate consumption on mean serum glucose level with the effect of fat consumption on mean serum triglyceride level. Here's another one.

Chronic excessive consumption of carbohydrates relative to what are being burned results in excessive fat synthesis in the liver, resulting in excessively-high fasting serum triglyceride level, which is harmful.

Chronic excessive consumption of fats relative to what are being burned results in excessive cholesterol synthesis in the liver, resulting in excessively-high fasting VLDL, LDL & IDL level, which is harmful.

Seems legit.

Lipoproteins & apolipoproteins: E, by 'eck.

In December 2008, I wrote about Cholesterol And Coronary Heart Disease , where I used a limousine metaphor to describe how cholesterol & fat are transported around the body. Here's a diagram of a chylomicron lipoprotein "limousine". Chylomicrons transport dietary fat (triglycerides) & cholesterol from the gut to the liver & other tissues. As there's much more dietary fat than dietary cholesterol, the contents are mostly fat.

A chylomicron. T=Triglyceride C=Cholesterol. From http://en.wikipedia.org/wiki/Lipoprotein

The lipoprotein "limousines" vary a lot in size.

(a) VLDL (b) chylomicrons (c) LDL (d) HDL. 
From http://healthcorrelator.blogspot.co.uk/2011/11/triglycerides-vldl-and-industrial.html

Apolipoproteins are the "chauffeurs" which determine to where lipoproteins transport stuff.
Apo A is found mainly on HDL, which transports fat & cholesterol from tissues to the liver.
Apo B is found mainly on LDL, which transports cholesterol from the liver to tissues.
Apo C is found on HDL when fasted, but moves to chylomicrons & VLDL when fat is eaten.
Apo D is found mainly on HDL and is is associated with an enzyme involved in lipoprotein metabolism.
Apo E is found mainly on chylomicrons & IDL and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and into the blood. In the CNS, Apo E transports cholesterol to neurons. Defects in Apo E result in hyperlipidaemia , cardiovascular & neurological diseases, and is the E referred to in the title.

There's also Apo H, which is a β-glycoprotein involved in the binding of cardiolipin. It has nothing to do with the above lipoproteins.

False dichotomies: serum cholesterol level vs all-cause mortality. Cause or effect?

Here are some plots from the MRFIT study.

From http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_Heart/PH709_Heart5.html

Although the relative risk (RR) for coronary heart disease (CHD) and cardiovascular disease (CVD) mortalities increase with serum total cholesterol (TC) level, all-cause mortality follows a U-curve.

According to Low Serum Cholesterol and Mortality: Which Is the Cause and Which Is the Effect?, certain illnesses that increase mortality lower TC levels. This is the Iribarren hypothesis.

According to Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study, TC that's low and is still low 20 years later results in a 64% increase in the RR for mortality relative to TC that's intermediate and is still intermediate 20 years later.

Table 4 Relative risk for mortality based on change in cholesterol between examinations three and four

Is low TC level the cause of, or the effect of fatal illnesses? I think that it's both. Cholesterol is an important substance, as a severe lack of it is bad news, as per Smith–Lemli–Opitz syndrome. If certain illnesses result in a depletion of cholesterol and cholesterol synthesis is too low, there's insufficient cholesterol to allow recovery.

Interestingly, TC that's low but is intermediate 20 years later results in a 30% increase in the RR for mortality, whereas TC that's low but is high 20 years later results in a 5% increase in the RR for mortality.

P.S. There's a false dichotomy for vitamin D level vs illness. Ditto for carbohydrates vs calories.

FAO the over-fat and/or those with metabolic syndrome: Big breakfast, medium lunch & small dinner is beneficial.

Breakfast like a King/Queen.

Go to work on an egg.

According to High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women.
"High-calorie breakfast with reduced intake at dinner is beneficial and might be a useful alternative for the management of obesity and metabolic syndrome." See the other PubMed studies listed in the above study, which corroborate it.

What about all the "artery-clogging" cholesterol in egg yolks? See Eat Whole Eggs All Day and Throw Your Statins Away? 375x Increased Dietary Cholesterol Intake From Eggs Reduces Visceral Fat & Promotes Healthy Cholesterol Metabolism.