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.

This is a diagram of a chylomicron or VLDL-c (high TG/C ratio) 'cos I couldn't find one for LDL-c!

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 (see image below), it's advisable to keep cholesterol synthesis to a reasonable level by keeping fat intake to a reasonable level (i.e. not Nutritional Ketosis!) and keeping LDL particle size to a reasonable level by keeping added sugar (e.g. sucrose & fructose) intake and rapidly hydrolysed/overcooked starches (e.g. amylopectin & maltodextrin) intake to a reasonable level (i.e. a level that's oxidised by the body without having a chronic excess). An acute excess of carbohydrate can be stored as liver/muscle glycogen, provided that mean carbohydrate intake is less than mean carbohydrate oxidation.

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

The Conflation Game.

Li-i-ife, is the name of the game, and I wanna play the game with you.....


People have been "grinding my gears" by conflating carbohydrates with sugars. All sugars are carbohydrates, but not all carbohydrates are sugars. See Carbs Carbs Carbs. to find out about the five basic different types of carbohydrates.

Krauss et al has been "at it" again. In Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia, at the bottom of Table 1 is "carbohydrate, 50% simple and 50% complex". The carbohydrates consisted of half simple (probably fructose, as that has the worst effect on particle size) and half starches (probably maltodextrin, as it rapidly hydrolyses into glucose).

The effect of such a sugary diet is as follows:-

The percentage of pattern B (small, dense) LDL particles increases significantly in proportion to the percentage of Dietary "carbohydrate". The implication of this study (also A very-low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins ) is that high-carb, low-fat diets are atherogenic.

I call "Shenanigans".

A high sugar diet is atherogenic, but carbohydrates from potatoes, rice, sweet potatoes/yams & beans (if not overcooked), actual whole grains (i.e not flour) & whole fruits aren't.

Carbs, Carbs, Carbs, Carbs and Carbs.

Carbohydrates seem to get the blame for everything nowadays. "Carbohydrates made me fat". "Carbohydrates burned-out my pancreas". "Carbohydrates raised my blood glucose". "Carbohydrates raised my blood triglycerides". "Carbohydrates stole mer jerb!". O.K, I made the last one up!
If carbohydrates are responsible for all of these bad things, then how come a diet of only potatoes had the opposite effect? See 20 Potatoes a day.

Also, Blue Zone populations eat a diet with a high percentage of total energy (%E) from carbohydrates. See Low serum insulin in traditional Pacific Islanders--the Kitava Study and The Kitava Study. The Kitavans eat ~70%E from carbohydrates, ~20%E from fats and ~10%E from proteins. They don't eat a significant amount of Western crap-in-a-bag/box/bottle.

Maybe it has something to do with the type of carbohydrates and with what they're eaten. In A very-low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins , (emphasis, mine) "The very-low-fat, high-carbohydrate experimental diet was designed to supply less than 10% of energy from fat (2.7% saturated, 3.7% monounsaturated, and 2.6% polyunsaturated), with 75% from carbohydrate (with equal amounts of naturally occurring and added simple and complex carbohydrate) and 15% from protein." Simple carbohydrates are sugars.

The experimental diet which did bad things contained 37.5%E from sugars. I declare shenanigans!

1. There are simple carbs, there are simple carbs and there are simple carbs. In the previous post, the graph of plasma triglycerides after an OGTT showed that 100g of glucose had no significant effect on plasma triglycerides over a 6 hour period. If it had been 100g of fructose, there would have been a significant increase in plasma triglycerides. Galactose is taken-up by the liver and has minimal effect on blood glucose, but I don't know its effect on plasma triglycerides.

2. There are complex carbs, there are complex carbs and there are complex carbs. Overcooked starch is high in amylopectin which is highly-branched, which means that it hydrolyses rapidly into glucose which gives it a very high glycaemic index. Raw & refrigerated potato starches have very low glycaemic indices, due to the presence of amylose, or other resistant starches. Rice contains a mixture of starches which varies with rice type, cooking time and subsequent refrigeration.

3. There are oligosachharides e.g. FOS.

4. There are polysaccharides e.g. inulin.

5. There is soluble fibre/fiber e.g. cellulose.

Although overeating sugars containing fructose & starches that rapidly hydrolyse into glucose makes the liver fatty, overeating fats also makes the liver fatty. See Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause.

It's the chronic over-consumption of crap-in-a-bag/box/bottle (high in sugars and/or starches and/or fats), not just carbohydrates, that causes over-fatness and other health problems.

Boiled potatoes & Area Under the Curve (AUC): some thoughts.

Here are three "curves"... a 4 x 1 rectangle, a 2 x 2 square and a 1 x 4 rectangle.

The AUC for all three "curves" = 4.

Imagine that the three curves are for blood glucose level increase above baseline vs time.

a) "X" grams of a high-Glycaemic Index (GI) carb e.g. glucose, maltodextrin or amylopectin result in a large glucose response that goes away rapidly, as the carbs leave the gut rapidly, pass into the blood rapidly and are cleared from the blood rapidly due to the large insulin response.

b) "X" grams of a 50:50 mixture of high & low-GI carbs result in a lower but longer sustained glucose & insulin response, as some carbs leave the gut rapidly but some carbs leave the gut slowly, pass into the blood slowly and are cleared from the blood slowly due to the small insulin response.

c) "X" grams of a low-GI carb e.g. amylose or resistant starch result in an even lower glucose & insulin response that is sustained for even longer, as the carbs leave the gut very slowly, pass into the blood very slowly and are cleared from the blood very slowly due to the very small insulin response.

Will a), b) & c) produce the same satiety? I think not. I think that a) results in lower satiation than b) and b) results in lower satiation than c). Whether returning hunger is caused by a sudden drop in blood insulin level or by a sudden drop in the amount of food in the gut, I don't know.

The reason for this post is A satiety index of common foods (scanned image of full study here) and the related study An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods.

In the first study, boiled potatoes produced the highest satiety, yet in the second study, boiled potatoes produced one of the highest glucose & insulin AUCs. How can this be? Consider the preparation method for the Russet potatoes:-
"Peeled, boiled for 20 min, and stored at 4 °C overnight; reheated in a microwave oven for 2 min immediately before serving."

Potato starch when refrigerated produces resistant starch RS3, which gives it a low GI (see item 605 in International table of glycemic index and glycemic load values: 2002). Therefore, refrigerated potatoes contain a mixture of high & low-GI starches. This, I believe, is why boiled, refrigerated & reheated potatoes produced the highest satiety. The combination of water, fibre & resistant starch kept hunger pangs away the longest. I suspect that boiled potatoes that are eaten without being refrigerated won't produce quite as much satiation, as they contain no resistant starch.

EDIT: From https://en.wikipedia.org/wiki/Resistant_starch#Definition_and_categorization :-
"RS3 Resistant starch that is formed when starch-containing foods are cooked and cooled, such as pasta. Occurs due to retrogradation, which refers to the collective processes of dissolved starch becoming less soluble after being heated and dissolved in water and then cooled."
RS3 forms a gel in the stomach, which delays stomach emptying. This is most likely the reason for the increased satiation.

Diabetes: which are the safest carbohydrates?

In my previous post, I stated that people with T2DM should eat ~150g/day of carbohydrate.

Soak & cook your own beans al-dente, for slowest release carbs.

See International table of glycemic index and glycemic load values: 2002. Below is a list of carbohydrates that have a low glycaemic load, or GL (GL = glycaemic index * grams of carbohydrate in the serving).

Non-nutritive sweeteners:

It's often claimed that non-nutritive sweeteners produce a cephalic phase insulin response. The mere anticipation of eating produces a cephalic phase insulin response. See How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. An insulin response suppresses serum NEFAs, so it's not all bad.

Sugars and Sugar alcohols:

Fructose is not recommended for people with T2DM, as it "barges its way" into the liver via Glu-T5 and fructokinase. People with T2DM who have a high fasting serum glucose level almost certainly already have full liver glycogen stores, so adding to them isn't advisable. Whole fruits (not juices) are fine.
Lactose has a virtually zero GL, isn't very sweet and has/hasn't a laxative effect in large quantities (lactase-dependent). Heating lactose turns it into lactulose.
Lactulose has a virtually zero GI, is sweet and has a laxative effect in large quantities.
Galactose is not recommended, as large amounts may accelerate ageing.
D-mannose has a virtually zero GI, is sweet and doesn't have a laxative effect in large quantities. It can be used to treat urinary tract infections (UTIs) caused by e.coli, due to the fact that the kidneys filter it out of the blood and pass it out in the urine. Mannose in urine reduces the adhesion of e.coli to the inside wall of the urinary tract. See Intervening with urinary tract infections using anti-adhesives based on the crystal structure of the FimH-oligomannose-3 complex.
Trehalose has a virtually zero/moderate GI, is sweet and has/hasn't a laxative effect in large quantities (trehalase-dependent).

Lactitol has a virtually zero GI and has a laxative effect in large quantities.
Sorbitol has a virtually zero GI and has a laxative effect in large quantities.
Xylitol has a virtually zero GI, minty overtones and reduces dental plaque. However, it has a laxative effect in large quantities.
Erythritol has a virtually zero GI, minty overtones and is wee'ed-out like D-mannose, so it doesn't have a laxative effect in large quantities.

Starches:

Note: Tinned starches are usually overcooked, so cook your own. Don't overcook starches, as that makes them faster-absorbing. Al dente is best.

Gram dhal a.k.a. chana dal.
Long-grain rice. Refrigerating boiled rice for 24 hours lowers the GL, by forming resistant starch. See item 275 in the table in the first link.
New potatoes. Refrigerating boiled new potatoes for 24 hours lowers the GL a lot, by forming resistant starch. See item 605 in the table in the first link. You can boil old potatoes, but they're probably not as good.
Pearl barley.
Sweet corn.
Beans.
Chickpeas.
Lentils.
Peas.
Starchy nuts e.g. peanuts , cashews and chestnuts.
Vegetables.
Root vegetables.
Raw carrots.

If even low-GL carbs spike BG too much, this indicates severe IR in liver and/or skeletal muscle. See Insulin Resistance: Solutions to problems.

The above lists also apply to people with T1DM who are having difficulty keeping their blood glucose level between 3 and 7mmol/L.

How eating sugar & starch can lower your insulin needs.

This is a bookmarking post. Jason Sandeman is a chef who had a couple of web-sites at Well Done Chef! and Jason Sandeman — Real Food For Your Life. He has Latent Autoimmune Diabetes of Adulthood (LADA), which has resulted in a total loss of his pancreatic beta cells which means that he has to inject insulin.

Now, it's generally believed in low-carb circles (and by myself) that people with Type 1 Diabetes Mellitus (T1DM) should minimise their intake of sugary & starchy carbohydrates as these promote wild fluctuations in blood glucose. See The problem with Diabetes.

Jason wrote the following comment on Richard Nikoley's blog. The relevant part is as follows:-
"Even more weird – now that I have introduced the starches into the diet – I have actually got better control now. I thought my insulin needs would go up – but they haven’t. They’ve gone down."

To which I replied:-"How about this for an explanation? You now have a well-controlled glucose input to your circulation via diet, which has suppressed the poorly-controlled glucose input to your circulation via hepatic glucose production."

Hepatic glucose production (HGP) is increased by Glucagon, Cortisol & Adrenaline/Epinephrine. These are secreted as blood glucose level falls below certain values in order to keep our brains alive. See Blood Glucose, Insulin & Diabetes.

As keeping our brains alive is rather important (!), the mechanism is fairly crude in operation and blood glucose can overshoot in a positive direction, as a bit of glycation is less harmful than brain death. See "Funny turns": What they aren't and what they might be. Hyperglycaemia requires insulin to lower blood glucose back to the normal range.

Therefore, eating some (but not too much) sugar & starch can result in lower blood glucose level and lower insulin secretion. Eating fibre/fiber (a carbohydrate) is also good for keeping blood glucose low, as only just mentioned in Fiber and Insulin Sensitivity. Ain't the human body weird?"

Fiber and Insulin Sensitivity.

Bluddy Americans. It's Fibre! But anyway....

Stabby the Raccoon posted the following study in a comment on CarbSane's blog. I thought that it was so interesting that I am linking to it here.

Fiber and Insulin Sensitivity.

This study has built-in cognitive dissonance.

The first Fig. suggests that cereal fibre is associated with a much lower RR for Type 2 Diabetes Mellitus (T2DM) and that fruit & veggie fibre aren't.

Schulze et al. 2007: Cereal Fiber RR = 0.6 - 0.7. Fruit Fiber RR = 0.9 - 1.05. Vegetable Fiber RR = 0.95 - 1.15 approx.

The next table suggests otherwise.

Andersson et al., 2007: Whole grain diet contained 112 g/d of whole grain, 18 g fiber. No effect of whole grains on insulin sensitivity.

Ebeling et al., 1988: 5 g/d granulated guar. No effect on insulin sensitivity.

Johnston et al., 2010: Resistant starch supplement -40g/d. Improved insulin sensitivity with resistant starch.

Landin et al., 1992: 30 g/d granulated guar, given in 3-10 g doses. Improved insulin sensitivity with guar diet.

Maki et al., 2011: High-resistant starch diet- 30 g/d, Low-resistant starch diet- 15 g/d. Improved insulin sensitivity with both resistant starch diets, but effect only reached statistical significance for men.

Nilsson et al., 2008: White bread enriched with barley fiber and 8g resistant starch, Barley kernel based bread. Improved glucose tolerance with resistant starch.

Pouteau et al., 2010: 28 g/d acetogenic fibers (acacia gum and pectin). No effect on insulin sensitivity.

Robertson et al., 2003: High-resistant starch diet- 60 g/d. Improved insulin sensitivity with resistant starch.

Weickert et al., 2006: Fiber-enriched with 31.2 g insoluble fiber. Improved insulin sensitivity with increased insoluble fiber.

In conclusion, the resistant starches found in high-amylose rices such as Basmati, refrigerated boiled rice & boiled potatoes, also rye & barley breads are beneficial in terms of reducing your RR for T2DM. Watch out, though. Too much dietary resistant starch can cause colic, flatulence & diarrhoea if your intestinal bacteria are knackered. You want fermentation to short-chain fatty acids to occur, not osmotic laxation! See Genetics of Food Intolerance.

Carbohydrates: Dogs' Doodads or Spawn of Satan?

Depending on which side of the fence you're on, Carbohydrates are either the Dogs' Doodads or the Spawn of Satan. As I get older, I prefer to sit on the fence. Let's start with the basics.


What are Carbohydrates?

Carbohydrates are so named because they have the generic formula (CH2O)n. C is carbon and H2O is water hence Carbo-Hydrate. There are several different types.

1) Sugars. There are monosaccharides, the most common being Glucose (a.k.a. Dextrose), Fructose and Galactose. There are disaccharides, the most common being Sucrose, Lactose and Maltose. Disaccharides are 2 monosaccharides linked by a glycosidic bond formed by a condensation reaction (removal of a water molecule, usually by an enzyme). Disaccharides have to be hydrolysed (have a water molecule added back in, usually by an enzyme) into monosaccharides before they can be absorbed in the gut.
Sugars are simple carbohydrates.

2) Starches. These are chains of glucose molecules linked by glycosidic bonds. Starches have to be hydrolysed into glucose molecules before they can be absorbed. There are unbranched chains like amylose which is also known as resistant starch. There are branched chains like amylopectin and maltodextrin. Glycogen is a branched chain "animal starch" that is synthesised inside muscle and liver cells and which can be rapidly converted back into glucose inside cells.

3) Non-Starch Polysaccharides (NSPs). These are also known as fibre/fiber and there are 2 types: soluble (e.g. pectin, beta-glucan & cellulose) and insoluble (e.g. bran). These aren't absorbed, but gut bacteria can feed on soluble fibre/fiber. Starches and NSPs are complex carbohydrates.

For more information, see https://en.wikipedia.org/wiki/Carbohydrate

The amount of carbohydrate that someone needs varies from person to person and increases with the intensity and volume of exercise done. See Everyone is Different. What are the best carbs to eat? "Complex" ones from "wholegrain" cereals? Not necessarily.


Simple vs Complex

TV ads for breakfast cereals bang on about the wholegrain goodness of complex carbohydrates releasing energy slowly. The terms "Simple" and "Complex" actually refer purely to the chemical structure of a carbohydrate and have nothing to do with how quickly they turn into blood glucose in the body. The Glycaemic Index (GI) (or Glycemic Index if you're American) relates to how quickly carbohydrates turn into blood glucose in the body. See https://www.mendosa.com/gilists.htm for a list of 750 foods and their GI & GL (GL = Glycaemic Load = GI/100 x carb content per serving). Here are a few extracts. Note: a GI of 55 is low; a GL of 10 is low.

The last three items in the list are all simple carbohydrates. As you can see, some wholegrain complex carbohydrates turn into blood sugar faster than simple carbs. This is because the wholegrains have been ground into powder which is rapidly digested and absorbed, despite the presence of fibre/fiber.

As fructose has such a low GI, does this mean that we can eat as much of it as we like? No! When we eat fructose, it passes from the small intestine into the portal vein and goes straight to the liver. As liver cells contain an enzyme called fructokinase (which has a high affinity for fructose), all dietary fructose is absorbed by the liver where it tops-up liver glycogen. Liver glycogen is also topped-up by glucose (obtained from the digestion of starchy carbohydrates). Once liver glycogen stores are full, any further fructose is converted into fats, which are stored as ectopic liver fat and also exported as triglycerides. High serum triglycerides are heart-unhealthy. See Cholesterol And Coronary Heart Disease.

Why is GI important? When we eat carbohydrates, they raise blood glucose levels. Pancreatic beta cells secrete a hormone called insulin, which allows more glucose to pass into cells (by moving Glu-T4 transporters inside the cells). When more glucose enters cells, glucose levels in the blood fall. It's a negative feedback loop. For millions of years, we lived on a diet of natural, unrefined carbohydrates and so the secretion of insulin never had to change blood glucose levels very rapidly.

When unnatural, refined, high-GI carbs are eaten, blood glucose levels rise much faster. This results in over-secretion of insulin (hyperinsulinaemia). This shuttles too much glucose into cells and results in.......low blood glucose, followed by low blood insulin. Rapidly-falling and low blood insulin levels cause feelings of severe hunger and cravings to eat more carbs. It's a vicious circle. Hyperinsulinaemia also has other bad effects on the body. See https://www.mercola.com/2001/jul/14/insulin.htm to learn about Insulin and its Metabolic Effects.

GI has a weakness because adding fats and some proteins to high-GI foods lowers the GI but can increase the insulin response. Saturated fats, monounsaturates and omega-6 polyunsaturates raise the insulin response to carbs.

There is another index called the Insulin Index (II). See https://www.mendosa.com/insulin_index.htm.
The II contains a few surprises. Some proteins (e.g. the whey in milk & yoghurt) produce a large insulin response. Insulinogenic proteins are also glucogenic, so they don't cause low blood glucose.

On the other hand, refrigerating some foods lowers their GI & II by changing the starch in them into resistant starch, even if the food is subsequently re-heated. Rice & potatoes are two such foods.

As the terms "simple" and "complex" are meaningless in terms of carbohydrates' effects in the body, I prefer to use the terms "slow" and "fast". In a nutshell, slow carbs are good and fast carbs are bad. These terms can be applied to proteins, too. Egg is slow and whey is fast. Sticking to mostly slow foods keeps blood glucose and insulin levels stable, which results in better appetite control and better health, too.

It was soaring serum insulin levels that were sending me to sleep after carby meals years ago. Postprandial hyperinsulinaemia results in amino acids from digested foods being shuttled into cells. However, L-tryptophan isn't shuttled into cells, so the level of this amino acid in the blood rises relative to others. As L-tryptophan competes with other amino acids to cross the blood-brain barrier, now that the competition has been removed, more L-tryptophan enters the brain. It's converted into 5-hydroxytryptophan (5-HTP), then serotonin & melatonin. High melatonin levels in the brain cause sleepiness.

So remember, "Right carbs, right amounts, right times."