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.

I'm NOT a lipophobe, I'm a very naughty boy!

First, postprandial triglycerides again. From Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women, here's a plot of HR for future CHD vs TG's at various times after eating.

Hazard ratio (HR) and 95% confidence interval (CI) for highest vs lowest tertiles of triglyceride level (see Table 3 for values), adjusted for age, blood pressure, smoking, hormone use, levels of total and high-density lipoprotein cholesterol, diabetes mellitus, body mass index, and high-sensitivity C-reactive protein level.

Notice how the HR falls with increasing time from last meal. As TG's ≥12 hours after eating are a surrogate for Insulin Resistance (IR) and the HR is only 1.04 (95% CI 0.79 - 1.38), this strongly suggests that IR is not a significant factor.

It's been suggested that IR might increase PP TG's in the 2 - 4 hour period due to impaired clearance. According to Fig. 3B in Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism, TG clearance in healthy men doesn't significantly start until after 4 hours has elapsed. Therefore, an impairment in TG clearance isn't going to make a significant difference to TG level in the 2 - 4 hour period.

Second, the reason why I'm having to repeat myself is due to Cholesterol: Do chylomicrons clog your arteries? (2), where I've been called "my resident lipophobe". As I drink Gold Top milk (5.2g of fat/100mL) and eat pork including belly slices (you know, those strips of pork with a lot of fat on them), I'm being attacked for something that I'm not.

What I'm criticising is dietary extremism. Eating fats in foods is fine by me, but eating sticks of Kerrygold butter and/or dumping loads of butter and/or MCT oil into coffee to achieve "Nutritional Ketosis" is not a good idea. Anyway, here's an amusing spoof on Bulletproof coffee.

Carbs Carbs Carbs.

The following video of Boys Boys Boys by Sabrina Salerno is NSFW in parts.


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 my job". 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 junk-foods.

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!

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.

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.

EDIT: There are oligosachharides e.g. FOS. There are polysaccharides e.g. inulin and 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 junk-foods (high in sugars and/or starches and/or fats), not just carbohydrates, that causes over-fatness and other health problems.

Ultra-high-fat (~80%) diets: Fat storage, and a delicious analogy.

Fat storage:

Here's a plot of mean (±SEM) plasma insulin concentrations during an oral-glucose-tolerance test (OGTT) when preceded by either a high-fat (▪) or a high-carbohydrate (□) evening meal and during an oral-fat-tolerance test (OFTT) when also preceded by either a high-fat (•) or a high-carbohydrate (○) evening meal.

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

100g of glucose produces a large spike in insulin concentration and 40g of fat produces no significant spike in insulin concentration. According to Gary Taubes' insulin hypothesis of obesity, in the absence of a significant spike in insulin concentration, fat cannot be stored.

Here's a plot of mean (±SEM) plasma triacylglycerol concentrations during an oral-fat-tolerance test (OFTT) when preceded by either a high-fat (•) or a high-carbohydrate (○) evening meal (from the previous post).

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

Average plasma triacylglycerol concentration over 0 to 360min is ~1.3mmol/L (~116mg/dL in US units).

Plasma triacylglycerol concentration falls to baseline between 240min and 360min. OGTT's and OFTT's are performed with the subjects at rest for the duration of the test.

Referring to It's all in a day's work (as measured in Joules) , at rest the subject is burning ~1kcal/min with ~95% of it coming from fat, making a fat-burning rate of ~0.11g/min.

At a fat-burning rate of ~0.11g/min, it would take ~360min for plasma triacylglycerol to fall to baseline if the 40g of fat from the OFTT was only being burned and not being stored. As shown above, it only takes ~120min to fall to baseline. Therefore, fat from the OFTT that isn't burned is stored in ~120min in the absence of a significant insulin spike. Q.E.D.

A delicious analogy:

Here's a plot of mean (±SEM) plasma glucose concentrations during an oral-glucose-tolerance test (OGTT) when preceded by either a high-fat (▪) or a high-carbohydrate (□) evening meal and during an oral-fat-tolerance test (OFTT) when also preceded by either a high-fat (•) or a high-carbohydrate (○) evening meal (from the previous post).

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

The OGTT (100g of glucose) produces a large spike in plasma glucose concentration which lasts for ~210min before returning to baseline. Higher plasma glucose concentrations glycate more than lower plasma glucose concentrations. Average plasma glucose concentration over 0 to 360min is higher with the OGTT than with the OFTT, therefore there is more glycation damage with the OGTT than with the OFTT. Don't regularly consume 100g or more of glucose!

Here's a plot of Mean (±SEM) plasma triacylglycerol concentrations during an oral-glucose-tolerance test (OGTT) when preceded by either a high-fat (▪) or a high-carbohydrate (□) evening meal.

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

Average plasma triacylglycerol concentration over 0 to 360min is ~1.0mmol/L (~89mg/dL in US units).

Although the plasma triacylglycerol concentration after consuming a high-carbohydrate evening meal is slightly higher than after consuming a high-fat evening meal, the two plots above are essentially flat, indicating that none of the 100g of glucose consumed was turned into fat by de novo lipogenesis (DNL) within 6 hours.

As discussed in the previous post, higher plasma triacylglycerol concentrations are more atherogenic than lower plasma triacylglycerol concentrations. Average plasma triacylglycerol concentration over 0 to 360min is higher with the OFTT than with the OGTT, therefore there is more atherogenicity with the OFTT than with the OGTT.
Don't regularly consume 40g or more of fat!

An interesting study that involved humongous fat consumption was Response of body weight to a low carbohydrate, high fat diet in normal and obese subjects , which used up to 600g of fat/day. It's possible to lose weight on an ultra-high-fat diet, but average plasma triacylglycerol concentrations would have been extremely high. Fasting TG's reduce on an ultra-high-fat diet, probably due to suppression of endogenous TG synthesis by exogenous TG intake.

Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

The good:

Here's a plot of mean (±SEM) plasma glucose concentrations during an oral-glucose-tolerance test (OGTT) when preceded by either a high-fat (▪) or a high-carbohydrate (□) evening meal and during an oral-fat-tolerance test (OFTT) when also preceded by either a high-fat (•) or a high-carbohydrate (○) evening meal.

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

An OGTT (100g of glucose dissolved in water) causes a large disturbance in blood glucose level for up to 2 hours. Ditto for insulin (see Fig. 2).

An OFTT (40g of fat as cream) doesn't cause a significant disturbance in blood glucose level. Ditto for blood insulin (see Fig. 2).

The bad:

Here's a plot of mean (±SEM) plasma triacylglycerol concentrations during an oral-fat-tolerance test (OFTT) when preceded by either a high-fat (•) or a high-carbohydrate (○) evening meal.

From Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

An OFTT (40g of fat as cream) causes a significant rise in blood triacylglycerol (a.k.a. TAG a.k.a. triglycerides a.k.a. TG's) level for up to 4 hours. Is this a problem? Definitely, maybe. From Cholesterol And Coronary Heart Disease , "Cholesterol-depleted particles oxidise faster than large cholesterol-rich ones." Chylomicrons are triglyceride-rich, cholesterol-depleted, as that's the composition of the fat in the diet.

The ugly:

Here's evidence that excessive postprandial TG's raise the risk factor for CHD:- See Fig. 1 in Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women.

Here's more evidence that postprandial saturated fatty TG's raise the risk factor for CHD:- See Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling.

See also Postprandial triglyceride-rich lipoprotein changes in elderly and young subjects.,
Effect of a single high-fat meal on endothelial function in healthy subjects.,
Postprandial lipemia: emerging evidence for atherogenicity of remnant lipoproteins.,
Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men.,
Evidence for a cholesteryl ester donor activity of LDL particles during alimentary lipemia in normolipidemic subjects.,
Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes.,
Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress.,
High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis.,
Impact of postprandial hypertriglyceridemia on vascular responses in patients with coronary artery disease: effects of ACE inhibitors and fibrates.,
[Influence of postprandial hypertriglyceridemia on the endothelial function in elderly patients with coronary heart disease].,
Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size.,
Association between fasting and postprandial triglyceride levels and carotid intima-media thickness in type 2 diabetes patients.,
[Correlation of lipemia level after fat loading with manifestation of atherosclerosis in coronary arteries].,
Postprandial hypertriglyceridemia and carotid intima-media thickness in north Indian type 2 diabetic subjects.,
Association between postprandial remnant-like particle triglyceride (RLP-TG) levels and carotid intima-media thickness (IMT) in Japanese patients with type 2 diabetes: assessment by meal tolerance tests (MTT).,
Postprandial lipemia and remnant lipoproteins., 
Elevated levels of platelet microparticles in carotid atherosclerosis and during the postprandial state.,
Postprandial metabolic and hormonal responses of obese dyslipidemic subjects with metabolic syndrome to test meals, rich in carbohydrate, fat or protein.,
Atherosclerosis, diabetes and lipoproteins., 
Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol.,
Post-prandial hypertriglyceridemia in patients with type 2 diabetes mellitus with and without macrovascular disease.,
A hypertriglyceridemic state increases high sensitivity C-reactive protein of Japanese men with normal glucose tolerance.,
CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against diabetic dyslipidemia and atherosclerosis., 
[Trends of evaluation of hypertriglyceridemia -from fasting to postprandial hypertriglyceridemia-].,
The effects of dietary fatty acids on the postprandial triglyceride-rich lipoprotein/apoB48 receptor axis in human monocyte/macrophage cells.

See also What Is the Significance of Postprandial Triglycerides Compared With Fasting Triglycerides? , Uncovering a Hidden Source of Cardiovascular Disease Risk and Postprandial Lipoproteins: The storm after the quiet!

A counter-argument is that the subjects in the above studies were eating carbohydrate, and that postprandial TG's aren't atherogenic if you're not eating much carbohydrate. Definitely, maybe. In the absence of carbohydrate, there is still glucose in the blood, thanks to the liver. Also, some carbohydrates don't spike blood glucose (or fructose) level. It's pure speculation that the subjects in the above studies had high blood glucose at the same time as high postprandial TG's. As Insulin Resistance/Metabolic Syndrome and/or a high-sugar diet raise fasting TG's, and there was no significant association between fasting TG's and the risk factor for CHD, this suggests that the subjects had no significant metabolic derangement and were not eating excessive amounts of sugar.

Also, some people's LDL levels go extremely high on a very-low-carb, very-high-fat diet. See Lipidaholics Anonymous Case 291 Can losing weight worsen lipids? A very high LDL level results in a high LDL particle count, even if the particles are large (Type A). A high LDL particle count is a strong risk factor for CHD. See also Fig. 1 in Some Metabolic Changes Induced by Low Carbohydrate Diets.

It's possible to get Coronary Artery Calcium (CAC) scans, to measure the amount of calcified plaque in coronary arteries. While a high CAC value means lots of plaque, a zero CAC value doesn't necessarily mean zero plaque, as young people and people with a high Vitamin K2 intake don't have significant calcification. See Stenosis Can Still Exist in Absence of Coronary Calcium.

Update 26th July 2014: See Page 10 of  HIGH CARBOHYDRATE DIETS: MALIGNED AND MISUNDERSTOOD - Nathan Pritikin. Read the text, starting with:-
"Could such a cream meal precipitate an angina attack because the oxygen-carrying capacity of the blood is lowered?"
The answer appears to be "Yes."

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.

Respiratory Exchange Ratio (RER) explained.

Science!

What the heck is this?

RER has been mentioned a few times on this blog. By measuring the rate of CO2 exhaled and the rate of O2 inhaled, it's possible to work out how many kcals/min the body is generating from food at any instant and from what fuel mixture.

An RER of 0.700 means that 100% of energy is being generated from fat.
An RER of 1.000 means that 100% of energy is being generated from carbohydrate aerobically.
An RER of >1.000 means that 100% of energy is being generated from carbohydrate, some aerobically and some anaerobically.

How does this work? Fats are an ester of fatty acids + glycerol. Acid + Alcohol = Ester + Water.

Saturated fatty acids (the easiest type to calculate) have the generic formula CH3(CH2)nCOOH, where n can be from 0 to 16. Here are some saturated fatty acids and their n values:- Acetic (0), Propionic (1), Butyric (2), Lauric (10), Myristic (12), Palmitic (14) and Stearic (16). The total number of carbon atoms in each fatty acid is n+2. Stearic acid is mostly CH2s, so I'll approximate fat to n(CH2).

n(CH2) + 3/2n(O2) = n(CO2) + n(H2O) + Heat. The ratio of CO2 to O2 is 2/3, so RER = 0.666.

As fats contain things other than CH2 (e.g. glycerol CH2OHCHOHCH2OH), this raises RER to 0.700. Burning protein gives an RER = 0.800.

Carbohydrates have the generic formula n(CH2O), where n = 6 for glucose.

n(CH2O) + n(O2) = n(CO2) + n(H2O) + Heat. The ratio of CO2 to O2 is 1.000, so RER = 1.000.

So how on earth can Eskimos have an RER = 0.600? I have a theory. When hydrogen is oxidised, water only is produced. There is no CO2, so RER = 0.000. Therefore, if some hydrogen was being burned (by gut bacteria, say), this could result in RER falling below 0.700. Maybe...

Obesity is multi-factorial, spectra and other stuff.

This post is a hotch-potch of thoughts that are currently whizzing around in my brain.

1) Obesity: Like just about everything in life, obesity is multi-factorial. Each factor may have only a small impact on obesity. Tackling one factor alone won't solve the problem. Every factor has to be tackled, one at a time.

So, New York City Mayor Michael Bloomberg announcing a ban on sales of sugary drinks larger than 16 ounces in restaurants, delis, sports arenas, and movie theaters won't solve the obesity problem, but it will help.

EDIT: In shops and supermarkets in the UK, tobacco products now have to be kept out of sight. I'd like to see the same thing happen to Crap-In-A-Bag/Box/Bottle (CIAB).

2) Spectra: As also mentioned in my first link, there is a spectrum of fatness in the general population which probably follows a bell distribution curve. From skinniest to fattest, there are people who are:-
Extremely skinny. Very skinny. Skinny. A bit skinny. Average. A bit fat. Fat. Very fat. Extremely fat.

If you take somebody in a category who isn't currently consuming CIAB and introduce CIAB to their diet, what happens? They move to a category to the right. Therefore, it's possible for there to be very skinny people who consume CIAB. Therefore, anybody who (or should that be Wooo?) states that the existence of very skinny people who consume CIAB is proof that Food Reward doesn't exist is wrong.

3) Other stuff: I am concerned with people overlooking postprandial (a.k.a. nonfasting) triglycerides (a.k.a. triacylglycerols a.k.a. TAGs a.k.a. TGs) after eating large amounts of fat. According to Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women, serum TGs 2-4 hours post-meal are very significantly associated with Cardiovascular Events (fully adjusted hazard ratio [95% confidence interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P < 0.001 for trend]).

After 4 hours post-meal, serum TGs are cleared from circulation by being burned by muscles and/or by being stored in fat cells. See Figure 3B in Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism.

Uh-oh! There may be trouble ahead...

I won't deny that I'm not very active. On days that I don't visit my mum, I spend many hours reclining on a sofa with a lap-top on a small table, surfing the internet. I make sloths look hyperactive!

I thought that this wasn't a problem as I also don't eat very much (as I'm so engrossed rummaging through the vast amount of information out there) and I'm maintaining a relatively stable weight.

Then I read Sedentary Physiology at Obesity Panacea which lead me to Sedentary Physiology Part 1 – Not Just The Lack of Physical Activity , full study HERE.

"Hamburg et al. (2007) examined the effect of 5 days of complete bed rest on metabolic health in 22 adult volunteers. Study participants remained in bed for over 23.5 h per day, rising only for matters of personal hygiene. At the completion of the study, despite no changes in body weight, they experienced significant increases in total cholesterol, plasma triglycerides, glucose, and insulin resistance. The changes in carbohydrate metabolism were particularly pronounced, with participants experiencing a 67% greater insulin response to a glucose load following the 5-day intervention."

The thing is, I've never liked sports & formal exercise. In infant school, exercise involved running around in the playground. That, I could do. In primary school, exercise involved running around in the playground, some PE and some outdoor sports (rounders & cricket, using a tennis ball). That, I could also do, although my short legs made me rubbish at running. In secondary school, in addition to PE, there were sports such as football, rugby, cricket, hockey, tennis, swimming & cross-country running. That, I utterly hated (tennis was just about bearable) and so to avoid doing them, I developed an art for forging sick notes in my mum's handwriting. This improved my normal handwriting, so some good came of it. So, what to do?

As toilet breaks force me off the sofa, I shall drink more to make me wee more often. I shall also use the upstairs toilet during the day and the downstairs toilet during the night. See also Eat Less, Move More: Solutions to problems.

We are not all the same.

Cont'd from Everyone is Different.

Lyle (McDonald) brought the following study to my attention to illustrate that "We are not all the same":- Some Metabolic Changes Induced by Low Carbohydrate Diets. On a very-low-carb diet, one subject’s total cholesterol rose to 12.9mmol/L (500mg/dL in US units). The others didn't.
See also LDL cholesterol goes sky high on fatty diet.

I posted the study in various blogs to make the above point. Here are some of the replies I got:-
"Lyle? Lyle McDonald? Is that where you got that study, Nigel?" and... "I’m usually a pretty polite guy, Nigel. But based on this quote from the beginning of the study you mentioned, the people who wrote this study were a bunch of f**kwads, and really don’t deserve our attention. It’s a hatchet job."
"That was a weird study (1967) what I could make of it." and... "The men did all the stages but the women only did 3 stages of the diet."
"The fats were mostly omega-6 PUFA 13-35 grams worth..."
"The report you cite is so old and out of date that it makes me cry..."

My point was well & truly missed. I got the distinct impression that people thought I was criticising very-low-carb, high-fat diets. I wasn't. The simple fact is that there is no "One True Diet" that suits absolutely everybody. In the olden days everywhere & in poor countries nowadays, people that ate/eat the wrong diet for their body died/die young. Nowadays in rich countries, they get put on drugs e.g. oral hypoglycaemics (to lower blood glucose) & hypolipidaemics (to lower blood cholesterol/triglycerides).

Please note that omega-6 PUFAs tend to lower serum cholesterol rather than raise it, as per Fig. 2 of Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review. However, don't rush off and eat shed-loads of omega-6 PUFA (e.g. corn oil) in the mistaken belief that it will make you live any longer. See (1971) Incidence of cancer in men on a diet high in polyunsaturated fat - Pearce.

Finally, for a little light relief, here is the latest result for Google Fight between "Healthy "low-fat diet"" and "Healthy "low-carb diet"". Oh, YES!

Cont'd on Everyone is Different, Part 2.

Fats: Spawn of Satan or Dogs' Doodads?

From http://ajcn.nutrition.org/content/65/5/1628S.full.pdf

Fats get a lot of bad press in the media. There are so many adverts with "X% fat-free" or "only 1g of fat per Jaffa Cake" as if that's going to stop you from getting fat when you "om nom nom" your way through a whole box of the things!

Saturated fats are usually described as "bad" and polyunsaturates are usually described as "good". This is simplistic. Everything is bad in excess, even polyunsaturates. The thing about fats is that there are four basic types (saturates, monounsaturates, ω-6 polyunsaturates and ω-3 polyunsaturates) and they need to be consumed in roughly the right proportions for optimum health. Suffice it to say, the majority of people in the West do not eat them in anywhere near the right proportions. So, what exactly are fats?


Fats

Fats are an ester of glycerol (CH₂OH-CHOH-CH₂OH) & 3 fatty acids, and are also known as triglycerides (TG's) or triacylglycerols (TAG's).

1 molecule of glycerol + 3 molecules of fatty acid = 1 molecule of triglyceride + 3 molecules of water.

It's the fatty acids that determine whether a fat is saturated, monounsaturated etc. The four different types of fatty acid have a CH₃ at one end and a COOH at the other. The difference is in the middle section.

Saturated fatty acids have a middle section consisting of CH₂'s. Here's a diagram for Stearic acid (the predominant fatty acid in beef):-

__H H H H H H H H H H H H H H H H H O
H-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-O-H
__H H H H H H H H H H H H H H H H H


Monounsaturated fatty acids have one C=C bond in the middle, which is usually (but not always) 9 from the left-hand end, resulting in monounsaturates often being referred to as ω-9's, as ω is the last letter of the Greek alphabet. Here's a diagram for Oleic acid (the predominant fatty acid in olive oil):-

__H H H H H H H H_____H H H H H H H O
H-C-C-C-C-C-C-C-C-C=C-C-C-C-C-C-C-C-C-O-H
__H H H H H H H H H H H H H H H H H


ω-6 polyunsaturated fatty acids have two or more C=C bonds in the middle, with the last one always being 6 from the left-hand end. Here's a diagram for Linoleic acid (the predominant fatty acid in sunflower oil):-

__H H H H H_____H_____H H H H H H H O
H-C-C-C-C-C-C=C-C-C=C-C-C-C-C-C-C-C-C-O-H
__H H H H H H H H H H H H H H H H H


ω-3 polyunsaturated fatty acids have three or more C=C bonds in the middle, with the last one always being 3 from the left-hand end. Here's a diagram for Alpha-linolenic acid (the predominant fatty acid in flax-seed oil):-

__H H_____H_____H_____H H H H H H H O
H-C-C-C=C-C-C=C-C-C=C-C-C-C-C-C-C-C-C-O-H
__H H H H H H H H H H H H H H H H H


These diagrams are slightly misleading. Where there is a C=C bond, there are two H's on the "underside" only of the molecule. This asymmetry causes the H's to repel each other and bend the molecule into a V-shape at each C=C bond. C=C bonds with H's on the same side are known as "cis" bonds. The above molecule is really cis, cis, cis (c,c,c) Alpha-linolenic acid. The other type of C=C bond is known as "trans" and looks like the following diagram:-

__H H H___H H___H H___H H H H H H H O
H-C-C-C=C-C-C=C-C-C=C-C-C-C-C-C-C-C-C-O-H
__H H___H H___H H___H H H H H H H H


This is a diagram of trans, trans, trans (t,t,t) Alpha-linolenic acid. As the H's are on opposite sides of the molecule, they do not repel each other and the molecule is straight, as shown above. Note that saturated fatty acid molecules are naturally straight. Therein lies the problem with trans-fatty acids. They're straight, like saturated fatty acids, but they have unsaturated bonds, which are prone to peroxidation. See http://www.cyberlipid.org/perox/oxid0002.htm WARNING! Heavy-duty organic chemistry!

Our bodies take trans-fatty acids and incorporate them into cell membranes as if they were saturated fatty acids. This results in atherogenicity (artery-clogging), damage to the immune system and other health problems. Trans-fatty acids are found in partially-hydrogenated vegetable oils, so any cooking/spreading fats which have the word "hydrogenated" high-up in the ingredients list should be avoided. These are bad fats.

There are naturally-occurring trans-fatty acids made by bacteria in the stomachs of ruminant animals, like Conjugated Linoleic Acid (CLA). This looks a bit like the diagram below:-

__H H H H H_____H___H H H H H H H H O
H-C-C-C-C-C-C=C-C=C-C-C-C-C-C-C-C-C-C-O-H
__H H H H H H H___H H H H H H H H H


This has one of the C=C bonds shifted to the left and also has one cis bond and one trans bond, so the molecule is always bent. CLA has possibly beneficial properties, but human trials show mixed results. It's certainly not artery-clogging, so don't let anyone put you off eating butter from grass-fed cows (e.g. Anchor or Kerrygold butter) by saying that it has trans-fats in it. CLA is a harmless trans-fat.


Saturated fat consumption should be about 10% of total calories. This is because, even though saturated fats are not essential (our bodies can synthesise them), this guarantees adequate synthesis of sex hormones. Total polyunsaturate consumption should be about 5% of total calories, with a ω-6:ω-3 ratio of between 1:2 and 4:1. As ω-3's are found in greater quantities than ω-6's only in flax-seeds (a.k.a. linseeds) and oily fish, and many people eat way too little or no oily fish (and who, other than body-builders and some vegetarians/vegans, eats flax-seeds?), the ω-6:ω-3 ratio in the West is ~20:1. This is due to the widespread consumption of meats, eggs & milk from grain-fed animals, grains, nuts and seeds. There are high rates of heart disease and other inflammatory diseases in the West, as ω-6's end up in series 1 & 2 prostaglandins, and series 2 prostaglandins are pro-inflammatory. ω-3's end up in series 3 prostaglandins, which are anti-inflammatory.

So eat up yer oily fish if you're not vegetarian or vegan. Otherwise, eat up yer ground-up flax-seeds!

Monounsaturates can make up about 15% to 35% of total calories, depending on activity levels. From the histogram in Everyone is Different, sedentary people, on average, burn twice as much energy from fats as from carbohydrates.

So, if 25% of energy comes from protein say, 25% of energy can come from carbohydrates, and 50% can come from fats, i.e. a 2:1 ratio of fats:carbs. The cyclists at the left-hand end of the histogram in Chapter 1 would do best on 25% protein, 15% carbohydrate, 60% fat, when sedentary, whereas the cyclist at the right-hand end of the histogram would do best on 25% protein, 60% carbohydrate, 15% fat, when sedentary. When active, more carbs are needed by everyone.

Which fats contain which fatty acids? See http://homepage.ntlworld.com/nigel.kinbrum/comparison-of-fats.gif for a Comparison of Dietary Fats. See http://www.apag.org/oleo/fatsoils.pdf for tables of Properties & Composition of Vegetable & Special Oils and Properties & Composition of Animal & Marine Fats & Oils.

For high-temperature cooking, saturates are the least likely to oxidise (when they're on fire, they're oxidising!), followed by monounsaturates, then ω-6's, with ω-3's being the most likely to oxidise. An oil doesn't have to be smoking, to be oxidising. Alpha-linolenic acid oxidises to varnish at room temperature without smoking, which is why linseed oil is used to varnish cricket bats and dilute putty. The best non-animal fat for high-temperature cooking is Coconut Oil, followed by Palm Oil and then Olive Oil.

Extra-Virgin Olive Oil (EVOO) has a lower smoke point than refined Olive Oil (due to higher levels of free fatty acids), but has higher levels of polyphenol antioxidants, which makes it heart-healthy.

Oils high in polyunsaturates shouldn't be heated to temperatures greater than 100°C, as polyunsaturates can change from the cis configuration to the trans configuration at 102°C. See http://www.harricksci.com/sites/default/files/pdf/application_notes/FatIR_App-Notes_ATR_Oil-Analysis.pdf

Cholesterol And Coronary Heart Disease

Cholesterol & coronary heart disease are mentioned a lot in the media. Unfortunately, most of what you see & hear is either completely wrong, or dumbed-down so much that it's inaccurate.

Fat & cholesterol don't stick to the insides of artery walls like grease on the inside of a drainpipe. This article explains what cholesterol is, how arteries get blocked and how to minimise the risk of having a heart attack or ischaemic stroke.


What is cholesterol?

Cholesterol is a large, waxy molecule (C₂₇H₄₅OH) consisting of a hydrocarbon (fat-soluble) tail, a middle section consisting of four carbon rings (the steroid bit) and an alcohol (water-soluble) group on the end. Cholesterol is a powerful anti-oxidant and is what bile acids, mineralcorticoids, glucocorticoids and sex hormones are made from.

Cholesterol is "chauffeured" around the body in lipoprotein "limousines". Lipoproteins are lipo (fat-soluble) at one end, protein (water-soluble) at the other end and they form a spherical shell around their contents with the lipo end pointing inwards and the protein end pointing outwards. The shell is like the body of the limousine. In the shell, there are apo(lipo)proteins which are like the chauffeur, as they determine where the particles are taken up. HDL has apo A in its shell which makes it get taken up by receptors in the liver. LDL has apo B in its shell which makes it get taken up by receptors in cells, artery walls etc. The passengers are cholesterol, cholesteryl esters, phospholipids and triglycerides. These limousines have different types, like chylomicrons, VLDL, LDL, IDL & HDL, the difference being the type & amount of apo(lipo)protein and the relative proportions of cholesterol & the other passengers. There are also sub-groups of each type.

The different variants are affected by serum triglycerides. High serum triglycerides (caused by a chronic over-consumption of sugary & starchy carbohydrates for activity level) result in cholesterol-depleted, triglyceride-rich particles and low serum triglycerides result in cholesterol-rich, triglyceride-depleted particles. As cholesterol is a powerful antioxidant, small cholesterol-depleted particles (Type B) oxidise faster than large cholesterol-rich ones (Type A).

Oxidised LDL particles are "bad cholesterol" and are swallowed by scavenger macrophages. These expand into foam cells, which become embedded in the intima of artery walls. Other processes occur which cause cholesterol & calcium to accumulate as a plaque inside the media of artery walls. To see a cross-section through an artery wall, click HERE and scroll down to the bottom of the page. Unoxidised LDL particles are not swallowed by scavenger macrophages, so unoxidised LDL particles are not "bad cholesterol". In young people, plaques of cholesterol with no calcium can accumulate within artery walls, making Coronary Artery Calcium (CAC) scans ineffective. See Stenosis Can Still Exist in Absence of Coronary Calcium.

Plaques force the inner artery wall inwards, making the artery narrower, impeding the flow of blood through it. This can cause angina pectoris (pain in the chest) as the heart is starved of oxygen, or vascular dementia as the brain is starved of blood. The cap covering the plaque may rupture, causing chunks of plaque to circulate and block coronary arteries (causing a heart attack), or cerebral arteries (causing an ischaemic stroke).

It's possible to reduce serum triglycerides significantly by eating lots of long-chain omega-3 fats from oily fish. These inhibit the conversion of glucose into triglycerides. Inhibiting the conversion of glucose into triglycerides can result in increased blood glucose levels (not good - see below) if sugary/starchy carbohydrate intake is too high. Solution? Reduce sugary/starchy carbohydrate intake to suit activity level.


Why do foam cells embed themselves into the intima of artery walls?

Arteries are elastic, muscular tubes which stretch a bit each time the heart pumps and contract again between beats. They also relax & constrict to control the flow of blood through them. When you get cold, they constrict to reduce the flow of blood to the skin to prevent excessive heat loss. When you get hot, they open to increase the flow of blood to the skin to increase heat loss.

Foam cells don't go just anywhere. They embed themselves into damaged areas of artery walls. This is a good thing, otherwise damaged artery walls could rupture, causing a haemorrhage.


What damages artery walls?

Chronically-high blood pressure.
Chronically-high blood glucose.
Chronically-high blood free radicals.
Chronically-high blood homocysteine.
Chronically-low blood antioxidants.
Chronically-high blood pro-oxidants.
Chronically-low blood anti-inflammatories.
Chronically-low Vitamin K2.
Chronically-high LDL due to hypothyroidism or other factors.


How can I reduce damage to my artery walls?

1) Have blood pressure (BP) tested regularly. There's one problem with having your BP taken in a GP's surgery and that is 'white-coat hypertension' where the stress of having your arm squeezed by the cuff sends your BP up! If you buy your own BP monitor (Lloyds pharmacy sell a fully automatic BP monitor with standard cuff for £9.99), you can become accustomed to using it and overcome white-coat hypertension. 5,000iu/day of Vitamin D3 can reduce BP by making artery walls more elastic. 4g/day of Epsom Salts provides 400mg/day of Magnesium, which acts as a smooth muscle relaxant, reducing BP & cardiac arrhythmias.

2) Have blood glucose (BG) tested regularly. If you're lucky, you may be able to get a HbA1c test. This shows accumulated damage to red blood cells by blood glucose.

3) Don't smoke! Apart from lung cancer, chronic obstructive pulmonary disease & emphysema, smoking speeds the oxidation of LDL.

4) Take a B-complex containing B6, B12 & folic acid, which lowers serum homocysteine levels.

5) Eat a diet rich in anti-oxidants from coloured veggies (beta-carotene), fruits (Vitamin C + bioflavonoids), tomatoes (lycopene), nuts & seeds (gamma-tocopherol & copper), Brazil nuts (selenium), beer/wine in moderation (muscle relaxant), green tea (polyphenols), cocoa/dark chocolate (polyphenols & copper), onions/garlic (quercetin) etc. See Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50.

6) In men and non-menstruating women, too much iron in the blood relative to copper is pro-oxidant, so don't supplement with iron. Menstruating women have the opposite problem.

7) Take about 2g/day of long-chain omega-3 fats from oily fish, or about 20g/day of flaxseed oil if male, or about 10g/day of flaxseed oil if female. Please note that tinned tuna contains virtually zero omega-3 fats. See Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care.

8) Eat a diet rich in Vitamin K2, to make calcium go into bones & teeth, instead of into artery walls, kidneys & brain. For good sources of Vitamin K2, see HERE. Note: Warfarin/Coumadin works by depleting Vitamin K, so lots of Vitamin K2 makes Warfarin/Coumadin ineffective.

9) If you're feeling tired and are gaining weight for no obvious reason, get serum thyroid hormone levels tested (TSH, FT4 & FT3 preferably), as low thyroid hormones down-regulate LDL receptors, resulting in LDL particles lingering in the blood for longer than usual. This increases LDL-C, LDL-P (particle count) and the oxidation of the particles. See Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis.


What about Benecol & Flora Pro-Activ?

These yoghurts & spreads contain plant sterols/stanols, which reduce total serum cholesterol by up to 15%. However, LDL quality is more important than LDL quantity (up to a point) and there is no evidence that these foods save lives.


What about statins?

Statins (HydroxyMethylGlutarate Coenzyme-A Reductase inhibitors) reduce serum cholesterol. They also have anti-inflammatory & anti-clotting effects by reducing levels of the non-sterol derivative mevalonate and subsequent products. Click HERE to see the cholesterol synthesis pathway. Statins save lives in people who have had a heart attack and in men between the ages of 30 and 60. However, younger & older men and women do not get a significant reduction in deaths, (though heart-attack deaths may be reduced) and there can be undesirable side-effects (muscle pains, memory loss etc). I strongly recommend that anyone taking statins, supplements with at least 100mg/day of Co-Q10, as the synthesis of this vital substance is reduced. Note that fish oils have anti-inflammatory, anti-clotting and anti-arrhythmia actions, but don't suppress the production of Co-Q10.


What about dietary cholesterol?

When cholesterol is eaten, the liver produces less cholesterol. An average egg contains about 250mg of cholesterol. The vast majority of people (who don't have genes for familial hypercholesterolaemia) can eat two eggs a day without significantly affecting their serum cholesterol & triglyceride levels. See Effect of dietary egg on human serum cholesterol and triglycerides, and Eat Whole Eggs All Day and Throw Your Statins Away? 375x Increased Dietary Cholesterol Intake From Eggs Reduces Visceral Fat & Promotes Healthy Cholesterol Metabolism. People with the ApoE4/E4 polymorphism are more sensitive to dietary fat & cholesterol raising serum LDL, and cannot eat fat & cholesterol willy-nilly.

There are a couple of sites that have CVD risk calculators, JBS2 and QRISK®2-2013. The National Institute for Clinical Excellence (NICE) no longer recommends the use of JBS2, as it's overly-pessimistic. Note that CVD mortality isn't the same thing as overall mortality. Slightly higher-than-"normal" total cholesterol level is associated with lower overall mortality, according to Research finds ‘raised’ cholesterol to be associated with a reduced risk of death.