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.

Siri-Tarino et al, Forests & Trees and "Eureka!" moments.

Here's Fig. 2 from Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease:-

Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between saturated fat intake in relation to coronary heart disease and stroke.

The above "Forest" plot has a subtotal RR of 1.07 (95% CI 0.96 1.19). The overall conclusion is that there's no association between saturated fat intake and the RR for CHD. Hmmm.

I looked at the data in Table 3. Of the 16 studies contributing to the CHD results, only 3 of them specify high sat fat intakes over a wide range. The results from these 3 studies are as follows:-

Pietinen et al: RR=0.93 (95% CI 0.6, 1.44).
Mann et al: RR=2.77 (95% CI 1.25, 6.13).
Boniface et al: Pooled RR = 1.37 (95% CI 1.17, 1.65).

The results from Pietinen et al are statistically-insignificant (95% CI values are way above & below 1) with an overall slight protective effect. The results from Mann et al have a RR >> 1 with both 95% CI's >1 and the results from Boniface et al have a RR >1 with both 95% CI's >1.

Other studies either have sat fat intakes varying from very low to low, or specify mean/median sat fat intakes without values for highest & lowest tertiles/quartiles/quintiles etc. Other studies have results that are statistically-insignificant.

However, there are some studies that show a slight protective effect of small amounts of sat fats. How come?

Thanks to George Henderson, I had a "Eureka!" moment. He posted a link to Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis.

Here's Fig. 1 from that study.

HRs and 95% CI's of CVD risk according to quintiles of energy-adjusted SF from different sources (n = 5209).

The Meat SF plot has a net positive slope (bad news, but the range of intake is very small), the Butter & Plant SF plots are random, but the Dairy SF plot has a net negative slope (good news). Dairy saturated fats in amounts of up to 10g/day are protective against CHD. As the Dairy sat fat intake is too small to have a significant effect on lipids, what's the mechanism? I think that it's Vitamin K2. See Chowdhury et al, More forests & more trees and more "Eureka!" moments with cheese.

When you average out the results from all studies, the result is null. This is data dilution statistics.

EDIT: See also Study: Saturated Fat as Bad as Sugar!

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.

Reversing type 2 diabetes, the lecture explaining T2D progression, and how to treat it.

Julianne Taylor of Paleo & Zone Nutrition posted the following excellent lecture on Facebook:-

Eating Through The Myths: Food, Health and Happiness - Taylor, Prof. R., Berlin, 28-Sep-12

Salient points:

1) It's a chronic calorie excess (of carbohydrates and/or fats) that causes problems.
2) Motivation, motivation, motivation!
3) Both diet and exercise are important. See Move More: Solutions to problems.
4) You can't outrun your fork. See The 5th Myth of Modern Day Dieting: You Can Outrun Your Fork.
5) Underlying Insulin Resistance needs to be addressed. See Insulin Resistance: Solutions to problems.

See also Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol, and Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause.

For more information on Prof. Taylor's work, see Reversing Type 2 Diabetes.

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.

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. Note that the effect of a preceding high-carbohydrate meal on fasting TG's is only +0.1mmol/L. Is high postprandial TG's a problem? Definitely, maybe. From Cholesterol And Coronary Heart Disease , "Cholesterol-depleted particles oxidise faster than large, cholesterol-rich ones." Chylomicrons, chylomicron remnants & VLDL-C are triglyceride-rich, cholesterol-poor, as that's the composition of the fat in the diet.

The ugly:

Here's evidence that excessive postprandial TG's significantly raise the relative risk (RR) 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 RR 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.

According to Very Low-Carbohydrate and Low-Fat Diets Affect Fasting Lipids and Postprandial Lipemia Differently in Overweight Men, there's a ~50% reduction in postprandial TG's after adaptation to a very-low-carb, very-high-fat diet. However, mean energy intake was only 1,850kcals/day. The subjects were in a 500kcal/day energy deficit and the %E from fat was only 60%.

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."