Low-carbohydrate diets: Green flags and Red flags.

Fun with flags. But first, a poem!
Atkins Antidote
 
Eating low carbohydrate what threat that poses?
Do my friends think I’m suffering from halitosis?
I’ve got these sticks for measuring ketoacidosis
I’m taking supplements but I don’t know what the dose is

I’m trying hard to keep in a state of ketosis
I’m not sure what the right amount of weight to lose is
I’m sure I’ve put on a pound just through osmosis
Is eating this way risking osteoporosis?

Are my kidneys wrestling with metabolic acidosis?
My store of liver glycogen I don’t know how low is
Who knows what the glycemic load of oats is?
Does anyone know if I can eat samosas?

Ian Turnbull (whose poetry is better than his science!)

I do. The answer's "No!" :-D

From https://forum.nationstates.net/viewtopic.php?f=23&t=13567&start=8925

The Green flags... 

1. For a person with Insulin Resistance, an ad-libitum low-carb diet results in more weight loss than an ad-libitum high-carb diet.

See How low-carbohydrate diets result in more weight loss than high-carbohydrate diets for people with Insulin Resistance or Type 2 Diabetes , for an explanation.

2. For a person with Type 1 Diabetes Mellitus (T1DM), a lowish-slowish-carb (~150g/day) diet results in minimal disturbances to blood glucose levels and minimal bolus insulin doses.

See Diabetes: which are the safest carbohydrates? , to see which foods should comprise the ~150g/day.

3. For a person with LADA or MODY, see 2.

4. For a person with Type 2 Diabetes Mellitus (T2DM), a LCLF 600kcal/day Protein Sparing Modified Fast can normalise BG in 1 week and reverse T2DM in 8 weeks (provided there are sufficient surviving pancreatic beta-cells). See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168743/
"After 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003)." and
"Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min−1 m−2)."

After 8 weeks, the diet is gradually changed to a healthy balanced diet containing carbs.

See also https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)33102-1/fulltext and Roy Taylor - Reversing the irreversible: Type 2 diabetes and you. 4th Oct 2014

Compare the above results with the inferior results obtained in A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes, which is 10 weeks of VLCVHF Nutritional Ketosis.


As Insulin Resistance is multi-factorial, ALL of the potential causes need to be addressed. Once this has been done, IR should be reversed, allowing restrictions on dietary carbohydrate intake to be lifted. See also Can supplements & exercise cure Type 2 diabetes?

The Red flags...

The low-carb diet is a temporary patch to ameliorate the symptoms of IR/IGT/Met Syn/T2D, a bit like replacing a blown fuse by sticking a nail in its place, to allow the house to function while you fix the problem by fitting a new fuse. Although a house functions with a nail instead of a fuse, it's not a good idea to spend the rest of your life without a fuse to protect the house from fire in the event of a short-circuit.

So, why do LCHF'ers want to spend the rest of their lives using a temporary patch to ameliorate the symptoms of their IR/IGT/Met Syn/T2D?

Long-term use of very-low-carb, very-high-fat, low protein diets (a.k.a. Nutritional Ketosis) is not recommended.

1. Cortisol and adrenaline levels increase due to insufficient glucose production from dietary protein, resulting in gradually-increasing fasting BG level. See How eating sugar & starch can lower your insulin needs and Survival of the Smartest (part 2) - Dr Diana Schwarzbein.

2. If you do too much high-intensity exercise, you may momentarily black-out, fall and hurt yourself. See "Funny turns": What they aren't and what they might be.

3. Insulin Resistance is bad and should be reversed, if at all possible. See Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

4. T2D causes carbohydrate intolerance and fat intolerance, resulting in high postprandial BG and high postprandial TG. See Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity.

5. Dyseverythingaemia isn't fixed. See When the only tool in the box is a hammer.

6. High-fat diets with no energy deficit result in high postprandial TG & high LDL-c. Postprandial lipaemia & high LDL-c are atherogenic. See Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

7. Permanently-high NEFA (a.k.a. FFA). See Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, very-low-carbohydrate diet.

This raises the RR for Sudden Cardiac Death.

This also depletes beta cells causing loss of the 1st phase insulin response. See Chronic Exposure to Free Fatty Acid Reduces Pancreatic b Cell Insulin Content by Increasing Basal Insulin Secretion That Is Not Compensated For by a Corresponding Increase in Proinsulin Biosynthesis Translation.

Loss of the 1st phase insulin response causes Impaired Glucose Tolerance (IGT). See β-Cell dysfunction vs insulin resistance in type 2 diabetes: the eternal “chicken and egg” question

IGT causes high postprandial blood glucose after eating incidental carbohydrates. This is Metabolic Inflexibility, which isn't good.

8. Natural selection increases the incidence of a genetic impairment in the Inuit which reduces ketosis, inferring that reduced ketosis is an evolutionary advantage. Watch Inuit genetics show us why evolution does not want us in constant ketosis.

That's all for now.

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 (Fig. 1).

Fig. 1 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 short-term increase in blood glucose level. Ditto for insulin (see Fig. 2 ▪ & □ below).

Fig. 2 from Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

An OFTT (40g of fat as cream) doesn't cause a significant increase in blood glucose level (see Fig. 1 • & ○ above). Ditto for blood insulin (see Fig. 2 • & ○ above).

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 (Fig. 3).

Fig. 3 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 increase in blood triacylglycerol (a.k.a. TAG a.k.a. triglyceride a.k.a. TG) level for 3 hours. Note that the effect of a preceding high-carbohydrate meal on fasting TG is only +0.1mmol/L. Is high postprandial TG 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 high postprandial TG is atherogenic. See Fig. 1 in Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women.

People who have Insulin Resistance &/or type 2 diabetes have impaired postprandial clearance of glucose and TG, which is atherogenic. Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity.

Here's evidence that postprandial saturated fat TG is atherogenic. 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? and Uncovering a Hidden Source of Cardiovascular Disease Risk.

A counter-argument is that the subjects in the above studies were eating carbohydrate, and that postprandial TG isn't atherogenic if you're not eating much carbohydrate. Definitely, maybe. In the absence of carbohydrates, there is still glucose in the blood, thanks to the liver and kidneys. 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. As Insulin Resistance/Metabolic Syndrome and/or a high-sugar diet raise fasting TG, and there was no significant association between fasting TG 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 after adaptation to a low-carb, high-fat diet. However, mean energy intake was 1,850kcals/day, the subjects were in a 500kcal/day energy deficit and %E from fat was 60%.

Some people's LDL becomes very high on low-carbohydrate high-fat diets. See 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.

See also Page 10 of  HIGH CARBOHYDRATE DIETS: MALIGNED AND MISUNDERSTOOD - Nathan Pritikin.
"Could such a cream meal precipitate an angina attack because the oxygen-carrying capacity of the blood is lowered?"
The answer is "Yes."

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.