In starvation or ketosis, protein should have NO EFFECT on blood glucose level, not RAISE it.

From Blood Sugar is Stable:-

In a healthy person, BG (blood glucose) is held at a fairly constant value with slowly-varying glucose inputs (except after high-GL meals, which produce rapidly-varying glucose inputs) by a NFB (negative feed-back) loop. See Blood Glucose, Insulin & Diabetes.

When protein is eaten, this produces a glucagon response from pancreatic alpha cells, which tries to raise blood glucose level by stimulating the liver to convert liver glycogen plus water to glucose. Protein also produces an insulin response from pancreatic beta cells, which tries to lower blood glucose level by a) increasing glucose uptake from the blood and b) inhibiting HPG (hepatic glucose production). The net result is no change in BG level.

In extended fasting or on VLC (very low carbohydrate)/ketogenic diets, there's no liver glycogen left after ~1 day.
∴ The glucagon response has no effect on HGP.

The insulin response still has an effect, until physiological IR* develops.
∴ Blood glucose tries to decrease, but the HPAA keeps it steady by raising cortisol level.

RE How eating sugar & starch can lower your insulin needs: Blood glucose level on a VLC/ketogenic diet can be RAISED, due to the BG NFB HPAA (hypothalamic pituitary adrenal axis) loop not having a precise set point with the cortisol/adrenaline response (hyperglycaemia is not fatal, whereas hypoglycaemia can be fatal, as the brain always needs some glucose to function (~50%E from glucose)).

So, how come people on LCHF (low carbohydrate, high fat) diets can have normal or slightly low BG levels?

1. Luck. The BG NFB HPAA loop isn't very precise.

2. Excessive intake of Booze. Ethanol inhibits HGP (dunno about RGP (renal glucose production)).

3. Insufficient intake of Protein. This deprives the liver & kidneys of glucogenic amino acids (Alanine & Glutamine are the 2 main ones), forcing BG down and making the HPAA run open-loop and raise cortisol level. There's another source of Alanine & Glutamine available - Lean Body Mass. Uh-oh!


Consuming more protein on extended fasting or a VLC/ketogenic diet can result in higher BG level for three reasons.

1. It allows the HPAA to run closed-loop, as it's supposed to.

2. The lack of a 1st phase insulin response in people with IR/IGT/Met Syn/T2DM* results in a temporary BG level spike with the intake of rapidly-absorbed proteins e.g. whey. There's an unopposed glucagon response, until the 2nd phase insulin response begins.

See http://care.diabetesjournals.org/content/early/2015/11/29/dc15-0750.abstract

*Long-term drastic carbohydrate restriction kills the 1st phase insulin response! See http://carbsanity.blogspot.co.uk/2013/10/insulin-secretion-in-progression-of.html

P.S. This only applies to people who have sufficient liver glycogen, due to them eating some (50 to 100g/day, say) carbohydrate.

3. Hepatic Insulin Resistance results in the insulin response inadequately suppressing Hepatic Glucose Production. As 50g of protein (an 8oz steak, say) yields ~25g of glucose from glucogenic amino acids, there's an increase in the amount of glucose entering circulation, which raises BG level.

See http://bja.oxfordjournals.org/content/85/1/69.long

Keto Clarity: Your Definitive Guide to the Benefits of a Low-Carb, High-Fat Diet - My "Review".

I haven't bought the book - surprise, surprise!

From http://www.amazon.com/Keto-Clarity-Definitive-Benefits-Low-Carb/dp/1628600071/

If anybody thinks that I can't review this book because I haven't read it, you really haven't been paying attention! Here's what I wrote in reply to JoAnn Schreffler's comment:- N.B. Hyperlinks added.

Exactly!

Gluconeogenesis also isn't very accurate in terms of generating blood glucose.
Sometimes, it can result in high blood glucose.
http://nigeepoo.blogspot.co.uk/2012/04/how-eating-sugar-starch-can-lower-your.html

To reduce blood glucose, reduce protein intake. Unfortunately...

1) Minimising dietary protein starves the liver & kidneys of gluconeogenic precursors.
2) Blood glucose level drops.
3) The pituitary gland secretes ACTH.
4) ACTH stimulates the adrenal cortex to secrete cortisol.
5) Cortisol cannibalises LBM* to create gluconeogenic precursors.
*LBM = Lean Body Mass = muscles & organs.
This doesn't sound like a good idea to me.

Also, ultra-high-fat diets are not healthy.
http://nigeepoo.blogspot.co.uk/2014/06/ultra-high-fat-80-diets-good-bad-and.html
http://nigeepoo.blogspot.co.uk/2014/07/nutritional-ketosis-what-is-it-good-for.html
http://nigeepoo.blogspot.co.uk/2014/08/ketogenic-diets-and-sudden-cardiac-death.html

Low-carb diets with up to 50%E from fats are fine. There's no Metabolic Advantage to ketogenic diets and there are many disadvantages to long-term ketogenic diets. If you suffer from refractory epilepsy, a medically-supervised ketogenic diet is fine. Branched Chain Amino Acids can be added as adjunctive therapy, as they are ketogenic.
http://www.ncbi.nlm.nih.gov/pubmed/19687389

I have no axe to grind against Jimmy Moore. I hate pseudoscience and sadly, Jimmy's book is full of it. Check the list.
http://nigeepoo.blogspot.co.uk/2014/06/guest-post-science-versus-pseudoscience.html
I practise science and I back up everything I say with quality peer-reviewed evidence. If you don't like it, tough.
Science doesn't care if you believe in it or not. It's still valid. I expect that my comment will be down-voted by pseudoscientific thinkers & cholesterol denialists.
http://nigeepoo.blogspot.co.uk/2014/06/guest-post-denialism-as.html
I don't care if you believe in it or not. It's still valid.

I'm an omnivore. I'm NOT a vegan, just so's you know!


I've only just added the last line, as I've noticed a tendency for some (stupid) Amazon commenters to accuse an author of being a Veg*n, when they don't agree with the review!

Dear ItsTheWoo, how do you do?

This post is attacking what I consider to be faulty reasoning. It's not a personal attack on ItsTheWoo, who I like (even though she drives me up the wall, sometimes!).

From http://hypetrak.com/2011/10/mayer-hawthorne-how-do-you-do-full-album-stream/

See What I believe and what I don't.
The basic The Energy Balance Equation:- Change in body stores = E_in - E_out
For a detailed mathematical analysis of weight change, see Completing the trine: vive la différence!

From Back to black, CIAB, pharmaceutical drug deficiencies & nerds:-
Where body weight is concerned, calories count (but don't bother trying to count them).
Where body composition is concerned, partitioning counts.
Where health is concerned, macronutrient ratios, EFAs, minerals, vitamins & lifestyles count.


The faulty reasoning is in Dear Nigel and other CICO zealots: you are ignorant. Charming!

I'll quote passages from it and refute them, one by one.

• "With a zero caloric deficit, there is zero weight change"

"FACT: Calories neither determine weight OR body composition with certainty. Nigel / some CICO zealots may agree body composition changes are privy to nutrition, but wt is 100% controlled by calories. This is something they pretty much made up and biological science does not at all support this idea. Calories neither control body composition OR body weight/mass with any certainty. The bulk consumed with fork and spoon does not need to stick on your body in the form of a mass laden tissue, ever."
Calories determine weight change. See Bray et al shows that a calorie *is* a calorie (where weight change is concerned). It would have been nice if Fig. 6 had contained a plot of "Effect of energy intake on change in body weight", but it didn't.
LBM = Lean Body Mass
FM = Fat Mass = Body Fat
Weight change = LBM change + FM change
Weight change varies from ~+3.5kg (@ +2,500kJ/d) to ~+9.1kg (@ +5,900kJ/d).
(Maximum weight increase)/(minimum weight increase) = 2.6
(Maximum kJ/day increase)/(minimum kJ/day increase) = 2.36
∴ A calorie IS a calorie (where weight change is concerned).
∴ Insufficient protein can result in loss of LBM (bad).

The main thrust of ItsTheWoo's argument is that inter-personal variations in weight gain from subject to subject, invalidates Bray's conclusion. It doesn't.
Some subjects become more energetic on a 40% caloric surplus, which increases their NEAT & TEA, which increases their Eout, which reduces their weight gain.
Some subjects don't change their energy on a 40% caloric surplus, which doesn't change their NEAT & TEA, which results in intermediate weight gain.
Some subjects become less energetic on a 40% caloric surplus, which decreases their NEAT & TEA, which decreases their Eout, which increases their weight gain.

I believe that the Insulin Sensitivity (IS) of the subject determines which category they fall into and by how much. The higher the IS, the higher the energy, as high IS results in low serum insulin, which minimises sedation. Energy Balance always applies.

I've never stated that Calories exactly determine weight change. That's a strawman.
I've never stated that Calories determine body composition. That's a strawman.

•  " Every subject [in bray's overfeeding study] gained weight (mostly fat mass) during the 40% energy excess overfeeding period. "

"Again, making crap up. There is NO RULE IN BIOLOGY which states all consumed energy must be retained as body mass. Indeed most typical people gain fat during overfeeding (with great resistance/inefficiency of fat gain), but it is indeed possible to hardly gain any or none at all as in constitutional thinness. What happens during calorie consumption among different people (and perhaps, different DIETS and different TIMES and different ENDOCRINE situations...) is a wild card determined by the biology i.e. neuroendocrine functions of the animal in question. There is NOTHING about physics which reflects / informs physiology other than the basic fact the latter exists within the former (which, again, tells us NOTHING ultimately). How organisms process consumed nutrition is not a physics question. There is no freakin' law of physics or physiology for that matter which states nom nom time = thigh chub. You don't have to wear that pizza as a popeye's muscle or as a shelf butt."
Somewhere within all of the irrelevant waffle about rules & laws, ItsTheWoo raises an interesting point. Although a caloric surplus is always required for weight gain, eating more Calories can sometimes result in zero weight gain. How so? From ItsTheWoo's link:-
"Conclusion: This data is the first to demonstrate a resistance to weight gain in constitutional thinness (CT) population in response to 4-week fat overfeeding, associated with an increase in resting energy expenditure and an emphasised anorexigenic hormonal profile.
In CT people, their energy expenditure increases in line with their energy intake. Therefore, even though they're eating more Calories, there's no caloric surplus, therefore there's no weight gain. Energy Balance always applies.

• "Yes, kcals do get wasted. You don't understand things quantitatively i.e. how many kcals get wasted."

"I know anxious/obsessional people like the safe feeling of balancing calories. The fact reality is more complex and you can't just enter things in a phone app and be ASSURED of what is going on in your body, doesn't invalidate the truth of the fact metabolic reactions are more complex THAN CALORIES.

Just because it is *impossible* for a reasonable free living human to quantify all of the metabolic, endocrine, nervous system factors influencing adipocyte growth changes does not mean they don't fucking exist."
ItsTheWoo left out my calculations. Here they are:-"if I eat 2000 calories of a ketogenic diet in 3 hrs, most of it is wasted as heat, physical energy (I know, because I am EXTREMELY warm/energetic) and then the rest of time i am using a relatively greater percent of stored fat."
Do you know at what rate you're burning-off extra energy intake as heat energy output when you're "EXTREMELY warm/energetic"? Here's an estimate:-
If the mean TEF for your meal is 11% (assuming your meal is 50%E protein & 50%E fat), that's 220kcals (921kJ) "wasted" as heat energy. That'll make you feel EXTREMELY warm, as 220kcal raises the temperature of 57kg of water (your body) by 3.84°C.

A 2,000kcal meal (a whole day's worth of food) takes a lot longer than 3 hours to digest & absorb. I'll guesstimate it as 24 hours. 921kJ of extra heat power over the course of 24 hours = 10.7W, which is an increase of 17.7% over your normal Metabolic Rate of ~60W heat power (~1kcal/minute).
It's easy to "prove" something by being vague. That's PSEUDOSCIENCE. I do science. If you do the maths, you can see that, of the 2,000kcal ketogenic meal, most of it isn't wasted as heat, because if most of it is wasted as heat, ItsTheWoo would spontaneously combust!

• "Dr. Robert C. Atkins made the same fundamental cock-up when he said that humans pissed-out loads of kcals of ketones each day, giving a Metabolic Advantage to ketogenic diets."

"1) The advantage of a ketogenic diet (non-fasting) does exist, so it's not a 'cock up", even if his mechanism was wrong.
2) If atkins was wrong (you pee out all LCHF food) who cares? That was 30+ years ago. He was a cardiologist who observed a VLC diet made him slim. He used his medical education to hypothesize a reason why. His hypothesis was wrong, but his observations were right. This happens all the time in science or basic human reasoning; make observations, form hypothesis. The hypothesis may be wrong, the findings are STILL RIGHT (i.e. low carb diets DO make slim, just not via peeing away ketones)."
1) There is no Metabolic Advantage to ketogenic diets. See http://www.jbc.org/content/92/3/679.full.pdf
2) Atkins' observations were wrong. See The Battle of the Diets: Is Anyone Winning (At Losing?)
a) Low-Carb diets work better than High-Carb diets for people who are Insulin Resistant.
b) Low-Carb diets work worse than High-Carb diets for people who are Insulin Sensitive.
c) Low-Carb diets work the same as High-Carb diets for everybody in Metabolic Ward Studies.
If there's a Metabolic Advantage to ketogenic diets, they would work better than high-carb diets all the time. They don't. See How low-carbohydrate diets result in more weight loss than high-carbohydrate diets for people with Insulin Resistance or Type 2 Diabetes for my hypothesis, which explains a), b) and c).

Ketogenic Diets and Sudden Cardiac Death.

Last night, thanks to comments on my previous post, I stumbled across The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism, then a Google search led me to Sudden Cardiac Death and Free Fatty Acids.

The following graph is Figure 1 from Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet.

Nice Insulin, shame about the FFAs.

From the first link above:-
"Current ketogenic diets are all characterized by elevations of free fatty acids, which may lead to metabolic inefficiency by activation of the PPAR system and its associated uncoupling mitochondrial uncoupling proteins."

From the third link above:-
"Weight loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs."

See also Elevated plasma free fatty acids predict sudden cardiac death: a 6.85-year follow-up of 3315 patients after coronary angiography, and Circulating Nonesterified Fatty Acid Level as a Predictive Risk Factor for Sudden Death in the Population.

I think that's quite enough bad news for a Friday afternoon.


EDIT: So much for fat being a "clean-burning" fuel for the heart. Some people believe that, because dietary fats pass from the small intestine, via the Lacteals, to circulation at the Subclavian vein, this means that the heart prefers to burn fatty acids.

From Page 10 of HIGH CARBOHYDRATE DIETS: MALIGNED AND MISUNDERSTOOD:-

Did you know that Human erythrocytes (red blood cells) are loaded with cholesterol and that it can contribute towards atherosclerosis? See https://twitter.com/Drlipid/status/496625195738619904.

See also Evidence for a cholesteryl ester donor activity of LDL particles during alimentary lipemia in normolipidemic subjects. This is more evidence that very high fat meals are atherogenic, which is relevant to Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

The Ketogenic Diet: Uses in Epilepsy and Other Neurologic Illnesses.

Fools claim that I am anti-ketogenic diets. Am I ****! beta-Hydroxybutyric acid has its uses...

From http://www.fuelforthought.co/the-ketogenic-diet-uses-in-epilepsy-and-other-neurologic-illnesses-2/

From The Ketogenic Diet: Uses in Epilepsy and Other Neurologic Illnesses:-

"Inconsistencies in studies attempting to correlate seizure protection with levels of ketone bodies suggest that another mechanism may be involved in the diet’s beneficial effects on seizures. Several mechanisms have been proposed, including changes in ATP production making neurons more resilient in the face of metabolic demands during seizures; altered brain pH affecting neuronal excitability; direct inhibitory effects of ketone bodies or fatty acids on ion channels; and shifts in amino acid metabolism to favor the synthesis of the inhibitory neurotransmitter GABA."

GABA is an interesting neurotransmitter, as it's the chief inhibitory neurotransmitter in the mammalian central nervous system.

I know of two other substances that enhance GABA's effects - Alcohol and Benzodiazepines.


In conclusion:

I'm in favour of ketogenic diets under medical supervision, as therapy for neurologic conditions etc.

I'm not in favour of ketogenic diets under lay supervision, as a supposed aid for weight loss.

Jumping through hoops, and my Blog List.

I'm seeing a curious thing. The VLC "camp" seems to be "jumping through hoops" to prove a point.

From http://davidbressler.com/2013/08/26/easier-harder/

From Neuron fuel and function (emphasis & formatting, mine):-
"Ketones and lactate do not drive reverse electron flow through complex I. Glucose can. Palmitate certainly can. What you want from a metabolic fuel depends on the remit of your cell types. Neurons within the brain preserve information by their continued existence.

This is best done by burning lactate or ketones. NOT glucose and, of course, not FFAs.

Anyone who claims that glucose is the preferred metabolic fuel of the brain has not though (sic) about what a neuron has to do and what an astrocyte actually does do. Or much about the electron transport chain."

Basically, glucose is bad mmm-kay. Also, anyone who claims that glucose is the preferred metabolic fuel of the brain is a dumb-ass. Damn our livers & kidneys churning out glucose! Are they trying to kill us?

∴ Carbohydrates are bad and must be avoided at all cost! This, of course, is utter nonsense.

Glucose can drive reverse electron flow through complex I. Can means that it's possible. Is it probable?

On a hypercaloric Western diet of excessive crap-in-a-bag/box/bottle, yes.

On a Kitavan diet of ~70%E from tubers, no.

On a diet of Basmati rice & beans, no.

On a diet of whole fruits, no.

See also Another crash and burn on low carb paleo and CrossFit. Enough of the 'carbs are evil' nonsense. Carbphobia is hurting a lot of people.

I have a list of blogs that I read on a regular basis. As a result of the bad science & cherry-picking displayed in various VLC blogs, I have deleted them from my Blog List.

See also Guest post: Denialism as Pseudoscientific Thinking.

How low-carbohydrate diets are (incorrectly) explained to work.

Having explained how low-carbohydrate diets work, here are a few ways in which they don't work.

Uh, nope!

1. Hormonal clogs: This is a term used by Jonathan Bailor. I don't think he's referring to wooden shoes! The "clog", I'm guessing, is supposedly caused by that dastardly hormone insulin. Uh, nope!

See the following plots of RER vs exercise intensity after being on high-fat diet or low-fat diet.

RER = 0.7 ≡ 100%E from fat. RER ≥ 1.0 ≡ 100%E from carb.

The low-fat diet results in higher RER, so the body is burning a higher %E from carb and a lower %E from fat.

However, this doesn't make any difference to weight loss, as it's merely a substrate utilisation issue. In addition, when the body is burning a higher %E from carb, this depletes muscle glycogen stores faster, which lowers RER during the course of the exercise. So, it's not a problem.


2. Insulin: This is Gary Taubes' hypothesis. Insulin makes your body store carbohydrates as body fat. Uh, nope!

The only time that there's significant hepatic DNL is when there's chronic carbohydrate over-feeding. If you eat sensibly, there's no significant hepatic DNL.


3. A Calorie isn't a Calorie, where weight change is concerned: This is Richard D Feinman's hypothesis. "A calorie is a calorie" violates the second law of thermodynamics, therefore there's a metabolic advantage with low-carbohydrate diets. Uh, nope!

Where to start? Evelyn Kocur knows her Physics, so I'll start there. See The first law of thermodynamics (Part 1) and The first law of thermodynamics (Part 2).

From Second Law of Thermodynamics:-
"Living organisms are often mistakenly believed to defy the Second Law because they are able to increase their level of organization. To correct this misinterpretation, one must refer simply to the definition of systems and boundaries. A living organism is an open system, able to exchange both matter and energy with its environment."

People on ketogenic diets excrete very few kcals as ketone bodies. See STUDIES IN KETONE BODY EXCRETION. There is no significant Metabolic Advantage with low-carbohydrate diets.

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.