Thursday, August 11, 2016

Protein catabolism should generate an RQ of around 0.8

Anyone who has read Martha's story and put her narrative together with the folks in Phinney's 1980 study will have immediately wondered: How many of Phinney's subjects were lactating? Even just a little bit?

I think we can say, pretty categorically, that none of them were lactating. Gluconeogenesis from lipid is very likely to have been occurring but obviously (now) this can only drop the RQ when the glucose produced is not being oxidised. Clearly my initial idea expressed in the Phinney post is wrong.

Martha is easy, her child took the sugars hence the spectacularly low RQ. Trying to explain why a protein supplemented fast should drop the RQ below 0.69 needs a little more thought.

This is what Phinney thought might be happening under moderate exercise:

"The low RQ value of 0.66 observed during the final exercise test was surprising, as long chain fatty acid oxidation occurs at an RQ of 0.69. (The only common fuel oxidized at a lower ratio is ethanol at 0.67). The answer to this disparity may lie, at least in part, in the rise in serum ketone concentration observed during exercise. As the hepatic production of ketones from long-chain fatty acids occurs at an RQ of zero, a net retention of ketones in body fluids will result in a reduction in observed RQ due to non steady-state conditions. By calculating the increase in the whole body ketone pool associated with exercise, one can account for approximately half of the decrement of CO2 production that would be necessary to explain the decrease in RQ below 0.69. Other factors that could contribute to this low RQ include losses of ketones in the urine and loss of acetone in the breath after decarboxylation of acetoacetate in the blood, as well as CO2 utilized in urea genesis".

However, the non steady state accumulation of ketones does not apply to the at-rest readings from the Eskimo in Heinbecker's study.

I'd like to have a guess at the more "steady state" condition.

Full oxidation of a "typical" protein such as albumin produces a value of around 0.8 for the RQ. So I've invented a single mythical amino acid which gets close to the average RQ of protein. It looks like this:


Two of these amino acids oxidise using nine molecules of oxygen to give one molecule of urea and seven molecules of CO2, giving an RQ of 0.78. If this was replaced with a dietary equivalent the RQ would stay around 0.8 and the RQ of 0.69 from saturated fat would be increased somewhat. If the oxidised amino acid was not replaced the RQ change would be exactly the same but muscle wastage would occur.

What if, as a ketosis induced protein sparing effect, certain non-essential amino acids, were synthesised from urea plus carbon from fats plus a little oxygen. I'm not suggesting for a moment that this is exactly what happens, but the equation must balance whatever pathways might be used.

I've spent quite some time with scraps of paper working out how much oxygen has to be added to a couple of -CH2-CH2- moieties from saturated fat, along with a urea molecule, to reassemble the above pair of amino acids. "Mythical" protein turnover...

It takes 3O2 and liberates one CO2.

Combining this with the 9 O2 and 7 CO2 from oxidation, the whole repalcement of this amino acid would use:

12 O2 and generate 8 CO2 giving and an RQ of 0.67.

So the replacement of one "typical" amino acid using part of the acyl-chain of a saturated fatty acid generates an RQ of 0.67.

That's getting us somewhere below 0.69, what then matters is how general this effect might be which obviously depends on protein turnover, protein intake, protein quality and anything else anyone can think of. The value is pushed further down by the loss of oxygen rich ketone molecules through the breath and urine.

I'm very aware that minor errors in logic or arithmetic might alter the above calculations.

What an RQ well below 0.69 speaks very clearly against is gross muscle catabolism (which pushes the RQ upwards towards 0.80). Clearly, muscle loss does occur but I can see no reason why muscle loss should be an essential pre requisite for fat oxidation during fasting. The ability to minimise muscle loss under fasting (or ketogenic eating) might just provide some advantage on an evolutionary basis.

Marking out amino acid oxidation (ie loss of protein) as an essential pre requisite to fatty acid oxidation (in the absence of carbohydrate) suggests a rather odd view of reality. If it were correct it should show as elevated RQ's above 0.69 in proportion to the amount of amino acid oxidation which might be going on.

Which is not the case.


Edit for raphi: the arithmetic:


Kindke said...

I found this study sometime ago which I thought was interesting, PPARa and ketosis are ofcourse intimately linked.

Hepatic amino acid-degrading enzyme expression is downregulated by natural and synthetic ligands of PPARĪ± in rats.

Peter said...

Kindke, link won't work. But if FFAs burn in the flame of OA, how could ketosis suppress protein degradation???? *sarcasm*


August said...

I am doing a little experiment with exogenous ketones because of something things that I have heard. Things that culminated in me finding this study:

Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.

If it actually works in terms of building muscle, the government will probably ban it.

Peter said...

Makes you wonder where, and why, that strange concept that ketogenic diets promote muscle loss comes from.

What's the agenda? Who benefits from decrying ketogenic diets?


kellyt said...

Well. Yes, you're right to suspect the agenda of those who decry the nutritional-keto state or the fasting-keto state in the face of mountains of evidence to the contrary... But, much of the erroneous info and concepts out there regarding the odious effects of fasting and VLC lifestyles simply comes from the lack of understanding that there is a very clear difference between fasting/nutritional-ketosis and STARVING.

August said...

Shall we herd cats, or herd sheep?

I don't know if cats ever go keto, but they are supposedly obligate carnivores.
Dogs are easier to herd, and they've got amylase.
Oh dear, I just wrote animal 'facts' on a vet's blog.

I wonder if humans on high fructose corn syrup score higher than sheep on herdability?

Peter said...

"I wonder if humans on high fructose corn syrup score higher than sheep on herdability?"

Yes. You sound like Kwasniewski!


Rattus said...

Ketogenic diets might cause muscle loss because they destroy appetite and create inadvertent calorie restriction. Or maybe a person eats too much protein, turns a lot of it into glucose, and never fully adapts and starts eating their muscle tissue rather than their fat? For me its all about the fat to protein ratio, IF to maintain insulin sensitivity, etc.

raphi said...

i scribbled some notes down to really wrap my head around your explanation and would like to see your calculations (if useful/possible)

this whole RQ thing is really intriguing

NY said...

JK does not like ketones. Am I losing muscle while trying to live on the edge of ketosis(around 80g carbs a day) and similar amount of protein. I'm 6 feet tall and weigh 100KG with 36" waist.

Peter said...

Rattus, yes, calorie restriction may well cause muscle loss, one has to be careful where to attribute "blame"

NY, there are a lot of reasons why being "almost" in ketosis might be better than being fully ketogenic. Personally I think there are trade offs and I doubt there is a clear answer. I must comment JK is frighteningly accurate an awful lot of the time. But vanity does not want me in the 70-84kg range of weight for my height. 64 ish is my current weight which could be described as too low.

raphi, I'll see what I can do in terms of tidying them up. Might be running out of time tho', got to put up tents etc in preparation for heading off camping in a weeks time. This w/e might be busy!


John Velden said...

Nitrogen excretion falls off a cliff during prolonged fasting.
A significant portion of the remaining fasting nitrogen loss is for maintaining pH, giving a buffering solution reduces nitrogen loss.

With prolonged fasting growth hormone is significantly elevated which increases lipolysis and spares lean mass.

It really seems like the body tries to retain lean mass during a fast and rely on fatty acid for energy as much as possible.

Peter said...

raphi, screencap of the arithmetic is now edited on to the end of the post. I'm not suggesting any specific pathway for AA synthesis, just that these are the numbers of atoms needed. I'm unsure if I should have included one or so H on the -CH2-CH2- which would require a little more O2.

John, thanks, that makes a lot of sense. Page 11 seems to argue against fat burning in the flame of amino acid derived oxaloacetate, to say the very least


raphi said...


thanks for posting the sums. There isn't much of that sort of 'math' in my Molecular Biology course so i'm glad to learn it here.

About prolonged fasting and muscle catabolism...i've observed in myself and recall seeing some data to that effect, whereby the muscle loss incurred during fasting is much easier to regain than when trying to gain an equivalent amount from ones normal baseline-fed state. Good old homeostasis.... According to my iffy bathroom scale, I oscillate between 77-80kg (for ~182cm) and got down to 75-76kg on my longest (5-day) fast last November. Probably 1 week later (certainly less than 2) I was back to my normal weight, making no particular changes to my usual food and exercise habits. So regardless of whether prolonged fasting is more or less catabolic, I think the fears are largely overblown. Intermittent fasting is no worry whatsoever.

Enjoy the outdoors with the family Peter, I'm in Stoke-on-Trent at the moment and it's (*gasp*) sunny :D

Tiny said...

What is the possibility despite adaptation to ketosis, digestion is impaired, made inefficient, and blood flow to the brain, and so HFD detrimental to cognition, such as working memory? I'm considering studying under exam conditions scientific fields whilst being keto, and questioning how this might be affected subsequently.

Peter said...

I'm too old for exams but my wife passed FRCPath under ketosis a year ago. And a few other things over the years, PhD etc...


John Velden said...

Muscle cells contain multiple nuclei, resistance training or steroids can increase the number of nuclei in individual muscle cells via recruitment from satellite cells.
The more nuclei an individual muscle cell contains the less stimulus is required to support a given level of muscle protein synthesis.

Muscle cells are not generally lost to atrophy they simply shrink but importantly the nuclei remain so as soon as stimulus resumes and protein supply is sufficient they rapidly refill.
So called "muscle memory".
I have experienced this myself after a rotator cuff injury meant no pressing for six months. My pecs basically deflated from atrophy but as soon as I could resume pressing they went back to normal after several weeks using very low weight and volume compared to what it took to build them in the first place.

Fat is usually very easy to digest. Anecdotally many people on the keto reddit rave about the mental clarity keto diet gives them in comparison to the SAD.

George Henderson said...

A keto diet is high in fat, or so I've read. Fat has the highest somatostatin 28 response of the macros, and somatostain 28 inhibits proteolysis.

Ensinck JW, Vogel RE, Laschansky EC, Francis BH. Effect of Ingested Carbohydrate, Fat, and Protein on the Release of Somatostatin-28
in Humans. Gastroenterology. 1990;98:633-638.

Shaw JHF, Wolfe RR. Metabolic Intervention in Surgical Patients: An Assessment of the Effect of Somatostatin, Ranitidine, Naloxone, Diclophenac, Dipyridamole, or Salbutamol Infusion on Energy and Protein Kinetics in Surgical Patients Using Stable and Radioisotopes. Ann Surg. 1988;207(3):274-82.

Heindorff H, Billesb0lle P, Ligard Pedersen S, Hansen R, Vilstrup H. Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy. Gut. 1995;36:766-770.

Also, alpha oxidation of fatty acids yields propionate and the odd-chain SFAs associated with metabolic health. Propionate is oxaloacetate precursor normally derived from branched chain amino acids, so any alpha-oxidation is sparing protein, mainly from muscle.

Note odd-chain SFAs in serum do not exactly match ratio in ruminant fat but may be more general marker for whole ruminant foods, other wholefoods, and fasting.

Passthecream said...

Hmm, hydrogenated mutton fat, wonder what that's like?

Rattus said...


You might already be aware of this study:

Summary is that a high PUFA diet resulted in significantly higher blood glucose levels than a high SFA diet. I've read about average blood glucose rising on a ketogenic diet, and was thinking that maybe this is a function of how much PUFA the individual is consuming. I've noticed negative effects from eating too many egg yolks, so I can imagine eating a lot mayo, avocado, almonds, bacon, pork, and vegetable oil would turn a healthy ketogenic diet into a not so healthy one.

Obviously the elevated fasting blood glucose could be purely a result of CHO restriction, which I think you cited as the reason for consuming some glucose everyday, but from what I've noticed from too many egg yolks and olive oil, the inadvertent PUFA may play a more important role.