Saturday, February 07, 2015

Ketosis and Protein

I just wanted to throw out a few comments about the inhibition of ketogenesis by protein. The obvious effect, that of stimulating gluconeogenesis, appears to be at best a partial explanation of what happens.

I've long been interested in how amino acids feed into (and are derived from) the citric acid cycle and related pathways. Clearly any amino acid which metabolises to oxaloacetate within the liver is simply going to remove that void in the citric acid cycle (oxaloacetate deficiency) which results in acetyl-CoA being diverted to ketogenesis. Aspartate is one such. Those metabolising to pyruvate are also going to do essentially the same thing. There is no need for increased gluconeogenesis in this scenario. Gluconeogenesis may happen at a increased rate. It may not. Providing a source of oxaloacetate in the liver mitochondria will stop ketogenesis, whatever gluconeogenesis does, whatever insulin does.

Personally I am very ketoadapted. I've drifted in and out of ketosis since just after that start of the current century, probably around the summer of 2001 if I recall correctly. I find carbohydrate restriction effortless. Limiting to 30-40 grams per day is easy. Protein limitation is much more difficult. With about 20grams of protein in each breakfast and a few grams derived from cream, chocolate or macadamias at lunch time this does not leave a huge allowance for meat intake at suppertime. At around 65kg bodyweight nowadays keeping to 1g/kg is not the easiest target. A decent steak and I miss it. Life is too short to stress about this, but I certainly don't eat steak every day. Urinary ketones are always there at the + or ++ level. Exercise (distance walking) usually gives +++ as does the evening meal post prandial period, unless there have been excess chips with supper or I've gone significantly over my protein limit.

So I've limited protein, mildly, for years. My degree of keto adaptation still allows free generation of ketone bodies, certainly to a level where I can detect acetoacetate in my urine.

For some reason the concept of amino acids being derivatives of (and inputs towards) the TCA pulls me back to Nick Lane's ideas, the origin of life and the throwing together of metabolism. I'm willing to buy the reduction of CO2 by H2 to give formate as the starting point of metabolism. There is an energetic cost to this initial step but once going it's all down hill, energetically, to pyruvate. Many amino acids are formed from pyruvate and close derivatives. This makes sense. Evolution doesn't plan but does progress within the framework of what is available.

In modern biology DNA doesn't do very much other than replicate (I simplify). RNA is much more active, it carries the message out, assembles itself in to ribosomes and does all of the picking and choosing of amino acids etc to make a protein. I like to think of DNA as a rather stable "hard copy" of the information which was originally carried by the less stable RNA. As such DNA is the fossilisation of the amino acid preferences of primordial RNA. Written in to DNA are the remnants of what was probably a chemical associations of RNA with specific amino acids. If DNA specifies a cytosine at the start of a triplet then the amino acid chosen via transport RNA will be derived from alpha-ketoglutarate, if an adenine the coded amino acid will be oxaloacetate derived, if thymine it comes from pyruvate and if guanine the amino acid will be derived from any one of several possible small molecules. The second base specifies how hydrophobic/hydrophilic the chosen amino acid might be and these two cover a high proportion of the biological amino acids. The third base is degenerate, i.e. it doesn’t carry any specific information but does allow a wider pool of amino acids to be selected.

I'm afraid this is all rather cool to me.

I love these glimpses in to the early mish-mash of chemicals and how they might have interacted before life became seriously organised. What you can and cannot say about LUCA, the last universal common ancestor, and the first steps away from prebiotic chemistry, is largely determined by such biochemical fossils.

All of this random musing came from wondering whether amino acids might supply oxaloacetate and so suppress ketosis. Some do.

Well. Eating a steak is not very ketogenic. It’s hard to separate this from the origins of metabolism and of life, for me anyway,

Peter

74 comments:

Profe.Sana said...

Great post

LC Loyal said...

I have a heavy cream habit on a strict low carb diet which completely stalls any weight loss, but I love it. Through some internet research I came to understand that it is likely the excess protein stalling the ketosis. So my question is, if eating a steak is not ketogenic what actual edible foods are?

LC Loyal said...

I have a heavy cream habit on a strict low carb diet which completely stalls any weight loss, but I love it. Through some internet research I came to understand that it is likely the excess protein stalling the ketosis. So my question is, if eating a steak is not ketogenic what actual edible foods are?

Murray said...

I too had come to a similar viewpoint on DNA and cytoplasm. I find it helpful to make an analogy between the cell and a university and say the DNA is the library and the protein dynamics in the cytoplasm are the active research by the professors and graduate students. This means the body and evolution are driven by protein dynamics, not DNA mutation. DNA stores published results of active research for posterity and helps educate and guide the next generation of cytoplasm dynamics. After all, DNA presumably evolved from protein dynamics.

Tomasz Marciniak said...

And how about high protein, calorie restricted diets (low fat, low carbs)?

Calorie restriction should trigger ketone production, won't it? It's even true for high-carb low calorie restricted diets.

mnature said...

Peter, as a random question, have you ever found that body temperature has much effect on the various ways that a body can assimilate food? That is, in most scientific values, there is a standard temperature and pressure that is presumed. So, is the same true of biological effects, where there are certain assumptions as to body temperature, blood pH, etc.?

George Henderson said...

I concur; entering the Krebs cycle at pyruvate is exactly what glucose does to inhibit ketogenesis; oxaloacetate is the sweet spot - any amino that supplies these is antiketogenic.
There is no requirement for GNG, in fact won't GNG remove oxaloacetate?

Peter said...

LC Loyal, just watch calories. Acute fat exposure may not provoke an acute insulin surge but it's got to go somewhere. Once it's in your adipocytes getting it back out again is not just limited to insulin. Really, Wooo knows much more about this than I do but leptin and your sympathetic nervous system have a role in extracting it again. What a never-obese athlete can get away with may not be quite the same as a person using LC because they need/want to lose weight...

Murray, I'm working back through the references from Nick Lane's publications (all available from his web site) and once you start to go in to the details of what can and cannot be said about protometabolism and pre cellular evolution are completely fascinating. How and why the rotary ATP-ase developed is amazing. And how you might get a high energy electron on to an FeS cluster to allow the reduction for CO2 to CO to begin methanogenesis. It's all quite distracting from the crumbling of the arterycloggingsaturatedfat error and the rejection of statins as wonder drugs, both of which appear to be ongoing currently.

mnature, I'm not sure that (outside of anaesthesia or heroin addiction) that core body temperature varies that much. While cold thermogenesis is undoubtedly very real I doubt it moves core body temp enough to affect reaction kinetics. Hormonal effects would (I guess) overwhelm this effect. Have you seen the clip of Natalia Avseenko skinny-dipping to about 20 metres under arctic ice for over 10 minutes (borrowing various heavily insulated divers' auxiliary regulators during the swim). Whatever happened to metabolism under these conditions, this degree of limb cooling produced progressive muscle pain each time she repeated it...

George, yes, but that is supposed to be the fate of excess protein. Doesn't really seem to be what happens does it?

Peter

Team Kruse said...

Statin message is getting out Peter. The data is just no in the correct journals.http://www.ncbi.nlm.nih.gov/pubmed/25655639

Team Kruse said...

pH and temperature drastically affect piezo electric cell effects (collagen) but not flexoelectric effects (enzymes). There is a huge difference in enzyme kinetics because of water's ability to proton tunnel via tautomerization. Enzymes simply cannot work without water surrounding them. Atoms are engines of creation because they absorb and radiate all types of energy so they must play by flexoelectric rules. The key is their organization within a cell to take full advantage of the thermodynamics of the environment they are found in. The physics of organisms can enrich biologic understanding when we marry its ability to carry information and energy to and fro. The cell membrane is a non-equilibrium structure with an enormous electrical potential gradient across it. the inner mitochondrial membrane has two radically different cell membranes for a very specific reason. It also has atoms in it that allow for it to act like a topologic insulator. This gradient makes it ideal to carry both information and energy to the rest of the cells in tissues.

Team Kruse said...

Now deep water and cold thermogenesis link the thermodynamic ledge to the quantum ledge in all life. Peter alluded to the amazing abilities we observe in people free diving in this environment. This is my wheelhouse and what I write about in my blog. We are all incredibly linked to water in amazing ways. Do you know what they are? Your body has amazing capabilities in water, that they lose in air, and we have some aquatic reflexes left in us as proof of this connection. I have already introduced you to one of these reflexes in the Cold Thermogenesis protocol called the mammalian dive reflex.
This reflex does something rather amazing all mammals. Their blood pressure drops because their heart rate slows when they are placed in a water environment. In fact, the linkage to water goes all the way to longevity and performance in mammals who use it. Water exercising and diving has a life-lengthening effect on humans and many other animals because of its relationship to pressure. Pressure in water also happens to increase our magnetic effect in mitochondria in water. When the water is cold the effect is magnified because cold temps is linked to the Curie temperature principle. Modern science has now shocked itself by finding long lived life in deep freezing polar water under pressure covered by miles of ice cut off from the sun. http://www.scientificamerican.com/article/discovery-fish-live-beneath-antarctica1/

Can cold weather or water alone or seasonal changes in weather affect blood pressure?

Medicine currently believes blood pressure generally is higher in the winter and lower in the summer. They do because low temperatures cause your blood vessels to narrow — which increases blood pressure because more pressure is needed to force blood through your narrowed veins and arteries. This is true when you are air breathing. Ironically, it is completely false when you are in cold water doing cold thermogenesis. I have telling people this for ten years now. Your environment dictate how biochemistry can work.


Air pressure certainly affects the freezing temperature. The higher the pressure, the lower the freezing temperature. Since it will take water longer to reach the lower temperature, I'd expect that it would freeze more slowly. But air is made up of gas and it turns out Cold Thermogenesis in water has another shocking effect. Boyle’s law is null and void in water environments. Robert Boyle’s equation predicted the behavior of gases at various pressures, and it indicated that the pressure at a hundred feet of water would shrink an air breathing mammals lungs to the point of collapse. The Japanese Ama have been free diving for close to 3500 years in 150 feet of the pacific ocean which is cold. Most do it nude and none of the have died doing so. Not only that, they are very long lived and there has never been one reported case of Multiple sclerosis in these women.

Team Kruse said...

In 1962, Per Scholander, a Swedish-born researcher working in the United States, gathered a team of volunteers, covered them with electrodes to measure their heart rates, and poked them with needles to draw blood. Scholander had seen the biological functions of Weddell seals reverse in deep water; the seals actually seemed to gain oxygen the longer and deeper they dove. This seemed very counterintuitive to him based upon his beliefs. Scholander wondered if water could trigger this effect in humans. He started his experiment by leading volunteers into a huge water tank and monitoring their heart rates as they dove down to the bottom of the tank. Water triggered an immediate decrease in heart rate.

You might be asking why this is so important. Cold thermogenesis has another effect when you use movement in cold water to couple it to the water temperature. Seals and walrus use this and so do humans. None of them seem to realize it. In Scholander’s experiments, he told the volunteers to hold their breaths, dive down into the tank, strap themselves into an array of fitness equipment submerged at the bottom of the tank, and do a short, vigorous high intensity workouts. In every cases he tested, no matter how hard the volunteers exercised, their heart rates still plummeted.

This discovery was as significant as it was unanticipated. On land, exercise greatly increases heart rate. In water, the exact opposite reaction takes place. The deeper the humans dove the lower their heart went while exercising. The deeper one goes into water the more pressure builds up around our bodies and organs to condense the tissues that make up our anatomy. The volunteers’ slower heart rates meant that they used less oxygen and therefore could stay underwater longer. This ability is exactly what the Japanese Ama use to free dive to collect oysters for the villages for the last few thousand years. Why? Links back to the three quantum gases we still use: H2S, NO, and CO in low O2 environments.

Ash Simmonds said...

Ah back to protein and ketosis, the eternal fight!

"Excess" protein is a uniquely "brain metabolism fkd" or "struggling low carber" who can't lay off the nuts/seeds and treats problem.

I've been promising for a while to collate and summarise all the research on keto vs gluco potential aminos, I think it'll be a hugely important ketard topic in the next year or so.

I'll get to it oneday...

Ash Simmonds said...

Ah back to protein and ketosis, the eternal fight!

"Excess" protein is a uniquely "brain metabolism fkd" or "struggling low carber" who can't lay off the nuts/seeds and treats problem.

I've been promising for a while to collate and summarise all the research on keto vs gluco potential aminos, I think it'll be a hugely important ketard topic in the next year or so.

I'll get to it oneday...

Team Kruse said...

Ash this protein ketosis links directly to ubiquination via tautomers of water protons.

Tucker Goodrich said...

OK, I'm a bit confused, having had the "too much protein suppresses/prevents ketosis" argument for a while now.

I've not seen any evidence to support the premise. Now you're repeating it. I'd be curious to see why you think so.

"Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum."
http://www.ncbi.nlm.nih.gov/pubmed/18175736

Peter said...

Hi Tucker,

I’m not sure there are any hard data that you or I can cite on the question. My interest really comes from the ability of a number of amino acids to supply oxaloacetate to the TCA and what this might do to ketosis. My feeling is that you would have to run two theoretically ketogenic diets head to head with the protein to fat ratio differing but carbohydrate content kept the same. This has not been done to my knowledge in humans. As far as I can see you really do have to severely restrict protein to get rats in to ketosis without MCT oils. Humans seem a little different.

For humans I would suggest a high protein diet might be close to the 299 grams per person per day reported in table 4 of Paal Røiri’s text "Eskimo-kostholdets betydning for dødeligheten av hjerteog karsykdommer". There is no information on ketones in the thesis, that I can see (I don't read Norwegian), but I can read a protein content from a table!

The study you cite runs "high" protein at an average intake of 123 g/d in a group of people with a mean BW of 111 kg. That’s not far from the sort of level of protein which, in myself, certainly does not suppress ketosis. So no surprises or pointers there.

Currently I’m interested in oxaloacetate and ketosis as relates to anecdote and you don’t yet have the data you need.

Time will tell.

Peter

Tucker Goodrich said...

Thanks, Peter. Makes sense.

karl said...

Pedro wrote:
"amino acids to supply oxaloacetate"

Do we have a list of which ones?

This is of particular interest to me - I've been doing some weightlifting (Google Rippetoe ) and one thing that seems to be a consistent comment is to make muscle gains, one needs an excess of protein - not enough protein and sore muscles and no gains result.

But information of which proteins is lacking.

Maintaining - gaining muscle mass is very important as one ages - loss of strength is a great predictor of early death (makes BMI look silly).

High stress resistance training changes insulin sensitivity very rapidly - 20 min 3 times a week beats walking for an hour everyday.

I have greatly increased my strength, but the excess protein is also causing fat gain. I am starting to think that the type of protein matters greatly. In weight lifting circles they talk about three things:

BCAA (branched chain amino acids )
Creatine
glutamine

My hunch is this is the other side to the same coin.

ItsTheWooo said...

Fabulous entry Peter,
very useful for my own applications as you know (protein kaplow) it is possible protein may simply stop hepatic ketogenesis independent of glucose/insulin.

I agree so much protein restriction is the hardest part of keto. Most newbs are such newbs they dont even know you should limit meat, and are ever preoccupied with pop tarts and cereal for inexplicable reasons. Steak > pop tarts by far.

Best compromise for me is to eat ALL THE MEATS in a short period of time, avoid them early in day/otherwise so i do like "protein fasting" (e.g. eating of keto foods until night when my ratios are more atkins). Cal restriction/exercise affords some leeway. Of course, MEDZ like kratom which are Ca+ blockers and seem to mimic keto to a degree.

I just don't get these blogs like amber/zooko and the all meat thing. Very clear for me: if I eat the steaks, the pee is trace ketone. If I eat the fat oil bacon, the avocado and macadamia, or the cheesecake... the pee is purple.


Also, in between the "eating the steak" and the trace pee is often a CNS kaplow or two of some degree or other. Almost 2 weeks ago was fairly tragic in fact. It's a reliable and consistent effect.

Also neato speculation of microscopic life building blocks processing randomness chaos into order on a protein hinge. Many visualizations for woo A+.

Tucker Goodrich said...

"I agree so much protein restriction is the hardest part of keto."

And from all evidence I've seen, it's unnecessary except for certain conditions.

Moreover, urine's not a great guide to serkum ketone levels...

I gather that you just feel much better? Have you ever done serum blood testing? I'm genuinely curious, as this notion that ketosis requires protein restriction seems turns people off, but I have yet to find any confirmation...

ItsTheWooo said...

Tucker -

The internet largely made up that urine ketones are "useless". I have experimented and the two match up fairly well, although with a time lag for urine for obvious reasons.

I dont feel like padding the pockets of companies selling blood ketone strips, which is a useless neurotic tool and urine suffices.

50 urine strips: 6 dollars
3 blood strips: 6 dollars

Fuck that noise.



Yes, when I eat protein my pee strips fade to trace. OTOH if I restrict protein, my pee is purple.

All these keto gurus who eat meat wondering why urine stops changing color:

It's cuz you're eating meat, duh.

Restrict meat and eat macmadamia/cado/chocolate bacon and report back.

George Henderson said...

To reverse this:

If you do have gluconeogenesis going on at the same time that you're oxidising FAA in large amounts, as in uncontrolled T1D, aren't you extracting oxaloacetate from the TCA cycle to make that glucose?
Which will see more ketone bodies produced from those FFA, the more glucose you make?
Hence DKA?

Perry B said...

Tucker,
I find that restricting protein is very necessary to stay in ketosis ( blood ketones > 0.5); And, I do spend the money to do the ketone blood tests regularly. I’d expect the amount of protein restriction needed to stay in NK is going to vary from person to person, like a lot of things.

Now, my goal is to keep the morning fasting blood ketone reading above 1.5. This requires a pretty significant protein restriction, but for me it’s well worth it. Typical protein containing foods during a day are: 4 oz of grass feed beef, 1-2 oz each of cheese & bacon…not much, but I’ve gotten used to eating this way. I have almost no hunger, and normally little craving for protein. If I do get a craving for protein, it is several hours after I‘ve had a little too much protein.

I’m a 69 year old male. I’ve had blood sugar regulation problems since at least my 20’s ( reactive hypoglycemia) and was overweight until I discovered low carb eating via Gary Taubes “Why We Get Fat”. About 4 years ago I started eating low carb. Weight’s gone from 230 lbs to 170 lbs. and has been stable for the last 2 ½ years.

The most visible change is the weight loss, but from a health perspective, it’s really the gradual, invisible changes which have been most significant.

The blood sugar swings every few hours with their highs; and then the following hunger and down-swings in energy are a distant memory. In the past, before I started down this road, low energy and a tired feeling in the afternoon had become a normal part of life. Now, my energy and blood sugar are very stable throughout the day. There were a lot of other small health problems which gradually disappeared over time.

I lost most of the weight while eating low carb, but not trying to be in nutritional ketosis, NK.

I started trying to be in NK 3 years ago. It took me the better part of a year to get pretty consistently into NK (> 0.5). I was restricting protein to the amount recommended by Phinney & Volek; eventually I discovered that for me, that was still too much protein.

Before I started down the NK path, I was having more and more ‘senior moments’. Now, my memory and cognitive ability are clearly better than they were 3 years ago. They are still not as good as 15-20 years ago, but noticeably better than 3 years ago, and I‘ve continuing to experience very gradual improvement.

For me the health and cognitive benefits make staying in NK well worth it. I do have to be pretty careful about the protein intake, and of course carbs; most of the time it’s not difficult. If I do get tempted and have a little too much protein, I can get ketones back up over 1.5 in a day or two.

ItsTheWooo said...

Excellent story Perry.

IMO the metabolic fails who are very fat or very old tell the truth. Young people who are very obesity resistant (e.g. max weight problem is only like, 50+ pounds) tend to have AWESOME keto even eating tons of meat, but for lardos like woo or older folks like you...to get even a MINIMAL ketosis there is none of this 'all meat carnivory" bullshit.


I've met plenty of older women in fact who went form "keto" to "carnivore" and invariably they report ketones go KAPUT/taper off significantly. But a thinner, younger woman might not see that because her metabolism is better.

Woo is fairly young, but my metabolism is AWFUL so yes, very easily the moment I steak party it's a keto fail.

Anyway, very good story and IMO ketosis is primarily for NEUROLOGICAL HEALTH as well as CANCER... simple low carb/eating meat is ideal for weight and appearance, simply because if you eat lots of protein it is least fattening of foods and/or promotes a lean body composition. I have more muscles without trying just by eating a meat based diet...but the brain fails from ruining ketosis are not worth it.


One more suggestion, sometimes to improve keto it's not about restricting MORE but EATING MORE FAT. In other words, you might be able to eat a tad more protein if you really make sure to pair it with fats.

As with a high protein intake, I find over eating in keto = almost no fat gain. I gain some but farrr less than I would even low carb.

ItsTheWooo said...

Excellent story Perry.

IMO the metabolic fails who are very fat or very old tell the truth. Young people who are very obesity resistant (e.g. max weight problem is only like, 50+ pounds) tend to have AWESOME keto even eating tons of meat, but for lardos like woo or older folks like you...to get even a MINIMAL ketosis there is none of this 'all meat carnivory" bullshit.


I've met plenty of older women in fact who went form "keto" to "carnivore" and invariably they report ketones go KAPUT/taper off significantly. But a thinner, younger woman might not see that because her metabolism is better.

Woo is fairly young, but my metabolism is AWFUL so yes, very easily the moment I steak party it's a keto fail.

Anyway, very good story and IMO ketosis is primarily for NEUROLOGICAL HEALTH as well as CANCER... simple low carb/eating meat is ideal for weight and appearance, simply because if you eat lots of protein it is least fattening of foods and/or promotes a lean body composition. I have more muscles without trying just by eating a meat based diet...but the brain fails from ruining ketosis are not worth it.


One more suggestion, sometimes to improve keto it's not about restricting MORE but EATING MORE FAT. In other words, you might be able to eat a tad more protein if you really make sure to pair it with fats.

As with a high protein intake, I find over eating in keto = almost no fat gain. I gain some but farrr less than I would even low carb.

Tucker Goodrich said...

Thanks, Woo and Perry.

I've also been pursuing NK for several years now.

My wife has also, and is now on the Medifast high-protein modified fast (ketotic) program, which is working well for her, despite being about as un-Paleo as you can get. That program, and ones like it, have been in use for decades...

I'm personally of the opinion that if I do the right thing, the right result will happen, so I don't test by own urine or blood for ketones. Much like Perry describes, I feel like crap if I eat too much carbs, so I avoid them. I also do fasted endurance training (several hours worth of running, typically) to fix and improve my metabolism. So I'm pretty sure that after a 12-16 hr fast and then a long run I'm in ketosis. :)

But in my wife's case, we've tested her a lot, and haven't seen any particular benefit from protein restriction in her urine levels. And yes, guided by Jimmy Moore's example, and some other reading, we tried that first.

So yeah, I agree that the anecdotes indicate that for some, it can be helpful, but as a general statement, I'd like to see some harder evidence that it's necessary.

And "necessary" doesn't mean, "I'd like my levels to be X, so I must restrict protein", because for most cases there doesn't appear to be a benefit from keeping ketones to X level. They naturally fluctuate.

One of the endurance athletes I'm aware of followed the advice to protein restrict, and wound up with all the symptoms of protein deficiency, so their is a real risk to it, as well as it being

I'll further note that the folks with the most experience with a ketogenic diet for neurological reasons appear to have given up on the protein restriction avenue:

"The regimen restricted them to 15 grams of carbohydrates a day. “That’s a few strawberries, some vegetables, or a bit of bread,” says Kossoff. The diet offers most of its calories from fat-eggs, meats, oils and heavy cream-with as much protein and no-carb beverages as patients want...."

http://www.hopkinsmedicine.org/news/media/releases/Modified_Atkins_Diet_Can_Cut_Epileptic_Seizures_in_Adults

Tucker Goodrich said...

"The internet largely made up that urine ketones are "useless"."

Woo, it's not "the internet", it's from Phinney & Volek's book.

"Over time, urine ketone excretion drops off... This decline in urine ketones happens over the same time-course that renal uric acid clearance returns to normal ... and thus may represent an adaptation in kidney organic acid metabolism in response to sustained carbohydrate restriction.

"These temporal changes in how the kidneys handle ketones make urine ketone testing a rather uncertain if not undependable way of monitoring dietary response/adherence. Testing serum for beta-hydroxybutyrate is much more accurate but requires drawing blood, and it is expensive because it is not a routing test that doctors normally order.

"A non-invasive alternative is to measure breath acetone concentration..."

Page 164, Kindle edition, "The Art and Science of Low Carbohydrate Living".

I understand that there are now some breath acetone monitors, but haven't looked into it myself.

Richard Nikoley said...

I love it.

Well, we're in luck though, because Mike Eades is fixing' to show—all while getting caught up in tar babies, soon as he's done poisoning the well—how all y'all don't understand basic biochemistry, and you can eat 30%+ replete calories from protein and still be in ketosis.

Moreover, the absence of detectable ketones are in fact MOAR evidence that ketosis is in play.

http://www.proteinpower.com/drmike/miscellaneous/catching-2/

Tucker Goodrich said...

Richard: "... you can eat 30%+ replete calories from protein and still be in ketosis."

I guess he's right about a lot in that post. Including how you don't know what you're talking about.

Ketosis on a 30% protein diet:
"Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum."
http://www.ncbi.nlm.nih.gov/pubmed/18175736

Richard Nikoley said...

Tucker:

You and Ash feel free to argue with Peter and Woo.

I'm simply pointing out sides, and from where I sit, Peter and Woo have the science; you, Ash, and Eades have a lot of feelings about ketosis.

Even Bill Lagakos posted about high protein and ketosis and that high protein requires caloric restriction.

Here's the real rub. Particularly for fatties, VLC is very effective at ad libitum caloric restriction where the subject doesn't even realize they're calorie restricted. Calorie restriction of sufficient levels (>500-600) puts you in objective purple even on a sugar diet.

This is a big monkey wrench for you. (I actually learned this from Wooo, way back when, when people eating nothing but potatoes were peeing purple.) We said woa, Wooo said "duh, dummies."

For me, as folks compile and add up the science, ketosis happens when:

1. starvation/caloric restriction regardless of dietary composition.

2. Replete calories, but n a way that keep direct glucose low (VLC) AND keep gluconeogenesis low (LP, < 15ish% for intermittent, < 10%ish for objective).

Tucker Goodrich said...

"Even Bill Lagakos posted about high protein and ketosis and that high protein requires caloric restriction."

Richard, you and Duck have an annoying habit of making up facts to support your positions. This is what he wrote:

"The above studies show that protein doesn’t kill ketones."

http://caloriesproper.com/dietary-protein-ketosis-and-appetite-control/

Richard Nikoley said...

"you and Duck have an annoying habit"

What a coincidence.

Happy to be in good company.

BTW, can you explain to me, metabolically, how ketones are "killed?"

Where does the metaphor meet the science of metabolism.

Thanks.

Tucker Goodrich said...

"BTW, can you explain to me, metabolically, how ketones are "killed?""

Read the link for a change, Richard. Read something...

Richard Nikoley said...

OK, so you're not going to answer the question. So annoying.

I have read it, though it doesn't matter and your insistence I do is hand waving on top of arguing biochemistry be metaphor.

High protein requires caloric restriction to pee purple.

As far as peeing metaphors, I'm still unsure about that.

Tucker Goodrich said...

"OK, so you're not going to answer the question. So annoying."

I didn't say it. Lagakos did. Are you familiar with the term "quotation"?

Go ask him to explain it, if you can't understand what he wrote in the post.

You continue to make Dr. Eades' point more and more valid.

Richard Nikoley said...

"I didn't say it. Lagakos did."

How annoying.

So let me get this straight. YOU quote someone else's metaphor, and refuse to explain what YOU MEAN.

Got it. Convenient.

High protein requires caloric restriction to attain objective purple.

Use all the metaphors you like, and I'll keep pointing out that you use metaphors.

Tucker Goodrich said...

"High protein requires caloric restriction to attain objective purple."

Still wrong.

So you make a statement that's false based on the scientific evidence which is presented to you, you make some foolish comments about metaphors, and then repeat your erroneous claim.

BTW, Bill wasn't using a metaphor, it was hyperbole.

Richard Nikoley said...

"Still wrong."

Take it up with Peter in this post, then. i suspect you won't

Melchior Meijer said...

Previously I reported I drift in and out of ketosis on a Lindeberg style paleo diet. Maelan Fontes and Tommy Jönsson report that wheat elicits a paradoxical post prandial glucagon excursion (normally it's suppressed post prandially).

Glucagon inhibits ketogenesis in normal people.

"In the normal subjects, the glucagon infusion resulted in stimulation of insulin secretion indicated by rising levels of immunoreactive insulin and C-peptide immunoreactivity. Arterial glycerol concentration (an index of lipolysis) declined markedly and net splanchnic total ketone production was virtually abolished."

Wheat contains also potent insulin mimicking agents. I suspect the stuff makes normal, physiologically expected/needed periods of ketosis (humans are ketogenic beasts by trade) difficult if not impossible.

Melchior Meijer said...

Traditional Inuit didn't have a particularly very long life span.

http://wholehealthsource.blogspot.nl/2008/07/mortality-and-lifespan-of-inuit.html

Now we know they probably have lost the otherwise normal human capability of ketogenesis. There must have been some sort of trade off for this strange trait, but the lack of ketosis would neatly explain the absence of longevity.

Too much glycolysis going on :-). Keep gorging on beans and taters, Richard! It really enhances your glucose metabolism.

Richard Nikoley said...

"Keep gorging on beans and taters"

Assuming the conclusion, AKA begging the question, AKA circular reasoning.

Beyond that, all those poor Blue Zone folks, all of which eat legumes and most eat potatoes. Poor souls.

raphi said...

For an additional angle on the gluconeogenic potential of certain amino acids, see the correlation observed by Thomas Seyfried between the malate-asparatate shuttle & glycolytic activity (https://www.dropbox.com/s/749w1fduyuz97a1/GNG%20substrate.png?dl=0). Here's (https://www.dropbox.com/s/qbtgkurp8684ech/malate-aspartate%20shuttle.png?dl=0) a little diagram of how these are transported in and out of the mitochondria to the cytoplasm (and vice versa).

raphi said...

Dr.Westman thinks that the reason why ketones didn't appear in the Inuit studies is because, when properly adapted, 'losing' ketones in urines is wasteful & thus does not occur. For comparison, people burning a preponderance of sugar aren't expected to have sugar in their pee (glycosuria).

Peter & Woo still observe acetoacetic acid in their pee & they're certainly 'keto adapted' by now (I'm guessing I do to - haven't tested in ages because I still have a few blood strips left to use). I'm not sure what to make of this: is it in fact reasonable to expect ketones to not appear in urine when well adapted? My guess is yes, but it still remains to be shown AFAIK.

Richard Nikoley said...

"Dr. Westman thinks..."

Well, perhaps it will motivate him to actually study, rather than speculate in an attempt to explain away Occam's Razor.

Once that's out of the way, then he can explain why there's no measured acetone in breath, either.

I'm guessing that keto adaptation is so very profound that not only do Inuit metabolize 100% of ketones themselves, but every little trace of by-product of that metabolization.

Then, after that, he can explain how ketones get from say, the liver to the brain, without using the blood as transport. Hey, maybe they have a "transporter!"

This is getting unbelievably ridiculous. It's getting to the point where absence of evidence is even more evidence for certain existence.

raphi said...

@Richard Nikoley,

Enjoy your certainty

Richard Nikoley said...

"Enjoy your certainty"

That's a real laf. All the while you clamor to to maintain the certainty you, Eades, Westman and Volek clamor to maintain via magical speculation, in the light of numerous challenges to that certainty. Even more laf: 80% of what Duck and I ever posted in 17 posts is quotes from literature actually studying Inuit over 100 years. Eades references Stefansson's NYT obituary, and even though over a dozen studies on the Inuit exist going back to early 1900's the ONLY thing Volek has EVER referenced is Stefansson's writings—writing that left out his son, the one he abandoned in the Arctic at the age of 9.

The only thing I'm really certain of is that y'all have a lot of explaining to do. Eades has been going to do so for 10 months, but he's so busy and "cursed of knowledge" he just can't get to it (the 20 books he reads per month are getting in the way).

When are you going to come to grips with the possibility they're dancing around nude, counting on you and others to remark about their fine set of new clothes?

Richard Nikoley said...

Should any truly inquiring mind wish to actually investigate the matter, rather that simply relying o Eades, Volek, Phinney, Westman, et all to spoon feed them, see here:

http://freetheanimal.com/2015/02/fixin-theres-traffic.html#comment-700077

Just to be clear, Eades' comment I cited means either he's lying and counts on people to lap it up, or he didn't actually read most of the stuff he claims to be able to settle without taxing your inferior brains, and just knows there was nothing to see there because, the NYT would have posted dirt on Stefansson if it existed, because they have done so before (no shit: THAT was his "argument").

The saddest thing is that Tar Baby has to point out what a dismal performance Eades is putting up, because nobody can stand the strong possibility that he's just wrong and has been wrong for a very long time, and simply won't admit it.

Ask yourself why he never read any of those dozen plus studies, and just took Stewfansson's word for it. Ask yourself why he's written books, never delved at all.

Was it just very convenient for him?

That's what I think. Occam's Razor there, too.

Richard Nikoley said...

More for inquiring minds:

The exclusive immortal personality that was Stefansson. So profoundly self aggrandizing and "adventuresome" that he was willing to shit on a lot of people, including an Eskimo wife and son, to attain the notoriety he wanted more. ...And, because it was convenient, got folks like Eades, Westman, Volek, and Phinney to completely and utterly ignore 100 years of actual published research by 18 scientists, three of them including a Nobel Prize winner, one of the first specialists in diabetes, and Stefanson's own doctor.

http://www.isuma.tv/DID/community/CambridgeBay/arctic-dreamer

But, got ahead and marvel at their fine sets of new clothes.

Melchior Meijer said...

Dick, Duck & the Relentless Paleo Bashers.

Richard, it's quite certain that many full blooded Inuit have a very hard time to get in ketosis. I don't think Michael Eades denies this. Although there must be a good reason they evolved this trait, it should also have huge disadvantages.

Your beloved peasants in those mythical Blue Zones lived long lives because they al most certainly ate rather little, moved a lot and went through daily bouts of mild ketosis. A lot of beta oxidation going on, if you ask me.

Of course many of these folks still had rotten teeth (first hallmark of a species incompatible diet) and auto immune diseases.

I rode my bicycle from Amsterdam to the North Cape and back on macaroni and lentils. I did fine (apart form my teeth, which suffered badly). If I would eat this fare now, 25 years later, to my hearts content, I'm sure I would soon look and feel like an old man with a pathetic potbelly.

Richard Nikoley said...

"I don't think Michael Eades denies this."

Then you haven't been paying attention.

Dismissed.

Melchior Meijer said...

Okay, point fo you. He actually seems to deny that. I Glossed over it. He should embrace it. It goes a long way to prove his core point: that ketosis is very important for humans. No one really seems to care about that. Beta oxidation is protective, but maybe less so without proper ketone signaling (Mobbs).

Richard Nikoley said...

Breathing is very important for humans.

It does not follow that therefore, everyone should hyperventilate. Nor, that hyperventilation is the optimal use of oxygenation.

Melchior Meijer said...

Richard, I did not see that one coming :-). While listening to Tim Noakes (always good to begin the day with a decent dose of confirmation) on my morning run, I predicted that you would answer something along the lines of: too much oxygen is toxic, but that does not imply you should stop breathing (referring to my suspicion that too much glycolysis is A Very Bad Thing).

I don't say constant ketosis is necessary or even healthy. Based on the reasoning by Cunnane and the findings of Mobbs I argue that humans need intermittent ketosis to avoid degeneration/premature aging. Maybe intermittent fasting is enough, I don't know and I don't want to bet on it myself.

By the way (don't really know why I say this), I used to be a glider pilot. Went solo when I was 15. I absolutely like your flying gigs.

Richard Nikoley said...

"I argue that humans need intermittent ketosis to avoid degeneration/premature aging"

They also need to look both ways before they cross the street, a practice that has proven very effective in undercutting all-cause mortality rates.

It does not follow that we ought spend most of our day crossing streets, practicing the "look both ways" method.

L. Amber Wilcox-O'Hearn said...

Thank you for your thoughts on this, Peter. It's a topic I've thought about a lot. I spent a lot of time trying to get at the mechanism of protein inhibiting ketosis, and refuted some popular ideas in a series of articles starting here. The effects of protein are not very straightforward, and surely not linear.

I'm not sure if Wooo's carnivory shot was intended for me (I can't imagine who else), but I am in mild ketosis every time I check. I used to worry about getting deep BOHB levels, but I don't worry about it much these days, and I don't want to spend the money to keep measuring. My ketonix breath meter is essentially always in the red.

L. Amber Wilcox-O'Hearn said...

Peter said: "My feeling is that you would have to run two theoretically ketogenic diets head to head with the protein to fat ratio differing but carbohydrate content kept the same."

Yes! I once asked (prominent researcher X) if he knew of any experimental evidence directly showing that protein reduced ketogenesis (not that I thought it wasn't true, necessarily, I just wanted something to cite), and he said of course it does, look what happens when you go from fasting to a PSMF. But this conflates calorie restriction with protein restriction.

Even in the scenario you suggest above, there is a question of whether any effect seen would be coming from increased fat vs. decreased protein. The three of those factors (calories, protein and fat) are interdependent, and I'm not sure how to design an experiment that addresses all of them.

L. Amber Wilcox-O'Hearn said...

Peter also said "As far as I can see you really do have to severely restrict protein to get rats in to ketosis without MCT oils. Humans seem a little different."

This is a point that I think is extremely relevant for cancer patients. Rats need calorie / protein restriction to get into ketosis enough to suppress tumours. Humans don't need calorie restriction or much protein restriction to get into comparable ketosis.

HOWEVER, if you tell a cancer patient that to do a ketogenic diet to suppress tumours they have to calorie or protein restrict, it's going to be a huge hardship. As Keys demonstrated, the effects of calorie restriction are bad enough without the burden of severe illness, that regular people can hardly manage!

In my opinion, that's a setup for failure. The diet will be too hard, and they will quit completely — and die — when they probably could have eaten more, stayed in ketosis and significantly increased their chances of survival.

I think it's urgent that this be tested. Take two groups of humans with cancer and give one CR/PR keto therapy, and the other ad lib. See who drops out and the effectiveness rate of those who stay in.

Richard Nikoley said...

"This is a point that I think is extremely relevant for cancer patients."

Indeed it is, since cancer cells love ketones.

Go to Google scholar and punch in "ketones cancer cells"

Have fun.

Richard Nikoley said...

"But this conflates calorie restriction with protein restriction."

Oh my. Ketosis in the mammalian model, evolutionarily, is ALL about calorie restriction, which is to say, starvation. HFLC is just red carpet stuff.

I wonder how many HFLC folks have been on a 300 calorie deficit, but 50%+ protein diet (280-300g daily for me), LC, with fat making up the difference AND, fasting 18 hours every day for fun. It's called "Leangains." Martin Berkhan. I did it for 6 months or so and I doubt anyone would pee purple. In fact, with that much protein, my BG was always high.

Keep waffling.

Tucker Goodrich said...

"Keep waffling."

Richard, perhaps you should test. These LCHF guys did:

"Negative energy balance promotes ketosis even with relatively high protein intake. Phinney showed this in obese patients in 1980. He fed them a very low calorie diet for 6 weeks; 50% of the calories came from protein, the rest fat."

http://caloriesproper.com/dietary-protein-ketosis-and-appetite-control/

Ash Simmonds said...

I hate to unsubscribe from otherwise great topics on fantastic blogs like this, but getting such dullwitted email responses constantly does my head in.

Yes, I've done my research on cancer:

--> Cancer, carbs, ketones, and all that shit

Ciaoabunga.

Richard Nikoley said...

@ Tucker

In high enough caloric deficit, one can pee purple on a sugar diet. Indeed, lots of folks doing the "potato hack" found out firsthand because 1,300 - 1,500 kcal seemed to be the upper limit for most on how much non-fat-laden potato they could eat and they found themselves in deep purple.

When eating in balance, both carb and protein restriction is necessary.

@Ash

The point is Cancer eats everything, including ketones, and for years all we ever heard was the mantra that "sugar feeds cancer." It's true, but it's. It the only thing and so LC is not the ant-Cancer panacea it's been put forth as being.

Richard Nikoley said...

...Gosh.

Sorry all and Peter I effed the last couple sentences of that comment on an iPhone. I'm sure you can sort out what I meant.

Tucker Goodrich said...

Well if you're refuting this statement:

"I did it for 6 months or so and I doubt anyone would pee purple. In fact, with that much protein, my BG was always high."

Then we're finally in agreement!

But then you go and say this:

"When eating in balance, both carb and protein restriction is necessary."

There's no evidence that protein restriction is necessary to achieve ketosis. If you have some, please present it. I've already presented evidence that it's not, so the ball's in your court.

Richard Nikoley said...

@Tucker

I'm not interested. I've posted tons of stuff on it. You're welcome to take it up with Peter and Bill. Also, the thousands of high protein LC eaters who can't get into ketosis b/c they either eat too much, or too much proten, or both.

I guess you dismiss the thousands of anecdotes in dozens of comment threads over many years on that, as well as much other stuff like how Moore had to restrict protein.

As for my deal, my average kcal deficit was only about 200 daily, not enough to be in Ketosis at only 30g carb, but 270-300g protein.

But whatever. I seriously could not even begin to care what you think. I've never seen your mind change on a single thing in years and I doubt it ever will in years to come.

Melchior Meijer said...

"Oh my. Ketosis in the mammalian model, evolutionarily, is ALL about calorie restriction, which is to say, starvation."

Richard, this is not true. Humans are special animals in this respect. For the 15th time, human infants need ketones for their exploding brain. Why do I drift in and out ketosis on an ad libitum Lindeberg style paleo diet, while actually gaining some muscle (Freeletics)? But maybe you know it better than Stephen Cunnane, who studied human brain evolution his entire career.

As to ketones and cancer: do you dismiss the observations made by people like Seyfried, Fine and D'Agostino?

Richard Nikoley said...

"Richard, this is not true. Humans are special animals in this respect. For the 15th time, human infants need ketones for their exploding brain."

Ketones are useful for everyone, for tiding over from one food opportunity to another. That's it main function. Or, stated another way, to throttle down gluconeogenesis.

But you need to check Peter's posts and comments on the CPT1a mutation, which, curiously, is most dangerous to infants. This is why those with the mutation need regular needed and were typically breast fed longer than typical.

So while very useful (for reasons stated—not to engage in weird panacea-dietary excursions), apparently not essential so long as starvation or extreme food scarcity is in play.

"Why do I drift in and out ketosis"

Probably for the same reason most people do, provided they can stop stuffing their faces for 12 hours or so—I like taking it to 24-36 hours sometimes.

Another thing is, I don't know anyone normal who eats exactly 2,500 calories per day. Some days, normal people eat 1,300 and other days, 3,500. Combine that 1,200 kcal deficit with a good 10-hour soak between linens and you've got a ketogenic situation—perfectly physiological, as Peter might put it.

What I really resent is what I see as hijacking ketosis as some exclusive realm of LC dieting when in reality, it's a survival adaptation to being without food for some time, such that lean tissue isn't excessively wasted in order to make glucose.

"As to ketones and cancer: do you dismiss the observations made by people like Seyfried, Fine and D'Agostino?"

Not necessarily, though last I heard, some of the brain cancer stuff hasn't been panning out as hoped. Though, admittedly, I don't follow that stuff closely any longer.

L. Amber Wilcox-O'Hearn said...

Saying ketosis is a "survival adaptation to being without food for some time" is an assumption. It may just as well be that eating starches is a "survival adaptation for being without food for some time."

L. Amber Wilcox-O'Hearn said...

Melchior's point about ketosis in human infants is very relevant. I just wrote (another) post about that: http://www.ketotic.org/2015/03/meat-is-best-for-growing-brains.html

Tucker Goodrich said...

"Saying ketosis is a "survival adaptation to being without food for some time" is an assumption. It may just as well be that eating starches is a "survival adaptation for being without food for some time.""

It's not an assumption, but a statement of biologic fact.

And you're right about starches, it's why they're known as "fallback foods". They're what you eat when you can't get what you'd really like to be eating.

Matthew Bowles said...

So lets see. Eating meat takes you out of ketosis, but protein is necessary, so you have to eat some at some point.

Killing and eating an animal in the wild kind of has a rhythm to it that might be relevant:

Chase animal [persistence style].

Kill animal.

Eat parts that degrade fastest.

Preserve parts that degrade slowest.

So organ meats and muscle meats might get eaten first, in a narrow time window.

The fat is more stable, less susceptible to spoiling, and so can be made into pemmican, cheese, etc. Pemmican was often eaten before/during the hunt, according to some stuff I've read on natives.

The model of gorging on protein rich muscle meat and organ meat, followed by eating fatty pemmican/jerky, kind of seems like what you are shooting for in a sense.

Matthew Bowles said...

What I was trying to say above, in short, is that:

Meat/organs must be eaten in a shorter time window because more perishable.

Fat more stable, so traditionally eaten during a longer time window, i.e., throughout the day.

=

Most of day(s) spent in ketosis, eating fat for energy, until animal is killed at the end of the day, or after several days.

Matthew Bowles said...

Also that act of chasing animal, i.e. persistence hunting, induces even deeper state of ketosis via exercise.

pemmican + persistence hunting = deep ketosis

Animal organs/meat are eaten = brief respite from ketosis.