My dear readers, the website/blog update has run into some snags. Rather than continuing to keep you waiting, though, I’m going to publish new posts and I’ll worry about transitioning them over later on. And since it’s been a few months since I last posted anything of substance, I’ve decided to drop this enormous, enormous post on you to make up for that lost time—and it might take you equally long to read it. Sorry about that, but hey, I haven’t written anything meaningful since May, so, depending on your point of view, this post is either a gift or a punishment. As I’ve said in the past, if you’re an insomniac or a cubicle dweller with lots of time to kill, you’re welcome. (The rest of you, go get yourself a cup of coffee or tea, come back, and get comfy.)
I’ve been meaning to write this post for over a year, but it’s such a big topic and so much can go wrong that the thought of tackling it all was enough to make me not write it. But it’s gotten to the point that I’m tired enough of seeing the same questions asked and the same myths propagated over and over on various keto and low carb forums that I’ve decided this needs to be done, no matter how painful I might find it. Because seeing nonsense and fearmongering regarding the role of protein in low carb or ketogenic diets is even more painful. So if finally managing to organize my thoughts into some kind of coherent prose means I never have to read the phrase, “too much protein turns into sugar” ever again, it will be worth it.
So that’s what’s on tap today, kids: Gluconeogenesis.
That’s right, friends, it’s time to do some myth-busting surrounding the whacked-out notion that protein—lean protein, in particular (like a skinless chicken breast, or tuna canned in water)—is the metabolic equivalent of chocolate cake. (Or cotton candy, or gummy bears, or any other insanely sugary thing that might raise your blood glucose and insulin far more than protein does.)
Of all the myths and misinformation I wish we could kill, strap to a block of concrete, and push off the side of a boat in very deep, shark-infested waters, the protein = sugar thing is close to the top. In the LCHF world, I see many under-eating protein, particularly when fat loss is the goal. Not weight loss, but fat loss. ‘Cuz, let’s face it: when people say they want to “lose weight,” what they mean is that they want to lose fat. They want to be leaner. As many a chronic dieter can confirm—particularly those who chronically follow low calorie, low-protein diets—you can lose plenty of “weight,” but unless you retain your lean muscle tissue and/or add more lean tissue, you might end up TOFI—thin outside, fat inside.
Ain’t no one got time for that!
So I’m going to do my best to talk about the science in layperson-friendly terms, and do what my goal always is in writing about this stuff: to explain it the way I would want someone to explain it to me, if I were new to all this.
Before we get into things, allow me to say upfront that I don’t understand everything about this topic. I have many unanswered questions, myself. But in the hopes of dispelling growing fears around a myth that has gotten completely out of hand in KetoLand™, I’m going to share the little bit of knowledge I do have with anyone who happens to stumble upon this post. If you know someone who’s in need of a smack upside the ketone-fueled head in regard to today’s topic, please feel free to send them the link to this post if you find it educational, or share it wherever you think appropriate. Not only will I try to explain things clearly, but I will include links to several helpful posts from other people, most of whom are way smarter than I am, and who go more deeply into the published research on this. (So if you’re interested in more of the technical details, read through the posts I’ll be linking to at the end of this.)
Oooookay, here we go!
Before we even get into gluconeogenesis (GNG), let’s cover a couple of basic things so we can keep our heads about us.
It is true that most amino acids can be converted into glucose. (Leucine and lysine cannot. More on this in a bit.) But you know what else can be converted into glucose? Glycerol. The glycerol molecule from triglycerides (fats). Triglycerides—the form that dietary fats take—consist of three fatty acids joined to a glycerol molecule (hence their name, tri-glyceride). When triglycerides are broken apart (such as needs to happen in order to liberate the fatty acids so they can be burned/oxidized), you’re left with individual fatty acids and the glycerol. The fatty acids get burned or used for some other purpose, and two glycerols can be combined to make one glucose molecule. Yes, you read that correctly: the glycerol backbones from two triglycerides can make glucose. This isn’t something that happens to a huge extent, but it can happen. Funny how you never hear about this possibility when people are warning you not to eat more than 20 grams of protein in a meal, but see nothing wrong with encouraging you to glug down a cup of coffee loaded with 400 calories of butter and coconut oil.
So if you’re worried about GNG from “too much protein,” then you should also be worried about it from too much fat. (But the truth is, you shouldn’t worry about GNG from either of these things.)
Proteins and amino acids have many possible fates in the body. It is not a binary choice between:
- Turn into muscle
- Turn into glucose
No, no, no, no, no.
With protein typically taking such an undeserved beating in keto circles, let’s take a look at some of the vital functions of proteins and individual amino acids:
- Skeletal muscle structure (e.g., biceps, glutes, quadriceps, triceps)
- Smooth muscle structure (e.g., muscles lining the GI tract and blood vessels)
- Connective tissue structure (e.g., ligaments, tendons)
- Bone structure (bones ain’t just calcium, folks)
- Structure of hair, skin, and nails
- Hormones or building blocks for hormones (e.g., insulin, glucagon, thyroxine [thyroid hormone], human growth hormone)
- Enzymes (which account for just about every process in every tissue in your body; you are probably most familiar with digestive enzymes, but there are approximately eight hundred kazillion enzymes in the body that do all sorts of other things, and they are all proteins)
- Building blocks for neurotransmitters (e.g., serotonin, dopamine, norepinephrine)
- Antibodies (immune system – the antibodies you have to measles, chicken pox, mumps, polio, or whatever else, are proteins)
- Energy substrate – they can be used for fuel, either via gluconeogenesis or by being converted into things that feed into the biochemical process by which our cells generate energy (more on this in a bit)
So, you see, there is a lot for protein to do.
Protein is so, so underrated, I cannot tell you! There’s enough to cover in this post without going into the details on that, but just know that if you are using a low carb or ketogenic diet—or any other diet, for that matter—with a goal of fat loss, protein is your best friggin’ friend. You already know you need to keep carbs low in order to keep insulin low-ish and be a “fat burner” rather than a “sugar burner.” But if you overdo it on dietary fat, sure, you’ll still be a fat burner, but you’ll be burning the fat from your fork, not from your fanny. So if you’re having a hard time losing body fat even on a low carb diet, cut back a bit on fat. Give your body a reason to tap into its own stores. The one thing you don’t want to cut back on is protein. (Just to clarify, people using a ketogenic diet as medical therapy for a specific condition might have a reason to moderate protein intake. This is a different story from fat loss!)
We’ll get to gluconeogenesis in a bit, I promise. First, let’s look at the fate of amino acids as energy substrates—that is, fuel.
Fates of Dietary Amino Acids
“Since amino acids can not be stored in the body for later use, any amino acid not required for immediate biosynthetic needs is deaminated [nitrogen is removed] and the carbon skeleton is used as metabolic fuel (10-20 % in normal conditions) or converted into fatty acids via acetyl CoA. The main products of the catabolism of the carbon skeleton of the amino acids are pyruvate, oxaloacetate, α-ketoglutarate, succinyl CoA, fumarate, acetyl CoA and acetoacetyl CoA.” (H.D. Urquiza Hernandez, MD, PhD)
From the list above, oxaloacetate, α-ketoglutarate, succinyl CoA, fumarate, and acetyl CoA can all feed into the Krebs cycle, which is the process by which ATP (energy) is generated in the mitochondria. (In biochem speak, they are called “Krebs cycle intermediates.”) The carbon atoms from amino acids can be converted into these “energy precursors,” and the nitrogen atoms can be turned into urea (a waste product) and excreted, or they can be used to build nitrogen-containing compounds, such as the “nitrogenous bases” that are part of the physical structure of your DNA double helixes. (Pyruvate can be converted into acetyl CoA, which feeds into the Krebs cycle.)
I suspect the use of amino acids as Krebs intermediates is largely responsible for the “meat sweats”—the thermic effect of protein (when you get really hot after eating a very large amount of protein), via uncoupling, but that is a topic for the true nerds among you and most of you can probably ignore this. But if you know anything about this, please tell me in the comments. I would love to understand why meat has such a high thermic effect, and if it is related in any way to mitochondrial uncoupling.
Bottom line: think back to the list of functions/fates for proteins & amino acids. It’s definitely not limited to “build your biceps” or “turn into sugar.”
On to Gluconeogenesis
We need to define our term before we get started.
Let’s break the word down: Gluconeogenesis.
Gluco – glucose
Neo – new
Genesis – creation
So gluconeogenesis is just that: the creation of new glucose. For our purposes, it is the creation of glucose from other molecules that are not, and were not, glucose—such as amino acids and glycerol.
Do not confuse GNG with glycogenolysis, which breaks down thusly:
Glycogeno – glycogen
Lysis – breaking apart
You all know glycogen is the stored form of carbohydrate in the body, right? (Stored in the liver and skeletal muscles.) Glycogen is just long strands of glucose molecules joined together, with smaller strands branching out from longer main strands. Bottom line: glycogen is just lots of glucose molecules attached to each other. Glycogenolysis is the splitting of glycogen into individual glucose molecules. It is different from gluconeogenesis in that the glucose that comes from glycogen was already glucose. (Some of the glucose that winds up stored as glycogen may have initially started out as amino acids or glycerol, but for the sake of simplicity, let’s just focus on the fact that in the end, it’s glucose. The point is, when you break down glycogen, that is not GNG, because it started out as glucose in the first place. This is an important point we’ll revisit in a bit.)
Here’s an excerpt from a post by Amber and Zooko on Ketotic.org I had the pleasure of meeting them both at the Ancestral Health Symposium last year, after having been a fan of their meticulously referenced writing for a couple of years:
- "How does excess GNG affect blood sugar levels? Blood sugar levels are important because too much sugar in the blood at a given time can cause damage to cells.
- Does producing more glucose via GNG ultimately lead to either using more glucose for fuel, or storing it as fat?
So when people worry about protein causing excess GNG, what they are really worrying about is that protein will adversely affect their blood sugar levels, or that they are going to use more glucose for fuel than they intended, or that they will store it as unwanted fat.”
I would add to this that apart from protein’s influence on blood glucose, people are worried about its influence on insulin. (Because as I wrote about in the insulin series, it’s pretty common for people to have normal glucose, but sky-high insulin, and chronically elevated insulin has some pretty gnarly effects totally unrelated to what’s going on with glucose.)
With regard to GNG, all of these are valid points, and it’s completely reasonable for us to wonder about them. It is not reasonable, however, to start equating protein—lean protein, in particular—with angel food cake.
Just because amino acids can be converted into glucose doesn’t mean they will be. Gluconeogenesis doesn’t happen “just ‘cuz.”
In a well-regulated body, GNG doesn’t happen because it can; it happens when it needs to. The process is demand-driven, not supply-driven.
What does that mean? It means that just because there are amino acids coming into the body, and some of those amino acids can be converted into glucose doesn’t mean they will be. And it especially doesn’t mean this conversion will happen immediately upon digestion. Remember what we said: the glycerol backbone of triglycerides (fats!) can be made into glucose, too, but nobody seems all that worried about this when they’re asking for extra butter on top of their butter, with a side of butter.
Don’t confuse a rise in blood glucose with gluconeogenesis. Protein we eat doesn’t automatically and instantaneously become glucose.
News flash: as stated earlier, the amino acids leucine and lysine cannot be converted into glucose. They are “ketogenic amino acids,” because they can be converted into ketones, but not glucose. Does that mean you should run to your favorite supplement shop and get a bunch of leucine and lysine in order to boost your ketone levels? No. Because these aren’t automatically converted into ketones—in the same way that the glucogenic amino acids are not automatically converted into glucose.
The amino acids alanine, arginine, asparagine, aspartic acid, cysteine, glutamate, glutamine, glycine, histidine, methionine, proline, serine, and valine are exclusively glucogenic. They cannot be converted into ketones but they can be converted into glucose, when the body needs more glucose than it has readily available.
The amino acids isoleucine, phenylalanine, threonine, tryptophan, and tyrosine are glucogenic and ketogenic: they can be turned into glucose or ketones, whichever the body happens to need.
Hat tip to Amber & Zooko for this excerpt from “The relationship between gluconeogenic substrate supply and glucose production in humans”:
“Our data so far indicate that under almost any physiological situation, an increase in gluconeogenic precursor supply alone will not drive glucose production to a higher level, suggesting that factors directly regulating the activity of the rate-limiting enzyme(s) of glucose production normally are the sole determinants of the rate of production; hence, there will be no increase in glucose production if the increase in gluconeogenic precursor supply occurred in the absence of stimulation of the gluconeogenic system.” (Emphasis added.)
In plain English: gluconeogenesis doesn’t happen “just ‘cuz.” Just because there are amino acids present that can be converted into glucose doesn’t mean they will be, unless the body needs glucose. And what signals whether the body needs glucose—that is, the “factors directly regulating the activity of the rate-limiting enzyme(s) of glucose production”—which “normally are the sole determinants of the rate of production,” are hormones.
In the same way that ketosis doesn’t happen just because someone eats a lot of fat, gluconeogenesis doesn’t happen just because someone eats a lot of protein. The hormonal state has to be primed to make this happen. After all, we know fats can be metabolized into ketones, but the vast majority of people out there consuming high-fat, high-carb diets are not generating a whole lot of ketones, right? And why not? Because the hormonal state of the body is in control of this. If your insulin is high from eating a bagel, then the cream cheese on that bagel is not going to make ketones, capice? [The exception here is MCT oil, which might be metabolized into ketones even in the presence of elevated insulin, but that is a topic for another day.])
And if the hormonal state is primed to make GNG happen, you better be damn glad it does happen. See, this is what keeps us alive when we fast, or pretty much just on a very low carb or even zero carb diet. If you’re eating close to zero carbohydrate—which is very much possible—your liver and muscles will still have glycogen, but where did that glycogen come from, if you’re not eating any carbs? It had to come from other things being turned into glucose, and then stored as glycogen. Thank goodness for GNG, eh? If GNG didn’t happen on a low carb diet, not only would you not be able to exercise, but you would also probably straight-up die.
If you’d like to check out a (formerly) type-2 diabetic eating very large amounts of protein in one sitting, with basically no impact on blood glucose (or, actually, a beneficial impact!), see what Steve Cooksey (“Diabetes Warrior”) is doing. He does a lot of fasting and intense workouts, so take his experience in that context. He’s not sitting around all day and pounding large boluses of protein every three hours. But this ought to be enough to put the nail in the coffin of “too much protein turns into sugar.” (Steve eats plenty of protein and has been off all diabetes meds for years. In fact, as you’ll see from that link, he’s doing an experiment now where he’s eating zero plant foods at all, except for the occasional wine. No vegetables, no nuts, no avocado, nada. He’s deriving a very large percentage of his total calories from protein and he is thriving—with totally normal blood sugars.)
The hormonal response to eating protein
Let’s talk about what happens when we eat protein. In order to understand the mechanisms at work, it’ll be helpful for us to come at it from that good ol’ evolutionary perspective.
Let’s say it’s a few thousand years ago, and you’re out doing your hunting and gathering. (In this case, more hunting than gathering.) Let’s say you score a kill and you’ve got yourself and your tribal buddies an animal to chow down on. You are likely about to eat this source of protein and fat by itself, since this is long before the era wherein it became weird to eat meat, and only meat, without, say, a baked potato or a pile of rice. Maybe you’re not even having a side of spinach or broccoli, because it’s the Paleolithic Era and no one thinks they need a “vegetable side dish” to go with the antelope or caribou meat they’re about to enjoy. (Or whatever animals they ate back then.)
Insulin, as you know, helps to get glucose into cells. But insulin also helps amino acids get into cells. That’s part of what insulin does: it pushes nutrients into cells. It’s supposed to do this. If you like flexing your biceps in front of the mirror or taking selfies of your swole calves, be grateful that insulin does this.
Okay, so we’re eating protein in the absence of carbohydrate. Insulin is rising gently and gradually because insulin is going to help escort amino acids out of the bloodstream and into cells. But insulin isn’t selective. Meaning, insulin can’t choose to escort only amino acids into cells. Along with those amino acids, it will also help get glucose out of the bloodstream and into cells. But since we’re not eating carbohydrates and our blood glucose is healthily low (because Pop-Tarts and Mountain Dew and Chinese food delivery and Facebook haven’t been invented yet and nobody is insulin resistant and hyperglycemic), if this protein-induced rise in insulin takes a bunch of glucose out of the blood, we could end up with a serious—fatal, even—case of hypoglycemia. (We are assuming these cavepeople are not in a super-deep ketogenic state, wherein high ketones might protect against this.)
In order to prevent this potentially fatal fall in blood glucose, the pancreas secretes a hormone called glucagon. Glucagon is a “counter-regulatory” hormone to insulin. Whereas insulin lowers blood glucose, glucagon raises it. One of the ways it raises it is through glycogenolysis—breaking down liver glycogen into individual glucose molecules and releasing them into the bloodstream. (I told you we’d come back to this.) This is totally fine; glucagon is supposed to do this. If glucagon didn’t do this, you’d probably die from hypoglycemia in your sleep, or after more than about two days of fasting. (No matter how “keto” you are, some of your cells will always need some glucose. Think about it: there’s a reason your BG never goes to zero, even when you’re awash in ketones.) In order to keep BG from going dangerously low, glucagon comes to the rescue to raise BG. Not to spike it, mind you, just to balance the blood glucose-lowering effects of insulin, so that, on balance, your BG remains normal when you eat protein. (And also so that it remains normal when you eat nothing at all.)
Protein elevates insulin, which lowers blood glucose, but thankfully glucagon is there to tell the liver to release a bit of glucose, thus keeping your BG steady. (I say elevates insulin because I refuse to use the word “spikes,” because protein does raise insulin and BG, but these relatively small and totally physiologically NORMAL rises hardly qualify as “spikes.” And any rise in insulin and BG from protein—even a low-fat protein, such as cottage cheese, skinless chicken, or whey protein—is nothing compared to those most people would see from, say, cotton candy or sugar cubes.)
Bill Lagakos, PhD, who writes the excellent Calories Proper blog, penned one of my favorite lines of all time on this subject: “Dietary protein-derived amino acids have a purpose, and that purpose is not carbs.”
Protein takes time to digest
The glucose in the bloodstream immediately after protein consumption is not the product of gluconeogenesis. Assuming little to no concurrent carbohydrate ingestion, the glucose in the blood after protein consumption comes from glycogen. (Liver glycogen, specifically. Glycogen stored in muscles can only be used to power activity in those muscles. It cannot be broken down and released into the bloodstream. Only liver glycogen does this.) Because that’s what glucagon does: it tells the liver to break glycogen down into glucose and release it into the blood so you don’t pass out after eating a big steak and nothing but a big steak. (You know what else glucagon does? It stimulates lipolysis and ketogenesis—two things most of us love. More on this in a bit.)
Protein takes a long time to digest. There’s a reason it’s so satiating. (People say fat is the most filling and satiating. You’ve probably seen this everywhere: “If you’re hungry, eat more fat!” I have not found this to be true at all. Protein is what fills me up, or maybe protein with fat, but fat, by itself, does nothing for me. Massive amounts of butter don’t fill me up. Massive amounts of mayonnaise don’t fill me up. But a big steak? A big pork chop? I’ll be plenty full after that, even without adding any extra fat to it.) YMMV, but if your digestion is so quick that within 30 minutes, a 12-ounce steak has been entirely dispatched by your stomach acid, moved on to the small intestine, and the individual amino acids have been absorbed into the portal circulation to be delivered to your liver, and the liver has converted them into glucose, and they’ve been sent out into your bloodstream—all within 30 fast minutes—then you, my friend, should charge scientists to study you, because you are quite the physiological oddity!
Bottom line: IT DOESN’T HAPPEN THAT FAST. If your blood glucose rises after a high-protein meal, it’s not because the amino acids you just ate have “turned into sugar.” It’s the glycogen being released by your liver, under the influence of glucagon. It’s your liver, doing exactly what your liver is supposed to do when you eat protein.
Now, to be clear, protein does affect insulin and blood glucose. We know it does, because type 1 diabetics have to account for protein—not just carbohydrate—when they bolus their pre-meal insulin. But again, this isn’t because the protein they plan to ingest is going to immediately turn into sugar and “spike” their BG. It has more to do with the hormonal effects of protein, which is likely why it’s so difficult to avoid highs and lows when you’re dealing with exogenous insulin. Even people managing T1D with a low carb or ketogenic diet—which dramatically reduces the amount of insulin needed, and also reduces the frequency and severity of highs and lows—will still have highs and lows from time to time. Because it’s a very delicate hormonal balancing act, and it’s difficult enough for non-diabetics, let alone those who depend on the complex calculus of bolusing injected insulin. Type 1 diabetics have to be very careful when calculating their insulin needs to cover for protein, because the rise in BG is a bit less, and much more gradual than they typically experience from a big blast of sugar.
Managing blood glucose: the insulin and glucagon dance
I’m copying & pasting an exchange from the aforementioned Calories Proper blog. The comment comes from Marty Kendall, who has an excellent site of his own (Optimising Nutrition), and has developed some really, really useful indices regarding the insulinogenic properties of various foods.
Marty: “Seems to me that the majority of proteins not used by the body for growth and muscle repair will end up being turned into glucagon / glucose and end up requiring insulin to be used for energy or stored as fat at some point.”
Bill: “Marty, it is not the glucose derived from amino acid gluconeogenesis that induces insulin secretion! Specific amino acids act directly on the beta cells to induce insulin secretion. The glucose from amino acid gluconeogenesis doesn't appear until long after the insulin response, and it usually ends up in hepatic glycogen.” (Emphasis added.)
NICE, huh? The glucose in the blood immediately after protein consumption comes largely from hepatic (liver) glycogen, and in the very neat way a healthy human body has of regulating itself, if/when gluconeogenesis does occur, long after digestion of protein, most of it just goes to replace the liver glycogen that was diminished in the first place.
BUT: this is what happens in a healthy, properly regulated body. If we’re talking about type 1 and type 2 diabetics, it’s a different story.
Take type 1 diabetes:
Type 1 diabetics secrete little to no insulin. That means they have no way of countering the effects of glucagon. (This is why their BG goes so high. It’s glucagon run amok, and I wrote about it here.) So if a T1 diabetic eats a lot of protein in one sitting, they will have a big blood glucose rise. In the absence of insulin, the glucagon secretion induced by protein is going to tell the liver to keep pumping out glucose, nonstop, and maybe also tell skeletal muscle to break down proteins to release amino acids that can be used as fuel or sent to the liver, to be converted into glucose. Adipose tissue (fat cells) will also hemorrhage fatty acids, because glucagon stimulates lipolysis. All around, this is bad news, and it’s why T1 diabetics waste away without insulin pretty much no matter what they eat. Protein stimulating glucagon release is, at least in part, why T1 diabetics have to bolus their insulin to match their protein intake in addition to their carbohydrate intake. (This is what spurred Marty Kendall to start creating his super-extra-awesome insulin index of foods – it was to help his wife, who has T1D, better regulate her BG.)
What about type 2 diabetes?
Or, rather, not “type 2 diabetes,” per se, but in insulin resistance. (Remember, you can be insulin resistant without being officially diagnosed as a T2 diabetic, but only because the way T2 diabetes is diagnosed is totally misguided.) For the sake of simplicity, I’ll use the term T2 diabetic here to imply a state of insulin resistance.
Insulin resistance is somewhat compartmentalized, right? For example, the muscles and the liver can become resistant to the effects of insulin, but for many people, adipose tissue (fat cells) doesn’t become insulin resistant. We know they’re still insulin sensitive because they continue to take up and store fat. (It’s actually a little more complex than this, but I’ll save the details for a post I have coming up on new insights into the etiology of T2D.)
In a T2 diabetic with hepatic insulin resistance, the liver doesn’t respond adequately to insulin anymore, so it doesn’t get the message to stop putting out glucose. [In T1D, this happens because folks have little to no insulin. In T2D, there’s plenty of insulin, but the liver basically ignores it. So it ends up being almost the same as T1 – at the level of the liver, insulin no longer counterbalances the effects of glucagon, so glucose continues to be released into the blood. The diabetes medication metformin is designed to target this issue: it inhibits hepatic/liver release of glucose.)
I recommend this video for an absolutely frikkin’ fascinating lecture on glucagon, and the importance of glucagon and insulin working in concert to regulate BG. I had my mind blown several times while watching. Well worth your time if you want to understand this stuff. (Be sure to start it at the beginning if that link starts you halfway through.)
Glucagon: A Dieter’s Best Friend
Lest you start thinking glucagon is the enemy (there is far too much black and white thinking in the keto world), glucagon stimulates lipolysis (breaking down fat) and ketogenesis—two things most of us really love and even go out of our way to make happen more (such as via fasting or exercise.) Glucagon rises as blood glucose and insulin fall. Insulin is a storage hormone; glucagon is a mobilizing hormone. Insulin generally tells the body to put things into cells; glucagon tells the body to pull things—like fat—out of cells. (This is why it’s so damn hard to mobilize fatty acids—that, is to burn fat—when your insulin levels are high all the time.) Glucagon mobilizes glucose and fatty acids. (And when fatty acids are mobilized, ketones are likely to follow, even if only at a low level.) In the short term, dietary protein reduces ketogenesis—but only temporarily, because of the insulin. Insulin tells us to store, and you don’t break down fuels at the same time you’re storing them. Except for when you eat protein and have a very slight anti-ketogenic effect in the presence of glucagon, glucagon is pro-ketogenic. Remember: glucagon is a counter-regulatory hormone to insulin. As insulin levels decrease, glucagon levels rise. Except in response to dietary protein, glucagon generally rises when we don’t have fuel coming in: between meals, overnight, during a fast, etc. It does this so we can “feed” on our stored glucose and fat during these times. That’s kinda the whole point. We like glucagon. (Glucagon is only a “problem” in T1D, when there’s not enough insulin to keep it in check, so the body is in a constant state of uncontrolled catabolism [breaking itself down, wasting away]).
What about ketosis?
In addition to concerns about “spiking” blood glucose and insulin, many in the keto community are worried about eating a large amount of protein because it might “kick them out of ketosis.” There is so much wrong with this, I hardly know where to start. If your goal is fat loss, this is a non-issue. Period. You do not need to be in ketosis to lose body fat. As I have written about ad nauseam in other posts, ketones are the result, not the cause, of breaking down fat, so you have no reason to chase high ketones for the sake of high ketones. (If you are using a ketogenic diet as medical therapy and you require maintenance of a certain threshold level of ketones for clinical efficacy, that is a different situation.)
My friend Mike Berta said it well:
“Excess protein is mainly oxidized and burned for energy. This results in lower ketone levels because ketosis relies on ‘fat derived’ fuels. The body will not create many ketones when there is an excess amount of non-fat derived energy. This does not mean that the protein you eat is turning into sugar or that you are going to be ‘kicked out of ketosis’ for a week. This just means that protein calories still count.” (Note from Amy: you might see an acute drop in ketone levels, but first, who cares, and second, you’ll be right back to ketosis as soon as insulin comes back down. And remember: if your goal is fat loss or overall wellness, it’s more important to be fat-adapted than to be in ketosis 24/7.)
“Even in diabetics, therapeutic levels of ketones are not more important than maintenance of lean body mass. Don’t under eat protein in your chase for ketones at the expense of lean mass. Lean mass is very important and drives our metabolism. Ketones do not cause fat loss; they are the result of fatty acids being broken down in the body. You can have very high levels of ketones but eat too much food and there will be no net reduction in body fat.”
As my friends at KetoGains say: “Chase results, not ketones.”
Up next, and some additional resources
Now that we’ve cleared up at least some of the craziness around GNG, believe it or not, there are a couple of other issues people worry about with regard to protein consumption. Namely:
- A “high” protein intake is harmful for the bones and kidneys.
- Protein activates scary-sounding pathways and hormones like mTOR and IGF-1, potentially increasing risk for cancer (IGF-1) and decreasing longevity (mTOR).
Most people are probably much more concerned about the GNG/glucose/insulin stuff we covered here, but I know some of you wonder about these other issues, too. So I’ll tackle them in a separate post.
In the meantime, if you’d like to nerd out further on protein and GNG (including study data and more scientific detail than I provided here), this selection of great reading and videos will make you very happy—and keep you busy for a while:
- KetoGains: Gluconeogenesis wont kick you out of ketosis
- KetoGains: Protein Over-consumption in Ketogenic Diets Explained
- KetoGains: Will this kick me out of ketosis?
- Break Nutrition: What is gluconeogenesis? How does does it control blood sugars?
- Keto Sister: Keto problems: Too much protein?
- Ketotic.org: If You Eat Excess Protein, Does It Turn Into Excess Glucose?
- Ketotic.org: Protein, Gluconeogenesis, and Blood Sugar
- Ketotic.org: Protein, Ketogenesis, and Glucose Oxidation
- Optimising Nutrition: Why do my blood sugars rise after a high-protein meal?
- Optimising Nutrition: The blood glucose glucagon and insulin response to protein
- Calories Proper: Dietary protein does not negatively impact blood glucose control
- Video: Donald Layman, PhD speaking about protein at the British Columbia Dairy Association’s Nutrition Forum. (Layman is one of my favorite go-to experts on protein, and this is an excellent look at protein recommendations. Nutshell: most of us are nowhere close to a “high” protein intake.)
- Video: Glucagon - Professor Roger Unger, Rolf Luft Award Prize Lecture 2014
Disclaimer: Amy Berger, MS, CNS, NTP, is not a physician and Tuit Nutrition, LLC, is not a medical practice. The information contained on this site is not intended to diagnose, treat, cure, or prevent any medical condition and is not to be used as a substitute for the care and guidance of a physician. Links in this post and all others may direct you to amazon.com, where I will receive a small amount of the purchase price of any items you buy through my affiliate links.