September 20, 2017

Ketogenesis, Measuring Ketones, and Burning Fat vs Being in Ketosis




This post is long overdue.

I cannot tell you how many emails I get from people fretting over their ketone levels. It’s time to set the record straight on this issue. I wish there was someplace I could refer people for reliable information on this subject, but I haven’t come across a blog post or podcast interview that explains things satisfactorily. At least, not to my satisfaction. And that is and always has been my goal in writing my blog: I explain things the way I would want someone to explain them to me, if I were new to all this. And since no one—as far as I know, anyway—has tackled this subject the way I would, I finally had to just sit down and write this. If you feel it’s educational, please share it in the low carb and/or ketogenic circles you frequent, because I know this issue comes up all the time in ketogenic forums and Facebook groups. (And if you know of other good resources on this topic, feel free to provide a link in the comments, and I’ll update this post to include it.)

Okay, here goes.

There are few issues more controversial regarding ketogenic diets than whether you should measure your ketones. There are valid reasons to measure, but there are also a lot—a lot—of misconceptions about measuring ketones and how to interpret the data. So let’s get into when and why it’s a good idea to measure, who doesn’t need to measure, and most important, what the numbers mean. (I said who “doesn’t need to” measure rather than who shouldn’t measure because if you want to measure, then go ahead. There’s really no should or shouldn’t here. But if you choose to measure, you need to understand how to interpret and understand the numbers so you don’t jump to illogical and false conclusions.)     


I will also be covering the difference between being fat adapted versus in ketosis. I tried to do it in a few posts awhile back, but I think I the way I explain it here is much better because I will show you the biochemical pathways involved so you will be able to see how it actually works. My hope is that this will go from a vague concept in your mind to, “Oh! NOW I get it!” And you will understand very clearly how you can absolutely, positively have a fat-based metabolism and lose body fat even if you’re not in ketosis. 



Who Should Measure and Why


The first thing to ask yourself is why you are measuring.

This goes hand-in-hand with why you are following a ketogenic diet and what you’re looking to accomplish. Some goals might necessitate measuring ketones, while it’s a waste of money unimportant for others.

More and more people are experimenting with ketogenic diets as adjunct therapy for a number of issues, including migraines, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, cancer, diabetes (type 2 and type 1), PCOS, GERD, cardiovascular disease and more. Some of these conditions might be positively impacted only when ketone levels reach a certain threshold, while others might respond favorably to a general reduction in dietary carbohydrate load and inflammatory foods with no particular emphasis on staying in ketosis and no requirement to do so. If you’re using a ketogenic diet to help manage a specific condition, measuring ketones can give you information about how your ketone levels affect your signs and symptoms. You might discover that you need to stay above a certain level in order to notice improvement, and you might be able to identify particular foods or activities (e.g., fasting, exercise) that either help you do that or that take you further from that goal.

On the other hand, if you’re using a ketogenic diet primarily for fat loss, it’s not necessary to measure your ketones. Ketones are the result, not the cause, of breaking down fat. Having higher ketones doesn’t guarantee you’ll lose more body fat or lose it more quickly, so your ketone level tells you nothing about how effective your diet is for reaching that particular goal. Remember: ketones come from breaking down fat, which is great, but if your ketone level is high, you can’t be sure whether it’s from burning the fat on your body or from the fat on your plate. (Or in your fat-loaded coffee, if you’re into that.) A scale, not a ketone meter, is your best tool for gauging weight loss, and if you’re going for fat loss, a tape measure is even better. The knowledgeable people in the KetoGains community have a saying for fat loss: “Chase results, not ketones.”

It’s also not necessary to measure ketones if you’re using a low carb or ketogenic diet to deal with disorders related to insulin resistance, which include such diverse issues as PCOS, gout, hypertension, erectile dysfunction, benign prostate hyperplasia/hypertrophy (BPH), and possibly inner-ear and balance disorders, like vertigo, tinnitus, and Ménière’s disease. These conditions are driven primarily by chronic hyperinsulinemia, so the main thing that helps them is lowering insulin. Once more, for effect: what’s responsible for improvement in these conditions is the lowering of insulin, not the presence of ketones.   

That being said, it’s not a terrible idea to measure ketones anyway, at least for a little while. You might find you have better energy, think more clearly, have no carb cravings, have a more positive and optimistic outlook, and just plain feel better when your ketone levels are higher, and you’ll only know if you measure. If you feel especially great at a particular moment, you can test to see if maybe your ketones are a bit higher than usual, and this would tell you that you, personally, feel your best when your ketones are on the high end of normal. And if that’s the case, then you can prioritize specific foods or behaviors that help you stay there. But you still wouldn’t have to measure forever. Once you identify what does and does not work for you, you’re good to go. (For a while, anyway. Things change over time.)  


The second thing to keep in mind:

In their book, The Art and Science of Low Carbohydrate Living, prominent low carb and ketogenic researchers Jeff Volek, PhD, RD and Stephen Phinney, MD, PhD write that the range for nutritional ketosis is a blood level of beta-hydroxybutyrate (BOHB) of 0.5-5.0 mmol/L – a tenfold difference! You might feel beneficial effects of ketosis anywhere inside this range, so don’t be discouraged if your ketone level is relatively low. What matters is how you feel or whether your health condition is improving, not your ketone level.

People vary widely in their bodies’ tendency to produce higher ketones. Some people’s bodies simply generate ketones more readily than others’. Some people—usually young, athletic males—can generate a relatively large amount of ketones even while consuming more carbohydrate than would be considered a ketogenic diet level. (As Chris Masterjohn, PhD, said, “Pizza couldn't kick me out of keto when I was in the gym all the time.”) Other people might have to fast, take MCT oil, or employ other measures to get to that same ketone level. Don’t compare your results to someone else’s, and don’t let anyone “ketone shame” you on social media. It’s not a contest or a race. Someone might feel like a total rock star with BOHB at “only” 0.6, while someone else might not notice any difference unless their ketones are above 2.0. It’s entirely individual and the only competition you’re in is to feel your best.


And a third thing: ketone levels fluctuate throughout the day.

So if you’re testing only once or even twice a day, you have a very limited view of what your body is doing all the rest of the time. (And considering the price of blood ketone test strips, most people don’t test blood ketones multiple times throughout the day. If you have a money tree in your backyard and want to test five times a day, I’ll kindly point you to the “donate” button on my blog, haha! Also, I’ve never been to Greece…) Most people find that urine ketones are highest in the morning and blood ketones are highest later in the day, but there’s individual variation with this.

Several things can affect ketone levels fairly quickly. For example, eating a fat-rich meal—especially if it contains MCT oil or coconut oil—can elevate ketones in short order. (In fact, MCT oil will do it even if you’re eating a lot of carbs, and obviously, so will exogenous ketones, which might be great as medical therapy, but which I do not recommend for fat loss, and which deserve their own post someday. Or you can just read Marty Kendall’s on this subject, which is fabulous.) Some people find that exercise raises ketones, and for many people, fasting will raise them too. Exogenous ketones in the form of ketone salts or esters will raise ketones, but using exogenous ketones doesn’t give you any insight into how your body produces its own ketones. (You could eat a bagel, take exogenous ketones and then, sure, you’ll see high ketones on your meter, but I don’t recommend this strategy.)


How to Interpret
Ketone Measurements


Measuring ketone levels can give you information about how your diet, sleep, stress levels, and exercise affect you. But don’t take the numbers at face value. It’s critically important that you understand how to interpret what you see, or you run the risk of coming to false conclusions—for example, that your ketone levels aren’t high enough, or that a certain food “kicked you out of ketosis.” Or maybe even more important, that you are somehow failing at your low carb or ketogenic diet because you rarely—if ever—see “high” levels (e.g., >2.0-3.0mmol/L)

Let’s start with measuring urine ketones—a contentious issue! If you’re measuring urine ketones (acetoacetate), remember that these ketones are being excreted, meaning, they’re not being used as fuel in the body. (You are literally peeing them out.) So this isn’t really the best gauge for how you’re metabolizing ketones. Plus, you might notice less of a color change on the urine test strips over time, and maybe even get to a point where there’s no change. This doesn’t necessarily mean you’re not in ketosis anymore; it might mean that your body has become better at using ketones and is therefore wasting less of them in your urine. So rather than being disappointed, you could take this as a good sign. (Keep in mind, though, that many people find the color still does change even when they’ve been keto for years. It might not be dark purple very often, but they’ll see light pink—subtle, but still a noticeable change. And some people who’ve followed ketogenic diets over the long term notice very little lightening of the color. So YMMV.)

That being said, urine test strips do serve a purpose. They’re great to use when someone is new to keto. Seeing that little square turn pink or purple can be a big morale boost and serve as encouragement to stick with this way of eating. It’s visible proof that their body has made the switch from “sugar burner” to “fat burner,” and they’ll feel like they’re on the right track even if they haven’t lost any weight or had other noticeable benefits yet. (This can be especially motivating for the newbies because most people will see pink or purple on these things within about 2-3 days of starting keto if they’re brand new to it, and that might precede fat loss, reduction in joint pain, clearer skin, and some of the other effects of going low carb. So it can be a positive reinforcement before anything else starts to change.)

For interpreting blood ketones, there are a couple of pitfalls. Ketones are a fuel—just like glucose and fats. The level of ketones measured in the blood reflects the dynamic between ketone production and ketone utilization. Here’s a real-world example: well-trained athletes and people who are very metabolically healthy might not see high blood ketones because their bodies are using the ketones at nearly the same rate they’re being produced. This means the ketones don’t have a chance to build up in the blood. Instead of interpreting this as someone not being able to get into “deep ketosis” and thinking it’s a problem, we could just as easily see it as something good: their bodies are efficient at using the ketones.

People with hyperglycemia have high blood glucose because their cells aren’t taking up and using glucose, right? So the glucose just lingers in the blood. But for some reason, when it comes to ketones, we automatically think that a buildup in the blood is a good thing. (I’m not saying it’s not a good thing. I’m just pointing out the contradiction. Again, I fully recognize that there are medical conditions that might require a certain sustained level of blood ketones. So all I’m doing is raising an interesting point.)



The (Fatty Acid) Elephant in the Room



Ah! We have come to the most important part of this post.

There’s an often overlooked but critically important point that rarely gets discussed: free fatty acids.

The body runs on three primary fuels, but we can measure only two of them ourselves. We can measure ketones and blood glucose, but the one that provides the majority of energy in people on ketogenic diets is the one we can’t measure: fatty acids (fats).

There are meters to measure glucose and ketones, but there are no fatty acid meters—at least, not yet. So if you feel great and have good energy, no carbohydrate cravings, your moods are stable, and any symptoms you’ve had in the past remain resolved, but you regularly see ketones at the low end of the range, or perhaps not even in the range of nutritional ketosis at all, there’s a chance your body is humming along just fine on a high amount of fatty acids. So WHO CARES what your ketone level is?

When you’re new to a ketogenic diet, many different cells and tissues will use ketones for fuel. After a while, though, skeletal muscles (like your quads, glutes, and triceps) and cardiac muscle cells (that is, your heart) will preferentially use fats/fatty acids in order to spare ketones and glucose for tissues that can’t use fats, or don’t use that much of them—such as the brain. And if the brain is taking up ketones efficiently, they might not build up in the blood. Plus, evidence is emerging that some ketone production happens within the brain itself: cells called astrocytes break down fats into ketones and then export the ketones to be used as fuel by neurons. (Lauric acid, the predominant fatty acid in coconut oil, seems to be an especially good substrate for this, which is likely why it’s so helpful for Alzheimer’s and other neurodegenerative conditions.) All of this is localized inside the brain, where none of the home measuring devices can assess it. So if you feel great but you don’t see a high ketone level, trust that your body and brain are doing exactly what they’re supposed to do—taking up their optimum fuels.

Finally, keep in mind that ketones are a product of incomplete oxidation (“burning”) of fats. If you’re following a solid ketogenic diet, getting plenty of exercise and good sleep, but you rarely see high ketones, it could be that your body is better at completely metabolizing fatty acids, so there aren’t a lot of ketones being generated in the first place.

If you want to nerd out on the biochem of how this works, read on. If you are terrified at the mere thought of nerding out on the details, skip this section and start back up again where it says “How to Proceed.” I encourage you to put on your proverbial galoshes and wade through this as best you can, though. Even if you don’t grasp all of it (frankly, I don’t grasp all of it either!), you’ll be able to pick up a few things here and there. And the reason I wrote this post is because I am tired—so tired—of hearing people make outlandish claims about ketones and ketosis when they lack even a rudimentary understanding of the pathways and mechanisms involved. Don’t be one of those people.



Ketogenesis: How and Why Do We Make Ketones?
Also: Fat Adaptation versus Ketosis



(A crude diagram of what I’m about to describe is below, so don't worry if you don't understand this just yet. It'll make more sense when you see it.)

Ketones are produced when the amount of acetyl CoA produced from beta-oxidation of fatty acids exceeds the amount of oxaloacetate (OAA) available to keep the Krebs cycle going. If you have enough OAA available, you’ll fully metabolize the fatty acids and produce ATP from them. (“Hepatic ketogenesis is a spillover pathway for β-oxidation-derived acetyl-CoA generated in excess of the liver’s energetic needs.”) OAA can come from many difference sources. Glucose is one of them. (Glucose is converted to pyruvate, and pyruvate can be converted to OAA.) This is where that phrase “fats burn in the flame of carbohydrate” comes from. But fats don’t burn in the flame of carbohydrate; they burn in the flame of OAA, and guess where else OAA can come from? Amino acids! Yes, amino acids, from the protein everyone is so damn terrified of eating on a ketogenic diet. Amino acids can be used as substrates for pyruvate synthesis or OAA synthesis, or if they are converted into glucose via gluconeogenesis, they can be made into pyruvate again. It’s all very neat…lots and lots of overlapping pathways. (Good diagram of all this on the first page here.)

Either way, when you have enough OAA to keep the Krebs cycle running in the liver, it keeps running. And in running, it uses acetyl CoA derived largely from fats. So you are still “burning fat.” You are still “running on fat,” even if you are not generating lots of ketones. This is why you do not need to be on a super-strict ketogenic diet to be fat-adapted or to lose body fat. Capice? You need to keep carbohydrate low enough that your body is forced to turn to a different fuel source (fat), and you need to keep insulin low enough that your body can use this other fuel source. (Remember, insulin inhibits lipolysis.)


Most of us can accomplish this very nicely on a diet that is low carb, but not necessarily super-strict ketogenic. It’s also why protein might “kick you out of ketosis,” but for most people, this is not a problem, because the reason you are not producing high ketones is because the amino acids from protein (and glucose released from the liver under glucagon signaling from protein ingestion) are providing your liver with enough OAA to keep burning the fats, so the fats are not “spilling over” into ketone production. This explains why ketones are said to result from the “incomplete oxidation of fatty acids.” You are still oxidizing them; you’re just not sending them into the Krebs cycle in the liver. Instead, they will be made into ketones and exported from the liver into the circulation to be taken up by some other tissue’s cells, where they will be converted back into acetoacetyl CoA, then back into acetyl CoA, and used in the Krebs cycle in that cell. We cool now? (The liver produces ketones, but it doesn’t really use ‘em. It provides this nifty service for other cells.)

(FOR THE LOVE OF ALL THAT'S HOLY, SOMEONE PLEASE VOLUNTEER TO HELP ME WITH GRAPHICS!)


What you see in this very simplified diagram:
In order to keep the Krebs cycle going, acetyl CoA must condense with OAA. If there isn’t enough OAA to keep the cycle going, acetyl CoA is instead made into acetoacetyl CoA and then into ketones. “Ketones are produced when there is no longer enough oxaloacetate in the mitochondria of cells to condense with acetyl CoA formed from fatty acids.” (Source.) If there is enough OAA, then acetyl CoA—which is still coming from the breakdown of fats—goes through the cycle as normal. You must understand that some of this acetyl CoA came from fatty acids.

You are still “burning fat” even though you are not generating high ketones.

I have to emphasize this point because I saw a comment on Twitter the other day wherein someone said something to the effect of, “If I’m not in ketosis, then I’m storing fat.”

Whoa, whoa … WHAT?

I had already been planning to write this post for several months, but that comment is what got me to finally sit my fanny down and do it.

As I have written about eight hundred times in other posts, you do not need to be generating high levels of ketones to be metabolizing fat. The body does not operate in a binary system where the two choices are:
(1)  Maintain deep ketosis …or…
(2)  Become obese

Hello? *Tap tap.* Is this thing on?

Just because you’re not in ketosis doesn’t mean you’re somehow not metabolizing fat so that the only other possible destination for it is to be stored. To be honest with you, my dears, I wrote this post partially to try and help people understand how this works, but mostly to save myself from having to read dumb shi stuff on the interwebs that nobody has the patience to try and correct in 140-character installments.

If you need to be on a ketogenic diet to manage a serious medical condition, then be on a ketogenic diet and take deliberate action to maintain high ketones. If you want to lose body fat or improve insulin/blood glucose issues, then keep your BG and insulin low. These two approaches are not the same.

Now, before anyone gets all worked up over this, if you find that you, personally, need to keep your carbs (or your protein) very, very low in order to lose fat and/or maintain a body composition you’re happy with, fine. Do that. But please do not—repeat, do not—scare other people into thinking they are gigantic failures if they’re doing “everything right” and their bloodwork is the stuff of legends, but their ketones stay on the low side.

Clear as mud?

Chris Masterjohn has a great video on how ketones are synthesized if you want to really geek out. Chris’s video lessons are fantastic, but don’t get in over your head if you don’t care about the real nitty-gritty. I’m linking for the people who might want to dive deep. If you’re doing a low carb or ketogenic diet for fat loss or your general health and the last thing you want is a biochemistry lesson, steer clear!

Remember what I said earlier: it’s possible ketones build up in the bloodstream when other tissues are not taking them up as quickly as they’re generated. As I mentioned, it’s pretty common for highly trained, athletic people to not see high ketones. Perhaps this is because they are fully oxidizing the fats, their other tissues are taking in the ketones efficiently, or both.

Whatever the reason, it sure ain’t because they’re “doing it wrong.”  



How to Proceed


To sum up: It might be helpful to measure ketones if you are using a ketogenic diet to manage a specific health concern. It’s less crucial to measure if you’re aiming for fat loss or overall wellbeing, but even then, there are valid reasons to measure, particularly if you’d like to see if there’s a correlation between your ketone levels and your mood, energy levels, food cravings, etc. The important thing is to understand the numbers you see. And the good news is, once you establish whether there’s a correlation between your ketone levels and good things happening to your body and brain, you don’t have to keep testing. Once you know which foods and activities work best for you, you can stick to them unless and until they stop working so well. (It’s true, folks. Even on keto, our bodies change, circumstances change, and what worked like magic at one time might not be right for you at some point in the future. Be flexible and open to change.) You can check in now and then with your meter just to see where you are, but you don’t need to test every day, forever.

I must stress, however, that I am not a fan of people measuring ketones if their goal is fat loss. Why make this more complicated than it needs to be, especially if you’re going to freak out if your ketones are “only” a certain level? I wrote this post to explain how to interpret the numbers, not as an endorsement or encouragement for everyone to measure. If you want to measure, have at it, but please do so with a desire to understand what the data are telling you, and take a deep breath before you post an anxious and fearful cry for help on your favorite keto forum.



P.S.

In a study run by the people at Virta Health (of which Dr. Phinney is the founder and Chief Medical Officer), type 2 diabetics who followed a ketogenic diet for 10 weeks saw impressive reductions in HbA1c, fasting glucose, triglycerides, and body weight. (Doesn’t look like they measured insulin; it’s too bad; that would have been nice to see.) Not only that, but from the study:

“The majority of participants (234/262, 89.3%) were taking at least one diabetes medication at baseline. By 10 weeks, 133/234 (56.8%) individuals had one or more diabetes medications reduced or eliminated.” (Including insulin!)

“Baseline HbA1c level was 7.6% (SD 1.5%) and only 52/262 (19.8%) participants had an HbA1c level of <6.5%. […] At follow-up, 47.7% of participants (125/262) achieved an HbA1c level of <6.5% while taking metformin only (n=86) or no diabetes medications (n=39).” (This is a big improvement. HbA1c <6.5 is no longer classified as diabetic. A1c between 5.7 and 6.4 is "pre-diabetic," so many of these individuals were still pre-diabetic, but that is movement in the right direction for sure.)

I am sharing this with you because these participants were issued blood ketone meters for the study, and the mean BOHB level during the 10 weeks was… wait for it… 0.6 mmol/L.

Now, granted, these subjects were overweight adults with T2 diabetes. The goal was not to win the CrossFit Games or to compete in a physique competition. Some of these folks were in pretty bad shape, metabolically speaking. The goal was fairly modest: to evaluate “whether individuals with T2D could be taught by either on-site group or remote means to sustain adequate carbohydrate restriction to achieve nutritional ketosis as part of a comprehensive intervention, thereby improving glycemic control, decreasing medication use, and allowing clinically relevant weight loss.”

Well, by those criteria, the subjects did stunningly well. If you are so inclined, check out the full text and take a look at the chart on p.8 – THAT IS AMAZING. People decreased or eliminated meds left and right, including insulin. NICE! And all that with ketones at a whopping 0.6. (As for the cases of increased doses of meds or people adding new meds, I'm guessing that was likely because people eliminated more powerful or more harmful meds and switched to milder ones -- because they didn't need the more powerful ones anymore.) 

The changes from baseline to the 10-week mark are pretty damn impressive. For many of the subjects, A1c, fasting glucose, body weight, and some of the other parameters were substantially reduced from baseline, but were still high at the end of the study. As I said, many “improved” from T2D to pre-diabetes, but it was only 10 weeks – less than 3 months’ time. This is actually remarkable. Think what could happen given more time. (Funding a study can be a huge undertaking, so the fact that they were able to finance it for as long as they did is great.)   

Would these people have had even better results if their ketones were higher? *Shrug.* If so, I would posit the higher ketones would have been a result, not the cause, of improved glucoregulation and insulin signaling. All I’m saying is that they achieved pretty damn impressive results with a mean ketone level barely within the range for nutritional ketosis. (Some subjects likely were higher here and there during the study duration; only the mean is provided.)  

Eat the things you know you can eat; avoid the things you know you should avoid, and the improvements will come – with or without ketones. 



P.P.S. I am considering starting a Patreon account to fund the many hours of otherwise unpaid time that goes into posts like this. Since I haven't done that yet, if you found this post or some of my others valuable, please consider making a contribution to this effort via PayPal. There's a button in the sidebar on the right on my site, or you can simply use your PayPal account (I think you can sign in as a guest if you don't have one) and send to my email address: tuitnutrition@gmail.com. Any and all amounts are welcome and appreciated. If you can only spare $2, that buys me a cup of coffee, which I assure you, is a great contribution to my writing efforts! 






Remember: Amy Berger, M.S., 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. 

55 comments:

  1. Thank you for another well-written post that breaks down the basics of the low-carb/ketogenic lifestyle. Your manner of explaining is incredibly helpful for the layperson who wants to continue the journey into health, to support others, and to keep it real.

    ReplyDelete
  2. Totally agree. I tested awhile in 2010/11 but when I 'straight lined' ketones I stopped. IF people want to measure ketones... fine, but making it a requirement adds complexity that discourages some from even attempting to follow low carb.

    Of course it lines the pockets of those that promote ketosis in books, seminars and products...

    ReplyDelete
  3. I think it also changes over time. At one time, I could use the urine strips, but I gave up using them long ago, as I had many tests where urine showed nothing but both breath and blood indicated I was in ketosis. And now, after almost 4 years in low carb/getting nearer and nearer to zero carb/all meat, I am out of ketosis more often than I'm in it, particularly if I eat high protein meats. If I ramp up the fat or fast a while, I can get to higher BOHB levels, but not that high, usually 1.0 or less. The last time I got over 1.0 was about a month ago, and I ate high fat one day; the next morning, I had 2.8. I fasted that day, and by 1pm, my ketones were already down to 1.1.

    I'm still testing higher protein, low carb, and that's where it gets tricky: I'm no longer in ketosis after a day of high protein meals. Is that bad or good? Not sure. I'm getting a continuous glucose monitor to see if that can shed light on this, and I wish I could take home insulin tests to clarify this issue even further.

    Here's another similar article:

    http://www.marksdailyapple.com/why-am-i-getting-low-ketone-readings-on-a-ketogenic-diet/

    ReplyDelete
    Replies
    1. This comment has been removed by the author.

      Delete
    2. Why are you doing all this? The whole point of this post was to help people see that very few of us have a reason to micromanage these sorts of things unless you are using this diet as a *medical therapy.* This kind of constant measuring and tracking simply isn't necessary for most of us. If you enjoy it and you feel it adds something positive to your life, keep at it. But as I wrote here, you have to understand how to *interpret* the results so you don't make yourself crazy. Of course your ketones are lower when you eat higher protein. That tends to be how it works in most people. (With some exceptions, but most people...higher protein, lower ketones, but STILL FAT ADAPTED.) You read that part about OAA, right? ;-)

      Delete
    3. I found the comment interesting from Anonymous as I too have begun experimenting with zero carb. I happen to wear a CGM which I used to help tune my previous ketogenic diet and enjoyed the easy feedback. I am not surprised to see in my own case large protein meals also kick me out of ketosis, but I have seen a marked increase in FBS from 80 to 100 since adopting this WOE. Otherwise feel great, but don't like the increase here.

      Delete
  4. Thanks for this post. Was just digging into this the other day to try to understand.

    I like the part where you say there are 3 pathways: glucose, fatty acids, and ketones. But then you seem to say that the ketone part only happens when there is 'excess' fatty acids. I wonder if that is really true.

    If you are on a keto diet, especially a strict one, don't you need the ketone pathway (which originates mostly in the liver) to be running in parallel to the main fatty acid pathway that happens in our tissues? This would seem to be necessary to generate ketones for use in the brain. Given importance of the brain, possibly even given some preference to generate enough ketones for it.

    But I guess you get then into some sort of interplay between how much glucose is around and/or can be generated via gluconeogenesis. And/or maybe the brain supplies its own ketones via the possible mechanism you mention?

    I looked for a chart that might pull all these pathways together, but couldn't find one that was just right. This was closest and highlights the Krebs Cycle in tissue vs the separate process that occurs in liver to generate ketones. http://www.jlr.org/content/50/Supplement/S138/F1.large.jpg

    Very complicated stuff.

    ReplyDelete
    Replies
    1. I think you missed something. I didn't say ketogenesis comes from excess fatty acids. I said it comes from insufficient OAA.

      And yes, ketogenesis can happen at the same time as fatty acid oxidation. Breaking down and oxidizing fats *has to* happen before ketogensis *can* happen. The human body is not binary. Many overlapping processes occur in tandem. It is not ketones *or* fats, but both. Man, I thought for sure this post was long enough and detailed enough to explain this but I guess it wasn't. You will have many pathways running at once. As a very, very general example: even when you are in "deep ketosis," you are STILL METABOLIZING GLUCOSE. Some of the acetyl CoA comes from fats, but you will also still be performing glycolysis and generating pyruvate & acetyl CoA that way. Think about it: some cells do not even *have* mitochondria, which is where fats are oxidized, so they *have to* run on glucose. So the human body is very elegant and lots of things go on at the same time, at different levels, in different tissues and cell types.

      If I can leave readers with any take home message, that is it: this is not a binary. on/off, yes/no thing. Human biochemistry is wonderfully elegant and complex. Tons of overlapping pathways, redundancies, and feedback loops.

      Delete
    2. And when I say "ou are still metabolizing glucose," I don't mean that to say that glucose is your primary fuel. Only that you will never get to a point where there is no glucose being used in these various pathways. Even if you are on a "zero carb" diet and ingest little to no exogenous glucose, your body will *make* the glucose it needs, because...well...it needs it. We don't need to get it from 300 grams a day worth of bagels and soda, but we do need some, and that's the beauty of gluconeogenesis.

      Delete
    3. Thanks for your follow-up thoughts. They are helpful. You seem slightly annoyed at me, so I will leave it there.

      Delete
    4. I don't think she seemed annoyed with you in the slightest. She just gave you some further explanation and clarification.

      Delete
    5. John, check out Peter Attila's eatingacademy.com if you haven't already. He's a practicing physician/former surgeon and an athlete. Very detailed blogs on nutritional ketosis. This one is very in-depth about ketones and carbs coexisting http://eatingacademy.com/sports-and-nutrition/ketones-carbohydrates-can-co-exist. May clear things up for you.

      Monica

      Delete
  5. I've never measured ketones - just kept my carbs around 30-50g a day. The big problem the modern diet causes is hyperinsulinmia. Cut the carbs, up the protein and fat, don't worry about ketones at all- it's a distraction to the untrained eye (which most of us are) as Amy has shown. Keep it simple folks

    ReplyDelete
  6. Thank you SOOOO much! Your article is a great tool for so many people who've gotten an incorrect understanding of the process or of the purposes of measuring ketones! I now have a place to point people who want something in depth, accurate and easy to read. :-)

    ReplyDelete
  7. After measuring my heart out for 18 months and averaging 0,223 mmol, I absolutely guarantee that 39 kilo of fat did not just fly off. FFA is the way :-)

    ReplyDelete
  8. I love the way you tackle the nonsense, Amy. This is one more excellent way of looking at this ketones vs. ketosis thing, and I wish more people would get off their high-horses and accept that there isn't only "one way" to interpret this topic. In my case, in transitioning to a ketogenic diet starting back in June, my REAL goal was just to keep my sugar intake to less than 30g per day. My second goal was to eliminate grain-based and bad carbs. Sooooo, a friend with Stage IV brain cancer said, "Jim, that sounds an awful like my ketogenic diet. You should give it a try." So here I am, a little more than 3 months later, still making the transition because I haven't perfected the keto way of eating in my life, but I AM averaging less than 20g of sugar and 30g of net carbs per day. I'm wearing clothes that haven't fit in more than a year, and seeing a weight on the scale I haven't seen in almost four years. I had a blood panel a month ago, and my A1C is no longer in the pre-diabetic range. But here's why I'm writing this post. For more than two months I was checking my urine ketones at random times during the day, and never once did I see a color darker than a very pale or light pink. So for whatever reason, and it could be more than one, everything you wrote about NOT obsessing with the color on a keto stick applies to me.

    ReplyDelete
  9. You might like this...
    http://tabletopwhale.com/2017/05/16/a-galaxy-of-molecules.html
    I cannot figure out how to post this other than anonymously!
    Daisy Brackenhall

    ReplyDelete
  10. We need to talk about how "fanny" does not travel well across the pond :D
    Daisy

    ReplyDelete
    Replies
    1. Oh no, haha! What did I say? I traveled through the UK and Ireland about 20 years ago and I know several things don't "translate" correctly between British and American English. I chuckle to think what my British readers are thinking... Aaaaah!

      Delete
    2. Um I don't know about in the UK, but in Australia it means another part of a female anatomy....ahem. I am unsure if I should explain further!
      Dale

      Delete
    3. It is my favourite. My sister used to have endless fun telling people what they would be saying if they used that word in the UK - also Australia, NZ. It is not a part of your anatomy that you would normally talk about in public although you do also sit on it! :D
      Daisy

      Delete
    4. My wife was rather embarrassed several years ago when she worked for a stint in New York (we're from the UK). Inevitably she made an error one day and called out to see if anyone had a rubber. Of course later she found out that she should have used the word 'eraser'!!

      Delete
  11. Great article. I got a ketone meter this year- after being in and out of keto on and off since mid 2011. I promised myself I'd test to see what my levels were for the 10 strips that came with the meter and then not test. Just some data to confirm or disprove that I was indeed in ketosis via blood. I am, and I come and go- as I thought.

    The good news is my Keto meter also has Hemoglobin and Hematocrit- I can run too low ( paid blood donation) and I carry a SNP or two that could result in too high of readings). So I can now use the same meter to test H&H quarterly, a few more ketone readings and I'll be good for many years.

    I'm a Medical Technologist in real life, so point of care testing too much and my data collecting ways could have been expensive. This validates my decision to be very limited in my ketone testing. I like the Keto gains motto, a lot. My LCHF with IF combo has me feeling well and maintaining that weight loss over 5.5 years. All that talk about weight loss, we need more about long term weight maintenance- and I think your article is valuable info for the long haul.

    Thanks for a great article and keep up the good work. Glad you are considering a Patreon account.

    ReplyDelete
  12. Hi Amy,
    Just found a fresh start-up "Keto-mojo" with the FDA approved quite affordable keton-meter and strips.
    https://keto-mojo.com/pages/about-us

    ReplyDelete
    Replies
    1. Whoa. It would seem to me that advertisements for a blood ketone meter (that hasn't even been released yet) would be antithetical to the content and spirit of Amy's brilliant post.

      Delete
  13. Thanks so much for another great post, Amy. I always find another huge chunk of the puzzle when I read your stuff (and usually get a chuckle or two out of it while learning, which I love). I've never measured, but I've read the comments you speak of and it has caused so much confusion and doubt. This article has helped all of that angst melt away--thanks, again!

    ReplyDelete
  14. I REALLY appreciate your post, this was very informative. I do however have a question maybe you can answer regarding using a ketogenic diet for weight loss. It makes sense to me to keep the carbohydrate low, protein moderate however, when you're trying to get your body to "use/burn" it's own fat instead of the fat you're eating should you keep your fat intake on the lower side since the body doesn't necessarily care where it gets its fat from? I'm not necessarily talking about "bullet proof" coffee or drinking coconut oil etc .. just in general when you eat meals .. Also, I've been adding intermittent fasting which seems to be a great tool as well. Thanks for your input! Misty

    ReplyDelete
    Replies
    1. Hey Misty, funny you should ask...
      If you're new to my blog, I wrote a post about this exact thing last month! It was the previous post before this one, in fact. (Link below.)
      You don't need to micromanage how much fat you're eating unless you happen to be eating a great deal of it and are struggling to lose body fat. If you're happy with the results you're getting, then carry on. If not, then some people find it does help to ct back a bit, and as you've noted already for yourself, IF helps many people too.

      http://www.tuitnutrition.com/2017/08/how-to-cut-fat-on-keto.html

      Delete
    2. I actually just found your blog yesterday 😁 Thanks for responding. I'll look at that post and start looking through your other ones as well. I appreciate it.

      Delete
  15. Great post Amy. I have lived my life in ketosis for fifteen years now ever since Dr Atkins and chemist shops actually refusing to sell you ketostix unless you could prove you were diabetic. Which I'm not obvs. After spending 15 years worth of pee on ketostix I still use them, I still find it exciting and motivating to watch them go deep purple in my case. No pink here :) I absolutely agree with you on your point about what are you measuring... the easiest way to get a real ketostix glow is to eat a lot of fat and dial down the exercise. It creates beautiful ketones... but what's the point?

    ReplyDelete
  16. Talking of fatty acids, you write:

    "[...] they will be made into ketones and exported from the liver into the circulation to be taken up by some other tissue’s cells, where they will be converted back into acetoacetyl CoA, then back into acetyl CoA, and used in the Krebs cycle in that cell."

    If I understand correctly, the other cells will need OAA to metabolise ketones. Where will it come from? The liver didn't have anymore OAA but the other cells do? I'm confused.

    ReplyDelete
    Replies
    1. Good question. I do think this can actually happen...different cells can be running different metabolic processes to different degrees. (For example, because red blood cells have no mitochondria, they can not metabolize fats or ketones at all and must use glucose or other fuels. Also, I should've been clearer: it's not that the liver has *no* OAA. I can't imagine a situation where a hepatocyte would have *zero* OAA. It's more that there's just not *enough* OAA to take all of the acetyl CoA that came from a fatty acid and put it through the Krebs cycle. That extra/leftover acetyl CoA goes into ketogenesis [or some other pathway.] But your question still stands, because then we would ask if the other cells have sufficient OAA.)

      To be 100% honest with you, I'm not sure of the answer, but I do know that different cells do different things. (This makes me feel better about having written, "frankly, I don’t grasp all of it either!" I wasn't lying. I have many questions, myself. In this post, I was mostly trying to just help people see why it's not always productive to get worked up over low ketone levels.) This is a good question, though, and I'll see if I can get an answer. I can ask some people who are way smarter than I am. ;-)

      Delete
  17. Incredible post!! Thank you so much! So informative and helpful. I printed it out, highlighted and made inites. Saving hard copy for sure!

    ReplyDelete
    Replies
    1. Glad it was helpful. :) I've gotten some good questions here that make me realize I have more to learn, though. (It never ends.) Mostly it's just interesting to note how differently individual people respond to different intakes of protein and carbs. I follow Steve Cooksey, a (former) type 2 diabetic who achieved damn good BG control with low carb, then keto, and has been doing "zero carb" for a few months now, with *massive* intakes of protein, and better blood sugar than ever! But then other people see very different things. It's very difficult to make recommendations for clients now.

      Delete
  18. Bravo, Amy! We newbies to a keto diet need this boost of confidence to keep on our path of LCHF living although our ketones measure inconsequential levels. 35 lbs of fat loss later, I found when I ate a high fat/high protein meal my ketones skyrocketed. But high protein is not the keto protocol,so I would dial the protein way back although I CRAVED the protein yet was afraid to eat it. I realized a BMI of 21 (from 31) implementing KETO and IMF relentlessly for four months. Recently, I had an NMR Lipid Panel and other blood work. Although my lipid measurements were fabulous, my ferritin levels were extremely low (explains my hair loss) and some indications of heart muscle duress (NT-proBNB). And I believe these two medical concerns stem from inadequate protein. We all have different body chemistry, and if I had to do this weight loss protocol over again, I would measure ONLY my blood glucose and NOT ketones. Weight gain can be due to insulin spikes to certain foods in your diet and each of us react differently to individual foods. For example, coconut oil can spike blood sugar in certain people. In others, it enhances ketones. Your won't know which foods kick you out of ketosis unless you measure your blood sugar. Throw away the ketone stix, measure your blood sugar after meals, pay attention to what your body is innately messaging you, and keep off the scales. If your clothes don't fit anymore, you are losing weight! And be cautious as to which keto guru you choose to follow for your education. My vote is for Amy Berger!

    ReplyDelete
    Replies
    1. Thanks, Nancy! I do NOT want t be anyone's "guru." I have so much to learn and have so many questions remaining about all this, myself. You know what they say" "The more I learn, the less I know." But I try to be honest about what I don't know and use my blog to share the little bits of knowledge I do have -- specifically about some of these biochemical processes and pathways, because when people have a better sense of how complex this is, and all the interconnected and overlapping feedback loops in the human body, maybe they'll see none of this is as straightforward or black & white as they think it is.

      Thanks for reading. :) I try to keep things rational around here.

      Delete
    2. I love rational. I beg someone of your intellect, dogged ability to investigate, and
      ease of communicating the English language to research specifically the APOE4 allele and its effect on lipid metabolism. Members of that conundrum are so wary of saturated fats, such as coconut oil and other so-called healthy fats, that we shy away from them. We are swimming in a sea of confusion as to what fats are safe for us to eat. If you join the APOE4.info, you can read our comments: https://www.apoe4.info/forums/viewtopic.php?f=4&t=570 Have a blessed day.

      Delete
    3. Oh, I know the E4 forum. In fact, I usually refer people to it when they ask me anything about E4. I think Julie Gregory is probably the world's expert on those issues and has probably done more research than anyone, including the professionals and "experts." I don't think I would be able to tell anyone anything useful that she isn't already talking about.

      Overall, I think staying away from sugar and refined grains is far more important than worrying about the composition of dietary fats for the E4s. The fat is a secondary issue...I think controlling blood glucose & insulin should be primary, and then people can try to modulate the kinds of fat they eat.

      As for the people whose cholesterol goes sky high on a high fat diet or specifically with saturated fat, I recommend Dave Feldman's work, which I'm sure is probably discussed on the E4 forum. We don't seem to have any evidence that "high cholesterol" (including high LDL) is harmful at all in the context of a body with low insulin, low glucose, low inflammation... But I'm not an MD and I'm not super well-versed in the E4 issue, so I hesitate to say more.

      Delete
    4. Concur entirely - as a medic and keen "fan" of Dr Malcolm Kendrick (author and blogger of the Great Cholesterol Con) I really no longer care what anyone's so called cholesterol levels are. Firstly we don't measure cholesterol but the carriers of cholesterol - akin to trying to calculate the population of London by measuring the number of buses, cars taxis etc on the road- not likely to be that accurate. Secondly even the alleged link with certain particle sizes and oxidised levels is undoubtedly missing the point -producing this type of lipoprotein is as a consequence of the mechanisms that contribute to atheroscleosis (such as inflammation) not that these particles subtypes cause atherosclerosis - no-one thinks that having two yellow fingers causes lung cancer.
      Frankly I ignore lipid profile apart from confirming where we might need to address other factors such as inflammation -

      Delete
    5. Thanks for weighing in Dave. I'm a fan of Kendrick as well, and the more I learn, the more I think this entire cholesterol thing is just such a load of nonsense. People are being medicated with a very very dangerous drugs with terrible side effects over numbers that seem largely meaningless.

      Don't get me started on the connections between statin drugs and dementia. It's practically genocide.

      Delete
  19. Hi Amy. I tried to understand what you were saying,but I cant really put it all together. Ive been low carbing for 4 years (on and off). Back to it properly last 18 months. Lost 25 kilos, but hardly lost 2 kilos since January. Started investigating & it seems I was eating too much protein and not enough fat. Have been trying to understand all this over the last two weeks and am still bit confused. there are so many differing opinions out there. Could you please answer this question: my carbs are under 20g...am I supposed to count protein and fat grams per day as well.?? Some say moderate protein and HIGH fat. Others disagree. So at the moment im not sure exactly what I should be doing. I have lost 1 kilo in 11 days since reducing protein and increasing fat intake. So I tend to think I was overdosing on protein.Im also not sure why I need to increase fat intake. why cant my body just use what ive already got ?. I would love your opinion as I just want it sorted out and then I can carry on my merry way. thank you in advance. Lindy (sorry I could only select "Anonymous" for some reason.

    ReplyDelete
    Replies
    1. Hi Lindy, I can't comment without knowing what your current weight is, also your age, are you taking any medications? I need to know a lot more about you before saying anything. How much more are you looking to lose? Are you already at a healthy weight and just want to lose a little more for your own reasons, or are you still significantly overweight?

      You might want to give this a read as well: http://www.tuitnutrition.com/2017/02/fat-loss-new-perspective.html (Links don't seem to work here in the comments, so just copy & paste that into your browser.)

      Delete
  20. i wouldve liked to see explained the part where you can burn fat even though you have high carb diet.
    how does that work, and whats the difference in efficiency between low carb and high carb regarding fat burning ? u can use intervals 5-20% etc
    thanks

    ReplyDelete
    Replies
    1. People whose blood glucose and/or insulin doesn't rise dramatically after a high carb meal can burn fat even with a high carb intake. Insulin sensitivity is a spectrum: some people have a much higher "carb tolerance" than others and can remain lean and metabolically healthy even with a high carb intake.

      However, just because someone remains thin on a high carb diet doesn't mean they're automatically healthy. Yes, many people *will* be healthy, but many will also be "TOFI" - thin outside, fat inside. They are thin on the outside, but have the metabolic profile of someone very unhealthy: http://www.tuitnutrition.com/2015/10/its-the-insulin-6.html

      I'm not sure what you mean by "efficiency." Generally speaking, fat is a more efficient fuel than carbohydrate. This is what the "respiratory quotient" measures -- oxygen consumed in metabolism. The closer it is to 1 (the higher it is), the more someone is burning carbohydrate, and the lower it is, the more their body is being fueled by fat.

      Delete
    2. im talking about fat burning. i know all the health benefits, just concernedd with fat burning atm.
      do you have an estiamtion as how much % fat is burned from low carb vs high / moderate carb? if theres one

      Delete
    3. I'm still not sure I understand the question. Everybody burns different fuels at different rates anyway.
      You might be interested in this video with regard to fat-adapted athletes and how much fat they burn compared to carbohydrate: https://www.youtube.com/watch?v=2398ztuI1Cc

      Not sure the results are suitable to extrapolate to "normal" humans doing a low carb diet, but it's all I have...
      Other than that, I don't have an answer for you. Sorry.

      Delete
  21. Thank you, thank you, thank you, Amy! I love your humility, and sense of humor! Your writing is informative, inspiring, and FUN! Thank you for taking the time to explain this process. I am heading over to PayPal to buy you several cups of coffee. Kudos!

    ReplyDelete
    Replies
    1. Thanks! Coffee is always great. :D
      Glad the writing is helpful. That's what I try to do!

      Delete
  22. I wonder to what extent the low ketones seen in athletes are due to their preference for higher protein intake. Protein provides Krebs intermediates to increase cycle throughput and take acetyl-CoA away from the ketogenesis route.

    If the ketone concentration is low the utilisation by the brain will be low. The flux in the bloodstream will also be low and surely a constraint ?

    The only indication that supply and demand a matched is a constant concentration in blood (at any level).

    ReplyDelete
  23. Have you ever checked into the Virta Program? I'm involved in a clinical trial with that now.

    ReplyDelete
  24. Of course I find your blog after dropping $100 on a keto meter and strips. Still gonna use it just won't freak out if it shows .3 mm/l on the meter one morning if I feel great. I've lost 20 pounds since going keto so I must be doing something right.

    ReplyDelete
    Replies
    1. Testing is fine. I'm not opposed to testing; only to people testing and freaking out, and coming to all sorts of illogical conclusions because they don't even have the most basic understanding of the mechanisms at work.

      Sounds like you're doing great though. You can measure if you like, but now maybe you know a little bit more about how to interpret the numbers you see.

      Delete
  25. Hello Amy, thanks for an excellent post. I do track ketones but mostly because I'm a bit of a data fiend. That said, after reading something Marty wrote a couple years ago on optimizing nutrition I'm much more of a breath test fan. His argument was that breath ketones measures your actual ability to use them as energy which seems to match your statements that blood tests are more about what's roaming around in your bloodstream waiting to be used. You hadn't mentioned breath ketone testing so I was curious about your thoughts. Thanks for a great read.

    ReplyDelete