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Ketosis – advantaged or misunderstood state? (Part I)

Ketosis – advantaged or misunderstood state? (Part I)
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As The Eating Academy approaches its first birthday in about a month, I figured it was as good a time as any to put together some thoughts on a subject I get asked about with great frequency.  (For those wondering when I’ll get to Part X of The Straight Dope on Cholesterol, the answer is, “hopefully before the end of the year.”) A few months ago I was planning a post along the lines of “the 10 things you need to know about ketosis,” but I’m now thinking that might be putting the proverbial cart before the horse.  So, let’s start with a more fundamental set of questions. In part I of this post I will see to it (assuming you read it) that you’ll know more about ketosis than just about anyone, including your doctor or the majority of “experts” out there writing about this topic.

Before we begin, a disclaimer in order: If you want to actually understand this topic, you must invest the time and mental energy to do so.  You really have to get into the details.  Obviously, I love the details and probably read 5 or 6 scientific papers every week on this topic (and others).  I don’t expect the casual reader to want to do this, and I view it as my role to synthesize this information and present it to you.   But this is not a bumper-sticker issue.  I know it’s trendy to make blanket statements – ketosis is “unnatural,” for example, or ketosis is “superior” – but such statements mean nothing if you don’t understand the biochemistry and evolution of our species.  So, let’s agree to let the unsubstantiated statements and bumper stickers reside in the world of political debates and opinion-based discussions.  For this reason, I’ve deliberately broken this post down and only included this content (i.e., background) for Part I.

What is ketosis?

Ketosis is a metabolic state in which the liver produces small organic molecules called ketone bodies at “sufficient” levels, which I’ll expand upon later.  First, let’s get the semantics correct. The first confusing thing about ketosis is that ketone bodies are not all – technically — ketones, whose structure is shown below. Technically, the term ketone denotes an organic molecule where a carbon atom, sandwiched between 2 other carbon atoms (denoted by R and R’), is double-bonded to an oxygen atom.

Conversely, the term “ketone bodies” refers to 3 very specific molecules: acetone, acetoacetone (or acetoacetic acid), and beta-hydroxybutyrate (or beta-hydroxybutyric acid), shown below, of which only 2 are technically ketones.  (The reason beta-hydroxybutyrate, or B-OHB, is not technically a ketone is that the carbon double-bonded to the oxygen is bonded to an –OH group on one side, technically making B-OHB a carboxylic acid for anyone keeping score.)

Now, back to the real question at hand.  Why would our body make these substances? To understand why or when the body would do this requires some understanding of how the body converts stored energy (the food we eat or the energy we store in our body, i.e., fat or glycogen) into phosphate donors.  For a refresher on this process, please refer to the video in this post, specifically the section from 2:15 to 13:30.

The ATP issue

As you may recall, about 60% of the energy we expend, say 1,800 kcal/day for someone consuming 3,000 kcal/day in weight balance, is purely devoted to keeping us alive by generating enough ATP (“energy currency”) to do 2 things: allow ion gradients to function and allow muscular relaxation.  So, obviously we can’t tolerate – literally even for one minute – insufficient ATP production.  In fact, one of the most potent toxins known to man (cyanide) exerts its effect on this process by inhibiting the electron transport chain which generates the bulk of the ATP our body produces.  Even the most transient interruption of this process is fatal.

Take home message #1: No ATP, even for 1 minute, equals no life.

The brain issue

The brain is a particularly greedy organ when it comes to energy requirement. To put this comment in perspective consider the following: though our brain represents only about 2% of our body mass, it accounts for about 20% of our energy expenditure.  (In children, by the way, this may be closer to 40-50% of basal metabolic demand.) So, beyond the ATP issue, above, there is a substrate issue with the brain as neurons derive most of their energy from glucose.  While there is emerging evidence that neurons can also oxidize fatty acids directly in small amounts and may even prefer lactate (over glucose), these two substrates do not approach the levels of consumption by neurons that glucose does.  So, for the purpose of this discussion, let’s just focus on the need of the body to provide glucose to the brain.

You’ll recall, from the point I made above, that my brain requires about 400 to 500 kcal of glucose per day (100 to 120 gm).  You’ll also recall (from the video, above) that I can store about 100 to 120 gm of glucose in my liver.  While I can store much more in my muscles, (on the order of about 300 to 350 gm), because muscles lack the enzyme glucose-6-phosphatase, glucose stored in muscle as glycogen is unable to re-enter the bloodstream and is meant for the muscle and the muscle alone to use.  In other words, muscle glycogen is a stranded asset of glucose in the body to be used only by the muscle.

So, if I’m deprived of a dietary source of glucose, I depend solely on my liver to release glycogen (a process known as hepatic glucose output, or HGO).  How long can HGO supply my brain with sufficient glucose? It depends on a few things that impact both the “source” and the “sink” of glucose.  Other competing sinks for glucose (e.g., activity level, thermogenic needs) and sources (e.g., glycerol and gluconeogenic amino acid availability) can make a difference for a while. But, in a state of starvation we’ve only got about one to three days before we’re in trouble.  If our brain doesn’t get a hold of something else, besides glucose, we will die quite unceremoniously.

Take home message #2: No glucose for 24-72 hours equals the need for something else the brain can use instead (that is not fat or protein, since neurons can’t oxidize fat and the last thing we want to do is start muscle wasting at a geometric rate).

The Krebs Cycle

This poses a real evolutionary dilemma.  We need an enormous amount of energy just to not die, but the single most important organ in our body (also quite energy hungry in its own right) can’t access the most abundant source of energy in our body (i.e., fat) and is, instead, almost solely dependent on the one macronutrient we can’t store beyond a trivial amount (i.e., glucose). Obviously our species wouldn’t be here today, blogging for example, if this were the end of the story. But, to understand how we survived requires one more trip down biochemistry memory lane.  In the figure below (also included and described in the video) I gloss over a pretty important detail.

metabolism

How, exactly, does our body take pyruvate (from glucose) or acetyl CoA (from fat) and generate so much ATP?  The answer lies in the beauty of the Krebs Cycle, which feeds into a process called the electron transport chain (or ETC), I alluded to above.  Since the adage ‘you can’t get something for nothing’ is as true in biochemistry as it appears to be in life, to get all that ATP (i.e., stored energy in the form of the phosphate bond), we need to give up something.  What the ETC does give up, as its name suggests, is electrons.  Through a series of redox reactions the ETC trades the stored energy held by electrons going from higher to lower energy states in exchange for the chemical energy stored in the bonds of the third phosphate group on an ATP molecule.

To think of it another way, if you start with stored energy – glucose or fat, for example, which if burned in calorimeter will give off varying amounts of heat – and you’re willing to convert their carbon, hydrogen, and oxygen molecules into another form with less energy – water and carbon dioxide which, if burned, produce very little heat – it’s a fair trade!  The ETC is simply the vehicle that allows our body to make the switch.

In a car, by contrast, it’s much simpler.  The engine combusts the hydrocarbon (e.g., gasoline) directly and in one flash liberates the heat contained within the hydrogen-carbon and carbon-carbon bonds in exchange for carbon dioxide, water vapor, and a few other things.

If you take a look at the figure, below, you’ll get a sense of the moving pieces involved in this cyclic transfer process.  Molecules shuffle back and forth, around the cycle, and kick off spent carbon (carbon dioxide, termed “waste”) and reducing agents (e.g., conversion from NAD+ to NADH) for the ETC.

Under conditions of abundant glucose (and sufficient insulin sensitivity) the brain is primarily converting glucose to pyruvate (left side of figure).  Pyruvate is then shuttled into the mitochondria and converted into acetyl CoA with the help of a very important enzyme called pyruvate dehydrogenase (PDH).  I’m going to come back to this enzyme, in part II of this series, because this is where the story gets very interesting.  Acetyl CoA (which is also a direct byproduct of fatty acid breakdown) is then combined with oxaloacetate and so begins the Krebs Cycle, which generates all the reducing agents to feed the ETC and generate massive amounts of ATP.

Where do the ketones come in?

In the absence of acetyl CoA (several ways this can happen, including substrate shortage, as I’m describing here) we evolved a cool trick.  Our liver can make – out of fat or protein, though we much prefer to use fat so we can spare our protein and prevent severe muscle wasting – something called beta-hydroxybutyrate, one of the 3 ketone bodies I described above.

B-OHB and acetoacetate (see figure below from this paper by Cahill and Veech, 2003) are produced by the liver from long and medium chain fatty acids and released into the bloodstream.

Acetoacetic acid and B-OHB live in reversible equilibrium (on the left), but once acetoacetate is converted to acetone (on the right) there’s no going back.

Now take a look at the figure below, from this 2001 paper. This is another rendition of the figure above showing the Krebs Cycle, but here you can see where B-OHB and acetoacetate enter the picture.

The reason a starving person can live for 40-60 days is precisely because we can turn fat into ketones and convert ketones into substrate for the Krebs Cycle in the mitochondria of our neurons. In fact, the more fat you have on your body, the longer you can survive.  As an example of this, you may want to read this remarkable case report of a 382 day medically supervised fast (with only water and electrolytes)!  If we had to rely on glucose, we’d die in a few days.  If we could only rely on protein, we’d live a few more days but become completely debilitated with muscle wasting.

The graph below, also from the Cahill and Veech paper, shows the blood chemistry of a person starving for 40 days.  Within about 3 days, a starving person’s level of glucose stops falling.  Within about 10 days they reach a steady-state equilibrium with B-OHB levels exceeding glucose levels and offsetting most of the brain’s need for glucose. In fact, the late George Cahill did an experiment many years ago (probably would never get IRB approval to do such an experiment today) to demonstrate how ketones can offset glucose in the brain. Subjects with very high levels of B-OHB (about 5-7 mM) were injected with insulin until glucose levels reached 1 mM (about 19 mg/dL)!  A normal person would fall into a coma at glucose levels below about 40 mg/dL and die by the time blood glucose reached 1 mM.  These subjects were completely asymptomatic and 100% neurologically functional.

The last point I’ll make on the starving patient is that, as you can see in the figure below, the glucose level normalizes at about 65-70 mg/dL (about 3.7 mM) within days of fasting, despite no sources of exogenous glucose.  Why?  Because with so much fat being converted into B-OHB and acetoacetic acid by the liver, a significant amount of glycerol (the 3-carbon backbone of triglycerides) is liberated and converted by the liver into glycogen.  As an aside, this is why someone in nutritional ketosis – even if eating zero carbohydrates – still has about 50-70% of a normal glycogen level, as demonstrated by muscle biopsies in such subjects.

Take home message #3: We evolved to produce ketone bodies so we could not only tolerate but also thrive in the absence of glucose for prolonged periods of time.  No ability to produce ketone bodies = no human species.

Last point of background: Everything I’ve just presented is based on data from starving subjects.  As most of you reading this know, if one restricts carbohydrate intake, typically to less than about 20-50 gm/day (dependent on timing and carbohydrate composition), and maintains modest but not high protein intake (because protein is gluconeogenic – i.e., protein in excess will be converted to glycogen by the liver), one can induce a state referred to as “nutritional ketosis” with similar physiology to what I’ve just presented without resorting to starvation.  Why you’d do this is something I will discuss later.

One other housekeeping issue: Ketosis versus DKA?

In an earlier post I explained the difference between nutritional ketosis (NK) and diabetic ketoacidosis (DKA). If this distinction is not clear, I’d suggest giving this earlier post a quick skim for a refresher.  DKA is a pathologic (i.e., harmful) state that results from the complete or near absence of insulin.  This occurs in the setting of type 1 diabetes or very end-stage type 2 diabetes, and often as the result of a physiologic insult (e.g., an infection) where the patient is not receiving sufficient insulin to bring glucose into their cells.  A person with a normal pancreas, regardless of how long they fast (including the fellow I reference above who fasted for 382 days!) or how much they restrict carbohydrates, can not enter DKA because even a trace amount of insulin will keep B-OHB levels below about 7 or 8 mM, well below the threshold to develop the pathologic acid-base abnormalities associated with DKA. Let me reiterate, it is physiologically impossible to induce DKA in anyone that does not have T1D or very, very, very late-stage T2D with pancreatic “burnout.”

Embarrassing admission: I remember exactly where I was sitting in a clinic at Johns Hopkins in 2002 explaining to (admonishing, really) a patient who was on the Atkins diet how harmful it was because of DKA.  I am so embarrassed by my complete stupidity and utter failure to pick up a single scientific article to fact check this dogma I was spewing to this poor patient. If you’re reading this, sir, please forgive me. You deserved a smarter doctor.

In Part II of this post I’ll tackle the questions I know folks still have on their mind (below). Until then, re-read this post to make sure you really understand this physiology.  You’re already 10 steps ahead of the next person.

  1. Is there a “metabolic advantage” to being in ketosis?
  2. Are there dangers of being in ketosis?
  3. What are the most important things you need to know about getting into (or staying in) ketosis?
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About the Author:

Peter Attia, M.D., is the co-founder and President of the Nutrition Science Initiative (NuSI), a non-profit based in San Diego, CA. He received his B.Sc. from Queen's University in Canada and his M.D. from Stanford Medical School in California. After his surgical residency in general surgery at Johns Hopkins he worked as a consultant at McKinsey & Company. He founded NuSI with scientific journalist Gary Taubes in 2012.

Discussion

  1. Gus  November 26, 2012

    As usual, a great article. Had a lecture in endocrinology today and, although he conceded the difference between nutritional ketosis and DKA, he claimed that he had seen ‘severe CNS effects’ in those who attempted ketosis, and wouldn’t recommend it. I wonder if you’ve ever come across the use of a glucagon shot with high protein intake as a means for losing fat? Keep busting myths!

    (reply)
    • Peter Attia  November 26, 2012

      Not familiar with the glucagon injection strategy. Our body is pretty good at making it, though, but in theory very high levels of glucagon (for example, as seen in a rare tumor called a glucagonoma) do produce profound wasting. Problem is, the wasting is both of fat and muscle.

    • melancholy aeon  November 27, 2012

      @Gus

      “he claimed that he had seen ‘severe CNS effects’ in those who attempted ketosis,”

      Bwah-ha-ha-ha! I eat 1650 calories a day (‘cuz I’m female) in the ratio of 85% fat (25% of saturated), 12% protein, 3% carbs. My blood ketones average 2.4 in the morning and about 4.1 at night. I have been eating this way since I read Volek’s Art of Performance in May. I lift weights once a week and right now am leg pressing 310.

      When not spending my days cavorting about in my size 9 Calvin Klein skirts and super-skinny True Religion jeans, I’m holding down a job as a tech executive, learning a foreign language, and spending time with one of my friends planning a book project about logic.

      So please tell your doctor that I have indeed observed “CNS symptoms” – mostly an increased ability to focus for long periods of time without getting mentally tired, improved memory, and an ability to think on my feet more quickly. In all day meetings everyone else is constantly snacking on the cookies & Mexican food – I’m eating coconut oil. At 5pm, I’m calm, ready to keep going, and want to finish the action items, whereas everyone else gets really cranky, complains how mentally tired they are and has to end the meetings so they can review the final numbers-based decisions the next morning. With more cookies.

      Even if I hadn’t lost a lot of weight eating like this, I would do it again in a heartbeat solely for the mental benefits alone. So that’s your “CNS symptoms” for you. :)

    • simik  November 28, 2012

      @melancholy aeon
      Those ‘severe CNS effects’ could be just keto-flu.

    • Fi  November 28, 2012

      @melancholy aeon: Yes! Me too – exact same story (except I read Mark Sisson’s fat adaptation blog posts then bought the book). 1700 (give or take a few hundred) cals a day, 70% fat normally. I train hard (bodyweight and bar calisthenics) four or five times a week. Strength gains and recovery both excellent and the consistent energy is just the best. thing. evar. Don’t mind if I drift out of ketosis for a few days (social events, or just feel like eating a fat pile of sweet potato) but I mostly stay in it.

      I’m curious (I don’t know any women who are fat adapted so excuse the questions) – do you do carb ups? Have you noticed any change in your menstrual cycle or other hormone profiles? How did you eat before you changed? How have your family handled it? Do you get weird questions about your diet at work?!

    • melanchyaeon  November 29, 2012

      @simik
      “Those ‘severe CNS effects’ could be just keto-flu.”

      A headache is a severe effect? Lawd luv a green-eyed duck! That’s exaggeration for sure. I myself have always had a cup of broth a day, so I never suffered from it. There’s absolutely no need to suffer to from it.

      @fi
      Don’t know any women? Hang out in the right places. :) I guess a lot of ultramarathon people do it, tho’ that’s not my crowd obviously.

      ” do you do carb ups?”
      No, never. Why lose the mental advantage? Rosedale speculates about a lot of other benefits too.

      “Have you noticed any change in your menstrual cycle or other hormone profiles?”
      Yes, my PMS vanished, as Phinney said it would. Because PMS and menopause are both related to inflammation – he’s actually an expert on this topic, but no one hardly ever asks him about it. It also became shorter, lighter and now always arrives on the same day. It comes and goes unnoticed for me now, not the trauma it used to be.

      “How did you eat before you changed?”
      WAPF. I spent days and days making sourdough rye bread by hand to try to ferment out all the anti-nutrients. Each loaf of bread took 5 days to make. Tasted great, but really exhausting. Even then I had no energy. Only later did I learn I had the COMT & HLA-DQ gluten intolerance genes, even tho’ I don’t have classic celiac. I also switched from raw milk to goat kefir. I drink 1 oz kefir a day and have raw cream in my coffee.

      “How have your family handled it?”
      My husband went with me. He built a lot of impressive muscle doing the Total Immersion swimming at Stanford, eating right at 50 total carbs. ‘Cuz guys have that advantage. So he’s cool with it. He wears 30-inch raw Japanese denim.

      “Do you get weird questions about your diet at work?!”

      Of course not. Besides, my lunches look quite normal – 2 oz. tuna and 3 oz. green veggie or salad. No one would bat an eye. There’s nothing strange about this diet. I mostly eat like Julia Child now, actually.

      Like most Silicon Valley workplaces, we are very diverse and to comment on what other people eat would be extremely rude. We have Hindus, Sikhs, Muslims, Buddhists, Russian Orthodox Christians, Jains, Jews, vegans, Filipinos who eat pork skin, Cantonese & Taiwanese who eat duck feet. . . it would be career suicide to step into that minefield. :)

      Best wishes.

    • john pelley  July 10, 2014

      Use caution when “experts” lecture to you. Ask them to clarity. For example, what were the serious CNS effects. Many students complain that my biochemistry lectures give them serious CNS effects! I agree with Peter regarding the evolution among many of us who are experts by credentials, but not by experience. There is an old saying that “the physicians that really know about nutrition are the ones with a nurse who has a weight problem.” In my case, I didn’t really start learning real world biochemistry until I was diagnosed with prostate cancer (I’m OK, 10 yrs out from surgery) but especially last year when my lipid labs came back with particle (dense) LDL off the chart. That is when I found Peter’s work along with Volk, Phinney, Westman, etc. Needless to say my lectures are going to be considerably changed this year. I even have a suggested viewing guide to recommend for the students as outside learning. I believed I was teaching the right thing and much of what I have taught is pretty good stuff, very nutrition oriented. But, I no longer trust my expertise. Now, I am constantly digging.
      As a final thought about those “serious CNS effects.” I have found that since becoming ketoadapted that I started suffering cramps in my legs when sleeping. This never had happened during a history of running (I am 71 yo, runner for 30 years, bodybuilder, yoga, … you get the picture). It seems that the severe, and healthy, suppression of insulin release downregulates a protein called sodium/potassium ATPase that is needed for the kidney to conserve electrolytes, especially potassium and magnesium. The depletion of potassium from within muscle cells leads to the cramping. magnesium deficiency also contributes. But now to the CNS issues. The electrolyte depletion also produces CNS disturbance and accounts for much of the “off” feeling when becoming ketoadapted. Guess how easy this is to remedy? I take both bouillon and potassium supplements and magnesium and the cramps are gone and i feel great.
      Hope this helps those who are just learning this stuff. The world needs more physicians like Peter.

  2. Caroline  November 26, 2012

    Peter,
    Thank you for an excellent article.
    I wish you would have been my professor in grad school!!
    Looking forward to Part II

    (reply)
    • Peter Attia  November 26, 2012

      Part II should be pretty interesting!

    • OAllen  July 11, 2014

      TO: john pelley July 10, 2014 above If you want a paradigm shift in exercise and health, checkout Dr. Doug McGuff’s book and youtube videos. Peter recently recommended the book. My paradigm shifts were caused by Dr. Bernstein three years ago that led to Gary Taubes and Peter. Dr. McGuff caused my shift 3 months ago. Living is being ready for the next one

    • Peter Attia  July 12, 2014

      I’ll second that. I’ve become friends with Doug and find his work very interesting.

  3. Adam Turetzky  November 26, 2012

    Hi, does taking Metformin interfere with this process in any way?

    (reply)
    • Peter Attia  November 27, 2012

      Good question. I’ve never seen this specifically studied. Metformin inhibits HGO, but I’m not sure it’s directly enhances ketosis (in theory, if HGO is suppressed enough, you’d think it might help). But I do not know.

  4. Kris  November 26, 2012

    Great post, an efficient trip down biochem memory lane. Look forward to part 2.

    “As an aside, this is why someone in nutritional ketosis – even if eating zero carbohydrates – still has about 50-70% of a normal glycogen level, as demonstrated by muscle biopsies in such subjects.”

    Didn’t know that before, very interesting. That explains why my performance in the gym doesn’t suffer that bad when I go extremely low on the carbs. After the initial ketoadaptation period I’m performing pretty near my previous higher-carb levels.

    (reply)
    • Peter Attia  November 27, 2012

      Yes, though we don’t know how much liver glycogen they have (since we can’t really justify liver biopsies). Indirectly, though, it’s clear that even without any carbs, HGO is preserved, so there must still be some glycogen turnover in the liver.

  5. Mark  November 26, 2012

    I had a lecture on anorexia a few days ago, and our (psychiatrist) teacher told us that she had a boy who was on “one of those primal diets, of meat and nuts, eating 500kcal a day”. (He had a mental disorder…and it was used to lambast my dietary preference). She went into a discussion of how we need a “balanced diet” of meat, vegetables, and grains.

    I spoke to her at the break and corrected her on what a “primal diet” was, but tried explained that there is no “need” for grains (let alone the possible GI dangers; let’s not try to convert someone in one fell swoop). I said I hover around 100g carbs a day as I put on weight and try to cut it down to 50g when I want to lose weight (I’m anywhere between 205-225, 5-10% fat…depending on the season and our test schedules). She said that’s dangerous, your body needs glucose, you’ll go into DKA, etc (need grains for insulin, balance, energy…)

    She said I should get a CBC and CMP because it’s probably not good for me. “Well I’ve been eating this way for about 4 years now, sleep great, never sick, and am doing well in medical school…so…um…could it be that you’re wrong?” We agreed to disagree.

    This mindset is pervasive…and oddly enough, I have only heard this rhetoric from physicians of at best average health and fitness levels admonishing their patients for being overweight on the exact same type of diet!

    (reply)
    • Peter Attia  November 27, 2012

      I used to be her…

    • Daniel  November 15, 2013

      I blame the left wing. I know a lot of people are going to hate me for saying this, but it’s the left wing that has taken over most of our research and research labs. And while that wouldn’t necessarily be a bad thing because, hey, we always need to improve our science, and the right-wing isn’t going to invest in it as much, somebody needs too. Unfortunately, the left wing also if chalk full of all those special interest groups that have everything to lose when what they’ve been fighting for over the last several years, some even decades, suddenly find out they’re wrong, that the exact opposite is very plausibly true.

      They aren’t just going to take that science lying down. They’re going to do even what the good ole Thomas Eddison himself did, and that’s to use whatever political power and influence they can possibly muster to try and get that science either discredited or to come under question at least. They are going to use their political allies influence and power over research funding and labs and schools to do whatever they can to prove themselves right, their opposition wrong, and to make their opposition sound as psuedo-science, bought-out, and brainwashed as possible.

      It’s not that they’re necessarily greedy, evil, or selfish, although, by now, most probably are, it’s simply that they are threatened, and they’ve believed a certain way for so long, and have so much personal stake riding on this belief, that they cannot accept that it could be wrong. And some are just comfortable with the life, and have become greedy and scared of losing it. It’s how a lot of science regarding controversial things has gotten skewed. Look throughout history, modern societies of the day are often full of people trying to subvert, in some way, science that they feel will affect their place and power in society. That’s just part of the imperfection of mankind.

      Now that this research is beginning to see the light of day, not because it was in some textbook or learned in nutrition classes, or because the peer-reviewed journal entries made huge wide-spread public attention, but almost exclusively due to the number of common people who have looked at it’s science, tested it out on themselves, and have decided to follow it because of how well it worked and is working for them.

      Without all all of the common people benefiting and demonstrating the reality of this, it would still be considered pseudo-science by the leading scientific authorities of our day, and in fact, it sort of is. Bu inevitably, it seems to be working it’s way out in spite of all of that, and one day it’s going to hurt some left-wing special interest groups in a large way.

      Fortunately, the nutrition and anti-meat special interest groups are not as powerful as some others are, and they’re slowly giving way to the overwhelming abundance of evidence that is mounting up due to the everyday common people who are using this ketogenic idea.

      I imagine that inevitably, health classes in elementary, middle, and high schools all across the U.S. will be teaching this alternative diet as a healthy alternative to carb-based diets.

  6. Paul  November 26, 2012

    Peter,
    Once again you present an excellent and well written post. Thank you for all you do. I feel I learn something new everytime i jump onto your website. I have a question for you if you have the time. Hypothetically, if one were practicing nutritional ketosis for a few months and was fully adapted, could they then drop some dietary fat intake to speed up body composition changes(fat loss)?

    Thanks again for the blog.

    (reply)
    • Peter Attia  November 27, 2012

      It’s possible, but hard to know given how many things might also change. All things equal, this seems to be the case.

    • Edward  November 29, 2012

      @ Paul.
      That would constitute what is called a “fat fast.” For few days only, try to get up to 90% of your calories from fat, preferably saturated, of course, and consume only around 1,000 calories. This is surprisingly difficult to do, the 90% part, because protein accompanies fat almost universally. I use slices of pepperoni sausage with dabs of cream cheese on them. I say only a few days because you could get into a state of muscle wasting if you go much longer. However, melancholy aeon’s experience might indicate otherwise. This helped me and some other people I know to break through what the Atkins people call a plateau.

    • melancholy aeon  November 29, 2012

      @Edward

      ” For few days only, try to get up to 90% of your calories from fat, preferably saturated, of course, and consume only around 1,000 calories. ”

      Wow, I would do recommend that. :) But if it works for you. . . n=1. I personally have a strong feeling that women over 5’2″ should never eat less than 1500 cals a day and men never less than 1800. Love your body, don’t throw it into a starvation crisis. I myself eat 3 meals and at least 1 snack every day (usually olives & chicken broth). I want my body to be happy and not freak out or slow my metabolism.

      Like many women, I also don’t do well with this fasting stuff. Too Kate Moss for me. :)

      Jimmy Moore is a fine example of how eating this way will change your body composition, replacing fat with muscle easily. :) He lost what? 40 pounds of fat and replaced with 6 pounds of muscle? He does skip lunch, but eats a truly enormous breakfast. . . .no calorie deprivation there. :)

    • Daniel  November 15, 2013

      @ melancholy aeon

      “I personally have a strong feeling that women over 5’2? should never eat less than 1500 cals a day and men never less than 1800. Love your body, don’t throw it into a starvation crisis.”

      Actually, I was reading somewhere online, you might have to google it, that doing 3 to 4 day fasts, like Biblical fasts, as in you eat nothing, is very possibly one of the most effective means of fighting cancer and preventing it.

      The article talked about the benefits to fighting and preventing cancer using a keto-dieting approach, saying that cancer survives best in a body with plenty of carbs, glucose, and proteins like glutamine found in many meats. It also talks about how the cancer can still survive in low-carb environment because of the glutamines and I think some other proteins that it can still use for energy. However, the article stated, I believe even quoted, (paraphrasing) that fasts like that make an almost impossible environment for cancer to thrive. The article went on to explain more specifics like that this and that forms or prevents the formation of, but the general message there was that there is potential being shown that having fasts like that can actually both prevent and fight cancer.

      It’s fascinating because much of science seems to indicate the reality of the what the Bible says. In this particular case, it reminded me of the fasting talked about in the Bible. Fasting was a part of the law that was finished and no longer necessary to be followed when the Messiah came. That’s the idea as spoken of by Paul behind why Christians no longer follow the law as the Jews were required too. Well, one of the aspects of the law was fasting regularly. It was actually more of a tradition than the law. However, the disciples who wrote the Bible after Christ ascended into heaven, they kept on with it and told all other Christians to continue fasting. In fact, Christ Himself stated that demons are cast out only by prayer and fasting. Now, fasting and prayer was for the sake of weakening the body and strengthening the spirit so that one’s body was not as strong as one’s spirit so that the spirit would win the battle, and one would have, essentially, the willpower to remain doing as is right in God’s eyes and not be led astray by their temptations.

      Well, interestingly enough, now it seems like there may also be a rather incredible health benefit from doing periodic fasting of a such magnitude, and that is the potential for making an inhospitable and deadly environment for any cells that happen to turn into cancers that perhaps we are unaware. After all, cancer is not detected on the DNA level. It’s detected by finding and abnormal growth that’s already been there for some time, and then testing it’s tissues for malignancy.

      I just thought that was fascinating and compelling enough to post along with the main idea of this post. I do hope I have not offended anyone, but as I would tolerate anothers trying to relate this to Atheism and the benefits inherent in an evolutionary evaluation of our current diet, i.e. the Paleo diet, I would hope to be given the same toleration.

  7. Dave  November 26, 2012

    Dr. Attia,

    First, thank you all of the work you do in synthesizing the medical literature for “the rest of us.” I was really excited to see that you were starting a new series on ketosis! I’ve recently gotten my hands on some ketone urinalysis strips and a blood keto-glocometer, which I plan to use in measuring my fat-burning status while trying to lose weight.

    Will you by any chance be talking about the suitability of ketogenic diets for pregnant and postpartum women? My wife and I have both been utilizing low carb diets for some time now (though my wife doesn’t have any weight to lose and has a higher daily carb intake) and she is 8-months pregnant. On various websites I’ve seen it asserted, usually with little to no supporting evidence, that a ketogenic diet can have negative effects on the baby in utero. I think it was based on the assumption that the brain “needs” glucose and thus brain development could be affected by low glucose in the mother or something? We were also told by a lactation consultant that low carb intake is an issue for breastfeeding – that it can decrease milk production. This was also mentioned recently by a well-known paleo author/blogger, who suggested that ketosis during pregnancy can decrease prolactin levels. But, again, no sources for this were provided.

    Do you have any thoughts on these issues?

    (reply)
    • Peter Attia  November 27, 2012

      I do not have, or have at least, have not seen, data examining this question. I would safely say that a low GI diet is not only safe in pregnancy, but almost certainly beneficial. David Ludwig from Harvard is currently designing a very exciting trial to look at some of these effects, especially as they relate to the long-term risk of obesity in children.

    • lockard  November 27, 2012

      Stay out of ketosis to reduce the chance of inadequate calorie and nutrient intake. Ketosis can be a helpful tool for weight loss, but, as you say, you don’t need to be losing weight right now. Besides, eating fewer calories means fewer chances to obtain the nutrients you and your baby need. I’ve also heard rumblings that a very low carb ketogenic diet can reduce prolactin. Prolactin is the “milk hormone”; it regulates your milk supply. For men trying to avoid gynecomastia (man boobs)? Sure, they’ll want to reduce prolactin, but in breastfeeding mothers, prolactin is normally quite high and it should stay that way. If you hope to grow a small human from infancy, you need to produce ample amounts of milk. It isn’t guaranteed that going into ketosis will depress your milk production, but it’s not worth the risk.

      Just eat your Primal carbs to stay out of ketosis. Though there are health benefits to ketosis in specific conditions (epilepsy, certain cancers, neurological disorders, obesity), I wouldn’t include “breastfeeding motherhood” among them. If you’re interested in the health benefits of ketosis, realize that simply breastfeeding – especially for longer than six months – is strongly associated with a bevy of health benefits for the mother, including weight loss, protection from breast cancer, protection from ovarian cancer, and lowered heart disease risk. So, providing ample milk to enable long duration breastfeeding is your safest bet.

      Read more: http://www.marksdailyapple.com/workout-break-raw-milk-banana-breakfast-ketosis-in-breastfeeding-and-bikram-yoga/#ixzz2DRpUynEg

    • melancholy aeon  November 27, 2012

      @Dave

      “Do you have any thoughts on these issues?”

      Why not talk to any of the several women we all know who in fact have done this? Dr. Andreas Eenfeldt’s wife is breastfeeding their extremely healthy and amazingly calm baby now on 50 total carbs; during the pregnancy she was eating 30 total carbs.

      Dr. Jay Wortman’s wife also was low carb during her pregnancy and lactation; their little girl has been raised totally low carb. You should see her ski – at the age of 2.

      There are some quite prominent low-carb moms around and I suggest you talk to them. :) Best wishes.

    • Jacob  December 2, 2012

      n=1, but my experience is that this isn’t something to be too concerned about. My wife is at between 50-100g CHO/day and breastfeeding. We don’t test for ketosis, so I do not know how much she’s in that state — I’m guessing she cycles in and out of it. But I can say that low-carb high-fat has been a-ok. Mom and baby are both healthy and happy. Baby won’t sleep, but I doubt that’s a ketosis thing :)

    • Dave  December 3, 2012

      @melancholy aeon

      “Why not talk to any of the several women we all know who in fact have done this?”

      “There are some quite prominent low-carb moms around and I suggest you talk to them. Best wishes.”

      Did I miss a low-carb parent meet n’ greet or something? I was recently put in contact with Dr. Wortman but I don’t know any others. Feel free to introduce me.

      Dave

    • Elton  December 3, 2012

      My wife and I have been low-carb about 8 years. When she was pregnant with our first child she was told by everyone that she should eat whatever her body wanted. Her doctors told her pretty much the same thing. So she started eating lots of french fries and pastries. She ended up with gestational diabetes. As soon as she had to start checking her blood a few times a day, she quickly cut out her carbs and went back to her normal 30g a day. The nurses couldn’t understand where her gestational diabetes went!

      For her second pregnancy she stuck to low carbs and the diabetes never came back.

      Oh and both of our sons have above average intelligence, but I might be biased ;)

    • Daniel  November 15, 2013

      @ Dave,

      As one person to another, I have no special qualifications to say one way or the other, but why even take the chance? We know from all of recorded human history, for certainty, no question, that a diet in everything, carbs, proteins, fats, vitamins, minerals, everything naturally food to us in more than ample supply is beneficial to a developing child. We all know this, so why even take a chance that maybe you might be depriving your child of something necessary.

      Two main ideas I wish people, especially women in the privileged free-world would learn regarding weight. Pregnant women are supposed to get fat and/or fatter, and babies are supposed to be fat little adorable tubs of lard. Now most seem to realize that babies are supposed to be fat, but many many seem not to realize that pregnant mothers are also supposed to get fat and/or fatter. After the child is born, and nursing won’t be affected or ideally when nursing is no longer and issue, then it doesn’t matter so much unless we’re worrying about starvation the next winter, but we’ve progressed out of that lifestyle for quite some time now.

      Just as a matter of common sense, I would recommend that no pregnant woman worry about diet at all except to ensure that they get every and all nutrients possibly provided in our food. Whether that means gaining weight or not, the focus shouldn’t be weight or even later weight loss, but instead solely on getting all of the nutrients possible, all of the vitamins, minerals, fats, carbs, and proteins that are offered in our wide world of natural foods. I say natural for obvious reasons. Our babies don’t need diacytal or color red 6, but they certainly need cholesterol, all the various fats, sugars, both complex and simple carbs, all the vitamins and minerals, all the proteins. And just to be safe, I’d stay on that focus until after nursing. Then, I’d get back on the keto-diet and watch my diet.

      But that’s just me.

  8. Robb Wolf  November 26, 2012

    DOC! Great article. i think I mentioned this to you but when i did the Discovery channel show and was on day 8 of starvation they tested my blood glucose and it waas 33. they were shocked and re-checked it three times.

    (reply)
    • Peter Attia  November 27, 2012

      Robb, thanks so much. Yes, I do remember you sharing this. You were almost as low as the Cahill subjects below 20 mg/dL!

  9. David Snetman, M.D.  November 27, 2012

    Peter, just an FYI, when I was studying biochem in med school, I found the process of glycolysis and the krebs cycle you present above much more intelligible when the roles of pyruvate/acetyl CoA and NAD+/NADH were emphasized (as in this diagram from wikipedia: http://en.wikipedia.org/wiki/File:Catabolism_schematic.svg ). You hinted at the importance of pyruvate/acetyl CoA above, and I would love to see you expand on this point, as I found that the importance of this molecule cannot be over-emphasized in understanding metabolism in general and ketosis in particular. However, maybe it’s beyond the scope of an article intended for the general public; I remember sweating over this stuff for weeks until it made sense. Not sure if that’s encouraging or discouraging?

    (reply)
    • Peter Attia  November 27, 2012

      Yes, David, this is a helpful figure. Thanks for sharing. I, too, remember being utterly confused by the when first presented to me.

  10. Lacie  November 27, 2012

    I’m so glad you’re doing this series. You’re probably focused on ketosis for healthy people, but this seems like a good place to share my experiences, as my partner has Parkinson’s and this launched us into an in-depth exploration of ketosis as one possible way to halt or reverse neurodegenerative diseases. Dr. Mary Newport’s n=1 experiment feeding coconut oil to her husband who has had Alzheimer’s for 11 years now was our springboard, and from there I dove into Bill Veech’s voluminous published research on ketones – did you know he actually worked in Dr. Hans Krebs’s lab with the man himself and published a report about it? Veech also worked on a project with the US Department of Defense to explore using synthetic ketone esters as food for the troops (those MREs get pretty heavy to hump around). Oddly enough, DoD was the only place he could get funding to study ketosis; NIH sponsored a small trial but had no further interest. The epileptic children’s diet from Johns Hopkins was another touchstone, and Dr. Dominic D’Agostino has done some work with ketosis for ALS patients. The upshot is that there’s so much evidence that BhB fixes broken brains that I’m wondering why the scientific world isn’t all over it. I think most physicians fear ketosis, and my partner’s psychiatrist actually told him at their last appointment that brains can only run on glucose…sigh. Diet-wise we’ve settled on a low-carb approach (about 50 grams a day) with a ketogenic adjunct such as coconut oil, MCT oil, or AAKG (Arginine alphaketoglutarate) to correct for eating a normal protein intake. Without the adjunct, he’s unable to maintain the necessary 2.0 mmo/l or higher ketone level constantly enough to have a therapeutic effect on the PD. We use a handwriting test since it’s easy to compare and hard to overcome with placebo effect. The results have been very encouraging. Sometimes we ask ourselves, “so why isn’t everyone else doing this? Are we fooling ourselves? Or are they?” Neurodegenerative disease isn’t very pleasant so it’s hard to believe someone would refuse to give up crackers to avoid it. Thanks for letting me share, and I hope this isn’t too off topic.

    (reply)
    • Peter Attia  November 27, 2012

      Lacie, you’re actually touching on one of the topics I plan to explore in Part II. I’ve spent a lot of time with Veech and Clarke and the DOD exploring the opportunity of ketone esters to take nutritional ketosis to the next level, both for prevention (e.g., TBI) or performance enhancement. Definitely look forward to exploring this topic with folks. You’re definitely hitting on an important point.

    • Edward  November 29, 2012

      Hi Lacie,

      Can you or anyone else post how much AAKG is effective at boosting ketosis?

      Thanks,

      Edward

    • Lacie  December 1, 2012

      @Edward, 12-15 grams of AAKG powder per day allows a 225-lb. male to eat 100g of protein and 30-50g of carb a day and still get 2 mmo/l ketones on the meter. 1/2 cup per day of coconut oil or MCT oil will do the same thing but with major stomach upset that you don’t get with AAKG.

      I don’t take a ketogenic adjunct; I prefer to just drift in and out of ketosis and eat my usual low carb diet. But my partner doesn’t have a choice – every day he’s not in ketosis, he’s losing brain cells. I’ve read some cautions about taking AAKG more than 60 days at a time on bodybuilding sites, but I can’t find any PubMed articles that say so. Plenty of articles that say it doesn’t work for building muscle, but that’s not what he’s using it for. Interestingly, several articles say that AAKG ramps up insulin secretion – I don’t get how it can do that and still induce ketosis.

    • TwitchyFirefly  January 20, 2013

      Lacie, I was so happy to run across your comment. I have been searching for detail about ketosis and neurodegenerative disease. There is quite a lot of exciting information about brain-based disease like ALS, Parkinson’s, Alzheimer’s, and of course epilepsy, but very little concerning peripheral neuropathy like I have (multifocal motor neuropathy, which is assumed to be autoiummune; it’s often misdiagnosed as ALS).

      I was already low-carb for a year before my diagnosis (thanks to Good Calories, Bad Calories; I was not overweight), and after that, having read more and more about the neuroprotective effects of ketone bodies, I went zero-carb and have been that way for two years. At my age of 58 it’s supposed to be hard to generate high levels of ketones, and my ketostix usually indicate Trace or Small, despite generous amounts of coconut oil and some MCT oil on a daily basis.

      So your comments about AAKG and “therapeutic” levels of ketones are very intriguing to me, and I would love to find out more.

  11. AT  November 27, 2012

    Hi Peter,

    so when ingesting glucose, at what ratio does it get stored as glycogen into muscle vs the liver? Which of the two takes priority? Seems when attempting keto-adaptation we would only prefer it concentrated in the liver so that the brain can do its thing..

    (reply)
    • Peter Attia  November 27, 2012

      Great question. Priority is probably driven by 2 main factors: 1) insulin sensitivity (i.e., which cells are more insulin sensitive — muscle or liver — probably get first pick), and 2) capacity for storage (i.e., which organ is more depleted).

    • Annlee  November 28, 2012

      Peter (http://high-fat-nutrition.blogspot.com/) has done quite a bit on peripheral (I believe that means muscular) insulin resistance on low carb diets. He’s lately been focusing heavily on the ETC. Worth reading his entire archive.

  12. Laura  November 27, 2012

    Hi Peter,
    Thanks for such an informative article! I wonder if you have any ideas about whether low-carb-triggered migraines may be related to this shift in primary substrate that the brain uses. The first couple of times I did Atkins, I got a migraine headache the 1st couple of days, before starting to feel okay, and then after a couple of weeks, starting to feel great (probably ketoadaptation). (I do get migraines occasionally under other circumstances too.) I found this seeming triggering of a migraine by shifting to low-carb interesting (as well as annoying!). I wonder if these headaches are similar to the ‘Yom Kippur’ headache, and I think some people also refer to a ‘first day of Ramadan’ headache? I know these headaches might be due to dehydration or electrolyte changes, but maybe sometimes instead to a shift into ketosis transiently affecting brain metabolism in an annoying way? Anyway, I’ve been doing some form of low-carb now for most of the last 22 months- sometimes in ketosis, other times not (at least by measuring blood ketones). Now I find that if I indulge in more carbs for a week or 2 and then go back to strict low-carb, I don’t seem to get these headaches as much. I do try now to ‘ramp down’ my carbs over a couple of days, rather than going cold turkey. Maybe that helps? Or maybe I’m now more metabolically flexible? If anything, I’m less careful about taking in broth etc the first couple days of low-carb, so I don’t think it is some change along those lines. I’m curious to hear your thoughts.

    (reply)
    • Peter Attia  November 27, 2012

      Very interesting, Laura. There definitely are enough possible things going on that it would be hard to know for sure which change or set of changes in the culprit. I’m not an expert in migraines (vs. other headache mechanisms, for example), so that’s the first place I’d look to see what generally causes that particular type of headache, then see if there is a possible mechanism of action linking the change in substrate? Seems very testable, though.

  13. Mark  November 27, 2012

    Dr. Attia,
    Thanks for another great post. I’ve been in nutritional ketosis for about a year now, and have lost over 40 pounds. I think my diet (80/20 fat to protein) and supplements (sodium and magnesium) are dialed in, and I feel great.

    I still have about 15-20 pounds of excess fat I would like to lose. Getting down to my current weight was effortless, but I think I’ve reached an equilibrium. Is there anything I can do to move the metabolic needle? Has metformin been studied for this purpose? Thanks for your help.

    (reply)
    • Peter Attia  November 27, 2012

      The only thing I see metformin doing at this point is further reducing HGO, but if you’ve already fixed your underlying insulin resistance, I’m not sure how much more benefit you’ll get. This situation has not been studied.

    • Edward  November 29, 2012

      @Mark
      Check out my previous post about doing a “fat fast.”

  14. Alta  November 27, 2012

    Hello Dr. Attia,

    Thanks for your excellent ongoing work.

    I love wine. I also love ketosis. Can the two co-exist?

    Since first learning about all this a few years back I’ve been trying to read up and understand how ketosis is affected by alcohol. Is there new info about this? I’ve read a lot of what seem to be educated guesses, such as that alcohol pauses ketosis without throwing you out of it, and that it can give you a false positive read, at least with the urine strips.

    I’m asking not about sweet mixers and beer which I know have their own issues beyond just the ethanol, but more about the ethanol itself I guess. If ethanol is neutral in its effect, I would think that straight hard liquor would be the low carb drink of choice rather than dry wine. Is the only reason that dry wine is recommended over say vodka and lime as the go to “if-you-must-drink-on-low-carb-have-this” drink that wine has a health halo (whether deserved or not) compared with hard liquor?

    I’ve read that alcohol is a carb and also that it is not a carb but is like carb. (?) Also I know of “The Drinking Man’s Diet” and that Dr. Atkins said you had to cut out booze to lose, at least in the early stages. So many contradictions! Are the mechanisms just not yet understood? It’s something I’m really curious about above and beyond trying to find a way to justify drinking some wine. : >

    (reply)
    • Peter Attia  November 27, 2012

      Yes, in moderation. It does dependent on how sweet the wine is and how much you consume. A reasonably dry red wine might only be about 3-5% sugar by weight, so a glass or two isn’t going to take you out of ketosis.

    • b-nasty  November 27, 2012

      My basic understanding is that alcohol puts a damper on GNG in the liver, possibly due to the liver dealing with metabolizing the alcohol and alcohol metabolites. This is a good read: http://ajpendo.physiology.org/content/275/5/E897.full

      I think a lower HGO when you aren’t eating much glucose leads to feeling really awful…a hypothesis I can confirm personally. If I carb-load before large amounts of alcohol consumption, I feel okay. If not, I feel absolutely miserable.

    • Peter Attia  November 27, 2012

      I think this is only the case if you’re not in “firm” ketosis. All the suppression of HGO in the world is not an issue if your brain has sufficient access to B-OHB. This gets to one of the questions someone posed about flirting with ketosis. This is one of potential drawbacks experienced by some (though not all).

    • Fi  November 28, 2012

      In my experience I can have two or three glasses of wine (dependent on daily activity) without going out of ketosis. I normally drink dry red wine.

  15. Tom Nikkola  November 27, 2012

    Outstanding post once again Peter! I’ll be sure to promote this series to our dietitians at Life Time like I did for your Straight Dope on Cholesterol series. Thanks for taking the time to write these in ways that make them easy not just to understand but to use to explain to others.

    (reply)
    • Peter Attia  November 27, 2012

      Thanks very much, Tom. Part II should offer, possibly, more interesting stuff for most readers not obsessed with the details.

  16. geo  November 27, 2012

    Peter,
    The laymen parts of this article are exactly what I had hoped to hear. I’ve been keto since May and have learned how to “depend solely on my liver to release glycogen” based on reviewed daily blood tests. I’ve seen a gradually steady glucose level as time endures. Foods I eat don’t spike my glucose nearly as much. Less than 5 carbs + 180 protien + fat. I’m still learning slowly the types of fat available. The list goes on of all the benefits keto has done for my life. Ok, enough venerating. I just wish I could find a good doctor who I don’t have to wrestle with on this topic.

    Geo.

    (reply)
    • geo  November 27, 2012

      Typo: ’5 carbs’ was ment to be ’50 carbs’.

  17. Josh.O  November 27, 2012

    In the final, pre-references section (“Future Uses of ?OHB”) of the Cahill, Veech paper (“Ketoacids? Good Medicine?”), they address some problems that they have with the ketogenic diet. It’s only been a few months, but I don’t share their view that this diet is difficult to maintain. I’m not concerned about the serum cholesterol issue, but please speak to the the purported association with kidney stones.

    (reply)
    • Peter Attia  November 27, 2012

      Will do so in the next part.

    • Lacie  November 27, 2012

      Josh, I can speak to the difficulty of maintaining a truly ketogenic diet, as my Parkinson’s partner and I are veteran low carbers but had a hard time of it. The problem is to be therapeutic for illness, you have to stay above 2.0 mmo/l at all times. If you eat even a speck of protein or carb, you go out of ketosis and are right back where you started. The epileptic children’s diet is more or less devoid of protein, and although we like fat as much as any good caveman, life without protein is malnutrition, not to mention boring. Athletes and other healthy people can drift in and out of ketosis, which allows them to eat a steak once in a while.

    • melancholy aeon  November 27, 2012

      @ Lacie

      “Josh, I can speak to the difficulty of maintaining a truly ketogenic diet, as my Parkinson’s partner and I are veteran low carbers but had a hard time of it. The problem is to be therapeutic for illness, you have to stay above 2.0 mmo/l at all times. If you eat even a speck of protein or carb, you go out of ketosis and are right back where you started.”

      Not so. I eat between 50-60g of protein a day (an egg every morning and then 2 2oz servings of fish or meat for lunch and dinner plus some chicken broth and cream) and reliably stay at 2.1 or above with ease. If you struggle with ketosis eating “even a speck” of protein or carb, you’re not eating enough fat. :)

    • Lacie  November 28, 2012

      @Melancholy, I think the ability get into dietary ketosis varies a lot between individuals, and there’s a lot we don’t know about it due to lack of studies. Particularly, I wonder how metabolic flexibility, age, and cellular damage from years of following conventional wisdom figure into the equation.

      At over 100 grams of fat per day for me and twice that for my partner, we’re not sparing the butter, but the ketone meter doesn’t lie.

    • Joshua  November 28, 2012

      Lacie – regarding B-OHB availability, have you tried MCT supplementation? Has it made any difference?

    • Lacie  November 29, 2012

      @Josh, MCT oil works great but it’s really hard on the stomach. Coconut oil only slightly less so. AAKG has been fantastic, no side effects other than a slightly stinky odor, dissolves easily in water, partner’s ketones consistently above 2 mmo/l with up to 50g carb per day and 100g protein. Easy peasy. I heard about it from Dr. Dominic D’Agostino, Ph.D. researcher at University of South Florida; nobody else seems to know it’s such a potent ketogenic. I do wish there were more studies on it; lots of broscience but not much else.

  18. Bob West  November 27, 2012

    Hi Peter,

    Another good post that ties a lot of things together. Thanks for the technical deltail and the relevance.

    I have noticed a few posts now and again about alcohol. I have noticed especially posts on wine, and your replies. I hope I can add to the discussion:

    While I was using a blood tester to check my BOHB levels, I found that after a few days I could maintain about 3.0, which is well into ketosis. (I’ve always been able to go into ketosis easily.) At that level I would easily lose weight daily. However, if I had more than a glass or two of red wine per day, my BOHB would stay about the same, but the weight loss would stop. This was a reliable connection, which I tested several times (all in the cause of science, of course… :) )

    Clearly, since my BOHB level was NOT affected, but my rate of weight loss was, I was not being knocked out of ketosis by the wine, but I was certainly being knocked out of weight loss. I would say that the small amount of sugar in the wine was not the culprit, since I was still measurably well into ketosis. If the problem were the residual sugar in wine, it would have taken me out of ketosis.

    So, provisionally, I am advancing the hypothesis that the moderate ethanol level in dry red wine has the effect, in ketosis, of stopping net body fat loss even though it does not stop ketosis. This is odd, because being in ketosis means you’re using fat from somewhere. That opens up a world of speculation:

    - This may only be me. That’s the problem with any n=1 experiment: I may just be weird.
    - We know that ethanol gets converted in the liver to triglycerides (which are fats) that get sent out to the rest of the body. Does that offset the fat-burning effect of ketosis on other fat stores? I think that would take a lot of triglycerides, perhaps more than accountable for from the ethanol (I’m not drinking THAT much wine), but maybe not.
    - Many papers have reported that ethanol increases insulin resistance, including in the liver; liver insulin resistance would affect (increase) liver release of glucose (HGO). Does increased liver release of glucose play a part here, even though the body is, overall, still in ketosis? That’s an odd balancing act, since more glucose output should lower ketosis, but, maybe….
    - There may another liver-related phenomenon at work, since ketones are produced in the liver in the first place. Why fat stores are not being used in that case is still not clear.
    - Of course, there’s the usual option that we may have something here that is observed, but is not yet understood.

    I certainly don’t know. I just know that if I drink very much wine while in ketosis (more than 2 glasses of very dry red), it will flat stop my weight loss; if I don’t then the weight loss is pretty reliable. And I also know, from direct BOHB testing, that the red wine intake is not stopping my ketosis (BOHB level). So I, at least, can still be solidly ketotic but not lose weight if I am using more than a fairly small amount of [red] wine (which is all that I have tested for); but if I am not using the wine, and if I am ketotic, the weight will come off.

    (Note: wine has a surprising amount of calories; a bottle of wine — which is quite a lot of wine, of course — has about 500 calories (kcal’s). So it could creep up on you.)

    This is just meant to be an additon to the general converstation… I don’t think that any of this definitively settles any question. A NuSI-style trial, with the proper controls and protocols, is necessary to get a real handle on this, and many other, questions. But I hope it helps someone besides me to address the issue, and maybe adjust their intakes with this in mind.

    Thanks for your time,
    Bob.

    (reply)
    • Peter Attia  November 27, 2012

      Bob, very interesting observation. Thanks very much for sharing with folks. I’m curious if others share your experience.

    • Michael  November 27, 2012

      Bob,

      Thanks for your insight about drinking wine while in ketosis. I too seek scientific truth through running an adequate number of clinical trials on myself. :) I have been in nutritional ketosis for the past couple of months. My B-OHB levels are not as high as yours (avg. around 1.5) but I have consistently lost weight during this time. I do drink 2 glasses of white wine most every night. I know there is some commentary to be inserted here, but I digress. My understanding regarding alcohol is that the liver will stop any fat burning until the alcohol (aldehydes) are metabolized. Hence the increased levels of acetones on urine ketone strips after ingestion. But this should only be a relatively short period (depending on the amount of alcohol consumed) I would think. Would I probably lose more weight and have higher blood ketone levels if I did not consume alcohol on a consistent basis? My sense is most likely. My question to you is how long a period of time did you consume alcohol before you noticed a halt in weigh loss? And secondly, how long did it take for the weight loss to resume after eliminating the alcohol? You must keep very accurate tallies of your weight every day. I do not weigh myself often as there can be many variables involved. It would drive me crazy to worry about a pound here and there. But that is just me. I can just tell by the way I look and feel and how my clothes fit. Maybe I should do a more scientific approach to really see if my weight loss will increase sans alcohol. Right now, for me, it’s about carb restriction (obviously) and the type of exercise I am doing. Let me know if you have anymore insight. Thanks, Michael

    • Bob West  November 27, 2012

      Michael,

      While losing weight I would weigh and record myself every morning, and check BOHB a couple of times during the day. Naturally, I didn’t necessarily lose weight every day, but the trend was evident.

      On a day when I had, let’s say, more than about 2 glasses of wine at night, the next morning my weight usually would not have changed, or sometimes would have ticked up a bit. If I kept that up for several days running, the downward trend in weight would be stopped until I backed off on the wine. Then weight loss would resume almost at once. It was just that simple. I seem to be OK with 1 or 2; above that and I’m above my threshold. Experimenting with just skipping wine entirely worked better in weight-loss terms, but has a downside…

      Your mileage may vary.

      I have no real idea why this works this way, but it seems to, for me.

      Bob.

    • Vasco Névoa  November 28, 2012

      One hypothesis would be that we have evolved a hepatic cell priority system for getting rid of toxins like ethanol. If the liver’s metabolic capacity is 100% dedicated to clearing ethanol from the blood, this would probably prevent it from performing ketotic production. Once the industrial spill is taken care of, it happily resumes ketotic duty. I get a feeling this is just a question of resource allocation priority.

  19. Ben Greenfield  November 27, 2012

    Fantastic post, Peter. I did not realize the significant extent to which glycerol from ketosis can be used for liver glycogen formation. Fascinating.

    (reply)
    • Peter Attia  November 27, 2012

      It probably plays a very small role outside of starvation (unless you’re a bear or a whale). During nutritional ketosis, most glycogen formation probably comes from the limited glucose ingestion and gluconeogensis of amino acids.

  20. Preben  November 27, 2012

    Very interesting article, doc!
    I can’t wait to show this to my collegue who was telling me how dangerous my diet was because sometimes went in to the “nutritional ketosis state” and then out (I love fruit too much).
    I tried to explain the difference between ketosis and DKA, but he wouldn’t believe me, because his doctor said it differently.

    Later in the discussion we touched a different subject. That fat cells, once created, never disappear. They just change in size (volume of TG). I’ve tried to google around and I’ve found some, not very reliable sources, which say you can only reduce the size of your fat cells, not the total number. This was the reason why obese people who lost great amounts of body fat easier falls back to obesity compared to naturally thin people.

    Are you planning an article or paragraph in an article devoted to this subject?

    Looking forward to part II

    (reply)
    • Peter Attia  November 27, 2012

      Not in the immediate future, as this issue of fat cells is a bit tangential to this topic (which I’m struggling like crazy to explore in less than 10,000 words). Hope this post can help you have an honest discussion with your friend.

  21. Gretchen  November 27, 2012

    Please clarify how you get 2 ATP from reducing pyruvate to lactate. Thanks.

    (reply)
    • Peter Attia  November 27, 2012

      See this figure for glycolysis: http://en.wikipedia.org/wiki/File:Glycolysis2.svg
      Note that part of this process requires ATP, while part of it liberates ATP. The net, however, is a gain of ATP.

    • Gretchen  November 28, 2012

      Peter, The cited Wickipedia pathway shows glucose to pyruvate, and that gives net 2 ATP. But your figure shows 2 ATP in the step from pyruvate to lactate.

    • Peter Attia  November 28, 2012

      Both happen. Glucose to pyruvate yields 2 (net) ATP. If pyruvate does not enter the mitochondria to become acetyl CoA (not enough cellular oxygen), then it converts to lactate for an additional 2 ATP. Hence, aerobic metabolism is much more efficient, but anaerobic still gives you something.

    • Gretchen  November 29, 2012

      My question is *how.* Pyruvate is *reduced* to lactate, regenerationg NAD+, which can then feed back into glycolysis to produce more ATP. Is that what you mean? But you still need more glucose to get more ATP.

      It’s not really a gain in energy, because you’re sacrificing an NADH (worth about 2 ATP) in order to regenerate the NAD+. But the diagram makes it look as if you get ATP directly.

      I don’t want to belabor this, but I’m really puzzled.

    • Peter Attia  November 29, 2012

      In that sense, there is no such thing as a gain in energy, as the laws of thermodynamics tell us. The ATP (the energy we want) is generated by reducing pyruvate (NADH + H+ –> NAD+) to lactate, which liberates CO2 and ATP

  22. Ken  November 27, 2012

    It doesn’t seem as though most of the “Biggest Loser” participants found significant long term ketosis. Some have kept the weight off but most are starting to gain it back. I didn’t look closely but it doesn’t appear that any used low carb as a way to lose weight. Sorry if this comment is not in the appropriate section but I wasn’t sure where to put it and I thought it was interesting.

    http://today.msnbc.msn.com/id/40423712/ns/today-entertainment/t/biggest-loser-where-are-they-now/#.ULTAfo77A8F

    (reply)
    • Peter Attia  November 27, 2012

      BL patients were on very low calorie diets, but not specifically ketogenic, so I suspect they were not in ketosis. As to why they regain weight, that’s an entirely separate (and longer) discussion, but speaks to the reality of weight loss: calorie restriction have very low long-term success.

  23. Kyle  November 27, 2012

    As usual, another great post Peter. So my question is from an athletes point of view. If I am in Ketosis and I am a distance runner, will consuming carbs like a gel or SS (during a race) help boost the Krebs Cycle during an 18, 30 or 50 mile run to further burn fat for energy? The one thing I am not sure of is if the carb is used up by the muscle or it is actually transferred to the mitiocondria to keep the Krebs Cycle buring fat to produce said energy

    (reply)
    • Peter Attia  November 27, 2012

      If in ketosis, you’re better off consuming a carb during the event that will have the lowest impact on insulin levels to have he least interference with ketone production. This is one reason I prefer SS for in-race glycogen top-off over, say, a conventional glucose source.

    • Kyle  November 27, 2012

      Understood. I am not a fan of the gut churn/cramp up during a race when a glucose source is trying to digest. Not sure if this is the fourm to discuss this but, what about taking a free form amino acid/s to boost energy levels along with SS? I know amino acids can be converted via the Krebs’ cycle to glucose for energy or for storage as glycogen and fat. So during times of increased stress due to trauma, exercise, starvation and/or disease states, amino acids can be catabolized into intermediates to produce energy.

    • Peter Attia  November 27, 2012

      At most a few gm of BCAA might help, but not sure much more than that is needed for the type of exercise you’re doing.

    • Peter Attia  November 27, 2012

      Ahhh…you’re getting a bit ahead. Yes, I was planning to address this in a subsequent post (maybe part 3)? I know Kieran Clarke and Richard Veech personally, and am very familiar with Delta G (ketone ester). I will get to this eventually.

    • Edward  November 29, 2012

      Sounds like a real boon to us low carb types. I would love to get some.

  24. Fredrick Hahn  November 27, 2012

    Hi Peter –

    Q: If you are in true nutritional ketosis, might it be harmful to the brain to drink alcohol as this will halt ketone production and at the same time, not provide glucose. IOW, if one is relying on ketone bodies for fuel, could halting their production without a concomitant intake of carbohydrate be harmful?

    (reply)
    • Peter Attia  November 27, 2012

      I guess it depends how much alcohol. Even in full-fledged ketosis, your brain still has access to glucose, so you’re never exclusively dependent on B-OHB.

  25. Jason  November 27, 2012

    My apologies if this is not directly related to your article, which was very straight forward and easy to follow, thank you (Very interesting about the liver still being 50%-70% full in ketosis. The body must trigger the generation of ketones before al the glucose is drained from your body :) I wonder what the threshold is for that…). But I wonder if you had any comment on the following ketogenic issues (if not I understand your time is quite limited).

    - Various sources claim the ‘butter’ range for nutritional ketosis is around 3mmol. I seem to hang around 0.5-1.0. I finally got a meter and have been experimenting with the timing. Ketosis has done wonders for my endurance but I was surprised after a 24-fast with a 5 1/2 hour mountain run in between I was surprised to see my ketone levels only at 0.2 right before dinner ! The highest I have had is 1.0 after a 24 hr. fast with only a 2 hr run in the morning. Is there some credibility to the idea that you become for ‘efficient’ using ketones over time so you body produces less ? Or does that mean I still don’t have things tweaked ? (Insulin resistance? Never had any metabolic syndrome markers before embarking on the diet).

    - Has their been any research in regards to ketosis vs. mental disorders like anxiety attack ? I have a friend who is on Paxil and tried to go ‘ketogenic’. They got “pretty” good at cutting out carbs but it seems whenever things finally seemed to start happening it triggers the beginnings of a panic attack so they would dive for the carbs and it would clear up (low glucose ?). I wonder if it is harder to get over the ‘hump’ when someone has low serotonin levels.

    - I keep reading about thyroid issues vs. ketosis. I have another friend who is on synthetic hormone and when they tried to go ketogenic their T3 levels took a dive (TSH went up) which then resulted in their LDL to sky rocket (as I have read low thyroid means you cannot clear out the cholesterol as well ? Not sure about this). Do you know of any additional research done with ketosis/starvation and thyroid reactions ? I think it makes sense T3 would drop since there is less oxidative stress on the body.

    Thanks so much for your time,
    Jason

    (reply)
    • Peter Attia  November 27, 2012

      I’ll address at least a subset of these in part II.

    • lorraine  November 28, 2012

      Jason, on the thyroid issue, this panel discussion on safe starches from the Ancestral Health Symposium gets into the low carb and thyroid issue pretty well. Dr. Ron Rosedale challenges the position taken by others that a change in thyroid values with a low carb diet is indicative of pathology. His position is that it’s adaptive.
      http://vimeo.com/52872503

      There’s also a paper in the journal, Medical Hypothesis (2004) 62, 871-75, which I find most cogent that describes the metabolism of dietary carbohydrate as highly thyroxin demanding, and that T3 especially is carbohydrate dependent. So therefore, reductions in dietary carbohydrate reduce the requirement for T3. This paper discusses studies in which reductions in T3 were not followed by increases in symptoms or signs of thyroid deficiency.

      I have been treated for hypothyroidism for quite a long time, and am currently on no medical support for thyroid imbalance since eating VLC. My numbers became almost hyper-thyroid looking, although I had no symptoms. My conclusion is that thyroid tests become as difficult to interpret as some other tests (like LDL particle) under the conditions of ketosis.

    • Bill  November 29, 2012

      “My conclusion is that thyroid tests become as difficult to interpret as some other tests (like LDL particle) under the conditions of ketosis.”

      Thyroid tests are difficult to interpret regardless of ketosis. My own endocrinologist has called the failure to recognize this the single biggest mistake in the history of medicine:

      http://www.amazon.com/gp/product/1578263875/ref=ox_sc_act_title_4?ie=UTF8&smid=ATVPDKIKX0DER

    • Jason  November 30, 2012

      Thanks a lot Lorraine and Bill, those were useful links.

      Unfortunately my friend with hypothyroidism did not do a thyroid test right before going on the diet so the doctor is blaming the elevated TSH levels on the diet. I am not sure if the high TSH levels were already present beforehand. It certainly makes sense that T3 levels would drop with less oxidative stress and the body would adapt to that.

      I get the feeling some doctors just have the formula of high TSH = add more synthetic hormone. I am not qualified to argue with that but it sounds awfully close to the high cholesterol = need statins argument.

      Anyway, thanks again.
      Jason

    • Hemming  December 21, 2012

      Hi Jason,

      As I’ve also written further down. I had anxiety attacks too and felt somewhat depressed in the adaption phase. After I started supplemented with magnesium it completely went away and my mood improved. This could simply be a general adaption to ketosis too, I can’t say for sure if one or the other was the biggest factor. I’m supplementing with less magnesium now and continue to feel great.

  26. Sydney  November 27, 2012

    Could you please comment on fiber intake? Do you find fiber supplements necessary or desirable? If so, which ones?

    (reply)
    • Peter Attia  November 27, 2012

      I get more than enough from my vegetables.

  27. Canuck  November 27, 2012

    HI Peter,

    What a great post – I feel like it’s really ‘closing the circle’ for me on so much that I’ve read on your website.

    I wanted to (humbly) suggest a sub-topic that could be addressed in your part 2. Perhaps something on the impact of an intermittent high-carb meal on one’s ketotic state. For me, this would help in thinking about the practicality of a low-carbohydrate diet. I’m often able to keep very stringently to low/no carbs, but there are some situations where this just isn’t possible (usually for social reasons). I’d really love to better understand the process by which an intermittent high-carb meal can ‘kick’ you out of nutritional ketosis, the threshold (i.e. how much carb will take you out of ketosis), and how long it takes to get back in.

    Thanks!

    (reply)
    • Peter Attia  November 27, 2012

      I’ll try to remember to include this in the final part. Short answer is it highly depends on the quality of the carbs and the timing of ingestion (e.g., right after a long workout or just before bed). Candy bar vs. almonds. These factors, and others, make all the difference in the world.

    • Amy B.  November 28, 2012

      Mark Sisson covered some good info related to this in one of Jimmy Moore’s “Ask the Low Carb Experts” podcasts. The title was “Ketosis: Devil or Angel.” (You can get it for free from iTunes or probably straight from Jimmy’s site.)

      Mark explained that once you’ve been fat/keto-adapted for a while, your body has the “metabolic machinery” in place to move more easily in and out of ketosis than, say, someone jumping into low-crab from the standard American diet. Once you build that cellular machinery (especially additional mitochondria) and your body is sort of “trained” to run on fat, an occasional high-carb meal isn’t that big a deal. (Depending, of course, on *why* you’re ketotic — like if you’re trying to treat/control a serious condition.) There seems to be some dispute about how long it takes to get back into ketosis after a high-carb meal or an all-out binge. Sisson seems to think it doesn’t take that long because you still have the basic machinery in place and your body overall is still fat-adapted. Others (don’t recall exactly who, but it might have been Stephen Phinney or another LC researcher) think it takes a lot longer.

    • Annlee  November 28, 2012

      I do a fair amount of business travel, with customer-facing lunches and dinners. A pleasant smile works wonders – “No, thanks – I’m fasting today. Please – go ahead.” And I sip my bottled water. And smile all the way – because I feel great.

    • alan  November 28, 2012

      @Canuck
      i , like amy, have read both dr. volek/phinney and mark sisson.
      i had an all out three days binge while in ketosis and it took me more than two weeks to get back on track fully. i had all my muscles full of water, well swollen and my energy level was extremely low. my body switched straight away from fat burning to glycogen, therefore when i re-started eating low carb i could not even do a quarter of the sport i did until three days before as my body expected gucose but i was just giving fat and gluconeogenesis is not so immediate.
      another time i had one day all carbs and it took me about one week.
      you can try for yourself, but it is not pleasant at all.
      i have also overeaten for two days “allowed food”, in the form of cream, fatty cheese and nuts, but i found no water retention, little energy reduction and back on my way in two days. only hunger ( leptin-grehlin i suppose) was a little awry.

      alan

  28. Joshua  November 27, 2012

    Thanks for the post Dr. Attia. You may be already planning to cover this topic, but one thing I’ve been wondering about is whether there is any disadvantage (performance, metabolic, or otherwise) to being on the border of ketosis and sugar-burning vs. solidly in one camp or the other. I’ve had success with weight loss by reducing carbs to 50-100, but I’m only just over half-way through my planned loss, and I’m trying to plan ahead for any walls I might encounter on my way.

    (reply)
    • Peter Attia  November 27, 2012

      Probably depends very highly on the individual.

  29. Amy B.  November 28, 2012

    Hey Dr. Attia,

    “Long time listener, first time caller,” as they say. I discovered your blog through Robb Wolf, after he mentioned your (insanely incredible) series on cholesterol. I’ve been devouring your site as fast as I can…kind of like a pat of butter on a spoon all by itself, which I’ve been known to devour, too!

    Anyway, I just wanted to say that you have a real gift for attacking the nitty-gritty science head-on but also translating what it all *means* it comes to what we should and shouldn’t put in our mouths. If I was one tenth as prolific as you are, I’d be dangerous. (In a good way.)

    I just finished up a master’s in nutrition, and I thought the biochem was going to be the most challenging part of it. Turns out I was FASCINATED by it all and can’t get enough, so your site is truly a refuge in the sea of misinformation that’s out there about nutrition and health. You’re exactly right about Richard Feynman — you can’t argue with the science. And when it comes to the unfathomable mess we’ve gotten ourselves into with the utterly nonsensical low fat, whole grain paradigm, the only way we’re gonna dig ourselves out is for the science to win. Not the politically correct recommendations, the moral grandstanding, or even what we *wish* were true or sounds logical on paper. (I mean, let’s face it, to someone who knows nothing about biochem and physiology, it *makes sense* that fat should make you fat…) So I’m especially grateful to you and Gary Taubes for starting NuScI. Can’t wait to see where things go.

    And one last thing…sorry to talk your ear off, but I want to make sure I tell you that the quote below might just be the single greatest thing I’ve read on a nutrition/health blog — and I read *a lot* of them! Kudos for your humility and intelligence. If only all doctors had the curiosity to question the “facts.” You’re a rare breed!

    “Embarrassing admission: I remember exactly where I was sitting in a clinic at Johns Hopkins in 2002 explaining to (admonishing, really) a patient who was on the Atkins diet how harmful it was because of DKA. I am so embarrassed by my complete stupidity and utter failure to pick up a single scientific article to fact check this dogma I was spewing to this poor patient. If you’re reading this, sir, please forgive me. You deserved a smarter doctor.”

    (reply)
    • Peter Attia  November 28, 2012

      Amy, I’m so delighted the world of nutrition professionals is now one person richer by your addition. Thanks so much for kind words and I’m delighted to play even a tiny part in your ongoing education.

  30. Andrew  November 28, 2012

    Peter, it is such a privilege to have access to your work. I just wonder how many hours of sleep you get.
    I am really pleased you are doing something on ketosis.
    I reduced my carbs signicantly a year ago and have lost 50% of my body fat and reduced my weight by 13kg. Since starting a full ketogenic diet 3 months ago, the best thing has been a 65% reduction in my triglycerides and a 35% increase in my HDL. I know this isn’t the whole story but here in New Zealand we don’t have NMR.
    As a typical obsessive physician, I have been regularly checking my ketones and blood sugars and am really impressed how tightly controlled blood sugars are despite a very low carb intake and even after prolonged exercise. Physiology and biochem have never been so interesting! I had a steroid injection in an injured shoulder recently. I was really surprised by my blood sugar which shot up to around 8.2mmol/l and stayed high for about 2 weeks. I would have expected this to increase insulin levels and kick me out of ketosis but my ketones stayed up throughout this time although lower than average. Turns out steroids exert their effects on blood sugar by inducing insulin resistance in the liver and muscles, but also prevent the ketone-supressant effect of insulin.
    A thing that has really surprised me about being in ketosis is the mental/mood effects – specifically euphoria which kicks in at elevated ketone levels -seems to be above about 2 mmol/l. It is quite noticeable and almost disruptive to normal work. Conversely, I notice definitely lower mood when my ketones are low, typically early in the day. This effect does not seem to be diminishing with time.
    Anyway, keep up the good work – it is really appreciated.

    (reply)
    • Peter Attia  November 28, 2012

      Andrew, thanks so much sharing your experience. Great to know the pool of physicians out there who understand this is growing. As for sleep…probably not enough but MUCH more than residency!

  31. Mark M.  November 28, 2012

    Peter:

    You mention reading 5 or 6 scientific articles a week. How do you find these articles and how do you separate the good from the bad?

    Mark

    (reply)
    • Peter Attia  November 28, 2012

      Actually, my pile-up list is about 20 papers per week, but I try to winnow it down to 5 to 6 based on topics I need to learn more about and the quality of the work. I try to assess this quickly be reading the abstract and methods, plus knowing something about the author.

  32. Ann  November 28, 2012

    Hi Peter and thank you for a wonderful post, so well explained for someone like me with no biochemical or medical background. I have T2D with normal (non-diabetic) blood glucose and an HbA1c of 5.0 and have been keto-adapted for about 6 months or more, testing B-OHB since early June. Results were consistently over 2.0 at any time of the day with a highest recording of 3.4. So as the strips are expensive and I was keeping an accurate diary, recording a KR of 2.2-2.3 consistently, I stopped testing. This afternoon, after 6 weeks without testing, I bought a packet of 10 beta-ketone strips and tested, getting a horrible fright when the result was 6.3.

    So I was very relieved to read your statement about only T1s and very late stage T2s being at risk of DKA. Thank you for the timeliness of that statement. :)

    This series is very exciting, and although I’ve tried to read a lot about ketosis, I had several light-bulb moments while reading part 1. Bring on part 2!

    (reply)
    • Peter Attia  November 28, 2012

      Ann, you must be eating very few overall calories to reach those levels? The reason I assume this is because with 30-50 gm of carb and, say, 100 gm of protein in your diet, levels this high would very difficult to achieve. I must admit, I’m kind of jealous! As you’ll see in part II, you are achieving benefits from ketosis that most people living at 1 to 2 mM do not.

  33. Darryl  November 28, 2012

    Amazing but in all honesty … how can you understand all this … what our body does …, and still say evolved with a straight face. Cracks me up.
    Excellent write up yet again.

    (reply)
  34. Gunhild  November 28, 2012

    @ Andrew,

    I experimented with being in NK for a few weeks some time ago, but got out of it. My number one reason for wanting to do it again is definitely the oh-so-happy mood – euphoria as you call it is the right word. I was so balanced. Unexpected, delightfully good mood :-)

    (reply)
  35. Greg  November 28, 2012

    Peter, I’ve learned more from your blog than I could have ever imagined.
    Thank you! Keep up the amazing work.

    P.s Spelling error in paragraph 8 Glucose-6-phophatase = Glucose-6-phosphatase

    (reply)
    • Peter Attia  November 28, 2012

      Great catch, Greg. Thank you.

  36. Greg Bledsoe  November 28, 2012

    Peter-

    This is an excellent article. Thanks for the great work. I am loving your blog. -Greg

    (reply)
    • Peter Attia  November 28, 2012

      Thanks very much, Greg. Very glad Stuart was able to re-connect us.

  37. lorraine  November 28, 2012

    Thanks, Doc. A great explanation of how we get to ketones. I think that if people reading your post are a little blown away by the metabolic pathways, maybe they can read Dr. Eades great conceptual article on metabolic ketosis from his blog first (or read it afterward, and then come back again for a second read on this one). I’ve been hoping for a couple of years now that someone would do a really comprehensive explanation of the biochemistry of ketosis for the lay person. As much as I’m a huge fan of Drs. Volek and Phinney, I’ve been disappointed that they’ve not had at it with more detail, especially in Art and Science of Low Carb Living, which is also aimed at clinicians. Now, with the combination of the Eades post, the degree to which Volek and Phinney do get into it, and here, people can fully wrap their brains around how it works and why it’s normal physiology.

    One of the things I actually still hear about as a disadvantage or danger of ketosis, is that ketones are “partially burned fats” or “inefficiently burned fats”, whatever that means. I’ve tried to do a lot of ‘splainin of this concept, which seems to have gotten started back in the day of early body building circles and has persisted. In any event, you can’t really explain what’s wrong with that statement unless you look at the metabolic pathways and show folks that ketones are made *after* beta oxidation, which means that the fatty acids have been completely metabolized. Getting folks accustomed to seeing metabolic pathways by posting them here is enormously helpful in the end, even if initially folks go to total brain block when they first see one.

    Warning: Nit Pick Coming Up – in your second table showing the two routes of glycolysis, which you describe as aerobic and anaerobic, and define as sufficient oxygen vs. insufficient oxygen respectively – sorry, but this makes us exercise physiology types nuts. Just because anaerobic or rapid glycolysis * can* make ATP without oxygen, doesn’t mean there’s insufficient oxygen. Whether or not a substrate is being metabolized oxidatively or glycolytically is determined by all kinds of things irrespective of O2, including rate of demand or product feedback inhibition someplace else in the stream of any particular pathway. To quote Brook and Fahey, in the canon Exercise Physiology, “The early experimentation and terminology has led to some confusion in contemporary physiology……..The terms aerobic (O2) and anerobic (without O2) refer to the test tube conditions used by early researchers to speed up or slow down glycoolysis. In real life, pyruvate and lactate pools are in equilibrium, and the rapidity of glycolysis largely determines the product formed (p 73-4)”. So, I understand that the aerobic/anaerobic nomenclature is more familiar, but it’s completely misleading because it implies that the non-oxidative pathway performs when there’s insufficient oxygen, rather than that we have a pathway that uses oxygen to make ATP, but we also have a pathway that can make ATP without using oxygen. There is also evidence that there’s never insufficient O2, showing that even at VO2max when glycolytic pathways are running full bore, that there’s still at least 2Torr oxygen pressure in the mitochondria. So better terms to use are oxidative or slow glycolysis, and non-oxidative or rapid glycolysis.

    (reply)
    • lorraine  November 28, 2012

      Peter, please indulge me more on this aerobic vs. anaerobic thing, because thinking of it more, it’s actually quite important, and the use of those terms is misleading. So the take home is that whether or not glucose runs down to pyruvate or to lactate has nothing to do with availability of oxygen, it has to do with how fast you need ATP. It’s a fast vs. slow issue.

      As stated above, even at VO2 max, 2Torr O2 pressure exists in the mitochondria, quite sufficient to continue to produce ATP via the electron transport chain, which does continue, even when ATP is simultaneously being made by rapid (anaerobic) glycolysis…..glucose > lactate. So there’s always enough O2 even at maximal demand for ATP.

      Conversely, if the route of glycolysis was oxygen dependent, then there would be no reason for the healthy human to make ATP via rapid (anaerobic) glycolysis at rest. And yet, we do. Certainly you make less lactate at rest than someone with metabolic disease who’s a sugar burner by virtue of not being able to access their fat, but you make it none the less. If the route of glycolysis was related to whether or not sufficient oxygen was available, then you’d never do glucose > lactate at rest when plenty of oxygen is available.

      The real reason to change the nomenclature from aerobic to slow glycolysis, and anaerobic to rapid glycolysis is because no matter what the route, there is zero oxidation until you get to the electron transport chain. So glucose to pyruvate is non-oxidative or anaerobic also. So is FFA to Acetyl-CoA, and whatever it is that I can’t now remember amino acids go thru to get to Acetyl-CoA. Even the TCA cycle is anaerobic. Look at your own TCA pathway above. No oxidation until the ETC (one oxygen radical indicated at the ETC cytochrome). So everything north of the ETC -, where AMP and ADP undergo oxidative phosphorylation to ATP – is anaerobic, no matter what your route or substrate. Therefore to say that glucose > lactate is anaerobic, and glucose > pyruvate is aerobic, is false (because that part of the pathway is also anaerobic, not becoming “aerobic” or oxidative until it gets past the TCA cycle and into the electron transport chain).

      The meaningful difference in the routes has to do with the speed with which one needs to get ATP out. So it’s obvious that the aerobic or oxidative, or SLOW, pathways, are just that – slow. There are so many more intermediary substrates that can get hung up by product feedback inhibition in all of the various routes and cycles down to the ETC, and so many more enzymes that can be affected by increases in temperature or decreases in pH. So even though one gets so many more ATP’s per unit of substrate out of the slow pathways, you know, they’re slow, and more prone to log jam. Well, that’s a bummer if you need to sprint to the finish or, if a diabetic for example, to walk across the street. So we have this nifty rapid route that makes ATP without the electron transport chain, and therefore, doesn’t need oxygen (even though there may be plenty of oxygen available). You only get 2 ATP’s out per lactate, but it could make the difference between getting done what the muscle is demanding because that route gets it done fast.

      I hope you can understand why I’ve made a pain of myself on this.

    • Peter Attia  November 29, 2012

      Yes, agree with your point and the criticism of my overly simple explanation. I guess one way to think about, though I agree with your assertion about speed, is contrasting 2 people with different VO2 profiles (to power, or some other output metric). The person with the higher VO2 has a greater ability to uptake and utilize O2 at the cellular level, presumably. They would therefore presumably be able to undergo oxidative metabolism under greater energy demand.

    • lorraine  November 29, 2012

      Yes, that’s true, but it’s not the point I’m making (or failing to make, lol). Your label on your second figure indicating that “anaerobic” (or non-oxidative, or rapid) glycolysis occurs under the condition of insufficient oxygen is incorrect – that’s the point I’m trying to make. Rapid glycolysis occurs under all conditions of cellular oxygen. You do glucose > lactate all day long, even at rest while you’re reading this, so you’re making lactate right now, even under the condition of sufficient cellular oxygen. Rapid glycolysis is a pathway that just doesn’t happen to use oxygen, even though oxygen may be readily available for use (and is, in fact, simultaneously being used in parallel metabolic pathways like slow glycolysis, or beta oxidation). It’s just a short and quick pathway to crank out some ATP, and it just doesn’t happen to need oxygen to do it. But it is not reflective of insufficient cellular oxygen. So the label is wrong. All the ATP pathways are running all the time, under all conditions (high/low cellular oxygen, rest, exercise etc) – some of them use oxygen to make ATP, and one of them doesn’t need to.

      There are, in fact, conditions under which O2 delivery to or utilization by the cell is compromised, and rapid glycolysis becomes more greatly utililzed in those conditions. A couple of these, of course, are high intensity exercise and metabolic disease, but these are not the only conditions under which we do rapid glycolysis. That pathway is used all day long to some degree by healthy people, at rest or in submaximal exercise, under conditions of more than enough cellular oxygen, the rapid glycolysis pathway is just not using that oxygen to make its ATP.

      Thanks for your patience.

  38. Manel Gonzalez  November 28, 2012

    Peter,

    Thanks for your posts.
    I read the whole series of cholesterol in 2 nights, my wife was mad at me…

    I am following a paleo diet for almost 3 years, and I started IF (I skip 2 meals twice a week) 2 months ago, and as I eat low carb, I may be in the treshold of ketosis.

    I write from Barcelona, where this diet is seen as something bizarre (my friends make a lot of funny comments…)

    I feel great, but there is one issue; they tell me I am having bad breath. Do you think it can be because of the cetone in the breath?

    (reply)
    • Peter Attia  November 29, 2012

      Might be the acetone. May be transient.

  39. Ann  November 29, 2012

    Hi Peter

    Quote: Ann, you must be eating very few overall calories to reach those levels? The reason I assume this is because with 30-50 gm of carb and, say, 100 gm of protein in your diet, levels this high would very difficult to achieve. I must admit, I’m kind of jealous! As you’ll see in part II, you are achieving benefits from ketosis that most people living at 1 to 2 mM do not.

    Thanks for that reply, Peter. I eat between 1500 and 1700 calories a day, with an F:P:C ratio of around 83:12:5. Protein is around 50 grams a day, carbs 17-25 and saturated and monounsaturated fats make up the rest. I walk 6.25km most mornings, before breakfast and starting out in a fasting state, 12-13 hours since I last ate. I’m relying on Calorie King to calculate the F:P:C ratio for me and I also rely on their database for most of the nutrition data. Oh and I’m actively losing weight. I hope to learn how to make the transition to maintenance without compromising my blood glucose numbers at some stage during your series. :)

    I’m really looking forward to Part II, and thanks again for a great blog!

    (reply)
  40. Donna  November 29, 2012

    Peter,
    Thank you for this posting. I wish I had your clarity of thinking and writing as you always seem to manage to make dense topics more accessible.
    Over the past year (a year? wow) I have learned more from you, rereading Gary’s book, and devouring the Art and Science of Low Carbohydrate living than in all the years I studied nutrition to the point I could have passed the exams to be a registered dietitian.

    One of the best things I like about your blog is the fact that in your writing you don’t force a certain way of eating. You said you were amazed that ‘what I eat’ is the most read blog. That does not surprise me as so many of us act like ‘educated lemmings’ (I include myself in that since I can just imagine I just insulted many people including myself) and want someone to tell us what to eat. You refuse to do that. You ask that we devise an eating pattern that works for our individual bodies based on current understanding of nutrition not blindly follow someone else’s meal plan.

    I hope someday that the kind of testing you have discussed in many of your replies and postings becomes the norm. Right now I cannot have many of the tests you describe because my doctor sees no need for them and refuses to sign the form for them. He once told me that one test I asked for had no valid use yet I read here that it can be useful. I do not have the funds to get testing done privately. Furthermore, he does not understand nutritional issues and falls back on the standard low fat, eat miniscule diet rules. And no, I cannot change doctors. The current health plan I am under makes that difficult. So I fall back on my current studies and hope that I am doing the right thing for my body.

    Again, Peter, thank you for this posting and for all your hard work as you come up on your anniversary. And a thank you to your wife for allowing you to spend so much time with all of us.

    (reply)
    • Peter Attia  November 29, 2012

      Understood. Hang in there.

  41. Uncle Roscoe  November 29, 2012

    Dr. Attia, Thank you for the explanation of ketosis and the ketogenic diet.

    Ketogenic dieting is effective because it reduces circulating glucose while reducing glycation. These are effects of a widespread western problem, insulin resistance. Ketogenic dieting, however, does little to address insulin resistance, the cause of circulating glucose and glycation. Insulin resistance is caused by insulin mimetic proteins, like WGA in wheat and concavalin A in legumes. These proteins enter the circulatory system because they set up an innate immune reaction in the small intestine. The reaction causes the intestinal walls to become porous.

    Limiting sugars helps treat the problem, but eliminating harmful carb-related proteins cures the problem.

    (reply)
    • Whitefox  November 30, 2012

      Interesting. But on the topic of WGA, I believe practically all of it is destroyed by heating, is it not? Certainly other proteins survive the heating process, but not that one (if i recall correctly). So if some proteins cause the porousness (like zonulin release due to gluten, etc.), what proteins are the actual insulin mimetics? Could the cause be LPS activity by gram-negative bacteria causing the porousness/immune reaction, or is that secondary to the types of proteins you mention?

    • Uncle Roscoe  November 30, 2012

      Actually my post was overly simplistic for a rigorous analysis. The food peptides which mimic insulin in the bloodstream are not necessarily the peptides which cause the zonulin dump in the small intestine. They come from other associated peptide sequences, such as the sequences in hyphal wall protein 1 (HWP1), from the same foods. And yes, there is evidence that, for many people, the bacteria and fungi which colonize around these proteins can initiate the zonulin dump. They would probably be associated with interim steps using oligosaccharides and glutamates to prepare the intestinal epithelium.

      There is experimental evidence that in a vacuum WGA is degraded by heat. There is also experimental evidence that it is not degraded in vivo …..in real world situations. There is strong evidence associating ingested WGA with other non-insulin mimetic bloodstream effects, like cartilage degradation and red blood cell clumping. So I’m saying no, in vivo a huge amount of WGA gets into the bloodstream when we ingest wheat.

  42. Mark Bosma  November 30, 2012

    Excellent information, as always! I’ll look forward to part II of the series. This should be a valuable resource to pass along to all of the people that give me a “You’re on a what kind of diet?”.

    (reply)
  43. Bjarte Bakke  December 2, 2012

    Great post again Peter. Ketosis content aside I particularly enjoy the humbleness of your “embarrasing admission”. We’ll very likely make more mistakes and instead of hiding them let’s be transparent.

    Thanks again and regards from Norway!

    (reply)
  44. Ian Butterworth  December 2, 2012

    I am experimenting with ketosis myself and find it an interesting journey. How do you find it feels mentally?

    Also today I see that some contrary points have been posted by Arthur Devaney saying that fat in the diet encourages inflammation. http://artdevanyonline.com/1/post/2012/12/those-high-fat-paleo-diets.html

    This has me wondering about it all. Is the overall “loading” of the liver from fat or carbohydrates going to have an effect on us over time?

    (reply)
  45. kang  December 2, 2012

    peter,

    Diagnosed with T2 DM in 2010, and on low carb diet since then, T2 completely reversed. But every time I got into ketosis (less than 30 carbs), I got heart palpitation, especially after a meal. Any idea how to work around the problem ?

    Thanks!

    Kang

    (reply)
    • Peter Attia  December 2, 2012

      A number of things are possible, but you should certainly have your doctor confirm that you are not low in potassium, which is a common side effect of ketogenic diets if not supplementing sodium and magnesium.

  46. Sam  December 2, 2012

    Thank you Dr. Attia. Very informative. My wife is a PhD in neuroscience and she is enjoying the reading a lot! Looking forward to read part 2, particularly for the aspect of the cori cycle.

    Thanks again!

    Sam

    (reply)
  47. Dave  December 3, 2012

    @melancholy aeon

    “Why not talk to any of the several women we all know who in fact have done this?”

    “There are some quite prominent low-carb moms around and I suggest you talk to them. Best wishes.”

    Did I miss a low-carb parent meet n’ greet or something? I was recently put in contact with Dr. Wortman but I don’t know any others. Feel free to introduce me. :)

    Dave

    (reply)
  48. Alex  December 4, 2012

    Hi Dr. Attia,

    After reading your blog I changed my diet and feel great. I am not in ketosis. I thought many times if I should try to get into it by further lowering my carb intake. One thing bothers me a little is I remember somewhere I read that ketonbody is produced by the liver and can be used by all organs except the liver. I wonder where does the liver get its nutrient if one is in ketosis for the long term. Will it have any negative impact on the liver at all? Thanks.

    (reply)
    • Peter Attia  December 4, 2012

      B-OHB production by the liver does not harm it.

  49. Jeff B.  December 4, 2012

    I’ve read through quite a few pages on this site but one question I have is;

    How much daily fat is too much for the heart? I have a high metabolism and I’m struggling to maintain my current weight. I realize most people go on keto to lose weight, but I went on because sugar-free improves my skin condition (rosacea)

    (reply)
    • Peter Attia  December 4, 2012

      I’m not sure what dietary fat has to do with the heart.

    • Maryann  December 4, 2012

      Hi Peter, would you have any input on the standard recommendation (HDL Labs) for a person with Apo 3/4 to go on a very low fat diet? Thank you very much, maryann

    • Peter Attia  December 5, 2012

      It’s not clear to me that is based on great data. If anything, it may be polymorphisms in apoA-II that could (?) determine dietary fat sensitivity. The defect with apoE 4 (3/4 or 4/4) is one of the LDL receptor. Such patients, to varying degrees, have more difficulty clearing LDL-P from circulation.

  50. Marilyn  December 4, 2012

    Peter, I’m glad you’re doing this series, and am looking forward to future posts. One thing that seems unclear to me is the frequently-expressed idea of “going in and out of ketosis” — kind of like turning a switch on and off, or going through a swinging door. Is it really like that; or is it a more gradual shifting of things? What exactly happens in that transition?

    (reply)
    • Peter Attia  December 5, 2012

      It’s actually pretty quick, assuming you ingest a food that results in much insulin secretion.

  51. James  December 4, 2012

    Love this blog Dr. Attia, very interesting, and extremely informative even for those not previously educated in these areas (albeit I do find some of the biochemistry a bit confusing haha). I am very interested in nutrition and biology, as well as fitness, even more so because my girlfriend has PCOS, and a family member was recently diagnosed with type 2 diabetes. I believe myself to be someone genetically predisposed to insulin sensitivity or having a higher portion of LPL on muscle tissue, like you have described your wife. Similarly no matter what or how much I eat, I just don’t seem to gain much weight at all (very slight subcutaneous fat is all), albeit I am only 22 and I assume I could still develop an insulin resistance if I ate in a certain manner (I don’t know).

    You say you have cured your insulin resistance from your dietary changes based on the tests you took. Strictly out of curiosity, I wonder what would happen (hypothetically speaking) if you changed back to your diet before making any changes, given the fact that you are very insulin sensitive now. I assume your insulin resistance developed over time based on the fact that you were in such great shape in high school. How long do you think it would take to get back to the insulin resistance you had before beginning your journey? I assume a can of soda would be far less detrimental to you now, as opposed to before?

    Professional fitness models have a methodical practice when preparing for a competition or photo shoot, and over time they develop a vast knowledge for what affects their body composition. One thing they always do is perform a significant amount of cardio through low-moderate intensity aerobic exercise, in the belief that they are burning fat. Given your hypothesis and personal experience, you believe this is actually having little to no beneficial effect on their body’s fat content? They do carb-restrict also of course, so you believe that the only real fat loss they are seeing is through their carbohydrate restriction?

    (reply)
    • Peter Attia  December 5, 2012

      Great question. The recent blog post of Mike Eades suggests I may even gain back more weight than I lost with enough time…

  52. kelly  December 4, 2012

    very cool of you to admit that you didn’t give your patient the right advice way back when. Congratulations on being an open minded clinician!!! We need more people like you to take care of patients. It is not easy to admit that you could have been wrong. :)

    (reply)
    • Peter Attia  December 4, 2012

      Cool, but sad… If you make as many mistakes I have do/have, you have lots of practice admitting it.

  53. Stephen  December 4, 2012

    My doctor was horrified when I told him about my low carb/high fat diet and along with the usual arguements against it, he said it exacerbated Panic Disorder, a complicated biological condition. He was mum when I asked him how, but have you heard this previously?
    Also, after being practically chased out of a Health Food store after asking if they had a low-carb section, I went to my local Trader Joe’s, where I feasted on their wonderful Almond Butter. At checkout, they had a dark chocolate bar which had 0g of Sugars listed, but had 13g of carbs listed. Then it said that it only had 2g of “effective carbs”, but it had only 1g fiber content. What are effective carbs, and should I buy this next time?
    TIA

    (reply)
    • Peter Attia  December 5, 2012

      EC is the difference between total carb, sugar, and alcohol sugar (where present). TJ’s AB is great.

    • Hemming  December 7, 2012

      Hi Stephen,

      From my own personal experience I’ve tried the panic disorder. My own explanation to this is mineral deficiency (especially magnesium). I don’t know if you have actually had attacks of panic disorder but I can assure that what I’ve tried is something you want to avoid. I would assume your doctor’s concern goes back to that he knows that a low carb/high fat diet could potentially leave you deficient in those minerals.

  54. Malin  December 5, 2012

    Hi Peter ,
    For me it is all about the potassium entering the muscle cells by insulin.
    Once the potassium is in there the faulty channels do not repolarize and my muscles paralyse.
    The condition is hypo kaleamic periodic paralysis.
    It is genetic.Treatment is with acetazolamide and potassium supplements and avoidance of triggers.
    Triggers can be exercise, environmental temperatures, hormones ,sodium and many things but mostly it is to do with carbohydrates or long gaps between meals.
    The liver releasing glycogen stimulates insulin ,right?
    I have found I get fewer attacks on approx 15 g of carbs / 24 hrs. I have been doing this for about 18 months.my BMI is at a steady 20, similar to what it used to be when I ate carbs.However,my exercise tolerance is still very limited,peior to this condition kicking in I used to run marathons.

    Does having too much protein cause glycogen and thus insulin to be released?
    What is your vie on the insulin index, scares me that beef is so high and considering cutting out dairy altogether
    My husband eats Paleo and although I like peanut butter now that I know about the omega3 vs omega6 ratios I may limit my intake.We use coconut oil,great stuff.
    Do you think being ketogenic should help prevent the potassium influx into the muscles?

    Thank you for your thoughts.
    Malin

    (reply)
  55. raw cyclist  December 5, 2012

    peter, will you take on this challenge?

    http://www.youtube.com/watch?v=AfgRQzArvb0

    (reply)
    • mike  December 5, 2012

      I have absolutely nothing against the high fruit eaters in this world. In my view, the diet that works for you, makes you happy and perform the way you like is fine with me. However, am I the only one that realizes a low fat, high fruit diet is indirectly a high fat, low protein diet?

      Correct me if I’m wrong, but my understanding is that excess fructose beyond what is stored as glycogen is converted by the liver into triglyceride. Since fructose doesn’t have a dramatic insulin response and high fruit eaters aren’t eating many sugars or aminos acids that directly stimulate insulin secretion, these triglycerides are readily available to be used for energy should the need be present. So in other words, providing that they adhere strictly to their diet, they maintain access to their fat stores in a similar fashion as would a low carb, high fat individual. But, they are forced to keep protein low, dietary fat low and make sure they don’t add in much glucose because any one of these could bring about the adverse effects of excess fructose ie. fatty liver and everything that follows

      I personally follow a low carb, high fat diet because its just flat out easier to live with, and in my view (possibly others as well) a more efficient means of reaching a similar (dare I say superior) metabolic flexibility, while allowing the inclusion of more protein to support muscle growth.

    • Peter Attia  December 5, 2012

      There is a tremendous misunderstanding of the metabolism of fructose vs. fructose + glucose. The topic was done no favors by the “famous” Hellerstein paper from ’98 or ’99 looking at de novo lipogensis (DNL). Flawed methodology grossly underestimated DNL. The revised version of this paper (“A Dual Sugar Challenge Test for Lipogenic Sensitivity to Dietary Fructose” — J Clin Endocrinol Metab 96: 861–868, 2011) is actually the correct one. For those interested in this topic, who can’t wait until I write about in detail, get the paper and go straight to figure 5). Simply astonishing.

  56. Thomas  December 5, 2012

    Hey Peter
    Great article.

    I am big fan of the Danish version of rye bread, being that I am Danish :)
    I bake my own version of this bread with the following ingredients, it`s delicious.
    Sunflower seeds, Pumpkin Seeds, Sesame seeds, Flax seed, Almonds, Walnuts, Eggs, Olive oil, Salt

    This bread is really high in fat but also contains some carbs, so my question is. Will this bread eaten in moderation effect ketosis?

    (reply)
  57. Sam  December 5, 2012

    Dr. Attia,

    Just found this paper from 2010 online: Diet-dependent acid load, Paleolithic nutrition, and evolutionary health promotion (http://ajcn.nutrition.org/content/91/2/295.full) and here is an interesting paragraph:

    “The striking prevalence of osteoporosis in Inuit skeletal remains from the early contact period (8) is especially pertinent to the observations of Ströhle et al (1) because plant foods are necessarily scarce in circumpolar environments. In East Africa, late Paleolithic plant-to-animal energy intake ratios would have approximated 50:50, and diet-dependent net endogenous acid production (NEAP) would have been alkaline—the norm for human biochemistry, physiology, and bone health. In contrast, for traditional Inuit HGs, whose subsistence derived overwhelmingly from aquatic and animal sources, NEAP would have been acidic, contributing to their osteoporosis.”

    It seems that while ketosis might be man’s natural state, plant base food have to be more abundant (close to a 50:50 ration) which would also reduce the need for suplementation.

    Sam

    (reply)
    • Peter Attia  December 5, 2012

      Interesting, but probably worthy of more comment than I can provide at the moment.

    • Sam  December 12, 2012

      Dr. Attia,

      I sent my comments to a friend of mine who is in med school and reads your blogs and here is his take on it:

      “As for the article, I’m gonna play devil’s advocate here: I definitely think eating enough vegetables is necessary. However, the article does make a jump in assuming that it was the NEAP that caused the osteoporosis. There are too many variables to do so, and it seems to be a bit oversimplified.. It could also be that there food supply variety is quite limited compared to someone from say east Africa where they had access to necessary vitamins found in the the wider array of foods consumed, both plant and animal sources alike (not to mention fungi). Besides this what about effects on the bones from living in limited light while usually completed covered and the subsequent possible effects from vitamin D depletion (although they could find ample supplies in foods like cod liver)? A person in Africa would have no problem with synthesizing endogenous vitamin D, while that of someone in polar latitudes would have to supplement through diet.

      Now in terms of the diet… the protein consumption of someone going low carb should not be more than that the typical diet. Fat should replace the carbs. Not protein. Increased protein intake has been associated with an array of metabolic issues and has even been implicated in longevity studies. One study set out to test the hypothesis that reduced caloric intake correlated with increased longevity. Turned out that there was no correlation (although people still claim this). What they did find was that was an inverse relationship between protein intake and longevity, assuming one was consuming baseline protein levels.

      Lastly, ketosis does not actually change the blood pH by any significant level. This is not to be confused with diabetic ketoacidosis which will result in a drop. The blood of someone in dietary ketosis stays very much in alkaline range. If levels fall too low in a non-diabetic individual, insulin is released and will then prevent any more fat mobilization. Fat will not longer be burned (instead stored) and pH will return within physiological limits. So all of that said, a keto diet should not result in significant drop in blood pH. The body will be sure to maintain homeostasis within proper pH range, assuming one’s pancreas functions normally.

      There are probably other factors at work in regards to northern latitude osteoporosis. Today we know better. Anyone living north of Virginia should be taking ~2000IU of Vit D a day. Some say that even this is too low. There are also other factors that could be at play such as manganese intake, genetic predisposition, the methods of sampling used by the researchers quoted in the study (done back in 1966), work conditions, etc. Point being, there are just too many other variables at work for the other of the paper to state that is a result of NEAP.

      Regardless, I would be sure to get adequate intake of veggies while keeping protein intake within normal ranges. Excessive protein could lead to a slew of problems along with increasing your insulin levels which could kick you out of ketosis. ”

      Sounds like an Attia Jr., doesn’t he? :)

      By the way, he told me that he learned more from your blogs on cholesterol than in his med school lipids class!!

      Final question, after 3 weeks I am still going through the keto flu and want to get out of this limbo asap. Is there any of your blogs that adresses this particular issue of keto adaptation?

      Thank you!!!

      Sammy

    • Peter Attia  December 12, 2012

      Sammy, in case of “flu” I usually do the following:
      1. Document I’m actually “in” ketosis (B-OHB consistently over 0.5 mM, and ideally over about 1.0 mM)
      2. If the above is true, protein levels are usually not excessive
      3. Ensure adequate sodium (easy via bouillon) and magnesium.
      See other comments for details on the above.

    • BC  August 5, 2013

      Thank you for finding this! Exactly! 50/50 ratio (or a tad more carbo to prevent ketosis). See my comments on Dr. Sears and Zone above.

  58. mike  December 5, 2012

    This is the best health related blog out there by far! What’s the ETA on part II? I’m chomping at the bit for more info

    (reply)
    • Peter Attia  December 5, 2012

      Hopefully within 2 weeks. It takes about 20 hours to write one of these posts.

  59. mike  December 5, 2012

    Cool, I will wait patiently. I hope you know that your efforts are not only greatly appreciated, but noble. We need more people like you in this world to save us from the havoc created by the last fifty years of junk nutritional advice.

    (reply)
  60. Malin  December 6, 2012

    Hi Peter,
    Having read a few more of your articles and comments there on I realise you do not answer questions which can be considered to be asking for medical advice.
    I fully understand this,having worked as a GP and Accident and Emergency doctor all my working life.
    I am sorry if you think I am asking for medical advice,I am not.
    I would welcome your thoughts since I have been unable to find the answers in my search of scientific papers.
    If you still find you should not answer ,well maybe I have introduced you to a medical condition of which you may not have been previously aware
    Regards
    Malin

    (reply)
    • wayne  May 6, 2014

      I see a former Emergency responder is in this discussion thread. I posted the following question on the facebook page “Ketosis & The Ketogenic Diet Community”.
      —————–
      Should I wear a medical braclet or something so that an emergency responder (like Malin) would know that I am on the ketogenic diet? If the emergency responder gave me a blood test could he be alarmed at the results and possibly make a mistaken diagnosis concerning my condition?
      I know people who are diabetic that wear a diabetic bracelet. I’m new to group. Has this already been discussed? I came to Ketosis via The Grain Brain book.

  61. oriana  December 6, 2012

    I would like to hear more about eating fruit diets. I was on one and every time I would add food I would gain immediately. It made me want to eat all of the time even after 10 bananas at a sitting. I never could get why I would gain on no fat fruit. I only lost if I ate only fruit all day and nothing else. I know many are going to this who have eating disordered thinking.

    (reply)
  62. Julia  December 6, 2012

    Hi Peter,
    I am wondering what your thoughts are on the effect of diet on blood pH. There is a lot of talk out there about alkaline vs. acid forming foods in the blogs and among certain MDs. Do you have any knowledge on this topic? I am concerned since it seems a ketogenic diet would tend to the acidic side (and potentially leech calcium from bones??).

    Thank you for all you do!

    (reply)
    • Peter Attia  December 6, 2012

      I’ve discussed in various comments throughout the blog. Will address in a post at some point, I’m sure.

  63. Mark  December 6, 2012

    Hey Peter, great post, something that is still not clear to me though is can ketones be metabolised anaerobicly or only aerobicly?

    (reply)
    • Peter Attia  December 7, 2012

      Only with oxygen in the mitochondria.

    • Mark  December 7, 2012

      Awesome thanks for the clarification, I read every post u write and am always impressed, but the thing that always impresses me the most is how on top of comment questions u are. Great job!

    • Peter Attia  December 7, 2012

      Too much to comment on right now. May pen a letter to BMJ editorial board to point out the (obvious) flaws with this study.

  64. JohnJ  December 7, 2012

    A ketogenic diet appear to have so many benefits here is another one.

    http://www.sciencedaily.com/releases/2012/12/121206142025.htm

    ScienceDaily (Dec. 6, 2012) — Scientists at the Gladstone Institutes have identified a novel mechanism by which a type of low-carb, low-calorie diet — called a “ketogenic diet” — could delay the effects of aging. This fundamental discovery reveals how such a diet could slow the aging process and may one day allow scientists to better treat or prevent age-related diseases, including heart disease, Alzheimer’s disease and many forms of cancer.

    (reply)
    • Mark  December 7, 2012

      Does ketosis delay aging, or does eating a carbohydrate rich diet accelerate aging?

    • Peter Attia  December 7, 2012

      Excellent question, and I must admit, I do not know the answer. It could be a bit of both, which would be my guess. In fact (and perhaps this prompted your questions), a hot shot paper came out in Science today, titled “Suppression of Oxidative Stress by ?-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor” which suggests the B-OHB, specifically, is what prevents aging.

  65. Anna Friebe  December 7, 2012

    I just wanted to clarify that ketone body metabolism is nothing specific to humans. In fact it is present in all mammals and most vertebrates, but absent in most invertebrates.

    http://www.biolbull.org/content/195/1/12.short

    The fact that we have this adaptation to survive without food/ carbohydrates for a while does not tell us much about whether it is healty to be in ketosis, and if so for how long. Gluconeogenesis is an even older adaptation to solve the same problem.

    (reply)
  66. G. Suarez  December 8, 2012

    First of all thank you for such an informative website. I have a couple of questions. Through the course of many years, can consumption of CAFO meats, laced with antibiotics and growth enhancers, influence this process in any way? If so how? What about our exposure to chemicals such as phtalates etc.? OK one more, sorry about that, What would be the physiological process(or multiple ones) that would explain why there are individuals that no matter how bad they eat maintain very little SAT and a high degree of muscularity, in spite of not exercising. I think we need to look into why these individuals seem to defy physiological principles.

    (reply)
    • Peter Attia  December 8, 2012

      1. Possibly, but no real data to support or refute.
      2. Ditto.
      3. Muscle vs. adipose vs. hepatic insulin resistance; anabolic factors, things we don’t understand. Why are some people tall and others short? This question is interesting, but probably less relevant than trying to figure out why we’re in the epidemic we’re in.

  67. Rafe Armstrong  December 10, 2012

    Hi Peter.

    First off thanks so much for all your efforts with this websit/blog. I have learned a great deal here in a short amount of time. I am a family practice physician and triathlete. While I have advised patients on the merits of a low carbohydrate diet for quite sometime, I never realized there were potential implications for athletes until I stumbled upon the Phinney and Volek low carbohydrate performance book. After I read it, I immediately decided to give it a try as I have gut issues in long Ironman races and also fatigue issues in the latter part of the run due to not being able to continue to absorb enough calories as a carbo burner. This all seemed like a potential logical solution for me. I quickly found your site after searching for all the information I could find. I finished Ironman Florida the first of November and started my ketogenic diet right after than so I am about 5 weeks in right now. After a week of doing mostly nothing, I started back training with just very low level stuff. Obviously initally it was tough, but it has r not gotten much better yet. I tried to do a 25K trail race this past weekend and after 30 minutes my legs were trash. Cramped and hurting worse than I have ever experienced. I expected to be slower than usual, but this was really bad. 40min slower than last year. I am using the sodium. I also used UCAN. Should I expect more or do I just need to give it more time? Also I have been checking ketones, and while I am staying under 50gm of carbs I am only getting 0.2-0.6 most of the time. Got to 0.8 or 0.9 one time I think. I just don’t know what to expect or really where to go from here. I want to keep trying this as I really think if I can truly become a fat burner rather than a carb burner, I have a lot to benefit. Just frustrated right now. Heart rate is high and light efforts feel hard.
    Any advise or encouragement is appreciated!!!
    Rafe Armstrong

    (reply)
    • Peter Attia  December 14, 2012

      Rafe, definitely sounds like something is not right, especially with such low ketone levels. To fuel the type of work you’re doing, you’d probably want fasting levels between 1 and 2 mM. Post training I’d expect you to be north of 4 or 5 mM. Unfortunately, I’m not really equipped to troubleshoot like this. The other thing to keep in mind is that you may require a greater period of adaptation (it took me about 3 or 4 months). You may also consider some MCT oil if you’re not already.

  68. Chris  December 10, 2012

    IFIK? John Hopkins been reading this blog.

    Hartman and his colleagues examined six children between the ages of 2 and 7, all of whom were on the ketogenic diet and still experiencing seizures. They asked the children to fast every other day. Four out of the six children saw a reduction in the number of seizures of between 50 and 99 percent. Half of the subjects kept up the fasting regimen for two months or more.

    http://www.ibtimes.com/new-study-supports-fasting-treatment-seizures-kids-928171

    (reply)
    • Peter Attia  December 10, 2012

      Hopkins pioneered this treatment for drug-resistant epilepsy. It’s not regarded as standard of care for children who do not respond to multi-drug therapy.

  69. Edward  December 10, 2012

    I wasn’t sure where to put this but it is a sobering thought for anyone who is an endurance athlete. Evidence of short and possibly long term changes in RV function in the hearts of endurance athletes:
    http://eurheartj.oxfordjournals.org/content/early/2011/12/05/eurheartj.ehr397.short

    (reply)
  70. Tim C  December 11, 2012

    Edward,

    That’s a disturbing study, but sobering. Confirms what Mark Sisson has been saying about chronic cardio too.

    (reply)
  71. kang  December 11, 2012

    Peter,

    Any comments on this Harvard study ? it looks pretty convincing, though it was done on mice, the pictures shown significant atherosclerosis for the low carb group.

    Vascular effects of a low-carbohydrate high-protein diet

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741266/

    (reply)
    • Peter Attia  December 12, 2012

      It sure does look interesting. I think the thing we need to be VERY mindful of when looking at studies is this is the following:
      1. Mice are herbivores and did not evolve eating much fat, so when we feed them lots of fat it may be harmful for them. This does not translate to humans.
      2. The high fat chow these mice eat is typically composed of 20-30% sucrose by weight meaning, while it’s still high in fat, it’s really high in sugar (that’s how they get the mice to eat it, I’m told by folks who do these experiments). So it’s also not clear how much the sugar is interfering with the fat.

    • Andrew  December 12, 2012

      One interesting aspect of that study is that the LCHP and Western Diet (WD) groups had no significant difference in traditional serum CV riskmarkers , yet the LCHP developed significantly more atherosclerosis.

      Perhaps that should have measured LDL-P!

  72. Stephen  December 12, 2012

    Hemming,
    I’m not sure what you mean by “tried PD”, but I assume English is not your first language.
    My doc didn’t mention magnesium, but I’ll ask him about it- thanks for the advice.
    I’d suggest reading the studies Dr. Donald F. Klein of Columbia University has done, whose scientific rigor would even make Peter quake. ; – )

    (reply)
    • Hemming  December 14, 2012

      You’re quite right, I’m Danish :)
      I simply meant having had a panic attack.

  73. Andrew  December 13, 2012

    This is maybe a bit off topic but it does have a connection to ketosis so hope it’s OK. I have a question about changes in my lipid profile which I don’t understand but hope that someone can shed some light on. I’m not looking for medical advice but just wonder if anyone can help. Since adopting a ketogenic diet in mid-September my lipids appeared to improve as expected- my TG dropped to 44 from 115 when I was taking Lipitor, my HDL had increased to 111 from a previous 59. My LDL has always been a bit elevated even on statins but had not really changed at 158. My ApoB was .97 g/l which I assumed as maybe OK. My TC was elevated at 278 but I didn’t think this was a huge issue with high HDL and low TG. I had the lipids checked again this week at my family doctor’s request and got what looks like a nasty surprise. My TC has increased to 321, my LDL to 209, and my ApoB to 1.38. My ApoA, which was not measured previously, is now 2.22. Both the Apo levels are well above the local labs normal range. There have been 2 lifestyle changes in the interval between the 2 sets of measurements which may be responsible. I have started a weights programme – not flipping 450kg tyres but still reasonably strenuous. The other change is that I have been taking AAKG for the last 2 weeks as a kind of N=1 experiment to see if it stabilised my ketosis as suggested in a post I saw somewhere. It seems counterintuitive that exercise should adversely affect lipids, so I wonder if AAKG could cause these changes. Does anyone have any experience with AAKG or other helpful suggestions? My diet has been unchanged for 3 months and I have not increased my calorie intake. Sorry about the lengthy post.

    (reply)
    • TwitchyFirefly  January 20, 2013

      I’m not an expert, but I have learned to mistrust the LDL measurement in many blood lipid tests. Unless they are measuring the LDL directly, it’s actually a *calculated* value based on certain assumptions that can lead to a wildly wrong LDL number, up to +100 if I recall correctly)

    • Peter Attia  January 21, 2013

      True, but that’s not the main reason to distrust it. See the cholesterol series to understand why.

  74. steve  December 14, 2012

    been strick low carb for almost 2 years and just had my nmr blood test and im not very happy with the results, i do not think this type of eating is right foe me. im naturally thin and very active.
    LDL-P 2734, LDL-C 126, HDL-C 75, tri’s 92, total colesterol count 219, HDL-P 45.6, small LDL-P 1087, LDL size 21.2 nm, LP-IR 23. i feel my intake of saturated fat is to blame here. im going very strick low fat and upping carbs and i will have another nmr test performed in 4-6 weeks. any thoughts would be greatly appreciated.

    (reply)
    • Peter Attia  December 14, 2012

      I’ll be addressing this issue in part X of the cholesterol series.

    • KevinF  December 18, 2012

      Of course an interesting question Steve is, what was your LDL-P count BEFORE you went low-carb? Seems like everyone goes low carb first, then discovers Dr. Attia or Dr. Dayspring in their studies and learns about the NMR, and then gets their first LDL-P count after being well along into the diet change. FWIW, my first LDL-P count bested yours, at about 2850. Four months later it’s below 1300. The difference? Statins.

  75. Richard Hanks  December 17, 2012

    Dr. Attia, do you have any thoughts on or experience with cyclic ketogenic diets?

    Is whether one is actually really in a full state of ketosis if there are short periods of high carbohydrate intake intermittently thrown in?

    Do you see any benefit to the CKD vs. long-term ketosis for weight loss? Some who advocate a CDK believe the punctuated periods of high insulin in an otherwise ketotic state raises fat-burning hormones and improves thyroid function. Any thoughts?

    (reply)
    • Peter Attia  December 18, 2012

      I think the thyroid issue may be a red herring, though there may be other benefits to doing so. I am not sure there is enough clinical data to support or refute (common theme, huh?).

  76. Tamsin  December 22, 2012

    I have struggled to get my blood ketones above .3 despite eating a high fat, low carb and mod protein diet. I recently got an email from Prof Tim Noakes stating that he had once got his levels up to 2 only when he was in a fasted state or eating no carbs or protein at all just fat. He found that eating any protein at all was enough to kick him out of ketosis. Are some of us just not designed to be able to get into ketosis. It is extremely frustrating.

    (reply)
    • Peter Attia  December 23, 2012

      From the perspective of evolution, we’ll pretty much all do the same thing in response to starvation, which is shown the figure from the Veech, Cahill paper. I think what you may be describing is, as you suggest, more about the gluconeogenic response to protein than the ability to make ketones.
      I have not spoke to Tim about this, so I can’t comment on his experience. There are a few tricks I recommend for folks struggling. I’ll try to detail them in a subsequent post.

  77. Andrew  December 24, 2012

    Sorry to bang on about lipid profiles going haywire on a ketogenic diet, but it seems “unfair ” that something that seems to be so good for you can adversely affect you -as it may have done in my case with elevation in ApoB and LDL. On listening to Dr Dayspring on a podcast on Jimmy Moore’s site, he says that some individuals do this for reasons unknown.
    I have a question related to ApoB levels in relation to ApoA1 levels. I am completely on board with the ApoB level and hence LDL-P , indicating risk of atherogenesis. However, it seems to me that ApoA1 and hence HDL may counteract some of that risk, but ApoA1 rarely gets mentioned. Would this be the result of ApoA associated HDL particles scavenging cholesterol from intimal foam cells? The AMORIS and INTERHEART studies showed that the ApoB/ApoA1 ratio was the best predictor of fatal MI and this applied at all levels of either of the Apos. This seems to suggest that the ApoA1 level adds information on CV risk over that supplied by ApoB alone. I would be so pleased if someone could clarify this for me. In my case my ApoB is 1.38 suggesting high risk whereas my Apob/ApoA ratio is .62 suggesting relatively low risk – so which is more informative?

    (reply)
  78. Tammy Benedetti  December 29, 2012

    Wondering if you have any insight. I am going to schedule an appointment with my Gyn for some labs ( I think he will order any tests I want whereas my internist will order only what she thinks I need). Here’s my issue: I have been eating paleo/primal and strength and conditioning(powerlifting/HIIT) for years with decent success. I have not ever been able to maintain my “goal weight” of 160-165#(5′ 8″ht), but was stuck at 175-178(started out at 260#) which I was “ok” with. Since July of this year, I have gained weight no matter what I do(currently up to 190#). I even tried a VLC diet, eating less than 20gm total carbs for 2 weeks and did not lose an ounce(spot check of calories and macros was 1900cal with 17/146/135 carb/protein/fat). I am deathly afraid of gaining more and ending up where I started. I am still eating well (spot check of calories puts me at 1600-2000cal/day with carbs 100-150gm coming from fruits and vegetables), and working out hard (seeing good gains in strength). Do you have any input as to what labs I should have drawn or what the problem could be?? PLEASE HELP ME!!!!!!

    (reply)
  79. Nan  January 21, 2013

    Absolutely the best description of the many I’ve read on ketosis. We non-scientist/medicos really appreciate such a clear rendering of the information. All I know is that I feel great on ketones after the first couple of headachy days (a couple aspirin usually does the trick). Thank you.

    PS- Everyone who teaches has at some point realizes to their shame that they taught in error, but learning comes with trial and error, even for the teacher. At least you saw the error, and sadly too many won’t even try.

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  80. Sara Garrett  February 16, 2013

    I have a question I have not found an answer to. There has always been this notion that lowering calories past a certain point will decrease metabolism. I see the logic in this ….. if you are not in nutritional ketosis. If when in NK you are burning reserve fuel in the form of body fat and your body does not know the difference between fat fuel that comes from the diet and fat fuel that comes from your fat stores….. wouldn’t it be impossible to decrease your metabolism if you decrease you calorie intake to say 800/day. As long as you were holding protein intake to what it should be….. and holding all other variables constant shouldn’t your metabolism also hold constant.

    (reply)
    • Peter Attia  February 19, 2013

      Very difficult to say…one could argue that as your weight drops, so too does energy expenditure, as you’re moving less weight around. Look at the work of Rudy Leibel and Michael Rosenbaum for this.

  81. Ken  March 19, 2013

    Hi Dr.Attia! I’ve been in ketosis for a little over 3 months now, I plan on trying to make this a long term way of life, the benefits are too great to go back to dealing with the glucose/insulin rollercoaster. My question is this: I’ve lost about 25 pounds and i’m trying to stabilize my weight because i’m getting pretty thin and would like to add muscle. I know you hit the gym and are ketotic so I was wondering what you do to add/keep muscle and what you would suggest. I’m going to start using creatine to add some hydration in the muscles so that would be a little bit of a starting point for me…Please let me know, I appreciate all the info!-Ken

    (reply)
    • Peter Attia  March 20, 2013

      Check some of the other comments in response to similar questions. Protein type, protein amount, and protein timing all play a role. Of course, training plays a role, also, so “being in the gym” isn’t really enough…it’s probably more about how one trains, in addition to the other points.
      I don’t think ketosis is the optimal state for hypertrophy, but it’s certainly possible.

  82. Heidi C.  April 3, 2013

    Hi Dr. Attia! I’ve really enjoyed your website & blog — thanks for dedicating so much energy to sharing this info. My husband is Type 1 Diabetic (diagnosed at 30, he is now 49). After I saw a collective report of 5 years of A1Cs, in which NONE were below 8 (the most recent was 9.2) I knew we had to make a drastic change. He is very fit / athletic and shows no (apparent) complications…yet. But continuing at those levels, there will be no avoiding them. His endocrinologist wants him on a pump… but that’s the extent of his guidance. After much research last month, I literally stumbled upon the primal/paleo diet, and later on your ketogenic “experiment” as well as work done by Dr. Richard K. Bernstein (T1D endocrinologist). Three weeks ago, both my husband and I (in support of his efforts) began eating a strict paleo diet, but I am struck by how little information is available for Type 1 diabetics on low-carb diets. I absolutely do NOT want to do more harm than good… and I thoroughly understand the difference between ketogenic & ketoacidosis — as long as he’s testing & taking insulin he requires, he’s safe. My concern is over clotting changes in his blood, or any other factors which may be affected by our new way of eating. We are both committed to making this a permanent change, and (other than occasional light-headedness) we both feel better. Do you have any trusted resources you can share, for the management of T1D using a ketogenic diet? Thanks in advance for your reply — we have scheduled him with a different endocrinologist to help track his info… hopefully she does not push the American Diabetic Association’s high-carb “just take more insulin” diet.

    (reply)
    • Peter Attia  April 7, 2013

      Heidi, certainly being a T1D poses a few extra challenges, but I know a number of folks with T1D who have absolutely changed their life with this dietary approach, all based on the approach of Dr. Bernstein. Someone with T1D will always require insulin, of course, but it’s not uncommon to reduce requirement by 80% over just a few months.

      A friend of mine is the most obsessive T1D I know and I’ve been begging him to start a blog specifically for T1D patients…hopefully he will soon. He’s so completely knowledgeable about the ins and outs. For many years he would fly from Florida (where he lives) to NY to see Dr. B.

    • leslie  September 1, 2013

      Sure there is: Bernstein’s Diabetes Solution

  83. Another Doc  April 16, 2013

    Peter, was it only last Wednesday that I read about your TEDMED talk and decided to read your articles? Seems like much longer. I am a 50 yo female physician (psychiatry internal medicine actually) and have been working with patients to help them reach their weight loss goals. I’ve been frustrated (and so have they) at what they feel are conflicting messages on what to eat and how to lose weight. Many have failed so many times that I’m amazed that they keep coming back to my support group.
    About 15 years ago I took off an extra 35lbs and am at a good weight and have maintained it without too much trouble. My diet consists of nearly pure carbs, as much sugar as I can eat. Every time I eat them I think to myself, “Wow, you are setting a bad example.” Still, I continued to do it. I couldn’t even give up Chocolate for Lent!
    Something in what I read on Wednesday really clicked with me. I’m not sure what it was, probably the mention of all that I, as a physician, already know….with a new twist in my mind about the true gravity of what I was subjecting my body to every day…specifically high insulin levels.
    In any case, starting Wednesday I decided that I wasn’t going to eat sugar anymore, and was going to try to go VERY low carb….and somehow I have managed to do it! I thought that I craved sugar and carb and couldn’t survive without them. I even joked about how I could never have been a pioneer because there wasn’t any way to transport the amount of Ice Cream that I needed. Since I changed my mind on Wednesday, when I even think of eating carbs (which actually isn’t very often), I think something along the lines of, “what other poison do you want to add to that.” and whatever excuse I was giving to myself just melts away and I don’t do it.
    Up to one week ago I was snacking ALL the time, ALL the time. Starting Wednesday I told myself to Not do that. I eat 3 meals a day, I log my calories in an online program and it looks like I’ve been eating about 65carbs/day. I’ve been HUNGRY a couple of times, but have NOT been craving sugar. I’ve walked past the candy jar 100 times….and when typically I would have grabbed a piece of candy every time, I haven’t had ONE, NOT ONE since Wednesday.
    I’m not sure where this is leading, but I think that I can do this for the rest of my life…and I won’t have to keep berating myself for eating foods that I know have no nutritional value and actually harm me. Thanks for thinking about this. I will try to keep up with your research, seems like you’ve got an open mind and if you find a better idea you will let us know.

    (reply)
  84. Patricia  April 27, 2013

    Hi Peter,

    I live in the UK and I recently read Gary Taubes book on”why we get Fat”. I know the book mentioned Ketosis briefly, anyway great book!

    I have previously been on a Ketogenic diet Which involved only have meal replacement four times per day, which equaled 500 calories per day and I did this diet for >12 weeks straight. Excellent diet lost >4 stones in weight! Experienced the high energy, no afternoon blues, my sleep apnea went and of course loved my new wardrobe!

    Now I’m at a place of having regained all the weight and an extra stone, tiredness has returned etc.
    This time round I want to be in control! I know Ketogenic diet works! But just need to adapt it to real food!

    Please can you show me, literally? I get the science (to a point) but translating into know practically what to buy in a supermarket , with all these labels with “hidden sugar” or substances to which our bodies would respond to it as sugar/starch, is so confusing.

    Please help ;-)

    (reply)
    • Peter Attia  April 28, 2013

      Do you mean fly to the UK and move in with you and “literally” show you? :) I think I’m doing all I can, Patricia. Looks like you’ve already figured it out.

  85. Felix  April 27, 2013

    I don’t know if I should be picky with the chemistry but it is “acetoacetate” and not “acetoacetone” in the technical part on top.
    acetoacetone would be the same thing with a CH3 group instead of the OH group on the right

    anyway it was very interesting to read

    (reply)
  86. Patricia  April 28, 2013

    Hi Peter,

    Lol! Literally in terms of what do I need to consider, in terms of calories per day. The number of calories you consume, you’ve said related to your lifestyle or the level if training you did. I work in an office and I do minimal exercise. The diet I did previously was 500 calories per day. In an earlier post someone mentioned basal metabolic rate. Does this need to be considered in order for me to consume the right ratios. This is the part that’s a little confusing.

    How do I translate all this information to literal day to day planning of meals (what should be included) to achieve ketosis with real food.

    Thank u :-)

    (reply)
    • David Nelsen  April 29, 2013

      Patricia, I’ll give you my 2 cents. I wouldn’t worry too much about caloric intake especially at first. The primary thing you need to do the first few weeks is to start eating a healthy low carb diet. Don’t worry about portion size when you’re adapting. You will naturally start eating less over time as you get use to the new way of eating. Don’t just zone in on a few different recipes, give yourself a variety of things to eat. There are a lot of good resources on the web for healthy low carb eating. See this blog and Mark Daily Apple for starters. You will not lose weight as fast as on the 500 cal per day diet, but the weight will come off and if you continue to follow the plan you will have a lifestyle you can maintain. Good luck. Dave

  87. Patricia  April 30, 2013

    Thanks Dave ;-)

    (reply)
  88. Sarah  June 26, 2013

    Don’t feel too bad about the DKA incident at Johns Hopkins, Peter. Not all of us listen to our doctors anyway! I was in the hospital a few years ago with pneumonia, refused the Prednisone, refused the Heparin, refused something else I don’t remember what, reluctantly accepted the antibiotics, refused the food (mystery mashed potatoes and chocolate cake) they made me sign legal papers, they had someone come “talk sense” to me – and then the doctor – exasperated and exhausted herself – told me that I was being unreasonable in thinking that I needed SLEEP (nurses repeatedly waking me up for their constant checks.) I even made my husband bring a jar of coconut oil from home. Needless to say I wasn’t one of the “good” patients. :)

    Thanks for the great TED talk, which led me to here, because I didn’t know about you. I am very happy to see that you have teamed up with Gary Taubes, who wrote my favorite book of all time, GCBC. (A couple of others, Dr. Eades and Dr. Lustig – glad to see him getting some play in the media too.)
    I did the same thing that you did: I experimented on myself. I’ve been phasing back and forth between low-carb and zero-carb, depending on the season, for several years now, and have found myself naturally falling into cycles of IF too. Most days I only want to eat one main meal, some days I eat more, some seasons I eat a few more veggies (summer.) I lost a bunch of weight (50 lbs), cured my husband’s gout (he isn’t happy about giving up his dried fruit snacks, but the memory of severe pain serves as an excellent incentive) and my Lyme disease is 95% in remission with no antibiotics – (if I eat even a little bit of sugar however, the twinges of pain manifest within a couple of hours.) We have no other health problems, take no prescriptions at all, we feel great, and our brains are clear.

    But despite our results, our friends and family all think we are crazy to eat the way we do, so I am very glad to see yet another doctor who “gets it.” Bless you and Gary T. both.

    (reply)
    • Peter Attia  June 26, 2013

      Thanks very much, Sarah. We may be crazy, actually.

  89. Charlotte  June 29, 2013

    thank you Peter for explaining nutritional ketosis. I am on a ketogenic diet myself since app. 10 months (with HCG which also leads to nutritional ketosis and VLCD for maintance) having lost 75 Pounds so far.
    Dr. Jan Kwasniewsky, a polish doctor has a very good book on ketogenic diet, promoting a high fat, moderate protein and very low carbohydrate diet (Title: the optimal diet). He also claims high success with T1D.
    Simply written for any layman to understand with recepes (typical polish so not to everybodies taste, but can easily be altered).
    I am also a T2D, but off all medication since I started the ketogenic diet.
    I have one question: I was told that being in lypolysis and being ketogenic is not the same. To me it makes no sense but maybe I am missing an important point.

    (reply)
    • Peter Attia  June 29, 2013

      Correct. Future blog post will explain this.

  90. Sofie  July 5, 2013

    “In fact, the late George Cahill did an experiment many years ago (probably would never get IRB approval to do such an experiment today) to demonstrate how ketones can offset glucose in the brain. Subjects with very high levels of B-OHB (about 5-7 mM) were injected with insulin until glucose levels reached 1 mM (about 19 mg/dL)! A normal person would fall into a coma at glucose levels below about 40 mg/dL and die by the time blood glucose reached 1 mM. These subjects were completely asymptomatic and 100% neurologically functional.”
    +
    Cancer eats sugar.
    =
    Cure for cancer?

    (reply)
    • Peter Attia  July 5, 2013

      Will address in part III of this series.

  91. Ellen Poage  July 15, 2013

    I just found this study and it distressed me. I have been doing this low card diet <80 for 2 weeks. Its been a struggle. Never realized what a sweet tooth I had. Anyway, I'm doing fine, not thriving yet, but persistent, and I found this article. I attached a description. Anyway I do worry about bone density but mostly I worry about acid environment. I have been testing pH and it runs low…

    http://www.familypracticenews.com/news/child-adolescent-medicine/single-article/bone-growth-affected-by-ketogenic-diet-in-children-with-epilepsy/841b08dd834bb1dc8c081231f9af7f7c.html

    VITALS
    Major finding: Participants on the ketogenic diet demonstrated a mean bone mineral density lumbar Z-score decrease of 0.1756 units/year. Bone loss was greater in children who had higher baseline Z-scores (–0.28 vs. –0.04 units/year).

    Data source: A prospective, longitudinal study of 29 children who were treated with the ketogenic diet for more than 6 months during 2002-2009.

    Disclosures: The study was partially funded by Pfizer Australia. Dr. Mackay did not have any financial disclosures.

    The findings highlight the risks of a ketogenic diet, which relies on fat metabolism to induce ketoacidosis. A neutral pH is necessary to mobilize calcium from bone, Dr. Mackay said.

    (reply)
    • Peter Attia  July 16, 2013

      Ellen, I’m reasonably familiar with this literature, though a few explanations may exist:

      1. (relative?) Protein deficiency, which is pretty common on these diets for this population;
      2. Suitability of these diets in children which rapid bone growth (vs. adults);
      3. I did not read the study, but if not a randomization, not sure “matched controls” didn’t have other differences in their lives to cause the difference in bone density (e.g., activity).

  92. Robin  July 26, 2013

    Thank you so much for this blog and all of the amazing information.

    I have two questions related to nutritional ketosis:

    Thomas Seyfried and others suggest that to reap the metabolic benefits of ketosis (particularly for the brain to be able to utilize B-OHB), that one must be in a state of “therapeutic” ketosis where the blood ketones are higher than blood glucose. He suggests a 3 day fast to get the glucose low enough to achieve that “therapeutic” state. My question is, my blood glucose is usually in the low 80′s and my B-OHB is most always between 2-4 (Except maybe first thing in the morning). Does this mean I am not reaping the metabolic benefits of ketosis, especially my brain? Should one really aim to be in this optimal therapeutic range where glucose ketones are higher than glucose? I thought I was doing quite well, but now I’m not sure what the goal really is. Is it just having ketones in the 2 or above range or do we want Blood Glucose to get as low as 55-65 mg?

    My second question is that Seyfried, Dominique D’Agostino, etc, suggest that a ketogenic diet is only EFFECTIVE if calories are restricted to between 1,000-1,500 calories/day. They say that eating an “unrestricted” caloric ketogenic diet can be quite harmful. I would love some clarification about this. IF I ate that few calories, my weight would drop (and it did) beyond what I believe is optimal. I am working hard to eat over 1600 calories/day to get back up to a weight of 114 lbs for my 5’3 height. But then this results in what they refer to as an “unrestricted ketogenic diet”, which they suggest, like I said, doesn’t get you any of the metabolic benefits of ketosis. Please help to clarify. I am so confused!!

    (reply)
    • Peter Attia  July 26, 2013

      To question 1, I’m not sure about that, but I’d love to see the data. Without starvation or extreme caloric restriction, it’s difficult to get BHB (in mM) higher than glucose (in mM). Not impossible, but at least for me, it only happens after a very long bike ride at about 60-65% VO2 max. So while I agree that a threshold is probably necessary, which is likely much higher than the typical 0.5 to 1.0 mM most people think of, I’m not sure this rule applies. Furthermore, in most folks BHB and AcAc exist in a 1:1 ratio, so while we measure BHB in plasma, we ought to double it (roughly) to calculate total ketones. Under this assumption, I’d have an easier time believing this.

      As to your second question I can’t really speak for them, but I know Dominic (not Dominique) well. In fact, I’ll be spending 2 days with him next week. So I guess I can ask him.

  93. Robin  July 26, 2013

    Hi Peter,

    With regards to question 1, I’m glad to hear this isn’t your experience either! What do you mean by a 1:1 ratio with BHB and AcAC? Isn’t the later something yo measure on a urine stick? How would you get a number for that?

    I’d love to hear what Dom says about keeping calories between 1,000-1,500 to get the benefits of ketosis. I’m wondering if he’s referring to patent’s with cancer – in which case the answer to question 1 might be the same. Please let me know how he responds.

    One other question: A practitioner I work with recommends protein pulsing (avoiding protein 2-3/days a week). This is supposed to have huge benefits for the immune system, etc. I have started doing that at least twice/wk. by simply eating more fat and getting my protein down to about 4-5% of my intake. I’m curious if you know anything about this way of restricting protein. Interestingly, I’ve observed that on the mornings following a non protein day, my ketones are significantly more elevated. Would love your thoughts.

    Lastly, do you have a calculation for figuring out the amount of protein you eat per day. I’ve read that one only needs around .8-1 gram per kg of lean body mass. For me, who recently had my body mass tested, this would only amount to 39 grams of protein/day. I”ve also read that one should get about .6-1kg per LB (instead of kg) of lean body mass. If I went with this calculation, then I’d be getting more like 55 grams of protein/day. I find this issue very confusing. I’d love your thoughts about calculating optimal protein amounts.

    Thanks so much. I really appreciate being able to have this dialogue.
    Best,
    Robin

    (reply)
    • Peter Attia  July 27, 2013

      Yes, AcAc is more typically measured in urine, but this is qualitatively. It can be measured quantitatively in blood, but is typically only done for research purposes.

  94. robin  July 27, 2013

    HI Peter,

    I’d love your thoughts about the second part of the question of skipping protein altogether 2-3 days /week (Ron Migurney has a book about this called Protein cycling). Apparently this activates the immune system and good stuff happens, including increased autophagy, etc. .

    I’m wondering if you have any thoughts about the possible negative effects of skipping protein 2-3/days/ week – and whether you think it is important tn to eat protein every day in order to maintain muscle mass. I am 5’3 and weigh about 114. I also have osteoporosis, so am very concerned about maintaining and gaining lean muscle mass. My body fat percentage is 22.9 and my lean muscle mass is 87 lbs.

    I’d love your thoughts about the protein skipping as well as what you’d suggest in terms of protein amount. I’ve been eating about 55 grams of protein/day when I do eat protein (12% of calories). Not sure if this is sufficient or not. I do high intensity strength training 2x/week and interval cardio 1x/week, Am I getting too little, too much, etc, for my goal of maintaining my weight and muscle mass?

    Much appreciative of your help with sorting this out!!

    (reply)
    • Peter Attia  July 27, 2013

      I have no insight to this, but can’t imagine a great rationale for skipping protein, especially if physically active.

  95. Marion  August 12, 2013

    Since being on low carb, high fat diet, I have had leg cramps. I take supplements of Ca, Mg, K, Vit. D regularly. Then I read about sodium deficiency caused by this diet so started drinking 1 tspn Bovril in a mug of hot water twice a day. This worked dramatically for a few weeks but then the cramps came back at night but not nearly as severely. As I have osteopaenia, I am concerned about taking too much salt as it can cause Ca loss from the bones. What should I do?

    (reply)
    • Torben Deumert  August 17, 2013

      The fact that the muscle cramps were gone temporarily seems to indicate that you removed the cause of your cramps. Given that this happened once you increased sodium, the sodium or the sodium in conjunction with at least one of the other supplments seems to be the responsible for the reduction in cramps.
      Because there are several causes for muscle cramps, what you can do is to test for yourself what brings you relief. Try increasing/reducing one supplement at a time to figure out which one helps. I would do it for several weeks, so you can see if it really helps.
      There are four things I noticed (which are missing from your post):
      1. You say you take your supplements regularly. What does that mean exactly? Regularly could mean “every 2 hours” and it could mean “every year on 15th Feb”.
      2. What dosages are you taking?
      3. Which form are you taking?
      4. When are you taking them? (Meaning: approx. which time of the day?)

      The reason I am asking these question is that I noticed for myself that they matter. Several years ago I had leg cramps several times a month, although this happened primarily during winter. There are several things I noticed during this time:
      1. Mg really helps. Nowadays, I take about 400mg of Mg about 1h before bedtime; sometimes I additionally take 100mg-200mg during the day, which I put in my drinking water; to which I also add salt (about 2g-4g/day, depending on what I eat, my exercise level, the temperature etc.). Mg was – for me – the most important supplement. I chose MgCl as a form, because I could use it topically or in a bath, it definitely works for me and it’s inexpensive (depending on brand, of course)
      2. Cold feet/legs. One of the most most important triggers I noticed for myself are cold feet/legs. You might wanna make sure your feet or at least legs stay warm during the night. Long pants and maybe even socks can help a lot.
      3. Sodium does help me. I added the 2g-4g of salt/day when I got into ketosis. I seem to do better by not overdoing salt, but especially when I am sweating a lot due to exercise and/or weather, 2g don’t seem to be enough. Given that you are taking potassium, you might also want to experiment with reducing K instead of increasing sodium to see how the sodium/potassium ratio does affect you.

      I don’t know anything about osteopaenia, but I don’t think it would heart to try a little more salt/Bovril for some time to see if it helps. I would be surprised if a few grams of salt a day would cause or be detrimental for osteopaenia in someone who eats healthy and takes D3 and K2 as a supplement. Maybe high intensity exercise would also help in increasing bone density, although osteopaenia in itself does not seem to be a problem as long as it doesn’t progress to osteoporosis.

      Those are just a few thoughts. Maybe some of it can help. It seems to me that you are on the right track. And testing things for yourself really is the best thing you can do; especially when it comes to things like muscle cramps which seem to be caused by a lot of different factors.

  96. Torben Deumert  August 21, 2013

    Hi Peter,
    I am wondering if you are aware of any ideas of how to measure the state of keto-adaptation. I find the current approach of “get your blood ketone levels >=0.5mmol/l and wait 2-4 weeks in the hopes of being keto-adapted” a bit lacking and am wondering if you are aware of any work being done to improve this situation.
    I also think that the argument against urine ketone sticks is also true for blood ketone sticks to a lesser degree, in that blood BOHB levels only tell you how much is there, but neither how much is produced nor (which is probably the most important information) how much is actually used. So measuring blood ketone levels, while a step up from ketostix, seems to be only a stopgap and we will probably need something better for accurately assessing the state of ketosis in the future. Given that nutritional ketosis seems to catch the interest of many people, hopefully more work will be done in this field.

    (reply)
    • Peter Attia  August 21, 2013

      I am not. The “real” way would probably involve some combination of muscle biopsy and complex serum assays. I’m not sure the numbers — levels or duration — are perfect. A more conservative estimate based on my experience is: morning fasting levels of BHB between 1 and 2 mM repeatedly and about 3-6 months.

  97. Julia  August 23, 2013

    Peter, if you have had your pancreas surgically removed can you live without insulin if you follow a ketogenic diet? If so, can a Type 1 diabetic also survive without insulin on ketogenic diet?

    (reply)
    • Peter Attia  August 23, 2013

      No, one needs insulin to live. I’ve seen a few anecdotal cases of people with T1D on KD being free of insulin, but it suggests they have a tiny bit of beta cell function remaining.

  98. Richard S.  August 24, 2013

    Peter.

    What do you think of ApoE tests and the implications from them? Specifically, do you think that genotype might explain our individual reactions to diets, meds, alcohol, etc.? (Many sites and researchers are suggesting that we should take ApoE genotype into account for all those things, but I’m sleptical until I see more research.)

    My test came back as ApoE 2/4, which some say is the same as being a 3. Since only 2% of the population is like me (2/4), I doubt anyone will do a definitive study to confirm that anytime soon. From my n=1 experience, the no-carb, high-fat, moderate exercise approach is working fine. I was on a clear path toward metabolic syndrome before I found this blog. I’ve had great success since, and I’m not inclined to change because someone says ApoE 3′s (and 2/4′s) should eat more carbs and less fat.

    Would you mind telling us what you think of these tests, and what type you are?

    Thanks!

    Richard

    (reply)
    • Peter Attia  August 24, 2013

      It’s one of the few genes I pay attention to since it gives, I believe, actionable information. The 2/4 allele combo is an interesting one. As you note, it’s about 2% of the population (by contrast 2/2 is 1% of the population, about the same as 4/4), so we’re not sitting on piles of data. I am mostly use apoE for 3/4 and 4/4 alleles. I’m a 3/3.

  99. Maryann  August 26, 2013

    Hi Peter, by “actionable” do you mean that you agree with studies that recommend avoiding saturated fat for 3/4, 4/4? How is this compatable with low-carb? Thank you

    (reply)
    • Peter Attia  August 26, 2013

      I don’t think apoE is the right gene to give us insight into SFA. If anything, I’d look at apoCIII.

  100. Maryann  August 26, 2013

    What is your approach to Apo E 3/4 and 4/4? Thank you

    (reply)
    • Peter Attia  August 26, 2013

      Very patient specific. No formula.

  101. Just wondering  September 5, 2013

    Hello. :)I just came across your site. Thanks so much!
    I am wondering if you have heard of the K-E diet. It’s where they insert a pediatric nasal tube and you get MCT oil and a powder for 10 days. Puts you into ketosis and you lose about a pound or two a day. Is this dangerous? On the urine sticks you will get to the very dark purple the 150 for 5-8 days. Depending on the person. You take nothing by mouth except for water and chicken broth. What do you think of this? A what point would muscle wasting occur? How often do you think you could do it? Thanks so much!!
    http://kediet.com/

    (reply)
  102. Sean Mackesey  September 8, 2013

    Thanks for a fantastic and very informative article Peter. I just wanted to point out a slightly ambiguous/confusing line: “Molecules shuffle back and forth, around the cycle, and kick off spent carbon (carbon dioxide, termed “waste”) and reducing agents (e.g., conversion from NAD+ to NADH) for the ETC.”. It sounds from this as if there is a “spent reducing agent”, when really there is an oxidizing agent (NAD+) that has been “spent” and thus become a reducing agent (NADH). This is potentially quite confusing for someone new to chemistry. I’d change the wording to “kick off reducing agents (NADH, generated from the oxidizing agent NAD+) for the ETC and spent carbon (carbon dioxide, termed “waste”).”

    (reply)
    • Peter Attia  September 9, 2013

      Thanks, Sean. Will try to modify at some point.

  103. Lynn  October 12, 2013

    I’m a Type 2 diabetic. I can’t get into ketosis. My liver seems determined to keep adding glucose even when my glycogen stores should have been depleted. I was eating a diet with a ketogenic ratio of over 2. My blood glucose never normalized, and after at least 10 days on this diet, my liver was still capable of raising my BG by 60+ points mg/dl from vigorous exercise. My ketostix and NovaMax meter showed that I never got to a good ketosis level. I finally stopped the diet because I was worried about what part of my body my liver was taking apart to get the raw material to make glucose. I want the benefits of ketosis. How can I control my liver? Help!

    (reply)
  104. kris  October 17, 2013

    You mentioned that too much protein would prevent ketosis, wouldn’t too much protein turn into fat or be toxic, aren’t ketones created once you begin gluconeogenesis, the latter requires energy, and then most of the body then runs on ketones except the brain.Of course if your diabaetic, you will have hepatic gluconeogensis, I’m not exactly sure if metformin would then have a positive or negative effect in the blood sugar, since met rarely causes low blood sugar, does the met stop working or stop interfering with liver dumping , or does that body become very insulin resistance and dump a lot of glucose in the body?

    There doesn’t seem to be a clear answer.

    (reply)
    • Peter Attia  October 17, 2013

      Protein to fat is a virtually non-existent pathway outside of massive overfeeding. True, protein “overfeeding” (i.e., beyond the amino acid requirement of the body) will result in GNG, some of which can technically result in DNL, but this is pretty small.

  105. Kristin Andersen  October 21, 2013

    Hello, I’m just starting to read the information and it’s a bit overwhelming and challenging to understand. I am 50 and need to now begin taking care of myself instead of my family. I am a full time English teacher and cared for my mother in the last 5 years of her life, which was exhausting. One of my former students has lost 75 pounds and she suggested I start here by reading your article. Now where do I begin the life style change and weight loss program?

    (reply)
    • Peter Attia  October 21, 2013

      Kristin, hopefully much of the info you need is all within this blog and other place it directs to.

    • Yossi Mandel  October 21, 2013

      Kristin, from a fellow beginner: Start by watching Dr. Attia’s TEDMED talk to understand the underlying concept. Then read his journey following the “about me” link for his personal nutrition journey. You can get another overview at http://www.dietdoctor.com/lchf. While you’re working on it, read all the posts here one at a time to learn how to troubleshoot and how to find and read the science studies that will help you troubleshoot. Good luck!

  106. Ahmed  October 21, 2013

    Hi Peter, I am really proud of you , I came to your site yesterday accidently and was so amazed of your knowledge and way of thinking. I am type 1 diabetic and following low carb on and off until I decided to follow a under 40 low carb diet strictly and that was 4 days ago ,,,my BS numbers since then is so great between 80 to 110 and my novo doses goes down from 35 to 8 a day or so, my question to you is I am very stubborn in losing weight, what else should I do to lose weight .
    Also my dr. is scaring me about ketoacidosis too much, I know the difference very well but because I do swim every day so I am afraid that DKA may happen or no , I do not know I am confused…also my lipid profile is always crazingly high (like 100 TG) I have to take medication to lower it…should I stop it cos I started the very low carb diet or no>>.I will take your word as advice as Drs. here in middle east lack this kind of information that you have Sir…thanks and Again I am really proud of you

    (reply)
    • Peter Attia  October 21, 2013

      Ahmed, ketosis requires very careful management for someone with T1D. You must have your doctor’s support. I’m not sure you need to restrict CHO this much. Would suggest you look at the book by Dr. Richard Bernstein.

  107. Ahmed  October 21, 2013

    sorry I mean 1000 TG

    (reply)
  108. kris  October 24, 2013

    Pete, you weren’t clear , people,doctors,dietitians, are saying that you are already in ketosis as long as you carbs are low, because in order for protein to convert into glucose the body needs energy which results in ketones, being produced, the body then adopts to using the ketones and saving the glucose for the necessary organs.

    Of course then there is the situation where there is not much protein to convert, but many state that is under-desirable because it uses your muscles for glucose. Then of course there is of a disorder being that your body is doing hepatic gluconeogensis which is treated by metformin, there is confusion and even fitness websites promoting the use of metformin.

    (reply)
    • Peter Attia  October 24, 2013

      Sorry, Kris, my brevity usually means I’ve addressed the point multiple times elsewhere. Hopefully someone else chimes if you can’t find it.

  109. kris  October 27, 2013

    Maybe I could be clearer, the claim that excess protein turns into glucose and inhibits ketosis may not true, of course the term excess is used loosely, as excess doesn’t necessarily mean 12 pounds of meat a day, but can mean more than say 50 gram.

    Dietary Proteins Contribute Little to Glucose Production, Even Under Optimal Gluconeogenic Conditions in Healthy Humans , http://diabetes.diabetesjournals.org/content/62/5/1435.abstract.

    Also, energy is needed in order for gluconeogensis to occur, thus ketones are already being generated and used by the body and glucose for the brain and vital organs, when this occurs cells become insulin resistant because they are running on fat and directing glucose to the brain, (Sort of like a traffic roadblock and alternate route), fasting bs is elevated but not very high and hba1c is usually normal and post meal glucose.

    (reply)
  110. Josh  November 21, 2013

    I have Type 1 Diabetes. Is it dangerous for me to enter nutritional ketosis? Could it potentially kick me over to DKA quicker if my blood sugar rises or if I mis-dose my insulin injection?

    (reply)
    • Peter Attia  November 21, 2013

      Refer to book by Dr. Richard Bernstein.

  111. jane  November 22, 2013

    I’ve just come across your blog. Thanks for the science. I have finally got into ketosis, by following Dr Phinney’s guideline. It has been a week now and i did have carb flu one night, but increased my salt intake and now feel awsome! Never felt this good since my 20′s. I have begun mountain biking and am interested in your biking experiments. You say you ingested carbs on this particular ride. I have read of ultra runner running 50 milers and more on just plain water or maybe a few carbs. Have you done any more tests when ingesting fewer or more cabs at different times?
    Thanks again I’ll keep reading your inspiring blog

    (reply)
    • Peter Attia  November 22, 2013

      Yes, described in post about carbs and ketosis.

  112. QueenBee  November 29, 2013

    Amazing !! I am in 2nd week phase 1 on atkins and a pharmacist tried to convince me to get off it when I asked about a ketone monitor…many thanks for the detailed analysis! U gave me faith in what I’m doing! Bless u !

    (reply)
  113. Evan Jay  December 7, 2013

    Dr. Attia:

    Let me preface by saying I wasn’t sure where to post this comment, so I picked this topic as it is one I’ve read probably 10 times now.

    I just finished reading the “2013 AHA/ACA/TOS Guidelines for the Management of Overweight and Obesity in Adults” which has been accepted for publication, but not yet printed. (I obtained it via the Obesity Society website if you are interested.) I found it quite interesting, they have finally made a statement that a LOW FAT diet is no better than a LOW CARB diet for weightloss. Furthermore, they make it very clear that the lack of research is upsetting and the need for more research on the concept of low carbohydrate diets is definitely necessary. With all the current data on changes in carbohydrate, and specifically added sugar intake, I have yet to come across an organization who came out and actually contradicted what the government’s recommendation is for a healthy diet/weight loss. Although it didn’t say a low carbohydrate diet is superior, it DID say that a low fat diet is NOT superior for weightloss. While I do understand (or think I do) how the concept of nutritional ketosis is beneficial to weight (fat) loss, I do wonder how relevant a non-ketogenic, low carb diet is for weightloss. That being said, I sure hope NuSi has something brewing!

    This is all with no regard to the link with metabolic syndrome, insulin resistance, and the diseases that going along with them. In fact, it stated that not enough evidence is available to make a recommendation on preventing CVD. Another first-time contradicting statement as far as I am aware (which may not be fully up-to-date). I like your take on obesity, as a signal for disease rather than a disease in itself. It makes me wonder why there is so little attention given to the link between diet and metabolic syndrome related diseases as opposed to all the attention given to diet and obesity. Do you think this will change? or is it changing?

    I am currently in the process of starting an organization at my University to promote this current movement based on the quality research and statistics that we do have. Throughout meetings with various health care professionals I have come to the conclusion that until the general public can back off the concept of “cut fat and eat whole grains instead” any effort to suggest a new style of diet will be useless. That being said, national organizations like the AHA/ACC/TOS making such “radical” statements is a great place to start. So I guess my purpose for this post was just that…to spread the statements made in this article.

    If you have time to read it, or have already done so, please let me know your opinion and their recommendations. I’d love to hear what you have to say.

    Thanks as always,

    Evan Jay, PA-s

    (reply)
    • Peter Attia  December 9, 2013

      Evan, I have read it. Unfortunately. I say ‘unfortunately’ because I find it to be almost complete void of evidence and, worse than that, downright ignoring of the vast evidence that does not seem to port with the incoming bias of the committee. Definitely not he high point of my day/week/month when I slog through it, though it sure provides motivation of push harder and faster at NuSI.

  114. Andrew  January 3, 2014

    Wow, great article!
    I turned to a permanent modified ketogenic diet 3 months ago after suffering from necrotizing pancreatitis 3 years ago. II lost 34 kgs of weight as I didn’t eat anything much in hospital (3 months in ICU!)
    I had >95% of my pancreas removed and the gall bladder removed also.
    Up until 3 months ago, pain was really affecting me as well as very nasty and serious digestive issues. I was prescribed oxycodone and having constant pain as well as taking pantoprazole and imodium to ease the digestion.
    Thankfully, I am not a diabetic, but the ketogenic diet has stopped the pain and digestion problems.
    I am also fat malabsorpent (as showed in a triolene test), so the fat levels have to be watched.
    I have lost 4 kgs of fat which is nice but I’m really liking the fact that I’m not in pain anymore just by watching the sugar and carb intake.

    (reply)
  115. Martin Söderholm  February 6, 2014

    In the anaerobic vs aerobic graphic, you seem to indicate that the fermentation of pyruvate to lactate yields 2 ATP. But that’s not correct is it?

    http://cl.ly/image/2w3H3p2l1N1M

    (reply)
    • Peter Attia  February 7, 2014

      What should it be?

    • John Pelley  March 26, 2014

      Correct. The production of lactate does not produce ATP, but instead serves the function of recycling NADH back into a form that can be used in glycolysis in order to keep its production of ATP going. The lactate is circulated back to the liver where it is converted into glucose to maintain blood sugar.

      As a personal note: I am a new subscriber and intend to recommend this blog to our first year medical students at Texas Tech where I teach metabolism.

  116. Greg  March 2, 2014

    Ok, so I’ve been in ketosis for 4 weeks now. If these past few days are any indication, this has cured a 12 year run of abysmal health with multiple chronic exhaustion related health issues. I was completely sidelined, couldn’t work, exercise, marginalized, always feeling uncomfortable. I was the walking wounded. A far cry from my ultra running and 80 hr work weeks. 12 years of this, 25 Drs, no one suggested metabolic syndrome, pre-diabeties, insulin issues, although my signs, symptoms, and blood tests display some near and sometimes out of range results. I was a carb junkie. Thank goodness for the internet. Can’t wait to see what month 2 brings.

    (reply)
    • Peter Attia  March 3, 2014

      Wow, sounds more dramatic a change than most folks experience.Thanks for sharing.

  117. Greg  March 4, 2014

    Peter,

    Do you think my dramatic change could be relative to how far down the scale and duration of chronic illness I was experiencing? I’m keen to understand if all this time I was in fact in a state of metabolic syndrome or even borderline given my own personal unique physiology.
    A review of lab results these last 10 years; (I copy my results and self experiment, a lot)
    Triglycerides; 164, 142, 140, but also several in the 80-115 mg/dl range
    HDL; 43, 47, 48, 49, also several in the low to high 50s
    Fasting Glucose; 118, 108, 100, 99, 95, 90, 91, 88, 75, 81
    A1C; 5.7, 5.7 in last 2 years, 10 years ago one test 5.5
    BP; consistently 150-160/100-110, I was 140/90 whole adult life including ultra running days, but also high carb
    Weight; shot up 50 lbs when this all began 12 yrs ago, waist went from 34 to 42

    I seem to be over, under, boarderline but don’t know what that really means. I intend keeping on the keto plan, early results FEEL good. But I’m afraid to go back to the Drs who allowed this situation to continue as they all point back to the SAD/exercise strategy, what’s the point. So it would be nice to confirm with some degree accuracy, if I have in fact nailed down the root cause. Of course considering nothing is precisely 100%.

    Your thoughts are greatly appreciated.

    Greg

    (reply)
  118. pone  April 2, 2014

    Type 2 diabetes is primarily a disease where the liver overproduces glucose endogenously. There may also be insulin resistance in response to carbohydrates ingested, but after some time glucose comes back to a set point that is too high. Is there any evidence that on a ketogenic diet the level of endogenous glucose of a type 2 diabetic will reset lower?

    There are plenty of blogs where the authors are type 2 diabetics and saw exactly this effect. Does anyone do a study on a larger group and quantity the effect?

    (reply)
  119. Tracey  April 14, 2014

    Hi Peter,
    Could you please explain how sugar alcohols found in sweetners affect ketoadaptation.
    Thanks look forward to your reply

    (reply)
    • Peter Attia  April 15, 2014

      See post on artificial sweeteners.

  120. Jessica  May 2, 2014

    Hey Peter,
    I have read a ton of your posts/articles but I am having trouble understanding the relationship between carbs and ketosis. Specifically I am referring to the amount of carbs consumed per individual and how it affects their blood ketone levels. It seems that some people can consume large quantities of carbs and stay in ketosis, while others struggle to remain in ketosis with very limited carb quantities? In addition, from reading your articles, its seems that the longer you are in ketosis the more carbs you can add (I am thinking about the evolution of your “what I eat articles”)?
    On a personal note I am struggling to reach optimal ketosis, even while limiting my total carb intake to less than 20 grams. I have also immediately felt more energized after eating green beans (and the like). The following mornings my blood ketone measurements are close to .9. Basically I am asking if it is possible for an individual to be THAT sensitive to carbs that something like green beans could kick one out of ketosis.
    I would really appreciate a response to this note.
    Thanks for your time!
    Jessica

    (reply)
  121. Stephanie  May 2, 2014

    HEADACHES! I too have a very difficult time staying in Ketosis and keeping blood sugar in the acceptable range even with under 20 carbs per day. I have been very strict with low carbing for over three months and basic low carbing for almost 3 years now. Within the last 3 weeks (since I have really become very constantly strict) I have started having terrible headaches. The headaches are so bad I am having a hard time working and I don’t like to take tylenol or other over the counter remedy. They really don’t help either. I have searched your website and didn’t come up with “low carb headaches”. I am aware that when you first start, fatigue and headaches can be common but this has developed more recently. Actually when I first started I had boundless amounts of energy and now it is very low. I wake with no headache and it develops around 11:00 and continues to get worse throughout the day and then I start all over again. I have rotated my diet to be sure it is not food sensitivities but nothing. Can you please give me any insight as to how I can correct this problem…add more carbs — reduce fat –. Thank you so much! P.S. I drink over half my body weight in water and also consume bone broth soup regularly.

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  1. Nutritional Ketosis Experiment: Day 2  November 27, 2012
  2. Peter Attia series on ketosis | it's the satiety  November 27, 2012
  3. Motivational | see darren run  November 28, 2012
  4. Ketosis – Advantaged or misunderstood state? (Part I) - The Eating Academy | Peter Attia, M.D. | Bacon is health food | Scoop.it  December 1, 2012
  5. The Food Revolution – AHS 2011 | Whole Food Diets  December 2, 2012
  6. Monday’s WOD  December 3, 2012
  7. Low-carb, high-fat, wheat-free, paleo-ish, primal-ish, ketogenic diet links - We live here now.  December 7, 2012
  8. Ketosis – advantaged or misunderstood state? (Part II) « The Eating Academy | Peter Attia, M.D. The Eating Academy | Peter Attia, M.D.  January 1, 2013
  9. Ketosis: Fear, Uncertainty and Doubt - Ketopia  January 14, 2013
  10. Why can't I look like Mark Sisson!?!?! - Page 25 | Mark's Daily Apple Health and Fitness Forum page 25  January 23, 2013
  11. Question about Keytones  January 28, 2013
  12. What is “IF” « CrossFit Rhodes  February 1, 2013
  13. Ketogenic Diets for Cancer and Beyond » Diagnosis: Diet  February 3, 2013
  14. should we feed kids as if they are “elite”? « Primal Goalkeeping || 'Keeper Central  February 21, 2013
  15. Low carb + lower fat - Page 24 | Mark's Daily Apple Health and Fitness Forum page 24  February 21, 2013
  16. Low Carb - FTR Poker Forums  March 2, 2013
  17. Keto-brain?!!! :) - Page 2  March 2, 2013
  18. this is not a meal plan | Primal Goalkeeping || 'Keeper Central  March 16, 2013
  19. Thirteen Weeks, Week 7: Ketosis! | Fat of The Land  April 2, 2013
  20. Ketosis Friendly Cheesecake  May 1, 2013
  21. Low Carb Triathlon Training  May 26, 2013
  22. Shieldmaid’s Guide to PaleoWorld | Shieldmaid  May 31, 2013
  23. 5 Most Common Low-Carb Mistakes (And How to Avoid Them)  June 24, 2013
  24. 2 x 5 rules for Low Carbers  June 25, 2013
  25. What I eat. - Sondra Rose: Happy Mind • Healthy Body • Wise Heart  June 27, 2013
  26. 5 Most Common Low-Carb Mistakes (And How to Avoid Them) | Health Impact News  June 28, 2013
  27. 5 Most Common Low-Carb Mistakes (And How to Avoid Them) | Chiropractic Care Cartersville GA  June 29, 2013
  28. Top 10 Evidence-Based Health Benefits of Coconut Oil  July 8, 2013
  29. VLC to jump start fat burning? | Mark's Daily Apple Health and Fitness Forum page  July 8, 2013
  30. How to carb up without starches | Mark's Daily Apple Health and Fitness Forum page  July 13, 2013
  31. The cause of obesity re-conceptualized. It’s not all about calories. | The Meal Matters Most  July 23, 2013
  32. How excessive carbs and insulin can make you fat and/or ill!  July 30, 2013
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  35. Benefits of Coconut Oil | Best Workout Gear  August 2, 2013
  36. What is the Best Creatine To Take to Maximize Muscle and Strength Gains? | Efficient Gains  August 5, 2013
  37. Interesting Reading | Diet Junkie Gets Real?  August 11, 2013
  38. Low Carb High Fat (LCHF) Links « Jeff Gilbertson  August 14, 2013
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  41. Cyclical Ketogenic Diet – Best Bodybuilding Diet Ever? | Fitness Baron - Build Muscle, Burn Fat and Look Great  September 12, 2013
  42. 45: John Kiefer & Dr. Rocky Patel | Cyclical Ketogenic Diets For Health And Performance | Jimmy Moore Presents: Ask The Low-Carb Experts  September 13, 2013
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  44. Eat yourself to a better life | Rethinking Truth  December 8, 2013
  45. Low Carb High Fat (LCHF) Links « links for healthy living  December 29, 2013
  46. Links for December 29th through January 8th  January 9, 2014
  47. 5 Most Common Low-Carb Mistakes (And How to Avoid Them)  January 19, 2014
  48. How to make a fat cell less not thin: the lessons of fat flux « The Eating Academy | Peter Attia, M.D. The Eating Academy | Peter Attia, M.D.  January 22, 2014
  49. Is Coconut Oil Bad For You?| Diammi.com  January 24, 2014
  50. Emagrecer de Vez | Por Que Você Retém Líquidos? | Emagrecer de Vez  January 24, 2014
  51. A few questions on Ketosis | Mark's Daily Apple Health and Fitness Forum page  January 27, 2014
  52. Hi! I'm new to the site! - Page 23  January 30, 2014
  53. Top 10 Evidence-Based Health Benefits of Coconut Oil « Roatan Dream Homes  February 2, 2014
  54. O que realmente é Cetose? | Dia a Dia Low Carb  February 5, 2014
  55. Links for December 22nd through February 1st  February 6, 2014
  56. Top 10 Evidence-Based Health Benefits of Coconut Oil | Coach Michael Gowan  March 4, 2014
  57. Ketosis | Ginkgoil  March 11, 2014
  58. Ketosis vs. Diabetic Ketoacidosis | abradl31  March 29, 2014
  59. Ketosis | Defeating Diabetes  March 30, 2014
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  63. What is Ketosis? Part One  April 29, 2014
  64. Flour-less Banana Pancakes | Love, Natalia  June 10, 2014
  65. Coconut Oil Health Benefits | Nourish | Balance | Heal  June 27, 2014
  66. Health Benefits of Coconut and its oil | girlssblogdotcom  July 4, 2014
  67. 10 Health Benefits of Coconut Oil |  July 19, 2014
  68. How losing weight and adopting a ketogenic diet has changed my life. – xhelensarahx | www.xhelensarahx.com  July 21, 2014