Ketosis in a Nutshell – Part 1, What’s Up?

Macadamia integrifolia (Macadamia Nut) - culti...

- - an inside joke – macadamia nuts are popular among those seeking ketosis.

We Newly Have Practical Access to a Potentially Major Health Intervention

CLUNK  - – Click, click … whirrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr …….

The recent adoption of home testing of blood ketones as a tool in the use of nutritional ketosis is like a missing gear being dropped into place. Many streams of knowledge and progress are brought together in a new and newly workable way.

Ketosis and Nutritional Ketosis – What is this?

You can learn to eat in a way that causes you to burn a lot of fat while burning low amounts of glucose. In the process, your liver will produce ketones, these will travel in your blood stream (ketosis) and be burned for energy. You have altered your “nutrition” to be in a state of “ketosis” – thus the term “nutritional ketosis”. This is also referred to as eating a “ketogenic diet”. When you do this over time, you gradually become more adapted to functioning in this state. This is called being “keto-adapted”.

This is all entirely different from diabetic ketoacidosis, which is a very serious medical emergency that can develop very rapidly and is potentially fatal. Ketoacidosis is precipitated by dehydration in the context of insulin deficiency. A person who is not deficient in insulin function will not develop ketoacidosis.

It seems to be talked about a lot recently. Why the buzz?

This is an eating strategy that can act as powerfully as a medication.

This eating strategy may improve your sense of well-being and physical performance.

It may be useful in many more situations, involving many more people, than we thought.

It has now become much more practical to use as a long-term choice than we thought.

Known and Potential Uses:

(1) Medical

When considering what we know of nutritional ketosis, plus what new insights and research suggest, nutritional ketosis has or may have a substantial role to play in:

  • blood sugar control
  • management of metabolic syndrome
  • visceral fat control
  • obesity
  • appetite control
  • epilepsy, in both children and adults
  • Alzheimer’s Disease and some other neurological conditions
  • and what others unknown?

(2) General Well-Being

Besides the above, many people who have become keto-adapted report that they just feel a lot better over-all. Many report improved energy levels, mood or mental clarity.

(3) High Performance

Beyond that, being in nutritional ketosis can mean improved physical performance, particularly in endurance activities. Competitive athletes are making use of this.

Great – But is it Usable? Is it Practical Long Term?

The key to unlocking the great potential for benefit is that nutritional ketosis must be a realistic, practical option for long-term use. This has been the major block. Why consider it as an option for people to use if it just seems to be much more of a burden that a help?  Why do a lot of research about something that won’t be used?  It must be worthwhile – the benefits must be worth the “costs” in effort, limitations, risks, etc.

The key criticism of ketogenic diets and thus of the use of nutritional ketosis as a health tool or medical treatment has been that they are “too difficult” and not worthwhile over time.

(1) Poor testing options mean we have not been able to accurately assess either long term benefits or long term practicality.

A “ketone” is a type of molecule, not just one molecule. However, the tests measure just one of the types of ketone molecules that the body produces when in ketosis.

Until recently, the only test for ketosis that could be used day-to-day at home was urine test strips. Blood ketone testing could be done at a medical lab, but this was too expensive and awkward for routine use. The trouble is, urine test strips are not very useful for monitoring the level of ketosis once a person has become adapted over weeks to being in ketosis.

The reason ketone test strips were developed and marketed is so people with diabetes can test themselves for ketones and so have early warning if they are headed for ketoacidosis and need to seek urgent medical attention. The urine strips test for a molecule called acetoacetate, which shows up in the urine right away when someone is just going into ketosis or has been in ketosis a short time. For diabetics, this works very well and is a cheap, convenient test (at least, for those people with diabetes who are not chronically in low-level ketosis from choosing to eat in a way to be in nutritional ketosis).

When people eat in a way to develop ketosis, the body adapts to this. Part of this adaptation is that the metabolism of the various ketone molecules changes. The level of acetoacetate molecules go down, so that, for example, the person can be in a low level of ketosis and yet this might not show on a urine test strip.  In this situation, use of blood ketone testing provides much better information.  Blood ketone home monitors test for a different ketone molecule called beta-hydroxybutyrate.

Blood ketone home monitors have been available for a while, but have been little known outside of the field of diabetes and even then, not widely used. Their potential role as a tool in the use of nutritional ketosis has only recently arisen as a topic.

The particular trigger for this was the publication in April 2012 of the influential book The Art and Science of Low Carbohydrate Performance by Jeff S. Volek, PhD, RD and Stephen D. Phinney, MD, PhD. Subsequently, awareness and interest in the topic has surged in the wake of the reports by Jimmy Moore of the very widely followed blog Livin” La Vida Low Carb, detailing of his personal experiences with using blood ketone testing. Jimmy Moore’s n=1 Experiments: Nutritional Ketosis Day 91-120

(To be fair, I should acknowledge that the first mention I saw of blood ketone testing meters was on Dr. Peter Attia’s site in March 2012.)

(2) Any medical treatment that cannot be well monitored or adapted to the individual over time will always appear less effective and more burdensome than it truly need be.

It may be that the benefits of nutritional ketosis have been masked by lack of ability to monitor or target the degree of ketosis properly for individual tolerance and benefit. That is, perhaps the lack of good testing options has meant that the way ketosis has been used has made that it appear less effective than it really can be and, at the same time, more difficult or burdensome to live with than need be.

Deliberately eating in a way to cause ketosis has basically been used in two ways:

  • as a medical treatment for epilepsy, in which extremely strict diets were used
  • as part of a low carbohydrate weight control plan (Atkins Diet), of which ketosis is a major tenant. The lack of ability to accurately test to see if a person stays in ketosis over time, and the degree of ketosis, has likely been a source of confusion and inconsistency – likely major factors in the degree of variability in people’s responses and how people do over time.

(3) Blood ketone testing brings individuals a better chance of finding lasting benefit.

Consider a person who has benefits from being in sustained ketosis (being keto-adapted). If that person is going in and out of ketosis or having wide fluctuations in their degree of ketosis, those benefits will come and go in confusing, unpredictable ways.  In this case they may well find that the efforts and costs (things they give up, changes in their life, any side-effects and risks, etc.) are not worthwhile over time. If they choose to abandon their efforts to be in ketosis, they then get zero benefits.

If they can use home testing of whether they are in ketosis and the degree of ketosis, they can use this to more accurately perceive any benefits. With more effort and time they can get a reasonable idea of what level of ketosis is associated with what degree of benefit. In terms of the costs, they will have realized what eating patterns or other factors are required for them to be able to be in ketosis or at certain levels of ketosis. From experience, that person can begin to form a judgement of what the balance of benefit versus cost is for them. There is a better chance that they may find at least some level of benefit that they are able to enjoy long term because they are able to choose a level of costs that they personally find worthwhile.

The benefits a person can notice for themselves will often be only part of the story.  Assessment by their physician, possibly including lab tests and other investigations, is a necessary part of considering what the benefits have been.  Even then, some of the benefits may be difficult to evaluate and some may be slow to develop and only evident over years.

Similarly, it is dangerous and unwise to assume that the harms and burdens a person notices themselves are the whole picture. Again, assessment by a physician, possibly including lab tests and other investigations, is a necessary part of considering what harms there have been and what the ongoing risks are. Even then, there may be unrecognized or hidden harms that do not become evident until some years later

(4) Blood ketone testing will open up progress in understanding and research.

People can communicate with each other and with their health providers much more effectively about their experiences with nutritional ketosis.  Researchers can target new questions and new areas of potential benefit.

For example, many research studies have been done to evaluate the benefits of low carbohydrate diets. Yet, none of them have used monitoring of blood ketone levels as a tool to evaluate the presence or depth or variability of nutritional ketosis despite the fact that it is one of the key proposed beneficial mechanisms of low carbohydrate programs. (** see addendum below for correction)  Again, consider the fact that if a person is unknowingly moving in and out of ketosis they are likely to find this very disruptive and un-satisfactory, which could well lead to abandonment of the intended eating plan and a perception that it is not worthwhile.

So, There is Promise  – What are the Risks or Concerns?

We are in the early stages of understanding about nutritional ketosis and how this might be useful for general well-being or medical purposes. The potential for benefit seems to be large.

What we already know for sure is that some people’s bodies seem to adapt well to ketosis and some people’s do not. There are some people for whom nutritional ketosis is not suitable.

We need to learn much more about possible side-effects and potential for harm, especially long-term. We do already know about some side-effects and harms that can develop that we need to be cautious about – for example dehydration, exaggerated  medication effects and serious problems with sodium and potassium. There is considerable potential for harm from un-recognized long-term deficiencies of essential nutrients, as feeling “full” does not in any way mean that one is well “filled” with the essential vitamins and minerals.

As with everything else in health and medicine, there is wide variation between people in the benefits and the harms that any individual may personally experience.

The trade-offs and cautions and risks (an incomplete list):

  • this requires following a very specific eating pattern, and this needs to be learned
  • that eating pattern needs to be consistent over time, with little use of “breaks” or “holidays” from the eating pattern
  • it takes a while for your body to adapt to using ketones for fuel and, until then, you may have side-effects and feel tired or unwell
  • you will be more susceptible to dehydration, to low blood sugar, and to potentially serious problems with the “electrolytes” sodium, potassium, calcium and magnesium. If you don’t take the time and effort to learn about these things,and are not prepared to be disciplined about them, do not consider proceeding.  Beyond that, there are medical conditions and medications and herbal (and other) therapies that can mean you are even more susceptible to these problems, and these must be considered. Nutritional ketosis is not appropriate in all situations.
  • there are certain situations or medical conditions that would mean that you should not use nutritional ketosis (or should do so only with knowledgable professional help). One particularly critical consideration is that there are certain medications that may need to be changed or doses adjusted before starting and possibly at frequent intervals in the first days, weeks and months.
  • you will need to put some time and effort into learning how to not harm yourself with poor nutrition while eating this way. Feeling full does not in any way mean that your full nutrient requirements are being met. Poor nutrition can be hidden and not produce warning signals that are obvious or easily understood. Our ability to monitor with lab tests how well you are stocked with the many essential vitamins and minerals is remarkably poor.
  • children and pregnant women require special consideration beyond the scope of this article.

This is an incomplete list. Even 5 years from now, it will not be possible for anyone to produce a complete list. The full risks of harm from nutritional ketosis, especially over a prolonged time, are not known. Have caution.

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** Addendum Sep 29/12  – Touched by an Angel – Thank-you to Jenny Ruhl for gently pointing out my carelessness in this paragraph.  What I wrote was not correct as stated and what I wrote did not match very closely what I was trying to express.  I’ll take another stab at it.  – Many studies have been done to investigate the usefulness of the “low carb diet” approach to weight loss. These fall into two types. One type of study is basic research – “what can we demonstrate happens when we carefully do “x””.  “How does the body respond under these circumstances?” They are done on relatively small numbers of people and under close supervision.

The other type of study is designed to see how useful the intervention “x” proves to be in larger numbers of people in something closer to a real-world situation  – this intervention “x” may have certain effects on the body, but is it useful under practical circumstances?  When you offer this to people, do the benefits play out as expected?  As part of this – do people continue with the intervention or do they abandon it for one reason or another?  As it turns out, generally in these larger studies there are many people who do not follow the low carb eating plan as instructed for very long into the study period.

These results form a major justification for the continued claim and perception that “low carb diets” may be theoretically useful but fail in the long run, and they fail specifically because people find they are not able to stay with the diet plan.

“Low carbohydrate diets” are not necessarily ketogenic diets, although they may be, and this causes confusion and error.  From what I recall, the emphasis in these larger studies is on the “low carb intake” rather than on the “dietary ketosis” itself.  If you go back to Dr. Atkins’ 1972 book, he strongly emphasized the critical role of ketosis, with low carb being the means to that end. Then you have to ask yourself, what is being tested?  I think the question has been muddied, which, if so, would certainly compromise the usefulness of the research results.  In research, it is all about the question.  If people aren’t taught that ketosis is the central target, how to be in ketosis and then adequately supported in understanding, trouble-shooting and individualizing their lifestyle/health/diet program to optimize their ability to attain and maintain ketosis, then what is being tested may be any manner of other useful questions about various degrees of limitation of carbs in the diet, but the results of the study will have no meaning towards questions about dietary ketosis.  Having people do urine ketone testing may or may not represent this level of focus and support.

For example, the description of the low carb diet used in the 2008 study published in the New England Journal of Medicine, in which they did use urine ketone testing:

“This low-carb, non-calorie restricted diet aimed to provide 20g/day of carbohydrates during the induction phase (first 2 months), and returned to this level of severe carb restriction after each religious holiday. At other times participants were instructed to increase carbs gradually up to maximum of 120g/day to maintain the weight loss. Total calories, protein and fat intake from any source (except industrial -trans fats) were not limited.”

This is a brief summary of the “low carb diet” used in this study:

Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.

Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B, Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM, Blüher M, Stumvoll M, Stampfer MJ; Dietary Intervention Randomized Controlled Trial (DIRECT) Group.

N Engl J Med. 2008 Jul 17;359(3):229-41. Erratum in: N Engl J Med. 2009 Dec 31;361(27):2681.

PMID: 18635428  Free Article

They were testing a more liberal version of the “Atkins diet”, which is a perfectly valid thing to do.  There are many aspects of the whole ball of wax referred to loosely as “low carb” that are in need of study.  They were not trying to study ketosis and they did not claim to have learned anything about the value or effects of sustained ketosis.  In the full text, they only report the urine ketone level at baseline (pre-diet) and at 24 months.  I don’t see any mention of urine ketone testing at any other time or of the participants using at-home urine ketone testing as a way to monitor whether they are in ketosis or as a way to prompt any changes in what they are doing.  Of course, a part of the reason for this may be the awareness of the imprecision of urine ketone testing in milder states of ketosis once a period of adaptation to ketosis has passed.

Given that they are reporting on their results with a “low carbohydrate diet”, even though they did not study ketosis, the results may be mis-interpreted as applying to sustained ketosis.

If people are unknowingly and inconsistently moving in and out of ketosis, it would be expected that they would experience the appearance and disappearance of both welcome effects and unwelcome side-effects.  It would be expected, in that circumstance, for weight and appetite and energy levels to fluctuate widely.  This could be expected to be very discouraging and result in many people abandoning the diet.  The sudden jump in hunger when moving out of ketosis would often lead to even greater food intake, putting the person firmly out of ketosis.  Carbohydrate craving in this circumstance can simply be a sign of moving out of ketosis, but, without proper education and awareness about ketosis, is likely to always be interpreted as an emotional desire for carbs or as “missing them” too much (which can also happen).

I hope that the increase generally in research and interest related to ketosis, along with the availability of home blood ketone meters, will lead to :

  • a clearer framing of the question and study design, taking the above into consideration – are they studying ketosis or not
  • if they are NOT studying ketosis, a recognition of the importance of a study design that does not ignore the possible confounding factor of ketosis
  • if they are proposing to be studying ketosis, or Dr. Atkins’ original claims, a recognition that teaching the study participants a “low carb diet” or “very low carb diet” and having it “sort of” followed is not any longer an acceptable proxy for studying a “ketogenic diet”

*******************************************

To be continued …. Part 2

Important Note: This article is written to promote discussion. It is not intended to be medical advice. It is not intended to promote the use of a ketogenic diet or nutritional ketosis by any specific individual. Any person who would like to consider the use of a ketogenic diet or nutritional ketosis should first seek the advice of their personal physician. This article is an overview and does not provide enough information for anyone to use for clinical decision-making.

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

The Terms

“Ketosis”  means there are “ketones” in your blood. People have at least a very small amount of ketones in their blood all the time. Generally, the word “ketosis” is only used when the ketones are more than just the usual very low day-to-day background level.

“Ketones”  are a type of molecule you produce in your metabolism. They are produced in the liver during the breakdown of fat molecules. These ketones do not show up in the blood at more than trace levels unless there is a lot of fat being broken down in the presence of low supplies of glucose. Insulin stops the production of more than trace amounts of ketones, and insulin levels are higher with increasing amounts of glucose.  Ketones are a valuable fuel molecule and an essential part of our metabolism. They are not directly harmful in any way except if they reach extremely high levels, which can only happen in diabetes (see “ketoacidosis”).

Ketones can be used for fuel by almost all the organs and cells of the body. One of the especially important things about them is that they are the only fuel besides glucose that the brain can use. The brain uses ketones for a fuel very readily, but ketones can not be used in all the ways that the brain uses glucose, so there is always a need for an adequate, normal level of blood glucose (some other cells also need glucose, such as the retina and the red blood cells).

“Ketone bodies”  – In chemistry, there are many, many molecules that are of the type classed as ketones.  When we refer to “ketones” in your body, by common usage we are specifically meaning three molecules named acetoacetate, acetone and beta-hydroxybutyrate.  Technically beta-hydroxybutyrate does not fit the definition for ketones. Functionally, beta-hydroxybutyrate acts like a ketone in that it can readily be metabolized back to acetoacetate, thus acting as sort of a transit or storage form of ketones. The term “ketone bodies” is useful in that it has been used as a catch-all phrase to refer to these specific three molecules (one of which is a ketone supplier, rather than a ketone itself). (Note: this description amended Sep 29/12)

“Ketoacidosis”  is a very serious, potentially fatal condition that can occur in people with diabetes. Having insulin in the blood to stops ketones from going very high, so people who produce enough of their own insulin will not develop very high ketone levels no matter how they change their food intake. Even people in starvation do not get ketoacidosis (unless they are diabetic).

“Nutritional ketosis” or “dietary ketosis” means that, because of what you have or haven’t eaten, your body is making more of the type of molecule called “ketones”. This distinguishes ketosis caused by reasons outside the body from ketosis produced by abnormal function of the body (deficiency of insulin).

“Depth of ketosis”  or “degree of ketosis” refers to how much the level of ketones in the blood rises.  You are “deeper in ketosis” as your blood level rises higher.

“Keto-adaptation”  is a term coined by researcher Dr. Stephen Phinney M.D. to refer to the fact that it takes some weeks and up to 2-3 months for a person’s body to fully adapt to functioning in a state of nutritional ketosis. That is, to become adapted to using fats and ketones as the predominant fuel, instead of the usual situation, where glucose is used as the predominant fuel. Part of keto-adaptation is that there is a normal, steady  blood level of glucose, with the glucose coming mostly from sources within the body, rather than coming mostly from the digestion and absorption of glucose from food.

9 thoughts on “Ketosis in a Nutshell – Part 1, What’s Up?

  1. Thank you for this article Dr Dea. Will your Part 2 discuss where we can obtain this device for home use? I’d love to get my hands on one! I know I experience all the positive effects of being in a “keto-adaptive” state you mention in your article , it would be great to monitor it at home! I run a fine line between hypoglycemia (caused by hyperinsulinemia) in the presence of too many carbs *for me* , and and at lovely place of “keto-adaption”. That is where my insulin levels never spike thus:
    no hypoglycemic episodes,
    decreased appetite ,
    no panic attacks due to compensatory adrenaline spikes from hypoglycemia (so MOOD is much better),
    and the list goes on and on…
    I look forward to Part 2!

    • Hi Linda and thanks for your comment. Yah, I love being keto-adapted, too. Ketophile, for sure. You can see my posts from May on blood ketone testing by clicking the catagory “ketosis as haven” or I have a page on Resources and Supplies at my site My Keto Haven http://myketohaven.com/resources-and-supplies/ You’re right, though, I don’t say much about how to get the meter itself. I was a bit surprised when I was able to just get one at my local pharmacy. However, that particular pharmacy is the regional main pharmacy for a major chain – the are also the only place in town I have been able to find the strips and they only ever carry 2 boxes at a time of the strips. I have the impression that this resource (blood ketone monitoring) is actually very little used in the diabetic community – at least not here. I really get the impression that there aren’t many people in town besides me buying the test strips. The first 2 boxes I got were only a few months from their expiration dates.
      I know you can also find the testing meters online – try a diabetes supply outlet. The price issue is not the meter, it is the testing strips. So don’t let the price of the meter itself sway your decision. Find out which test strips you can find at the best prices. I read reviews online and tried to decide about the meters. Basically, the Abbott (Medisense) strips seemed to be more readily accessible in my experience in Canada. Sometimes you can get the meter free or very low cost if you buy a large box of glucose test strips at the same time – which is useful to watch out for lows or drops.
      When I first saw mention of blood ketone meters on Peter Attia’s site (then War on Insulin) I think it was February, but, since his site has been re-organized with the switch to Eating Academy, I was only able to link to his post from early March, which I don’t think was his first mention. Since I’d never heard of these meters, my first instict was to look to buy it online. The costs of the strips quoted at US sites, such as Amazon, was so high that I waisted time trying to choose between the two meters and trying to price compare. I decided I would stop dithering and try to pick up a meter when I went to Denver in April for the ASBP and Nutrition and Metabolism meetings. Of course, I picked up a hot off the press copy of Phinney and Volek’s book there, which made me want my new toy all the more. After all that time looking online and waisting time, I was so surprised to just be able to ask for it at that pharmacy and they had one, with testing strips at $20 per box!
      There is so little knowledge about the ins and outs of maintaining optimal keto-adaptation that we will all have to knock our heads together and try to find insights from each other’s experiences. The glucose lows or drops followed by stress hormones I think is going to turn out to be important for a number of the people who don’t easily cruise in the sweet zone. I imagine your heard Jenny Ruhl comment on this in relation to exercise last week on Jimmy Moore’s Ask the Low Carb Experts. I look forward to hearing more about your experiences.

      • Yes, I listened to Jenny Ruhl comments on the podcast ( her experiences rang so true for me!) and just recently ordered her book for my Kindle. Thank you for pointing me towards where to find the blood ketone meter and what to look for (it seems like it’s like buying a printer- the printer is cheap , where they “get” you is buying the replacement ink!).
        I will check out more of your posts in your different categories for more info. So glad for the info you have already provided! Thanks again!

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