The Ketogenic Diet

The Ketogenic Diet

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The Ketogenic Diet

 Over the past few decades practitioners and researchers have been searching for the holy grail of macros for fat loss. During that search, the Ketogenic Diet has been extensively studied because it is an interesting tool as it “hacks” an aspect of our physiology.

Is that hack something that conveys additional weight loss benefits?

We dive into the research and talk about the practical applications of ketogenic diets.

Now before we dive in I want to be honest about personal stance and plant a flag in the middle of the open. I am going to be upfront about my stance before you dive into this article so you can gauge my level of bias and take the writing below with whatever level of salt you feel necessary.

I don’t hate the Ketogenic Diet.

I find it to be a tool that can be used successfully in some context and unsuccessfully in others.

Now with that out of the way lets dive into the science

 

What is the Ketogenic Diet?

A full, deep, nuanced discussion of what exactly the ketogenic diet is beyond the scope of this article. However a basic understanding of if is necessary and for those of you who are new to the concept let me break it down quick and dirty (a lot of this is borrowed from our previous article on the same topic)

Ketosis is a metabolic state that occurs when dietary carbohydrates are in such low quantities that your body must rely almost exclusively on fatty acid oxidation and ketone metabolism to produce ATP.

You have tissues in your body that can utilize either carbohydrates or fat and function fairly well (e.g. muscle tissue)*. You also have tissues in your body that use glucose really well but can’t really function on fatty acid metabolism (e.g. your brain). This is part of the reason why regulating blood glucose is pretty important (there are more reasons but lets keep it to the point).

Now when you run out of dietary sources of glucose (e.g. dietary carbohydrates) and your body runs low on its stores of glucose (e.g. muscle and liver glycogen) you body has to find ways to provide fuel to tissues like the brain.  It accomplishes this task by producing ketone bodies that are released into the blood for our brain and other tissues that don’t utilize fat for energy.

The ketogenic diet allows us to survive on no food intake for long periods. When we look at ketosis from a biochemical and physiological standpoint one could argue that the ketosis is essentially a survival strategy/mechanism. I think that is an appropriate way to look at it as it is indeed a survival adaptation and that raises some interesting questions. However, that doesn’t necessarily mean it is a bad thing.

Additionally, to the point of this article, the ketogenic diet allows us to live for long periods of time on virtually no carbohydrate intake. Thus, we can live with insulin levels much lower than normal.

  CICO vs Hormones

The real crux of the ketogenic diet hangs on the underlying theory of obesity and what is the primary driver of fat storage.

Currently, there are two popular ideas that are viewed to be in direct conflict. The first is the Calories-In-Calorie-Out model of fat mass regulation. The second is the Hormone Model (aka the carbohydrate-insulin model).

The Calories-In-Calories-Out (CICO) theory of fat mass regulation relies on the first law of thermodynamics and treats the body as a bomb calorimeter. It essentially states that body weight, and in essence body fat, is simply an equation of “what you eat” versus “what you expend”.  See the figure below for a graphical summary

cico

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The Hormone Theory of Fat Mass Regulation (often called the carbohydrate-insulin theory of obesity) suggests that calories are not what dictate fat mass, it is the hormones in your body, mainly insulin, that predicts it. See below for graphical summary

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Let us distill these to theories down to a sentence each:

  • CICO: A calorie is a calorie, it does not matter what type of calorie it is, they are all equivalent.
  • Hormone Theory: The accumulation of fat mass is a result of dietary carbohydrates leading to elevated insulin levels which shifts metabolism into fat storage and away from fat oxidation.

We are going to be unpacking these and their respective roles in body fat regulation in a future post but for now lets move on.

 Testing The Hypotheses

Both of these models lead to testable predictions, the hallmark of science.

I think it is most appropriate to borrow the words from someone far smarter and well versed on this topic here (Dr. Kevin Hall), “A logical consequence of the carbohydrate-insulin model is that decreasing the proportion of dietary carbohydrate to fat without altering protein or calories will reduce insulin secretion, increase fat mobilization from adipose tissue, and elevate oxidation of circulating free fatty acids. The altered metabolic and endocrine milieu is therefore predicted to relieve the state of cellular internal starvation** resulting in decreased hunger, increased body fat loss and increased energy expenditure. In contrast, a more conventional model asserts that a calorie is a calorie, meaning that isocaloric exchanges between dietary carbohydrate and fat will not substantially influence energy expenditure or body fat”.

Essentially, if the Hormone Theory is right, right lowering carbohydrates and equally increasing fat will have a greater advantage for fat loss; if the CICO model is right then there will be no difference. Graphical summary below

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The Hormone Model is, in essence, the whole impetus for the Ketogenic Diet

 The Data

While there is indeed a rich history of ketogenic diets in research (we will discuss this below), only recently have we seen studies conducted with a high enough level of control to provide enough hard data to answer this question.

The most recent studies conducted addressing the role of the ketogenic diet are the two studies conducted by Dr. Kevin Hall.

Since science is an iterative process and the chronological nature of learning is important let us start with the first study.

Study 1

The first study was essentially a cross-over design where people were fed either a restrictive carbohydrate diet or a restrictive fat diet for 6 days after 5 days on a  baseline diet.

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To summarize the findings from this study, they found that decreasing carb intake did lead to increased fatty acid oxidation and decreased carbohydrate oxidation; however, reducing fat intake led to a slightly bigger loss in body fat than the group that restricted carbohydrates.

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To real important finding from this study was that an increase in fatty acid oxidation (one of the measurements that is considered a benefit of the ketogenic diet) doesn’t necessarily result in more fat loss, in fact it may be the opposite.

Study 2

This study is one of the most tightly controlled and well-designed dietary studies done to date. Metabolic wards, metabolic chambers, DEXA, doubly labeled water, multisite, mutli-investigator, and well done statistics . . . this is the Cadillac of dietary studies.

Briefly, “Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein”.

In this study the subjects lost about 0.8 kg of body weight (with 0.5 kg from body fat) during the 15 days of the high carbohydrate baseline diet. The ketogenic diet led to a rapid weight loss of 1.6 kg due to water weight loss as only 0.2 kg of body fat were lost during the 15 day ketogenic diet).

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So during this study the participants lost about 1 pound of body fat during the 15 days on the higher carbohydrate diet while they only lost about ½ pound on the ketogenic diet. This all occurred despite lower insulin levels and higher ketone bodies present during the duration of the ketogenic diet phase. This suggests that the ketogenic diet does not offer a metabolic advantage for weight loss during this time frame either.

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Practical Applications

  • The Ketogenic Diet is a Tool

I am going to repeat my statement from the introduction. I don’t hate the Ketogenic Diet, the diet is a tool that can be used successfully in some context. It doesn’t make sense to hate a dietary tool.

It can be used appropriately or inappropriately. If you are a practitioner know the scope and circumstances in which you should and should not use this tool

  • The Ketogenic Diet can Result in Fat Loss

I am going to be completely objective here. There are a host of studies showing that ketogenic diets work for weight loss.

Let me repeat that; YES you can lose weight on a ketogenic diet (we shall discuss this in depth below). But that is not the focal point here.

  • The Ketogenic Diet does not Convey a Meaningful Metabolic Advantage

As stated immediately above the Ketogenic Diet can result in fat loss. The real question is, does the ketogenic diet convey a large or meaningful advantage over other dietary modalities for weight loss?

Based on the data we currently have I believe the answer is no.

  • The Ketogenic diet as a Medical Therapy

From my understanding and knowledge of the literature, the Ketogenic Diet was initially used as a therapeutic agent for difficult to control seizures in pediatric patients.

Brain metabolism different than the metabolism of other organs and it appears that ketone metabolism in the brain conveys a therapeutic benefit in many neurological conditions.

Additionally, there are some pilot studies showing benefit for ketogenic diets in patients with brain tumors (specifically glioblastoma multiforme).

The studies need to be interpreted with the appropriate context because cancer is a multi genotype, multi phenotype, multi metalobic type disease. There is data to show that some tumor types actually can survive and thrive on ketone metabolism (1, 2, 3). Much more research needs to be done in the clinic and at the bench before practitioners start prescribing the ketogenic diet to people with cancer.

 

The Wrap Up

 The Ketogenic Diet is a nutritional tool that can be used to drive a caloric deficit in people who find the dietary framework agreeable and executable.

It doesn’t seem to convey magical weight loss properties but it can be used in specific contexts for fat loss more effectively when it results in higher adherence.

View it as a tool, employ it in the right situations!

 

 

*We also need to stop throwing around phrases like, “The brain/heart prefers ketone bodies over glucose and fatty acids”. Your cells don’t prefer anything. Cellular metabolism is a function of chemistry, set in a biological setting (thus the whole notion biochemistry). Chemistry doesn’t prefer anything, it proceeds “forward” based on specific conditions and certain properties (remember physicsàchemistryàbiologyàphysiology with each later phenomena an emergent one from the previous one)

**Cellular Internal Starvation as a theory for driving epistemic hunger and obesity is a loosely held together hypothesis with substantial contradictory data. This will be touched on in future articles

18 thoughts on “The Ketogenic Diet

  • Was there any consideration of the studies and theory that there is a period of ketogenic adaptation, such as with the Voltek study published in June of 2015? I also did not see mention of how ketosis was measured, since many of the ketogenic theories are predicated upon the state of ketosis being maintained for some period of time? The main reason I pose these questions is that it has been discussed in other studies the principle that, fat mobilization and use as substrate happens after a period of adaptation for which 15 days seems not sufficient.

    • We did take that idea into consideration. The idea of “keto adaptation” has been thrown around a lot but very few people actually know what the means and how to interpret it. The original paper by Phinney in 1983 made the claim that adaptation occurred fairly rapidly (Less than 4 weeks http://www.sciencedirect.com/science/article/pii/0026049583901051). I have yet to come across substantial evidence that a ketogenic diet provides a meaningful benefit for weight loss when compared to a isocaloric, protein clamped, non-ketogenic diet.

  • Do you have a favorite diet, or is it more dependent on individual genetics and physiology?
    The Keto is the only diet that has had tremendous impact on my weight loss.

  • Brad, give the ketogenic diet a try yourself. This is the best way to know how it works. :)

    • I’ve tried it. 3 times in my life. for 16 weeks each time. Once during a “bulking” phase, once during a “cutting phase”, and once during a, “Get strong as possible” phase.

  • Brad –

    Good article overall but I think it’s important to emphasize that not everyone in the “hormonal” camp is necessarily stating that CICO is sufficient to explain obesity.

    Even critics of the Insulin Hypothesis (like Stephan Guyenet) would agree with some of what Taubes is saying – it’s just that they believe CICO is an important part of the equation, the over eating is driven by the brain and changes to the brain and the hormone of interest is leptin.

    They would agree that refined and processed foods are to blame – but the culprit goes beyond refined carbs. They would also be equally critical of the idea that CICO explains obesity –

    There’s a lot of researchers who would fall into this “leptin / hormone / neurological” view of what drives over eating and subsequently – obesity.

    Your article is excellent – and I appreciate the balanced view. I just wanted to bring up this point because it seems many evidence based folks don’t actually understand that there are legitimate lines of evidence and Scientists doing research that look at things beyond obesity as an accounting problem.

    • Hey Mike! Thanks so much for the cogent, on point comment. I completely agree with you. The CICO model is essentially the overarching umbrella that we have to fit our theories of obesity in. There are a lot of things that dictate energy out, including hormones. I am actually working on a piece to cover this idea and show those pieces and their relative importance (it is going to take me a while as it is a super complex topic and a ton of data to wade through). I briefly cover this in the video I did on the topic (https://www.facebook.com/sciencedrivennutrition/posts/1251382168220046). Although to be fair the topic gets more lip service and a brief nod to the factors than a good deep explanation. I also cover this a bit but in a different light in my article (sciencedrivennutrition.com/lose-fat-and-gain-muscle/) and show the breakdown of CICO in the real world.

  • The second study is stupid. You can’t compare both diet this way. The Keto diet is started after already 4 weeks(8400 kcal!) of calorie restriction, we all know that the resting metabolism slow down with calorie restriction. Also as mention before there is time to be keto adapted. Let’s do the same study starting with the Keto diet first, I think this will be funny.

    • “The second study is stupid” is not a sound argument and clearly shows your biases up front and doesn’t add anything helpful to the discussion.

  • I’m certainly not a nutritionist.

    My understanding though is that CICO is kind of the baseline model; the starting point as it were; regardless of diet if Calories in are far greater than calories out weight (maybe better discussed as totally stored chemical energy, as activity level and type affect the actual tissue types showing gains) will be gained. If Calories in are lower than calories out then weight (again possibly better discussed as total stored chemical energy) will be lost.

    On top of CICO though there are conversion efficiencies; a very basic interpretation the hormonal model. IE if I eat 1000 calories of simple sugars those can be metabolically burned, stored or wasted. If I eat 1000 calories of fats those can be burned, metabolically burned or wasted. The ratio of carbs to fats to proteins to fiber etc. changes the efficiency of conversion to stored energy. The simplified theory being that simple sugars convert to body fat at a higher efficiency than ingested fats do, so 1000 calories of glucose ends up being 900 calories of adipose tissue while 1000 calories of fat ingested only becomes 800 calories worth of adipose tissue. This study would show that the numbers I’m using may in fact be backwards (note these numbers were only chosen to show ordinality, they are not real); with the same caloric intake a high carb diet is actually converted less efficiently. There are of course other effects though; appetite suppression for one. Most people don’t track their food intake to the calorie; in fact most probably don’t track it at all. If eating a higher proportion of fat reduces overall appetite then perhaps it is just CICO after all that makes these diets work.

    I’ve seen people on variations of the keto diets lose a lot of body fat very quickly. I’ve also seen people on them show no change other than general fatigue. My hesitation has always been with risk side of things; diabetics dropping 40 pounds in 2 months for example.

    I would point out that most readers of these pages probably fall into the fitness/nutrition nerd category and as such have a better idea of what they’re eating and expending than a more general population. I’d also point out that the cited studies were done on people considered obese. The effects of this type of diet might be different on someone considered obese and inactive than they are on someone who is in a “cut phase” and already generally physically fit, and continuing to get strenuous exercise throughout the diet. I’m not saying that anything about the studies or your discussion of them is wrong, just that very specific results don’t always extrapolate to larger populations.

    Not really a question here; more my brain dumping my own confusion on the matter all over the comments section.

  • Awesome article! I feel as you say that it isn’t a magical solution or fat loss miracle. It should be used but not praised as the only or fastest way to lose weight. I used it once for a contest prep and it was pretty great in regards to feeling satiated and not always looking forward to the next meal. I actually hit some PR’s as well during the keto cut. I just felt flat all the time and didn’t have any intensity in the gym. Thanks again for the article.

    Chris

    • Hi Chris! thanks for the story and the honest self reflection! I love that you did an objective appraisal!

  • Hello, I enjoyed the objective information. My question is: how does a layman person know, if this is the tool he should employ?

    • Honestly, trial and error is not a bad method to use in this case. Just be open to “experimenting” and if it doesn’t work, move onto the next tool.

  • Brad, I enjoyed this article, but coming from a livestock husbandry background, I have been educated to believe ketosis is bad – it’s a medical emergency, typically of dairy stock, brought on by (a) onset of heavy lactation shortly after parturition, and/or (b) improper feeding/malnutrition. I was taught that it should be treated immediately, or risk the death of your production animal and/or her offspring (supplemental feeding of offspring is often necessary in spite of the body mobilizing all available resources to increase lactation).

    I am having a very hard time reconciling using what veterinarians consider a metabolic disorder in an intentional manner for human body fat management – it may be more of an emotional resistance based on this aspect of my prior education than anything else. That being said, I feel like I would need some more answers that seem to be getting left out of the discussion. Questions like: How long is it safe to be in ketosis? To what degree is it safe? When should you abandon it and seek emergency medical attention? What is the proper exit strategy if you’ve reached your goal, in terms of weight/fat loss? Is there any actual good guidance on the appropriate range of carbs to keep you in the ‘safe’ zone of ketosis (if there is such a thing)? Here is a link to a veterinary perspective on this condition, if you’re unfamiliar with seeing it from that side. http://www.dairyaustralia.com.au/Animal-management/Animal-health/Animal-health-fast-facts/Sudden-drop-in-milk-production/Ketosis.aspx

    • Hi Jessica! You raise several excellent questions surrounding this topic. For starters, ruminants have a different metabolic physiology than humans and I am not well versed enough in veterinary medicine to really answer your questions in livestock but I can answer your latter ones that regard humans.

      1) How long is it safe to be in ketosis? Honestly, we really don’t have good, well-controlled experimental evidence to give you a solid answer. There are studies showing “well tolerated” out to two years, but there are also studies showing fairly severe adverse outcomes at 4-6 months so I think it something that needs to ideally be used with caution when implemented long term and should include routine visits with a physician to monitor specific metabolic parameters (thyroid, sex hormones, mineral metabolism, etc.). The “safe zone” of nutritional ketosis also hasn’t been well defined and there are manners of cycling in and out throughout the week and each person has a different carbohydrate threshold of intake that “kicks them out” of ketosis. It is for many of these reasons that I rarely recommend the strategy as a long term solution to clients. One can achieve similar results on a much less stringent approach without as much ‘worrying’.

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