What’s a ketogenic diet?


A diet is ketogenic when it is very high in fat, high enough to cause a change in your metabolism whereby more fat is turned into ketone bodies rather than being directly oxidized into a form of cellular energy called ATP. Like fats, these ketone bodies (or ketones) can also be oxidized to make ATP.  

For this metabolic switch to happen, not only must there be a lot of calories coming from fat, it’s also important that few calories come from carbs and protein (particularly the carbs). This metabolic switch that happens on a ketogenic diet is called ketosis.

There isn’t just one specific ketogenic diet. In fact, you can be on a carnivorous ketogenic diet or one one where most calories are derived from plants. Here are examples of the ratio of dietary fat-to-carbs-to-protein that can induce ketosis.

Traditional Ketogenic Diet for epilepsy

Non-Medical Ketogenic diet

These percentages of fat, carbs and protein are estimates, not fixed values. Many factors affect what ratios of the macronutrients get one person into ketosis and not another.

Not only does does the particular macronutrient split differ from person to person, factors like sleep, exercise, stress, genetics and more come into to play too.

How do I know if I’m in ketosis?


The level at which one is ‘in ketosis’ can be a somewhat arbitrary value. However, there are molecules whose concentration you can measure to set a (somewhat arbitrary) threshold. If you have more than >0.5 mmol/L of a molecule called ?-hydroxybutyrate in your blood, the consensus is that you’re in ketosis [1]. You can also measure how much acetone is in your breath and acetoacetate in your pee. The concentrations at which these indicate ketosis are even less clear [2].

There isn’t just one kind of ketogenic diet and different people get into ketosis more or less easily

What’s a ketone?


A ketone is a kind of molecule we make from fat. The process that builds ketones is called ketogenesis. Ketones then get shipped to little energy producing organelles bathed in oxygen within our cells.

Once in there, ketones get oxidized to generate ATP through a process called β-oxidation. They also get broken down into other molecules that get fed into the citric acid cycle. The process that breaks ketones down is called ketolysis. Chemically speaking, the central feature of a ketone is its ‘parent structure’ (the double-bond between a carbon atom and an oxygen atom).

From this structure, two other carbon-contain chemical groups branch off of it. People often talk about there being three ketones yet technically there only acetone and acetoacetate (AcAc) are ketones, not ?-hydroxybutyrate (BhB). The latter is more of a straight chain monocarboxylic acid, in case you were wondering.


What are the side-effects of ketogenic diet?


Technically a side-effect is a less harmful adverse effect, and so considered of secondary importance compared to main therapeutic effects [3]. Bluntly put, a side-effect is worth it whilst adverse events aren’t.

Nevertheless, we’ll use both terms interchangeably. The answer to what are the side-effects of a ketogenic diet cannot simply be a list of symptoms. To understand why, consider how you’d react if I asked you

what are the side-effects of an omnivorous diet based on whole-foods (animals, nuts, fruit and vegetables’?

You’d probably look at me puzzled since ‘everyone knows’ that it’s a healthy diet, and so why would there be anything inherently wrong with it? It’s assumed to work with human biology just fine. Ketogenic diets, based mostly on whole-foods, also work fine with human biology. In other words, they’re evolutionarily coherent, just like omnivorous diets are.

That being said, we must consider the context within which a ketogenic diet is adopted because this affects our reaction to it. Is the ketogenic diet being used therapeutically to treat epilepsy or cancer? Is a person with an inherent genetic defect in fat metabolism attempting a ketogenic diet? Is the person going from a processed carb heavy standard american diet to a ketogenic one? What about a healthy person on a ketogenic diet for a few months? These questions highlight areas of the spectrum along which to expect life threatening side-effects to no side-effects.

Keto-flu: scenario 1


When weaning off of a diet high in processed (hence poor quality) carbs like a standard American diet, people can experience flu-like symptoms for a couple of days to a few weeks. This is known as the keto-flu, which includes but isn’t limited to the following symptoms:

  • Fatigue
  • Muscle cramps
  • Peeing a lot (diuresis)
  • Feeling dizzy/light-headed
  • Headaches
  • Low blood sugar (hypoglycemia)
  • Constipation (or diarrhea less commonly)

The higher the degree of processing that goes into refining starchy carbs like wheat flour, the worse your blood sugar and insulin response will be when eating them.

When you ditch them, probably decreasing your total carbs, your physiology must adapt to accommodate this shift in fuel source.

It is thought that this and other stuff we don’t yet understand causes the keto-flu. In a sense it’s probably more prudent to call it carbohydrate withdrawal syndrome.

There’s also an argument to be made that starting a low carb or ketogenic diet entails metabolizing more total fat than your body is used to, leading to a temporary struggle to meet energy demands and thus contributing to the keto-flu.

Rare genetic mutations and severely ill people: scenario 2


Medical corner cases. They’re all too often hell for the afflicted, interesting and useful to researchers and commonly misused by people embroiled in ideological battles. Enter the attempt at nuance.

We must be careful to parse inherently negative effects of the diet from the inevitably negative effects of disease

This care was not taken by collaborators Sarah Ballantyne and Denise Minger when publishing their ketogenic diet literature review [4].

Their interpretation of what side-effects can be attributed to the diet is terribly confounded (meaning it’s a mess of associations). Their list seriously lists death (!) as a long-term side-effect.

Lets focus on something more informative, like John Hopkin’s recent list of side-effects in 10 out of 15 children studied whilst following a ketogenic diet to manage their severe epilepsy [5]

  • constipation
  • weight loss
  • low blood sugar
  • high cholesterol in the blood
  • low sodium levels in the blood

Some of these symptoms, like high cholesterol in the blood, are arguably not problems depending on the specifics of the situation. Others, like constipation, are usually temporary or due to the highly processed nature of the diet. Others still, like weight-loss, can be a benefit for some but not others depending on their starting body composition for example.

Not only is a therapeutic ketogenic diet for epilepsy a great treatment option, but many of these symptoms dissipate upon improving the clinical version of the diet by using more nutrient dense food options [see Andrew Scarborough for example].

Not only must go beyond mere correlations, we need a plausible mechanistic basis from which to test the idea that a ketogenic diet has inherent side-effects. This is currently lacking.

Now, relatively rare medical conditions like primary carnitine deficiency, where fat metabolism is severely impaired, makes adopting a ketogenic diet impossible.

In such a genetic context the side-effect can be death. The following rare genetic cases also aren’t compatible with such a high-fat diet [6]

  • Carnitine translocase deficiency
  • Beta-oxidation defects
  • Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGS) deficiency
  • Carnitine palmitoyltransferase (CPT) I or II deficiency
  • Long-chain 3-hydroxyacyl-CoA deficiency
  • Medium-chain 3-hydroxyacyl-CoA deficiency
  • Pyruvate carboxylase deficiency  Porphyria
  • Medium-chain acyl dehydrogenase deficiency (MCAD)
  • Long-chain acyl dehydrogenase deficiency (LCAD)
  • Short-chain acyl dehydrogenase deficiency (SCAD)

In addition to uncommon genetic defects, there are medical conditions that warrant caution when adopting the diet. Adapting to the diet may require medical supervision for the following issues, even if the diet is posed to benefit the person down the road

  • Impaired fat digestion
  • Poor nutritional status
  • History of pancreatitis
  • Active gall bladder disease
  • Impaired liver function
  • History of kidney failure
  • Pregnancy and lactation
  • Gastric bypass surgery
  • Abdominal tumors
  • Decreased gastrointestinal motility

Lets single out pregnancy and lactation. It is better to adopt the diet before pregnancy as adapting to it whilst pregnant is a considerable added stress. This is a case where a knowledgeable doctor’s assistance is crucial.

A well-formulated low carb or ketogenic diet can be fine during pregnancy and lactation but both pregnancy/lactation and adopting any new diet represent important physiological shifts.

Normal people on a long-term ketogenic diet: scenario 3


This scenario essentially does not require a list of side-effects. This is not to say that the diet is optimal or cannot carry with it pitfalls, it is just to say that when properly formulated there is no evidence currently that a ketogenic or low carb diet is any more likely to cause micronutrient deficiencies or metabolic mayhem than an equally well-formulated omnivorous diet based mostly on whole-foods. The operative words here are well-formulated and whole-foods.

Is all that fat on ketogenic bad for your heart?


The large (total and proportional) amount of fat you eat on a ketogenic diet will not increase your risk for heart disease. If you eat the wrong kinds of fats, like those typically found in processed foods, there’s good evidence that this will harm your heart [7, 8]. Examples of those fats are canola oil, sunflower oil, soybean oil, margarine, many trans-fats and peanut oil.

These are bad for your health whatever your diet, but having lots of sugar on top makes things even worse [9].

A well-formulated ketogenic diet will contain a selection of fats that provide a balanced omega-6-to-omega-3 ratio. When the latter is balanced, you can have the right cell membrane fluidity [10], appropriate blood clotting as well as pro- and anti-inflammatory responses [11,12].

Most importantly, avoid the bad fats mentioned above to get the right omega-6-to-omega-3 balance that’s estimated to be between 1:1 and 3:1 [13]. Then make sure you eat a variety of animals foods, like beef, sardines and eggs. These should provide the required doses of essential omega-3 fats, recommended at less than 1 to 2 percent of total daily calories [14, 15].

Examples of added fats that are good to eat on a ketogenic diet are butter, lard, coconut oil, heavy cream, olive oil, cacao and avocado oil.

Is a ketogenic diet the only way I can get into ketosis?


There are several ways to be in ketosis aside from a ketogenic diet.

  1. Be a new-born baby fed breast-milk [16]
  2. Fast [17] (meaning, don’t eat)
  3. Use up your glycogen by exercising [18]
  4. Take exogenous ketones [19] (pop a ketone pill)

Our history with ketosis – is it unnatural?


Ketosis is simply a metabolic state. It is normal for humans to be in and out of ketosis. During human evolution, there would be times where we’d be in and out of ketosis for many reasons. For instance, seasonal changes often meant sugary and starchy foods were not available year round for our ancestors. An absence of such foods pushed early humans to meet their energy demand with higher-fat diets since dietary energy needs are nearly entirely met by fat or carbs, with protein being only marginally useful for this purpose.

Furthermore, fatty nutrient dense foods like meat, seafood and in particular offal (the weird animal bits like liver), were seen as delicacies [20] and thus highly prized.

Populations living further North had to adapt to less vegetation growing around them and to the kind of animals capable of living in this environment. This meant many human tribes relied substantially more on hunting larger, fattier animals rather than on gathering smaller, leaner game (like birds and insects! [21]).

Consider this too: all of the essential micro and macronutrients for humans are found in adequate quantities in the flesh of animals, not plants. To successfully nourish themselves, humans had to do so within a framework called optimal foraging theory.

In their case, this biased their food gathering efforts towards foods of animal origin. These kind of foods happen to be low in carbs and thus conducive to ketosis. Keep in mind though that the argument for ketosis isn’t as simple as “we were sometimes ketogenic back in our past so it must be good for us now”.

Nevertheless, the story of human evolution does support the idea of ketosis being a normal metabolic state. In other words, it passes the first evolutionary filter.

Do ketogenic diets or ketosis have medical benefits?


Yes. Modern science has now uncovered several good reasons to eat a ketogenic diet. How much time you need to spend in ketosis (and for what reasons) is still an open question. Nevertheless, it has been shown to potently lower inflammation, probably due to its effect on the NLRP3 inflammasome [22]. The absence of dietary carbs and ketogenesis can powerfully lower high blood sugar [23].

It’s so good at doing this that people taking blood sugar lowering meds need to let their doctor know if they decide to experiment with a ketogenic diet. Ketogenic diets are also known to effectively lower insulin resistance [24], which is especially beneficial for the obese and diabetic.

Particularly interesting for the obese is the fact that ketones (those molecules produced from fat on a ketogenic diet) can normalize appetite and lessen cravings [25]. More and more cancer research is revealing its cancer-fighting properties [26]. It’s still unclear if it’s powerful enough as a stand-alone therapy for some patients, although the trend indicates a majority of patients will benefit from ketogenic diets (and fasting) when combined with other meds.

One the the first historical uses of ketogenic diets was for epileptic seizure control [27]. Check out the wonderful series of blog posts written on this subject by cancer researcher Dominic D’Agostino and his writer colleague Travis Christofferson [28]. It appears that ketogenic diets reverse symptoms of many diseases, possibly slowing the progression of many of the chronic modern ones [29].

Ketogenic diets and ketosis has a long history with our species and today it’s still a reasonable dietary option

Don’t I need lots of carbs to exercise?


No. A better question is “Is a ketogenic diet optimal?” Or “Is a ketogenic diet equally beneficial for everyone?” Those are questions we cannot yet answer. But we have some clues. For instance, higher peak fat oxidation rates [30] have been measured in keto-adapted athletes . It remains to be confirmed whether or not this translates to increases in endurance capacity. Keto-adapted athletes are people who’ve been on a ketogenic diet long enough for their performance to return to baseline following the days to weeks long dip that often happens when transitioning from a higher-carb diet.

In that same vein of exercise questions, people also ask “Won’t my Crossfit workouts tank, bro?” Beyond the transition period, probably not (see our post on carbs and high-intensity training for more).

Ignoring pro or con anecdotes for a moment, there’s no strong evidence suggesting that strength or power losses occur long-term on ketogenic diets. Mind you, strength and power aren’t the same same as ‘glycolytic efforts’. Nevertheless, as we’ve already mentioned, beyond the first few weeks of adaptation to a lack of dietary carbohydrates [31], there doesn’t seem to be any sustained drop in power or strength [32]. Some high-level gymnasts really seem to love what ketogenic diets did for their performance [33]!

Should I feel guilty about eating fatty foods?


No. Just make sure you eat healthy fats (see our Good fats Bad fats series). Even better, in Nina Teicholz’s book you will find out, in riveting detail, why modern food supplies are filled with unhealthy fats [34]. Despite this unfortunate reality, remember that a big part of life is enjoying food. So…

Enjoy tasty, rewarding, hyperpalatable, hedonic food…that’s healthy – it exists!

After a long day of hard work, enjoy that juicy, rare steak. If you so desire, accompany  it with some fresh garden kale with onions delicately sautéed in butter. Maybe you’re feeling more like fish, so feed yourself a slab of poached salmon with olive oil drizzled over a side of sweet & sour peppered cabbage.

Strangely, I often hear that if such meals are indeed healthy, it must be because they’re not that rewarding or not that palatable and thus don’t cause us to overeat. This puzzles me. Speaking for myself, sometimes my mouth waters simply at the thought of them. I genuinely find high-fat meals hyperpalatable, rewarding and get hedonic pleasure from them.

I like Dr.Baker’s quip (@SBakerMD on Twitter). He remarked on how his dogs never get tired of the same old delicious raw red meat he feeds them every day. These animals (whose diet is very similar to our own [35]) never seem to get palate fatigue. Interesting…

Lastly, get inspired!

Check out the athlete and mad-scientist hybrid that is Dominic D’Agostino PhD [35]. He’s leading cutting edge research on ketosis and deadlifted 500 lbs (227 kg) for 10 reps after a 7-day fast [36].

– We recommend visiting http://www.ketogenic-diet-resource.com for more information on how a ketogenic diet can help you meet a variety of health goals


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