Nutritional Ketosis, Part I – the State of being a Superman

Bacon, eggs, fat

What is a ketogenic diet? 

If you regularly follow articles on health and nutrition, you have undoubtedly heard about ketosis.  In the last several years, the interest around ketogenic diets has been rising constantly, with more and more studies done and data available to critically assess their effectiveness.

When people hear the word “diet”, the first objective they associate it with is losing weight.  But ketogenic diets are more than just methods of weight-control.  They have profound therapeutic effects on certain medical conditions and, generally, represent an evolutionary advantage that has allowed our species to survive and thrive.

Unfortunately, with typical dietary choices of today – driven largely by clever marketing messages and hidden agendas of large food corporations trying to convince you that eating their stuff is the best thing you can do and you should really ignore any potential health implications – ketosis has become a forgotten skill.

Which, in the era of overwhelming proliferation of metabolic disorders and other debilitating diseases, puts those who do not consider following at least some form of a ketogenic diet at higher risk.

This article is an attempt to change the current state of affairs.   Ketosis is a vitally important metabolic state – and knowing when and how to use it is something that you definitely want to do if you care about your physical and cognitive performance.

So, let’s take a closer look at what ketosis is and why you might be interested in it.

Energy production pathways

Your body constantly requires energy.  Every single little process in every cell needs fuel– even when you seem to be doing absolutely nothing.  You need energy not only to move your body by contracting your muscles, but also for cell division, maintaining heartbeat, digestion and, most importantly – brain function, which controls most of these functions anyway.

The “energy currency” used for these processes is a molecule of ATP (adenosine triphosphate) – a carrier molecule that captures the energy from food and supplies that energy in its molecular bonds to power all biological processes.

ATP production is always ongoing because it is required to supply energy that keeps you alive – such “behind-the-scenes” energy expenditure is often referred to as “resting energy expenditure” or “resting metabolic rate”.    If ATP production stops for even a short period of time – you die.

About 60% of all the energy you expend is used for only two important functions: maintaining transmembrane electrical potential, called an ion gradient (ion gradients facilitate several important biological processes like nerve conduction, muscle contraction, hormone secretion, and sensory processes) and allowing muscular relaxation (yes, you use up ATP merely to keep your muscles relaxes – that’s why rigor mortis sets in after death, when ATP production stops).

We have previously covered metabolic processes by which ATP is produced.  Briefly, beyond the first several seconds fueled by ATP-PC energy system, those are:

  1. Anaerobic glycolysis
  2. Aerobic glucose oxidation
  3. Aerobic fat oxidation

Each of these processes frees up ATP.  The actual number of ATP molecules depends on the substrate – anaerobic glycolysis produces four ATP molecules, aerobic glucose oxidation – 36 ATP molecules and aerobic fat oxidation may yield significantly more – the total number depends on the length of a fatty acid chain – for instance, arachidonic acid can yield 163 ATP molecules.

Energy for your Brain

A lot of that resting energy expenditure is related to maintaining the activity of your most important organ – your brain.  The adult brain, while representing only about 2% of the body by weight, accounts for about 20% of total energy expenditure.   This is understandable – your brain controls pretty much everything in your body and it needs a lot of power to do so.

Generally speaking, fat is a more efficient substrate for energy production (as you have seen above, it yields more energy and you typically have much more of it than glucose).  The problem however is that fatty acid molecules, unlike glucose, cannot cross the blood brain barrier to be oxidized in the mitochondria of the brain neurons.  For that reason, brain neurons get most of their energy from glucose.

The glucose your brain uses for energy can come from external sources (with food) or internal storage.  That internal storage is largely represented by your liver glycogen.  Although muscle tissue also stores a decent amount of glycogen overall, it is not available to other tissues because muscle tissue lacks the enzyme glucose-6-phosphatase, necessary to release glucose into the blood, so glycogen stored in muscles is used to supply energy only to those same muscles.

The amount of glycogen your liver can store depends on several factors, but usually lasts for powering your basal metabolism for 18-24 hours (depending on several factors, such as activity level, thermogenic needs, availability of gluconeogenic amino acids, etc.).  We are, however, well aware of fasts that last way more than that – in fact, we know that an average person can survive without food for many weeks.   Where does energy for the brain come from in cases like that?

Enter ketone bodies

Fortunately for our species, our livers can produce three types of ketone bodies from fat (and a few selected amino acids): acetone, acetoacetate, and beta-hydroxybutyrate (B-OHB).

Ketones, as it turns out, have no problem crossing the blood brain barrier and serve as a perfect food for our brain (to be exact – they get converted into acetyl-CoA – a substrate for the Krebbs cycle that generates massive amounts of ATP – but these details are beyond the scope of this particular discussion).

So a more accurate statement is that our brains function on glucose and ketones (in fact our brains may even prefer ketones – more on this further).

How to induce ketosis

The typical way you enter ketosis is by restricting carbohydrates for some time (there is also, technically, a way to have ketone bodies in your system by consuming exogenous ketones – but for the purposes of this discussion we are not going to consider this scenario).  Once your body’s glycogen reserves near depletion your body eventually stops relying on glucose as the source of energy and starts using fat as the main source.  Your brain, in particular, starts utilizing more beta-hydroxybutyrate and less glucose.

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Depending on the timing and frequency of your total carb intake, you can have 20 to 40 grams of carbs per day and still remain in ketosis (in most cases, however – probably closer to 20 grams).  Once you start exceeding these limits, insulin produced to shuffle that glucose inside your cells shuts off the production of ketone bodies.

Keto-adaptation

The shift from glucose to ketone bodies usually takes a couple of days – in the initial stages of keto-adaptation, blood glucose levels are maintained by liver glycogen released as glucose into your bloodstream and through gluconeogenesis from fat (and, sometimes, protein).  The brain does not utilize ketones for energy at that point, although it does utilize ketones for lipid synthesis.

After about 48 hours of carb restriction, the brain actually starts utilizing energy from ketones more directly and reserves glucose only for when absolutely necessary.  Even on a purely ketogenic diet, your blood glucose never goes to zero (for the reasons mentioned in “Ketosis and Ketoacidosis” below).

During the initial stage of keto-adaptation it is common to experience a “gap” in energy levels – so if you are just starting to teach your body to preferentially utilize fat, you may feel a bit low on energy for a few days.  Once the body fully transitions, though, most people not only re-gain their energy, but actually report higher levels of it – along with improved mental clarity (among other benefits to be discussed soon).

You can speed up keto-adaptation by consuming exogenous ketones or medium-chain triglycerides (such as in MCT oil) which are very quickly and easily converted into ketone bodies by the liver for immediate use.  In addition, to speed this up, you might consider depleting your glycogen reserves by exercising and not replenishing carbs thereafter.

“No carbs” doesn’t mean hunger

Ketosis is an anti-starvation mechanism.  Starvation, from a purely biological sense, happens when your cells do not get energy – and, given that most of the time that energy is represented by glucose, absence of glucose represents starvation – until your cells are able to get the energy from other sources.

Not all cells can use ketone bodies for energy.  Red blood cells, for instance, do not have mitochondria and cannot either oxidize fat or use ketone bodies within the Krebs cycle.  So certain parts of our biology will always depend on glucose – those are in a vast minority, though.  Ketones can fuel the most energy hungry components – such as your brain and your muscles – perfectly well.

Hunger is a mechanism that signals lack of nutrients and the necessity to replenish energy reserves.  It is typically driven by falling blood glucose levels and suggests that you eat food to release glucose into the blood – and the cycle continues.

Once you start severely restricting carbohydrates (and you would be surprised how quickly you can reach your limit of 20-30 grams of carbs per day even eating very savory vegetables and nothing obviously sweet – you can check carb content of the foods you eat using any of the popular online nutrition data providers (such as nutrition.self.com, for instance), your cells, previously dependent on glucose, will be in starvation mode and if you don’t do anything about it – metabolic downshifts and other detrimental effects of typical prolonged “caloric restriction” will follow (as discussed in the article on calorie counting).

This is not the goal with ketosis.  The goal is to swap one type of fuel for a different type of fuel, but not to restrict the total amount of fuel that your body gets.  The way out of this is simple – you substitute removed carbs with added fats.

Fats keep you satiated (and the good ones taste awesome!) and make it far easier to cope with a sudden disappearance of your typical comfort foods.  You may still have cravings for a lot of carbs (largely psychological and a result of the addictive nature of carbs and how they affect your brain programming), but those would not be the same as real hunger.  You can be full and satisfied without eating carbs and the cravings will disappear very soon.

How much fat do you eat on a ketogenic diet?  Hold on to your chairs – because traditional strict ketogenic diets ask for about 80% of total consumed “calories”.  Of the remaining 20% – about 10%-15% would come from protein and about 5%-10% would come from carbs.  For comparison, a typical average “westernized” non-ketogenic diet would probably look like 60% carbs, 20% fats and 20% protein.

Because I do not like to talk about calories, let’s translate this into more relevant measurements.   We already mentioned that on the average, you should restrict your carbs to 20-30 grams per day (more precise proportions can only be determined with blood ketone testing to verify your numbers), restrict your protein consumption to about 0.8 – 1.0 grams per kg of body weight (which, incidentally, is very close to guidelines we have discussed when we talked about building muscle) and add fat “to satiety”, which means – as much as you want to feel full.

Eating more fat sounds extremely counterintuitive to most people who have been taught for decades that fats are bad for you because they increase cholesterol and lead to cardiovascular disease (false claims, which we have addressed in the past).  In fact, this may sound completely sacrilegious for people who thought they have been following a healthy diet (which, unfortunately, in many cases  is represented by “low-fat” stuff).  But we have, many times in the past, covered the benefits of healthy fats, such as coconut oil, butter, and fatty meat.

Sorry, ketosis fueled by inflammatory vegetable oils is really not a healthy option, so please don’t consider that.

But, you might ask – what if you restrict carbs and instead of eating such high amounts of fat you just eat a bit more protein?  Unfortunately, eating too much protein will take you out of ketosis as much as eating too much carbs.  The reason is that protein can relatively easily be converted into glucose by your liver through gluconeogenesis – and elevated blood glucose levels triggering insulin release shut off ketosis.  That’s why the proportion of protein on a strict ketogenic diet is so small.

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What if you are a competitive athlete or generally like to lift heavy weights (which you should), which require (and, typically, build) muscle mass?  Can you do that on so little protein?  We will discuss this as a separate topic in Part II, but for now – there are two factors related to protein consumption in ketosis that you need to consider.

First, remember that ketones and glucose can – and do – coexist, it’s just that as one rises, the other one drops with almost perfect inverse correlation.  Which means that even if you do convert some extra protein into glucose and lower your ketone bodies concentration – you can still remain largely ketogenic, just to a lesser extent, while retaining most of the benefits from reducing carbs (such as less free radical damage, reduced glycation, more stable energy levels, etc.) even if you consume more protein than would typically be suggested to remain in ketosis.

Second, the small amount of protein required to stay in ketosis may not be that small anyway – and that’s especially true if you engage in resistance exercise that increases your demand for protein to build muscle tissue – under the conditions of abundant energy supply from fat, the more protein your muscles (as well as your other biological processes) would require, the less will be broken down and utilized to produce glucose.

So, unless you are trying to tame your hunger by consuming more protein than now, as opposed to more fat – that should not be an issue.  Again, the best method to gauge the effectiveness of your efforts around maintaining ketosis would be testing your blood (this can be done using portable – albeit not always cheap – devices).

Ketosis and Ketoacidosis

If you are healthy – even when you are in ketosis – your blood glucose level will never reach zero.   To generate ketone bodies, your liver uses long and medium chain fatty acids which come from triglycerides released from your fat cells.  Triglycerides are fatty acid chains linked by a “backbone” glycerol molecule.  When triglycerides undergo lipolysis, which separates fatty acids from glycerol, the liver not only uses fatty acids to create ketone bodies, but it also uses this released glycerol to make glycogen through gluconeogenesis.  Glycogen can then be released into the bloodstream as glucose – as it typically would.

Consequently, the release of glucose from liver glycogen in healthy individuals raises insulin which helps shuffle that glucose into the tissues that need it.   Insulin release provides a feedback loop that shuts off the production of ketone bodies and gets rid of excess ketones through urine.  As such, in healthy individuals, the production of ketone bodies is self-regulated.

Because of the feedback loop, beta-hydroxybutyrate levels in a state of nutritional ketosis remain between 0.5 and 3.0 mM – which is far from being enough to shift the blood pH balance and cause harm.

Now picture the scenario when insulin is not produced (as is typical for Type I diabetics, for instance).  Without insulin – whatever glucose (either from exogenous sources or as released from glycogen stores) may be circulating in the blood, it cannot be shuffled inside the cells and is simply not available to the starving tissues.  What happens when you go into starvation?  Your body starts making ketone bodies.  But given the lack of insulin (still), this process never slows down and more and more ketone bodies are produced.  Ketone bodies are highly acidic – so when beta-hydroxybutyrate levels approach 15 to 25 mM, the resulting pH imbalance leads to ketoacidosis which overwhelms pH buffering capacity of the body and creates a potentially life-threatening metabolic derangement.  In addition, because in type 1 diabetics circulating blood glucose is still high, it causes osmotic diuresis and the removal of water and electrolytes from the blood resulting in potentially fatal dehydration.

Based on this, several sources (and even many doctors) may cite ketosis as a dangerous state to be in.  An important thing to understand, however, is that ketosis – an important evolutionary mechanism to protect against cellular starvation – is not the same as ketoacidosis, despite the fact that, in people with no or limited insulin production, it may lead to one.

Although nutritional ketosis is often blamed for ketoacidosis by poorly informed individuals and, thus, positioned as a dangerous state to be in, what you need to understand is that ketoacidosis in diabetic patients is not a result of following ketogenic diet. In fact, even if Type 1 diabetics eat plenty of glucose, because on a cellular level this glucose is unavailable due to the lack of insulin, they naturally shift toward ketosis anyway. Conversely, exogenous insulin typically administered to Type 1 diabetics immediately shuts down the production of ketone bodies and clears out the excess through urine.

Keep this in mind next time you hear about the alleged “dangers” of ketosis.

The multiple benefits of ketosis

Most people turn to ketogenic diet (or, at least, start restricting carbs as much as they can) to lose weight.  Or, put more precisely – to get rid of extra body fat.

But besides weight loss, ketogenic diets are considered healthier because they promote a non-atherogenic lipid profile (i.e. lower risk of arterial plaques), lower blood pressure, improve blood glucose and insulin sensitivity, do not alter renal or liver functions, have many neurological benefits in central nervous system, do not produce osteoporosis and improve performance in aerobic sports.

Furthermore, inducing ketosis through dietary modification leads to improvements in glycemic control and medication reduction or full elimination for patients with type 2 diabetes – better than with the low glycemic index diet.

In Part II we will start looking into some of these specific benefits in more detail.