The Case For The Ketogenic Diet

Graham Ryan

21 Feb 2018

Whether you’ve personally experimented with a ketogenic diet, or are just trying to sort out what this word “keto” is and why it seems to be everywhere all of the sudden, it would be hard not to be aware in some way that ketogenic diets have exploded in popularity in the past year.

I’ll use the bulk of this article to look into the most compelling research that supports the seemingly too-good-to-be-true experiences people report after switching to a keto diet, but first I’ll start with a cliff-notes to give some context to the uninitiated.

What Is “Keto”?

By default, the human body and brain run on sugar/carbohydrates (specifically, glucose) as the primary source of metabolic energy. Unless you fast for a prolonged period or do something weird with your diet, the body will rarely depart from glucose-burning metabolism.

Ketosis, on the other hand, is the metabolic state in which the body and brain are primarily using fats for energy. This is largely driven by the liver turning fats into ketones, which can then be used to power cellular metabolism in place of glucose.

How Does One Get Into Ketosis?

The fastest way to get the body to switch in to ketosis is pretty simple: just stop eating.

After 24 hours of fasting, most people’s livers will have started breaking down fats to form ketones, and blood ketone levels will be above (or close to) the level generally considered to be the lower end of “nutritional ketosis”.

While fasting is the route most people (myself included) recommend for getting into a state of ketosis, it can also be achieved by adjusting one’s diet. (Check out this guide for more on the benefits of fasting).

Depending on the person and their activity level, consistently eating somewhere in the range of 65-80% of your daily calories from fat will get you into a state of ketosis. This is considered a “ketogenic” diet.

Even with 80+% of calories coming from fat, switching the body into ketosis can take days to weeks, and the process of getting there can be challenging, generally characterized by low energy levels. (entering ketosis via fasting mitigates or eliminates this for most people).

Why Go Keto?

The reasons for following a ketogenic diet are best broken into two categories: the practical and the technical.

The Practical Answer

When you talk to someone who has had success with a ketogenic diet, generally the first thing they will tell you is that they simply feel better.

When they work, ketogenic diets reliably improve metabolic energy levels, mood and brain function. While not a “weight-loss” diet, ketogenic diets do make it easier for a lot of people to lose unwanted body fat.

The Technical Answer

At a fundamental level, ketones are a more efficient source of energy than glucose. They improve the functioning of our mitochondria (the cell’s metabolic power plants), generating less waste to produce a given amount of metabolic energy. [1]

Zooming out a bit, ketosis has a huge list of benefits for the body and brain. Ketones suppress inflammation and help cells to resist oxidative damage.

Ketones have also been shown to have antidepressant, stress-reducing and neuroprotective activity in the brain. Ketosis also has positive effects on genetic expression, slowing several genetic processes broadly correlated to “aging”. [2][3][4]

I will go as far as to say that - for the people for whom the diet “works” (which is admittedly not everyone) - ketosis is a fundamentally superior way to run the human body and brain.

Why go keto? In depth, Part 1: Metabolic/Energy/Mood Benefits

Why do people consistently report that switching to a ketogenic diet improved their energy levels? Let’s look at a few reasons

Stability Of Metabolic Energy (i.e. exiting the carbohydrate roller coaster)

When the body is running on carbohydrates, it’s essentially on a metabolic roller coaster ride.

Here’s how the roller coaster works: When you eat a meal containing carbohydrates, within 30-90 minutes, the bulk of those carbohydrates have been turned into glucose and are circulating in the bloodstream. There is an abundance of energy available, so the body releases insulin (via the pancreas) to get things under control.

In response to insulin, muscle and liver cells take in the glucose and store it, either as glycogen or triglycerides. This stabilizes blood sugar levels for a while, but eventually as the brain and the muscles use more blood sugar, circulating glucose will drop below ideal levels.

The brain senses its energy supply diminishing and freaks out, directing the body to release ghrelin (the hunger hormone) and cortisol (the stress hormone). Predictably, you start to feel hungry and stressed/moody (i.e. “hangry”) and likely start planning how to get some food in your system asap.

Some bodies are better than others at keeping blood sugar levels stable, but everyone on a non-keto diet goes through this cycle to some degree, multiple times a day, every day.

Switching to ketosis is a total revolution for some people because this perpetual cycle of fluctuating mood/energy/hunger that they’ve taken for granted as a fundamental and inescapable reality of human existence...simply goes away.

When the body is switched over to ketosis, metabolic energy supplies are much, much more stable. In general, the liver will just keep chugging along, turning fats (both from food and stored body fat) into ketones at a relatively consistent rate.

Owing largely to this consistency in metabolic energy, people on keto diets often experience pretty dramatic improvements in brain performance, as well as improved mood + emotional stability.

Reduced Inflammation

Our mitochondria are our cellular power plants, using ketones or glucose to produce ATP (which powers essentially everything the cell does).

Few things have been shown to suppress mitochondrial function quite as reliably and effectively as persistent inflammation in the body. [5]

Beyond this, as we’ll explore further later on, inflammation negatively impacts brain performance and emotional health, so perceived energy will take a dip along with metabolic energy.

The research is pretty convincing: ketosis is fundamentally a lower-inflammation state than carbohydrate-driven metabolism.

In the past few years, researchers have uncovered the mechanisms behind this. One of the primary ketones produced by the liver, β-hydroxybutyrate (BHB), suppresses activation of one of the body’s primary pro-inflammatory pathways, known as the NLRP3 inflammasome. [6]

But that’s not all! Ketosis also lowers something known as the NADH-to-NAD+ ratio. This, in turn, activated a protein called CtBP that has the effect of suppressing a number of genes involved in inflammation pathways. [7]

Improved Mitochondrial Function

In addition to reducing inflammation, there is evidence that ketosis supports our cellular power plants in other ways.

Ketosis has been shown to increase mitochondrial efficiency relative to glucose metabolism, and increase production of new mitochondria (mitochondrial biogenesis). [8]

Why go keto? In depth, Part 2: Anti-Aging Benefits

Most people simply accept “aging” as inevitable, and perhaps at some level it is.

That being said, aging is also the cumulative effect of hundreds or even thousands of individual metabolic and genetic processes, and it appears ketosis can slow or reverse at least some of these.

Inhibition of HDACs

Histone deacetylases (HDACs) are enzymes that, as their name suggests, deacetylate our histones.

That sentence doesn’t mean anything to you? Let me explain…

Histones are the proteins responsible for correctly “packaging” our DNA, an important part of ensuring that only the genes that the cell intends to express actually get expressed.

Histones need to be deacetylated for proper gene expression to occur, but this is supposed to happen in a highly regulated fashion. As we get older, HDAC’s tend to accumulate in our cells, leading to unregulated deacetylation and unintended gene expression.

In the most innocuous scenario, this leads to cellular inefficiency and waste that will eventually cause a cell to become dysfunctional or die. In a less innocuous scenario, HDAC accumulation leads to tumor growth and cancer.

You can probably see where this is going: The ketone BHB inhibits HDACs, leading to the slowing of several markers of epigenetic aging. [9]

Reduced Oxidative Stress

One of the primary factors driving aging at the cellular level is an accumulation of oxidative molecules. When this happens, essential cellular components are damaged and stop functioning properly.

As mentioned above, ketosis has been shown to lower the NADH-to-NAD+ ratio in most cell types. Besides having an anti-inflammatory effect, the lowering of this ratio also makes the intracellular environment less oxidative, thus reducing oxidative stress on the cell. [8][10]

In addition to this, BHB has been shown to stimulate a key antioxidant pathway (Nrf2), meaning oxidative stress would be further reduced. [11]

Why go keto? In depth, Part 3: Brain Health + Performance

The aforementioned improvements in metabolic energy available to the brain will produce the most significant brain performance enhancement, but ketosis offers some brain benefits beyond simple energy-availability.

Antidepressant + Stress-Reduction

The ketone BHB has a particularly strong anti-inflammatory effect in the brain, which a 2017 study correlated with reduced depressive and anxiety behavior in rats. [12]

This is consistent with the recent theory that clinical depression is fundamentally a neuroinflammation-driven disease. [13]

Neuroprotective

There is quite a bit of research showing ketones to exert a neuroprotective effect.

A 2009 study showed a ketogenic diet to reduce neuronal apoptosis, reduce brain edema, and improve sensorimotor and cognitive outcomes in rats that suffered brain injuries. [14]

Why go keto? In depth, Part 4: Body Composition

Despite not being a “weight loss diet” per-se, loads of keto adherents report great success in making positive changes to their body composition.

There are a number of metabolic and hormonal shifts the diet produces that explain this.

Improved Mitochondrial Function In Adipose Tissue

While fats are stored throughout nearly all tissues in the body, when we think “body fat”, it’s generally adipose tissue we’re thinking about.

If adipose tissue is healthy and efficient, stored fat can be “burned” much more readily. After a month on the ketogenic diet, mitochondrial size (an indicator of metabolic efficiency) in adipose tissue both increase in the range of 40-60%. [15]

Hypocaloric Eating Made Easier

As I see it, this is the core of why people have such success losing body fat on keto diets.

Regardless of what diet you’re following, you’re almost certainly going to have to eat a diet that is hypocaloric (taking in less calories than are used in a day) to reduce your body fat.

Eating a hypocaloric diet when you’re on carbohydrate metabolism is HARD for most people. Your blood sugar crashes, meaning you feel moody and low-energy and, obviously, you’re hungry for long stretches of the day.

This all changes on a keto diet. As discussed in the section above, when you’re not on the blood sugar roller coaster, energy levels and mood stay much more stable and hunger is comparatively insignificant.

This means it is infinitely easier for most people to eat hypocaloric and still maintain normal energy levels, mood and brain function when on a keto diet.

Decreased Body Weight, Maintained Strength

In virtually any sport, if you can generate the same amount of power (i.e. muscular strength) while decreasing your body mass, you’ll be at a competitive advantage. Runners will run faster, basketball players will jump higher, gymnasts will be more explosive, etc.

There are a few studies (on both gymnasts and endurance athletes) showing that ketogenic diets allow athletes to better maintain power while losing body mass compared to athletes on traditional diets. [16][17]

Ready To Try Out Ketosis?

Great! But temper your excitement a bit. While some people can start a ketogenic diet and feel great from day one, for the majority of us, switching over is not automatically easy.

That being said, there are a number of techniques you can use to accelerate the rate at which your body adapts to using ketones for energy.

The smoother the transition and the better your body is at making and using ketones, the more likely you are to have success and stick with a keto diet. If you’re going to go through the trouble to experiment at all, you might as well do it intelligently and give the diet a true try.

I’ve put together a protocol for transitioning to ketosis based on my own 5+ years of going on and off keto, as well as helping dozens of other people do the same. You can see that protocol here: Entering Ketosis: A Protocol For Making The Switch Smoothly And Intelligently.

Stay Synchro,

Graham Ryan