With heavy coverage in the media, ketogenic diets are all the rage right now.
And for a good reason; for some people, they truly work.
But what do all these different terms like ketogenesis and ketone bodies actually mean?
Firstly, this article takes a look at what the ketogenesis pathway is and what ketone bodies do.
Following this, it will examine six potential health benefits of ketones and nutritional ketosis.
What is Ketogenesis?
Ketogenesis is a biochemical process through which the body breaks down fatty acids into ketone bodies (we’ll come to those in a minute).
Synthesis of ketone bodies through ketogenesis kicks in during times of carbohydrate restriction or periods of fasting. When carbohydrate is in short supply, ketones become the default energy source for our body.
Ketogenesis may also occur at slightly higher levels of carbohydrate intake, but for the full benefits, it is better to aim lower.
When ketogenesis takes place, the body produces ketone bodies as an alternative fuel to glucose.
This physiological state is known as ‘nutritional ketosis’ – the primary objective of ketogenic diets.
There are various methods you can use to test if you are “in ketosis”.
What Are Ketone Bodies?
Ketone bodies are water-soluble compounds that act as a form of energy in the body.
There are three major types of ketone body;
- Acetone (a compound created through the breakdown of acetoacetate)
The first thing to remember is that these ketones satisfy our body’s energy requirements in the same way that glucose does.
However, unlike glucose, ketone bodies have no impact on blood sugar or insulin levels.
Although we often hear that carbohydrate is “essential” for energy — it isn’t. Our body can meet its energy needs through fat too.
Note: This doesn’t mean all carbs are inherently bad for you; they aren’t.
Potential Health Benefits of Ketogenesis and Entering Ketosis
Firstly, the process of ketogenesis and the subsequent production of ketones changes the whole way in which our body operates.
After adapting to ketosis, the body starts using ketones for energy rather than glucose, and this may have numerous positive benefits.
Although ketosis has many potential advantages, this article will focus on six of the leading benefits.
1. Ketone Bodies May Help Treat Alzheimer’s Disease
In other words, they are referring to Alzheimer’s as insulin resistance of the brain.
The idea is that the condition is similar to type 2 diabetes, where our body becomes resistant to insulin; the only difference is that with Alzheimer’s it happens in the brain (5).
Insulin resistance signifies that we cannot metabolize carbohydrate correctly, and so our brain becomes starved of energy (glucose).
This results in;
- Glucose building up in the brain (hyperglycemia) and causing oxidative stress/damage
- Brain cells starve and die as they cannot utilize energy (glucose) at a sufficient rate
Can Ketones Provide an Alternative Fuel For the Damaged Brain?
This research examines the idea that the Alzheimer’s brain cannot adequately function on glucose.
However, through ketogenesis, the body can produce ketone bodies that provide a source of energy that the brain can utilize.
This shouldn’t be taken to mean “low carb diets cure Alzheimer’s”, but they may potentially play a role to help treat the disease.
There are numerous studies in this area—some of which are still ongoing—that find;
- “A ketogenic diet is a safe intervention that is well supported by science to bypass the brain’s deteriorating usage of energy”. However, whether it can limit the onset or progression of Alzheimer’s is not known at this time (6).
- Ketones have a neuroprotective mechanism in which they block amyloid, a kind of plaque that builds up in the brain in Alzheimer’s cases (7).
- Ketone bodies show benefit in both animal and human clinical trials, but it is a new area of research. Additionally, a randomized controlled trial demonstrates that Alzheimer’s patients taking a ketone supplement show improved cognition (8, 9).
2. Reliably Reduces Blood Glucose and Insulin Levels
Blood glucose levels need to be very low for the induction of ketogenesis.
Therefore, when the body is producing ketone bodies, blood glucose levels will be minimal.
In the presence of low blood sugar levels, the amount of insulin the body releases will also fall.
As shown above, in type 2 diabetics, a diet higher in fat results in significantly less insulin release.
Benefits of Reducing Blood Glucose Levels
So, why does reducing our blood sugar and insulin have benefits?
First, there is a difference between short-term insulin release (natural) and high fasting insulin levels.
Higher fasting blood glucose and hyperinsulinemia (constantly elevated insulin levels) have links to most chronic diseases;
- Individuals who have the highest serum concentration of insulin have a 62% increased risk of cancer mortality.
- Hyperinsulinemia has links to increased cancer mortality independently of diabetes. In other words, high fasting blood sugar and insulin levels are damaging to everyone — whether diabetic or not (10).
- A large number of studies support the association between type 2 diabetes with cancer risk and mortality (11).
- Higher insulin levels result in more pro-inflammatory effects, and there are close links between hyperinsulinemia and vascular diseases such as cardiovascular disease (12).
- Hyperinsulinemia may be “a unifying theory of chronic disease” as it is involved in the pathways of most modern disease (13).
There are various ways to reduce blood sugar/insulin, and it is not only a nutritional consideration – exercise, sleep and even stress all play a role.
However, studies show that ketogenic diets reliably reduce fasting blood-glucose and insulin levels.
3. Ketone Bodies Regulate Mitochondrial Metabolism
In every cell of our body, mitochondria play the role of creating approximately 90% of the energy we—and our cells—need (14).
In short, they break down carbohydrates and fatty acids and convert them into a usable form of energy (adenosine triphosphate — ATP).
The mitochondria are imperative to our overall health, and they play critical protective roles in our cells.
For example, they control apoptosis (cell death). This process is essential to balance the number of cells in our body — especially for damaged cells.
In particular, uncontrolled cell growth can lead to cancer, and modern research is showing that mitochondrial dysfunction is central to a range of chronic diseases (15).
Can Ketone Bodies Help Protect Against Mitochondrial Dysfunction?
Once ketogenesis gets underway and the body starts producing ketone bodies, some significant changes take place.
For one thing, mitochondria prefer to use fat for energy as it is easier to process into ATP.
- Ketone bodies stimulate and improve mitochondrial respiration and function.
- Ketones exert an antioxidant effect in mitochondria and help inhibit oxidative stress which can lead to dysfunction and disease.
- Caloric restriction is known to have longevity benefits. In times of calorie restriction, our mitochondria begin burning fat rather than glucose. Therefore, these longevity benefits may also apply when restricting carbohydrate to induce ketogenesis.
4. Ketone Bodies, Hunger, and Food Cravings
For some people, fighting the temptation to eat these foods is a daily battle.
However, many followers of the ketogenic diet claim that they can effortlessly go all day without eating, and this makes losing weight easier.
So, why does this happen?
Is it the satiating effect of protein?
Or perhaps the lack of ultra-processed foods? Or is there something else going on?
Can the Presence of Ketones Directly Suppress Appetite?
- The ‘hunger hormone’ ghrelin typically rises during weight loss and increases food cravings. However, in a recent study, this increase was suppressed in dieters in ketosis, despite a caloric deficit.
- In the same study, the satiety hormones leptin and amylin rose despite the participants losing weight. After reintroducing carbohydrate, satiety hormones fell, and hunger hormones quickly increased.
- A high presence of ketone bodies may provide a signal to inhibit the body’s production of hunger hormones.
- A meta-analysis and systematic review of available trials suggest appetite suppression through ketosis is plausible. However, a ‘minimal level of ketosis‘ may be required to achieve this effect.
5. Reduced Triglycerides and Increased HDL
You may have heard about “good cholesterol and bad cholesterol,” but these markers are not thought to be adequate as a predictor of risk.
That said, what does constitute the optimal predictor of cardiovascular risk?
Many experts have their theories, but the science isn’t set in stone at this time – and I don’t think the LDL vs HDL ratio should be entirely discounted.
However, specialists have long believed that LDL vs. HDL is “sub-optimal” as a risk factor. And over recent years, triglycerides to HDL has emerged as a much more reliable marker (22);
- A 2015 study found that the triglyceride to HDL ratio is the most significant independent marker of cardiovascular mortality (23).
- In a study involving 374 high-risk heart patients, there was no significant relationship between total cholesterol and the extent of coronary disease. Additionally, there was an extremely significant statistical link from total triglycerides and the triglyceride/HDL ratio (24).
How Does Being in Ketosis Affect HDL/Triglycerides?
A low level of HDL and a high amount of circulating triglycerides reliably track with high amounts of insulin in the blood (24).
In other words, when we reduce our blood glucose levels, insulin typically falls, and the HDL/triglyceride ratio improves.
The scientific literature generally shows that ketogenic diets favorably impact cardiovascular risk;
- In a study of obese subjects, a sub-20-gram carbohydrate ketogenic diet decreased total cholesterol, LDL cholesterol, triglycerides, and blood glucose. In contrast, there was a significant increase in HDL. This study lasted 56 weeks, and health markers were consistent through seven different tests at eight-week intervals (25).
- A 6-week study of healthy weight men showed that a ketogenic diet of 8% carbohydrate significantly increased HDL levels without impacting LDL or total cholesterol (26).
6. Ketone Bodies and Mental Health/Conditions
There is a notable amount of anecdotal evidence regarding ketogenic diets and mental health.
In particular, many people claim that entering ketosis improved their mental clarity, focus, eliminated brain fog and relieved depression.
But is this just anecdotal, or is there science behind it too?
- Following ketogenesis, intracellular sodium concentrations fall as the body enters ketosis. Significantly, this is the same effect that all mood stabilizers have (27).
- In human subjects, a randomized, controlled trial found that a low carbohydrate diet induces a statistically significant improvement in mood. Compared to a low-fat intervention group, the low-carb dieters also experienced fewer mood swings and irritability (28).
- In animal studies, rats feeding on a ketogenic diet displayed fewer symptoms of depression than those on a control diet. These rats also exhibited the same improvements in positive behavior as rats treated with antidepressants (29).
- Prenatal exposure to a ketogenic diet reduces anxiety, depression, and blood glucose levels as an adult (animal study) (30).
- Four randomized, controlled trials involving 289 people show that ketogenic diets may be beneficial for epilepsy patients. In brief, the studies show that being in ketosis provides short to medium term benefits in seizure control (31).
In addition to these six benefits of ketone bodies, there are various other positive impacts that being in ketosis may have on health.
They may also be beneficial for sporting performance.
But the most important thing to remember is that all diets are just the sum of their parts.
Any diet that proves sustainable and helps to improve your daily dietary choices will have positive health effects.
No matter what type of eating plan you favor, the important thing is to primarily focus on whole, unprocessed foods.
To put it differently, whether a ketogenic diet is healthy or not depends on the quality of foods you are including.