Science

Ketones: Types and Their Role in Human Metabolism

Ketones: Types and Their Role in Human Metabolism

Previous Article: What Is Ketosis: Understanding the Science Behind This Natural Process

Main Page (Index): Ketosis: The Complete Guide

Next Article: The Science Behind The Metabolic Process of Ketosis

People who’ve heard about the keto diet often ask: What are ketones? Ketones have become a hot topic since the low-carb, high-fat diet went mainstream. They say that ketones give you energy, help you burn fat, boost your brain function and more.

But is this true?

To satisfy your curiosity, we’re going to discuss the different types of ketones and their various roles. This guide should help you appreciate their benefits for your health.

Let’s dive in.


formation-of-ketone-bodies

What Exactly Are Ketones?

In a nutshell, ketones are the byproducts of fat metabolism. They serve as your alternative fuel source when you follow a ketogenic diet or undergo prolonged fasting.

The formation of ketones happens in the mitochondria of your liver. We call this formation process “ketogenesis”.

Here’s how your body produces ketones:

  • When you significantly limit your dietary carbohydrates or are in starvation mode, your body starts to run out of glycogen. Note that glycogen is the storage form of glucose [1].
  • As glycogen stores diminish, your body starts to look for ways to create more glucose to keep functioning. In this case, it taps into non-carbohydrate sources such as lactate and glycerol through a process called gluconeogenesis [1].
  • Ketogenesis starts when carbohydrates are further depleted. Since your glycogen stores have already been used up, your body now turns to its stored fat [1].
  • The hormone lipase causes the release of triglycerides from your fat cells. Triglycerides break down into free fatty acids. Now, these free fatty acids enter your bloodstream [1, 2].
  • Your liver absorbs these fatty acids so it can break them down to create ketones. So any time you need energy, your non-hepatic tissues utilise ketones. These tissues include your heart, skeletal muscles, brain and kidneys [1, 2, 3].

3 different types of ketones

We’ve already given you the definition of ketones. You also know that ketone bodies increase when glucose is low. Ketones supply you with energy.

Now, you might be wondering: What specific ketone bodies does my liver produce? There are three types, including:


the-liver-produces-three-types-of-ketones

1. Beta-hydroxybutyrate (BHB)

As the most abundant ketone body, BHB makes up 78% of ketones in your blood. Beta-hydroxybutyrate is derived from acetoacetate which is another ketone body [4].

Many people who want to enter ketosis faster supplement with exogenous BHB. As you can tell, the ketone body BHB is a favorite because of its wide array of advantages.


2. Acetoacetate (AcAc)

Like BHB, acetoacetate is considered a main ketone body. AcAc is the first ketone that your body produces and will either be converted into BHB or acetone [5].

That said, acetoacetate is important. Without it, we cannot experience the positive effects of ketones since the other ketone bodies are derived from it.


3. Acetone

As we mentioned earlier, acetone is another byproduct of acetoacetate. However, acetone is the least abundant. Unlike BHB and AcAc, acetone does not provide you with energy. Instead, you excrete acetone through your breath or urine [1].

If you’re wondering why you get bad breath when you first enter ketosis, that’s due to acetone exiting your body. While your body doesn’t use acetone, we still consider it important because it lets you know that you’re already in ketosis.


where do ketones come from

Ketones and Their Role in Metabolism: What Are Ketones Used For?

Ketones help you in many ways, and that is why we aim to increase them using nutritional ketosis. Again, they provide energy to your tissues when carbohydrate supply runs low.

Let’s explore the various uses of ketones:


1. Increase mitochondrial mass

Mitochondria are vital structures inside your cells. Their main role is to generate energy in the form of ATP. Aside from that, they also moderate the growth and death of your cells [6].

Research shows that increasing mitochondrial mass protects us against diseases like Type 2 Diabetes and Alzheimer’s by improving cell energy efficiency and protecting against free radicals. Cells that are exposed to ketone bodies tend to produce more ATP [7, 8, 9].


2. Act as anti-seizure agents

Did you know that ketosis has already been used in the 1920s? Physicians realized that starvation decreased seizure activity. With that, they found a way to mimic the metabolism of fasting - through nutritional ketosis [10].

Ketones possess anticonvulsant properties. They reduce and stabilize the excitability of your synapses, thereby controlling seizures [11].


3. Reduce hunger and appetite

Dr. Zane Andrews, a neuroendocrinologist at Monash University, revealed an important finding [12]:

Eating more carbohydrates and sugars damage your appetite-suppressing cells. When these cells get damaged, you tend to eat more.

people-who-eat-a-very-low-carbohydrate-diet-have-suppressed-ghrelin

This is another scenario where we get to appreciate the role of ketones. Many researchers believe that ketones reduce appetite by acting on the brain directly [13].

Here’s another interesting finding: People who eat a very-low-carbohydrate diet and achieve BHB levels of at least 0.3mM have suppressed ghrelin, the main appetite hormone [13].


4. May benefit the failing heart

Evidence shows that the failing heart is energy-starved. During heart failure, the heart is less able to use fatty acids which are its main energy source. With that, it turns to ketone bodies to get fuel [14].

The American Heart Association published a study. The study showed that mice that were given a ketogenic diet for up to 15 weeks were able to avoid cardiac hypertrophy and heart failure [15].


ketone-bodies-formation

5. Reduce inflammation in your body

Inflammation is your body’s way of protecting you from tissue damage and infection. The problem is, too much of it can lead to certain diseases. These diseases include stroke, heart disease, rheumatoid arthritis, and lupus [16].

What’s interesting is that your diet can fight inflammation. You may be wondering: How does ketosis reduce inflammation?

Beta-hydroxybutyrate is the answer. BHB gets rid of inflammation by inhibiting the NLRP3 inflammasome [17].

The NLRP3 inflammasome is a protein complex that triggers cell death and releases cells that promote inflammation [18].


6. Can increase memory

Beta-hydroxybutyrate provides your brain with more energy than glucose. This explains why neurological diseases resulting in impaired glucose utilization can benefit from BHB [19, 20].

A 2004 study showed that when older adults with memory disorders consumed MCT (medium-chain triglycerides), their ketone body levels increased. This increase in ketones helped the subjects improve their ability to better recall previously read text [20].


7. Act as antioxidants

Another amazing thing to know about ketone bodies is that they possess an antioxidant capacity, protecting healthy cells from getting damaged. A 2008 study found out that acetoacetate and beta-hydroxybutyrate scavenge free radicals [21].


nutritional-ketosis-can-stop-tumor-growth

8. Prevent cancer from progressing

Unlike healthy cells, cancer cells cannot use ketones for fuel. This makes cancer cells unable to survive. It is because of this that researchers hypothesize that nutritional ketosis can stop tumor growth [22].

Patients who had advanced metastatic cancers experienced partial remission when they ate a carb-restricted keto die.

You know what’s interesting about the study? When the patients entered a deeper level of ketosis, their condition stabilized. The disease didn’t progress [22].

So how do ketones “starve” cancer cells? The answer is that they inhibit glycolysis - the main process in which cancer cells produce energy. Cancer cells show a high rate of glycolysis [22].


9. May lower blood sugar levels

It’s no secret that reducing carbohydrates stabilizes your blood glucose. But do higher ketone levels have the same effect?

Researchers from the University of British Columbia and the University of Oxford demonstrated that a ketone ester drink controls blood glucose by reducing spikes in glucose blood levels [23].

In the study, two healthy individuals consumed a ketone monoester supplement on two occasions. After 30 minutes, they consumed a drink containing 75 grams of sugar [23].

The result? The blood glucose of the participants only lowered on the day they took the ketone drink (and not the placebo) [23].

This of course was tested on patients who had consumed carbohydrates. For those following the Keto diet, your blood sugar levels will already be normalised by your reduced sugar and carbohydrate intake.


Conclusion

As you can see, ketones are worth appreciating for their many health benefits. While there are three types of ketones, only BHB and AcAc are used by the body. Acetone doesn’t have any use, and it exits the body through the breath or urine.

Finally, don’t forget to speak with a physician who can assist you with nutritional ketosis if you wish to experience the positive effects of ketones.


Takeaways

  • Ketones serve as an alternative metabolic fuel during starvation or when you follow a low-carb and high-fat diet.
  • The formation of ketone bodies occurs in the liver. We call this process ketogenesis.
  • Tissues that can use ketones include your skeletal muscles, heart, brain and kidneys.

References:

  1. Dhillon KK, Gupta S. Biochemistry, Ketogenesis. Last update: 2019 April 21 - https://www.ncbi.nlm.nih.gov/books/NBK493179/
  2. Conger C. When We Lose Weight, Where Does the Lost Weight Go? 2008 May 8 - https://health.howstuffworks.com/wellness/diet-fitness/weight-loss/lost-weight1.htm
  3. Diapedia. Ketone body metabolism. https://www.diapedia.org/metabolism-and-hormones/51040851169/ketone-body-metabolism
  4. Mayo Clinic Laboratories. Beta-Hydroxybutyrate, Serum. https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/9251
  5. ScienceDirect. Ketone Bodies. https://www.sciencedirect.com/topics/neuroscience/ketone-bodies
  6. Rogers K. Mitochondrion. https://www.britannica.com/science/mitochondrion
  7. ScienceDirect. Mitochondrial Biogenesis. https://www.sciencedirect.com/topics/neuroscience/mitochondrial-biogenesis
  8. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. 2010 June 14 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883043/
  9. Frey S et al. The addition of ketone bodies alleviates mitochondrial dysfunction by restoring complex I assembly in a MELAS cellular model. 2017 January - https://www.sciencedirect.com/science/article/pii/S0925443916302812
  10. Wheless JW. History of the ketogenic diet. 2008 November - https://www.ncbi.nlm.nih.gov/pubmed/19049574
  11. Simeone TA, Simeone KA, Rho JM. Ketone Bodies as Anti-Seizure Agents. 2017 April 10 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505793/
  12. Monash University. Killer Carbs: Scientist Finds Key To Overeating As We Age. 2008 August 22 - https://www.sciencedaily.com/releases/2008/08/080821110113.htm
  13. Bailey B, Volek J, Phinney S. The Science of Nutritional Ketosis and Appetite. 2018 July 25 - https://blog.virtahealth.com/ketosis-appetite-hunger/
  14. Aubert G et al. The Failing Heart Relies on Ketone Bodies as a Fuel. 2016 January 27 - https://www.ahajournals.org/doi/10.1161/circulationaha.115.017355
  15. Zhang Y et al. Abstract 18046: Ketogenic Diet Rescues Heart Failure Induced by Loss of the Mitochondrial Pyruvate Carrier 1. 2018 June 9 - https://www.ahajournals.org/doi/abs/10.1161/circ.136.suppl_1.18046
  16. Szalay J. What Is Inflammation? 2018 October 19 - https://www.livescience.com/52344-inflammation.html
  17. Yamanashi T et al. Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses. 2017 August 9 - https://www.ncbi.nlm.nih.gov/pubmed/28794421
  18. Yang Y et al. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. 2019 February 12 - https://www.nature.com/articles/s41419-019-1413-8
  19. Fan S. The fat-fueled brain: unnatural or advantageous? 2013 October 1 - https://blogs.scientificamerican.com/mind-guest-blog/the-fat-fueled-brain-unnatural-or-advantageous/
  20. Reger MA et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. 2004 March - https://www.ncbi.nlm.nih.gov/pubmed/15123336
  21. Haces ML et al. Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions. 2008 January 26 - https://www.ncbi.nlm.nih.gov/pubmed/18339375
  22. Poff AM et al. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. 2014 May 14 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235292/
  23. The Physiological Society. Ketone drink could help diabetics by lowering blood sugar. 2018 February 13 - https://www.sciencedaily.com/releases/2018/02/180213223357.htm

Join Over 200,000 Fans

Sign up for the Kiss My Keto mailing list to get free keto resources, recipes, and strategies from the largest keto brand in the world.