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The Keto Diet: Is it Really Safe?

Trending new diets or magical solutions have proved over time that they work for a while and sadly the side effects and long term damage also outweighs the benefits. However people as with every commodity of modern life want to find quick easy solutions for everything when in fact we realize that the old patterns were the ones that proved to be healthier!

At least in the realm of nutrition there's a lot of ground to be covered now that the epigenetic science is giving us a lot of information in terms of the marks that we can do to our genes and the possible trigger effects that these epigenetic changes will have in the long term!

What is the core message of the keto diets in terms of your biochemical processes?

We all possess and amazing capacity to use all our nutrients in the correct amount as well as trying to balance them inside of our body and to perform those amazing tasks we have our metabolic pathways to do it!

So, let's begin with the journey of the fats, which is the main focus of the ketogenic diets, eating animal fat in order to be processed and obtain energy from it! Reduce to levels (many times dangerous) the ingestion of carbohydrates and force our body to burn the fat and protein to produce ketone bodies and carbohydrates respectively to use them as energy!

When we eat fat our metabolism drives those fats to the mitochondria with an amazing carrier or transporter, named carnitine, carnitine allow the fatty acids to get inside of the mitochondria and then produce an energetic compound named Acetyl-CoA which can have to destinations either it will go the Krebs Cycle which is one of your most important metabolic pathways that feeds the production of proteins, plenty of amino acids, the nucleus of the Hemoglobin, named Porphyrin, produces also your building blocks for the DNA and RNA your nucleotides, and finally it is a central pool to distribute essential compounds to practically all of our body functions!

Inside of this amazing metabolic cycle, the Acetyl-CoA is going to be disassembled and it will give rise to many other intermediate compounds which will be the precursors for all the molecules mentioned above! In the journey that cycle will produce 3 molecules of NADH, 1 molecule of FADH and 1 molecule of GTP (which is also energy and a cousin of the ATP).

The energy molecules of NADH and FADH will be then transported to our amazing bank to be transformed into the currency of our body, ATP. Each molecule of NADH will produce 3 ATP's and each molecule of FADH will produce 2 ATP.

Therefore the total amount of ATP's produced by each of the Acetyl-CoA is 12. Which is plenty of energy per molecule! Now let's clarify something here when fats are oxidized in the mitochondria, depending of the length of the fatty acid is the amount of Acetyl-CoA that I will obtain.

Meaning that If I consume a fatty acid of 18 carbons, picture a necklace of pearls, where each pearl is 1 Carbon molecule. That fatty acid will produce 9 molecules of Acetyl-CoA which in turn will give me (9 x 12) = 108 molecules of ATP per fatty acid that is an amazing amount of energy that your body produces through the burning of fats!

That's why the supporters of Keto Diet show off that is a more intelligent way to use our energy as well as allowing your body to burn your "extra fat" as you would not have the carbohydrates to rely on!

Secondly Acetyl-CoA can also enter another pathway in your the mitochondria of your liver and this pathway is known as Ketogenesis, meaning generation of ketone bodies, this pathway in the ketogenic scheme and without the availability of carbohydrates is a salvage or resource pathway that will allow the production of these chemical compounds (ketone bodies) to be fueled and transported to extra hepatic tissues such as your brain, your heart, your kidneys, your skeletal muscle and your lungs.

Therefore from two different sources of burning the fat or using the fat as your favorite energy fuel, you will have energy for your maintenance functions.

Now that you know the biochemical basis of this ketogenic scheme, is time to explain the but's and the possible restrictions in terms of maintaining this kind of nutritional scheme for prolonged periods of time (more than 3 months).

Ketone bodies could be these kind of compounds, this is just to give you the tools to become your own expert and not to be fooled by people without the correct preparation to prescribe a nutritional scheme such as this diet!

We have 3 main ketone bodies produced which are acetoacetate, β-hydroxy-butyrate and acetone these energetic compounds are produced to the oxidation and some other chemical steps from 2 molecules of Acetyl-CoA.

Therefore if you have a good amount of fat, which is the basic advice that many people give in terms of following this scheme, you will either produce energy through the burning of fat or through the production of ketone bodies to be able to feed other organs!

However and as mentioned above, if we are only consuming proteins and fats, our body will have an excess of ketone bodies and not much availability of some carbohydrate intermediate compounds which are also essential for the production of other cellular structures such as receptors, essential pentoses for the production of nucleotides (your building blocks of your DNA and RNA) which in turn will allow your whole body to be repaired or for the production of proteins, and some structures named channels which are also produced of carbohydrates backbones!

So many of those processes in the long run will be affected, that is what people that recommend the keto scheme are missing in addition of new evidence that overproduction of ketone bodies has an epigenetic downsize and allow some of the genes to be methylated or acetylated which turn them off and stops the production of healthy proteins!

Posttranslational modifications (PTMs) are key mechanisms for epigenetic regulation, and link cellular metabolism to gene expression in health and disease. Widely characterized histone lysine modifications include acetylation (Kac) and methylation (Kme). Classically, acetylation of histone lysine residues disrupts electrostatic interactions between the DNA backbone and lysine-rich nucleosomes, opening chromatin to transcriptional machinery. Kme, on the other hand, may condense or open chromatin, depending on the histone site and methylation stoichiometry (1).

In addition, additional short- chain acylations on histones have been identified over the last decade, whose genome-wide effects on transcription continue to be characterized These PTMs, including lysine propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation (Ksucc), malonylation, glutarylation, hydroxy-methylglutarylation (Khmg), crotonylation, and β-hydroxybutyrylation (Kbhb) may all regulate gene expression, and are directly related to the availability of their corresponding acyl-CoAs, because negatively charged acyl-CoA species are highly reactive metabolites (1).

As mentioned above all of these chemical modifications that are just cause of excessive accumulation of ketone bodies in addition of the generation of many Acyl-CoA species that are also part of the oxidation of fats will in turn trigger many of the "tagging" mechanisms by the residues of the excessive metabolism of fats which will predispose you to build up over a period of time to accumulate these kind of "tags" until one of your key genes to produce certain metabolic proteins will suffer the consequence, giving as a result a worn out organ (liver or kidney) which is essential for all your metabolic functions. In addition to that, as we all know this silent "DNA tags" will not give any signs until it is too late to do something or to repair the damage!

Therefore before you embark in a nutritional scheme or regime as drastic as the ketone diet, do it for a small period of time (less than 4 months) do it with specialists that more than knowing nutrition, also have an expertise in the biochemical and metabolic functions or your body and that keep you monitored in terms of the accumulation of these chemical compounds (ketone bodies and Acyl-CoA's) which should not be in excess in or bodies.

When our bodies have a high amount of ketone bodies, provoked by nutritional ketosis (more than 240 mg/dL) we should start paying attention to other signs or symptoms in our bodies such as glucose levels in blood, fatigue, frequently becoming ill, poor concentration or memory problems, etc. if we are not using ketone bodies as we should be under this kind of scheme and instead we're allowing the accumulation of them, we certainly will lead our organs such as the liver and kidneys to start with to start showing the effects!

Moreover, people that are submitted to this kind of nutritional diet, very high in fats and protein, lowering the amounts of carbohydrates to very small percentages also have some symptoms when starting the diet, such as: bad breath, headaches, thirst, and stomach complains to mention the most common.

As we also mentioned above this kind of nutritional scheme with the nature of the chemical compounds produced such as the ketone bodies and the acyl-CoA's which both have an acid character (more the ketone bodies) will also acidify the pH of your fluids meaning that you can have also some long term consequences such as reflux, a sensation of sourness, and more to worry about if you feel an intense burning sensation in your throat.

Also, these ketone bodies, in excessive amounts will start producing a slow motion damage in your kidneys, your gallbladder, and to end with some liver issues which most likely will start with some of your metabolic enzymes being unable to process certain types of foods!

Who, how and when it is recommended?

With all the previous information, you should know by now if this diet is for you, however to make it more clear and specific will navigate under some of the additional recommendations.

  • Switching to any kind of specific or restricted nutritional regime should be supervised not only at the level of loosing weight and external appearances, you should also trust more when the specialist is keeping a biochemical score of your progress, in addition of looking at some essential parameters such as your attention, energy levels, sleeping patterns and any kind of physiological disturbance that you may have;

  • Moreover, this kind of diet, should be performed just for a short period of time, with the risk of having a rebound effect that will frustrate you or even worse show you that you no longer are able to process certain kinds of food which you used to have no issue (of course that if you don't tolerate simple sugars or processed foods, that is a blessing for you);

  • It has to be implemented with small steps and changes in your eating behaviors and taking out some of the nutrients carefully and gradually so your body can adjust and you also reduce the levels of the side effects;

  • It is clear, that at least for the time being, this kind of nutritional scheme is not for all your life and will not be the end of your issues with food, a lot of research is missing more in terms of long terms effects in specific organs such as liver, gallbladder, and kidneys as well as in the epigenetic realm!;

  • Research has proven and tested this kind of diet for patients with Alzheimer, Seizures, Parkinson, Diabetes type 2, and other mental illnesses, of course under medical supervision and with a good monitoring scheme of any biochemical parameters relevant to the disease!;

  • Finally, and as mentioned before, carbohydrates (at least complex and the ones in fruits) cannot be ruled out or vetted completely and we need some of them in order to produce many of more complex molecules such as receptors, channels that allow the transport of nutrients, nucleotides (your building blocks of DNA), and to feed some essential metabolic pathways such as the pentose phosphate pathway which will level up your NAD levels and help reduce a very important molecule that will protect your body from oxidative reactive species, the glutathione, which will be a subject of another article soon!

In summary, not every kind of regime serves a multipurpose so far, not all the nutritional schemes will fit everyone, any of them should be implemented just because you read about it, because you saw a commercial ad or because some kind of "wellness guru" tells you is the best, nowadays you have the power to verify information, to search in more serious information whether is good or bad, or there are some things to be settled!

To end with, this article is intended to give you more information to decide, to know more about your internal processes and to give more tools to embark in your own and personal journey of knowing your body, listening to the messages and checking more how it is internally!


1. Ruan, H.-B., & Crawford, P. A. (2018). Ketone bodies as epigenetic modifiers. Current Opinion in Clinical Nutrition and Metabolic Care, 21(4), 260–266.

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