Keto Diet for the Brain

Nowadays the ketogenic diet is getting more and more popular. Some people claim that carbohydrates are harmful and should be eliminated or reduced. The ketogenic diet may be the answer to these doubts. Believe it or not, but back in 2020, “keto” was the most googled food-related topic in the world. Apart from supporting weight loss it is supposed to have many other benefits. It may improve brain health by boosting energy levels, increasing the ability to focus and supporting cognitive functions. In the following article I will try to investigate this issue. We will discover what keto diet is all about, how it affects the human body and whether it can actually improve cognitive functions of the brain.

What is the ketogenic diet all about?

The keto diet is a low-carb and high fat approach. It leads to a change in metabolic state of the body which is similar to the effect of starvation. In both cases, there is an increased production of ketone bodies, which provides an alternative source of energy. The body gets into ketosis. What is it exactly? Stay tight as I will explain it in more detail.

What is ketosis, then?

The main purpose of a ketogenic diet is to enter ketosis – a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. The physiological concentration of ketone bodies is about 0,05 mM and increases after prolonged exercise or 24-hour fasting. Nutritional ketosis is defined as sustained blood ketone levels of 1-7 mM. It is achieved when the body is fueled mainly by fats instead of carbohydrates. Low blood glucose concentrations result in a decrease in insulin levels. It then leads to the release of free fatty acids (FFAs) and glycerol from the adipocytes caused by hormone-sensitive lipase. The released FFAs then undergo beta-oxidation in the mitochondria of hepatocytes and acetyl-CoA is formed. Normally this compound is incorporated into the Krebs cycle by oxaloacetate. However, if the amount of carbohydrates supplied with food is low, the hepatic pool of oxaloacetate is utilized in gluconeogenesis – the synthesis of glucose. The accumulated acetyl-coA is then used for ketogenesis – the production of ketone bodies. As you can see, it is a pretty complex chain of different metabolic reactions that can be influenced by our eating habits.

Ketosis occurs primarily in the liver, and to some extent in the kidneys. Cells producing ketone bodies have an increased expression of the key enzyme of the process – 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2). The ketone bodies include acetone, acetoacetic acid and beta-hydroxybutyric acid. The first one produces acetylacetone, which can then be converted by decarboxylation to acetone or reduced to beta-hydroxybutyrate. The produced compounds are released from the liver into the circulatory system. What happens next? Well, acetone, as a volatile substance, is mainly removed from the body by the lungs and kidneys, while acetylacetone and beta-hydroxybutyrate are transported to extrahepatic tissues. In the mitochondria they are used to reconstitute acetyl-CoA molecules, which will become incorporated into the Krebs cycle and ATP production. 

The ketogenic diet principles to consider

We have already established the biochemistry of the ketogenic diet. What does it look like in practice? Well,  in keto there is such a reduction in the supply of carbohydrates that induces increased production of ketone bodies. This usually requires reducing the amount of carbs to 10% of the energy value of the diet. For example, for a total energy requirement of 2000 kcal, the daily portion of carbohydrate intake should not exceed 50 g. In the initial phase it should be limited even to 20 g, so that the body can adapt and enter a state of ketosis. Generally, popular ketogenic resources suggest that the macronutrients ratio is 4:1 or 3:1. The first option means that for every 4 g of fat there is a 1g of protein and carbohydrates. About 86% of energy needs are covered by fat, 2-4% by carbohydrates and the rest by protein. In a 3:1 ratio, for every 3 grams of fat consumed, 1 gram of combined carbohydrate and protein is allowed. 

In the keto diet it is recommended to eat 3 meals per day at regular intervals. Each meal should contain similar amounts of macronutrients. Fluids are limited to 60-65 ml per kilogram of body weight per day. Besides water you can drink coffee, tea and some fruit as well as vegetable juices. In this diet it is allowed to eat good quality meat, fish and seafood, vegetables, oils, fats and dairy. Since we have figured out what we can eat, the next question is what to avoid. The keto diet excludes sweets and sweetened beverages, grains, alcohol, starchy vegetables and fruits (except blueberries, strawberries, currants, raspberries and blackberries) because these products will take you out of ketosis. 

Diet and the brain – a crucial link

The ketogenic diet is very restrictive and difficult to sustain. You may now be wondering if it is really worth following. Well, it has been proven that this dietary model has beneficial effects on the brain and shows neuroprotective properties. Many ketogenic diet followers report increased energy levels and ability to focus as well as reduced anxiety and depression. The underlying mechanism has not been fully explained. It may be associated with altering the ratio of two central nervous system neurotransmitters – GABA and glutamate in favor of GABA. Glutamate is responsible for stimulating the body while GABA is the main inhibitory neurotransmitter. Lack of concentration and fatigue can be caused by an incorrect ratio of these substances – an excess of glutamate versus too little GABA.

Research shows that an increase in the concentrations of ketone bodies in the blood helps rebalance GABA and glutamate levels. This is caused by increased production of GABA, which reduces the excitations of neurons in the brain. It results in a greater ability to focus and improves stress resilience. According to the researchers, beta-hydroxybutyrate itself has neuroprotective effects as it prevents neurons from damage. Another crucial compound for the brain are omega-3 and omega-6 fatty acids. They are structural components of the neuronal membrane. They also have anti-inflammatory and antioxidant properties. It has been proven that they contribute to reducing the expression of pro-inflammatory and pro-apoptotic factors, while increasing the activity of neurotrophic factors such as BDNF, GDNF and NT-3. All of the above-mentioned mechanisms may be responsible for the protective effect of the ketogenic diet on the nervous system and brain. 

Ketogenic diet vs neurological diseases 

The ketogenic diet is a proven tool in the treatment of many diseases. It plays a significant role in metabolic disorders associated with glucose transport and utilization – glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency. In addition, it has been shown to be effective in the treatment of drug-resistant epilepsy and numerous neurodegenerative diseases (such as Alzheimer’s disease and Parkinson’s disease), stroke, traumatic brain injury, brain stem damage, multiple sclerosis, headaches and sleep disorders. The mechanisms of neuroprotective action are not fully explained. Scientists assume that they are caused by the same processes I explained in the previous section. Neurodegenerative diseases are often accompanied by mitochondrial dysfunction and reduced energy production. The ketogenic diet stabilizes synaptic activity by improving mitochondrial function and increasing ATP production. It controls blood sugar spikes, which can aggravate the symptoms of Alzheimer’s and Parkinson’s disease. It has been observed that consumption of high glycemic index food promotes beta-amyloid deposition in the brain in Alzheimer’s patients. Ketogenic diet helps to reduce this process, which can contribute to delaying mild cognitive impairment and even full blown Alzheimer’s disease. In multiple sclerosis, neurons abnormally capture and metabolize glucose, so ketone bodies provide a better source of energy. Beneficial effect of a ketogenic diet in the treatment of drug-resistant epilepsy is associated with increased production of GABA. It causes reduced neuronal excitability, which helps to suppress seizures. 

Does keto work for everyone?

You need to remember that a ketogenic diet is demanding and can be hard to maintain. It can lead to serious side effects. Especially at the beginning, keto should be approached with great caution, as we do not know how your body will react. The diet should always be supervised by a doctor and a clinical nutritionist. You should also perform a complete blood test before starting the diet. To avoid side effects, the diet is introduced gradually, which usually takes from 1 to 4 weeks. 

There are a number of contraindications to this dietary model. These include:

1. liver disorders (as it may cause liver injury and worsen the symptoms of liver disease)
2. kidney disorders (it may worsen kidney disease and has been linked with kidney stone development)
3. pancreatic disorders, such as inflammation or hyperinsulinism
4. familial hypercholesterolemia
5. eating disorders in the past
6. pregnancy and breastfeeding
7. inborn metabolic disorders such as impaired beta-oxidation of fatty acids (including LCHADD, VLCADD, MCADD, CPT1, CPT2), disorders of gluconeogenesis (e.g. pyruvate carboxylase deficiency, glycogenoses)
8. diabetes as it may increase the risk for diabetic ketoacidosis 
9. heart conditions 

When it comes to side effects, the most common ones include constipation, fatigue, dizziness, weakness, nausea, diarrhea and stomach pain. They are known as “keto flu” and may appear two to seven days after starting a ketogenic diet. It can also cause irritability due to the restriction of carbohydrate supply which can lead to latent acidosis, hypoglycemia and mineral deficiencies. Note that it is a restrictive dietary model that requires full commitment and careful meal planning. Lastly, it is not the cheapest choice – the use of good quality fats is pricey and not everyone can afford it. 

Is it really worth it?

The ketogenic diet has both advantages and disadvantages. Research shows that the brain needs fat and therefore it is a good choice for supporting cognitive functions. It is also a promising therapeutic strategy for a variety of neurological disorders. However, it comes with many limitations, so everyone should assess whether it will be suitable for them. At the end of the day, it should be approached consciously and gradually.