As already described on the page Sugar & Carbohydrates, the brain is the major energy consumer in the human body (approx. 25% of the resting energy consumption), although it only accounts for 2% of the body mass. It is particularly easy to provide this energy via blood sugar (glucose). However, a major problem in today’s Western diet is flooding the body with sugar and resulting disorders in sugar metabolism, such as insulin resistance and type 2 diabetes mellitus, which can also negatively affect energy supply in the brain, and are a major risk factor for Alzheimer’s disease. Some researchers have even referred to Alzheimer’s as “type 3 diabetes” or “cerebral diabetes”. The good news is that the brain can use other energy sources, particularly ketone bodies, which are provided by the liver. Ketone bodies can be used for energy by neurons even when the use of glucose is already limited.
Ketone bodies, or ketones for short, are formed in the mitochondria of liver cells from fats, or more precisely from fatty acids, via the process branching off from ß-oxidation. This process produces the three ketones acetoacetate, beta-hydroxybutyrate and acetone. Their chemical structures are shown in Figure 1. The production starts when the insulin level in the blood decreases and the hormone glucagon increases, especially if the sugar stores (glycogen stores) in the liver have previously been used up. This is the case, for example, during starvation metabolism (e.g. during periods of fasting), but also during low carbohydrate intake and intensive physical training. The body is now in physiological ketosis, which is an alternative supply program for the body to keep it energized and alive during periods of energy and/or carbohydrate shortage. However, this physiological state should not be confused with ketoacidosis, an excessive and dangerous ketone formation that can occur in cases of absolute insulin deficiency, such as untreated type 1 diabetes. In ketoacidosis, up to 10 times more ketone bodies are produced than in ketosis, and at the same time the blood is overacidified, a life-threatening condition! In contrast, the state of physiological ketosis is characterized by ketone concentrations of about 0.5 – 3 mmol/l in the blood, which are harmless.
Figure 1: Chemical structures of physiologically formed ketones
The ketone bodies formed in the liver ultimately represent an alternative form of transport for energy carriers. This is because after uptake by the cell (CNS and muscle tissue), the ketone bodies are broken down again to acetyl-CoA via enzymes and used in the citrate cycle and the respiratory chain to obtain the cell fuel ATP. This is the reason why the human brain can function well even with greatly reduced carbohydrate intake via fat conversion in the liver. This in turn also explains the healing and detoxifying effect of fasting.
But ketones are not only fuels: they also protect neurons from oxidative stress, have an anti-inflammatory effect and promote the formation of new nerve cells. Ketones are therefore a very good alternative to sugar, especially since their combustion is more effective because they produce more energy equivalents in the form of ATP per oxygen molecule than glucose and fewer free radicals are formed. However, this requires good mitochondrial health, because the utilization of ketones also relies on these cellular power plants. Switching from sugar to ketone utilization is therefore a natural process by which the healthy aging brain also fills any existing energy gaps – if it is provided with enough ketones. To do this, it needs fat, either from the body’s depots or from food.
The utilization of fats and ketones has saved the lives of our ancestors during food shortages over millions of years of evolution. For us, every night when we sleep and do not eat, it ensures that we stay healthy and that our body can repair itself. Such an energy-consuming and sensitive organ as the human brain would be inconceivable with a single, fluctuating energy source such as glucose. That is why neurons can also use ketones as well as lactic acid (lactate) and acetate for energy production.
Since ketones are predominantly formed from fat (especially effectively and quickly from MCT oils), we should either eat enough fat or connect our brain to the body’s fat reserves so that it can be evenly and safely supplied with energy, building and protective substances and easily survive gaps in supply with sugar. A nice side effect is that cravings do not occur when there is nothing to eat, because the body then simply switches to utilizing its fat deposits. This is not about badmouthing the sugar metabolism or wanting to bypass it completely. The latter would not be possible at all. Ketones could supply the brain with 60 to 70 percent of the calories it needs, but the rest must come from sugar. But if we manage to keep our metabolism flexible so that it can easily switch back and forth between the different fuels, we give it the ability to better cope with energy crises. In this respect, fasting, during which more ketones are produced, can also be seen as good metabolic training for the brain.