06 February 2018

There will be no additives

Fasting prolongs the life of mice. What about people?

Polina Loseva, "The Attic"

"Those who eat little live long, because with a knife and fork we dig our own grave," says Count Cagliostro in Mark Zakharov's film. The relationship between the amount of food and life expectancy is found even in those organisms that do not know how to use a knife and fork. Questions immediately arise: how little do you need to eat? How does it work? And most importantly – what to do if you still want to eat?

Everyone already knows that eating a lot is harmful. Isn't something else unclear?

Overeating is really not worth it, it's true. When someone in our understanding "eats a lot", he gets more energy than he spends. At the same time, excess energy is stored in the form of fat. Obesity, in turn, brings with it a friendly company of concomitant diseases. But that's not the point right now. Back in 1935, it was discovered that animals that eat less than they expend energy live longer than their relatives who observe balance. Since then, in such a simple way, it has been possible to prolong the life of many animals, from yeast and worms to mice and monkeys. What about people?

The events of the XX century provided us with data that no one ordered. One of these random experiments was the World Wars. The population of some countries did not suffer serious losses during the fighting, but at the same time experienced a shortage of food. So, during the First World War, due to the cessation of trade with the United States and Britain, Copenhagen residents were forced to eat less than usual for two years. After that, the government's food adviser estimated that the death rate in the capital of the Danish Kingdom decreased by 34%. During the Second World War, residents of occupied Norway were restricted in food, and the number of deaths caused by diseases of the circulatory system fell by 30% compared to pre–war time - according to Norwegian researchers, largely due to a forced diet. The third unforeseen experiment unfolded in Japan. Back in the late twentieth century, the number of centenarians in Okinawa was 4-5 times more than in other civilized countries. The mortality rate of the elderly was lower, and the average life expectancy was higher, not only compared to other countries, but also compared to other Japanese islands. At the same time, it turned out that a typical Okinawan diet (lots of vegetables and fruits, fish, soy, rice) contains fewer calories than in other regions of Japan, not to mention the United States. However, in the 60s, American soldiers brought with them the culture of fast food; it also penetrated to Okinawa. As a result, at the beginning of the XXI century, those born in Okinawa can no longer expect to live longer than others.

Eating little is how much?

The main thing is not to confuse calorie restriction with starvation and malnutrition. First, a person should not starve. Scientists talk about reducing the caloric content of the diet by an average of 20-30%. That is, a person in this case consumes 20-30% less energy than he spends. A logical question arises: why then does the person not end at all? Below we will tell you how, with a lack of nutrition, the body begins to spend resources more efficiently. Secondly, it is necessary that the diet includes all the necessary groups of substances (proteins, fats, carbohydrates, vitamins, etc.). This is clearly seen in the above examples. Why did scientists start from the history of the inhabitants of Scandinavia during the world Wars? Because even though they were experiencing food restrictions, their diet was still full. They had the opportunity to eat, for example, fresh vegetables and fish. It's the same story with the people of Okinawa.

In fact, the planned experiments with people were also carried out. For example, in the framework of the CALERIE project (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy – a full-fledged study of the long-term effects of reducing energy consumption), volunteers tried for several months to reduce calorie intake by 25%, sometimes combining it with physical exercise. These studies are recent, so data on mortality will not appear soon. But already at the end of the first experiments, it became clear that those who ate less had a reduced likelihood of developing cardiovascular diseases and diabetes (that is, the concentration of marker substances in the blood became lower) compared to the control group. More severe restrictions were also investigated: in the Minnesota starvation experiment project, people consumed 40% less than necessary (on average, they ate 1800 calories/ day, and spent 3000 calories/ day). In this case, the researchers were just trying to recreate the situation of starvation during the world wars. The results did not look particularly encouraging, as expected – weakness, swelling, depression, behavioral disorders. However, after returning to a normal diet, they disappeared. But interestingly, half of the participants in this experiment, having reached the age of 80, then lived eight years longer than expected.

How do I find out how much energy I spend?

If you do not participate in the relevant experiment, it will not be possible to measure the energy consumption of your lifestyle on your own. In the laboratory, there are several techniques, most of which are reduced to measuring the amount of carbon dioxide emitted by humans. It is formed as a result of cell respiration, that is, the breakdown of nutrients to produce energy. For example, you can put the subject in a sealed room and watch how the concentration of carbon dioxide will change there. However, in order to simulate everyday activity, you will have to install exercise machines and treadmills in the room. In order not to build a room, you can use the double-labeled water method. It is a water molecule consisting of heavy isotopes of hydrogen and oxygen. We inject labeled water into the body, and after a while we measure the amount of isotopes in the blood. Over time, there will be fewer of them. At the same time, we know that hydrogen can leave the body mainly in the composition of water, and oxygen – also in the composition of carbon dioxide. Therefore, we calculate how much oxygen the body has lost, and subtract the amount of hydrogen lost. We get the amount of carbon dioxide that the body exhaled, and we already recalculate it by the amount of energy expended.

But what if you don't have a sealed room or labeled water? You can try to measure how much you usually eat. In experiments with animals, scientists measure consumption ad libitum, that is, to a state of saturation. We are not mice, and it is often not the need for energy that makes us eat, but many other factors (habits, socialization, depression, etc.). Nevertheless, you can track how much food you need – in calories, of course, to stop feeling hungry.

Then you can subtract 20-25% from this value. So you will get the number of calories you need to get daily if you decide to get into the skin of an Okinawan centenarian.

What kind of food should I eat?

The cells of our body can digest everything, but with different efficiency and speed. Let glucose enter the cell. At the first stage (glycolysis), the cell splits it slightly and receives energy immediately. At further stages (respiration), the cell splits it to the end and receives much more energy. But for this it is necessary to activate the mitochondria (it is in them that this splitting occurs) and use oxygen (it is for this process that we need it). Therefore, if a cell has enough glucose, it can afford not to split it all to the end, but to get energy easier and faster. Of course, she will not be able to stop breathing altogether, but she may "skew" the ratio of glycolysis / respiration in favor of the former. But if there is not enough glucose, then you have to use it more efficiently and make breathing more intense. Proteins and fats differ in that it is impossible to get energy from them quickly, it is necessary to go all the way to the mitochondria with them.

Therefore, when we reduce the calorie content of food, first of all we need to reduce the amount of carbohydrates. In a radical version, this leads to a ketogenic diet (which we recently wrote about), when there are very few carbohydrates, but a lot of fats. The benefits of this diet are still difficult to assess. It has long been used for the treatment of epilepsy, and in the prevention of neurodegenerative diseases, it has shown itself well. Nevertheless, it is quite difficult to withstand it, and there is no data on the life expectancy on it yet. So, the main thing is to reduce the amount of carbohydrates, but also to avoid radical distortions or their complete disappearance from the diet.

How does life extension work?

It seems that this is the most difficult question to which the final answer is still being sought. But in short, calorie restriction puts the cell on alert. That's how it happens. When a cell lacks glucose, it needs to actively breathe. Mitochondria use a lot of oxygen for this. Oxygen also easily forms free radicals – molecules that actively enter into chemical reactions. Free radicals attack all surrounding molecules, and damage begins to accumulate in the cell. This is called oxidative stress. If the stress is severe, there is too much damage, and the cell can prematurely age or commit suicide. And if it is weak, then the cell mobilizes its resources to cope with it. First, the cell produces antioxidants – substances that neutralize radicals. Secondly, the cell triggers autophagy – the process of partial digestion of its own proteins and organelles. This allows you to get rid of accumulated damage. Thirdly, genes that stimulate survival and prolong cell life begin to work. If we now imagine that the troubles did not end there and more severe hunger, cold or damage occurred, then the cell meets them ready for battle. Protective mechanisms are already working in her, she tolerates serious stress more easily and, as a result, lives longer. And if this process occurs in every cell, then the effect affects the body as a whole.

Are there any other advantages to not eating enough?

Sure. Oxidative stress affects not only the rate of cell aging. For example, it accompanies many neurodegenerative diseases. Therefore, calorie restriction can help prevent their occurrence. And even in healthy people who eat less, verbal memory and the division of stem cells in the brain improves. In addition, with a lack of food, the cells become more sensitive to insulin. Insulin stimulates the cells to capture sugar from the blood, and if there is not enough sugar, then at the signal you need to start grabbing more actively. This reduces the risk of developing type 2 diabetes, in which cells stop responding to insulin and blood sugar accumulates. Finally, oxidative stress is at the root of inflammation, so calorie restriction dampens the immune response. In some studies, it turned out that short-term fasting before and after abdominal operations improves their outcome and wound healing. Calorie restriction not only motivates ordinary cells to survive, but also hits tumor cells. The metabolism of cancer cells changes, they switch to the rapid breakdown of glucose. Therefore, when its concentration in the blood drops, the chances of tumor survival also fall.

What if I can't eat less?

Train your willpower or wait for more convincing evidence that calorie restriction works. But if it so happens that you can't eat less for medical reasons, then you can look for a way out. There are several medicinal analogues of fasting, but – be vigilant! – none of them is yet recommended for use without sufficient indications. In other words, it seems that it will not work out yet to lose weight and prolong life with pills alone. The effect similar to calorie restriction is provided by the drug rapamycin. It blocks one of the key proteins that signals to the cell that there is enough food. It is used in transplants to avoid organ rejection. But if there is no need to suppress the immune system, it is better not to abuse it. Rapamycin's relatives, temsirolimus and everolimus, are approved in America for the treatment of cancer. Metformin is a drug that helps to lose weight with type 2 diabetes (decreased sensitivity to insulin). It can work as an analogue of fasting, but it is still unknown how effective it is in healthy people who do not suffer from diabetes. And so far he has reliably extended his life only to mice. The only drug that can be taken without indications is resveratrol. But it is a dietary supplement, and its effectiveness has not yet been confirmed by clinical studies.

What is the result? Apparently, consuming fewer calories is really useful if you do not suffer from serious illnesses. But pills are not enough here, so you will have to strain your willpower. For detailed instructions, you can contact your doctors or the calorie restriction society. And you can always sign up as a volunteer for a clinical trial – they will definitely follow you there.

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