Orexin / hypocretin and its relationship with sleep, intake and mood

Orexin / hypocretin and its relationship with sleep, intake and mood

The orexin, also known as hypocretin, is a polypeptide neuronal hormone that is found in the posterior hypothalamus and is made up of thirty amino acids. The hypothalamus plays an important role in maintaining a whole series of functions such as thirst, appetite, libido and sleep regulation.

Functions of hypocretin / orexin

Hypocretin neurons stimulate wakefulness, alertness, hunger, the search for rewards and promotes healthy glucose balance.

Increase metabolism

Orexin too increases our metabolism and body temperature, since hypocretin makes us increase oxygen consumption. So when we feel tired, fatigued or cold, our orexin levels are lower.

It influences the feeling of hunger

Hypocretin too increases the feeling of hunger, and this occurs through increased expression of neuropeptide Y found in the arcuate nucleus of the hypothalamus. Some animal studies show that low orexin levels cause obesity, even when fewer calories are consumed. This is one of the factors why sugar consumption makes us fat. Eating sugar causes your blood level to rise, and this in turn helps suppress orexin, which is why after a short time after taking refined sugars, the decrease in hypocretin makes us feel more fatigued and inactive than normal (a metabolic curve is generated in which sugar initially adds energy to us, and then exerts a rebound effect generating more fatigue than would be usual). So instead of burning calories through action, it induces us to rest.

It can generate insomnia or narcolepsy

Studies have shown that Too high amounts of orexin in the hypothalamus produce insomnia, while the lack of hypocretin causes narcolepsy, autoimmune disease that destroys orexin neurons.

Orexin levels too influence the feeling of sleep after meals. High blood glucose levels, such as those that appear after a large meal, can deactivate brain cells that normally secrete substances that keep us awake and alert.

Denis Burdakov and his team studied the operation of orexins in 2007, observing how these neurons are less active during the night.

Previous research had shown that glucose could inhibit hypocretins, but it was not known how sensitive they were. The research of Budakov put showed the extreme sensitivity of orexins to slight changes in glucose levels such as those that occur in the blood during the daily cycles of food and fasting. Apparently, orexin activity shuts down due to glucose increases we experience after meals.

This interaction between glucose and orexin explains, in addition to being sleepy after a meal, the insomnia when hungry, since the activity of neurons is greater due to lack of blood glucose.

It influences anxiety and addiction

Low orexin levels influence the urge to smoke and drink alcohol in cases of addiction. Recently it has also been associated with reward mechanisms, as it is proven that a abnormally high activity of hypocretins leads to anxiety states which can lead to the use of addictive substances.

As we can see, the hypocretin system interacts with many other body systems, which makes it so important.

Influence mood

In addition, it has also been found that high orexin levels make us be happier and have a better mood usually.

How to improve orexin levels


If you live in a country where sunlight is not scarce throughout the year, you are in luck, just going out for a walk for at least half an hour, you are already assimilating all its benefits almost without realizing it.

But if you live in places where sunlight is scarce at certain times of the year, then you can replace it with a bright light device.

Lack of sunlight is related to seasonal affective disorder (SAD) and depression.

It has recently been shown that bright lights, like sunlight, increase orexin levels and that it is the probable mechanism by which it is effective for seasonal depression.


A study conducted in 2007 showed that acidification of the blood increases the excitability of orexin, while alkalinization depresses it.

So, anything that increases hydrogen ions and therefore acidity and CO2 will increase our hypocretin levels. Exercise, especially regular exercise, increases CO2 and lactate, which makes our blood more acidic.

Even the increase in CO2 in the atmosphere due to the increase in pollution can increase orexin activation, which means that currently we have a slight increase in hypocretin activation than in the past.

Eat foods with lactate

Lactate is a source of energy and a regulator of the orexin system. Lactate release from astrocytes plays a fundamental part in the balance of brain activity and energy supply.

Lactate is a salt that occurs naturally in some cheeses by combining lactic acid and calcium carbonate. It has a great biological importance since it is constantly produced during metabolism and when exercising. Lactate concentration increases when tissues, mainly muscle, have an energy demand that exceeds the availability of oxygen in the blood.

Lactate is therefore found in cheeses and probiotic foods, in addition to being used routinely in the food industry (shown with code E 327). Some processed foods that contain lactate are: Powdered milk, cheeses, wine, cider, distilled spirits with more than 15% alcohol, dairy products such as yogurt, ice cream, soups, baking powder, bakery products, peanut butter or Peanut butter, desserts made with egg, beer and malt beverages, some food supplements.

Restrict glucose and increase fructose

A high concentration of glucose can block or silence the activity of orexin neurons. For this reason the main way to activate orexin is to restrict foods with excess glucose.

Foods with glucose are part of those that have carbohydrates. These carbohydrates are subsequently broken down into glucose molecules by our body to produce energy.

Experts recommend that most of the carbohydrates consumed should come from the complex carbohydrates such as starches and natural sugars. These should replace those foods with glucose that come from the processed or refined sugars, which also do not have vitamins, minerals and fibers. On the contrary, refined sugars are referred to as "empty calories" since they do not have or provide very little nutritional value.

Foods that contain healthy glucose:

  • Pasta.
  • Whole bread.
  • Whole grains and whole grains.
  • Legumes.
  • The potatoes.
  • Dairy products such as milk, yogurt and cheese.
  • Vegetables contain glucose in their starch form, which is the way plants store energy. Starchy vegetables include corn, squash and zucchini. Vegetables with low starch content are asparagus, celery, cucumbers, green beans, eggplants, mushrooms, Brussels sprouts, cabbage, cauliflower, red and green peppers, onions and tomatoes, among others.
  • Grapes.
  • The honey It is one of the foods with glucose since it is made up of approximately 38% glucose.

Foods that contain unhealthy glucose:

  • Cake shop
  • Salty appetizers
  • Whole milk
  • White bread
  • Fried food

Parallel, Fructose is a simple carbohydrate, also known as fruit sugar or levulose. It has the same chemical formula as glucose or blood sugar, stimulates taste buds and produces a sweet sensation, but it is much healthier.

Studies have found that regular consumption of fructose increases orexin levels. In addition, 25% of the fructose consumed is converted into lactate, which as we know, has increasing effects of hypocretin.

Fructose foods:

  • Fresh and dried fruit
  • Some drinks: caffeinated drinks and soft drinks of all flavors such as soft drinks, carbonated drinks and fruit drinks contain fructose.
  • Processed foods: Some commercially prepared foods may contain high levels of fructose, such as tomato sauce, condiments, soups, sweet, frozen pickles, canned foods, breads and cookies. Prepared baked goods such as pies, cookies, energy bars, croissants or donuts generally contain high levels of fructose.
  • Sauces and dressings: Some foods such as sweet and sour sauce, barbecue sauce, molasses, as well as salad dressings, jellies and fruit jams may have high fructose content.
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