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Updated: Apr 16, 2023

How this little-known hormone keeps you awake, warm, and happy

Orexin (also known as hypocretin) is a neurotransmitter involved in the regulation of arousal, wakefulness and appetite. The human brain contains 10,000 to 20,000 neurons that produce orexin.

What Orexin Does


Researchers found that high levels of Orexin A are associated with happiness, while low levels have been tied to depressed moods.

Type 1 narcolepsy, where the patient suffers short losses of muscle tone, is mainly caused by the lack of orexin in the brain due to the destruction of orexin producing cells. Orexin A levels max out during positive emotion, social interaction, and anger, the same behaviors that induce cataplexy in narcoleptics.


Orexin is directly tied to feeling awake and alert. When mammals (including humans) are sleep deprived, orexin levels drop down to minimal levels.

In studies where monkeys are deprived sleep, giving them Orexin A through a nasal spray effectively erased all signs of sleep deprivation, allowing them to perform on tests the same as well rested monkeys.

Energy & Metabolism

Any research on mammals with orexin shows an immediate increase in movement of any individual given extra orexin.

Orexin 🡆 more energy 🡆 more activity 🡆 more calories burned from activity

Brown fat is a beneficial fat that most adults have in small amounts that helps us regulate body temperature, namely helping us stay warm in cooler environments by increasing our body temperature. This heating (thermogenesis) ends up burning a significant amount of calories and also regulates appetite and improves insulin sensitivity. Orexin helps to activate brown fat to start working, which increases our metabolism. It also helps us stay warm, so if you feel cold and tired all the time, low levels of Orexin may be playing a part.


The Pathways for Orexin

Orexin cells are stimulated by protein intake.

Amino acids (especially non essential amino acids) remove K-ATP (the Orexin Blocker) and also boost Orexin directly via Amino Acid transporters.

Protein Orexin and Energy pathway

Orexin cells are blocked by sugar intake.

Sugar activates K-ATP which blocks Orexin production.

How sugar blocks Orexin and makes us sleepy

Adding Protein will help prevent a sugar slump.

Adding protein to carbs will block much of the sleepy side effects of sugar. The higher the protein to carb ratio, the better the blocking ability.

How protein helps us stay awake


How to Boost Orexin


protein rich foods on white background

To recap: Orexin can be boosted by increasing protein intake. Protein without carbs has an orexin boosting effect (along with other alertness boosting benefits, see here for more). Protein consumed with carbohydrates helps to offset the Orexin drop-off (and the subsequent Carb Coma) that carbs by themselves will cause.



Exercise has been shown to increase energy and reduce appetite, and Orexin most likely plays a part in it's abilities. Exercise raises orexin levels in humans as well as other mammals.

There is an additional connection to lactate.


Fermented Foods

On the same note for raising lactate in the body, fermented foods that include lactobacilli (also known as acid-loving or lactic acid bacteria) will create lactate as a byproduct in the probiotic foods they are in.



Milk and Water Kefir


Sauerkraut & Kimchi

Raw Pickles and Vinegar with the Mother


Reduce Your Inflammation

Chronic inflammation is tied to lower levels of Orexin, which explains some of the fatigue and lack of energy that goes along with it. (R, R, R)

Signs of chronic inflammation include chronic pain, fatigue, insomnia, mood disorders, gastrointestinal issues like reflux/diarrhea/constipation, frequent illness/infections, or unintentional weight gain/loss.

If you are experiencing chronic inflammation, work with health professionals to figure out the underlying cause to be able to treat it. It may involve switching to an anti-inflammatory diet, treating underlying deficiencies or infections, and other treatments depending on the cause. TK link for anti-inflammatory blog


Natural & Bright Light Exposure

Bright light and sunlight stimulates Orexin - to such a large amount that it is currently suspected to be a major reason why bright light therapy is so effective for treatment of Depression and Seasonal Affective Disorder/SAD. (R, R)



Caffeine activates orexin, which is one of several ways caffeine wakes us up. Best sources are natural caffeinated drinks like coffee and tea, which also serve up a dose of inflammation-lowering antioxidants.


Possible ways to increase Orexin


Theoretically, achieving Ketosis should assist with Orexin production, if only due to the carb suppression vs protein activation described above.

No carbs = no carb suppression.

However, full human trials on Ketosis and Orexin have not been performed as of this writing, though there are some promising signs from animal research.

Carb/Caloric Restriction, Fasting

As described above, glucose levels block Orexin production. It is the main way researchers use to activate orexin in test subjects. (R, R)

Caloric Restriction & fasting might also work. The hypothesis is that under low-calorie conditions, glucose is routed to the most important organs (like the brain) and prevents the Orexin blockage. Additionally, falling glucose levels stimulate Orexin neurons.


Fiber, especially fermentable fiber like resistant starch is turned into butyrate (which may be energizing) in our guts and activates GLP-1, which is a hormone that activates Orexin when it reaches the brain. Animal studies suggest that GLP-1 functions much like Orexin.


A Note About Food Intake

Orexin has been tied to increased appetite but is generally balanced out by leptin and is also counteracted by it's activation of brown fat, which has appetite regulating functions. If we are activating Orexin by consuming protein, protein has its own appetite suppressing abilities. For more information, see here.


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