Orexin, also known as hypocretin, is a neuropeptide.
It plays a crucial role in regulating your sleep-wake cycle, reward and motivation, and the stress response.
Orexin consists of two neuropeptides, orexin-A and orexin-B.
They’re both produced in the hypothalamus, a region of the brain responsible for various functions, including sleep and wakefulness.
Orexin has a significant impact on brain function and mental health.
Higher orexin levels can lead to improved sleep, better mood and motivation, enhanced stress response, and potential cognitive benefits.
Meanwhile, low orexin levels have been associated with numerous medical conditions and sleep disorders.
By understanding and implementing strategies to increase orexin levels, you can improve your brain function and overall mental health.
In this article, we’ll explore how to increase orexin levels naturally.
The article includes four main sections:
The various functions of orexin and how it affects your brain function and mental health
The benefits of increasing orexin
The medical conditions and symptoms associated with low orexin levels
The 14 best research-backed ways to boost your orexin levels
Read on to learn more and discover how you can naturally improve your orexin levels
What Does Orexin Do? How Does It Affect Your Brain Function and Mental Health?
Orexin plays a critical role in various physiological functions. Some of the main functions of orexin include:
Sleep-wake regulation: Orexin plays a vital role in maintaining wakefulness and stabilizing sleep-wake cycles. It keeps you awake during the day and promotes a smooth transition between sleep stages at night. During the day, it stimulates arousal-promoting neurons in different brain regions. Conversely, at night, it stimulates sleep-promoting neurons in the brain (32-34).
Reward and motivation: Orexin has been implicated in the brain's reward system, which is responsible for feelings of pleasure and motivation. It may play a role in the regulation of mood and motivation, as well as in addiction and compulsive behaviors. Research shows that orexin interacts with the mesolimbic dopamine system and modulates dopamine release (35-37).
Stress response: Orexin is also involved in the hypothalamic-pituitary-adrenal (HPA) axis, which is the body's primary stress response system. It can help modulate the release of stress hormones such as cortisol. It also interacts with other neurotransmitter systems, such as serotonin, and norepinephrine. As a result, orexin can impact how your brain responds to stressors, and could potentially contribute to stress-related mental health issues such as anxiety disorders and depression (38-40).
The Benefits of Increasing Orexin
Producing more orexin can provide several benefits, especially if you have low orexin levels or disruptions in orexin function.
The potential benefits of increasing your orexin levels include:
Improved sleep: Higher orexin levels can help stabilize your sleep-wake cycle, leading to increased alertness during the day and better sleep quality at night. This may be particularly beneficial for individuals with sleep disorders like narcolepsy or insomnia (41-43).
Better mood and motivation: Increased orexin levels may help improve mood and motivation, which could benefit individuals with mood disorders such as depression or anxiety (44-46).
Improved stress response: Higher orexin levels can help balance the release of stress hormones such as cortisol, which could lead to better stress management and overall well-being (47-49).
Potential cognitive benefits: Some studies suggest that orexin plays a role in cognitive functions like learning and memory. So increasing your orexin levels could contribute to improved cognitive performance (50-52).
Conditions and Symptoms Associated with Low Orexin Levels
Low levels of orexin or disruptions in orexin function have been linked to several health conditions, primarily sleep disorders and conditions related to sleep-wake regulation.
As a result, researchers are exploring orexin-targeted therapies to treat certain medical disorders and health conditions.
Some of the health conditions associated with low orexin levels include:
Narcolepsy: Low levels of orexin (or disruptions in its function) have been linked to narcolepsy, a condition characterized by excessive daytime sleepiness and sudden attacks of muscle weakness. Researchers have found low levels of orexin-A in individuals with narcolepsy (53-55).
Sleep apnea: Obstructive sleep apnea is a sleep disorder characterized by repeated interruptions in breathing during sleep due to the collapse of the upper airway. Some research suggests that alterations in orexin function may contribute to the development of sleep apnea (56-58).
Insomnia: Insomnia is a sleep disorder characterized by difficulty falling asleep, staying asleep, or experiencing non-restorative sleep. Some research suggests that disruptions in orexin function may be involved in the development of certain types of insomnia (59-61).
Mood Disorders: Some studies suggest that orexin may be involved in mood regulation, with alterations in orexin function potentially contributing to mood disorders such as depression and anxiety (62-64).
Chronic fatigue syndrome (CFS): Some studies suggest that alterations in orexin function may play a role in the development or severity of CFS (65-66).
Fibromyalgia: Some studies have suggested that disruptions in orexin function may contribute to the development or severity of fibromyalgia (67-68).
Parkinson's disease: Some research has found alterations in orexin levels in individuals with Parkinson's disease, suggesting that disruptions in orexin function may be involved in the development or progression of the disorder (69-71).
Alzheimer's disease: Some studies have suggested that alterations in orexin function may contribute to the development or progression of Alzheimer's disease (72-74).
Attention deficit hyperactivity disorder (ADHD): Some research has suggested that disruptions in orexin function may contribute to the development or severity of ADHD (75-76).
Migraine: Some studies have suggested that disruptions in orexin function might play a role in the development or severity of migraine (77-79).
Perhaps you struggle with one or more of these conditions or symptoms.
The good news is that you’re not powerless.
You can do something about it.
You have the power to increase your orexin levels and improve your brain function and mental health.
All you need to do is implement some of the strategies below.
Many of these methods have been helpful to me over the years.
And they can help you too.
Let’s jump into them.
14 Proven Ways to Increase Orexin Levels Naturally
1. Exercise
Exercise can have a positive impact on orexin levels and overall brain health.
Research shows that regular physical activity can influence neurotransmitter systems, including orexin.
Some studies also suggest that exercise can increase orexin release and increase orexin levels in the brain.
In one study, researchers found that exercise increased orexin A levels in the hypothalamus.
The authors suggested that the increased orexin A levels might be responsible for promoting wakefulness and enhancing energy expenditure during physical activity (1).
Research has also found that orexin neurons are activated during physical activity, suggesting a possible link between exercise and increased orexin release (2).
Some researchers have suggested that orexin plays a role in promoting physical activity, potentially through increased release during exercise (3).
Exercise has also been shown to protect against cognitive decline and dementia, promote neurogenesis, help reverse brain damage, and promote the regeneration of myelin.
So not surprisingly, exercise is recommended by many experts and it’s often their number one piece of advice for optimal brain health.
My usual advice is to find a sport or exercise routine that you enjoy, so that you’ll stick with it consistently.
2. Intermittent Fasting and/or Caloric Restriction
Intermittent fasting or food restriction are other ways to increase orexin release.
Studies suggest that intermittent fasting can increase orexin levels and improve wakefulness.
One study found that fasting increased orexin levels, which led to increased wakefulness (4).
Researchers have also highlighted that orexin neurons are sensitive to changes in blood glucose levels. By fasting, you can increase orexin release, which can lead to increased arousal and wakefulness (5).
Increased orexin levels due to fasting is believed to be adaptive. Since orexin promotes wakefulness and arousal, it would then help an individual search for food during periods of food scarcity (6).
Researchers have also investigated the effects of caloric restriction on orexin-A levels.
The researchers found that after a 2-week period of 40% caloric restriction, orexin-A levels in the hypothalamus were significantly increased (31).
I typically don’t recommend restricting calories too much because it can add too much stress on the body, which can ultimately end up making chronic illness worse in the long run.
Intermittent fasting is much more preferable than simply reducing and restricting calories.
I often eat all my food for the day within an 8-hour window, and then fast for the rest of the day.
The best way to start fasting is by eating dinner around 6, not eating anything after that before bed, and then eating a regular breakfast the next day. That should give you about 12-14 hours of fasting time.
3. Maintain a Healthy Body Weight
Obesity has been linked to disruptions in orexin function.
In one study, researchers found that obese individuals had lower levels of orexin compared to non-obese individuals, and that this decrease was associated with poorer sleep quality and daytime sleepiness (7).
Another study found that obese individuals had lower levels of orexin in their cerebrospinal fluid (CSF) compared to non-obese individuals, and that this decrease was correlated with insulin resistance and other markers of metabolic dysfunction (8).
So if you want to optimize your orexin levels, you should strive to achieve and maintain a healthy body weight by following a balanced diet and exercising regularly.
Make sure you download my free food guide so that you know what foods you should be eating for optimal brain function and mental health.
4. Sunlight
There is some evidence to suggest that exposure to sunlight, particularly in the morning, can increase orexin levels in the brain.
In this study, participants were exposed to either bright light or dim light for 90 minutes in the morning before a simulated night shift. The researchers found that exposure to bright light significantly increased orexin levels in the participants' cerebrospinal fluid, and that this increase was associated with improved cognitive performance during the night shift (9).
In an animal study, rats were exposed to either light or darkness during the day, and their brain levels of various neurotransmitters, including orexin, were measured. The researchers found that exposure to light significantly increased orexin levels in the rats' hypothalamus, a brain region that plays a key role in regulating sleep and wakefulness (10).
I personally get sunlight every single day during the spring and summer months.
It’s important to get the sunlight in your eyes to trigger the release of neurotransmitters.
So make sure you don’t wear contacts, glasses or sunglasses when you go outside.
It’s especially important to do this in the morning because it sets your circadian rhythm
5. Limit Blue Light Exposure
Blue light is emitted by screens on smartphones, tablets, and computers.
There is evidence to suggest that exposure to blue light, particularly in the evening or nighttime, can suppress orexin levels and disrupt sleep-wake cycles.
In one study, researchers found that exposure to blue light in the evening suppressed orexin levels in rats and altered their circadian rhythms.
The researchers suggested that these effects may be due to the inhibitory effects of blue light on melatonin, a hormone that is involved in regulating sleep-wake cycles and is known to interact with orexin pathways (11).
In another study, researchers investigated the effects of evening blue light exposure on orexin levels and sleep in humans.
The researchers found that exposure to blue light for two hours in the evening significantly reduced orexin levels and delayed the onset of sleep compared to exposure to dim light (12).
These findings suggest that blue light exposure in the evening may disrupt orexin-mediated sleep-wake cycles in humans.
Overall, while blue light exposure can have beneficial effects on mood and cognitive performance during the daytime, it is important to limit exposure to blue light in the evening and night time to avoid disrupting sleep and orexin-mediated processes.
This can be achieved by avoiding bright screens and electronic devices before bedtime, and by using blue-light blocking glasses or filters on electronic devices.
6. Reduce Inflammation
There is evidence to suggest that chronic inflammation can affect orexin-mediated processes.
In one study, researchers found that inflammation caused by lipopolysaccharide (LPS), a bacterial endotoxin, reduced orexin levels in the hypothalamus of rats.
The researchers suggested that this effect may be due to the inhibitory effects of inflammation on the production and release of orexin (13).
Another study looked at the relationship between inflammation, orexin, and sleep in humans.
The researchers found that higher levels of the inflammatory marker C-reactive protein (CRP) were associated with lower levels of orexin and poorer sleep quality.
The authors suggested that inflammation may disrupt orexin-mediated sleep-wake cycles and contribute to the development of insomnia (14).
There are many causes of chronic inflammation, including infections, toxic mold, brain injuries, and leaky brain.
But one of the most common causes – and the one you have the most control over – is your diet.
That’s why I recommend following an anti-inflammatory diet and limiting foods that can trigger inflammation in the gut and brain.
You should also remove processed food from your diet, and increase your intake of vegetables, fruits, wild fish, grass-fed beef and organic chicken.
Check out my Free Grocery Shopping Guide for Optimal Brain Health for a full list of anti-inflammatory foods.
Other steps you can take to reduce inflammation include reducing stress, exercising, improving gut health, treating infections and getting enough sleep.
Make sure you also check out this article for 23 effective ways to reduce inflammation in the brain.
7. Protein and Amino Acids
There is evidence to suggest that certain amino acids, particularly the branched-chain amino acids (BCAAs), can affect orexin-mediated processes.
In one study, researchers investigated the effects of BCAA supplementation on orexin levels and metabolic function in humans.
The researchers found that BCAA supplementation increased orexin levels in the participants' cerebrospinal fluid
The authors concluded that BCAAs stimulate orexin production and release (15).
I personally take BCAA protein powder throughout the day when I don’t have access to a source of high-quality protein.
Another study looked at the effects of the amino acid tryptophan on orexin levels and sleep-wake cycles in rats.
The researchers found that tryptophan supplementation increased orexin levels in the rats' hypothalamus, and that this increase was associated with improved sleep-wake cycles and cognitive performance.
The authors concluded that tryptophan stimulates orexin production and release, and that this may contribute to its effects on sleep and cognition (16).
Some healthy foods that contain tryptophan include bananas, chicken, turkey and dark chocolate.
Personally, supplementing with tryptophan never helped me. In fact, it always seemed to make me worse. It gave me asthma and acne and actually increased my chronic inflammation and depression.
However, some people do see their mental health and sleep improve when they increase their intake of tryptophan. So it shouldn’t be completely disregarded.
So supplementing with tryptophan is worth a shot if you haven’t tried it yet. Just be aware of possible side effects.
If you want, you can also try supplementing with 5-HTP instead of tryptophan, as some people respond better to it.
5-HTP is included in this supplement.
8. Omega-3 Fatty Acids
Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients found in fatty fish, fish oil supplements, and some plant-based sources.
They are essential, meaning your body cannot create them and you have to get them from food or supplements.
They’re the highest quality fats for the brain, playing a critical role in brain function and inflammation.
So making sure you get more omega-3s is one of the most important actions you can take to support your brain and nervous system.
Many studies show that they significantly reduce brain inflammation; improve memory, mood and cognition; and protect against mild cognitive impairment, dementia and Alzheimer's disease.
Some studies suggest that omega-3 fatty acids can also impact orexin levels.
One study found that a high-fat diet rich in omega-3 fatty acids can increase the expression of prepro-orexin mRNA in the hypothalamus (17).
Another study found that omega-3 fatty acids modulate the activity of the brown adipose tissue (BAT).
Orexin plays a role in regulating BAT activity, and so omega-3 fatty acids could potentially influence the orexinergic system through this pathway (18).
Omega-3 fatty acids are found in cold water fish such as salmon, black cod, sablefish, sardines and herring.
Unfortunately, most people don't consume enough of these foods.
So supplementing with krill oil should be considered.
Krill oil is a special kind of fish oil that readily crosses the blood-brain barrier. I’ve tried tons of fish oil supplements, and I recommend krill oil over all the others.
9. Cold Exposure
Research suggests that exposure to cold temperatures can increase orexin levels.
In one study, researchers found that cold exposure leads to an increase in orexin-A in the cerebrospinal fluid (CSF) (19).
Another study found that exposure to cold temperatures increased orexin levels in the participants' blood (20).
Researchers have also found that regular cold exposure increases wakefulness and alertness during the day, and that these effects are associated with increased orexin activity in the brain (21).
To practice cold exposure, you can try taking cold showers or spending time in a cool environment.
But make sure you do so safely and within your comfort limits.
I personally take a cold shower every day.
During the winter, I’ll also go outside for short periods of time with hardly any clothes. It boosts my dopamine and increases my motivation.
You don’t have to be that extreme though.
You can start by finishing your next shower with one minute of cold water.
See how it feels, and then over time, increase the amount of time you turn off the hot.
It can be a bit painful.
But the beneficial effects end up being worth it.
Another way is to stick your face, hand or foot in ice cold water.
Or you can try cold plunges, cold baths and even cryotherapy if you want.
Find what works best for you and do it regularly.
10. Berberine
Berberine is a natural alkaloid found in plants like goldenseal, barberry, and Oregon grape.
It has various health benefits, including anti-inflammatory, anti-diabetic, and anti-obesity effects.
Researchers have found that berberine increases the expression of orexin-A and its receptor OX1R in the hypothalamus (22).
I’ve experimented with varying dosages of berberine. I personally didn’t notice any profound brain and mental health benefits, but I have heard good things from others.
11. Acetylcholine
Acetylcholine is a neurotransmitter that plays an important role in many physiological processes, including sleep, memory, and attention.
There is evidence to suggest that acetylcholine interacts with orexin-mediated processes in the brain.
Researchers investigated the effects of acetylcholine on wakefulness and orexin levels.
They found that activation of acetylcholine neurons in the brain increased orexin release and promoted wakefulness, while inhibition of acetylcholine neurons decreased orexin release and promoted sleep.
The authors concluded that acetylcholine plays a key role in regulating orexin-mediated processes involved in sleep-wake cycles and cognitive function (24).
Another study looked at the effects of acetylcholine on cognitive function and orexin levels in humans.
The researchers found that blocking acetylcholine receptors impaired cognitive performance and decreased orexin levels in the participants' cerebrospinal fluid (26).
Research also shows that activation of muscarinic acetylcholine receptors on orexin neurons led to increased orexin neuron firing (25).
So it’s quite clear that acetylcholine can interact with orexin pathways and contribute to wakefulness, cognitive function, and attention.
So make sure you read my previous article all about increasing acetylcholine in the brain. In it, I share the 27 best ways to boost acetylcholine, and those strategies will indirectly increase orexin as well.
You can read that previous article here.
12. Galantamine
Galantamine is an alkaloid isolated from the plant Galanthus woronowii.
It’s an acetylcholinesterase inhibitor, which means it works by increasing the levels of acetylcholine in the brain.
Researchers have examined the effects of galantamine on the activation of human orexin OX1 and OX2 receptors.
In their experiments, they found that galantamine facilitated the action of orexin-A at OX2 receptors but not at OX1 receptors (23).
This suggests that galantamine has some modulatory effects on the orexinergic system through its influence on OX2 receptors.
Galantamine is commonly used to treat Alzheimer's disease and other cognitive disorders due to its ability to improve memory and cognitive function.
So if you’re looking to improve your memory, it’s a good option.
13. Estrogen
Estrogen, a primary female sex hormone, has been found to influence various physiological functions, including the regulation of sleep-wake cycles, mood, and appetite.
There is also evidence to suggest that estrogen can interact with the orexinergic system, leading to changes in orexin levels.
In one study, researchers investigated the effects of estrogen on orexin neurons.
The researchers found that the administration of estrogen significantly increased the number of orexin-expressing neurons in the lateral hypothalamic area.
This study provides evidence that estrogen can influence orexin levels (27).
Another study looked at the effects of gender and gonadal hormones on prepro-orexin mRNA expression in rats.
Researchers found that the expression of prepro-orexin mRNA was higher in female rats than in male rats and that ovariectomy led to a decrease in prepro-orexin mRNA levels.
But when ovariectomized rats were treated with estradiol, a form of estrogen, the expression of prepro-orexin mRNA was restored, suggesting that estrogen plays a significant role in regulating orexin synthesis (28).
I recommend both men and women get their hormone levels checked regularly, and then optimize them if they want to optimize their brain function and feel their best.
You can check your estrogen levels here.
14. Vagus Nerve Stimulation
Vagus nerve stimulation (VNS) is another way to influence your orexinergic system.
The vagus nerve is the tenth cranial nerve and plays a crucial role in regulating many physiological functions, including heart rate, digestion, and mood.
Vagus nerve stimulation (VNS) is a therapeutic technique used to treat epilepsy, depression, and other conditions.
Researchers have investigated the effects of long-term VNS on sleep-wake behavior and orexin expression in a rat model of epilepsy.
The researchers found that VNS reduced the number of seizures, increased wakefulness, and decreased the duration of sleep.
In addition, VNS-treated rats showed an increase in orexin-A expression in the lateral hypothalamus (29).
Another study further explored the role of orexin in VNS-induced wakefulness in rats.
The authors reported that the administration of an orexin receptor antagonist reduced the VNS-induced increase in wakefulness (30).
These studies suggest that the orexinergic system is involved in mediating the effects of VNS on sleep-wake behavior.
Read this article for 13 ways to stimulate your vagus nerve.
Deep breathing with the EmWave2 device is my favourite way.
Enjoy This Article? You Might Also Like My FREE Food Guide for Optimal Brain and Mental Health!
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