<\/a>Definition<\/span><\/h3>\nThe brain contains about 10,000 to 20,000 neurons in the hypothalamus<\/a>, but axons from these neurons extend throughout the entire brain and spinal cord, where there are also receptors for orexin.<\/p>\nScience suggests that brain orexin\/hypocretin neurons stimulate wakefulness<\/strong>, alertness<\/strong>, eating, reward-seeking, and healthy glucose balance [R<\/a>].<\/p>\n<\/a>What Does it Do?<\/strong><\/span><\/h3>\nOrexin is not just any molecule in our body. Some scientists say that whenever we\u2019re tired or fatigued, orexin is suppressed [R<\/a>].<\/p>\nIt\u2019s not like orexin is one of the many systems that stimulate wakefulness. It\u2019s considered to be by far the most significant stimulator of wakefulness. Histamine<\/a> is also involved, but orexin activates the histamine system [R<\/a>].<\/p>\nResearchers suspect that there are many hormones and other systems in the body that interact with orexin.<\/p>\n
Therefore, the orexin system seems to be central to productive human functioning and good mood. However, orexin\u2019s role is a relatively recent discovery. Larger human studies are needed to better understand its effects on health [R<\/a>].<\/p>\n<\/a>Narcolepsy <\/strong><\/span><\/h3>\nThere are two main types of narcolepsy: type 1 and type 2. Measuring orexin levels helps diagnose type 1 narcolepsy [R<\/a>].<\/p>\nDoctors need the following to diagnose type 1 narcolepsy [R<\/a>]:<\/p>\n\n- Hypersomnia (extreme sleepiness)<\/li>\n
- Cataplexy (episodes of muscle weakness in response to emotional stimuli), and\/or<\/li>\n
- Orexin (hypocretin-1) concentrations in the CSF (cerebrospinal fluid) of 110 pg\/mL or less<\/li>\n<\/ul>\n
The exact cause of narcolepsy is still unknown. Unproven, experimental theories suggest that narcolepsy may result from immune imbalance, specifically an elevated Th2<\/a> immune system, in some people. Another study found elevated TNF<\/a> and IL-6<\/a> [R<\/a>, R<\/a>].<\/p>\n<\/a>Beyond Wakefulness<\/span><\/h3>\nLimited research suggests that orexin also increases metabolism and body temperature. According to this theory, people that feel cold<\/a> and tired may, among other factors, have low orexin [R<\/a>].<\/p>\nOrexin also seems to increase hunger via increased neuropeptide Y<\/a> expression in the arcuate nucleus of the hypothalamus [R<\/a>].<\/p>\nAnimal models suggest that low levels of orexin cause obesity<\/a>, even when fewer calories are consumed. This hasn\u2019t been confirmed in humans [R<\/a>].<\/p>\nOne hypothesis posits that orexin is a significant factor in why consuming sugar makes people fat. They claim that this is because people feel tired after eating sugar, since it causes blood sugar levels to spike and orexin to fall. So, instead of burning calories, people go to sleep<\/a>. Although plausible, this hypothesis has yet to be tested [R<\/a>].<\/p>\nAnother team of researchers claimed that higher levels of orexin-A cause people to be happier. They\u2019re still lacking solid data, though, since this theory is mainly based off the fact that the incidence of depression<\/a> is higher in narcolepsy.<\/p>\nYet another stream of research found that orexin and its receptors may decline with age. Plus, orexin may cause people to increase oxygen use because it might increase metabolism. Future research has yet to clarify and solidify all these findings [R<\/a>, R<\/a>].<\/p>\n<\/a>Factors that May Increase Orexin<\/strong><\/span><\/h2>\n<\/a>When to See a Doctor<\/span><\/h3>\nIf your goal is to increase orexin to improve your fatigue – or extreme exhaustion-related issues – including those of chronic fatigue or depression – it\u2019s important to talk to your doctor, especially low energy levels are significantly impacting your daily life.<\/p>\n
Your doctor should diagnose and treat any underlying conditions causing your symptoms.<\/strong><\/p>\n<\/a>Precautions & Limitations<\/span><\/h3>\nRemember that the existing evidence does not suggest that low orexin causes fatigue or mood disorders.<\/p>\n
There\u2019s also no precise way to measure orexin levels outside of research studies and diagnosing type 1 narcolepsy. For narcolepsy, a healthcare professional has to take a person\u2019s cerebrospinal fluid, which is an invasive procedure reserved only for specific cases.<\/p>\n
Complex disorders like chronic fatigue syndrome always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.<\/p>\n
Additionally, changes in nerve tone and brain chemistry are not something that people can change on their own with the approaches listed here. Instead, the factors mentioned in this article are meant to improve energy levels and support overall mental health and well-being. Most are backed up only by limited human or animal studies.<\/p>\n
Therefore<\/strong>, you may try the strategies listed below if you and your doctor determine that they could be appropriate<\/strong>. Read through the approaches we bring up and discuss them with your doctor before trying them out. This is particularly important if you plan to take any dietary supplements.<\/p>\nSupplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don\u2019t guarantee that they\u2019re safe or effective.<\/p>\n
Finally, have in mind that none of these strategies should ever be done in place of what your doctor recommends or prescribes.<\/p>\n
<\/a>1) Resolving Chronic Inflammation<\/strong><\/span><\/h3>\nResearch suggests a link between orexin and chronic inflammation. Persistent, low-grade inflammation also seems to be tightly tied to fatigue and low cellular energy, according to recent scientific findings [R<\/a>, R<\/a>].<\/p>\nElevated inflammation from cytokines like IL-1b<\/a> and TNF<\/a> is hypothesized to cause fatigue by the suppression of orexin neurons [R<\/a>, R<\/a>, R<\/a>, R<\/a>].<\/p>\nJust before the normal time of sleep<\/a> onset for rats, TNF levels in brain tissue were shown to be 10-fold higher than their daily minimum. This hasn\u2019t been verified in humans, though [R<\/a>].<\/p>\nIf you are experiencing chronic inflammation, work with your doctor to resolve the underlying issue causing your symptoms.<\/p>\n
<\/a>2) Exercise<\/strong><\/span><\/h3>\nGetting regular, moderate exercise is good for overall health. We know from experience that it makes us feel energized, and some scientists think orexin might be one of the reasons.<\/p>\n
Limited human studies back this theory up: exercise was able to increase orexin levels in the human bloodstream [R<\/a>].<\/p>\nAdditionally, exercise seems to increase orexin in the cerebrospinal fluid of rats, dogs, and cats [R<\/a>].<\/p>\nResearchers think that the source of orexin might be directly released from the pituitary into the bloodstream, leaked from the cerebrospinal fluid, or produced by the gut or pancreas. More research is needed [R<\/a>].<\/p>\nExercise temporarily acidifies our blood (increases lactate<\/a>), which is hypothesized to increase the firing of orexin neurons [R<\/a>].<\/p>\nInterestingly, orexin A may cross the blood-brain barrier. Theoretically, if it’s elevated in the blood after exercise, it may also be elevated in the brain [R<\/a>].<\/p>\n<\/a>3) Natural Light – Get Outside<\/strong><\/span><\/h3>\nBright light (for example, from the sun) increases orexin, and animal research suggests that this is the likely mechanism by which it\u2019s effective for depression and seasonal affective disorder (SAD). Proper human data are still lacking to back up this mechanism, though [R<\/a>].<\/p>\n<\/a>4) Fermented Foods <\/strong><\/span><\/h3>\nWe spoke about lactate as a \u201cbackup generator\u201d before<\/a>.<\/p>\nLactate<\/a> is a critical energy source and a likely regulator of the orexin system. Scientists think that lactate release from astrocytes plays an integral part in balancing brain activity and energy supply [R<\/a>].<\/p>\nAccording to one theory, supplying orexin neurons with lactate can stop glucose from blocking orexin neurons. Lactate might disinhibit and sensitize these orexin neurons for future excitation. This hasn\u2019t been proven in humans, however [R<\/a>, R<\/a>].<\/p>\nOne study hypothesized that orexin neurons only \u201csee\u201d glucose changes when the levels of other energy molecules are low, whereas high energy levels can stop glucose from regulating orexin cells [R<\/a>].<\/p>\nHere are some fermented foods that likely contain lactate:<\/p>\n
\n- Kombucha<\/li>\n
- Sauerkraut<\/li>\n
- Pickles<\/li>\n<\/ul>\n
Kombucha has lactate, pyruvate, butyrate<\/a>, ATP. Studies are investigating whether it has other \u201cenergy-related molecules\u201d as a result of the fermentation process. Anecdotally, many people say this fermented Eastern drink refreshes and energizes them [R<\/a>].<\/p>\nAdditionally, certain probiotics<\/a> like Lactobacilli produce lactate.<\/p>\nOn the other hand, various minerals can be formulated into lactate salts, such as Calcium<\/a> lactate and Magnesium<\/a> lactate.<\/p>\n<\/a>5) Protein<\/strong><\/span><\/h3>\nIt\u2019s a good idea to get adequate amounts of healthy protein foods on a daily basis. Various amino acids are hypothesized to affect orexin signaling, but there are no clinical studies to determine their impact.<\/p>\n
Researchers believe that amino acids excite orexin neurons through a few mechanisms, though this has yet to be confirmed in humans [R<\/a>].<\/p>\nAn animal study gave branched-chain amino acids (BCAAs), which are precursors to glutamate<\/a> synthesis, to brain-damaged mice. BCAAs reinstated activation of orexin neurons and improved wake deficits in mice with mild brain injury. Human data are lacking [R<\/a>].<\/p>\nIn the lab, nonessential amino acids were more potent in activating orexin cells than essential amino acids [R<\/a>].<\/p>\nOne theory states that amino acids may block glucose suppression of orexin because they tell the neurons that there\u2019s enough energy around [R<\/a>].<\/p>\nIn cells, scientists ordered them this way – from most to least effective:<\/p>\n
\n- Glycine<\/a><\/li>\n
- Aspartate<\/li>\n
- Cysteine (NAC<\/a>)<\/li>\n
- Alanine<\/li>\n
- Serine<\/li>\n
- Asparagine<\/li>\n
- Proline<\/li>\n
- Glutamine [R<\/a>]<\/li>\n<\/ul>\n
However, we have no way to know how each one affects orexin activity in complex beings. This hasn\u2019t been researched.<\/p>\n
<\/a>6) Carb and Caloric Restriction<\/strong><\/span><\/h3>\nTheoretically, elevated glucose concentration might block or silence the activity of orexin neurons [R<\/a>].<\/p>\nIn lab animals, the principal way to activate orexin is by restricting glucose [R<\/a>].<\/p>\nThe hypothesis is that under low-energy conditions such as starvation, it could be advantageous for ingested glucose to suppress the orexin-driven net energy expenditure, thereby ensuring that more fundamental processes (such as keeping the brain alive) receive enough glucose.<\/p>\n
Conversely, when the brain has plenty of fuel (perhaps signaled by high levels of pyruvate and\/or lactate), there may be little advantage in coupling glucose fluctuations to orexin activity, since under these conditions, acute changes in glucose levels would be compensated by other energy molecules [R<\/a>].<\/p>\nIn addition, scientists think that orexin neurons are stimulated by falling glucose levels [R<\/a>].<\/p>\nHypothetically, people who eat less or practice some degree of caloric restriction may have higher orexin because their body senses they\u2019re not getting enough calories, which activates this system. Proper human data are needed, though [R<\/a>].<\/p>\n<\/a>7) Maintaining Healthy Weight<\/strong><\/span><\/h3>\nSome researchers consider that losing extra weight may help increase orexin and energy levels.<\/p>\n
This is based on the theory that Leptin<\/a> inhibits orexin. High leptin levels are characteristic of being overweight, while leptin levels tend to drop as a result of weight loss<\/a> [R<\/a>].<\/p>\nHowever, many other factors also affect leptin levels and weight and the exact role of orexin has yet to be determined.<\/p>\n
<\/a>8) Fiber<\/strong><\/span><\/h3>\nGLP-1 is a gut hormone that can activate\/excite orexin neurons in the hypothalamus (which increases orexin). Scientists think it might be useful in making us feel satiated as well, which may make us eat less and further activate orexin.<\/p>\n
It\u2019s possible that GLP-1 functions like orexin and sometimes works instead of it, though this hasn\u2019t been confirmed in humans [R<\/a>].<\/p>\nResistant starch<\/a> may increase GLP-1<\/a> and also produces butyrate<\/a>. It\u2019s also acidic. Hypothetically, this might block glucose-induced suppression of orexin [R<\/a>, R<\/a>, R<\/a>].<\/p>\nAnecdotally, people say high-butyrate foods or drinks (like kombucha) increase energy levels after a big meal.<\/p>\n
<\/a>9) Having Fun <\/strong><\/span><\/h3>\nA study in dogs found having fun or play was able to increase orexin, while the same level of exercise wasn\u2019t able to [R<\/a>].<\/p>\nThe study concluded that motor and cardiovascular changes might not sufficient to elevate orexin, so they hypothesize that the emotional aspects of yard play account for the observed increase in orexin [R<\/a>].<\/p>\nResearch hasn\u2019t yet measured the effects of fun activities on orexin in humans.<\/p>\n
<\/a>10) Vagus Nerve Stimulation<\/strong><\/span><\/h3>\nVagus nerve stimulation<\/a> seemed to decrease daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury in limited studies. More clinical trials are needed and whether or not vagus nerve stimulation affects orexin signaling is still unknown [R<\/a>].<\/p>\nIn comatose rats after traumatic brain injury, vagus nerve stimulation promoted the recovery of consciousness [R<\/a>].<\/p>\nThe effects were thought to be, in part, mediated by the increase of orexin-A and its receptor (OXR1) in the prefrontal cortex [R<\/a>].<\/p>\n<\/a>11) Green Tea<\/strong><\/span><\/h3>\nCaffeine<\/a> was found to activate orexin, which isn\u2019t surprising given that it\u2019s the most widely-consumed stimulant worldwide. It\u2019s found in both coffee and green and black tea<\/a>, but green tea is the highest in antioxidants among the three [R<\/a>, R<\/a>].<\/p>\n<\/a>12) Omega 3s<\/strong><\/span><\/h3>\nA study found that in healthy people, there was a correlation between omega 3s and orexin A (but not in narcoleptics) [R<\/a>].<\/p>\n<\/a>Experimental (Lacking Evidence)<\/strong><\/span><\/h3>\nThe following factors are theoretical or anecdotal. They aren\u2019t backed up by solid science, and some are not generally associated with well-being. <\/strong><\/p>\nFor example, we recommend against bag breathing and high fructose intake but think that they\u2019re interesting to mention for informational purposes.<\/p>\n
We also highly recommend against the use of nicotine for any indication other than smoking cessation. Nicotine is highly addictive and its harms outweigh any benefits.<\/p>\n
Keto diets and cold exposure are not harmful as long as you get a green light from your healthcare provider.<\/p>\n
<\/a>Bag Breathing\/CO2<\/sub><\/h4>\nCO2<\/sub> increases after eating carbohydrates. Macronutrient profile aside, CO2<\/sub> increases after breathing into a bag [R<\/a>].<\/p>\n<\/a>Fructose<\/h4>\nAnimal studies suggest that long-term fructose consumption (bingeing) increases orexin [R<\/a>].<\/p>\nAlso, 25% of fructose consumed turns into lactate, which is hypothesized to have orexin-increasing effects [R<\/a>].<\/p>\nFructose, fructans, and FOS might also excite orexin neurons by increasing GLP-1<\/a>, thereby potentially increasing wakefulness [R<\/a>, R<\/a>].<\/p>\nRaw honey<\/a> has some fructose. However, heavy fructose consumption is not healthy.<\/p>\n<\/a>Cold Exposure<\/h4>\nIn rats, 30 min of cold stress increased the expression of orexin [R<\/a>].<\/p>\nAlthough the effects of cold showers on orexin activity and wakefulness haven\u2019t been studied, many people advocate for this traditional cooling method.<\/p>\n
It usually takes a while to get accustomed to fully cold showers, though. Some people say it\u2019s good to dip your face in cold water for starts.<\/p>\n
Remember to consult your healthcare provider first, though. Most doctors recommend against cold showers in people with heart disease or in those at risk. That\u2019s because sudden cold exposure can restrict blood vessels, which may raise heart rate and blood pressure.<\/p>\n
<\/a>Keto Diet<\/h4>\nNo studies about ketosis<\/a> and orexin specifically have been published.<\/p>\nNonetheless, some people claim that a keto diet may stimulate orexin since they report feeling subjectively more awake.<\/p>\n
Keto advocates say that if they get into ketosis, glucose levels will likely be low, which is more likely to activate orexin. This hasn\u2019t been proven, though.<\/p>\n
Second, advocates claim that ketones are \u201cenergy-related molecules\u201d that would theoretically signal to the brain that there\u2019s not a famine, which should activate orexin\u2026 in theory. This is thought to be the underlying logic for why lactate allegedly prevents orexin suppression.<\/p>\n
Third, ketones are acidic, so people say that this will also increase orexin. Remember that no human data back them up, though.<\/p>\n
In animals, ketosis increases ghrelin<\/a>. Ghrelin activates orexin [R<\/a>]. However, human studies show that ketosis doesn\u2019t increase ghrelin [R<\/a>].<\/p>\nKetosis results in elevated ATP in animals, which activates orexin. Human data are lacking [R<\/a>].<\/p>\n![\"Ketogenic](\"https:\/\/selfhacked.com\/blog\/app\/uploads\/2018\/02\/ketogenic-diet-changes.jpeg\")
<\/p>\n
<\/a>Forskolin<\/h4>\nAlthough forskolin<\/a> is a popular \u201cwakefulness promoter,\u201d its effects on sleepiness and orexin levels in humans haven\u2019t been proven.<\/p>\nForskolin is hypothesized to increase cyclic AMP, including in the area where orexin neurons are. This might, in theory, activate these neurons (long-term potentiation) and increase wakefulness [R<\/a>].<\/p>\nOrexin binds to orexin 1 receptors to stimulate neurons by activating cAMP [R<\/a>].<\/p>\nHowever, another study did not find this to be true [R<\/a>].<\/p>\n<\/a>Dopamine<\/h4>\nA study examined the ability of dopamine agonists to activate orexin neurons in the rat. The study found that both D1 and D2 receptors may be suf\ufb01cient to activate orexin neurons [R<\/a>].<\/p>\nHowever, when dopamine<\/a> binds to other receptors, it can suppress orexin (alpha-2 receptor). So, it seems to depend on the receptors and much more research is needed.<\/p>\nMucuna<\/a>, tyrosine, Rhodiola<\/a>, and SAM-e<\/a> allegedly increase dopamine, but their effects on orexin are unknown [R<\/a>].<\/p>\n<\/a>Investigational Supplements<\/h4>\n
Science suggests that brain orexin\/hypocretin neurons stimulate wakefulness<\/strong>, alertness<\/strong>, eating, reward-seeking, and healthy glucose balance [R<\/a>].<\/p>\n Orexin is not just any molecule in our body. Some scientists say that whenever we\u2019re tired or fatigued, orexin is suppressed [R<\/a>].<\/p>\n It\u2019s not like orexin is one of the many systems that stimulate wakefulness. It\u2019s considered to be by far the most significant stimulator of wakefulness. Histamine<\/a> is also involved, but orexin activates the histamine system [R<\/a>].<\/p>\n Researchers suspect that there are many hormones and other systems in the body that interact with orexin.<\/p>\n Therefore, the orexin system seems to be central to productive human functioning and good mood. However, orexin\u2019s role is a relatively recent discovery. Larger human studies are needed to better understand its effects on health [R<\/a>].<\/p>\n There are two main types of narcolepsy: type 1 and type 2. Measuring orexin levels helps diagnose type 1 narcolepsy [R<\/a>].<\/p>\n Doctors need the following to diagnose type 1 narcolepsy [R<\/a>]:<\/p>\n The exact cause of narcolepsy is still unknown. Unproven, experimental theories suggest that narcolepsy may result from immune imbalance, specifically an elevated Th2<\/a> immune system, in some people. Another study found elevated TNF<\/a> and IL-6<\/a> [R<\/a>, R<\/a>].<\/p>\n Limited research suggests that orexin also increases metabolism and body temperature. According to this theory, people that feel cold<\/a> and tired may, among other factors, have low orexin [R<\/a>].<\/p>\n Orexin also seems to increase hunger via increased neuropeptide Y<\/a> expression in the arcuate nucleus of the hypothalamus [R<\/a>].<\/p>\n Animal models suggest that low levels of orexin cause obesity<\/a>, even when fewer calories are consumed. This hasn\u2019t been confirmed in humans [R<\/a>].<\/p>\n One hypothesis posits that orexin is a significant factor in why consuming sugar makes people fat. They claim that this is because people feel tired after eating sugar, since it causes blood sugar levels to spike and orexin to fall. So, instead of burning calories, people go to sleep<\/a>. Although plausible, this hypothesis has yet to be tested [R<\/a>].<\/p>\n Another team of researchers claimed that higher levels of orexin-A cause people to be happier. They\u2019re still lacking solid data, though, since this theory is mainly based off the fact that the incidence of depression<\/a> is higher in narcolepsy.<\/p>\n Yet another stream of research found that orexin and its receptors may decline with age. Plus, orexin may cause people to increase oxygen use because it might increase metabolism. Future research has yet to clarify and solidify all these findings [R<\/a>, R<\/a>].<\/p>\n If your goal is to increase orexin to improve your fatigue – or extreme exhaustion-related issues – including those of chronic fatigue or depression – it\u2019s important to talk to your doctor, especially low energy levels are significantly impacting your daily life.<\/p>\n Your doctor should diagnose and treat any underlying conditions causing your symptoms.<\/strong><\/p>\n Remember that the existing evidence does not suggest that low orexin causes fatigue or mood disorders.<\/p>\n There\u2019s also no precise way to measure orexin levels outside of research studies and diagnosing type 1 narcolepsy. For narcolepsy, a healthcare professional has to take a person\u2019s cerebrospinal fluid, which is an invasive procedure reserved only for specific cases.<\/p>\n Complex disorders like chronic fatigue syndrome always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.<\/p>\n Additionally, changes in nerve tone and brain chemistry are not something that people can change on their own with the approaches listed here. Instead, the factors mentioned in this article are meant to improve energy levels and support overall mental health and well-being. Most are backed up only by limited human or animal studies.<\/p>\n Therefore<\/strong>, you may try the strategies listed below if you and your doctor determine that they could be appropriate<\/strong>. Read through the approaches we bring up and discuss them with your doctor before trying them out. This is particularly important if you plan to take any dietary supplements.<\/p>\n Supplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don\u2019t guarantee that they\u2019re safe or effective.<\/p>\n Finally, have in mind that none of these strategies should ever be done in place of what your doctor recommends or prescribes.<\/p>\n Research suggests a link between orexin and chronic inflammation. Persistent, low-grade inflammation also seems to be tightly tied to fatigue and low cellular energy, according to recent scientific findings [R<\/a>, R<\/a>].<\/p>\n Elevated inflammation from cytokines like IL-1b<\/a> and TNF<\/a> is hypothesized to cause fatigue by the suppression of orexin neurons [R<\/a>, R<\/a>, R<\/a>, R<\/a>].<\/p>\n Just before the normal time of sleep<\/a> onset for rats, TNF levels in brain tissue were shown to be 10-fold higher than their daily minimum. This hasn\u2019t been verified in humans, though [R<\/a>].<\/p>\n If you are experiencing chronic inflammation, work with your doctor to resolve the underlying issue causing your symptoms.<\/p>\n Getting regular, moderate exercise is good for overall health. We know from experience that it makes us feel energized, and some scientists think orexin might be one of the reasons.<\/p>\n Limited human studies back this theory up: exercise was able to increase orexin levels in the human bloodstream [R<\/a>].<\/p>\n Additionally, exercise seems to increase orexin in the cerebrospinal fluid of rats, dogs, and cats [R<\/a>].<\/p>\n Researchers think that the source of orexin might be directly released from the pituitary into the bloodstream, leaked from the cerebrospinal fluid, or produced by the gut or pancreas. More research is needed [R<\/a>].<\/p>\n Exercise temporarily acidifies our blood (increases lactate<\/a>), which is hypothesized to increase the firing of orexin neurons [R<\/a>].<\/p>\n Interestingly, orexin A may cross the blood-brain barrier. Theoretically, if it’s elevated in the blood after exercise, it may also be elevated in the brain [R<\/a>].<\/p>\n Bright light (for example, from the sun) increases orexin, and animal research suggests that this is the likely mechanism by which it\u2019s effective for depression and seasonal affective disorder (SAD). Proper human data are still lacking to back up this mechanism, though [R<\/a>].<\/p>\n We spoke about lactate as a \u201cbackup generator\u201d before<\/a>.<\/p>\n Lactate<\/a> is a critical energy source and a likely regulator of the orexin system. Scientists think that lactate release from astrocytes plays an integral part in balancing brain activity and energy supply [R<\/a>].<\/p>\n According to one theory, supplying orexin neurons with lactate can stop glucose from blocking orexin neurons. Lactate might disinhibit and sensitize these orexin neurons for future excitation. This hasn\u2019t been proven in humans, however [R<\/a>, R<\/a>].<\/p>\n One study hypothesized that orexin neurons only \u201csee\u201d glucose changes when the levels of other energy molecules are low, whereas high energy levels can stop glucose from regulating orexin cells [R<\/a>].<\/p>\n Here are some fermented foods that likely contain lactate:<\/p>\n Kombucha has lactate, pyruvate, butyrate<\/a>, ATP. Studies are investigating whether it has other \u201cenergy-related molecules\u201d as a result of the fermentation process. Anecdotally, many people say this fermented Eastern drink refreshes and energizes them [R<\/a>].<\/p>\n Additionally, certain probiotics<\/a> like Lactobacilli produce lactate.<\/p>\n On the other hand, various minerals can be formulated into lactate salts, such as Calcium<\/a> lactate and Magnesium<\/a> lactate.<\/p>\n It\u2019s a good idea to get adequate amounts of healthy protein foods on a daily basis. Various amino acids are hypothesized to affect orexin signaling, but there are no clinical studies to determine their impact.<\/p>\n Researchers believe that amino acids excite orexin neurons through a few mechanisms, though this has yet to be confirmed in humans [R<\/a>].<\/p>\n An animal study gave branched-chain amino acids (BCAAs), which are precursors to glutamate<\/a> synthesis, to brain-damaged mice. BCAAs reinstated activation of orexin neurons and improved wake deficits in mice with mild brain injury. Human data are lacking [R<\/a>].<\/p>\n In the lab, nonessential amino acids were more potent in activating orexin cells than essential amino acids [R<\/a>].<\/p>\n One theory states that amino acids may block glucose suppression of orexin because they tell the neurons that there\u2019s enough energy around [R<\/a>].<\/p>\n In cells, scientists ordered them this way – from most to least effective:<\/p>\n However, we have no way to know how each one affects orexin activity in complex beings. This hasn\u2019t been researched.<\/p>\n Theoretically, elevated glucose concentration might block or silence the activity of orexin neurons [R<\/a>].<\/p>\n In lab animals, the principal way to activate orexin is by restricting glucose [R<\/a>].<\/p>\n The hypothesis is that under low-energy conditions such as starvation, it could be advantageous for ingested glucose to suppress the orexin-driven net energy expenditure, thereby ensuring that more fundamental processes (such as keeping the brain alive) receive enough glucose.<\/p>\n Conversely, when the brain has plenty of fuel (perhaps signaled by high levels of pyruvate and\/or lactate), there may be little advantage in coupling glucose fluctuations to orexin activity, since under these conditions, acute changes in glucose levels would be compensated by other energy molecules [R<\/a>].<\/p>\n In addition, scientists think that orexin neurons are stimulated by falling glucose levels [R<\/a>].<\/p>\n Hypothetically, people who eat less or practice some degree of caloric restriction may have higher orexin because their body senses they\u2019re not getting enough calories, which activates this system. Proper human data are needed, though [R<\/a>].<\/p>\n Some researchers consider that losing extra weight may help increase orexin and energy levels.<\/p>\n This is based on the theory that Leptin<\/a> inhibits orexin. High leptin levels are characteristic of being overweight, while leptin levels tend to drop as a result of weight loss<\/a> [R<\/a>].<\/p>\n However, many other factors also affect leptin levels and weight and the exact role of orexin has yet to be determined.<\/p>\n GLP-1 is a gut hormone that can activate\/excite orexin neurons in the hypothalamus (which increases orexin). Scientists think it might be useful in making us feel satiated as well, which may make us eat less and further activate orexin.<\/p>\n It\u2019s possible that GLP-1 functions like orexin and sometimes works instead of it, though this hasn\u2019t been confirmed in humans [R<\/a>].<\/p>\n Resistant starch<\/a> may increase GLP-1<\/a> and also produces butyrate<\/a>. It\u2019s also acidic. Hypothetically, this might block glucose-induced suppression of orexin [R<\/a>, R<\/a>, R<\/a>].<\/p>\n Anecdotally, people say high-butyrate foods or drinks (like kombucha) increase energy levels after a big meal.<\/p>\n A study in dogs found having fun or play was able to increase orexin, while the same level of exercise wasn\u2019t able to [R<\/a>].<\/p>\n The study concluded that motor and cardiovascular changes might not sufficient to elevate orexin, so they hypothesize that the emotional aspects of yard play account for the observed increase in orexin [R<\/a>].<\/p>\n Research hasn\u2019t yet measured the effects of fun activities on orexin in humans.<\/p>\n Vagus nerve stimulation<\/a> seemed to decrease daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury in limited studies. More clinical trials are needed and whether or not vagus nerve stimulation affects orexin signaling is still unknown [R<\/a>].<\/p>\n In comatose rats after traumatic brain injury, vagus nerve stimulation promoted the recovery of consciousness [R<\/a>].<\/p>\n The effects were thought to be, in part, mediated by the increase of orexin-A and its receptor (OXR1) in the prefrontal cortex [R<\/a>].<\/p>\n Caffeine<\/a> was found to activate orexin, which isn\u2019t surprising given that it\u2019s the most widely-consumed stimulant worldwide. It\u2019s found in both coffee and green and black tea<\/a>, but green tea is the highest in antioxidants among the three [R<\/a>, R<\/a>].<\/p>\n A study found that in healthy people, there was a correlation between omega 3s and orexin A (but not in narcoleptics) [R<\/a>].<\/p>\n The following factors are theoretical or anecdotal. They aren\u2019t backed up by solid science, and some are not generally associated with well-being. <\/strong><\/p>\n For example, we recommend against bag breathing and high fructose intake but think that they\u2019re interesting to mention for informational purposes.<\/p>\n We also highly recommend against the use of nicotine for any indication other than smoking cessation. Nicotine is highly addictive and its harms outweigh any benefits.<\/p>\n Keto diets and cold exposure are not harmful as long as you get a green light from your healthcare provider.<\/p>\n CO2<\/sub> increases after eating carbohydrates. Macronutrient profile aside, CO2<\/sub> increases after breathing into a bag [R<\/a>].<\/p>\n Animal studies suggest that long-term fructose consumption (bingeing) increases orexin [R<\/a>].<\/p>\n Also, 25% of fructose consumed turns into lactate, which is hypothesized to have orexin-increasing effects [R<\/a>].<\/p>\n Fructose, fructans, and FOS might also excite orexin neurons by increasing GLP-1<\/a>, thereby potentially increasing wakefulness [R<\/a>, R<\/a>].<\/p>\n Raw honey<\/a> has some fructose. However, heavy fructose consumption is not healthy.<\/p>\n In rats, 30 min of cold stress increased the expression of orexin [R<\/a>].<\/p>\n Although the effects of cold showers on orexin activity and wakefulness haven\u2019t been studied, many people advocate for this traditional cooling method.<\/p>\n It usually takes a while to get accustomed to fully cold showers, though. Some people say it\u2019s good to dip your face in cold water for starts.<\/p>\n Remember to consult your healthcare provider first, though. Most doctors recommend against cold showers in people with heart disease or in those at risk. That\u2019s because sudden cold exposure can restrict blood vessels, which may raise heart rate and blood pressure.<\/p>\n No studies about ketosis<\/a> and orexin specifically have been published.<\/p>\n Nonetheless, some people claim that a keto diet may stimulate orexin since they report feeling subjectively more awake.<\/p>\n Keto advocates say that if they get into ketosis, glucose levels will likely be low, which is more likely to activate orexin. This hasn\u2019t been proven, though.<\/p>\n Second, advocates claim that ketones are \u201cenergy-related molecules\u201d that would theoretically signal to the brain that there\u2019s not a famine, which should activate orexin\u2026 in theory. This is thought to be the underlying logic for why lactate allegedly prevents orexin suppression.<\/p>\n Third, ketones are acidic, so people say that this will also increase orexin. Remember that no human data back them up, though.<\/p>\n In animals, ketosis increases ghrelin<\/a>. Ghrelin activates orexin [R<\/a>]. However, human studies show that ketosis doesn\u2019t increase ghrelin [R<\/a>].<\/p>\n Ketosis results in elevated ATP in animals, which activates orexin. Human data are lacking [R<\/a>].<\/p>\n Although forskolin<\/a> is a popular \u201cwakefulness promoter,\u201d its effects on sleepiness and orexin levels in humans haven\u2019t been proven.<\/p>\n Forskolin is hypothesized to increase cyclic AMP, including in the area where orexin neurons are. This might, in theory, activate these neurons (long-term potentiation) and increase wakefulness [R<\/a>].<\/p>\n Orexin binds to orexin 1 receptors to stimulate neurons by activating cAMP [R<\/a>].<\/p>\n However, another study did not find this to be true [R<\/a>].<\/p>\n A study examined the ability of dopamine agonists to activate orexin neurons in the rat. The study found that both D1 and D2 receptors may be suf\ufb01cient to activate orexin neurons [R<\/a>].<\/p>\n However, when dopamine<\/a> binds to other receptors, it can suppress orexin (alpha-2 receptor). So, it seems to depend on the receptors and much more research is needed.<\/p>\n Mucuna<\/a>, tyrosine, Rhodiola<\/a>, and SAM-e<\/a> allegedly increase dopamine, but their effects on orexin are unknown [R<\/a>].<\/p>\n<\/a>What Does it Do?<\/strong><\/span><\/h3>\n
<\/a>Narcolepsy <\/strong><\/span><\/h3>\n
\n
<\/a>Beyond Wakefulness<\/span><\/h3>\n
<\/a>Factors that May Increase Orexin<\/strong><\/span><\/h2>\n
<\/a>When to See a Doctor<\/span><\/h3>\n
<\/a>Precautions & Limitations<\/span><\/h3>\n
<\/a>1) Resolving Chronic Inflammation<\/strong><\/span><\/h3>\n
<\/a>2) Exercise<\/strong><\/span><\/h3>\n
<\/a>3) Natural Light – Get Outside<\/strong><\/span><\/h3>\n
<\/a>4) Fermented Foods <\/strong><\/span><\/h3>\n
\n
<\/a>5) Protein<\/strong><\/span><\/h3>\n
\n
<\/a>6) Carb and Caloric Restriction<\/strong><\/span><\/h3>\n
<\/a>7) Maintaining Healthy Weight<\/strong><\/span><\/h3>\n
<\/a>8) Fiber<\/strong><\/span><\/h3>\n
<\/a>9) Having Fun <\/strong><\/span><\/h3>\n
<\/a>10) Vagus Nerve Stimulation<\/strong><\/span><\/h3>\n
<\/a>11) Green Tea<\/strong><\/span><\/h3>\n
<\/a>12) Omega 3s<\/strong><\/span><\/h3>\n
<\/a>Experimental (Lacking Evidence)<\/strong><\/span><\/h3>\n
<\/a>Bag Breathing\/CO2<\/sub><\/h4>\n
<\/a>Fructose<\/h4>\n
<\/a>Cold Exposure<\/h4>\n
<\/a>Keto Diet<\/h4>\n
<\/p>\n<\/a>Forskolin<\/h4>\n
<\/a>Dopamine<\/h4>\n
<\/a>Investigational Supplements<\/h4>\n