What is Norepinephrine?
Norepinephrine (NE) also known as noradrenaline (NA) is an excitatory neurotransmitter and a neuromodulator which also can act as a hormone. Norepinephrine is categorized in the monoamine group of neurotransmitters with the others being dopamine (DA), epinephrine (adrenaline) and acetylcholine.
Norepinephrine, dopamine, and epinephrine are monoamine neurotransmitters, also categorised as catecholamines. These neurotransmitters are released in minute amounts from the brain and peripheral nervous system. They play an important role in arousal, emotion, and cognition.
Norepinephrine is one of the main neurotransmitters that deals with the stress response (fight or flight) but also involved in various other functions such as concentration, alertness, attention, memory and learning. It is also involved in other bodily functions such as glucose release from tissue, heart rate, blood pressure and other vital functions.
Norepinephrine synthesis depends on dopamine and requires the dopamine β-hydroxylase enzyme.
It is produced in the adrenal glands and is released from the adrenal medulla into the blood as a hormone.
In the brain norepinephrine is produced in the brainstem area and near the spinal cord.
In the central nervous system and the sympathetic nervous system it acts as a neurotransmitter where it is released from noradrenergic neurons and project throughout the brain and spinal cord.
Norepinephrine and epinephrine work on the same receptors known as adrenoreceptors (also known as adrenergic receptors). These receptors are found on plasma membrane as both epinephrine and norepinephrine are water soluble. These receptors are g-protein-coupled receptors (GPCRs).
GPCRs are membrane receptors which are used by cells to respond to external signals (extracellular) and convert them to internal responses (intracellular). They are involved in various chemicals and functions found in the body which includes hormones, neurotransmitters as well as signals related to vision, smell and taste.
Very small amount of norepinephrine or epinephrine are needed to begin having effect on these receptors.
Different types of adrenergic receptors are found in different parts of the body each having a specific function depending on the part in which the receptor is found in.
Medications are available which affect these different receptors by either stimulating or inhibiting specific subtypes.
Various medications are available that act on these adrenoceptors to induce different effects within the body. There are 5 types of adrenoceptors known as alpha-1, alpha-2, beta-1, beta-2 and beta-3. Adrenoceptors can be found in the tissues around the body with many different effects. The following are some of the main parts with their various effects.
The alpha adrenoceptors (α) are involved in vasoconstriction and are found on blood vessels.
Beta-1 adrenoceptors (β1) are found on the heart. β1 causes the heart rate to accelerate which can occur when excited. Beta blockers are medications prescribed for certain heart conditions which slow down heart rate by blocking this receptor.
Beta-2 adrenoceptors (β2) are found on the bronchioles in the lungs. β2 is involved in bronchodilatation (bronchioles dilate). Some asthma medications in the form of asthma inhalers stimulate this receptor.
Beta-3 adrenoceptors (β3) are found on brown fat (adipose tissure) and is involved in thermogenesis. Brown fat is a type of fat that produces heat and is activated when cold. High amount of this fat is found in newborn babies.
Norepinephrine converts to epinephrine and along with the hormone cortisol induces the physiological effects of an adrenaline rush.
Although norepinephrine is almost identical to epinephrine, norepinephrine acts more as a neurotransmitter and stimulates release of epinephrine whereas epinephrine functions like a hormone. They are like the Bonnie and Clyde of neurotransmitters which if left out of control and can cause significant chaos.
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[R]Health Benefits of Norepinephrine
Essential for stress response
One of the main function of norepinephrine is as an excitatory neurotransmitter responsible for the fight or flight response to stress in the form of a threat or danger.
Norepinephrine is a stress hormone which is released when in fear and the activation of the fight or flight system. [R]
Norepinephrine helps to mobilize the brain and body for action.
A classic scenario in which norepinephrine is activated is when humans or mammals are in situations where they face a threat or some situation that alerts them to any danger. In this fearful state the fight or fight chemicals which includes norepinephrine are activated and released. It creates an alert state to perform some action to deal with the threat or danger. Norepinephrine is mostly found in the sympathetic nervous system and sometimes referred to as the fight or flight system.
The threat is first registered in the brain and the response to the threat begins in the hypothalamus which sends signals to the sympathetic nerves (fight or flight nerves) that move downwards into the spinal cord. From the spinal cord the neurons move only to the thoracic level and down to the lumbar region. The neurons do not move to any other parts below the lumbar region.
The signals are sent out from the spinal cord to the parts of the body that need to respond in times of high stress levels where fight or flight nerves are activated.
The parts of the body that respond to fight or flight or involved with release of norepinephrine are the muscles, blood vessels, heart, airways, pupils and the skin. The norepinephrine neurons at this stage tell the body parts what to do by binding to the specific organ.
In the eyes the release of these signals cause the pupils to dilate so that more light can reach the eyes, the purpose of this action is to help get a clearer more expanded view of the surroundings to help decide if the oncoming threat means the person or animal needs to fight or runaway, basically deciding on fight or flight actions.
The manifestation of norepinephrine can be seen in the skin where signals to blood vessels causes them to constrict so that the body part that will need more blood can be supplied such as the muscles which can help with running away. When blood is moved away from the skin it also helps avoid excess bleeding when cut or injured under potential threat. The skin can take on a pale appearance in this situation.
In a state of heightened fear the heart pumps harder and faster which helps deliver more oxygenated blood to the muscles which will help to flee from a situation that activates fight or flight nerves.
The airways are involved in this response by increasing the respiratory rate. The individual in this situation will be breathing deeper and faster as the airways relax and expand to draw in more oxygen to carry in the blood and pump to the heart which can supply it to the needed muscles.
Once norepinephrine noradrenaline is released it sends signals to the adrenal glands which stimulates the release of epinephrine (adrenaline) hormone into the bloodstream. If this hormone gets into the bloodstream it circulates throughout the body acting in a similar way to norepinephrine in a fight or flight stress situation i.e dilating pupils, opening up airways, increasing heart rate until the situation calms down or the person or animal is out of danger.
Functions in behaviour and social relationships
Norepinephrine plays an important role in behaviour through its role in executive functioning which impacts social relationships. Along with its involvement in the stress response it is also involved in modulation of vigilance. [R]
Mental illnesses such as depression which can be affected by levels of norepinephrine affect social relationships and altered levels may lead to social dysfunction which can greatly impact quality of life.
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Studies have shown that norepinephrine has some effects on social behaviour and moral decisions. [R]
Supports learning
Norepinephrine is involved in attention, focus, decision making, learning and involved in long term memory.
Norepinephrine helps with learning through its role in modifying synapses which are the connections between nerve cells. Synapses are important to form and consolidate memories which can influence learning.
One study shows how norepinephrine is linked to the formation of fear memory where the release of norepinephrine is consistent in a continuous state of vigilance. [R] [R]
Involved in decision making
Much of norepinephrine’s function is involved in the decision making process. [R] [R]
Altered levels of norepinephrine can also determine whether a gambler is likely to become addicted or knows when to stop gambling which is also shaped by an individual’s genetic makeup. Norepinephrine in the brain is associated with aversion to financial loss when there are sufficient or higher levels of norepinephrine transporters with lower amounts of norepinephrine.
Similar to gambling addiction norepinephrine also plays a role in relationships and may have similar effects as with gambling addiction based on the amount of norepinephrine. Dopamine is also involved in falling in love which is the main neurotransmitter substrate for norepinephrine. Whilst dopamine is involved in pleasure, norepinephrine can heighten the feelings of excitement.
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[https://pubmed.ncbi.nlm.nih.gov/20200382/] [https://www.nejm.org/doi/full/10.1056/nejmoa0907118] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750074/]Increases motivation
Norepinephrine is implicated in motivation and synthesised from dopamine which is also involved in the modulation of motivation and reward system. Low levels can cause lethargy and make a person feel demotivated.
Norepinephrine enhances arousal through the beta and alpha-1 receptors.
Norepinephrine has stimulating effects and is important for energy, drive and alertness.
Supports cognitive functions
Norepinephrine modulates arousal, attention, learning and memory which all have an impact on mental skills as well as behaviour.
Norepinephrine functions are involved in regulating cognition and intellect. A deficiency is linked to neurodegenerative diseases.
Norepinephrine can promote neuroplasticity in the brain.
Higher levels of norepinephrine and serotonin have shown to increase cognitive functions. SNRIs and SSRIs have both shown to improve executive functions which includes working memory, flexible thinking, and self-control. [R]
Many studies are showing a link between norepinephrine and cognitive functions. One study shows the attentional shift in rats when noradrenergic system is activated. [https://pubmed.ncbi.nlm.nih.gov/2167690/] [R] [R] [R]
The locus coeruleus which is the primary source of norepinephrine plays a role in the regulation of cognitive performance. [R]
Supports the immune system
Norepinephrine modulates the immune response and has shown to reduce inflammation when released in the brain. Some neurodegenerative conditions such as Alzheimer’s disease have low levels of norepinephrine. In AD there is a loss of up to 70% of cells that project norepinephrine.
Norepinephrine acts as an anti-inflammatory agent in brain tissue, suppressing cytokines. [R]
Supports bodily functions
Norepinephrine plays a significant role in motor output. Norepinephrine has an effect on many bodily functions and organs.
Norepinephrine release contracts blood vessels increasing blood flow to skeletal muscle which can increase brain oxygen levels.
It can increase the force of skeletal muscle contraction. It can increase rate and force of contraction of the heart, heart rate, and blood pressure.
It also increases levels of glucose in the blood and performs this action by increasing production of glucose in the liver, releases glucose from tissue and increases the glucose uptake in the skeletal muscles.
It also increases levels of fat in the blood and in fat cells increase fat burning. In brown adipose tissue it increases calories burned to generate body heat.
In the eyes norepinephrine is involved in dilating pupils and increasing production of tears which keeps eyes moist.
In the kidneys norepinephrine is involved in the release of renin and retains sodium in the bloodstream.
Norepinephrine in the stomach and intestines is involved in reducing digestive activity and decreases in gastrointestinal mobility.
Norepinephrine is important to prevent fainting (syncope) which may be the result of low blood pressure and heart rate. Norepinephrine can increase heart rate and blood pressure.
A surge of norepinephrine can lead to feelings of happiness and euphoria (intense feelings of joy and happiness).
Agonist / Synergist
Amino acids Phenylalanine, tyrosine, lysine, methionine
Other Cocaine, exercise, stress, nicotine, carnitine
Probiotics Escherichia, bacillus species
Medications Norepinephrine reuptake inhibitors (NRIs), Norepinephrine-dopamine reuptake inhibitors (NDRIs), Selective serotonin reuptake inhibitors (SSRIs), Serotonin-norepinephrine reuptake inhibitors (SNRIs), Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs), Tricyclic antidepressants Amphetamines, Steroids, Psychostimulants (ADHD medications)
Dopamine is required for the synthesis of norepinephrine which helps improve symptoms of depression.
Dopamine is the main precursor for norepinephrine and follows the catecholamines pathway. To see all cofactor nutrients that support dopamine synthesis see Dopamine.Dopamine synthesis requires phenylalanine or tyrosine and other cofactors which include vitamin B9 (folate), iron, vitamin B3 (niacin), vitamin B6 (pyridoxal phosphate), and zinc.
Tyrosine is converted to dopamine once it reaches the neurons and continues along the catecholamines pathway to synthesise norepinephrine.
The enzyme tyrosine hydroxylase at the pre-synaptic nerve ending is essential in the synthesis of norepinephrine and needs electrical activity along the nerve to increase amount of this enzyme.
Tyrosine hydroxylase enzyme, increases with the sense of touch around the body and helps to synthesise norepinephrine.
Phenylalanine is a precursor to neurotransmitters dopamine, epinephrine and norepinephrine.
Tyrosine can be synthesised from phenylalanine or obtained directly from food source. It converts to dopamine and needs sufficient amounts of biopterin, vitamin B3, copper and vitamin C for conversion.
DL-phenylalanine has been used for chronic depression and may improve mood and this is directly from its conversion into tyrosine and then into norepinephrine. It is an important component of the catecholamines synthesis and also needed for dopamine production which helps with focus and uplifting mood. Tyrosine is also useful for anxiety.
Phenylethylamine or PEA is also involved in the release of norepinephrine.
Dopamine to Norepinephrine Synthesis
Dopamine needs dopamine beta hydroxylase (DBH) enzyme and cofactors calcium, copper and vitamin C (ascorbic acid) for conversion to norepinephrine.
Vitamin C is one of the main vitamins needed for healthy adrenal glands where this vitamin is also found in high concentrations. [R]
Vitamin C is needed to convert dopamine into norepinephrine.
The enzyme dopamine β-hydroxylase can be found in the adrenals and the brain as well as being present in other organs such as the heart. [R]
Copper is needed by enzymes that control dopamine.
Adequate amounts of copper is needed for the functions of the brain. It is an essential mineral in the growth and development of the brain. Having too little or too much of this mineral can lead to a decline of cognitive functions and has been linked to neurological disorders such as such as Menke’s disease, Wilson’s disease and Alzheimer’s disease. [https://pubmed.ncbi.nlm.nih.gov/24440710/] [R] [R] [R]
The enzyme dopamine β-hydroxylase (DBH) needs copper to synthesize the neurotransmitter norepinephrine from dopamine.
Dopamine beta hydroxylase also needs calcium as well as ascorbic acid in order to convert to norepinephrine which helps to improve mood and reduce symptoms of depression. [R]
Norepinephrine requires S-Adenosylmethionine (SAMe) to convert into epinephrine
The catecholamines pathway depends on sufficient amounts of the amino acid phenylalanine or tyrosine.
The conversion of these amino acids then require vitamin B9 (folate), iron, vitamins B3 (niacin), vitamin B6 (pyridoxal phosphate), zinc, copper vitamin C (ascorbic acid), and methionine (or active form SAMe) to help with the synthesis of dopamine and then conversion to norepinephrine and epinephrine. This strengthens the catecholamines pathway and may prevent development of neurodegenerative conditions such as Parkinson’s disease and Alzheimer’s disease.
Other nutrients that may help the synthesis of norepinephrine from dopamine are lysine, magnesium, and manganese. [https://pubmed.ncbi.nlm.nih.gov/10827223/].
Zinc and copper need to be balanced
Iodine along with selenium plays a very important role in the thyroid by supporting and maintaining its functions in the body. Iodine is needed for T4 and T3 production. In the brain these hormones are needed to activate neurotransmitters acetylcholine and others such as dopamine, norepinepherine, serotonin and GABA. Deficiency in iodine is linked to poor cognitive functions and intellectual disability.
A deficiency in thyroid hormones T4 and T3 can lead to depression, anxiety and low energy.
Folate or folic acid is needed for healthy new cells and for the synthesis of neurotransmitter norepinephrine including other neurotransmitters such as acetylcholine and serotonin.
Some parts of the brain needed for cognitive functions such as memory and learning are affected by folate deficiency. Additionally high homocysteine levels have been associated with neurological disorders which can also be an indicator for low levels of B12 and other deficiencies such as B6 and B9.
Vitamin B12 is a cofactor needed for the production of dopamine and other neurotransmitters which includes, norepinephrine, GABA and serotonin.
Chromium plays a role in the release of norepinephrine which may help with depression related to low norepinephrine.
Chromium helps produce insulin needed for glucose metabolism.
Molybdenum plays a role in norepinephrine metabolism.
Aldehyde dehydrogenase enzyme is involved in the breakdown of serotonin, melatonin, dopamine, norepinephrine and epinephrine.
Aldehyde dehydrogenase is needed to process acetaldehyde (a byproduct of alcohol) into acetic acid.
Aldehyde dehydrogenase enzyme requires molybdenum.
Exercise for at least an hour each day may increase norepinephrine levels.
Cold showers may increase norepinephrine levels [https://pubmed.ncbi.nlm.nih.gov/911386/] [Rhttps://pubmed.ncbi.nlm.nih.gov/17993252/]
Adequate sleep. Following healthy sleep patterns and restoring a healthy circadian rhythm with appropriate wake sleep patterns can boost neurotransmitters.
Daytime nap may increase levels of norepinephrine
Probiotic strains involved in the synthesis of norepinephrine include Escherichia and Bacillus species.
Monoamine oxidase (MAO) is a copper-containing enzyme which deactivates the catecholamines norepinephrine, epinephrine, and dopamine after their function has ended which reduces norepinephrine levels. Although this effect is antagonistic it is also necessary to support healthy catecholamine levels and to keep it in check.
MAO inhibitors inhibit the action of this enzyme and thereby prevents breakdown of norepinephrine which allows the brain to utilise this neurotransmitter.
Nicotine increases acetylcholine which helps with dopamine release, and subsequent release of norepinephrine as well as serotonin.
Acetylcholine in small amounts stimulates the release of important neurotransmitters which includes dopamine and norepinephrine.
Norepinephrine reuptake inhibitors (NRIs) are used to treat major depressive disorder (MDD), anxiety, panic disorder, narcolepsy, and ADHD. Medications include Strattera (atomoxetine).
Norepinephrine-dopamine reuptake inhibitors (NDRIs) are used for clinical depression, ADHD, and narcolepsy. Examples of medications include Focalin (dexmethylphenidate) and Wellbutrin (bupropion).
Selective serotonin reuptake inhibitors (SSRIs) are used to tread MDD and anxiety disorders. An example of the medication prescribed includes Zoloft (sertraline).
Serotonin-norepinephrine reuptake inhibitors (SNRIs) can be used to treat bipolar depression, MDD, ADHD, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), chronic nerve pain, and fibromyalgia. Example of medications include Cymbalta (duloxetine) and Savella (milnacipran). SNRIs increase both serotonin and norepinephrine.
Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs) are used to treat depression but may also be used for the treatment of ADHD, chronic pain, and obesity. Examples of medications include Effexor (venlafaxine) and Serzone (nefazodone).
Norepinephrine is needed for the synthesis and release of melatonin in the pineal gland during sleep. [R]
Inositol can help regulate mood through its involvement in the manufacturing of serotonin, melatonin, dopamine, norepinephrine, acetylcholine and GABA. These neurotransmitters require inositol for transmitting messages between the brain cells. A deficiency of inositol has been linked to various mental health problems which includes depression, anxiety and panic attacks where many of the neurotransmitters are out of balance.
To balance effects of norepinephrine and or epinephrine using essential oils that promote relaxation may be beneficial. Vetiver, frankincense, and lavender can improve sleep, reduce anxiety, lower heart rate and blood pressure and may have anti-inflammatory effects.
Monoamine oxidase (MAO) is a copper-containing enzyme which deactivates the catecholamines (norepinephrine, epinephrine, and dopamine) after their function has ended which reduces dopamine levels. MAO inhibitors inhibit the action of this enzyme and thereby prevents breakdown of dopamine which allows the brain to utilise this neurotransmitter.
As dopamine levels increase the neurotransmitters serotonin, norepinephrine, glutamate, GABA endorphins, endocannabinoids and oxytocin also increases.
Epinephrine (aka adrenaline) and norepinephrine (aka noradrenaline) are made from dopamine and continue on with the catecholamines pathway.
Carnitine increases norepinephrine. Carnitine is produced in the liver and kidneys from the amino acids lysine and methionine. [R]
When norepinephrine increases neurotransmitter glutamate, endorphins, dopamine, endocannabinoids and oxytocin also increase.
When norepinephrine increases hormones cortisol, adrenaline, DHEA, estrogen also increase.
Healthy adrenal functioning is needed for the catecholamines synthesis.
The adrenals are important glands involved in producing dopamine, other neurotransmitters that act like hormones such as epinephrine (adrenaline), cortisol and sex hormones.
The adrenals are found located above the kidneys, are small and walnut shaped. Chronic stress overtime can cause adrenal fatigue or burnout which can cause back pain that can be felt below the rib cage on the left or right side.
Stress of various kinds can stimulate and overwork the adrenal glands which may lead to high production of cortisol. This means the adrenals may focus solely on producing cortisol whilst putting the brakes on other hormone synthesis such as sex hormones as well as neurotransmitters.
Stress from work, academic studies, disease or emotional stress can all elevate cortisol levels.
To keep the adrenals healthy it is essential to manage stress especially if dealing with chronic stress.
High sugar or high fructose corn syrup consumption stresses adrenal glands.
Alcohol consumption and deep fried food also stresses the adrenal glands and should be limited or avoided.
Vitamin C and the amino acid methionine are essential for healthy adrenal function.
Healthy adrenal glands are needed for the catecholamines synthesis especially norepinephrine and epinephrine as well as supporting synthesis of the stress hormone cortisol.
Norepinephrine converts to epinephrine. See Epinephrine file for the cofactors needed for this synthesis.
Avoiding caffeine as it reduces epinephrine and norepinephrine.
Antagonists
Minerals Copper
Neurotransmitters acetylcholine, dopamine (in excess), serotonin, 5-HTP, GABA
Hormones Progesterone, estrogen
Medications Beta blockers, Alpha blockers
Other L-theanine, NAC, Inositol, Omega-3 fatty acids, caffeine, Adrenal fatigue / adrenal burnout, MAO, MAOIs, Catechol-O-methyltransferase (COMT) enzyme
The effects of norepinephrine can be reduced by taking L-theanine which has a calming effect as well as inositol. NAC helps increase antioxidant glutathionine
Adrenal fatigue or adrenal burnout impairs the functions of the adrenal glands which can reduce production of norepinephrine or epinephrine leading to symptoms of deficiency
Caffeine is antagonistic towards norepinephrine and epinephrine and has shown to get depleted via urine after caffeine administration [R]
Copper in excess may prevent dopamine synthesis. Excess copper are more likely in women with depression and especially postpartum depression which is linked to the sharp increase without levels normalizing in some women after giving birth. Insufficient dopamine will impair norepinephrine synthesis.
Beta blockers are medications used for conditions such as glaucoma, migraine, and cardiovascular related health condition.
Alpha blockers are medications used for anxiety disorder, panic disorder, post-traumatic stress disorder (PTSD) and also used for cardiovascular conditions.
When norepinephrine increases the neurotransmitters serotonin, acetylcholine and GABA decrease.
When norepinephrine increases the hormones progesterone, estrogen, testosterone and thyroid hormones decrease.
Progesterone contraceptives is linked to depression. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163405/]
When dopamine is the dominant neurotransmitter it inhibits release of norepinephrine.
BCAAs (branched chain amino acids includes leucine, isoleucine and valine) compete with phenylalanine and tyrosine which can impact levels of neurotransmitters found in the brain that follow the catecholamines pathway which include dopamine, epinephrine and norepinephrine.
Dopamine inhibits norepinephrine and if enough copper is not available this may prevent conversion to norepinephrine.
Copper helps to convert the dopamine into norepinephrine which lowers dopamine levels in the brain. Copper in excess may prevent dopamine synthesis. Excess copper are more likely in women with depression and especially postpartum depression which is linked to the sharp increase without levels normalizing in some women after giving birth.
Cocaine is a re-uptake inhibitor and blocks the re-uptake of dopamine, norepinephrine and serotonin. [R]
Amphetamines can increase dopamine, serotonin and norepinephrine however excess can lead to neurotransmitter depletion or toxicity dependent on nutritional cofactors. [R] [R]
MDMA (ecstasy) releases serotonin, norepinephrine and dopamine but inhibits their transport which increases concentrations which can cause toxic build-up of neurotransmitters. [R] [R] [R] [R]
Caffeine increases the activity of dopamine as well as other neurotransmitters such as serotonin, norepinephrine, epinephrine and acetycholine. This increase in activity can cause a significant rise in these neurotransmitters and can pose a problem with excess circulating neurotransmitters and or deplete nutrients that act as cofactors for the synthesis of each neurotransmitter.
5-HTP significantly depletes levels of the catecholamines dopamine, norepinephrine, and epinephrine. 5-HTP stops functioning if dopamine depletion is great enough. [R]
Decreased estrogen causes the hypothalamus to release norepinephrine which lowers acetylcholine, dopamine, and serotonin causing common symptoms of PMDD and PMS such as insomnia, fatigue, depression. [R]
Catechol-O-methyltransferase (COMT) enzyme is involved in the breakdown of catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine.
MAOIs prevent or inhibit breakdown of norepinephrine increasing the neurotransmitter levels
Food Sources of Norepinephrine
Norepinephrine is synthesized from dopamine.
A diet with adequate protein and other essential nutrients are needed to help maintain dopamine levels. It is important to get sufficient levels of the amino acid phenylalanine and tyrosine.
Phenylalanine can be found in most high protein food and some plant based food source. It is more abundant in animal based food than in plant based food source. Animal based food source include beef, chicken, fish (herring), dairy products such as cheese, egg, cottage cheese and chocolate. Plant based food source include almonds, peanuts, apple, avocado, baked beans, soya bean, soy proteins, banana beet, carrot, parsley, pineapple, spinach, tomato.
Mammalian breast milk contains phenylalanine.
Tyrosine which is derived from phenylalanine can also be found in food. Animal protein contain the highest amount of tyrosine.
Animal food source of tyrosine are similar to phenylalanine source and includes beef, pork, turkey, duck, chicken, fish, eggs, yoghurt, cottage cheese, cheese and milk.
Wild meat such as game and venison contain higher amounts of tyrosine.
Plant based tyrosine food source includes almonds, pumpkin seeds, sesame seeds, peanuts, soya bean, soy proteins, soya products, chocolate, apples, apricot, asparagus, avocado, baked beans, legumes, capsicum, carrots, spinach, alfalfa, beet, lettuce, parsley, watercress, leek, cucumber, banana, strawberries, cherries, fig and watermelon.
There is too little tyrosine in most plant based foods such as cereals, grains, fruits and vegetables.
Phenylethylamine can be found in chocolate and cheese but is unable to reach the brain due to breaking up quickly through digestion.
Aspartame contains phenylalanine. Aspartame is an artificial sweetener found as replacement to sugar in some sugar free sodas and foods as well as some medications. However this may not be a beneficial source of phenylalanine as various studies have linked high amounts to certain health problems.
It is important to eat high protein foods to ensure adequate dopamine production.
Eating a diet with adequate cofactor nutrients is also necessary to support dopamine synthesis.
Other foods that may increase dopamine include green leafy vegetables, green tea, lima beans, oatmeal and wheatgerm.
To keep the catecholamines pathway strong and healthy it is also important to get sufficient levels of methionine.
Food intake of iron and zinc is also needed to help with synthesis of dopamine.
Food intake of vitamin B3, vitamin B6, vitamin B9, B-complex and vitamin C are water soluble and must be replenished daily.
A diet of foods with sufficient copper levels and vitamin C will help with the conversion of dopamine to norepinephrine.
Recommended Daily Allowance
There are no set amounts of recommended neurotransmitters. Neurotransmitter synthesis depend on the nutrients obtained from the diet or supplementation. Brainwave frequencies and other practices such as meditation can also affect levels of neurotransmitters.
Neurotransmitters are made from protein and amino acids. They also need other cofactors such as vitamins and minerals for synthesis.
Dietary protein is therefore essential and getting adequate, sufficient supply of all nutrients in the correct balance is essential.
A healthy adult needs between 40 and 70 grams of daily protein intake. This can go up to as much as 90 grams for active and athletic people.
Diet and nutritional supplementation can be tweaked to meet the requirement of necessary nutrients and ensuring adequate levels of neurotransmitters.
Neurotransmitters operate at different times of the day and are largely dictated by light exposure. Serotonin and dopamine are produced mostly during daylight hours. During dark hours the serotonin converts to melatonin and more GABA is present.
Brainwaves also correspond with the different neurotransmitters. In the morning the brain has alpha waves which increase to beta waves throughout the day. Gamma waves may also facilitate the daylight hours and ideal for higher learning. The alpha and beta waves facilitate acetylcholine and dopamine.
Other factors such as the seasons and a woman’s monthly menstrual cycle can also determine the amount of specific neurotransmitters needed and at which point of the cycle. For example in the luteal phase GABA is the primary inhibitory neurotransmitter as this part of the phase we see a spike in the hormone progesterone which works synergistically with this calming neurotransmitter. Serotonin will also be present at this time as well as more conversion into melatonin to facilitate sleep.
Dopamine will be more available during the follicular phase which seems to increase with the rise of the female reproductive hormone estrogen.
In northern climates during winter with the lack of sunlight there is likely to be a lower production of serotonin or higher amounts of this may convert to melatonin possibly through daylight hours shortening. This may pick up slightly as spring emerges. Many people also find that spring makes them feel motivated.
Everyone is unique and a person’s life experience may dictate more of what neurotransmitter may be required on any given day. An example is a highly stressed person is very likely to be needing more serotonin and dopamine and possibly other neurotransmitters as the chronic stress quickly depletes all neurotransmitters and can lead to a state of depression.
Checking deficiency levels of neurotransmitters can help determine what may be needed along with using brainwave measuring device which uses electroencephalography (EEG) may help identify the neurotransmitters needed and balancing levels.
The difference in amounts of brain neurotransmitters found in men and women indicate that men need more dopamine than women and women need more serotonin than men.
Dopamine rises during the day and is low during the evening and in sleep. In women dopamine rises along with estradiol (estrogen) which rises in the follicular phase and peaks around ovulation.
Norepinephrine is an excitatory neurotransmitter and levels are found to be lowest during sleep but rise during wakefulness. Under situations of stress or danger there is a higher level of norepinephrine.
When there is no stress or very little stress norepinephrine and epinephrine levels remain low. Towards mid-morning levels begin to rise and peak in the afternoon. Levels are low closer to bedtime in the evening.
High levels of norepinephrine occur during ovulation and early luteal phase which is also the point where dopamine and estrogen levels peak. There is also a relationship of norepinephrine and melatonin. Melatonin is higher during luteal phase. [R]
Norepinephrine Supplementation
Sufficient neurotransmitter substrate is essential for restoring levels of neurotransmitters. It is important to support dopamine synthesis as this is needed to convert to norepinephrine.
Glandular adrenal rebuilders can help support adrenal health. Many supplements and cofactors for the health of adrenal glands are available. Vitamin B5 can also support adrenal health and is needed to help produce cortisol.
Nutritional co factors or agonists for norepinephrine are available in most supplemental forms. These include vitamin C and copper.
A high quality vitamin B-complex as well as single individual B vitamins may help support norepinephrine and other neurotransmitter production.
A healthy diet and where necessary supplements can maintain a healthy catecholamines pathway.
Deficiency Symptoms of Norepinephrine
Low levels of norepinephrine along with serotonin are involved in depression.
Signs and symptoms of norepinephrine (noradrenaline) deficiency include:
The following health conditions are linked to norepinephrine deficiency:
- ADHD [R]
- Parkinson’s disease
- Alzheimer’s disease [R] [R] [R]
- Schizophrenia [R]
- Bipolar disorder
- Diabetes
- Depression [R]
- Fibromyalgia
- Hypoglycemia (low blood sugar)
- Migraines or headaches
- Restless leg syndrome RLS
- Sleep disorders [R]
Parkinson’s disease and diabetes cause norepinephrine neurons to degenerate which can lead to slow heart rate (bradycardia) and low blood pressure (hypotension).
Causes of deficiency include:
- Prolonged stress
- Chronic or extreme stress
- Tyrosine deficiency
- Antipsychotics
- Adrenal exhaustion or adrenal fatigue
- Aging
Prolonged or chronic stress can cause underactivity of the stress response system (desensitization). [R] [R] [R] [R]
Cerebral aging, decline in cognitive functions and loss of behavioural adjustment are linked to a deficiency of norepinephrine. [R]
Both norepinephrine and serotonin activity is found to be lower in bipolar disorder.
People with Parkinson’s disease are found to be low on dopamine, serotonin, norepinephrine and low tyrosine hydroxylase. Parksinson’s is mostly treated with L-dopa which is found to deplete tyrosine, tryptophan, 5-hydroxytryptophan (5-HTP), serotonin and sulfur amino acids cysteine and methionine. Studies have shown that taking L-dopa with 5-HTP, L-tyrosine, L-cysteine and cofactors have shown to be effective. [R]
Depression can be a balancing act between the two neurotransmitters serotonin which needs tryptophan and norepinephrine which needs tyrosine or phenylalanine. There needs to be a healthy balanced ratio of both neurotransmitters. In some cases taking high doses of tryptophan to increase serotonin can cause psychiatric and depressive symptoms to become worse when other neurotransmitters such as dopamine or norepinephrine may be deficient. If serotonin levels are low then tryptophan use may be very helpful and reduce associated symptoms of deficiency but if norepinephrine or dopamine is low these symptoms can be made worse, in this case tyrosine or phenylalanine should help address symptoms associated with depression.
Although some medications such as tricyclic antidepressants and MAOIs increase levels of serotonin, norepinephrine and dopamine they have many side effects which may be prolonged with long term use. In this case it is important to address the underlying cause which is more than often inadequate nutritional intake.
Chronic stress over stimulates the sympathetic nervous system which can deplete dopamine, norepinephrine and epinephrine. Chronic stress uses up reserves of important neurotransmitters for stress such as norepinephrine. Symptoms of chronic stress include anxiety, insomnia, inflammation, weight gain, high blood pressure and a weakened immune system [R]
Dopamine inhibits the effects of norepinephrine. Norepinephrine helps regulate melatonin production. Too much dopamine will prevent norepinephrine synthesis which will decrease synthesis and release of melatonin.
In the clinical setting norepinephrine, in a medicinal form which can be intravenously injected is used for medical conditions which includes urgent conditions that require immediate medical attention such as a cardiac arrest. However, it can cause serious side effects due to errors in dosing. [R]
Toxicity Symptoms of Norepinephrine
High levels of norepinephrine may be a common factor in most of the population as more and more health conditions associated with high levels are diagnosed.
High levels of any single neurotransmitter can lower levels of other neurotransmitters causing an imbalance and deficiency symptoms of other neurotransmitters.
Norepinephrine releases in response to stressful events but can also release in response to excitement which can increase feelings of euphoria or feelings of intense happiness. Its release is accompanied by various physiological changes that happen in the immediate response.
The locus ceruleus found in the brain stem is partly responsible for its release and is the source of most norepinephrine pathways within the brain.
Signs and symptoms of excess norepinephrine include:
- High blood pressure
- Anxiety
- Sweating
- Excessive sweating
- Heart palpitation
- Rapid heartbeat
- Irregular heartbeat
- Panic attacks
- Hyperactivity
- Shaking
- Pale face
- Headaches
- Heart damage
- Kidney damage
- Aches and pains
- Poor Sleep (insomnia)
- Concentration difficulty
- Focus problems
- Depression
- Anxiety
- Anger
Having high levels of norepinephrine or epinephrine can cause severe headaches, elevate blood pressure and increase anxiety symptoms.
A surge or bursts of norepinephrine can lead to negative symptoms such as panic attacks, raised blood pressure, and hyperactivity, however positive symptoms include excitement and euphoria (feeling joyful or very happy).
Panic attack is simply the stress response to the danger of a bear or other threat except in this situation there is no actual threat.
Conditions linked to high levels of norepinephrine include the following:
- Depression
- Post-traumatic stress disorder (PTSD)
- Attention deficit-hyperactivity disorder (ADHD)
Causes of toxicity:
- Chronic / prolonged stress
- Tumours (Pheochromocytoma)
- Cancer (Neuroblastoma)
- Obesity
- Monoamine oxidase A (MAO) deficiency
- MAOi
- Post-traumatic stress disorder (PTSD)
- Substance abuse
- Grief (bereavement)
Norepinephrine is released during stressful events and cause a variety of symptoms.
Initially stress activates the stress response causing surges of norepinephrine and other stress hormones such as cortisol. However if the stress is severe or it is prolonged this will eventually use up both norepinephrine, epinephrine and cortisol causing a deficiency. Excessive stress can lower cortisol levels (known as hypocortisolism). People with chronic prolonged stress can experience low energy (lethargy), fatigue (during the day), apathy and difficulty with concentrating and focus. Eventually the adrenal glands will not function properly due to adrenal exhaustion or adrenal fatigue caused by prolonged stress.
The stress response system activates when faced with severe stress which increases levels of norepinephrine as well as stress hormones.
Stress can increase arousal which intensifies the emotional reaction to stress, leading to emotional instability.
Stress can also have detrimental impacts on sleep causing insomnia. Stress is also linked to anxiety, depression and irritability.
Fear and anger emotions which can trigger the fight or flight response are related to stress and may be present as a result of norepinephrine release.
People can be under physical or emotional stress. Usually physical stress is related to an external outer threat such as being near a frightening bear, however this same response may be present when the body is under stress from the accumulation of harmful toxins.
The other catecholamines that release during the stress response include dopamine and epinephrine and these too may increase with a norepinephrine toxicity.
Some medical conditions such as Pheochromocytoma and Neuroblastoma cause the adrenal glands to produce and secrete catecholamines epinephrine and norepinephrine.
Pheochromocytoma are catecholamine producing tumours which causes the adrenal glands to produce excess epinephrine and norepinephrine which can be detected by a blood test. Symptoms of these tumors include headache, sweating, palpitations and high blood pressure. If left untreated or not diagnosed excess catecholamines fatal cardiovascular conditions. [https://pubmed.ncbi.nlm.nih.gov/17514588/]
Catecholamine urine testing (CATU) is a urine test to check for catecholamines level in the urine and performed over a period of 24 hours.
Neuroblastoma is a catecholamine secreting cancer which tends to occur mostly in children. Enzyme levels that help with the conversion of norepinephrine to epinephrine are lacking in Neuroblastoma cells.
Some research has shown that the early stages of bereavement are linked to increased levels of catecholamines and cortisol which is a stress hormone.
During the process of grief stress hormones are significantly raised which can be accompanied with a host of symptoms including back pain, joint pain, headaches, and stiffness.
Stress hormones have the same effect in the body as broken heart syndrome. They can stun the muscles which can cause stiffness.
Norepinephrine is involved in the emotions of fear and anger. Aggression is also involved in the stress or fight or flight response. [https://pubmed.ncbi.nlm.nih.gov/21713063/] [https://pubmed.ncbi.nlm.nih.gov/9491941/]
Monoamine oxidase A (MAO) is involved in the breakdown of the neurotransmitters serotonin, dopamine, epinephrine and norepinephrine, after their function has ended.
Study on a Dutch family with a genetic defect causing a deficiency of MAO-A (needed to degrade serotonin and norepinephrine) showed an increase of anger (related to Norepinephrine) and suppression of fear (linked to high serotonin).
The men in this family had double the normal levels of norepinephrine and nine times the normal levels of serotonin. The high norepinephrine made them get angry easily and the high serotonin almost completely eliminated any feelings of fear. This combination resulted in high aggression and violent behavior. They get angry and have no fear of the consequences of attacking those who make them angry. [R] [R] [R] [R] [R] [R]
Many activities can overstimulate the reward system such as shopping, gambling, watching TV shows (binge watching), social media, using mobile devices, taking drugs and other activities that feel good so that the behaviour is then repeated. Whilst doing these activities raises dopamine levels if addictions are formed it can quickly use up cofactors needed for dopamine synthesis. Some people may have too much dopamine which is not converting to norepinephrine which can cause an imbalance. A high conversion of dopamine to norepinephrine also poses issues.
When shopping after making a purchase this can help release endorphins and dopamine which can quickly become addictive and compulsive shopping may be repeated in order to induce the same reward and feeling a rush of instant gratification. Usually the behaviour will be repeated regardless of financial consequences as seen similarly with gambling. Norepinephrine which is the second neurotransmitter synthesised in the catecholamines pathway has a link with feeling aversion to financial loss and may be implicated in addictive behaviour.
It is believed that emotional responses to gains and “loss aversion” varies widely between people. Some studies have found that people with lower levels of the norepinephrine transporter in their brain but higher norepinephrine levels have a different response to those who have higher norepinephrine transporter and lower norepinephrine. The studies reveal that gamblers have less aversion to monetary loss which can cause more problems with gambling addiction. In the study participants with less norepinephrine displayed loss aversion with their emotional responses to losses heightened.
Low levels of NE transporters and higher levels may pave the way for addiction. Studies have shown that people with lower levels of the norepinephrine transporter in their brain have less aversion to monetary loss which can make them more prone to develop a gambling addiction. The low levels of NE transporters means less extracellular norepinephrine is absorbed and circulates in the brain. People with higher levels of NE transporters have less norepinephrine in the brain and display aversion to financial or monetary loss and are less likely to be addicted to gambling. [R] [R]
Norepinephrine levels have been found to be high in pathological gamblers. [R]
Catecholamines which include the neurotransmitters dopamine, epinephrine and norepinephrine are important in stress responses (fight-or-flight). These neurotransmitters get your body ready for fight-or-flight emergencies. If there are high levels of dopamine then potentially this level of dopamine may convert to more norepinephrine which can cause symptoms of excess. Although these catecholamines have important functions in the body high levels can lead to high blood pressure, headaches, sweating, pounding of the heart, chest pains and anxiety.
Monoamine oxidase A (MAO) is involved in the breakdown of the neurotransmitters dopamine, epinephrine, norepinephrine, and serotonin after their function has ended. Stress initiates higher production of catecholamines which require more MAO for degradation so the body can return to a calm state.
When humans or animals are frightened the catecholamines specifically norepinephrine and epinephrine are squirted into circulation to increase heart rate, breathing rate, and blood pressure to get ready for fighting or running away. If the MAOs are deficient or absent then these neurohormones or neurotransmitters do not break down and remain in circulation for a long time which causes a prolonged state of panic and anxiety.
Low or insufficient levels of MAO will cause a continuous circulation of catecholamines.
Chronic stress which increases norepinephrine levels and smoking increases risk of cancer and suppresses cancer inhibiting GABA [R]
Studies have shown that norepinephrine system plays a role in decision making. [R]