Epinephrine

What is Epinephrine?

Epinephrine (EPI) also known as adrenaline is an excitatory neurotransmitter and a neuromodulator which can also act as a hormone. Epinephrine is categorized in the monoamine group of neurotransmitters with the others being dopamine (DA), Norepinephrine (noradrenaline) 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, attention, memory and learning. Epinephrine is very similar to norepinephrine however it functions more as a hormone rather than a neurotransmitter.

Synthesis of epinephrine occurs in the adrenals and is made from the substrate dopamine and dopamines subsequent conversion to norepinephrine which can stimulate the release of epinephrine.

Epinephrine (Adrenaline) is also involved in the fight or flight response and activated in a stressful or fearful situation such as being under attack by a wild bear and prepares the body for physical activity to prepare to fight or flee from the situation.

Epinephrine is involved in the stress response along with cortisol. Cortisol gets released in pulses in pulsatile signals. [R]

Epinephrine is mostly produced in the adrenal glands and has peripheral functions working in other parts of the body. Within the brain epinephrine helps with communication of neurons.

Epinephrine is released by the medulla of the adrenal glands when the nerves connected to the glands are activated.

Epinephrine is released in response to strong emotions such as fear and anger or any forms of stress. As a hormone it releases into the bloodstream. This causes various physiological changes such as increased heart rate, muscle strength, blood pressure, blood vessel constriction, bronchodilation and sugar metabolism.

This neurohormone is essential to control the body's response to stress and released upon activation of the fight or flight system.

Epinephrine is released while becoming angry or when in a state of fear in response to a physical threat (such as being in the presence of a lion).

Excitement can also cause a release of epinephrine.

Noise and bright lights can cause release of epinephrine. [R] [R]

High rise of temperatures can cause release of epinephrine and epinephrine can increase body temperature.

Epinephrine is found in small amounts in the body and very little may be needed for its functions with increasing amounts causing health issues.

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).

A very small amount of norepinephrine or epinephrine are needed to begin having effect on these receptors.

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.

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 bronchodilation (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.

The main chemical difference between epinephrine and norepinephrine is that epinephrine has a methyl group attached to its nitrogen whilst norepinephrine has a hydrogen atom attached to the nitrogen.

[ R]

Health Benefits of Epinephrine

Essential for stress or ‘fight or flight’ response

One of the main function of norepinephrine is as an excitatory neurotransmitter responsible for the fight or flight response to stress from a threat or danger. The activation of norepinephrine in the body manifests in the physiological changes to help prepare the body in the fight or flight situation.

Once norepinephrine 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.

Epinephrine increases the heart rate and force or strength of heart contraction.

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 oxygen around the body where it is needed by the muscles.

Epinephrine also helps release glucose in the liver which provides energy to the muscles.

Epinephrine effects only last for several minutes and the release is sometimes referred to as an adrenaline rush. This rush helps to act accordingly in an emergency situation.

Adrenocorticotrophic hormone (ACTH) is released by the sympathetic nervous system under stress which then stimulates release of epinephrine.

Supports the immune system

Epinephrine helps boost the immune system which is linked to the rush of adrenaline felt in the body. Along with cortisol, epinephrine boosts the immune system and may help slow down the aging process.

Horror movies have been shown in a study to boost the immune system. Epinephrine release increases white blood cells in response to fear or excitement.

Enhances cognitive functions

Epinephrine can help with various cognitive functions such as improving memory. When epinephrine is released it increases activity in the limbic system of the brain which includes the hypothalamus, the hippocampus, the amygdala and other areas of the brain which have control over long term memory as well as emotional responses and behaviour.

It can help with memory and improve neuroplasticity.

Supports motivation and energy levels

Similar to norepinephrine, epinephrine can also increase motivation. Along with cortisol and epinephrine regulates energy and focus levels. This is beneficial and can reduce feelings of lethargy which can be associated with feeling demotivated.

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 is also needed to synthesise epinephrine and follows the catecholamines pathway.

Epinephrine is important for glycogen metabolism

The hormone insulin is the main hormone that converts glucose to glycogen which lowers blood glucose levels. Whilst insulin is involved in the production of glycogen it inhibits its breakdown.

Epinephrine as a hormone helps with the breakdown of glycogen. The production and breakdown of glycogen occurs in liver cells. The other hormone involved in glycogen breakdown is glucagon.

The process of breakdown occurs through a step by step process with epinephrine first binding to external part of a liver cell which causes a conformational change. Once the receptor changes shape it is able to bind a G protein making it active. G protein activation causing another conformational change with allows adenylate cyclase to bind. Activation of adenylate cyclase leads to the binding of ATP. The process continues adenylate cyclase breaking down ATP into Cyclic AMP (cAMP). Cyclic AMP activates protein kinase a protein needed for the activation of phosphorylase. Phosphorylase is needed for the breakdown of glycogen to glucose. [https://www.ncbi.nlm.nih.gov/books/NBK26912/]

Supports bodily functions

The actions of epinephrine take place on the same body tissues as norepinephrine and are similar.

The release of epinephrine increases heart rate, increases blood pressure, expands air passages of the lungs which increases respiratory rate, dilates pupils, redistributes blood to the muscles, increases fat and glucose metabolism.

The increase of blood glucose and fatty acid levels stimulated by epinephrine provides energy for cells. [R]

Epinephrine receptors when activated can also cause the breakdown of glycogen in the liver.

Epinephrine is involved in the contraction and relaxation of smooth muscle cells (i.e. heart, arteries, and veins). This function is controlled through epinephrine receptors.

Contraction takes place when calmodulin (calcium binding protein) binds to calcium ions when the concentration is ten times larger than normal in the cell. Calcium-Calmodulin complex causes the activation of the myosin light chain kinase (MLCK). The MLCK phosphorylates the LC2 which causes contraction. [R] [R]

All this is done through epinephrine binding to epinephrine receptor and following the same pathway as in the breakdown of glycogen to glucose (SEE Epinephrine is important for glycogen metabolism). It involves activation of Cyclic AMP which activates a protein kinase needed for the activation of phosphorylase and allows phosphorylating of the MLCK. This causes the Calcium-Calmodulin complex to be inactive which causes the relaxation of smooth muscle tissue making epinephrine a useful treatment for cardiac arrests, asthma, and anaphylactic shock patients.

Medical uses of epinephrine

Epinephrine has had many clinical and medicinal uses both in current times and in ancient traditional medicine such as in herbal remedies.

Epinephrine is strictly regulated in the body and very high levels can have lethal effects which is why medications containing epinephrine need to be prescribed by a doctor for severe health conditions or conditions requiring emergency treatment such as anaphylactic shock, cardiac arrest or extreme asthma.

Epinephrine is available as Ephedra, Ephedrine and Ma Huang but their availability may be subject to laws in specific countries where there may be a ban or requiring prescription.

Epinephrine has been used in various life threatening medical emergencies. Epinephrine has been used intravenously during cardiac arrest to help increase blood flow through the coronary artery.

Epinephrine is essential for maintaining cardiovascular homeostasis as it is able to divert blood to tissues under stress.

As a medicine epinephrine may be used during a cardiac arrest. Intravenous solution of epinephrine when injected increases pressure of the coronary artery which increases blood flow however increasing epinephrine dose has also shown to cause severe side effects that can cause damage to the heart and the brain.

It has been used for anaphylactic shock which occurs during an allergic reaction where the heart muscle becomes weaker or the veins are constricted preventing blood to flow throughout the body. The administration helps the blood to start flowing through the body and as a medicine helps in the treatment of shock as it acts as a vasoconstrictor.

People with severe asthma unable to breathe due to swelling or inflammation lungs are able to inhale small amounts of epinephrine through inhalers which help with bronchodilation and offering a temporary relief from an emergency situation. As well as acting as a bronchodilator, epinephrine also is antispasmodic which is helpful in cases of bronchial asthma.

The effects of epinephrine in all these emergency cases provide temporary relief and require hospitalization for further treatment as epinephrine has a short half-life.

Agonist / Synergist

Minerals Magnesium, Copper, Molybdenum

Vitamins B5, B9, B12, D

Amino acids Methionine

Hormones Cortisol, Adrenocorticotrophic hormone (ACTH)

Herbs Ephedra, Ephedrine and Ma Huang

Medications Pseudoephedrine, Epipen

Other Exercise, stress, SAMe, MAO, MAOIs, breathing practices, yoga, cold showers, thrilling adventurous activities, horror movies

The main precursors for epinephrine is dopamine and norepinephrine. See dopamine and norepinephrine for agonists which are cofactors that support the synthesis of these neurotransmitters.

Fear or excitement causes release of epinephrine

Norepinephrine to Epinephrine Synthesis

Norepinephrine requires Phenylethanolamine – N-methyltransferase enzyme and cofactors SAMe, Mg and Cortisol. SAMe (S-Adenosyl-l-methionine) cofactors needed for synthesis include vitamin B9, B12 and methionine.

SAMe (s-adenylsylmethionine) is made from the essential amino acid methionine.

Acetylcholine has some influence over methionine production.

Methionine plays an important role in the dopamine or catecholamines pathway.

Methionine is a building block for the neurotransmitter epinephrine (adrenaline) and donates a methyl group (-CH3) to norepinephrine (noradrenaline) for epinephrine production.

Epinephrine is an excitatory neurotransmitter produced when stressed or excited. It activates fight or flight mode within the body characterized by increased heart rate, blood flow and blood pressure and releasing a boost of energy. Stress can impair adrenal function and also deplete methionine. Methionine also controls the adrenal glands.

Vitamin D has role in regulating various hormones and neurotransmitters essential for brain health and preventing depression. These include epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine and serotonin. The adrenal gland regulates tyrosine hydroxylase which is the rate limiting enzyme involved in the production of neurotransmitters which is achieved by the gland with activated vitamin D.

A deficiency of this vitamin can lead to depression and seasonal affective disorder (SAD).

Adrenocorticotrophic hormone (ACTH) activates tyrosine hydroxylase and dopamine-B-hydroxylase which stimulates epinephrine release and also stimulates cortisone production in the adrenals.

Molybdenum plays a role in epinephrine 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.

Vitamin B5 (Pantothenic acid) which is also known as the anti-stress vitamin is involved in the production of hormones in the adrenal glands. Cortisol is a hormone produced by the adrenal gland which is needed to balance the effects of stress. Various nutrients which includes pantothenic acid are needed by the adrenal glands in the manufacturing of important hormones such as cortisol, progesterone and epinephrine. High levels of stress can rapidly deplete pantothenic acid and produce symptoms of adrenal fatigue. Supplementing with additional amounts of this nutrient can help replenish these essential hormones. [R] [R]

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 epinephrine which allows the brain to utilise this neurotransmitter.

Folate (natural active form of vitamin B9) regulates tetrahydrobiopterin (BH4 or THB) levels. Methylfolate is the form that can cross the blood brain barrier and available as a supplement which can help with BH4 levels.

BH4 plays a vital role in cognitive functions and is needed by enzymes in the body that help with dopamine and serotonin synthesis. BH4 is also used by enzymes nitric oxide synthases (NOS) that help to form nitric oxide (NO). It is also an essential cofactor for aromatic amino acid hydroxylases.

Folate deficiency can decrease BH4 levels which will reduce synthesis of dopamine and serotonin. [R]

Nutrients that support BH4 levels include folate or the supplement Methylfolate (MTHF), Curcumin and vitamin C.

Methyl folate prevents oxidation of BH4 into BH2. Ensuring adequate supply of NOS enzymes will also help prevent breakdown of BH4.

BH4 plays an important role in both heart and cognitive health.

Rapid breathing techniques that involve quick inhalations and then exhalation help with the release of epinephrine

Rapid breathing protocol involves cyclic inhale and exhale. The participant practicing the technique needs to inhale and then release quickly for about 25 to 30 times repeatedly. This will cause the body to feel warm.

The participant is to exhale then hold breath for 15 to 20 seconds then do the 25 to 30 rapid breaths, exhale and hold. Then 25 to 30 breaths again, exhale and hold for 15 to 20 seconds and repeat until the body feels warm.

In yoga this practice is known as kapalabhati breath or the skull shining meditation

Kapalabhati yogic breath meditation helps stimulate epinephrine. This meditation involves in sitting down comfortably straightening the spine using yogic seated positions such as Sukhasana and Virasana. If it is uncomfortable to sit on the floor sitting on a chair is fine. Deeply inhale through the nostrils and then force out the breath in a short burst. One breath in and out can be counted as 1 contraction. Continue doing between 60 or 70 contractions or whatever is most comfortable. The main aim is around 100 repetition of inhale and exhale per minute. Finish by deeply inhaling and exhaling through the mouth. The exercise may be repeated according to level of experience.

Sufi breathing technique with or without dikhir meditation also uses a similar breathing technique. A basic breathing technique involves three repetitions of rapid breathing with an exhale using a name or word (of religious scripture). With the exhale the word or name chosen is chanted along the exhale of breath. After three repetitions hold breath for about 10 seconds and then release with a big exhale making an optional aaah sound which may force out breath.

Watching horror movies can cause a release of epinephrine causing a surge commonly known as an adrenaline rush.

Cold showers can help release epinephrine or cause an adrenaline rush.

Epinephrine is available as Ephedra, Ephedrine and Ma Huang

Ephedra equisetina (also known as Ma Huang) a desert shrub used as Chinese medicine for more than 5,000 years contains substances that act similar to epinephrine and on its receptors.

Ephedrine is a protein extracted from Ma Huang which functions similar to epinephrine. Two types of extracts available are ephedrine and pseudoephedrine.

Ma Huang is a popular dietary herbal supplement for weightloss which can suppress appetite and stimulate thyroid gland which can increase thermogenic metabolism.

The adrenal glands release epinephrine into the blood stream. This increases the body’s temperature which will burn more calories.

Ephedrine is used to relieve asthma and stimulates the sympathetic nervous system.

Pseudoephedrine is used as a nasal decongestant

Antagonists

Antagonists for dopamine and norepinephrine will impact levels of epinephrine

Adrenal exhaustion or adrenal fatigue will reduce epinephrine production

Chronic or prolonged stress will deplete epinephrine levels

MAO

Impaired SAMe (S-Adenosyl-l-methionine) production or deficiency

Food Sources of Epinephrine

Epinephrine follows the catecholamines pathway and requires the same food source as dopamine the main precursor.

Norepinephrine is synthesized from dopamine which then converts to epinephrine which requires foods with sufficient amounts of vitamin B9, B12, methionine and magnesium.

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.

It is important to support the diet with adequate nutritional support for the synthesis of dopamine and norepinephrine.

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.

Foods sources that contain nutrients should be eaten for adequate norepinephrine to epinephrine synthesis. These nutrients and cofactors include magnesium, vitamin B5, B9, vitamin B12 and methionine.

Magnesium can be found in many plant and animal foods and in beverages. Magnesium can be found in legumes, nuts, seeds, whole grains, and in green leafy vegetables such as spinach. It can also be found in salmon, halibut, chicken and beef. Some foods such as breakfast cereals are fortified with magnesium. Foods that have been processed such as wholegrains where the nutrient rich germ and bran is removed will have lower amounts of magnesium.

Foods that contain adequate amounts of dietary fiber provide magnesium. Cooking food slowly helps to release magnesium making absorption more bioavailable.

Magnesium can also be found in tap water however this may not be readily absorbed by the body as it is in an inorganic form which the body may not readily utilize. Bottled spring water also contains magnesium and amounts will vary in accordance to different brands.

Vitamin B5 is found in a wide variety of foods in both animal and plant based foods. These include broccoli, kale, cauliflower, avocados, tomatoes, lentils, soy beans, sweet potatoes, nuts, seeds, wholegrains, wheat germ, offal (liver, kidney from beef and pigs), turkey, chicken, ducks, salmon, yoghurt and milk.

Foods that contain significant amount of vitamin B9 (folate) include liver, legumes (lentils, beans, peas), whole grains (brown rice), poultry, pork, lamb, cheese, eggs, shellfish, leafy green vegetables (spinach, turnip greens, asparagus, kale), broccoli, cabbage, brussels sprouts, beetroot, brewer's yeast and oranges. Vegetables containing folate are better eaten raw or lightly steamed as heat destroys folate or folic acid. Folic acid can be found in many fortified foods such as cereals and bread which can be found on the food label.

Vitamin B12 can be found mostly in animal foods which includes meat, poultry, liver, fish, eggs and dairy. B12 can be found in high amounts in lamb liver, beef liver, clams, oysters, wild salmon, herrings, trout and canned sardines.

There are no B12 in nuts, seeds and fruits. Vegetables are also a poor source of B12 which a very minimal amount contained in mushrooms.

Some foods such as cereals may be fortified with vitamin B12, however this may be an inactive form which some people may be unable to utilize.

Foods high in methionine also help with epinephrine synthesis and can be found in beef, chicken, liver, ham, pork, sardines, salmon, eggs, cottage cheese, milk, yoghurt, soy, soya bean, brazil nuts, sesame seeds, brussel sprouts, cabbage, cauliflower, chives, garlic, watercress, broccoli, spinach apples and pineapple.

Recommended daily allowance

Epinephrine has shown to remain stable throughout the menstrual cycle in women and may increase during ovulation when luteinizing hormone peaks and after a norepinephrine surge.

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 effect 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.

High levels of norepinephrine occur during ovulation and early luteal phase which is also the point where dopamine and estrogen levels peak. Around this point or after sufficient norepinephrine is synthesised it will convert to epinephrine. There is also a relationship of norepinephrine and melatonin. Melatonin is higher during luteal phase. [R]

Epinephrine 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 and then finally to epinephrine.

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. Cortisol is also needed to help with the conversion of norepinephrine to epinephrine.

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.

SAMe supplements are available however body can also synthesise SAMe with cofactors B9, B12, and Methionine. Magnesium supplements can also support epinephrine production.

A healthy diet and where necessary supplements can maintain a healthy catecholamines pathway.

Deficiency Symptoms of Epinephrine

The following are signs and symptoms of epinephrine deficiency:

Fatigue
Depression
Pain
Apathy
Anxiety
Changes in blood pressure
Migraine
Low blood sugar (hypoglycaemia)

The following are health conditions linked to epinephrine deficiency:

Fibromyalgia
Restless legs syndrome
Sleep disorders

EpiPens are a medicine containing an injectable dose of epinephrine used for treating symptoms of anaphylaxis.

People with allergies or asthma and have a family history of anaphylaxis are at a higher risk and require a shot of epinephrine.

Causes of epinephrine deficiency include:

Impaired conversion of catecholamines
Tyrosine deficiency
Cofactor nutrients deficiency
Impaired adrenal glands and function

Low levels of epinephrine may make it difficult to respond to stress appropriately.

Adrenaline has been administered via airway in patients with severe cardiac disease [R]

Toxicity Symptoms of Epinephrine

Epinephrine which was previously referred to as adrenaline is most commonly associated with the feeling of an adrenaline rush.

Roller coaster rides, bungee jumping or other thrilling exciting feat can cause what is known as an adrenaline rush which is a surge of epinephrine, dopamine and cortisol. This combination of chemicals in the brain can cause the participant to feel a natural high which can boost energy levels and increase alertness.

Adrenaline junkies are defined by their need to feel an adrenaline rush by taking part in activities that induce the release of epinephrine which can cause heightened feelings of excitement. These types of people usually partake in dangerous activities such as bungee jumping.

An adrenaline rush or release of epinephrine can also occur as a result of stress and tumours. These can also be experienced at night when levels should naturally be low. It can also be raised at inappropriate times.

Signs and symptoms of high levels of epinephrine include the following:

Anxiety
Rapid heartbeat (increased heart rate)
Heart palpitations
Shaking
High blood pressure
Sweating
Pale face
Weight loss
Weight gain
Heart disease
Headache (extreme or severe)
Impaired response to stress

Epinephrine increases may lead to metabolic syndrome and hypercortisolemia which can manifest with weight gain.

Fear creates a physiological response which has various physical manifestations such as increased heart rate, high blood pressure and other tell-tale signs similar to high epinephrine.

During the stress response the stress hormone cortisol is also released.

Causes of high epinephrine include:

Chronic / prolonged stress
Tumours (Pheochromocytoma)
Monoamine oxidase A (MAO) deficiency
MAOi
Post-traumatic stress disorder (PTSD)

Relaxation techniques, meditation, yoga, slow breathing, getting fresh air and taking walks can help tone down the effects of an adrenaline rush if it becomes too heightened or intense.

In women continued stress in the luteal phase will increase the production of cortisol and epinephrine which in turn will delay menstruation causing irregular cycles.

Ephedra is a popular herbal ingredient in weight loss formulas and associated with deaths in people who have taken excess.

It is also the source of ephedrine which is a powerful pharmaceutical stimulant drug. Too much of these powerful stimulants have severe adverse effects and can even cause death.

People using supplements are more likely to use products containing ephedra as it may be added to sports performance supplements.

These products containing ephedra can potentially cause surges of adrenaline rush and feel more energetic however this may then be followed by the adverse effects of having more in the body than can be handled.

Taking these formulas and in excess can cause rapid heart rate, arrhythmia with a fast and irregular heart rate which may be experienced for many hours as well as other symptoms linked to high levels of epinephrine.

These drugs or herbal formulas are not recommended to take for prolonged periods of time and should be avoided by people with thyroid disorders, diabetes or other endocrine disorders, high blood pressure, glaucoma, prostate problems, asthma (on medication) and those with heart problems. It can also adversely affect even healthy people.

These products may be marketed as "health" or weight loss products. If in doubt always check the label for any herbal weightloss products to see if it contains ephedra.

Ephedra can cause adverse effects in people with thyroid disease who are also affected by low levels of potassium.

Potassium depletion is linked to endocrine and thyroid health problems and cause long-term weight gain.

Increases in serum epinephrine can cause a depletion of potassium (hypokalemia). Low potassium can cause endocrine and thyroid disturbances and cause long-term weight gain. [R]

Ephedrine can increase metabolism similar in the way prolonged exercise does.

Although ephedrine could enhance athletic abilities through its effects on bodily functions such as expanding the lungs, enhancing muscles and providing energy through the release of glucose and create the feeling of an adrenaline rush long term use can be destructive towards health.

Ephedra or Ephedrine can act rapidly within the body producing immediate results and taking high amounts suddenly can lead to many symptoms of high epinephrine.

Many colleges and educational boards or institutions related to athletes have banned the use of ephedra or ephedrine.

Ma Huang has been banned by the FDA due to its negative effects and cannot be purchased in the US. The ban may have also been imposed by other countries.

Ephedrine in excess can cause the same symptoms as epinephrine as it increases the levels of this neurochemical. Symptoms include an increase in blood pressure and heart rate simultaneously causing dizziness, insomnia, and headaches.

Exercise can increase epinephrine and an increase is also seen during stress. This increase of epinephrine increases the need for tyrosine in sufficient amounts.

Epinephrine has shown to increase plasma cholesterol levels. When epinephrine and cortisol levels increase cholesterol levels also increase.