Neurotransmitter Imbalance Leading to Cortisol Deficiency and Imbalance

By: Michael Lam, MD, MPH; Dorine Lam, RDN, MS, MPH

Cortisol Deficiency can even affect the firing of neuronsNeurotransmitters (NTs) are chemicals in the brain that act as messengers, transmitting signals between the neurons, allowing communication to take place with the multitude of organ systems functioning within the body. These are potent neurochemicals that regulate nearly every function in the body including, physical and cognitive performance, weight, the perception and response to pain, sleep patterns and our emotional and mental state of being.

Scientific research reveals that malfunctions in neurotransmission, such as an imbalance, deficiency, or disruption are very common these days and are the root cause of many commonly found health conditions. When our neurotransmitters are not working at optimum levels our mind and body cannot communicate clearly and effectively. It is estimated that about 80 percent of people have some form of imbalance in their neurotransmitters. Fortunately, only a small number are clinically symptomatic and debilitating.

Brain function will be affected whenever there is dysfunction of poorly functioning NTs or malfunctioning hormonal axis that are the ultimate conduit upon which NTs exert their effect, such as the hormonal hypothalamic-pituitary-adrenal axis (HPA). This paper will examine both defects in a setting of Adrenal Fatigue Syndrome.

How our Nerves Communicate With Each Other

Before we can fully comprehend the effect neurotransmitter problems can have on us, we first need to understand how they communicate with each other. We can compare our nervous system to the electrical system in our homes. Nerve cells communicate with each other via tiny circuits called neuronal pathways. What’s different is that our nerve cells don’t touch each other, they come close but there is a gap between them called a synaptic cleft. The neuron sending the message is the presynaptic cell or axon, and the neuron receiving the message is the postsynaptic cell, or dendrite.

The direction of communication is one-way and to assist the message to make it across the synapse from the presynaptic cell to the postsynaptic cell, chemicals called neurotransmitters are used. For example, a typical synaptic transmission using the neurotransmitter serotonin would involve a presynaptic cell producing serotonin from tryptophan (an amino acid), accumulating the serotonin into small vesicles, which are in the terminals at the end. When your brain sends a signal (an action potential) it goes down the presynaptic cell and arrives at the end terminals. Upon arrival, serotonin is released and fills the synaptic cleft, crosses and binds with its serotonin receptors located on the surface of the postsynaptic cell. When there is adequate serotonin binding to its receptors, a certain minimum threshold level is attained, and the signal (action potential) will arrive in the cell and continue to be propagated by moving on to the next cell. The goal is for the signal to reach its intended target, like skeletal muscle fibers in order to cause movement.

To avoid having the nerve in a constant state of being on, the excess serotonin molecules in the synaptic cleft are eliminated by monoamine oxidase (MAO) enzymes plus a process called catechol-O-methyl transferase (COMT). Some of the remaining serotonin does return to the presynaptic cell in a process of absorption called reuptake. As the serotonin level reduces, the nerve signal is turned off and the system resets to baseline. The communication system is now ready to receive another signal or action potential. The classes of antidepressants that block the reuptake process, leading to increased serotonin, are called SSRIs or selective serotonin reuptake inhibitors. They include drugs called Lexapro, Prozac, Paxil, and Zoloft.

Neurotransmitters 101

The body’s main neurotransmitters are:

  • Dopamine (DA) acts as precursor to norepinephrine and adrenaline
  • Norepinephrine (NE) the workhorse NT for the sympathetic nervous system
  • Adrenaline (A) the NT for the sympathomedullary nervous system
  • Acetylcholine (ACh) the NT for the parasympathetic nervous system
  • Serotonin (5-HT) the body’s feel good NT

We now study each of these in more detail, starting with a group called catecholamines. Catecholamines are a grouping of NTs, which are very often referred to as the stress hormones. They are all derived from tyrosine, an amino acid. These neurotransmitters have the ability to act faster than cortisol, a hormone that responds to stress. The key catecholamines are dopamine, norepinephrine, and adrenaline.

Dopamine is a vital neurotransmitter as well as a precursor to norepinephrine. Dopamine released in the brain acts as a natural reward for pleasurable experiences like when having sex or dining on a delicious meal. It can also be released in response to neutral stimuli and as a result, pleasure becomes associated with those stimuli.

When dopamine is released in excess amounts in the brain, the effects can be anxiety, hyperactivity, and paranoia.

When dopamine levels are low, the effects can be addiction, cravings, compulsive behavior, depression, and inability to concentrate or focus.

Norepinephrine (NE) is an important neurotransmitter that helps to regulate attention and arousal, and plays a part in the fight-or-flight response. It acts both as a neurotransmitter and a hormone. In the brain, it functions as an excitatory NT, putting the body in a state of mental alert. It is produced and acts in the brain to prepare the individual to deal with a perceived threat. It also travels outside the brain. Once outside, it acts as a hormone and plays an important role in increasing heart rate and blood pressure, dilating eye pupils, dilating air passages in lungs, and narrowing blood vessels. It is the main controller that facilitates the actions required for day-to-day stress that we take for granted, such as standing up quickly without feeling dizzy from a reclining position.

If someone is living under ongoing stressful conditions, a long-term excess of norepinephrine in the brain can result. Such is the case of Adrenal Fatigue Syndrome, especially in the moderate to advanced stages. Chronic excess of norepinephrine is called sympathetic overtone. It can cause cellular and tissue inflammation, higher blood pressure, symptoms of hyperthyroidism, and panic attacks.

On the other side of the spectrum, if there is a deficiency of norepinephrine over a long period it may cause behavioral problems, secondary hypothyroidism, immunological imbalance, and impaired cognitive functioning.

Adrenaline (A), also called epinephrine, plays the key role in the urgent fight-or-flight reaction that takes place physiologically in the body in response to an immediate threat when survival is perceived to be at risk. It is the chemical daughter of norepinephrine. Their actions are similar, but adrenaline is much more potent. This hormone is secreted in the adrenal glands under the direction of the HPA axis and produces a rapid rise in blood pressure, rapid heartbeat, and stimulates the release of glucose in the liver. This is the hormone of last resort as far as the body is concern when it is under imminent danger. The more danger the body is perceived to be in, the more adrenaline will be released. Those who are in very advanced stages of AFS are invariably flooded with adrenaline internally. Symptoms include heart palpitations, dizziness on standing, and panic attacks.

Acetylcholine (ACh) is a major neurotransmitter for the parasympathetic nervous system (PNS) and helps the body carry out the day to day housekeeping functions for stimulation of rest-and-digest or feed-an-breed activities that occur when the body is at rest, especially after eating, including urination, sexual arousal, bowel movements, and digestion.

Serotonin is an important neurotransmitter and it is affected by Cortisol DeficiencySerotonin is a monoamine neurotransmitter synthesized in specific neurons in the brain, central nervous system and in enterochromaffin cells located in the gastrointestinal tract. It is also called the feel good NT. Inside the brain, the pineal gland is the center for serotonin production. Throughout the entire central nervous system, serotonin has a vital role as an effective neurotransmitter in modulating a number of different areas:

  • Anger
  • Aggression
  • Appetite
  • Body temperature
  • Erection and ejaculation
  • Mood
  • Sexuality
  • Sleep
  • Stimulation of vomiting

Serotonin is also a precursor to melatonin. Once they have completed their task a reuptake or reabsorption of the hormone takes place. Serotonin effectively in make us feel calm and basically good naturally. It helps the mind to relax so that we can easily fall asleep and stay soundly asleep.

Serotonin and melatonin are produced in the body from tryptophan, an amino acid. As we have already discussed, a person who doesn’t have any serotonin cannot produce abundant amounts of melatonin. The ability to convert from one type to another depends on a variety of nutritional cofactors and coenzymes.

For a person to feel well, the overall serotonin level cannot be too high or too low. Chronic excess of serotonin over a long period of time may result in:

  • Behavioral problems
  • Cardiovascular problems
  • Hormonal and immunological imbalances

A long-term depletion or deficiency in serotonin can cause:

  • Depression
  • Gastrointestinal problems
  • Hormonal imbalances
  • Imbalances in the immune system
  • Inflammation
  • Insomnia due to low melatonin
  • Onset of various medical conditions

Inhibitory vs. Excitatory Neurotransmitters

NTs generally fall into two groups when classified by their actions:

  • Inhibitory NT—Serotonin, glycine, and GABA fall into this category. When we have plenty of these in our system we feel good. These NTs also assist with our sleep and contribute to our sense of self-esteem. When these become depleted in our system we can become angry, depressed and suffer from insomnia.
  • Excitatory NT—These neurotransmitters keep us focused, alert, motivated, and help our memory. They include catecholamines (dopamine, adrenaline, and norepinephrine), and glutamate. A low level of dopamine causes impaired short-term memory, a low sex drive, difficulty with numbers and general fatigue. A shortage of norepinephrine will bring on depression, a lack of motivation and ambition, and an increased likelihood of becoming dependent on caffeine and other stimulants. If we have too much norepinephrine then we can arouse panic and have difficulty sleeping. Many street drugs work by stimulating this pathway.

For the body to be in optimum health, NTs of opposing actions need to be perfectly balanced.

L-Glutamate (glutamic acid) is the most vital excitatory neurotransmitter functioning in the brain and performs a significant role in brain chemistry. It is released by a variety of neurons and acts to stimulate other neurons during synapses. The more glutamate, the higher will be the levels of excitation. If the excitatory neurotransmitters reach excessively high levels, a state of excitotoxicity exists. This is when the neuronal activation has reached such a high level that the stimulated firing of neurons has become neurologically damaging. Many of the illicit or prescription drugs that abusers take affect either one or both neurotransmitters and cause stimulating or tranquilizing effects on the brain.

On the other end of the spectrum, molecules such as GABA and taurine are part of the inhibitory NTs. GABA is derived from glutamine and synthesized when the active form of vitamin B6 (P5P) is present. Inhibitory NTs inhibit or prevent the firing of neurons. It plays a critical role in the regulation of neuronal excitability throughout the entire nervous system so that the body does not operate in a continuous state of high or excitment. They reduce anxiety and promote calmness.

Symptoms of NT Imbalance or Deficiency

Your mental health will suffer from Cortisol DeficiencyThere may be over sixty different mental and physical illnesses associated with a deficiency or imbalance in neurotransmitters, including:

  • Addiction in any form, including sex, sugar, gambling, drugs, alcohol, caffeine, smoking (nicotine), carbohydrate addiction and/or binge eating
  • Advanced stages of Adrenal Fatigue Syndrome
  • Fibromyalgia
  • General malaise
  • Irritable bowel syndrome
  • Memory impairment (forgetfulness)
  • Obsessive-compulsive disorder (OCD)
  • Parkinson’s disease
  • Tourette’s syndrome

In particular, neuroscience research has proven strong association between low levels of serotonin and/or norepinephrine with the following mental conditions:

  • Anorexia
  • Anxiety
  • Bulimia
  • Chronic pain
  • Depression or mood disorders
  • Fibromyalgia
  • Insomnia or sleep disorders
  • Migraines
  • Obesity
  • Panic attacks
  • Premenstrual tension
  • Restless legs syndrome
  • Bipolar disorder
  • Cognitive disorders
  • Depression

Diagnosing NT Imbalance

It is fairly easy to determine the levels of most neurotransmitters in the body by testing a sample of urine. However, interpreting the results is not easy and often can be very confusing because the clinical correlations are not very accurate or definitive. For example, levels of neurotransmitters in urine vary rapidly in reaction to both stress chemistry and diet-related changes that affect the pH.

Other valid reasons why particular neurotransmitters may be outside their reference range would include:

  • When neurotransmitters are used they are destroyed and this process takes much longer than its production, which results in higher levels of the neurotransmitters when measured
  • Due to a fungal or yeast infection, a neurotransmitter can be transformed into a false form and be included in laboratory tests
  • Both viral and bacterial infections can destroy neurotransmitters, lowering the real value
  • Other neurotransmitters or certain neurochemicals can suppress a neurotransmitter, lowering the real value
  • If the supply of oxygen is decreased to some parts of the brain, the neurotransmitters will be affected

Clearly, sensitivity and specificity of NT testing by urine has much to improve and is a science very much in progress. It does give us a little glimpse of the NT world within. Clinical correlation is key to make the most sense with laboratory studies, as they can be misleading and confusing on their own.

Restoring NT Imbalance

NT deficiencies can be replenished with amino acids, dietary, and lifestyle changes. NT excess can be helped by lifestyle modifications as well as compounds that calm NT release. It all comes down to balancing so that the excitatory NTs are in balance with the inhibitory NTs. Bias in any direction is not desirable. Most NT imbalances reflect underlying pathology. Comprehensive strategies of NT rebalance needs to also correct the underlying root cause.

To correct specific NT imbalances, what is needed is to first identify the defective pathway. Clinicians experienced in NT physiology find that a detailed history usually provides the best information to commence NT repletion when depletion is suspected. Expansive testing may not be needed provided the patient is closely tracked and monitored by an experienced clinician. NT imbalance usually presents in a set of clinical behaviors with general recognizable patterns. Experienced clinicians will be able to ascertain this.

NT Repletion Prescription Medications

Cortisol deficiency may require medicationThe two main classes of NT repletion medications designed to overcome depression and anxieties are SSRIs and SNRIs. SSRIs include drugs such as Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Paroxetine (Paxil and Pexeva), and Sertraline (Zoloft). SNRIs include desvenlafaxine (Pristiq), duloxetine (Cymbalta), and venlafaxine (Effexor and Effexor XR).

SSRIs work by inhibiting the reabsorption of serotonin. By causing the body to feel good, they ease symptoms of moderate to severe depression and anxiety disorders. SNRIs work by inhibiting the reabsorption of not one but two important brain chemicals: serotonin and norepinephrine, which is why these drugs are sometimes called dual reuptake inhibitors, or dual-acting antidepressants, and tend to be a bit stronger. Because SNRIs affect two neurotransmitters, they may be an effective form of treatment for those who have failed to respond to single-acting antidepressants, such as SSRIs. Some research suggests that patients with severe depression may respond better to an SNRI.

Possible side effects for both SSRIs and SNRIs include nausea, muscle weakness, tremor, heart palpitation, increased blood pressure and heart rate, headache, dry mouth, fatigue, excessive sweating, constipation, and fluid retention. Women who are nursing or pregnant should avoid taking SNRIs, as they are passed into breast milk. Certain SSRIs may be better options for pregnant or nursing mothers. People with liver problems or high blood pressure will need liver function monitoring periodically via blood tests. Those on aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, and blood-thinning medications such as warfarin (Coumadin) should use SNRIs with caution as SNRIs may inhibit blood clotting, thus increasing the risk of severe bleeding from a cut or scrape.

One of the major problems associated with both SSRIs and SNRIs over time is dependency as well as worsening NT depletion, the very problem it is supposed to solve. More and more medication is required with greater and greater depletion leading to a vicious cycle of progressively more medication needed with less and less effect. Typically, there is a short honeymoon with lesser depression within a few weeks. Six to nine months later, however, the crude awakening begins. The patient literally wakes up to returned depression. The patient tries to quit the SSRI, such as Zoloft, and finds that they feel worse than ever. The SSRI never solved the underlying problem of NT deficiency but simply temporarily increased the level of NT by blocking its metabolism at the synapses. As more SSRI comes on board with daily intake, the MAO system increases the breakdown of serotonin with no additional nutritional intake of serotonin precursors for replenishment. The overall intersynaptic levels of NT gradually decline, when they fall below the threshold needed to keep the patient disease free, the depression returns with vengeance.

This problem can be resolved with prescribing the proper amino acids and nutrients—the building blocks of NTs, and the benefits of the medications will resume within one to two weeks. Sad to say this is seldom the path taken by conventional medicine. Instead a larger dose or more potent medication is prescribed, again masking the underlying root problem of NT depletion. Over time, sufferers become over medicated and sedated, but depression continues.

Those who are currently on SSRIs and SNRIs should not abruptly stop their treatment to avoid withdrawal symptoms that can be very hard to bear. Take a step back and look at the big picture. A comprehensive plan is needed to replenish deficiency and rebalance NTs to prevent depression from worsening. Underlying chronic problems commonly associated with NT imbalance, such as chronic fatigue, infection, or Adrenal Fatigue Syndrome, should be addressed so the root cause is dealt with properly. Natural compounds can be administered, but titrated to match the body’s state of function each step along the way. Medications can be tapered off slowly as the body returns to optimal function and root problems resolve. Timing is key, and premature cessation can bring on withdrawal and other negative side effects. Remember that an NT imbalance is more often than not secondary to some other underlying disease, which is why most NT self corrects once the underlying condition is resolved.

Natural NT Repletion Supplementation

NT repletion can be satisfied with the use of natural compounds for those low on specific NTs. This can be accomplished by way of nutritional supplements, in particular amino acids, that are the foundation precursor or modulators of NTs. Athletes wishing peak performance heading into an intense workout or competition requiring extreme focus sometimes take five to ten grams of amino acid powder to fortify themselves for that reason. Amino acid supplementation, however, can cause over-stimulation and trigger crashes if the body is weak. They can lead to insomnia and panic attacks. Amino acid supplements are the most commonly deployed to accomplish this goal. They include 5-HTP, DLPA, DPA, GABA, glutamine, L-theanine, tryptophan, or tyrosine.

Amino acid repletion is usually taken in conjunction with a variety of other vitamins and minerals because they work together and need one another to support good brain function. For example, pyridoxal-5-phosphate is needed for the conversion of tryptophan to serotonin.

Repletion therapy must be carried out carefully and no one should take matters into their own hands without the proper guidance. Most failures occur under inexperienced hands. For example, if you take 5-HTP and no other supplement(s), or if you take improperly balanced 5-HTP, you can easily deplete the dopamine in your system. If you take L-DOPA alone, or improperly balanced L-DOPA, you can easily deplete the serotonin in your system, as well as the L-tryptophan, sulfur-based amino acids, and tyrosine.

How the HPA Axis Affects our Neurotransmitters

The hypothalamic-pituitary-adrenal (HPA) hormonal axis connects sensory signals (such as smell) received from the outside world into NTs in the brain that further travel to various organs and trigger the release of over fifty hormones that help the body deal with daily living and stress. Remember that stress can be physical or emotional. Moreover, perceived stress is a more powerful trigger of the HPA axis than actual stress. The HPA axis is put in overdrive and the adrenal glands overburdened if the body is exposes to chronic stress. If the stress is unrelieved, the adrenal glands becomes overburdened and eventually tire over time.

Adrenal Fatigue Syndrome represents the end result of the body’s neuroendocrine response to stress. In early stages of AFS, anti-stress hormone cortisol output from the adrenal cortex rises as the adrenal glands are put in overdrive because of the HPA axis. In advanced stages of AFS, cortisol depletion sets in as the HPA becomes dysregulated and the adrenal glands reach exhaustion, a state of cortisol deficiency. This is when adrenal epinephrine and brain NT norepinephrine output takes center stage as the body enters the flight-or-fight alarm response.

Neurotransmitter Balance and Adrenal Fatigue Syndrome

HPA axis dysregulation from chronic stress is associated closely with NT regulation. For one to function properly, the other must be in balance and synchronization. Without proper balance, the overall condition can easily worsen.

For example:

  • Because it increases serotonin 5-HTP is widely used to make you feel better. Your body maintains a balance of serotonin and cortisol production. Your adrenal glands—the hormone glands responsible for cortisol production—contain receptors that sense the levels of serotonin in your bloodstream. Upon exposure to serotonin, your adrenal glands release cortisol into your bloodstream. As a result, taking 5-HTP—and increasing your body’s serotonin levels—also affects cortisol and increases your body’s cortisol levels. This can be negative to someone who is suffering from early stages of AFS where cortisol output is already higher than normal. Further increase in cortisol can lead to a catabolic state.
  • Increases in glutamine will lead to increased glutamate, the excitatory neurotransmitter. This is undesirable as most in advanced AFS are already in an excitatory state from excessive circulation of norepinephrine and epinephrine. Further excitation can increase fatigue and trigger adrenal crashes. Furthermore, glutamine also suppresses cortisol release. At a time when there is cortisol deficiency due to lack of production in the depleted adrenals and more is welcome, this is contrary to the need of increased cortisol output as part of the AFS recovery process from advanced stages.
  • Many people have negative outcomes when they take 5-HTP and glutamine as well as L-theanine. These are supposed to raise GABA, an inhibitory NT and reduce anxiety commonly experienced by those with advanced AFS. However, these three compounds often cause paradoxical reactions instead. They can trigger adrenal crashes and further over stimulation of the excitatory pathways for reasons not known instead of inhibiting it. This negative chain reaction can make a whole range of symptoms much worse. The reverse can happen. Taking in more GABA when laboratory levels already show high GABA levels may produce clinically positive results of relaxation for reasons not known.

We are still very much in the infancy of NT research. There is much we do not know. What is clear is that NTs are very much interconnected with each other. While we have some good understanding on the physiology of each NT individually, overall clinical outcomes remain hard to project with accuracy. This is especially true in the advanced AFS setting or for those most at risk due to concurrent chronic conditions in which the body is already on edge in an alarm response. The slightest adjustments of NTs can upset the internal NT balance that is fragile at best. Any additional intrusion into the already fragile internal homeostasis, such as receptor disorders or extracellular matrix congestion, can lead to exaggerated or paradoxical responses. Severe anxiety and fatigue can be triggered as the risk of an adrenal crash increases.

A positive attitude is essential when dealing with Cortisol deficiencyAn example of this is with selective serotonin reuptake inhibitors (SSRIs) antidepressant medications, which are very helpful in treating panic attacks. SSRIs cause serotonin levels to rise. Over time, this is not an effective way of treating stress because you’ll develop a tolerance and even with more antidepressant medication, the body just becomes desensitized to the added availability of serotonin during the neurotransmission, and the depression and fatigue persists. This negative scenario is frequently seen in people who are put on antidepressants by their private physician while AFS is overlooked, resulting in a worsening of their depression.

NT Balance Strategy When HPA Axis Imbalance and AFS are Present

When HPA axis dysregulation, NT imbalance and advanced AFS are all present at the same time an autonomic nervous system is in high gear, the clinical picture becomes very convoluted and complex. For example, overemphasis on NT repletion can trigger excitotoxicity and adrenal crashes. Too little NT repletion can retard the overall AFS recovery. Too much adrenal support can trigger NT excitation, and too little adrenal support will lead to increased NT repletion dependency. Regular NT pathways are disrupted in a body that is fragile and sensitive.

A carefully planned and balanced approach after an in depth history is taken is best with focus placed on both NT repletion and helping the body heal from AFS concurrently. The more advanced the AFS, the more focus and priority should be placed on healing the AFS first.

For example, amino acids and herbal remedies can be detrimental if the adrenals are not stabilized first or if the liver is congested and the extracellular matrix polluted. If you want to decrease your levels of norepinephrine while at the same time increasing serotonin levels, then certain supplements would not be advised. For example, people often try to treat depression by supplementing with St. John’s Wort, but if they have extremely high levels of norepinephrine, it’s not a good idea since this would increase their norepinephrine levels even more by their association with the HPA axis which can be put in overdrive during the process.

Sometimes people use melatonin to help them sleep. Melatonin begins with the turning on of sympathetic nerve tracks in the brain that secrete the NT norepinephrine which in turn stimulates cells it the pineal gland to produce melatonin. This may not be problematic for some, but for those in advanced AFS where the body is already flooded in a sea of norepinephrine, any excess can make insomnia worse and trigger adrenal crashes.

Therefore, a comprehensive recovery plan needs to have components that address NTs, HPA axis dysregulation, adrenal function, liver congestion, extracellular matrix pollution, dietary concerns, environmental toxins etc., to be effective long term.

Wired and Tired

One of the classic signs or NT imbalance in a setting of advanced AFS is a state called wired and tired. There are several mechanisms that can lead to this state, one of which is NT imbalance.

Advanced AFS sufferers are typically in a state of constant fatigue, but yet unable to fall asleep. Those who are able to fall asleep typically wake up after a few hours and are unable to return to sleep easily. In the morning, they are unrefreshed as a result. Furthermore, many are anxious during the day, with energy slumps in the afternoon. When it is time to go to sleep, the body is again wired and tired. It may take a long time to fall asleep, only to be awakened in a few hours and once more the cycle repeats itself. This can go on for years. Over time, the body becomes weakened. Sleep medications are often required, and over time, dependency and tolerance issues develop.

In addition to NT imbalance, which is a causative factor of poor sleep, research has shown that much of the wired and tired state is the result of a body flooded in stimulatory catecholamines. Other contributing factors include liver congestion and extracellular matrix pollution. When the body alarm response is activated because of stress, a state of sympathetic overtone (high norepinephrine typical of early Stage 3C AFS) or reactive sympathetic response (high norepinephrine and adrenaline typical of late Stage 3C AFS) is prevalent. Other symptoms associated with this state include heart palpitations, reactive hypoglycemia, posturalorthostatic hypotension, and dizziness.

Normalizing a body in this wired state is a very challenging process because the body is often hypersensitive at this stage so that the smaller adjustment in NT can trigger exaggerated responses in some and paradoxical responses in others. Most failure in resolving this state of wired and tired comes from the failure to recognize NT function, dosage error, improper delivery system, and a mentality of trying to fix the sleep or anxiety problems rather than looking at insomnia and anxiety as part of the overall consequence of a body in full state of alarm. Because this alarm state is twenty-four seven, successful resolution involves a twenty-four seven approach.

It should be clear that NT balancing is a highly technical aspect of nutritional medicine requiring in-depth clinical experience due to its complexity and lack of well correlated scientific clinical markers. The rather simplistic approach of simply replenishment of what appears to be depleted on the surface based on laboratory testing seldom works and in fact can worsen the overall condition over time.

A comprehensive plan is necessarily tedious, time consuming and all encompassing because we are dealing with chemicals that have wide ranging ramifications throughout the body. Most NT imbalances have underlying root causes that need to be addressed to effect long-term healing. This is especially true when NT occurs in a setting of AFS. Fortunately, once NTs are stabilized, the recovery program can be discontinued. The younger the sufferer, the faster is the recovery. Unfortunately, most people tend to underestimate or are unaware of the long-term negative consequences of NT imbalance. Many heath care practitioners are not well educated in this aspect of medicine. Sufferers are put through many trial and error attempts, which can worsen the overall condition.


Neurotransmitter balance is a key to vitality and optimum health. Imbalanced NT is a common occurrence in advanced stages of AFS. Balancing NTs requires a thorough knowledge of each specific NT and its interaction with others because all NTs are connected biochemically. Laboratory studies of NTs need clinical correlation to be useful. A detailed history by an experienced physician is far more accurate. The proper use of food, micronutrients, lifestyle, and exercise can help restore proper NT balance. Always remember that NT imbalance is more often than not secondary to an underlying disease, and that is why most NTs self correct once the underlying condition is resolved.

© Copyright 2014 Michael Lam, M.D. All Rights Reserved.