Brain Boosting Supplements and Adrenal Fatigue Syndrome – Part 5

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

Read Part 1 | Part 2 | Part 3 | Part 4 | Part 6

Brain Boosting Supplements for Natural NT Repletion

While medications may be too harsh for those with Adrenal Fatigue, there may be natural alternative brain boosting supplements to help replenish neurotransmittersNT repletion can be satisfied with the use of natural compounds and brain boosting supplements for those low on specific NTs. This can be accomplished by way of nutritional brain boosting 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 brain boosting supplements are the most commonly deployed to accomplish this goal. Brain boosting supplements include 5-HTP, DLPA, DPA, GABA, glutamine, L-theanine, tryptophan, or tyrosine.

There are many ways to replete brain boosting supplements, as the following examples will show:

  • Listening to loud music while working out
  • Getting involved in exciting, fast-moving or violent video games or movies before going to bed
  • Playing computer games for several consecutive hours
  • Staring at a computer monitor for most of your workday
  • Listening to background music
  • Constantly using artificial, fluorescent lighting in your home or workplace

Amino acid repletion is usually taken in conjunction with a variety of other vitamins and minerals and brain boosting supplements 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. One must always be aware of the balances of brain boosting supplements and always seek advice from one’s primary medical physician.

Natural NT Repletion Toolbox

Brain boosting supplements may include Vitamin B1. B Vitamins. For those that need assistance in the methylation processes of melatonin and of the catecholamines, the amino acid S-Adenosyl methionine (SAMe) can help or you can try methionine and vitamin B12. An active form of vitamin B12 can be found in Methyl-B12, so that could be useful as well.

Active forms of B vitamins are more potent since they are more useable than non-active forms and can be part of the brain boosting supplements family. The active forms don’t need to be converted into the form that the body actually uses. They can be utilized by the body as they are, or with fewer steps. This is a benefit for those who are strong and healthy. They may be too excitatory for those with weak adrenals. B vitamins therefore have to be carefully chosen to match the body’s need to be successful.

NT repletion supplements can be found in the following B vitamins:

Active vitamin B6 —pyridoxal-5’-phosphate (P5P)
Active vitamin B9 —5-methyltetrahydrofolate (5-MTHF)
Active vitamin B2 —flavin mononucleotide (FMN)
Active vitamin B3 —nicotinamide adenine dinucleotide (NAD or NADH)
Active vitamin B5 —pantothenic acid or pantethine

Alert: Too much vitamin B can cause crashes. Those who are weak and sensitive have to be extra careful. Side effects include anxiety, heart palpitations, and insomnia.

2. 5-HTP. Because serotonin does not cross the blood-brain barrier, it cannot pass into its specified pathways in the central nervous system when taken orally. However, the amino acid tryptophan, along with its metabolite 5-HTP or 5-hydroxytryptophan, which serotonin is derived from, does have the ability to cross the blood-brain barrier.

It is not usually advised that tryptophan be taken as a supplement, but 5-HTP is recommended widely as an effective serotonergic agent and is safe for the most part when taken in small doses. It is helpful to take 5-HTP before bedtime in order to help you relax before going to sleep. It can give you enough serotonin so that the melatonin you need can be produced. For some, it is also helpful to take small doses of 5-HTP throughout the day to help in the production of serotonin and to keep you relaxed.
Recommended dosage: When starting out with 5-HTP it is very important to begin with a very low dose and gradually work your way up. The dosage between individuals can vary from 50 to 200 mg per dose, depending on the person’s needs and what they can safely tolerate.
Alert: High dosages of 5-HTP (e.g., 200 mg or higher) may also cause nausea and stomach cramps. This is why some prefer to take slow release 5-HTP brain boosting supplements at bedtime. These symptoms may only occur at certain points in the day, e.g., at bedtime and not during the day, during the night or in the early hours of the morning if more is taken then. When taken in extremely high doses 5-HTP can cause serotonin toxicity or serotonin syndrome, and this can literally be fatal.

3. Melatonin. Melatonin is a hormone made from serotonin yet 5-HTP is a precursor to serotonin and thus can increase melatonin levels. In order to produce melatonin and the required coenzymes and co-factors, the body requires a certain amount of serotonin as a primer. A certain level of serotonin in the body is needed by many for them to relax enough to go to sleep and when melatonin is produced internally after sleep has initiated, it helps you to stay asleep. A deficient production of melatonin can result in anxiety and mood disorders, lowered basal body temperature, insomnia, elevated estrogen/progesterone ratio, and immune suppression associated with cancer. Excess melatonin is associated with seasonal affective disorder (SAD), lowered estrogen/progesterone ratio, low thyroid and adrenal function, and hypotension.

Melatonin levels may be lessened by Adrenal Fatigue and brain boosting supplements may become necessaryMelatonin is widely used as a sleep aid. The sleep promoting effects of melatonin are most apparent only if a person’s melatonin levels are low. In other words, taking melatonin is not like taking a sleeping pill or even 5-HTP. It will only produce a sedative effect when melatonin levels are low. By enhancing sleep quality, melatonin enhances NT stability and balance.

Alert: When taking melatonin, you have to be very careful regarding the dosage. Some people are able to absorb and assimilate melatonin quite easily and thus only need a fraction of a milligram. Other people need as much as 50 mg to get the desired effect. In other words, the effect is not linear in response. Some trial and error is required in the hands of an experienced clinician. Those who experience a hangover in the morning with melatonin should take it two hours before sleep rather than at bedtime.

4. GABA, Glutamate, Glutamine. The neurotransmitters in the brain doing most of the work are glutamate (also called glutamic acid) and GABA. Over 50 percent of the synapses in the brain release glutamate, while 30 percent to 40 percent release GABA. GABA is an inhibitor and thus calming. Glutamate is excitatory and stimulatory. In healthy individuals, GABA and glutamate will be in balance in the brain with regard to their absolute concentrations and their relative ratios. Problems arise if the ratio is imbalanced. For example, if GABA production is reduced, a higher glutamate to GABA ratio in the brain will increase, leading to a sense of being wired. A GABA deficiency over a long period of time is linked to the following excitatory or stimulatory effects:

If GABA is deficient in the body it can be supplemented by using a supplemental form of GABA. Each of us may have different amounts of GABA in the brain that is considered normal. There are no accepted medical tests to determine if we have too much or too little GABA activity. Excessive use of street drugs, alcohol, and prescription drugs are associated with low GABA activity and thus a state of excitation. Caffeine, in particular, inhibits the release of GABA and allows the increase of excitatory neurotransmitters.

GABA, glutamine and glutamate are intimately involved in a cycle that ultimately determines the level of each in the body. Neurons are not able to perform new synthesis of the neurotransmitters glutamate and GABA from glucose. The glutamate-GABA-glutamine cycle is a metabolic pathway that describes the release of glutamate or GABA from neurons, which are then taken up into astrocytes (star shaped glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of glutamate or GABA. This cycle therefore determines whether more GABA or more glutamate is produced.

Think of glutamic acid, glutamine and GABA as three members of a close-knit family with three very different personalities. Glutamic acid is a non-essential amino acid (the body can manufacture it when things are working right) that is also an excitatory neurotransmitter. Its cousin GABA has an opposite personality—it calms our nerves and relaxes us. Glutamine is the source for both of them—the body can make either glutamic acid or GABA from glutamine, depending on what is needed. Glutamine therefore is the gatekeeper chemical that determines the amount of GABA and glutamate levels to be produced to keep them in balance.

In some people brain boosting supplements can cause more symptomsIf you are in a state of anxiety caused by sympathetic overtone (as commonly seen in advanced AFS) or a severe inflammatory state, glutamine’s focus will be shifted automatically to make more GABA to calm the body in theory, which will in turn lower your glutamate level, and help calm you down. Unfortunately, this pathway can be disrupted because an inflammatory state can cause dysregulation of the cycle itself, leading to excess production of glutamate levels instead. This is why it is very hard to predict the overall net effect of glutamine and it is not unusual for a variety of outcomes when taken by seemingly homogeneous populations. This happens most frequently in a body with chronic weakness, such as that of AFS. This may explain why some people do well with GABA brain boosting supplements, but others can have paradoxical reactions. Similarly, glutamine is also a support for GI health, but it may increase glutamate and cause anxiety as well.
Generally speaking, if you keep the total amount of glutamate in your body under control, you can prevent excitation responses. For example, excessive glutamate in Chinese food prepared with flavoring enhancer monosodium glutamate (MSG), dubbed the Chinese restaurant syndrome can cause nervousness, headaches, numbness, facial pressure, and anxiety.

Excessive GABA can result in a number of detrimental effects including:

  • Breathing problems
  • Immune system imbalance
  • Impairment in muscular movement
  • Memory problems
  • Onset of any number of medical conditions

Recommended dosage: Take 100 to 1000 mg in divided doses. GABA is commonly elevated in sufferers with advanced AFS. It is not clear why. Supplementing with GABA may not seem wise, but many have clinically reported benefit under these situations, especially for daytime anxiety control. Taking L-theanine is a lot more helpful in this situation and probably safer than other brain boosting supplements. It’s just weaker all around as it needs to be converted into GABA and serotonin. It is not recommended that GABA be taken in high doses (500 mg or more) at bedtime as it can cause an alert state and possibly stimulate the production of other neurotransmitters that may prevent falling asleep.

5. L-Theanine. L-theanine is another amino acid and a precursor to serotonin. It also helps in the production of GABA and dopamine. Theanine is related to another non-essential amino acid, glutamine. It is considered to be psychoactive since it has the ability to penetrate the blood-brain barrier.

As an alternative to GABA or L-glutamine to support a calming of the brain, one can take the amino acid L-theanine. L-theanine is converted to several useful calming and mood-elevating substances in the brain, including GABA. Therefore, one can use theanine as a kind of bank shot to bypass the blood brain barrier issue with respect to GABA.

Because L-theanine is known for helping to relieve stress and provide relaxation it is used in some sleep remedies in conjunction with low dose 5-HTP, GABA, melatonin, and calming herbs like passionflower and valerian root.

Recommended dosage: Take 200 to 400 mg once or twice daily. Those with advanced AFS need to be on alert for paradoxical reactions. Stop supplementation if this occurs.

Brain boosting supplements can calm the body6. Taurine. Taurine is an amino acid that calms the nervous system by facilitating the production of the neurotransmitter GABA. By helping to raise GABA levels, taurine allows the body to manage anxiety so that your thoughts don’t go spiraling out of control and you don’t experience the associated cortisol and adrenaline spikes seen in Adrenal Fatigue Syndrome.

Take taurine for better sleep, but make sure you are getting a magnesium supplement that your body can absorb as well. Together these nutrients are the answer to abolish stress, calm the nervous system, and help you sleep better. You’ll also have an overall improved mood. People who are deficient in either magnesium or taurine are at greater risk for depression and poor motivation.

Magnesium is well known to calm the nervous system, while countering fatigue. Similarly, taurine raises GABA levels, calming the nervous system and lowering anxiety and stress hormones that hinder rest.

Recommended dosage: A 500 to 2000 mg dosage range has shown efficacy, although the upper limit for toxicity is placed at a much greater level and high doses are well tolerated. The upper limit for which one can be relatively assured no side effects will occur over a lifetime has been suggested to be 3 grams a day. Taurine is a natural diuretic and may cause excessive urination and drop in blood pressure in high amounts.

7. Glycine. Glycine is one of the most common amino acids found within human proteins. It is particularly important clinically in supporting healthy digestive and central nervous systems and chronic fatigue. Within the central nervous system glycine works together with taurine and GABA as an inhibitory neurotransmitter. It interferes with the hyperexcitability of the CNS neurons by regulating chloride and potassium balance. It has been shown to be beneficial for disorders such as hyperactivity, anxiety, obsessive-compulsive disorder, schizophrenia, bipolar, and epilepsy. Due to its neuro-inhibitory effect, glycine calms the brain and is thus helpful in treating depression and insomnia as well. Glycine also helps in supplying glucose to the body and thus helps to alleviate fatigue.

Recommended dosage: Take 1 to 3 grams for anxiety or sleep. Up to 100 grams is needed for schizophrenia.

8. L-DOPA / Tyrosine. L-DOPA has the capability of penetrating the blood-brain barrier and is the precursor of dopamine and as we know, dopamine is involved in the production of noradrenaline, which converts into adrenaline. Supplementing with L-DOPA can increase the levels of dopamine in the system, but it won’t necessarily increase the levels of norepinephrine over the levels of adrenaline. Many factors are involved in balancing the equilibrium in the nervous system so it isn’t that straightforward.

Instead of supplementing with L-DOPA, you can supplement with the amino acid tyrosine, which is a precursor of L-DOPA. Tyrosine contains many different proteins but it is not as effective since it must go through an additional step in order to produce L-DOPA. Tyrosine brain boosting supplements may be considered for someone having below normal reference ranges of it and if there are no clinical contraindications.

Recommended dosage: Take 500 to 5000 mg daily in divided doses. Up to 20 grams has been used by researchers to improve cognitive function.

Alert: Overuse of tyrosine can push the body into an over-excitatory state and trigger an adrenal crash, panic attack, and heart palpitations. Don’t take L-tyrosine if you have problems with chronic headaches or bellyaches because the supplement might trigger these conditions. If you have problems with hyperthyroidism, such as with Graves’ disease, avoid tyrosine.

Adrenal Fatigue can lead to imbalances of cortisol throughout the day for many sufferers, which brain boosting supplements may help9. Neuromodulators and Precursors. The following are commonly used:

  • Estrogen directly influences brain function through estrogen receptors located on neurons in multiple areas of the brain. At neuronal synapses, estrogen increases the concentration of neurotransmitters such as serotonin, dopamine, and norepinephrine. It affects their release, reuptake, and enzymatic inactivation. It also increases the number of receptors for these neurotransmitters.
  • Phenylalanine (PHE) is a precursor to catecholamines such as dopamine, norepinephrine and epinephrine. If an amino acid analysis shows that levels of phenylalanine are low, then supplementing with it or eating foods rich in phenylalanine may be of help. Foods rich in PHE are meat, poultry, fish, dairy, soybeans, seeds and nuts. Aspartame, an artificial sweetener is also rich in phenylalanine but this is not advised. In general, PHE is seldom recommended because there are superior alternatives.
  • Phosphatidylcholine (Lecithin), N-acetyl-L-cysteine (NAC), and acetyl-L-carnitine are all precursors to acetylcholine, the NT of the parasympathetic nervous system.

Phosphatidyserine (PS) is derived from soy lecithin a component of cell membranes. PS is helpful in repairing damaged cell membranes as well as repairing the cortisol receptors located in the hypothalamus. When cortisol levels are too high it is believed this elevation damages the receptors, which impairs the hypothalamus’ ability to detect when levels of cortisol are too high and to correct the problem. The stronger the phospholipid layer of the cell, the more efficiently the NTs can be transported. PS can be used successfully to help calm elevated cortisol levels at night and induce sleep. Nonetheless, for reasons that are not well understood paradoxical responses are common.

As simple as it may seem, most self-navigating natural NT repletion programs fail, just as most medications that attempt repletion of NTs also fail over time. Those who are under stress, in particular, are at risk of failure. Sufferers of adrenal fatigue are most vulnerable, especially in advanced stages when their HPA hormonal axis is deranged. It is clear that a body under stress will negatively impact the effectiveness of any NT balancing program and in particular, SSRIs and brain boosting supplements. A comprehensive NT balancing program must take this into account to be successful. Let us study why.

Read Part 1 | Part 2 | Part 3 | Part 4 | Part 6

© Copyright 2015 Michael Lam, M.D. All Rights Reserved.

Dr. Lam’s Key Question

Performance boosting supplements are generally anabolic and stimulatory in nature. They can throw off the natural balance of neurotransmitter, leading to insomnia and anxiety. These compounds, therefore, are not recommended unless under the guidance of a doctor and for short term use.

Melatonin levels may be lessened by Adrenal Fatigue and brain boosting supplements may become necessary
5 -
I am amazed at the detailed descriptions of the stages of Adrenal Fatigue and in particular Stage 3 Adrenal Exhaustion. It so accurately describes my experience and I feel less crazy and have more understanding. I have not seen this anywhere else. I am grateful for this more detailed and comprehensive overview.
However, at the same time, I am also completely overwhelmed with the website content! There's a lot of repeating information, and SO many articles that my adrenal fatigued brain just can't deal with it. There is just way too much, so I gave up trying to find the information I needed. I need things simpler, less scattered, less content and shorter articles in order to just get through it.
Also, there are several warnings against improper supplement and herb usage, but no specifics about that. I am seeing an herbalist in my area but they did not have these same warnings. But I am still struggling a lot too, so I am now worried about the herbs causing my symptoms to be worse, but I can't handle that new stressor. I need to feel less stressed in order to get well! I guess I need to buy the book to find out this information? But the book being 500 pages looks overwhelming too. But I may get it anyway.