The endocrine system in the body controls hormonal and neurotransmitter production and regulation.
In a general sense, a hormone is a cholesterol-based molecule that is released by cells in one part of the body, typically a gland, that affect cells in another part of the body. Some hormones are also produced within the nervous system. Hormones are transported around the body via the blood.
'Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor protein, resulting in the activation of a signal transduction mechanism that ultimately leads to cell type-specific responses.'
Neurotransmitters are chemicals that amplify, relay and modulate signals between a neuron and another cell, within the nervous system. They are generally either amino acids or peptides based on amino acids.
Hormones are the thermostats and regulators of the body's metabolism, and their production and balance is controlled by the hypothalamus in the brain. The hypothalamus releases neurotransmitters, which provide instructions to the various glands and regulate their hormone production. These glands include the pituitary gland (located in the brain), the pineal gland (also in the brain), the adrenal glands (one located on each kidney), the thyroid gland (located in the neck), ovaries in females (I think you know where these are) and testicles in males (are they those two...? [Aaron: "Yes!!"]...Ooooh!). The Pituitary gland (a protrusion of the hypothalamus) also produces a neurotransmitter oxytocin, which appears to be important in the hypothalamus' own performance.
A general introduction to the endocrine system can be viewed at the links below.
Some of the effects that hypothalamic dysfunction can have on the various organs and systems of the body are summarised in the diagram below. Inadequate neurotransmitter and hormone production may also negatively impact one's mitochondrial function. These topics are examined in more detail on this page and other pages in the Health Section.
Ironically, the major factor behind fatigue in supposedly healthy and those who are chronically fatigued is usually hormonal and neurotransmitter imbalance, namely underactive adrenal and thryoid glands. Probably around 70% of people with CFS have underactive adrenal and thyroid glands. It is however unfashionable to focus on this, and some 'experts' prefer to focus on factors like candida or food allergies alone. The CFS web page on psychological management looks into stress, over activity and lack of rest periods as a factor for adrenal burn out. There are many other factors contributing to the stressing of the adrenals glands and impaired neurotransmitter production in general, such as heavy metal toxicity (particularly for the Dopamine/GABA and Serotonin pathways and energy production in the brain), excessive Glutamate and Aspartate intake (results in excitotoxicity and disrupts brain chemistry), excessive free radicals, psychological and physical stress, high carbohydrate diet (especially sugar), nutritional deficiencies, inadquate digestive and amino acid conversion processes, prolonged periods of hunger between meals (3 large, square meals a day approach), recreational/legal drug use (caffeine, alcohol, certain anti-depressants, marijuana, speed, meth, cocaine etc.), and birth control pills etc.
Melatonin is naturally synthesized in the pineal gland from the amino acid tryptophan (derived from serotonin) by the enzyme 5-hydroxyindole-O-methyltransferase. Melatonin is also manufactured by the retina, lens and gastrointestinal tract. Melatonin has a variety of functions in the body, including regulating sleep (inducing tiredness prior to sleep), boosting the immune system and as a powerful anti-oxidant.
The thyroid gland produces two primary thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Thyroid hormone underproduction is known as hypothyroidism, and may cause symptoms such as fatigue, confusion, achiness, intolerance to cold and constipation. T4 is converted in the body to T3, the active version of the thyroid hormone. In run down patients, the body may not be able to convert T4 into T3. Many thyroid hormone tests tend to focus on the T4 levels in the blood and thus may not provide useful results.
The adrenal glands, located adjacent to the kidneys, produce a number of hormones and neurotransmitters, including cortisol, noradrenaline, adrenaline (the three main stimulatory neurotransmitters), dopamine (a neurotransitter and stress hormone precusor), DHEA-S (growth hormone), aldosterone and estrogen and testosterone. Dopamine, norepinephrine and epinoephrine are classed as Catecholamines, which are tyrosine-based 'stress neurotransmitters produced by the adrenal glands during times of psychological stress or low blood sugar levels (often referred to as 'stress hormones'.
Cortisol
Noradrenaline
Dopamine
DHEA-S
Aldosterone
Symptoms of adrenal and pituitary hormone insufficiency include fatigue, poor ability to respond to stress with subsequent 'crashing', achiness and recurrent infections, hypoglycemia, frequent urination, constant thirst (despite high water intake), inability to retain fluids and salt effectively, low blood pressure, insomnia and dizziness when first standing up. Symptoms may be exacerbated by going between meals for too long or excessive caffeine intake.
The testes in men produce a number of male sex hormones, called androgens, including testosterone. Testerone plays a number of roles in both men and women, but in the concentrations present in men, it assists in skeletal and muscular growth.
A continual constriction around the 'balls' in men may result in more than just lowered sperm count. As well as being uncomfortable, it may also contribute to decreased hormone production and possibly even damage to the valves in the blood vessels of the epididymis (the coiled tubes at the back of the testicle) - called Varicocele.
The testicles are on the outside of the body in order to provide a slightly lower temperature for optimum sperm production, but it also makes them vulnerable! It is strange that popular culture has valued the cut of trousers and ability to hide an erection at inopportune moments over comfort and the health of the testicles, particularly when sitting down (when one's jeans/trousers are pinched in the groin region). Loose fitting underwear and baggy trousers are much better for your balls! Office or sedentiary jobs greatly exaccerbate this problem with close fitting underwear and trousers/jeans.
The main hormones discussed below can be considered to have slightly slower or longer term actions than the neurotransmitters, which tend to govern the daily and indeed moment to moment functioning of the brain and brain chemistry; but with notable exceptions, for example, Cortisol. Indeed, many neurotransmitters are actually called hormones, including the Catecholamines produced by the Adrenal Glands. So terminology is somewhat ambiguous.
DHEA-S
Aldosterone
Cortisol
Testosterone
Oestrogen
Thyroxine (T4)
Triiodothyronine (T3)
Insulin
etc.
Some of the above hormones are discussed below.
Cortisol
Cortisol is the primary stress hormone. Cortisol increase blood sugar levels and blood pressure and also controls immune function. The adrenal glands produce more cortisol in response to stress. Increased cortisol production is part of the fight or flight mechanism and allows us to effectively deal with stress. Of course, overproduction of cortisol through extended periods of stress will result in adrenal burnout and the eventual underproduction of cortisol and other adrenal hormones. CFS patients are said not to produce much if any cortisol in response to stress (fight or flight) triggers at the time.
Cortisol is a corticosteroid hormone produced in the adrenal cortex (part of the adrenal gland). It is commonly known as the 'stress hormone'. It is involved in the response to anxiety and stress, controlled by the CRH (Corticotropin-releasing hormone). Elevated cortisol levels tend to increase blood pressure and blood sugar, and reduces the immune responses/capability. Compared with the neurotransmitter adrenaline, it is very slow acting, in neurological terms. Adrenaline can be released in a small fraction of a second, whereas Cortisol requires a whole second to be secreted. Cortisol tends to be more implicated in the long term fight or flight response that afflicts that with long term stress or adrenal burn out (e.g. many CFS patients).
Thyroid Hormones - Thyroid HormonesThyroxine (T4) and Triiodothyronine (T3)
The thyroid gland produces two primary thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Thyroid hormone underproduction is known as hypothyroidism, and may cause symptoms such as fatigue, confusion, achiness, intolerance to cold and constipation. T4 is converted in the body to T3, the active version of the thyroid hormone. In run down patients, the body may not be able to convert T4 into T3. Many thyroid hormone tests tend to focus on the T4 levels in the blood and thus may not provide useful results.
DHEA-S
DHEA-S is a growth hormone, and associated with feeling good and muscle growth, and natural production decreases with age, but dramatically so with CFS sufferers.
Dehydroepiandrosterone (DHEA) is a multi-functional steroid hormone, and together with DHEA-S (sulphate ester version of DHEA) is the most abundant steroid found in humans.
DHEA and DHEA-S are produced by the adrenal glands and de novo inside the brain. DHEA functions as an androgen receptor and through its metabolites, can undergo conversion to testosterone and the estrogens estrone and estradiol. It is also a neurosteroid. DHEA-S is generally known as the growth hormone, levels of which tend to decline in humans with age.
DHEA is classed as an anabolic steroid (or rather a precursor to such hormones), in contrast to Cortisol, which is a hormone end product and is catabolised (broken down). DHEA can act as a calming agent as opposed to Cortisol which tends to have the reverse effect on the body.
Aldosterone
Aldosterone helps in fluid and salt retention in the body (as well as vaspressin produced by the pituitary gland, an anti-diuretic hormone (ADH)).
A number of toxic substances can disrupt the endocrine system and interfere with (i.e. inhibit) hormone production or actually mimic the action of the hormones themselves, thereby falsely elevating levels of certain hormones or what the body perceives to be these hormones, beyond their references values. Please see below a list of chemicals (including pesticides and industrial chemicals) that are classified as 'endocrine disrupting chemicals'. In some animals, such as frogs, birds, fish and molluscs, they have produced infertility and gender changes.
Below is a link to an article about the US National Research Council's (NRC) first-ever published review of the fluoride/thyroid literature. It concludes that there is clear evidence that small amounts of fluoride, at or near levels added to U.S. water supplies, present potential risks to the thyroid gland (i.e. the endocrine system / hormonal balance).
Hormones are manufactured from cholesterol as can be seen in the diagram above. Whilst cholesterol is the initial building block, it can also be seen that all hormones are manufactured from Pregnenolone, which is made from cholesterol. This is why (good) cholesterol is an important part of our diets.
Pregnenolone is prohormone (a hormone precursor) and steroid hormone. Pregnenolone formation is dependent on the process of hydroxylation and cleavage of cholesterol side-chain. This is dependent on the cytochrome P450scc enzyme, which is located in the mitochondria of our body's cells, and also controlled by pituitary tropic hormones, ACTH, FSH and LH. Other Cytochrome P450 enzyme functions, relating to oxidation of toxins inside the body's cells and in the liver, and problems associated with impairment of this function, are discussed on the Inefficient Liver Function page. Steroidogenesis (creation of steroid hormones), summarised in the diagram at the top of this section, is shown in more detail below.
Pregnenolone supplementation can be used to normalise imbalanced hormone production in some highly stressed individuals who produce insufficient Cortisol. Supplementation is discussed further below. Phosphatidyl Serine (PS) acts to facilitate the repair of the cortisol receptors in the hypothalamus. It is believed that cortisol receptors become damaged by elevated cortisol levles, reducing the ability of the hypothalamus to detect and correct excessive cortisol levels. Pregnenolone supplementation is discussed further in the Hormone and Prohormone Supplementation section.
When it comes to measuring one's hormone levels, there is considerable debate as to the best method. Most tests involve testing one's saliva, which is broadly representative of one's interstitial fluid as a whole. Some tests do test the actual blood levels. However, it is really the cellular levels that we are interested in, or the rate of cellular absorption and utilisation of these hormones. For example, if the hormone in question is being absorbed and utilised as quickly as it is being produced, then the blood and saliva levels may well read low even if an elevated amount of the hormone is being produced. Some thus argue that the results from muscle testing should override any laboratory test results specifically related to ascertaining cellular hormone needs or problems.
Let us summarise the main Neurotransmitters below. The following chemicals and causes are investigated in the Neuro-Lab Analysis of Brain Chemistry (Comprehensive) urine test. Please see the Identification page for more information.
The main neurotransmitters are:
Adrenaline (A)
Noradrenaline (NA)
Dopamine (DA)
Serotonin (5-HT)
Gamma-Amminobutyric Acid (GABA)
Acetylcholine (Ach)
Whilst most of the above neurotransmitter levels can be ascertained relatively reliably from the blood or urine, for example, Acetyl Choline levels may not be accurately measured this way, as it is hard for Choline to cross the blood-brain barrier, where the brain can produce Acetyl Choline. Thus Acetyl Choline may be present in the body and tissues in high levels but not actually in the brain where it is most required.
Some articles examining the main neurotransmitters and their effects are found at the links below.
The neurotransmitter metabolites are the products of neurotransmitter utilisation, i.e. their deactivation. The patterns of the respective metabolites therefore provide us with information about the activities of these neurotransmitters. Any long term imbalanced utilisation of neurotransmitters will contribute to the establishment of an imbalance in the level of neurotransmitters, and thus an impaired nervous system functioning. The pattern of the metabolites can therefore be used to identify such problems and to intimate treatment recommendations. Some of the neurotransmitter metabolites are summarised below.
Neurotransmitter precursors are the compounds from which the body manufacturers the neurotransmitters, either directly or indirectly. The pattern of the precursors influences the pattern of the neurotransmitters, and thus nervous system functioning. A defiency in a precursor can act as a bottleneck in the presence of a particular neurotransmitter's creation and utilisation. Similarly, an excess in a precursor of a particular neurotransmitter can partly explain why levels of that neurotransmitter are too high.
Precursors to Dopamine (DA), Adrenaline (A) and Noradrenaline (NA) - DOPA, Phenylalanine, Tyrosine
Precursors to Serotonin (5-HT) - 5-HTP and Tryptophan
Precursors to Acetylcholine (Ach) - Phosphatidyl Choline, Acetyl group amino acids such as Acetyl-L-Carnitine (ACL) or N-Acetyl-L-Cysteine (NAC)
Various neuroactive substances are involved in different aspects of nervous system functioning. These are classified as neuromodulators and neurotransmitters. Some of these substances are examined below.
Phenylethylamine - indirect sympathetomimetic displacing NA and DA from their cells
Ascorbic acid (Vitamin C) - anti-oxidant; pro-oxidant in high levels
N-Acetyl-dopamine - marker of acetylation, associated with anti-cancer process
N-Acetyl-5-OH-tryptamine - direct melatonin precursor
Adenosine - ATP precursor, inhibitory neurotransmitter, high levels also indicate low insulin levels
Histamine - mediator of allergic and pain reactions, also a potent vasodilator
O-Methyl-Serotonin - anti-cancer properties
Kynurenic acid - inhibitor of excitation, antagonist of the neurotoxin -quinolinic acid)
N-Methyl-D-Aspartic Acid (NMDA) - an excitotoxin that mimicks the action of Glutamate; downregulates the GABA pathway and promotes the influx of Calcium and Nitric Oxide into cells, increasing Peroxynitrite levels
Substances which mimmick the effects of neurotransmitters may contribute to certain neurotransmitters being outside their reference ranges and other possible harmful effects.
The presence of neurotoxins may cause neurological damage as well as potentially causing certain neurotransmitters to be outside their reference range.
Bufotenine
5-7-Dihydroxytryptamine
Epinine - acts like Dopamine
6-Hydroxydopamine
Indole-acrylic acid
Indican
Methylated-5HT-derivatives
N-Methyl-R-Salsolinol
Nitro Serotonin derivative
Nitro-tyrosine
Phthalates
Quinolinic acid
Tartaric acid
THP
Lipofuscin, a lipid waste molecule, that tends to accumulate in the cellular membranes of the brain, heart and lungs with age, can block neurotransmitter release in the nervous system. It is not a toxin in of itself, but can accelerate cellular degeneration and ageing by dehydration and overheating.
Other possible explanations as to why certain neurotransmitters are outside of their reference ranges include:
Utilisation (and therefore destruction) of the neurotransmitter is much faster than its production, resulting in a low level of that neurotransmitter
Utilisation (and therefore destruction) of the neurotransmitter is much slower than its production, resulting in a high level of that neurotransmitter
Transformation of a neurotransmitter into it's false form on account of a fungal/yeast infection
Destruction of a neurotransmitter on account of the presence of a viral infection
Destruction of a neurotransmitter on account of the presence of a bacterial infection
Suppression of a neurotransmitter by other neurotransmitters or neurochemicals
Decreased oxygen supply to some parts of the brain
The interrelationships of the different neurotransmitters and indeed hormones, and the biochemical processes the lead to the creation and regulation are extremely complex (endocrine system, bodily hormonal regulation, neurological system and brain chemistry). It is extremely complex and finely balanced. Too much or too little can be very damaging for the nervous system. If this is a subject that interests you, we would strongly encourage further reading.
Gamma-aminobutyric acid (GABA) 'is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays an important role in regulating neuronal excitability throughout the nervous system.'
L-Glutamate (or Glutamic acid) is the most important excitatory neurotransmitter in the brain and plays an important part in brain chemistry. It is released by many different types of neurons and stimulates other neurons at the synapses. The excitatory neurotransmitters act to stimulate the next neuron (i.e. postsynaptic neuron) to fire an electrical impulse.
Inhibitory neurotransmitters tend to inhibit firing of neurons. The most important of these is GABA, which is synthesised from Glutamine in the presence of Active Vitamin B6 (P5P). GABA is examined more on the Adrenal and Endocrine Systempage. Taurine is another, which performs many vital functions in the body, including nutritional metal transport into the cells. Taurine is examined in more detail on the Nutritional Deficiencies page.
GABA and Glutamate levels are balanced in the brain both in terms of absolute concentrations and relative ratios in a healthy individual. A P5P deficiency can thus result in an elevated Glutamate to GABA ratio in the brain and elevated levels of excitotoxicity. Excitotoxicity is the term used when the levels of the excitatory neurotransmitters are too high, at which point the level of neuronal activation or induced firing of neurons become neurologically damaging. Excitotoxins, specifically free glutamate, and the neurological damage they can cause, are examined on the Excitotoxins section on the Nutritional page, with respect to Glutamate and MSG.
Whilst Glutamic acid (Glutamate) and Aspartic acid (Aspartate) are excitotoxins, and part of the excitatory pathway, molecules such as GABA (and Taurine) are part of the inhibitory pathway, and in a healthy human work in a fine balance. Both GABA and Glutamic acid are manufactured from Glutamine. Please see the Glutamine and Glutamic acid section on the Nutritional Deficiencies page for more information. CFS and ME are believed to be hyper-excitory states, often with insufficient GABA production, resulting in neurological damage over time. Excessive free glutamate and MSG consumption in such cases is clearly an extremely a very bad idea.
'Glutamate and GABA (gamma-aminobutyric acid) are the brain's major "workhorse" neurotransmitters. Over half of all brain synapses release glutamate, and 30-40% of all brain synapses release GABA. Since GABA is inhibitory and glutamate is excitatory, both neurotransmitters work together to control many processes, including the brain's overall level of excitation. Many of the drugs of abuse affect either glutamate or GABA or both to exert tranquilizing or stimulating effects on the brain.'
GABA is produced in the brain. Long term excess may result in memory difficulties, impairment of muscular movement, breathing problems, immune system imbalance and the onset of various pathological conditions. Long term deficiency is very often associated with memory problems, anxiety, insomnia, immune system imbalance and behavioural problems.
Studies on mice have revealed that the heavy metal Mercury increases the release of endogenous glutamate, inhibit glutamate uptake, reduce mitochondrial activity, and decrease ATP levels.
'Mercury compounds disrupt neuronal glutamate transport in cultured mouse cerebellar granule cells', Elena Fonfria, M.Teresa Vilaro, Zoila Babot, Eduard Rodriguez-Farre, Cristina Sunol (2004).
Catecholamines are a group of neurotransmitters (often referred to as 'stress hormones') manufactured from the amino acid Tyrosine. These are faster acting than the hormone Cortisol, discussed above.
Noradrenaline (NA), also known as Norepinephrine, is another major neurotransmitter that aids in the regulation of attention and is a component in the fight or flight response. It normally produces effects such as increased heart rate, increased blood pressure, dilation of pupils, dilation of air passages in the lungs and narrowing of blood vessels in non-essential organs. It is also produced in the brain. Long term excess may lead to increased blood pressure, cellular/tissue inflammation, hyper-thyroidism and even panic attacks. Long term deficiency may cause impaired cognitive functions, behavioural problems, immunological imbalance, hypothyroidism and the onset of various pathological conditions.
Adrenaline (A), a.k.a. Epinephrine, is another component of the short term fight or flight physiological response. It is the hormone secreted in the adrenal gland that raises blood pressure, produces a rapid heartbeat, promotes the release of glucose from the liver, and acts as a neurotransmitter when the body is subjected to danger or stress. It is also produced in the brain. Long term excess may lead to anxiety, cardiovascular issues, accumulation of abnormal cells in the body and problems associated with glucose utilisation. Long term deficiency may result in fatigue, depression, the accumulation of abnormal cells in the body and digestive problems.
Dopamine is a neurotransmitter and also precursor to noradrenaline and adrenaline. It is primarily manufactured by the adrenal glands and also in the nervous system.
'Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment and reinforcement to motivate a person proactively to perform certain activities. Dopamine is released (particularly in areas such as the nucleus accumbens and prefrontal cortex) by naturally rewarding experiences such as food, sex...and neutral stimuli that become associated with them.'
'Low levels of dopamine can cause depression, loss of motor control, loss of satisfaction, addictions, cravings, compulsions, poor attention and focus. When dopamine levels are elevated symptoms may manifest in the form of anxiety, paranoia, or hyperactivity.'
Dopamine is also produced in the brain and kidney. Long term excess is very often associated with over-activation of the immune system, inflammation, and hormone imbalance. Long term deficiency may cause impairment of certain muscular movement, memory problems, mood swings, immunological and hormonal imbalances, kidney issues and even development of certain pathological medical conditions.
Acetylcholine (Ach) is one of the major neurotransmitters and is essential for brain development. Its functions include muscle activation and a neuro-modulator for plasticity and excitability. It is produced in the brain.
Long term excess of Acetylcholine may be associated with exhaustion of pancreatic activity, inflammation of tissues/cells, auto-immune disorders, behavioural problems and the onset of various pathological conditions. Long term (and also short term) deficiency may result in decreased learning ability, decreased mental awareness and decreased memory function.
The heavy metal Mercury impairs Acetylcholine Esterase (a.k.a. Acetylcholinesterase) function. Acetylchloine Esterase is the enzyme that allows deactivation of cholingeric neurons to return to resting state after activation. Thus, if Acetylchloine Esterase function is inhibited by Mercury, then levels of Acetyl Choline may build up, causing continuous stimulation of the muscles, glands and central nervous system. Mercury can also inhibit impair cholinergic metabolism (i.e. metabolism relating to Acetyl Choline). See the Toxicity page for more information.
The above diagram is a simplification of the conversion of the main neurotransmitters. There are however a number of alternative pathways in catecholamine metabolism, resulting in the creation of various metabolites. The complete pathways are discussed below (Source: Genova Diagnostics' Optimum Nutrition Evaluation report).
Phenylalanine (amino acid), the precursor to Tyrosine, is converted to Tyrosine by the Phenylalanine hydroxylase (PAH) enzyme using molecular oxygen and Tetrahydrobiopterin (BH4) as substrates.
Tyrosine (amino acid, a.k.a. TYR), if converted at all, is always converted to the neurotransmitter L-DOPA by the Tyrosine Hydroxylase (TH) enzyme using Tetrahydrobiopterin (as BH4) and B3 as NADPH.
Dopamine can either be converted to the neurotransmitter Noradrenaline (Norepinephrine) (with Cu and ascorbate); or it can be converted to the metabolite 3-methoxy-tyramine and then Homovanillic Acid (using MAO (B2 as FAD)).
Noradrenaline (Norepinephrine) can be converted to either the neurotransmitter Adrenaline (Epinephrine) (using CH3 (SAM, methionine, Mg)); or the metabolite Normetanephrine (using Mg, CH3 (SAM, methionine, Mg)).
Adrenaline (Epinephrine) is converted to the metabolite Metanephrine (using CH3 (SAM, methionine, Mg)).
Normetanephrine is converted to the metabolite 3-methoxy-4-hydroxy-phenylglycoaldehyde (using MAO (B2 as FAD)).
3-methoxy-4-hydroxy-phenylglycoaldehyde is converted to either the metabolite 3-methyl-4-hydroxyphenylglycol (using B3 as NAD) or the metabolite Vanilmandelic Acid (using B2 (as FAD), Mo, Fe).
Let us examine the example of Vanilmandelic Acid (VMA or 3-methoxy-4-hydroxymandelic acid), a metabolite detected in the Neuro-Lab Analysis of Brain Chemistry (Comprehensive) and the Genova Diagnostics' Optimum Nutrition Evaluation. VMA is a normal urine metabolite of the adrenal catecholamine noradrenaline (norepineprine). It is one of two possible end metabolites of Norepinephrine that can be measured.
Subnormal VMA levels may occur in mental depression, mood swings, bipolar disorders, or other conditions or illnesses relating to catecholamine insufficiency or imbalance. Low VMA can be a downstream result of the deficient formation of its upstream counterparts, whether this is a low level of dietary tyrosine ingested, or deficient formation of DOPA, dopamine or noradrenaline; deficient methylation of S-adenosylmethionine (SAM); MAO inhibition; or perhaps even excessive conversion into adrenaline. Nutritional factors related to deficient production of noradrenaline include inadequate levels of: phenylalanine, Pyridoxal-5-Phosphate (active vitamin B6), ascorbic acid and copper. Copper is also a cofactor for the enzyme dopaimine beta-hydroxylase which is involved in the conversion of dopamine to noradrenaline. In those with a Copper deficiency, noradrenaline (and adrenaline) formation can be slow or erratic. Fatigue may also be present if the required adrenaline stimulus of glycogenolysis is deficient.
Elevated VMA levels may occur in cases of Neuroblastoma (Neuroblastic tumors) - cancer of the Adrenal Medulla. Please see the Tumors section below for more information.
Excessive Vanilloid Receptor stimulation is one possible contributary factor to elevated Nitric Oxide levels, which could result in the instigation of the NO/ONOO- cycle (i.e. elevated Peoxynitrite levels and oxidative stress). Please see the Nitric Oxide, Superoxide and Peroxynitrite page for more information.
Methylation is a requirement for the metabolism (i.e. synthesis) of catecholamines. If one's methylation capability is impaired for nutritional or other reasons, then one's catecholamine metabolism will become impaired, with numerous other knock on effects on the body and indeed the brain. Adrenaline is first methylated by S-adenosylmethionine (SAM), requiring an enzyme activated by magnesium. The resulting metabolite metanephrine is then oxidised (deaminated) by the enzyme monoamine oxidase (MAO). This step requires vitamin B2 in the coenzyme (redox cofactor) form Flavin Adenine Dinucleotide (FAD).
Aldehyde dehydrogenase then removes hydrogen to form VMA, requiring vitamin B2 as FAD, iron, molybdenum and vitamin B3 in the coenzyme (oxidising agent) form Nicotinamide Adenine Dinucleotide (NAD+).
Serotonin is another precursor to melatonin. Serotonin is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS), i.e. brain, and enterochromaffin cells in the gastrointestinal tract. Seratonin molecules are secreted into nerve cell conjunctions called synapses and are reabsorbed once they have carried their 'information' across the synapse. Seratonin is produced by the conversion of the amino acid tryptophan and 5-hydroxytryptophan (5-HTP), mainly in the digestive tract but also in the pineal gland. Within the brain, the pineal gland is the richest site for serotonin production in the brain. In the central nervous system, serotonin plays an important role as a neurotransmitter in the modulation of anger, aggression, body temperature, mood, sleep, sexuality (e.g. erection and ejaculation), appetite, and metabolism, as well as stimulating vomiting. Serotonin is a hormone that makes us feel good and calm naturally. It helps the mind to calm down so that one can fall asleep easily and stay asleep.
As a general rule, when serotonin levels are high, melatonin levels are low and vice versa. Clearly if serotonin levels are extremely low around the clock, then there is less serotonin to convert to melatonin, so melatonin levels are often low as a result also. The relationship between serotonin and melatonin production is examined on the following web site.
Long term excess of serotonin may result in cardiovascular problems, hormonal and immunological imbalances and even behavioural problems. Long term deficiency of serotonin may result in depression, stress, insomnia (i.e. too little melatonin production, inflammation, gut problems, hormonal imbalances, immune system imbalances and the onset of various pathological conditions. As melatonin is produced from serotonin, then if the body does not produce enough serotonin, there is not going to be enough melatonin being produced either.
Serotonin and Melatonin are both manufactured by the body from the amino acid Tryptophan. The diagram below is a simplification of Serotonin Metabolism and neurotransmitter conversion.
A more comprehensive view of the Serotonin branch of the above diagram can be seen in this second diagram below.
Some of the additional conversion pathways and resulting metabolites in Serotonin Metabolism are listed below.
Tryptophan (amino acid), if converted at all, is always converted to 5-hydroxytryptophan (amino acid, intermediate, serotonin precursor) (using Fe, B3 as NADPH, biopterin)
5-Hydroxytryptophan (5-HTP) if converted at all, is always converted to the neurotransmitter Serotonin (a.k.a. 5-hydroxytryptamine or 5-HT) (using P5P).
Serotonin, if converted at all, is converted into one of 3 byproducts:
Melatonin (N-acetyl-5-methoxytryptamine) (using Acetyl, CoA (Mg, Cysteine, B5)) (then using CH3 ((SAM), (methionine, Mg))
5-Hydroxyindoleacetic Acid (using P5P, MAO (B2 as FAD))
5-methyloxy-3-indoleacetate (using CH3 ((SAM) (Methionine, Mg))) (then using P5P, MAO (B2 as FAD))
As has been stated above, one cannot produce significant amounts of Melatonin if one does not first have any Serotonin. And the ability to convert from one form to another is dependent on a number of nutritional cofactors and coenzymes. 5-HTP can be taken in supplemental form, but it needs to be converted into Serotonin and then Melatonin to be effective. Similarly, throwing more dietary L-Tryptophan is not necessarily going to boost Serotonin or Melatonin levels if those pathways are impaired.
Adequate levels of Active B3 are often not present in CFS patients, meaning that conversion from Tryptophan to 5-HTP may be impaired. Inadequate levels of P5P (Active B6), a frequent occurrence in CFS patients, may also result in a reduction in efficiency of converting 5-HTP to Serotonin. In addition, the conversion of Serotonin into Melatonin or other metabolites is dependent on the process of Methylation, which is often impaired in individuals with CFS, for example.
It can be seen that it is more sensible to supplement 5-HTP than L-Tryptophan because it saves on one conversion step in its metabolism. In the same way that active forms of B-vitamins are more useful than than non-active forms, as they do not have to be converted to the form that is actually used by the body; and can be utilised as they are; or at least with the minimum of steps.
The heavy metal Mercury blocks the 5-HT2 Serotonin receptors.This will have a serious effect on the utilisation of Serotonin in the body. Please see the Toxicity page for more information.
Adrenaline stress is generally that the state which is a result of the increase in secretion of adrenaline into the blood stream from the adrenal medulla - the centre of each adrenal gland. It is often the result of a long term 'fight or flight' response, i.e. prolonged overactivity of the Sympathetic Nervous System. In rare cases it is the result of Adrenal Pheochromocytomas (adrenal medulla tumors). Adrenaline stress has profound, adverse effects on physical, emotional and mental health. These arise because of the following effects of elevated Adrenaline levels:
Persistent release of glucose from the liver, stimulated by presence of adrenaline. Blood sugar levels may be increased (hyperglycaemia) if there is an insulin deficiency or insulin resistance. Glucose can also appear in the urine (glucosuria) when the levels of cortisol and/or thyroid hormones become elevated. In such cases, the ability of the kidney to retain glucose is impaired. Any long-term hyperglycaemia and glucosuria will have adverse effects on the brain and body functioning. Some of the glucose could be converted into fat, but of course, an accumulation of excesive fat in some parts of the body can also be very detrimental to health. An increase in the supply of glucose to the brain will result in the over-production of some neuroactive substances which create an imbalanced functioning of the brain. This has a knock on effect in terms of hormonal, gastro-intestinal, cardiovascular and immunological problems.
Regular stimulation of the beta-adrenergic receptors by adrenaline. These receptors are found on the cells of the heart, lung, skeletal muscles, brain-stem and blood vessels. When these beta-adrenergic receptors are over-active, excitatory signals are generated in these parts of the body and brain. This results in an increased heart rate or abnormal heart rhythms (often observed in CFS patients), anxiety, migraine and muscle tremor, with a corresponding increase in blood circulation and lung function. In many cases, an excessive supply of oxygen to a cell will stimulate oxidation. If there is a deficit in the levels of antioxidant protection (i.e. SOD and Glutathione) in the cells, then excessive oxidation will lead to free radical damage and oxidative stress (OS), which is a major mechanism of many disease conditions (e.g. diabetes, cancer, cardio-vascular and neuro-degenerative diseases).
Regular release of vital immunological and blood cells from the bone marrow. This regular activation of the release mechanism occurs when the beta-adrenergic receptors located on the bone marrow become up-regulated (i.e. activated) by adrenaline. This eventually results in lympho-proliferative syndrome, for example, an increase in the levels of CD4-, CD8- and TCR-alpha-beta+ T lymphocytes and B lymphocytes. CD4- and CD8- T-helper cells are not able to self-tranform into effective T-helper cells in response to antigens. Insufficient immunmunity against foreign infections is a real possibility.
As discussed on this page, the glands of the endocrine system can become depleted, worn out and function very poorly. Poor blood circulation to these areas may also be present. It is not uncommon for some CFS sufferers feel cold in the kidney area, indicating a reduction in blood (and hence Qi) circulation to that area. According to Dr Paul Cheney's Cardiac Insufficiency Hypothesis, blood circulation to the thyroid gland is sacrificed first in the sequential sacrifice of blood supply to the various organs/systems of the body, in order to preserve blood pressure and to protect the heart, which has a decreased/decreasing mitochondrial function and hence output. Of course, this pattern does not fit every CFS case. However, the general theme does seem to suggest blood circulation problems to the endocrine system glands in many such cases.
Tumors present on the actual glands, typically the adrenal cortex or the thyroid gland, are not that uncommon, in the population as a whole, and indeed in CFS cases. Most tumors of the endocrine system glands (e.g. adrenal glands or thyroid gland) are benign and are not malignant (cancerous), although clearly their presence does tend to indicate that there is a problem in that area, and most probably wider ranging too, regardless of whether they are benign or malignant.
The exact mechanism of tumor formation is clearly very complex. Many proponents of natural medicine point to the gradual accumulation of Toxins in the body, which can cause conditions like breast cancer tumors or brain tumors etc. It is clearly some complex combination of factors, including general biochemical impairment, but more specifically, of the immune system. Poor blood/lymph circulation is in many ways equivalent to a poor immune system, as the blood itself carries immune system cells and proteins to the afflicted areas. In addition, dysbiotic and harmful microbial activity is often associated with low oxygen environments and poor blood circulation, the majority of such organisms being anaerobic in nature. Contrary to the beliefs of the majority of the population, tumors do not just 'come out of nowhere', and there are likely to be factors other than genetics and 'bad luck' operating, including a variety of environmental and dietary factors, and internal biochemical imbalances. Most medical researchers are still unclear as to the main reasons for tumor formation for many specific types of tumor.
As can be seen below, hormone and neurotransmitter testing, as well as the testing for neurotransmitter metabolites, can provide valuable information when possibly detecting the potential influence of a tumor one's endocrine system dysfunction. Most CFS cases probably do not involve glandular tumors but it is likely because of the numerous factors mentioned above that they may well be more likely than the 'average' person to develop such a tumor, which can further complicate one's condition.
Adrenocortical adenoma, a type of benign tumor of the adrenal cortex, is quite common, and is found typically in 1-10% of persons at autopsy. It can result in a variety of endocrine system disturbances, producing glucocorticoids, mineralcorticoids and/or sex steroids, resulitng in conditions such as Cushing's syndrome (hypercorticism, i.e. elevated Cortisol levels), Conn's syndrome (hyperaldosteronism, i.e. elevated Aldosterone levels), inappropriate sexual hormone shift (i.e. virilisation of females and feminisation of males), and precocious (early) puberty.
Adrenocortical adenoma's counterpart, Adrenocortical carcinoma (ACC), is a highly aggressive form of cancer of the adrenal cortical cells. Statistically it is not that significant, as it affects 1-2 people per million of population.
The adrenal medulla, located at the centre of each adrenal gland, can be afflicted by two main types of tumor. The adrenal medulla is primarily responsible for producing Adrenaline (Epinephrine).
The first of these is Neuroblastoma, an aggressive form of cancer of immature neuroblastic cells. Neuroblastic cells as the precursors of neurons or nerve cells. It's prevalence is quite rare, with 650 new cases reported in the USA annually. It mainly afflicts young infants, but also tends to afflict the elderly. Physically it can be identified in its later stages as a rapidly enlarging abdominal growth (from the kidney area). Neuroblastic tumors tend to produce extremely elevated levels of precursors to the stress-associated neurotransmitters, the Catecholamines. The main precursors that are elevated in such circumstances are Vanillylmandelic Acid (VMA) and Homovanillic Acid. Please see the
Catecholamines section above for more information about VMA. Neuroblastoma may also produce severely watery (vasoactive intestinal peptide-based) diarrhea.
Pheochromocytoma is a neoplasm (abnormal proliferation of cells) similar to the chromaffin cells of the mature adrenal medulla. 90% of Adrenal Pheochromocytomas are benign, the other 10% being malignant. Approximately 0.5% of newly diagnosed patients with hypertension (elevated blood pressure) have pheochromocytoma. The most common age group for the afflicted is 30 to 40 years of age. Pheochromocytomas tend to produce very large amounts of of the catecholamines (stress hormones) Adrenaline (Epinephrine) and Noradrenaline (Norepinephrine). Whilst the Pheochromocytoma may itself not be life-threatening, the downstream effects on the endocrine system, blood pressure and cardiac arrhythmia, in certain cases. Symptoms may include some of those that are often associated with Adrenaline Stress, including headaches, palpitations, anxiety attacks, sweating, weight loss and tremors. Adrenal Pheochromocytomas also tend to produce elevated levels of the Catecholamine metabolites VMA and metanephrines (an Adrenaline/Epinephrine metabolite).
Thyroid cancer or neoplasm usually refers to four different kinds of malignant tumors of the thyroid gland:
- papillary
- follicular
- medullary
- anaplastic
The former two types are the most common. Their growth is slow, and may recur, but are in general not fatal to the under 45s. Anaplstic umors are fast-growing and aggressive. Thyroid nodules are in general detected by ultrasound guided fine needle aspiration (USG/FNA). Typical conventional treatments include radioactive iodine supplementation and also high dosage Thyroxine (T4) therapy.
Many adults have small nodules in their thyroids (on the throat). 95% of these nodules are benign. According to the Annals of Internal Medicine (1998), approximately 4-7% of the US popuation has benign thyroid modules.
www.annals.org/cgi/content/full/128/5/403
However, the other 5% of these thyroid nodules are malignant. Thyroid cancer in the early stages takes the form of such a malignant nodule. Statistics for the USA show that thyroid cancer affects 0.01% of the population (of those detected). Malignant nodules tend not to secrete thyroid hormones.
Thyroid nodules tend to occur concurrently with hypothyroidism (often associated with an autoimmune condition, or Iodine deficiency, insufficient thyroid blood circulation (Cardiac Insufficiency, or too much Iodine uptake by the tumors), but also hyperthyroidism (e.g. Toxic Thyroid adenoma: benign tumor) and hypothyroidism.
Those suffering from severe adrenal dysfunction and mitochondrial disorders may not deal with stress very effectively, on account of rapid mitochondrial depletion and ATP to ADP blocking, and also either not producing enough stress hormones when they are needed or not utilising or responding well to the quantity of stress hormones produced. This may be triggered by a single short event, certain types of social interaction, or simply overdoing things physically without a break, concentrating or studying for too long, or other causes.
In many cases, because the body did not produce enough adrenal hormones when they were needed, it may overcompensate after the event by continuing to produce them. The result may be a variety of unpleasant feelings including anxiety, stress, buzzing headache, inability to relax (no matter what relaxation techniques are tried), breathlessness, 'alertness' (like a sensation of being alert and awake but unable to function), the 'shakes', inability to concentrate, mental and physical weakness, inability to feel good (drop in serotonin), inability to fall sleep or even stay asleep, feeling of 'impending doom', and/or an overall awful 'impaired but hyped up' sensation.
This sensation may occur shortly after the initial trigger has been and gone and may last minutes, hours or in some cases a day or number of days. It is an involuntary rollercoaster ride which is highly unpleasant. Ironically, because the sensation often occurs after the trigger has been and gone, the person may assume a false confidence that he or she is able to weather this trigger or event and has the strength to deal with it, and may not choose to avoid the situation. It is usually only after the situation has been or towards the end of the event that the person may realised he has 'overcooked it'. A very slight sensation of the above may start to manifest itself, and is a warning to the person to stop immediately whatever they are doing that is making them ill. And if the person does not stop whatever it is he or she is doing that the body is no longer able to cope with, the sensation will usually intensify more quickly or become much worse when it does arrive in full force. Depending on the individual, the sensation 'adrenal burnout after effect' (hormonal chaos) may gradually turn from those described above to just fatigue, weakness and headache (with the adrenal part dissipated) after several hours/days, indicating a major drop in the body's overall qi levels and hormone levels. The exact nature and severity of the sensations and pattern clearly vary from individual to individual.
The sensation is very frustrating and may in some cases trigger an anger response or negative mood swing. Especially when it seems that the body never really recovers in between and a hundred or thousand such 'crash' cycles are experienced. Individuals with such severe adrenal disorders and mitochondrial dysfunction may either frequently 'crash' or may try to avoid the situations that cause it to happen in the first place (which is often only a partially successful strategy) or a bit of both, and may become depressed as a result of experiencing these cycles over many years. It is advisable to seek appropriate treatment before one's condition deteriorates to this extent. This is discussed below.
The pineal gland, in conjunction with the adrenal glands, governs the body's day and night cycles (circadian rhythm), i.e. body clock. The pineal gland is supposed to produce its peak melatonin output at bedtime, at around 11pm normally. The adrenal glands are supposed to produce their peak amount of cortisol and other stimulatory neurotransmitters in the morning, and to stop production during the night. The problem is where the pineal gland is not producing enough melatonin. The brain does not calm down as easily and it is harder to fall asleep. Equally, if not enough serotonin is produced, then the person will not feel relaxed enough to fall asleep either. Strong light has been shown to reduce melatonin production and increase seratonin production, and so artificial light late in the evenings or switching on a light in the bathroom to urinate in the middle of the night will make it harder to get to sleep again, as relatively high melatonin levels are required to get to sleep and stay asleep during the night. It is only when the levels of melatonin drop off in the morning that the body signals the brain to wake up and stay awake (for the day to come).
Feeling good and awake in the morning and during the day is a result of a complex combination of stimulatory and other neurotransmitters, and the absence of melatonin. Those patients with adrenal hormone insufficiency, the right balance and quantities of cortisol, noradrenaline and serotonin are not produced during the day, causing the person to feel fatigued and unable to deal with stress effectively, resulting in frequent 'crashes'. Because not enough cortisol is produced during the day, the adrenal glands are still producing cortisol, noradrenaline and often excessive adrenaline at night. This is coupled with the lack of melatonin being produced at night, meaning that the person wakes frequently, feeling awake and finds it very difficult to get back to sleep. Such a person may sleep a couple of hours a night, waking up anywhere between once and ten times a night, and perhaps only half-sleeping most of the night. During some nights, if the person is not able to deal with a source of stress adequately during the day or evening, on account of too few stimulatory neurotransmitters, it is likely that the person will be producing these during the night to compensate and get no sleep at all. This is the feeling where one knows that one won't get a wink of sleep all night when one goes to bed. See the CFS web page on insomnia for tips on effectively managing insomnia. The net effect is that the person cannot cope well with stress, has not had a proper night's sleep since the condition began (in turn making the condition worse - a downward spiral) and feels shattered all day.
The good news is that hormone and neurotransmitter imbalances and deficiencies can be effectively treated. This is normally a case of stimulating one or more specific conversion pathways which are not functioning correctly or sufficiently. Identifying what conversion pathway is impaired will tell us what broad category of treatment to pursue. Treatment can be performed through a variety of methods, homeopathically, nutritionally, adaptogenic herbs and plant/fish/animal extracts, through therapies that work on the body's electromagnetic field as outlined on the electromagnetic page and therapies that work on the body's qi (energy) levels as outlined on the energetic therapies page, light therapy, NLP Techniques (e.g. Amagdala Retraining), as well as brain wave entrainment technologies (particularly those that focus on Theta wave frequencies). These same treatments and supplements are often used to treat women with menopausal problems. One should also consider boosting mitochondrial function, which will have a positive knock on effect on the endocrine system.
L-Phenylalanine (PHE), the amino acid precursor to L-Tyrosine, which is itself a precursor to the neurotransmitters Dopamine and the Catecholamines. If Phenylalanine levels are low (have an amino acid analysis performed to verify), then supplementation with Phenylalanine or consuming Phenylalanine-rich foods may help. PHE-rich foods include poultry, meats, fish, soy beans, dairy, nuts and seeds (also the artificial sweetener Aspartame - but this is not recommended!)
L-Tyrosine (TYR) supplementation - if Tyrosine levels are low (c/f amino acid urine analysis), then one may benefit from TYR supplementation. However, just because Tyrosine levels are low does not mean that low levels of its precursor, Phenylananine, are to blame. It could be a problem with conversion of PHE to TYR, e.g. a B3 deficiency or lack of Tetrahydrobiopterin (BH4 - not recycled/regenerated from its oxidised form of Biopterin). Be that as it may, one may elect to bypass the limitation of the conversion process and simply put more TYR into the body. L-Tyrosine may be supplemented directly. Another type of TYR supplement is Acetyl-L-Tyrosine which is reputed to be more effectively absorbed into the nervous system and brain than simply L-Tyrosine. Many adrenal herbal supplements contain added Tyrosine - check the ingredients.
If total Tetrahydrobiopterin (BH4) levels are too low, then eating more purine-rich foods may help - as it is synthesised from Guanosine Triphosphate, a purine nucleotide. Too high a purine intake can of course result in Gout. In addition, as BH4 is claimed to be used up in lowering the body's ammonia levels (ammonia being produced when protein is digested), then one may want to limit one's total daily protein intake to RDA levels or thereabouts in order to preserve one's BH4 as much as possible. Biopterin can also be directly supplemented, e.g. Cardiovascular Research's Norival product, which contains 25mcg of Biopterin as well as N-Acetyl-L-Tyrosine and B6. Norival contains Biopterin to assist in the conversion of Tyrosine to L-DOPA. See the Immunity page for more information on BH4.
The amino acid S-Adenosyl methionine (SAM) or Methionine and Vitamin B12 (Methyl-B12 is an active form of B12) to assist in the methylation processes of Catecholamines and Melatonin.
B-vitamins, especially Pyridoxal-5-Phosphate (P5P - active Vitamin B6); 5-Methyl-TetraHydroFolate (5MTHF) (active Vitamin B9); Flavin Mononucleotide (FMN) (an active form of Vitamin B2); Nicotinamide Adenine Dinucleotide (NAD) (an active form of Vitamin B3 - also available in NADH form); and also Pantothenic Acid (Vitamin B5 - or as Pantothene form). 5-MTHF, B12 and P5P are best taken together as they work on similar processes.
Phosphatidyl Choline (Lecithin), N-Acetyl-L-Cysteine (NAC), Acetyl-L-Carnitine are all precursors to Acetylcholine (Acetyl Choline).
Phosphatidyl Serine (PS) is a component of cell membranes, which is derived from Soy Lecithin. As well as helping to repair cell membranes, it also acts to facilitate the repair of the cortisol receptors in the hypothalamus. It is believed that cortisol receptors become damaged by elevated cortisol levles, reducing the ability of the hypothalamus to detect and correct excessive cortisol levels.
Essential minerals, and in particular Magnesium, Potassium, Calcium, Sodium, Manganese etc. and trace minerals such as Copper
Iodine
etc.
Of course, your nutritional requirements depends on what amino acids and nutrients are deficient in your body, and one should aim to look at what is deficient or too high, rather than just arbitrarily taking the above because you feel tired and believe you do not produce enough neurotransmitters. There may be other reasons why you are not producing enough neurotransmitters and hormones, even though enough precursors and cofactors are available in your body. It may not be the raw ingredients that are deficient but substances associated with the pathway of production that may be relevant.
Those suffering from circadian rhythm problems are often chronically deficient in magnesium and P5P (Vitamin B6). B6 is required as part of the production of melatonin, and a chronic deficiency in B6 can often result in sleeping problems. B-vitamin requirements and amino acid conversion is examined on the Nutritional Deficiencies page, in the Amino Acid Conversion and Homocysteine Metabolism sections.
'Food sources of dopamine increasing tyrosine include almonds, avocados, bananas, dairy products, lima beans, pumpkin seeds, and sesame seeds. Dopamine is easily oxidized. Foods that are rich in antioxidants such as fruits and vegetables may help protect dopamine-using neurons from free radical damage. Many healthcare professionals recommend supplementing with vitamins C, vitamin E, and other antioxidants. Foods such as sugar, saturated fats, cholesterol, and refined foods interfere with proper brain function. Consumption of saturated fats and cholesterol should also be reduced because they can clog the arteries to the brain, heart, and other organs. Caffeine must also be avoided by persons with depression. Caffeine is a stimulant which initially speeds up neurotransmission, raises the amount of serotonin, and elevates mood.'
The term adaptogen is used by herbalists to refer to a natural herb product that is proposed to increase the body's resistance to stress, trauma, anxiety and fatigue. Adaptogns help to restore the hypothalamic cortisol receptor sensitivity. In the past, they have been called rejuvenating herbs, qi tonics, rasayanas, or restoratives. In Traditional Chinese Medicine they are often referred to as 'Qi tonics'.
Adaptogens are useful for balancing the endocrine system as well as boosting the immune system (white blood cells).
Examples of such adaptogenic herbs and extracts are listed below.
bovine (cow) or porcine (pig) glandulars, including adrenal cortex, pituitary, orchic and hypothalamus glands. Product containing such extracts include Nutri-West Core Level Adrenal, Enzymatic Therapy (Fatigued to Fantastic)'s Adrenal Stress End, NutriCology Dr Wilson's Dynamite Adrenal, and perhaps even Maxam Labs CRS (ingredients not known - not tested by me either) etc.
Stabilium, a.k.a. Garum Amoricum, a fish extract and an ancient remedy for stress and fatigue.
Herbs:
Licorice (liquorice) Root Extract (Glycyrrhizin)
Gotu Kola
Rhodiola rosea root extract
Chamomile flower extract
Shativari
Ashwaghanda root extract
Schizandra berry extract
Holy Basil (Ocimum sanctum a.k.a. Tulsi) leaf (containing triterpenoic acids - including ursolic and oleanolic acids)
Eleuthero root extract (e.g. all above herbs contained in Jarrow Forumulas' Adrenal Optimiser)
Ginseng (the various types of ginseng have different properties, including hot or cold energy etc.)
Cordyceps sinensis (caterpillar fungus), e.g. in dedicated supplements or in a combination supplement such as Metagenics Adreset
Echinacea
Ginkgo biloba
Dong quai (Angelica sinensis)
Gynostemma pentaphyllum (a.k.a. Jiaogulan, Amachyasuru or 'Immortality Herb'), e.g. Organic Jiaogulan or China Life's Amachazuru Five Leaf Tea
Astralagus
Royal Jelly
Lingzhi mushroom, also known as Chinese Wild Red Reishi Mushroom, Wild Ling Zhi, Ganoderma Lucidum, Lingzhi, ling zhi,rei shi or yeongji.
Traditional Chinese Medicine (TCM) herbs and tonics, mainly of Chinese origin, but not necessarily, some of which actually include the above herbs, but balanced with other herbs, and indeed considering the whole body, other organs, hot/cold energy, dampness and meridians as a whole etc. rather than just the adrenal glands and thyroid as many western herbalists would focus on in this context. In the long term TCM is probably most effective at a permanent resolution.
It is extremely important to note that the above adaptogenic herbs and extracts generally tend to stimulate the adrenal glands in a broad spectrum manner, perhaps with some exceptions. If your adrenal glands are consistently producing too little of all the main neurotransmitters, i.e. Adrenaline, Dopamine Noradrenaline and the hormone Cortisol, then stimulating the adrenal glands with adaptogens would probably be quite sensible. However, if one's neurotransmitter production is severely out of balance, e.g. there is very little Dopamine or Noradrenaline being produced, but Adrenaline production is sky high (e.g. 10 times higher than the normal maximum reference range limit), then stimulating the adrenal glands would most likely create even more Adrenaline, which would be extremely bad. In such instances, one would seek to try to reduce the amount of adrenaline, which is probably suppressing other neurotransmitter production/retention, and to assist the pathways to the production of the desired neurotransmitters nutritionally. To determine such levels, one should have a neurotransmitter test arranged by one's practitioner.
Certain types of treatments, e.g. TCM herbs need not promote adrenaline levels, and it depends on what herbs are used and selected (e.g. a TCM herbalist may choose to omit Ginseng, Cordiceps or Honey Fried Licorice Root). Indeed some homeopathic medicines (e.g. 'Fawn' Wild Child Essence or Medorrhinum) are geared towards treating such conditions, without stimulating adrenaline (or perhaps acetylcholine) production. These medicines can be tailored to the exact requirements without any bad effects, if of course the practitioner knows what he is doing, which is not necessarily a given.
The exact type of treatment/supplement your body requires at any particular point in time may vary, and it may require one or more specific supplements or treatments from each area (i.e. structural, chemical or electromagnetic). A combination of smaller quantities of different adaptogenic herbs and supplements may work more effectively than a larger quantity of the same supplement, working on your adrenals in different ways - but may be harder to balance the quantity in this manner. Your specialist should be able to provide you with guidance on this, for example using kinesiology to determine what and how much is required.
Licorice is believed according to Traditional Chinese Medicine (TCM) to be beneficial for those who are Qi Deficient. Licorice in particular is widely used in CFS treatment and in Traditional Chinese Medicine (depending on the exact prescription). It has Cortisol-like effects without the downsides of excess Cortisol. It is sometimes used to boost the immune system, particularly to fight viral infections.
Be aware that some adaptogenic herbs, particularly licorice, can raise blood pressure more than one wants, and excessive usage has been associated with hypertension and even death (on account of excessive hypertension). So take note of what adaptogenic herbs your adrenal supplements contain, and in what quantities, and the dosage you are taking, whether they have a tendency to induce hypertension or not, and the relative effect it has on your heart, if you are suffering from Cardiac issues. Perhaps buy a Blood Pressure Monitor, which are relatively inexpensive.
It is usual to take adrenal supplements twice a day (approximately the same dosage each time), in the morning and lunchtime/early afternoon. As a general rule, adaptogenic herbs and adrenal supplements, when taken in correct dosage, often help in maintaining one's energy levels, a general feeling of calm and relaxation (better ability to cope with stress) and better sleep at night. An adrenal supplement may however not be necessary in your particular case, it depends on what the body needs at a particular point in time and what is happening in the endocrine system. It is of course best/recommended to seek professional consultation about type and dosage. In a crude sense, you can establish the maximum dosage yourself by increasing the intake by one increment each day of a specific adrenal stimulating supplement (that your naturopath has determined is right for you), until you find that at the end of one day's regime you cannot get to sleep. You have just exceeded your maximum tolerated dosage. Subtract one increment/capsule and that is your maximum daily dosage. If you have reached/exceeded your maximum tolerated adrenal stimulating supplement dosage on one particular day and cannot get to sleep that night, if you continue on the same dosage for several days or fail to reduce the dosage sufficiently to the level that is tolerated by the body over several days, then the resulting overstimulation of the adrenal glands coupled with no sleep for several days may be enough to send you into a 'crash' which may take days or weeks to recover from. Use your common sense! It is better to be over-cautious and conservative than over confident, overly aggressive and reluctant to reduce a dosage. Maximum tolerated dosage and optimal dosage are not necessarily the same thing! Please note that your body's requirement for a dosage or particular supplement can change over time. If you experience adrenal over-stimulation one night and cannot sleep, and you have not been stressed or overdoing things, then consider reducing your adrenal supplement dosage the next day and see what happens.
Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the blood-brain barrier. However, the amino acid tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, can cross the blood-brain barrier.
Tryptophan is not generally recommended to take as a supplement, but 5-HTP is widely recommended and is relatively safe in small doses and effective as a serotonergic agent. 5-HTP can be taken at night to aid in relaxation prior to sleep (and to provide enough serotonin so that the required melatonin can also be produced), in addition to small amounts during the day to aid in seratonin production and aid in relaxation. This can greatly contribute to the healing process.
Overdosing on serotonin may induce a very severe, temporary panic attack, however it is not physically damaging. High dosages of 5-HTP (e.g. 100mg or higher) may also cause nausea and stomach cramps. This is why some prefer to take slow release 5-HTP 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.
Care should be taken if one is already taking anti-depressants. According to Doctor's Best, a supplement manufacturer, 5-HTP should not be used concurrently with MAO inhibitors, Selective Serotonin Reuptake Inhibitors (SSRIs), or other anti-depressant medications. It should also not be used by anyone taking any of the category of medications known as "triptans". One should be very careful about the dosage of 5-HTP and start off with very low dosages and work one's way up in small increments. Dosages may vary between 50mg and 200mg, depending on the individual's requirements and tolerances. Do not take more than you need. Extremely high dosages (silly dosages) can result in a condition Serotonin Syndrome or Serotonin Toxicity, and this can be fatal. Deaths associated with Tryptophan usage in the past are no doubt attributed to Serotonin Syndrome.
Melatonin can be legally purchased outside of the EU, but is illegal for retail sale within the EU (prescription only). It can be ordered by mail order from outside the EU discretely, as customs declarations do not have to state what kind of supplements a package contains, although this web site is in no way endorsing illegal activity of course! ;-) Melatonin is relatively safe to take in small doses and is shown in the vast majority of CFS patients to aid with sleep and thus help in the healing process.
Melatonin is usually taken together with 5-HTP. This way, one is replacing the lack of Melatonin in the body (albeit in a non-natural form), but also providing a serotonin precursor (5-HTP), which can itself hopefully be metabolised by the body to some degree into serotonin and also to some extent melatonin (serotonin being a precursor to melatonin). The body needs enough Serotonin in order to produce Melatonin (along with the requisite co-factors and coenzymes). Some level of Serotonin is also required by many people in order to feel relaxed enough to get to sleep, the Melatonin producing part of that tired feeling. L-Theanine, mentioned below, in small doses, may also provide a feeling of calm and relaxation, somewhat different to Serotonin, partly due to GABA production, to aid in sleep.
One should be very careful about the dosage of melatonin. Some people absorb and assimilate it very easy and only require a fraction of a milligram, whereas others require much more, up to 9mg. It is best to be careful with the dosages of both 5-HTP and Melatonin, and start off with a low dosage and notice the effects, and if necessary build up slowly. The dosages are very much dependent on the individual, and ideally your naturopath or consultant should advise what to start with, and what is right for you. Some people recommend valerian, hops or kava kava tablets. I would personally recommend avoiding these, as your body may not be able to assimilate them properly, and they have energetic side effects and properties, even though they are natural, which over time can actually disrupt the body's energetic balance (c/f Traditional Chinese Medicine). Too much adrenal gland stimulation may also prevent you from sleeping, so this needs to be closely regulated.
Melatonin is apparently one of the active compounds in Barley shoots. How much is actually in the grass component of Barley (i.e. Barley Grass), I am not sure, but it is likely to be somewhat less. Barley Grass and Wheat Grass are used in the Asphalia Sleep product.
GABA of course be supplemented if it is deficient, in supplemental form, e.g. GABA or PharmaGABA-Pro. GABA is the main neurotransmitter that is involved in reducing Peroxynitrite overproduction (through inhibiting excitotoxicity and overstimulation of the NMDA receptors). Dopamine (a precursor to GABA) and Noradrenaline production itself is often adversely affected by the presence of Mercury in the body, on account of decreased enzymatic activity in the presence of Mercury.
I have tried both and Pharma-GABA is perhaps twice as effective weight for weight, but then again is more expensive. Dosages of course should be very low, in the order of 50mg to 1000mg, depending on exactly how much the body requires. Too much can be toxic and 'overload the brain'. Too much GABA can produce a strange 'gluey' sensation in the brain, and a 'buzzing' sensation for a few hours, gradually fading away (i.e. becoming somewhat toxic or problematic), which overrides the normal calming effect of GABA at low dosages. Too little GABA production and too little supplementation may be evident with feelings of anxiety, inability to relax or calm the brain etc.
GABA should not really be taken late in the evening (i.e. a few hours or less before retiring for the night as it may interfere with one's sleep, even in very small doses - it may wake one up and perhaps even stimulate other neurotransmitter production that is detrimental to the act of falling asleep); and L-Theanine is much more preferable in this context (and perhaps generally as it is 'safer' and weaker (as it has to be converted to GABA and Serotonin)). Be careful about the dosage of GABA if you are already taking L-Theanine throughout the day. GABA, taken in the correct dosage (assuming a deficit is present and there is a requirement to take it in the first place), is a different kind of brain calming agent to Serotinin and has a different feel to it.
The amino acid L-Theanine is another precursor to serotonin but also assists in GABA and dopamine production. Theanine is related to Glutamine, another non-essential amino acid. Because it can cross the blood-brain barrier it is regarded as being psychoactive. It is commonly found in tea leaves (Camellia sinensis), and also in the basidiomycete mushroom Boletus badius. The tea variety Gyokuro has the highest concentration of Theanine of all teas. Teas generally however contain tannins which may impede one's ability to fall asleep. L-Theanine is reputed to increase relaxation and relieve stress, and as a result it is found in some sleep formulas instead of 5-HTP, together with a variety of herbs, such as Enzymatic Therapies (Fatigued to Fantastic)'s Revitalizing Sleep Formula, or in dedicated L-Theanine supplements.
DiMethylAminoEthanol (DMAE), a.k.a. DiMethylEthanolAmine, is an alkaline organic compound and precursor of Choline. It is believed that it is methylated (CH3 added) to produce Choline in the brain. Choline is converted into the neurotransmitter AcetylCholine (ACh) in the brain, using the enzyme Choline Acetyl Transferase (CAT). Acetyl-L-Carnitine helps to increase CAT activity and the Acetyl part of the molecule is a precursor to Ach.
DMAE crosses the blood brain barrier (BBB) much more easily than Choline. The brain can convert DMAE into Choline as and when required. DMAE is also a powerful hydroxyl free radical scavenger, especially when incorporated into tightly packed cell membranes where most free radical damage is sustained. The liver converts DMAE to Choline as and when required for the rest of the body. Bacteria in the GI tract do not digest/ferment DMAE. DMAE also prevents Choline from being irreversibly oxidised to Betaine (TMG), thus maintaining the body's Choline levels. Choline also plays a vital role in cell membrane lipids. Ach is associated with memory and learning.
DMAE is usually supplemented in its salt form, e.g. with Para-AminoBenzoic Acid (PABA). PABA is not nutritionally significant and humans cannot utilise it to produce folate as other species can. DMAE can thus be supplemented to boost Acetylcholine production in the brain, if required. One example includes TwinLab DMAE H3. Another is a combination product by Maxam Labs called NG-Rx that includes a small amount of DMAE. Some mitochondrial herbal supplements include added DMAE, e.g. Jarrow Adrenal Optimizer. Taking too much DMAE in one go or during the course of a day may result in severe neurological disturbances including headaches, seeing stars, feeling like you have stared at several bright lights, patches of your vision disappearing and so on. These are results of too much Acetylcholine, i.e. neurotoxicity and imbalance. Martin Pall has theorised that excessive ACh (perhaps via excessive DMAE or Centrophenoxine supplementation) can upregulate Peroxynitrite inflammation (hyper-excitement of the Muscarinic ACh receptors). Always be very cautious with your dosing!
An altenative to taking DMAE is the anti-ageing drug Centrophenoxine, which is a fusion of DMAE and Parachlorophenoxyacetate (pCPA) - a synthetic auxin compound. This is reputed to be carried over into the nervous system more effectively than oral DMAE. Please see the Centrophenoxine section on the Detox page for more information.
L-DOPA is the precursor to Dopamine. Dopamine, as stated above, is used to produce Noradrenaline, which itself can be converted to Adrenaline. L-DOPA is able to cross the blood-brain barrier. Whilst L-DOPA supplementation can boost Dopamine levels, that is not to say that one will necessarily boost Noradrenaline over Adrenaline levels, as it depends on the cofactors involved and the nervous system as to how the exact equilibrium pans out. L-DOPA is found in significant concentrations in the Mucuna pruriens or Velvet bean. Mucuna extracts are usually used in L-DOPA supplements and are typically around 15% L-DOPA. An alternative to L-DOPA supplementation is to supplement the amino acid Tyrosine, which is itself a precursor to L-DOPA. Tyrosine is a constituent of many dietary proteins, although it requires an additional step to produce L-DOPA and is generally not as effective. One may want to consider Tyrosine supplementation if one's Tyrosine levels in the body are below normal reference ranges. One can purchase dedicated Mucuna supplements. One excellent product I have tried by Maxam Labs is NG-Rx (Neural Regeneration Spray). It contains small amounts of Phosphatidyl Choline, Phosphatidyl Serine, N-Acetyl L-Carnitine, DMAE, Acetyl Serine, L-Tyrosine, Ginko And Mucuna Extracts - which seems to be more effective in my experience than taking larger quantities of these constituents supplementally (producing a generally more balanced result). NG-Rx gave me much more energy for about a week and after that time it just gave me a mild headache, regardless of dosage.
Supplementation of neurological system neurotransmitters should however only be done by a trained professional and should not be taken nonchalantly by the individual. Neurotransmitters are regulated by the brain and too high concentrations can be toxic and in some cases cause epileptic fits etc. A skilled professional may be able to help restore healthy endocrine and neurological system functioning based on a series of tests of one's hormone, amino acid and neurotransmitter levels, and careful and balanced supplementation.
It has been observed in some cases, that the supplementation of hormones and/or neurotransmitters to replace deficits (e.g. HRT) has resulted in increased proper biochemical function and balance, which in turn stimulates the processes that create the hormones and neurotransmitters themselves in the first place, resulting in one requiring to take less and less of the hormones or neurotransmitters over time (hopefully). This is often achieved in conjunction with other targetted treatments such as nutritional and otherwise.
The quality of hormones may vary and some claim to be more bioavailable and 'natural' than others. One example of an Aldosterone hormone supplement is bio-identical or compounded Aldosterone - from Kripps Pharmacy. This is in contrast to Florinef, a synthetic version of Aldosterone with various reported side effects, which would be a vastly inferior choice. There have been some reports in the press of hormone replacement therpay (HRT) resulting in an increased risk of a heart attack.
Be sure to discuss your strategy with your specialist and realise that each practitioner may take a slightly different approach. Find the approach that suits you and your body best. There are clearly many different ways to achieve the same end, and it need not be through direct replacement of hormones and neurotransmitters but by stimulating and normalising their production. Each case is unique and must be considered on its own merits.
Taking synthetically manufactured hormones correctly is a way of easing side effects of hormonal insufficiency. They are of course relieving symptoms and not actually curing the problem of insufficient stimulatory and growth hormone production. They are not stimulating the adrenal glands. This is akin to a bald person wearing a toupe, rather than growing new hair (if this were possible)! The person feels young as long as he is wearing the toupe, but deep down he knows he is still bald! Steal the toupe and the person doesn't look young anymore! The same could be said of taking 5-HTP and melatonin, but studies show that they effectively target what CFS sufferers are actually lacking. Growth and stimulatory hormone supplementation is much more complicated. The body requires a multitude (many 100s) of different hormones and precursors in the correct concentations. If the body is not producing enough, and the patient wishes to augment the levels, then one must undergo a hormonal blood test to ascertain what the actual hormonal levels are, and not just randomly prescribe an arbitrary amount of a popular hormone in the hope that it will make the person feel better. It is in all likelihood going to create a large neurotransmitter imbalance.
Some specialists recommend the use of adrenal or thyroid hormones and claim excellent results in patients. The effectiveness of hormones such as Keto-7 DHEA (Dehydroepiandrosterone) is inconsistent at best if taken randomly or arbitrarily. Some patients who take DHEA Keto-7 feel much worse with splitting headaches, extreme exhaustion and heart palpatations. Of course, it ultimately depends on whether you are actually deficient in a hormone such as DHEA or not. This is quite common with those who read about DHEA and CFS on the internet, take a 'standard' dose and end up much worse than before. If you take extra DHEA when you do not have any significant deficit in DHEA production, then you are inducing a DHEA imbalance, which results in some of the symptoms described above. However, if taken correctly, i.e. after determining that there is indeed a requirement for them, then they can provide some support to the body's overall recovery process (in conjunction with other therapies and supplementation regimes). For example, in 2006, I purchased some Keto-7 DHEA and took the recommended starting dosage daily and started to feel slightly better. After a couple of days however, I felt extremely fatigued (exhausted) and had bad headaches and palpatations, as well as skin rashes, and immediately desisted in taking any more. After a week I had recovered and got back to where he was before. Clearly this is an example of exceeding the dosage required by the body. In 2009, I was muscle tested by my consultant and it was determined that I required 2 x 10mg of micronized DHEA (by Vital Nutrients) in the morning, and a few months later, 2 x 25mg, and this served to improve my overall condition. An increase in the requirement for DHEA and Pregnenalone may indicate a shift in metabolism towards more anabolic pathways, as opposed to catabolic pathways, which is generally a positive development.
Keto-7 DHEA is available in the EU by prescription only in 5mg or 10mg dosages, and is not permitted freely for sale. It is however available for sale outside of the EU.
I have myself supplemented Pregnenolone, a Vital Nutrients' supplement, in the order of 10mg, between 1-3 capsules twice a day. At certain points, I did not take any, as the body did not require any. I felt that this helped my general hormonal balance, energy levels and stress adaptation. Sometimes, on days when I had overdone it, and he felt an 'adrenal' type rollercoaster coming along, after too much concentration for example, at a time when I was feeling fatigued, then a feeling of extreme breathlessness (like a lack of oxygen) would also follow and feeling of hormonal and/or neurotransmitter chaos in my brain. Taking one capsule of Pregnenolone in such instances alleviated all such symptoms. I have myself experimented, and breathing O2 makes little difference, or if it does, one feels worse when coming off the O2 and simply delays the onset of the inevitable unpleasant adrenal-type rollercoaster ride. However, taking the Pregnenolone afterwards made this feeling of urgent O2 requirement simply disappear. Sexual activity itself may not be advisable for people who are very ill with CFS or related conditions. However, in the instance that one does engage in sexual activity, to mitigate any (sometimes extremely unpleasant) problems that may arise afterwards on account of the body using up all its own pregnenolone to produce the hormones required for sex, may leave the body with nothing to create cortisol afterwards (and possibly other hormones). Taking a small amount of pregnenolone in such instances may completely alleviate all adverse symptoms. Of course, the above is something you should discuss with your practitioner and not just independently do yourself. Since the above, I have not had such struck by lightning style benefits from taking extra pregnenolone, presumably as the overall picture is more complex, but it does still help if I have over-concentrated on something when my brain has low energy or insufficient neurotransmitters (up to a point). If I have really overdone it, then it does not generally help very much at all.
Pregnenolone of course does not just help to raise Cortisol levels, but as a prohormone it can raise any and all hormone levels as required. If there is a bottleneck in the conversion of cholesterol to pregnenolone, then low level Pregnenolone supplementation may be beneficial in a given individual. For example, I took an oral dosage of 2 x 10mg of Pregnenolone, twice a day, at one point during my treatment. Clearly any type of hormone supplementation must be carefully monitored, and too high pregnenolone supplementation levels may result in a variety of side effects, including aggressiveness, headaches, restlessness, acne, hair loss, facial hair growth in women, infertility, increased levels of estrogen, raised LDL (bad cholesterol), liver damage, raised blood pressure, etc. Pregnenolone supplementation when it is not required or too high Pregnenolone supplementation may in addition result in elevated Cortisol levels, which may result in elevated sensation of stress and damage to the Cortisol receptors, stopping the body's natural ability to detect high Cortisol and to naturally lower it.
Keto-7 DHEA is available in the EU by prescription only in 5mg or 10mg dosages, and is not permitted freely for sale. It is however available for sale outside of the EU.
An article on Phoenix CFS by Cort Johnson investigating research and findings on low Cortisol levels in CFS patients, and Cortisol supplementation/therapy can be found at the link below.
Herbs to promote calming Neurotransmitter release:
A number of herbs can be taken prior to going to bed to assist in falling asleep, as they can promote relaxation and alpha wave production. Herbs can be taken in tincture form, in tea form, in capsule form or even as a foot bath). The smell as well as the chemical action of these herbs may assist in relaxation and better quality of sleep. Such herbs include:
- Lemon Balm (Melissa officinalis)
- Valerian (Valeriana officinalis) root extract
- Passionflower (Passiflora incarnata) leaf and flower extract
- Hops (Humulus lupulus) flower extract
- Wild lettuce (lactuca virosa) leaf extract (found in some adrenal supplements also)
- Jamaican Dogwood (Piscidia piscipula) root extract etc.
- Lavender (Lavandula angustifolia)
- Tall fescue (Festuca arundinacea) - a European grass species, formerly contained in Asphalia products Natural Sleep and Natural Protection (which now just use Barley Grass and Wheat Grass).
Products may include Enzymatic Therapy (Fatigued to Fantastic)'s Revitalizing Sleep Formula or the common product Kalms (which also contains sugar!) I have used such formulations in the past, and whilst they indeed did help with relaxation and better quality of sleep, being herbs, they also have energetic qualities (c/f TCM, hot and cold energy), and as a result, when used regularly for months or years, may severely upset the body's energetic system. I personally felt like I had a constant background sense of malaise, like a 'wall' of some kind, and this disappeared immediately I stopped taking Kalms (having taken them continuously for 2-3 years or so). So whilst herbs can help, they should not be used for extended periods in my opinion.
Basal (waking) body temperature can provide a good indication of endocrine system health, and can be one of many way of identifying issues and measuring one's progress during treatment. The sensor of an electronic thermometer can be placed deep in the arm pit upon the moment of waking in the morning and held there (bring your upper arm onto your side to hold it in there and to keep maximum contact area) until a final peak temperature is reached, which can take up to 5 minutes (alternatively you can insert a regular thermometer into your rectum if you prefer!) Take readings every day for a couple of weeks. Use a chart (a graph) where temperature is on the vertical axis (e.g. 94.0F - 99.0F or 34.5C to 37.2C). Each 'square' or unit on the vertical axis should correspond to a tenth of a degree. This axis does not have to reach zero ;-) unless you have been frozen for medical research! The horizontal axis is the date, each square represents a day. Notice any changes in your dietary or supplement/treatment regime and the effect they have on your basal body temperature. The optimal basal temperature can be in the range 97.6F to 98.2F or 36.5C to 36.8C. A consistently low basal body temperature is usually indicative of hypothyroidism (low thyroid function). An unstable basal body temperature is usually indicative of adrenal dysfunction and low adrenal gland activity. Unstable and low temperatures usually indicates both low adrenal and thyroid activity. Please note that measuring basal body temperature is different from measuring daytime body temperature, which is usually higher (as the metabolic rate increases slightly when we are awake), with its optimal range in a healthy person at around 98.6F to 98.8F or 37.0C to 37.1C. The Metabolic section on Dr Rind's web site below examines this process in more detail. Please note that I am not endorsing everything on Dr Rind's site, in particular EDTA Chelation for heavy metal detoxification, which is of course a different story entirely.
Mitochondrial dysfunction can also be a contributary factor in hypothalamic dysfunction. It is a good approach to treat multiple factors to CFS and related conditions, when building up the body, rather than focussing on one factor, as they are nearly always interlinked.
As you can see above, supporting the adrenal glands during treatment is critical, and treatment should be effectively customised for you by your naturopathic doctor or consultant. Self-prescription may be ineffective and may over-stimulate your adrenal glands and may exaccerbate hormonal imbalances rather than correct them. Failure to make progress in returning the hormonal balance (i.e. feeling good) during the course of one's treatment however can often indicate excessive heavy metal toxicity. Excessive heavy metals in the body tend to diminish hormone production, and if they are present, adrenal recovery is virtually impossible without undergoing a full detoxification process. This is something a good naturopath or consultant can advise you on and should notice.
Below is a general overview of adrenal function and supplementary synethetic hormones from Dr Mercola's web site:
Clearly, biochemical factors such as the endocrine system are a major factor in our wellbeing, and ensuring its proper functioning through detoxification, proper nutrition, rest and so on is of key importance. Of course, psychological factors also affect the endocrine system, and the ability of the individual to reside in a place of wellbeing is clearly in one's interest. How exactly one chooses to go about achieving this is up to the individual. Western societies tend to excessively rely on external triggers, for example, movies, music, alcohol, drugs, certain situations to arise and rules to be met etc., in order to change our state of mind to something positive, happy, blissful and enlightened. Such states of mind rarely last very long if they are achieved at all. In addition, proper physical discipline and development is of help in maintaining a healthy endocrine system. The concept of attachment to the outside events and people of the world from Zen Buddhism may be useful, in that generating a constant state of spiritual enlightenment and wellbeing which is not reliant on external factors and addictions (taking responsibility oneself rather than relying on external triggers or a spiritual figure or God) may well prove more rewarding. Even monotheistic religions appear to have a high level of attachment to various religious concepts, rituals, traditions etc. However, each has its benefits and cultural bias. It is clearly up to the individual how much attachment they want to have to external sources and ideas in their lives, and what addictions they choose to embrace.
Sleep cycles and the processes that occur during sleep, as well as tips on alleviating insomnia and other sleep disorders are examined on the dedicated Insomnia page. This page also includes an examination of dosages of 5-HTP, Melatonin and L-Theanine, which can assist in falling asleep and staying asleep.
Sufficient Exposure to Natural Light and Seasonal Affective Disorder (SAD):
Believe it or not but lighting and exposure to light can make a huge difference to how you feel and your mood, for biochemical and psychological reasons. It is recommended to get AT LEAST 30-60 minutes of natural light a day (around 10,000 lux).
The approximate lux values for different times of the day are quoted at the web site below.
Apart from changing one's mood, and altering our neurotransitter and hormone balance and production, sufficient skin exposure to natural light is a prerequisite for the body's own production of vitamin D. Natural production of vitamin D is preferable to oral supplementation. But perhaps dietary sources are better still. Vitamin D deficiency is not uncommon and is a major contributary factor behind a wide variety of different diseases and conditions. Please see the Nutritional page for more information about vitamin D and the benefits and dangers of exposure to UV Light. Over exposure to UV Light can result in immune system suppression and DNA damage.
I have found that during the summer, when sunbathing safely and moderately for short periods, it helps to increase his energy levels and sense of wellbeing, (albeit with a slightly restless or tingling feeling). As discussed on the Insomnia page, exposure to natural daylight or a strong artificial blue light (usually white light with a hint of blue) helps to reduce/stop melatonin production in the pineal gland, thus helping to restore improved melatonin production at night when it should be being produced. Exposure to natural light or an artificial blue light can therefore be beneficial first thing in the morning. The latter being particularly useful if one gets up early or during the winter when it is still dark upon rising. Blue SAD lights have been shown to be useful tools in restoring natural sleep cycles and are discussed on the Insomnia page.
However, according to Traditional Chinese Medicine, too much exposure to strong sunlight can result in an increase in one's 'hot energy' or yang, and in some patients may result in an unsettled spirit, restless, agitated or short tempered, and an increased inability to sleep. I have found that too much sunbathing or exposure to light during the day can cause major problems getting to sleep at night. This is particularly pertinent if one's adrenaline levels are too high, when excessive strong sun exposure will merely exaccerbate the problem.
Let us examine what types of light bulbs are available on the market.
The vast majority of modern homes are fitted with standard 'yellow' incandescent light bulbs. These do not replicate the broad spectrum of wavelengths found in natural light. They were in broad terms intended to when they were first invented. Without sufficient natural light and prolonged exposure to standard light bulbs, one can often end up feeling depressed or stressed. This is known as Seasonal Affective Disorder (SAD). It is especially prevalent in countries closer to the poles where there are very few hours of natural light in the winter. But it of course affected a huge proportion of the population who spend far too much time indoors, working in offices, and driving everywhere, and wearing sunglasses every time the sun comes out (whether to look cool or out of convenience when driving etc)! Of course, when the UV levels are quite high, or where there is considerable reflection, sunglasses should be worn to avoid retina damage. So it is a fine balance. Too little light exposure can potentially result in Vitamin D deficiency, neurotransmitter and hormone imbalances, and improper neurological associations (i.e. an unhealthy perspective). When was the last time you saw an animal wearing sunglasses? In CFS patients, or those with related conditions, many may stay indoors for extended periods of time, which often leads to further depression or stress on account of the above.
In addition, many domestic environments are far from inspiring in their size, cleanliness, familiarity, degree of clutter, smell and decoration! The air is lower in oxygen content than the outside air, and higher in carbon dioxide and airbourne toxins. Modern or 1970s style decoration is often hardly rich in character or inspiring. Animals and humans are designed to exist in changing, fluid environments, surrounded by changing weather patterns, and changing/growing flora and fauna. It is not so natural for a human being to be in a sanitised and unchanging environment, which is common with sedentiary living and buildings and offices. A wallpapered or painted wall of a house can only be so interesting! Conversely, natural materials or better still, plant life has infinitely more texture of visual interest. It engages the senses more. One should bear this in mind, and that everyone requires a change of scene, as discussed in the section above on Gentle Exercise.
The recommended option for obtaining one's daily light requirements using artificial lighting (i.e. if one cannot guarantee sufficient exposure to outside light every day) is an SAD (Seasonal Affective Disorder) fluorescent light box. These normally contain a UV Filter which typically filters out over 99% of harmful UV rays, and also a balast to avoid flickering that can cause headaches. One should not stare directly into the SAD light box, but sit in front of it, reading, meditating or otherwise. In contrast, all other light sources that do not have UV filters produce small amounts of UV, including incandescent bulbs, full spectrum bulbs and even 10,000 lux SAD desk lamps.
One can easily transform one's home by fitting full spectrum or broad spectrum light bulbs. These are energy saving light bulbs that in the case of full spectrum fully replicate the wavelengths of natural light including low levels of UV. Certain types of broad spectrum light bulbs do not give off UV wavelengths of light, but how harmful the levels of UV A and UV B emitted from full spectrum light bulbs are is hotly debated. Full or broad spectrum bulbs may be more expensive than the normal energy saving bulbs that are more readily available. Purchasing bulbs is relatively cheap. There are various types of full spectrum light available, like dedicated light boxes or full spectrum desk lamps, but these are hugely expensive for what they are and the benefit is debatable over simply buying full spectrum light bulbs and fitting them around your house. Some suppliers of full spectrum light bulbs can be found on the links page or of course by browsing the web.
A comparison of the wavelengths emitted by full spectrum bulbs compared with natural light and incandescent bulbs can be seen at the link below.
My personal experience with full spectrum bulbs is that I purchased some and fitted them all over his house, and loved them. I used them continuously for 4 or 5 months, after which I became rather fed up with them (an inexplicable dislike to some quality of the light) and reverted back to regular incandescent light bulbs. Instead, I make sure he gets enough natural daylight and get's out the house enough and breathes in fresh air instead!
The SAD Association web site is listed below. Please note that BlackSpy does NOT personally recommend taking anti-depressants for any condition, let alone something that can be prevented by changing a lightbulb or being outdoors more! No jokes about how many doctors prescribing anti-depressants does it take to change a lightbulb please.
Dr Mercola has an article about full spectrum bulbs on his web site, although his assertion that the UV component from full spectrum bulbs haven't done him is hardly scientific!
A discussion of issues surrounding mercury emissions from fluorescent lighting can be found on the Toxins page. This potentially affects SAD lighting and full spectrum or energy saving light bulbs.
One should also consider the environmental impact of purchasing bulbs that contain mercury, as there is currently way to recycle this mercury effectively and cheaply, and also potential health aspects. Please see the Toxicity page for more information.
Everyone wants to feel good. And preferably all the time! People have different ideas, strategies, habits, rules and beliefs about how this should be achieved. However, very few people actually achieve this. The sensation sought is that resulting from sufficient (or temporarily excessive) serotonin production. Insufficient serotonin production depending on severity may result in feeling less than great all the time or in worse cases depressed.
Some people take drugs like MDMA, speed or LSD to feels some temporary elevation in seratonin levels, whilst having low levels and feeling less than great the rest of the time. Some people try to dull their senses with marijuana or downers so they feel some temporary relief and respite and can hide from their personal pain and lack of self-belief. Ironically the actual 'high' from marijuana doesn't last very long and the vast majority of the time being 'stoned' is feeling just tired with a slight headache and buzzing sensation in the head. Great! (Please see the toxicity web page and the Drugs page in the psychology section for an examination of the effects of drug use). Some people get drunk to feel good temporarily and the hang over is the least of their problems. Some people take anti-depressants like SSRIs which are addictive and bad for one's health. Some people try to have very healthy lifestyles and eat organic foods to achieve a feeling of wellbeing and being 'wired' and 'on a buzz' all the time, but never quite reach that feeling. Some people rely on religious experience and participation in religious events to feel good (this is not to say that they are not valid and beneficial activities in themselves, good in absolute terms). Some people have to play music constantly in order to feel slightly better, but this is tiring and when the music stops... Some people are workaholics. Some people have to take regular baths to feel relaxed and good. Some people are addicted to watching television or watching movies. Some people rely on having as much sex as possible to feel good, which is partly dependant on their 'ability to deliver the goods'. Some people rely on over-eating or comfort foods like chocolate to feel good and release endorphins. Some people take part in charity work.
Wanting to feel good, to be distracted from one's normal state of mind or experience a new state of mind is something that unites everyone in the world! However, as is frequently the case, people may want similar things, but the 'means' of getting them divides people. The irony is that none of the above strategies are likely to be entirely successful in getting the person what he wants. It is only when we address the core issue of hormonal dysfunction that we can actually feel good virtually all the time.
Recreational drugs, legal and illegal, work by temporarily disrupting neurotransmitter activity or by mimmicking neurotransmitters. If they didn't do this, they wouldn't be drugs, they wouldn't 'work' and people wouldn't take them! This is why people with increasing hormonal imbalance seek to continue to take recreational drugs occasionally/regularly/all the time in order to feel 'good', as it provides temporary hormonal states of pleasure. Taking drugs damages your internal organs and aforementioned glands to varying degrees, toxifies your body and disrupts your endocrine system, actually lowering your normal serotonin production, and frequently increasing present psychological problems and inducing new ones which result in decreased serotonin production again. Comfort foods put pressure on your adrenal glands and often cause toxicity and digestive problems. If I could wave a magic wand so you could feel great all the time, you'd probably say yes and quit your possibly destructive strategies you've been using to try to achieve this in the past. However, it may not be a magic wand, and it requires some leg work on your behalf, but it is indeed possible as can be seen on this web site. It is however up to you. No one can force you to address your underlying health issues. You have to be motivated and really want it. And then actually do something about it! I want to wave the magic wand for your personally, that's why this web site is here! Take it or leave it. It is your choice.
Clinical depression is frequently associated with low levels of seratonin. Prozac is the best-known and most widely used member of the class of anti-depressant drugs known as Selective Serotonin Re-Uptake Inhibitors (SSRI) - not to be confused with the ticker symbol for Standard Silver Resources, Inc.) SSRIs block serotonin uptake, so that the concentration of serotonin is boosted in the synapse. This has been shown to relieve the symptoms of depression in many patients. However, it is not 'curing' depression.
Let us assume that depression is caused by a psychological and biochemical factors. In a sense it is largely meaningless to just look at what initially caused depression, as a biochemical initiator of depression (e.g. lack of natural serotonin production) will make the person feel awful, often resulting in the formation of beliefs around feeling depressed. So whether the beliefs or focus on sad or painful events caused the depression or not or are just a result of the depression, they are present, as are biochemical causes, and both must be dealt with to ensure a full recovery. Many of the psychological problems are likely to disappear once the endocrine system is functioning properly, but some level of psychological realignment and belief scrubbing/replacement and control of how one focusses is probably required. In fact, most people would benefit from this, whether they want to admit it or not! This is why motivational coaching has such a profound effect in the workplace and in people's personal lives. Please see the psychology section for further information. Many people prefer to lock themselves away emotionally so no one else ever really gets under their skin and questions their core beliefs about themselves and their personal focus.
SSRIs like Prozac may see some 'success', or rather hiding of symptoms, the negative effects include addiction and in many cases MORE suicidal thoughts (even if the actual suicide rate may decrease amongst prozac users). In addition, the presence of an SSRI will also have a number of harmful physical effects on the organs of the body. By focussing on serotonin and ignoring the rest of the complex endocrine system, any other problems in the endocrine system are likely to worsen. There may well be other biochemical factors involved in the person's condition that are never explored. Long term endocrine problems impact one's health severely and are likely to worsen over time if not treated.
Sufferers of CFS and some related conditions are likely by default to suffer from some level of depression, just because of the decreased ability to function in one's usual activities, the psychological impact this has over many months or years as the condition worsens and especially if the person has no belief that anything can be done to cure him (please see the psychology web page for an examination of psychological issues for CFS sufferers). In addition, most CFS sufferers have low hormonal levels in any case, and this will affect serotonin levels. Without enough serotonin levels, the person will not feel good very often, which in itself is not psychologically helpful. A CFS patient must determine if hormonal dysfunction applies to him with the help of an experienced specialist and stimulate the endocrine system accordingly, as part of an overall programme of diagnosis and treatment.
It has been observed in sufferers of manic depression that lithium levels in the blood and tissues are lower than normal. In fact most people have low lithium levels. Supplementation with lithium orotate or aspartate is not uncommon for manic depression patients. This form of lithium is organic and more easily absorbed than the inorganic form lithium carbonate. Lithium is not a drug, as commonly believed, but a light valency 1 alkaline metal in the same group of the periodic table as sodium and potassium. It is a 'non-essential' nutritional element that in low levels can contribute to depression. It is therefore a nutritional issue and not psychological. In the strictest sense, Lithium is not a nutritional element but appears to have a calming effect on the nervous system and on mood balance in very low concentrations. However, it is a toxic element and in higher concentrations can exhibit more overt toxic characteristics. Like anything else, if a patient is to receive lithium, it is prudent to find out what the tissue levels actually are to start with. In addition, it is unlikely that treating lithium \'deficiency' alone, if present, will completely cure a manic depressive or anyone else with this deficiency. Other health problems, such as other nutritional element deficiencies, hormonal imbalance etc. have to be identified and treated also. Please see the nutritional deficiencies page and toxicity page for further information about nutritional and toxic element levels and their effects.
In addition, studies have shown that a group of sufferers of depression have been cured with high doses of the Omega 3 fatty acid EPA over a period of weeks. There are likely many nutritional/lifestyle factors involved. I would recommend avoiding any doctor or general practitioner who recommends anti-depressants or sleeping pills, as they are unlikely to undertand how to treat you correctly, even if they perhaps mean well. It is a little like asking a 13 year old physics student to repair a fault in the Space Shuttle.
Below are some case studies of people who suffered from Depression, but after taking EFAs felt immediately much better. This includes Merrill Osmond.
There is some evidence to suggest that TNF Alpha, a pro-inflammatory cytokine produced by the body, is responsible for auto-immune diseases as well as depression. TNF Alpha as a side effect, destroys serotonin, and is now being considered a major cause in SSRI resistant depression.
Clearly to properly treat depression, it is highly likely that proper stimulation of hormone production and a return to proper endocrine function will largely cure the depression. However, this isn't as simple or as profitable as merely prescribing a single 'one size fits all' drug like Prozac. Many general practitioners prescribe anti-depressants and sleeping pills to CFS sufferers and sufferers or related conditions, as they believe that their problems are primarily psychological. This shows a total lack of understanding of the underlying conditions of sufferers and reinforces the idea that the medical establishment isn't actually interested in people's health but to sell them drugs and cover up their symptoms just enough so that they can continue as consumers and workers as normal part of our society. Much as taking anti-depressants is fundamentally a bad idea, at least there is some comprehension by doctors of the issue of low serotonin levels in sufferers of depression and conditions like CFS. However it is the wrong way to go about increasing the body's serotonin levels, and it ignores all the other endocrine and other specific health problems that have been examined on this web site. There are many good, positive ways to treat the endocrone system, which are examined above.
Supplementation with 5-HTP (described above) during the day may help produce additional serotonin and alleviate the symptoms of depression without any negative habit forming aspects of SSRIs. It may also help greatly in SSRI resistant depression.
A definition of clinical depression and the most commonly applied treatments can be found at Wikipedia. Please note that this web site is not endorsing the vast majority of the treatments described. Please click on the link below.
