A Case Study Attacks Stress, Anxiety, and Tremor with pathway amino acids, choline (lecithin) and co-factors.
A middle-aged female with a family history of anxiety and Parkinson’s Disease developed a tremor and mild pain in her left arm. She had a history of painful joint injuries and anxiety due to job-related stress. She obtained little exercise and used ibuprofen (Advil) therapy for the joint pain. At work she occasionally painted the interior of homes, often inhaling the fumes. She reported awakening in the morning with an upper body tremor and a cold left arm. Her fists would be tightened and her hands tingly. During the day, her extra-ocular muscles were painful and she had difficulty focusing. She experienced somewhat normal energy levels during the early part of each day and then fatigued. Athletic stress, work place stress, intense mental concentration, painting, an emotional event, sugar or deep-fried food ingestion stimulated the tremor and reduced her energy levels. At bedtime, upon turning off the lights, she experienced vertical gaze problems.
Her daily vitamins included vitamin B complex (100mg b.i.d. (twice daily)), vitamin C (500mg t.i.d. (three times daily)), amino acids (1500mg t.i.d), fish oil (1g), calcium citrate (600mg), calcium phosphate (600mg), iron (65mg), coenzyme Q10 (200mg), lysine (500mg), beta-carotene (10,000 IU), zinc (50mg), and a multi-vitamin.
She has a family member who has been on standard of care therapy for Parkinson’s Disease for the past 7 years but the disease has progressed. To alleviate her left arm tremor, she began ingesting choline and lecithin in increasing amounts, until the tremor subsided. During the first weeks of therapy, she experienced a mild frontal lobe headache, more significant on the right side. Stressful days would be followed by the upper body shiver and left arm tremor, the next morning upon awakening. Sugar ingestion stimulated the tremor within an hour. A stressful work situation stimulated the upper body tremor. She slept quite heavily during the first two months of choline and lecithin therapy. Attempts to reduce the choline and lecithin dosages re-established the tremor.
During the third month of therapy, heavy stress continued at work. She was anxious and had a negative outlook. To alleviate the sleepiness brought on by the choline/lecithin supplements, provide more energy, and support the dopamine pathway, she began taking tyrosine. To fortify the serotonin pathway and improve her mental outlook, she added 5-hydroxytryptophan (5-HTP). There were positive results the first day. With the tyrosine and 5-HTP, she was able to perform more of her normal daily activities. In time, with the combination of these supplements, the natural oils returned to her skin and menses became painless. She continued to decrease stress levels and overwork. She rested frequently.
The adrenal glands are responsible for producing many neurotransmitters. They are small walnut shaped glands resting on top of the kidneys which produce cortisone and neurotransmitters in response to stress. To help her adrenals, she began taking a bovine adrenal rebuilder, the amino acid methionine (controls the adrenals), minimal amounts of sugar, no high fructose corn syrup, no deep-fried foods nor alcohol.
At the beginning of the fourth month, she continued 95% tremor free. Her left arm continued to experience mild pain depending upon sugar and choline/lecithin levels. She experienced improvement in her daily energy level and her arm tremor and pain resolved almost completely. The left arm would experience some irritability after stressful days or skipped choline/lecithin supplements.
At 4 ½ months post tremor initiation, the subject was pricked with a garden thorn. It appeared that her blood had thinned. She had experienced no side effects of choline (nausea, vomiting, diarrhea, sweating, increased sweating, or salivation (Livestrong Website)) nor side effects of lecithin (rash, low blood pressure, diarrhea, vision problems, fainting or loss of appetite (Headquarters Website)). However, internet research showed that blood thinning may occur with choline/lecithin. She began using ibuprofen and aspirin sparingly. She decreased her dosage of lecithin, however, the tremor returned. She resumed the lecithin dosage and purchased a multi-vitamin containing vitamin K and increased green food consumption. (Vitamin K which is found in greens is important in the blood clotting process).
At five months post tremor her left arm was the same temperature as her right arm upon awakening. The fists and tingling findings were infrequent. The left arm continued to have some irritability after stressful events. Exposure to paint fumes initiated the tremor. Relief from tremors, extraocular fatigue, body twitches, and spontaneous crying was found with additional choline and lecithin. She experienced some daily facial flushing and left sided chest pain/pressure with exercise. Knowing methionine is stored in the heart, she reduced her daily methionine intake.
More research as to the benefits of choline, lecithin, methionine, and tyrosine to improve neurological health may be beneficial. Urine amino acid testing is available and would be important to utilize more frequently to determine amino acid levels pre and post amino acid or pharmaceutical therapy. Better availability of a urine amino acid neurotransmitter test that specifically provides tyrosine, tryptophan, choline and co-factor levels vital to support the three important neurotransmitter pathways would be beneficial. We expect that Wellness 2020 will bring these advancements. For a complete discussion of Wellness 2020 see the home page of http://www.wheatfreediseasefree.com.
Nerves are key to communication within the body. They tell a muscle to move or an organ to function. It takes two nerves, one from brain cortex to the spinal cord and a second from the spinal cord to the foot, to make the foot move. Nerves communicate through chemicals similar to a car battery. The nerve running from the brain to the spinal cord will pass a chemical called a neurotransmitter to the nerve running between the spinal cord and the foot to stimulate the receiving neuron. Neurotransmitters travel from the sending neuron to the receiving neuron through a gap (cleft) and they are frequently recycled back into the sending neuron to use again. The adrenal glands play a key role in producing neurotransmitters from amino acids and dietary protein.
Electricity traveling through a battery or a house is either turned on or off, making man’s design of current either excitatory or off. The Creator’s design is a bit more elaborate in that it involves both excitatory and inhibitory transmissions. Epinephrine, acetylcholine, and glutamate are mainly excitatory neurotransmitters while dopamine, norepinepinephrine, and GABA (gaba-amino-buteric-acid) are inhibitory.
On the Concussion Brain Food post at http://www.wheatfreediseasefree.com we discussed the importance of Omega-3 fatty acids (cell membrane formation), B-complex (nerve formation), and Amino Acids (protein/neurotransmitter formation) for healthy brain and nerve tissue. This Neurotransmitter paper examines the three main neurotransmitter production pathways: ACETYLCHOLINE, DOPAMINE, and SEROTONIN and the amino acids and vitamins required to keep these cells healthy and alive.
THREE NEUROTRANSMITTER PATHWAYS:
I. Production of ACETYLCHOLINE:
Phosphatidylcholine (Lecithin) —-> Glycerophosphatidylcholine —> Choline
Then, Choline + Acetyl Coenzyme A —-> ACETYLCHOLINE
Acetylcholine functions as both an inhibitory and excitatory neurotransmitter controlling many of the body’s nerves including excitatory skeletal muscle contraction and inhibitory actions on the heart and brain. The body can convert phosphatidycholine (lecithin) to glycerophosphatidylcholine and then to choline. The body makes the acetylcholine neurotransmitter by adding acetyl coenzyme A to choline. Choline is used for cell communication and used to produce phosphatidylcholine and sphingomyelin which make cell membrane (Linus Pauling Institute). Choline contributes to the production of the myelin coating around nerves (Oshida K et al., 2003) and it supports the folate pathway to produce DNA (Institute of Food, Medicine, and Nutrition Board, 1998). The three neurotransmitter pathways described in this paper appear to depend upon each other’s viability. Acetylcholine, for example, has an important role in activating the Dopamine Pathway. Normal levels of the dopamine pathway neurotransmitters may not be produced without sufficient levels of acetylcholine to act as a stimulus (Patrick RL et al.,1971). Low choline and dopamine levels have been implicated in Parkinson’s Disease (Zurchovsky L, 2012).
Choline is an essential nutrient and it is water soluble, therefore must be replenished daily in the diet. Choline is found in foods such as eggs, fish, liver, milk, wheat germ, and quinoa and is available as a supplement as choline or lecithin. Since choline plus acetyl coenzyme A make acetylcholine, sufficient quantities of both must be present. Adequate intake levels of choline for healthy individuals are 425-550mg/day (Linus Pauling Institute).
Low choline levels have been found to correlate with anxiety, intelligence and worry (Coplan JD et al., 2012). Liver and muscle damage (Sha W et al., 2010) athlerosclerosis, neurological disorders (Ziesel SH, et al., 2009), infertility (Johnson AR et al., 2012), and growth impairment (De Simone R et al, 1993) are promoted with deficiencies. Those who do not eat enough whole eggs may be at risk (Hasler CM et al., 2000). Choline is in high demand during pregnancy and helps to prevent neural tube defects (Pitkin RM, 2007).
Choline, B9 (folate), B12 (pyridoxal phosphate), and methionine have key roles in the methyl donor system and cancer protection (Kadaveru K, 2012). Diets rich in choline may lower the risk for breast cancer (Xu X et al., 2009), promote REM sleep (Kushikata F, 2006), and memory (Zhang W et al., 2012). Choline has been used as a treatment for Alzheimer’s disease (Zhang W, 2012), and stroke (Gutierrez-Fernandez et al., 2012). Choline is being studied to help treat traumatic brain injury. Choline or lecithin can be useful in treating neurological disorders characterized by inadequate release of acetylcholine such as Tardive Dyskinesia (described as involuntary, repetitive facial or limb movements, Growdon JH,1978). A single meal containing lecithin increases concentrations of choline and acetylcholine in rat adrenals and brain tissue (Hirsch MJ, 1978) Perinatalcholine is neuroprotective for seizures, depression, and the effects of alcohol (Glenn MJ et al., 2012). Ninety percent of humans in a research study conducted had choline below adequate levels (Zeisel, 2009).
II. Production of SEROTONIN:
Tryptophan hydroxylase Dopa Decarboxylase
Vitamin B3, B9, Iron and Calcium Zinc, Vitamin B6 and C, Magnesium
Tryptophan ——> 5-Hydroxytryptophan (5-HTP) ——–> SEROTONIN (5-HT, 5 -Hydroxytryptamine)
.(Enzymes and cofactors required to produce 5-HTP and 5-HT from the Understand and Cure Website.)
Tryptophan, an essential amino acid for humans, makes serotonin. It must be included in the diet, humans are unable to produce it. Tryptophan is found in eggs, spirulina, fish, poultry, nuts, seeds, organic soybeans, milk, and cheese.
To convert tryptophan into 5-HTP and produce serotonin (5-HT, 5-hydroxytryptamine) an enzyme called tryptophan hydroxylase(TPH) is required with the cofactors vitamin B3 (niacin), B6 (pyridoxal-5-phosphate), B9 (folate), vitamin C (ascorbic acid), magnesium, iron, and calcium. High fructose corn syrup may decrease absorption of trytophan from the gut (Ledochowski M, et al., 2001) thereby reducing the quantity of TPH enzyme and serotonin produced. The Parkinson’s medication carbidopa-levadopa (Drugs.Com Website) is known to interfere with tryptophan, thus TPH and serotonin production.
Ninety percent of serotonin is stored in the chromaffin cells of the intestines (Donnerer J, et al., 2006) where it regulates digestion and maintains stomach function. Additionally, the remainder of serotonin is found in platelets and the central nervous system where serotonin is produced in the raphe nuclei and pineal gland of the brain (Neurophysiology Website). Nerve axons from the raphe nuclei cover the entire length of the brainstem and extend to all parts of the brain including the cerebellum and spinal cord where serotonin influences memory, learning, behavior, mood (well-being, happiness), appetite, sleep and regulates insulin (Young SN, 2007).
When a sending neuron releases serotonin to stimulate a receiving neuron, the neurotransmitter travels out the sending neuron, across a gap or cleft to receptors on the receiving neuron. By design the neurotransmitter is quickly reabsorbed back into the sending neuron and recycled. A drug that modifies this normal physiology by keeping serotonin in this gap between the neurons longer is called a serotonin re-uptake inhibitor (SSRI). The result of a SSRI is to create the physiological impression that more serotonin is present thus continuing the stimulation of the receiving neuron. Many antidepressants, anti-anxiety drugs and post-traumatic stress drugs function in this manner. These drugs do not produce more serotonin to resolve a deficiency, but create the illusion that more is present.
Should the body be deficient or low on serotonin, only ingesting the proper foods or supplementing the diet with tryptophan or 5-HTP provides more serotonin to the brain and intestines. Studies have shown that a change in only 10% of the number of serotonin transporters will affect anxiety levels (Lesch KP, et al., 1996). Research shows that supplementing tryptophan or 5-HTP (available at nutritional stores) helps to maintain serotonin levels and aids with depression and anxiety (Murphy SE, et al., 2006). Providing adequate nutrients is important to maintaining healthy cells and production pathways.
III. Production of DOPAMINE, NOREPINEPHRINE, and EPINEPHRINE:
*Vitamin B9 Vitamin B9, iron Vitamin B3 & B6, zinc
Phenylalanine ——> Tyrosine —————-> DOPA ——————> DOPAMINE
Vitamin C S-Adenylmethionine (SAMe)
Dopamine ————> NOREPINEPHRINE ——————-> EPINEPHRINE
(* Required reaction cofactors are listed above the arrows in italics.)
This is a complicated pathway in that if sufficient amounts of the amino acid phenylalanine or tyrosine, vitamin B9 (folate), iron, vitamins B3 (niacin) + B6 (pyridoxal phosphate), zinc, vitamin C (ascorbic acid), and methionine (used to produce SAMe) are all present, then the three catecholamine neurotransmitters in this pathway (dopamine, norepinephrine and epinephrine (adrenaline)) are produced to keep the pathway cells strong. If production falls and pathway cells die off (apoptosis) Parkinson’s Disease or Altzheimer’s may develop.
Phenylalanine is found in fish, beef, chicken, milk, cheese, eggs, and nuts (www.livestrong.com/article/317897-list-of-foods-that-contain-phenylalanine/).
Tyrosine is found in beef, pork, turkey, duck, fish, egg whites, cheese, milk, and soy milk (www.livestrong.com/article/81485-foods-Ityrosine/).
Methionine is essential amino acid required in the diet. It is found in popcorn, grass fed meat, brown rice, organic oranges, and yogurt. SAMe (s-adenylsylmethionine) is made from methionine. It’s production is influenced by the neurotransmitter acetylcholine produced in the Acetylcholine Pathway described above. Methionine is also found in wheat and can be a deficiency in a wheat free diet. Methionine controls the adrenal glands which are the first responders under stress conditions. Stress may deplete methionine stores. Methionine chelates metals and neutralizes harmful chemicals. Painters and those exposed to chemicals may require additional methionine to neutralize these chemicals. Methionine is critical for donating a methyl group (-CH3) to norepinephrine to produce epinephrine in the Dopamine Pathway giving the body energy. Adrenals that are subjected to low levels of methionine may be a contributing factor to Adrenal Insufficiency, Tremor, and Parkinson’s Disease.
Vitamin B3, Vitamin B6, Vitamin B9. B-complex vitamins are water soluble and must be ingested daily.
Foods highest in Vitamin B3 (niacin) can be found at http://www.healthaliciousness.com/articles/foods-high-in-niacin-vitamin-B3.php.
Foods highest in Vitamin B6 (pyridoxal phosphate) can be found at http://www.healthaliciousness.com/articles/foods-high-in-vitamin-B6.php.
Foods highest in Vitamin B9 (folate) are found at
Vitamin C is water soluble and must be ingested daily. Vitamin C food sources are listed at http://www.healthaliciousness.com/articles/vitamin-C.php. Vitamin C is the major vitamin keeping the adrenal organs healthy.
Zinc is an important mineral. There is an informative web site listing zinc foods at http://www.healthaliciousness.com/articles/zinc.php.
Iron food sources are listed at http://www.healthaliciousness.com/articles/food-sources-of-iron.php.
Dopamine is quickly degraded and excreted in the urine. While there is some re-uptake, dopamine must be continually replenished. Dopamine is produced in the adrenals, gastrointestinal tract, neurons, and brain generating either excitatory or inhibitory nerve impulses. It has important roles in reward and punishment brain activity, increased heart rate and blood pressure, sleep, mood, attention, working memory, learning, problem-solving, social behavior, cognition, voluntary movement, pain, and motivation.
Dopamine deficiency causes decline in memory, attention, problem-solving and sociability. Insufficient dopamine biosynthesis in the dopaminergic neurons can cause Parkinson’s Disease (Grace AA, 1984). Stress increases the depletion of dopamine stores (Furuyashiki T, 2012). Dopamine plays a role in pain processing (Viisanen H, et al., 2012 ),
Norepinephrine (noradrenaline) can be produced from tyrosine or phenylalanine in the presence of vitamin B9 (folate), iron, vitamin B3 (thiamine), vitamin B6 (pyridoxal phosphate), and zinc. Norepinephrine is a neurotransmitter produced in the adrenal glands which helps control the body’s sympathetic system. This system is responsible for the “fight or flight response” to danger (Guyton A, 2006). Norepinephrine is a stress hormone (Tanaka M, et al., 2000). Its release increases heart rate, releases glucose from tissue, increases blood flow to skeletal muscle and brain oxygen levels.
Norepinephrine is important to prevent fainting (syncope) by preventing a drop in heart rate to maintain blood pressure. Neurons project throughout the brain and spinal cord.
Norepinephrine has a role in behavior, motivation, attention, focus, decision making, learning, motor output, response to performance error, negative feedback, monetary loss, cost benefit evaluation, task difficulty and the decision making process (Devauges V, et al., 1990) (Lutzenberger, W, et al., 1987) (Usher M, et al., 1999) (Eisenberger M, et al., 2003)(Falkenstein M, et al., 1991)(Genring WJ, et al., 1993) (Neurophysiologica 35), (Nieuwenhuis, S, et al., 2003). It has different actions upon different cell types. Low levels of this neurotransmitter have a role in depression along with serotonin.
Norepinephrine is reabsorbed and degraded within seconds. It works as an anti-inflammatory agent in brain tissue, suppressing cytokines. In Alzheimer’s Disease the norepinephrine producing cells may be affected (Szot P, et al., 2012).
Epinephrine (adrenaline) is an important component of the sympathetic fight or flight system. Production of epinephrine occurs in the adrenals from phenylalanine and tyrosine. It acts on most all body tissues. Epinephrine increases blood glucose and fatty acid levels which provide energy for cells (Sabyasachi S, 2007). Plasma levels of epinephrine may increase 10-fold during exercise and perhaps by 50-fold during stress requiring an ample supply of tyrosine (Raymondos, K, 2008) (Baselt, 2000). Epinephrine is released during times of “physical threat, excitement, noise, bright lights, and high temperatures” (Nelson L, 2004). Stress causes the sympathetic nervous system to stimulate adrenocorticotrophic hormone (ACTH) which stimulates epinephrine release (by activating tyrosine hydroxylase and dopamine-B-hydroxylase). It also stimulates cortisone production by the adrenals.
One study found that catecholamines (neurotransmitters derived from tyrosine in the dopamine pathway) in rat adrenals took …FOUR DAYS … yes, FOUR DAYS … to recover their original levels after being chemically depleted, and the regeneration of these neurotransmitters required acetylcholine (Patrick RL, et al., 1970). A human taking a heavy examination may require several days to restore normal neurotransmitter levels, yet universities schedule mid-term and final exams on consequentive days allowing no time for neurotransmitter restoration. When human adrenals are stressed they may take a significant amount of time and resources to regenerate neurotransmitters and cortisol.
Tyrosine, vitamin B-complex, vitamin C, zinc, iron, and methionine or SAMe can be purchased at a health food store to supplement the diet and maintain a healthy dopamine pathway.
“Parkinson’s Disease is associated with the depletion of tyrosine hydroxylase, dopamine, serotonin, and norepinephrine” and “administration of L-dopa may deplete L-tyrosine, L-tryptophan and 5-hydroxytryptophan (5-HTP), serotonin and sulfur amino acids (cysteine, methionine)” (Hinz M, et al., 2011). Researchers found that co-administration of L-dopa with 5-HTP, L-tyrosine, L-cysteine and cofactors enabled more effective treatment for Parkinson’s Disease by allowing optimal dosing of L-dopa for symptom relief without the barriers imposed by side effects and adverse reactions. (Hinz M et al., 2011)
THE CRITICAL ADRENALS:
We have discussed three important pathways for producing neurotransmitters. The organs most responsible for this job are the adrenals. The adrenals are critical to brain health. They are small, walnut shaped glands positioned on top of the kidneys. Back pain can be felt below the rib cage on either side when the adrenals are over-stressed. These organs produce neurotransmitters, sex hormones, and cortisol. Under athletic, academic, work-related, emotional, food-related, disease or inflammation-related stress conditions, the adrenals are the first to respond by producing high amounts of cortisol. The body tends to prioritize, so high cortisol production may come at the cost of reduced sex hormone and neurotransmitter production. We may see this in the triathlete with sporadic menses or the businessperson or student with high anxiety levels. The adrenals are prioritizing cortisol production to cope with the acute or chronic stress over the production of sex hormones and neurotransmitters
Upon the realization that these tiny organs are responsible for handling these vital functions, keeping the adrenals healthy becomes of critical importance. We have described the three neurotransmitter pathways to reinforce the importance of providing the proper amino acids and vitamins to the body to keep these pathways alive and well. Cells die off when adequate nutrients are not present. Vitamin C and the amino acid methionine are important for general adrenal function. Methionine is found in wheat, so wheat free diets may be deficient in methioinine. Glandular adrenal rebuilders are available at health food stores. Sugar, high fructose corn syrup, alcohol, and deep fried food consumption stress out the adrenals and make them work hard. There is an excellent book written by Dr. James Wilson, entitled “Adrenal Fatigue – The 21st Century Stress Syndrome”, (Smart Publications, 2001). A future http://www.wheatfreediseasefree.com post will discuss adrenal insufficiency, methionine and a wheat free diet. Restoring adrenal health and providing sufficient neurotransmitter substrate may be critical to restoring neurotransmitter supplies and eliminating disease. More research should be completed and better monitoring of neurotransmitter nutrient pathways through physician and home based testing would be helpful.
Street Drugs, Nicotine, Caffeine, and Neurotransmitters:
The street drug cocaine is a triple re-uptake inhibitor in that it blocks the re-uptake of serotonin, dopamine and norepinephrine (Fattore L, et al., 2009 ). Street drugs can increase dopamine levels 10 fold and temporarily cause psychosis (Williams). Amphetamines are similar in structure to dopamine. MDMA (ecstasy) releases serotonin, norepinephrine and dopamine and then inhibits their transport which increases concentrations within cell cytoplasm (Bogen IL, et al., 2003) (Fitzgerald JL, et al., 1990).
Amphetamines increase the concentrations of dopamine, serotonin and norepinephrine possibly by reversing the transport of dopamine and serotonin back into the gap or cleft between the neurons (Florin SM, 1994) (Jones S, et al., 1999). Dextromorphan, a cough suppressant, works as an SSRI (Schwartz AR, et al., 2008). LSD is a serotonin agonist in that it stimulates the serotonin receptor on the receiving neuron by mimicking serotonin (Titeler M, et al., 1988). Caffeine increases activity of serotonin, acetycholine, epinephrine, dopamine, and norepinephrine. Nicotine is thought to increase acetylcholine and dopamine levels. Street drugs, caffeine, and nicotine force the body to release stores of neurotransmitters and then keep the neurotransmitter in circulation by inhibiting the reuptake. Again, these drugs are not making more neurotransmitter but they are depleting current stores and tricking the body into thinking there is more chemical. The only way to enable the body to produce more neurotransmitters is to provide the proper nutrients through diet or supplements.
Analysis Unique to the Wheat Free Diet:
Many individuals damage their adrenals through alcohol, sugar, high fructose corn syrup, deep fried foods, low vitamin C and low nutrient intake causing depression, fatigue and eventually tremor. The case above is unique, because this patient eats a healthy diet with the exception of wheat which contains the amino acids methionine and lysine. Thus, her diet may be deficient in methionine. However, nutritiondata.com shows detailed analysis that if she consumes meat, ample methionine should be present. Unlike earlier times, most cattle and fish are no longer raised in the wild. Do they still contain adequate amino acids? If this subject typically eats meat, containing several grams of amino acids per day, why would 500mg – 1g of supplemental methionine improve her condition?
Additionally, methionine is responsible for chelating harmful chemicals such as those found in paint. She may require additional methionine to detoxify the fumes. This subject is highly stressed which would cause the adrenals to produce more cortisone. Regulation of the adrenal-pituitary-hypophyseal axis requires methionine. Perhaps a combination of low dietary intake plus a high methionine requirement resulted in damaging her adrenals and a reduction of neurotransmitter production.
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Photograph: Jordanelle Reservoir, Park City, Utah
A Special Thanks to Billie Jay Sahley PhD. and her books on amino acids including her book “The Anxiety Epidemic” for inspiring research with neurotransmitter pathways, substrates and cofactors.
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