Bone Nutrients:

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Calcium

Medicine often points the finger to high sodium levels as being contributory to heart disease when in fact the culprit may be low calcium, potassium or magnesium levels. These nutrients work as a team to make nerve impulses conduct and muscles contract. These minerals must be present concurrently and in adequate amounts.

Potassium, magnesium and calcium levels can be measured in blood serum. However, the calcium blood measurement is not so useful, because when blood calcium is low, the body takes calcium out of bone to raise the blood calcium levels. When bone tissue is broken down in this manner, both calcium and phosphate are released from the bone into the blood stream, thus elevating blood serum levels. This regulation process is great to keep nerves conducting and muscles contracting. However, the process weakens bones because it removes calcium and phosphate. If this calcium and phosphate are never replaced, bone breakdown and eventually osteoporosis results.

Since blood calcium measurements do not give us an accurate indication of whether calcium levels are being maintained through dietary methods or from bone storage, medicine measures bone calcium levels through density scanning techniques such as DEXA scan. DEXA scan measurements that are between +1 and -1 are considered normal. Measurements between -1 and -2.5 are considered osteopenic (reduced bone mass) and measurements less than -2.5 are considered osteoporosis. More information can be found on http:// http://www.niams.nih.gov/health_info/bone/Bone_Health/bone_mass_measure.asp.

Noticeable physical indications of low blood calcium levels include muscle cramps, restless legs and broken bones. Muscles need adequate calcium, sodium, and potassium to contract and relax. Calcium supplements help relax a muscle cramp. This is due to lactic acid build up during exercise. Calcium may bind lactic acid, relaxing the muscle and releasing the cramp. Sparkling water and club soda, given their alkali nature, also help to neutralize the lactic acid relieving a muscle cramp. While massaging and stretching a tight muscle feels good, this may damage the fibers. Muscle relaxation and contraction is best restored when adequate minerals are provided. While a calcium supplement and alkali water, club soda, or sparkling water may be a temporary remedy to relieve muscle cramps or restless legs, a long term dietary and supplement plan will be important to maintain muscle, bone, and nerve health.

Calcium Sources

Because calcium is critical to humans, the bones have been cleverly designed to be the body’s mini storage units for calcium. We maintain these storage units and blood calcium levels through food intake and supplementation. Some of the best calcium foods according to WebMD are “cheese, yogurt, milk, sardines, dark leafy greens (spinach, kale, turnips, and collard greens) and orange juice”. You can find specific food calcium and nutrient information on NutritionData.com. Some of the best calcium supplements contain calcium citrate, calcium phosphate, and magnesium. Many supplements contain calcium carbonate which is lime. Current calcium recommendations range from 1000mg – 1500mg/day. Vitamin D also has an important role in transporting calcium into bone.

Collagen

While calcium supplementation is frequently recommended. It is less recognized that calcium citrate and phosphate are important supplements, given that they constitute a larger percentage of bone. The remaining portion of bone is composed of collagen. The collagen component of bone is never mentioned, yet it comprises anywhere from 10-30% of bone. Collagen is a flexible tissue found in young bone, tendons and ligaments. Collagen is found throughout the body in tissues, organs, joints, gums and teeth. In addition to calcium citrate and phosphate to make the calcium salts in bone, we need all of the nutrients to maintain the collagen network found in bone. The collagen network is formed by vitamin C and the amino acids lysine, proline and glycine. Collagen fibers can be damaged by injury, repetitive use, stretches or strains when muscles are weak. Collagen can additionally be damaged by our immune system. This is due to the attachment of wheat gluten to collagen fibers throughout the body. Our immune system sees wheat gluten and wheat defense proteins as foreign invaders. This causes the secretion of immune system chemicals contributing to arthritis, asthma, and many organ diseases. (More information can be found on http://www.wheatfreediseasefree.com.)

In summary, all of the nutrients: calcium citrate, phosphate, magnesium, vitamin D, vitamin C, lysine, proline and glycine must be present concurrently to build flexible collagen and healthy bone tissue. They can be found in a variety of foods and these supplements are available at nutrition stores. (Teeth may be a lysine storage site, and adequate lysine and vitamin C levels may contribute to gum and teeth health.)

So, we discussed calcium’s importance to muscle and nerves, and the body’s brilliant regulation mechanism for calcium such that when blood calcium levels are low, the body removes calcium from bone to maintain the blood calcium levels. As we mentioned, this regulation mechanism is great for maintaining nerve and muscle function, but not so great at maintaining bone strength and density. A good visual analogy might be a Corvette production line. All of the parts to build the Corvette must be supplied to build the car. If one part is missing, the technicians and robots build what may look like a car and feel like a car, but may not function like a car. One small part may make the difference. Bones and collagen work the same way. They are composed of many “parts” (calcium citrate, phosphate, magnesium, vitamin D, vitamin C, lysine, glycine, and proline). All nutrients must be supplied in adequate amounts for your body to build bone, tendon and ligaments. If “parts” are missing, the body may build structures that look like bone, tendon and ligaments, but they might not function that way. Bones may break easily and muscles may cramp easily. Restless legs may result. Tendons may tear. Adequate parts produce beautiful, zero to 60mph in 4 seconds Corvettes, and adequate nutrients produce healthy, functional bones, tendons and ligaments.

Why is Calcium Removed from Bone ??

As we discussed, our bodies remove calcium from bone tissue to maintain critical muscle and nerve function. This eloquent measure is likely designed to work temporarily when dietary/ supplemental calcium is insufficient. Alas, in osteoporosis, this calcium removal measure is apparently being forced to work long term. There is a second important reason calcium may be lost from bone. Many of our foods are acidic. The blood is carefully regulated to be around pH of 7.4, this is critical for chemical pathways. Acidic foods would drive the blood pH below 7.4.  Recycled bone calcium contains bicarbonate which acts as a pH buffer in the blood to balance these acidic foods, maintaining the pH. Alkali water, club soda, and sparkling water all bind acid to help maintain this normal blood pH. This process might be somewhat like bath water. If the bath water is too hot, cold water can be mixed with hot water to neutralize it’s effect. Finally, calcium can be removed from bone and excreted when the adrenals are fatigued. Both mental and physical stress, can fatigue the adrenals. Our high consumption modified grain and sugars fatigues our adrenals. As a result, calcium leaves the body.

Calcium Buildup in Tissues Other than Bone

Often, calcium builds up in tissues other than bone. Calcium buildup is found in breast tissue, kidney stones, gallstones, cysts and many other tissues, where it doesn’t belong. Why? What should we do? Should we reduce calcium intake to reduce this tissue buildup? Interestingly, calcium buildup in the wrong tissues appears to occur when individuals have insufficient dietary/supplemental calcium intake. Researchers have found that increasing dietary calcium and supplements decreases calcium buildup in the wrong tissues and increases calcium buildup in the right place, bone (Gul and Monga, 2014).

Your curious mind may ask, why is calcium showing up in the wrong tissues when dietary/ supplemental calcium levels are low? We would like to propose a theory to answer this question. We know that when blood calcium levels are low, recycled calcium (and phosphate) being released from bone to raise blood calcium levels. It is likely that the recycled bone calcium is structurally different from the calcium we eat in food and/or supplement, and possibly the recycled calcium from bone cannot be redeposited into bone tissue once blood levels normalize. Perhaps, the body can’t easily excrete excess recycled bone calcium, thus it builds up in tissues where it doesn’t belong. Certainly, releasing calcium from bone, to maintain blood calcium levels, was meant to be a temporary measure, not a long term process.

What is the impact of having recycled calcium delivered to the wrong tissues? “Insufficient intake of dietary calcium (<600mg/day) can increase… the risk of stone formation“, (Gambara, 2016). Gambara confirms that “stone formation is frequently associated with other diseases of affluence such as hypertension, osteoporosis, cardiovascular disease, metabolic syndrome, and insulin resistance.” Research studies such as the 2012 NHANES find “a 70% increase from the 1994 NHANES” in urinary tract stone disease, (Gul and Monga, 2014). Thus, our calcium deficiencies are worsening. These researchers report that “newer research is finding that stones are associated with several serious morbidities”.

Researchers have found that calcium buildup in the form of hydroxyapatite in breast tissue contributes to breast cancer (Cooke, 2003). Let’s repeat this sentence. Calcium build up in breast tissue is involved with breast cancer. One in eight women will have breast cancer. Researchers also recognize that radiation can modify healthy cells and turn them into uncontrollable cancerous cells. Mammograms contain radiation and radiation damage is additive in the body. Researchers have found that citrate and phosphate may have a role in removing hydroxyapatite deposits in breast tissue.  In one research study, women taking phosphate bone density drugs had reduced incidence of breast cancer.

How to Deliver Calcium to Bone

Given this information, how shall we best increase calcium in our bones and decrease calcium tissue deposits and stones?

One common solution, is to take a calcium supplement such as calcium citrate and/or calcium phosphate. Bone is composed of calcium citrate, calcium phosphate, magnesium, vitamin D, and collagen (vitamin C, lysine, proline, and glycine). It used to be that many calcium supplements were composed of calcium carbonate. Calcium carbonate is lime. Many supplements are now changing ingredients to calcium citrate or calcium phosphate. We need both.

Why calcium citrate? Citrate works in two ways. First, citrate is a buffer. Therefore, when the blood pH is low, citrate will buffer the pH and calcium will not be pulled from bone tissue to normalize pH. Alkali water, club soda or sparking water are alkali drinks that help to increase blood pH. Secondly, calcium citrate is found to combine well with phosphate and collagen components to make bone. Calcium citrate appears to be a key strength component in bone tissue. More information on citrate properties: https://www.sciencedaily.com/releases/ 2011/06/110608153548.htm. Finally, citrate and phosphate help remove calcium buildup in the wrong tissues: http://www.ncbi.nlm.nih.gov/pubmed/?term=breast%2C+hydroxyapetite %2C+citrate%2C+phosphate. Researchers found that citrus bioflavonoids and lemon peel inhibit stone formation: http://www.ncbi.nlm.nih.gov/pubmed/?term=27241030. This is critical information to the long term prevention calcium build up in the wrong tissues and maybe critical to the long term prevention of breast cancer. Many calcium supplements are now calcium citrate.

Calcium phosphate is the other important component of bone. Calcium citrate and phosphate can be found in supplements. Researchers have found that citrate and phosphate may have a role in removing hydroxyapatite deposits in breast tissue. These deposits found on mammograms may contribute to the formation of breast cancer. In one research study, women taking phosphate bone density drugs had reduced incidence of breast cancer.

The Linus Pauling Institute has found that many other minerals and vitamins are found in bone such as magnesium, fluoride, sodium, vitamin A, D and K. More information can be found on: http://lpi.oregonstate.edu/mic/micronutrients-health/bone-health#minerals. More individuals than recognized may be deficient in vitamin A, as seen in dry eyes and in vitamin K as seen in nose bleeds. (Caution: vitamin K, found in leafy green vegetables, allows the blood to clot when vessels are damaged. Blood thinners interfere with vitamin Ks ability to clot blood. Ingesting additional vitamin K interferes with blood thinner drugs)

Secondly, drink plenty of fluids to produce at least 2.5L of urine per day (Gul and Monga, 2014). Gul recommends avoiding the colas which are acidic, yet not being quite as concerned with the “citric acid containing sodas, which include most clear soft drinks.” As we learned above, citric acid found in lemons and limes can be beneficial to bone health.

Remember that if you are eating a lot of protein, taking amino acids for brain or sports health, or drinking wine your blood may be more acidic which will pull carbonate from your bones to buffer the pH of your blood. So you may want to increase your calcium citrate or alkali water, club soda, and/or sparkling water consumption to balance these actions.

Finally, stressing your adrenals, the little walnut shaped organs that sit on top of your kidneys, (the adrenals produce neurotransmitters) results in the loss of calcium. Minimizing both mental stress activities and physical stress, often caused by the consumption of manufactured wheat and sugar, will help the adrenals. High glucose (grains, sugars) levels result in high stone levels (Gul and Monga, 2014).

References:

Cooke MM1, McCarthy GM, Sallis JD, Morgan MP. Phosphocitrate inhibits calcium hydroxyapatite induced mitogenesis and upregulation of matrix metalloproteinase-1, interleukin-1beta and cyclooxygenase-2 mRNA in human breast cancer cell lines. Breast Cancer Res Treat. 2003 May;79(2):253-63.

Gambaro G1, Trinchieri A2., Recent advances in managing and understanding nephrolithiasis/ nephrocalcinosis. F1000Res. 2016 Apr 18;5. pii: F1000 Faculty Rev-695. doi: 10.12688/ f1000research.7126.1. eCollection 2016

Gul Z1, Monga M2., Medical and dietary therapy for kidney stone prevention.
Korean J Urol. 2014 Dec;55(12):775-9. doi: 10.4111/kju.2014.55.12.775. Epub 2014 Nov 28.

Additional Materials:

Citrate helps reduce stone formation:

http://www.ncbi.nlm.nih.gov/pubmed/?term=22908773 http://www.ncbi.nlm.nih.gov/pubmed/?term=26614113

http://www.ncbi.nlm.nih.gov/pubmed/?term=20576821 http://www.ncbi.nlm.nih.gov/pubmed/?term=21747586

http://www.ncbi.nlm.nih.gov/pubmed/?term=17509313 http://www.ncbi.nlm.nih.gov/pubmed/?term=26582172 http://www.ncbi.nlm.nih.gov/pubmed/?term=27072174 http://www.ncbi.nlm.nih.gov/pubmed/?term=25855777 http://www.ncbi.nlm.nih.gov/pubmed/?term=26439475 http://www.ncbi.nlm.nih.gov/pubmed/?term

Chronic alcohol use may weaken bones: http://www.ncbi.nlm.nih.gov/pubmed/1854370.

EGCG (epigallocatechin gallate) found in green tea shows promise inhibiting the formation of kidney stones in rats:

http://www.ncbi.nlm.nih.gov/pubmed/?term=26281564 http://www.ncbi.nlm.nih.gov/pubmed/?term=16047215 http://www.ncbi.nlm.nih.gov/pubmed/?term=26898643

Mediterranean/fruit/vegetable diet may protect against stone formation: http://www.ncbi.nlm.nih.gov/pubmed/24502605

Disclaimer: The ERB is a literature research team presenting the findings of other researchers. The ERB is not licensed medical nor dietary clinicians and will not give medical nor dietary advice. Any information presented on this website should not be substituted for the advice of a licensed physician or nutritionist. Users of this website accept the sole responsibility to conduct their own due diligence on topics presented and to consult licensed medical professionals to review their material. We make no warranties or representations on the information presented and should users utilize this research without consulting a professional, they assume all responsibility for their actions and the consequences.

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Neurotransmitter Pathways affecting Concussion, TBI, Stress, Depression, Tremor, Stroke, and Anxiety

securedownloadNeurotransmitter Brain Food:  Rebuilding  the Acetylcholine (Choline or Lecithin),  Serotonin (5-HTP or tryptophan)  and Dopamine (Tyrosine) Neurotransmitter Pathways.  

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.

Neurotransmitter  Discussion:

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.

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THREE NEUROTRANSMITTER PATHWAYS:

I.  Production of  ACETYLCHOLINE:

                  Phosphatidylcholine (Lecithin)   —->  Glycerophosphatidylcholine   —> Choline   

                    Then,  Choline  +   Acetyl  Coenzyme A  —->   ACETYLCHOLINE

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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).

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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)

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.(Enzymes and cofactors required to produce 5-HTP and 5-HT from the Understand and Cure Website.)

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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:

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                                          *Vitamin B9             Vitamin B9, iron               Vitamin B3 & B6, zinc                     

                     Phenylalanine  ——>  Tyrosine   —————->   DOPA     ——————>   DOPAMINE 

                                   

                                          Vitamin C                                            S-Adenylmethionine (SAMe)
                     Dopamine  ————>   NOREPINEPHRINE ——————->  EPINEPHRINE

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(*  Required reaction cofactors are listed above the arrows in italics.)

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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

http://www.healthaliciousness.com/articles/foods-high-in-folate-vitamin-B9.php.

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)

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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.

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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.  

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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.

Case Study References:

Livestrong website:  http://www.livestrong.com/article/458050-choline-risks/

Headquarters Website:  http://www.nutritionalsupplementshq.com/soy-lecithin-side-effects/

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Acetylcholine References:

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De Simone R, Aloe L.  Influence of ethanol consumption on brain nerve growth factor and its target cells in developing and adult rodents. Source Istituto di Neurobiologia, Consiglio Nazionale delle Ricerche, Rome, Italy.  Ann Ist Super Sanita. 1993;29(1):179-83.

Glenn MJ, Adams RS, McClurg L. Source Department of Psychology, Colby College, 5550 Mayflower Hill Dr., Waterville, ME 04901, USA. Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats. Brain Res. 2012 Mar 14;1443:52-63. Epub 2012 Jan 17.

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Guttierez-Fernández M, Rodríguez-Frutos B, Fuentes B, Vallejo-Cremades MT, Alvarez-Grech J, Expósito-Alcaide M, Díez-Tejedor E. Source Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neurosciences Area of IdiPAZ, Health Research Institute, Autónoma University of Madrid, Madrid, Spain. CDP-choline treatment induces brain plasticity markers expression in experimental animal stroke. Neurochem Int. 2012 Feb;60(3):310-7. Epub 2011 Dec 30.

Hasler CM (October 2000). “The changing face of functional foods”. Journal of the American College of Nutrition 19 (5 Suppl): 499S–506S. PMID 11022999.

Hirsch MJ, Wurtman RJ. Lecithin consumption increases acetylcholine concentrations in rat brain and adrenal gland. Science. 1978 Oct 13;202(4364):223-5.

Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for Thiamine, Riboflavin, Niacin, Bitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Washington, DC: National Academies Press;1998

Johnson AR, Lao S, Wang T, Galanko JA, Zeisel SH.  Source Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.  Choline dehydrogenase polymorphism rs12676 is a functional variation and is associated with changes in human sperm cell function.PLoS One. 2012;7(4):e36047. Epub 2012 Apr 27.

Kadaveru K, Protiva P, Greenspan EJ, Kim YI, Rosenberg DW.  Source  Molecular Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030. Dietary Methyl Donor Depletion Protects Against Intestinal Tumorigenesis in ApcMin/+ Mice.  Cancer Prev Res (Phila). 2012 Jul;5(7):911-20. Epub 2012 Jun 7.

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Linus Pauling Institute. http://lpi.oregonstate.edu/infocenter/othernuts/choline//

Oshida K, Shimizu T, Takase M, Tamura Y, Shimizu T, Yamashiro Y. Effects of dietary sphingomyelin on central nervous system myelination in developing rats. Peditr Res. 2003; 53:589–593

Pitkin RM. Folate and neural tube defects. Am J Clin Nutr 2007;85(1):285S-288S.  (PubMed)

Sha W, da Costa KA, Fischer LM, Milburn MV, Lawton KA, Berger A, Jia W, Zeisel SH.Source Bioinformatics Research Center, University of North Carolina at Charlotte, USA.Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline. FASEB J. 2010 Aug;24(8):2962-75. Epub 2010 Apr 6.

Xu X, Gammon MD, Zeisel SH, Bradshaw PT, Wetmur JG, Teitelbaum SL, Neugut AI, Santella RM, Chen J.  Source  Department of Community and Preventive Medicine, Box 1057, Mt. Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. High intakes of choline and betaine reduce breast cancer mortality in a population-based study.  FASEB J. 2009 Nov;23(11):4022-8. Epub 2009 Jul 27.

Zeisel SH, da Costa KA. Source  Department of Nutrition at the Nutrition Research Institute, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.  Nutr Rev. Choline: an essential nutrient for public health. 2009 Nov;67(11):615-23.

Zhang W, Bai M, Xi Y, Hao J, Liu L, Mao N, Su C, Miao J, Li Z. Early memory deficits precede plaque deposition in APPswe/PS1dE9 mice: involvement of oxidative stress and cholinergic dysfunction. Source Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi’an City, Shaanxi Province 710038, China. Free Radic Biol Med. 2012 Apr 15;52(8):1443-52. Epub 2012 Feb 2.

Zurkovsky L, Bychkov E, Tsakem EL, Siedlecki C, Blakely RD, Gurevich EV. Cognitive effects of dopamine depletion in the context of diminished acetylcholine signaling capacity. Dis Model Mech. 2012 Aug 3. [Epub ahead of print]

Serotonin References:
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Bogen IL, Haug KH, Myhre O, Fonnum F (2003). “Short- and long-term effects of MDMA (“ecstasy”) on synaptosomal and vesicular uptake of neurotransmitters in vitro and ex vivo”. Neurochemistry International 43 (4–5): 393–400. doi:10.1016/S0197-0186(03)00027-5. PMID 12742084.
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Donnerer J, Lembeck F (2006). The chemical languages of the nervous system: history of scientists and substances. Karger Publishers. pp. 161–. ISBN 978-3-8055-8004-5. Retrieved 23 May 2011
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Fattore L, Piras G, Corda MG, Giorgi O (2009). “The Roman high- and low-avoidance rat lines differ in the acquisition, maintenance, extinction, and reinstatement of intravenous cocaine self-administration”. Neuropsychopharmacology 34 (5): 1091–101. doi:10.1038/npp.2008.43. PMID 18418365.
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Fitzgerald JL, Reid JJ (1990). “Effects of methylenedioxymethamphetamine on the release of monoamines from rat brain slices”. European Journal of Pharmacology 191 (2): 217–20. doi:10.1016/0014-2999(90)94150-V. PMID 1982265.
.
Florin SM, Kuczenski R, Segal DS (August 1994). “Regional extracellular norepinephrine responses to amphetamine and cocaine and effects of clonidine pretreatment”. Brain Res. 654 (1): 53–62. doi:10.1016/0006-8993(94)91570-9. PMID 7982098.
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Jones S, Kauer JA (November 1999). “Amphetamine depresses excitatory synaptic transmission via serotonin receptors in the ventral tegmental area”. J. Neurosci. 19 (22): 9780–7. PMID 10559387.
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Ledochowski M, Widner B, Murr C, Sperner-Unterweger B, Fuchs D (2001). “Fructose malabsorption is associated with decreased plasma tryptophan”. Scand. J. Gastroenterol. 36 (4): 367–71. doi:10.1080/003655201300051135. PMID 11336160.
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Murphy SE, Longhitano C, Ayres RE, Cowen PJ, Harmer CJ.  “Tryptophan supplementation induces a positive bias in the processing of emotional material in healthy female volunteers.” Source Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.  Psychopharmacology (Berl). 2006 Jul;187(1):121-30. Epub 2006 May 4.
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Neurophysiology Website:  http://www.neurophysiology.ws/neuroactivechemicals.htm
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Schwartz AR, Pizon AF, Brooks DE (September 2008). “Dextromethorphan-induced serotonin syndrome”. Clinical Toxicology (Philadelphia, Pa.) 46 (8): 771–3. PMID 19238739.
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Titeler M, Lyon RA, Glennon RA (1988). “Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens”. Psychopharmacology (Berl.) 94 (2): 213–6. PMID 3127847.
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Tryptophan Foods Website:  http://www.healthinformationnews.com/health_by_category/Nutrition/nutrition_pages/Foods_High_Tryptophan.html.
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Dopamine Pathway References:

Barch, DM; Braver, TS; Nystrom, LE; Forman, SD; Noll, DC; Cohen, JD (1997). “Dissociating working memory from task difficulty in human prefrontal cortex”. Neuropsychologia 35 (10): 1373–80. doi:10.1016/S0028-3932(97)00072-9. PMID 9347483.

Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 545–547. ISBN 0-9626523-7-7.

Devauges V, Sara SJ, Activation of the noradrenergic system facilitates an attentional shift in the rat. Behav. Brain Res., 1990 Jun 18;39(1):19–28.

Eisenberger, N. I.; Lieberman, M. D.; Williams, K. D. (2003). “Does rejection hurt? An FMRI study of social exclusion”. Science 302 (5643): 290–2. Bibcode 2003Sci…302..290E. doi:10.1126/science.1089134. PMID 14551436.

Falkenstein M, Hohnsbein J, Hoorman J, Blanke L. (1991). Effects of crossmodal divided attention on late ERP components: II. Error processing in choice reaction tasks. Electroencephalogr. Clin. Neurophysiol. 78:447–55

Furuyashiki T, “Roles of Dopamine and Inflammation-Related Molecules in Behavioral Alterations Caused by Repeated Stress”.  Source Department of Pharmacology, Kyoto University Graduate School of Medicine, Japan.  Pharmacol Sci. 2012 Sep 15. [Epub ahead of print]

Gehring, WJ; Goss, B; Coles, MGH; Meyer, DE; Donchin, E. (1993). “A neural system for error detection and compensation. Psychol”. Sci 4: 385–90.

Grace AA, Bunney BS (1984). “The control of firing pattern in nigral dopamine neurons: single spike firing” (pdf). Journal of Neuroscience 4 (11): 2866–2876. PMID 6150070

Guyton, Arthur; Hall, John (2006). “Chapter 10: Rhythmical Excitation of the Heart”. In Gruliow, Rebecca (Book). Textbook of Medical Physiology (11th ed.). Philadelphia, Pennsylvania: Elsevier Inc.. p. 122. ISBN 0-7216-0240-1.

Hinz M, Stein A, Uncini T. Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; “Amino acid management of Parkinson’s disease: a case study.” Int J Gen Med. 2011 Feb 28;4:165-74.

Lutzenberger, W., Elbert, T., Rockstroth, B. (1987). A brief tutorial on the implications of volume conduction for the interpretation of the EEG. Journal of Psychophysiology, 33. S56

Nelson, L.; Cox, M. (2004). Lehninger Principles of Biochemstry (4th ed.). New York: Freeman. p. 908. ISBN 0-7167-4339-6

Nieuwenhuis, S.; Aston-Jones, G.; Cohen, J. D. (2005). “Decision making, the P3, and the locus coeruleus-norepinephrine system”. Psychological Bulletin 131 (4): 510–32. doi:10.1037/0033-2909.131.4.510. PMID 16060800.

Patrick RL, Kirshner N (1970). “Acetylcholine-Induced Stimulation of Catecholamine Recovery in Denervated Rat Adrenals after Reserpine-Induced Depletion.”  Department of biochemistry, Duke University Medical Center, Durham, North Carolina.  Molecular Pharmacology, 7, 389-396.

Raymondos, K.; Panning, B.; Leuwer, M.; Brechelt, G.; Korte, T.; Niehaus, M.; Tebbenjohanns, J.; Piepenbrock, S. (2000). “Absorption and hemodynamic effects of airway administration of adrenaline in patients with severe cardiac disease”. Ann. Intern. Med. 132 (10): 800–803. PMID 10819703.

Sabyasachi Sircar (2007). Medical Physiology. Thieme Publishing Group. pp. 536. ISBN 3-13-144061-9.

Szot P, “Common factors among Alzheimer’s disease, Parkinson’s disease, and epilepsy: possible role of the noradrenergic nervous system.”  Northwest Network for Mental Illness Research, Education, and Clinical Center, Veterans Administration Puget Sound Health Care System, 1660 S Columbian Way,Seattle, WA 98108, U.S.A Epilepsia. 2012 Jun;53 Suppl 1:61-6. doi: 10.1111/j.1528-1167.2012.03476.x.

Tanaka M, et al. (2000). Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. doi:10.1016/S0014-2999(00)00569-0

Usher, M.; Cohen, J. D.; Servan-Schreiber, D.; Rajkowski, J.; Aston-Jones, G. (1999). “The role of locus coeruleus in the regulation of cognitive performance”. Science 283 (5401): 549–54. Bibcode 1999Sci…283..549U. doi:10.1126/science.283.5401.549. PMID 9915705.

Viisanen H, Ansah OB, Pertovaara A. “The role of the dopamine D2 receptor in descending control of pain induced by motor cortex stimulation in the neuropathic rat”. Source Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki, FIN-00014 Helsinki, Finland.  Brain Res Bull. 2012 Nov 1;89(3-4):133-43. doi: 10.1016/j.brainresbull.2012.08.002. Epub 2012 Aug 9.

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Street Drugs, Nicotine, Caffeine, Alcohol and Neurotransmitters:

Bogen IL, Haug KH, Myhre O, Fonnum F (2003). “Short- and long-term effects of MDMA (“ecstasy”) on synaptosomal and vesicular uptake of neurotransmitters in vitro and ex vivo”. Neurochemistry International 43 (4–5): 393–400. doi:10.1016/S0197-0186(03)00027-5. PMID 12742084.

Fattore L, Piras G, Corda MG, Giorgi O (2009). “The Roman high- and low-avoidance rat lines differ in the acquisition, maintenance, extinction, and reinstatement of intravenous cocaine self-administration”. Neuropsychopharmacology 34 (5): 1091–101. doi:10.1038/npp.2008.43. PMID 18418365.

Fitzgerald JL, Reid JJ (1990). “Effects of methylenedioxymethamphetamine on the release of monoamines from rat brain slices”. European Journal of Pharmacology 191 (2): 217–20. doi:10.1016/0014-2999(90)94150-V. PMID 1982265.

Florin SM, Kuczenski R, Segal DS (August 1994). “Regional extracellular norepinephrine responses to amphetamine and cocaine and effects of clonidine pretreatment”. Brain Res. 654 (1): 53–62. doi:10.1016/0006-8993(94)91570-9. PMID 7982098.

Jones S, Kauer JA (November 1999). “Amphetamine depresses excitatory synaptic transmission via serotonin receptors in the ventral tegmental area”. J. Neurosci. 19 (22): 9780–7. PMID 10559387.

Schwartz AR, Pizon AF, Brooks DE (September 2008). “Dextromethorphan-induced serotonin syndrome”. Clinical Toxicology (Philadelphia, Pa.) 46 (8): 771–3. PMID 19238739.

Titeler M, Lyon RA, Glennon RA (1988). “Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens”. Psychopharmacology (Berl.) 94 (2): 213–6. PMID 3127847.

Williams:  http://www.williams.edu/imput/synapse/pages/IIIB5.htm

Copyright © 2012.  All rights reserved.

12-02-12

To request specific dosage data for this case study, please send an email to wheatfreediseasefree@gmail.com.

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.

Disclaimer:  The ERB is a literature research team presenting the findings of other researchers. The ERB is not licensed medical nor dietary clinicians and will not give medical nor dietary advice.   Any information presented on this website should not be substituted for the advice of a licensed physician or nutritionist.  Users of this website accept the sole responsibility to conduct their own due diligence on topics presented and to consult licensed medical professionals to review their material.  We make no warranties or representations on the information presented and should users utilize this research without consulting a professional, they assume all responsibility for their actions and the consequences.