Natural treatments for Anxiety.

IS ANXIETY A FACT OF LIFE? I don't think so. Readers have requested we address the subject of relieving anxiety by using the amino acids Taurine, & GABA, and Vitamin B3 (Niacin). Though setting out to do this, by the time anxiety & taurine were finished, the news was too long, so GABA & B3 will have to wait. Taurine has many other benefits, so if anxiety is not your interest you may want to skip ahead to the Taurine section. I would not begin helping someone with anxiety by giving these single agents alone, & indeed they may not need to be given. Suffice it to say, when you are physically healthy & biochemically balanced you should have no symptoms of anxiety unless you find yourself in an extremely emergent situation. Those under 18 or over 38 who suddenly develop anxiety which disrupts their normal activity may have one of the medical illnesses which can include anxiety & should have appropriate medical evaluation. Apparently, many in our society are anxious because minor tranquilizers are one of the most widely prescribed group of drugs & among the most problematic when regularly used long term, which, unfortunately, they often are. They are highly addicting & over time risk adding to the very symptoms they were originally intended to alleviate. Though the Physicians Desk Reference warns of their addictive potential & suggests only intermittent or short term usage, these warnings are often ignored. Some of these tranquilizers are Xanax, Klonopin, Ativan, Valium, Librium. Tranxene, as well as some of the sleeping meds. PHYSIOLOGICAL OR PSYCHOLOGICAL ANXIETY, OR BOTH? It helps to distinguish whether the anxiety begins with physical symptoms such as racing heart, sweaty palms, shaking, nervous stomach, restlessness, tension, etc. & then perhaps spreads to associated thoughts & fears. Or does it begin with fearful anxious thoughts & spread to become a physiological reaction? Or is it only manifested by thoughts with no physical component or physical symptoms with little associated fear thoughts. When there is a usual thought onset to the symptoms, besides doing all of the next recommended items, it is important to decondition your thought patterns. There are many techniques for doing this. My current favorite is the use of Hypnoperipheral Processing reprogramming tapes. This is a combination of hypnosis & Neurolinguistic Programming. It is a powerful & effective tool for change! You can find such tapes at http://www.metamodels.com/maps/hpp.html. I would suggest the series "Changing Emotions" & "Feeling Better". We also clarify the timing of the anxiety. Is it all the time, or at certain times of the day or night? Is it only in very specific situations? I had a patient who only had severe anxiety when going out in the car. We found she was sensitive to auto fumes & when we had her wear a carbon filtered mask to keep out the fumes, she was able to go out without any anxiety. What percentage of agoraphobics are having their symptoms as a reaction to a specific chemical environment? All of this detective work helps to clarify how much is physical, how much is psychological, or even how much is a psychological conditioned response to a physical trigger. Is the problem related to blood sugar instabilty, which I see quite often & commonly has a pattern of middle of the night, early a.m. or mid-afternoon symptoms. Or is it related to food sensitivities? Is there is a personal or family history of allergies or is a person repetitively eating the same foods, or many of the high allergen foods, such as milk, cheese, wheat, eggs? We also look for a history of high caffeine, alcohol, or sugar intake , or a general junk food diet. Is there a premenstrual or menopausal component? Is the person on medications which can cause anxiety as a side effect? WHAT DOES NUTRITION HAVE TO DO WITH ANXIETY? It is known that deficiencies of certain nutrients can cause anxiety, so begin by improving your diet. Those nutrients are: Vitamins B1, B3, B6, B12, folic acid, calcium, magnesium, phosphorus, omega-3-fatty acids, such as fish or flax seed oil, & certain amino acids, such as L-tryptophan, taurine, GABA. Too much calcium can also cause anxiety. First, clean up your diet. With your diet improvement you may want to add a good multivitamin mineral, an extra B complex, & an omega-3-fatty acid to basically cover most of the above listed nutrients. You would then only add extra items if all of the above failed to make a difference after 2 weeks. My first choice would be extra magnesium & the next choice would be taurine. WHAT IS TAURINE? Taurine is an amino acid which plays a major role in the brain as an "inhibitory" neurotransmitter & neuromodulator. It is similiar in structure to the amino acids GABA & L-Glycine, which are also neuroinhibitory. This means it helps to calm or stabilize an excited brain. Taurine stabilizes nerve cell membranes thus depressing the firing of brain cells & dampening the nerve cell action of the excitatory amino acids, glutamate, aspartate, & quinolinate. Taurine acts by regulating the sodium & potassium concentration in the cells & the magnesium level between the cells. This has everything to do with the electrical activity of the cells & subsequent communication between cells. By this mechanism, it has anti-anxiety & anti-convulsant activity. It has also been found useful in some cases of migraine, insomnia, agitation, restlessness, irritability, alcoholism, obsessions, depression, hypomania/mania. Dosage is from 500 mg twice daily to a total of 5000 mg daily in 3-4 divided doses, though I rarely recommend that high a dose. The total ideal body pool of taurine for adults is 12,000- 18,000 mg. Since taurine also affects the hypothalamus to help regulate body temperature, a higher dose can decrease your temperature & give chilliness, so be aware of that. Taurine also plays a role in memory & increases the level of a memory neurotransmitter, acetylcholine, in the brain (in animal studies). HOW DO YOU GET TAURINE? Taurine is highly concentrated in animal & fish protein or organ meats. Strict vegetarians can be at risk for taurine deficiency. Your body can make taurine in the liver & brain from the amino acids, L-Cysteine, & L-Methionine. Three enzymes are involved in the conversion, all requiring the pyridoxal-5-phosphate form of Vitamin B6 for this conversion. A B6 deficiency can thus cause a taurine deficiency. Some studies suggest humans are dependent upon dietary taurine to maintain "adequate" taurine reserves. Females tend toward lower taurine levels than males as their production pathways don't work as efficiently. Taurine is closely bound to zinc & manganese so deficiencies of either of these can interfere with its' utilization. Likewise, zinc & manganese enhance the effects of taurine. Taurine is the amino acid present in highest concentration of all amino acids in the fetal & newborn brain, which is the most dependent upon taurine & the least able to synthesize it.. The developing infant must derive taurine from the placenta, the newborn, from breast milk or taurine fortified formula. It is low in cow's milk. Taurine is essential for proper development of the central nervous system & the eyes. Nursing mothers especially need taurine as it stimulates prolactin to promote lactation, which is an interesting twist of nature, since infants need it so much. ( We could speculate that a mother unable to lactate may be taurine deficient, among other possibilites, & the infant is thus protected from receiving taurine deficient breast milk) Premature infants are especially prone to taurine deficiency. WHAT ELSE INFLUENCES TAURINE LEVELS? MSG can decrease taurine. Trauma, surgery, radiation therapy, burns, muscle diseases, steroid use, intestinal dysfunction with bacterial overgrowth of the small bowel can all lead to excess loss of taurine in the urine & subsequent deficiency. The medications Thorazine (a major tranquilizer) & Chloroquine (an antimalarial) can reduce taurine levels. Some depressed patients have decreased taurine. WHAT ELSE DOES TAURINE DO? EYES: It is in high concentration in the eyes where it has multiple functions to maintain normal retinal structure & function. Depletion leads to degeneration of the photoreceptor cells. Degenerative changes in the retinas of taurine deficient cats & dogs resemble retinitis pigmentosa. Taurine may be helpful in preventing cataracts. Age related macular degeneration has responded favorably to "injected" taurine as reported by American Biologics Mexico Hospital. CARDIOVASCULAR: Taurine is the most abundant amino acid in the heart, a particularly electrically excitable tissue, as are the brain & eye. Since taurine participates in electrical stabilization of the cell membranes & the normal regulation of nerve-muscle interaction, it is useful in heart irregularities & mitral valve prolapse, acting similarly to a calcium channel blocker (a class of drugs used in CV Disease) Taurine also helps control high blood pressure & is useful in congestive heart failure. DIABETES: Taurine affects carbohydrate metabolism. It potentiates the effect of insulin, enhances glucose utilization & glycogen (stored glucose) synthesis. FAT METABOLISM: Taurine reduces cholesterol by forming bile acids which are the end products of cholesterol breakdown & are the only route for eliminating cholesterol from the body. This action requires a functioning gall bladder. Taurine has an inhibitory effect on the formation of cholesterol gall stones. It is required for efficient fat absorption & solubilization. It is helpful in states of fat malabsorption such as with cystic fibrosis & other pancreatic deficiency syndromes. DETOXIFICATION: Taurine conjugates & detoxifies various internal & external toxic compounds & may help chemical sensitivities. ANTIOXIDANT: Taurine plays a major role in protecting cell membranes from oxidative attack. STRESS: It can inhibit the release of adrenalin & thus help with anxiety in this way, as well as protecting from other adverse effects of too much adrenalin. MISC: Acts as an immune stimulant to increase Natural Killer Cell Activity & Interleukin 2. Controls cell volume & osmolality. Is involved in the regulation of iron metabolism. Modulates levels of serum copper. TAURINE CAN ALSO STIMULATE RELEASE OF STOMACH ACID SO YOU SHOULD AVOID IF YOU HAVE ULCERS OR GASTRITIS. BE HAPPY!! Priscilla Slagle M.D.

B6/P5P is a pseudo phenolic

Title: The effects of pyridoxal-5-phosphate on sulfotransferase activity: actions on tyrosyl protein sulfotransferase and phenol sulfotransferase. Authors: Rosemary H Waring, Robert M Harris and Victoria L Griffiths, School of Biosciences, University of Birmingham, Birmingham. B15 2TT. UK Introduction Sulfotransferase enzymes use PAPS (3’-phospho-adenosive-5’-phosphosulfate) to transfer sulfate residues onto a wide variety of substrates. TPST substrates require sulfation for efficient function while sulfation by SULT 1A1 greatly alters substrate properties, usually decreasing their activity. a) Tyrosylprotein sulfotransferase (TPST) Substrates - tyrosine residues on gastrin, cholecystokinin, mucin proteins Methods TPST activity was measured (using gastrin as substrate) with radiolabelled 35S-PAPS as sulfate donor; assays were incubated at 37°C for 40 minutes. All assays were performed in quadruplicate). Enzyme sources were a) platelet pellets prepared by centrifugation from time-expired platelet packs from the Birmingham Blood Transfusion Service and b) human colon adenocarcinoma HT-29 cells which synthesise mucin proteins and are thought to be the best model for the human g.i. tract. These were grown in McCoys 5A medium supplemented with 10% fetal bovine serum and glutamine/penicillin/streptomycin at 37°C till confluent, then harvested and centrifuged to give a cell membrane pellet. This was resuspended in phosphate buffered saline, then sonicated before assay. Cells were also grown after confluence for 24 hours with varying concentrations of P5P. P5P was also added directly to the platelet assay (0-2.5μM) MgCl2 was added at varying concentrations (0-5μM) before the start of the TPST assay. Results TPST activity was present in both human platelets and HT-29 cells. This enzyme activity was inhibited in the presence of P5P (Fig. 1). Direct effects of MgCl2 on the assay are shown in Fig. 2. As can be seen, MgCl2 concentration had no significant effects on the TPST activity of HT-29 cells but activated TPST activity in platelets (there are different isoforms of the enzyme). The concentration of 0.4μM P5P was then chosen as showing clear reduction of TPST activity in initial experiments (See Fig. 1). Human platelets were treated directly with this concentration while the HT-29 cells were incubated with it for 24h. Varying amounts of MgCl2 were then added to the assays (see Fig. 3). As can be seen, levels of MgCl2 at 0.5μM or greater removed the inhibition caused by 0.4μM P5P. Enzyme assays and Western blotting with specific anti-TPST antibodies showed that P5P did not affect the expression of TPST. All results were carried out in quadruplicate and are expressed as means ± SD. (SD <= 5.3%). b) SULT1A1 (Phenolsulphotransferase) Substrates – Phenols, catecholamines, flavonoids, steroids. Methods SULT1A1 activity was measured using 4-nitrophenol as a substrate (this also picks up any of the SULT1A2 isoform, although this is only present to a small extent in platelet preparations). Again radiolabelled 35S-PAPS was used in the assay as a sulfate donor. The enzyme sources were cytosols from platelets and HT-29 cells, prepared as before and assayed under standard conditions. Results SULT1A1 activity was present in both human platelets and HT-29 cells. This activity was inhibited by P5P (Fig. 4). However, this inhibition was only significant in the platelets; the HT-29 cell SULT1A1 seemed relatively unaffected. Treatment with MgCl2 (1.0μM) on cells exposed to 1.0 μM P5P restored the activity in platelets (Fig. 6) but had no significant effects in the HT-29 cells, which in any case were not greatly affected by the P5P (Fig. 4) SULT1A1 activity in platelets was almost unaffected by MgCl2 although SULT1A1 activity in HT-29 cells decreased slightly with increasing Mg (Fig. 5). Our previous studies have shown that the isoenzymes in these tissues have different activities and slightly different properties. Incubation of HT-29 cells with P5P had no effect on enzyme expression, as seen by Western blotting and enzyme activity. All results were carried out in quadruplicate and are expressed as means ±SD. (SD <= 5.4%). Conclusions 1. Platelet and HT-29 cells show TPST activity which is inhibited by P5P, though only the platelet isoform is greatly affected. This inhibition is reversed by MgCl2 in roughly equimolar amounts. 2. Platelet and HT-29 cells show SULT1A1 activity which is inhibited by P5P, although only the platelet isoform is greatly affected. Again this inhibition is reversed by MgCl2 in roughly equimolar amounts. 3. Neither TPST nor SULT1A1 expression is altered by P5P, which only affects the enzyme activity directly. 4. From the literature, P5P has a pseudo-phenolic structure which is believed to interact with those phenol sulfotransferases for which phenolic rings are a substrate. However, addition of Mg2+ may form a complex which no longer interacts with the enzyme. From the therapeutic point of view, Mg2+ ions should be supplied in at least a 2:1 ratio with P5P to reverse any inhibition and activate those sulfotransferases which respond to increased magnesium levels particularly the platelet enzymes.