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Neurological Support via 5-HTP and cofactors.

A proprietary blend of nutrients aimed at supporting a positive neurological response, including calming brain activity and providing an overall sense of well-being is provided by this unique formula. It includes an exclusive combination of Taurine, L-Theanine, 5-HTP, Vitamin C, Vitamin [B.sub.6], Folate, Vitamin [B.sub.12], Magnesium, Zinc and Selenium, along with superoxide dismutase and catalase, important antioxidant enzymes.

Anxiety disorders affect as many as eighteen percent (18%) of Americans. Of these, mental disorders account for four out of the ten leading causes of disability in the US and other developed countries. While generalized anxiety disorder is the most common anxiety disorder that affects older adults, other disorders including obsessive compulsive disorder (OCD), panic disorder, post-traumatic stress disorder and social anxiety disorder are also common. (1)

OCD is thought to affect between 2-3% of the general population and is the fourth most common psychiatric illness. In obsessive compulsive disorder, people become trapped in "endless cycles of repetitive thoughts and behaviors," which can cause distress and anxiousness. Because of this, the disease can become potentially disabling. Although many of these patients are prescribed serotonin reuptake inhibitors (SSRIs), it is estimated that 40-60% of patients do not respond adequately to this type of therapy. (3)

Taurine is a sulfur-containing compound, produced in the liver. It is a major constituent of bile, and accounts for up to 0.1% of total human body weight. It is utilized by the body in the conversion of cholesterol to bile salts, and is a required component for normal functioning of multiple tissues, including the heart, brain, eyes, liver, kidney, intestine, adrenal glands and vascular system. (4,5.6) Functionally, it is associated with the protection of tissues from damage resulting from inflammatory reactions, via a reaction with HOCl/[OCl.sub.-] to form taurine chloramines, which confers cellular protection via the regulation of pro-inflammatory mediators, including TNF-alpha and NF-Kappa B. (7,8,8,10,11) Studies have also associated its use with other forms of cellular protection, including the inhibition of leukocyte apoptosis, (12) and it has also been noted to exert anti -anxiety effects. (13)

Vitamin [B.sub.6] and its derivative pyridoxal 5'-phosphate (PLP) are essential to over 100 enzymes, most of which are involved in protein metabolism. Supplementation with B vitamins, including vitamin [B.sub.6], could effectively reduce elevated homocysteine levels. Vitamin [B.sub.6] is a water-soluble vitamin first isolated in the 1930s. The term vitamin [B.sub.6] refers to six common forms, namely pyridoxal, pyridoxine (pyridoxol), pyridoxamine, and their phosphorylated forms. The phosphate ester derivative pyridoxal 5'-phosphate (PLP) is the bioactive coenzyme form involved in over 4% of all enzymatic reactions. P5P is the coenzyme form of [B.sub.6] for most vitamin [B.sub.6] dependent enzymes in the body. Recent studies suggest that vitamin [B.sub.6] might help reduce the risk of late-life despair.

In addition to the above actions of the B-vitamins, vitamin [B.sub.6] can be particularly beneficial in the management of anxiety. Vitamin [B.sub.6] is important in the synthesis of the neurotransmitters [gamma]-aminobutyric acid (GABA), serotonin, dopamine, norepinephrine and epinephrine. Messenger molecules or neuropeptides are thought to link the immune, endocrine and central nervous system, and these messenger molecules are tranmitted through virtually all bodily fluids.

Additionally, vitamin [B.sub.6] plays an important role as a "physiological mediator of steroid hormone function." For individuals requiring vitamin [B.sub.6], [B.sub.6] Phosphate may be a beneficial addition to the daily diet.

Other B vitamins, including vitamin [B.sub.12] and folate, also play many important roles in neurological function, including their participation in one-carbon metabolism. Most studies that relate hyperhomocysteinemia with Alzheimer's disease and other causes of dementia report positive results with [B.sub.12] supplementation. Elevatedlevels of homocysteine in the blood increase the risk of these diseases. Added to this, "increased levels of homocysteine in the blood is also a recognized risk factor for stroke and other vascular complications. Thus, there is a possible relationship between vitamin [B.sub.12] deficiency and vascular diseases."

L-Theanine was discovered as a constituent of green tea in 1949 and was approved in Japan in 1964 for unlimited use in all foods, including chocolates, soft drinks and herb teas, with the exception of infant foods. It also provides a unique umami (brothy or savory) taste and flavor to green tea infusion. Theanine accounts for 50% of the total amino acids in green tea leaves. According to Drugs.com, "L-theanine may help relieve stress by inducing a relaxing effect without drowsiness and may also possess immunologic attributes. Theanine may also have effects on the cardiovascular system and play a preventative role in malignancy; however, limited clinical information is available to support these claims." (14) It is recognized that "individuals who take an l-theanine supplement have increased alpha-brain wave activity in the brain, which is sign of enhanced relaxation." (15)

Studies have also reported an anti-anxiety effect using a single dose of theanine, in the range of 200 to 250 mg. Although the bioactive compounds most known in tea are catechins and caffeine, L-theanine is now recognized as the component that contributes to tea's positive effects, including relaxation, cognitive performance, emotional status, and sleep quality, along with immune, cardiovascular and metabolic support. It has also been recognized that "L-theanine exhibits a molecular structure nearly identical to glutamate, an excitatory neurotransmitter. While its molecular mechanisms await thorough delineation, scientists believe L-theanine's structural distinction allows it to act as a "Trojan horse" at glutamate-responsive proteins and receptors. (16) As such, it may compete with glutamate to balance its excitatory effects. In preclinical studies L-theanine also supports healthy levels of serotonin, dopamine and GABA in the brain. (16) Human clinical studies, have also demonstrated the benefits of L-theanine in both objective and subjective indices of relaxation.

5-HTP is a compound synthesized from the amino acid tryptophan and is a precursor to the neurotransmitters serotonin and melatonin. Vitamin [B.sub.6] is required as a cofactor in the conversion of 5-HTP to serotonin. In animal studies 5-HTP has been found to be taken up by the brain from the blood, and readily decarboxylated into serotonin. (17) 5-HTP appears to have equal efficacy to antidepressant medication, but without the drug risks and side effects. (18) One study demonstrated that 5-HTP strongly suppressed appetite for three days following dosing. During a 90-day open trial, 5-HTP alone was also found to be effective in reducing the number of tender points, anxiety, pain intensity, fatigue, and in improving the quality of sleep. (p < .01). (20) 5-HTP has also been demonstrated to have a beneficial effect on migraine, but the drug propanolol was found to do a better job, while the combination of both, propanolol and 5-HTP did the best. (21) In all studies examined, 5-HTP has been noted to not have the side effects found with medication.

NOTE: 5-HTP is not recommended with MAO inhibitors or other antidepressants.

Selenium is an allotropic metal, that can form many compounds with both oxygen and sulfur. Like Vitamin E, selenium plays an important role in detoxification of peroxides and free radicals. It is also an essential component in the selenoproteins, including selenophosphate and selenocysteine, with vitamin [B.sub.6] as the catalyst. (22) As noted previously, the enzyme glutathione peroxidase is also a selenoprotein, which has been widely studied as it plays an important function in cell membrane stability. (22) Glutathione peroxidase is also of major importance to the maintenance of red blood cell redox state. A decline in the activity of Glutathione peroxidase is a sensitive indicatory of selenium status. (22) There are thirteen different selenoproteins, although it has been estimated that approximately 36% of the total selenium in the body is associated with glutathione peroxidase. "Selenium is also an integral part of the enzyme Typel iodothyronine deiodinase, which catalyzes the deiodination of the iodothyronines, notably the deiodination of thyroxine (T4) to triiodothyronine (T3), the most active of the thyroid hormones. In selenium deficient animals type I synthesis is markedly impaired, which is reversed when selenium is restored to the diet." (23) Additionally, under these same conditions, the ratio of T3 to T4 is altered, with more T4 and less T3 in deficient animals. However, unlike iodine deficiency, in this deficiency state, there is no thyroid enlargement, typical of iodine deficiency. In one study, it was found that there was a "strong association between plasma selenium and tim-ed performance-based assessments, whereby lower levels of selenium were significantly associated with decreased performance in neurological tests of coordination among older adults." (24)

Potential critical roles of Se and selenoproteins in the brain have been suggested. Human studies have correlated plasma Se status as being "positively associated with coordination and motor speed in elderlies." Additionally, in various brain regions of the Parkinson's disease (PD) mouse model, studies have demonstrated "differential responses", which provide critical selenotranscriptomic profiling for the future functional investigation of individual selenoprotein in PD etiology. Emerging evidence has linked Se and selenoproteins to PD. One study noted "a wide range of changes in selenotranscriptome in a manner depending on selenoproteins and brain regions. While Selv mRNA was not detectable and Diol & 3 mRNA levels were not affected, 1, 11 and 9 selenoproteins displayed patterns of increase only, decrease only, and mixed response, respectively, in these brain regions of PD mice." (25)

The combination of these select nutrients support a positive neurological response, including soothing of brain activity, thus assists in providing an overall sense of well -being.

About the Author

Dr. Rachel Olivier serves as a Physician Advisor for Biotics Research Corporation, a position she has held for over sixteen years. As a Physician Advisor she serves to educate and provide professional leadership for physicians and practitioners, in an effort to improve product understanding. She serves as Biotics' chief consultant, advisor and technical expert, and also writes technically oriented papers, training curriculum, and product support material for practitioners and members of the sales team. In addition to this role, she also maintains a part-time nutritional practice, Healthstone Wellness, where she guides patients on lifestyle interventions and provides nutritional consultations. She holds a Masters degree in Molecular Biology from University of Southwestern Louisiana (currently the University of LA), along with a traditional Naturopathic Degree from Honolulu University, and a PhD in nutrition from California University. She can be contacted at (800) 231-5777 or via email at rolivier@bioticsresearch.com.

References:

(1.) https://adaa.org/about-adaa/press-room/facts-statistics.

(2.) https://my.cle velandclinic.org/health/diseases/9490-obsessive-compulsive-disorder.

(3.) Carvalho AF, Cavalcante JL, Castelo MS, et al. Augmentation strategies for treatment-resistant depression: a literature review. J Clin Pharm Ther. 2007;32(5):415-28.

(4.) Ronzio R.The Encyclopedia of Nutrition and Good Health. 2nd Edition. 2003.

(5.) Jhiang SM, Fithian L, Smanik P, McGill J, Tong Q, Mazzaferri EL. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett. 1993 318:139.

(6.) Sturman JA. Taurine in development. Physiol. Rev. 1993 73:119.

(7.) Park E, Schuller-Levis G, Quinn MR. Taurine chloramine inhibits production of nitric oxide and TNF-alpha in activated RAW 264.7 cells by mechanisms that involve transcriptional and translational events. J. Immunol. 1995 154:4778.

(8.) Park E, Alberti, J, Quinn MR, Schuller-Levis G. Taurine chloramine inhibits the production of superoxide anion, IL-6 and IL-8 in activated human polymorphonuclear leukocytes. Adv. Exp. Med. Biol. 1998 442:177.

(9.) Kim C, Park E, Quinn MR, Schuller-Levis G. The production of superoxide anion and nitric oxide by cultured murine leukocytes and the accumulation of TNF-alpha in the conditioned media is inhibited by taurine chloramines. Immuno-pharmacology. 1996 34:89.

(10.) Marcinkiewicz J, Grabowska A, Bereta J, Bryniarski K., Nowak B. Taurine chloramine downregulates the generation of murine neutrophil inflammatory mediators. Immunophar-macology. 1998 40:27.

(11.) Barua M, Liu Y, Quinn MR. Taurine chloramine inhibits inducible nitric oxide synthase and TNF-alpha gene expression in activated alveolar macrophages: decreased NF-kappaB activation and IkappaB kinase activity. J. Immunol. 2001167:2275.

(12.) Cetinera M, Senere GA, Sehirlie O, Eksioglu-Demiralpa E, Ercanb F, Sirvancib S, Gedikf N, Akpulatc S, Tecimerc T, Yegend BC.

(13.) Zhang CG, Kim S.-J. Taurine Induces Anti-Anxiety by Activating Strychnine-Sensitive Glycine Receptor in vivo. Ann Nutr Metab 2007 51:379-386. https://doi.org/10.1159/000107687.

(14.) https://www.drugs.com/npc/l-theanine.html.

(15.) http://www.raysahelian.com/theanine.html.

(16.) Nathan PJ, Lu K, Gray M, Oliver C. The neuropharmacology of L-theanine (N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2):21-30.

(17.) Arai R, Karasawa N, Nagatsu T, Nagatsu I. Exogenous L-5-hyroxytryptophan is decarboxylated in neurons of the substantia niagra pars compacta and locus coeruleus of the rat. Brain Res. 1995 Jan 9; 669 (1): 145-149.

(18.) A functional-dimensional approach to depression, comparing 5-HTP to fluvocarnine. Psychopathology. 1991; 24:53-81.

(19.) Pi W, Lin C. Effects of monoamine precursors on food intake in male rats. Clin J Physiol. 1993; 36 (3): 171-176.

(20.) Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study. J Int Med Res. 1992 Apr; 20 (2): 182-189.

(21.) Maissen C, et al. Comparison of the effect of 5 hydroxy-tryptophan and propanolol with interval treatment of migraine. Schweiz Med Wochenschr. 1991 121 (43): 1585-1590.

(22.) Berdanier C. Advanced Nutrients Micronutrients. CRC Press 1998. p. 205.

(23.) Berdanier C. Advanced Nutrients Micronutrients. CRC Press 1998. p. 207.

(24.) Shahar A, Patel KV, Semba RD, Bandinelli S, Shahar DR, Ferrucci L, Guralnik JM. Plasma selenium is positively related to performance in neurological tasks assessing coordination and motor speed. Mov Disord. 2010 Sep 15;25(12):1909-15. doi: 10.1002/mds.23218.

(25.) Zhang X, Ye Y-L, Zhu H, Sun S-N, Zheng J, Fan H-H, Wu H-M, Chen S-F, Cheng W-H, Zhu J-H. Selenotranscriptomic Analyses Identify Signature Selenoproteins in Brain Regions in a Mouse Model of Parkinson's Disease. PLoS ONE. 2016 11(9):e0163372. http://doi.org/10.1371 /iournal.pone.0163372.

by: Rachel Olivier, MS, ND, PhD
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