Page 1, 2
Methodology and Technical Considerations
While there are multiple methods available for the measurement of catecholamines, liquid chromatography (LC) coupled with tandem mass spectrometry remains the gold standard (Li 2014) for these and many other biological analytes (Grebe et al. Clin Biochem Rev. 2011 Feb;(32): 5–31.). The proper collection and handling of urine specimens prior to laboratory receipt is of the utmost importance for accurate results. The kidney functions in the synthesis of not only amino acids, but also peptides and proteins. Thomas et al. (2010) report that, for urinary proteins, relative standard deviations were lowest for 24-hour collection and first morning collections, while second collection and spot urine samples had much higher variability. The same may or may not be true for urinary neurotransmitters; research is needed in this area. As an important site of amino acid synthesis (approximately 50% of plasma tyrosine is synthesized in the kidneys), renal synthesis also contributes to the plasma concentrations of the neuroactive amino acids glycine and glutamate (Van de Pol et al. 2004).
At Doctor's Data, a small study (n = 10) performed to assess the utility of 24-hour urinary neurotransmitter testing, as specified by Mayo Clinical Laboratories, was shown to be more clinically relevant when compared with second morning void samples. The second morning void samples showed 3 clear outliers with elevated catecholamine levels, when their 24-hour results demonstrated no such increase in the excreted catecholamines. When diet and lifestyle information was reviewed and input, the three subjects with elevated second morning catecholamines had all experienced long commutes to work, when compared with the rest of the cohort! As the purpose of urinary neurotransmitter testing is to evaluate clinically significant elevations or deficiencies in neurotransmitter status, it appears that either true first morning void (i.e., after being in bed without arising × 8 hours) or 24-hour urine neurotransmitters may be more clinically relevant.
A study of PTSD subjects (Young et al. 2004) used a novel method of collecting 24-hour urine catecholamines for study, choosing to collect urine in 8-hour increments. Urine collection for a 32-hour stay at a sleep center was made in four parts as Young et al. report: "The first collection covered the first night, the second collection covered 8 hours from rising to early afternoon, the third collection covered the late afternoon and evening, and the fourth, the second night. The procedure provided total 24-hour measures and had the added capacity to provide separate timed measures that captured the morning surge (in the 8 AM hour) and the evening low (in the 8 PM hour) for an examination of effects related to diurnal phase." This method of collection and +analysis requires further study, and may ultimately prove clinically useful.
The ingestion of certain foods may affect the results of urinary neurotransmitter testing, and the avoidance of specific foods is recommended by the Mayo Clinic Medical Laboratories and other medical laboratories analyzing neurotransmitters (Table 1). Any medication meant to affect neurotransmitters (such as reuptake inhibitors, etc.) may alter neurotransmitter levels from baseline levels; it is the clinical decision of the prescribing physician whether to discontinue (by safely tapering off) any such medications prior to testing.
Table 3: Specific foods to avoid as recommended by the Mayo Clinic Medical Laboratories
Serotonin: avocados, dates, eggplant, all fruit [including bananas, cantaloupe, grapefruit, kiwifruit, melons, pineapple, plantains, plums], all nuts [including hickory nuts, butternuts, pecans, walnuts], and tomatoes and tomato products) within 48 hours of sample collection.
Catecholamines: caffeinated beverages, and nicotine, tyrosine rich foods, such as nuts, bananas, or cheese. Foods should be avoided for 48 hours, caffeine and nicotine for at least 12 hours prior to sample collection.
New methods, such as capillary electrophoresis, electrochemical detection, enzyme immunoassay, chemiluminescence detection, and fluorescence detection, are being developed but may not have sufficient large-scale clinical studies yet to assist with the clinical interpretation of results (Tsunoda 2006). None of these technologies has been found superior to the LC-tandem mass spectrometry gold standard. In addition, different methodologies often use different reference values, which make the comparison of a result using one set of reference values to a result using a different set of reference values virtually impossible and clinically questionable (Katayev 2010).
Conclusion
Urinary neurotransmitters provide an overall assessment of a patient's ability to synthesize and metabolize neurotransmitters, which must occur in both the peripheral nervous system and behind the blood–brain barrier. Altered patterns of urinary neurobiogenic amines may highlight the need for precursor amino acids or nutritional cofactors essential for synthesis and metabolism. Alterations in urinary neurotransmitter status may result from a variety of conditions, including metabolic disorders, mood/behavioral disorders, environmental exposures, or (rarely) the presence of certain tumors. Evaluation of neurotransmitters may provide the clinician with increased clarity about patient health, functional status, and nutritional needs.
Disclosure
The author, Andrea Gruszecki, ND, is employed in the Scientific Support Department at Doctor's Data Inc.
References
Audhya T, Adams JB, Johansen L. Correlation of serotonin levels in CSF, platelets, plasma, and urine. Biochim Biophys Acta. 2012;1820(10):1496–1501.
Berry MD. The potential of trace amines and their receptors for treating nerological and psychiatric diseases. Rev Recent Clin Trials. 2007;2(1):3–19.
Cansev M, Wurtman RJ. Aromatic amino acids in the brain. Chapter 4 in: Handbook of Neurochemistry and Molecular Neurobiology. Springer US; 2007.
Castro-Diehl C, Diez Roux AV, Seeman T, et al. Associations of socioeconomic and psychosocial factors with urinary measures of cortisol and catecholamines in the Multi-Ethnic Study of Atherosclerosis (MESA). Psychoneuroendocrinology. 2014;41:132–141 .
Dhakal R, Bajpai VK, Baek K-H. Production of GABA (γ – Aminobutyric acid) by microorganisms: a review. Brazi J Microbiol. 2012;43(4):1230–1241.
Dorszewska J, Prendecki M, Oczkowska A, et al. Polymorphism of the COMT, MAO, DAT, NET and 5-HTT genes, and biogenic amines in Parkinson's disease. Curr Genom. 2013;14(8):518–533.
Dvořáková M, Ježová D, Blažíček P, et al. Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): Modulation by a polyphenolic extract from pine bark (Pycnogenol®) Nutritional Neuroscience. June–Aug 2007;10(3–4):151–157.
Eisenhofer G, Huysmans F, Pacak K, et al. Plasma metanephrines in renal failure. Kidney Int. 2005;67:668–677.
Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004;56(3):331–349.
Enaw JOE, Smith AK. Biomarker development for brain-based disorders: recent progress in psychiatry. J Neurol Psychol. 2013;1(2).
Ghanizadeh A. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism. Dis Markers. 2013;35(5):281–286.
Goldstein DS, Eisenhofer G, Kopin IJ. sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther. 2003;305(3):800–811.
Grebe S, Singh R. LC-MS/MS in the clinical laboratory –where to from here? Clin Biochem Rev 2011 Feb;(32):5–31.
Hansen MB. The enteric nervous system II: gastrointestinal functions.
Pharmacol Toxicol. 2003;92(6):249–257.
Hyland K. Inherited disorders affecting dopamine and serotonin: critical neurotransmitters derived from aromatic amino acids. J Nutr. 2007;137(6):1568S–1572S.
Hyman SE. Primer – neurotransmitters Curr Biol. 2005;15(5)R154–R158.
Inoue K, Lupski JR. Genetics and genomics of behavioral and psychiatric disorders. Curr Opin Genet Dev. 2003;13 (3):303–309.
Jedlitschky G, Greinacher A, Kroemer HK. Transporters in human platelets: physiologic function and impact for pharmacotherapy Blood. 2012;119(15):3394–3402.
Kakizawa S. Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor, a calcium release channel, through non-enzymatic post-translational modification by nitric oxide. Front Endocrinol. 2013;4:142.
Katayev A, Balciza C, Seccombe DW. Establishing reference intervals for clinical laboratory test results: is there a better way? Am J Clin Pathol. 2010;133(2):180–186.
Kheirandish-Gozal L, McManus CJT, Kellermann GH, Samiei A, Gozal D. Urinary neurotransmitters are selectively altered in children with obstructive sleep apnea and predict cognitive morbidity. Chest. 2013;143(6):1576–1583.
Li XS, Li S, Wynveen P, Mork K, Kellermann G. Development and validation of a specific and sensitive LC-MS/MS method for quantification of urinary catecholamines and application in biological variation studies. Anal Bioanal Chem. 2014;406(28):7287–7297.
Lyte M. Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS pathogens. 2013;9(11):e1003726. Accessed 15 June 2015.
Marc DT, Ailts JW, Campeau DCA, Bull MJ, Olson KL. Neurotransmitters excreted in the urine as biomarkers of nervous system activity: Validity and clinical applicability. Neurosci Biobehav Rev. 2011;35(3):635–644.
Masi CM, Rickett EM, Hawkley LC, Cacioppo JT. Gender and ethnic differences in urinary stress hormones: the population-based Chicago Health, Aging, and Social Relations Study. J Appl Physiol. 2004;97(3):941–947.
Mayo Foundation for Medical Education and Research [website]. Catecholamine fractionation, free, 24 hour, urine 5-hydroxyindoleacetic acid (5-HIAA), 24 hour, urine. http://www.mayomedicallaboratories.com/index.html. Accessed 15 June 2015.
Niu Q, Zhang H. Benzo[a]pyrene-induced neurobehavioral function and neurotransmitter alterations in coke oven workers. Occup Environmental Med. 2009;67(7):444–448.
Paul SM. GABA and glycine. In: Davis KL, Charney D, Coyle J, Nemeroff C, eds. Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia: Lippincott, Williams, & Wilkins; 2002.
Putschögl FM, Gaum PM, Schettgen T, et al. Effects of occupational exposure to polychlorinated biphenyls on urinary metabolites of neurotransmitters: A cross-sectional and longitudinal perspective. Int J Hyg Environ Health. 2015;218(5):452–460.
Rao AV, Bested A, Beaulne T, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009;1(1):6.
Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE. Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters. J Pharmacol Exper Ther. 2012;341(1):251–262.
Saulnier DM, Ringel Y, Heyman MB, et al. The intestinal microbiome, probiotics and prebiotics in neurogastroenterology. Gut Microbes. 2013;4(1):17–27.
Stover PJ. Influence of human genetic variation on nutritional requirements. Am J Clin Nutr. 2006;83(2):436S–442S.
Thomas CE, Sexton W, Benson K, Sutphen R, Koomen J. Urine collection and processing for protein biomarker discovery and quantification. Cancer Epidemiol Biomarkers Prev. 2010;19(4):953–959.
Trachte GJ, Uncini T, Hinz M. Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population. Neuropsychiatr Dis Treat. 2009;5:227–235.
Tsunoda M. Recent advances in methods for the analysis of catecholamines and their metabolites. Anal Bioanal Chemistry. 2006;386(3):506–514.
Van de Poll MCG, Soeters PB, Deutz NEP, Fearon KCH, Dejong CHC. Renal metabolism of amino acids: its role in interorgan amino acid exchange. Am J Clin Nutr. 2004;79(2):185–197.
Watts SW, Morrison SF, Davis RP, Barman SM. Serotonin and blood pressure regulation. Pharmacol Rev. 2012;64(2):359–388.
Yuan H, He S, He M, et al. A comprehensive study on neurobehavior, neurotransmitters and lymphocyte subsets alteration of Chinese manganese welding workers. Life Sci. 2006;78 (12):1324–1328.
Young EA, Breslau N. Cortisol and catecholamines in posttraumatic stress disorder: an epidemiologic community study. Arch Gen Psychiatr. 2004;61(4):394–401.
Page 1, 2 |
