kynurenic acid and Disease Models, Animal studies

Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool.
kynurenic acid : A quinolinemonocarboxylic acid that is quinoline-2-carboxylic acid substituted by a hydroxy group at C-4.

Disease Models, Animal: Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.

Research Excerpts

Excerpt	Relevance	Reference
"It has been shown that a possible pathogenetic mechanism of neurodegeneration in the mouse model of glaucoma (DBA/2J) may be an alteration of kynurenic acid (KYNA) in the retina."	8.02	Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma. ( Avitabile, T; Choragiewicz, T; Fiedorowicz, M; Grieb, P; Kamińska, A; Kocki, T; Nowakowska, D; Rejdak, R; Toro, MD; Turski, WA; Wertejuk, K; Wełniak-Kaminska, M; Zweifel, S, 2021)
" In rodents, KMO deficiency induces a depression-like behavior and increases the levels of kynurenic acid (KA), a KYN metabolite formed by kynurenine aminotransferases (KATs)."	8.02	Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of α7 nicotinic acetylcholine receptors by kynurenic acid. ( Fujigaki, H; Fujigaki, S; Hasegawa, M; Hirakawa, M; Hoshi, M; Kosuge, A; Kubota, H; Kunisawa, K; Kurahashi, H; Mori, Y; Mouri, A; Murakami, R; Nabeshima, T; Nakano, T; Niijima, M; Saito, K; Yamamoto, Y, 2021)
"A chronic increase in circulating angiotensin II (Ang II) activates an aldosterone-mineralocorticoid receptor-ouabain neuromodulatory pathway in the brain that increases neuronal activation in hypothalamic nuclei, such as the paraventricular nucleus (PVN) and causes progressive hypertension."	7.79	Central mineralocorticoid receptors and the role of angiotensin II and glutamate in the paraventricular nucleus of rats with angiotensin II-induced hypertension. ( Gabor, A; Leenen, FH, 2013)
"Our findings demonstrate that the increase in fatigue which occurs because of excessively elevated brain tryptophan can be further amplified by the use of synthetic KYNA and QUIN."	7.78	Essential role of excessive tryptophan and its neurometabolites in fatigue. ( Azechi, H; Board, M; Yamamoto, T, 2012)
"Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression."	7.78	Sub-chronic dietary tryptophan depletion--an animal model of depression with improved face and good construct validity. ( Bermudez, I; Franklin, M; Gaburro, S; Murck, H; Singewald, N, 2012)
"The brain levels of the endogenous excitotoxin quinolinic acid (QUIN) and its bioprecursor, the free radical generator 3-hydroxykynurenine (3-HK), are elevated in early stage Huntington disease (HD)."	7.73	Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. ( Bates, GP; Graham, RK; Guidetti, P; Hayden, MR; Leavitt, BR; MacDonald, ME; Schwarcz, R; Slow, EJ; Wheeler, VC; Woodman, B, 2006)
"Kynurenic acid (KA) is a tryptophan metabolite that has been shown to exert anti-inflammatory effects in macrophages and endothelial cells."	5.62	Endogenous metabolite, kynurenic acid, attenuates nonalcoholic fatty liver disease via AMPK/autophagy- and AMPK/ORP150-mediated signaling. ( Abd El-Aty, AM; Hong, SA; Jeong, JH; Jung, TW; Kim, MJ; Kim, TJ; Pyun, DH, 2021)
"Sepsis was characterized by significantly elevated ROFA scores, while the increased BBB permeability and plasma S100B levels demonstrated brain damage."	5.62	Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats. ( Boros, M; Czakó, BL; Dookhun, D; Fülöp, F; Gál, KG; Glenz, RJ; Gulácsi, L; Juhász, L; Kaszaki, J; Lőrinczi, B; Nászai, A; Poles, MZ; Rutai, A; Szabó, A; Szatmári, I; Tallósy, SP; Vécsei, L, 2021)
" Furthermore, brain kynurenic acid levels and KATs activities were evaluated in experimental model of hypothyroidism, induced by chronic administration of 0."	5.56	Experimental hypothyroidism raises brain kynurenic acid - Novel aspect of thyroid dysfunction. ( Tomczyk, T; Urbańska, EM, 2020)
"Kynurenic acid (KYNA) is an endogenous excitatory amino acid receptor blocker, which may have an anti-inflammatory effect."	5.42	Kynurenic acid modulates experimentally induced inflammation in the trigeminal ganglion. ( Csáti, A; Edvinsson, L; Fülöp, F; Tajti, J; Toldi, J; Vécsei, L; Warfvinge, K, 2015)
"Pain is a complex experience composed of sensory and affective components."	5.39	Opposing roles of corticotropin-releasing factor and neuropeptide Y within the dorsolateral bed nucleus of the stria terminalis in the negative affective component of pain in rats. ( Hara, T; Ide, S; Kaneda, K; Koseki, K; Maruyama, C; Minami, M; Naka, T; Ohno, A; Tamano, R; Yoshioka, M, 2013)
"Kynurenic acid is an endogenous glutamate antagonist with a preferential action at the glycine-site of the N-methyl-D-aspartate-receptor."	5.34	The kynurenic acid hypothesis of schizophrenia. ( Engberg, G; Erhardt, S; Linderholm, K; Nilsson, L; Schwieler, L, 2007)
"However, they do not affect clonic seizures with preserved righting reflexes."	5.29	Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis: III. The action of kynurenic acid and glutamic acid diethylester. ( Kusá, R; Mares, P; Roztocilová, L; Velísek, L, 1995)
"It has been shown that a possible pathogenetic mechanism of neurodegeneration in the mouse model of glaucoma (DBA/2J) may be an alteration of kynurenic acid (KYNA) in the retina."	4.02	Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma. ( Avitabile, T; Choragiewicz, T; Fiedorowicz, M; Grieb, P; Kamińska, A; Kocki, T; Nowakowska, D; Rejdak, R; Toro, MD; Turski, WA; Wertejuk, K; Wełniak-Kaminska, M; Zweifel, S, 2021)
" In rodents, KMO deficiency induces a depression-like behavior and increases the levels of kynurenic acid (KA), a KYN metabolite formed by kynurenine aminotransferases (KATs)."	4.02	Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of α7 nicotinic acetylcholine receptors by kynurenic acid. ( Fujigaki, H; Fujigaki, S; Hasegawa, M; Hirakawa, M; Hoshi, M; Kosuge, A; Kubota, H; Kunisawa, K; Kurahashi, H; Mori, Y; Mouri, A; Murakami, R; Nabeshima, T; Nakano, T; Niijima, M; Saito, K; Yamamoto, Y, 2021)
" These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease in microglial quinolinic acid production that is correlated with plasmatic peripheral production."	3.91	Microglial production of quinolinic acid as a target and a biomarker of the antidepressant effect of ketamine. ( Abdel-Ahad, P; Blatzer, M; Callebert, J; Chrétien, F; Danckaert, A; de Maricourt, P; De Medeiros, GF; Gaillard, R; Jouvion, G; Langeron, O; Launay, JM; Maignan, A; Petit, AC; Sharshar, T; Van Steenwinckel, J; Verdonk, F; Vinckier, F, 2019)
" One of the factors recently recognized to influence metabolism and weight gain is kynurenic acid (KYNA), an agonist of G protein-coupled receptor (GPR35)."	3.91	Kynurenic acid as the neglected ingredient of commercial baby formulas. ( Bednarski, J; Debinska, I; Dobrowolski, P; Gawel, K; Kocki, T; Milart, P; Paluszkiewicz, P; Raban, M; Smolinska, K; Tomaszewska, E; Turska, M; Turski, WA; Walczak, K, 2019)
"Sensitive and comprehensive measurement of systemic metabolites of tryptophan, phenylalanine and glutamate metabolism in biological samples is effective for understanding the pathogenesis of depression and other neurological diseases."	3.91	Development of an underivatized LC-MS/MS method for quantitation of 14 neurotransmitters in rat hippocampus, plasma and urine: Application to CUMS induced depression rats. ( Han, XM; Lu, YN; Qin, YJ; Rang, Y; Wang, NX; Zhai, XJ; Zhang, XL; Zhu, Y, 2019)
" Notably, the anti-parasitic drugs pyrimethamine and sulfadiazine, a standard treatment of toxoplasmosis, significantly reduced 3-HK and KYNA levels in the brain of infected mice when applied between 28 and 56 days post-infection."	3.80	Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: implications for schizophrenia. ( Fang, Q; Harris, TH; Horning, KJ; Hunter, CA; Notarangelo, FM; Schwarcz, R; Thomas, MA; Wilson, EH, 2014)
"A chronic increase in circulating angiotensin II (Ang II) activates an aldosterone-mineralocorticoid receptor-ouabain neuromodulatory pathway in the brain that increases neuronal activation in hypothalamic nuclei, such as the paraventricular nucleus (PVN) and causes progressive hypertension."	3.79	Central mineralocorticoid receptors and the role of angiotensin II and glutamate in the paraventricular nucleus of rats with angiotensin II-induced hypertension. ( Gabor, A; Leenen, FH, 2013)
"Effects of systemic injection of the glycine(B) agonist, d-serine, the GlyT-1 glycine transporter inhibitor, ALX-5407, and the glycine(B) antagonist, L-701,324, were tested for the effects on EtOH-induced ataxia, hypothermia, and loss of righting reflex (LORR) duration in C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mice."	3.79	Probing the modulation of acute ethanol intoxication by pharmacological manipulation of the NMDAR glycine co-agonist site. ( Camp, M; Debrouse, L; Grant, SG; Gunduz-Cinar, O; Holmes, A; Hurd, B; Kiselycznyk, C; Mishina, M; Plitt, A; Todaro, A, 2013)
"Our findings demonstrate that the increase in fatigue which occurs because of excessively elevated brain tryptophan can be further amplified by the use of synthetic KYNA and QUIN."	3.78	Essential role of excessive tryptophan and its neurometabolites in fatigue. ( Azechi, H; Board, M; Yamamoto, T, 2012)
"Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression."	3.78	Sub-chronic dietary tryptophan depletion--an animal model of depression with improved face and good construct validity. ( Bermudez, I; Franklin, M; Gaburro, S; Murck, H; Singewald, N, 2012)
"Sprague-Dawley rats were randomized to control, untreated colitis (ic TNBS), colitis fed with 2% PC-containing diet (3 days pre-treatment +3 days treatment after TNBS induction), colitis with kynurenic acid treatment (on day 6, n = 7) groups."	3.78	[Comparative study of novel therapeutic possibilities in animal experimental model of inflammatory bowel disease]. ( Boros, M; Erces, D; Ghyczy, M; Kaszaki, J; Kovács, T; Tiszlavicz, L; Tőkés, T; Varga, G; Vécsei, L, 2012)
"The inflammatory and motility changes in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis were studied in anaesthetized Wistar rats following treatment with the natural NMDA-R antagonist kynurenic acid (KynA) or SZR-72, a blood-brain barrier-permeable synthetic KynA analogue."	3.76	N-Methyl-D-aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat. ( Boros, M; Erces, D; Fazekas, B; Fülöp, F; Fülöp, M; Kaszaki, J; Kovács, T; Varga, G; Vécsei, L, 2010)
"As a first step in the exploration of this approach, we examined the effect of 4-chloro-kynurenine (4-Cl-KYN), which is converted by astrocytes to the potent NMDA glycine-site antagonist 7-chloro-kynurenic acid (7-Cl-KYNA), on the in vivo epileptiform evoked potentials in the CA1 region of rats with chronic limbic epilepsy (CLE)."	3.73	In situ-produced 7-chlorokynurenate has different effects on evoked responses in rats with limbic epilepsy in comparison to naive controls. ( Bertram, EH; Schwarcz, R; Williamson, JM; Wu, HQ; Zhang, DX, 2005)
"The brain levels of the endogenous excitotoxin quinolinic acid (QUIN) and its bioprecursor, the free radical generator 3-hydroxykynurenine (3-HK), are elevated in early stage Huntington disease (HD)."	3.73	Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. ( Bates, GP; Graham, RK; Guidetti, P; Hayden, MR; Leavitt, BR; MacDonald, ME; Schwarcz, R; Slow, EJ; Wheeler, VC; Woodman, B, 2006)
"The anticonvulsant activity of felbamate against sound-induced seizures was studied in the DBA/2 mouse model."	3.69	Excitatory amino acid neurotransmission through both NMDA and non-NMDA receptors is involved in the anticonvulsant activity of felbamate in DBA/2 mice. ( Aguglia, U; Bertorelli, R; De Sarro, A; De Sarro, G; Ongini, E, 1994)
"Kynurenic acid (KA) is a tryptophan metabolite that has been shown to exert anti-inflammatory effects in macrophages and endothelial cells."	1.62	Endogenous metabolite, kynurenic acid, attenuates nonalcoholic fatty liver disease via AMPK/autophagy- and AMPK/ORP150-mediated signaling. ( Abd El-Aty, AM; Hong, SA; Jeong, JH; Jung, TW; Kim, MJ; Kim, TJ; Pyun, DH, 2021)
"Sepsis was characterized by significantly elevated ROFA scores, while the increased BBB permeability and plasma S100B levels demonstrated brain damage."	1.62	Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats. ( Boros, M; Czakó, BL; Dookhun, D; Fülöp, F; Gál, KG; Glenz, RJ; Gulácsi, L; Juhász, L; Kaszaki, J; Lőrinczi, B; Nászai, A; Poles, MZ; Rutai, A; Szabó, A; Szatmári, I; Tallósy, SP; Vécsei, L, 2021)
"elegans model of Alzheimer's disease."	1.62	Two human metabolites rescue a C. elegans model of Alzheimer's disease via a cytosolic unfolded protein response. ( Casford, S; Chia, S; Dobson, CM; Habchi, J; Joshi, P; Labbadia, J; Limbocker, R; Mannini, B; Perni, M; Vendruscolo, M, 2021)
"Hypoxic-ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates."	1.62	The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy. ( Berkecz, R; Domoki, F; Körmöczi, T; Kovács, V; Pénzes, A; Remzső, G; Tóth-Szűki, V; Vécsei, L, 2021)
"Kynurenic acid (KYNA) is a KP metabolite synthesized by kynurenine aminotransferases (KATs) from its biological precursor kynurenine and acts as an endogenous antagonist of N-methyl-D-aspartate and α7-nicotinic acetylcholine receptors."	1.62	Prenatal Kynurenine Elevation Elicits Sex-Dependent Changes in Sleep and Arousal During Adulthood: Implications for Psychotic Disorders. ( Baratta, AM; Ditty, AL; Milosavljevic, S; Mong, JA; Pocivavsek, A; Rentschler, KM; Wagner, NTJ; Wright, CJ, 2021)
"Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients."	1.56	Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice. ( Houck, JA; Johnson, GC; MacLean, PS; Nagaraj, RH; Nahomi, RB; Nam, MH; Pantcheva, MB; Rakete, S; Rankenberg, J; Stankowska, DL, 2020)
"Kynurenic acid (KYNA) is an L-tryptophan metabolite with neuromodulatory activities, regulating the release of neurotransmitters such as glutamate, dopamine (DA), and acetylcholine (Ach)."	1.56	Antidepressant-like effects of kynurenic acid in a modified forced swim test. ( Bohár, Z; Martos, D; Tanaka, M; Telegdy, G; Vécsei, L, 2020)
" Furthermore, brain kynurenic acid levels and KATs activities were evaluated in experimental model of hypothyroidism, induced by chronic administration of 0."	1.56	Experimental hypothyroidism raises brain kynurenic acid - Novel aspect of thyroid dysfunction. ( Tomczyk, T; Urbańska, EM, 2020)
"However, in Alzheimer's disease (AD), NSCs lose plasticity and thus possible regenerative capacity."	1.48	3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues Aβ42-Induced Loss of Human Neural Stem Cell Plasticity. ( Antos, CL; Bhattarai, P; Brandt, K; Bray, L; Celikkaya, H; Chen, X; Cosacak, MI; Dahl, A; Freudenberg, U; Friedrichs, J; He, S; Hollak, H; Kizil, C; Kurth, T; Lin, W; Mashkaryan, V; Papadimitriou, C; Thomas, AK; Werner, C; Zhang, Y, 2018)
"With the increase in incidence of type 1 diabetes (T1DM), there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease."	1.48	Metabolomics and Lipidomics Study of Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in Purine and Tryptophan Metabolism Prior to Disease Onset. ( Acharjee, A; Cooke, A; Griffin, JL; Koulman, A; Murfitt, SA; Roberts, LD; Sawyer, Y; Wang, X; Zaccone, P, 2018)
" To obtain pharmacokinetic data, KA-1, KA-2 and KYNA concentrations were measured following KA-1 or KA-2 injection."	1.46	A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: a behavioral, immunohistochemical and pharmacokinetic study. ( Bajtai, A; Bohár, Z; Fejes-Szabó, A; Fülöp, F; Laborc, K; László, AM; Mándity, I; Nagy-Grócz, G; Párdutz, Á; Szatmári, I; Szentirmai, M; Vécsei, L; Veres, G; Zádori, D, 2017)
"Kynurenic acid (KYNA) is an endogenous excitatory amino acid receptor blocker, which may have an anti-inflammatory effect."	1.42	Kynurenic acid modulates experimentally induced inflammation in the trigeminal ganglion. ( Csáti, A; Edvinsson, L; Fülöp, F; Tajti, J; Toldi, J; Vécsei, L; Warfvinge, K, 2015)
" In the first series we determined the dose-response and time course effects of intrathecally administered KYNA (10-100 μg), D-(-)-2-amino-5-phosphonopentanoic acid (AP5; an NMDA receptor antagonist; 10-200 μg), methyllycaconitine (MLA; an alpha 7 nicotinic receptor antagonist; 100-200 μg) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzoquinoxaline-7-sulfonamide (NBQX; an AMPA/kainate receptor antagonist; 1-20 μg)."	1.42	The inimitable kynurenic acid: the roles of different ionotropic receptors in the action of kynurenic acid at a spinal level. ( Bohar, Z; Horvath, G; Kekesi, G; Pardutz, A; Petrovszki, Z; Safrany-Fark, A; Tar, L; Tuboly, G; Vecsei, L, 2015)
"Hypoglycemia is a common adverse event and can injure central nervous system (CNS) white matter (WM)."	1.40	Novel hypoglycemic injury mechanism: N-methyl-D-aspartate receptor-mediated white matter damage. ( Brown, AM; Chen, S; Evans, RD; Hamner, MA; Ransom, BR; Yang, X; Ye, ZC, 2014)
"Pain is a complex experience composed of sensory and affective components."	1.39	Opposing roles of corticotropin-releasing factor and neuropeptide Y within the dorsolateral bed nucleus of the stria terminalis in the negative affective component of pain in rats. ( Hara, T; Ide, S; Kaneda, K; Koseki, K; Maruyama, C; Minami, M; Naka, T; Ohno, A; Tamano, R; Yoshioka, M, 2013)
"Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs."	1.39	Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. ( Barnes, C; Bergman, J; Ferré, S; Fratta, W; Goldberg, SR; Justinova, Z; Kangas, BD; Mascia, P; Panlilio, LV; Parashos, A; Pistis, M; Redhi, GH; Scherma, M; Schwarcz, R; Secci, ME; Solinas, M; Tanda, G; Wu, HQ; Zara, T, 2013)
"Methylene blue (MB), has been shown to modulate aggregation of amyloidogenic disease proteins."	1.38	Methylene blue modulates huntingtin aggregation intermediates and is protective in Huntington's disease models. ( Agrawal, N; Aron, R; Finkbeiner, S; Glabe, C; Lau, A; Lotz, GP; Marsh, JL; Muchowski, PJ; Necula, M; Sontag, EM; Thompson, LM; Tran, A; Yang, G, 2012)
"Only kynurenine-treated rats were impaired in acquiring the extra-dimensional shift (saline, 8."	1.38	Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. ( Alexander, KS; Bruno, JP; Schwarcz, R; Wu, HQ, 2012)
" As it did not induce any appreciable side-effect at the protective dose applied in a chronic dosing regime in this mouse model, it appears worthy of further thorough investigations with a view to eventual clinical trials."	1.37	Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse model of Huntington's disease. ( Freund, TF; Fülöp, F; Klivényi, P; Nyiri, G; Szatmári, I; Szonyi, A; Toldi, J; Vécsei, L; Zádori, D, 2011)
"In a transgenic mouse model of Alzheimer's disease, JM6 prevents spatial memory deficits, anxiety-related behavior, and synaptic loss."	1.37	Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. ( Adame, A; Andrews-Zwilling, Y; Flik, G; Giorgini, F; Guidetti, P; Hsieh, EW; Huang, SY; Huang, Y; Laue, G; Lee, J; Louie, JY; Masliah, E; Moussaoui, S; Muchowski, JM; Muchowski, PJ; Notarangelo, FM; Patrick, C; Rassoulpour, A; Sathyasaikumar, KV; Scearce-Levie, K; Schwarcz, R; Truong, J; Wu, HQ; Wu, T; Zwilling, D, 2011)
"Obesity is intimately associated with hypertension; increases in blood pressure are closely related to the magnitude of weight gain."	1.36	Role of excitatory amino acid input in rostral ventrolateral medulla neurons in rats with obesity-induced hypertension. ( Dewa, A; Suhaimi, FW; Yusof, AP; Yusoff, NH, 2010)
"Probenecid treatment significantly reduced the neuronal loss and the number of neuronal intranuclear aggregates."	1.35	Neuroprotective effects of probenecid in a transgenic animal model of Huntington's disease. ( Klivenyi, P; Vamos, E; Vecsei, L; Voros, K; Zadori, D, 2009)
"Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the alpha7-nicotinic acetylcholine receptor at low concentrations."	1.34	Elevations of endogenous kynurenic acid produce spatial working memory deficits. ( Alling, TE; Bucci, DJ; Chess, AC; Simoni, MK, 2007)
"Kynurenic acid is an endogenous glutamate antagonist with a preferential action at the glycine-site of the N-methyl-D-aspartate-receptor."	1.34	The kynurenic acid hypothesis of schizophrenia. ( Engberg, G; Erhardt, S; Linderholm, K; Nilsson, L; Schwieler, L, 2007)
"This relationship is altered in Parkinsonism and in levodopa-induced dyskinesias (LID), resulting in an upregulation of corticostriatal glutamatergic function."	1.33	Effect of kynurenine 3-hydroxylase inhibition on the dyskinetic and antiparkinsonian responses to levodopa in Parkinsonian monkeys. ( Bédard, PJ; Grégoire, L; Guidetti, P; Izzo, E; Rassoulpour, A; Samadi, P; Schwarcz, R, 2005)
"Astrogliosis probably accounts for their enhanced production in chronically epileptic rats."	1.33	Kynurenate and 7-chlorokynurenate formation in chronically epileptic rats. ( Bertram, EH; Goodman, JH; Rassoulpour, A; Scharfman, HE; Schwarcz, R; Wu, HQ, 2005)
"Ten minutes of global cerebral ischemia did not modify the interaction between KAIN and KYNA."	1.33	Kynurenic acid attenuates NMDA-induced pial arteriolar dilation in newborn pigs. ( Bari, F; Busija, DW; Domoki, F; Guidetti, P; Nagy, K; Schwarcz, R, 2006)
"The importance of this mechanism in neuropathic pain remains unclear."	1.33	Antiallodynic effects of NMDA glycine(B) antagonists in neuropathic pain: possible peripheral mechanisms. ( Chizh, BA; Christoph, T; Englberger, W; Reissmüller, E; Schiene, K, 2005)
"These results indicate that memory deficits induced by both hypoxia and PTZ involve NMDA receptor activation."	1.31	Glycine(B) receptor antagonists and partial agonists prevent memory deficits in inhibitory avoidance learning. ( Capdevila, J; Skolnick, P; Trullas, R; Viu, E; Zapata, A, 2000)
"The decrease in the seizure threshold for pentylenetetrazole during diazepam withdrawal was inhibited by pretreatment with MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate), 7-chlorokynurenic acid and ifenprodil."	1.30	Recovery of decreased seizure threshold for pentylenetetrazole during diazepam withdrawal by NMDA receptor antagonists. ( Misawa, M; Suzuki, T; Tsuda, M, 1997)
"However, they do not affect clonic seizures with preserved righting reflexes."	1.29	Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis: III. The action of kynurenic acid and glutamic acid diethylester. ( Kusá, R; Mares, P; Roztocilová, L; Velísek, L, 1995)

Research

Studies (114)

Authors

Clinical Trials (10)

Trial Overview

Trial Outcomes

Auditory Evoked Potentials - P50 Ratio (P50 S2/P50 S1 Amplitude) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	12 (10.53)	18.2507
2000's	29 (25.44)	29.6817
2010's	56 (49.12)	24.3611
2020's	17 (14.91)	2.80

Authors	Studies
Solinski, HJ	1
Dranchak, P	1
Oliphant, E	1
Gu, X	1
Earnest, TW	1
Braisted, J	1
Inglese, J	1
Hoon, MA	1
Abrams, RPM	1
Yasgar, A	1
Teramoto, T	1
Lee, MH	1
Dorjsuren, D	1
Eastman, RT	1
Malik, N	1
Zakharov, AV	1
Li, W	1
Bachani, M	1
Brimacombe, K	1
Steiner, JP	1
Hall, MD	1
Balasubramanian, A	1
Jadhav, A	1
Padmanabhan, R	1
Simeonov, A	1
Nath, A	1
Poles, MZ	1
Nászai, A	1
Gulácsi, L	1
Czakó, BL	1
Gál, KG	1
Glenz, RJ	1
Dookhun, D	1
Rutai, A	1
Tallósy, SP	1
Szabó, A	1
Lőrinczi, B	1
Szatmári, I	5
Fülöp, F	8
Vécsei, L	15
Boros, M	5
Juhász, L	1
Kaszaki, J	5
Siddiqui, T	1
Bhattarai, P	2
Popova, S	1
Cosacak, MI	2
Sariya, S	1
Zhang, Y	2
Mayeux, R	1
Tosto, G	1
Kizil, C	2
Szabo, M	1
Lajkó, N	1
Dulka, K	1
Mihály, A	1
Gulya, K	1
Copeland, EN	1
Watson, CJF	1
Whitley, KC	1
Baranowski, BJ	1
Kurgan, N	1
MacNeil, AJ	1
MacPherson, REK	1
Fajardo, VA	1
Allison, DJ	1
Dey, S	3
Dubey, V	3
Dixit, AB	3
Tripathi, M	3
Chandra, PS	3
Banerjee, J	3
Nahomi, RB	1
Nam, MH	1
Rankenberg, J	1
Rakete, S	1
Houck, JA	1
Johnson, GC	1
Stankowska, DL	1
Pantcheva, MB	1
MacLean, PS	1
Nagaraj, RH	1
Tanaka, M	1
Bohár, Z	3
Martos, D	1
Telegdy, G	1
Tomczyk, T	1
Urbańska, EM	2
Shoaib, M	1
Choudhary, RC	2
Choi, J	1
Kim, N	1
Hayashida, K	1
Yagi, T	1
Yin, T	1
Nishikimi, M	1
Stevens, JF	1
Becker, LB	1
Kim, J	1
Pyun, DH	1
Kim, TJ	1
Kim, MJ	1
Hong, SA	1
Abd El-Aty, AM	1
Jeong, JH	1
Jung, TW	1
Fiedorowicz, M	1
Choragiewicz, T	1
Turski, WA	3
Kocki, T	3
Nowakowska, D	1
Wertejuk, K	1
Kamińska, A	1
Avitabile, T	1
Wełniak-Kaminska, M	1
Grieb, P	1
Zweifel, S	1
Rejdak, R	1
Toro, MD	1
Mori, Y	1
Mouri, A	1
Kunisawa, K	1
Hirakawa, M	1
Kubota, H	1
Kosuge, A	1
Niijima, M	1
Hasegawa, M	1
Kurahashi, H	1
Murakami, R	1
Hoshi, M	1
Nakano, T	1
Fujigaki, S	1
Fujigaki, H	1
Yamamoto, Y	1
Nabeshima, T	1
Saito, K	1
Rentschler, KM	1
Baratta, AM	1
Ditty, AL	1
Wagner, NTJ	1
Wright, CJ	1
Milosavljevic, S	1
Mong, JA	1
Pocivavsek, A	1
Kovács, V	1
Remzső, G	1
Körmöczi, T	1
Berkecz, R	1
Tóth-Szűki, V	1
Pénzes, A	1
Domoki, F	2
Lima, VSS	1
Mariano, DOC	1
Vigerelli, H	1
Janussi, SC	1
Baptista, TVL	1
Claudino, MA	1
Pimenta, DC	1
Sciani, JM	1
Joshi, P	1
Perni, M	1
Limbocker, R	1
Mannini, B	1
Casford, S	1
Chia, S	1
Habchi, J	1
Labbadia, J	1
Dobson, CM	1
Vendruscolo, M	1
Yaksh, TL	1
Schwarcz, R	13
Snodgrass, HR	1
Herajärvi, J	1
Anttila, T	1
Dimova, EY	1
Laukka, T	1
Myllymäki, M	1
Haapanen, H	1
Olenchock, BA	1
Tuominen, H	1
Puistola, U	1
Karihtala, P	1
Kiviluoma, K	1
Koivunen, P	1
Anttila, V	1
Juvonen, T	1
Murfitt, SA	1
Zaccone, P	1
Wang, X	1
Acharjee, A	1
Sawyer, Y	1
Koulman, A	1
Roberts, LD	1
Cooke, A	1
Griffin, JL	1
Wu, X	1
Muthuchamy, M	1
Reddy, DS	1
Kakall, ZM	1
Pilowsky, PM	1
Farnham, MMJ	1
Papadimitriou, C	1
Celikkaya, H	1
Mashkaryan, V	1
Bray, L	1
Brandt, K	1
Hollak, H	1
Chen, X	1
He, S	1
Antos, CL	1
Lin, W	1
Thomas, AK	1
Dahl, A	1
Kurth, T	1
Friedrichs, J	1
Freudenberg, U	1
Werner, C	1
Marciniak, S	1
Wnorowski, A	1
Smolińska, K	2
Walczyna, B	1
Turski, W	1
Paluszkiewicz, P	2
Parada-Turska, J	1
Rojewska, E	1
Ciapała, K	1
Mika, J	1
Milart, P	1
Dobrowolski, P	1
Tomaszewska, E	1
Debinska, I	1
Gawel, K	1
Walczak, K	1
Bednarski, J	1
Turska, M	1
Raban, M	1
Verdonk, F	1
Petit, AC	1
Abdel-Ahad, P	1
Vinckier, F	1
Jouvion, G	1
de Maricourt, P	1
De Medeiros, GF	1
Danckaert, A	1
Van Steenwinckel, J	1
Blatzer, M	1
Maignan, A	1
Langeron, O	1
Sharshar, T	1
Callebert, J	1
Launay, JM	1
Chrétien, F	1
Gaillard, R	1
Han, XM	1
Qin, YJ	1
Zhu, Y	1
Zhang, XL	1
Wang, NX	1
Rang, Y	1
Zhai, XJ	1
Lu, YN	1
Rogers, TD	1
Dickson, PE	1
McKimm, E	1
Heck, DH	1
Goldowitz, D	1
Blaha, CD	1
Mittleman, G	1
Ahmed, Z	1
Gabor, A	1
Leenen, FH	1
Ide, S	1
Hara, T	1
Ohno, A	1
Tamano, R	1
Koseki, K	1
Naka, T	1
Maruyama, C	1
Kaneda, K	1
Yoshioka, M	1
Minami, M	1
McTighe, SM	1
Neal, SJ	1
Lin, Q	1
Hughes, ZA	1
Smith, DG	1
Liautard, C	1
Scalmani, P	1
Carriero, G	1
de Curtis, M	1
Franceschetti, S	1
Mantegazza, M	1
Justinova, Z	1
Mascia, P	1
Wu, HQ	6
Secci, ME	1
Redhi, GH	1
Panlilio, LV	1
Scherma, M	1
Barnes, C	1
Parashos, A	1
Zara, T	1
Fratta, W	1
Solinas, M	1
Pistis, M	1
Bergman, J	1
Kangas, BD	1
Ferré, S	1
Tanda, G	1
Goldberg, SR	1
Yang, X	1
Hamner, MA	1
Brown, AM	1
Evans, RD	1
Ye, ZC	1
Chen, S	1
Ransom, BR	1
Notarangelo, FM	2
Wilson, EH	1
Horning, KJ	1
Thomas, MA	1
Harris, TH	1
Fang, Q	1
Hunter, CA	1
Wang, YK	1
Shen, D	1
Hao, Q	1
Yu, Q	1
Wu, ZT	1
Deng, Y	1
Chen, YF	1
Yuan, WJ	1
Hu, QK	1
Su, DF	1
Wang, WZ	2
Zavitsanou, K	1
Lim, CK	1
Purves-Tyson, T	1
Karl, T	1
Kassiou, M	1
Banister, SD	1
Guillemin, GJ	1
Weickert, CS	1
Liu, BB	2
Luo, L	2
Liu, XL	2
Geng, D	2
Liu, Q	2
Yi, LT	2
Tuboly, G	3
Tar, L	1
Safrany-Fark, A	1
Petrovszki, Z	2
Kekesi, G	3
Pardutz, A	2
Horvath, G	3
Yang, C	1
Zhang, JR	1
Chen, L	1
Ge, SN	1
Wang, JL	1
Yan, ZQ	1
Jia, D	1
Zhu, JL	1
Gao, GD	1
García-Lara, L	1
Pérez-Severiano, F	1
González-Esquivel, D	1
Elizondo, G	1
Segovia, J	1
Dugan, AM	1
Parrott, JM	1
Redus, L	1
Hensler, JG	1
O'Connor, JC	1
Sharma, RK	1
Gulati, K	1
Ravi, K	1
Li, CF	1
Chen, XM	1
Chen, SM	1
Mu, RH	1
Csáti, A	1
Edvinsson, L	1
Toldi, J	4
Tajti, J	1
Warfvinge, K	1
Beaumont, V	1
Mrzljak, L	1
Dijkman, U	1
Freije, R	1
Heins, M	1
Rassoulpour, A	6
Tombaugh, G	1
Gelman, S	1
Bradaia, A	1
Steidl, E	1
Gleyzes, M	1
Heikkinen, T	1
Lehtimäki, K	1
Puoliväli, J	1
Kontkanen, O	1
Javier, RM	1
Neagoe, I	1
Deisemann, H	1
Winkler, D	1
Ebneth, A	1
Khetarpal, V	1
Toledo-Sherman, L	1
Dominguez, C	1
Park, LC	1
Munoz-Sanjuan, I	1
Bortolotti, P	1
Hennart, B	1
Thieffry, C	1
Jausions, G	1
Faure, E	1
Grandjean, T	1
Thepaut, M	1
Dessein, R	1
Allorge, D	1
Guery, BP	1
Faure, K	1
Kipnis, E	1
Toussaint, B	1
Le Gouellec, A	1
Liu, XC	1
Erhardt, S	2
Goiny, M	1
Engberg, G	2
Mathé, AA	1
Veres, G	1
Fejes-Szabó, A	1
Zádori, D	3
Nagy-Grócz, G	1
László, AM	1
Bajtai, A	1
Mándity, I	1
Szentirmai, M	1
Laborc, K	1
Mandel, DA	1
Schreihofer, AM	1
Sas, K	1
Robotka, H	1
Rózsa, E	1
Agoston, M	1
Szénási, G	1
Gigler, G	1
Marosi, M	2
Kis, Z	2
Farkas, T	2
Gao, L	1
Wang, HJ	1
Zucker, IH	1
Wang, W	1
Vamos, E	2
Voros, K	1
Klivenyi, P	2
Varga, G	4
Erces, D	3
Fazekas, B	2
Fülöp, M	1
Kovács, T	3
Yang, GY	1
Woo, YW	1
Park, MK	1
Bae, YC	1
Ahn, DK	1
Bonfa, E	1
Suhaimi, FW	1
Yusoff, NH	1
Dewa, A	1
Yusof, AP	1
Martins, MA	1
De Castro Bastos, L	1
Melo, NE	1
Tonussi, CR	1
Nyiri, G	1
Szonyi, A	1
Freund, TF	1
Campesan, S	1
Green, EW	1
Breda, C	1
Sathyasaikumar, KV	2
Muchowski, PJ	3
Kyriacou, CP	1
Giorgini, F	2
Zwilling, D	1
Huang, SY	1
Guidetti, P	5
Lee, J	1
Truong, J	1
Andrews-Zwilling, Y	1
Hsieh, EW	1
Louie, JY	1
Wu, T	1
Scearce-Levie, K	1
Patrick, C	1
Adame, A	1
Moussaoui, S	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation[NCT05866575]		136 participants (Anticipated)	Interventional	2023-06-01	Not yet recruiting
Pilot Study of Glycine Augmentation in Carriers of a Mutation in the Gene Encoding Glycine Decarboxylase[NCT01720316]	Phase 2	2 participants (Actual)	Interventional	2012-12-10	Completed
Targeting a Genetic Mutation in Glycine Metabolism With D-cycloserine[NCT02304432]	Early Phase 1	2 participants (Actual)	Interventional	2015-09-27	Completed
Randomized Controlled Experimental Trial Designed to Test the Effects of Probiotics on Mood[NCT03539263]		39 participants (Actual)	Interventional	2016-12-20	Completed
Understanding the Neurocognitive Effects of Fecal Microbiota Transplantation in Major Depressive Disorder Patients With and Without Irritable Bowel Syndrome[NCT05174273]	Phase 2/Phase 3	180 participants (Anticipated)	Interventional	2022-04-06	Recruiting
The Safety and Effectiveness of Probiotic Supplementation on Bipolar Depression: a Proof of Concept Randomized Controlled Trial[NCT02155972]	Phase 2	16 participants (Actual)	Interventional	2013-05-31	Terminated (stopped due to The trial was terminated because of inability to recruit the needed number of participants)
"Proof-of-Concept Stress & Anxiety Dampening Effects of Lpc-37"[NCT03494725]		120 participants (Actual)	Interventional	2018-04-10	Completed
A Clinical Trial to Evaluate the Safety and Tolerability of Fecal Microbiota Transplantation in a Population With Obsessive-compulsive Disorder[NCT05720793]	Phase 2	20 participants (Anticipated)	Interventional	2023-06-01	Recruiting
A Randomized Controlled Trial of the Safety and Efficacy of Fecal Microbiota Transplantation in a Population With Bipolar Disorder[NCT03279224]	Phase 2/Phase 3	35 participants (Actual)	Interventional	2018-01-01	Active, not recruiting
A Pilot Study to Assess the Efficacy of Subanesthetic Doses of IV Ketamine in the Treatment Drug Resistant Epilepsy[NCT05019885]	Phase 2	6 participants (Anticipated)	Interventional	2022-08-26	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Auditory evoked potentials amplitude: P50 ratio (S2/S1). Participants were assessed at baseline and in week 6 of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	ratio (Number)
Auditory ERPs Amplitude (Deg) Baseline: Subject 2	44.51
Auditory ERPs Amplitude (Deg) 6 Weeks of Glycine: Subject 2	35.67

Auditory evoked potentials amplitude: P300 at fz, cz, and pz; N100 at fz and cz; P200 at fz and cz; P50 S1 and S2 amplitude; mismatch negativity (MMN) at fz and cz. Participants were assessed at baseline and in week 6 of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Auditory Evoked Potentials in Gammas Oscillations (the Power Spectrum is Measured in Microvolts Squared) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	microvolts (Number)
	P300 amplitude at fz	P300 amplitude at cz	P300 amplitude at pz	N100 amplitude at fz	N100 amplitude at cz	P200 amplitude at fz	P200 amplitude at cz	P50 S1 amplitude	P50 S2 amplitude	MMN amplitude at fz	MMN amplitude at cz
Auditory ERPs Amplitude (Deg) 6 Weeks of Glycine: Subject 2	3.74	6.6	5.57	-4.71	-3.89	6.29	7.8	2.2	0.78	-1.004	-1.322
Auditory ERPs Amplitude (Deg) Baseline: Subject 2	-0.635	6.53	5.34	-3.93	-3.62	1.662	6.59	2.76	1.23	-3.356	-4.13

Auditory evoked potentials gamma: G40 hz phase locking at fz and cz; G20 hz phase locking response at fz and cz G30 hz phase locking response at fz and cz. Participants were assessed at baseline and in week 6 of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Auditory Evoked Potentials in Latency (Msec) at BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF TREATMENT WITH GLYCINE

Intervention	microvolts squared (Number)
	G40 fz	G40 cz	G20 fz	G20 cz	G30 fz	G30 cz
Auditory ERPs Gamma 6 Weeks of Glycine: Subject 2	0.255	0.29	0.107	0.108	0.177	0.242
Auditory ERPs Gamma Baseline: Subject 2	0.135	0.168	0.023	0.03	0.19	0.163

Auditory evoked potentials latency: P300 at fz, cz, and pz); N100 at fz and cz); P200 at fz and cz. Participants were assessed at baseline and in week of open-label glycine treatment. (NCT01720316)
Timeframe: Recordings at baseline and week 6 of glycine

Brain GABA Metabolite Levels (GABA/Creatine Ratio: GABA/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	msec (Number)
	P300 latency at fz	P300 latency at cz	P300 latency at pz	N100 latency at fz	N100 latency at cz	P200 latency at fz	P200 latency at cz
Auditory ERPs Latency (ms) 6 Weeks of Glycine: Subject 2	300.78	293	294.92	94	94	205	203
Auditory ERPs Latency (ms) Baseline: Subject 2	279.3	279.3	279.3	97.66	91.8	197.27	193.4

Magnetic resonance spectroscopy GABA/Cr. Participants were assessed 1) pre-glycine treatment (baseline) and 2) in week 6 of open-label glycine treatment measured in posterior occipital cortex. (NCT01720316)
Timeframe: Baseline and week 6 of glycine

Brain Glutamate Metabolite Levels (Glutamate/Creatine Ratio: Glu/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Intervention	ratio (Number)
	Baseline GABA/Cr	Week 6 of glycine tx GABA/Cr
Subject1: Brain GABA/CR Ratio- Baseline/Week 6 of Glycine	0.16	0.22
Subject2: Brain GABA/CR Ratio- Baseline/Week 6 of Glycine	0.27	0.24

magnetic resonance spectroscopy - glutamate metabolite level. Participants were assessed 1) pre-glycine treatment and in week 6 of open-label glycine treatment. Measured in posterior occipital cortex. (NCT01720316)
Timeframe: baseline and week 6 of glycine

Brain Glycine/CR Ratio

Intervention	ratio (Number)
	Baseline brain glutamate/Cr ratio	Week 6 brain glutamate/Cr ratio
Subject1: Brain Glutamate/CR Ratio- Baseline/Week 6 of Glycine	0.98	0.84
Subject2: Brain Glutamate/CR Ratio- Baseline/Week 6 of Glycine	2.053	1.13

magnetic resonance spectroscopy: glycine/creatine ratio. Participants were assessed at 1) BASELINE PRE-GLYCINE TREATMENT: pre-glycine challenge drink, 60 minutes post challenge drink, 80 minutes post challenge drink, 100 minutes post challenge drink, and 120 minutes post challenge drink (0.4 g/kg up to max of 30 g); and 2) IN WEEK 6 OF OPEN-LABEL GLYCINE TREATMENT: pre-glycine dose, and 60 minutes, 80 minutes, 100 minutes and 120 minutes post daily dose of glycine. Measured in posterior occipital cortex (NCT01720316)
Timeframe: baseline (pre-challenge, 60, 80, 100, 120 minutes post-challenge), and week 6 of glycine (pre-dose and 60, 80, 100, 120 minutes post-dose

Brief Psychiatric Rating Scale (BPRS) Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Positive and Negative Symptom Scores at Baseline and at 2, 4, and 6 Weeks During Intervention 1, Intervention 2, and During Open-label Glycine

Intervention	ratio (Number)
	Baseline - pre-challenge drink	Baseline 60 minutes post challenge drink	Baseline 80 minutes post challenge drink	Baseline 100 minutes post challenge drink	Baseline 120 minutes post challenge drink	Week 6 of glycine - pre-glycine dose	Week 6 of glycine - 60 minutes post glycine dose	Week 6 of glycine - 80 minutes post glycine dose	Week 6 of glycine - 100 minutes post glycine dose	Week 6 of glycine - 120 minutes post glycine dose
Subject 2:Brain Glycine/CR Ratio at Baseline/Week 6 of Glycine	0.5691	0.3918	0.6428	0.6363	0.9559	0.3235	0.3807	0.5591	0.4142	0.3545
Subject1: Brain Glycine/CR Ratio at Baseline/Week 6 of Glycine	0.2558	0.6157	0.6631	0.5938	0.6953	0.6573	0.2983	0.4577	0.5751	0.3842

Total BPRS score measures severity of 18 psychiatric symptoms. Each symptom is scored 1-7 with the total score ranging from 18-126. 18 means no symptoms and 126 means very severe symptoms. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within and after each treatment period

Clinical Global Impression (CGI) Severity Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	units on a scale (Number)
	BPRS at baseline	BPRS at 2 weeks intervention 1	BPRS at 4 weeks intervention 1	BPRS at 6 weeks intervention 1	BPRS, end of washout1	BPRS at 2 weeks intervention 2	BPRS at 4 weeks intervention 2	BPRS at 6 weeks intervention 2	BPRS, end of washout2	BPRS at 2 weeks open label	BPRS at 4 weeks open label	BPRS at 6 weeks open label	BPRS, end of washout3
Glycine, Then Placebo	39	38	32	21	22	37	31	37	32	23	22	21	19
Placebo, Then Glycine	46	38	39	28	34	32	20	23	24	20	18	19	23

Clinical Global Impression (CGI) severity scores measure severity of mental illness on a scale of 1-7 where 1 means normal, not at all ill, 2 means borderline mentally ill, 3 means mildly ill, 4 means moderately ill, 5 means markedly ill, 6 means severely ill and 7 means among the most extremely ill patients. (NCT01720316)
Timeframe: CGI at baseline and at 2 weeks, 4 weeks, and 6 weeks per treatment period

Clinical Global Impression (CGI) Therapeutic Effect Scores at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	units on a scale (Number)
	CGI severity score at baseline	CGI severity score at 2 weeks intervention 1	CGI severity score at 4 weeks intervention 1	CGI severity score at 6 weeks intervention 1	CGI severity score, end of washout1	CGI severity score at 2 weeks intervention 2	CGI severity score at 4 weeks intervention 2	CGI severity score at 6 weeks intervention 2	CGI severity score, end of washout2	CGI severity score at 2 weeks open label	CGI severity score at 4 weeks open label	CGI severity score at 6 weeks open label	CGI severity score, end of washout3
Glycine, Then Placebo	4	4	3	2	2	4	4	4	4	3	3	2	2
Placebo, Then Glycine	4	4	4	4	4	4	4	3	3	3	3	2	2

Clinical Global Impression (CGI) therapeutic effect scores measure degree of improvement as marked (1), moderate (5), minimal (9) or unchanged/worse (13). (NCT01720316)
Timeframe: at 2 weeks, 4 weeks, and 6 weeks within each treatment period

Depression Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	score (Number)
	CGI therapeutic effect at 2 weeks intervention 1	CGI therapeutic effect at 4 weeks intervention 1	CGI therapeutic effect at 6 weeks intervention 1	CGI therapeutic effect, end of washout1	CGI therapeutic effect at 2 weeks intervention 2	CGI therapeutic effect at 4 weeks intervention 2	CGI therapeutic effect at 6 weeks intervention 2	CGI therapeutic effect, end of washout2	CGI therapeutic effect at 2 weeks open label	CGI therapeutic effect at 4 weeks open label	CGI therapeutic effect at 6 weeks open label	CGI therapeutic effect, end of washout3
Glycine, Then Placebo	13	5	5	5	13	13	13	13	5	5	1	1
Placebo, Then Glycine	5	5	5	5	13	5	5	5	1	1	1	1

Hamilton Depression Scale measures severity of depression symptoms. The sum of ratings for 9 depression symptoms are measured on a scale from 0-2 with 0 meaning no symptoms and 2 meaning some level of severity of that specific symptom. The rating for 1 depression symptom is measured on a scale from 0-3 with 0 meaning no symptoms and 3 meaning a severe level of that specific symptom. The sum of ratings for 11 depression symptoms are measured on a scale from 0-4 with 0 meaning no symptoms and 4 meaning a severe level of that specific symptom. The three sums are added to produce an overall depression rating scale score ranging from 0-65. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period

Glycine Plasma Amino Acid Levels at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Intervention	units on a scale (Number)
	Depression symptoms at baseline	Depression symptoms at 2 weeks intervention 1	Depression symptoms at 4 weeks intervention 1	Depression symptoms at 6 weeks intervention 1	Depression symptoms, end of washout1	Depression symptoms at 2 weeks intervention 2	Depression symptoms at 4 weeks intervention 2	Depression symptoms at 6 weeks intervention 2	Depression symptoms, end of washout2	Depression symptoms at 2 weeks open label	Depression symptoms at 4 weeks open label	Depression symptoms at 6 weeks open label	Depression symptoms, end of washout3
Glycine, Then Placebo	18	17	11	3	1	19	5	7	3	2	2	1	2
Placebo, Then Glycine	12	5	5	0	3	3	2	1	1	1	1	1	0

Plasma glycine levels; normal range is 122-467 nM/mL (NCT01720316)
Timeframe: At baseline, during glycine treatment, during placebo treatment and during open-label glycine

Mania Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Intervention	nM/mL (Number)
	Baseline	Glycine double-blind	Placebo	Glycine open-label
Glycine Then Placebo	216	410	194	516
Placebo Then Glycine	271	761	347	634

Young Mania Rating Scale (YMRS) measures severity of manic symptoms. The sum of ratings for 7 symptoms of mania is measured on a scale from 0-4 and the sum of 4 symptoms of mania is measured on a scale from 0-8 to yield a total score ranging from 0-60, with 0 meaning no manic symptoms and 60 meaning severe manic symptoms. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period

Neurocognitive Function at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Intervention	units on a scale (Number)
	Manic symptoms at baseline	Manic symptoms at 2 weeks intervention 1	Manic symptoms at 4 weeks intervention 1	Manic symptoms at 6 weeks intervention 1	Manic symptoms, end of washout1	Manic symptoms at 2 weeks intervention 2	Manic symptoms at 4 weeks intervention 2	Manic symptoms at 6 weeks intervention 2	Manic symptoms, end of washout2	Manic symptoms at 2 weeks open label	Manic symptoms at 4 weeks open label	Manic symptoms at 6 weeks open label	Manic symptoms, end of washout3
Glycine, Then Placebo	4	1	0	0	0	17	0	2	2	1	0	0	0
Placebo, Then Glycine	7	7	6	0	0	0	0	0	0	0	0	0	0

Scores on each of 8 domains of cognitive function (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, social cognition, overall composite). Scores are T scores ranging from 0-100, with 50 representing the mean for a population based on a normal distribution; standard deviation of 10. Only overall composite score is entered. (NCT01720316)
Timeframe: At baseline, during glycine treatment, during placebo treatment and during open-label glycine

Positive and Negative Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks During Intervention 1 (Glycine or Placebo), Intervention 2 (Glycine or Placebo), and During Open-label Glycine

Intervention	units on a scale (Number)
	Participant 1	Participant 2
Baseline	45	48
Composite Score on Glycine, Double-blind	52	52
Composite Score on Glycine, Open-label	49	46
Composite Score on Placebo	52	55

Positive and Negative Symptom Scale (PANSS) measures positive and negative symptoms of schizophrenia. The sum of ratings for seven positive symptoms are measured on a scale from 7-49 with 7 meaning no symptoms and 49 meaning severe symptoms. (NCT01720316)
Timeframe: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period and after each treatment period

Auditory Evoked Potentials - P50 Ratio (P50 S2/S1) (Amplitude)

Intervention	units on a scale (Number)
	Positive symptoms at baseline	Positive symptoms at 2 weeks intervention 1	Positive symptoms at 4 weeks intervention 1	Positive symptoms at 6 weeks intervention 1	Positive symptoms, end of washout1	Positive symptoms at 2 weeks intervention 2	Positive symptoms at 4 weeks intervention 2	Positive symptoms at 6 weeks intervention 2	Positive symptoms, end of washout2	Positive symptoms at 2 weeks open label	Positive symptoms at 4 weeks open label	Positive symptoms at 6 weeks open label	Positive symptoms, end of washout3
Glycine, Then Placebo	13	12	9	8	7	12	11	14	14	9	9	7	7
Placebo, Then Glycine	19	20	19	13	13	12	10	11	11	8	7	8	8

Auditory evoked potential amplitude: P50 ratio (P50 S2/S1) (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts)

Intervention	ratio (Number)
	P50 ratio: Baseline	P50 ratio: Week 8 of DCS
First Open Label DCS	44.51	30

Auditory evoked potential amplitude: P300 at fz, cz, and pz; N100 at fz and cz; P200 at fz and cz; P50 S1 and S2; mismatch negativity (MMN) at fz and cz. (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Auditory Evoked Potentials in Gamma Oscillations (the Power Spectrum is Measured in Microvolts Squared)

Intervention	microvolts (Number)
	P300 at fz: Baseline	P300 at cz: Baseline	P300 at pz: Baseline	N100 at fz: Baseline	N100 at cz: Baseline	P200 at fz: Baseline	P200 at cz: Baseline	P50 S1: Baseline	P50 S2: Baseline	MMN at fz: Baseline	MMN at cz: Baseline	P300 at fz: Week 8 of DCS	P300 at cz: Week 8 of DCS	P300 at pz: Week 8 of DCS	N100 at fz: Week 8 of DCS	N100 at cz: Week 8 of DCS	P200 at fz: Week 8 of DCS	P200 at cz: Week 8 of DCS	P50 S1: Week 8 of DCS	P50 S2: Week 8 of DCS	MMN at fz: Week 8 of DCS	MMN at cz: Week 8 of DCS
First Open Label DCS	-0.635	6.529	5.340	-3.926	-3.615	1.662	6.591	2.759	1.23	-3.356	-4.130	3.030	6.810	6.620	-3.260	-3.940	8.200	8.160	1.36	0.4	-3.330	-1.540

Auditory evoked potential gamma: G40 hz phase locking at fz and cz; G30 hz phase locking at fz and cz; G20 hz phase locking at fz and cz (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Auditory Evoked Potentials in Latency (Msec)

Intervention	microvolts squared (Number)
	G40 hz phase locking at fz: Baseline	G40 hz phase locking at cz: Baseline	G30 hz phase locking at fz: Baseline	G30 hz phase locking at cz: Baseline	G20 hz phase locking at fz: Baseline	G20 hz phase locking at cz: Baseline	G40 hz phase locking at fz: Week 8 of DCS	G40 hz phase locking at cz: Week 8 of DCS	G30 hz phase locking at fz: Week 8 of DCS	G30 hz phase locking at cz: Week 8 of DCS	G20 hz phase locking at fz: Week 8 of DCS	G20 hz phase locking at cz: Week 8 of DCS
First Open Label DCS	0.135	0.168	0.190	0.163	0.023	0.030	0.344	0.381	0.168	0.19	0.01	-0.01

Auditory evoked potential latency: P300 at fz, cz, and pz; N100 at fz and cz; P200 at fz and cz. (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Brain Glycine/CR Ratio

Intervention	msec (Number)
	P300 at fz: Baseline	P300 at cz: Baseline	P300 at pz: Baseline	N100 at fz: Baseline	N100 at cz: Baseline	P200 at fz: Baseline	P200 at cz: Baseline	P300 at fz: Week 8 of DCS	P300 at cz: Week 8 of DCS	P300 at pz: Week 8 of DCS	N100 at fz: Week 8 of DCS	N100 at cz: Week 8 of DCS	P200 at fz: Week 8 of DCS	P200 at cz: Week 8 of DCS
First Open Label DCS	279.297	279.297	279.297	97.656	91.797	197.266	193.359	294.920	294.000	294	87.9	88.000	212.890	212.000

Proton magnetic resonance spectroscopy at 4T: brain glycine/CR ratio. Participants were assessed at baseline (pre-glycine challenge dose and 60, 80, 100 and 120 minutes post glycine dose) and in week 8 of of open-label DCS treatment: pre-DCS dose, and 60, 80, 100 and 120 minutes post DCS dose. Measured in posterior occipital cortex. (NCT02304432)
Timeframe: Baseline and Week 8 of DCS treatment

Brief Psychiatric Rating Scale (BPRS) Scores

Intervention	ratio (Median)
	Baseline	Baseline at 60 minutes	Baseline at 80 minutes	Baseline at 100 minutes	Baseline at 120 minutes	Week 8 of DCS: Baseline	Week 8 of DCS: 60 minutes	Week 8 of DCS: 80 minutes	Week 8 of DCS: 100 minutes	Week 8 of DCS: 120 minutes
Open Label DCS	0.41245	0.50375	0.65295	0.61505	0.8256	0.10977	0.248885	0.32609	0.32052	0.312155

Total BPRS score measures severity of 18 psychiatric symptoms. Each symptom is scored 1-7 with the total score ranging from 18-126. 18 means no symptoms and 126 means very severe symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Brief Psychiatric Rating Scale (BPRS) Scores

Intervention	units on a scale (Median)
	Baseline BPRS	2 weeks BPRS	4 weeks BPRS	6 weeks BPRS	8 weeks BPRS	10 weeks BPRS	12 weeks BPRS	14 weeks BPRS	16 weeks BPRS	18 weeks BPRS	20 weeks BPRS	22 weeks BPRS	24 weeks BPRS
First Open Label DCS	37	25	26	24	24.5	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	31.5	30.5	28	25.5	26	26.5	26	25.5	28.5	27	25	24.5	26.5

Total BPRS score measures severity of 18 psychiatric symptoms. Each symptom is scored 1-7 with the total score ranging from 18-126. 18 means no symptoms and 126 means very severe symptoms. (NCT02304432)
Timeframe: Baseline, 2, 4, & 6 weeks (crossover periods)

Clinical Global Impression (CGI) Severity Scores

Intervention	units on a scale (Number)
	Baseline BPRS for first intervention	2 weeks BPRS for first intervention	4 weeks BPRS for first intervention	6 weeks BPRS for first intervention	Baseline BPRS for second intervention	2 weeks BPRS for second intervention	4 weeks BPRS for second intervention	6 weeks BPRS for second intervention
DCS First, Then Placebo	26	25	25	26	39	45	45	38
Placebo First, Then DCS	29	35	33	35	36	30	27	28

CGI severity scores measure severity of mental illness on a scale of 1-7 where 1 means normal, not at all ill, 2 means borderline mentally ill, 3 means mildly ill, 4 means moderately ill, 5 means markedly ill, 6 means severely ill and 7 means among the most extremely ill patients. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Clinical Global Impression (CGI) Severity Scores

Intervention	units on a scale (Median)
	Baseline CGI	2 weeks CGI	4 weeks CGI	6 weeks CGI	8 weeks CGI	10 weeks CGI	12 weeks CGI	14 weeks CGI	16 weeks CGI	18 weeks CGI	20 weeks CGI	22 weeks CGI	24 weeks CGI
First Open Label DCS	4	2	2	2	2	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	2.5	2.5	2.5	2.5	2.5	3	2.5	2	2.5	2.5	2.5	2.5	2.5

Depression Symptom Scores

Intervention	units on a scale (Number)
	Baseline CGI for first intervention	2 weeks CGI for first intervention	4 weeks CGI for first intervention	6 weeks CGI for first intervention	Baseline CGI for second intervention	2 weeks CGI for second intervention	4 weeks CGI for second intervention	6 weeks CGI for second intervention
DCS First, Then Placebo	2	2	2	2	3	3	3	3
Placebo First, Then DCS	1	3	3	3	3	2	2	2

Hamilton Depression Scale (HAM) measures severity of depression symptoms. The sum of the ratings for 9 depression symptoms is measured on a scale of 0-2 with 0 meaning no depression symptoms and 2 meaning some level of severity of that specific symptom. The rating for one depression symptom is measured on a scale of 0-3 with 0 meaning no depression symptoms and 3 meaning a severe level of that specific symptom. The sum of ratings for 11 depression symptoms is measured on a scale of 0-4, with 0 meaning no symptoms and 4 meaning a severe level of that specific symptom. The three sums are added to produce an overall depression rating scale score ranging from 0-65. Higher scores indicate worse depression symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Depression Symptom Scores

Intervention	units on a scale (Median)
	Baseline HAM	2 weeks HAM	4 weeks HAM	6 weeks HAM	8 weeks HAM	10 weeks HAM	12 weeks HAM	14 weeks HAM	16 weeks HAM	18 weeks HAM	20 weeks HAM	22 weeks HAM	24 weeks HAM
First Open Label DCS	5	1.5	1	0.5	1.5	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	0.5	1	1	0	2.5	0	0	0	3.5	0	0	0	0

Mania Symptom Scores

Intervention	units on a scale (Number)
	Baseline HAM for first intervention	2 weeks HAM for first intervention	4 weeks HAM for first intervention	6 weeks HAM for first intervention	Baseline HAM for second intervention	2 weeks HAM for second intervention	4 weeks HAM for second intervention	6 weeks HAM for second intervention
DCS First, Then Placebo	0	1	0	0	2	12	9	2
Placebo First, Then DCS	4	5	2	10	0	0	0	0

Young Mania Rating Scale (YMRS) measures severity of manic symptoms. The sum of the ratings for 7 symptoms of mania is measured on a scale of 0-4 and the sumof 4 symptoms of mania is measured on a scale of 0-8 to yield a total score ranging from 0-60, with 0 meaning no manic symptoms and 60 meaning severe manic symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Mania Symptom Scores

Intervention	units on a scale (Median)
	Baseline YMRS	2 weeks YMRS	4 weeks YMRS	6 weeks YMRS	8 weeks YMRS	10 weeks YMRS	12 weeks YMRS	14 weeks YMRS	16 weeks YMRS	18 weeks YMRS	20 weeks YMRS	22 weeks YMRS	24 weeks YMRS
First Open Label DCS	2	1	1	0	0	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	0	0	0	0	0	0	0	0	0	0	0	0	1

Neurocognitive Function

Intervention	units on a scale (Number)
	Baseline YMRS for first intervention	2 weeks YMRS for first intervention	4 weeks YMRS for first intervention	6 weeks YMRS for first intervention	Baseline YMRS for second intervention	2 weeks YMRS for second intervention	4 weeks YMRS for second intervention	6 weeks YMRS for second intervention
DCS First, Then Placebo	0	0	0	0	0	0	0	0
Placebo First, Then DCS	1	0	0	0	4	1	1	1

Scores on each of 8 domains of cognitive function (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, social cognition, overall composite). Scores are T scores ranging from 0-100, with 50 representing the mean for a population based on a normal distribution, standard deviation of 10. Higher scores signify better functioning. (NCT02304432)
Timeframe: Baseline and Week 8 of open-label DCS treatment

Positive and Negative Symptom Scores

Intervention	T scores (Median)
	Baseline Processing Speed	Baseline Attention/Vigilance	Baseline Working Memory	Baseline Verbal Learning	Baseline Visual Learning	Baseline Reasoning/Problem Solving	Baseline Social Cognition	Baseline Overall Composite Score	Week 8 of open-label DCS Processing Speed	Week 8 of open-label DCS Attention/Vigilance	Week 8 of open-label DCS Working Memory	Week 8 of open-label DCS Verbal Learning	Week 8 of open-label DCS Visual Learning	Week 8 of open-label DCS Reasoning/Problem Solving	Week 8 of open-label DCS Social Cognition	Week 8 of open-label DCS Overall Composite Score
Open Label DCS	48.5	44.5	38.5	54	50.5	52.5	48	46.5	52.5	47.5	50.5	43.5	54.5	66.5	44.5	51.5

Positive and Negative Symptom Scale (PANSS) measures positive and negative symptoms of schizophrenia. The sum of ratings for seven positive symptoms is measured on a scale from 7-49 with 7 meaning no symptoms and 49 meaning severe symptoms.The sum of ratings for seven negative symptoms is measured on a scale from 7-49 with 7 meaning no symptoms and 49 meaning severe symptoms. (NCT02304432)
Timeframe: Baseline & at 2, 4, 6 & 8 Weeks during open-label phase 1 and every 2 weeks up to 24 weeks during open label phase 2

Positive and Negative Symptom Scores

Intervention	units on a scale (Median)
	Baseline positive	Baseline negative	2 weeks positive	2 weeks negative	4 weeks positive	4 weeks negative	6 weeks positive	6 weeks negative	8 weeks positive	8 weeks negative	10 weeks positive	10 weeks negative	12 weeks positive	12 weeks negative	14 weeks positive	14 weeks negative	16 weeks positive	16 weeks negative	18 weeks positive	18 weeks negative	20 weeks positive	20 weeks negative	22 weeks positive	22 weeks negative	24 weeks positive	24 weeks negative
First Open Label DCS	14.5	14.5	10	12	10.5	12	9	12	9	12	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Second Open Label DCS	11	14	11	14	10.5	13.5	9	13	9.5	12	10.5	13	11	12	10	12	10.5	12	10.5	12	10.5	12	9.5	12	10	12

Change of Diastolic Blood Pressure (BP) in Response to the TSST

Intervention	units on a scale (Number)
	Baseline positive for first intervention	Baseline negative symptoms for first intervention	2 weeks positive for first intervention	2 weeks negative for first intervention	4 weeks positive for first intervention	4 weeks negative for first intervention	6 weeks positive for first intervention	6 weeks negative for first intervention	Baseline positive for second intervention	Baseline negative for second intervention	2 weeks positive for second intervention	2 weeks negative for second intervention	4 weeks positive for second intervention	4 weeks negative for second intervention	6 weeks positive for second intervention	6 weeks negative for second intervention
DCS First, Then Placebo	10	15	10	15	10	15	10	15	15	18	15	18	15	18	14	18
Placebo First, Then DCS	11	9	12	15	11	13	13	13	13	13	10	11	9	11	9	11

Efficacy of the intake of Lpc-37 on reduction of the increase of the diastolic BP in response to the TSST compared to placebo. (NCT03494725)
Timeframe: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake

Change of Mood Scale Scores Over the Course of the Treatment

Intervention	mmHg (Mean)
	Pre-TSST -3min	Post-TSST +1min
Lpc-37	79.13	90.38
Placebo	78.41	88.36

"Efficacy of the intake of Lpc-37 on the increase of mood scale scores over the course of the treatment~Measured with a daily online diary. Mood was rated by participants on an 11-point scale (0-10; very bad to very well) and monitored through the washout phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a better mood. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one average value for each week and participant. Values reflect summary measures for mood ratings on a scale from 0 to 10 for the averaged ratings per participant and week." (NCT03494725)
Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Change of Perceived Health Status Scores Over the Course of the Treatment

Intervention	score (Mean)
	Week 1 (run-in)	Week 2 (run-in)	Week 3 (treatment)	Week 4 (treatment)	Week 5 (treatment)	Week 6 (treatment)	Week 7 (treatment)
Lpc-37	7.31	7.53	7.66	7.77	7.73	7.90	7.77
Placebo	7.27	7.49	7.46	7.53	7.50	7.40	7.55

"Efficacy of the intake of Lpc-37 on the increase of perceived health status scores over the course of the treatment.~Measured with a daily online diary. Health status was rated by participants on an 11-point scale (0-10; not at all to very) and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a high perceived health.Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for perceived health status on a scale from 0 to 10 for the averaged ratings per participant and week." (NCT03494725)
Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Change of Perceived Productivity Scores Over the Course of the Treatment

Intervention	score (Mean)
	Week 1 (run-in)	Week 2 (run-in)	Week 3 (treatment)	Week 4 (treatment)	Week 5 (treatment)	Week 6 (treatment)	Week 7 (treatment)
Lpc-37	7.80	7.89	7.88	7.91	8.05	8.11	7.91
Placebo	7.86	7.92	7.92	8.01	7.92	7.73	7.75

"Efficacy of the intake of Lpc-37 on the increase of perceived productivity scores over the course of the treatment~Measured with a daily online diary. Productivity was rated by participants on an 11-point scale (0-10; not at all to very) and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a higher perceived productivity. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group.Time is coded as a continuous variable with one value for each day and participant. The values reflect summary measures for perceived productivity on a scale from 0 to 10 for the averaged ratings per participant and week." (NCT03494725)
Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Change of Reported Number of Sleep Disruptions Over the Course of the Treatment

Intervention	score (Mean)
	Week 1 (run-in)	Week 2 (run-in)	Week 3 (treatment)	Week 4 (treatment)	Week 5 (treatment)	Week 6 (treatment)	Week 7 (treatment)
Lpc-37	6.98	7.34	7.53	7.48	7.59	7.57	7.50
Placebo	7.15	7.29	7.30	7.34	7.43	7.31	7.32

"Efficacy of the intake of Lpc-37 on the decrease of reported number of sleep disruptions over the course of the treatment measured with a daily online diary (mean of week summary).~Sleep disruptions were monitored through the wash-out phase (Week 1 and 2) and the subsequent treatment phase (Weeks 3-7). In the count version, the value can be 0 or a natural number for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for sleep disruptions (count) for the summed counts per participant and week." (NCT03494725)
Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total)

Intervention	sleep disruptions per participant & week (Mean)
	Week 1 (run-in)	Week 2 (run-in)	Week 3 (treatment)	Week 4 (treatment)	Week 5 (treatment)	Week 6 (treatment)	Week 7 (treatment)
Lpc-37	7.30	5.50	4.89	5.43	3.52	3.80	4.66
Placebo	6.09	5.49	5.11	4.30	3.53	4.02	5.83

"Efficacy of the intake of Lpc-37 on the decrease of sleep disruptions over the course of the treatment measured with a daily online diary (Proportion (yes/total)).~Sleep disruptions were monitored through the wash-out phase and the subsequent treatment phase for each week. In the binary version, the value is either Yes or No for each day and each participant.~Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant.~The proportion of participants with at least one sleep disruption by treatment group is given, treatment commenced after week 2. Data listed here reflect the proportion of participants who answered Yes (e.g. 0,477 * 44 = 20.99 participants answered with Yes in week 1 in the Lpc-37 group)." (NCT03494725)
Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Change of sAA in Response to the TSST

Intervention	Proportion of participants (yes/total) (Number)
	Week 1 (run-in)	Week 2 (run-in)	Week 3 (treatment)	Week 4 (treatment)	Week 5 (treatment)	Week 6 (treatment)	Week 7 (treatment)
Lpc-37	0.477	0.435	0.354	0.367	0.306	0.279	0.290
Placebo	0.465	0.426	0.418	0.310	0.292	0.331	0.389

Efficacy of the intake of Lpc-37 on reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo. (NCT03494725)
Timeframe: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake

Change of Salivary Cortisol in Response to the TSST

Intervention	U/ml (Mean)
	Pre-TSST -2min	Post-TSST +1min	Post-TSST +10min	Post-TSST +20min	Post-TSST +30min	Post-TSST +45min
Lpc-37	154.04	246.29	146.53	130.11	125.19	141.13
Placebo	161.67	270.55	158.85	141.49	138.48	148.15

Efficacy of the intake of Lpc-37 on reduction of the increase of salivary cortisol in response to the TSST compared to placebo. (NCT03494725)
Timeframe: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake

Change of Sleep Duration Over the Course of the Treatment

Intervention	nmol/L (Mean)
	Pre-TSST -2min	Post-TSST +1min	Post-TSST +10min	Post-TSST +20min	Post-TSST +30min	Post-TSST +45min
Lpc-37	4.79	6.96	9.48	9.89	8.04	6.21
Placebo	4.82	6.85	8.97	9.21	7.71	6.16

"Efficacy of the intake of Lpc-37 on the increase of sleep duration over the course of the treatment.~Sleep duration was monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for Sleep duration for the averaged ratings per participant and week" (NCT03494725)
Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Change of Sleep Related Recovery Scores Over the Course of the Treatment

Intervention	min (Mean)
	Week 1 (run-in)	Week 2 (run-in)	Week 3 (treatment)	Week 4 (treatment)	Week 5 (treatment)	Week 6 (treatment)	Week 7 (treatment)
Lpc-37	447.27	444.01	449.45	450.62	454.50	450.88	445.60
Placebo	447.45	448.13	456.90	459.81	457.26	450.16	459.66

"Efficacy of the intake of Lpc-37 on the increase of sleep related recovery scores over the course of the treatment.~Measured with a daily online diary. Sleep related recovery was rated by participants on an 11-point scale (0-10; not at all to very) and monitored throughout the wash-out phase (Week 1 and 2) and the subsequent treatment phase (weeks 3-7). High scores indicate a high recovery.~Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for sleep related recovery for the averaged ratings per participant and week." (NCT03494725)
Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Change of STAI-State Scores in Response to the TSST

Intervention	score (Mean)
	Week 1 (run-in)	Week 2 (run-in)	Week 3 (treatment)	Week 4 (treatment)	Week 5 (treatment)	Week 6 (treatment)	Week 7 (treatment)
Lpc-37	6.71	7.07	7.32	7.30	7.36	7.42	7.31
Placebo	6.91	7.15	7.27	7.29	7.36	7.10	7.28

"Efficacy of the intake of Lpc-37 on reduction of the increase of STAI-State scores in response to the TSST compared to placebo.~Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1=not at all to 4=very true. The score range is 20-80; Higher scores indicate more anxiety." (NCT03494725)
Timeframe: 10 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake

Change of Systolic BP in Response to the TSST

Intervention	score (Mean)
	Pre-TSST -10min	Post-TSST +1min
Lpc-37	36.09	42.38
Placebo	36.83	43.60

Efficacy of the intake of Lpc-37 on reduction of the increase of the systolic BP in response to the TSST compared to placebo. (NCT03494725)
Timeframe: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake

Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST)

Intervention	mmHg (Mean)
	Pre-TSST -3min	Post-TSST +1min
Lpc-37	115.11	127.47
Placebo	114.33	129.19

Efficacy was defined as a lower increase in HR in response to the TSST following intervention with Lpc-37, compared to placebo. (NCT03494725)
Timeframe: Continuous measurement starting 20 minutes before and ending 20 minutes after the TSST after 5 weeks of product intake. Mean values were calculated per group at seven-time windows before, during and after the TSST

Change of VAS Anxiety Scores in Response to the TSST

Intervention	bpm (Mean)
	Pre-TSST -20min	Pre-TSST -10min	Pre-TSST -3min	during TSST (Interview)	during TSST (Arithmetic)	Post-TSST +10min	Post-TSST +20min
Lpc-37	74.84	88.15	97.34	107.56	102.77	93.32	75.88
Placebo	74.34	86.69	97.62	105.66	100.81	90.81	74.97

"Efficacy of the intake of Lpc-37 on reduction of the increase of VAS anxiety scores in response to the TSST compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety." (NCT03494725)
Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Change of VAS Exhaustion Scores in Response to the TSST

Intervention	score (Mean)
	Pre-TSST -10min	Interview TSST (during)	Post-TSST +1min
Lpc-37	6.80	20.85	10.68
Placebo	8.50	22.47	11.74

"Efficacy of the intake of Lpc-37 on reduction of the increase of VAS exhaustion scores in response to the TSST compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion." (NCT03494725)
Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Change of VAS Insecurity Scores in Response to the TSST

Intervention	score (Mean)
	Pre-TSST -10min	Interview TSST (during)	Post-TSST +1min
Lpc-37	21.18	19.20	22.12
Placebo	19.79	21.30	25.68

"Efficacy of the intake of Lpc-37 on reduction of the increase of VAS insecurity scores in response to the TSST compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity." (NCT03494725)
Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Change of VAS Stress Perception Scores in Response to the TSST

"Efficacy of the intake of Lpc-37 on reduction of the increase of VAS Stress perception scores in response to the TSST compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress." (NCT03494725)
Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Changes in Pre and Post Treatment BAI Scores

"Efficacy of the intake of Lpc-37 on the reduction of Beck Anxiety Inventory (BAI) scores compared to placebo.~Measured with the german version of the Beck Anxiety Inventory as a self-rating scale designed to measure anxiety. It comprises 21 sentences describing feelings that can occur when being anxious. These sentences are rated on a four-point rating scale ranging from 0=not at all to 3=severely, considering the last 7 days. The score range is 0-63; Higher scores indicate higher anxiety." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment DASS Anxiety Scores

"Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) anxiety scores compared to placebo.~Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.~Items are answered on a four point rating scale ranging from 0 = not at all to 3 = very much. Scores of each scale are calculated by summing the scores for the relevant items.~The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The items are 2, 4, 7, 9, 15, 19, 20, 23, 25, 28, 30, 36, 40, 41 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment DASS Depression Scores

"Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) depression scores compared to placebo.~Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.~Items are answered on a four point rating scale ranging from 0 = not at all to 3 = very much. Scores of each scale are calculated by summing the scores for the relevant items.~The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The items are 3, 5, 10, 13, 16, 17, 21, 24, 26, 31, 34, 37, 38, 42 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment DASS Stress Scores

"Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) stress scores compared to placebo.~Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.~Items are answered on a four point rating scale ranging from 0 = not at all to 3 = very much. Scores of each scale are calculated by summing the scores for the relevant items.~The stress scale (items) is sensitive to levels of chronic non-specific arousal.The stress scale items are 1, 6, 8, 11, 12, 14, 18, 22, 27, 29, 32, 33, 35, 39 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment Diastolic BP

Efficacy of the intake of Lpc-37 on the reduction of diastolic BP. (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores

"Efficacy of the intake of Lpc-37 on the reduction of Perceived Stress Scale (PSS) scores compared to placebo.~Measured with the german version of the PSS as a psychological instrument for measuring stress perception. It assesses how unpredictable, uncontrollable and overloaded participants perceived their lives to have been within the last month. The PSS comprises 14 items that are answered on a five-point rating scale ranging from 0 = never to 4 = very often. Individual scores on the PSS can range from 0 to 56 with higher scores indicating higher perceived stress." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment STAI-state Scores

"Efficacy of the intake of Lpc-37 on the reduction of State-Trait-Anxiety-Inventory (STAI)-state scores compared to placebo.~Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1=not at all to 4=very true. The score range is 20-80; Higher scores indicate more anxiety." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment Systolic BP

Efficacy of the intake of Lpc-37 on the reduction of systolic blood pressure (BP). (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment VAS Anxiety Scores

"Efficacy of the intake of Lpc-37 on the reduction of VAS anxiety scores compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment VAS Exhaustion Scores

"Efficacy of the intake of Lpc-37 on the reduction of VAS exhaustion scores compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment VAS Insecurity Scores

"Efficacy of the intake of Lpc-37 on the reduction of VAS insecurity scores compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

Changes in Pre and Post Treatment VAS Stress Perception Scores

"Efficacy of the intake of Lpc-37 on the reduction of Visual Analog Scale (VAS) stress perception scores compared to placebo.~Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from not at all to highly. The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress." (NCT03494725)
Timeframe: Before and after 5 weeks of study product intake.

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures

"Efficacy of the intake of Lpc-37 on the reduction of the difference of cortisol at 8 pm values to the respective mean before and after 5 weeks of treatment~Efficacy for the CAR variable cortisol at 8 pm is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy." (NCT03494725)
Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures

"Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol Awakening Response (CAR) area under the curve with respect to the ground (AUCg) values to the respective mean before and after 5 weeks of treatment.~The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCg is the total area under the curve of all measurements (i.e., the intensity or magnitude of the response).~Efficacy for the CAR variables AUCg is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy." (NCT03494725)
Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures

"Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol at Awakening values to the respective mean before and after 5 weeks of treatment~Efficacy for the CAR variable cortisol at awakening is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy." (NCT03494725)
Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures

"Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR area under the curve with respect to the increase (AUCi) values to the respective mean before and after the treatment.~The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCi is calculated with reference to the baseline measurement and it ignores the distance from zero for all measurements and emphasizes the changes over time. Efficacy for the CAR variables AUCi is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy." (NCT03494725)
Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)

Intervention	number of participants (Number)
	Baseline (<25% quantile)	Baseline (25% - 75% quantile)	Baseline (>75% quantile)	End of Study (<25% quantile)	End of Study (25% - 75% quantile)	End of Study (>75% quantile)
Lpc-37	4	20	29	3	28	22
Placebo	6	23	26	7	18	30

Article	Year
Integrative hypothesis for Huntington's disease: a brief review of experimental evidence. Physiological research, 2007, Volume: 56, Issue:5 Topics: Animals; Calcium; Cell Death; Disease Models, Animal; Energy Metabolism; Excitatory Amino Acids; Hum	2007
Metabolism and neuropathologic significance of quinolinic acid and kynurenic acid. Biochemical Society transactions, 1993, Volume: 21, Issue:1 Topics: Animals; Disease Models, Animal; HIV Infections; HIV-1; Humans; Kynurenic Acid; Neuritis; Neuroimmun	1993

kynurenic acid and Disease Models, Animal

Research Excerpts

Research

Studies (114)

Authors

Clinical Trials (10)

Trial Overview

Trial Outcomes

Auditory Evoked Potentials - P50 Ratio (P50 S2/P50 S1 Amplitude) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Auditory Evoked Potentials in Gammas Oscillations (the Power Spectrum is Measured in Microvolts Squared) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Auditory Evoked Potentials in Latency (Msec) at BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF TREATMENT WITH GLYCINE

Brain GABA Metabolite Levels (GABA/Creatine Ratio: GABA/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Brain Glutamate Metabolite Levels (Glutamate/Creatine Ratio: Glu/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT

Brain Glycine/CR Ratio

Brief Psychiatric Rating Scale (BPRS) Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Positive and Negative Symptom Scores at Baseline and at 2, 4, and 6 Weeks During Intervention 1, Intervention 2, and During Open-label Glycine

Clinical Global Impression (CGI) Severity Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Clinical Global Impression (CGI) Therapeutic Effect Scores at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Depression Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Glycine Plasma Amino Acid Levels at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Mania Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period

Neurocognitive Function at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine

Positive and Negative Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks During Intervention 1 (Glycine or Placebo), Intervention 2 (Glycine or Placebo), and During Open-label Glycine

Auditory Evoked Potentials - P50 Ratio (P50 S2/S1) (Amplitude)

Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts)

Auditory Evoked Potentials in Gamma Oscillations (the Power Spectrum is Measured in Microvolts Squared)

Auditory Evoked Potentials in Latency (Msec)

Brain Glycine/CR Ratio

Brief Psychiatric Rating Scale (BPRS) Scores

Brief Psychiatric Rating Scale (BPRS) Scores

Clinical Global Impression (CGI) Severity Scores

Clinical Global Impression (CGI) Severity Scores

Depression Symptom Scores

Depression Symptom Scores

Mania Symptom Scores

Mania Symptom Scores

Neurocognitive Function

Positive and Negative Symptom Scores

Positive and Negative Symptom Scores

Change of Diastolic Blood Pressure (BP) in Response to the TSST

Change of Mood Scale Scores Over the Course of the Treatment

Change of Perceived Health Status Scores Over the Course of the Treatment

Change of Perceived Productivity Scores Over the Course of the Treatment

Change of Reported Number of Sleep Disruptions Over the Course of the Treatment

Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total)

Change of sAA in Response to the TSST

Change of Salivary Cortisol in Response to the TSST

Change of Sleep Duration Over the Course of the Treatment

Change of Sleep Related Recovery Scores Over the Course of the Treatment

Change of STAI-State Scores in Response to the TSST

Change of Systolic BP in Response to the TSST

Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST)

Change of VAS Anxiety Scores in Response to the TSST

Change of VAS Exhaustion Scores in Response to the TSST

Change of VAS Insecurity Scores in Response to the TSST

Change of VAS Stress Perception Scores in Response to the TSST

Changes in Pre and Post Treatment BAI Scores

Changes in Pre and Post Treatment DASS Anxiety Scores

Changes in Pre and Post Treatment DASS Depression Scores

Changes in Pre and Post Treatment DASS Stress Scores

Changes in Pre and Post Treatment Diastolic BP

Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores

Changes in Pre and Post Treatment STAI-state Scores

Changes in Pre and Post Treatment Systolic BP

Changes in Pre and Post Treatment VAS Anxiety Scores

Changes in Pre and Post Treatment VAS Exhaustion Scores

Changes in Pre and Post Treatment VAS Insecurity Scores

Changes in Pre and Post Treatment VAS Stress Perception Scores

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures

The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures

Reviews

Other Studies