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Protein-source tryptophan as an efficacious treatment for social anxiety disorder: A pilot study
Abstract
Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.
... The earlier phytochemical investigations on C.moschata suggested the presence of active compounds such as mono-unsaturated fatty acids (MUFA) like oleic acid (18:1), amino acids as tryptophan and glutamate, antioxidants as vitamin E, B-complex group of vitamins such as thiamine, riboflavin, pantothenic acid, vitamin B6 (pyridoxine) and folate, essential minerals like copper, manganese, potassium, calcium, iron, magnesium, zinc, and selenium [45]. ...
... In addition, Pumpkin seeds contain glutamate, which is required in the synthesis of gamma-amino butyric acid (GABA), an anti-stress neurochemical that helps reduce anxiety, irritability, and induce a state of analgesia [45]. ...
... This anti-inflammatory effect could be explained by Craig et al. [45] who reported that, the constituents tocopherol " vitamin E " ( recorded by high level in the RP-HPLC analysis of seeds in our study) and selenium may have protective functions towards the oxidative degradation of lipids, vitamins, hormones, and enzymes. ...
Family Cucurbitaceae is one of the most important families known for its edible fruits. It was, therefore, deemed of interest to carry out phytochemical and pharmacological studies on one of its species which is Cucurbita moschata Duchesne as one of widely used edible plants. Phytochemical screening of its seeds and fruits pulp revealed the presence of carbohydrates, saponins and steroids in considerable amounts in both of them. GLC analysis for lipoidal content of seeds revealed that lauric acid was the major saturated fatty acid while oleic and linoleic acids were the major unsaturated fatty acids. Vitamin A and E were estimated using RP-HPLC analysis. The highest vitamin E concentration was found in the petroleum ether extract (PEE) of the seeds while the highest vitamin A concentration was observed in 70% aqueous methanolic extract (AME) of seeds. Pharmacological investigation revealed that, AME of Cucurbita moschata Duchesne seeds and fruits pulp have favorable anti-inflammatory activities without notable ulcerogenic effect; that usually associated the anti-inflammatory drugs; based on their antioxidant properties. Moreover, there are remarkable analgesic and antidepressant activities recorded for AME of its seeds.
... A maioria dos estudos foi conduzida nos Estados Unidos (N = 13), com amostras variando de 7 a 619 sujeitos (mediana 84), com idades entre 18 e 75 anos (média de 30 a 35). Na maior parte dos estudos, foram utilizadas amostras clínicas 18,19,[27][28][29][30][31][32][33] ou amostras provenientes da população geral 23,[34][35][36][37][38][39][40][41] , e em quatro estudos 9,42-44 foram incluídas amostras mistas. Os demais estudos 20,45-50 não descreveram a procedência da amostra utilizada. ...
... Os aminoácidos avaliados, segundo a tabela 5, foram a d-cicloserina (N = 2) 29,35 e o triptofano (N = 1) 40 , sendo a primeira associada à terapia de exposição. O tratamento utilizando d-cicloserina + terapia de exposição apresentou resultados significativamente superiores ao do placebo quanto a melhora dos sintomas de ansiedade social, impressão clínica global e performance na atividade de falar em público. ...
... Os efeitos ansiolíticos do triptofano foram demonstrados em modelos animais e humanos há longa data, porém os estudos envolvendo o uso do triptofano no tratamento do TAS são mais recentes. No estudo conduzido por Hudson et al. 40 , os resultados evidenciados não foram muito satisfatórios. Em virtude da ausência de estudos anteriores com o mesmo objetivo, sugere-se a necessidade de maiores estudos para confirmação dos resultados encontrados. ...
BACKGROUND: Social anxiety disorder (SAD), despite its low detection rates and high level of associated comorbidities, is considered a treatable condition. Although the condition's response to several drug classes is well established, the algorithms for the treatment of SAD require regular updating. OBJECTIVE: To perform a systematic literature review on the efficacy of pharmacological treatments for SAD based on controlled trials published between 2005 and 2010. METHOD: Searches were performed in the electronic databases PsycInfo, Lilacs, and Medline using the search terms "social phobia or social anxiety and treatment". RESULTS: In accordance with the inclusion criteria adopted, 29 articles were included and analyzed. The following drugs, grouped according to class, proved efficient to treat SAD: a) SSRIs: escitalopram, fluvoxamine, citalopram, GR205171, and sertraline; b) SNRI: venlafaxine; c) MAOIs: phenelzine, moclobemide; d) amino acids: f-cycloserine; and (e) anticonvulsants: tiagabine. DISCUSSION: The use of SSRIs and SNRIs to treat SAD is well established and these are still considered the first-line treatment for the condition; however, evidence suggests the future potential of D-cycloserine and anticonvulsants, whose efficacy must be confirmed by further controlled trials. The action profiles of the different medications used to treat SAD at the neurobiological level, as well as that of associated treatments, need to be explored in greater depth.
... g/mol Hydrophobic substance [56] One of the diseases frequently appearing in the population is depression; in this regard, a useful method could be the monitoring of the Phe, Tyr, and Trypt AAs, respectively [38]. This psychological affliction can manifest itself through various symptoms, such as concentration problems, insomnia, and sadness [57,58]. The causes of its emergence can reside in various sources: biological, genetic, environmental, and social-psychological factors [59]. ...
... Special attention should be paid to people who suffer from PKU, which is an inherited disorder caused by excessive accumulation of Phe in the human [56] One of the diseases frequently appearing in the population is depression; in this regard, a useful method could be the monitoring of the Phe, Tyr, and Trypt AAs, respectively [38]. This psychological affliction can manifest itself through various symptoms, such as concentration problems, insomnia, and sadness [57,58]. The causes of its emergence can reside in various sources: biological, genetic, environmental, and social-psychological factors [59]. ...
Recently, the studies on developing sensors and biosensors—with an obvious interdisciplinary character—have drawn the attention of many researchers specializing in various fundamental, but also complex domains such as chemistry, biochemistry, physics, biophysics, biology, bio-pharma-medicine, and bioengineering. Along these lines, the present paper is structured into three parts, and is aimed at synthesizing the most relevant studies on the construction and functioning of versatile devices, of electrochemical sensors and biosensors, respectively. The first part presents examples of the most representative scientific research focusing on the role and the importance of the phenylalanine, tyrosine, and tryptophan amino acids, selected depending on their chemical structure and their impact on the central nervous system. The second part is dedicated to presenting and exemplifying conductor polymers and molecularly imprinted polymers used as sensitive materials in achieving electrochemical sensors and biosensors. The last part of the review analyzes the sensors and biosensors developed so far to detect amino acids with the aid of conductor polymers and molecularly imprinted polymers from the point of view of the performances obtained, with emphasis on the detection methods, on the electrochemical reactions that take place upon detection, and on the electroanalytical performances. The present study was carried out with a view to highlighting, for the benefit of specialists in medicine and pharmacy, the possibility of achieving and purchasing efficient devices that might be used in the quality control of medicines, as well as in studying and monitoring diseases associated with these amino acids.
... For these reasons, L-TRP was selected to be products or nutraceuticals containing TRP can be administered in the case of depression caused by the new coronavirus (SARS-CoV-2) [11]. For these reasons, L-TRP was selected to be detected as fast as possible from pharmaceutics by a new device: a compound which contributes to preventing neuropsychiatric disorders led by the lack of AA, such as depression [12], anxiety [13], insomnia [14], attention deficit hyperactivity disorder (ADHD) [15], the premenstrual syndrome [16] and Parkinson's disease [17]. The physicochemical properties of TRP are very important, being important features for accurate detection. ...
... Inventions 2021, 6, × FOR PEER REVIEW 2 of 13 products or nutraceuticals containing TRP can be administered in the case of depression caused by the new coronavirus (SARS-CoV-2) [11]. For these reasons, L-TRP was selected to be detected as fast as possible from pharmaceutics by a new device: a compound which contributes to preventing neuropsychiatric disorders led by the lack of AA, such as depression [12], anxiety [13], insomnia [14], attention deficit hyperactivity disorder (ADHD) [15], the premenstrual syndrome [16] and Parkinson's disease [17]. The physicochemical properties of TRP are very important, being important features for accurate detection. ...
This study describes the development of a new sensor with applicability in the determination and quantification of yjr essential amino acid (AA) L-tryptophan (L-TRP) from pharmaceutical products. The proposed sensor is based on a carbon screen-printed electrode (SPCE) modified with the conductor polymer polypyrrole (PPy) doped with potassium hexacyanoferrate (II) (FeCN). For the modification of the SPCE with the PPy doped with FeCN, the chronoamperometry (CA) method was used. For the study of the electrochemical behavior and the sensitive properties of the sensor when detecting L-TRP, the cyclic voltammetry (CV) method was used. This developed electrode has shown a high sensibility, a low detection limit (LOD) of up to 1.05 × 10−7 M, a quantification limit (LOQ) equal to 3.51 × 10−7 M and a wide linearity range between 3.3 × 10−7 M and 1.06 × 10−5 M. The analytical performances of the device were studied for the detection of AA L-TRP from pharmaceutical products, obtaining excellent results. The validation of the electroanalytical method was performed by using the standard method with good results.
... Diazepam binds at the alpha subunit and take a part of opening events of chloride ion which associated conductance and inhibition of the action potential (Braestrup & Squires, 1977). The earlier phytochemical investigations on Cucurbita moschata suggested the presence of active compounds such as mono-unsaturated fatty acids like oleic acid (18:1), amino acids as tryptophan and glutamate, anti-oxidants as vitamin E, B-complex group of vitamins such as thiamine, riboflavin, pantothenic acid, vitamin B6 (pyridoxine) and folate, essential minerals like copper, manganese, potassium, calcium, iron, magnesium, zinc, and selenium (Hudson, Hudson, & MacKenzie, 2007). ...
... Trigonelline, isolated from pumpkin paste (Yoshinari, Sato, & Igarashi, 2009), elevates the seizure threshold in rats, indicating that it may act as a sedative (Czok, 1974). In addition, Pumpkin seeds contain glutamate, which is required in the synthesis of gamma-amino butyric acid (GABA), an anti-stress neurochemical that helps reduce anxiety, irritability, and induce a state of analgesia (Hudson et al., 2007). Regarding the anxiolytic activity, our study proved the significant anxiolytic activity of the Cucurbita moschata flowers extract may be attributed to its reported tryptophan content (Woodward et al., 1993). ...
Using classical characters to express contemporary mood and
ideology is one of the main characteristics of Lord Alfred Tennyson’s poetry.
In many of his poems, it is seen that he has portrayed the mood of loneliness,
depression, and frustration drawing on classical characters from mythology.
This paper is an attempt to review two of the lovesick mythological
characters who are suicidally depressed in Tennyson’s poetry - “Oenone”
and “Tithonus”. The paper will briefly discuss the mythical background of
the two characters, their faults, etc. to denote a moral message to the
modern readers.
... A maioria dos estudos foi conduzida nos Estados Unidos (N = 13), com amostras variando de 7 a 619 sujeitos (mediana 84), com idades entre 18 e 75 anos (média de 30 a 35). Na maior parte dos estudos, foram utilizadas amostras clínicas 18,19,[27][28][29][30][31][32][33] ou amostras provenientes da população geral 23,[34][35][36][37][38][39][40][41] , e em quatro estudos 9,42-44 foram incluídas amostras mistas. Os demais estudos 20,45-50 não descreveram a procedência da amostra utilizada. ...
... Os aminoácidos avaliados, segundo a tabela 5, foram a d-cicloserina (N = 2) 29,35 e o triptofano (N = 1) 40 , sendo a primeira associada à terapia de exposição. O tratamento utilizando d-cicloserina + terapia de exposição apresentou resultados significativamente superiores ao do placebo quanto a melhora dos sintomas de ansiedade social, impressão clínica global e performance na atividade de falar em público. ...
Despite its low detection rates and high frequency of comorbid conditions, social anxiety disorder (SAD) is regarded as a treatable condition. This chapter describes the findings of controlled studies published between 2005 and 2011 concerning the treatment of SAD in adults. The results of studies with children and adolescent samples are also examined, although without time or methodological limits. According to their class, the drugs that proved efficient for the treatment of adult SAD include (a) Selective Serotonin Reuptake Inhibitors (SSRIs): escitalopram, fluvoxamine, citalopram, GR205171, and sertraline; (b) Selective Serotonin and Noradrenaline Reuptake Inhibitors (SSNRIs): venlafaxine; (c) Monoamine Oxidase Inhibitors (MAOIs): phenelzine and moclobemide; (d) Amino Acids: D-cycloserine; and (e) Anticonvulsants: tiagabine. Few studies enrolled children and adolescents, but the most promising treatments seem to be those using SSRIs. In general, the use of SSRIs and SSNRIs is well established and these continue to be the first-line treatments for SAD. D-cycloserine and anticonvulsants, however, have yielded encouraging results that should be replicated in future trials. The action of the different drugs at the neurobiological level and that of combined treatments remain to be further explored.
... Dietary interventions rich in Trp have also demonstrated good antidepressant/anxiolytic effects. Certain natural products such as deoiled gourd seeds (Trp: 22 mg/g protein) in combination with glucose can improve individual social anxiety and achieve clinical effects similar to those of medical-grade Trp (5). Compared with other food protein sources, whey protein or whey-derived protein contains a relatively high concentration of Trp, which is superior in relieving stress (6). ...
Objectives
Sunflower seeds provide tryptophan-rich proteins with the potential to protect against depression. Tryptophan is a precursor of serotonin and a substrate for the production of indole derivatives by gut microbiota. This study aimed to investigate the association between the depression-alleviating effects of deoiled and dechlorogenic sunflower seeds (DSFS) and regulation of gut microbiota.
Materials and Methods
Male C57BL/6J mice were fed a diet comprising a source of soy protein (normal and model control), DSFS or whey protein concentrate (positive control) for 7 weeks, and chronic stress-induced depression was induced.
Results
Feeding the DSFS diet prevented depression-like behaviors, intestinal barrier damage, elevated plasma corticosterone, and reduced hippocampal serotonin levels in mice. Meanwhile, Feeding the DSFS diet significantly altered the gut microbiota structure, characterized by elevated relative abundances of Ileibacterium valens , Ruminococcus flavefaciens , Clostridium scindens , and Olsenella massiliensis , which were inversely associated with depressive behaviors and markers of mucosal barrier damage. DSFS also altered the gut metabolite profile, prevented depression-induced gut L -tryptophan depletion, and upregulated its metabolite indoleacetaldehyde.
Conclusion
Feeding the DSFS diet prevented depression in mice by remodeling the gut microbiota and bacterial tryptophan metabolism.
... Of the studies assessing the effect of tryptophan depletion, 10 involved individuals with anxiety disorders; five reported no effect while five reported a worsening of anxiety symptoms. Of the studies administering a tryptophan supplement, two involved individuals with anxiety disorders [35,36]; both studies reported improvement. ...
Anxiety disorders are the most common group of mental disorders. There is mounting evidence demonstrating the importance of nutrition in the development and progression of mental disorders such as depression; however, less is known about the role of nutrition in anxiety disorders. This scoping review sought to systematically map the existing literature on anxiety disorders and nutrition in order to identify associations between dietary factors and anxiety symptoms or disorder prevalence as well as identify gaps and opportunities for further research. The review followed established methodological approaches for scoping reviews. Due to the large volume of results, an online program (Abstrackr) with artificial intelligence features was used. Studies reporting an association between a dietary constituent and anxiety symptoms or disorders were counted and presented in figures. A total of 55,914 unique results were identified. After a full-text review, 1541 articles met criteria for inclusion. Analysis revealed an association between less anxiety and more fruits and vegetables, omega-3 fatty acids, “healthy” dietary patterns, caloric restriction, breakfast consumption, ketogenic diet, broad-spectrum micronutrient supplementation, zinc, magnesium and selenium, probiotics, and a range of phytochemicals. Analysis revealed an association between higher levels of anxiety and high-fat diet, inadequate tryptophan and dietary protein, high intake of sugar and refined carbohydrates, and “unhealthy” dietary patterns. Results are limited by a large percentage of animal and observational studies. Only 10% of intervention studies involved participants with anxiety disorders, limiting the applicability of the findings. High quality intervention studies involving participants with anxiety disorders are warranted.
... On the other hand, D-Trp has been known as an important precursor of many indole-containing drugs and natural drugs [24]. Selective and sensitive discrimination and quantification of Trp enantiomers is of great importance in different areas of research, like pharmacology, physiology, biology, and food safety [25,26]. ...
A room temperature ultrasound-assisted method was applied to synthesize L- and D-cysteine-capped CdSe quantum dots (QDs). The QDs were characterized by XRD, FT-IR, and TEM. They have diameters of 5–7 nm and are shown to be viable probes for highly selective chiral recognition of tryptophan (Trp) enantiomers by fluorometry. The green fluorescence of the capped QDs (with excitation/emission maxima at 380/527 nm and 380/520 nm for L-Cys and D-Cys QDs, respectively) is differently quenched by D- and L-Trp in a high selective manner, with negligible interference by other species. The calibration plots and corresponding Stern-Volmer plots for both Trp enantiomers were investigated by two different approaches: In the first, each individual enantiomer was tested. In the second, each enantiomer was tested in the presence of a 100-folds excess of the other enantiomer. The detection limits for the recognition of L- and D-Trp are 4.2 and 4.7 nM, respectively, for the first approach. In the presence of the other enantiomer, the LODs are 4.4 and 4.8 nM. The linear range extends from 0.1 to 15 μM for both enantiomers.
Graphical abstractSchematic representation of tryptophan (Trp) chiral recognition process. The fluorescence (green, ON) of D- and L-Cys (cysteine)-capped CdSe QDs is quenched (black, OFF) through a preferential and selective interaction with L- and D-Trp, respectively.
... pepo) are further used to treat benign prostatic hyperplasia (29) and overactive bladder (30), especially in German speaking countries where pumpkin seed is officially, since a few decades, in the German Pharmacopeia (Granu Fink ® ) (31). Finally, because of the high tryptophan content, pumpkin seeds might ease depression, anxiety, nervous irritability and insomnia (6,32,33). Furthermore, they have shown to improve the iron status (34) and have blood-coagulatory effects (6,35). Their multiflorane-type triterpenes have melanogenesis inhibitory activity and thus may be potential skin whitening agents (36). ...
Food allergy to pumpkin seed is considered very rare, and only some isolated case reports have so far been published. We report here a case of food anaphylaxis to pumpkin seed in an eightyear- old boy, who tolerated all other edible seeds, peanut and tree nuts, as well as pulp of different kinds of pumpkins and other fruits of the Cucurbitaceae family. From this observation, a review of the botanical, historical, medicinal and allergenic aspects of pumpkin and its seeds is proposed. With the advent of diets rich in omega-3 and omega-6 polyunsaturated fatty acids, edible seeds like pumpkin seed have been incorporated in the modern diet. Their incremental use in the food-processing industry might contribute to an increase in food allergy to pumpkin seed in the future.
... This reduction will be processed by the multinetwork and will be reduced to the same three dimensional gradient. The hyperactivation and hypoactivation gradients can then be empirically compared, even though the gradient recall functions originate synthetically in the artificial cognitive system (Hudson et al. (2007)). ...
... In individuals with autism, further decreasing their brain serotonin by acute depletion of tryptophan exacerbates symptoms such as repetitive behaviors and facial recognition patterns revealing a continuing requirement for serotonin in modulating these behaviors (188,189). Furthermore, tryptophan supplementation has been shown to reduce social anxiety, which could be relevant to individuals with ASD (190,191). Together, these data provide strong and convincing evidence for a causal role of tryptophan-derived serotonin in regulating many social behaviors and support the proposal that supplemental interventions affecting the serotonin pathway may lead to improvements in a wide range of social behaviors in ASD. ...
Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.-Patrick, R. P., Ames, B. N. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.
... A recent pilot crossover RCT tested the acute effects of a tryptophan-rich protein (de-oiled gourd seed, 22 mg per g of protein) combined with glucose (Hudson et al. 2007). This preparation has a clinical effect similar to pharmaceutical-grade tryptophan. ...
IntroductionBackground and History of YohimbineSafety and Tolerability of Yohimbine HydrochlorideFear Conditioning and Extinction LearningYohimbine and Emotional LearningYohimbine in Animal Studies of ExtinctionYohimbine Augmentation of Exposure Treatment in HumansConclusion
References
... A recent pilot crossover RCT tested the acute effects of a tryptophan-rich protein (de-oiled gourd seed, 22 mg per g of protein) combined with glucose (Hudson et al. 2007). This preparation has a clinical effect similar to pharmaceutical-grade tryptophan. ...
IntroductionThe Potential of Dietary SupplementsAims of the Current ReviewNutritional SupplementsHerbal and Botanical SupplementsConclusion
References
... One small pilot study has evaluated deoiled pumpkin seed (a rich source of tryptophan) as a treatment for social phobia [51]. The study was a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between experimental sessions. ...
Anxiety disorders are prevalent mental disorders that are a significant burden on the community. There are effective treatments available, but many people do not seek treatment and there is a lack of professionals available to provide evidence-based treatment to all those with anxiety disorders. Recently, there has been increased attention on ways to cost effectively meet the demand for treatment with minimal cost to health services. Self-help efforts have been proposed to play a role, either as an initial minimal treatment in stepped-care models of treatment, or as strategies undertaken by an individual to prevent a full disorder developing. This review examines what is known from randomized controlled trials about the efficacy of self-help interventions for anxiety disorders.
... Natural products, containing large amounts of tryptophan, were used in some research studies. Deoiled gourd seed combined with glucose was found to improve social anxity (26), and alpha-lactalbumin enriched whey protein improved cognitive performance instress-vulnerable subjects (27). It is also possible to increase brain serotonin levels by providing tryptophan rich foods in the diet. ...
An evidence-based guide for laypeople on psychological, medical, complementary and lifestyle interventions for anxiety disorders.
We aimed to evaluate the antidepressant activity of sunflower seed protein (SFSP), a protein rich in tryptophan (TRP), in mice model and we explored a possible mechanism of action. Male C57BL/6J mice were subjected to chronic unpredictable mild stress (CUMS) and were supplemented with diet of SFSP as the main protein source. SFSP improved CUMS-induced depressive-like behavior, comparable to whey protein (WPC). This effect is related to an increase in serotonin, dopamine, norepinephrine, acetylcholine and brain-derived neurotrophic factor in SFSP-treated mice. These changes accompanied improvements in inflammatory abnormalities and oxidative stress. SFSP increased aromatic amino acid and the ratio of tryptophan to neutral amino acids. Furthermore, the antidepressant-like effect of SFSP was involved in lipid, nucleotide, and amino acid metabolisms. In summary, SFSP can be as effective as WPC for improving depression by increasing aromatic amino acids and monoamine neurotransmitters, improving oxidative stress and inflammation, and regulating abnormal metabolites to normal levels.
Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction.-Patrick, R. P., Ames, B. N. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar, schizophrenia, and impulsive behavior.
© FASEB.
The Endler Multidimensional Anxiety Scales (EMAS) are derived from an interactional model of personality that proposes that anxiety is a function of the interaction of person and situation variables. The EMAS distinguish between state and trait anxiety and assume that both are multidimensional constructs. The EMAS were administered to 2,009 students in a neutral situation. Three factor analyses were performed to clarify the empirical relation between state and trait anxiety and the variables within the 2 domains. Results support the distinction between state and trait anxiety. Factor analysis of the state items provided support for the separate dimensions of cognitive and autonomic state anxiety. Factor analysis of the trait items provided support for trait anxiety multidimensionality. Four congruent factors were associated with increases in state anxiety in 4 general situations: Social Evaluation, Physical Danger, Ambiguous, and Daily Routines.
We report on a series of three patients with an unusual syndrome of eosinophilia and myalgia associated with the oral ingestion of tryptophan that was recognized in New Mexico in October 1989. All three patients, who were women 37 to 44 years of age, had severe muscle pain, muscle weakness, mouth ulcers, and striking eosinophilia (more than 8 X 10(9) cells per liter). Other manifestations included fever, abdominal pain, dyspnea, skin rash, and elevated serum concentrations of aminotransferase and aldolase. The women had been taking tryptophan in doses of 1.2 to 2.4 g a day for three weeks to 2 1/2 years. The discontinuation of tryptophan and the initiation of glucocorticoid treatment resulted in improvement, but all three women were still symptomatic three to five months later. Tests for trichinosis and other parasites and for allergic and connective-tissues disorders were negative, and serum immunoglobulin concentrations and erythrocyte sedimentation rates were normal. A muscle biopsy in one patient and biopsies of the vagina, liver, and other abdominal organs in another revealed eosinophilic infiltration, as well as the extracellular deposition of eosinophil-granule major basic protein. All three patients had elevated serum and urinary levels of this protein and eosinophil-derived neurotoxin, indicative of eosinophil degranulation. The syndrome of eosinophilia and myalgia in association with the ingestion of tryptophan that was seen in these three patients is a newly recognized adverse effect of tryptophan ingestion. Our identification of this association in these patients led to the discovery of an epidemic of what is now called the eosinophilia-myalgia syndrome.
The glycemic index (GI) is a ranking of foods based on their glycemic effect compared with a standard food. It has been used to classify carbohydrate foods for various applications, including diabetes, sports, and appetite research. The purpose of these tables is to bring together all of the published data on the GIs of individual foods for the convenience of users. In total, there are almost 600 separate entries, including values for most common Western foods, many indigenous foods, and pure sugar solutions. The tables show the GI according to both the glucose and white bread (the original reference food) standard, the type and number of subjects tested, and the source of the data. For many foods there were two or more published values, so the mean +/- SEM was calculated and is shown together with the original data. These tables reduce unnecessary repetition in the testing of individual foods and facilitate wider application of the GI approach.
Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine.
Randomized, double-blind, placebo-controlled trial.
Thirty individuals with major depressive disorder.
Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo.
Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures.
During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness.
Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.
This chapter presents a study involving the cysteine and tryptophan amino acid analysis of ABRF92-AAA. The 1992 ABRF amino acid analysis test sample was bovine pancreatic chymotrypsin, and was chosen because of its relatively high Cys and Trp content. The Sigma preparation was dissolved in 0.1% trifluoroacetic acid, dialyzed against the same solvent to remove salts, the concentration determined by amino acid analysis and 56 μg (2.2 nmol) aliquots of chymotrypsin dried in small plastic tubes using a Savant Speed Vac. The sample was sent as an unknown to 231 ABRF facility directors for analysis using amino acid analysis methods of their choice. Each participating laboratory was asked to report pmol of amino acids found using their standard analysis method, and to quantify Cys and Trp using additional methods and analyses. The standard analysis results formed the major part of most facilities' composite data, and absolute yield of protein and average error was calculated from these data. In a few instances, the standard data set was patently inferior to that obtained by the Cys or Trp method, and the better data set was used to calculate yield of protein and average error.
This completely rewritten classic text features many new examples, insights, and topics including mediational, categorical, and multilevel models. Substantially reorganized, this edition provides a briefer, more streamlined examination of data analysis. Noted for its model comparison approach and unified framework based on the general linear model, the book provides readers with a greater understanding of a variety of statistical procedures. This consistent framework, including consistent vocabulary and notation, is used throughout to develop fewer but more powerful model building techniques. The authors show how all analysis of variance and multiple regression can be accomplished within this framework. The model comparison approach provides several benefits: It strengthens the intuitive understanding of the material, thereby increasing the ability to successfully analyze data in the future; It provides more control in the analysis of data so that readers can apply the techniques to a broader spectrum of questions; It reduces the number of statistical techniques that must be memorized; It teaches readers how to become data analysts instead of statisticians. The book opens with an overview of data analysis. All the necessary concepts for statistical inference used throughout the book are introduced in Chapters 2 through 4. The remainder of the book builds on these models. Chapters 5-7 focus on regression analysis, followed by analysis of variance (ANOVA), mediational analyses, nonindependent or correlated errors, including multilevel modeling, and outliers and error violations. The book is appreciated by all for its detailed treatment of ANOVA, multiple regression, nonindependent observations, interactive and nonlinear models of data, and its guidance for treating outliers and other problematic aspects of data analysis. Intended for advanced undergraduate or graduate courses on data analysis, statistics, and/or quantitative methods taught in psychology, education, or other behavioral and social science departments, this book also appeals to researchers who analyze data. A protected website featuring additional examples and problems with datasets, lecture notes, PowerPoint presentations, and class-tested exam questions is available to adopters. This material uses SAS but can easily be adapted to other programs. A working knowledge of basic algebra and any multiple regression program is assumed. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Abstract— The brain levels of each of the aromatic and branched-chain amino acids change 2 h after fasting rats begin to consume either a carbohydrate-fat diet or a similar diet containing 18% or 40% protein. Carbohydrate-fat ingestion elevates the concentrations of each of the aromatic amino acids in brain, while substantially depressing those of the branched-chain amino acids. The inclusion of protein in this diet suppresses the increases in brain aromatic amino acids and attenuates the decreases in the branched-chain amino acids. The changes in the brain level of each neutral amino acid following the ingestion of any of these diets correlate extremely well with the effects of the diet on the serum neutral amino acid pattern, specifically on the serum concentration ratio of each neutral amino acid to the sum of the other neutral amino acids. The diet-induced changes in the brain level of each of the amino acids also correlate surprisingly well with the calculated rate of brain influx for each amino acid.
Second derivative spectroscopy has been used to resolve the complex protein spectrum in the near-ultraviolet region and the contributions of the three aromatic chromophores have been evaluated.
A method for the direct quantitative determination of phenylalanine and tryptophan in proteins has been carried out. Phenylalanine determination has been carried out in the spectral region between 250 and 265 nm, where there are no significant contributions from other aromatic chromophores. Tryptophan determination has been performed in the 290–295-nm region and the experimental values have been corrected for the presence of tyrosine.
The results obtained on 10 highly purified proteins have been found in good agreement with those obtained from sequence analysis.
Plasma and brain levels of tryptophan and other large neutral amino acids, and brain levels of serotonin and 5-hydroxyindoleacetic acid (5 HIAA) were measured in groups of adult cynomolgus monkeys 1 hr after they ingested one of four doses of a tryptophan-carbohydrate mixture. The doses had been administered once daily for 13 weeks. Dose-related increments occurred in plasma tryptophan, the plasma ratio of tryptophan to the sum of other large neutral amino acids, and in brain tryptophan levels. In contrast, the plasma ratios and brain levels of the other neutral amino acids each declined. Serotonin and 5 HIAA levels increased significantly, and in a dose-related manner in the brainstem and striatum, but not in cortex or hypothalamus. The results suggest that while tryptophan administration can stimulate serotonin production in primate brain, the effect may be restricted to certain brain regions. They also suggest that the transport of the large neutral amino acids into brain occurs via a competitive mechanism similar to that for other mammals.
Sleep laboratory and outpatient studies of the hypnotic efficacy of the amino acid L-tryptophan are reviewed, with particular emphasis on evaluation of therapeutic effectiveness in the treatment of insomnia. In younger situational insomniacs, whose sleep problem consists solely of longer than usual sleep latencies, L-tryptophan is effective in reducing sleep onset time on the first night of administration in doses ranging from 1 to 15 g. In more chronic, well-established sleep-onset insomnia or in more severe insomnias characterized by both sleep onset and sleep maintenance problems, repeated administration of low doses of L-tryptophan over time may be required for therapeutic improvement. In these patients, hypnotic effects appear late in the treatment period or, as shown in some studies, even after discontinuation of treatment. The improvement in sleep measures post-treatment has given rise to use of a treatment regimen known as "interval therapy", in which L-tryptophan treatment alternates with an L-tryptophan-free interval until improvement occurs. The absence of side effects and lack of development of tolerance in long-term use are important factors in the decision to embark upon a trial of L-tryptophan treatment. In addition, L-tryptophan administration is not associated with impairment of visuomotor, cognitive, or memory performance, nor does it elevate threshold for arousal from sleep.
We compared the effects on the ratio of plasma tryptophan to large neutral amino acids (trp:LNAA) of two different carbohydrate meals (sucrose or starch, 120 g) and a contrasting meal of fat + protein given at breakfast to 10 healthy adults. Plasma glucose and insulin were also measured. The trp:LNAA ratio rose after both carbohydrate meals (p less than 0.001). Glucose and insulin peaks were higher after sucrose than starch, and trp:LNAA rose correspondingly higher (sucrose +34% and starch +20%, p less than 0.05). The ratio declined 45% after the fat + protein meal. At 180 min, absolute ratio values were twofold higher after carbohydrate (sucrose 0.133 and starch 0.127) than after fat + protein (0.057). Similar results were found with the same meals given in the evening. Our results suggest that high-carbohydrate meals have an influence on serotonin synthesis. We predict that carbohydrates with a high glycemic index would have a greater serotoninergic effect than carbohydrates with a low glycemic index.
L-tryptophan is an essential amino acid which is the metabolic precursor of serotonin. Because of the evidence that serotonin deficiency may be an aetiological factor in some sorts of affective disorder and that serotonin is important in the biochemistry of sleep, L-tryptophan has been suggested as a "rational" anti-depressant and as a "natural" hypnotic. This paper reviews the biochemistry and pharmacology of L-tryptophan as well as the literature of the clinical trials that have been conducted with it and suggests that, by itself, L-tryptophan may be useful in mild cases of depression accompanied by endogenous features and cases of bipolar disorder resistant to standard treatments. It also potentiates the monoamine oxidase inhibitors and possibly the serotonergic tricyclic drugs. L-tryptophan may improve the depressed mood of Parkinsonian patients and has a clinically useful hypnotic action. There is evidence it may be useful in organic mental disorders induced by levodopa. Dosage schedules, contraindications and complications are discussed.
When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.
Brain serotonin cocentrations at 1 p.m. were significantly elevated 1 hour after rats received a dose of L-tryptophan (12.5
milligrams per kilogram. intraperitoneally) smaller than one-twentieth of the normal daily dietary intake. Plasma and brain
tryptophan levels were elevated 10 to 60 minutes after the injection, but they never exceeded the concentrationis that occur
nocturnally in untreated aninmals as result of their normal 24-hour rhythms. These data suggest that physiological changes
in plasma tryptophan concentration influenice brain serotonin levels.
The determine the effect of different foods on the blood glucose, 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers. Blood glucose levels were measured over 2 h, and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose. The largest rises were seen with vegetables (70 +/- 5%), followed by breakfast cereals (65 +/- 5%), cereals and biscuits (60 +/- 3%), fruit (50 +/- 5%), dairy products (35 +/- 1%), and dried legumes (31 +/- 3%). A significant negative relationship was seen between fat (p less than 0.01) and protein (p less than 0.001) and postprandial glucose rise but not with fiber or sugar content.
Six healthy, nonobese, fasting subjects each received, on different days 0, 6, 12.5, 25, or 50 g of glucose (Glucola) in a total volume of 100 ml. Blood was taken at intervals and assayed for plasma levels of the branched-chain amino acids (valine, isoleucine and leucine); the other major large neutral amino acids (LNAA) (methionine, phenylalanine, tyrosine and tryptophan); and, in some cases, insulin and glucose. Insulin levels were significantly elevated 30 min after consumption of 12.5, 25, or 50 g of glucose, and were higher after the 50 g dose than after 12.5 g. Changes in plasma glucose concentrations were small and did not correlate with glucose dose. Mean percent reductions of LNAA tended to exhibit dose-dependence, most clearly observed after 120 min. In some subjects as little as 6 g of glucose transiently decreased LNAA concentrations. Branched-chain amino acids were most sensitive, decreasing by 35%-41% after 50 g of glucose. Plasma tryptophan concentrations fell only by 23%, hence the ratio of plasma tryptophan to other plasma LNAA (which affects brain serotonin synthesis) increased significantly.
A 10 week double blind study of 24 agoraphobics and 16 social phobics all on clomipramine compared the effect of adding tryptophan or placebo. Tryptophan did not potentiate the beneficial effect of clomipramine on phobic avoidance, phobic fears or the incidence of panic attacks. Neither was the presence of depression a factor of outcome.
This study tested the hypothesis that patterns of xenobiotic metabolism in patients with eosinophilia-myalgia syndrome (EMS) differed from healthy control subjects. We determined the genotypes of 27 EMS patients with EMS and 114 control subjects for the cytochrome P450 CYP2D6 polymorphism. The metabolic phenotypes of patients with EMS for S-mephenytoin hydroxylation (n = 17) and dapsone acetylation (n = 19) were determined and compared with 29 healthy control subjects. The incidence of the CYP2D6 poor metabolizer genotype (mutant/mutant) was 0.185 in patients with EMS and 0.061 in control subjects (Mantel-Haenszel, chi 2 = 7.213, p = 0.007). The mephenytoin S/R ratios were 0.39 +/- 0.23 in patients with EMS versus 0.18 +/- 0.13 in control subjects (p < or = 0.005). There was no difference in dapsone acetylation between the two groups. A pattern of xenobiotic metabolism may play a role in the pathogenesis of EMS, but the precise role that it plays remains unclear.
The structural characterization of a number of contaminants of L-tryptophan (Trp) associated with eosinophilia myalgia syndrome has been performed for the first time by the powerful structural elucidation technique of tandem mass spectrometry coupled with on-line HPLC (LC-ESI-MS/MS). The identity of the contaminants: peaks UV-5, 3-(phenylamino)alanine, (PAA); E 1,1'-ethylidenebis(tryptophan); 200, 2-(3-indolylmethyl)-L-tryptophan; (all identified as case related) and peaks 1, 3-carboxy-1,2,3,4-tetrahydro-beta-carboline; 2, 3-carboxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline; 100, 2-(2,3 dihydroxy-1-[3-indolyl]propyl)-L-tryptophan; and 300 and 400, diastereomers of 3-carboxy-1-[3-indolyl-methyl]-1,2,3,4-tetrahydro-beta-carboline, have been confirmed by this technique. By comparison of tandem MS (MS/MS) data from these compounds with the MS/MS data of several other impurities, we have structurally characterized peaks CC, KK and OO, as well as two previously unreported components labeled as peak P18 and peak P31. Peak P18 was unresolved from the large Trp peak and has been characterized as indole-3-ethylamine. Peak P31 was previously unresolved from peak 200, a case related compound and therefore its structure is of extreme importance. This compound has been tentatively identified as 2-(3-indolyl)-L-tryptophan.
Prospective studies have demonstrated that anxiety predicts sudden cardiac death, but the mechanism underlying this increased risk is unclear. This study examined whether anxiety is associated with reductions in vagal control of heart rate in healthy volunteers.
Trait anxiety (T-ANX) was measured, using the Spielberger State-Trait Anxiety Inventory (STAI), in 93 healthy men and women 25 to 44 years of age. Power spectral analysis was used to measure two indices of vagal control: baroreflex control of heart rate (BRC) and respiratory sinus arrhythmia (RSA).
High trait anxiety (T-ANX > 41, N = 23) was associated with significantly reduced vagal control of the heart, compared with low trait anxiety (T-ANX < 31, N = 22), as indicated by a 36% reduction in BRC (p< .001) and an 8% reduction in RSA (p<.05). Furthermore, T-ANX scores were negatively correlated with levels of BRC (r = -.30, p<.005), and levels of RSA (r = -.26, p <.05).
These findings provide evidence that trait anxiety is associated with reductions in vagal control of the heart. Additional studies are needed to examine whether low vagal control is involved in the increased risk of sudden cardiac death associated with anxiety.
Intact protein rich in tryptophan was not seen as an alternative to pharmaceutical grade tryptophan since protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier (BBB). Deoiled gourd seed (an extremely rich source of tryptophan-22 mg tryptophan/1 g protein) was combined with glucose, a carbohydrate that reduces serum levels of competing LNAAs which was then compared to pharmaceutical grade tryptophan with carbohydrate as well as carbohydrate alone.
Objective and subjective measures of sleep were employed to measure changes in sleep as part of a double blind placebo controlled study where subjects were randomly assigned to one of three conditions: (1) Protein source tryptophan (deoiled gourd seed) in combination with carbohydrate; (2) pharmaceutical grade tryptophan in combination with carbohydrate; (3) carbohydrate alone.
Out of 57 subjects 49 of those who began the study completed the three week protocol.
Protein source tryptophan with carbohydrate and pharmaceutical grade tryptophan, but not carbohydrate alone, resulted in significant improvement on subjective and objective measures of insomnia. Protein source tryptophan with carbohydrate alone proved effective in significantly reducing time awake during the night.
Protein source tryptophan is comparable to pharmaceutical grade tryptophan for the treatment of insomnia.
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