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Background: The causes of functional constipation (FC) in adults are unclear, but changes in the gut microbiome may play an important role. The present study aimed to assess the relationship between urinary metabolites of dopamine and serotonin and some dysbiosis indicators in patients with FC. The study included 40 healthy women and 40 women with FC aged 21–46 years. Methods: Urinary levels of homovanillic acid (HVA), 5-hydoxyindoleacetic acid (5-HIAA), p-hydroxyphenylacetic acid (PhAc), and 3-indoxyl sulfate, as final metabolites of dopamine, serotonin, and indole pathway, respectively, were determined using the LC-Ms/Ms method. However, hydrogen–methane and ammonia breath tests were performed. The GA-map Dysbiosis Test was used to identify and characterize the dysbiosis index (DI). Results: In patients with FC, the DI was significantly higher than in the control group: 4.05 ± 0.53 vs. 1.52 ± 0.81 points (p < 0.001), but the number of many types of bacteria varied among individuals. The levels of HVA were higher, while 5-HIAA levels were lower in patients. Moreover, the HVA/5-HIAA ratio had a positive correlation with DI as well as with the severity of symptoms. Conclusions: In patients with functional constipation, the balance in dopamine and serotonin secretion is disturbed, which is associated with changes in the gut microbiome.

Although migraine belongs to the main causes of disability worldwide, the mechanisms of its pathogenesis are poorly known. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective auxiliary markers to support clinical diagnosis. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. We chose the interictal phase as the episodic migraine patients were recruited from the outpatient clinic and had monthly migraine days as low as 1–2 in many cases. Migraine patients displayed lower urinary levels of 5-HIAA (p < 0.01) and KYNA (p < 0.05), but KYN and QA were enhanced, as compared with the controls (p < 0.05 and 0.001, respectively). Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios (p < 0.001 for all). Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score and monthly migraine and monthly headache days. There was a negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be further explored to assess its suitability as an easy-to-determine marker of migraine.

(1) Background: The elderly suffer from functional constipation (FC), whose causes are not fully known, but nutritional factors may play a role. The aim of the present study was to assess the effect of a low FODMAP diet supplemented with L-tryptophan (TRP) on its metabolism and symptoms of functional constipation in elderly patients. (2) Methods: This study included 40 people without abdominal complaints (Group I, controls) and 60 patients with FC, diagnosed according to the Rome IV Criteria (Group II). Two groups were randomly selected: Group IIA (n = 30) was qualified for administration of the low FODMAP diet, and the diet of patients of Group IIB (n = 30) was supplemented with 1000 mg TRP per day. The severity of abdominal symptoms was assessed with an abdominal pain index ranging from 1 to 7 points (S-score). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (3-IS) in urine were determined using the LC-MS/MS method. (3) Results: In Group II, 5-HIAA concentration in urine was lower, and KYN and 3-IS concentrations were higher than in the control group. A negative correlation was found between the S-score and urinary concentration of 5-HIAA (p < 0.001), and 3-IS concentration was positively correlated with the S-score. However, the correlation between the S-score and 3-IS concentration was negative (p < 0.01). After a dietary intervention, 5-HIAA concentration increased in both groups, and the severity of symptoms decreased, but the decrease was more pronounced in Group IIB. (4) Conclusion: A low FODMAP diet supplemented with L-tryptophan has beneficial effects in elderly patients suffering from functional constipation.

Abstract Background Optimal composition of intestinal bacteria is an essential condition for good health. Excessive growth of these bacteria can cause various ailments. The aim of this study was to assess the mental state and gastrointestinal complaints of patients with small intestinal bacterial overgrowth (SIBO) in relation to tryptophan metabolism and rifaximin treatment. Methods 120 subjects, aged 23–61 years, were enrolled in the study, and divided into 3 groups, 40 individuals each: healthy subjects (Controls), patients with SIBO and chronic diarrhea (SIBO-D), and with chronic constipation (SIBO-C). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The mental state of patients was assessed using the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D). L-tryptophan (TRP) and its metabolites: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), xanthurenic acid (XA) and quinolinic acid (QA) were measured in urine by liquid-chromatography-tandem mass spectrometry and related to creatinine level. Patients with SIBO were recommended to take rifaximin for 10 days at daily dose 1200 mg, and this cycle was repeated in subsequent two months. Results Mild and moderate anxiety, as well as mild depression were diagnosed in all SIBO patients. Changes in TRP metabolism were also observed in these patients. Specifically, an increase in the activity of the serotonin pathway of TRP metabolism in the group SIBO-D was observed. The SIBO-C patients showed an increase in the concentration of KYN, XA and QA. 5-HIAA/TRP and KYN/TRP ratios significantly decreased in group SIBO-D, and KYN and QA levels decreased in group SIBO-C after treatment with rifaximin. The levels of anxiety and depression decreased in both groups. Conclusion Rifaximin treatment of SIBO patients ameliorated their mood disorders and gastrointestinal aliments underlined by changes in tryptophan metabolism. Trial registration Retrospectively registered (if applicable).

Patients with a mixed type of irritable bowel syndrome (IBS-M) experience constipation and diarrhea, which alternate between weeks or months. The pathogenesis of this syndrome is still little understood. The aim of the study was mainly to evaluate the urinary excretion of selected tryptophan (TRP) metabolites during the constipation and diarrhea periods of this syndrome. In 36 patients with IBS-M and 36 healthy people, serum serotonin level was measured by ELISA and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN) and indican (3-IS) were determined using the LC-MS/MS method. The levels of all above metabolites were higher in the patient group, and increased significantly during the diarrheal period of IBS-M. In particular, the changes concerned 5-HIAA (3.67 ± 0.86 vs. 4.59 ± 0.95 mg/gCr, p < 0.001) and 3-IS (80.2 ± 17.4 vs. 93.7 ± 25.1 mg/g/Cr, p < 0.001). These changes coexisted with gut microbiome changes, assessed using hydrogen-methane and ammonia breath tests. In conclusion, the variability of TRP metabolism and the gut microbiome may cause the alternation of IBS-M symptoms.

Migraines display atypical age dependence, as the peak of their prevalence occurs between the ages of 20–40 years. With age, headache attacks occur less frequently and are characterized by a lower amplitude. However, both diagnosis and therapy of migraines in the elderly are challenging due to multiple comorbidities and polypharmacy. Dietary components and eating habits are migraine triggers; therefore, nutrition is a main target in migraine prevention. Several kinds of diets were proposed to prevent migraines, but none are commonly accepted due to inconsistent results obtained in different studies. The ketogenic diet is featured by very low-carbohydrate and high-fat contents. It may replace glucose with ketone bodies as the primary source of energy production. The ketogenic diet and the actions of ketone bodies are considered beneficial in several aspects of health, including migraine prevention, but studies on the ketogenic diet in migraines are not standardized and poorly evidenced. Apart from papers claiming beneficial effects of the ketogenic diet in migraines, several studies have reported that increased levels of ketone bodies may be associated with all-cause and incident heart failure mortality in older adults and are supported by research on mice showing that the ketogenic diets and diet supplementation with a human ketone body precursor may cause life span shortening. Therefore, despite reports showing a beneficial effect of the ketogenic diet in migraines, such a diet requires further studies, including clinical trials, to verify whether it should be recommended in older adults with migraines.

Age-related macular degeneration (AMD) is a largely incurable disease and an emerging problem in aging societies. It occurs in two forms, dry and wet (exudative, neovascular), which may cause legal blindness and sight loss. Currently, there is not any effective treatment for dry AMD. Meanwhile, repeated intravitreal injections with antibodies effective against vascular endothelial growth factor A (VEGFA) slow down wet AMD progression but are not free from complications. (-)-Epigallocatechin-3-gallate (EGCG) is an active compound of green tea, which exerts many beneficial effects in the retinal pigment epithelium and the neural retina. It has been reported to downregulate the VEGFA gene by suppressing its activators. The inhibition of mitogen-activated protein kinases 1 and 3 (MAPK1 and MAPK3) may lie behind the antiangiogenic action of EGCG mediated by VEGFA. EGCG exerts protective effects against UV-induced damage to retinal cells and improves dysfunctional autophagy. EGCG may also interact with the mechanistic target rapamycin (MTOR) and unc-51-like autophagy activating kinase (ULK1) to modulate the interplay between autophagy and apoptosis. Several other studies report beneficial effects of EGCG on the retina that may be related to wet AMD. Therefore, controlled clinical trials are needed to verify whether diet supplementation with EGCG or green tea consumption may improve the results of anti-VEGFA therapy in wet AMD.

(1) Background: A low-FODMAP diet is often recommended in the treatment of irritable bowel syndrome, but it does not improve abdominal symptoms in all patients, and an alternative diet is desirable. The purpose of this study was to evaluate the efficacy of a low-FODMAP diet with a concomitant reduction in tryptophan (TRP) intake in irritable bowel syndrome with diarrhea predominance (IBS-D) in relation to its metabolism via the serotonin and kynurenine pathways. (2) Methods: 40 healthy people (Group I, Controls) and 80 patients with IBS-D were included in the study. IBS-D patients were randomly divided into two groups of 40 each (Groups IIA and IIB). In Group IIA, the low-FODMAP diet was recommended, while in Group IIB, the same diet was recommended but with limited TRP intake for 8 weeks. The TRP intake was analyzed with the use of the nutritional calculator. Abdominal complaints were assessed using the Gastrointestinal Symptom Rating Scale (GSRS-IBS), and psychological status was simultaneously determined using two scales: the Hamilton Anxiety Scale (HAM-A) and the Hamilton Depression Scale (HAM-D). TRP and its metabolites: 5-hydoxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were measured in urine using liquid chromatography tandem mass spectrometry (LC-MS/MS). (3) Results: The consumption of TRP per mg/kg/b.w./24 h has decreased in Group IIA from 20.9 ± 2.39 to 17.45 ± 2.41 (16.5%) and in Group IIB from 21.3 ± 2.33 to 14.32 (34.4%). Significantly greater improvement was found after nutritional treatment in patients in Group IIB as compared to Group IIA (GSRS score: 38.1% vs. 49.8%; HAM-A: 38.7% vs. 49.9%; HAM-D: 13.8% vs. 35.0%; p < 0.01). Reducing TRP intake showed a negative correlation with the degree of improvement in the GSRS score. (4) Conclusions: Lowering the TRP content in a low-FODMAP diet may be useful in treating IBS-D.

(1) Background: L-tryptophan is a substrate for the synthesis of many biological compounds through the serotonin and kynurenine pathways. These compounds have a significant influence on gastrointestinal functions and mental processes. The aim of the study was to evaluate the urinary excretion of selected tryptophan metabolites in patients with constipation-predominant and diarrhoea-predominant irritable bowel syndrome (IBS-C and IBS-D, respectively), related to somatic and mental symptoms. (2) Methods: 120 people were included in the study and three groups were distinguished, with 40 individuals each, including healthy subjects (controls), patients with IBS-C and patients with IBS-D. The Gastrointestinal Symptoms Rating Scale (GSRS-IBS) was used to assess the severity of abdominal symptoms. The Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) were used to evaluate the mental state of patients. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), L-tryptophan and the following metabolites in urine, related to the creatinine level, were measured: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA). (3) Results: In both groups of patients with IBS, changes in tryptophan metabolism were found as compared to the control group. We observed an increase in the activity of the serotonin pathway and a positive correlation between the 5-HIAA level and the GSRS score (p < 0.01) and HAM-A score (p < 0.001) in IBS-D patients. The IBS-C group was characterized by a higher concentration of kynurenines (KYN, QA) in urine. Moreover, the QA (p < 0.001) and KYNA (p < 0.05) levels were correlated with the HAM-D score among IBS-C patients. (4) Conclusions: Various changes in the tryptophan metabolism pathway can determine the differences in the clinical picture of irritable bowel syndrome. These results should be included in the nutritional and pharmacological treatment of this syndrome.

Lymphocytic colitis (LC) is a gastrointestinal (GI) tract disease with poorly known pathogenesis, but some environmental and lifestyle factors, including certain dietary components, may play a role. Tryptophan is an essential amino acid, which plays important structural and functional roles as a component of many proteins. It is important in the development and maintenance of the body, in which it is metabolized in two main pathways: kynurenine (KYN) and serotonin. In this work, we explored the effect of reducing of TRP in the diet of patients with LC with mood disorders. We enrolled 40 LC patients who had a normal diet, 40 LC patients with the 8-week diet with TRP content reduced by 25% and 40 controls. All LC patients received budesonide at 9 mg per day, and the severity of their GI symptoms was evaluated by the Gastrointestinal Symptoms Rating Scale. Mood disorders were evaluated by the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA), in urine were determined. Budesonide improved the GI and mental states of LC patients, and the diet with reduced TRP content further amended these symptoms. Dietary intervention decreased the concentration of 5-HIAA by about 50% (3.4 vs. 6.3) and QA by about 45% (3.97 vs. 7.20). These changes were correlated with a significant improvement in the profitable action of budesonide on gastrointestinal and mental health of LC patients as they displayed significantly lower GSRS, HAM-A and HAM-B scores after than before the intervention—10.5 vs. 32, 11.0 vs. 21 and 12 vs. 18, respectively. In conclusion, a reduction in TRP intake in diet may improve GI and mental symptoms in LC patients treated with budesonide and these changes may be mediated by the products of TRP metabolism.

The elderly often suffer from sleep disorders and depression, which contribute to mood disorders. In our previous work, we showed that elderly individuals with mood disorders had a lower intake of TRP and recommended a TRP-based dietary intervention to improve the mental state of such individuals. In this work, we assessed the impact of a TRP-rich diet on the mental state of, and TRP metabolism in, elderly individuals with mood disorders. Forty elderly individuals with depression and sleep disorders and an equal number of elderly subjects without mood disorders were enrolled in this study. TRP intake was evaluated with the nutrition calculator. Patients with mood disorders had a lower TRP intake than their normal counterparts and received a TRP-rich diet with TRP content of 25 mg per kilogram of the body per day for 12 weeks. The mental state was assessed before and after this dietary intervention with the Hamilton Depression Rating Scale (HAM-D) and the Insomnia Severity Index (ISI). At those times, urinary levels of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), L-kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were determined by liquid chromatography with tandem mass spectrometry and related to creatinine level. After TRP-based dietary intervention, the score of ISI and HAM-D decreased by more than half. A correlation analysis reveals that TRP, 5-HIAA, and KYNA might have anti-depressive action, while KYN and QA—pro-depressive. The levels of TRP, 5-HIAA, and KYNA in urine of mood disorder patients increased, while the levels of KYN and QA decreased. In conclusion, dietary consumption of adequate amount of tryptophan has a beneficial effect on mental health of the elderly with mood disorders and improves metabolism of this amino acid. Therefore, a TRP-enriched diet may be considered as a component of the treatment of elderly individuals with mood disorders.

Targeting calcitonin gene-related peptide (CGRP) and its receptor by antibodies and antagonists was a breakthrough in migraine prevention and treatment. However, not all migraine patients respond to CGRP-based therapy and a fraction of those who respond complain of aliments mainly in the gastrointestinal tract. In addition, CGRP and migraine are associated with obesity and metabolic diseases, including diabetes. Therefore, CGRP may play an important role in the functioning of the gut-brain-microflora axis. CGRP secretion may be modulated by dietary compounds associated with the disruption of calcium signaling and upregulation of mitogen-activated kinase phosphatases 1 and 3. CGRP may display anorexigenic properties through induction of anorexigenic neuropeptides, such as cholecystokinin and/or inhibit orexigenic neuropeptides, such as neuropeptide Y and melanin-concentrating hormone CH, resulting in the suppression of food intake, functionally coupled to the activation of the hypothalamic 3′,5′-cyclic adenosine monophosphate. The anorexigenic action of CGRP observed in animal studies may reflect its general potential to control appetite/satiety or general food intake. Therefore, dietary nutrients may modulate CGRP, and CGRP may modulate their intake. Therefore, anti-CGRP therapy should consider this mutual dependence to increase the efficacy of the therapy and reduce its unwanted side effects. This narrative review presents information on molecular aspects of the interaction between dietary nutrients and CGRP and their reported and prospective use to improve anti-CGRP therapy in migraine.

(1). An essential component of any treatment for patients with irritable bowel syndrome (IBS) is an adequate diet. Currently, a low FODMAP diet is recommended as a first-line therapy, but it does not relieve abdominal discomfort in all patients, and alternative nutritional treatment is required. The purpose of this study was to evaluate the effect of a tryptophan-lowering diet (TRP) on abdominal and mental symptoms in patients with irritable bowel syndrome with predominant diarrhea (IBS-D). (2). The study included 40 patients with IBS-D, and 40 healthy subjects served as a baseline for IBS-D patients, after excluding comorbidities. The TRP intake was calculated using the nutritional calculator. The severity of abdominal symptoms was assessed using the gastrointestinal symptom rating scale (GSRS-IBS). Mental state was assessed using the Hamilton anxiety rating scale (HAM-A), the Hamilton depression rating scale (HAM-D), and the insomnia severity index (ISI). The serum levels of serotonin and melatonin and the urinary excretion of their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 6-sulfatoxymelatonin (aMT6) were determined by the ELISA method. The severity of symptoms and laboratory data were analyzed before and after a 12 week diet with tryptophan restricted to a daily dose 10 mg per kilogram body weight. (3). Compared to the control group, patients with IBS-D had a higher serum level of serotonin (198.2 ± 38.1 vs. 142.3 ± 36.4 ng/mL; p < 0.001) but a similar level of melatonin (8.6 ± 1.1 vs. 9.4 ± 3.0 pg/mL; p > 0.05). The urinary excretion of 5-HIAA was also higher in patients with IBS-D patients (7.7 ± 1.5 vs. 6.0 ± 1.7 mg/24 h; p < 0.001). After nutritional treatment, both the serum serotonin level and the urinary 5-HIAA excretion significantly decreased (p < 0.001). The severity of the abdominal symptoms and anxiety also decreased, while the HAM-D score and the ISI score remained unchanged (4). Lowering the dietary intake of tryptophan may reduce abdominal complaints and does not alter the mental state of IBS-D patients.

Introduction Helicobacter pylori infection induces clinical symptoms in 15–20% of subjects, and the reason for this variation is still not clear. The aim of the present study is to evaluate the expression of tryptophan hydroxylase (TpH-1) in gastric mucosa of patients with symptomatic and asymptomatic H. pylori infection in relation to the intensity of bacterial colonization and severity of dyspeptic symptoms. Material and methods Ninety subjects (aged 35–49 years) were enrolled in the study and separated into 3 groups of 30 subjects each. Group I – healthy volunteers without H. pylori infection, group II – subjects with asymptomatic H. pylori infection, group III – H. pylori-infected patients with dyspeptic symptoms, mainly fasting and nocturnal epigastric pain. To diagnose H. pylori infection the urea breath test (UBT-13C) and histological analysis were performed. The level of mRNA expression of tryptophan hydroxylase (TpH-1) was estimated in gastric mucosa with RT-PCR. Results The expression of this enzyme in antral mucosa was 2.69 ±0.97 in group I, 2.28 ±0.69 in group II (p > 0.05) and 4.40 ±1.64 in group III (p 0.05) and 3.40 ±1.51 (p < 0.001), respectively. In group III a positive correlation was found between intensity of H. pylori colonization and TpH-1 expression as well as between TpH-1 expression and severity of dyspeptic symptoms. Conclusions Increased expression of TpH-1 in gastric mucosa plays a role in pathogenesis of chronic dyspepsia.

The causes of depression are diverse and are still not fully understood. Recently, an increasing role is attributed to nutritional and inflammatory factors. The aim of this study was to evaluate selected metabolites of the tryptophan kynurenine pathway in depressive patients with small intestinal bacterial overgrowth (SIBO). The study involved 40 healthy people (controls) and 40 patients with predominant small intestinal bacterial overgrowth (SIBO-D). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The severity of symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS–IBS) and the Hamilton Depression Rating Scale (HAM-D). The concentration of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) in urine was determined using an LC–MS/MS method, before and after cyclic treatment with an antibiotic drug, rifaximin, for three months. The number of intraepithelial lymphocytes (IELs) in the duodenum and small intestinal mucosa, fecal calprotectin (FC) and serum level of C-reactive protein (CRP) were also determined. In patients with SIBO, a higher level of KYN and QA were found as compared to the control group. These two groups also differed in KYN/TRP (higher in SIBO) and KYNA/KYN ratios (lower in SIBO). A positive correlation was found between HAM-D and the number of IELs and the level of FC. Treatment with rifaximin improves the kynurenic pathway, as well as abdominal and mental complaints. Therefore, small intestinal bacterial overgrowth can be a cause of abdominal symptoms, but also mental disorders.

Dietary vitamin D3 has attracted wide interest as a natural compound for breast cancer prevention and therapy, supported by in vitro and animal studies. The exact mechanism of such action of vitamin D3 is unknown and may include several independent or partly dependent pathways. The active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D, calcitriol), binds to the vitamin D receptor (VDR) and induces its translocation to the nucleus, where it transactivates a myriad of genes. Vitamin D3 is involved in the maintenance of a normal epigenetic profile whose disturbance may contribute to breast cancer. In general, the protective effect of vitamin D3 against breast cancer is underlined by inhibition of proliferation and migration, stimulation of differentiation and apoptosis, and inhibition of epithelial/mesenchymal transition in breast cells. Vitamin D3 may also inhibit the transformation of normal mammary progenitors into breast cancer stem cells that initiate and sustain the growth of breast tumors. As long noncoding RNAs (lncRNAs) play an important role in breast cancer pathogenesis, and the specific mechanisms underlying this role are poorly understood, we provided several arguments that vitamin D3/VDR may induce protective effects in breast cancer through modulation of lncRNAs that are important for breast cancer pathogenesis. The main lncRNAs candidates to mediate the protective effect of vitamin D3 in breast cancer are lncBCAS1-4_1, AFAP1 antisense RNA 1 (AFAP1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein-coding RNA 511 (LINC00511), LINC00346, small nucleolar RNA host gene 6 (SNHG6), and SNHG16, but there is a rationale to explore several other lncRNAs.

The mechanisms of migraine pathogenesis are not completely clear, but 31P-nuclear magnetic resonance studies revealed brain energy deficit in migraineurs. As glycolysis is the main process of energy production in the brain, mitochondria may play an important role in migraine pathogenesis. Nutrition is an important aspect of migraine pathogenesis, as many migraineurs report food-related products as migraine triggers. Apart from approved anti-migraine drugs, many vitamins and supplements are considered in migraine prevention and therapy, but without strong supportive evidence. In this review, we summarize and update information about nutrients that may be important for mitochondrial functions, energy production, oxidative stress, and that are related to migraine. Additionally, we present a brief overview of caffeine and alcohol, as they are often reported to have ambiguous effects in migraineurs. The nutrients that can be considered to supplement the diet to prevent and/or ameliorate migraine are riboflavin, thiamine, magnesium ions, niacin, carnitine, coenzyme Q10, melatonin, lipoic acid, pyridoxine, folate, and cobalamin. They can supplement a normal, healthy diet, which should be adjusted to individual needs determined mainly by the physiological constitution of an organism. The intake of caffeine and alcohol should be fine-tuned to the history of their use, as withdrawal of these agents in regular users may become a migraine trigger.

Migraine, the leading cause of disability in the population aged below 50, is associated with functional gastrointestinal (GI) disorders (FGIDs) such as functional nausea, cyclic vomiting syndrome, and irritable bowel syndrome (IBS). Conversely, changes in intestinal GI transit may cause diarrhea or constipation and are a component of the autonomic symptoms associated with pre- and post-dorsal phases of migraine attack. These mutual relationships provoke a question on a common trigger in migraine and FGIDs. The kynurenine (l-kyn) pathway (KP) is the major route for l-tryptophan (l-Trp) metabolism and transforms l-Trp into several neuroactive compounds. Changes in KP were reported in both migraine and FGIDs. Migraine was largely untreatable, but several drugs approved lately by the FDA, including monoclonal antibodies for calcitonin gene-related peptide (CGRP) and its receptor, create a hope for a breakthrough in migraine treatment. Derivatives of l-kyn were efficient in pain relief with a mechanism including CGRP inhibition. KP products are important ligands to the aryl hydrocarbon receptor (AhR), whose activation is implicated in the pathogenesis of GI and migraine. Toll-like receptors (TLRs) may play a role in migraine and IBS pathogeneses, and KP metabolites detected downstream of TLR activation may be an IBS marker. The TLR4 signaling was observed in initiating and maintaining migraine-like behavior through myeloid differentiation primary response gene 88 (MyD88) in the mouse. The aim of this review is to justify the view that KP modulation may provide common triggers for migraine and FGIDs with the involvement of TLR, AhR, and MyD88 activation.

The continuous increase in life expectancy results in a steady increase of cancer risk, which consequently increases the population of older adults with cancer. Older adults have their age-related nutritional needs and often suffer from comorbidities that may affect cancer therapy. They frequently are malnourished and present advanced-stage cancer. Therefore, this group of patients requires a special multidisciplinary approach to optimize their therapy and increase quality of life impaired by aging, cancer, and the side effects of therapy. Evaluation strategies, taking advantage of comprehensive geriatric assessment tools, including the comprehensive geriatric assessment (CGA), can help individualize treatment. As epigenetics, an emerging element of the regulation of gene expression, is involved in both aging and cancer and the epigenetic profile can be modulated by the diet, it seems to be a candidate to assist with planning a nutritional intervention in elderly populations with cancer. In this review, we present problems associated with the diet and nutrition in the elderly undergoing active cancer therapy and provide some information on epigenetic aspects of aging and cancer transformation. Nutritional interventions modulating the epigenetic profile, including caloric restriction and basal diet with modifications (elimination diet, supplementary diet) are discussed as the ways to improve the efficacy of cancer therapy and maintain the quality of life of older adults with cancer.

The role of serotonin in the pathogenesis of depression is well-documented, while the involvement of other tryptophan (TRP) metabolites generated in the kynurenine pathway is less known. The aim of this study was to assess the intake and metabolism of TRP in elderly patients with mood disorders. Ninety subjects in three groups, 30 subjects each, were enrolled in this study: controls (healthy young adults, group I) and elderly individuals without (group II) or with (group III) symptoms of mild and moderate depression, as assessed by the Hamilton Depression Rating Scale (HAM-D) and further referred to as mood disorders. The average TRP intake was evaluated with the nutrition calculator. Urinary levels of TRP, 5-hydroxyindoleacetic acid (5-HIAA), L-kynurenine (KYN), kynurenic acid (KynA), xanthurenic acid (XA), and quinolinic acid (QA) were determined by liquid chromatography with tandem mass spectrometry and related to creatinine level. The average daily intake of TRP was significantly lower in group III than the remaining two groups, but group III was also characterized by higher urinary levels of KYN, KynA, XA, and QA as compared with younger adult individuals and elderly patients without mood disorders. Therefore, mild and moderate depression in the elderly may be associated with a lower intake of TRP and changes in its kynurenine metabolic pathway, which suggests a potential dietary TRP-based intervention in this group of patients.

Zinc supplementation is reported to slow down the progression of age-related macular degeneration (AMD), but there is no general consensus on the beneficiary effect on zinc in AMD. As zinc can stimulate autophagy that is declined in AMD, it is rational to assume that it can slow down its progression. As melanosomes are the main reservoir of zinc in the retina, zinc may decrease the number of lipofuscin granules that are substrates for autophagy. The triad zinc–autophagy–AMD could explain some controversies associated with population studies on zinc supplementation in AMD as the effect of zinc on AMD may be modulated by genetic background. This aspect was not determined in many studies regarding zinc in AMD. Zinc deficiency induces several events associated with AMD pathogenesis, including increased oxidative stress, lipid peroxidation and the resulting lipofuscinogenesis. The latter requires autophagy, which is impaired. This is a vicious cycle-like reaction that may contribute to AMD progression. Promising results with zinc deficiency and supplementation in AMD patients and animal models, as well as emerging evidence of the importance of autophagy in AMD, are the rationale for future research on the role of autophagy in the role of zinc supplementation in AMD.

Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.

Estrogen deficiency is considered to be the main cause of increased appetite and increased weight in postmenopausal women. In this period, reduced secretion of melatonin (MEL) was also observed. The aim of the study was to evaluate the secretion of melatonin, 17-β estradiol and follicle-stimulating hormone (FSH) in relation to body mass index (BMI) in pre- and postmenopausal women. The study included 90 women divided into three equal groups: group I (control)—women without menstrual disorders, group II—postmenopausal women without change in appetite and body weight, group III—postmenopausal women experiencing increased appetite and weight gain. In each patient, serum melatonin, 17-β-estradiol, FSH and urine a 6-sulfatoxymelatonin (aMT6s) were determined. Compared to the control group, the level of melatonin and estradiol was statistically lower. The FSH level was higher than in the groups of postmenopausal women. No significant correlation was found in all groups between the level of melatonin and the levels of estradiol and FSH. A negative correlation was found between aMT6s excretion and BMI, and a positive correlation between the level of FSH and BMI, mainly in overweight women. The obtained results indicate a significant effect of melatonin deficiency on the process of weight gain in postmenopausal women and justify its use in treatment of these disorders.

Aim of the study : We evaluated the effect of melatonin supplementation on the nutritional status of postmenopausal women. Material and methods: The study included 56 women (51-65 years) and 25 healthy women (27-36 years). The emotional state was assessed using Hamilton Depression Rating Scale (HAM-D), the quality of sleep using Insomnia Severity Index (ISI). Body mass index (BMI) and waist-hip ratio (WHR) were also calculated. The patients were divided into 3 groups: group I (control) – 25 women with normal body weight, group II – 26 postmenopausal women with normal body weight, group III – 30 postmenopausal women with high body weight. In women from group II and III, routine laboratory tests, levels of thyroid-stimulating hormone (TSH), 17-estradiol, prolactin, follicle-stimulating hormone (FSH) and the concentration of 6-hydroxymelatonin sulphate (6-HMS) in day/night urine fractions were determined. On the day of the examination, women remained on a liquid diet (1800 kcal). Next, a balanced diet of 1500 kcal and 5 mg of melatonin administration were recommended. The follow-up examinations were performed after 4, 8, 12, 16, 20 and 24 weeks. Results : The patients from groups II and III showed similar mild levels of anxiety and depression and a significant degree of sleep disorders. In group III, lower urinary 6-HMS excretion was observed at night. In both groups a negative correlation was found between urinary 6-HMS excretion and the degree of sleep disorders. After 24 weeks, a statistically significant improvement of quality of sleep was obtained. A negative correlation was detected between urinary 6-HMS excretion and BMI. Conclusion : Melatonin supplementation contributed to body weight reduction.

Two clinical forms of functional dyspepsia (FD) are listed in the Rome III criteria: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), differing in the recurrence of ailments depending on the diet. Continuous EPS (CEPS) is observed in some EPS patients, also at night, but its cause is still unknown. We showed previously that melatonin (MEL) homeostasis may be associated with FD. In the present work we evaluated selected components of melatonin homeostasis in patients with CEPS. The study included 30 patients with CEPS, 21 women and nine men, aged 21–49 years and 30 control subjects (EPS excluded); organic and mental diseases, as well as Helicobacter pylori infection, were excluded in both groups. The average severity of abdominal pain in the last three months was estimated in a 10-point scale (Visual Analog Scale). The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), the main components of MEL homeostasis, were determined in gastric mucosa with real time PCR. The fasting serum level of MEL (at 09:00 a.m.) and circadian urine excretion of 6-sulfatoxymelatonin (6-HMS) were determined with ELISA. AANAT expression in antral mucosa of control subjects was 1.76 ± 0.41, in the gastric body 1.35 ± 0.38, and in the dyspeptic group 1.42 ± 0.38 (p < 0.05) and 0.92 ± 0.55 (p < 0.05), respectively. HIOMT expression in the control was 2.05 ± 0.70 in the antrum and 1.57 ± 0.69 in the body and in the CEPS group, it was: 1.51 ± 0.57 (p < 0.05) and 0.74 ± 0.31 (p < 0.001), respectively. MEL concentration (pg/mL) was 9.41 ± 3.09 in the control group and 5.62 ± 1.34 (p < 0.01) in the CEPS group. Urinary 6-HMS excretion (μg/24 h) was 11.40 ± 4.46 in the controls and 7.68 ± 2.88 (p < 0.05) in the CEPS. Moreover, a negative correlation was found between the tested parameters and severity of epigastric pain. These results indicate that patients with CEPS may display low level of AANAT and HIOMT expression in gastric mucosa, resulting in decreased MEL synthesis.

Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine-N-acetyltransferase (AANAT), and N-acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis. The study included 30 healthy subjects (group C), 30 patients with severe ulcerative colitis (group UC), and 30 patients with lymphocytic colitis (group LC). The diagnosis was based on endoscopic, histological, and laboratory examinations. Biopsy specimens were collected from right, transverse, and left parts of the colon. The levels of mRNA expression, TPH1, AANAT, and ASMT were estimated in the colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by the photometric method. The expression of TPH1, AANAT, and ASMT in colonic mucosa in UC and LC patients was significantly higher than in healthy subjects. Significant differences were found in the urinary aMT6s excretion: group C—13.4 ± 4.8 µg/24 h, group UC—7.8 ± 2.6 µg/24 h (p < 0.01), group LC—19.2 ± 6.1 µg/24 h (p < 0.01). Moreover, a negative correlation was found between fecal calprotectin and MT6s—in patients with UC − r = −0.888 and with LC − r = −0.658. These results indicate that patients with UC and those with LC may display high levels of melatonin-synthesizing enzymes in their colonic mucosa, which could possibly be related to increased melatonin synthesis as an adaptive antioxidant activity.

Cirrhotic patients exhibit disturbed melatonin homeostasis, which may lead to sleep disturbances, but an influence on the hepatic encephalopathy has not been elucidated. Aim. In the present study, the association of melatonin levels in serum and ascitic fluid and ammonia concentration related to the intensity of hepatic encephalopathy (HE) was investigated. Material and Methods. The study included 90 alcoholic patients with hepatic encephalopathy and 30 healthy volunteers (C). Patients were divided in three groups according to 0–4 West-Haven Score: HE1 (n=28), HE2 (n=30), and HE3 (n=32). Melatonin was measured by radioimmune assay. Results. In fasting patients with hepatic encephalopathy we noted higher melatonin serum levels [pg/mL] than in healthy subjects groups: C—11.3 ± 3.9, HE1 – 34.3 ± 12.2 (P