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This study aimed to investigate whether psychological distress, whole-grain consumption and tryptophan metabolism are associated with participants undergoing weight management intervention. Seventy-nine women and men (mean age 49·7 (sd 9·0) years; BMI 34·2(sd 2·5) kg/m2) participated in a 7-week weight-loss (WL) period and in a 24-week weight maintenance (WM) intervention period. Whole-grain consumption was measured using 4 d food diaries. Psychological distress was assessed with the General Health Questionnaire-12 (GHQ), and participants were divided into three GHQ groups based on the GHQ scores before WL. Tryptophan metabolites were determined from the participants’ fasting plasma using liquid chromatography-MS. GHQ scores were not associated with the whole-grain consumption. A positive association was observed between the whole-grain consumption and indole propionic acid (IPA) during the WM (P = 0·033). Serotonin levels were higher after the WL in the lowest GHQ tertile (P = 0·033), while the level at the end of the WM was higher compared with other timepoints in the highest GHQ tertile (P = 0·015 and P = 0·001). This difference between groups was not statistically significant. Furthermore, levels of several tryptophan metabolites changed within the groups during the study. Tryptophan metabolism changed during the study in the whole study group, independently from the level of psychological distress. The association between whole-grain consumption and IPA is possibly explained by the effects of dietary fibre on gut microbiota. This broadens the understanding of the pathways behind the health benefits associated with the intake of whole grains.

Type 2 diabetes and depression co-occur in a bidirectional manner. Curcumin supplements exhibit antidepressant effects that may mitigate depression by modulating neurotransmitters and reducing inflammatory and oxidative stress pathways. This study aimed to evaluate the efficacy of curcumin in improving depression severity in obese type 2 diabetes patients. The study employed a randomized, double-blind, placebo-controlled trial design with 227 participants. The primary end-point was depression severity assessed using the Patient Health Questionnaire-9. Biomarkers were measured at baseline and at 3-, 6-, 9-, and 12-month intervals. The biomarkers assessed were serotonin levels, pro-inflammatory cytokines (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha), antioxidant activities (total antioxidant status, glutathione peroxidase, and superoxide dismutase), and malondialdehyde. After 12 months, the curcumin group exhibited significantly improved depression severity (p = 0.000001). The curcumin group had higher levels of serotonin (p < 0.0001) but lower levels of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha (p < 0.001 for all) than the placebo group. Total antioxidant status, glutathione peroxidase activity, and superoxide dismutase activity were elevated in the curcumin group, whereas malondialdehyde levels were greater in the placebo group (p < 0.001 for all). These findings suggest curcumin may have antidepressant effects on obese type 2 diabetes patients.

Abstract Objective The aim of this study was to evaluate the effects of acupuncture treatment on serum levels of serotonin and substance P (SP) as well as on clinical parameters in patients with fibromyalgia (FM). Methods This is a randomized controlled clinical trial. Seventy-five women with FM were randomized into one of three kinds of acupuncture treatment: real acupuncture group (AcG), sham acupuncture group (ShG), and simulated acupuncture group (SiG). Treatments were applied semiweekly for four weeks. The serum levels of serotonin and SP were evaluated before and after the eight sessions. Patients were clinically assessed by visual analog scale (VAS), the number of tender points (NTP), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), and Nottingham Health Profile (NHP) at baseline, after the last treatment, and one and three months after completion of all treatments. Results Serum serotonin values increased significantly after treatment in AcG and ShG (P < 0.001 and P < 0.01, respectively). The increase in the AcG was also different from both of the other groups (P < 0.01). While SP levels decreased in the AcG, they increased in the SiG (P = 0.001). In the AcG, significant improvements were found in almost all clinical outcomes after treatment. These usually continued for three months. In the ShG, there were also significant changes on the NTP, VAS, FIQ, and BDI scores after treatment. Improvements on the NTP and FIQ scores lasted for three months. In the SiG, significant improvements were found only in the NTP, VAS, and BDI scores after treatment. Conclusions Acupuncture, rather than sham or placebo acupuncture, may lead to long-term improvements on clinical outcomes and pain neuromediator values. Changes in serum serotonin and SP levels may be a valuable explanation for acupuncture mechanisms in FM treatment.

Constipation is a functional disorder of the gastrointestinal system characterized by difficult bowel movements, infrequent defecation, reduced water content, and hard stools. This study aims to evaluate the preventive effects of fermented gold kiwis (FGK) on loperamide-induced constipation in rats and investigate its efficacy in improving constipation symptoms in human patients through a randomized clinical trial. In the animal study, FGK was administered orally at doses of 50, 125, and 250 mg/kg to constipated rats for two weeks, resulting in significant improvements in constipation parameters. FGK increased serum serotonin and acetylcholine levels and suppressed increases in serum dopamine concentration. FGK also upregulated mRNA expression of the serotonin-synthesizing receptors 5-HT3R and 5-HT4R and suppressed the expression of the dopamine 2-receptor (D2R) in the duodenum. Furthermore, FGK inhibited inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In the clinical trials, the improvement in constipation symptoms was evaluated using the gastrointestinal symptom rating scale (GSRS). Clinical trial participants reported significant improvements in constipation symptoms after receiving FGK. These findings suggest that FGK effectively relieves constipation in both animals and humans, indicating its potential as an effective dietary supplement.

Introduction Although there is clear evidence for the serotonergic regulation of descending control of pain in animals, little direct evidence exists in humans. The majority of our knowledge comes from the use of serotonin (5-HT)-modulating antidepressants as analgesics in the clinical management of chronic pain. Objectives Here, we have used an acute tryptophan depletion (ATD) to manipulate 5-HT function and examine its effects of ATD on heat pain threshold and tolerance, attentional manipulation of nociceptive processing and mood in human volunteers. Methods Fifteen healthy participants received both ATD and balanced amino acid (BAL) drinks on two separate sessions in a double-blind cross-over design. Pain threshold and tolerance were determined 4 h post-drink via a heat thermode. Additional attention, distraction and temperature discrimination paradigms were completed using a laser-induced heat pain stimulus. Mood was assessed prior and throughout each session. Results Our investigation reported that the ATD lowered plasma TRP levels by 65.05 ± 7.29% and significantly reduced pain threshold and tolerance in response to the heat thermode. There was a direct correlation between the reduction in total plasma TRP levels and reduction in thermode temperature. In contrast, ATD showed no effect on laser-induced pain nor significant impact of the distraction-induced analgesia on pain perception but did reduce performance of the painful temperature discrimination task. Importantly, all findings were independent of any effects of ATD on mood. Conclusion As far as we are aware, it is the first demonstration of 5-HT effects on pain perception which are not confounded by mood changes.

Objectives: Concurrent with global aging epidemics, cognitive decline has become an increasing public health concern. Dietary supplementation may offer neuroprotective benefits, and 5-hydroxytryptophan (5-HTP) has gained interest due to its role in serotonin synthesis, thereby regulating cognitive function and mood. However, there is limited evidence on its effect on cognitive function, especially among older Asian adults. Therefore, the study aimed to investigate the effects of 5-HTP supplementation on cognitive function and mood in Singaporean older adults. Methods: This was a single-blinded, 12-week randomized controlled trial, and 30 participants (66 ± 3 years) were randomly assigned to consume 100 mg of 5-HTP daily or not consume it. Cognitive function and mood were assessed via the Montreal Cognitive Assessment (MoCA), Geriatric Anxiety Inventory (GAI), and Geriatric Depression Scale (GDS). Cognitive function-related blood biomarkers, including amyloid beta (Aβ)40, Aβ42, gamma-aminobutyric acid, and serotonin, were also determined. Results: A significant time effect was observed in the MoCA score, which was mainly explained by a significant increase in the 5-HTP group (week 0 vs. week 12: 26.6 ± 1.4 a.u. vs. 27.6 ± 1.4 a.u., p < 0.05). Moreover, the 5-HTP group showed a significant increase in serum serotonin levels. Additionally, the GDS score improved in the 5-HTP group (week 0 vs. week 8: 1.2 ± 1.7 a.u. vs. 0.7 ± 1.2 a.u., p < 0.05). However, no effects on GAI and other biomarkers were observed. Conclusions: 5-HTP supplementation can enhance cognitive performance and reduce symptoms of depression in Singaporean older adults, potentially through serotonergic modulation. However, given the relatively small sample size (n = 30) and short-term (12-week) intervention, these findings should be interpreted cautiously, and further long-term studies with a larger sample size are warranted to confirm these preliminary results.

Objective: Obesity induces insulin resistance (IR), the key etiologic defect of type 2 diabetes mellitus (T2DM). Therefore, an incidence of obesity-induced diabetes is expected to decrease if obesity is controlled. Although Metformin is currently one of the main treatment options for T2DM in obese patients, resulting in an average of 5% weight loss, adequate weight control in all patients cannot be achieved with Metformin alone. Thus, additional therapies with a weight loss effect, such as acupuncture, may improve the effectiveness of Metformin. Subjective: We designed this randomized clinical trial (RCT) to compare the effects of Metformin monotherapy with that of Metformin and acupuncture combined therapy on weight loss and insulin sensitivity among overweight/obese T2DM patients, to understand whether acupuncture plus Metformin is a better approach than Metformin only on treating diabetes. To understand whether acupuncture can be an insulin sensitizer and, if so, its therapeutic mechanism. Results: Our results show that Metformin and acupuncture combined therapy significantly improves body weight, body mass index (BMI), fasting blood sugar (FBS), fasting insulin (FINS), homeostasis model assessment (HOMA) index, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, glucagon-like peptide-1 (GLP-1), resistin, serotonin, free fatty acids (FFAs), triglyceride (TG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and ceramides. Conclusions: Consequently, Metformin and acupuncture combined therapy is more effective than Metformin only, proving that acupuncture is an insulin sensitizer and is able to improve insulin sensitivity possibly by reducing body weight and inflammation, while improving lipid metabolism and adipokines. As a result, electro-acupuncture (EA) might be useful in controlling the ongoing epidemics in obesity and T2DM.

Purpose Acute exercise improves selective aspects of cognition such as executive functioning. Animal studies suggest that some effects are based on exercise-induced alterations in serotonin (5-HT) secretion. This study evaluates the impact of different aerobic exercise intensities on 5-HT serum levels as well as on executive functioning considering 5-HT as a potential mediator. Methods 121 young adults (23.8 ± 3.6 years) were examined in a randomized controlled trial including three exercise intervention (35 min) groups (low intensity, 45 % of the maximal heart rate (HR max ); moderate intensity, 65 % HR max ; high intensity, 85 % HR max ) and one control group. 5-HT levels and response inhibition (measured by a computerized Stroop test) were assessed pre- and post-intervention. Results There was a significant ( p  = 0.022) difference between groups regarding serum Δ5-HT levels. Post hoc tests indicated significant ( p  = 0.013) higher 5-HT serum levels for the high-intensity group compared to the control group while other groups did not differ significantly from each other. Serum Δ5-HT levels and exercise intensity were shown to be linearly associated through polynomial contrast analysis ( p  = 0.003). Furthermore, ANOVA revealed a significant difference for Stroop parameter reading ( p  = 0.030) and a tendency for reverse Stroop effect ( p  = 0.061). Correlation analysis showed that augmented 5-HT levels were associated with improved results in response inhibition. Conclusions This study indicates that intensive acute exercise increases serum 5-HT levels compared to a control group. These findings might be relevant for many other related research fields in exercise science, since 5-HT receptors are expressed on many different cell types including endothelia and immune cells.

Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n  = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n  = 17), and (3) mothers who were not depressed and untreated (ND, n  = 29). Fetal movement was assessed using a standardized ultrasound imaging and rating protocol. Maternal and cord blood platelet 5-HT levels were obtained from all participants. For the SRI + DEP group, maternal and infant plasma drug concentrations and an estimate of third-trimester maternal SRI drug exposure were obtained. As expected, substantially lower median platelet 5-HT levels were observed in the DEP + SRI group than in the non-exposed, combined ND and DEP groups. In non-exposed mothers and infants, platelet 5-HT levels were not affected by the presence of maternal depression. Lower maternal and infant platelet 5-HT levels were associated with more immature fetal movement quality. Although these data are limited by small sample size, the bioeffect index of in vivo platelet 5-HT transporter inhibition appears to provide a valuable approach for elucidating and possibly predicting the effects of gestational SRI exposure on fetal and perinatal neurobehavior.

Background The development of postpartum depression has been linked to fluctuations in the levels of neurotransmitters in the human body, such as 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (Norepinephrine, NE), and brain derived neurotrophic factor (BDNF). Research has indicated that the antidepressant effect of esketamine are mediated by monoamine transmitters and neurotrophic factors. Therefore, we postulate that intravenous administration of esketamine in patients with postpartum depression may alter the serum concentrations of these neurotransmitters. Methods Three hundred fifteen patients with postpartum depression were selected and divided into two groups based on randomized numerical expression: esketamine (E) group (0. 25 mg/kg esketamine) and control (C) group (a same volume of 0.9% saline), all the drugs were pumped for 40 min. After the end of drug pumping, all patients were continuously observed for 2 h. Changes in serum levels of 5-HT, DA, NE, BDNF were recorded before drug administration and on the 3rd day after drug administration. The scores of Edinburgh Postnatal Depression Scale (EPDS) were calculated before drug administration, and on the 3rd day and on the 30th day after drug administration. Dizziness, headache, nausea, vomiting, drowsiness, and feeling of detachment occurred were recorded within 2 h after drug administration. Results Before drug administration, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (0. 91 ± 0. 19 vs. 0. 98 ± 0. 21, P  = 0. 181), (2. 38 ± 0. 35 vs. 2. 32 ± 0. 32, P  = 0. 491), (3. 07 ± 0. 89 vs 3. 02 ± 0. 88, P  = 0. 828), (39. 79 ± 7. 78 vs 41. 34 ± 10. 03, P  = 0. 506). On the third day post-medication, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (1. 42 ± 0. 35 vs. 0. 96 ± 0. 24, P  < 0. 001), (3. 99 ± 0. 17 vs. 2. 41 ± 0. 28, P  < 0. 001),(5. 45 ± 0. 81 vs 3. 22 ± 0. 76, P  < 0. 001),(44. 36 ± 9. 98 vs 40. 69 ± 11. 75, P  = 0. 198). Before medication, the EPDS scores were (16. 15 ± 3. 02 vs 17. 85 ± 3. 89, P  = 0. 064). on the third day after medication, the Group E had significantly reduced scores (12. 98 ± 2. 39 vs 16. 73 ± 3. 52, P  < 0. 001). On the 30rd day after medication, EPDS scores between the two groups were (16. 34 ± 3. 43 vs 16. 91 ± 4. 02, p  = 0. 203). Within 2 h of medication, the rate of adverse events was similar between the two groups. Conclusions Small doses of esketamine can increase the serum concentration of 5-HT,DA,BDNF, and in the short term, decrease EPDS scores, and improve postpartum depressive symptoms. Trial registration Retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2300078343, 2023/12/05).