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Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: a randomized controlled trial.
Shin, JH, Kim, CS, Cha, L, Kim, S, Lee, S, Chae, S, Chun, WY, Shin, DM
The Journal of nutritional biochemistry. 2022;99:108854
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Disturbances in a person’s mood interrupts their personal well-being and the ability to participate in social interactions, leading to physical health problems such as chronic diseases. The role of diet as a mood regulator has received a great deal of interest. Certain dietary components have been shown to reduce anxiety and depression and improve quality of life. The aim of this study was to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. This study is a randomized controlled trial. Participants who met the criteria for eligibility were randomly assigned to one of three groups: (1) control group (CON, n=14); 2) 85% cocoa chocolate group (DC85, n=18); and 3) 70% cocoa chocolate group (DC70, n=16). Results show that daily intake of dark chocolate significantly reduced negative affect in the DC85, but not in the DC70. Furthermore, gut microbial diversity was significantly higher in DC85 than the CON. Authors conclude that dark chocolate has prebiotic effects by restructuring the diversity and composition of the gut microbiome, which may in turn improve mood via the gut-brain axis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- To highlight the potential benefits of high cocoa content dark chocolate in relation to mental states
- To promote more awareness of how dietary habits may impact emotional wellbeing
- To emphasise the importance of microbiota and the gut-brain axis regarding dietary habits.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
The authors highlight that dark chocolate has been continually identified for its effects on mood. However, there is a dearth of evidence concerning the emotional impact of daily consumption of dark chocolate. Hence, the impact of dark chocolate consumption on daily mood, focusing on the gut-brain axis, is being investigated in this study.
Objectives
- To evaluate the correlation between the effect on emotional state after consuming dark chocolate and the gut microbiota in healthy adults
- To identify alterations in the composition and diversity of the microorganisms in the gastrointestinal tract on account of dark chocolate intake.
Study Design
A randomised controlled trial was performed at Seoul National University from July to December 2017, This involved. consumption of two types of dark chocolate (70% and 85% cocoa content). Subjects in the treatment groups were blinded although investigators and the control cohort were unblinded.
Participants
117 individuals were screened. However, 48 healthy males and females aged 20-30 years were eligible at baseline.
Interventions
- Subjects (n=16): Consumed 30g/day of 70% cocoa chocolate for 3 weeks
- Participants (n=18): Consumed 30g/day of 85% cocoa chocolate for 3 weeks
- Participants (n=14): The control group consumed no chocolate for 3 weeks.
Main Health Outcomes Measured
- Mood states were quantified via the Positive and Negative Affect Schedule in tandem with Microbiota analysis pre- and post-experiment
- Body composition analysis and dietary assessment were also conducted pre- and post-intervention
- Faecal 16S rRNA sequencing analysis of bacterial genomic DNA was conducted for the cohort who consumed 85% cocoa chocolate and the control arm to evaluate the association between the mood-altering effects of dark chocolate and the gut microbiota
- Statistical tests were performed based on intention-to-treat analysis. The Chi-squared test, Kruskal-Wallis test, one-way ANOVA, unpaired t-test and Mann-Whitney U test were employed for inter-group analysis. Spearman's correlation analysis was used to assess the association between gut microbiota composition and mood scores and P<.05 was considered statistically significant.
Results
- Daily intake of dark chocolate substantially diminished negative emotional states in the cohort consuming 85% cocoa content, but not in the 70% cocoa treatment arm
- Gut microbial diversity was substantially greater in the 85% cacao cohort than the control group (P<.05)
- Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were decreased in the 85% cacao cohort than the control arm (P<.05).
- Furthermore, it was observed that changes in negative affect scores were inversely correlated with diversity and relative abundance of Blautia obeum (P<.05).
Conclusions
The observations suggest that consumption of dark chocolate with a higher cocoa content may induce prebiotic effects due to its capacity to restructure the diversity and composition of the gut microbiota. Furthermore, consuming dark chocolate with a higher cocoa might exert a positive effect on negative emotional states through the gut-brain axis.
Clinical practice applications:
- To inform practitioners of the benefits of 30g/day high (85%) cocoa chocolate consumption and its potential positive impact on mood through the gut-brain axis
- To educate clients regarding the potential benefits of daily high cocoa content chocolate consumption and its possible favourable effect on emotional states associated with gut microbiota.
Considerations for future research:
- More extensive research could investigate interventions of a longer period
- Further studies could evaluate if any difference exists between cocoa and cacao consumption and emotional states via the gut-brain axis, and the strength of any associations
- Interventions could investigate which strains of bacteria that high cocoa content dark chocolate may affect.
Abstract
Dark chocolate has long been recognized for its mood-altering properties; however, the evidence regarding the emotional effects of daily dark chocolate intake is limited. Therefore, we aimed to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. Two different dark chocolates (85% and 70% cocoa content) were tested in this study. In a randomized controlled trial, healthy adults (20-30 y) consumed either 30 g/d of 85% cocoa chocolate (DC85, n=18); 70% cocoa chocolate (DC70, n=16); or no chocolate (control group, CON; n=14); for 3 weeks. Mood states were measured using the Positive and Negative Affect Schedule (PANAS). Daily consumption of dark chocolate significantly reduced negative affect in DC85, but not in DC70. To assess the association between the mood-altering effects of dark chocolate and the gut microbiota, we performed fecal 16S rRNA sequencing analysis for the DC85 and CON groups. Gut microbial diversity was significantly higher in DC85 than CON (P<.05). Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were reduced in DC85 compared to CON (P<.05). Furthermore, we found that the observed changes in negative affect scores were negatively correlated with diversity and relative abundance of Blautia obeum (P<.05). These findings indicate that dark chocolate exerts prebiotic effects, as evidenced by its ability to restructure the diversity and abundance of intestinal bacteria; thus, it may improve negative emotional states via the gut-brain axis.
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Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants.
Chandika, P, Tennakoon, P, Kim, TH, Kim, SC, Je, JY, Kim, JI, Lee, B, Ryu, B, Kang, HW, Kim, HW, et al
Marine drugs. 2022;(10)
Abstract
Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.
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Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.
Kim, CS, Cha, L, Sim, M, Jung, S, Chun, WY, Baik, HW, Shin, DM
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;76(1):32-40
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Aging is characterized by progressive decline in biological functions of the organism. Diet is one of the critical lifestyle factors for physical and mental well-being throughout the life span, including later life. The aim of this study was to investigate the effects of probiotics consumption on intestinal and brain health in elders over the age of 65. This study is a randomised, double-blind, placebo-controlled, multicentre trial. All participants, study coordinators, and researchers were blinded throughout the entire study. Sixty-three participants were randomized, with 31 and 32 subjects in the placebo and probiotics group, respectively. Results demonstrate that probiotics have system-wide effects on the gut–brain axis in healthy community-dwelling older adults by promoting cognitive and mental health and changing the gut microbial composition. Authors conclude that their findings provide evidence that probiotics have health-promoting properties as part of a healthy diet in the general population of independently living older adults.
Abstract
Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults.
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Escherichia coli small molecule metabolism at the host-microorganism interface.
Gatsios, A, Kim, CS, Crawford, JM
Nature chemical biology. 2021;(10):1016-1026
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Abstract
Escherichia coli are a common component of the human microbiota, and isolates exhibit probiotic, commensal and pathogenic roles in the host. E. coli members often use diverse small molecule chemistry to regulate intrabacterial, intermicrobial and host-bacterial interactions. While E. coli are considered to be a well-studied model organism in biology, much of their chemical arsenal has only more recently been defined, and much remains to be explored. Here we describe chemical signaling systems in E. coli in the context of the broader field of metabolism at the host-bacteria interface and the role of this signaling in disease modulation.
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Effectiveness of liraglutide 3 mg for the treatment of obesity in a real-world setting without intensive lifestyle intervention.
Park, JH, Kim, JY, Choi, JH, Park, HS, Shin, HY, Lee, JM, Kim, JW, Ko, HJ, Chon, S, Kim, BK, et al
International journal of obesity (2005). 2021;(4):776-786
Abstract
OBJECTIVE We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea. METHODS People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values. RESULTS The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m2, and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: -2.94 kg and -1.08 kg/m2 at 2 months; -4.23 kg and -1.55 kg/m2 at 4 months, and -5.14 kg and -1.89 kg/m2 at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%). CONCLUSIONS In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.
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Effects of Pyrroloquinoline Quinone (PQQ) Supplementation on Aerobic Exercise Performance and Indices of Mitochondrial Biogenesis in Untrained Men.
Hwang, PS, Machek, SB, Cardaci, TD, Wilburn, DT, Kim, CS, Suezaki, ES, Willoughby, DS
Journal of the American College of Nutrition. 2020;39(6):547-556
Abstract
Objective: Pyrroloquinoline quinone (PQQ) is a novel supplement involved in processes such as mitochondrial biogenesis and cellular energy metabolism. Since endurance exercise and PQQ exhibit similar mechanisms for mitochondrial biogenesis, it is plausible that PQQ may have ergogenic value. Therefore, the purpose of this study was to examine the effects of a six-week endurance exercise training program on mitochondrial biogenesis and aerobic performance in non-endurance-trained males.Methods: Twenty-three males were randomized to consume 20 mg/day of PQQ or placebo (PLC). Both groups followed a supervised six-week endurance exercise training program. Body composition was assessed by dual-energy-x-ray-absorptiometry (DEXA). Aerobic exercise performance and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a biochemical marker for mitochondrial biogenesis, were assessed before and after the six-week endurance training/supplementation program.Results: There were no significant differences between groups in aerobic performance after endurance-training (p > 0.05). However, there were significant improvements in peak oxygen consumption (VO2peak) and total exercise test duration after endurance-training, irrespective of group (p < 0.05). The PQQ group had a significant increase in PGC-1α protein levels from baseline to post endurance training compared to PLC (p < 0.05). Furthermore, the PQQ group had higher PGC-1α protein levels after 6 weeks of endurance training compared to PLC (p < 0.05).Conclusions: Supplementation of PQQ does not appear to elicit any ergogenic effects regarding aerobic performance or body composition but appears to impact mitochondrial biogenesis by way of significant elevations in PGC-1α protein content.
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Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial.
Sim, M, Kim, CS, Shon, WJ, Lee, YK, Choi, EY, Shin, DM
Scientific reports. 2020;10(1):12130
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Oxidative stress indicates a state where excessive reactive oxygen species (ROS) overwhelm the biological antioxidant capacity, leading to disruption of ROS homeostasis and cellular damage. The aim of this study was to investigate the effects of hydrogen-rich water (HW) consumption in healthy adults through the extensive analyses of antioxidant capacity, peripheral blood mononuclear cell subsets and their transcriptome profile and to compare the effects of HW consumption with those of plain water (PW) consumption. This study is a 4-week, parallel-designed, randomized, double-blind, and placebo-controlled trial. The enrolled participants were randomly assigned to either the PW group (n=19) or the HW group (n=22). Results show that four-week consumption of HW induced a substantial increase in the antioxidant capacity and a decrease in oxidative stress of DNAs, although no significant results were found in the comparison of an intervention (HW) and the placebo (PW) group. Furthermore, the frequencies of apoptotic cells were significantly reduced by HW. Authors conclude that consumption of HW may promote biological antioxidant capacity for adults >30 years more than younger individuals.
Abstract
The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20-59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2'-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.
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Effects of Topical Prostaglandin Analog on Macular Thickness Following Cataract Surgery with Postoperative Topical Bromfenac Treatment.
Park, KS, Kim, KN, Kim, KM, Lee, HM, Lee, SB, Lee, NH, Kim, CS
Journal of clinical medicine. 2020;(9)
Abstract
PURPOSE To evaluate changes in macular thickness in patients continuing prostaglandin analog (PGA) treatment during the perioperative period involving bromfenac treatment. METHODS Patients with glaucoma who were using a topical PGA were randomly assigned to two groups in this randomized controlled trial: PGA continuing study group and PGA discontinued glaucoma control group. Patients without ocular diseases other than cataract were enrolled into the non-glaucomatous group. After the cataract surgery, the patients used bromfenac twice per day for 4 weeks. Optical coherence tomography was performed in all patients preoperatively and at 1 month postoperatively. Changes in macular thickness were compared among the three groups. RESULTS There were 32 eyes in the study group, 33 eyes in the glaucoma control group, and 58 eyes in the non-glaucomatous group. We found statistically significant postoperative changes in central macular thickness in all groups (4.30 ± 8.01 μm in the PGA continuing group, 9.20 ± 13.88 μm in the PGA discontinued group, and 7.06 ± 7.02 μm in the non-glaucomatous group, all p < 0.008), but no significant difference among the three groups (p = 0.161). Cystoid macular edema occurred in only one patient in the non-glaucomatous group (p = 0.568). CONCLUSIONS Continuous use of PGAs during the perioperative period was not significantly associated with increased macular thickness after uncomplicated cataract surgery. In the absence of other risk factors (e.g., capsular rupture, uveitis, or diabetic retinopathy), discontinuing PGAs for the prevention of macular edema after cataract surgery with postoperative bromfenac treatment is unnecessary in patients with glaucoma.
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Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with MYL2-R58Q-Mediated Apical Hypertrophic Cardiomyopathy Show Hypertrophy, Myofibrillar Disarray, and Calcium Perturbations.
Zhou, W, Bos, JM, Ye, D, Tester, DJ, Hrstka, S, Maleszewski, JJ, Ommen, SR, Nishimura, RA, Schaff, HV, Kim, CS, et al
Journal of cardiovascular translational research. 2019;(5):394-403
Abstract
Hypertrophic cardiomyopathy (HCM), characterized by unexplained left ventricular hypertrophy, is one of the most common heritable cardiovascular diseases. The myosin regulatory light chain (MYL2) mutation R58Q has been associated with severe cardiac hypertrophy and sudden cardiac death (SCD). Herein, we provide the first patient-specific, induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of MYL2-R58Q. The MYL2-R58Q iPSC-CMs were nearly 30% larger than control iPSC-CMs at day 60. The percentage of myofibrillar disarray and cells with irregular beating in MYL2-R58Q iPSC-CMs was significantly higher than that in control cells. MYL2-R58Q iPSC-CMs had significantly decreased peak ΔF/F0 of calcium transients and delayed decay time than controls. Additionally, the L-type Ca2+ channel (LTCC) (ICa,L) density at 0 mV was reduced significantly by 45.3%. Overall, the MYL2-R58Q iPSC-CMs recapitulated the HCM phenotype by exhibiting hypertrophy, myofibrillar disarray, increased irregular beating, decreased [Ca2+]i transients, and unexpectedly a nearly 50% reduction in LTCC peak current.
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Necrotizing Enterocolitis Pathophysiology: How Microbiome Data Alter Our Understanding.
Kim, CS, Claud, EC
Clinics in perinatology. 2019;(1):29-38
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Abstract
Necrotizing enterocolitis is a major cause of mortality and morbidity in the preterm infant population. The gut microbiome is of particular interest in research surrounding necrotizing enterocolitis, because variations in the intestinal microbiota seem to correlate with the risk of inflammation and disease. Recent advances in non-culture-based genomic sequencing have also allowed for more intricate analyses of the intestinal microbiome. Its evolution seems to be influenced by intrauterine and extrauterine factors, ranging from antenatal antibiotic exposure to type of enteral feeds. Ultimately, these alterations in the gut microbiome have the potential to result in devastating diseases like necrotizing enterocolitis.
