Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes-secondary analysis of a randomized placebo-controlled parallel intervention trial.

BACKGROUND: Aronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes. RESULTS: Forty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile. CONCLUSION: In linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions.

Immunomodulatory Effects of Aronia Juice Polyphenols-Results of a Randomized Placebo-Controlled Human Intervention Study and Cell Culture Experiments.

Dietary polyphenols, which are present in Aronia melanocarpa, have been associated with various beneficial effects on human health including antioxidant, antiviral, and anti-inflammatory activities. We aimed to investigate the immunomodulatory effects of aronia juice polyphenols in a randomized placebo-controlled human intervention study and cell culture experiments. A total of 40 females were asked to consume either 200 mL of aronia juice or a placebo drink for six weeks and were investigated again after a washout period of another six weeks. We observed that only half of the participants tolerated the aronia juice well (Vt) and the other half reported complaints (Vc). The placebo (P) was generally tolerated with one exception (p = 0.003). Plasma polyphenol levels increased significantly in Vt after the intervention (p = 0.024) but did neither in P nor in Vc. Regulatory T cell (Treg) frequencies remained constant in Vt and P during the intervention, whereas Tregs decreased in Vc (p = 0.018). In cell culture, inhibiting effects of ferulic acid (p = 0.0005) and catechin (p = 0.0393) on the differentiation of Tregs were observed as well as reduced activation of CD4-T cells in ferulic acid (p = 0.0072) and aronia juice (p = 0.0163) treated cells. Interestingly, a CD4+CD25-FoxP3+ cell population emerged in vitro in response to aronia juice, but not when testing individual polyphenols. In conclusion, our data strengthen possible individual hormetic effects, the importance of the food matrix for bioactivity, and the need for further investigations on possible impacts of specific physiological features such as the gut microbiota in the context of personalized nutrition.

Oxidative Status in Adult Anorexia Nervosa Patients and Healthy Controls-Results from a Cross-Sectional Pilot Study.

Oxidative stress describes an imbalance of reactive oxygen species (ROS) and antioxidative defence systems. Recently, the consequences of oxidative stress have become a central field of research and have been linked to the genesis of multiple psychiatric diseases. Some oxidative stress parameters have not been investigated before in anorexia nervosa (AN) patients, including the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) and polyphenols (PPm). In this cross-sectional pilot study, we evaluated these markers together with total peroxides (TOC), antioxidative capacity (TAC), endogenous peroxidase activity (EPA) and antibodies against oxidized LDL (oLAb) in serum samples of 20 patients with AN compared to 20 healthy controls. The antioxidative capacity was significantly decreased in AN patients, with a mean TAC of 1.57 mmol/L (SD: ±0.62); t (34) = -2.181, p = 0.036) compared to HC (mean = 1.91 mmol/L (SD: ±0.56), while the other investigated parameters were not significantly different between the two groups. In AN patients, TAC correlated with EPA (rsp = -0.630, p = 0.009). This study suggests that there is an antioxidative deficiency in AN patients. In this respect, there is a demand for interventional studies to determine whether antioxidants can be used as add-on therapy in the treatment of AN.

'An Apple a Day'?: Psychiatrists, Psychologists and Psychotherapists Report Poor Literacy for Nutritional Medicine: International Survey Spanning 52 Countries.

Nutritional interventions have beneficial effects on certain psychiatric disorder symptomatology and common physical health comorbidities. However, studies evaluating nutritional literacy in mental health professionals (MHP) are scarce. This study aimed to assess the across 52 countries. Surveys were distributed via colleagues and professional societies. Data were collected regarding self-reported general nutrition knowledge, nutrition education, learning opportunities, and the tendency to recommend food supplements or prescribe specific diets in clinical practice. In total, 1056 subjects participated in the study: 354 psychiatrists, 511 psychologists, 44 psychotherapists, and 147 MHPs in-training. All participants believed the diet quality of individuals with mental disorders was poorer compared to the general population (p < 0.001). The majority of the psychiatrists (74.2%) and psychologists (66.3%) reported having no training in nutrition. Nevertheless, many of them used nutrition approaches, with 58.6% recommending supplements and 43.8% recommending specific diet strategies to their patients. Only 0.8% of participants rated their education regarding nutrition as 'very good.' Almost all (92.9%) stated they would like to expand their knowledge regarding 'Nutritional Psychiatry.' There is an urgent need to integrate nutrition education into MHP training, ideally in collaboration with nutrition experts to achieve best practice care.

Interleukin-6 Gene Expression Changes after a 4-Week Intake of a Multispecies Probiotic in Major Depressive Disorder-Preliminary Results of the PROVIT Study.

Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.

Body modification in Germany: prevalence, gender differences and attitude towards cosmetic surgery.

BACKGROUND: The most popular body modifications are tattoos and piercings and their prevalence has increased in recent years. The current study gathered statistics regarding tattoing, piercing and body-hair removal, differentiated by gender and attitude towards cosmetic surgery. METHODS: The study was based on 2512 individuals and was performed as a population-based survey with the assistance of a demographic consulting company. In addition to sociodemographic questions, specific issues concerning body modification were asked. RESULTS: Men get tattoos more frequently while women more often choose piercings and body hair removal. Women are catching up in the tattoo department and one can no longer observe age differentiations among the younger age groups. Instead there is a decrease in piercings among men. Body hair removal is widespread above all women. People with body modifications tend to be more open-minded about cosmetic surgery. CONCLUSIONS: Tattoos and piercings continue to be the most popular body modification among young adults. The number engaged in tattooing is rising while piercings are still popular among women. Individuals being engaged in body modification are prone to consider cosmetic surgery procedures.

Psychobiology of Attachment and Trauma-Some General Remarks From a Clinical Perspective.

Attachment refers to a psychobiological principle that is deeply rooted in evolutionary development; it is thought to contribute a major advantage in the survival of the social group. Within individual development it indicates a primary motivational system that guides the initial transactions between mother and baby and furthermore mediates affective attunement and regulation. Psychosocial learning, in close interaction with genetics and epigenetics, also develops a decisive foundation for further brain development of the infant. Finally, the attachment pattern established forms an enduring, relational context for later affective, cognitive, and social development of the child. As an unconsciously active matrix for future personal relationships it has a particular impact on the comprehensive psychological functions of empathy and mentalization. Early adverse and traumatic experiences or major emotional neglect may lead to different levels of security versus insecurity or disorientation-disorganization of the attachment pattern that corresponds to characteristic features of neurobiological regulation.

[Anxiety disorders - clinical and neurobiological aspects].

Anxiety disorders are considered among the most common psychiatric disorders in general population. They may be characterized by prominent subjective suffering, frequent chronic courses of illness, increased rates of comorbid other psychiatric disorders and somatic diseases, a distressing amount of psychosocial disabilities, in all, a challenging high burden of disease. Anxiety disorders have principally to be conceptualized within a multifactorial biopsychosocial model. Various psychological and psychosocial approaches have contributed to a multi-layered understanding of various major predisposing, eliciting, and maintaining factors in the course of illness. Modern neurobiological research has significantly broadened and deepened the aetiopathogenetic complexity of anxiety disorders. The main focus of this short review is on neural fear- and anxiety circuits, neurotransmitter systems, neuroendocrine and inflammatory stress systems, genetics and epigenetics that characterize the general basis of fear and anxiety regulation and their dysregulation in anxiety disorders. Anxiety disorders may be effectively treated both by psychotherapeutic and pharmacological approaches. Basic principles and general guidelines in the treatment of anxiety disorders are being presented.

The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature.

INTRODUCTION: Individuals suffering from psychiatric disorders experience high levels of illness burden and a significantly reduced quality of life. Despite targeted psychopharmacological strategies and complementary psychotherapeutic procedures only moderate effects are obtained, and the risk of relapse is high in many patients. Worldwide, psychiatric diseases such as depression are continuously increasing, challenging the personal life of the affected as well as their families, but also whole societies by increasing disability, early retirement and hospitalization. According to current scientific knowledge psychiatric disorders are caused by a multifactorial pathogenesis, including genetics, inflammation and neurotransmitter imbalance; furthermore, also lifestyle-associated factors gain rising importance. In line with this, there is growing evidence that the gut microbiota and nutrition have an impact on the onset and course of psychiatric disorders. AIM: This narrative review highlights the important role of nutrition in psychiatric care and underlines the significance of nutritional advice in the multifactorial, biopsychosocial treatment of patients. It focuses on current dietary interventions such as the Mediterranean diet, dietary supplements and modifications of the gut microbiota with pre-, pro- and postbiotics. RESULTS: Recent studies support the connection between the quality of diet, gut microbiota and mental health through regulation of metabolic functions, anti-inflammatory and antiapoptotic properties and the support of neurogenesis. Dietary coaching to improve mental health seems to be an additional, cost-effective, practical, nonpharmacological intervention for individuals with psychiatric disorders. CONCLUSION: The use of nutritional interventions in psychiatry equips therapists with a promising tool for both the prevention and treatment of psychiatric disorders. Besides pharmacological therapy, psychotherapy and physical activity, nutritional interventions are an important pillar in the multifactorial, biopsychosocial treatment of psychiatric disease and could be used as a potential therapeutic target.

Differences Between Psoriasis Patients and Skin-healthy Controls Concerning Appraisal of Touching, Shame and Disgust.

Psoriasis is a chronic skin disease associated with high levels of psychological distress and considerable life impact. Feelings of shame and stigmatization can lead to avoidance of social activity and intimacy. In this study, the questionnaire TSD-Q was used to evaluate pleasure in touching oneself and in a partnership, parental touching during childhood and (skin-related) shame and disgust. Skin-related disgust and shame were significantly higher in psoriatic patients than in healthy controls. Moreover, psoriasis-patients scored significantly lower than skin-healthy controls concerning appraisal of self-touching and parental touching. In contrast, psoriasis-patients scored higher concerning appraisal of touching in a partnership. Due to the fact that low self-esteem might enhance the negative evaluation of touch and the feelings of shame and disgust, psychological interventions should be integrated in the treatment of psoriasis.

Psychological factors associated with acute and chronic central serous chorioretinopathy.

BACKGROUND: Central serous chorioretinopathy (CSC) has been associated with several psychological factors. But previous psychological data are limited and mainly restricted to male patients and small sample size. In this study we investigated psychosomatic complaints, personality factors, life events, and stress coping in acute and chronic recurrent CSC patients. METHODS: Ninety-five patients (71 men, 24 women) with either acute or chronic CSC were evaluated regarding critical life events before diagnosis, psychosomatic complaints, personality traits and coping style. The characteristics of CSC patients were compared with a control group comprising 75 patients (46 men, 29 women) suffering from acute or chronic ophthalmic disorders other than CSC. RESULTS: Compared with patients of the control group, CSC patients reported more psychosomatic problems, unfavourable stress coping strategies and critical life events as well as elevated tension, aggression, strain, emotional instability and achievement orientation. Except for aggression the observed characteristics were more pronounced in acute than in chronic CSC patients. CONCLUSIONS: The appearance of CSC may be associated with an accumulation of stressful life events with an unfavourable coping style and distinctive personality factors. Acute CSC is related to more unfavourable stress coping and more physical complaints compared to its chronic course. Elevated aggression may imply one potential risk factor for CSC manifestation and also may have an adverse effect with its chronification.

Influence of patient-related and surgery-related risk factors on cognitive performance, emotional state, and convalescence after cardiac surgery.

BACKGROUND: Cardiac surgery may account for complications such as cognitive impairment, depression, and delay of convalescence. This study investigated the influence of different risk factors on cognitive performance, emotional state, and convalescence. METHODS: We included 83 patients undergoing cardiac surgery who had no indication of postoperative delirium. Psychometric testing was performed 1 day before and 7 days after surgery. Neuron-specific enolase (NSE) levels were measured 1 day before and 36 h after surgery. RESULTS: Depression score increased after surgery, but patients showed no clinically significant depression. Postoperative cognitive performance correlated with postoperative depression level and preoperative cognitive performance. Forty-three percent of patients showed postoperative decline. Older patients exhibited a higher postoperative increase in NSE concentrations. Patients undergoing coronary artery bypass grafts or combined procedures exhibited more medical risk factors than those undergoing valve surgery alone. The number of bypass grafts was associated with time of hospitalization, and the number of patient-related risk factors correlated with stay in intensive care unit. CONCLUSIONS: For elderly patients undergoing cardiac surgery, older age, total preexisting medical risk factors, and surgery duration seem to be the most important factors influencing cognitive outcome and convalescence. Results show that, also for patients without postoperative delirium, medical risk factors and intraoperative parameters can result in delay of convalescence.

"Add-On"-therapy with an individualized preparation consisting of free amino acids for patients with a major depression.

The efficacy of a deficit oriented add-on therapy with free amino acids in depressive patients treated with the antidepressant Remeron was evaluated. About 40 in-patients were investigated by a randomised double-blind placebo-controlled study during 4 weeks. Plasma levels of 20 amino acids and measures of depression, suicidal behaviour and aggression were surveyed on admission and after a 4 weeks' therapy with Remeron plus an individualized amino acid mixture or placebo. The preparation of the amino acid mixture was based on an aminogram and consisted of essential amino acids plus vitamins and trace elements as co-factors for the amino acid metabolism. Patients of the experimental group showed a significantly better improvement of depression and a higher responder rate than those of the placebo group. The results suggest that oral application of a deficit oriented amino acid mixture can improve the therapeutic outcome of an antidepressant. Furthermore, lacking side effects of the amino acids resulting also in a better patient compliance may improve the benefit/risk ratio.

Evaluation of conditions associated with glycated hemoglobin values below the reference range.

BACKGROUND: Evaluation of conditions associated with glycated hemoglobin (HbA1c) values below the reference range in HbA1c determinations. METHODS: Over a time period of 5 years, HbA1c results were determined with the ion-exchange high-performance liquid chromatography (HPLC) method HA-8140 Menarini. RESULTS: Of approximately 20 000 HbA1c results analyzed, 9 were below the reference range. The reason for HbA1c values below the reference range was found to be liver cirrhosis in 6 patients, anemia with hematological neoplasms in 2 patients, and elevated fetal hemoglobin > 1.5% in one patient. The silent hemoglobin (Hb) variant Hb Graz in 6 patients, Hb Sherwood Forest in 1 patient, homozygote HbS in one patient, and gross hypertriglyceridemia in one patient demonstrated no HbA1c result. CONCLUSIONS: In patients with liver cirrhosis, HbA1c measurements should be used with caution when evaluating long-term glucose control, and samples with suspected Hb variants should be analyzed by hemoglobin electrophoresis. Our study underscores the need for clinical laboratories and physicians to be aware of the limitations of their HbA1c assay methods as well as of the importance of visual inspection of ion-exchange chromatograms to detect HbA1c values below the reference range and abnormalities caused by the interference factors described here.

Silent hemoglobin variants and determination of HbA(1c) with the high-resolution program of the HPLC HA-8160 hemoglobin analyzer.

OBJECTIVES: Evaluation of HbA1c determination with an automated ion-exchange high-performance liquid chromatography (HPLC) method in patients with clinically silent hemoglobin (Hb) variants. DESIGN AND METHODS: HbA1c values were determined with the Arkray HA-8160 ion-exchange HPLC using the high-resolution, 4.2-min beta-thalassemia screening mode in patients with silent hemoglobin (Hb) variants, namely, Hb Graz, Hb Sherwood Forest, Hb O Padova, and HbD. RESULTS: All of these hemoglobin variants caused additional peaks in the chromatograms, without HbA1c results in patients with Hb Graz and Hb Sherwood Forest, and demonstrated extra peaks with HbA1c results that were clinically too low for patients with Hb O Padova and in the patient with HbD. CONCLUSIONS: The development of this automated HPLC method modification with high-resolution beta-thalassemia screening mode aids identification of interference due to some clinically silent Hb variants in HbA(1c) determination.

Determination of glycated hemoglobin in clinically silent hemoglobin variants.

BACKGROUND: Evaluation of glycated hemoglobin determination methods in patients with clinically silent hemoglobin variants. METHODS: HbA1c results were determined with various methods, including a new enzymatic assay, a boronate affinity HPLC, immunoassays and ion-exchange HPLC in patients with the clinically silent hemoglobin variants Hb Graz, Hb Sherwood Forest, Hb D and Hb O Padova. RESULTS: The effect of hemoglobin variants on glycated hemoglobin determination was method-dependent. The enzymatic and boronate affinity HPLC method did not interfere with any of the variants evaluated. In contrast, Hb Graz interfered with all immunoassay and ion-exchange HPLC methods evaluated. The Tosoh ion-exchange HPLC method HLC-723 did not detect the late migrating Hb O Padova in the chromatogram, but this hemoglobin variant still interfered causing artificially low HbA1c results. CONCLUSIONS: Our study underscores the need for clinical laboratories and physicians to be aware of the limitations of their HbA1c assay methods as well as the importance of visual inspection of ion-exchange chromatograms to detect abnormalities caused by the hemoglobin variants. Samples with clinically silent Hb variants should be analyzed by a second method with a different assay principle, preferably a boronate affinity HPLC or an enzymatic assay.

Determination of glycated hemoglobin in patients with advanced liver disease.

AIM: To evaluate the glycated hemoglobin (HbA(1c)) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin. METHODS: HbA(1c) values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium. RESULTS: Forty percent of patients with liver cirrhosis had HbA(1c) results below the non-diabetic reference range by at least one HbA(1c) method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis) had HbA(1c) results below the non-diabetic reference range by at least one HbA(1c) method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA(1c) results were below the non-diabetic reference using at least one of the HbA(1c) methods. CONCLUSION: Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes, HbA(1c) results should be used in patients with advanced liver disease. HbA(1c) and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment.

Zotepine in Huntington's disease.

The authors report a patient with Huntington's disease (HD) presenting with severe chorea. The motor scale of the unified HD rating scale (UHDRS-I) revealed 81 points. Motor function clearly improved with zotepine, until she reached an UHDRS-I of 34 points on day 7 of treatment. The patient was stable for at least 12 weeks. The improvement includes all seven categories of the UHDRS-I, especially chorea, gait and oral function. This is the first description of zotepine in HD. Our findings suggest that zotepine is useful in the treatment of HD chorea. Controlled trials of its use in HD would be welcome.

Reduction of hepatic glycogen synthesis and breakdown in patients with agenesis of the dorsal pancreas.

In a family with agenesis of the dorsal pancreas only the mother presents with insulin-dependent diabetes mellitus, whereas her sons are glucose tolerant. We examined whether metabolic defects can be detected early in this disease. Plasma glucose profiles were obtained from patients with dorsal pancreas agenesis and from matched healthy subjects. Hepatic glycogen synthesis and breakdown were determined from the time course of glycogen concentrations using noninvasive (13)C nuclear magnetic resonance spectroscopy. Gluconeogenesis was calculated from the difference between glucose production (measured with D-[6,6-(2)H(2)]glucose) and glycogen breakdown. Frequently sampled iv glucose tolerance tests were performed to assess insulin secretion and sensitivity. The mean plasma glucose level was higher (12.9 +/- 0.4 vs. 5.9 +/- 0.1 mmol/liter), whereas the peak plasma insulin level was lower (236 vs. 397 +/- 23 pmol/liter) in the diabetic mother than in her nondiabetic sons and healthy subjects. In all patients, however, glycogen synthesis and breakdown were reduced by approximately 55% (P < 0.05) and 40% (P < 0.02), respectively. Gluconeogenesis (6.8 +/- 0.8 vs. 4.2 +/- 0.3 micro mol/kg.min; P < 0.05) and hepatic insulin clearance (6.8 +/- 1.3 vs. 2.8 +/- 1.0 ml/kg.min) were increased in all patients. In conclusion, patients with complete agenesis of the dorsal pancreas exhibit marked defects in hepatic glycogen metabolism, which are present even in the nondiabetic offspring.