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Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.

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This study explores the variances in the organic, chemical, and sensory attributes of fermented coffee beans, specifically examining how post-harvest processes influence cup quality. Coffee fruits from the Catuaí IAC-144 variety were processed using both natural coffee (NC) and pulped coffee (PC) methods. The fruits were then subjected to self-induced anaerobic fermentation (SIAF) using one of the following fermentation methods: solid-state fermentation (SSF) or submerged fermentation (SMF). Within these methods, either spontaneous fermentation (SPF) or starter culture fermentation (SCF) was applied. Each method was conducted over periods of 24, 48, and 72 h. For this purpose, two-hundred-liter bioreactors were used, along with two control treatments. Numerous parameters were monitored throughout the fermentation process. A comprehensive chemical profiling and sensory analysis, adhering to the guidelines of the Specialty Coffee Association, were conducted to evaluate the influence of these fermentation processes on the flavor, aroma, and body characteristics of the coffee beverage across multiple dimensions. Data analysis and predictive modeling were performed using machine learning techniques. This study found that NC exhibited a higher production of acids (citric, malic, succinic, and lactic) compared to PC, resulting in distinct chemical and sensory profiles. The decision tree showed that fructose and malic and succinic acids were identified as the main factors enhancing sensory notes during cupping. SMF promoted higher concentrations of lactic acid, while SSF led to increased ethanol content. Consequently, the SIAF process enhances the sensory quality of coffee, adding value to the product by generating diverse sensory profiles.

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Obesity is coupled with an altered redox state and low-level inflammation. Oxidative stress may increase pre-adipocyte proliferation, adipocyte differentiation and mature adipocyte size. Regarding inflammation, the dysregulation of cytokine production by adipose tissue takes place in obesity, which is promoted by oxidative stress. Polyphenols may exert a positive effect on obesity, not only by modulating the redox state, but also due to their anti-inflammatory activity. Coffee, which is one of the most consumed beverages, is very rich in phenolic compounds. Bioavailability studies on coffee phenols have shown that the most abundant group of metabolites in plasma and urine are dihydrocaffeic (DHCA), dihydroferulic (DHFA), and hydroxyhippuric (HHA) acids, the three acids of colonic origin. To better understand the antioxidant and anti-inflammatory properties of DHCA, DHFA, and HHA, an inflammation/oxidation model was set up in the pre-adipocyte 3T3-L1 cell line using tumor necrosis factor-α (TNF-α). After the exposure of 3T3-L1 cells to 0.5, 1, 5, and 10 µM of TNF-α at different times, the cell viability, interleukin (IL)-6 secretion, and the production of reactive oxygen species (ROS) and glutathione (GSH) were determined. Using the TNF-α prooxidant and proinflammatory conditions established (10 µM, 24 h), it was observed that the physiological concentrations (0.5, 1, 5, and 10 µM) of DHCA, DHFA, and HHA induced dose-dependent antioxidant effects according to the ROS, GSH, and antioxidant enzyme (glutathione peroxidase) results. In addition, reductions in the IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1) concentrations were observed to different extents depending on the metabolite (DHFA, HHA, or DHCA) and the concentration used. In conclusion, the main colonic metabolites from coffee chlorogenic acids may counteract TNF-α-induced inflammation and oxidative stress in the 3T3-L1 cell line, and thus, they present antiobesity potential.

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Age-related injuries are often connected to alterations in redox homeostasis. The imbalance between free radical oxygen species and endogenous antioxidants defenses could be associated with a growing risk of transient ischemic attack and stroke. In this context, a daily supply of dietary antioxidants could counteract oxidative stress occurring during ischemia/reperfusion injury (I/R), preventing brain damage. Here we investigated the potential antioxidant properties of coffee-derived circulating metabolites and a coffee pulp phytoextract, testing their efficacy as ROS scavengers in an in vitro model of ischemia. Indeed, the coffee fruit is an important source of phenolic compounds, such as chlorogenic acids, present both in the brewed seed and in the discarded pulp. Therefore, rat brain endothelial cells, subjected to oxygen and glucose deprivation (OGD) and recovery (ogR) to mimic reperfusion, were pretreated or not with coffee by-products. The results indicate that, under OGD/ogR, the ROS accumulation was reduced by coffee by-product. Additionally, the coffee extract activated the Nrf2 antioxidant pathway via Erk and Akt kinases phosphorylation, as shown by increased Nrf2 and HO-1 protein levels. The data indicate that the daily intake of coffee by-products as a dietary food supplement represents a potential nutritional strategy to counteract aging.

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Volatile and non-volatile compounds in coffee directly affect the beverage's quality. This study aimed to demonstrate how the organic acids and volatile profiles were impacted by coffee fermentation using four starter cultures (Meyerozyma caribbica (CCMA 0198), Saccharomyces cerevisiae (CCMA 0543), Candida parapsilosis (CCMA0544), and Torulaspora delbrueckii (CCMA 0684)) inoculated in two varieties of coffee (Bourbon Amarelo and Canário Amarelo) using natural and pulped natural processing methods and sensory perception. Real-time PCR (qPCR) was used to verify the dynamic behavior of yeast populations. Organic acids were detected using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) was used to detected volatile compounds. Sensory analysis was performed on the roasted coffee. Citric, malic, succinic, lactic, oxalic, isobutyric, and propionic acids and 105 volatile compounds were detected. At the beginning of fermentation, treatments with natural processing presented higher number of volatiles compounds. After fermentation, the main compounds groups were acids, alcohols, and aldehydes. The perception of sensory attribute (fruity, nutty, cocoa) varied with the coffee variety, type of processing, and type of inoculum. The use of yeasts is an alternative for sensorial differentiation of coffee variety Canário Amarelo and Bourbon Amarelo. The stainless-steel containers showed good results for coffee fermentation.

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Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources.

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Neurodegenerative diseases are associated with accumulation of amyloid-type protein misfolding products. Prion protein (PrP) is known for its ability to aggregate into soluble oligomers that in turn associate into amyloid fibrils. Preventing the formation of these infective and neurotoxic entities represents a viable strategy to control prion diseases. Numerous attempts to find dietary compounds with anti-prion properties have been made; however, the most promising agent found so far was curcumin, which is poorly soluble and merely bioavailable. In the present work, we identify 3,4-dimethoxycinnamic acid (DMCA) which is a bioavailable coffee component as a perspective anti-prion compound. 3,4-Dimethoxycinnamic acid was found to bind potently to prion protein with a Kd of 405 nM. An in vitro study of DMCA effect on PrP oligomerization and fibrillization was undertaken using isothermal titration calorimetry (ITC), dynamic light scattering (DLS) and circular dichroism (CD) methodologies. We demonstrated that DMCA affects PrP oligomer formation reducing the oligomer content by 30-40%, and enhancing SH-SY5Y cell viability treated with prion oligomers. Molecular docking studies allowed to suggest a site where DMCA is able to bind stabilizing PrP tertiary structure. We suggest that DMCA is a perspective dietary compound for prophylaxis of neurodegenerative diseases that needs further research. Copyright © 2017 John Wiley & Sons, Ltd.

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SCOPE: Although ingestion of coffee and its constituent chlorogenic acid (CGA) protects the retina from oxidative stress, the bioaccessibility and bioavailability of coffee metabolites are not well understood. The aim of this study was to determine which coffee metabolites reach the retina and protect against retinal degeneration. METHODS AND RESULTS: UPLC-MS/MS was used to detect CGA and coffee metabolites in the rat eye. The methyl thiazolyl tetrazolium assay and double staining with Hoechst and propidium iodide showed that CGA, caffeic acid (CA), and dihydrocaffeic acid (DHCA) protect retinal ganglion cells from hypoxia-induced damage. Western blots showed that treatment with coffee metabolites up-regulated anti-apoptotic proteins such as Bcl-2 and Bcl-XL and down-regulated pro-apoptotic proteins such as Bad, PARP, and cleaved caspase 3. Adult ICR mice were subjected to optic nerve crush-induced retinal ganglion cell death with intravitreal pre-treatment with coffee metabolites 1 day before and 1 h after the procedure. Retrograde Fluorogold(TM) labeling showed severe retinal ganglion cell loss after optic nerve crushing, and coffee metabolites significantly reduced damage to retinal ganglion cells. CONCLUSION: CGA and coffee metabolites, especially, CA, and DHCA, reach the eye, where they can significantly reduce apoptosis induced by hypoxia and optic nerve crush stress, and thus prevent retinal degeneration.

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