Common questions and misconceptions about caffeine supplementation: what does the scientific evidence really show?

Caffeine is a popular ergogenic aid that has a plethora of evidence highlighting its positive effects. A Google Scholar search using the keywords "caffeine" and "exercise" yields over 200,000 results, emphasizing the extensive research on this topic. However, despite the vast amount of available data, it is intriguing that uncertainties persist regarding the effectiveness and safety of caffeine. These include but are not limited to: 1. Does caffeine dehydrate you at rest? 2. Does caffeine dehydrate you during exercise? 3. Does caffeine promote the loss of body fat? 4. Does habitual caffeine consumption influence the performance response to acute caffeine supplementation? 5. Does caffeine affect upper vs. lower body performance/strength differently? 6. Is there a relationship between caffeine and depression? 7. Can too much caffeine kill you? 8. Are there sex differences regarding caffeine's effects? 9. Does caffeine work for everyone? 10. Does caffeine cause heart problems? 11. Does caffeine promote the loss of bone mineral? 12. Should pregnant women avoid caffeine? 13. Is caffeine addictive? 14. Does waiting 1.5-2.0 hours after waking to consume caffeine help you avoid the afternoon "crash?" To answer these questions, we performed an evidence-based scientific evaluation of the literature regarding caffeine supplementation.

Effect of Black Garlic Consumption on Endothelial Function and Lipid Profile: A Before-and-After Study in Hypercholesterolemic and Non-Hypercholesterolemic Subjects.

BACKGROUND: Black garlic is obtained from raw garlic (Allium sativum L.), by a fermentation process, under humidity and heat treatment, showing a high concentration of organosulfur compounds, which have been related to benefits in the prevention or delay of cardiovascular diseases (CVDs). The objective of the research was to evaluate whether long-term consumption of black garlic improves endothelial function and lipid profile in subjects with hypercholesterolemia. METHODS: Single center, controlled clinical trial with two branches: Hypercholesterolemia vs. Healthy condition. Sixty-two subjects of both sexes were distributed in two groups, the hypercholesterolemia group (n = 31) (total cholesterol (TC) range 200-300 mg/dL and low-density lipoprotein (LDL)-cholesterol range 135-175 mg/dL) and the healthy group (n = 31). The intervention consisted of the ingestion of 4 cloves of black garlic (12 g) daily for 12 weeks. RESULTS: significant increases in Apolipoprotein (Apo)A1 occurred in both groups: Hypercholesterolemia (Δ 11.8 mg/dL p < 0.001) vs Healthy (Δ 11.1 mg/dL p < 0.001). Besides, significant reductions for endothelial adhesion molecules monocyte chemoattractant protein-1 (MCP-1) (Δ -121.5 pg/mL p = 0.007 vs. Δ -56.3 pg/mL p = 0.015), intracellular adhesion molecule-1 (ICAM-1) (Δ -39.3 ng/mL p < 0.001 vs. Δ 63.5 ng/mL p < 0.001), and vascular cyto-adhesion molecule-1 (VCAM-1) (Δ -144.4 ng/mL p < 0.001 vs. Δ -83.4 ng/mL p = 0.061) were observed, for hypercholesterolemic and healthy subjects, respectively. CONCLUSIONS: These data show that black garlic consumption could improve some parameters related to endothelial function and lipid profile, which may have a favorable impact on the risk of CVDs, although more long-term studies are necessary to confirm.

Relato de caso de intoxicación con superwarfarinas: un desafío terapéutico / Managing Superwarfarin Poisoning: A Challenging Case

La intoxicación humana por rodenticidas anticoagulantes de acción prolongada, conocidos como superwarfarinas, provoca coagulopatía de prolongado manejo. Presentamos el caso de un hombre de 42 años que ingirió una dosis tóxica de rodenticida en un intento suicida, evolucionando con epistaxis, INR de 11,6 y necesidad de hospitalización. Durante 7 días se realizaron controles seriados de pruebas de coagulación, con optimización de diferentes dosis de suplementación de Vitamina K. El caso destaca la potencia y vida media prolongada (aproximadamente 6 semanas) de este tipo de anticoagulantes, hecho que requiere un control clínico regular y una adherencia al tratamiento satisfactoria.

Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a 42-year-old man who ingested a toxic dose of rodenticide in a suicide attempt, evolving with epistaxis, INR of 11.6, and needing hospitalization. For seven days, serial controls of coagulation tests were carried out, with optimization of different doses of Vitamin K supplementation. The case highlights this type of anticoagulant's potency and prolonged half-life (approximately six weeks), which requires regular clinical control and satisfactory treatment adherence.

Urinary excretion of organosulfur compounds after acute ingestion of black onion.

Onion (Allium cepa L.) and its newly derived product "black onion" are characterised by the presence of compounds with potential bioactivity, particularly organosulfur compounds (OSCs). However, little is known about the metabolism, distribution, and excretion of these compounds as they pass through the gastrointestinal tract. This study monitored healthy subjects after an acute intake of black onion and analysed the excretion of OSCs using UHPLC-HRMS. A total of 31 OSCs were detected in urine after the acute ingestion of black onion, the main components being S-methyl-L-cysteine sulfoxide (methiin) (13.6 ± 3.9 µmol), isoalliin (12.4 ± 4.7 µmol) and S-propyl-L-cysteine (deoxypropiin) (3.1 ± 0.7 µmol). Moreover, N-acetylated metabolites of the major OSCs detected in black onion, namely, N-acetyl-S-(1-propenyl)-L-cysteine sulfoxide (NAS1PCS) and N-acetyl-S-(1-propenyl)-L-cysteine (NAS1PC), were found in urine after black onion consumption. The N-acetylation reaction takes place in the kidneys and liver, and metabolism pathways are proposed to explain the excretion of OSCs in urine. The basis of the identification of OSCs as urinary metabolites after black onion consumption is described for the first time and provides the basis for further research.

Long-term supplementation with anthocyanin-rich or -poor Rubus idaeus berries does not influence microvascular architecture nor cognitive outcome in the APP/PS-1 mouse model of Alzheimer's disease.

Disruption of microvascular architecture is a common pathogenic mechanism in the progression of Alzheimer's disease (AD). Given the anti-angiogenic activity of berry (poly)phenols, we investigated whether long-term feeding of Rubus idaeus (raspberries) could ameliorate cerebral microvascular pathology and improve cognition in the APP/PS-1 mouse model of AD. Male C57Bl/6J mice (50 wild type, 50 APP/PS-1) aged 4-months were fed for 24-weeks, with a normal diet enriched with either 100 mg/day glucose (control diet) or supplemented with glucose and freeze-dried anthocyanin-rich (red) or -poor (yellow) raspberries (100 mg/day) and assessed/sampled post intervention. Cerebral microvascular architecture of wild-type mice was characterised by regularly spaced capillaries with uniform diameters, unlike APP/PS-1 transgenic mice which showed dysregulated microvascular architecture. Long-term feeding of raspberries demonstrated limited modulation of microbiota and no substantive effect on microvascular architecture or cognition in either mice model although changes were evident in endogenous cerebral and plasmatic metabolites.

Factores asociados con la recidiva de cáncer de mama en pacientes con cirugía conservadora / Factors associated with breast cancer recurrence in patients with conservative surgery

Resumen OBJETIVO: Identificar los factores asociados con la recidiva de cáncer de mama en pacientes con cirugía conservadora. MATERIALES Y MÉTODOS: Estudio observacional, de cohorte retrospectiva, efectuado a partir de expedientes de pacientes con cáncer de mama en estadios tempranos e intervenidas con cirugía conservadora. Parámetros de estudio: estadio, subtipo histológico, perfil de expresión de receptores hormonales, tiempo de seguimiento, recidiva y periodo libre de enfermedad. La tasa de recidiva, el periodo libre de enfermedad y la identificación de los factores asociados con recidiva se hicieron con análisis estadístico. RESULTADOS: Se estudiaron 53 pacientes con edad media de 51.0 ± 9.4 años. El subtipo histopatológico más frecuente fue el ductal en 49 de las 53 pacientes; en 48 de ellas los tumores fueron positivos para receptores de progesterona, en 7 de 53 para Her-2 y en 3 de 53 triple negativo. La tasa de recidiva de cáncer de mama fue de 13.2% (es decir: 7 de 53 pacientes). El tiempo libre de enfermedad en quienes recayeron fue de 30.6 ± 24.8 meses. En el análisis bivariado se asociaron significativamente con recidiva: los ganglios linfáticos positivos, la expresión de receptores de progesterona y de estrógenos, los tumores triple negativo y el tratamiento complementario con quimioterapia. En el análisis multivariado solo se asociaron con recidiva: tener un tumor triple negativo (OR = 51.8; IC95%: 4.9- 548.4; p = 0.001) y recibir quimioterapia (OR = 8.0; IC95%: 1.4-46.1; p = 0.020). CONCLUSION: Los factores asociados con la recidiva fueron los ganglios linfáticos positivos, la expresión de receptores de progesterona y de estrógenos, tumores triple negativo y recibir quimioterapia.

Abstract OBJECTIVE: To identify factors associated with breast cancer recurrence in patients undergoing conservative surgery. MATERIALS AND METHODS: Observational, retrospective cohort study conducted on the records of patients with early-stage breast cancer who underwent conservative surgery. Study parameters: stage, histologic subtype, hormone receptor expression profile, follow-up time, recurrence and disease-free period. Statistical analysis was performed to estimate recurrence rate and disease-free period and to identify factors associated with recurrence. RESULTS: Fifty-three patients with a mean age of 51.0 ± 9.4 years were evaluated. The most common histopathologic subtype was ductal in 49 of 53 patients; tumors were progesterone receptor positive in 48, Her-2 positive in 7 of 53, and triple negative in 3 of 53. The breast cancer recurrence rate was 13.2% (i.e., 7 of 53 patients). Disease-free time in those who relapsed was 30.6 ± 24.8 months. In bivariate analysis, positive lymph nodes, progesterone and estrogen receptor expression, triple-negative tumors, and adjuvant chemotherapy were significantly associated with recurrence. In multivariate analysis, only having a triple-negative tumor (OR = 51.8; 95%CI: 4.9-548.4; p = 0.001) and receiving chemotherapy (OR = 8.0; 95%CI: 1.4-58.4; p = 0.001) were associated with recurrence. CONCLUSION: Factors associated with recurrence were positive lymph nodes, expression of progesterone and estrogen receptors, triple-negative tumors, and receipt of chemotherapy.

Impact of Temperature on Phenolic and Osmolyte Contents in In Vitro Cultures and Micropropagated Plants of Two Mediterranean Plant Species, Lavandula viridis and Thymus lotocephalus.

In this study, in vitro cultures and micropropagated plants of two Mediterranean aromatic plants, Lavandula viridis L'Hér and Thymus lotocephalus López and Morales, were exposed to different temperatures (15, 20, 25, and 30 °C). The effect of temperature on the levels of hydrogen peroxide (H2O2), lipid peroxidation, and osmoprotectants (proline, soluble sugars, and soluble proteins), as well as on the phenolic profile by HPLC-HRMS and intermediates of the secondary metabolism (phenylalanine ammonia lyase (PAL) activity and shikimic acid content), was investigated. Moreover, the antioxidant activity of the plant extracts was also analyzed. Overall, considering the lipid peroxidation and H2O2 content, the extreme temperatures (15 and 30 °C) caused the greatest damage to both species, but the osmoprotectant response was different depending on the species and plant material. In both species, phenolic compounds and related antioxidant activity increased with the rise in temperature in the micropropagated plants, while the opposite occurred in in vitro cultures. L. viridis cultures showed the highest biosynthesis of rosmarinic acid (92.6 g/kgDW) at 15 °C and seem to be a good alternative to produce this valuable compound. We conclude that contrasting temperatures greatly influence both species' primary and secondary metabolism, but the response is different depending on the plant micropropagation stage.

Suplementación efectiva de vitamina D en pacientes con fractura tibial / Effective vitamin D supplementation in patients with tibial fracture

OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.

OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.

Grape seed extract supplementation modulates hepatic lipid metabolism in rats. Implication of PPARß/δ.

In mammals, the liver is involved in nutrient metabolism and in the regulation of lipid and glucose homeostasis. Multiple studies have described improvements in liver disorders after regular consumption of grape seed extract (GSE). GSE prevents or ameliorates hepatic metabolic dysfunction through AMPK activation, which reduces hepatic lipogenesis while enhancing hepatic lipid oxidation. However, the involvement of ChREBPß and PPARß/δ in these effects has not been fully elucidated. We aim to demonstrate that chronic consumption of GSE at low doses (25 mg kg-1 body weight per day) produces beneficial effects on hepatic glucose and lipid metabolism in young lean Wistar rats and that part of these effects involve ChREBPß inactivation and PPARß/δ activation. In our study, increased concentrations of structurally related (-)-(epi)catechin metabolites and 5-carbon ring fission metabolites were found in the serum of GSE-supplemented rats parallel with the reduction in triglycerides and leptin levels, hepatic cholesterol content and visceral adiposity. GSE supplementation inactivates ChREBP and GSK-3ß, which has been linked to improvements in hepatic lipid and glucose metabolism. Furthermore, the consumption of GSE promotes the expression of Pparß/δ, as well as Pgc-1α and Acox-1, which control hepatic lipid oxidation. Interestingly, pharmacological inhibition of PPARß/δ slowed the induction of Pgc-1α and Acox-1, as well as the activation of AMPK triggered by GSE consumption. Our data suggest that PPARß/δ activation is involved in the metabolic reprogramming effects of chronic GSE consumption in young rats, by modulating, at least, part of the transcriptional programs that maintain hepatic and systemic fuel homeostasis.

Effects of colonic fermentation on the stability of fresh and black onion bioactives.

The health properties related to onion intake are attributed mainly to the presence of bioactive compounds, particularly phenolic and organosulfur compounds (OSCs). The aim of this study was to investigate, for the first time, the effect of an in vitro colonic fermentation on the stability of phenolic and OSCs of fresh and black onion by ultra-high-performance liquid chromatography coupled with mass spectrometry with a linear ion trap (UHPLC-LIT-MS). Throughout colonic fermentation, fresh onion showed an increase in the total phenolic content of 45%, mainly due to an increase in the content of the flavonoid family, while the OSCs remained stable along the fermentation. Black onion presented a different behaviour, showing significant decreases in total (poly)phenol and OSC content, 22 and 48%, respectively. The main compounds found after the in vitro colonic fermentation of fresh onion were isorhamnetin (141 µmol L-1), quercetin (95 µmol L-1), 3,4-dihydroxybenzoic acid (53 µmol L-1), methionine sulfoxide (100 µmol L-1) and S-allylcysteine (SAC) (21.7 µmol L-1), whereas 3,4-dihydroxybenzoic acid (70 µmol L-1), 4-hydroxyphenylacetic acid (68 µmol L-1), methionine sulfoxide (82 µmol L-1) and S-propylmercapto-L-cysteine (SPMC) (10.1 µmol L-1) accounted for the highest concentrations of phenolics and OSCs in fermented black onion. These compounds, presumably present for their absorption and action at the colonic level, could be related to the health benefits of regular consumption of fresh and black onion.

In Vitro Colonic Fermentation of (Poly)phenols and Organosulfur Compounds of Fresh and Black Garlic.

The beneficial properties associated with garlic consumption have been related to the presence of bioactive compounds including (poly)phenols and organosulfur compounds (OSCs). This study aims to assess the effect of in vitro colonic fermentation on fresh and black garlic by determining the transformation of these compounds through ultrahigh-performance liquid chromatography coupled to mass spectrometry with a linear ion trap (uHPLC-LIT-MS). Colonic fermentation had a similar influence on the phenolic content of fresh and black garlic, with total respective decreases of 43.8% and 41.7%. Meanwhile, fermentation resulted in a significant decrease (33%) in OSCs in black garlic. Compounds such as 4-hydroxybenzoic acid, S-allylcysteine (SAC), and methionine sulfoxide were the phenolic compounds and OSCs with the highest concentration in fresh and black garlic after the in vitro fermentation. These compounds, potentially present at the colonic level, might be responsible for the systemic health benefits associated with the consumption of black and fresh garlic.

Impact of Metallic Nanoparticles on In Vitro Culture, Phenolic Profile and Biological Activity of Two Mediterranean Lamiaceae Species: Lavandula viridis L'Hér and Thymus lotocephalus G. López and R. Morales.

Nanoparticles (NPs) recently emerged as new chemical elicitors acting as signaling agents affecting several processes in plant metabolism. The aim of this work was to investigate the impact of the addition of copper oxide (CuO), zinc oxide (ZnO) and iron oxide (Fe3O4) NPs (<100 nm) at different concentrations (1, 5 and 10 mg/L) to the culture media on several morphological, physiological and -biochemical parameters of in vitro shoot cultures of Lavandula viridis L'Hér and Thymus lotocephalus G. López and R. Morales (Lamiaceae), as well as on phenolic profile and bioactivity (antioxidant and enzyme inhibition capacities). Although some decreases in shoot number and length were observed in response to NPs, biomass production was not affected or was improved in both species. Most NPs treatments decreased total chlorophyll and carotenoid contents and increased malondialdehyde levels, an indicator of lipid peroxidation, in both species. HPLC-HR-MS analysis led to the identification of thirteen and twelve phenolic compounds, respectively, in L. viridis and T. lotocephalus extracts, being rosmarinic acid the major compound found in all the extracts. ZnO and Fe3O4 NPs induced an increase in total phenolic and rosmarinic acid contents in T. lotocephalus extracts. Additionally, some NPs treatments also increased antioxidant activity in extracts from this species and the opposite was observed for L. viridis. The capacity of the extracts to inhibit tyrosinase, acetylcholinesterase and butyrylcholinesterase enzymes was not considerably affected. Overall, NPs had a significant impact on different parameters of L. viridis and T. lotocephalus in vitro shoot cultures, although the results varied with the species and NPs type.

Bioavailability of red wine and grape seed proanthocyanidins in rats.

This study explored plasma levels and urinary and fecal excretion of metabolites and microbial-derived catabolites over a 24 h period following the ingestion of red wine (RWP) or grape seed (GSP) proanthocyanidin-rich extracts by rats. In total, 35 structurally-related (epi)catechin metabolites (SREMs) and 5-carbon side chain ring fission metabolites (5C-RFMs) (phenyl-γ-valerolactones and phenylvaleric acids), and 50 phenolic acid and aromatic catabolites were detected after intakes of both extracts. The consumption of the RWP extract, but not the GSP extract, led to the appearance of a ∼200 nmol L-1 peak plasma concentration of SREMs formed from flavan-3-ol monomers. In contrast, ingestion of the GSPs, but not the RWPs, resulted in a substantial increase in microbiota-derived 5-carbon side chain ring fission metabolites (5C-RFMs) in plasma. 5C-RFMs, along with low molecular weight phenolic catabolites were detected in urine after ingestion of both extracts. The GSP and RWP extracts had respective mean degrees of polymerisation 5.9 and 6.5 subunits, and the RWP extract had an upper polymer size of 21 subunits compared to 44 subunits for the GSP extract. The differences in plasma metabolite profiles might, therefore, be a consequence of this polydispersity impacting on the microbiota-mediated rates of cleavage of the proanthocyanidin subunits and their subsequent metabolism and absorption. Urinary excretion of phenolic catabolites indicated that 11% of RWPs and 7% for GSPs were subjected to microbial degradation. In all probability these figures, rather than representing the percentage of proanthocyanidins that are completely degraded, indicate partial cleavage of monomer subunits producing a much higher percentage of shortened proanthocyanidin chains. Obtaining more detailed information on the in vivo fate of proanthocyanidins is challenging because of the difficulties in analysing unabsorbed parent proanthocyanidins and their partially degraded flavan-3-ol subunit chains in feces. Further progress awaits the development of improved purification and analytical techniques for proanthocyanidins and their use in feeding studies, and in vitro fecal and bacterial incubations, with radio and/or stable isotope-labelled substrates.

Changes in the antioxidant activity and metabolite profile of three onion varieties during the elaboration of 'black onion'.

This study aims to investigate whether the heat treatment applied during the production of black onion, a novel derived product made from fresh onion, produces changes in the content of flavonoids, organosulfur compounds, organic acids, water soluble sugars and amino acids in three onion varieties ('Shallot', 'Chata' and 'Echalion'). The total flavonoid content decreased up to 12-fold in black onions compared with fresh onions while the quantities of isoalliin, the main organosulfur compound in black onions, drastically increased during the process. Moreover, the levels of fructose and glucose significantly increased during the elaboration process, contributing to the sweetness of black onions. The influence of heating on their antioxidant capacity showed a decreasing trend of the ORAC antioxidant activity of onion, while ABTS and DPPH did not show a clear tendency. These results present a comprehensive phytochemical characterization of black onions, highlighting the significant influence of the heating process on their phytochemical composition.

Impact of a (poly)phenol-rich extract from the brown algae Ascophyllum nodosum on DNA damage and antioxidant activity in an overweight or obese population: a randomized controlled trial.

Background: Epidemiologic evidence suggests that a diet rich in (poly)phenols has beneficial effects on many chronic diseases. Brown seaweed is a rich source of (poly)phenols. Objective: The aim of this study was to investigate the bioavailability and effect of a brown seaweed (Ascophyllum nodosum) (poly)phenol extract on DNA damage, oxidative stress, and inflammation in vivo. Design: A randomized, double-blind, placebo-controlled crossover trial was conducted in 80 participants aged 30-65 y with a body mass index (in kg/m2) ≥25. The participants consumed either a 400-mg capsule containing 100 mg seaweed (poly)phenol and 300 mg maltodextrin or a 400-mg maltodextrin placebo control capsule daily for an 8-wk period. Bioactivity was assessed with a panel of blood-based markers including lymphocyte DNA damage, plasma oxidant capacity, C-reactive protein (CRP), and inflammatory cytokines. To explore the bioavailability of seaweed phenolics, an untargeted metabolomics analysis of urine and plasma samples after seaweed consumption was determined by ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Results: Consumption of the seaweed (poly)phenols resulted in a modest decrease in DNA damage but only in a subset of the total population who were obese. There were no significant changes in CRP, antioxidant status, or inflammatory cytokines. We identified phlorotannin metabolites that are considered potential biomarkers of seaweed consumption including pyrogallol/phloroglucinol-sulfate, hydroxytrifurahol A-glucuronide, dioxinodehydroeckol-glucuronide, diphlorethol sulfates, C-O-C dimer of phloroglucinol sulfate, and C-O-C dimer of phloroglucinol. Conclusions: To the best of our knowledge, this work represents the first comprehensive study investigating the bioactivity and bioavailability of seaweed (poly)phenolics in human participants. We identified several potential biomarkers of seaweed consumption. Intriguingly, the modest improvements in DNA damage were observed only in the obese subset of the total population. The subgroup analysis should be considered exploratory because it was not preplanned; therefore, it was not powered adequately. Elucidation of the biology underpinning this observation will require participant stratification according to weight in future studies. This trial was registered at clinicaltrials.gov as NCT02295878.

Effect of olive cultivar on bioaccessibility and antioxidant activity of phenolic fraction of virgin olive oil.

AIM: This study aims to characterize the phenolic profile and antioxidant capacity of seven monovarietal virgin olive oils (VOOs) and evaluate their in vitro gastrointestinal stability. METHODS: 'Picual', 'Blanqueta', 'Sevillana', 'Habichuelero', and 'Chetoui' olive cultivars were selected for VOO extraction. The oils were subjected to in vitro digestion. The recovery index (RI) of phenolic compounds after each digestion step and the bioaccessibility index (BI) were evaluated. In addition, the antioxidant activity of the bioaccessible fraction (BF) of VOOs was determined by DPPH, ABTS, and ORAC assays, as well as by studying the intracellular reactive oxygen species in Caco-2 cells. RESULTS: Differences were found in the composition of phenolic compounds in VOOs depending on cultivars. During the digestive process, important losses of phenolic compounds were observed between the buccal and duodenal steps, unlike HTy and Ty, which presented increased recovery due to the hydrolysis of secoiridoid derivatives. Differences in the bioaccessibility of phenolic compounds were found between varieties of VOOs. 'Sevillana' VOO had the highest total bioaccessibility (36%), followed by the 'Picual' (19%), 'Chetoui' (17%), 'Habichuelero' (10%), and 'Blanqueta' (8%) varieties. The BF of all the varieties of VOO showed similar radical ABTS scavenging capacity, 'Chetoui', and 'Blanqueta'-BF having the highest radical DPPH scavenging capacity, and 'Habichuelero' and 'Picual'-BF showing protective effects against the peroxyl radical measured by ORACFL assay. All VOO-BFs presented decreases in ROS levels in Caco-2 cells. CONCLUSIONS: Our results suggest differences in the bioaccessibility of phenolics from diverse VOO varieties, which could lead to different biological properties. Therefore, this study represents a first step toward the development of novel dietary strategies focusing on the phenolic supplementation of different VOOs to preserve human health.

New ß-orcinol depsides from Hypotrachyna caraccensis, a lichen from the páramo ecosystem and their free radical scavenging activity.

The new hypotrachynin A (1) and B (2) along with the known (+)-(9b-R)-usnic (3) and methylstictic acids (4) were isolated for the first time from Hypotrachyna caraccensis. Additionally, their potency and reactivity as DPPH• scavengers was determined by a kinetic study calculating their EC50 and second-order rate constants (k2). Considering 1-4 could be dermatological agents, their n-octanol-water partition coefficients and standard molar Gibbs free energies of transfer were calculated as estimation of their lipophilicity and skin penetration. Compounds 1, 3 and 4 were less potent than 2 (EC50 = 3.3014; 1.7540; 2.6652 vs 0.7376) as DPPH• scavengers, in turn 4, was the most reactive with a comparable k2 to the antioxidant BHT (k2 = (232 ± 24) × 10-2 vs (564 ± 12) × 10-2 M-1 s-1, respectively). Since 2 and 4 had an optimal lipophilicity and permeability for skin penetration, they might be developed as topical ingredients to prevent oxidative damage.

Bioavailability of orange juice (poly)phenols: the impact of short-term cessation of training by male endurance athletes.

Background: Physical exercise has been reported to increase the bioavailability of citrus flavanones.Objective: We investigated the bioavailability of orange juice (OJ) (poly)phenols in endurance-trained males before and after cessation of training for 7 d.Design: Ten fit, endurance-trained males, with a mean ± SD maximal oxygen consumption of 58.2 ± 5.3 mL · kg-1 · min-1, followed a low (poly)phenol diet for 2 d before drinking 500 mL of OJ containing 398 µmol of (poly)phenols, of which 330 µmol was flavanones. After the volunteers stopped training for 7 d the feeding study was repeated. Urine samples were collected 12 h pre- and 24 h post-OJ consumption. Bioavailability was assessed by the quantitative analysis of urinary flavanone metabolites and (poly)phenol catabolites with the use of high-pressure liquid chromatography-high resolution mass spectrometry.Results: During training, 0-24-h urinary excretion of flavanone metabolites, mainly hesperetin-3'-O-glucuronide, hesperetin-3'-sulfate, naringenin-4'-O-glucuronide, naringenin-7-O-glucuronide, was equivalent to 4.2% of OJ flavanone intake. This increased significantly to 5.2% when OJ was consumed after the volunteers stopped training for 7 d. Overall, this trend, although not significant, was also observed with OJ-derived colonic catabolites, which, after supplementation in the trained state, were excreted in amounts equivalent to 51% of intake compared with 59% after cessation of training. However, urinary excretion of 3 colonic catabolites of bacterial origin, most notably, 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic acid, did increase significantly when OJ was consumed postcessation compared with precessation of training. Data were also obtained on interindividual variations in flavanone bioavailability.Conclusions: A 7-d cessation of endurance training enhanced, rather than reduced, the bioavailability of OJ flavanones. The biological significance of these differences and whether they extend to the bioavailability of other dietary (poly)phenols remain to be determined. Hesperetin-3'-O-glucuronide and the colonic microbiota-derived catabolite 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic acid are key biomarkers of the consumption of hesperetin-O-glycoside-containing OJ and other citrus products. This trial was registered at clinicaltrials.gov as NCT02627547.

Bioavailability of Black Tea Theaflavins: Absorption, Metabolism, and Colonic Catabolism.

Data obtained with in vitro fecal incubations and a feeding study indicate black tea theaflavin and its galloyl derivatives are not absorbed in detectable amounts in either the upper or lower gastrointestinal tract. The theaflavin skeleton is comparatively resistant to degradation by colonic bacteria with a 67% recovery being obtained after a 24 h incubation, which yielded 21 phenolic and aromatic catabolites. The theaflavin galloyl moiety was removed by the microbiota, and the released gallic acid further transformed to 3-O- and 4-O-methyl gallic acids, pyrogallol-1-sulfate and pyrogallol-2-sulfate, which were excreted in urine in amounts equivalent to 94% of intake. The main urinary product potentially derived from breakdown of the theaflavin skeleton was 3-(4'-hydroxyphenyl)propionic acid. A number of the colonic catabolites originating from gallic acid and theaflavins has been reported to be bioactive in ex vivo and in vitro models with a variety of potential modes of action.

Personal and professional use of menopausal hormone therapy among gynecologists: A multinational study (REDLINC VII).

BACKGROUND: Previously, the REDLINC VI study showed that the main reason for the low use of menopausal hormone therapy (MHT) was its low rate of prescription by doctors. OBJECTIVE: To determine the use of MHT and perceived related risks among gynecologists. METHODS: A self-administered and anonymous questionnaire was delivered to certified gynecologists in 11 Latin American countries. RESULTS: A total of 2154 gynecologists were contacted, of whom 85.3% responded to the survey (n = 1837). Mean age was 48.1 ± 11.4 years; 55.5% were male, 20.3% were faculty members and 85% had a partner. Overall, 85.4% of gynecologists responded that they would use MHT if they had menopausal symptoms (81.8% in the case of female gynecologists) or prescribe it to their partner (88.2% in the case of male gynecologists; p < 0.001). Perceived risk related to MHT use (on a scale from 0 to 10) was higher among female than among male gynecologists (4.06 ± 2.09 vs. 3.83 ± 2.11, p < 0.02). The top two perceived reported risks were thromboembolism (women 33.6% vs. men 41.4%, p < 0.009) and breast cancer (women 38.5% vs. men 33.9%, p < 0.03). Overall, gynecologists reported prescribing MHT to 48.9% of their symptomatic patients (women 47.3% vs. men 50.2%, p < 0.03) and 86.8% currently prescribed non-hormonal remedies and 83.8% alternative therapies for the management of the menopause. Gynecologists who were older and academic professionals prescribed MHT more often. CONCLUSION: Although this Latin American survey showed that gynecologists are mostly supporters of MHT use (for themselves or their partners), this is not necessarily reflected in their clinical practice.