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1.
Food Funct ; 15(10): 5613-5626, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38722062

RESUMEN

Modification of dairy proteins during processing impacts structural assemblies, influencing textural and nutritional properties of dairy products, and release and availability of amino acids during digestion. By modifying only pH, acid heat-set bovine dairy gels with divergent textural properties were developed to alter protein digestion. In vitro assay confirmed faster digestion of protein from a firm gel (pH 5.65) versus a soft gel (pH 6.55). We hypothesised that firm gel (FIRM-G; pH 5.6) would result in greater indispensable amino acid (IAA) appearance in circulation over 5 h and corresponding differences in gastric myoelectrical activity relative to soft gel (SOFT-G; pH 6.2). In a randomised, single-blind cross-over trial, healthy females (n = 20) consumed 150 g of each gel; plasma amino acid appearance was assessed over 5 hours. Iso-nitrogenous, iso-caloric gels were prepared from identical mixtures of bovine milk and whey protein concentrates; providing 17.7 g (FIRM-G) and 18.9 g (SOFT-G) of protein per serving. Secondary outcomes included gastric myoelectrical activity measured by body surface gastric mapping, glycaemic, triglyceridaemic, and subjective appetite and digestive responses. Overall plasma IAA (area under the curve) did not differ between gels. However, plasma IAA concentrations were higher, and increased more rapidly over time after SOFT-G compared with FIRM-G (1455 ± 53 versus 1350 ± 62 µmol L-1 at 30 min, p = 0.024). Similarly, total, branched-chain and dispensable amino acids were higher at 30 min with SOFT-G than FIRM-G (total: 3939 ± 97 versus 3702 ± 127 µmol L-1, p = 0.014; branched-chain: 677 ± 30 versus 619 ± 34 µmol L-1, p = 0.047; dispensable: 2334 ± 53 versus 2210 ± 76 µmol L-1, p = 0.032). All other measured parameters were similar between gels. Peak postprandial aminoacidaemia was higher and faster following ingestion of SOFT-G. Customised plasma amino acid appearance from dairy is achievable by altering gel coagulum structure using pH during processing and may have minimal influence on related postprandial responses, with implications for targeting food design for optimal health. The Clinical Trial Registry number is ACTRN12622001418763 (https://www.anzctr.org.au) registered November 7, 2022.


Asunto(s)
Aminoácidos , Estudios Cruzados , Geles , Femenino , Humanos , Adulto , Concentración de Iones de Hidrógeno , Aminoácidos/sangre , Aminoácidos/química , Geles/química , Animales , Adulto Joven , Bovinos , Digestión , Calor , Proteínas de la Leche/química , Método Simple Ciego , Estómago/fisiología , Estómago/química , Leche/química
2.
Am J Clin Nutr ; 119(5): 1200-1215, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38452857

RESUMEN

BACKGROUND: Heat treatments of dairy, including pasteurization and ultra-high temperature (UHT) processing, alter milk macromolecular structures, and ultimately affect digestion. In vitro, animal, and human studies show faster nutrient release or circulating appearance after consuming UHT milk (UHT-M) compared with pasteurized milk (PAST-M), with a faster gastric emptying (GE) rate proposed as a possible mechanism. OBJECTIVES: To investigate the impact of milk heat treatment on GE as a mechanism of faster nutrient appearance in blood. We hypothesized that GE and circulating nutrient delivery following consumption would be faster for UHT-M than PAST-M. METHODS: In this double-blind randomized controlled cross-over trial, healthy female (n = 20; 27.3 ± 1.4 y, mean ± SD) habitual dairy consumers, consumed 500 mL of either homogenized bovine UHT-M or PAST-M (1340 compared with 1320 kJ). Gastric content volume (GCV) emptying half-time (T50) was assessed over 3 h by magnetic resonance imaging subjective digestive symptoms, plasma amino acid, lipid and B vitamin concentrations, and gastric myoelectrical activity were measured over 5 h. RESULTS: Although GCV T50 did not differ (102 ± 7 min compared with 89 ± 8 min, mean ± SEM, UHT-M and PAST-M, respectively; P = 0.051), GCV time to emptying 25% of the volume was 31% longer following UHT-M compared with PAST-M (42 ± 2 compared with 32 ± 4 min, P = 0.004). Although GCV remained larger for a longer duration following UHT-M (treatment × time interaction, P = 0.002), plasma essential amino acid AUC was greater following UHT-M than PAST-M (55,324 ± 3809 compared with 36,598 ± 5673 µmol·min·L-1, P = 0.006). Heat treatment did not impact gastric myoelectrical activity, plasma appetite hormone markers or subjective appetite scores. CONCLUSIONS: Contrary to expectations, GE was slower with UHT-M, yet, as anticipated, aminoacidemia was greater. The larger GCV following UHT-M suggests that gastric volume may poorly predict circulating nutrient appearance from complex food matrices. Dairy heat treatment may be an effective tool to modify nutrient release by impacting digestion kinetics. CLINICAL TRIAL REGISTRY: www.anzctr.org.au (ACTRN12620000172909).


Asunto(s)
Estudios Cruzados , Vaciamiento Gástrico , Calor , Leche , Pasteurización , Femenino , Animales , Humanos , Leche/química , Adulto , Bovinos , Método Doble Ciego , Nutrientes , Adulto Joven
3.
Mol Nutr Food Res ; 68(6): e2300583, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38389156

RESUMEN

SCOPE: Piper excelsum (kawakawa) has a history of therapeutic use by Maori in Aotearoa New Zealand. It is currently widely consumed as a beverage and included as an ingredient in "functional" food product. Leaves contain compounds that are also found in a wide range of other spices, foods, and medicinal plants. This study investigates the human metabolism and excretion of kawakawa leaf chemicals. METHODS AND RESULTS: Six healthy male volunteers in one study (Bioavailability of Kawakawa Tea metabolites in human volunteers [BOKA-T]) and 30 volunteers (15 male and 15 female) in a second study (Impact of acute Kawakawa Tea ingestion on postprandial glucose metabolism in healthy human volunteers [TOAST]) consume a hot water infusion of dried kawakawa leaves (kawakawa tea [KT]). Untargeted Liquid Chromatography-Tandem Mass spectrometry (LC-MS/MS) analyses of urine samples from BOKA-T identified 26 urinary metabolites that are significantly associated with KT consumption, confirmed by the analysis of samples from the independent TOAST study. Seven of the 26 metabolites are also detected in plasma. Thirteen of the 26 urinary compounds are provisionally identified as metabolites of specific compounds in KT, eight metabolites are identified as being derived from specific compounds in KT but without resolution of chemical structure, and five are of unknown origin. CONCLUSIONS: Several kawakawa compounds that are also widely found in other plants are bioavailable and are modified by phase 1 and 2 metabolism.


Asunto(s)
Fitoquímicos , Piper , Humanos , Cromatografía Liquida , Piper/metabolismo , Hojas de la Planta , Espectrometría de Masas en Tándem , Fitoquímicos/metabolismo
4.
Redox Biol ; 67: 102878, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37703668

RESUMEN

Cruciferous-rich diets, particularly broccoli, have been associated with reduced risk of developing cancers of various sites, cardiovascular disease and type-2 diabetes. Sulforaphane (SF), a sulfur-containing broccoli-derived metabolite, has been identified as the major bioactive compound mediating these health benefits. Sulforaphane is a potent dietary activator of the transcription factor Nuclear factor erythroid-like 2 (NRF2), the master regulator of antioxidant cell capacity responsible for inducing cytoprotective genes, but its role in glucose homeostasis remains unclear. In this study, we set to test the hypothesis that SF regulates glucose metabolism and ameliorates glucose overload and its resulting oxidative stress by inducing NRF2 in human hepatoma HepG2 cells. HepG2 cells were exposed to varying glucose concentrations: basal (5.5 mM) and high glucose (25 mM), in the presence of physiological concentrations of SF (10 µM). SF upregulated the expression of glutathione (GSH) biosynthetic genes and significantly increased levels of reduced GSH. Labelled glucose and glutamine experiments to measure metabolic fluxes identified that SF increased intracellular utilisation of glycine and glutamate by redirecting the latter away from the TCA cycle and increased the import of cysteine from the media, likely to support glutathione synthesis. Furthermore, SF altered pathways generating NADPH, the necessary cofactor for oxidoreductase reactions, namely pentose phosphate pathway and 1C-metabolism, leading to the redirection of glucose away from glycolysis and towards PPP and of methionine towards methylation substrates. Finally, transcriptomic and targeted metabolomics LC-MS analysis of NRF2-KD HepG2 cells generated using CRISPR-Cas9 genome editing revealed that the above metabolic effects are mediated through NRF2. These results suggest that the antioxidant properties of cruciferous diets are intricately connected to their metabolic benefits.


Asunto(s)
Antioxidantes , Factor 2 Relacionado con NF-E2 , Humanos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Isotiocianatos/farmacología , Estrés Oxidativo , Glutatión/metabolismo , Homeostasis , Glucosa
5.
Nutrients ; 14(23)2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36501198

RESUMEN

The chemical profiles of kawakawa (Piper excelsum) leaves were analysed through targeted and non-targeted LC-MS/MS. The phytochemical profile was obtained for both aqueous extracts representative of kawakawa tea and methanolic extracts. Sixty-four compounds were identified from eight leaf sources including phenylpropanoids, lignans, flavonoids, alkaloids and amides. Eight of these compounds were absolutely quantified. The chemical content varied significantly by leaf source, with two commercially available sources of dried kawakawa leaves being relatively high in phenylpropanoids and flavonoids compared with field-collected fresh samples that were richer in amides, alkaloids and lignans. The concentrations of pharmacologically active metabolites ingested from the traditional consumption of kawakawa leaf as an aqueous infusion, or from novel use as a seasoning, are well below documented toxicity thresholds.


Asunto(s)
Alcaloides , Lignanos , Piper , Cromatografía Liquida , Espectrometría de Masas en Tándem , Hojas de la Planta/química , Fitoquímicos/química , Alcaloides/análisis , Extractos Vegetales/química , Flavonoides/análisis , Lignanos/química
6.
Nutrients ; 14(16)2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-36014767

RESUMEN

Diets rich in cruciferous vegetables have been associated with a lower risk of incidence and progression of prostate cancer. Sulforaphane, an isothiocyanate derived from 4-methylsulphinylbutyl glucosinolate (glucoraphanin) that accumulates in certain of these vegetables, notably broccoli, has been implicated in their protective effects. Likewise, the consumption of garlic and its sulphur-containing compounds such as alliin have been associated with a reduction in risk of prostate cancer. In this study, we tested whether consuming glucoraphanin derived from broccoli seeds and alliin derived from garlic resulted in the occurrence of these potential bioactive compounds in the prostate, which may contribute to our understanding of the putative protective effects of these dietary components. We recruited 42 men scheduled for a trans-perineal prostate biopsy into a randomised, double-blinded, 2 × 2-factorial dietary supplement four-week intervention study, and 39 completed the study. The two active interventions were supplements providing glucoraphanin from broccoli (BroccoMax®) and alliin from garlic (Kwai Heartcare®). Following the intervention, prostate biopsy tissue was analysed for the presence of sulforaphane and its thiol conjugates and for alliin and associated metabolites. Sulforaphane occurred in significantly higher levels in the prostate tissue (both within the transition and peripheral zone) of men consuming the glucoraphanin containing supplements (p < 0.0001) compared to men not consuming these supplements. However, while alliin and alliin-derived metabolites were detected within the prostate, there was no significant difference in the concentrations of these compounds in the prostate of men consuming supplements derived from garlic compared to men not consuming these supplements.


Asunto(s)
Allium , Brassica , Neoplasias de la Próstata , Antioxidantes/metabolismo , Brassica/metabolismo , Cisteína/análogos & derivados , Glucosinolatos/metabolismo , Humanos , Imidoésteres/metabolismo , Isotiocianatos/metabolismo , Masculino , Próstata/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/prevención & control , Sulfóxidos
7.
Eur Urol Oncol ; 5(4): 412-419, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35450835

RESUMEN

BACKGROUND: Bacteria play a suspected role in the development of several cancer types, and associations between the presence of particular bacteria and prostate cancer have been reported. OBJECTIVE: To provide improved characterisation of the prostate and urine microbiome and to investigate the prognostic potential of the bacteria present. DESIGN, SETTING, AND PARTICIPANTS: Microbiome profiles were interrogated in sample collections of patient urine (sediment microscopy: n = 318, 16S ribosomal amplicon sequencing: n = 46; and extracellular vesicle RNA-seq: n = 40) and cancer tissue (n = 204). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Microbiomes were assessed using anaerobic culture, population-level 16S analysis, RNA-seq, and whole genome DNA sequencing. RESULTS AND LIMITATIONS: We demonstrate an association between the presence of bacteria in urine sediments and higher D'Amico risk prostate cancer (discovery, n = 215 patients, p < 0.001; validation, n = 103, p < 0.001, χ2 test for trend). Characterisation of the bacterial community led to the (1) identification of four novel bacteria (Porphyromonas sp. nov., Varibaculum sp. nov., Peptoniphilus sp. nov., and Fenollaria sp. nov.) that were frequently found in patient urine, and (2) definition of a patient subgroup associated with metastasis development (p = 0.015, log-rank test). The presence of five specific anaerobic genera, which includes three of the novel isolates, was associated with cancer risk group, in urine sediment (p = 0.045, log-rank test), urine extracellular vesicles (p = 0.039), and cancer tissue (p = 0.035), with a meta-analysis hazard ratio for disease progression of 2.60 (95% confidence interval: 1.39-4.85; p = 0.003; Cox regression). A limitation is that functional links to cancer development are not yet established. CONCLUSIONS: This study characterises prostate and urine microbiomes, and indicates that specific anaerobic bacteria genera have prognostic potential. PATIENT SUMMARY: In this study, we investigated the presence of bacteria in patient urine and the prostate. We identified four novel bacteria and suggest a potential prognostic utility for the microbiome in prostate cancer.


Asunto(s)
Microbiota , Neoplasias de la Próstata , Bacterias/genética , Humanos , Masculino , Microbiota/genética , Próstata/patología , Neoplasias de la Próstata/patología , ARN Ribosómico 16S/genética
8.
Nutrients ; 13(11)2021 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-34836365

RESUMEN

Inconsistent conclusions from infant sleep and feeding studies may influence parents feeding-related decisions. This study aimed to systematically review the existing literature on infant sleep and its relation to the timing of introduction to complementary foods and type of milk feeding to better understand their role(s) in infant sleep. Cohort, longitudinal, cross-sectional studies, and controlled trials were identified using online searches of five databases up to April 2020. Twenty-one articles with a total of 6225 infants under 12 months-of-age were eligible. Exclusively breastfed infants (≤6 months-of-age) had a greater number of night wakings, but most studies (67%) reported no difference in night-time and 24 h sleep duration compared to formula-fed infants. However, after 6 months-of-age, most studies (>65%) reported breastfed infants to sleep less in the night-time and over 24 h compared to formula-fed infants. Furthermore, studies reported no association between the timing of introduction to complementary foods and infant sleep duration (<12 months-of-age). Future studies using standardized methodologies and definitions, transdisciplinary expertise, and longitudinal design are required to better understand the complex role of feeding on sleep.


Asunto(s)
Alimentos Infantiles/estadística & datos numéricos , Fórmulas Infantiles/estadística & datos numéricos , Fenómenos Fisiológicos Nutricionales del Lactante/fisiología , Leche/estadística & datos numéricos , Sueño/fisiología , Animales , Lactancia Materna/estadística & datos numéricos , Femenino , Humanos , Lactante , Masculino , Leche Humana , Factores de Tiempo
9.
Int J Mol Sci ; 22(9)2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-34068765

RESUMEN

Epigenetics refers to the DNA chemistry changes that result in the modification of gene transcription and translation independently of the underlying DNA coding sequence. Epigenetic modifications are reported to involve various molecular mechanisms, including classical epigenetic changes affecting DNA methylation and histone modifications and small RNA-mediated processes, particularly that of microRNAs. Epigenetic changes are reversible and are closely interconnected. They are recognised to play a critical role as mediators of gene regulation, and any alteration in these mechanisms has been identified to mediate various pathophysiological conditions. Moreover, genetic predisposition and environmental factors, including dietary alterations, lifestyle or metabolic status, are identified to interact with the human epigenome, highlighting the importance of epigenetic factors as underlying processes in the aetiology of various diseases such as MetS. This review will reflect on how both the classical and microRNA-regulated epigenetic changes are associated with the pathophysiology of metabolic syndrome. We will then focus on the various aspects of epigenetic-based strategies used to modify MetS outcomes, including epigenetic diet, epigenetic drugs, epigenome editing tools and miRNA-based therapies.


Asunto(s)
Epigénesis Genética , Código de Histonas/genética , Síndrome Metabólico/genética , Metilación de ADN , Regulación de la Expresión Génica/genética , Predisposición Genética a la Enfermedad , Histonas/genética , Humanos , Síndrome Metabólico/patología , MicroARNs/genética
10.
Eur J Nutr ; 60(4): 2141-2154, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33067661

RESUMEN

PURPOSE: Brassica are an important food source worldwide and are characterised by the presence of compounds called glucosinolates. Studies indicate that the glucosinolate derived bioactive metabolite sulphoraphane can elicit chemoprotective benefits on human cells. Glucosinolates can be metabolised in vivo by members of the human gut microbiome, although the prevalence of this activity is unclear. Brassica and Allium plants also contain S-methylcysteine sulphoxide (SMCSO), that may provide additional health benefits but its metabolism by gut bacteria is not fully understood. METHODS: We examined the effects of a broccoli leachate (BL) on the composition and function of human faecal microbiomes of five different participants under in vitro conditions. Bacterial isolates from these communities were then tested for their ability to metabolise glucosinolates and SMCSO. RESULTS: Microbial communities cultured in vitro in BL media were observed to have enhanced growth of lactic acid bacteria, such as lactobacilli, with a corresponding increase in the levels of lactate and short-chain fatty acids. Members of Escherichia isolated from these faecal communities were found to bioconvert glucosinolates and SMCSO to their reduced analogues. CONCLUSION: This study uses a broccoli leachate to investigate the bacterial-mediated bioconversion of glucosinolates and SMCSO, which may lead to further products with additional health benefits to the host. We believe that this is the first study that shows the reduction of the dietary compound S-methylcysteine sulphoxide by bacteria isolated from human faeces.


Asunto(s)
Brassica , Microbiota , Cisteína/análogos & derivados , Heces , Glucosinolatos , Humanos
11.
Physiol Rep ; 8(13): e14482, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32643289

RESUMEN

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) begins with steatosis, where a mixed macrovesicular pattern of large and small lipid droplets (LDs) develops. Since in vitro models recapitulating this are limited, the aims of this study were to develop mixed macrovesicular steatosis in immortalized hepatocytes and investigate effects on intracellular metabolism by altering nutritional substrates. METHODS: Huh7 cells were cultured in 11 mM glucose and 2% human serum (HS) for 7 days before additional sugars and fatty acids (FAs), either with 200 µM FAs (low fat low sugar; LFLS), 5.5 mM fructose + 200 µM FAs (low fat high sugar; LFHS), or 5.5 mM fructose + 800 µM FAs (high fat high sugar; HFHS), were added for 7 days. FA metabolism, lipid droplet characteristics, and transcriptomic signatures were investigated. RESULTS: Between the LFLS and LFHS conditions, there were few notable differences. In the HFHS condition, intracellular triacylglycerol (TAG) was increased and the LD pattern and distribution was similar to that found in primary steatotic hepatocytes. HFHS-treated cells had lower levels of de novo-derived FAs and secreted larger, TAG-rich lipoprotein particles. RNA sequencing and gene set enrichment analysis showed changes in several pathways including those involved in metabolism and cell cycle. CONCLUSIONS: Repeated doses of HFHS treatment resulted in a cellular model of NAFLD with a mixed macrovesicular LD pattern and metabolic dysfunction. Since these nutrients have been implicated in the development of NAFLD in humans, the model provides a good physiological basis for studying NAFLD development or regression in vitro.


Asunto(s)
Ácidos Grasos/metabolismo , Glucosa/metabolismo , Hepatocitos/metabolismo , Gotas Lipídicas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Línea Celular Tumoral , Células Cultivadas , Hepatocitos/patología , Humanos , Gotas Lipídicas/patología , Enfermedad del Hígado Graso no Alcohólico/genética , Transcriptoma
12.
Nutr J ; 19(1): 41, 2020 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-32398091

RESUMEN

BACKGROUND: A diet rich in fruits and vegetables is recommended for cardiovascular health. However, the majority of Australians do not consume the recommended number of vegetable servings each day. Furthermore, intakes of vegetables considered to have the greatest cardiovascular benefit are often very low. Results from prospective observational studies indicate that a higher consumption of cruciferous vegetables (e.g. broccoli, cabbage, cauliflower) is associated with lower cardiovascular disease risk. This may be due to the presence of specific nutrients and bioactive compounds found almost exclusively, or at relatively high levels, in cruciferous vegetables. Therefore, the aim of this randomised controlled crossover trial is to determine whether regular consumption of cruciferous vegetables results in short-term improvement in measures related to cardiovascular disease risk, including ambulatory blood pressure, arterial stiffness, glycaemic control, and circulating biomarkers of oxidative stress and inflammation. METHODS: Twenty-five participants (50-75 years) with mildly elevated blood pressure (systolic blood pressure 120-160 mmHg) will complete two 2-week intervention periods in random order, separated by a 2-week washout period. During the intervention period, participants will consume 4 servings (~ 300 g) of cruciferous vegetables per day as a soup (~ 500-600 mL/day). The 'control' soup will consist of other commonly consumed vegetables (potato, sweet potato, carrot, pumpkin). Both soups will be approximately matched for energy, protein, fat, and carbohydrate content. All measurements will be performed at the beginning and end of each intervention period. DISCUSSION: The findings of this study will provide evidence regarding the potential cardiometabolic health benefits of cruciferous vegetables, which may contribute to the revision of dietary and clinical guidelines. TRIAL REGISTRATION: The trial was registered with the Australian New Zealand Clinical Trial Registry on 19th September 2019 (ACTRN12619001294145).


Asunto(s)
Brassicaceae , Hipertensión/dietoterapia , Hipertensión/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Verduras , Anciano , Australia/epidemiología , Biomarcadores/metabolismo , Presión Sanguínea , Estudios Cruzados , Femenino , Control Glucémico , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Rigidez Vascular
13.
Mol Nutr Food Res ; 63(20): e1900461, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31410992

RESUMEN

SCOPE: Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates-thioglycosides that accumulate within crucifers. The possible role of S-methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives. The hypothesis that consuming a broccoli soup results in the accumulation of sulfate (a SMCSO derivative) and other broccoli-derived metabolites in prostate tissue is tested. METHODS AND RESULTS: Eighteen men scheduled for transperineal prostate biopsy were recruited into a 4-week parallel single blinded diet supplementation study (NCT02821728). Nine men supplemented their diet with three 300 mL portions of a broccoli soup each week for four weeks prior to surgery. Analyses of prostate biopsy tissues reveal no detectable levels of glucosinolates and derivatives. In contrast, SMCSO is detected in prostate tissues of the participants, with significantly higher levels in tissue of men in the supplementation arm. SMCSO was also found in blood and urine samples from a previous intervention study with the identical broccoli soup. CONCLUSION: The consequences of SMCSO accumulation in prostate tissues and its potential role in prevention of prostate cancer remains to be investigated.


Asunto(s)
Brassica , Próstata/metabolismo , Sulfóxidos/metabolismo , Anciano , Allium , Suplementos Dietéticos , Glucosinolatos/metabolismo , Humanos , Imidoésteres/metabolismo , Isotiocianatos/metabolismo , Masculino , Persona de Mediana Edad , Oximas , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/prevención & control , Método Simple Ciego
14.
Molecules ; 24(13)2019 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-31269651

RESUMEN

This is the first report describing an analytical method for quantitative analysis of two naturally occurring sulphur compounds, S-methyl-l-cysteine (SMC) and S-methyl-l-cysteine sulfoxide (SMCSO), in human body fluids using isotope-labelled internal standards and liquid chromatography-mass spectrometry (LC-MS)/MS techniques. This method was validated according to the guideline of the Royal Society of Chemistry Analytical Methods Committee. It offers significant advantages including simple and fast preparation of human biological samples. The limits of detection of SMC were 0.08 µM for urine and 0.04 µM for plasma. The limits of detection of SMCSO were 0.03 µM for urine and 0.02 µM for plasma. The calibration curves of all matrices showed linearity with correlation coefficients r2 > 0.9987. The intra and inter day precisions in three levels of known concentrations were >10% and >20%, respectively. The quantification accuracy was 98.28 ± 5.66%. The proposed method would be beneficial for the rapid and accurate determination of the SMC and SMCSO in human plasma and urine samples using by isotope labelled internal standards.


Asunto(s)
Cromatografía Liquida/métodos , Cisteína/análogos & derivados , Espectrometría de Masas en Tándem/métodos , Adolescente , Adulto , Anciano , Cisteína/sangre , Cisteína/síntesis química , Cisteína/química , Cisteína/orina , Femenino , Humanos , Marcaje Isotópico , Masculino , Persona de Mediana Edad , Estándares de Referencia , Reproducibilidad de los Resultados , Adulto Joven
15.
Am J Clin Nutr ; 109(4): 1133-1144, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30982861

RESUMEN

BACKGROUND: Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. OBJECTIVE: We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. METHODS: Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. RESULTS: In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial-mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. CONCLUSION: Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143.


Asunto(s)
Brassica/metabolismo , Glucosinolatos/metabolismo , Imidoésteres/metabolismo , Isotiocianatos/metabolismo , Próstata/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Oximas , Neoplasias de la Próstata/metabolismo , Sulfóxidos , Transcripción Genética , Adulto Joven
16.
Mol Nutr Food Res ; 62(18): e1700911, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29266773

RESUMEN

SCOPE: Broccoli accumulates 4-methylsulphinylbutyl glucosinolate (glucoraphanin) which is hydrolyzed to the isothiocyanate sulforaphane. Through the introgression of novel alleles of the Myb28 transcription factor from Brassica villosa, broccoli genotypes have been developed that have enhanced levels of glucoraphanin. This study seeks to quantify the exposure of human tissues to glucoraphanin and sulforaphane following consumption of broccoli with contrasting Myb28 genotypes. METHODS AND RESULTS: Ten participants are recruited into a three-phase, double-blinded, randomized crossover trial (NCT02300324), with each phase comprising consumption of 300 g of a soup made from broccoli of one of three Myb28 genotypes (Myb28B/B , Myb28B/V , Myb28V/V ). Plant myrosinases are intentionally denatured during soup manufacture. Threefold and fivefold higher levels of sulforaphane occur in the circulation following consumption of Myb28V/B and Myb28V/V broccoli soups, respectively. The percentage of sulforaphane excreted in 24 h relative to the amount of glucoraphanin consumed varies among volunteers from 2 to 15%, but does not depend on the broccoli genotype. CONCLUSION: This is the first study to report the bioavailability of glucoraphanin and sulforaphane from soups made with novel broccoli varieties. The presence of one or two Myb28V alleles results in enhanced delivery of sulforaphane to the systemic circulation.


Asunto(s)
Brassica/química , Glucosinolatos/farmacocinética , Imidoésteres/farmacocinética , Isotiocianatos/farmacocinética , Adolescente , Adulto , Anciano , Alelos , Disponibilidad Biológica , Brassica/genética , Estudios Cruzados , Dieta , Método Doble Ciego , Femenino , Genotipo , Técnicas de Genotipaje , Glucosinolatos/sangre , Glucosinolatos/orina , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Humanos , Isotiocianatos/sangre , Isotiocianatos/orina , Masculino , Persona de Mediana Edad , Oximas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sulfóxidos , Espectrometría de Masas en Tándem , Adulto Joven
17.
Oncotarget ; 8(49): 84902-84916, 2017 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-29156692

RESUMEN

The human prostate gland comprises three distinct anatomical glandular zones, namely the peripheral, central and transitional zones. Although prostate cancer can arise throughout the prostate, it is more frequent in the peripheral zone. In contrast, hyperplasia occurs most frequently in the transitional zone. In this paper, we test the hypothesis that peripheral and transitional zones have distinct metabolic adaptations that may underlie their different inherent predispositions to cancer and hyperplasia. In order to do this, we undertook RNA sequencing and high-throughput metabolic analyses of non-cancerous tissue from the peripheral and transitional zones of patients undergoing prostatectomy. Integrated analysis of RNAseq and metabolomic data revealed that transcription of genes involved in lipid biosynthesis is higher in the peripheral zone, which was mirrored by an increase in fatty acid metabolites, such as lysolipids. The peripheral zone also exhibited increased fatty acid catabolic activity and contained higher level of neurotransmitters. Such increased capacity for de novo lipogenesis and fatty acid oxidation, which is characteristic of prostate cancer, can potentially provide a permissive growth environment within the peripheral zone for cancer growth and also transmit a metabolic growth advantage to newly emerging clones themselves. This lipo-rich priming may explain the observed susceptibility of the peripheral zone to oncogenesis.

18.
Food Chem ; 234: 38-45, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28551250

RESUMEN

Despite its importance in many areas of human metabolism, there are no recommended daily intake guide lines for sulphur. It is generally assumed that most dietary sulphur originates from intake of methionine and cysteine. We estimated sulphur intake from food diaries, and validated the results with the use of a duplicate diet analyses. Sulphur intake estimations were highly correlated with that obtain through an elemental analysis of duplicate diets, with a mean±sd daily intakes of 956±327.9mg estimated from diet diary analyses and 935±329.9mg estimated by a duplicate diet analyses. Sulphur intake from alliaceous and cruciferous vegetables contributed up to 42% of total sulphur intake. Daily intake estimation comparisons through diet diary analyses and duplicate diet for other elements showed good agreement, except for sodium and zinc, in which analyses of 24h diet dairies overestimated intake by 35% and 52%, respectively.


Asunto(s)
Dieta , Azufre/administración & dosificación , Verduras/química , Registros de Dieta , Humanos
19.
Mol Nutr Food Res ; 61(9)2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28296348

RESUMEN

SCOPE: We examined whether a Brassica-rich diet was associated with an increase in the relative abundance of intestinal lactobacilli and sulphate-reducing bacteria (SRB), or alteration to the composition of the gut microbiota, in healthy adults. METHODS AND RESULTS: A randomised crossover study was performed with ten healthy adults who were fed a high- and a low-Brassica diet for 2-wk periods, with a 2-wk washout phase separating the diets. The high-Brassica diet consisted of six 84 g portions of broccoli, six 84 g portions of cauliflower and six 300 g portions of a broccoli and sweet potato soup. The low-Brassica diet consisted of one 84 g portion of broccoli and one 84 g portion of cauliflower. Faecal microbiota composition was measured in samples collected following 2-wk Brassica-free periods (consumption of all Brassica prohibited), and after each diet, whereby the only Brassica consumed was that supplied by the study team. No significant changes to the relative abundance of lactobacilli were observed (p = 0.8019). The increased consumption of Brassica was associated with a reduction in the relative abundance of SRB (p = 0.0215), and members of the Rikenellaceae, Ruminococcaceae, Mogibacteriaceae, Clostridium and unclassified Clostridiales (p < 0.01). CONCLUSION: The increased consumption of Brassica vegetables was linked to a reduced relative abundance of SRB, and therefore may be potentially beneficial to gastrointestinal health.


Asunto(s)
Bacterias/aislamiento & purificación , Brassica , Microbioma Gastrointestinal , Sulfatos/metabolismo , Adolescente , Adulto , Estudios Cruzados , Dieta , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Mol Nutr Food Res ; 59(5): 918-26, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25851421

RESUMEN

SCOPE: Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. METHODS AND RESULTS: One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%, -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). CONCLUSION: Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C.


Asunto(s)
Brassica , LDL-Colesterol/sangre , Glucosinolatos/administración & dosificación , Imidoésteres/administración & dosificación , Proteínas Quinasas Activadas por AMP/fisiología , Anciano , Apolipoproteínas E/genética , Dieta , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oximas , Fosfohidrolasa PTEN/fisiología , Fosfatidilinositol 3-Quinasas/fisiología , Polimorfismo de Nucleótido Simple , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfóxidos
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