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1.
Proc Natl Acad Sci U S A ; 120(23): e2216932120, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37252983

RESUMO

Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion-repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.


Assuntos
Cacau , Dieta , Humanos , Idoso , Suplementos Nutricionais , Polifenóis , Biomarcadores , Método Duplo-Cego
2.
Glycoconj J ; 40(6): 645-654, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37991561

RESUMO

Cardiovascular disease (CVD) is a group of health conditions affecting the heart and vascular system with very high prevalence and mortality rates. The presence of CVD is characterised by high levels of inflammation which have previously been associated with increased plasma concentrations of N-acetyl neuraminic acid (Neu5Ac). While Neu5Ac has been studied in the context of CVD, Neu5,9Ac2 has not, despite being the second most abundant sialic acid in human plasma. A small-scale pilot study of thirty plasma samples from patients with diagnosed CVD, and thirty age and sex-matched healthy controls, was designed to gain insight into sialic acids as biomarkers for CVD and potential future areas of study. Each sample was assayed for Neu5Ac and Neu5,9Ac2 concentrations. Mean Neu5Ac and Neu5,9Ac2 concentrations were significantly elevated in patients with CVD compared to healthy controls (Neu5Ac: P < 0.001; Neu5,9Ac2: P < 0.04). Receiver operator curve (ROC) analysis indicated that both Neu5Ac and Neu5,9Ac2 have reasonable predictive power for the presence of CVD (Neu5Ac AUC: 0.86; Neu5,9Ac2 AUC: 0.71). However, while Neu5Ac had both good sensitivity (0.82) and specificity (0.81), Neu5,9Ac2 had equivalent specificity (0.81) but very poor sensitivity (0.44). A combination marker of Neu5Ac + Neu5,9Ac2 showed improvement over Neu5Ac alone in terms of predictive power (AUC: 0.93), sensitivity (0.87), and specificity (0.90). Comparison to a known inflammatory marker, high sensitivity c-reactive protein (hs-CRP: P-value: NS, ROC:0.50) was carried out, showing that both Neu5Ac and Neu5,9Ac2 outperformed this marker. Further to this, hs-CRP values were combined with the three different sialic acid markers to determine any effect on the AUC values. A slight improvement in AUC was noted for each of the combinations, with Neu5Ac + Neu5,9Ac2 + hs-CRP giving the best AUC of 0.97 overall. Thus, Neu5Ac would appear to offer good potential as a predictive marker for the presence of CVD, which the addition of Neu5,9Ac2 predictive power improves, with further improvement seen by the addition of hs-CRP.


Assuntos
Doenças Cardiovasculares , Ácido N-Acetilneuramínico , Humanos , Proteína C-Reativa/análise , Doenças Cardiovasculares/diagnóstico , Projetos Piloto , Ácidos Siálicos/metabolismo , Biomarcadores
3.
Nutr Res Rev ; 36(2): 340-350, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35730561

RESUMO

The NOVA classification of food items has become increasingly popular and is being used in several observational studies as well as in nutritional guidelines and recommendations. We propose that there is a need for this classification and its use in the formulation of public health policies to be critically discussed and re-appraised. The terms 'processing' and 'ultra-processing', which are crucial to the NOVA classification, are ill-defined, as no scientific, measurable or precise reference parameters exist for them. Likewise, the theoretical grounds of the NOVA classification are unclear and inaccurate. Overall, the NOVA classification conflicts with the classic, evidence-based evaluation of foods based on composition and portion size because NOVA postulates that the food itself (or how much of it is eaten) is unimportant, but rather that dietary effects are due to how the food is produced. We contend that the NOVA system suffers from a lack of biological plausibility so the assertion that ultra-processed foods are intrinsically unhealthful is largely unproven, and needs further examination and elaboration.


Assuntos
Fast Foods , Alimento Processado , Humanos , Manipulação de Alimentos , Dieta
4.
Chembiochem ; 23(5): e202100662, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-34874597

RESUMO

N-Acetylneuraminic acid (sialic acid, Neu5Ac) is one of a large, diverse family of nine-carbon monosaccharides that play roles in many biological functions such as immune response. Neu5Ac has previously been identified as a potential biomarker for the presence and pathogenesis of cardiovascular disease (CVD), diabetes and cancer. More recent research has highlighted acetylated sialic acid derivatives, specifically Neu5,9Ac2 , as biomarkers for oral and breast cancers, but advances in analysis have been hampered due to a lack of commercially available quantitative standards. We report here the synthesis of 9-O- and 4-O-acetylated sialic acids (Neu5,9Ac2 and Neu4,5Ac2 ) with optimisation of previously reported synthetic routes. Neu5,9Ac2 was synthesised in 1 step in 68 % yield. Neu4,5Ac2 was synthesised in 4 steps in 39 % overall yield. Synthesis was followed by analysis of these standards via quantitative NMR (qNMR) spectroscopy. Their utilisation for the identification and quantification of specific acetylated sialic acid derivatives in biological samples is also demonstrated.


Assuntos
Ácido N-Acetilneuramínico , Ácidos Siálicos , Espectroscopia de Ressonância Magnética , Ácidos Siálicos/química
5.
Curr Atheroscler Rep ; 24(2): 119-132, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35098451

RESUMO

PURPOSE OF REVIEW: An abnormal lipid profile is considered a main risk factor for cardiovascular diseases and evidence suggests that single nucleotide polymorphisms (SNPs) in the cholesteryl ester transfer protein (CETP) gene contribute to variations in lipid levels in response to dietary intake. The objective of this review was to identify and discuss nutrigenetic studies assessing the interactions between CETP SNPs and dietary factors on blood lipids. RECENT FINDINGS: Relevant articles were obtained through a literature search of PubMed and Google Scholar through to July 2021. An article was included if it examined an interaction between CETP SNPs and dietary factors on blood lipids. From 49 eligible nutrigenetic studies, 27 studies reported significant interactions between 8 CETP SNPs and 17 dietary factors on blood lipids in 18 ethnicities. The discrepancies in the study findings could be attributed to genetic heterogeneity, and differences in sample size, study design, lifestyle and measurement of dietary intake. The most extensively studied ethnicities were those of Caucasian populations and majority of the studies reported an interaction with dietary fat intake. The rs708272 (TaqIB) was the most widely studied CETP SNP, where 'B1' allele was associated with higher CETP activity, resulting in lower high-density lipoprotein cholesterol and higher serum triglycerides under the influence of high dietary fat intake. Overall, the findings suggest that CETP SNPs might alter blood lipid profiles by modifying responses to diet, but further large studies in multiple ethnic groups are warranted to identify individuals at risk of adverse lipid response to diet.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol , Nutrigenômica , Proteínas de Transferência de Ésteres de Colesterol/genética , HDL-Colesterol , Dieta , Gorduras na Dieta , Genótipo , Humanos , Lipídeos
6.
Bioorg Med Chem ; 30: 115882, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33376017

RESUMO

N-Acetyl neuraminic acid (sialic acid) is a monosaccharide generally found as the terminating unit on glycans, which in turn are found on the surface of cells and glycoproteins. These glycans aid in a variety of biological functions such as cell interactions and immune response. Sialic acid has been identified as a biomarker for cardiovascular disease, diabetes and a range of other inflammatory and degenerative conditions. It has also been identified as a marker for different types of cancer. Sialic acid levels vary depending on the level of inflammation present during the course of an inflammatory disease and it is overexpressed by tumours as a shield against the immune system. Since the discovery of sialic acid, numerous assays have been developed for the identification and quantification of different sialic acid derivative monosaccharides and these assays fall into four main groups: colorimetric, fluorometric, enzymatic and chromatographic/mass spectrometric, with much overlap between these. Given the importance of sialic acids in biological pathways, this review article critically appraises assays that are used to detect and quantify sialic acid and its derivatives. Thus it details the method, sensitivity, specificity and wider scope of a range of assays, and concludes by suggesting some future directions for assay development and application. In this way, insight is provided into assays that allow for the accurate quantitation of sialic acid in biological samples, which may facilitate identification of the roles of sialic acid in healthy and disease pathways.


Assuntos
Ácidos Siálicos/análise , Fluorometria , Humanos , Estrutura Molecular
7.
Eur J Nutr ; 60(4): 2087-2097, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33030577

RESUMO

PURPOSE: It has been suggested that a high intake of sugar or sweeteners may result in an unfavorable microbiota composition; however, evidence is lacking. Hence, in this exploratory epidemiological study, we aim to examine if intake of added sugar, sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) associate with the gut microbiota composition. METHODS: Participants (18-70 years) in the Malmö Offspring Study have provided blood, urine, and fecal samples and completed both web-based 4 day food records and short food frequency questionnaires. The gut microbiota was assessed by 16S rRNA sequencing, processed in QIIME and matched to Greengenes (v.13.8), giving 64 included genera after filtering. Intake of added sugar (n = 1371) (also supported by the overnight urinary sugar biomarker in a subgroup n = 577), SSBs (n = 1086) and ASBs (n = 1085) were examined as exposures in negative binomial regressions. RESULTS: Various genera nominally associated with intake of added sugar, SSBs, and ASBs. Only the negative association between SSB intake and Lachnobacterium remained significant after multiple testing correction. A positive association between SSB intake and the Firmicutes:Bacteroidetes ratio was also observed. CONCLUSION: In this wide population, the cross-sectional associations between added sugar and sweet beverage intake and the gut microbiota are modest, but the results suggest that SSB intake is associated negatively with the genus Lachnobacterium and positively with the Firmicutes:Bacteroidetes ratio. Larger studies, preferably using metagenomic sequencing, are needed to further evaluate if a link exists between intake of sugars and sweeteners and the human gut microbiota.


Assuntos
Microbioma Gastrointestinal , Bebidas Adoçadas com Açúcar , Adolescente , Adulto , Idoso , Bebidas Adoçadas Artificialmente , Bebidas , Estudos Transversais , Humanos , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Açúcares , Edulcorantes/efeitos adversos , Adulto Jovem
8.
Eur J Nutr ; 60(6): 3029-3041, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33464363

RESUMO

PURPOSE: To examine the association between fructose intake in adolescence and fatty liver indices (hepatic steatosis index (HSI), fatty liver index (FLI)) in young adulthood. METHODS: Overall, 246 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had a fasting blood sample in adulthood (18-36 years), at least two 3-day weighed dietary records for calculating fructose intakes and other fructose-containing sugars (total (TS), free (FS), added sugar (AS)) as well as two complete 24-h urine samples for calculating sugar excretion (fructose excretion (FE), fructose + sucrose excretion (FE + SE)) in adolescence (males: 9.5-16.5 years; females: 8.5-15.5 years) were analysed using multivariable linear regression analyses. RESULTS: On the level of dietary intake, no prospective associations were observed between adolescent fructose intake and both adult fatty liver indices, whereas higher FS intakes were associated with lower levels of HSI (Ptrend = 0.02) and FLI (Ptrend = 0.03). On the urinary excretion level, however, a higher FE (Ptrend = 0.03) and FE + SE (Ptrend = 0.01) in adolescence were prospectively related to higher adult FLI values. No associations were observed between adolescent sugar excretion and adult HSI. CONCLUSION: The present study does not provide unambiguous support for a detrimental impact of adolescent fructose intake on adult liver health. Nonetheless, further examinations estimating exposure by means of urinary excretion as well as dietary intake levels appear warranted.


Assuntos
Fígado Gorduroso , Frutose , Adolescente , Adulto , Registros de Dieta , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/etiologia , Feminino , Frutose/efeitos adversos , Humanos , Masculino , Sacarose , Adulto Jovem
9.
Br J Nutr ; 124(2): 164-172, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32102699

RESUMO

Trend analyses based on dietary records suggest decreases in the intakes of total sugar (TS), added and free sugar since 2005 among children and adolescents in Germany. In terms of age trends, TS intake decreased with increasing age. However, self-reported sugar intake in epidemiological studies is criticised, as it may be prone to bias due to selective underreporting. Furthermore, adolescents are more susceptible to underreporting than children. We thus analysed time and age trends in urinary fructose excretion (FE), sucrose excretion (SE) and the sum of both (FE + SE) as biomarkers for sugar intake among 8·5-16·5-year-old adolescents. Urinary sugar excretion was measured by UPLC-MS/MS in 997 24-h urine samples collected from 239 boys and 253 girls participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study cohort between 1990 and 2016. Time and age trends of log-transformed FE, SE and FE + SE were analysed using polynomial mixed-effects regression models. Between 1990 and 2016, FE as well as FE + SE decreased (linear time trend: P = 0·0272 and P < 0·0001, respectively). A minor increase in excretion during adolescence was confined to FE (linear age trend: P = 0·0017). The present 24-h excretion measurements support a previously reported dietary record-based decline in sugar intake since 2005. However, the previously seen dietary record-based decrease in TS from childhood to late adolescence was not confirmed by our biomarker analysis, suggesting a constant sugar intake for the period of adolescence.

10.
Br J Nutr ; 121(5): 549-559, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30688188

RESUMO

Wholegrain oats are known to modulate the human gut microbiota and have prebiotic properties (increase the growth of some health-promoting bacterial genera within the colon). Research to date mainly attributes these effects to the fibre content; however, oat is also a rich dietary source of polyphenols, which may contribute to the positive modulation of gut microbiota. In vitro anaerobic batch-culture experiments were performed over 24 h to evaluate the impact of two different doses (1 and 3 % (w/v)) of oat bran, matched concentrations of ß-glucan extract or polyphenol mix, on the human faecal microbiota composition using 16S RNA gene sequencing and SCFA analysis. Supplementation with oats increased the abundance of Proteobacteria (P <0·01) at 10 h, Bacteroidetes (P <0·05) at 24 h and concentrations of acetic and propionic acid increased at 10 and 24 h compared with the NC. Fermentation of the 1 % (w/v) oat bran resulted in significant increase in SCFA production at 24 h (86 (sd 27) v. 28 (sd 5) mm; P <0·05) and a bifidogenic effect, increasing the relative abundance of Bifidobacterium unassigned at 10 h and Bifidobacterium adolescentis (P <0·05) at 10 and 24 h compared with NC. Considering the ß-glucan treatment induced an increase in the phylum Bacteroidetes at 24 h, it explains the Bacteriodetes effects of oats as a food matrix. The polyphenol mix induced an increase in Enterobacteriaceae family at 24 h. In conclusion, in this study, we found that oats increased bifidobacteria, acetic acid and propionic acid, and this is mediated by the synergy of all oat compounds within the complex food matrix, rather than its main bioactive ß-glucan or polyphenols. Thus, oats as a whole food led to the greatest impact on the microbiota.


Assuntos
Avena/química , Bacteroidetes/efeitos dos fármacos , Bifidobacterium/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Grãos Integrais , Ácido Acético/metabolismo , Fezes/microbiologia , Fermentação/efeitos dos fármacos , Humanos , Polifenóis/farmacologia , Prebióticos , Propionatos/metabolismo , Proteobactérias/efeitos dos fármacos , beta-Glucanas/farmacologia
11.
Environ Health ; 18(1): 87, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623611

RESUMO

BACKGROUND: Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor. METHODS: Twenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (< 1.5 mg/L), whereas in week 2, nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight. At baseline, after 1 and 2 weeks, faeces and 24 h urine samples were collected for analyses of nitrate, apparent total N-nitroso compounds (ATNC), compliance markers, and genotoxic potential in human colonic Caco-2 cells. RESULTS: Urinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types. Furthermore, levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat (i.e. 1-Methylhistidine levels), or unprocessed white meat (i.e. 3-Methylhistidine). ATNC levels significantly increased during the high drinking water nitrate period, which was more pronounced in the processed red meat group. Genotoxicity in Caco-2 cells exposed to faecal water resulted in increased genotoxicity after the interventions, but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat. Furthermore, a positive correlation was found between the ratio of nitrate/vitamin C intake (including drinking water) and the level of ATNC in faecal water of subjects in the processed red meat group, but this was not statistically significant. CONCLUSIONS: Drinking water nitrate significantly contributed to the endogenous formation of NOC, independent of the meat type consumed. This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC. TRIAL REGISTRATION: Dutch Trialregister: 29707 . Registered 19th of October 2018. Retrospectively registered.


Assuntos
Água Potável/química , Carne , Nitratos/análise , Compostos Nitrosos/metabolismo , Adulto , Animais , Galinhas , Feminino , Humanos , Masculino , Carne/classificação , Produtos da Carne , Países Baixos , Músculos Peitorais , Projetos Piloto , Carne de Porco , Distribuição Aleatória , Perus , Adulto Jovem
12.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072023

RESUMO

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete's health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances.


Assuntos
Antioxidantes/administração & dosagem , Desempenho Atlético , Beta vulgaris/química , Nitratos/administração & dosagem , Adolescente , Adulto , Antioxidantes/química , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/urina , Suplementos Nutricionais , Feminino , Sucos de Frutas e Vegetais , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/química , Nitratos/urina , Nitritos/urina , Compostos Nitrosos/urina , Raízes de Plantas/química , Adulto Jovem
13.
J Nutr ; 153(7): 1848-1849, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37419548
14.
Proc Natl Acad Sci U S A ; 112(34): E4651-60, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26224837

RESUMO

Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of H2S/sulfide signaling, but their biosynthesis and relationship to NO remain enigmatic. We sought to characterize the nature, chemical biology, and bioactivity of key reaction products formed in the NO/sulfide system. At physiological pH, we find that NO and sulfide form a network of cascading chemical reactions that generate radical intermediates as well as anionic and uncharged solutes, with accumulation of three major products: nitrosopersulfide (SSNO(-)), polysulfides, and dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each with a distinct chemical biology and in vitro and in vivo bioactivity. SSNO(-) is resistant to thiols and cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers blood pressure. Polysulfides are both intermediates and products of SSNO(-) synthesis/decomposition, and they also decrease blood pressure and enhance arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases mainly N2O on decomposition; although it affects blood pressure only mildly, it markedly increases cardiac contractility, and formation of its precursor sulfite likely contributes to NO scavenging. Our results unveil an unexpectedly rich network of coupled chemical reactions between NO and H2S/sulfide, suggesting that the bioactivity of either transmitter is governed by concomitant formation of polysulfides and anionic S/N-hybrid species. This conceptual framework would seem to offer ample opportunities for the modulation of fundamental biological processes governed by redox switching and sulfur trafficking.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Óxidos de Nitrogênio/metabolismo , Sulfetos/metabolismo , Animais , Disponibilidade Biológica , Masculino , Nitrogênio/metabolismo , Ratos Wistar , Enxofre/metabolismo
15.
J Nutr ; 152(9): 2009-2010, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35939358
16.
Nutr Cancer ; 69(2): 289-298, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28094544

RESUMO

Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, α-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this nitroso compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.


Assuntos
Lythraceae/química , Carne/efeitos adversos , Extratos Vegetais/farmacologia , Lesões Pré-Cancerosas/dietoterapia , Vinho , Animais , Biomarcadores/urina , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , Fezes , Mucinas Gástricas/metabolismo , Peroxidação de Lipídeos , Masculino , Carne/análise , Lesões Pré-Cancerosas/induzido quimicamente , Ratos Endogâmicos F344 , alfa-Tocoferol/farmacologia
17.
Pharmacol Res ; 122: 127-129, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28610958

RESUMO

Nitrate (NO3-)-rich foods such as green leafy vegetables are not only part of a healthy diet, but increasingly marketed for primary prevention of cardiovascular disease (CVD) and used as ergogenic aids by competitive athletes. While there is abundant evidence for mild hypotensive effects of nitrate on acute application there is limited data on chronic intake in humans, and results from animal studies suggest no long-term benefit. This is important as nitrate can also promote the formation of nitrosamines. It is therefore classified as 'probably carcinogenic to humans', although a beneficial effect on CVD risk might compensate for an increased cancer risk. Dietary nitrate requires reduction to nitrite (NO2-) by oral commensal bacteria to contribute to the formation of nitric oxide (NO). The extensive crosstalk between NO and hydrogen sulfide (H2S) related metabolites may further affect nitrate's bioactivity. Using nitrate and nitrite concentrations of drinking water - the only dietary source continuously monitored for which detailed data exist - in conjunction with data of >14,000 participants of the EPIC-Norfolk study, we found no inverse associations with blood pressure or CVD risk. Instead, we found a strong interaction with sulfate (SO42-). At low sulfate concentrations, nitrate was inversely associated with BP (-4mmHg in top quintile) whereas this was reversed at higher concentrations (+3mmHg in top quintile). Our findings have a potentially significant impact for pharmacology, physiology and public health, redirecting our attention from the oral microbiome and mouthwash use to interaction with sulfur-containing dietary constituents. These results also indicate that nitrate bioactivation is more complex than hitherto assumed. The modulation of nitrate bioactivity by sulfate may render dietary lifestyle interventions aimed at increasing nitrate intake ineffective and even reverse potential antihypertensive effects, warranting further investigation.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/metabolismo , Nitratos/metabolismo , Nitrogênio/metabolismo , Sulfatos/metabolismo , Enxofre/metabolismo , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Dieta , Humanos , Óxido Nítrico/metabolismo , Nitritos/metabolismo
18.
J Nutr ; 151(3): 457-458, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33443289
19.
Br J Nutr ; 114(8): 1246-55, 2015 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-26348767

RESUMO

Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-mediated vasodilation (FMD)) that plateaued after 2 weeks. Subsequently, in a randomised, controlled, double-masked, parallel-group dietary intervention trial (Clinicaltrials.gov: NCT01799005), 100 healthy, middle-aged (35-60 years) men and women consumed either the CF-containing drink (450 mg) or a nutrient-matched CF-free control bi-daily for 1 month. The primary end point was FMD. Secondary end points included plasma lipids and blood pressure, thus enabling the calculation of Framingham Risk Scores and pulse wave velocity. At 1 month, CF increased FMD over control by 1·2 % (95 % CI 1·0, 1·4 %). CF decreased systolic and diastolic blood pressure by 4·4 mmHg (95 % CI 7·9, 0·9 mmHg) and 3·9 mmHg (95 % CI 6·7, 0·9 mmHg), pulse wave velocity by 0·4 m/s (95 % CI 0·8, 0·04 m/s), total cholesterol by 0·20 mmol/l (95 % CI 0·39, 0·01 mmol/l) and LDL-cholesterol by 0·17 mmol/l (95 % CI 0·32, 0·02 mmol/l), whereas HDL-cholesterol increased by 0·10 mmol/l (95 % CI 0·04, 0·17 mmol/l). By applying the Framingham Risk Score, CF predicted a significant lowering of 10-year risk for CHD, myocardial infarction, CVD, death from CHD and CVD. In healthy individuals, regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk, demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects.


Assuntos
Cacau/química , Endotélio Vascular/efeitos dos fármacos , Flavonóis/administração & dosagem , Adulto , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Onda de Pulso , Fatores de Risco , Resultado do Tratamento , Vasodilatação/efeitos dos fármacos
20.
Public Health Nutr ; 18(15): 2815-24, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25702697

RESUMO

OBJECTIVE: The objective of the present study was to investigate associations between sugar intake and overweight using dietary biomarkers in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). DESIGN: Prospective cohort study. SETTING: EPIC-Norfolk in the UK, recruitment between 1993 and 1997. SUBJECTS: Men and women (n 1734) aged 39-77 years. Sucrose intake was assessed using 7 d diet diaries. Baseline spot urine samples were analysed for sucrose by GC-MS. Sucrose concentration adjusted by specific gravity was used as a biomarker for intake. Regression analyses were used to investigate associations between sucrose intake and risk of BMI>25·0 kg/m2 after three years of follow-up. RESULTS: After three years of follow-up, mean BMI was 26·8 kg/m2. Self-reported sucrose intake was significantly positively associated with the biomarker. Associations between the biomarker and BMI were positive (ß=0·25; 95 % CI 0·08, 0·43), while they were inverse when using self-reported dietary data (ß=-1·40; 95 % CI -1·81, -0·99). The age- and sex-adjusted OR for BMI>25·0 kg/m2 in participants in the fifth v. first quintile was 1·54 (95 % CI 1·12, 2·12; P trend=0·003) when using biomarker and 0·56 (95 % CI 0·40, 0·77; P trend<0·001) with self-reported dietary data. CONCLUSIONS: Our results suggest that sucrose measured by objective biomarker but not self-reported sucrose intake is positively associated with BMI. Future studies should consider the use of objective biomarkers of sucrose intake.


Assuntos
Índice de Massa Corporal , Dieta/efeitos adversos , Sacarose Alimentar/efeitos adversos , Comportamento Alimentar , Obesidade/etiologia , Adulto , Idoso , Biomarcadores/urina , Registros de Dieta , Sacarose Alimentar/urina , Inglaterra , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias , Estado Nutricional , Obesidade/urina , Razão de Chances , Sobrepeso , Estudos Prospectivos , Fatores de Risco , Autorrelato
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