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The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study.
Bauersfeld, SP, Kessler, CS, Wischnewsky, M, Jaensch, A, Steckhan, N, Stange, R, Kunz, B, Brückner, B, Sehouli, J, Michalsen, A
BMC cancer. 2018;18(1):476
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Short-term fasting (STF) has been shown to protect healthy cells against the adverse effects of chemotherapy while making tumor cells more vulnerable to it. The present randomised pilot cross-over study was designed to assess the effect of a 60 hour STF on quality of life (QOL), well-being and fatigue in patients with gynaecological cancer undergoing chemotherapy. Group A was randomised to a STF during the first three of six scheduled chemotherapies (36 h before to 24 h after the chemotherapy) followed by non-calorie restricted nutrition during the following three chemotherapies. During the fasting period subjects received unrestricted amounts of water, herbal tea, 2x100cl vegetable juice and small standardized quantities of light vegetable broth with a maximum total daily energy intake of 350 kcal. Group B was allocated to a vice versa sequence of nutrition. All measurements were performed at baseline and eight days after each chemotherapy cycle. A variety of questionnaires were used for assessment of QOL, general well-being and fatigue. 34 patients with breast or ovarian cancer completed the study. Fasting was safe and all reported side effects were of low grade. STF led to a better tolerance to chemotherapy with less compromised QOL and reduced fatigue within the 8 days after chemotherapy. At the final consultation the majority of patients reported better tolerance to chemotherapy with STF. The authors conclude that STF during chemotherapy is feasible and has beneficial effects on QOL, well-being and fatigue.
Abstract
BACKGROUND This pilot trial aimed to study the feasibility and effects on quality of life (QOL) and well-being of short-term fasting (STF) during chemotherapy in patients with gynecological cancer. METHODS In an individually-randomized cross-over trial patients with gynecological cancer, 4 to 6 planned chemotherapy cycles were included. Thirty-four patients were randomized to STF in the first half of chemotherapies followed by normocaloric diet (group A;n = 18) or vice versa (group B;n = 16). Fasting started 36 h before and ended 24 h after chemotherapy (60 h-fasting period). QOL was assessed by the FACIT-measurement system. RESULTS The chemotherapy-induced reduction of QOL was less than the Minimally Important Difference (MID; FACT-G = 5) with STF but greater than the MID for non-fasted periods. The mean chemotherapy-induced deterioration of total FACIT-F was 10.4 ± 5.3 for fasted and 27.0 ± 6.3 for non-fasted cycles in group A and 14.1 ± 5.6 for non-fasted and 11.0 ± 5.6 for fasted cycles in group B. There were no serious adverse effects. CONCLUSION STF during chemotherapy is well tolerated and appears to improve QOL and fatigue during chemotherapy. Larger studies should prove the effect of STF as an adjunct to chemotherapy. TRIAL REGISTRATION This trial was registered at clinicaltrials.gov: NCT01954836 .
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Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.
Murtola, TJ, Vihervuori, VJ, Lahtela, J, Talala, K, Taari, K, Tammela, TL, Auvinen, A
British journal of cancer. 2018;118(9):1248-1254
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Studies have shown that people with diabetes mellitus have lower risk of developing prostate cancer compared with non-diabetics. Glucose metabolism (the process by which simple sugars found in food are processed and used to produce energy) may have an independent role in prostate cancer development and progression. The aim of this study was to investigate the associations between fasting blood glucose and glycaemic control and prostate cancer risk. The study recruited 80,144 men who were randomly assigned either to be screened with PSA at four-year intervals (the screening arm, 31,866 men) or to control arm with no intervention and followed through national registries (48,278 men). Results indicate an association between fasting blood glucose level and elevated prostate cancer risk. This association was more noticeable in the screening arm, and concerned both poorly and well-differentiated cancers. Furthermore, compared to the normoglycemic men, overall prostate cancer risk was elevated in diabetic, but not in pre-diabetic men. Authors conclude that diabetic fasting blood glucose level is associated with elevated prostate cancer risk in a population-based cohort of Finnish men.
Abstract
BACKGROUND Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycaemia is unclear. In this cohort study, we estimated PCa risk among men with diabetic fasting blood glucose level. METHODS Participants of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to laboratory database for information on glucose measurements since 1978. The data were available for 17,860 men. Based on the average yearly level, the men were categorised as normoglycaemic, prediabetic, or diabetic. Median follow-up was 14.7 years. Multivariable-adjusted Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for prostate cancer overall and separately by Gleason grade and metastatic stage. RESULTS In total 1,663 PCa cases were diagnosed. Compared to normoglycaemic men, those men with diabetic blood glucose level had increased risk of PCa (HR 1.52; 95% CI 1.31-1.75). The risk increase was observed for all tumour grades, and persisted for a decade afterwards. Antidiabetic drug use removed the risk association. Limitations include absence of information on lifestyle factors and limited information on BMI. CONCLUSIONS Untreated diabetic fasting blood glucose level may be a prostate cancer risk factor.
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Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention.
Abbaoui, B, Lucas, CR, Riedl, KM, Clinton, SK, Mortazavi, A
Molecular nutrition & food research. 2018;62(18):e1800079
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Worldwide, almost 400,000 cases of bladder cancer are diagnosed each year, with 150,000 deaths, a high rate of recurrence and a high treatment cost. This review article evaluates the literature regarding the potential role of cruciferous vegetables (broccoli, cauliflower, cabbages, pak choi, watercress, wasabi are all examples of cruciferous vegetables) in bladder cancer prevention and as an adjunct to current treatment protocols. In vitro studies have shown inhibition of bladder cancer cell reproduction, stalled cancer cell cycles, and cancer cell death by compounds in cruciferous vegetables, in particular sulphoraphane (known to be high in broccoli and broccoli sprouts) and erucin (available in rocket for example). Studies show an inverse relationship between cruciferous vegetable intake and risk of bladder cancer, with those consuming 2 or more portions per week having a 39% lower risk of bladder cancer than those who consume less than 1 portion per week. The review also looks at cooking method, with steaming, stir-frying and sauteeing protecting the important nutrients when compared to boiling. The authors call for pre-clinical studies to be performed, examining multiple formulations of cruciferous vegetables in a variety of bladder cancer models, looking at prevention in high risk groups and adjuvant to standard treatment protocols. Nutrition Practitioners may want to consider including regular intake of cruciferous vegetables in their client protocols.
Abstract
Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although not yet completely understood, many mechanisms of anticancer activity at the steps of cancer initiation, promotion, and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro-growth, pro-survival, pro-inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their antitumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden.
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The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial.
Myette-Côté, É, Durrer, C, Neudorf, H, Bammert, TD, Botezelli, JD, Johnson, JD, DeSouza, CA, Little, JP
American journal of physiology. Regulatory, integrative and comparative physiology. 2018;315(6):R1210-R1219
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Inflammation is associated with the pathogenesis of insulin resistance, type 2 diabetes (T2D), and related complications. Lifestyle therapy is a frontline treatment for improving glucose control in people with T2D. The main aim of this study was to determine whether reducing hyperglycaemia with a low-carbohydrate high-fat (LC) diet could lower markers of innate immune cell activation and systemic inflammation in people with T2D. A secondary aim was to examine if the combination of an LCHF diet with strategically timed postmeal walking was superior to an LCHF diet alone. The study is a randomised cross over study which enrolled Individuals with physician-diagnosed T2D to complete three short-term controlled-intervention periods. Sixteen participants were enrolled (men = 8 and women = 8) who were aged between 48 and 72 years. Results indicate that while LC and LC together with exercise (LC+Ex) led to superior improvements in glucose control and fasting proinsulin (the pro-hormone precursor to insulin) levels as compared with low-fat low glycaemic index diet (GL), all three diets (GL, LC and LC+Ex), appeared to lower a particular marker of cellular inflammation over the short-term. Authors conclude that an LCHF diet with or without daily postmeal walks improved four-day glycaemic control and fasting proinsulin levels compared with a GL diet.
Abstract
Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (-5%, P < 0.05), whereas both LC+Ex (-16%, P < 0.001) and LC (-12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: -32%, LC: -45%, and LC+Ex: -44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (-76%, P = 0.035) and a tendency for a reduction in LC (-70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (-27%, P = 0.001) and LC+Ex (-35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.
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Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk.
Frühbeck, G, Catalán, V, Rodríguez, A, Gómez-Ambrosi, J
Adipocyte. 2018;7(1):57-62
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Obesity is medically defined as a condition of abnormal or excessive fat accumulation in adipose tissue, of sufficient extent to produce adverse health consequences. Presently, adipose tissue has emerged as an extremely active endocrine organ, based on its ability to secrete a plethora of biologically active adipokines [a class of cytokine mediators that are predominantly secreted by adipose cells] such as leptin and adiponectin. Furthermore, obesity is characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Thus, the adiponectin/leptin ratio has been suggested as a marker of adipose tissue dysfunction. A dysfunctional adipose tissue, evidenced by a lower adiponectin/ leptin ratio, is a clear contributor to the low-grade chronic inflammation associated with metabolic syndrome. Authors conclude that this ratio is highly and negatively correlated with markers of low-grade chronic inflammation emerging as a useful estimator of obesity- and metabolic syndrome- associated cardiometabolic risk.
Abstract
Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk.
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Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population.
Johansson, I, Nilsson, LM, Esberg, A, Jansson, JH, Winkvist, A
Nutrition journal. 2018;17(1):110
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Dairy intake and mortality has been evaluated in many studies but the results have been inconclusive. The aim of this cross-sectional and longitudinal study was to evaluate the association between different types of dairy products and metabolic risk markers for cardiovascular disease. Utilising data from the Swedish Vasterbotten Intervention Programme, 90,512 participants completed a food frequency questionnaire and had metabolic risk markers measured for the cross-sectional component of this study. From this cohort, 27,682 subjects returned within 8-11 years to complete the longitudinal component. Dairy intake was further classified as non-fermented milk, fermented milk, cheese and butter. Based on this cross-sectional and longitudinal data, the likelihood of having an undesirable body mass index (BMI) decreased with increasing amount of total dairy, cheese and butter intake, but increased with increasing non-fermented milk intake. According to these results, the authors conclude confounding variables are likely influencing the association between dairy intake and metabolic disease and suggest future studies be stratified by dairy type.
Abstract
BACKGROUND The association between milk and dairy intake and the incidence of cardiometabolic diseases, cancer and mortality has been evaluated in many studies, but these studies have had conflicting results with no clear conclusion on causal or confounding associations. The present study aims to further address this association by cross-sectional and longitudinal evaluation of the associations between exposure to various types of dairy products and metabolic risk markers among inhabitants in northern Sweden while taking other lifestyle factors into account. METHODS Respondents in the Västerbotten Intervention Programme with complete and plausible diet data between 1991 and 2016 were included, yielding 124,934 observations from 90,512 unique subjects. For longitudinal analysis, 27,682 participants with a visit 8-12 years after the first visit were identified. All participants completed a validated Food Frequency Questionnaire. Metabolic risk markers, including body mass index (BMI), blood pressure, serum (S) cholesterol and triglycerides, and blood glucose, were measured. Participants were categorized into quintiles by intake of dairy products, and risk (odds ratios, OR) of undesirable levels of metabolic risk markers was assessed in multivariable logistic regression analyses. In longitudinal analyses, intake quintiles were related to desirable levels of metabolic risk markers at both visits or deterioration at follow-up using Cox regression analyses. RESULTS The OR of being classified with an undesirable BMI decreased with increasing quintiles of total dairy, cheese and butter intake but increased with increasing non-fermented milk intake. The OR of being classified with an undesirable S-cholesterol level increased with increasing intake of total dairy, butter and high fat (3%) non-fermented milk, whereas an undesirable S-triglyceride level was inversely associated with cheese and butter intake in women. In longitudinal analyses, increasing butter intake was associated with deterioration of S-cholesterol and blood glucose levels, whereas increasing cheese intake was associated with a lower risk of deterioration of S-triglycerides. CONCLUSIONS Confounding factors likely contribute to the demonstrated association between dairy intake and mortality, and other medical conditions and analyses should be stratified by dairy type.
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Association of dietary patterns, anthropometric measurements, and metabolic parameters with C-reactive protein and neutrophil-to-lymphocyte ratio in middle-aged and older adults with metabolic syndrome in Taiwan: a cross-sectional study.
Syauqy, A, Hsu, CY, Rau, HH, Chao, JC
Nutrition journal. 2018;17(1):106
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Metabolic syndrome, which is classified as having high blood pressure, obesity, high blood glucose and high cholesterol, is believed to be a consequence of the Westernised diet and lifestyle, which has become increasingly common place in several countries worldwide. The Westernised diet comprises of a high intake of saturated fats, meats, processed foods, sweets, salt and food additives, all of which can add to the burden of inflammatory processes. The objective of this cross-sectional study was to investigate associations evident between diet, body composition and metabolic measurements (such as BMI and blood pressure) with inflammatory markers; C-reactive protein and neutrophil-to-lymphocyte ratio (inflammatory markers that increase in response to inflammation), in adults diagnosed with metabolic syndrome. Researchers found that regardless of gender or age, there was a direct association with C-reactive protein and neutrophil-to-lymphocyte ratio and metabolic syndrome. The subjects who consumed a higher amount of ‘Westernised foods’ showed higher levels of inflammatory markers when compared to those who a consumed a more healthful diet.
Abstract
BACKGROUND Metabolic syndrome is commonly associated with inflammation. The underlying factors of inflammation in metabolic syndrome are not fully understood. The objective of the study was to determine the association of dietary patterns, anthropometric measurements, and metabolic parameters with inflammatory markers in middle-aged and older adults with metabolic syndrome in Taiwan. METHODS A total of 26,016 subjects aged ≥35 y with metabolic syndrome were recruited from Mei Jau institution between 2004 and 2013 for a cross sectional study. Metabolic syndrome was defined by the International Diabetes Federation. Multivariate logistic regression was performed to evaluate the association of dietary patterns, anthropometric measurements, and metabolic parameters with C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in men and women with metabolic syndrome. Crude and adjusted models were analyzed by gender. RESULTS The western dietary pattern, obesity, high body fat, high waist or hip circumference, and high waist-to-hip ratio were significantly associated with increased odds ratios of high CRP and NLR in both genders. High systolic or diastolic blood pressure (BP), low high-density lipoprotein-cholesterol (HDL-C), high low-density lipoprotein-cholesterol (LDL-C), high total cholesterol (TC), high serum triglycerides (TG), and high fasting blood glucose (FBG) were significantly correlated with increased odds ratios of high CRP in both genders. Low HDL-C, high LDL-C, high serum TG, and high FBG were significantly associated with increased odds ratios of high NLR in both genders. However, high systolic (OR = 1.124, 95% CI 1.047-1.206, P < 0.01) or diastolic BP (OR = 1.176, 95% CI 1.087-1.273, P < 0.001) and high TC (OR = 1.138, 95% CI 1.062-1.220, P < 0.001) were significantly correlated with increased odds ratios of high NLR only in men. CONCLUSIONS The western dietary pattern, obese-related anthropometric parameters, and most components of metabolic syndrome are positively associated with CRP levels and NLR in men and women with metabolic syndrome.
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A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight.
Joseph, TP, Chanda, W, Padhiar, AA, Batool, S, LiQun, S, Zhong, M, Huang, M
Integrative cancer therapies. 2018;17(2):200-209
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Globally, the morbidity and mortality rate because of cancer is increasing constantly. Life scientists are focusing more aggressively on the development of novel agents exhibiting antitumor and anti-metastatic (inhibiting the spread of cancer cells to new areas of the body) potential with no or minimal side effects. The main aims of the study were to: (i) briefly portray a picture of genetic alterations associated with specific signalling pathways and their role in the initiation and progression of cancer, and (ii) emphasize the antitumor potential of mushroom origin compounds in a signalling pathway-specific manner. Through the literature-based evidence presented in this review, authors can anticipate the molecular mechanism of different mushroom originated compounds, where they exhibit anticancer potential through modulating different nodes of specific signalling pathways, and thus affecting a variety of cellular processes. Authors conclude that the review provides the possible molecular insight of the action of mushroom origin compounds which may be helpful in designing anticancer arsenals from mushroom for combating cancer.
Abstract
Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity. Many researchers, including our own group, are focusing on the anticancer potential of different mushrooms and the underlying molecular mechanism behind their action. The aim of this review is to discuss PI3K/AKT, Wnt-CTNNB1, and NF-κB signaling pathways, the occurrence of genetic alterations in them, the association of these aberrations with different human cancers and how different nodes of these pathways are targeted by various substances of mushroom origin. We have given evidence to propose the therapeutic attributes and possible mode of molecular actions of various mushroom-originated compounds. However, anticancer effects were typically demonstrated in in vitro and in vivo models and very limited number of studies have been conducted in the human population. It is our belief that this review will help the research community in designing concrete preclinical and clinical studies to test the anticancer potential of mushroom-originated compounds on different cancers harboring particular genetic alteration(s).
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Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in individuals affected by overweight and obesity: a randomized controlled trial.
Kopf, JC, Suhr, MJ, Clarke, J, Eyun, SI, Riethoven, JM, Ramer-Tait, AE, Rose, DJ
Nutrition journal. 2018;17(1):72
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Poor diet is the leading risk factor for premature death and disability in the United States. Poor diets lead to metabolic syndrome and its associated diseases such as heart disease and diabetes. The purpose of this study was to determine the impact of increasing intake of wholegrains or fruit and vegetables against a typical Western diet on inflammatory makers and gut microbiota composition. The study was a randomized, parallel arm feeding trial which enrolled fifty-two participants. The subjects were randomized into three groups (control, wholegrains, and fruit and vegetables). Results indicate that the wholegrain and fruit and vegetable diets had significant positive impacts on inflammatory markers. Interestingly, while both treatment groups decreased inflammatory markers, each decreased a different biomarker. The treatments induced individualised changes in microbiota composition such that treatment group differences were not identified. Authors conclude that wholegrain and fruit and vegetable diets have a positive impact on metabolic health in individuals affected by overweight or obesity.
Abstract
BACKGROUND Whole grains (WG) and fruits and vegetables (FV) have been shown to reduce the risk of metabolic disease, possibly via modulation of the gut microbiota. The purpose of this study was to determine the impact of increasing intake of either WG or FV on inflammatory markers and gut microbiota composition. METHODS A randomized parallel arm feeding trial was completed on forty-nine subjects with overweight or obesity and low intakes of FV and WG. Individuals were randomized into three groups (3 servings/d provided): WG, FV, and a control (refined grains). Stool and blood samples were collected at the beginning of the study and after 6 weeks. Inflammatory markers [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), and high sensitivity C-reactive protein (hs-CRP)] were measured. Stool sample analysis included short/branched chain fatty acids (S/BCFA) and microbiota composition. RESULTS There was a significant decrease in LBP for participants on the WG (- 0.2 μg/mL, p = 0.02) and FV (- 0.2 μg/mL, p = 0.005) diets, with no change in those on the control diet (0.1 μg/mL, p = 0.08). The FV diet induced a significant change in IL-6 (- 1.5 pg/mL, p = 0.006), but no significant change was observed for the other treatments (control, - 0.009 pg/mL, p = 0.99; WG, - 0.29, p = 0.68). The WG diet resulted in a significant decrease in TNF-α (- 3.7 pg/mL; p < 0.001), whereas no significant effects were found for those on the other diets (control, - 0.6 pg/mL, p = 0.6; FV, - 1.4 pg/mL, p = 0.2). The treatments induced individualized changes in microbiota composition such that treatment group differences were not identified, except for a significant increase in α-diversity in the FV group. The proportions of Clostridiales (Firmicutes phylum) at baseline were correlated with the magnitude of change in LBP during the study. CONCLUSIONS These data demonstrate that WG and FV intake can have positive effects on metabolic health; however, different markers of inflammation were reduced on each diet suggesting that the anti-inflammatory effects were facilitated via different mechanisms. The anti-inflammatory effects were not related to changes in gut microbiota composition during the intervention, but were correlated with microbiota composition at baseline. TRIAL REGISTRATION ClinicalTrials.gov , NCT02602496 , Nov 4, 2017.
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Circulating bile acids in healthy adults respond differently to a dietary pattern characterized by whole grains, legumes and fruits and vegetables compared to a diet high in refined grains and added sugars: A randomized, controlled, crossover feeding study.
Ginos, BNR, Navarro, SL, Schwarz, Y, Gu, H, Wang, D, Randolph, TW, Shojaie, A, Hullar, MAJ, Lampe, PD, Kratz, M, et al
Metabolism: clinical and experimental. 2018;83:197-204
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Bile acids are produced in the liver and are important for the absorption of fat and fat-soluble vitamins. About 95% of bile acids are reabsorbed. Circulating plasma bile acids can affect glucose metabolism and inflammation, and are thought to play a role in the development of metabolic syndrome. The aim of this study was to evaluate how plasma bile acid levels are influenced by a diet rich in whole grains, legumes, fruit and vegetables (low glycaemic load, GL) compared to a diet high in refined grains and sugar (high GL). The study evaluated data from a previous double-blind randomised, cross over feeding trial. 80 healthy adults had the low or high GL diet for four weeks, and after a four-week washout period, received the other diet for four weeks. Three specific plasma bile acids, which are thought to have a positive impact on glucose metabolism, were higher in the low GL group compared to the high GL group. Some individual plasma bile acids were positively associated with HOMA-IR (a measure of glucose metabolism/insulin resistance). There was no significant association between bile acid concentrations and C-reactive protein (a marker of inflammation). The authors conclude that the increase in certain bile acids on the low GL diet may be beneficial and that this effect may be to some extent mediated by the impact of the higher fibre content of the low GL diet on the gut microbial metabolism, which affects plasma bile acid levels.
Abstract
OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied. MATERIALS AND METHODS We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18.5-25.0 kg/m2) and half overweight to obese (BMI 28.0-39.9 kg/m2). Participants consumed two four-week controlled diets in randomized order: 1) a whole grain diet (WG diet), designed to be low in glycemic load (GL), high in whole grains, legumes, and fruits and vegetables, and 2) a refined grain diet (RG diet), designed to be high GL, high in refined grains and added sugars, separated by a four-week washout period. Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography tandem mass spectrometry. Concentrations of glucose, insulin, and CRP were measured in fasting serum. Linear mixed models were used to test the effects of diet on bile acid concentrations, and determine the association between plasma bile acid concentrations and HOMA-IR and CRP. Benjamini-Hochberg false discovery rate (FDR) < 0.05 was used to control for multiple testing. RESULTS A total of 29 plasma bile acids were reliably detected and retained for analysis. Taurolithocholic acid (TLCA), taurocholic acid (TCA) and glycocholic acid (GCA) were statistically significantly higher after the WG compared to the RG diet (FDR < 0.05). There were no significant differences by BMI or sex. When evaluating the association of bile acids and HOMA-IR, GCA, taurochenodeoxycholic acid, ursodeoxycholic acid (UDCA), 5β‑cholanic acid‑3β,12α‑diol, 5‑cholanic acid‑3β‑ol, and glycodeoxycholic acid (GDCA) were statistically significantly positively associated with HOMA-IR individually, and as a group, total, 12α‑hydroxylated, primary and secondary bile acids were also significant (FDR < 0.05). When stratifying by BMI, chenodeoxycholic acid (CDCA), cholic acid (CA), UDCA, 5β-cholanic acid-3β, deoxycholic acid, and total, 12α-hydroxylated, primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals (FDR < 0.05). When stratifying by sex, GCA, CDCA, TCA, CA, UDCA, GDCA, glycolithocholic acid (GLCA), total, primary, 12α‑hydroxylated, and glycine-conjugated bile acids were significantly associated with HOMA-IR among women, and CDCA, GDCA, and GLCA were significantly associated among men (FDR < 0.05). There were no significant associations between bile acids and CRP. CONCLUSIONS Diets with comparable macronutrient and energy composition, but differing in carbohydrate source, affected fasting plasma bile acids differently. Specifically, a diet characterized by whole grains, legumes, and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA, TCA and GCA, ligands for FXR and TGR5, which may have beneficial effects on glucose homeostasis.