Omega-3 polyunsaturated fatty acids improve intestinal barrier integrity-albeit to a lesser degree than short-chain fatty acids: an exploratory analysis of the randomized controlled LIBRE trial.

PURPOSE: Adherence to the Mediterranean diet is associated with beneficial health effects, including gastrointestinal disorders. Preclinical studies suggest that omega-3 polyunsaturated fatty acids (n-3 PUFAs), found in Mediterranean foods like nuts and fish, improve intestinal barrier integrity. Here, we assessed possible effects of n-3 PUFAs on barrier integrity in a randomized controlled trial. METHODS: We studied 68 women from the open-label LIBRE trial (clinicaltrials.gov: NCT02087592) who followed either a Mediterranean diet (intervention group, IG) or a standard diet (control group, CG). Study visits comprised baseline, month 3, and month 12. Barrier integrity was assessed by plasma lipopolysaccharide binding protein (LBP) and fecal zonulin; fatty acids by gas chromatography with mass spectrometry. Median and interquartile ranges are shown. RESULTS: Adherence to the Mediterranean diet increased the proportion of the n-3 docosahexaenoic acid (DHA) (IG + 1.5% [0.9;2.5, p < 0.001]/ + 0.3% [- 0.1;0.9, p < 0.050] after 3/12 months; CG + 0.9% [0.5;1.6, p < 0.001]/ ± 0%) and decreased plasma LBP (IG - 0.3 µg/ml [- 0.6;0.1, p < 0.010]/ - 0.3 µg/ml [- 1.1; - 0.1, p < 0.001]; CG - 0.2 µg/ml [- 0.8; - 0.1, p < 0.001]/ ± 0 µg/ml) and fecal zonulin levels (IG - 76 ng/mg [- 164; - 12, p < 0.010]/ - 74 ng/mg [- 197;15, p < 0.001]; CG - 59 ng/mg [- 186;15, p < 0.050]/ + 10 ng/mg [- 117;24, p > 0.050]). Plasma DHA and LBP (R2: 0.14-0.42; all p < 0.070), as well as plasma DHA and fecal zonulin (R2: 0.18-0.48; all p < 0.050) were found to be inversely associated in bi- and multivariate analyses. Further multivariate analyses showed that the effect of DHA on barrier integrity was less pronounced than the effect of fecal short-chain fatty acids on barrier integrity. CONCLUSIONS: Our data show that n-3 PUFAs can improve intestinal barrier integrity. TRIAL REGISTRATION NUMBER: The trial was registered prospectively at ClinicalTrials.gov (reference: NCT02087592).

Changes in serum omega fatty acids on a Mediterranean diet intervention in patients with gingivitis: An exploratory study.

BACKGROUND: Omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) are precursors of pro- and anti-inflammatory lipid mediators. Serum PUFA levels could influence the severity of inflammatory oral diseases, such as gingivitis. OBJECTIVE: The study analyzed serum PUFA levels in a six-week randomized controlled trial in individuals on the Mediterranean diet (MedD), associations with the intake of specific foods, and possible correlations with oral inflammatory parameters. METHODS: Data from 37 study participants on either a MedD (MedDG; n = 18) or a "Western diet" in the control group (CG, n = 19) were analyzed. Dental examinations and serum analyses were performed at two time points, T1 (baseline) and T2 (week 6). Serum PUFA status, adherence to the MedD, and data from a Food Frequency Questionnaire were analyzed. RESULTS: Within the MedDG omega-6 fatty acid levels decreased significantly. In the overall sample, the proportional decrease in sites with bleeding on probing correlated weakly to moderately with the decrease in total omega-6 fatty acid level (Spearman's ρ = 0.274) and the decrease in gingival index correlated moderately with the decrease in linoleic acid level (Spearman's ρ = 0.351). Meat and fast-food consumption correlated positively with levels of various omega-6 fatty acids, whereas nut, fish, and dairy product consumption correlated positively with omega-3 levels. CONCLUSION: Adherence to a MedD was associated with a decrease in serum omega-6 levels, which positively affected the omega-6/omega-3 ratio. The MedD associated reduction in serum omega-6 levels may be a mechanism that favorably affects gingival inflammatory parameters.

Effect of the Mediterranean diet on gingivitis: A randomized controlled trial.

AIM: This study aimed to investigate the effects of a 6-week Mediterranean diet (MD) intervention on gingival inflammatory and anthropometric parameters of patients with gingivitis. MATERIALS AND METHODS: Forty-two participants were allocated to MD group (MDG) or control group (CG). After a 2-week equilibration period regarding dental care procedures, only MDG changed their diet to MD for 6 weeks, supported by a diet counselling. Gingival and anthropometric parameters were assessed at baseline (T0), Week 2 (T1, beginning of MD intervention), and Week 8 (T2). Adherence to MD was assessed by the Mediterranean Diet Adherence Screener (MEDAS); dietary behaviour was evaluated by the German Health Interview and Examination Survey for Adults Food Frequency Questionnaire (DEGS-FFQ). RESULTS: Plaque values remained constant in both groups. Inflammatory periodontal and anthropometric parameters decreased in the MDG only (gingival index: T1 1.51 ± 0.21, T2 1.49 ± 0.24; bleeding on probing: T1 51.00 ± 14.65, T2 39.93 ± 13.74; body weight: T1 79.01 ± 15.62, T2 77.29 ± 17.00; waist circumference: T1 84.41 ± 10.1, T2 83.17 ± 10.47 (p < .05). MEDAS revealed a sufficient diet adherence for MDG. CONCLUSION: Within this study, gingival inflammatory parameters were significantly reduced by MD, whereas plaque parameters remained constant. The diet counselling achieved sufficient adherence with beneficial changes in weight loss and waist circumference.

Biomarkers for assessment of intestinal permeability in clinical practice.

Intestinal permeability is an important diagnostic marker, yet its determination by established tests, which measure the urinary excretion of orally administered tracer molecules, is time consuming and can only be performed prospectively. Here, we aim to validate proposed surrogate biomarkers, which allow measuring intestinal permeability more easily. In this cross-sectional study, we included two independent cohorts comprising nonobese (Healthy cohort, n = 51) and individuals with obesity (Obesity cohort, n = 27). The lactulose/mannitol (lac/man) ratio was determined in all individuals as an established marker of intestinal permeability. Furthermore, we measured six potential surrogate biomarkers, being albumin, calprotectin, and zonulin, measured in feces, as well as intestinal fatty acid binding protein (I-FABP), lipopolysaccharide binding protein (LBP) and zonulin, measured in plasma. Correlation analyses and multiple linear regression models were conducted to assess possible associations between the established lac/man ratio and the proposed biomarkers by also evaluating a potential effect of age, body mass index (BMI), and sex. The lac/man ratio correlated with plasma LBP levels in all cohorts consistently and with the amount of fecal zonulin in overweight and obese individuals. Multiple linear regression models showed that the association between the lac/man ratio and plasma LBP was independent of age, BMI, and sex. Fecal zonulin levels were associated with the lac/man ratio as well as BMI, but not age and sex. Our data suggest plasma LBP as a promising biomarker for intestinal permeability in adults and fecal zonulin as a potential biomarker in overweight and obese individuals.NEW & NOTEWORTHY This study shows that biomarkers from blood and fecal samples are associated with the cumbersome established tests of intestinal permeability throughout different cohorts. Therefore, such biomarkers could be used to assess gut barrier function in prospective cohort studies and large-scale clinical trials for which tracer-based tests may not be feasible.

Precursor fractions of neurotensin and enkephalin might point to molecular mechanisms of cancer risk modulation during a lifestyle-intervention in germline BRCA1/2 gene mutation carriers.

BACKGROUND: Germline BRCA1/2 mutation carriers (gBMC) face increased cancer risks that are modulated via non-genetic lifestyle factors whose underlying molecular mechanisms are unknown. The peptides Neurotensin (NT) and Enkephalin (ENK)-involved in tumorigenesis and obesity-related diseases-are of interest. We wanted to know whether these biomarkers differ between gBMC and women from the general population and what effect a 1-year lifestyle-intervention has in gBMC. METHODS: The stable precursor fragments pro-NT and pro-ENK were measured at study entry (SE), after 3 and 12 months for 68 women from LIBRE-1 (a controlled lifestyle-intervention feasibility trial for gBMC involving structured endurance training and the Mediterranean Diet). The SE values were compared with a cohort of the general population including female subjects with and without previous cancer disease, non-suggestive for hereditary breast and ovarian cancer (OMA-reference). For LIBRE-1, we analysed the association between the intervention-related change in the two biomarkers and certain lifestyle factors. RESULTS: At SE, gBMC had a higher median pro-NT than OMA-reference (in the subgroups with previous cancer 117 vs. 91 pmol/L, p = 0.002). Non-diseased gBMC had lower median pro-ENK levels when compared to the non-diseased reference group. VO2peak and pro-NT 1-year change in LIBRE-1 were inversely correlated (r = - 0.435; CI - 0.653 to - 0.151; p = 0.004). Pro-ENK correlated positively with VO2peak at SE (r = 0.323; CI 0.061-0.544; p = 0.017). Regression analyses showed an inverse association of 1-year changes for pro-NT and Omega-6/Omega-3 (Estimate: - 37.9, p = 0.097/0.080) in multivariate analysis. CONCLUSION: Our results give first indications for lifestyle-related modification particularly of pro-NT in gBMC.

Physical activity and Mediterranean diet as potential modulators of osteoprotegerin and soluble RANKL in gBRCA1/2 mutation carriers: results of the lifestyle intervention pilot study LIBRE-1.

PURPOSE: Emerging evidence suggests that the progesterone-mediated receptor activator of nuclear factor κB (RANK)/soluble RANK ligand (sRANKL)/osteoprotegerin (OPG) pathway plays an important role in mammary carcinogenesis and is hyperactivated in germline (g)BRCA1/2 mutation carriers. We analyzed the effects of a 3-month intensive lifestyle intervention within the LIBRE-1 study on the serum levels of OPG and sRANKL and hypothesized that the intervention program provides a beneficial impact on the biomarkers by increasing OPG and reducing sRANKL serum concentrations. METHODS: Serum levels of OPG and sRANKL of 49 gBRCA1/2 mutation carriers were quantified using enzyme-linked immunosorbent assays. We used previously collected blood samples from participants of the prospective LIBRE-1 study, who were randomized into an intervention group (IG), increasing physical activity and adherence to the Mediterranean diet (MedD) through supervised sessions from study entry to the first study visit after 3 months and a usual-care control group (CG). Differences in biomarker levels before and after the 3-month intervention were tested within and between study groups. RESULTS: The lifestyle intervention resulted in a significant increase in OPG for participants in both the IG (q = 0.022) and CG (q = 0.002). sRANKL decreased significantly in the IG (q = 0.0464) and seemed to decrease in the CG (q = 0.5584). An increase in the intake of Omega-3 polyunsaturated fatty acids was significantly associated with an increase in OPG (r = 0.579, q = 0.045). Baseline serum levels of sRANKL were a strong predictor for the change of sRANKL in the course of the intervention (ß-estimate = - 0.70; q = 0.0018). Baseline physical fitness (assessed as VO2peak) might predict the change of OPG in the course of the intervention program (ß-estimate = 0.133 pg/ml/ml/min/kg; p = 0.0319; q = 0.2871). CONCLUSION: Findings from this pilot study seem to confirm our hypothesis by showing an increase in OPG and decrease in sRANKL over a 3-month lifestyle intervention and suggest that increased physical activity and adherence to the MedD are potent modulators of the biomarkers OPG and potentially sRANKL.

Energy Drinks Induce Acute Cardiovascular and Metabolic Changes Pointing to Potential Risks for Young Adults: A Randomized Controlled Trial.

BACKGROUND: Case reports suggest a link between energy drinks (EDs) and adverse events, including deaths. OBJECTIVES: We examined cardiovascular and metabolic effects of EDs and mixtures providing relevant ingredients of EDs compared to a similarly composed control product (CP) without these components. METHODS: This randomized, crossover trial comprised 38 adults (19 women, mean BMI 23 kg/m2, mean age 22 y). We examined effects of a single administration of a commercial ED, the CP, and the CP supplemented with major ED-ingredients at the same concentrations as in the ED. The study products were administered at 2 volumes, 750 or 1000 mL. RESULTS: Both volumes of the study products were acceptably tolerated with no dose-dependent effects on blood pressure (BP, primary outcome), heart rate, heart rate corrected duration of QT-segment in electrocardiography (QTc interval), and glucose metabolism. After ED consumption, 11% of the participants reported symptoms, in contrast to 0-3% caused by other study products. After 1 h, administration of an ED caused an increase in systolic BP (116.9 ± 10.4 to 120.7 ± 10.7 mmHg, mean ± SD, P < 0.01) and a QTc prolongation (393.3 ± 20.6 to 400.8 ± 24.1 ms, P < 0.01). Also caffeine, but not taurine or glucuronolactone, caused an increase in BP, but no QTc prolongation. The BP effects were most pronounced after 1 h and returned to normal after a few hours. All study products caused a decrease in serum glucose and an increase in insulin concentrations after 1 h compared to baseline values, corresponding to an elevation in the HOMA-IR (ED + 4.0, other products + 1.0-2.8, all P < 0.001). CONCLUSION: A single high-volume intake of ED caused adverse changes in BP, QTc, and insulin sensitivity in young, healthy individuals. These effects of EDs cannot be easily attributed to the single components caffeine, taurine, or glucuronolactone. This trial was registered at clinicaltrials.gov as NCT01421979.

[Comparison of a commercially available, formula-based nutritional therapy enriched with oats fiber with a non-formula isocaloric therapy to treat non-alcoholic fatty liver disease (NAFLD) - a randomized, controlled intervention trial]. / Vergleich einer kommerziell erhältlichen, Formula-basierten, mit Haferballaststoffen angereicherten Ernährungstherapie mit einer isokalorischen diätetischen Therapie ohne Formula zur Therapie der nicht-alkoholischen Fettlebererkrankung (NAFLD) ­ eine randomisierte, kontrollierte Interventionsstudie.

Non-alcoholic fatty liver disease (NAFLD) is mainly treated with caloric restriction and consecutive weight reduction. Protein, in exchange for starch and sugar as well as monounsaturated and long chain omega-3-fatty acids and prebiotic ß-glucan, are thought to be supportive.In a randomized controlled intervention study, two different dietary concepts were tested regarding effects on intrahepatic lipid content as well as on biochemical parameters in patients with a body-mass-index (BMI) > 30 kg/m2 and signs of fatty liver disease. The intervention group (IG, n = 17) received a commercially available formula diet supplemented with oats fibers. The control group (CG, n = 19) received a comparably restricted diet (approx. 1000 kcal/d) according to the "low glycemic and insulinemic diet" method.After twelve weeks, both interventions resulted into a reduction of BMI (IG: 33.8 ±â€Š2.9 to 29.3 ±â€Š2.5 kg/m2, CG: 33.7 ±â€Š2.8 to 30.1 ±â€Š3.2 kg/m2, both p < 0.001), as well as an improvement of liver and other metabolic functions. The hepatorenal index decreased in both groups, however, this reduction was more pronounced in the IG than in the CG (end of the study: 1.1 ±â€Š0.2 vs. 1.9 ±â€Š0.3, p < 0.05). A reduction of blood pressure only occurred in the IG (systolic from 136 ±â€Š15 mmHg to 122 ±â€Š11 mmHg, diastolic from 89 ±â€Š9 mmHg to 79 ±â€Š11 mmHg, both p < 0.01).In conclusion, we found that both dietetic interventions were similarly effective regarding weight reduction, but the formula diet with oats fibers was more effective regarding the reduction of intrahepatic lipid content and blood pressure than the control diet.

Feasibility of structured endurance training and Mediterranean diet in BRCA1 and BRCA2 mutation carriers - an interventional randomized controlled multicenter trial (LIBRE-1).

BACKGROUND: Women with pathogenic BRCA germline mutations have an increased risk for breast and ovarian cancer that seems to be modified by life-style factors. Though, randomized trials investigating the impact of lifestyle interventions on cancer prevention and prognosis in BRCA carriers are still missing. METHODS: We implemented a multicenter, prospective randomized controlled trial in BRCA1/2 patients, comparing a lifestyle intervention group (IG) with a control group (CG) with the primary aim to prove feasibility. Intervention comprised a structured, individualized endurance training alongside nutrition education based on the Mediterranean diet (MD) for 3 months, plus monthly group training and regular telephone contact during the subsequent 9 months. The CG attended one session on healthy nutrition and the benefits of physical activity. Primary endpoints were feasibility, acceptance and satisfaction over 12 months. Furthermore, effects on physical fitness, diet profile, body mass index (BMI), quality of life and perceived stress were investigated. RESULTS: Sixty-eight participants (mean age 41, mean BMI 23.2 kg/m2) were enrolled, of whom 55 (81%, 26 IG, 29 CG) completed 12 months. 73% (n = 26) participated in at least 70% of all intervention sessions. Predictors for drop-outs (19%; n = 13) or non-adherence (27%; n = 7) were not found. 73% rated the program highly and 80% would participate again. Severe adverse events did not occur. Positive effects in the IG compared to the CG were observed for secondary endpoints: BMI, MD eating pattern and stress levels. CONCLUSIONS: This lifestyle intervention was feasible, safe and well accepted. Positive results on eating habits, physical fitness and stress levels warrant a larger randomized trial. TRIAL REGISTRATION: The study has been retrospectively registered at ClinicalTrials.gov (reference: NCT02087592 ) on March 12, 2014. The first patient was included on February 24, 2014.

Smoking and physical inactivity increase cancer prevalence in BRCA-1 and BRCA-2 mutation carriers: results from a retrospective observational analysis.

BACKGROUND: The aim of this analysis in a pilot study population was to investigate whether we can verify seemingly harmful lifestyle factors such as nicotine and alcohol indulgence, obesity, and physical inactivity, as well as a low socioeconomic status for increased cancer prevalence in a cohort of BRCA 1 and 2 mutation carriers. METHODS: The analysis data are derived from 68 participants of the lifestyle intervention study LIBRE-1, a randomized, prospective trial that aimed to test the feasibility of a lifestyle modification in BRCA 1 and 2 mutation carriers. At study entry, factors such as medical history, lifestyle behavior, and socioeconomic status were retrospectively documented by interview and the current BMI was determined by clinical examination. The baseline measurements were compared within the cohort, and presented alongside reference values for the German population. RESULTS: Study participants indicating a higher physical activity during their adolescence showed a significantly lower cancer prevalence (p = 0.019). A significant difference in cancer occurrence was observed in those who smoked prior to the disease, and those who did not smoke (p < 0.001). Diseased mutation carriers tended to have a lower BMI compared to non-diseased mutation carriers (p = 0.079), whereas non-diseased revealed a significantly higher physical activity level than diseased mutation carriers (p = 0.046). DISCUSSION: The present data in this small cohort of 68 mutation carriers suggest that smoking and low physical activity during adolescence are risk factors for developing breast cancer in women with BRCA1 or BRCA2 mutation. Further data of the ongoing LIBRE 2 study are necessary to confirm these findings in a larger cohort of 600 mutation carriers.

No Difference in Tolerance between Wheat and Spelt Bread in Patients with Suspected Non-Celiac Wheat Sensitivity.

Individuals with suspected non-celiac wheat sensitivity (NCWS) often report better tolerance of spelt (Triticum aestivum ssp. spelta) compared to wheat (Triticum aestivum ssp. aestivum) bakery products. This experience has neither been validated nor explained on a molecular level. Therefore, we performed blinded wheat and spelt bread challenge in this patient group. Twenty-four adults with a history of NCWS but suspected spelt tolerance were challenged in a single-blinded crossover design over six weeks with six different study breads each at 300 g per day for 4 days followed by a washout phase of 3 days. Study breads comprised spelt and wheat breads made either after a traditional (T) or a current (C) recipe, resulting in four bread types plus a gluten-free bread with 1.5% added oligosaccharides (+FODMAP) and a gluten-free bread with 5% added wheat gluten (+Gluten). The main outcome parameter was the Irritable Bowel Syndrome-Severity Scoring System, which was higher than self-estimated by the participants after spelt bread consumption (p = 0.002 for T; p = 0.028 for C) and lower for wheat bread (p = 0.052 for T; p = 0.007 for C), resulting in no difference between wheat and spelt bread tolerance. The +FODMAP bread was better tolerated than both T breads (p = 0.003 for spelt; p = 0.068 for wheat) and equally well tolerated as both C breads and +Gluten breads after normalization to the washout scores. Neither signs of inflammation nor markers for intestinal barrier integrity were influenced. Our data do not confirm, on an objective basis, the differences in expected symptoms resulting from wheat and spelt products, suggesting a strong nocebo effect for wheat and a placebo effect for spelt.

Correction: Bartha et al. How to Measure Adherence to a Mediterranean Diet in Dental Studies: Is a Short Adherence Screener Enough? A Comparative Analysis. Nutrients 2022, 14, 1300.

The authors would like to make a correction in a recently published paper [...].

How to Measure Adherence to a Mediterranean Diet in Dental Studies: Is a Short Adherence Screener Enough? A Comparative Analysis.

This study aimed to evaluate the Mediterranean Diet Adherence Screener (MEDAS) in a study investigating the anti-inflammatory effect of a 6-week Mediterranean diet intervention on periodontal parameters. Data from a randomized clinical trial were analyzed for correlations between the MEDAS score and oral inflammatory parameters (bleeding on probing (BOP), gingival index (GI), and periodontal inflamed surface area (PISA)) and select nutrient intakes estimated by a food frequency questionnaire (FFQ) and a 24-h dietary recall (24dr). A mixed model, calculations of Spearman ρ, Lin's Concordance Coefficient (CC), and Mann-Whitney U test were used for the statistical analyses. The MEDAS score was significantly negatively correlated with periodontal inflammation (BOP: CoE −0.391, p < 0.001; GI −0.407, p < 0.001; PISA −0.348, p = 0.001) and positively correlated with poly unsaturated fatty acids/total fat, vitamin C, and fiber intake estimates obtained from the FFQ and 24dr (ρ 0.38­0.77). The FFQ and 24dr produced heterogeneously comparable intake results for most nutrients (CC 0­0.79, Spearman ρ 0.16­0.65). Within the limitations of this study, the MEDAS was able to indicate nutritional habits associated with different levels of periodontal inflammation. Accordingly, the MEDAS can be a sufficient and useful diet screener in dental studies. Due to its correlation with oral inflammatory parameters, the MEDAS might also be useful in dental practice.

Associations of Plasma Bioactive Adrenomedullin Levels with Cardiovascular Risk Factors in BRCA1/2 Mutation Carriers.

Background Cardiovascular disease (CVD) is an important cause of morbidity and mortality in breast cancer survivors. Effective screening modalities to identify CVD risk are lacking in this population. Adrenomedullin (ADM) has been suggested as a biomarker for subclinical cardiac dysfunction in the general population. Levels of ADM have been proven to be responsive to lifestyle changes that lead to improved cardiovascular health. As BRCA1/2 mutation carriers are deemed to be at an increased risk for CVD, the aim of this study was to examine plasma ADM levels in a cohort of BRCA mutation carriers and to assess their association with cardiovascular risk factors. Methods Plasma ADM concentrations were measured in 292 female BRCA1/2 mutation carriers with and without a history of breast cancer. Subjects were classified into high versus low ADM levels based on the median ADM level in the entire cohort (13.8 pg/mL). Logistic regression models were used to estimate the odds ratios (OR) of having elevated ADM levels by several cardiovascular risk factors. Results Of all women (median age: 43 years), 57.5% had a previous diagnosis of breast cancer. The median time between diagnosis and study entry was three years (range: 0 - 32 years). Women presenting with metabolic syndrome had 22-fold increased odds of having elevated ADM levels (p < 0.001). Elevated ADM levels were associated with lower cardiorespiratory fitness (OR = 0.88, p < 0.001) and several parameters of obesity (p < 0.001). ADM levels were higher in women who have ever smoked (OR = 1.72, p = 0.02). ADM levels were not associated with a previous diagnosis of breast cancer (p = 0.28). Conclusions This is the first study in BRCA mutation carriers that has linked circulating ADM levels to traditional cardiovascular risk factors. The long-term clinical implications of these findings are yet to be determined.

Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial.

BACKGROUND: The Mediterranean diet is associated with the prevention of diabetes, cardiovascular disease, and cancer, all of which are linked to intestinal barrier impairment. OBJECTIVES: Here, we hypothesize that the Mediterranean diet, possibly via the induction of short-chain fatty acids (SCFAs), improves intestinal barrier integrity. Furthermore, we aim to establish novel personalized nutrition advice based on machine learning algorithms. METHODS: We studied 260 women with intestinal barrier impairment. The women were allocated to follow either a Mediterranean diet or a control diet for 3 mo. Intestinal permeability was assessed by measuring lipopolysaccharide binding protein (LBP) in plasma and zonulin in feces. SCFA concentrations were analyzed in feces. Bi- and multivariate analyses and machine learning algorithms (random forest classification) were conducted. RESULTS: Particularly in the intervention group, adherence to the Mediterranean diet increased, whereas plasma LBP and fecal zonulin concentrations decreased (all q < 0.001 for the intervention group, all q < 0.1 for control group). In the intervention group, fecal SCFA concentrations increased (propionate + 19%; butyrate + 44%; both q < 0.001). Multivariate analyses showed that adherence to the Mediterranean diet was associated with SCFA concentrations (all q < 0.001) and inversely associated with LBP and zonulin concentrations (all q < 0.02). Mediation analyses identified propionate and butyrate as the key mechanistic link between diet and intestinal permeability integrity. Accordingly, using baseline SCFA data, we could predict the effect of the Mediterranean diet on intestinal permeability using a machine learning algorithm (receiver operating characteristic AUC: 0.78-0.96). CONCLUSIONS: Our data suggest that SCFAs are key mediators for the relation between diet and gut health. Assessment of SCFAs may form a basis for personalized nutrition in future clinical care. These results need to be verified in larger studies powered for this purpose, comprising different study populations. The trial was registered at clinicaltrials.gov as NCT02087592 and NCT02516540.

Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases.

High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.

Fatty acid profiles in erythrocyte membranes following the Mediterranean diet - data from a multicenter lifestyle intervention study in women with hereditary breast cancer (LIBRE).

BACKGROUND & AIMS: Evidence-based concepts to prevent breast cancer in women with BRCA1/2 mutations are limited. Adherence to a Mediterranean diet (MedD) has been associated with a lower risk for breast cancer, possibly due to a favorable fatty acid (FA) intake. Here, we studied in an at-risk population the effect of a lifestyle intervention that included the MedD on FA composition in red blood cell membranes (RBCM). METHODS: Data derived from the German multicenter trial LIBRE, from which 68 women were randomized into an intervention group (IG) trained for MedD and increased physical activity for 12 months, and a usual care control group (CG). Adherence to the diet was assessed after 3 and 12 months using the validated Mediterranean Diet Adherence Screener (MEDAS) and a food frequency questionnaire. RBCM FA were analyzed by gas chromatography with mass spectrometry. RESULTS: The MEDAS was increased in both groups after 3 months (IG: P < 0.001; CG: P = 0.004), and remained increased only in the IG after 12 months (P < 0.001). The food frequency questionnaire revealed an increased intake of omega-3 (n-3) FA at month 3 and month 12 in the IG (both P < 0.01), but not in the CG, in which intake of energy, protein and saturated FA decreased. In both groups n-6 FA in the RBCM decreased (P < 0.001), while n-9 FA increased (P < 0.001) and n-3 FA were unchanged. Women with higher consumption of fish had higher amounts of n-3 fatty acids in the RBCM. The MEDAS was inversely correlated with n-6 fatty acids. CONCLUSIONS: The RBCM FA composition was associated with dietetic parameters related to the MedD. Adherence to the MedD resulted in an altered, likely favorable FA composition. Our data suggest selected FA as biomarkers to monitor compliance to a dietetic intervention such as the MedD. CLINICAL TRIAL REGISTRY: The trial is registered at ClinicalTrials.gov (reference: NCT02087592).

[Diet in Chronic Kidney Disease - A Practical Guide]. / Ernährung bei chronischen Nierenerkrankungen: wann, was, wie.

Chronic kidney disease is associated with metabolic disorders. The nutrient requirement varies considerably and often it is not covered. This is why many patients experience severe deficiencies ("kidney disease wasting"), which limits their quality of life and prognosis. On the other hand sodium, potassium and phosphate must be limited. Nutritional therapy is a relevant part of the therapy.

Changes in Plasma Acylcarnitine and Lysophosphatidylcholine Levels Following a High-Fructose Diet: A Targeted Metabolomics Study in Healthy Women.

BACKGROUND: The consumption of high amounts of fructose is associated with metabolic diseases. However, the underlying mechanisms are largely unknown. OBJECTIVE: To determine the effects of high fructose intake on plasma metabolomics. STUDY DESIGN: We enrolled 12 healthy volunteers (six lean and six obese women, age 24⁻35 years) in a crossover intervention study. All participants carried out three diets: (1) low fructose (<10 g/day); (2) high fructose (100 g/day) from natural food sources (fruit); and (3) high fructose (100 g/day) from high fructose syrup (HFS). OUTCOME MEASURES: The primary outcome was changes in plasma metabolites measured by targeted metabolomics. RESULTS: High compared to low fructose diets caused a marked metabolite class separation, especially because of changes in acylcarnitine and lysophosphatidylcholine levels. Both high fructose diets resulted in a decrease in mean acylcarnitine levels in all subjects, and an increase in mean lysophosphatidylcholine and diacyl-phosphatidylcholine levels in obese individuals. Medium chain acylcarnitines were negatively correlated with serum levels of liver enzymes and with the fatty liver index. DISCUSSION: The metabolic shifts induced by high fructose consumption suggest an inhibition of mitochondrial ß-oxidation and an increase in lipid peroxidation. The effects tended to be more pronounced following the HFS than the fruit diet.

Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction.

BACKGROUND: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. OBJECTIVE: We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function. DESIGN: Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m2): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n = 13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI). RESULTS: The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (ρ = 0.55, P = 0.052), which correlated with FLI (ρ = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio. CONCLUSIONS: Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. This trial was registered at clinicaltrials.gov as NCT01344525.