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1.
Metabolome biomarkers linking dietary fibre intake with cardiometabolic effects: results from the Danish Diet, Cancer and Health-Next Generations MAX study.
Unión-Caballero, A, Meroño, T, Zamora-Ros, R, Rostgaard-Hansen, AL, Miñarro, A, Sánchez-Pla, A, Estanyol-Torres, N, Martínez-Huelamo, M, Cubedo, M, González-Domínguez, R, et al
Food & function. 2024;(3):1643-1654
Abstract
Biomarkers associated with dietary fibre intake, as complements to traditional dietary assessment tools, may improve the understanding of its role in human health. Our aim was to discover metabolite biomarkers related to dietary fibre intake and investigate their association with cardiometabolic risk factors. We used data and samples from the Danish Diet Cancer and Health Next Generation (DCH-NG) MAX-study, a one-year observational study with evaluations at baseline, six and 12 months (n = 624, 55% female, mean age: 43 years, 1353 observations). Direct associations between fibre intake and plasma concentrations of 2,6-dihydroxybenzoic acid (2,6-DHBA) and indolepropionic acid were observed at the three time-points. Both metabolites showed an intraclass-correlation coefficient (ICC) > 0.50 and were associated with the self-reported intake of wholegrain cereals, and of fruits and vegetables, respectively. Other metabolites associated with dietary fibre intake were linolenoyl carnitine, 2-aminophenol, 3,4-DHBA, and proline betaine. Based on the metabolites associated with dietary fibre intake we calculated predicted values of fibre intake using a multivariate, machine-learning algorithm. Metabolomics-based predicted fibre, but not self-reported fibre values, showed negative associations with cardiometabolic risk factors (i.e. high sensitivity C-reactive protein, systolic and diastolic blood pressure, all FDR-adjusted p-values <0.05). Furthermore, different correlations with gut microbiota composition were observed. In conclusion, 2,6-DHBA and indolepropionic acid in plasma may better link dietary fibre intake with its metabolic effects than self-reported values. These metabolites may represent a novel class of biomarkers reflecting both dietary exposure and host and/or gut microbiota characteristics providing a read-out that is differentially related to cardiometabolic risk.
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2.
Effects on cardiovascular risk factors of a low- vs high-glycemic index Mediterranean diet in high cardiometabolic risk individuals: the MEDGI-Carb study.
Costabile, G, Bergia, RE, Vitale, M, Hjorth, T, Campbell, W, Landberg, R, Riccardi, G, Giacco, R
European journal of clinical nutrition. 2024
Abstract
BACKGROUND The role of dietary Glycemic Index (GI), independently of fiber intake, in modulating cardiovascular disease (CVD) risk among non-diabetic individuals has not been fully elucidated. OBJECTIVE To evaluate the effects of a low- versus a high-GI diet, based on a Mediterranean dietary pattern, on cardiometabolic risk factors in individuals at high CVD risk, participating in the MEDGI-Carb intervention study. SUBJECTS AND METHODS 160 individuals, aged 30-69 years, BMI 25-37 kg/m2, with a waist circumference >102 cm (males) or >88 cm (females) and one feature of the metabolic syndrome, participated in a multi-national (Italy, Sweden, USA) randomized controlled parallel group trial. Participants were assigned to a low GI (< 55) or high-GI MedDiet ( > 70) for 12 weeks. The diets were isoenergetic and similar for available carbohydrate (270 g/d) and fiber (35 g/d) content. Fasting metabolic parameters were evaluated in the whole cohort, while an 8-h triglyceride profile (after standard breakfast and lunch) was evaluated only in the Italian cohort. RESULTS Blood pressure and most fasting metabolic parameters improved at the end of the dietary intervention (time effect, p < 0.05 for all); however, no differences were observed between the low- and the high-GI MedDiet groups (time x group effect; p > 0.05 for all). Conversely, the low-GI diet, compared with high-GI diet, significantly reduced the 8-h triglyceride profile (p < 0.017, time*group effect) that was measured only in the Italian cohort. However, it induced a reduction of plasma triglycerides after lunch (tAUC) that was of only borderline statistically significance (p = 0.065). CONCLUSIONS Consuming a low-GI in comparison with a high-GI MedDiet does not differentially affect the major cardiometabolic risk factors at fasting in individuals at increased cardiometabolic risk. Conversely, it could reduce postprandial plasma triglycerides. CLINICAL TRIAL REGISTRY NUMBER NCT03410719, ( https://clinicaltrials.gov ).
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3.
Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out.
Riccardi, G, Niccolini, GF, Bellizzi, MG, Fiore, M, Minni, A, Barbato, C
Diseases (Basel, Switzerland). 2023;(2)
Abstract
Background: Anosmia is defined as the complete absence of olfactory function, which can be caused by a variety of causes, with upper respiratory tract infections being among the most frequent causes. Anosmia due to SARS-CoV-2 infection has attracted attention given its main role in symptomatology and the social impact of the pandemic. Methods: We conducted systematic research in a clinicaltrials.gov database to evaluate all active clinical trials worldwide regarding drug therapies in adult patients for anosmia following SARS-CoV-2 infection with the intention of identifying the nearby prospects to treat Anosmia. We use the following search terms: "Anosmia" AND "COVID-19" OR "SARS-CoV-2" OR "2019 novel coronavirus". Results: We found 18 active clinical trials that met our criteria: one phase 1, one phase 1-2, five phases 2, two phases 2-3, three phases 3, and six phases 4 studies were identified. The drug therapies that appear more effective and promising are PEA-LUT and Cerebrolysin. The other interesting drugs are 13-cis-retinoic acid plus aerosolized Vitamin D, dexamethasone, and corticosteroid nasal irrigation. Conclusions: COVID-19 has allowed us to highlight how much anosmia is an important and debilitating symptom for patients and, above all, to direct research to find a therapy aimed at curing the symptom, whether it derives from SARS-CoV-2 infection or other infections of the upper airways. Some of these therapies are very promising and are almost at the end of experimentation. They also provide hope in this field, which not addressed until recently.
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4.
High Amylose Wheat Bread at Breakfast Increases Plasma Propionate Concentrations and Reduces the Postprandial Insulin Response to the Following Meal in Overweight Adults.
Costabile, G, Vetrani, C, Calabrese, I, Vitale, M, Cipriano, P, Salamone, D, Testa, R, Paparo, L, Russo, R, Rivellese, AA, et al
The Journal of nutrition. 2023;(1):131-137
Abstract
BACKGROUND High amylose starchy foods modulate the postprandial metabolic response in humans. However, the mechanisms of their metabolic benefits and their impact on the subsequent meal have not been fully elucidated. OBJECTIVE We aimed to evaluate whether glucose and insulin responses to a standard lunch are influenced by the consumption of amylose-rich bread at breakfast in overweight adults and whether changes in plasma short chain fatty acids (SCFAs) concentrations contribute to their metabolic effects. METHODS Using a randomized crossover design, 11 men and 9 women, BMI 30 ± 3 kg/m2, 48 ± 19 y, consumed at breakfast 2 breads made with high amylose flour (HAF): 85%-HAF (180 g) and 75%-HAF (170 g), and control bread (120 g) containing 100% conventional flour. Plasma samples were collected at fasting, 4 h after breakfast, and 2 h after a standard lunch to measure glucose, insulin, and SCFA concentrations. ANOVA posthoc analyses were used for comparisons. RESULTS Postprandial plasma glucose responses were 27% and 39% lower after breakfasts with 85%- and 70%-HAF breads than control bread (P = 0.026 and P = 0.003, respectively), with no difference after lunch. Insulin responses were not different between the 3 breakfasts, whereas there was a 28% lower response after the lunch following breakfast with 85%-HAF bread than the control (P = 0.049). Propionate concentrations increased from fasting by 9% and 12% 6 h after breakfasts with 85%- and 70%-HAF breads and decreased by 11% with control bread (P < 0.05). At 6 h after breakfast with 70%-HAF bread, plasma propionate and insulin were inversely correlated (r = -0.566; P = 0.044). CONCLUSIONS Amylose-rich bread reduces the postprandial glucose response after breakfast and insulin concentrations after the subsequent lunch in overweight adults. This second meal effect may be mediated by the elevation of plasma propionate due to intestinal fermentation of resistant starch. High amylose products could be a promising tool in a dietary prevention strategy for type 2 diabetes. THIS TRIAL WAS REGISTERED AT CLINICAL TRIAL REGISTRY AS NCT03899974 (https://www. CLINICALTRIALS gov/ct2/show/NCT03899974).
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5.
The effects of Mediterranean diets with low or high glycemic index on plasma glucose and insulin profiles are different in adult men and women: Data from MEDGI-Carb randomized clinical trial.
Vitale, M, Costabile, G, Bergia, RE, Hjorth, T, Campbell, WW, Landberg, R, Riccardi, G, Giacco, R
Clinical nutrition (Edinburgh, Scotland). 2023;(10):2022-2028
Abstract
BACKGROUND & AIMS Recent evidence suggests that the ability to regulate glucose and insulin homeostasis is different in men and women. Against this background, it has been hypothesized that the impact on daily plasma glucose and insulin profiles of the glycemic index (GI) of the habitual diet may differ according to sex. The aim of this study is to evaluate whether 8-h average plasma glucose and insulin profiles during a low- or a high-GI diet in individuals at high risk of developing type 2 diabetes are influenced by sex. METHODS We conducted a randomized, controlled, parallel group dietary intervention, comparing high-versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of 156 adults at risk for type 2 diabetes. For 12 weeks, 82 vs 74 participants consumed either a low-GI or high-GI Mediterranean diet, respectively. The two experimental diets contained the same quantity of available carbohydrate (270 g/d) and fiber (35 g/d) and the same foods and beverages, except for the major sources of starch that was specific to the low-GI and high-GI groups (pasta, brown rice, flatbread, all bran, and wheat bread plus rye and seeds, vs jasmine rice, potato, couscous, wholegrain bread, and rusks). At baseline and after the intervention plasma glucose and insulin profiles were evaluated for 8 h in the two intervention groups - separately for men and women - with both breakfast and lunch resembling food choices of the assigned diet. RESULTS One hundred fifty-six adults (82 women, 74 men) with at least two traits of the metabolic syndrome completed the intervention. In women, the high-GI induced significantly higher (23%, p < 0.05) 8-h average plasma glucose concentrations in comparison to the low-GI diet already on the first day of the intervention; the difference increased up to 37% (p < 0.05) after 12 weeks of diet. Conversely, there were no significant differences between the two diets in men. These results were confirmed by the two-way analysis of variance showing a statistically significant interaction between the effects of sex and diet on the glucose profile after breakfast and lunch (F = 7.887, p = 0.006). CONCLUSION The results of our intervention show that women, compared to men, are more sensitive to the metabolic effects of the dietary GI. This has a strong clinical and scientific relevance and, if confirmed in further studies, it might have important implications for dietary strategies for diabetes and cardiovascular disease prevention in the context of personalized nutrition. REGISTRATION NUMBER OF CLINICAL TRIAL Clinicaltrials.gov n. NCT03410719.
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6.
A wheat aleurone-rich diet improves oxidative stress but does not influence glucose metabolism in overweight/obese individuals: Results from a randomized controlled trial.
Costabile, G, Vitale, M, Della Pepa, G, Cipriano, P, Vetrani, C, Testa, R, Mena, P, Bresciani, L, Tassotti, M, Calani, L, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2022;(3):715-726
Abstract
BACKGROUND AND AIMS Aleurone is the innermost layer of wheat bran, rich in fiber, minerals, vitamins, phenolic compounds, and betaine. The metabolic effects of aleurone rich foods are still unknown. Our aim was to investigate the effects of consuming a Wheat Aleurone rich diet vs. a Refined Wheat diet for 8 weeks on fasting and postprandial glycemic and lipid metabolism, inflammation, and oxidative stress in overweight/obese individuals. METHODS AND RESULTS According to a randomized cross-over study design, 23 overweight/obese individuals, age 56 ± 9 years (M±SD), were assigned to two isoenergetic diet - Wheat Aleurone and Refined Wheat diets - for 8 weeks. The diets were similar for macronutrient composition but different for the aleurone content (40-50 g/day in the Wheat Aleurone diet). After each diet, fasting and postprandial plasma metabolic profile, ferulic acid metabolites and 8-isoprostane concentrations in 24-h urine samples were evaluated. Compared with the Refined Wheat Diet, the Wheat Aleurone Diet increased fasting plasma concentrations of betaine by 15% (p = 0.042) and decreased the excretion of 8-isoprostane by 33% (p = 0.035). Conversely, it did not affect the fasting and postprandial glucose, insulin and triglyceride responses, homocysteine, and C-Reactive Protein concentrations, nor excretion of phenolic metabolites. CONCLUSION An 8-week Wheat Aleurone Diet improves the oxidative stress and increases plasma betaine levels in overweight/obese individuals with an increased cardiometabolic risk. However, further studies with longer duration and larger sample size are needed to evaluate the benefits of aleurone-rich foods on glucose and lipid metabolism in individuals with more severe metabolic abnormalities. CLINICAL TRIAL REGISTRY NUMBER NCT02150356, (https://clinicaltrials.gov).
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Differential Glycemic Effects of Low- versus High-Glycemic Index Mediterranean-Style Eating Patterns in Adults at Risk for Type 2 Diabetes: The MEDGI-Carb Randomized Controlled Trial.
Bergia, RE, Giacco, R, Hjorth, T, Biskup, I, Zhu, W, Costabile, G, Vitale, M, Campbell, WW, Landberg, R, Riccardi, G
Nutrients. 2022;(3)
Abstract
A Mediterranean-style healthy eating pattern (MED-HEP) supports metabolic health, but the utility of including low-glycemic index (GI) foods to minimize postprandial glucose excursions remain unclear. Therefore, we investigated the relative contribution of GI towards improvements in postprandial glycemia and glycemic variability after adopting a MED-HEP. We conducted a randomized, controlled dietary intervention, comparing high- versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of adults at risk for type 2 diabetes. For 12 weeks, participants consumed either a low-GI or high-GI MED-HEP. We assessed postprandial plasma glucose and insulin responses to high- or low-GI meals, and daily glycemic variability via continuous glucose monitoring at baseline and post-intervention. One hundred sixty adults (86 females, 74 males; aged 55 ± 11 y, BMI 31 ± 3 kg/m2, mean ± SD) with ≥two metabolic syndrome traits completed the intervention. Postprandial insulin concentrations were greater after the high-GI versus the low-GI test meals at baseline (p = 0.004), but not post-intervention (p = 0.17). Postprandial glucose after the high-GI test meal increased post-intervention, being significantly higher than that after the low-GI test meal (35%, p < 0.001). Average daily glucose concentrations decreased in both groups post-intervention. Indices of 24-h glycemic variability were reduced in the low-GI group as compared to baseline and the high-GI intervention group. These findings suggest that low-GI foods may be an important feature within a MED-HEP.
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8.
Uncooked cornstarch for the prevention of hypoglycemic events.
Della Pepa, G, Vetrani, C, Lupoli, R, Massimino, E, Lembo, E, Riccardi, G, Capaldo, B
Critical reviews in food science and nutrition. 2022;(12):3250-3263
Abstract
Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases -i.e. glycogen storage diseases and other rare disorders - and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.
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9.
An Isoenergetic Multifactorial Diet Reduces Pancreatic Fat and Increases Postprandial Insulin Response in Patients With Type 2 Diabetes: A Randomized Controlled Trial.
Della Pepa, G, Brancato, V, Costabile, G, Salamone, D, Corrado, A, Vitale, M, Cavaliere, C, Mancini, M, Salvatore, M, Luongo, D, et al
Diabetes care. 2022;(9):1935-1942
Abstract
OBJECTIVE To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS According to a randomized controlled parallel-group design, 39 individuals with T2D, 35-75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet. RESULTS After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0-120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = -0.383; P = 0.023). CONCLUSIONS In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response.
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10.
Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach.
Vitale, M, Hanhineva, K, Koistinen, V, Auriola, S, Paananen, J, Costabile, G, Della Pepa, G, Rivellese, AA, Riccardi, G, Giacco, R
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(4):1156-1165
Abstract
BACKGROUND AND AIMS Wholegrain cereals have been implicated in the reduction of lifestyle-related chronic diseases risk including cardiovascular diseases and type 2 diabetes. Molecular mechanisms responsible for the beneficial health effects are not entirely understood. The aims of this study were 1) to identify new potential plasma biomarker candidate metabolites of wholegrain cereal foods intake and 2) to examine whether some putative metabolites associated with wholegrain foods intake may play a role in the improvement of cardiometabolic risk factors. METHODS AND RESULTS Analysis have been conducted in 54 individuals with metabolic syndrome of both genders, age 40-65 years, randomly assigned to 2 dietary interventions lasting 12-week: 1) wholegrain enriched diet (n = 28), and 2) refined-wheat cereals diet (control diet) (n = 26). Nontargeted metabolite profiling analysis was performed on fasting plasma samples collected at baseline and at the end of the experimental diets. Our data show that, at the end of the intervention, a higher intake of wholegrain (tertile 3) was significantly associated with a marked increase in several lipid compounds, as PC (20:4/16:1), LPC (20:4), LPC (22:6), LPC (18:3), LPC (22:5), and a phenolic compound (P < .05 for all). In the wholegrain group, higher concentrations of these metabolites (tertile 3 vs tertile 1 of each metabolite) were significantly associated with lower postprandial insulin and triglyceride responses (P < .05) by 29% and 37%, respectively. CONCLUSION These observations suggest a possible role of lipid and polyphenol metabolites in the postprandial metabolic benefits of wholegrains in subjects at high risk of cardiovascular disease. In addition, they provide insight into the role of these metabolites as potential candidate biomarkers of wholegrain foods. The study was registered on ClinicalTrials.gov (identifier: NCT00945854).