Archive

Research Area: Body Weight/Satiety

Mixed Nuts as Healthy Snacks: Effect on Tryptophan Metabolism and Cardiovascular Risk Factors.

Yang, J., R. Lee, Z. Schulz, A. Hsu, J. Pai, S. Yang, S.M. Henning, J. Huang, J.P. Jacobs, D. Heber, Z. Li., 2023. Mixed Nuts as Healthy Snacks: Effect on Tryptophan Metabolism and Cardiovascular Risk Factors. Nutrients. 15, 569; https://doi.org/10.3390/nu15030569.

We recently demonstrated that the consumption of mixed tree nuts (MTNs) during caloric restriction decreased cardiovascular risk factors and increased satiety. Tryptophan (Trp) metabolism has been indicated as a factor in cardiovascular disease. Here, we investigated the effect of MTNs on Trp metabolism and the link to cardiovascular risk markers. Plasma and stool were collected from 95 overweight individuals who consumed either MTNs (or pretzels) daily as part of a hypocaloric weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for an additional 12 weeks. Plasma and fecal samples were evaluated for Trp metabolites by LC–MS and for gut microbiota by 16S rRNA sequencing. Trp–kynurenine metabolism was reduced only in the MTNs group during weight loss (baseline vs. week 12). Changes in Trp–serotonin (week 24) and Trp–indole (week 12) metabolism from baseline were increased in the MTNs group compared to the pretzel group. Intergroup analysis between MTN and pretzel groups does not identify significant microbial changes as indicated by alpha diversity and beta diversity. Changes in the relative abundance of genus Paludicola during intervention are statistically different between the MTNs and pretzel group with p < 0.001 (q = 0.07). Our findings suggest that consumption of MTNs affects Trp host and microbial metabolism in overweight and obese subjects.

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Yaskolka, M.A., E. Rinott, G. Tsaban, H. Zelicha, A. Kaplan, P. Rosen,  I. Shelef, I. Youngster, A. Shalev,  M. Blüher, U. Ceglarek, M. Stumvoll, K. Tuohy, C. Diotallevi, U. Vrhovsek, F. Hu, M. Stampfer, I. Shai, 2021. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. doi: 10.1136/gutjnl-2020-323106

Objective: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/ processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. Design: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/ day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). Results: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18 month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups.  Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic- acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). Conclusion: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.

Branched-Chain Amino Acids in relation to food preferences and insulin resistance in obese subjects consuming walnuts: A cross-over, randomized, double-blind, placebo-controlled inpatient physiology study.

Tuccinardi, D., N. Perakakis, O.M. Farr, J. Upadhyay, C.S. Mantzoros, 2021. Branched-Chain Amino Acids in relation to food preferences and insulin resistance in obese subjects consuming walnuts: A cross-over, randomized, double-blind, placebo-controlled inpatient physiology study. Clin Nutr. 40(5):3032-3036.

Background & aims: To assess whether the concentrations of circulating Branched-Chain Amino Acids (BCAAs) change after walnut consumption and, whether these changes are associated with alterations in markers of insulin resistance and food preferences. Methods: In a crossover, randomized, double-blind, placebo-controlled study, ten subjects participated in two 5-day inpatient study admissions, during which they had a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts every morning. Between the two phases there was a 1-month washout period. Results: Fasting valine and isoleucine levels were reduced (p = .047 and p < .001) and beta-hydroxybutyrate levels were increased after 5-days of walnut consumption compared to placebo (p = .023). Fasting valine and isoleucine correlated with HOMA-IR while on walnut (r = 0.709, p = .032 and r = 0.679, p = .044). The postprandial area under the curve (AUC) of leucine in response to the smoothie consumption on day 5 was higher after walnut vs placebo (p = .023) and correlated negatively with the percentage of Kcal from carbohydrate and protein consumed during an ad libitum buffet meal consumed the same day for lunch (r = −0.661, p = .037; r = −0.628, p = .05, respectively). Conclusion: The fasting and post-absorptive profiles of BCAAs are differentially affected by walnut consumption. The reduction in fasting valine and isoleucine may contribute to the longer-term benefits of walnuts on insulin resistance, cardiovascular risk and mortality, whereas the increase in post-absorptive profiles with walnuts may influence food preference.

Are fatty nuts a weighty concern? A systematic review and meta-analysis and dose–response meta-regression of prospective cohorts and randomized controlled trials.

Nishi, S.K., E. Viguiliouk, S. Blanco Mejia, C.W.C. Kendall, R.P. Bazinet,  A.J. Hanley, E.M. Comelli, J. Salas Salvado, D.J.A. Jenkins, J.L. Sievenpiper, 2021. Are fatty nuts a weighty concern? A systematic review and meta-analysis and dose–response meta-regression of prospective cohorts and randomized controlled trials. Obes Rev. doi: 10.1111/obr.13330.

Nuts are recommended for cardiovascular health, yet concerns remain that nuts may contribute to weight gain due to their high energy density. A systematic review and meta-analysis of prospective cohorts and randomized controlled trials (RCTs) was conducted to update the evidence, provide a dose-response analysis, and assess differences in nut type, comparator and more in subgroup analyses. MEDLINE, EMBASE, and Cochrane were searched, along with manual searches. Data from eligible studies were pooled using meta-analysis methods. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Certainty of the evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Six prospective cohort studies (7 unique cohorts, n = 569,910) and 86 RCTs (114 comparisons, n = 5873) met eligibility criteria. Nuts were associated with lower incidence of overweight/obesity (RR 0.93 [95% CI 0.88 to 0.98] P < 0.001, “moderate” certainty of evidence) in prospective cohorts. RCTs presented no adverse effect of nuts on body weight (MD 0.09 kg, [95% CI -0.09 to 0.27 kg] P < 0.001, “high” certainty of evidence). Meta-regression showed that higher nut intake was associated with reductions in body weight and body fat. Current evidence demonstrates the concern that nut consumption contributes to increased adiposity appears unwarranted.

Mixed tree nut snacks compared to refined carbohydrate snacks resulted in weight loss and increased satiety during both weight loss and weight maintenance: A 24-week randomized controlled trial.

Wang, J., S. Wang, S.M. Henning, T. Qin, Y. Pan, J. Yang, J. Huang, C.-H. Tseng, D. Heber,  Z. Li, 2021. Mixed tree nut snacks compared to refined carbohydrate snacks resulted in weight loss and increased satiety during both weight loss and weight maintenance: A 24-week randomized controlled trial. Nutrients. 13(5), 1512; doi.org/10.3390/nu13051512

Mixed tree nuts (MTNs) are an excellent source of protein and healthy fat contributing to satiety. However, their relatively high caloric content might not be beneficial in a weight loss diet. The present study was designed to test whether including MTNs in a weight loss and maintenance program interferes with weight management compared to a refined carbohydrate pretzel snack (PS). We performed a randomized, controlled, two-arm study in 95 overweight individuals consuming 1.5 oz of MTNs or PS daily as part of a hypocaloric weight loss diet (−500 kcal) over 12 weeks followed by an isocaloric weight maintenance program for 12 weeks. Participants in both groups experienced significant weight loss (12 weeks: −1.6 and −1.9 and 24 weeks: −1.5 and −1.4 kg) compared to baseline in the MTN and PS groups, respectively. However, there was no difference in weight loss and other outcome parameters between the MTN and PS groups. The MTN group showed a significant increase in satiety at 24 weeks. Both groups had a decrease in diastolic blood pressure at 12 weeks. Participants in the MTN group showed significant decreases in heart rate at 4, 12, and 24 weeks. Plasma oleic acid was significantly increased at 12 and 24 weeks in the MTN group but only at 12 weeks in the PS group. Plasma MCP-1 was decreased significantly in the MTN group at 4 weeks. In summary, participants in both groups lost weight, but only the MTN intervention increased satiety at 24 weeks, enhanced retention, decreased heart rate, and increased serum oleic acid at 24 weeks.

Almond consumption affects fecal microbiota composition, stool pH, and stool moisture in overweight and obese adults with elevated fasting blood glucose: A randomized controlled trial.

Choo, J.M., C.D. Tran, N.D. Luscombe-Marsh, W. Stonehouse, J. Bowen, N. Johnson, C.H. Thompson, E.-J. Watson, G.D. Brinkworth, G.B. Rogers, 2021. Almond consumption affects fecal microbiota composition, stool pH, and stool moisture in overweight and obese adults with elevated fasting blood glucose: A randomized controlled trial. Nutr Res. 85:47-59.

Regular almond consumption has been shown to improve body weight management, lipid profile and blood glucose control. We hypothesized that almond consumption would alter fecal microbiota composition, including increased abundance and activity of potentially beneficial bacterial taxa in adults who are overweight and obese with elevated fasting blood glucose. A total of 69 adults who were overweight or obese with an elevated plasma glucose (age: 60.8 ± 7.4, BMI ≥27 kg/m2, fasting plasma glucose ≥5.6 to <7.0 mmol/L) were randomized to daily consumption of either 2 servings of almonds (AS:56 g/day) or an isocaloric, high carbohydrate biscuit snack for 8 weeks. AS but not biscuit snack experienced significant changes in microbiota composition (P= .011) and increases in bacterial richness, evenness, and diversity (P< .01). Increases in both the relative and absolute abundance of operational taxonomic units in the Ruminococcaceae family, including Ruminiclostridium (false discovery rate P = .002), Ruminococcaceae NK4A214 (P = .002) and Ruminococcaceae UCG-003 (P = .002) were the principal drivers of microbiota-level changes. No changes in fecal short chain fatty acid levels, or in the carriage of the gene encoding butyryl-CoA:acetate CoA-transferase (an enzyme involved in butyrate synthesis) occurred. Almond consumption was not associated with reduced gut permeability, but fecal pH (P= .0006) and moisture content (P = .027) decreased significantly in AS when compared to BS. Regular almond consumption increased the abundance of potentially beneficial ruminococci in the fecal microbiota in individuals with elevated blood glucose. However, fecal short-chain fatty acid levels remained unaltered and the capacity for such microbiological effects to precipitate host benefit is not known.

Neural correlates of future weight loss reveal a possible role for brain-gastric interactions.

Levakov G, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Zelicha H, Meiran N, Shelef I, Shai I, Avidan G., 2021. Neural correlates of future weight loss reveal a possible role for brain-gastric interactions. Neuroimage. 224:117403. doi: 10.1016/j.neuroimage.2020.117403.

Lifestyle dietary interventions are an essential practice in treating obesity, hence neural factors that may assist in predicting individual treatment success are of great significance. Here, in a prospective, open-label, three arms study, we examined the correlation between brain resting-state functional connectivity measured at baseline and weight loss following 6 months of lifestyle intervention in 92 overweight participants. We report a robust subnetwork composed mainly of sensory and motor cortical regions, whose edges correlated with future weight loss. This effect was found regardless of intervention group. Importantly, this main finding was further corroborated using a stringent connectivity-based prediction model assessed with cross-validation thus attesting to its robustness. The engagement of senso-motor regions in this subnetwork is consistent with the over-sensitivity to food cues theory of weight regulation. Finally, we tested an additional hypothesis regarding the role of brain-gastric interaction in this subnetwork, considering recent findings of a cortical network synchronized with gastric activity. Accordingly, we found a significant spatial overlap with the subnetwork reported in the present study. Moreover, power in the gastric basal electric frequency within our reported subnetwork negatively correlated with future weight loss. This finding was specific to the weight loss related subnetwork and to the gastric basal frequency. These findings should be further corroborated by combining direct recordings of gastric activity in future studies. Taken together, these intriguing results may have important implications for our understanding of the etiology of obesity and the mechanism of response to dietary intervention.

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Yaskolka M.A., E. Rinott, G. Tsaban, H. Zelicha, A. Kaplan, P. Rosen, I. Shelef, I. Youngster, A. Shalev, M. Blüher, U. Ceglarek, M. Stumvoll, K. Tuohy, C. Diotallevi, U. Vrhovsek, F. Hu, M. Stampfer, I. Shai, 2021. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. 0:1–11. doi:10.1136/gutjnl-2020-323106.

Objective: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/ processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. Design: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/ day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). Results: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18 month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups.  Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic- acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). Conclusion: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.

Effects of diet-modulated autologous fecal microbiota transplantation on weight regain.

Rinott, E., I. Youngster, A.Y. Meir, G. Tsaban, H. Zelicha, A. Kaplan, D. Knights, K. Tuohy, F. Fava, M.U. Scholz, O. Ziv, E. Reuven, A. Tirosh, A. Rudich, M. Blüher, M. Stumvoll, U. Ceglarek, K. Clement, O. Koren, D.D. Wang, F.B. Hu, M.J. Stampfer, I. Shai, 2020. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain. Gastroenterology. doi: https:// doi.org/10.1053/j.gastro.2020.08.041.

Background & Aims: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight loss phase. Methods: In the DIRECT-PLUS weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1) healthy dietary guidelines, (2) Mediterranean diet, and (3) green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both iso-caloric Mediterranean groups consumed 28g/day walnuts (+440mg/d polyphenols provided). The green-Mediterranean dieters further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai strain;100g/day) green shake (+800mg/day polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight regain phase (months 6–14). Secondary outcomes were gastrointestinal symptoms, waist-circumference, glycemic status and changes in the gut microbiome, as measured by metagenomic sequencing and 16s-rRNA. We validated the results in a parallel in-vivo study of mice specifically fed with Mankai, as compared to control chow diet. Results: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules over the transplantation period. No aFMTrelated adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6–14 (aFMT, 30.4% vs. placebo, 40.6%;P=.28), aFMT significantly attenuated weight regain in the green Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P=.02), but not in the dietary guidelines (P=.57) or Mediterranean diet (P=.64) groups (P for the interaction=.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89cm vs placebo, 5.05cm;P=.01) and insulin rebound (aFMT, 1.46±3.6µIU/ml vs placebo, 1.64±4.7µIU/ml;P=.04) in the green Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction=.04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight loss phase, and to prompt preservation of weight loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) following the aFMT. In mice, Mankaimodulated aFMT in the weight loss phase, compared with control diet aFMT, significantly prevented weight regain, and resulted in better glucose tolerance, during a high-fat-diet induced regain phase (P<.05 for all). Conclusions: Autologous FMT, collected during the weight loss phase and administrated in the regain phase, might preserve weight loss and glycemic control and is associated with specific microbiome signatures. High-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure.

Identifying usual food choice combinations with walnuts: Analysis of a 2005-2015 clinical trial cohort of overweight and obese adults.

Guan, V., E. Neale, L. Tapsell, Y. Probst, 2020. Identifying usual food choice combinations with walnuts: Analysis of a 2005-2015 clinical trial cohort of overweight and obese adults. Front Nutr. 7:149. doi: 10.3389/fnut.2020.00149.

Consumption of nuts has been associated with a range of favorable health outcomes. Evidence is now emerging to suggest that walnuts may also play an important role in supporting the consumption of a healthy dietary pattern. However, limited studies have explored how walnuts are eaten at different meal occasions. The aim of this study was to explore the food choices in relation to walnuts at meal occasions as reported by a sample of overweight and obese adult participants of weight loss clinical trials. Baseline usual food intake data were retrospectively pooled from four food-based clinical trials (n=758). A nut-specific food composition database was applied to determine walnut consumption within the food intake data. The Apriori algorithm of association rules was used to identify food choices associated with walnuts at different meal occasions using a nested hierarchical food group classification system. The proportion of participants who were consuming walnuts was 14.5% (n=110). The median walnut intake was 5.14 (IQR 1.10 – 11.45) grams per day. A total of 128 food items containing walnuts were identified for walnut consumers. The proportion of participants who reported consuming unsalted raw walnut was 80.5% (n=103). There were no identified patterns to food choices in relation to walnut at the breakfast, lunch or dinner meal occasions. A total of 24 clusters of food choices related to walnuts were identified at others (meals). By applying a novel food composition database, the present study was able to map the precise combinations of foods associated with walnuts intakes at mealtimes using data mining. This study offers insights into the role of walnuts for the food choices of overweight adults and may support guidance and dietary behavior change strategies.