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Beneficial effects of premeal almond load on glucose profile on oral glucose tolerance and continuous glucose monitoring: randomized crossover trials in Asian Indians with prediabetes.

Gulati, S., A. Misra, R. Tiwari, M. Sharma, R.M. Pandey, A.D. Upadhyay, H.C. Sati, 2023. Beneficial effects of premeal almond load on glucose profile on oral glucose tolerance and continuous glucose monitoring: randomized crossover trials in Asian Indians with prediabetes. European journal of clinical nutrition. 77(5):586–595. https://doi.org/10.1038/s41430-023-01263-1

Background: Rapid conversion from prediabetes to diabetes and frequent postprandial hyperglycemia (PPHG) is seen in Asian Indians. These should be the target of dietary strategies. Objectives: We hypothesized that dietary intervention of preloading major meals with almonds in participants with prediabetes will decrease overall glycemia and PPHG. Design: The study included two phases: (1) an oral glucose tolerance test (OGTT)-based crossover randomized control study, the effect of a single premeal almond load (20 g) given before OGTT was evaluated (n = 60, 30 each period). (2) The continuous glucose monitoring system (CGMS)-based study for 3 days including premeal almond load before three major meals was a free-living, open-labeled, crossover randomized control trial, where control and premeal almond load diets were compared for glycaemic control (n = 60, 30 in each period). The study was registered at clinicaltrials.gov (registration no. NCT04769726). Results: In the OGTT-based study phase, the overall AUC for blood glucose, serum insulin, C-peptide, and plasma glucagon post-75 g oral glucose load was significantly lower for treatment vs. control diet (p < 0.001). Specifically, with the former diet, PPHG was significantly lower (18.05% in AUC on OGTT, 24.8% at 1-h, 28.9% at 2-h post OGTT, and 10.07% during CGMS). The CGMS data showed that premeal almond load significantly improved 24-glucose variability; SD of mean glucose concentration and mean of daily differences. Daily glycaemic control improved significantly as per the following: mean 24-h blood glucose concentration (M), time spent above 7.8 mmol/L of blood glucose, together with the corresponding AUC values. Premeal almond load significantly decreased following: overall hyperglycemia (glucose AUC), PPHG, peak 24-h glycaemia, and minimum glucose level during night. Conclusion: Incorporation of 20 g of almonds, 30 min before each major meal led to a significant decrease in PPHG (as revealed in OGTT-based study phase) and also improved insulin, C-peptide, glucagon levels, and improved glucose variability and glycemic parameters on CGMS in participants with prediabetes.

Nuts, Energy Balance and Body Weight.

Baer, D.J., M. Dalton, J. Blundell, G. Finlayson, F.B. Hu, 2023. Nuts, Energy Balance and Body Weight. Nutrients. 15(5):1162. doi: 10.3390/nu15051162.

Over several decades, the health benefits of consuming nuts have been investigated, resulting in a large body of evidence that nuts can reduce the risk of chronic diseases. The consumption of nuts, being a higher-fat plant food, is restricted by some in order to minimize weight gain. In this review, we discuss several factors related to energy intake from nuts, including food matrix and its impact on digestibility, and the role of nuts in regulating appetite. We review the data from randomized controlled trials and observational studies conducted to examine the relationship between nut intake and body weight or body mass index. Consistently, the evidence from RCTs and observational cohorts indicates that higher nut consumption does not cause greater weight gain; rather, nuts may be beneficial for weight control and prevention of long-term weight gain. Multiple mechanisms likely contribute to these findings, including aspects of nut composition which affect nutrient and energy availability as well as satiety signaling.

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.

The impact of almonds and almond processing on gastrointestinal physiology, luminal microbiology, and gastrointestinal symptoms: a randomized controlled trial and mastication study.

Creedon, A. C., E. Dimidi, E.S. Hung, M. Rossi, C. Probert, T. Grassby, J. Miguens-Blanco, J.R. Marchesi, S.M. Scott, S.E. Berry, K. Whelan, 2022. The impact of almonds and almond processing on gastrointestinal physiology, luminal microbiology, and gastrointestinal symptoms: a randomized controlled trial and mastication study. Am. J. Clin. Nutr. 116(6):1790–1804. https://doi.org/10.1093/ajcn/nqac265

Background: Almonds contain lipid, fiber, and polyphenols and possess physicochemical properties that affect nutrient bioaccessibility, which are hypothesized to affect gut physiology and microbiota. Objectives: To investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition, and gut transit time. Methods: Healthy adults (n = 87) participated in a parallel, 3-arm randomized controlled trial. Participants received whole almonds (56 g/d), ground almonds (56 g/d), or an isocaloric control in place of habitual snacks for 4 wk. Gut microbiota composition and diversity (16S rRNA gene sequencing), SCFAs (GC), volatile organic compounds (GC-MS), gut transit time (wireless motility capsule), stool output and gut symptoms (7-d diary) were measured at baseline and endpoint. The impact of almond form on particle size distribution (PSD) and predicted lipid release was measured (n = 31). ResultsModified intention-to-treat analysis was performed on 79 participants. There were no significant differences in mean ± SD abundance of fecal bifidobacteria after consumption of whole almonds (8.7% ± 7.7%), ground almonds (7.8% ± 6.9%), or control (13.0% ± 10.2%; q = 0.613). Consumption of almonds (whole and ground pooled) resulted in higher mean ± SD butyrate (24.1 ± 15.0 μmol/g) than control (18.2 ± 9.1 μmol/g; P = 0.046). There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency, or gut symptoms. Almond form (whole compared with ground) had no effect on study outcomes. Ground almonds resulted in significantly smaller PSD and higher mean ± SD predicted lipid release (10.4% ± 1.8%) than whole almonds (9.3% ± 2.0%; P = 0.017). Conclusions: Almond consumption has limited impact on microbiota composition but increases butyrate in adults, suggesting positive alterations to microbiota functionality. Almonds can be incorporated into the diet to increase fiber consumption without gut symptoms.This trial was registered at clinicaltrials.gov as NCT03581812.

Reduction in serum LDL cholesterol using a nutrient compendium in hyperlipidemic adults unable or unwilling to use statin therapy: a double-blind randomized crossover clinical trial.

Kopecky, S.L., S. Alias, E. Klodas, P.J.H. Jones, 2022. Reduction in serum LDL cholesterol using a nutrient compendium in hyperlipidemic adults unable or unwilling to use statin therapy: a double-blind randomized crossover clinical trial. J. Nutr. 152(2), 458–465. https://doi.org/10.1093/jn/nxab375

Background: Many hyperlipidemic patients prescribed β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors (statins) are unable or unwilling to take them. A hedonically acceptable snack-based solution formulated from cholesterol-lowering food ingredients could represent a therapeutic alternative but has not been tested in this population. Objectives: To evaluate the effect of snacks containing a compendium of functional bioactives on fasting LDL cholesterol in statin candidates unwilling to use or intolerant to ≥1 statin drug. Secondary outcomes included changes in circulating total cholesterol (TC), triglycerides, HDL cholesterol, fasting glucose, insulin, and high-sensitivity C-reactive protein concentrations, as well as effects of single-nucleotide polymorphisms (SNPs) on outcome. Methods: This multicenter, randomized, double-blind, free-living crossover study was composed of 2 regimented phases of 4 wk each, separated by a 4-wk washout. Eighteen men and 36 women, with a mean ± SD age of 49 ± 12 y and mean ± SD LDL cholesterol of 131 ± 32.1 mg/dL, were instructed to ingest a variety of ready-to-eat snacks twice daily as a substitute for something they were consuming already. Other behavior changes were actively discouraged. Treatment products provided ≥5 g fiber, 1000 mg ω-3 (n-3) fatty acids, 1000 mg phytosterols, and 1800 μmol antioxidants per serving. Control products were calorie-matched like-items drawn from the general grocery marketplace. Serum lipids were measured at baseline and the end of each phase and compared using the ANOVA model. Compliance to study foods was confirmed by serum 18:3n-3 concentration assessment. Results: Comparing intervention phase endpoints, LDL cholesterol was reduced a mean ± SD of 8.80 ± 1.69% (P < 0.0001), and TC was reduced a mean ± SD of 5.08 ± 1.12% (P < 0.0001) by treatment foods compared with control foods, whereas effects on other analytes did not differ between treatments. SNPs were not significantly related to outcomes (P ≥ 0.230). Compliance with study foods was 95%. Conclusions: Consumption of hedonically acceptable snacks containing a compendium of cholesterol-lowering bioactive compounds can rapidly and meaningfully reduce LDL cholesterol in adult patients unable or unwilling to take statin drugs.

Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation.

Oliveras, T., I. Lázaro, F. Rueda, G. Cediel, D.L. Bhatt, M. Fitó, F. Madrid-Gambin, O.J. Pozo, W.S. Harris, C. García-García, A. Sala-Vila, A. Bayés-Genís, 2022. Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation. Sci. Rep. 12(1):4377. https://doi.org/10.1038/s41598-022-08453-0

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case-control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini-Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.

Key Area: Heart Health

Nut consumption in association with overall mortality and recurrence/disease-specific mortality among long-term breast cancer survivors.

Cong, W., K. Gu, F. Wang, H. Cai, W. Zheng, P. Bao, X.-O. Shu, 2022. Nut consumption in association with overall mortality and recurrence/disease-specific mortality among long-term breast cancer survivors. International Journal of Cancer.doi.org/10.1002/ijc.33824.

High nut consumption is associated with reduced total and certain cause-specific mortality in general populations. However, its association with cancer outcomes among long-term breast cancer survivors remains unknown. We examined the associations of nut consumption (including peanuts and tree nuts), assessed at 5-year postdiagnosis, with overall survival (OS) and disease-free survival (DFS) among 3449 long-term breast cancer survivors from the Shanghai Breast Cancer Survival Study, applying Cox regression analysis. During a median follow-up of 8.27 years post dietary assessment, there were 374 deaths, including 252 breast cancer deaths. Among 3274 survivors without previous recurrence at the dietary assessment, 209 developed breast cancer-specific events, that is, recurrence, metastasis or breast cancer mortality. At 5-year post dietary assessment (ie, 10-year postdiagnosis), regular nut consumers had higher OS (93.7% vs 89.0%) and DFS (94.1% vs 86.2%) rates. After multivariable adjustment, nut consumption was positively associated with OS (Ptrend = .022) and DFS (Ptrend = .003) following a dose-response pattern, with hazard ratios (95% confidence interval) of 0.72 (0.52-1.05) for OS and 0.48 (0.31-0.73) for DFS, for participants with greater than median nut intake compared with nonconsumers. The associations did not vary by nut type. Stratified analyses showed that the associations were more evident among participants with a higher total energy intake for OS (Pinteraction = .02) and among participants with early stage (I-II) breast cancers for DFS (Pinteraction = .04). The nut-DFS associations were not modified by estrogen receptor/progesterone receptor status or other known prognostic factors. In conclusion, nut consumption was associated with better survival, particularly DFS, among long-term breast cancer survivors.

The effects of peanuts and tree nuts on lipid profile in type 2 diabetic patients: A systematic review and meta-analysis of randomized, controlled-feeding clinical studies.

Xia, J.Y., J.H. Yu, D.F. Xu, C. Yang, H. Xia, G.J. Sun, 2021. The effects of peanuts and tree nuts on lipid profile in Type 2 diabetic patients: A systematic review and meta-analysis of randomized, controlled-feeding clinical studies. Front. Nutr. https://doi.org/10.3389/fnut.2021.765571

Background: Type 2 diabetes mellitus was found to be associated with metabolic disorders, particularly abnormal glucose and lipid metabolism. Dietary food choices may have profound effects on blood lipids. The primary objective of this study was to examine the effects of peanuts and tree nuts intake on lipid profile in patients with type 2 diabetes. Methods: According to preferred reporting items for systematic reviews and meta-analysis guidelines, we performed a systematic search of randomized controlled clinical trials and systematic reviews published in PubMed, Web of Science, Embase, Scopus, and Cochrane library, from inception through June 2021. Studies in populations with type 2 diabetes, which compare nuts or peanuts to a controlled-diet group were included. We used the mean difference with 95% CIs to present estimates for continuous outcomes from individual studies. In addition, we used the GRADEpro tool to evaluate the overall quality of evidence. Results: Sixteen studies involving 1,041 participants were eligible for this review. The results showed that peanuts and tree nuts supplementation did not induce significant changes in low-density lipoprotein-cholesterol (LDL-C) (mean difference = −0.11; 95%CI: −0.25 – 0.03, p = 0.117) and high-density lipoprotein-cholesterol (HDL-C) (mean difference = 0.01; 95%CI: −0.01 – 0.04, p = 0.400) in patients with type 2 diabetics. In addition, we found that peanuts and tree nuts intake may cause a significantly reduction in total cholesterol (TC) (mean difference = −0.14; 95%CI: −0.26 – −0.02, p = 0.024) and triglyceride (TG) (mean difference = −0.10; 95%CI: −0.17 – −0.02, p = 0.010). In the subgroup analysis, a significantly greater reduction in TC was observed in studies which duration was <12 weeks (mean difference = −0.22; 95%CI: −0.37 – −0.08, p = 0.002). The quality of the body of evidence was “moderate” for TC and TG, the quality of evidence for LDL-C and HDL-C were “low.” Conclusion: Our findings suggest that consuming peanuts and tree nuts might be beneficial to lower TC concentration and TG concentration in type 2 diabetics subjects. Furthermore, peanuts and tree nuts supplementation could be considered as a part of a healthy lifestyle in the management of blood lipids in patients with type 2 diabetes. Given some limits observed in the current studies, more well-designed trials are still needed.

The effects of almond consumption on inflammatory biomarkers in adults: A systematic review and meta-analysis of randomized clinical trials.

Fatahi, S., E. Daneshzad. K. Lotfi, L. Azadbakht, 2021. The effects of almond consumption on inflammatory biomarkers in adults: A systematic review and meta-analysis of randomized clinical trials. Adv. Nutr. doi:10.1093/advances/nmab158.

Conflicting findings have been reported regarding the effects of almond consumption on inflammatory markers. This study aimed to summarize the current literature to determine whether almond can affect inflammatory markers. A systematic search was carried out in PubMed, Scopus, and ISI Web of Science up to March 2021. Randomized clinical trials (RCTs) that compared almond with no almond consumption were included. The outcomes of interest were changes in circulating C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor Alpha (TNF-α), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) concentrations. The random-effects model was used to find the mean differences. Totally, 18 trials with 847 participants were eligible for the current analysis. Participant age ranged from 26.3 to 69.6 y. Combining 16 studies, almond consumption significantly reduced serum levels of CRP (WMD: -0.25 mg/L; 95% CI: -0.43, -0.06; I2 = 0.0% P-heterogeneity = 0.633). However, the beneficial effect of almond intake only occurred at doses <60 g/d. Pooling 11 effect sizes, almond interventions significantly decreased circulating IL-6 concentrations (WMD: -0.11 pg/mL; 95% CI: -0.21, -0.01; I2 = 19.9% P-heterogeneity = 0.254). In subgroup analyses, effects on CRP and IL-6 were not significant in unhealthy participants or those with obesity. In addition, almond consumption had no significant effect on TNF-α (WMD: -0.05 pg/mL; 95% CI: -0.11, 0.01; I2 = 0.0% P-heterogeneity = 0.893; n = 6), ICAM-1 (WMD: 6.39 ng/mL; 95% CI: -9.44, 22.22; I2 = 66.6% P-heterogeneity = 0.006; n = 7) or VCAM-1 (WMD: -8.31 ng/mL; 95% CI: -35.32, 18.71; I2 = 58.8% P-heterogeneity = 0.033; n = 6). In conclusion, almond consumption beneficially affects CRP and IL-6 concentrations in adults. However, it has no beneficial effect on TNF-α, ICAM-1, or VCAM-1. More trials are needed to determine the effects of almond on inflammation.

Effect of almond consumption on metabolic risk factors-glucose metabolism, hyperinsulinemia, selected markers of inflammation: a randomized controlled trial in adolescents and young adults.

Madan, J., S. Desai, P. Moitra, S. Salis, S. Agashe, R. Battalwar, A. Mehta, R. Kamble, S. Kalita, A.G. Phatak, S.A. Udipi, R.A. Vaidya,  A.B. Vaidya, 2021. Effect of almond consumption on metabolic risk factors-glucose metabolism, hyperinsulinemia, selected markers of inflammation: a randomized controlled trial in adolescents and young adults. Front. Nutr. 8:668622. https://doi.org/10.3389/fnut.2021.668622

A large percentage of the Indian population has diabetes or is at risk of pre-diabetes. Almond consumption has shown benefits on cardiometabolic risk factors in adults. This study explored the effect of almond consumption on determinants of metabolic dysfunction-blood glucose, lipids, insulin and selected inflammatory markers in adolescents and young adults aged 16-25 years from Mumbai city. This randomized controlled trial was conducted for a period of 90 days on individuals with impaired levels of fasting glucose levels between 100-125 mg/dL (5.6-6.9 mmol/L) and 2-h post-glucose value 140-199 mg/dL (7.8-11.0 mmol/L) and/or fasting insulin (≥15 mIU/ml)/stimulated insulin (≥80 mIU/ml). Of 1,313 individuals screened, 421 met the inclusion criteria, of which 275 consented to participate and 219 completed the trial. The trial was registered with Clinical Trials Registry India (CTRI) CTRI/2018/02/011927. The almonds group (n = 107) consumed 56 g almonds daily, the control group (n = 112) was provided an iso-caloric cereal-pulse based snack. At baseline and endline, blood glucose, insulin, HbA1c, LDL-c, HDL-c, total and ox-cholesterol, triglycerides, hs-CRP, IL-6, TNF-α, adiponectin, leptin were measured and HOMA-IR and FG:FI ratios were calculated. Dietary intakes were assessed. The anthropometric measurements, biochemical markers as well as macronutrient intakes did not differ significantly between the two groups at baseline. Almond consumption significantly decreased HbA1c, total cholesterol and LDL-c. Stimulated insulin decreased post-intervention in both groups, but the decrease was greater in the almonds group. Fasting glucose was reduced post intervention in the controls with no change in the almonds group. FG:FI ratio decreased in the almonds group. TNF-α and IL-6 decreased in the almonds group, while it increased in the control group. Our results showed that almonds reduced HbA1c, LDL-c and total cholesterol levels in just 12 weeks of consumption in these adolescents and young adults who were at risk for developing diabetes. Almonds can be considered as part of food-based strategies for preventing pre-diabetes. Clinical Trial Registration: ClinicalTrials.gov, identifier: CTRI/2018/02/011927.