Effects of mixed nut consumption on LDL cholesterol, lipoprotein(a), and other cardiometabolic risk factors in overweight and obese adults.

BACKGROUND AND AIMS: Elevated LDL-C, lipoprotein(a) [Lp(a)], and inflammation are associated with greater risk for atherosclerotic cardiovascular events. Consumption of individual nut types decreases these risk factors but knowledge about the effect of mixed nuts on Lp(a) is limited. The objective of this study was to determine the effects of consuming 42.5 g/day of mixed nuts on LDL-C, Lp(a), and inflammatory markers in individuals with overweight or obesity. METHODS AND RESULTS: In a 16-week randomized control trial, 29 participants with overweight or obesity (BMI 25-40 kg/m2) consumed either 42.5 g/day of mixed nuts (cashews, almonds, macadamia nuts, Brazil nuts, pecans, pistachios, walnuts, and peanuts) or 69 g/day isocaloric pretzels. Blood samples were collected at baseline, week 8, and week 16 for analysis on total cholesterol (TC), LDL-C, Lp(a), inflammation markers, glucose, insulin, adiponectin and liver function enzymes. No significant differences were seen in TC, LDL-C, HDL-C, Lp(a), or liver function enzymes between the two groups. Participants consuming mixed nuts had significantly lower body fat percentage and diastolic blood pressure, and higher adiponectin (all P ≤ 0.05). C-reactive protein (CRP) and 8-oxo-deoxyguanosis (8-oxodG) showed non-significant decreasing trends and total antioxidant capacity (TAC) had a non-significant increasing trend in the mixed nut group. CONCLUSION: Consumption of mixed nuts had no evidence of an effect on LDL-C or Lp(a) throughout the intervention. Notably, mixed nut consumption lowered body fat percentage without significant changes in body weight or BMI. Future studies with larger sample sizes investigating the changing trends of CRP, 8-oxodG, and TAC are warranted. CLINICAL TRIAL REGISTER: NCT03375866.

A calorie-restricted diet enriched with tree nuts and peanuts reduces the expression of CX3CR1 in peripheral blood mononuclear cells in patients with coronary artery disease.

Background: The modification of the gut microbiome has been proposed to alter immune response which is a key driver in low-grade inflammation as well as metabolic markers. This study was conducted to determine the effects of a low-calorie diet with and without nuts on some gut bacterial abundance, metabolic markers, and gene expression in peripheral blood mononuclear cells (PBMCs) in stable coronary artery disease patients with overweight or obesity. Methods: Overweight or obese patients with stable coronary artery disease of both genders were randomly allocated to a nut-free calorie-restricted diet as 25% of energy deficit (CRD) or a CRD enriched with 39-60 g/d of mixed nuts (CRDEN) for 8 weeks (32 patients in CRD and 35 patients in CRDEN). Mixed nuts consisted of equal amounts of unsalted pistachios, almonds, and peanuts. Microbiota analysis was performed by quantitative real-time polymerase chain reaction method on feces collected before and after the intervention, using primers targeting 16S ribosomal DNA of 4 different bacterial genera, including Bacteroides, Prevotella, Bifidobacterium, and Lactobacillus. We examined the plasma concentrations of glucose, insulin, adiponectin as well as expression of toll-like receptor-4 (TLR4) and fractalkine receptor (CX3CR1) in PBMCs. Results: A significant reduction in expression of CX3CR1 (p=0.04) and a tendency to lower expression of TLR4 in PBMCs (p=0.06) was observed in the CRDEN group at the end of the study compared to the CRD group. The abundance of fecal Prevotella also tended to increase in CRDEN compared to the CRD group (p=0.06). Plasma insulin and adiponectin had no significant changes. There was a positive correlation between fecal Prevotella abundance and plasma adiponectin at baseline (r=0.315, p=0.015) and the end of the study (r=0.380, p=0.003). Conclusion: Our results suggest that the inclusion of mixed tree nuts and peanuts in a low-calorie diet for 8 weeks led to a lower CX3CR expression in PBMCs in a cohort of overweight or obese patients with stable CAD. This finding provides another beneficial effect of diet supplemented with nuts on factors associated with inflammation. Trial registration: this clinical study has been registered at the clinical trial registration center (clinicaltrial.gov): NCT04078919 on September 6, 2019.

Mixed nut consumption improves brain insulin sensitivity: a randomized, single-blinded, controlled, crossover trial in older adults with overweight or obesity.

BACKGROUND: Improving brain insulin sensitivity, which can be assessed by measuring regional cerebral blood flow (CBF) responses to intranasal insulin, may prevent age-related metabolic and cognitive diseases. OBJECTIVES: This study aimed to investigate longer-term effects of mixed nuts on brain insulin sensitivity in older individuals with overweight/obesity. METHODS: In a randomized, single-blinded, controlled, crossover trial, 28 healthy adults (mean ± standard deviation: 65 ± 3 years; body mass index: 27.9 ± 2.3 kg/m2) received either daily 60-g mixed nuts (15 g of walnuts, pistachio, cashew, and hazelnuts) or no nuts (control) for 16 weeks, separated by an 8-week washout period. Throughout the study, participants were instructed to adhere to the Dutch food-based dietary guidelines. During follow-up, brain insulin action was assessed by quantifying acute effects of intranasal insulin on regional CBF using arterial spin labeling magnetic resonance imaging. Furthermore, effects on peripheral insulin sensitivity (oral glucose tolerance test), intrahepatic lipids, and cardiometabolic risk markers were assessed. RESULTS: Body weight and composition did not change. Compared with control, mixed nut consumption improved regional brain insulin action in 5 clusters located in the left (difference in CBF responses to intranasal insulin: -4.5 ± 4.7 mL/100 g/min; P < 0.001; -4.6 ± 4.8 mL/100 g/min; P < 0.001; and -4.3 ± 3.6 mL/100 g/min; P = 0.007) and right occipital lobes (-4.3 ± 5.6 mL/100 g/min; and -3.9 ± 4.9 mL/100 g/min; P = 0.028). A fifth cluster was part of the left frontal lobe (-5.0 ± 4.6 mL/100 g/min; P < 0.001). Peripheral insulin sensitivity was not affected. Intrahepatic lipid content (-0.7%-point; 95% CI: -1.3%-point to -0.1%-point; P = 0.027), serum low-density lipoprotein cholesterol concentration (-0.24 mmol/L; 95% CI: -0.44 to -0.04 mmol/L; P = 0.019), and systolic blood pressure (-5 mm Hg; 95% CI: -8 to -1 mm Hg; P = 0.006) were lower after the mixed nut intervention. CONCLUSIONS: Longer-term mixed nut consumption affected insulin action in brain regions involved in the modulation of metabolic and cognitive processes in older adults with overweight/obesity. Intrahepatic lipid content and different cardiometabolic risk markers also improved, but peripheral insulin sensitivity was not affected. This trial was registered at clinicaltrials.gov as NCT04210869.

Dietary intake of pistachios or mixed nuts results in higher systemic antioxidant capacity with minimal effects on bone in adolescent male rats.

Nutrition is a key determinant of bone health and attainment of peak bone mass. Excess oxidative stress induces bone loss while increasing antioxidant capacity promotes protective effects on bone. Nuts are rich in antioxidants; therefore, we tested the hypothesis that compared to a control diet high in fat (40 % energy) and cholesterol, diets containing isocaloric amounts of pistachios (8·1 % g/g) or mixed nuts (7·5 % g/g) for 8 weeks would result in greater bone health in male adolescent (3 weeks; a state of continued skeletal growth) Sprague-Dawley rats. We found no difference in bone mechanical properties among groups. Tibial apparent density was ~5 % higher in the pistachio and mixed nuts groups v. control (P < 0·05) with no clear difference detected for the femur. Expressions of genes known to impact bone turnover and serum bone turnover biomarkers were unaffected by either diet relative to control. Serum antioxidant capacity was ~2-fold higher in the pistachio and mixed nuts groups compared with control (P < 0·05) but were similar between groups. Therefore, pistachios and mixed nuts may increase tibial density, in part, due to increasing antioxidant capacity. Longer dietary interventions may be necessary to elicit detectable changes in other bones (e.g. femur) and to detect potential mechanisms for the possible bone protective effects of nuts.

Evaluation of the digestibility and antioxidant activity of protein and lipid after mixing nuts based on in vitro and in vivo models.

This study aimed to evaluate the change of digestibility and antioxidant activity of protein and lipid after mixing walnuts, cashews, and pistachios using in vitro and in vivo models. The results showed that mixed nuts significantly reduced the digested particle size and the degree of hydrolysis of protein and triacylglycerol compared to single nuts in vitro. As a consequence of co-digestion, bioaccessibility and antioxidant activity for amino acids and fatty acids were increased by 1.12-1.87 fold and 1.62-3.81 fold, respectively. In vivo studies, the mixed nuts diet increased the concentration of amino acids and fatty acids in the small intestine by 27.69%-158.26% and 18.13%-152.09%, respectively, and enhanced levels of antioxidant enzymes in the liver and serum, all without causing weight gain. These findings highlight the positive interaction between single and mixed nuts, where mixed nuts enhanced the digestibility and antioxidant activity of single nuts both in vitro and in vivo.

Effects of Mixed Nuts on Colonic Cell Proliferation and Ptgs2 and Rela Gene Expression.

BACKGROUND/AIM: Nut consumption is associated with lower risk of colorectal cancer (CRC). Previously, single nut varieties have been investigated but there is limited research on the consumption of a nut mixture and the underlying mechanisms. This study examined mixed nut consumption's effect on colonic cell proliferation, apoptosis, and gene expression involved in CRC. MATERIALS AND METHODS: Thirty 21-day old Sprague Dawley rats were divided into three groups: control (no nuts), pistachio or mixed nut for 8 weeks. Ki-67 quantitative immunostaining was used to mark proliferative cells and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptotic cells. Real-time quantitative polymerase chain reaction analysis was used to determine colonic gene expression of prostaglandin endoperoxide synthase 2 (Ptgs2), nuclear factor kappa-B p65 subunit (Rela), cyclin D1 (Ccnd1), peroxisome proliferator-activated receptor gamma (Pparg), O6-methylguanine-DNA-methyltransferase (Mgmt), 8-oxoguanine glycosylase (Ogg1), superoxide dismutase (Sod), and catalase (Cat). RESULTS: DNA damage, determined using 8-oxo-deoxyguanosin, was found to be lower in the mixed nut group only (p<0.05). Differences in proliferation and apoptosis among all three groups were not significant. Lower levels of the inflammatory marker, Ptgs2, were observed between the pistachio group and the control (p=0.035). The pistachio and mixed nut groups had lower levels of Rela compared to the control (p=0.029). Differences among diets for Ccnd1, Pparg, Mgmt, Ogg1, Sod, and Cat were not significant. CONCLUSION: Mixed nut consumption reduced DNA damage possibly via down-regulation of Rela inflammation gene expression without changes to colonic cell proliferation and apoptosis.

Mixed Nut Consumption May Improve Cardiovascular Disease Risk Factors in Overweight and Obese Adults.

Emerging research indicates that nuts are a source of health-promoting compounds demonstrating cardioprotective benefits. However, most studies have assessed the effect of single nuts rather than a nut mixture. The objective of this study was, therefore, to examine the effect of mixed-nut consumption on cardiovascular disease (CVD) risk factors in overweight and obese adults. In a randomized, parallel-arm, controlled trial, 48 participants consumed isocaloric (250 kcal) amounts of pretzels or mixed-nuts. Body weight (BW) (p = 0.024), BMI (p = 0.043), and insulin levels (p = 0.032) were significantly lower in the nut group compared to the pretzel group. Mixed-nut consumption also significantly reduced glucose (p = 0.04) and insulin (p = 0.032) levels after 4 and 8 weeks compared to baseline, respectively. Lactate dehydrogenase of the nut group was significantly lower than the pretzel group (p = 0.002). No significant differences were detected between groups for triglycerides, LDL-C, and HDL-C. However, pretzel consumption increased triglycerides (p = 0.048) from 4 weeks to 8 weeks. Moreover, LDL-C increased (p = 0.038) while HDL-C transiently decreased (p = 0.044) from baseline to 4 weeks. No significant lipid changes were detected within the nut group. Our results suggest that supplementing the diet with mixed-nuts could improve CVD risk factors by improving BW and glucose regulation in comparison to a common carbohydrate-rich snack without promoting the negative effects on lipids detected with pretzels.