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Research Nut: Walnuts

Consumption of tree nuts as snacks stimulates changes in plasma fatty acid profiles and adipose tissue gene expression in young adults at risk for metabolic syndrome

Widmer, A., K. Lillegard, K. Wood, M. Robles, R. Fan, F. Ye, J.R. Koethe, H.J. Silver, 2025. Consumption of tree nuts as snacks stimulates changes in plasma fatty acid profiles and adipose tissue gene expression in young adults at risk for metabolic syndrome. Clinical Nutrition. (48)25 – 34. https://doi.org/10.1016/j.clnu.2025.03.002.

Background and aims: The prevalence of metabolic syndrome has been increasing in young adults, concomitant with the occurrence of increased abdominal adiposity. We previously reported that consuming tree nuts, as replacement for typical high-carbohydrate snacks, reduces visceral fat and waist circumference in young adults who have one or more metabolic syndrome risk factors. We aimed to investigate the effects of tree nuts snack consumption on plasma and adipose tissue fatty acid profiles along with changes in the expression of adipose tissue genes involved in thermogenesis, glycemia, adipocyte signaling, lipolysis, and immunity. Methods: A randomized parallel-arm 16-week intervention trial was conducted in 84 adults aged 22-36 years. Participants in both groups were provided with caloric goals for weight maintenance, daily menus, and pre-portioned snacks at every other week visits with study registered dietitians. Changes in dietary fatty acid intakes, plasma and abdominal subcutaneous adipose tissue (SAT) triglycerides fatty acid profiles using gas-liquid chromatography, and the expression of 241 genes in abdominal SAT were evaluated. Results: Consuming tree nuts snacks increased mono- and polyunsaturated fatty acid intakes yielding a 9-fold greater dietary unsaturated to saturated fat ratio. The tree nuts snack group also had significantly greater improvements in plasma 16:1/16:0 ratio; plasma phospholipids oleic and gamma linolenic acid content; plasma diglycerides, triglycerides, and cholesterol esters oleic acid content; and total plasma monounsaturated fatty acids. While abdominal SAT only showed trends for increased oleic acid content and unsaturated to saturated fat ratio, the tree nuts snacks participants had altered expression of 13 genes in abdominal SAT that have roles in nutrient sensing, energy homeostasis, and vulnerability to obesity. Conclusions: Replacing typical high-carbohydrate snacks with tree nuts results in more favorable dietary, plasma, and adipose tissue fatty acid profiles that could aid in preventing the development of excess adiposity and cardiometabolic disease states including metabolic syndrome.

Visceral adipose tissue area and proportion provide distinct reflections of cardiometabolic outcomes in weight loss; pooled analysis of MRI-assessed CENTRAL and DIRECT PLUS dietary randomized controlled trials.

Klein, H., H. Zelicha, A. Yaskolka Meir, E. Rinott, G. Tsaban, A. Kaplan, Y. Chassidim, Y. Gepner, M. Blüher, U. Ceglarek, B. Isermann, M. Stumvoll, I. Shelef, L. Qi, J. Li, F.B. Hu, M.J. Stampfer, I. Shai, 2025. Visceral adipose tissue area and proportion provide distinct reflections of cardiometabolic outcomes in weight loss; pooled analysis of MRI-assessed CENTRAL and DIRECT PLUS dietary randomized controlled trials. BMC Med. 23(1):57. doi: 10.1186/s12916-025-03891-9.

Background: Visceral adipose tissue (VAT) is well established as a pathogenic fat depot, whereas superficial subcutaneous adipose tissue (SAT) is associated with either an improved or neutral cardiovascular state. However, it is unclear to what extent VAT area (VATcm2) and its proportion of total abdominal adipose tissue (VAT%) are distinguished in predicting cardiometabolic status and clinical outcomes during weight loss. Methods: We integrated magnetic resonance imaging (MRI) measurements of VAT, deep-SAT, and superficial-SAT from two 18-month lifestyle weight loss clinical trials, CENTRAL and DIRECT PLUS (n = 572). Results: At baseline, the mean VATcm2 was 144.8cm2 and VAT% = 28.2%; over 18 months, participants lost 28cm2 VATcm2 (- 22.5%), and 1.3 VAT% units. Baseline VATcm2 and VAT% were similarly associated with metabolic syndrome, hypertension, and diabetes status, while VAT% better classified hypertriglyceridemia. Conversely, higher VATcm2 was associated with elevated high-sensitivity C-reactive protein (hsCRP), while VAT% was not. After 18 months of lifestyle intervention, both VATcm2 and VAT% loss were significantly associated with decreased triglycerides, HbA1c, ferritin, and liver enzymes, and increased HDL-c levels beyond weight loss (FDR < 0.05). Only VATcm2 loss was correlated with decreased HOMA-IR, chemerin, and leptin levels. Conclusions: MRI follow-up of 572 participants over 18 months of weight loss intervention suggests that although increased VATcm2 and VAT% exhibit similar clinical manifestations, it might be preferable to examine VAT% when exploring lipid status, while VATcm2 may better reflect inflammatory and glycemic states.

Metabolisable energy from nuts and patterns of nut consumption in the Australian population: a secondary analysis of the 2011–12 National Nutrition and Physical Activity Survey.

Nikodijevic, C.J., Y.C. Probst, S.-Y. Tan, E.P. Neale, 2024. Metabolisable energy from nuts and patterns of nut consumption in the Australian population: a secondary analysis of the 2011–12 National Nutrition and Physical Activity Survey. J Hum Nutr Diet. 37: 538–549. https://doi.org/10.1111/jhn.13278

Background: Nut intake is not associated with increased body weight, which may be explained by their metabolisable energy, among other factors. Therefore, total energy intake may be overestimated among nut consumers. This study aimed to describe the metabolisable energy from nuts and nut consumption patterns in the Australian population. Methods: A nut‐specific database was expanded to include metabolizable energy of nuts (based on nut type and form) and applied to the 2011–12 National Nutrition and Physical Activity Survey (NNPAS). Participants were Australians aged 2 years and older from the 2011–12 NNPAS (n = 12,153, with n = 4,765 nut consumers). Mean metabolisable energy intake was compared with mean energy intake using Atwater factors in nut consumers. Additionally, nut consumption patterns were explored, including the proportion of nuts consumed at meals and snacks. Results: Among nut consumers, mean metabolisable energy from nuts based only on nut type was 241.2 (95% confidence interval [CI]: 232.0, 250.5) kJ/day and mean metabolisable energy considering both nut type and form was 260.7(95% CI: 250.2, 271.2) kJ/day. Energy intake from nuts using Atwater factors was 317.6 (95% CI: 304.8, 330.3) kJ/day. Nuts were more likely to be consumed at snack occasions, with approximately 63% of nut intake occurring as a snack. Conclusion: Application of metabolisable energy to the 2011–12 NNPAS has a significant impact on calculation of energy intake from nuts. Nut consumption patterns identified a majority of nut consumption occurring as snacks. These findings may inform strategies to support nut consumption in Australia.

Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial.

Pachter, D., A. Kaplan, G. Tsaban, H. Zelicha, A.Y. Meir, E. Rinott, G. Levakov, M. Salti, Y. Yovell, S. Huhn, F. Beyer, V. Witte, P. Kovacs, M. von Bergen, U. Ceglarek, M. Blüher, M. Stumvoll, F.B. Hu, M.J. Stampfer, A. Friedman, I. Shelef, G. Avidan, I. Shai, 2024. Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial. Am J Clin Nutr. 120(5):1029-1036. doi: 10.1016/j.ajcnut.2024.09.013.

Background: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 mo. Objective: The objective of this study was to explore the contribution of specific diet-induced parameters to brain-volume deviation from chronologic age. Methods: A post hoc analysis of the 18-mo DIRECT PLUS trial, where participants were randomly assigned to the following groups: 1) healthy dietary guidelines, 2) MED diet, or 3) green-MED diet, high in polyphenols, and low in red meat. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The green-MED group further consumed green tea (3-4 cups/d) and Mankai green shake (Wolffia globosa aquatic plant) (+800 mg/d polyphenols). We collected blood samples through the intervention and followed brain structure volumes by magnetic resonance imaging (MRI). We used hippocampal occupancy (HOC) score (hippocampal and inferior lateral-ventricle volumes ratio) as a neurodegeneration marker and brain-age proxy. We applied multivariate linear regression models. Results: Of 284 participants [88% male; age = 51.1 y; body mass index = 31.2 kg/m2; hemoglobin A1c (HbA1c) = 5.48%; APOE-ε4 genotype = 15.7%], 224 completed the trial with eligible whole-brain MRIs. Individuals with higher HOC deviations (i.e., younger brain age) presented lower body weight [r = -0.204; 95% confidence interval (CI): -0.298, -0.101], waist circumference (r = -0.207; 95% CI: -0.310, -0.103), diastolic (r = -0.186; 95% CI: -0.304, -0.072), systolic blood pressure (r = -0.189; 95% CI: -0.308, -0.061), insulin (r = -0.099; 95% CI: -0.194, -0.004), and HbA1c (r = -0.164; 95% CI: -0.337, -0.006) levels. After 18 mo, greater changes in HOC deviations (i.e., brain-age decline attenuation) were independently associated with improved HbA1c (β = -0.254; 95% CI: -0.392, -0.117), HOMA-IR (β = -0.200; 95% CI: -0.346, -0.055), fasting glucose (β = -0.155; 95% CI: -0.293, -0.016), and c-reactive protein (β = -0.153; 95% CI: -0.296, -0.010). Improvement in diabetes status was associated with greater HOC deviation changes than either no change in diabetes status (0.010; 95% CI: 0.002, 0.019) or with an unfavorable change (0.012; 95% CI: 0.002, 0.023). A decline in HbA1c was further associated with greater deviation changes in the thalamus, caudate nucleus, and cerebellum (P < 0.05). Greater consumption of Mankai and green tea (green-MED diet components) were associated with greater HOC deviation changes beyond weight loss. Conclusions: Glycemic control contributes to the neuroprotective effects of the MED and green-MED diets on brain age. Polyphenols-rich diet components as Mankai and green tea may contribute to a more youthful brain age.