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Research Nut: Walnuts

Consumption of tree nuts as snacks reduces metabolic syndrome risk in young adults: a randomized trial.

Sumislawski, K., A. Widmer, R.R. Suro, M.E. Robles, K. Lillegard, D. Olson, J.R. Koethe, H.J. Silver, 2023. Consumption of tree nuts as snacks reduces metabolic syndrome risk in young adults: a randomized trial. Nutrients. 15(24):5051. doi: 10.3390/nu15245051.

Metabolic syndrome (MetSx) and its chronic disease consequences are major public health concerns worldwide. Between-meal snacking may be a modifiable risk factor. We hypothesized that consuming tree nuts as snacks, versus typical carbohydrate snacks, would reduce risk for MetSx in young adults. A prospective, randomized, 16-week parallel-group diet intervention trial was conducted in 84 adults aged 22-36 with BMI 24.5 to 34.9 kg/m2 and ≥1 MetSx clinical risk factor. Tree nuts snacks (TNsnack) were matched to carbohydrate snacks (CHOsnack) for energy (kcal), protein, fiber, and sodium content as part of a 7-day eucaloric menu. Difference in change between groups was tested by analysis of covariance using general linear models. Multivariable linear regression modeling assessed main effects of TNsnack treatment and interactions between TNsnack and sex on MetSx score. Age, BMI, and year of study enrollment were included variables. There was a main effect of TNsnack on reducing waist circumference in females (mean difference: -2.20 ± 0.73 cm, p = 0.004) and a trend toward reduced visceral fat (-5.27 ± 13.05 cm2, p = 0.06). TNsnack decreased blood insulin levels in males (-1.14 ± 1.41 mIU/L, p = 0.05) and multivariable modeling showed a main effect of TNsnack on insulin. Main effects of TNsnack on triglycerides and TG/HDL ratio were observed (p = 0.04 for both) with TG/HDL ratio reduced ~11%. A main effect of TNsnack (p = 0.04) and an interaction effect between TNsnack and sex (p < 0.001) on total MetSx score yielded 67% reduced MetSx score in TNsnack females and 42% reduced MetSx score in TNsnack males. To our knowledge, this is the first randomized parallel-arm study to investigate cardiometabolic responses to TNsnacks versus typical CHOsnacks among young adults at risk of MetSx. Our study suggests daily tree nut consumption reduces MetSx risk by improving waist circumference, lipid biomarkers, and/or insulin sensitivity-without requiring caloric restriction.

Association of tree nut consumption with cardiovascular disease and cardiometabolic risk factors and health outcomes in US adults: NHANES 2011-2018.

Lopez-Neyman, S. M., N. Zohoori, K.S. Broughton, D.C. Miketinas, 2023. Association of tree nut consumption with cardiovascular disease and cardiometabolic risk factors and health outcomes in US adults: NHANES 2011-2018. Curr. Dev. Nutr. 7(10):102007. https://doi.org/10.1016/j.cdnut.2023.102007

Background: Tree nuts are nutrient dense, and their consumption has been associated with improvements in health outcomes. Objective: To estimate the usual tree nut intake and examine the association between tree nut consumption and cardiometabolic (CM) health outcomes in a nationally representative sample of US adults. Methods: Cross-sectional data were analyzed from a sample of 18,150 adults aged ≥ 20y who provided at least one reliable 24-h dietary recall and had complete data for the variables of interest in the NHANES 2011-2018. Tree nut consumers were defined as those consuming ≥ ¼ ounce/d (7.09 g). The National Cancer Institute Method was used to estimate the usual tree nut intake among consumers. Measurement error calibrated regression models were used to assess the association between tree nut consumption and each health outcome of interest. Results: Approximately 8% of all participants (n = 1238) consumed tree nuts and had a mean ± SE usual intake of 39.5 ± 1.8 g/d. Tree nut consumers were less likely to have obesity (31% vs. 40%, P < 0.001) and low high-density lipoprotein cholesterol (22% vs. 30%, P < 0.001) compared with nonconsumers. Moreover, tree nut consumers had a lower mean waist circumference (WC) (97.1 ± 0.7 vs. 100.5 ± 0.3 cm, P < 0.001) and apolipoprotein B (87.5 ± 1.2 vs. 91.8 ± 0.5 mg/dL, P = 0.004) than nonconsumers. After adjusting models for demographics and lifestyle covariates, the difference in WC between average intake (33.7 g/d) and low threshold intake (7.09/g) of tree nuts was -1.42 ± 0.58 cm (P = 0.005). Conclusions: Most US adults do not consume tree nuts, yet modest consumption was associated with decreased prevalence of cardiovascular disease and CM risk factors and improvement for some health outcome measures.

Effect of walnut supplementation on dietary polyphenol intake and urinary polyphenol excretion in the walnuts and healthy aging study.

Amen, R. I., Sirirat, R., Oda, K., Rajaram, S., Nwachukwu, I., Cofan, M., Ros, E., Sabate, J., & Haddad, E. H. (2023). Effect of walnut supplementation on dietary polyphenol intake and urinary polyphenol excretion in the walnuts and healthy aging study. Nutrients. 15(5):1253. https://doi.org/10.3390/nu15051253

Among all tree nuts, walnuts contain the highest total polyphenols by weight. This secondary data analysis examined the effect of daily walnut supplementation on the total dietary polyphenols and subclasses and the urinary excretion of total polyphenols in a free-living elderly population. In this 2-year prospective, randomized intervention trial (ID NCT01634841), the dietary polyphenol intake of participants who added walnuts daily to their diets at 15% of daily energy were compared to those in the control group that consumed a walnut-free diet. Dietary polyphenols and subclasses were estimated from 24 h dietary recalls. Phenolic estimates were derived from Phenol-Explorer database version 3.6. Participants in the walnut group compared to the control group had a higher intake of total polyphenols, flavonoids, flavanols, and phenolic acids in mg/d (IQR): 2480 (1955, 3145) vs. 1897 (1369, 2496); 56 (42,84) vs. 29 (15, 54); 174 (90, 298) vs. 140 (61, 277); and 368 (246, 569) vs. 242 (89, 398), respectively. There was a significant inverse association between dietary flavonoid intake and urine polyphenol excretion; less urinary excretion may imply that some of the polyphenols were eliminated via the gut. Nuts had a significant contribution to the total polyphenols in the diet, suggesting that a single food like walnuts added to habitual diet can increase the polyphenol intake in a Western population.

A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial. 

Hoffmann, A., A.Y. Meir, T. Hagemann, P. Czechowski, L. Müller, B. Engelmann, S.B. Haange, U. Rolle-Kampczyk, G. Tsaban, H. Zelicha, E. Rinott, A. Kaplan, I. Shelef, M. Stumvoll, M. Blüher, L. Liang, U. Ceglarek, B. Isermann, M. von Bergen, P. Kovacs, M. Keller, I. Shai, 2023. A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial. Metabolism. 145:155594. https://doi.org/10.1016/j.metabol.2023.155594S.

Background: The capacity of a polyphenol-enriched diet to modulate the epigenome in vivo is partly unknown. Given the beneficial metabolic effects of a Mediterranean (MED) diet enriched in polyphenols and reduced in red/processed meat (green-MED), as previously been proven by the 18-month DIRECT PLUS randomized controlled trial, we analyzed the effects of the green-MED diet on methylome and transcriptome levels to highlight molecular mechanisms underlying the observed metabolic improvements. Methods: Our study included 260 participants (baseline BMI = 31.2 kg/m2, age = 5 years) of the DIRECT PLUS trial, initially randomized to one of the intervention arms: A. healthy dietary guidelines (HDG), B. MED (440 mg polyphenols additionally provided by walnuts), C. green-MED (1240 mg polyphenols additionally provided by walnuts, green tea, and Mankai: green duckweed shake). Blood methylome and transcriptome of all study subjects were analyzed at baseline and after completing the 18-month intervention using Illumina EPIC and RNA sequencing technologies. Results: A total of 1573 differentially methylated regions (DMRs; false discovery rate (FDR) < 5 %) were found in the green-MED compared to the MED (177) and HDG (377) diet participants. This corresponded to 1753 differentially expressed genes (DEGs; FDR < 5 %) in the green-MED intervention compared to MED (7) and HDG (738). Consistently, the highest number (6 %) of epigenetic modulating genes was transcriptionally changed in subjects participating in the green-MED intervention. Weighted cluster network analysis relating transcriptional and phenotype changes among participants subjected to the green-MED intervention identified candidate genes associated with serum-folic acid change (all P < 1 × 10-3) and highlighted one module including the KIR3DS1 locus, being negatively associated with the polyphenol changes (e.g. P < 1 × 10-4), but positively associated with the MRI-assessed superficial subcutaneous adipose area-, weight- and waist circumference- 18-month change (all P < 0.05). Among others, this module included the DMR gene Cystathionine Beta-Synthase, playing a major role in homocysteine reduction. Conclusions: The green-MED high polyphenol diet, rich in green tea and Mankai, renders a high capacity to regulate an individual’s epigenome. Our findings suggest epigenetic key drivers such as folate and green diet marker to mediate this capacity and indicate a direct effect of dietary polyphenols on the one‑carbon metabolism.

Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice.

Lázaro, I., J. Bobi, M. Cofán, G. Kapravelou, A.J. Amor, J. Surra, C. Gómez-Guerrero, E. Ortega, J. Osada, A.P. Dantas, A. Sala-Vila, 2023. Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice. Front. Nutr. 10:1079407. https://doi.org/10.3389/fnut.2023.1079407

Introduction: The lower rates of cardiovascular disease in Southern Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques. Consumption of certain foods affects the progression and severity of atherosclerosis. We investigated whether the isocaloric inclusion of walnuts within an atherogenic diet prevents phenotypes predicting unstable atheroma plaque in a mouse model of accelerated atherosclerosis. Methods: Apolipoprotein E-deficient male mice (10-week-old) were randomized to receive a control diet (9.6% of energy as fat, n = 14), a palm oil-based high-fat diet (43% of energy as fat, n = 15), or an isocaloric diet in which part of palm oil was replaced by walnuts in a dose equivalent to 30 g/day in humans (n = 14). All diets contained 0.2% cholesterol. Results: After 15 weeks of intervention, there were no differences in size and extension in aortic atherosclerosis among groups. Compared to control diet, palm oil-diet induced features predicting unstable atheroma plaque (higher lipid content, necrosis, and calcification), and more advanced lesions (Stary score). Walnut inclusion attenuated these features. Palm oil-based diet also boosted inflammatory aortic storm (increased expression of chemokines, cytokines, inflammasome components, and M1 macrophage phenotype markers) and promoted defective efferocytosis. Such response was not observed in the walnut group. The walnut group’s differential activation of nuclear factor kappa B (NF-kappaB; downregulated) and Nrf2 (upregulated) in the atherosclerotic lesion could explain these findings. Conclusion: The isocaloric inclusion of walnuts in an unhealthy high-fat diet promotes traits predicting stable advanced atheroma plaque in mid-life mice. This contributes novel evidence for the benefits of walnuts, even in an unhealthy dietary environment.

Effect of nuts on gastrointestinal health. 

Mandalari, G., T. Gervasi, D.W. Rosenberg, K.G. Lapsley, D.J. Baer, 2023. Effect of nuts on gastrointestinal health. Nutrients. 15(7):1733. https://doi.org/10.3390/nu15071733

Nuts are high nutrient-dense foods containing healthy lipids, dietary fiber, and bioactive phytochemicals, including vitamins and minerals. Although the beneficial effect of nut consumption on different chronic diseases has been well documented, especially in relation to their cardiometabolic benefits, less scientific evidence is available on their possible beneficial effects on gastrointestinal health. In this narrative review, we summarize the most important findings and new research perspectives in relation to the importance of nut consumption on gastrointestinal health. The integrity of the cell wall structure, cell size and particle size after mastication are known to play a crucial role in energy, nutrient and bioactive release from nuts during digestion, therefore affecting bioaccessibility. Other mechanisms, such as cell wall composition, thickness and porosity, as well as stability of the membranes surrounding the oil bodies within the cell, are also important for energy extraction. As the undigested nutrients and phytochemicals are delivered to the colon, effects on gut microbiota composition are predicted. Although the overall effect of nut consumption on microbial alpha- and beta-diversity has been inconsistent, some scientific evidence suggests an increase in fecal butyrate after almond consumption, and a beneficial role of walnuts on the prevention of ulcerative colitis and protection against the development of gastric mucosal lesions.

Dietary walnuts preserve aspects of health span and alter the hippocampal lipidome in aged high-fat diet-fed mice.

Novaj, A., M.G. Engel, R. Wang, K. Mao, X. Xue, Y. Amir, G. Atzmon, D.M. Huffman, 2023. Dietary walnuts preserve aspects of health span and alter the hippocampal lipidome in aged high-fat diet-fed mice. Int. J. Mol. Sci. 24(3), 2314. https://doi.org/10.3390/ijms24032314

Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of health span and related biochemical markers (n = 10-19 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p < 0.05) and tended to temper the effects of HFD on liver weight gain (p < 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of health span in the context of a metabolic stressor with aging.

Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial. 

Pinar-Martí, A., F. Gignac, S. Fernández-Barrés, D. Romaguera, A. Sala-Vila, I. Lázaro, O.T. Ranzani, C. Persavento, A. Delgado, A. Carol, J. Torrent, J. Gonzalez, E. Roso, J. Barrera-Gómez, M. López-Vicente, O. Boucher, M. Nieuwenhuijsen, M.C. Turner, M. Burgaleta, J. Canals,  V. Arija, X. Basagaña , E. Ros, J. Salas-Salvadó , J. Sunyer, J. Julvez, 2023. Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial. EClinicalMedicine. 59, 101954. https://doi.org/10.1016/j.eclinm.2023.101954

Background: Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. Methods: We conducted a 6-month multi-school-based randomized controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioral development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11–16 years were randomized into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioral (socioemotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomization prognostic factors (including adherence) using generalized estimating equations. Findings: In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p < 0.0001). The per-protocol (adherence-adjusted) effect on improvement in attention score (hit reaction time variability) was −11.26 ms (95% CI = −19.92, −2.60; p = 0.011) for the intervention group as compared to the control group, improvement in fluid intelligence score was 1.78 (95% CI = 0.90, 2.67; p < 0.0001), and reduction of ADHD symptom score was −2.18 (95% CI = −3.70, −0.67; p = 0.0050). Interpretation Our study suggested that being prescribed eating walnuts for 6 months did not improve the neuropsychological function of healthy adolescents. However, improved sustained attention, fluid intelligence, and ADHD symptoms were observed in participants who better complied with the walnut intervention. This study provides a foundation for further clinical and epidemiological research on the effect of walnuts and ALA on neurodevelopment in adolescents.

Adding walnuts to the usual diet can improve diet quality in the United States: diet modeling study based on NHANES 2015-2018. 

Spence, L.A., B. Henschel, R. Li, C.D. Tekwe, K. Thiagarajah, 2023. Adding walnuts to the usual diet can improve diet quality in the United States: diet modeling study based on NHANES 2015-2018. Nutrients. 15(2):258. https://doi.org/10.3390/nu15020258

Background: The under-consumption of calcium, potassium, fiber, and vitamin D is considered a U.S. public health concern. Shifts in eating patterns that increase the consumption of vegetables, fruits, whole grains, nuts/seeds, and dairy products can help achieve the recommended intakes of these nutrients, leading to healthier diets. Objective: We assessed the impact of adding 1 ounce (28.35 g) of walnuts to usual diets on diet quality and nutrients of concern, including magnesium, fiber, and potassium. Methods: We utilized 24 h dietary recalls obtained from the What We Eat in America, National Health and Nutrition Examination Survey (NHANES) and modeled the addition of 1 ounce (28.35 g) of walnuts to the usual diets of no-nut consumers. No-nut consumers aged _4 years (n = 7757) from the 2015–2018 NHANES study were included. Population percentages with intakes below the estimated average requirement (EAR) values for calcium, magnesium, folate, and vitamin E and above the adequate intake (AI) values for potassium and fiber were examined. Diet quality was assessed using the Healthy Eating Index-2015 (HEI-2015). The National Cancer Institute method was used to estimate the usual and modeled intakes. Significant differences between usual (current) and modeled intakes were determined using non-overlapping 95% confidence intervals. All analyses included sample weights to account for the NHANES survey design. Results: Adding 1 ounce (28.35 g) of walnuts to the usual diet resulted in significant reductions in the percentages of adults with intakes below the EAR for magnesium and folate (69.6% vs. 52.0%; 49.2% vs. 40.6%, respectively), and increased the percentage of adults above the AI for potassium (22.8% vs. 26.5%). A similar trend was observed among children (4–18 years). HEI scores improved significantly from 49.1 (95% CI: 48.0–50.4) to 58.5 (95% CI: 57.5–59.6) in children and from 52.4 (95% CI: 51.0–53.8) to 59.2 (95% CI: 58.0–60.5) in adults. Conclusions: Adding 1 ounce (28.35 g) of walnuts to the usual diet of no-nut consumers improved the diet quality and adequacy of some under-consumed nutrients.

Long-term consumption of nuts (including peanuts, peanut butter, walnuts, and other nuts) in relation to risk of frailty in older women: evidence from a cohort study.

Wang, R., M.T. Hannan, M. Wang, A.W. Schwartz, E. Lopez-Garcia, F. Grodstein, 2023. Long-term consumption of nuts (including peanuts, peanut butter, walnuts, and other nuts) in relation to risk of frailty in older women: evidence from a cohort study. J. Nutr. 153(3): 820–827.

Background: Adherence to a healthy diet is inversely associated with frailty. However, the relationship between nuts, a key food group of Mediterranean diet, and frailty is unclear. Objectives: This study aimed to evaluate the association between nut consumption and frailty in an aging female population. Methods: This population-based observational study included nonfrail women (60 y old) in the NHS from 11 states of the United States.

Outcome was incident frailty, defined as having 3 of the FRAIL components (fatigue, lower strength, reduced aerobic capacity, multiple chronic conditions, and significant weight loss) and assessed every 4 y from 1992 to 2016. From 1990 to 2014, FFQs were used to assess the intakes of peanuts, peanut butter, walnuts (added in 1998), and other nuts at 4-y intervals. Exposure was total nut consumption, calculated as the sum of intakes of peanuts, peanut butter, walnuts, and other nuts and categorized into <1 serving/mo, 1–3 servings/mo, 1 serving/wk, 2 4 servings/wk, and 5 servings/wk. The relations of intakes of peanuts, peanut butter, and walnuts with frailty were also investigated separately. Cox proportional hazards models were used to assess the associations between nut consumption and frailty after adjusting for age, smoking, BMI, EI, diet quality, and medication use. Results: Among 71,704 participants, 14,195 incident frailty cases occurred over 1,165,290 person-years. The adjusted HR (95% CI) for consuming 5 servings/wk of nuts was 0.80 (0.73, 0.87), as compared with <1 serving/mo. Higher intakes of peanuts and walnuts, but not peanut butter, were also inversely associated with frailty. Conclusions: This large prospective cohort study showed a strong and consistent inverse association between regular nut consumption and incident frailty. This suggests that nut consumption should be further tested as a convenient public health intervention for the preservation of health and well-being in older adults.