Walnut Supplementation Research Articles

Regulation of Intestinal Inflammation by Walnut-Derived Bioactive Compounds.

Walnuts (Juglans regia L.) have shown promising effects in terms of ameliorating inflammatory bowel disease (IBD), attributed to their abundant bioactive compounds. This review comprehensively illustrates the key mechanisms underlying the therapeutic potential of walnuts in IBD management, including the modulation of intestinal mucosa permeability, the regulation of inflammatory pathways (such as NF-kB, COX/COX2, MAPCK/MAPK, and iNOS/NOS), relieving oxidative stress, and the modulation of gut microbiota. Furthermore, we highlight walnut-derived anti-inflammatory compounds, such as polyunsaturated fatty acids (PUFA; e.g., ω-3 PUFA), tocopherols, phytosterols, sphingolipids, phospholipids, phenolic compounds, flavonoids, and tannins. We also discuss unique anti-inflammatory compounds such as peptides and polysaccharides, including their extraction and preparation methods. Our review provides a theoretical foundation for dietary walnut supplementation in IBD management and provides guidance for academia and industry. In future, research should focus on the targeted isolation and purification of walnut-derived anti-inflammatory compounds or optimizing extraction methods to enhance their yields, thereby helping the food industry to develop dietary supplements or walnut-derived functional foods tailored for IBD patients.

Walnut supplementation increases levels of UCP1 and CD36 in brown adipose tissue independently of diet type.

Dietary interventions that modulate the brown adipose tissue (BAT) thermogenic activity could represent a promising therapy for metabolic disorders. In order to examine if dietary walnuts intake regulates the expression of BAT thermogenic markers levels in healthy and metabolically challenged (fructose fed) animals, rats were initially divided into the control and fructose-fed groups. After nine weeks, these groups were subdivided into the one kept on the original regimens and the other supplemented with walnuts. High-fructose diet resulted in an increased relative BAT mass and no change in UCP1 content, while the walnut supplementation increased the amount of UCP1 in BAT, but did not affect 5-HT, NA, DHPG content and DHPG/NA ratio regardless of the diet. Moreover, the CD36 levels were increased following the walnut consumption, unlike FATP1, GLUT1, GLUT4, and glycogen content which remained unchanged. Additionally, the BAT levels of activated IR and Akt were not affected by walnut consumption, while ERK signaling was decreased. Overall, we found that walnut consumption increased UCP1 and CD36 content in the BAT of both control and metabolically challenged rats, suggesting that FFAs represent the BAT preferred substrate under the previously described circumstances. This further implies that incorporating walnuts into the everyday diet may help to alleviate some symptoms of the metabolic disorder.

Effect of Walnut Supplementation on Dietary Polyphenol Intake and Urinary Polyphenol Excretion in the Walnuts and Healthy Aging Study.

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.

Dietary Walnuts Preserve Aspects of Health Span and Alter the Hippocampal Lipidome in Aged High-Fat Diet-Fed Mice.

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 healthspan 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 healthspan in the context of a metabolic stressor with aging.

Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart.

Increased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health.

The Effect of Walnut Supplementation on Dietary Polyphenol Intake in the Walnuts and Healthy Aging Study (WAHA)

ObjectivesThe effect of a daily walnut supplement on the intake of total dietary polyphenols and subclasses in a free-living elderly population. MethodsIn this 2-year prospective, randomized intervention trial, 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 habitual diet. Walnut group participants received 28, 42, or 56 g/d of packaged walnuts. Dietary polyphenols and subclasses were estimated from multiple unannounced 24-hours dietary recalls, and nutrient data were obtained using the Nutrition Data System for Research (NDSR) software version 2013 (Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN). Phenolic estimates were derived from Phenol-Explorer database version 3.6 (June 2015). All polyphenol intake variables were energy-adjusted, and Mann-Whitney tests were used for comparison between treatments. Total polyphenol rich foods were categorized into food groups and ranked from highest to lowest per contributing food sources. ResultsCompared to the control group, participants in the walnut group had a higher intake of total polyphenol, total flavonoids, flavanols, and phenolic acid in mg/d (IQR): 2480 (1955, 3145) vs 1897 (1369, 2496) (P < 0.001); 56 (42, 84) vs 29 (15, 54) (P < 0.001); 174 (90, 298) vs 140 (61, 277) (p = 0.036); and 368 (246, 569) vs 242 (89, 398) (P < 0.001) respectively. Food categories contributing to total dietary polyphenols per 100 grams of intake ranked from highest to lowest in mg/d (SD) were: beverages 846 (726), fruits 397 (334), nuts and seeds 344 (329), legumes 281 (619), vegetables 248 (258), grains 127 (139), chocolates 100 (233), spices 26 (77), and fats/oils 7 (6). ConclusionsThe walnut group had a higher intake of dietary polyphenols compared to those in the control group. Nuts and seeds were the third highest contributing source of total polyphenol in the diets of participants in this study, suggesting that a single food like walnuts added to the daily diet can increase polyphenol intake in a population. Funding SourcesThis study was supported by a grant from the California Walnut Commission, Sacramento, CA, USA.

Food and Nutrient Displacement by Walnut Supplementation in a Randomized Crossover Study.

The aim of this article is to evaluate the effect of a daily supplement of walnuts on the overall daily diet and nutrient profile of healthy adults. A randomized controlled trial with crossover design was conducted for two 6-month diet periods in southeast Californian communities. Subjects were randomized to receive a control diet or a walnut-supplemented diet, then switched. The walnut supplement represented approximately 12% of their daily energy intake. Trained nutritionists collected seven 24 h dietary recalls from each participant (a total of 14 recalls for both periods). Ninety participants were able to complete the study, including 50 females and 40 males. The average age of the participants was 54.3 years. Diets in the walnut period had significantly higher vegetable protein, total fat, total PUFA, PUFA 18:2, PUFA 22:6, and total dietary fiber (p < 0.05), while also exhibiting significantly lower PUFA 20:5. All mineral levels were higher on the walnut-supplemented diet. Calcium, phosphorus, magnesium, and zinc were, particularly, significantly higher among the walnut-supplemented group (p < 0.05). Displacement occurred in more than one-third of the entire nuts and seeds group; four-fifths of the non-alcoholic beverages and desserts groups; and the majority of the candy, sugar, and sweets group. Walnut supplementation can lead to favorable modifications in nutrient and food intake profiles that may contribute to chronic disease prevention. Nutrient and food displacement may be a mechanism to explain the favourable association between walnut intake and improved diet.

Effect of Ethanolic Extract of Walnut Leaves on Lipid Profile and Atherogenic index in Hypercholesterolemic Rats

Aims: To determine the effect of Ethanolic extract of walnut leaves on lipid profile i.e seum total cholesterol, triglycerides, Low density and high-density lipoprotein. Atherogenic index in Hypercholesterolemic rats was calculated using serum TC/HDL and LDL/HDL ratios. Methodology: Total 30 male Sprague Dawley rats were further divided into three groups (C, HC and EE) comprising ten rats per group. Group 1 (Control group, C). Group 2 (Hypercholesterolemic control, HC) and Group 3 (Ethanolic Extract Group EE) were fed high fat diet for 8 weeks before administration of walnut leaf extract. Ethanolic extract (EE) of walnut leaves was given in a dose of (200mg/kg) through gavage needle once daily for four weeks. Blood Sampling was done at the beginning (Baseline, after week 8 and week 12 to perform lipid profile. Results: Serum mid- cholesterol levels (08 weeks) in HC were significantly raised to 164±7.90 mg/dl (p&lt;0.001) as compared to 57.75±6.64mg/dl), which confirmed the development of hypercholesterolemia. Post-cholesterol levels of EE (after 12 weeks) was decreased to 52.8±4.42 mg/dl compared with 153.2±5.92 mg/dl in HC group in (p&lt;0.001). Group 3 had significantly lower levels of of serum triglycerides, LDL and high levels of HDL cholesterol (p&lt;0.001) as compared to HC group 2 and 12 weeks versus 8 weeks of EE of walnut supplementation. The atherogenic index calculated by serum TC/HDL and LDL/HDL ratios were significantly reduced (p&lt;0.001). Conclusion: Ethanolic extracts of walnut leaves have hypolipidemic effects decreasing serum cholesterol, triglycerides, LDL, serum TC/HDL and LDL/HDL ratios while elevating the good cholesterol HDL. Keywords: Atherogenic ratio, Cholesterol, Dietary Lipids, Lipoprotein metabolism, Walnut supplementation

Fructose-rich diet and walnut supplementation differently regulate rat hypothalamic and hippocampal glucose transporters expression.

Nutritional modulations may be considered a strategy to protect mental health. Neuronal homeostasis is highly dependent on the availability of glucose, which represents the primary energy source for the brain. In this study, we evaluated the effects of walnut intake and fructose-rich diet on the expression of glucose transporters (GLUTs) in two rat brain regions: hypothalamus and hippocampus. Our results show that walnut supplementation of fructose-fed animals restored the hypothalamic content of GLUT1 and GLUT3 protein. Furthermore, walnut intake did not affect increased hypothalamic GLUT2 content upon fructose consumption. These effects were accompanied by distinctive alterations of hippocampal GLUTs levels. Specifically, walnut intake increased GLUT1 content, whereas GLUT2 protein was decreased within the rat hippocampus after both individual and combined treatments. Overall, our study suggests that walnut supplementation exerted modulatory effects on the glucose transporters within specific brain regions in the presence of developed metabolic disorder. © 2021 Society of Chemical Industry.

Protocol for a randomized controlled trial to test the acceptability and adherence to 6-months of walnut supplementation in Chinese adults at high risk of cardiovascular disease

BackgroundConsumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China.MethodsThis protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups.ResultsTwo hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics.DiscussionThis trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention.Trial registrationNCT04037943Protocol version: v3.0 August 14 2019

Walnut Supplementation Restores the SIRT1-FoxO3a-MnSOD/Catalase Axis in the Heart, Promotes an Anti-Inflammatory Fatty Acid Profile in Plasma, and Lowers Blood Pressure on Fructose-Rich Diet.

The benefits of walnut (Juglans regia) consumption for metabolic health are known, but the molecular background underlying their putative antioxidant and anti-inflammatory/immunomodulatory effects is underexplored. We assessed that walnut supplementation (6 weeks) reverted unfavorable changes of the SIRT1/FoxO3a/MnSOD/catalase axis in the heart induced by fructose-rich diet (FRD). Intriguingly, Nox4 was increased by both FRD and walnut supplementation. FRD increased the cytosolic fraction and decreased the nuclear fraction of the uniquely elucidated ChREBP in the heart. The ChREBP nuclear fraction was decreased in control rats subjected to walnuts. In addition, walnut consumption was associated with a reduction in systolic BP in FRD and a decrease in fatty acid AA/EPA and AA/DHA ratios in plasma. In summary, the protective effect of walnut supplementation was detected in male rats following the fructose-induced decrease in antioxidative/anti-inflammatory capacity of cardiac tissue and increase in plasma predictors of low-grade inflammation. The current results provide a novel insight into the relationship between nutrients, cellular energy homeostasis, and the modulators of inflammatory/immune response in metabolic syndrome, emphasizing the heart and highlighting a track for translation into nutrition and dietary therapeutic approaches against metabolic disease.

Moderate walnut consumption improved lipid profile, steroid hormones and inflammation in trained elderly men: a pilot study with a randomized controlled trial.

The present study aimed to investigate the effect of walnut consumption on lipid profile, steroid hormones and inflammation in trained elderly men performing concurrent (resistance and endurance) training. Twenty healthy elderly males were divided into two matched groups, in a randomized controlled trial, that trained three sessions per week: concurrent training + dietary walnut consumption (15 g/day for six weeks, CTW: n = 10); concurrent training + control diet (CT: n = 10). Fasting blood samples were taken 48 hours before and after intervention for biochemical assessments. levels of high-density lipoprotein (HDL) increased only in CTW compared to baseline (19.8%, p < 0.01). Total cholesterol (TC), low-density lipoprotein (LDL) and triglyceride (TG) levels significantly decreased only for CTW (i.e., 13%, 18%, and 18.5% at p < 0.01 for all). Testosterone (T) increased after the training compared to pre-training for CTW and CT (10.3%, p < 0.01, 4.27% p < 0.05, respectively), but the increase was significantly higher in CTW (p < 0.05). Serum cortisol (C) was lower for CTW compared to CT (p < 0.01). C-reactive protein (CRP) decreased in CTW in comparison with CT. The present study revealed that 6-week moderate walnut supplementation (15 g/day) improved lipid profile, steroid hormones and systematic inflammation in aged men performing concurrent training. These findings could be attributable to the potential effect of polyunsaturated fatty acids (PUFA) contained in walnut (linoleic acid, n-6; linolenic acid, n-3).

Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts And Healthy Aging (WAHA) study: a randomized controlled trial

Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. The Walnuts And Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut intervention in cognitively healthy elders. We randomly allocated 708 free-living elders (63-79 y, 68% women) to a diet enriched with walnuts at ∼15% energy (30-60 g/d) or a control diet (abstention from walnuts). We administered a comprehensive neurocognitive test battery at baseline and 2 y. Change in the global cognition composite was the primary outcome. We performed repeated structural and functional brain MRI in 108 Barcelona participants. A total of 636 participants completed the intervention. Besides differences in nutrient intake, participants from Barcelona smoked more, were less educated, and had lower baseline neuropsychological test scores than those from Loma Linda. Walnuts were well tolerated and compliance was good. Modified intention-to-treat analyses (n=657) uncovered no between-group differences in the global cognitive composite, with mean changes of -0.072 (95% CI:-0.100, -0.043) in the walnut diet group and -0.086 (95% CI: -0.115, -0.057) in the control diet group (P=0.491). Post hoc analyses revealed significant differences in the Barcelona cohort, with unadjusted changes of -0.037 (95% CI: -0.077, 0.002) in the walnut group and -0.097 (95% CI: -0.137, -0.057) in controls (P=0.040). Results of brain fMRI in a subset of Barcelona participants indicated greater functional network recruitment in a working memory task in controls. Walnut supplementation for 2 y had no effect on cognition in healthy elders. However, brain fMRI and post hoc analyses by site suggest that walnuts might delay cognitive decline in subgroups at higher risk. These encouraging but inconclusive results warrant further investigation, particularly targeting disadvantaged populations, in whom greatest benefit could be expected.This trial was registered at clinicaltrials.gov as NCT01634841.

Dietary Walnut Supplementation Alters Mucosal Metabolite Profiles During DSS-Induced Colonic Ulceration.

Walnuts contain a complex array of natural compounds and phytochemicals that exhibit a wide range of health benefits, including protection against inflammation and colon cancer. In this study, we assess the effects of dietary supplementation with walnuts on colonic mucosal injury induced in mice by the ulcerogenic agent, dextran sodium sulfate (DSS). C57Bl/6J mice were started on the Total Western Diet supplemented with freshly-ground whole walnuts (0, 3.5, 7 and 14% g/kg) 2 weeks prior to a 5-day DSS treatment and walnut diets were continued throughout the entire experimental period. Mice were examined at 2 days or 10 days after withdrawal of DSS. In a separate study, a discovery-based metabolite profiling analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on fecal samples and colonic mucosa following two weeks of walnut supplementation. Dietary walnut supplementation showed significant effects in the 10-day post-DSS recovery-phase study, in which the extent of ulceration was significantly reduced (7.5% vs. 0.3%, p < 0.05) with 14% walnuts. In the metabolite-profiling analysis, walnuts caused a significant increase in several polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and 9-oxo-10(E),12(E)-octadecadienoic acid (9-oxoODA), as well as kynurenic acid. In colon tissue samples, walnuts caused a significant increase in the levels of S-adenosylhomocysteine (SAH) and betaine, important components of fatty acid β-oxidation. These metabolite changes may contribute in part to the observed protection against DSS-induced inflammatory tissue injury.

Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts

Cadmium, a heavy metal with no physiological function in the human body, is considered a bio-hazard. It is also considered to be a potent neurotoxin. The primary sources of cadmium exposure are diet and cigarette smoke. It has been postulated that nutritional deficiencies can increase the risk of cadmium toxicity. Nuts provide essential nutrients which are necessary for the maintenance of brain health in humans. The present study was designed to investigate the possible protective effects of almond and walnut supplementation on cadmium-induced neurotoxicity. Cadmium was orally administered at a dose of 50 mg/kg weekly with or without the supplementation of almond and walnut in rats. Intensities of depression‑ and anxiety-related behaviors were assessed by the forced swim test and light/dark transition test, respectively. Memory function was also evaluated by the elevated plus maze, Morris water maze and novel object recognition task. After four weeks of treatment it was observed that cadmium administration significantly induced depressogenic and anxiogenic behaviors. Memory function was also impaired by cadmium administration. Cadmium-treated rats exhibited reduced noradrenalin, dopamine and serotonin levels in the brain, whereas the levels of their respective metabolites were significantly increased. The dietary supplementation of almond and walnut at a dose of 400 mg/kg/day significantly attenuated cadmium-induced depression, anxiety and memory impairments. Neurochemical aberrations also normalized following supplementation with these nuts in rats. The present study demonstrates that long-term supplementation with almond and walnut provides essential nutrients which may overcome nutritional deficiencies and thereby reduce heavy-metal intoxication.

Effects of Long-Term Walnut Supplementation on Body Weight in Free-Living Elderly: Results of a Randomized Controlled Trial.

Objective: To assess the effects of chronic walnut consumption on body weight and adiposity in elderly individuals. Methods: The Walnuts and Healthy Aging study is a dual-center (Barcelona, Spain and Loma Linda University (LLU)), 2-year randomized parallel trial. This report concerns only the LLU cohort. Healthy elders (mean age 69 year, 67% women) were randomly assigned to walnut (n = 183) or control diets (n = 173). Subjects in the walnut group received packaged walnuts (28–56 g/day), equivalent to ≈15% of daily energy requirements, to incorporate into their habitual diet, while those in the control group abstained from walnuts. Adiposity was measured periodically, and data were adjusted for in-trial changes in self-reported physical activity. Results: After 2 years, body weight significantly decreased (p = 0.031), while body fat significantly increased (p = 0.0001). However, no significant differences were observed between the control and walnut groups regarding body weight (−0.6 kg and −0.4 kg, respectively, p = 0.67) or body fat (+0.9% and +1.3%, respectively, p = 0.53). Lean body mass, waist circumference, and waist-to-hip ratio remained essentially unchanged. Sensitivity analyses were consistent with the findings of primary analysis. Conclusion: Our findings indicate that walnuts can be incorporated into the daily diet of healthy elders without concern for adverse effects on body weight or body composition.

Walnut Supplementation in the Diet Reduces Oxidative Damage and Improves Antioxidant Status in Transgenic Mouse Model of Alzheimer's Disease.

Our previous study has shown beneficial effects of walnuts on memory and learning skills in transgenic mouse model of Alzheimer’s disease (AD-tg). To understand underlying mechanism, we studied here whether walnuts can reduce oxidative stress in AD. From 4 months of age, experimental AD-tg mice were fed diets containing 6% (T6) or 9% walnuts (T9) (equivalent to 1 or 1.5 oz, of walnuts per day in humans) for 5, 10, or 15 months. The control groups, i.e., AD-tg (T0) and wild-type (Wt) mice, were fed diets without walnuts. Free radicals, i.e., reactive oxygen species (ROS), lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed in these mice at different ages. AD-tg mice on control diet (T0) showed significant age-dependent increase in ROS levels, lipid peroxidation, and protein oxidation coupled with impaired activities of antioxidant enzymes [superoxide dismutase, catalase, and glutathione peroxidase] compared to Wt mice. Oxidative stress was significantly reduced in AD-tg mice on diets with walnuts (T6, T9), as evidenced by decreased levels of ROS, lipid peroxidation, and protein oxidation, as well as by enhanced activities of antioxidant enzymes compared to T0 mice. Long-term supplementation with walnuts for 10 or 15 months was more effective in reducing oxidative stress in AD-tg mice. Our findings indicate that walnuts can reduce oxidative stress, not only by scavenging free radicals, but also by protecting antioxidant status, thus leading to reduced oxidative damage to lipids and proteins in AD. Therefore, by reducing oxidative stress, a walnut-enriched diet may help reduce the risk or delay the onset and progression of AD.

Walnut supplementation reverses the scopolamine-induced memory impairment by restoration of cholinergic function via mitigating oxidative stress in rats: a potential therapeutic intervention for age related neurodegenerative disorders.

The brain is highly susceptible to the damaging effects of oxidative reactive species. The free radicals which are produced as a consequence of aerobic respiration can cause cumulative oxygen damage which may lead to age-related neurodegeneration. Scopolamine, the anti-muscarinic agent, induces amnesia and oxidative stress similar to that observed in the older age. Studies suggest that antioxidants derived from plant products may provide protection against oxidative stress. Therefore, the present study was designed to investigate the attenuation of scopolamine-induced memory impairment and oxidative stress by walnut supplementation in rats. Rats in test group were administrated with walnut suspension (400mg/kg/day) for four weeks. Both control and walnut-treated rats were then divided into saline and scopolamine-treated groups. Rats in the scopolamine group were injected with scopolamine (0.5mg/kg dissolved in saline) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM), and novel object recognition task (NOR) followed by estimation of regional acetylcholine levels and acetylcholinesterase activity. In the next phase, brain oxidative status was determined by assaying lipid peroxidation, and measuring superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Results showed that scopolamine-treatment impaired memory function, caused cholinergic dysfunction, and induced oxidative stress in rats compared to that saline-treated controls. These impairments were significantly restored by pre-administration of walnut. This study demonstrates that antioxidant properties of walnut may provide augmented effects on cholinergic function by reducing oxidative stress and thus improving memory performance.

Favourable nutrient intake and displacement with long-term walnut supplementation among elderly: results of a randomised trial.

Older adults tend to require fewer energy content and higher levels of nutrients to promote and maintain optimal health. Regrettably, dietary variety and quality are known to decline with advancing age. We conducted a 2-year prospective, randomised, dietary intervention trial where we asked free-living elderly subjects (63-79 years) on self-selected habitual diets to incorporate walnuts daily into their diet (15 % energy). We then compared their nutrient intake with that of a similar group of concurrent participants on self-selected habitual diets but abstaining from walnut consumption (control). No recipes or advice on use of nuts were provided. Dietary intake was assessed by multiple unannounced 24-h telephone dietary recalls. On average, walnut supplement consumption was 43 g/d or 1171·5 kJ (281 kcal). The mean daily energy intake was 954 kJ (228 kcal) higher in the walnut group than in the control group (P<0·001). Compared with control, participants in the walnut group reported significantly higher intake of total protein, vegetable protein, total PUFA and n-3 and n-6 PUFA; and significantly lower intake of total carbohydrate, animal protein, SFA, and Na. An estimated 19 % of total energy and 25 % of total fat from other food sources was displaced. Displacement of MUFA and total PUFA was 21 and 16 %, respectively. Thus adding a daily supplement of walnuts to an ad libitum diet of older adults can induce favourable modifications to the nutrient profile in a way that addresses declining nutrient intake associated with aging.

Metabolic and Blood Pressure Effects of Walnut Supplementation in a Mouse Model of the Metabolic Syndrome.

There is extensive evidence that walnut consumption is protective against cardiovascular disease and diabetes in the healthy population, but the beneficial effects of walnut consumption in individuals with the metabolic syndrome (MetS) remain uncertain. We compared a range of cardio-metabolic traits and related tissue gene expression associated with 21 weeks of dietary walnut supplementation in a mouse model of MetS (MetS-Tg) and wild-type (WT) mice (n = 10 per genotype per diet, equal males and females). Compared to standard diet, walnuts did not significantly alter food consumption or body weight trajectory of either MetS-Tg or WT mice. In MetS-Tg mice, walnuts were associated with reductions in oral glucose area under the curve (gAUC, standard diet 1455 ± 54, walnut 1146 ± 91, p = 0.006) and mean arterial blood pressure (MAP, standard diet 100.6 ± 1.9, walnut 73.2 ± 1.8 mmHg, p < 0.001), with neutral effects on gAUC and MAP in WT mice. However, in MetS-Tg mice, walnuts were also associated with trends for higher plasma cholesterol (standard diet 4.73 ± 0.18, walnut 7.03 ± 1.99 mmol/L, p = 0.140) and triglyceride levels (standard diet 2.4 ± 0.5, walnut 5.4 ± 1.6 mmol/L, p = 0.061), despite lowering cholesterol and having no effect on triglycerides in WT mice. Moreover, in both MetS-Tg and WT mice, walnuts were associated with significantly increased liver expression of genes associated with metabolism (Fabp1, Insr), cell stress (Atf6, Ddit3, Eif2ak3), fibrosis (Hgf, Sp1, Timp1) and inflammation (Tnf, Ptpn22, Pparg). In conclusion, dietary walnuts were associated with modest favourable effects in WT mice, but a combination of beneficial and adverse effects in MetS-Tg mice, and up-regulation of hepatic pro-fibrotic and pro-inflammatory genes in both mouse strains.