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Research Nut: Walnuts

A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change.

Razquin, C., J.A. Martínez, M.A. Martínez-González, J. Salas-Salvadó, R. Estruch, A. Marti, 2010. A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change. Eur J Nutr. 49(5):311-9.

Purpose Adiponectin gene variations have been associated with obesity. There are few interventional studies analyzing this association. The aim of this study was to analyze the effects of a nutritional intervention with Mediterranean-style diet and three (-4034A/C, +45T/G, and +276 G/T) adiponectin gene variants on 3-year body weight changes in high cardiovascular risk patients. Subjects and methods A total of 737 participants, aged 55–80 at high cardiovascular risk were assigned to a low-fat diet or to a Mediterranean-style diet (MD) groups, one with high intake of virgin olive oil (VOO) and the other with high intake of nuts. Anthropometric parameters were taken at baseline and after 3-year follow-up, and the genotyping of the -4034A/C, +45T/G, and +276 G/T polymorphisms was done. Results GG genotype of the +45T/G polymorphism was associated with 3-year higher body weight gain (B = 1.399; B = 0.043). TT genotype of the +276G/T polymorphism was linked to the highest 3-year body weight gain in men. Both Mediterranean diets appeared to reverse this effect (p for interaction = 0.053). Conclusion Adiponectin gene variation appeared to be associated with 3-year body weight changes in a high cardiovascular risk population. This association may be modulated by a nutritional intervention with a Mediterranean-style diet.

Effects of walnut consumption on endothelial function in type 2 diabetics: a randomized, controlled, cross-over trial.

Ma, Y., V.Y. Njike, J. Millet, S. Dutta, K. Doughty, J.A. Treu, D.L. Katz, 2010. Effects of walnut consumption on endothelial function in type 2 diabetics: a randomized, controlled, cross-over trial. Diabetes Care. 33(2):227-32.

Objective: To determine the effects of daily walnut consumption on endothelial function, cardiovascular biomarkers, and anthropometric measures in type 2 diabetics. Methods: This study was a randomized, controlled, single-blind, cross-over trial. Twenty-four participants with type 2 diabetes (mean age 58 years; 14 women, 10 men) were randomly assigned to one of the two possible sequence permutations to receive an ad libitum diet enriched with 56 g (366 kcal) of walnuts per day and an ad libitum diet without walnuts for 8 weeks. Subjects underwent endothelial function testing (measured as flow-mediated dilatation or FMD) and assessment of cardiovascular biomarkers before and after each 8-week treatment phase. The primary outcome measure was the change in FMD after 8 weeks. Secondary outcome measures included changes in plasma lipids, HbA1c, fasting glucose, insulin sensitivity, and anthropometric measures. Results: Endothelial function significantly improved after consumption of a walnut-enriched ad libitum diet compared to an ad libitum diet without walnuts (2.2 ± 1.7 % vs. 1.2 ± 1.6 %; p=0.04). The walnut-enriched diet increased fasting serum glucose, lowered serum total cholesterol and low-density lipoprotein cholesterol from baseline (10.0 ± 20.5 mg/dL; p=0.04, -9.7 ± 14.5 mg/dL; p<0.01; and -7.7 ± 10 mg/dL; p<0.01 respectively), though these changes were not significant when compared to an ad libitum diet without walnuts. There were no significant changes in anthropometric measures, plasma HbA1c, and insulin sensitivity. Conclusions: A walnut-enriched ad libitum diet improves endothelium-dependent vasodilatation in type 2 diabetics, suggesting a potential reduction in overall cardiac ris

Effect of whole walnuts and walnut-skin extracts on oxidant status in mice.

Bulló, M., M.R. Nogués, P. López-Uriarte, J. Salas-Salvadó, M. Romeu, 2010. Effect of whole walnuts and walnut-skin extracts on oxidant status in mice. Nutrition. 26(7-8):823-8.

Objective: To evaluate the effect of the intake of whole walnuts and walnut fractions on the oxidant status in mice. Methods: Thirty-six C57BL/6J male mice were randomized to be fed one of three diets: 1) a standard diet (control group), 2) a standard diet with 10% of whole walnuts (walnut-diet group), or 3) a standard diet with 2% of walnut skins (walnut-skin-diet group) for 8 wk. The plasma antioxidant capacity was measured by oxygen radical-absorbance capacity and plasma ferric-reducing antioxidant potential. Conjugated diene formation and reduced glutathione levels were also analyzed. Results: We observed no changes in plasma oxidation capability between the walnut and walnut skin groups with the exception of conjugated dienes. Plasma total antioxidant capacity and the ratio between reduced and oxidized forms of glutathione were lower in the walnut and walnut skin groups than in the control group. Conclusion: The decrease in the antioxidant burden observed in enzymatic and non-enzymatic antioxidant systems after sustained consumption of a whole-walnut or a walnut-skin diet in mice may be related to the plasma oxidation capability being maintained in the groups consuming the walnut diets.

Walnut extract inhibits LPS-induced activation of Bv-2 microglia via internalization of TLR4: possible involvement of phospholipase D2.

Willis, L.M., D.F. Bielinski, D.R. Fisher, N.R. Matthan, J.A. Joseph, 2010. Walnut extract inhibits LPS-induced activation of Bv-2 microglia via internalization of TLR4: possible involvement of phospholipase D2. Inflammation DOI: 10.1007/s10753-010-9189-0.

Walnuts are a rich source of essential fatty acids, including the polyunsaturated fatty acids alpha-linolenic acid and linoleic acid. Essential fatty acids have been shown to modulate a number of cellular processes in the brain, including the activation state of microglia. Microglial activation can result in the generation of cytotoxic intermediates and is associated with a variety of age-related and neurodegenerative conditions. In vitro, microglial activation can be induced with the bacterial cell wall component lipopolysaccharide (LPS). In the present study, we generated a methanolic extract of English walnuts (Juglans regia) and examined the effects of walnut extract exposure on LPS-induced activation in BV-2 microglial cells. When cells were treated with walnut extract prior to LPS stimulation, production of nitric oxide and expression of inducible nitric oxide synthase were attenuated. Walnut extract also induced a decrease in tumor necrosis-alpha (TNFα) production. We further found that walnut extract induced internalization of the LPS receptor, toll-like receptor 4, and that the anti-inflammatory effects of walnut were dependent on functional activation of phospholipase D2. These studies represent the first to describe the anti-inflammatory effects of walnuts in microglia, which could lead to nutritional interventions in the prevention and treatment of neurodegeneration.

Lifestyle counseling and supplementation with flaxseed or walnuts influence the management of metabolic syndrome.

Wu, H., A. Pan, Z. Yu, Q. Qi, L. Lu, G. Zhang, D. Yu, G. Zong, Y. Zhou, X. Chen, L. Tang, Y. Feng, H. Zhou, X. Chen, H. Li,W. Demark-Wahnefried, F.B. Hu, X. Lin, 2010. Lifestyle counseling and supplementation with flaxseed or walnuts influence the management of metabolic syndrome. J. Nutr. 140(11):1937-42. .

A healthy lifestyle may ameliorate metabolic syndrome (MetS); however, it remains unclear if incorporating nuts or seeds into lifestyle counseling (LC) has additional benefit. A 3-arm, randomized, controlled trial was conducted among 283 participants screened for MetS using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Participants were assigned to a LC on the AHA guidelines, LC + flaxseed (30 g/d) (LCF), or LC + walnuts (30 g/d) (LCW) group. After the 12-wk intervention, the prevalence of MetS decreased significantly in all groups: -16.9% (LC), -20.2% (LCF), and -16.0% (LCW). The reversion rate of MetS, i.e. those no longer meeting the MetS criteria at 12 wk, was not significantly different among groups (LC group, 21.1%; LCF group, 26.6%; and LCW group, 25.5%). However, the reversion rate of central obesity was higher in the LCF (19.2%; P = 0.008) and LCW (16.0%; P = 0.04) groups than in the LC group (6.3%). Most of the metabolic variables (weight, waist circumference, serum glucose, total cholesterol, LDL cholesterol, apolipoprotein (Apo) B, ApoE, and blood pressure) were significantly reduced from baseline in all 3 groups. However, the severity of MetS, presented as the mean count of MetS components, was significantly reduced in the LCW group compared with the LC group among participants with confirmed MetS at baseline (P = 0.045). Our results suggest that a low-intensity lifestyle education program is effective in MetS management. Flaxseed and walnut supplementation may ameliorate central obesity. Further studies with larger sample sizes and of longer duration are needed to examine the role of these foods in the prevention and management of MetS.

Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia.

Sala-Vila, A., M. Cofán, A. Pérez-Heras, I. Núñez, R. Gilabert, M. Junyent, R. Mateo-Gallego, A. Cenarro, F. Civeira, E. Ros, 2010. Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia. Am J Clin Nutr. 92:186-193.

Background: Low rates of incident ischemic heart disease (IHD) and cardiac death occur in Spain despite a high prevalence of cardiovascular risk factors. High consumption of unsaturated fatty acid–rich foods, such as olive oil, nuts, and seafood, might underlie this paradox. Objective: We investigated whether serum phosphatidylcholine enrichment in oleic, linoleic, α-linolenic, and n-3 (omega-3) long-chain polyunsaturated fatty acids (as biomarkers of olive oil, seed oil, walnut, and fish intake, respectively) relate to carotid atherosclerosis in Spanish subjects at risk of IHD. Design: In a cross-sectional study, we measured fatty acid concentrations in serum phosphatidylcholine and measured carotid intima-media thickness (IMT) by using ultrasound in 451 asymptomatic subjects (261 men, 190 women; mean age: 45 y) with primary dyslipidemia. Main and secondary outcomes were mean and maximum IMT in the common carotid artery (CCA) and other carotid segments, respectively. Results: Phosphatidylcholine fatty acid composition was similar to that reported for other Spanish populations. Multiple regression analyses showed that proportions of oleic and docosahexaenoic acids were inversely related to mean CCA IMT (P < 0.02, all) after adjustment for several confounders. In similar models, a-linolenic acid related inversely to mean and maximum internal carotid artery IMT (P < 0.05 for all). Linoleic and eicosapentaenoic acids were unrelated to IMT. Conclusions: Higher phospholipid proportions of oleic, α-linolenic, and docosahexaenoic acids showed inverse associations with IMT at specific carotid segments in subjects with primary dyslipidemia. High intakes of healthy fats might explain, in part, the Spanish paradox of low IHD rates in the face of a high burden of cardiovascular risk factors.

Carotid and femoral plaque burden is inversely associated with the α-linolenic acid proportion of serum phospholipids in Spanish subjects with primary dyslipidemia.

Sala-Vila, A., M. Cofán, I. Núñez, R. Gilabert, M. Junyent, E. Ros, 2010. Carotid and femoral plaque burden is inversely associated with the α-linolenic acid proportion of serum phospholipids in Spanish subjects with primary dyslipidemia. Atherosclerosis. 214:209-214.

Objective:  α-Linolenic acid (ALA), the vegetable n-3fatty acid, appears to have antiatherosclerotic prop- erties akin to those of marine n-3 fatty acids. A prior study in a US population with low fish intake showed an inverse association between ALA intake and carotid plaque. We examined the association between the ALA status and advanced carotid and femoral atherosclerosis in subjects at high cardiovascular disease risk from Spain, a country with low coronary heart disease (CHD) rates and high fish consumption. Methods: Cross-sectional study of 211 patients with primary dyslipidemia, with determination of fatty acid composition of serum phosphatidylcholine by gas chromatography and plaque outcomes (frequency, number, maximum height and sum of plaque heights) in carotid and femoral arteries by sonography. Results: In multivariate regression analyses after adjusting for age, gender, lipid genotype, BMI, smoking, hypertension, diabetes mellitus, APOE4 genotype, prior statin treatment, and serum proportions of other unsaturated fatty acids known to relate to atherosclerosis, the proportion of ALA showed an inverse association with the risk of carotid plaque (OR [95%CI] 0.66 [0.44–0.91]) and concomitant carotid and femoral artery plaque (0.57 [0.38–0.86]). Conclusion: The inverse relationship between ALA in serum phosphatidylcholine and plaque burden in carotid and femoral arteries supports its antiatherosclerotic effect independently of fish-derived n-3 fatty acids. However, whether ALA enrichment in phospholipids is beneficial per se or is a surrogate of the consumption of bioactive compounds in parent foods deserves further research.

Chronic and acute effects of walnuts on antioxidant capacity and nutritional status in humans: a randomized, cross-over pilot study.

McKay, D.L., C.-Y. O. Chen, K.-J. Yeum, N.R. Matthan, A.H. Lichtenstein, J.B. Blumberg, 2010. Chronic and acute effects of walnuts on antioxidant capacity and nutritional status in humans: a randomized, cross-over pilot study. Nutrition  Journal. 9:21-30.

Background: Compared with other common plant foods, walnuts (Juglans regia) are consistently ranked among the highest in antioxidant capacity. In vitro, walnut polyphenols inhibit plasma and LDL oxidation, while in animal models they lower biomarkers of oxidative stress and raise antioxidant capacity. A limited number of human feeding trials indicate that walnuts improve some measures of antioxidant status, but not others. Methods: A 19 wk, randomized crossover trial was conducted in 21 generally healthy men and postmenopausal women ≥50 y to study the dose-response effects of walnut intake on biomarkers of antioxidant activity, oxidative stress, and nutrient status. Subjects were randomized to receive either 21 or 42 g raw walnuts/d during each 6 wk intervention phase with a 6 wk washout between phases. Subjects were instructed to consume their usual diet, but refrain from eating any other tree nuts, seeds, peanuts, or ellagitannin-rich foods during the entire study, and other polyphenol-rich foods for 2 d prior to each study visit. Results: Compared to baseline levels, red blood cell (RBC) linoleic acid and plasma pyridoxal phosphate (PLP) were significantly higher after 6 wk with 42 g/d walnuts (P < 0.05 for both). Overall, changes in plasma total thiols, and other antioxidant biomarkers, were not significant with either walnut dose. However, when compared to fasting levels, plasma total thiols were elevated within 1 h of walnut consumption with both doses during the baseline and end visits for each intervention phase (P < 0.05 for all). Despite the observed increase in RBC linoleic and linolenic acids associated with walnut consumption, this substrate for lipid peroxidation only minimally affected malondialdehyde (MDA) and antioxidant capacity. The proportional changes in MDA and Oxygen Radical Absorbance Capacity (ORAC) were consistent with a dose-response effect, although no significant within- or between-group differences were observed for these measures. Conclusions: Walnut consumption did not significantly change the plasma antioxidant capacity of healthy, well-nourished older adults in this pilot study. However, improvements in linoleic acid and pyridoxal phosphate were observed with chronic consumption, while total plasma thiols were enhanced acutely. Future studies investigating the antioxidant effects of walnuts in humans are warranted, but should include either a larger sample size or a controlled feeding intervention.

Nuts and berries for heart health.

Ros, E., L.C. Tapsell, J. Sabaté, 2010. Nuts and berries for heart health. Curr Atheroscler Rep. 12:397–406.

Nuts are nutrient-dense foods with complex matrices rich in unsaturated fatty acids and other bioactive compounds, such as L-arginine, fiber, minerals, tocopherols, phytosterols, and polyphenols. By virtue of their unique composition, nuts are likely to beneficially impact heart health. Epidemiologic studies have associated nut consumption with a reduced incidence of coronary heart disease in both genders and diabetes in women. Limited evidence also suggests beneficial effects on hypertension and inflammation. Interventional studies consistently show that nut intake has a cholesterol-lowering effect and there is emerging evidence of beneficial effects on oxidative stress, inflammation, and vascular reactivity. Blood pressure, visceral adiposity, and glycemic control also appear to be positively influenced by frequent nut consumption without evidence of undue weight gain. Berries are another plant food rich in bioactive phytochemicals, particularly flavonoids, for which there is increasing evidence of benefits on cardiometabolic risk that are linked to their potent antioxidant power.

Nuts and healthy body weight maintenance mechanisms

Mattes, R.D., M.L. Dreher, 2010. Nuts and healthy body weight maintenance mechanisms. Asia Pac J Clin Nutr. 19(1):137-141.

Nuts are rich sources of multiple nutrients and phytochemicals associated with health benefits, including reduced cardiovascular disease risk. This has prompted recommendations to increase their consumption. However, they are also high in fat and are energy dense. The associations between these properties, positive energy balance and body weight raise questions about such recommendations. Numerous epidemiological and clinical studies show that nuts are not associated with weight gain. Mechanistic studies indicate this is largely attributable to the high satiety and low metabolizable energy (poor bioaccessibility leading to inefficient energy absorption) properties of nuts. Compensatory dietary responses account for 55-75% of the energy provided by nuts. Limited data suggest that routine nut consumption is associated with elevated resting energy expenditure and the thermogenic effect of feeding, resulting in dissipation of another portion of the energy they provide. Additionally, trials contrasting weight loss through regimens that include or exclude nuts indicate improved compliance and greater weight loss when nuts are permitted. Nuts may be included in the diet, in moderation, to enhance palatability, nutrient quality, and chronic disease risk reduction without compromising weight loss or maintenance.