Fisher, D.R., Poulose, S.M., Bielinski, D.F., Shukitt-Hale, B., 2014. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells. Nutr Neurosci. Aug 25. [Epub ahead of print]
The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defenses in brain is a critical factor in the declining neural function and cognitive deficit accompanying age. Previous studies from our laboratory have reported that walnuts, rich in polyphenols, antioxidants, and omega fatty acids such as alpha-linolenic acid and linoleic acid, improve the age-associated declines in cognition and neural function in rats. Possible mechanisms of action of these effects include enhancing protective signaling, altering membrane microstructures, decreasing inflammation, and preventing accumulation of polyubiquitinated protein aggregates in critical regions of the brain. In the current study, we investigated whether the serum collected from aged animals fed with walnut diets (0, 6, and 9%, w/w) would enhance protection on stressed BV-2 microglia in vitro. In the growth medium, fetal bovine serum was substituted with the serum collected from 22-month-old rats fed per protocol for 12 weeks. Walnut diet serum (6 and 9%) significantly attenuated lipopolysaccharide-induced nitrite release compared to untreated control cells and those treated with serum from rats fed 0% walnut diets. The results also indicated a significant reduction in pro-inflammatory tumor necrosis factor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase. These results suggest antioxidant and anti-inflammatory protection or enhancement of membrane-associated functions in brain cells by walnut serum metabolites.
Farvid, M.S., M. Ding, A. Pan, Q. Sun, S.E. Chiuve, L.M. Steffen, W.C. Willett, F.B. Hu, 2014. Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies. Circulation. 130(18):1568-1578.
Background: Prior studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. Methods and Results: We searched MEDLINE and EMBASE databases through June, 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we utilized unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) comparing the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310,602 individuals and 12,479 total CHD events including 5,882 CHD deaths. Comparing the highest to the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals (95% CI): 0.78-0.92; I²=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% CI, 0.71-0.89; I²=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% CI, 0.86-0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% CI, 0.82-0.94). Conclusions: In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose-response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.
Burns-Whitmore, B., E. Haddad, J. Sabaté, S. Rajaram, 2014. Effects of supplementing n-3 fatty acid enriched eggs and walnuts on cardiovascular disease risk markers in healthy free-living lacto-ovo-vegetarians: a randomized, crossover, free-living intervention study. Nutr J. 13(1):29.
Background: Plant and marine n-3 fatty acids (FA) may favorably modify select markers of cardiovascular disease risk. Whether supplementing the habitual diet of lacto-ovo-vegetarians (LOV) with walnuts (containing α-linolenic acid, ALA) and n-3 FA enriched eggs (containing primarily docosahexaenoic acid, DHA and ALA) would have equivalent effects on CVD risk factors is explored in this study. Methods: In this study, 20 healthy free-living LOVs following their habitual diet were randomly assigned in a crossover design to receive one of three supplements: n-3 FA enriched egg (6/week), walnuts (28.4 g, 6/week) or a standard egg, 6/week (control) for 8 weeks each with 4-wk washout between treatments. Erythrocyte membrane fatty acids, serum lipids and inflammatory markers were measured at the end of each treatment. Results: Dietary compliance was observed by an expected increase in erythrocyte membrane ALA following the walnut treatment and in DHA following the n-3 FA enriched egg treatment. Walnut treatment lowered serum triacylglycerol, total cholesterol and Apo B (p < 0.05) compared to the standard egg but not the n-3 FA enriched egg treatment. However, walnut treatment significantly reduced total: HDL cholesterol ratio compared to both egg treatments. There were no differences between treatments for any of the inflammatory markers. Conclusions: For LOV, a direct source of DHA such as n-3 FA enriched eggs seems necessary to increase membrane levels of DHA. However for producing an overall favorable blood lipid profile, daily consumption of a handful of walnuts rich in ALA may be a preferred option for lacto-ovo vegetarians.
Farvid, M.S., Ding, M., Pan, A., Sun, Q., Chiuve, S.E., Steffen, L.M., Willett, W.C., Hu, F.B, 2014. Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies. Circulation. 130(18):1568-1578.
BACKGROUND: Prior studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. METHODS AND RESULTS: We searched MEDLINE and EMBASE databases through June, 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we utilized unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) comparing the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310,602 individuals and 12,479 total CHD events including 5,882 CHD deaths. Comparing the highest to the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals (95% CI): 0.78-0.92; I²=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% CI, 0.71-0.89; I²=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% CI, 0.86-0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% CI, 0.82-0.94).CONCLUSIONS: In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose-response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.
Viguiliouk, E., C.W.C. Kendall, S.B. Mejia, A.I. Cozma, V. Ha, A. Mirrahimi, V.H. Jayalath, L.S.A. Augustin, L. Chiavaroli, L.A. Leiter, R.J. de Souza, D. J.A. Jenkins, J.L. Sievenpiper, 2014. Effect of tree nuts on glycemic control in diabetes: A systematic review and meta-analysis of randomized controlled dietary trials. PLOS ONE. DOI: 10.1371/journal.pone.0103376
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0103376
Background: Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent. Objective: To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes. Data Sources: MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014. Study Selection: Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR. Data Extraction and Synthesis: Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2). Results: Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts. Limitations: Majority of trials were of short duration and poor quality. Conclusions: Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.
Mejia, S.B. C.W.C. Kendall, E. Viguiliouk, L.S. Augustin, V. Ha, A.I. Cozma, A. Mirrahimi, A. Maroleanu, L. Chiavaroli, L.A. Leiter, R. J. de Souza, D.J. A. Jenkins, J.L. Sievenpiper, 2014. Effect of tree nuts on metabolic syndrome criteria: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. DOI:10.1136/bmjopen-2013-004660
http://bmjopen.bmj.com/content/4/7/e004660.full?keytype=ref%5B1%5D&ijkey=wszZ1mCN44mw0KO
Objective: To provide a broader evidence summary to inform dietary guidelines of the effect of tree nuts on criteria of the metabolic syndrome (MetS). Design: We conducted a systematic review and meta-analysis of the effect of tree nuts on criteria of the MetS. Data sources: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 4 April 2014). Eligibility criteria for selecting studies: We included relevant randomised controlled trials (RCTs) of ≥3 weeks reporting at least one criterion of the MetS. Data extraction: Two or more independent reviewers extracted all relevant data. Data were pooled using the generic inverse variance method using random effects models and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I2 statistic. Study quality and risk of bias were assessed. Results: Eligibility criteria were met by 49 RCTs including 2226 participants who were otherwise healthy or had dyslipidaemia, MetS or type 2 diabetes mellitus. Tree nut interventions lowered triglycerides (MD=−0.06 mmol/L (95% CI −0.09 to −0.03 mmol/L)) and fasting blood glucose (MD=−0.08 mmol/L (95% CI −0.16 to −0.01 mmol/L)) compared with control diet interventions. There was no effect on waist circumference, high-density lipoprotein cholesterol or blood pressure with the direction of effect favouring tree nuts for waist circumference. There was evidence of significant unexplained heterogeneity in all analyses (p<0.05). Conclusions: Pooled analyses show a MetS benefit of tree nuts through modest decreases in triglycerides and fasting blood glucose with no adverse effects on other criteria across nut types. As our conclusions are limited by the short duration and poor quality of the majority of trials, as well as significant unexplained between-study heterogeneity, there remains a need for larger, longer, high-quality trials.
Salas-Salvado´, J., M. Guasch-Ferre´, M. Bullo´, J. Sabate´, 2014. Nuts in the prevention and treatment of metabolic syndrome. Am J Clin Nutr. 100(suppl):399S–407S,
Nuts are rich in many bioactive compounds that can exert beneficial effects on cardiovascular health. We reviewed the evidence relating nut consumption and the metabolic syndrome (MetS) and its components. Nuts reduce the postprandial glycemic response; however, long-term trials of nuts on insulin resistance and glycemic control in diabetic individuals are inconsistent. Epidemiologic studies have shown that nuts may lower the risk of diabetes incidence in women. Few studies have assessed the association between nuts and abdominal obesity, although an inverse association with body mass index and general obesity has been observed. Limited evidence suggests that nuts have a protective effect on blood pressure and endothelial function. Nuts have a cholesterol-lowering effect, but the relation between nuts and hypertriglyceridemia and high-density lipoprotein cholesterol is not well established. A recent pooled analysis of clinical trials showed that nuts are inversely related to triglyceride concentrations only in subjects with hypertriglyceridemia. An inverse association was found between the frequency of nut consumption and the prevalence and the incidence of MetS. Several trials evaluated the effect of nuts on subjects with MetS and found that they may have benefits in some components. Compared with a low-fat diet, a Mediterranean diet enriched with nuts could be beneficial for MetS management. The protective effects on metabolism could be explained by themodulation of inflammation and oxidation. Further trials are needed to clarify the role of nuts in MetS prevention and treatment.
Nishi, S.K., C.W.C. Kendall, R.P. Bazinet, B. Bashyam, C.A. Ireland, L.S.A. Augustin, S. Blanco Mejia, J.L. Sievenpiper, D.J.A. Jenkins, 2014. Nut consumption, serum fatty acid profile and estimated coronary heart disease risk in type 2 diabetes. Nutrition, Metabolism & Cardiovascular Diseases. 24(8):845-852.
Background and aims: Nut consumption has been associated with decreased risk of coronary heart disease (CHD) and type 2 diabetes which has been largely attributed to their healthy fatty acid profile, yet this has not been ascertained. Therefore, we investigated the effect of nut consumption on serum fatty acid concentrations and how these relate to changes in markers of glycemic control and calculated CHD risk score in type 2 diabetes. Methods and results: 117 subjects with type 2 diabetes consumed one of three iso-energetic (mean 475 kcal/d) supplements for 12 weeks: 1. full-dose nuts (50e100 g/d); 2. half-dose nuts with half-dose muffins; and 3. full-dose muffins. In this secondary analysis, fatty acid concentrations in the phospholipid, triacylglycerol, free fatty acid, and cholesteryl ester fractions from fasting blood samples obtained at baseline and week 12 were analyzed using thin layer and gas chromatography. Full-dose nut supplementation significantly increased serum oleic acid (OA) and MUFAs compared to the control in the phospholipid fraction (OA: P = 0.036; MUFAs: P = 0.024). Inverse associations were found with changes in CHD risk versus changes in OA and MUFAs in the triacylglycerol (r = -0.256, P = 0.011; r = -0.228, P = 0.024, respectively) and phospholipid (r = -0.278, P = 0.006; r = -0.260, P = 0.010, respectively) fractions. In the cholesteryl ester fraction, change in MUFAs was inversely associated with markers of glycemic control (HbA1c: r = -0.250, P = 0.013; fasting blood glucose: r = -0.395, P < 0.0001). Conclusion: Nut consumption increased OA and MUFA content of the serum phospholipid fraction, which was inversely associated with CHD risk factors and 10-year CHD risk
Jaceldo-Siegl, K., E. Haddad, K. Oda, G.E. Fraser, J. Sabate´, 2014. Tree nuts are inversely associated with metabolic syndrome and obesity: The Adventist Health Study-2. PLoS ONE 9(1): e85133. doi:10.1371/journal.pone.0085133.
Objective: To examine the relationships of nut consumption, metabolic syndrome (MetS), and obesity in the Adventist Health Study-2, a relatively healthy population with a wide range of nut intake. Research Design and Methods: Cross-sectional analysis was conducted on clinical, dietary, anthropometric, and demographic data of 803 adults. MetS was defined according to the American Heart Association and the National Heart, Lung, and Blood Institute diagnostic criteria. We assessed intake of total nuts, tree nuts and peanuts, and also classified subjects into low tree nut/low peanut (LT/LP), low tree/high peanut (LT/HP), high tree nut/high peanut (HT/HP), and high tree/low peanut (HT/LP) consumers. Odds ratios were estimated using multivariable logistic regression. Results: 32% of subjects had MetS. Compared to LT/LP consumers, obesity was lower in LT/HP (OR = 0.89; 95% CI = 0.53, 1.48), HT/HP (OR = 0.63; 95% CI = 0.40, 0.99) and HT/LP (OR = 0.54; 95% CI = 0.34, 0.88) consumers, p for trend = 0.006. For MetS, odds ratios (95% CI) were 0.77 (0.47, 1.28), 0.65 (0.42, 1.00) and 0.68 (0.43, 1.07), respectively (p for trend = 0.056). Frequency of nut intake (once/week) had significant inverse associations with MetS (3% less for tree nuts and 2% less for total nuts) and obesity (7% less for tree nuts and 3% less for total nuts). Conclusions: Tree nuts appear to have strong inverse association with obesity, and favorable though weaker association with MetS independent of demographic, lifestyle and dietary factors.
Bao, Y., J. Han, F.B. Hu, E.L. Giovannucci, M.J. Stampfer, W.C. Willett, C.S. Fuchs, 2013. Association of nut consumption with total and cause-specific mortality. N Engl J Med. 369:2001-2011.
Background: Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. Methods: We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses’ Health Study (1980–2010) and 42,498 men in the Health Professionals Follow-up Study (1986–2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Results: During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. Conclusions: In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death.
