Archive

Research Area: Nutrient and Bioactive Composition

Replacing saturated fats with unsaturated fats from walnuts or vegetable oils lowers atherogenic lipoprotein classes without increasing lipoprotein(a).

Tindall, A.M., P.M. Kris-Etherton, K.S. Petersen, 2020. Replacing saturated fats with unsaturated fats from walnuts or vegetable oils lowers atherogenic lipoprotein classes without increasing lipoprotein(a). J Nutr. pii: nxz313. doi: 10.1093/jn/nxz313. [Epub ahead of print]

Bachground: Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood. Objectives: We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9). Methods: A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis. Results: Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets. Conclusions: In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9.

Angiopoietin-1 protects 3T3-L1 preadipocytes from saturated fatty acid-induced cell death.

Son, Y., J.M. Cox, J.L. Stevenson, J.A. Cooper, C.M. Paton, 2020. Angiopoietin-1 protects 3T3-L1 preadipocytes from saturated fatty acid-induced cell death. Nutr Res. 76:20-28.

Cross talk between endothelial cells and adipocytes is vital to adipocyte functions, but little is known about the mechanisms or factors controlling the process. Angiogenesis is a critical component linking the endothelium to healthy adipogenesis, yet it is not known if or how it is involved in adipocyte physiology. Therefore, the purpose of this study was to determine the effect of angiopoietin-1 (Ang-1) and -2 (Ang-2) as well as their receptor, Tie-2, on adipocyte physiology. 3T3-L1 pre- and mature adipocytes were found to express Ang-1, Ang-2, and Tie-2, which decrease upon polyunsaturated fatty acid treatment. Furthermore, 3T3-L1 cells treated with recombinant Ang-1 or Ang-2 increased expression of the antiapoptotic gene Bcl-x and decreased expression of the proapoptotic gene Casp-8. Next, preadipocytes were treated with saturated fatty acids (SFAs) to induce cell stress. SFA-mediated splicing of X-box-binding protein-1 was reduced by co-treatment with Ang-1, and cell viability was improved in the presence of SFAs + Ang-1. Taken together, these results indicate that Ang-1 may protect preadipocytes from SFA-induced apoptosis and endoplasmic reticulum stress.

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

Sala-Vila, A., C. Valls-Pedret, S. Rajaram, N. Coll-Padrós, M. Cofán, M. Serra-Mir, A.M. Pérez-Heras, I. Roth, T.M. Freitas-Simoes, M. Doménech, C. Calvo, A. López-Illamola, E. Bitok, N.K. Buxton, L. Huey, A. Arechiga, K. Oda, G.J. Lee, D. Corella, L. Vaqué-Alcázar, R. Sala-Llonch, D. Bartrés-Faz, J. Sabaté, E. Ro, 2020. Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts and Healthy Aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr. pii: nqz328. doi: 10.1093/ajcn/nqz328. [Epub ahead of print]

Background: Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Changes in nut consumption and subsequent cardiovascular disease risk among US men and women: 3 large prospective cohort studies.

Liu, X., M. Guasch-Ferré, J.P. Drouin-Chartier, D.K. Tobias, S.N. Bhupathiraju, K.M. Rexrode, W.C. Willett, Q. Sun, Y. Li, 2020. Changes in nut consumption and subsequent cardiovascular disease risk among US men and women: 3 large prospective cohort studies.
J Am Heart Assoc. 9(7):e013877. doi: 10.1161/JAHA.119.013877. Epub 2020 Apr 1.

Background: we aim to evaluate the association of within-individual changes in consumption of total and specific types of nuts and the subsequent risk of incident cardiovascular disease (CVD) in US men and women. Methods and Results: We included 34 103 men from the HPFS (Health Professionals Follow-Up Study) (1986-2012), 77 815 women from the NHS (Nurses’ Health Study) (1986-2012), and 80 737 women from the NHS II (1991-2013). We assessed nut consumption every 4 years using validated food frequency questionnaires. We used multivariable Cox proportional hazards regression models to examine the association between 4-year changes in nut consumption and risk of confirmed CVD end points in the subsequent 4 years. Per 0.5 serving/day increase in total nut consumption was associated with lower risk of CVD (relative risk [RR], 0.92; 95% CI, 0.86-0.98), coronary heart disease (RR, 0.94; 95% CI, 0.89-0.99), and stroke (RR, 0.89; 95% CI, 0.83-0.95). Compared with individuals who remained nonconsumers in a 4-year interval, those who had higher consumption of total nuts (≥0.5 servings/day) had a lower risk of CVD (RR, 0.75; 95% CI, 0.67-0.84), coronary heart disease (RR, 0.80; 95% CI, 0.69-0.93), and stroke (RR, 0.68; 95% CI, 0.57-0.82) in next 4 years. Individuals who decreased nut consumption by ≥0.50 servings/day had a higher risk of developing CVD (RR, 1.14; 95% CI, 0.99-1.32), coronary heart disease (RR, 1.06; 95% CI, 0.88-1.28), and stroke (RR, 1.28; 95% CI, 1.02-1.60) when compared with those who maintained their nut consumption. Conclusions: Increasing total consumption of nuts and intake of individual types of nuts (eg, walnuts, other tree nuts, and peanuts) was associated with a subsequent lower risk of CVD. These data support the role of nut intake in the primary prevention of CVD.