*2.4. Nut Consumption E*ff*ect on Endothelial Function and Inflammation Markers*

The studies, summarized in Table 4, proved that tree nut-enhanced diets can have beneficial effects on endothelial function or inflammatory markers [74–79]. Endothelial dysfunction, characterized by a decreased bioavailability of nitric oxide (NO), an endogenous vasodilator synthesized from the amino acid L-arginine, is linked with a greater risk of CV events [80]. Since tree nuts are a rich source of L-arginine, their intake might potentially improve endothelial dysfunction.

The trial of Ma et al. [74] on T2DM patients revealed that consumption of an ad libitum diet supplemented with 56 g walnuts daily for a period of 8 weeks significantly improved flow mediated dilation (FMD), a measure of endothelial function, as compared to a nut-free ad libitum diet. In a larger trial on overweight adults with visceral adiposity, the same research team found again that after daily ingestion of walnuts, FMD improved significantly (*p* = 0.019) as compared with the control diet, suggesting the potential for overall cardiac risk reduction [75]. Similarly, in hypercholesterolemic subjects, a diet with walnuts and walnut oil amended FMD (+34%) and reduced total peripheral resistance [81]. The study of Chen et al. [78] in patients with CAD established that almonds can also increase FMD, but did not significantly change C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), or E-selectin compared to control. These results align with a meta-analysis published by Neale et al. [82] where nut intake had a significant effect on FMD (*p* = 0.0004). Equally, a recent meta-analysis of RCTs showed that nut consumption significantly increased FMD (*p* = 0.001) [83]. Bhardwaj et al. [84] noticed that walnut and almond diets, besides positively effecting FMD, can also decrease soluble vascular cell adhesion molecules.



A—almonds; CI—confidence interval; CAD—coronary artery disease; CRP—C-reactive protein; F—women; FMD—flow-mediated dilation; NHS—Nurses' Health Study; HPFS—Health Professionals Follow-Up Study; IL-6—interleukin-6; M—men; RCT—randomized controlled trial; RR—relative risk; SBP—systolic blood pressure; TNF-α—tumor necrosis factor-α; W—walnuts.

While walnut and almond diets increased FMD, pistachios had no effect on this measure [38]. This fact was confirmed by the meta-analysis of Fogacci et al. [85] which did not notice a significant change in FMD, but the brachial artery diameter (BAD) significantly improved (*p* < 0.001) following pistachio consumption.

A very recent review [86] established that tree nut and peanut intake had the potential to improve vascular function, which was linked with increased risk of CVD.

In regard to inflammatory markers, the results of Liu et al. [76] proposed that the integration of almonds into a healthy diet in diabetic Chinese patients, as compared to the control diet, can decrease interleukin-6 (IL-6), TNF-α, and CRP. Both IL-6 and TNF-α are mediators of CRP synthesis in the liver. An increased IL-6 level was associated with insulin resistance, hyperglycemia, and T2DM [76]. The trial conducted by Sweazea et al. [77] concluded that almond intake, compared with control, significantly lowered CRP (*p* = 0.029) in diabetic U.S. patients, as well. In a recent study, Borkowski et al. [87] showed that walnuts can reduce the TNFα-mediated production of pro-inflammatory cytokines IL-6 and IL-8 in human adipocytes.

These findings are consistent with the results of a cross-sectional analysis which showed that higher tree nut and peanut intake was associated with decreased amounts of CRP and IL-6 [79]. However, the meta-analysis of Mazidi et al. [88] disclosed that nut consumption had no significant effect on CRP, IL6, TNF-α, and adiponectin, but significantly decreased leptin.

A low level of adiponectin, a protein with anti-inflammatory and anti-atherogenic properties secreted by adipocytes, is perceived as risk factor for CV events. An addition of 9 g of walnut oil or mixed plant oil in the diet increased adiponectin levels in T2DM subjects (+6.84% and +4.47%, respectively, compared to baseline) with borderline significance (*p* = 0.051) [89].

The favorable effects on inflammatory markers may be attributed to tree nuts, as a 12-week RCT on healthy mature adults with peanut intake failed to find any changes in inflammatory biomarkers [68].

The conclusion from these cohort and intervention studies is that the consumption of tree nuts and peanuts, with their high content of biologically active antioxidant compounds, should be encouraged for maintaining lower blood lipid counts and better biochemical and anthropometric parameters, in order to improve the prospect of cardiometabolic morbidity and mortality.
