Does Nut Consumption Reduce Mortality and/or Risk of Cardiometabolic Disease? An Updated Review Based on Meta-Analyses

Aim We aimed to determine if nut consumption decreases mortality and/or the risk of cardiometabolic diseases based on updated meta-analyses of epidemiological and intervention studies. Methods. An updated electronic search was conducted in PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library databases for original meta-analyses to investigate the effects of nut consumption on cardiometabolic disease in humans. Results. Seven new meta-analyses were included in this updated review. Findings similar to our previous review were observed, showing that nut consumption significantly decreased cardiovascular disease (CVD) mortality (−19% to −25%; n = 4), coronary heart disease (CHD) mortality (−24% to −30%; n = 3), stroke mortality (−17% to −18%; n = 3), CVD incidence (−15% to −19 %; n = 4), CHD [or coronary artery disease (CAD)] incidence (−17% to −34%; n = 8), and stroke incidence (−10% to −11%; n = 6) comparing high with low categories of nut consumption. Fasting glucose levels (0.08 to 0.15 mmol/L; n = 6), total cholesterol (TC; 0.021 to 0.30 mmol/L; n = 10), and low-density lipoprotein cholesterol (LDL-C; 0.017 to 0.26 mmol/L; n = 10) were significantly decreased with nut consumption compared with control diets. Body weight and blood pressure were not significantly affected by nut consumption. Conclusion. Nut consumption appears to exert a protective effect on cardiometabolic disease, possibly through improved concentrations of fasting glucose, total cholesterol, and LDL-C.

As we suggested, for a potential mechanism of action of nuts [3], MUFAs and PUFAs are candidates for favorable glucose control and reduction of appetite. Arginine and magnesium can contribute to improved inflammation, oxidative stress, endothelial function, and blood pressure. Polyphenols can lower the risk of type 2 diabetes mellitus (T2DM). The suggested schematic figure showing metabolic effects and effects on clinical endpoints based on our previous publication [3] is briefly described in   GPx, Glutathione peroxidase; GSSG, oxidized glutathione; HbA1c, glycosylated hemoglobin; HOMA-IR, homeostasis model assessment of insulin resistance; hs-CRP, high sensitivity C-reactive protein; LDL-C, low density lipoprotein cholesterol; IL-6, interleukin-6; MDA, malondialdehyde; MUFA, monounsaturated fatty acid; ORAC, oxygen radical absorbance capacity; PUFA, polyunsaturated fatty acid; SOD, superoxide dismutase; TC, total cholesterol; TG, triglyceride; TNF α, tumor necrosis factor alpha; VCAM-1, vascular cell adhesion molecule-1; ↑, increase; ↓, decrease.
This review aims to update our previous review of meta-analyses in order to determine the effect of nut consumption on cardiometabolic disease.

Materials and Methods
The literature search was conducted in PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library databases, restricted to full articles investigating meta-analyses of the effects of nut consumption on cardiometabolic diseases in humans. Only research articles written in English up to 11 November 2019 were included. The search terms included meta-analysis combined with nut(s) or tree nut(s) or almond(s) or Brazil nut(s) or cashew nut(s) or hazelnut(s) or macadamia(s) or peanut(s) or pistachio(s) or walnut(s) or mortality or incidence or CVD or coronary heart disease (CHD) or stroke or T2DM or hypertension or metabolic syndrome or obesity or blood pressure or glycemic control or glucose or lipids or inflammatory markers or endothelial function and flow-mediated dilation. Reference lists of chosen articles were also screened for related publications. A previous review [4] examined 34 meta-analyses, and this review added 7 new meta-analyses [5][6][7][8][9][10][11]. A flow chart for the identified studies is included in this review in Figure 2.

Coronary Heart Disease Mortality
A previous review [4] reported a 27-30% reduction in coronary heart disease (CHD) mortality from 2 meta-analyses of prospective studies [21,23]. When combined with the outcomes from a meta-analysis by Becerra-Tomas et al., 2019 [4], a reduction in CHD mortality ranged from 24% to 30%.
In a meta-analysis of 3 prospective studies [46-48] conducted by Schlesinger et al., 2019 [5], the association between nut consumption and the risk of overweight and obesity was found with an RR of 0.91 (95% CI 0.80, 1.03; I 2 = 25%) for the highest versus lowest nut consumption. The RR per 28 g/d of nut consumption was 0.78 (95% CI 0.58, 1.06; I 2 = 64%).

Glycemic Control
In a previous review [5], nut consumption was found to decrease fasting glucose levels by 0.08 to 0.15 mmol/L compared with control diets based on 3 meta-analyses [87][88][89] of RCTs.
In this present review, we have included very recent meta-analyses conducted by Tindall et al.  and showed no effect of almond consumption on fasting blood glucose compared with control, and only subjects with CVD risk at baseline showed significant reduction (net change −6.08 mg/dL; 95% CI −10.77, -1.40 mg/dL; I 2 = 0%, p heterogeneity = 0.94) at >42.5 g almond consumption (summary net change   Overall, nut consumption appears to decrease fasting glucose levels by 0.08 to 0.15 mmol/L compared with control diets.
In this present review, we included a meta-analysis conducted by Schwingshackl

Discussion
This present review is an updated review of meta-analyses that adds seven more recent meta-analyses aiming to clarify the effect of nut consumption on cardiometabolic disease. We found similar outcomes to our previous review when we combined new and previous meta-analyses investigating CVD mortality, CHD mortality, stroke mortality, CVD incidence, CHD (or CAD) incidence, and stroke incidence. In meta-analyses of interventions, nut consumption significantly reduced fasting glucose levels, TC, and LDL-C compared with controls. However, body weight and blood pressure did not differ after nut consumption compared with controls. Schwingshackl et al., 2018 [10] showed the beneficial effect of nut consumption in a network meta-analysis of 66 RCTs (86 publications with a total of 3595 subjects (280 subjects with T2DM)). Nuts ranked highest for LDL-C, TG, TC, HDL-C, fasting blood glucose, HbA1c, SBP, DBP, and C-reactive protein (CRP), in comparison with other food groups, including legumes, whole grains, fish, fruits and vegetables, refined grains, red meat, eggs, dairy, and sugar-sweetened beverages [10]. Clearly, nut consumption appears to decrease cardiometabolic risks.
The results from this present review suggest there needs to be further large clinical trials testing nuts as therapeutic agents for primary and secondary prevention of cardiovascular disease.

Conclusions
This updated review of meta-analyses found that nut consumption has beneficial effects on cardiometabolic disease with reduced CVD mortality, CHD mortality, stroke mortality, CVD incidence, CHD incidence and stroke incidence comparing high with low categories of nut consumption. It may be attributable to decreases in fasting glucose, total cholesterol and LDL-C.