Elsevier

Nutrition

Volume 54, October 2018, Pages 129-143
Nutrition

Review
Effects of nut consumption on selected inflammatory markers: a systematic review and meta-analysis of randomized controlled trials

https://doi.org/10.1016/j.nut.2018.02.017Get rights and content

Highlights

  • Nut consumption significantly reduced intercellular adhesion molecule (ICAM)-1 levels.

  • ICAM-1 reduction was possibly due to the effect of mixed nuts.

  • Nut consumption reduced ICAM-1 and vascular cell adhesion molecule-1 in long-term trials.

  • Long-term intake of mixed nuts is recommended.

Abstract

Objective

Several randomized controlled trials (RCTs) have assessed the effects of nut consumption on inflammatory markers. However, the results have been inconsistent. The aim of this meta-analysis of RCTs was to quantitatively evaluate the effects of nut consumption on selected inflammatory markers.

Methods

PubMed, Embase, Cochrane Library database, and Google Scholar were searched for published RCTs that reported the effects of nuts on inflammatory markers as primary or secondary outcomes in an adult population (aged ≥18 y). Summary estimates of weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis.

Results

Twenty-three RCTs met the inclusion criteria. Overall, nut consumption significantly reduced the levels of intercellular adhesion molecule (ICAM)-1 (WMD, −0.17; 95% CI, −0.32 to −0.03; P = 0.01), but had no significant effect on other inflammatory markers. In the subgroup analyses by nut types, mixed nuts had a significant effect on ICAM-1 reduction. The significant effect of nuts on ICAM-1 reduction was only observed in parallel, but not crossover RCTs. Additionally, nut consumption significantly reduced ICAM-1 and vascular cell adhesion molecule-1 levels in long-term (≥12 wk), but not short-term (<12 wk) RCTs. No significant heterogeneity or publication bias was observed in the studies included.

Conclusions

Nut consumption significantly reduced ICAM-1 levels, but had no effect on other inflammatory markers. More studies are needed to assess the effects of nuts on inflammation.

Introduction

Inflammation is a complex biological response of human body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, resulting in a disruption of tissue homeostasis [1]. Inflammation over a prolonged period that usually lasts weeks to months with the presence of lymphocytes and macrophages, vascular proliferation, fibrosis, and tissue destruction is called chronic inflammation. Inflammation plays an essential role in the development of many chronic and non-chronic diseases of major global disease burden, including atherosclerotic cardiovascular disease (CVD), cancer, diabetes, Alzheimer's disease, rheumatoid arthritis, asthma, and infectious diseases [2]. Vascular inflammation is activated by proinflammatory stimuli, such as saturated fat intake, hypercholesterolemia, hyperglycemia, obesity, and smoking, which induce the secretion of inflammatory cytokines. These cytokines in turn promote the generation of endothelial adhesion molecules and other chemoattractants [3]. It has been proposed that a prolonged overproduction of inflammatory cytokines without regulation might lead to several chronic diseases. It has been found that elevated levels of interleukin (IL)-6 and C-reactive protein (CRP) are associated with the development of atherosclerosis and type 2 diabetes [4]. Therefore, research on these cytokines as biomarkers in inflammation-related diseases is of great relevance for prevention of these diseases.

Since the first report of an association between nut consumption and lower risk for coronary heart disease in 1992 [5], extensive research has been conducted to investigate the effects of nuts on various health outcomes. Nuts are rich in unsaturated fatty acids and bioactive compounds, such as dietary fiber, vitamin E, and phytochemicals [6]. Epidemiologic studies have consistently observed that diets rich in a variety of nuts, such as the Mediterranean diet, are associated with a reduced all-cause mortality, incidence and mortality of CVD and cancer, and a reduced risk for type 2 diabetes [7], [8], [9], [10]. Potential mechanisms of CVD risk reduction include antiinflammatory, antioxidant, and antiatherogenic properties of compounds such as tocopherols, folic acids, and phytochemicals rich in nuts. Nut consumption has been found to have beneficial effects on CVD and diabetes risk factors, such as reducing low-density lipoprotein cholesterol (LDL-C) [11], [12], [13], blood pressure [11], [14], and visceral adiposity [15], and improving hyperglycemia and insulin resistance [16], [17] in previous randomized controlled trials (RCTs). Furthermore, nuts may play important anticarcinogenic roles, for instance, regulation of cell differentiation and proliferation, reduction of tumor initiation or promotion, DNA protection, and regulation of immunologic and inflammatory response [18].

Clinical and epidemiologic evidence also indicate that nut consumption improves profiles of inflammatory markers, with a daily dose of 30 g being able to confer benefits [19]. Mediterranean diets, in which walnuts, mixed nuts, or pistachios replaced olive oil, demonstrated improvements in one or more of inflammatory markers in some studies [13], [19], [20]. However, other studies showed no benefits on inflammatory markers, likely due to the relatively small sample size, insufficient intake of nuts or duration of intervention, and different types of nuts or subject groups of these trials [21], [22], [23]. Therefore, results of RCTs have not been consistent in showing the antiinflammatory benefit, and the precise effect of nut consumption on inflammation has not been well established.

Because inflammation plays an important role in the development of many diseases and health conditions, the protective effect of nuts against these diseases may be at least partially attributed to their antiinflammatory effect. In the present study, a meta-analysis of RCTs was performed to comprehensively assess the evidence and quantitatively estimate the effect of nut consumption on selected inflammatory markers.

Section snippets

Data sources and search strategy

The current meta-analysis was performed following the PRISMA criteria guidelines [24]. The relevant articles were identified by searching the databases of PubMed, Embase, the Cochrane Library database, and Google Scholar through April 2017. No language or other restrictions were set in literature search. Three groups of medical subject headings (MeSH) and non-MeSH keywords were used to search the databases: keyword group 1: “nut,” “almond,” “pistachio,” “cashew,” “macadamia,” “pecan,”

Search results

The literature search retrieved 1320 articles. After initial screening by title and abstract, 169 articles were identified for full-text review. Of these, 146 articles were excluded by applying the inclusion and exclusion criteria. Twenty-three RCTs, which included 1221 adults with the age range of 23 to 70 y, were included for the current systematic review and meta-analysis (Fig. 1).

Study characteristics

Table 1 presents the characteristics and the main outcomes of the 23 RCTs published between 2004 and 2015 [17],

Discussion

To the best of our knowledge, this is the first systematic review and meta-analysis to comprehensively analyze the effect of nut consumption on different inflammatory markers. This systematic review of 23 RCTs found that nut consumption significantly reduced the levels of ICAM-1 in the overall meta-analysis, but had no significant effect on other inflammatory markers, including CRP, VCAM-1, IL-6, TNF-α, and E-selectin. Subgroup analyses by different types and dose of nuts found that mixed nuts

Conclusion

The findings of the current meta-analysis may have important implications. Given the small number of studies examining the effects of specific nuts, more trials are needed to address the effects of different types of nuts on inflammation or cardiovascular risk. Although some pharmacologic treatments and exercise appear to be effective in reducing inflammation, healthy diets that include regular consumption of tree nuts, may protect against the possible consequences of low-grade inflammation.

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    This work was supported by grants from the National Natural Science Foundation of China (81402672), Shenzhen Science and Technology Planning Project (JCYJ20170306160008504), and Sanming Project of Medicine in Shenzhen (SZSM201611068). YX and XS designed the study and drafted and revised the manuscript. YX, JX, YK, SW, ZL, and SH identified relevant articles and extracted and analyzed data. JC, JY, JHK, SYW, EK, and GAC commented and revised the manuscript. All of the authors read and approved the final manuscript. The authors have no conflicts of interest to declare.

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