Systematic review
Mediterranean dietary pattern, inflammation and endothelial function: A systematic review and meta-analysis of intervention trials

https://doi.org/10.1016/j.numecd.2014.03.003Get rights and content

Abstract

Background

High adherence to a Mediterranean diet (MD) is associated with reduced all-cause and cardiovascular mortality risk. To our knowledge, there is no systematic review and meta-analysis of randomized controlled trials that has compared the effects of an MD on outcomes of endothelial function and inflammation.

Methods and results

Literature search was performed using the electronic databases MEDLINE, EMBASE, and the Cochrane Trial Register. Inclusion criteria were: randomized controlled trials, 19 + years of age, and minimum intervention period of 12 weeks. Study specific weighted mean differences (WMD) were pooled using a random effect model. Seventeen trials including 2300 subjects met the objectives. MD regimens resulted in a significantly more pronounced increase in flow mediated dilatation [WMD: 1.86%, 95% CI 0.23 to 3.48, p = 0.02; I2 = 43%], and adiponectin [WMD: 1.69 μg/ml, 95% CI 0.27 to 3.11, p = 0.02; I2 = 78%], while high-sensitive C reactive protein [WMD: −0.98 mg/l, 95% CI −1.48 to −0.49, p < 0.0001; I2 = 91%], interleukin-6 [WMD: −0.42 pg/ml, 95% CI −0.73 to −0.11, p = 0.008; I2 = 81%], and intracellular adhesion molecule-1 [WMD: −23.73 ng/ml, 95% CI −41.24 to −6.22 p = 0.008; I2 = 34%] turned out to be significantly more decreased.

Conclusion

The results of the present meta-analysis provide evidence that an MD decreases inflammation and improves endothelial function.

Introduction

The traditional Mediterranean diet (MD) first postulated by Ancel Keys in the 1960s [1] is defined by a high intake of virgin olive oil, vegetables, fruits, plant proteins, whole grains, fish, low-fat dairy, moderate alcohol intake, and low red meat consumption [2], [3]. The Prevención con Dieta Mediterránea, a large intervention trial including 7447 subjects, showed that an MD rich in olive oil or nuts reduced the risk of cardiovascular disease (CVD) by 30% when compared to the low fat counterparts [4]. Systematic reviews investigated the effects of an MD on cardiovascular risk factors in overweight, obese and type 2 diabetic (T2D) subjects reporting improvements of these outcome parameters [5], [6], [7], [8], [9].

Low-grade, chronic inflammation is essential in the development of atherosclerosis, the main cause of coronary heart disease. Inflammation appears to play a key role from the initial phase to the final lesions of this disease [10] and is characterized by the infiltration of macrophages, deposition of lipids, and thickening of the vascular wall in response to chemo-attractant cytokines [11]. Increased expression and activation of C-reactive protein (CRP), or pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) are associated with the development of atherosclerosis. A meta-analysis reported a significant association between elevated levels of IL-6, CRP and T2D risk, furthermore supporting the hypothesis that chronic inflammation is a predictor of T2D development [12]. Evidence from prospective cohort studies showed that endothelial dysfunction represents an independent risk factor for the development of many CVD [13]. Inflammation of the endothelium is regarded to play a major role in the destabilization of atherosclerotic lesions paving the way for future CVD events [13]. There is a causal link between inflammation, endothelial dysfunction and atherosclerosis. A meta-analysis reported a reduction of CRP for low- as compared to high glycemic index/load diets [14]. Furthermore, low carbohydrate diets were reported to impair flow mediated dilatation when compared to the corresponding effects of low fat diets [15]. From these observations, one may conclude that the decreased CVD mortality following MD can be explained by beneficial counter-regulatory effects of this regimen on inflammation and endothelial dysfunction. A review by the Cochrane Group concluded that the MD pattern reduces some cardiovascular risk factors in the primary prevention of CVD [16]. However, to our knowledge, there is no systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the effects of an MD on outcomes of endothelial function and inflammation. Thus, it was the aim of the present study to summarize the available data regarding the impact of MD on these parameters.

Section snippets

Search strategy

Queries of literature were performed using the electronic databases MEDLINE, EMBASE, and the Cochrane Library until February 22nd, 2014 with restrictions to RCTs, but not to language and calendar date using the following search terms: (“Mediterranean diet” or “diet” or “Mediterranean” or “score” or “pattern” or “adherence”) in combination with (“inflammation” or “endothelial” or “vascular”). This systematic review was planned, conducted, and reported in adherence to standards of quality for

Literature search

A total of 17 trials (20 reports) met the inclusion criteria and were analyzed in the systematic review [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42]. The detailed steps of the meta-analysis article selection process are depicted as a flow chart (Supplemental Fig. S2).

Characteristics of studies and participants

All studies were RCTs with a duration ranging between 12 weeks and 48 months, published between 2003 and 2013, and enrolling a total of 2300 subjects. The

Discussion

The present systematic review and meta-analysis showed that a Mediterranean dietary pattern significantly improved markers of inflammation such as CRP, IL-6, and AD as well as parameters of endothelial function measured as FMD and ICAM-1. Regarding the validity of these outcome parameters, consistent evidence indicates that CRP is an independent risk factor for CVD and CHD [43]. IL-6 is generally accepted as an acute phase inflammatory reactive protein produced upon stimulation by TNF-α and

Limitations

The findings of the present meta-analysis with respect to AD, FMD, ICAM-1, and E-selectin should be interpreted conservatively, since only two trials reported on the outcome of these parameters. Another major limitation often found in nutritional intervention trials is the heterogeneity of the study protocols. The RCTs included in the present analyses varied with regard to type(s) of diets used (energy restriction, isocaloric), definitions of MD, study population, intervention time (12–104

Conflict of interest

The authors declare to have no conflict of interest.

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