Randomization to 6-month Mediterranean diet compared with a low-fat diet leads to improvement in Dietary Inflammatory Index scores in patients with coronary heart disease: the AUSMED Heart Trial
Introduction
Chronic, low-grade systemic inflammation is a recognized risk factor for development of chronic diseases, including coronary heart disease (CHD) [1]. Dietary intakes have been shown to affect inflammation via both pro-inflammatory and anti-inflammatory mechanisms [2]. Healthy dietary patterns, which focus on foods rather than single nutrients, have been shown to be anti-inflammatory [3], [4]. Among these, the Mediterranean diet (MedDiet) has the strongest evidence for improvement in markers of inflammation [5], [6]. However, the effect of the MedDiet on biomarkers of inflammation is unclear in patients with CHD [7].
The Dietary Inflammatory Index (DII®) is a literature-derived dietary score which incorporates 45 nutritional factors that are known to modulate inflammatory markers, in either a pro- or anti-inflammatory manner [8]. This method of characterizing diet differs from other dietary pattern adherence scores as it was formulated based on findings evident in the literature relating diet to inflammatory cytokine signaling pathways. This is fundamentally different than patterns of food intake that are associated with a particular set of dietary recommendations (e.g., the Alternative Healthy Eating Index in relation to the American Food Pyramid) [9] or a culinary tradition (e.g., the MedDiet) [10]. Since its development, the DII has been applied to diet intake data in a variety of study cohorts to indicate associations with cardiovascular risk factors and CHD [11]. A higher (more pro-inflammatory) DII score has been associated with the inflammatory markers C-reactive protein (CRP) [12], tumor necrosis factor-alpha (TNF-α) [13], and interleukin (IL)-6 [14], incidence of metabolic syndrome, blood pressure and triglycerides [15], obesity [16], and greater incidence of cardiovascular events [17], [18], [19]. The DII offers an attractive alternative assessment tool to laboratory-based measurement of inflammatory cytokines, which are obtained through invasive means, tend to be costly, and are not routinely available in existing studies.
The DII also provides a method by which established dietary patterns can be compared for their probable anti-inflammatory effect. For instance, a one-day meal plan of a traditional MedDiet had a strong anti-inflammatory DII score [20] and greater MedDiet adherence has been negatively associated with DII scores [16], [21]. The DII also has been demonstrated to be inversely associated with healthy eating scores based on American dietary guidelines [9].
An improvement in DII score can therefore be achieved through healthy diet intervention, which in turn could reduce inflammation and other cardiometabolic risk markers, as well as prevent CHD. To our knowledge only two studies have assessed the impact of diet intervention on the DII. One of these trials showed short (2-month), but not longer-term (6-month), improvement in DII with vegetarian compared to omnivorous diets in a small cohort (n = 63) of overweight adults [22]. The other study of a large cohort (n = 14, 339) of post-menopausal women reported modest improvement in DII after 6-years on a low-fat diet [23]. Neither of these studies, however, assessed whether the reduction in DII score achieved with improved diet led to a change in inflammatory markers.
Current recommendations in Australia promote a low-fat diet for the prevention of CHD [24], for which there is some evidence to suggest this type of diet is associated with reduced DII scores [9]. A MedDiet, by nature of its composition, is likely to lead to a more anti-inflammatory DII score. The impact of adherence to a MedDiet on DII scores is of interest both because of the popularity of Mediterranean cuisine and concern about chronic, low-grade, systemic inflammation. Therefore, our objectives were to determine (1) how the DII score of a MedDiet compared with that of a low-fat diet, (2) the impact of randomization to an intervention with these two diets for 6 months on change in DII score and CRP and IL-6 (two inflammatory biomarkers on which the DII development was based) [8], and (3) the association between improvement in MedDiet adherence score and DII score, in an adult population with CHD. We hypothesized that the prescribed MedDiet model would have a lower DII score (i.e., greater dietary anti-inflammatory potential) than that of the low-fat diet and that this would translate to greater improvement in DII score and inflammation in participants randomized to the MedDiet intervention. We also hypothesized an association between improvement in MedDiet adherence and DII scores.
Section snippets
Study design
The AUStralian MEDiterranean Diet Heart Trial (AUSMED Heart Trial) is a multicenter, parallel design, randomized controlled trial (RCT) for the secondary prevention of CHD in a multi-ethnic Australian population (Australia and New Zealand Clinical Trials Register: ACTRN12616000156482, http://www.anzctr.org.au/). The trial involves 6-month intervention with a MedDiet versus low-fat diet and a 12-month follow up to assess the primary outcome of aggregate cardiovascular events. The present study
Participants
Fig. 1 demonstrates the randomization to diet study groups and completion of study appointments. Of the 35 participants randomized to the low-fat diet group, 31 started and 29 completed the intervention. Of the 37 participants randomized to the MedDiet group, 35 started and 27 completed the intervention. Participants dropped out for medical or family related issues or were lost to follow up. The drop-outs had a significantly higher pro-inflammatory DII score, with a mean baseline DII score of
Discussion
This study assessed both the theoretical and intervention effect on DII scores of a MedDiet versus low-fat diet in an Australian setting. Through analysis of our model meal plans, we demonstrated that the MedDiet had high anti-inflammatory potential whereas a low-fat diet had modest anti-inflammatory potential. In our pilot cohort of adult patients with CHD the MedDiet group adhered to the prescribed diet pattern and significantly reduced mean DII score after 6 months. By contrast, the low-fat
Acknowledgment
The authors are very grateful to all the participants of the study for their enthusiastic involvement and to the personnel of the affiliated hospital sites. We thank Cassandra Bendall for her assistance with data collection and entry, Jessica Radcliffe for her support during the data collection and entry process and Diana Navarro-Perez for her assistance with laboratory analyses. This work was supported by La Trobe University (Understanding Disease RFA Start-Up Grant, 2013. HLM was supported by
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