Effect of almond consumption on vascular function in patients with coronary artery disease: a randomized, controlled, cross-over trial

Chen et al. Nutrition Journal (2015) 14:61 DOI 10.1186/s12937-015-0049-5 RESEARCH Open Access Effect of almond consumption on vascular function in patients with coronary artery disease: a randomized, controlled, cross-over trial C-Y. Oliver Chen1,3*, Monika Holbrook2, Mai-Ann Duess2, Mustali M Dohadwala2, Naomi M Hamburg2, Bela F. Asztalos1, Paul E. Milbury1, Jeffrey B. Blumberg1 and Joseph A. Vita2ˆ Abstract Objective: Almonds reduce cardiovascular disease risk via cholesterol reduction, anti-inflammation, glucoregulation, and antioxidation. The objective of this randomized, controlled, cross-over trial was to determine whether the addition of 85 g almonds daily to a National Cholesterol Education Program (NCEP) Step 1 diet (ALM) for 6 weeks would improve vascular function and inflammation in patients with coronary artery disease (CAD). Research design and methods: A randomized, controlled, crossover trial was conducted in Boston, MA to test whether as compared to a control NCEP Step 1 diet absent nuts (CON), incorporation of almonds (85 g/day) into the CON diet (ALM) would improve vascular function and inflammation. The study duration was 22 weeks including a 6-weeks run-in period, two 6-weeks intervention phases, and a 4-weeks washout period between the intervention phases. A total of 45 CAD patients (27 F/18 M, 45–77 y, BMI = 20-41 kg/m2) completed the study. Drug therapies used by patients were stable throughout the duration of the trial. Results: The addition of almonds to the CON diet increased plasma α-tocopherol status by a mean of 5.8 %, reflecting patient compliance (P ≤0.05). However, the ALM diet did not alter vascular function assessed by measures of flow-mediated dilation, peripheral arterial tonometry, and pulse wave velocity. Further, the ALM diet did not significantly modify the serum lipid profile, blood pressure, C-reactive protein, tumor necrosis factor-α or E-selectin. The ALM diet tended to decrease vascular cell adhesion molecule-1 by 5.3 % (P = 0.064) and increase urinary nitric oxide by 17.5 % (P = 0.112). The ALM intervention improved the overall quality of the diet by increasing calcium, magnesium, choline, and fiber intakes above the Estimated Average Requirement (EAR) or Recommended Dietary Allowance (RDA). Conclusions: Thus, the addition of almonds to a NECP Step 1 diet did not significantly impact vascular function, lipid profile or systematic inflammation in CAD patients receiving good medical care and polypharmacy therapies but did improve diet quality without any untoward effect. Trial registration: The trial was registered with the ClinicalTrials.Gov with the identifier: NCT00782015. Keywords: Almonds, Coronary arterial disease, Dietary quality, Endothelial function, Inflammation, Oxidative stress * Correspondence: ˆDeceased 1 Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA 3 Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA Full list of author information is available at the end of the article © 2015 Chen et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Chen et al. Nutrition Journal (2015) 14:61 Background Coronary artery disease (CAD) is one of the most common causes of death in middle- and high-income countries [1]. Patients with CAD typically receive several medications as part of their treatment to protect against recurrent cardiac events and all-cause mortality. Lifestyle modifications comprised of regular participation in physical activity, diets low in fat and rich in plant foods and smoking cessation are recommended to complement polypharmacy regimens in the management of CAD patients [2]. Patients with CAD commonly have higher circulating cholesterol levels than their clinically healthy counterparts [3, 4]. Thus, patients with CAD are almost always treated with a hypocholesterolemic drug, usually a statin, and provided with recommendations for lifestyle modification for secondary prevention. Different dietary patterns, including the Mediterranean, DASH, and Portfolio Eating Plan diets, can complement statin therapy as well as provide other cardioprotective benefits [5, 6]. The American Heart Association recommends a diet rich in nuts, fruits and vegetables, and low in saturated fats for both primary and Fig. 1 CONSORT flow diagram Page 2 of 11 secondary prevention of CAD [7]. The Lyon Diet Heart Study was the first clinical trial to demonstrate that the Mediterranean diet is protective in the secondary prevention of CAD [8]. Among the variety of plant foods that may promote heart health, tree nuts are high in fiber, unsaturated fat, selected vitamins and minerals, and phytochemicals. This nutrient profile contributes to the observed reduction in risk of cardiovascular disease (CVD) among those who frequently consume nuts [9, 10]. Recently, the PREDIMED trial found that a Mediterranean diet supplemented with 30 g/day tree nuts (almonds, hazelnuts, and walnuts) decreased risk of cardiovascular events by 28 % [11]. Among tree nuts, almonds are rich in monounsaturated fat, fiber, α-tocopherol, copper and magnesium, and phytochemicals including phytosterols and polyphenols. Research on almonds suggests they may have beneficial actions on serum cholesterol, body weight, glucose homeostasis, inflammation, and oxidative stress [12, 13]. In addition to their macronutrient profile, almonds provide a good source of nutrients known to modulate Chen et al. Nutrition Journal (2015) 14:61 vascular function, including L-arginine, flavonoids, folic acid, and vitamin E. In a clinical trial of 60 healthy men with risk factors for CVD, Choudhury et al. [14] tested 50 g almonds/day for 4 weeks and found improved flowmediated dilatation (FMD). However, no studies are available that examine the effect of almonds on endothelial reactivity in patients with compromised vascular function. Therefore, we hypothesized that addition of 85 g/day almonds to a National Cholesterol Education Program (NCEP) Step 1 diet would improve vascular function in patients with CAD via an increase in nitric oxide (NO) availability and reduction in dyslipidemia, systemic inflammation, and/or oxidative stress. Methods and materials Subjects Patients with angiographically proven CAD were recruited from the cardiology practice at the Boston Medical Center in Boston, MA Fig. 1 Consecutive patients with CAD coming to the cardiology practice were assessed for eligibility. CAD was confirmed with obstruc (...truncated)