A Multi-Ingredient Nutritional Supplement in Combination With Resistance Exercise and High-Intensity Interval Training Improves Cognitive Function and Increases -3 Index in Healthy Older Men: A Randomized Controlled Trial
Authors: Tim Snijders
Hanna Fang
Kirsten E Bell
Adrian Chabowski
Stuart M Phillips
Jennifer J Heisz
Michael A Zulyniak
Gianni Parise
David J Allison
Journal: Frontiers in aging neuroscience (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: calcium; creatine; high-intensity interval training; n-3 polyunsaturated fatty acids; protein
Affiliations: Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada., Department of Kinesiology, McMaster University, Hamilton, ON, Canada., NUTRIM, Department of Human Biology, Maastricht University Medical Centre, Maastricht, Netherlands., Department of Medicine, McMaster University, Hamilton, ON, Canada., School of Food Science and Nutrition, University of Leeds, Leeds, United Kingdom., Department of Physiology, Medical University of Bialystok, Bialystok, Poland.

Abstract:  We aimed to evaluate the effect of multi-ingredient nutritional supplementation, with and without exercise training, on cognitive function in healthy older men. Forty-nine sedentary men [age: 73 ¬± 6 years (mean ¬± SD); body mass index: 28.5 ¬± 3.6 kg/m2] were randomized to consume a supplement (SUPP n = 25; 1500 mg n-3 polyunsaturated fatty acids, 30 g whey protein, 2.5 g creatine, 500 IU vitamin D, and 400 mg calcium) or control beverage (CON n = 24; 22 g maltodextrin) twice daily for 20 weeks consisting of Phase 1: SUPP/CON followed by Phase 2: 12-week resistance exercise training plus high-intensity interval training, while continuing to consume the study beverages (SUPP/CON + EX). At baseline, 6 weeks, and 19 weeks we assessed cognitive function [Montr√©al Cognitive Assessment (MOCA)], memory [word recall during the Rey Auditory Verbal Learning Test (RAVLT)], executive functions (working memory inhibition control), and nutrient bioavailability. We did not observe changes to any aspect of cognitive function after Phase 1; however, significant improvements in the following cognitive function outcomes were detected following Phase 2: MOCA scores increased (6 weeks: 23.5 ¬± 3.3 vs. 19 weeks: 24.4 ¬± 2.5, p = 0.013); number of words recalled during the RAVLT increased (6 weeks: 6.6 ¬± 3.6 vs. 19 weeks: 7.6 ¬± 3.8, p = 0.047); and reaction time improved (6 weeks: 567 ¬± 49 ms vs. 19 weeks: 551 ¬± 51 ms, p = 0.002). Although between-group differences in these outcomes were not significant, we observed within-group improvements in composite cognitive function scores over the course of the entire study only in the SUPP group (Œî = 0.58 ¬± 0.62, p = 0.004) but not in the CON group (Œî = 0.31 ¬± 0.61, p = 0.06). We observed a progressive increase in n-3 index, and a concomitant decrease in the ratio of arachidonic acid (ARA) to eicosapentaenoic acid (EPA) within erythrocyte plasma membranes, in the SUPP group only. At week 19, n-3 index (r = 0.49, p = 0.02) and the ARA:EPA ratio (r = -0.44, p = 0.03) were significantly correlated with composite cognitive function scores. Our results show that 12 weeks of RET + HIIT resulted in improved MOCA scores, word recall, and reaction time during an executive functions task; and suggest that a multi-ingredient supplement combined with this exercise training program may improve composite cognitive function scores in older men possibly via supplementation-mediated alterations to n-3 PUFA bioavailability. Clinical Trial Registration: http://www.ClinicalTrials.gov, identifier NCT02281331. 

Retracted: No

PubPeer comments:
 This paper has a 2019 correction, which reads:  The original version of this article unfortunately contained a mistake. During final figure preparation and manuscript sub- mission, the similar graphs (Fig. 6c) in different papers were accidentally switched. It was subsequently noted in a further review that Fig. 2a does not match with the hesperetin concentration. The corrected figures and graphs are herein (Figs. 2a, 6c). This correction does not affect the results or conclusions of the original paper. Here is the original Figure 2, with similarities noted to panels in Figure 4 of another paper by the same research group, i.e. Zhang J et al., Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species, Dig Dis Sci (2015), DOI: 10.1007 s10620-015-3696-7 - https: pubpeer.com publications D1B7268C1777BEDD62FEBA7E6E8A8E The three panels marked with colored boxes have all been replaced in the corrected version. Note that the duplications not only represented different cells (liver cancer cells vs. gastric cancer cells) but also different concentrations of Hereperetin treatments.  , 
 And here are the original Figures 6 (Dig Dis Sci) and 7 (Med Oncol) compared with each other. This error has also been corrected. I thank the authors for correcting this error.  ,