A Multi-Ingredient Nutritional Supplement in Combination With Resistance Exercise and High-Intensity Interval Training Improves Cognitive Function and Increases N-3 Index in Healthy Older Men: A Randomized Controlled Trial

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/m(2)] 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 [Montréal 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 (Δ = 0.58 ± 0.62, p = 0.004) but not in the CON group (Δ = 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.