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

Kirsten E Bell, Hanna Fang, Tim Snijders, David J Allison, Michael A Zulyniak, Adrian Chabowski, Gianni Parise, Stuart M Phillips, Jennifer J Heisz, Kirsten E Bell, Hanna Fang, Tim Snijders, David J Allison, Michael A Zulyniak, Adrian Chabowski, Gianni Parise, Stuart M Phillips, Jennifer J Heisz

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 [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.

Keywords: calcium; creatine; high-intensity interval training; n-3 polyunsaturated fatty acids; protein; resistance exercise training; vitamin D.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram. This chart depicts the movement of participants through the trial, which we conducted between December 2014 and September 2016.
FIGURE 2
FIGURE 2
Experimental design. Participants consumed either an experimental supplement (SUPP) or control (CON) beverage twice per day for 20 weeks (weeks 0–19, inclusive). Between weeks 7–18 (inclusive), participants completed a 12-week exercise training program. Exercise training consisted of RET twice weekly (Mondays and Fridays) and HIIT once per week (Wednesdays). At weeks –1 (baseline), 6, and 19 we assessed cognitive function and obtained a blood sample for the measurement of BDNF, 25(OH)D, and erythrocyte plasma membrane phospholipid composition. Phase 1: SUPP/CON took place between weeks 0–6, and Phase 2: SUPP/CON + EX took place between weeks 7–19. SUPP, supplement; CON, control; RET, resistance exercise training; HIIT, high-intensity interval training; BDNF, brain-derived neurotrophic factor; 25(OH)D, 25-hydroxyvitamin D.
FIGURE 3
FIGURE 3
Montréal Cognitive Assessment performance. Scores of 26 or more (out of a possible 30-point total) are considered normal; scores

FIGURE 4

Memory, assessed with the RAVLT.…

FIGURE 4

Memory, assessed with the RAVLT. (A) Sum of words recalled during Trials 1–5…

FIGURE 4
Memory, assessed with the RAVLT. (A) Sum of words recalled during Trials 1–5 (out of a possible 75-word total). (B) Number of words recalled following a 30 min delay (Trial 7; out of a possible 15-word total). (C) Number of words recognized in the 30-word visual recognition list (out of a possible 15-word total). Boxes (SUPP: gray; CON: white) represent interquartile (25th to 75th percentile) ranges, with the horizontal lines indicating the median. Whiskers represent the maximal and minimal values, and the cross indicates the mean. Dissimilar letters denote changes over time within a given treatment group (SUPP or CON). RAVLT, Rey Auditory Verbal Learning Test; SUPP, supplement; CON, control.

FIGURE 5

Working memory inhibition control (a…

FIGURE 5

Working memory inhibition control (a measure of executive functions), assessed with the Go-NoGo…

FIGURE 5
Working memory inhibition control (a measure of executive functions), assessed with the Go-NoGo Task. (A) Accuracy (i.e., percentage of correct responses) during “Go” trials. (B) Accuracy during “NoGo” trials. (C) Reaction time during correct “Go” trials. Boxes (SUPP: gray; CON: white) represent interquartile (25th to 75th percentile) ranges, with the horizontal lines indicating the median. Whiskers represent the maximal and minimal values, and the cross indicates the mean. Dissimilar letters denote changes over time within a given treatment group (SUPP or CON). SUPP, supplement; CON, control.

FIGURE 6

Change in composite cognitive function…

FIGURE 6

Change in composite cognitive function scores between baseline and 19 weeks. Composite cognitive…

FIGURE 6
Change in composite cognitive function scores between baseline and 19 weeks. Composite cognitive function scores were calculated using MOCA scores, delayed recall (Trial 7) performance on the RAVLT, and reaction time during correct “Go” trials during the Go-NoGo Task. Boxes (SUPP: gray; CON: white) represent interquartile (25th to 75th percentile) ranges, with the horizontal lines indicating the median. Whiskers represent the maximal and minimal values, and the cross indicates the mean. ∗ indicates a significant difference from no change (i.e., zero). SUPP, supplement; CON, control.
FIGURE 4
FIGURE 4
Memory, assessed with the RAVLT. (A) Sum of words recalled during Trials 1–5 (out of a possible 75-word total). (B) Number of words recalled following a 30 min delay (Trial 7; out of a possible 15-word total). (C) Number of words recognized in the 30-word visual recognition list (out of a possible 15-word total). Boxes (SUPP: gray; CON: white) represent interquartile (25th to 75th percentile) ranges, with the horizontal lines indicating the median. Whiskers represent the maximal and minimal values, and the cross indicates the mean. Dissimilar letters denote changes over time within a given treatment group (SUPP or CON). RAVLT, Rey Auditory Verbal Learning Test; SUPP, supplement; CON, control.
FIGURE 5
FIGURE 5
Working memory inhibition control (a measure of executive functions), assessed with the Go-NoGo Task. (A) Accuracy (i.e., percentage of correct responses) during “Go” trials. (B) Accuracy during “NoGo” trials. (C) Reaction time during correct “Go” trials. Boxes (SUPP: gray; CON: white) represent interquartile (25th to 75th percentile) ranges, with the horizontal lines indicating the median. Whiskers represent the maximal and minimal values, and the cross indicates the mean. Dissimilar letters denote changes over time within a given treatment group (SUPP or CON). SUPP, supplement; CON, control.
FIGURE 6
FIGURE 6
Change in composite cognitive function scores between baseline and 19 weeks. Composite cognitive function scores were calculated using MOCA scores, delayed recall (Trial 7) performance on the RAVLT, and reaction time during correct “Go” trials during the Go-NoGo Task. Boxes (SUPP: gray; CON: white) represent interquartile (25th to 75th percentile) ranges, with the horizontal lines indicating the median. Whiskers represent the maximal and minimal values, and the cross indicates the mean. ∗ indicates a significant difference from no change (i.e., zero). SUPP, supplement; CON, control.

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