Eur J Nutr (2016) 55:2021–2029 DOI 10.1007/s00394-015-1016-9 ORIGINAL CONTRIBUTION Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males Mudi H. Alharbi2 · Daniel J. Lamport1 · Georgina F. Dodd1 · Caroline Saunders3 · Laura Harkness3 · Laurie T. Butler1 · Jeremy P. E. Spencer2 Received: 26 February 2015 / Accepted: 5 August 2015 / Published online: 18 August 2015 © The Author(s) 2015. This article is published with open access at Springerlink.com Abstract speed was significantly better following the FR drink com- Purpose Epidemiological evidence suggests that chronic pared to the placebo. The effects of objective cognitive consumption of fruit-based flavonoids is associated with function were supported by significant benefits for subjec- cognitive benefits; however, the acute effects of flavonoid- tive alertness following the FR drink relative to the placebo. rich (FR) drinks on cognitive function in the immediate Conclusions These data demonstrate that consumption of postprandial period require examination. The objective was FR orange juice can acutely enhance objective and subjec- to investigate whether consumption of FR orange juice is tive cognition over the course of 6 h in healthy middle-aged associated with acute cognitive benefits over 6 h in healthy adults. middle-aged adults. Methods Males aged 30–65 consumed a 240-ml FR Keywords Flavonoids · Flavanones · Cognition · orange juice (272 mg) and a calorie-matched placebo in a Cognitive function · Orange juice randomized, double-blind, counterbalanced order on 2 days separated by a 2-week washout. Cognitive function and subjective mood were assessed at baseline (prior to drink Introduction consumption) and 2 and 6 h post consumption. The cog- nitive battery included eight individual cognitive tests. A Epidemiological data suggest that frequent consumption of standardized breakfast was consumed prior to the base- citrus fruits is associated with various health benefits such line measures, and a standardized lunch was consumed 3 h as a reduced risk of cardiovascular disease, cerebral infarc- post-drink consumption. tion and ischemic stroke [1–3]. Recently, there has also Results Change from baseline analysis revealed that per- been interest in the relationship between fruit consump- formance on tests of executive function and psychomotor tion and cognitive function [4], particularly given that fruits and juices provide a rich, easily available source of flavo- noids such as hesperidin and narirutin. Human research of Mudi H. Alharbi and Daniel J. Lamport are joint first authors. this field is in its infancy; however, recent reviews indicate that increased flavonoid consumption over the lifespan may * Daniel J. Lamport attenuate age-associated cognitive decline and the onset of [email protected] neurodegenerative disease [5, 6]. For example, increased Jeremy P. E. Spencer consumption of citrus fruits and orange juice was associ- [email protected] ated with better cognitive outcomes in a cross-sectional 1 School of Psychology and Clinical Language Sciences, analysis of 2031 females aged 70–74 [7]. University of Reading, Reading RG6 6AL, UK In support of the epidemiological evidence, a handful 2 Molecular Nutrition Group, School of Chemistry, of intervention studies in older adults with mild cogni- Food and Pharmacy, University of Reading, tive impairment indicate that daily intake of flavonoid-rich Reading RG6 6AP, UK (FR) juices over 12–16 weeks can benefit memory func- 3 PepsiCo Inc., Reading, UK tion [8–10]. Cognitive benefits following chronic fruit juice 1 3 2022 Eur J Nutr (2016) 55:2021–2029 consumption are not exclusive to adults with mild cogni- diabetes or any other endocrine disorder, dementia or mild tive impairment; improvements in global cognitive function cognitive impairment (mini–mental state examination [18] were observed in healthy older adults (mean age 67) fol- (MMSE) <26), current weight loss regime, vegetarian diet, lowing 8-week daily consumption of flavanone-rich orange regular intake of supplements including fish oil, fatty acid, juice (305 mg/day) relative to a low-flavanone control vitamins and minerals, any medication for hypertension, (37 mg) [11]. It has been hypothesized that increased cer- hyperlipidaemia, inflammation, hypercholesterolemia and ebral blood flow (CBF) and increased neural activity fol- hypercoagulation, and history or evidence of depression lowing consumption of flavonoid-rich drinks could provide (as indicated by the Brief Symptom Inventory, BSI). Pilot an underlying mechanism for the aforementioned cognitive data by our group with a sample size of 24 healthy adults benefits [9, 12]. In support of this, daily dietary supplemen- using the Digit Symbol Substitution Test (DSST) indicated tation of cocoa flavanols (900 mg/day) over 8 weeks was an effect size (eta squared) of 0.32 following consumption associated with increased cerebral blood volume in the den- of a fruit-based juice. Therefore, for a crossover design, tate gyrus of the hippocampus [13]. Crucially, concomitant assuming two-sided test criteria with alpha level 0.05 and improvements in pattern recognition were also observed, a correlation of 0.5 between repeated-measures test scores, such that response times were 630 ms quicker following for two treatment conditions and three time-point measure- high-flavanol relative to low-flavanol supplementation. This ments, a sample size of 24 would give power of at least provides evidence of possible causation between flavonoid 86 %. Recruitment commenced in June 2012 and termi- intake, increased CBF and behavioral effects. nated in December 2012. It remains to be seen whether acute cognitive benefits occur within the immediate postprandial phase following Design juice intake. However, acute improvements in memory and executive function have been observed in healthy young A randomized, double-blind, placebo-controlled, crosso- adults following consumption of flavonoid-rich cocoa- ver design was used, and good clinical practice and ethical based drinks and solids [14, 15]. The aim of the present principles were followed according to ICH and the Decla- research was to investigate whether consumption of FR ration of Helsinki (1996). There were two drink conditions: orange juice is associated with acute cognitive benefits placebo and FR orange juice, and measurements were taken in healthy middle-aged adults. Orange juice is one of the at three time points: baseline (prior drink consumption), 2 h most commonly consumed sources of flavonoids, and the post consumption and 6 h post consumption of the drink. potential for fruits and fruit-based drinks to enhance cog- All procedures were approved by the University of Reading nitive function or attenuate cognitive decline deserves Research Ethics committee (No. 12/06). investigation, particularly in healthy populations for whom very limited published data exist. The flavonoid concentra- Treatment drinks tion of whole oranges can be higher than the concentration found in orange juice [16], principally because the fibers in The 240-ml FR drink consisted of Tropicana Pure Premium orange act as an entrapping matrix [17]; thus, some of the Orange Juice with 5.5 g of added orange pomace fiber flavonoids are lost during the juicing process. Therefore, (240 ml) which contained a total of 272 mg flavonoids (see in the present study, the intervention drink is composed of Table 1 for drink composition). Analysis of the flavonoid whole processed juicing orange which retains the fiber, and content was performed by PepsiCo (Barrington, Illinois, thus delivers a high dose of flavonoids. USA). The orange pomace comprised of the micronized, edible part of the whole orange which is leftover during the production of Tropicana Pure Premium Orange Juice. The Subjects and methods pomace is rich in fiber (40:60 ratio of soluble to insoluble) and contains small amounts of micronutrients, and a high Participants proportion of the flavonoids found in whole orange. The control drink was prepared by dissolving a placebo mix Twenty-four healthy males were recruited from Reading, containing glucose, fructose, sucrose and 0.67 % citric acid UK, and surrounding areas. Two participants withdrew (for flavor purposes) in 240 ml of water. The drinks were following the completion of arm one due to work commit- closely matched for volume, taste, appearance, energy, glu- ments (data not included). Inclusion criteria were males cose, fructose and sucrose (see Table 1). The ingredients aged 30–65 (mean 51, SD 6.6), native English speaking, for both drinks (except water) were provided by PepsiCo BMI 25–32 kg/m2 (mean 28.3, SD 3.1), non-smokers. Inc. and were kept frozen ( 20 °C) until preparation. The − Exclusion criteria were history of stroke/myocardial infarc- drinks and randomization sequence were prepared at the tion, alcohol misuse, renal or bowel disease, pancreatitis, University of Reading by an independent researcher (AW) 1 3 Eur J Nutr (2016) 55:2021–2029 2023 Table 1 Nutritional composition of the high-flavonoid and placebo provided by the research team (350 kcal, 6.9 g fat of which drinks per 240 ml serving 3 g saturates, 52.1 g carbohydrate of which 9.7 g sugars, Flavonoid rich Placebo 19 g protein, 1.4 g fiber, 0.9 g salt) to avoid second meal cognitive effects [20]. For each test day, participants arrived Energy (kcal) 92.8 87.7 at 8:30 a.m. following a 12-h fast. During the fast, partici- Glucose (g) 5.1 5.36 pants were permitted to consume only water provided at Fructose (g) 6.12 6.38 screening. A standardized breakfast of croissants and low- Sucrose (g) 11.99 10.2 fat cream cheese was consumed upon arrival (24.5 g fat, Fiber (g) 5.50 – 10.1 g protein, 38.4 g carbohydrates, 415 kcal). The base- Vitamin C (mg) 80.17 – line cognitive battery commenced at 9:10 a.m. followed by Folate (mg) 65.28 – the consumption of the FR or control drink at 10:00 a.m. Total B-carotenes (mg) 0.26 – Instructions were to consume the whole drink within 5 min.