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Do specific dietary constituents and supplements affect mental energy? Review of the evidence

Heather E Gorby, Amy M Brownawell, Michael C Falk
DOI: http://dx.doi.org/10.1111/j.1753-4887.2010.00340.x 697-718 First published online: 1 December 2010

Abstract

The numbers of marketing claims and food, beverage, and drug products claiming to increase mental energy have risen rapidly, thus increasing the need for scientific specificity in marketing and food label claims. Mental energy is a three-dimensional construct consisting of mood (transient feelings about the presence of fatigue or energy), motivation (determination and enthusiasm), and cognition (sustained attention and vigilance). The present review focuses on four dietary constituents/supplements (Ginkgo biloba, ginseng, glucose, and omega-3 polyunsaturated fatty acids) to illustrate the current state of the literature on dietary constituents and mental energy. The strongest evidence suggests effects of Ginkgo biloba on certain aspects of mood and on attention in healthy subjects, as well as associations between omega-3 polyunsaturated fatty acids and reduced risk of age-related cognitive decline. Limitations of the current data and challenges for future research are discussed.

  • cognition
  • memory
  • mental energy
  • mood
  • motivation

INTRODUCTION

Lack of energy and motivation is often associated with diminished work productivity and reduced quality of life.1 Dietary supplements as well as food and beverage products reported to increase energy are well-established in the marketplace.2 Product claims regarding “energy” and/or “mental energy” have risen rapidly in recent years, thus increasing the need for scientific specificity. Until recently, the term mental energy was only loosely defined and appropriate assessment methods to study changes in mental energy status were not clearly described.

A series of workshops sponsored by the North American branch of the International Life Sciences Institute (ILSI) resulted in the development of a scientific definition of mental energy as “the ability to perform mental tasks, the intensity of feelings of energy and fatigue, and the motivation to accomplish mental and physical tasks”.3,4 Mental energy is a three-dimensional construct consisting of mood (transient feelings about the presence of fatigue or energy), motivation (determination and enthusiasm), and cognition (sustained attention and vigilance).3 However, all three do not need to be altered by a substance to affect mental energy. Appropriate techniques to measure mood,5 motivation,6 and cognition7 in relation to mental energy have been identified and reviewed. Following the recent definition of the term “mental energy”, a limited amount of published research has applied that definition. Previously, researchers referred to central nervous system arousal and activation in relation to foods and dietary constituents in place of a defined mental energy concept. While the current review focuses on the effects of specific foods, dietary constituents, and/or dietary supplements on mental energy, there are other approaches toward enhancing mental energy, such as exercise, adequate sleep, and brief afternoon naps.8,9

The present review stems from a project undertaken by ILSI to describe the scope of the published scientific literature on mental energy and to provide an assessment of the state of the science related to the effects of foods, dietary constituents, and/or dietary supplements on mental energy, as currently defined. A literature search was performed, as described in detail below, and relevant data were extracted. It was evident that insufficient data were available to perform a systematic review. Therefore, the data were summarized and limitations of the published studies were identified. The present review article describes the findings related to four select dietary constituents/supplements (Ginkgo biloba, ginseng, glucose, and omega-3 polyunsaturated fatty acids) to illustrate the state of the science regarding mental energy as a defined concept and to discuss the challenges for improving future research.

THE MENTAL ENERGY LITERATURE

Criteria for studies

At the request of ILSI, the Life Sciences Research Organization (LSRO) conducted a literature search and review on the relationships between the intake of foods, dietary constituents, and/or dietary supplements and mental energy. Studies were restricted to those with human subjects only and included both prospective and observational studies. Study subjects were limited to healthy adults aged 18 years and older, including seniors with managed disease (e.g., diabetes). Studies of seniors diagnosed with Alzheimer's disease or other dementia were excluded. Both oral ingestion and gastric infusion delivery methods were considered. Review articles and reports of original research evaluating the effects of genetics, pain, sleep, and/or disease on mental energy were excluded. Studies examining the effects of caffeine were also excluded from the current review, because caffeine has a clear dose-dependent effect on cognitive function that has been extensively reviewed elsewhere.10

Search methods for identification of studies

LSRO conducted the literature search using the PubMed and PsychInfo databases for articles cited through May 2010. Searches were conducted using Medical Subject Headings (MeSH) combined with key-word searches to capture all indexed studies (Table 1). Bibliographic searches were also conducted to ensure inclusion of all relevant studies. The initial search strategy retrieved approximately 2,500 primary articles. The abstracts were reviewed and studies were included if they investigated food, dietary constituent, or dietary supplement intake and used at least one measure of mood, cognition, and/or motivation. Full-text copies of the articles meeting those criteria were then screened for their suitability for inclusion and those meeting the inclusion criteria were manually cross-referenced. Two-hundred and sixty-five articles met the initial search criteria.

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Table 1

Search strategy used to identify the studies evaluated in the present review.

Search terms used in PubMed search enginePubMed search termsTotal hits
(brain OR cognition OR fatigue OR motivation OR mood OR affect) AND (food OR diet OR nutrition OR micronutrient OR supplement OR vitamin) Limits: Human, English, MESH terms Major Topics(“brain”[MeSH Major Topic] OR “cognition”[MeSH Major Topic] OR “fatigue”[MeSH Major Topic] OR “motivation”[MeSH Major Topic] OR “affect”[MeSH Major Topic] OR “affect”[MeSH Major Topic]) AND (“food”[MeSH Major Topic] OR “diet”[MeSH Major Topic] OR (“nutritional sciences”[MeSH Major Topic] OR “nutrition physiology”[MeSH Major Topic]) OR (“trace elements”[MeSH Major Topic] OR “micronutrients”[MeSH Major Topic]) OR “dietary supplements”[MeSH Major Topic] OR (“vitamins”[MeSH Major Topic] OR “vitamin k”[MeSH Major Topic] OR “vitamin d”[MeSH Major Topic] OR “vitamin a”[MeSH Major Topic])) AND (“humans”[MeSH Terms] AND English[lang])2,488

Data were extracted and entered into a database. Extracted information included study population, number of subjects, type and duration of the study, dosage/amount and timing of treatment or ingestion of food, and outcome measures for mood, cognition, and/or motivation. Timing and duration of ingestion of dietary constituents were categorized into five groups: short-term acute (<2 h), long-term acute (2–24 h), short-term chronic (2–7 days), moderate-term chronic (1–26 weeks), and long-term chronic (>26 weeks).

Outcome measures

Previous reviews recommended several instruments for measuring mental energy based on their prevalence in the literature.57 Studies included in the current review frequently evaluated mood using the Profile of Mood States (POMS) questionnaire (42 studies) and the Visual Analog Scale (VAS) (49 studies), but 25 additional instruments were also used. The cognitive measures most frequently used were tests of attention and vigilance; 12 different testing instruments were used to evaluate attention and 6 were used to evaluate vigilance. Cognitive performance outcomes were also included, such as memory and speed of information processing. Out of the initial 265 studies retrieved for the review, only two attempted to measure motivation. The measures used in these studies, i.e., “time spent trying to remember words”11 and pupil size,12 are not generally accepted measures of motivation. Given the lack of available data, no conclusions can be drawn about associations between dietary constituents/supplements and motivation, so this mental energy component is not discussed further in this review.

Description of included studies

The literature search revealed that changes in mental energy had been evaluated for 35 foods, dietary constituents, dietary supplements, and dietary factors (e.g., meal timing, caloric load, macronutrient composition). For 26 of these 35 foods/supplements/constituents, 10 or fewer studies were published for each. For 19 of those 26, fewer than 5 studies were published. As a result, insufficient evidence is available to evaluate mental energy claims for numerous foods, dietary constituents, and dietary supplements. The greatest amount of literature was available for Ginkgo biloba, glucose, carbohydrate, and ginseng. To illustrate the state of the mental energy literature, this review provides a detailed discussion of Ginkgo biloba (Table 2), ginseng (Table 3), and glucose (Table 4), as well as a popular supplement, omega-3 polyunsaturated fatty acids (PUFAs) (Table 5).

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Table 2

Summary of studies on Ginkgo biloba and mental energy.

ReferenceTreatmentOutcome measure(s)Results
Mood
 Burns et al. (2006)13Ginkgo biloba; extract, 40 mg, Gingkoforte; 24% ginkgo-flavonglycosides and 6% ginkgolides 3×/d (120 mg)POMSNo effect
 Cleza et al. (2003)14Ginkgo biloba; extract 120 mg, EGb 761; 2×/d (240 mg)Self-rated depression scale; POMS; subjective intensity scale-mood mental health: self-report on VAS; general health: self-report on VAS; quality of life: self-report on VASSubjects reported a more positive state, better mental health, and quality of life after taking Ginkgo biloba
 Cockle et al. (2000)15Ginkgo biloba; extract 120 mg, LI 1370Self-rated activities of daily living scale VASGinkgo biloba group felt better able to cope with daily living, and had reduced anxiety and depression
 Elsabagh et al. (2005)16Ginkgo biloba; extract 120 mg, 25% ginkgoflavonoids and 6% terpenoidsBond-Lader VASNo effect
 Elsabagh et al. (2005)17Ginkgo biloba; extract 120 mg, LI 1370; 25% total ginkgo flavonoids, 6% total terpene lactonesHospital anxiety and depression scale Bond-Lader VASNo effect
 Hartley et al. (2003)18Ginkgo biloba; extract 120 mg, LI 1370; 25% ginkgo flavonoids and 6% terpenoidsBond-Lader VASNo effect
 Hartley et al. (2004)19Ginkgo biloba; extract 120 mg/d GK501
Ginseng; extract 200 mg/d G115Bond-Lader VASNo effect
 Kennedy et al. (2000)20Ginkgo biloba; extract 120, 240, or 360 mg, GK501; 24% ginkgo-flavone glycosides and 6% terpene lactonesBond-Lader VASNo effect
 Kennedy et al. (2002)21Ginkgo biloba; extract 360 mg, GK501Bond-Lader VASGinkgo biloba group reported improved alertness and contentedness
 Kennedy et al. (2007)22Ginkgo biloba; extract 120 mg, 24% ginkgo-flavonol glycosides and 6% terpene lactonesBond-Lader VASGinkgo biloba associated with improved calmness
 Mix et al. (2000)23Ginkgo biloba; extract 180 mg/d, EGb 761Self-report questionnaire, moodNo effect
 Mix et al. (2002)24Ginkgo biloba; extract 60 mg, EGb 761 24% flavone glycosides, 6% terpene lactones and less than 5 ppm ginkolic acids, 3×/d (180 mg)Self-report questionnaire, moodNo effect
 Rigney et al. (1999)25Ginkgo biloba; extract 150 mg (50 mg 3×/d), 300 mg (100 mg 3x/d), 240 mg, 120 mgVAS120, 150, and 300 mg increased alertness on day 1; 120 mg and 150 mg decreased arousal on day 2
 Singh et al. (2004)26Ginkgo biloba; extract 40 mg, 2×/d (80 mg)Medical symptom questionnaire SF-12No effect
 Subhan et al. (1984)27Ginkgo biloba; extract 120, 240, or 600 mgVASNo effect
 Trick et al. (2004)28Ginkgo biloba; 3 groups: 1) Ginkgo biloba extract LI 1370: 120 mg for 4 months plus 6 months continuation; 2) Ginkgo biloba for 4 months plus stop taking for 6 months; 3) new treatment group: 6 months of Ginkgo bilobaSelf-rated activities of daily living scale VASGinkgo biloba improved scores on mood and self-assessed performance, longer duration (10 months) of treatment improved scores even further
Cognition
 Burns et al. (2006)13Ginkgo biloba; extract, 40 mg, Ginko Forte; 24% ginkgo-flavone glycosides and 6% ginkgolides 3×/d (120 mg)Subtests from the Woodcock-Johnson Psycho-Educational Battery-RevisedGinkgo biloba improved long-term memory in older adults (55–79 years). No effect in younger subjects
 Cieza et al. (2003)14Ginkgo biloba; extract 120 mg, EGb 761; 2×/d (240 mg)Digit connection test; word list test; increment threshold for visual stimuli; auditory choice reaction time; finger tapping tempo and speedGinkgo biloba improved reaction time
 DeKosky et al. (2008)29Ginkgo biloba; extract 120 mg, EGb 761; 2×/d (240 mg)MMSE; Clinical Dementia Rating; Ginkgo Evaluation of Memory Study Neuropsychological BatteryNo effect
 Dodge et al. (2008)30Ginkgo biloba; extract, 240 mg, 6% terpene lactones and 24% flavone glycosides, plus standard multivitamin with 40 IU of vitamin EMMSE; logical memory subscale: WMS-RNo effect
 Elsabagh et al. (2005)16Ginkgo biloba; extract 120 mg, LI 1370; 25% total ginkgo flavonoids, 6% total terpene lactonesSpatial working memory; mental flexibility and planning ability; PASAT; pattern recognition memory; spatial recognition memory; delayed recall of words and picturesAcute dose of Ginkgo biloba improved performance on a sustained-attention task and pattern-recognition memory task. After 6 weeks there were no effects on cognition
 Elsabagh et al. (2005)17Ginkgo biloba; extract 120 mg, 25% ginkgo flavonoids and 6% terpenoidsCategory generation Stockings of Cambridge test: CANTAB; immediate and delayed paragraph recall: WMS-R; delayed matching-to-sample task: CANTAB; picture recall task: PASAT; intra/extra dimensional shift task: CANTABGinkgo biloba improved executive function in a subset of participants (those in menopause 5 years or more)
 Hartley et al. (2003)18Ginkgo biloba; extract 120 mg, 25% ginkgo flavonoids and 6% terpenoidsImmediate and delayed paragraph recall: WMS-R; delayed matching-to-sample test: CANTAB; PASAT; common objects test Stockings of Cambridge test: CANTAB; intra/extra dimensional shift task: CANTABGinkgo biloba improved performance of non-verbal memory, frontal lobe function, and sustained attention. No effect on immediate or delayed paragraph recall or in delayed recall of pictures
 Kennedy et al. (2000)20Ginkgo biloba; extract 120, 240, or 360 mg, 24% ginkgo-flavone glycosides and 6% terpene lactonesCDR computerized assessment battery: speed of attention, quality of memory, speed of memory, accuracy of attentionBoth 240 and 360 mg improved speed of attention at 2.5 and 6 h. Many other time- and dose-specific changes in performance of other factors
 Kennedy et al. (2002)21Ginkgo biloba; extract 360 mg, GK501CDR computerized assessment battery: speed of attention, quality of memory, speed of memory, accuracy of attention serial Threes and serial SevensGinkgo biloba improved secondary memory performance and performance on serial threes and serial sevens
 Kennedy et al. (2007)31Ginkgo biloba; extract 120 mg, 24% ginkgo-flavone glycosides and 6% terpene lactonesCDR computerized assessment battery: speed of attention, quality of memory, speed of memory, accuracy of attention120 mg Ginkgo biloba improved “quality of memory” at 1 and 4 h, reduced “speed of attention” at 1 and 6 h
 Kennedy et al. (2007)22Ginkgo biloba; extract 120 mg, 24% ginkgo-flavonol glycosides and 6% terpene lactonesCDR computerized assessment battery: speed of attention, quality of memory, speed of memory, accuracy of attention, serial sevens, and serial threesNo effect
 Mix et al. (2000)23Ginkgo biloba; extract 180 mg/d, EGb 761Logical memory subtest: WMS-R; visual reproduction subtest: WMS-R; trail making task parts A and B; Stroop color taskGinkgo biloba improved speed of processing compared to placebo. Participants were also more confident in their ability to remember, as measured by a self-report questionnaire
 Mix et al. (2002)24Ginkgo biloba; extract 60 mg, EGb 761 24% flavone glycosides, 6% terpene lactones and less than 5 ppm ginkgolic acids, 3×/d (180 mg)Faces subtest: WMS-III; digit symbol coding: WAIS-III; block design subtest: WAIS-III; selective reminding taskGinkgo biloba enhanced delayed free recall and delayed recognition of non-contextual auditory-verbal material. Ginkgo biloba improved ability to remember faces. Ginkgo group rated their overall ability to remember as improved
 Moulton et al. (2001)32Ginkgo biloba; extract 60 mg, LI 1370, 2×/d (120 mg)Reading span and digit span forwards: WAIS-R; Sternberg memory scanning testNo effect
 Nathan et al. (2002)33Ginkgo biloba; extract 120 mg, GingkoforteCDR computerized assessment battery: simple reaction time, choice reaction time, numeric working memory, spatial memory; Rey auditory verbal learning task; picture recognitionNo effect
 Polich et al. (2001)34Ginkgo biloba; extract 40 mg, less than 5 ppm ginkgolic acid, plus folic acid, L-tyrosine, DMAE bitartrate, pantothenic acid, riboflavin, vitamin B6, vitamin B1, niacinamide, vinpocetine, niacinPicture naming; continuous performance task; inspection time; simple and choice response timeGinkgo biloba decreased response time on a working memory task
 Rigney et al. (1999)25Ginkgo biloba; extract 150 mg (50 mg 3×/d), 300 mg (100 mg 3×/d), 240 mg, 120 mgSternberg memory scanning task; word recall test; critical flicker fusion; choice reaction time; digit symbol substitution task; WAIS-R; Stroop color taskGinkgo biloba, except 150 mg, performed faster on the Sternberg memory scanning task on day 1, and 120 mg and 300 mg performed faster on day 2
 Santos et al. (2003)35Ginkgo biloba; extract 80 mg, 24% flavonoid, 6.1% terpenoidToulouse-Pieron concentrated attention Wisconsin card sorting test; verbal free recall; Rey-Osterrieth complex figure test; WAIS-R; WMS-R; Corsi block-tapping testGinkgo biloba improved global cognitive functioning, attention, and speed of information processing
 Scholey et al. (2002)36Ginkgo biloba; study 1: Ginkgo biloba extract (GK501, 24% ginkgo-flavone glycosides and 6% terpene lactones), 60 mg each; 6 capsule daily doses = 120, 240, or 360 mgSerial sevens; serial threesGinkgo biloba improved total number of subtractions during serial threes in a dose-response manner at 4 h
 Snitz et al. (2009)37Ginkgo biloba; extract 120 mg, EGb 761; 2×/d (240 mg)MMSE; clinical dementia rating; Ginkgo Evaluation of Memory Study Neuropsychological BatteryNo effect
 Solomon et al. (2002)38Ginkgo biloba; extract 40 mg, 3×/d (120 mg)Stroop color task; digit symbol substitution; WAIS-RdDigit span; WMS-R logical memory subscale; WMS-R visual reproduction subscale; WMS-R mental control; WMS-R California verbal learning test; Boston naming test; category fluencyNo effect
 Stough et al. (2001)39Ginkgo biloba; extract 120 mgSpeed of comprehension test; digit span; trail making test; Rey auditory verbal learning test; inspection time; simple reaction time; working memoryGinkgo biloba extract improved speed of information processing, working memory, and executive processing
 Subhan et al. (1984)27Ginkgo biloba; extract 120, 240, or 600 mgSternberg memory scanning test; choice reaction time; critical flicker fusion test600 mg of Ginkgo biloba improved performance on the Sternberg memory test
  • Abbreviations: CANTAB, Cambridge Neuropsychological Test Automated Battery; CDR, Cognitive drug research; MMSE, Mini-Mental State Examination; PASAT: Paced Auditory Serial Addition Test; POMS, Profile in Mood States; VAS, Visual Analog Scale; WAIS, Wechsler Adult Inventory Scale; WAIS-R, Wechsler Adult Inventory Scale-Revised; WMS-R, Wechsler Memory Scale-Revised.

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Table 3

Summary of studies on ginseng and mental energy.

ReferenceTreatment descriptionOutcome measure(s)Results
Mood
 Cardinal et al. (2001)40Ginseng; extract 200 mg or 400 mg, Panax ginseng G115PANAS; POMSNo effect
 Kennedy et al. (2001)41Ginseng; extract 200 mg, 400 mg or 600 mg, Panax ginseng G115VASBoth the 200 and 400 mg doses of ginseng significantly reduced alertness
 Kennedy et al. (2004)42Ginseng; extract 200 mg, Panax ginseng G115VASNo effect
 Reay et al. (2006)43Ginseng; extract 200 mg, Panax ginseng G115VASGinseng decreased fatigue
 Ussher et al. (1995)44Ginseng; extract 40 mg, Panax ginseng G115POMSGinseng increased vigor
Cognition
 D'Angelo et al. (1986)45Ginseng; extract 100 mg, Panax ginseng G115, 2×/dCancellation test; mental arithmetic; logical deduction; choice reaction time; auditory reaction time; tapping test; digit symbol substitution testGinseng improved performance for mental arithmetic processing
 Kennedy et al. (2001)41Ginseng; extract 200 mg, 400 mg, or 600 mg, Panax ginseng G115CDR computerized assessment battery: speed of attention, quality of memory, speed of memory, accuracy of attentionGinseng improved “quality of memory” at 400 and 600 mg; 200 and 600 mg of ginseng caused decrements in performance on “speed of attention” factor
 Kennedy et al. (2004)42Ginseng; extract 200 mg, Panax ginseng G115CDR computerized assessment battery: speed of attention, quality of memory, speed of memory, accuracy of attention; serial threes and serial sevens; logical reasoning; sentence verification taskGinseng improved task performance, enhanced speed of memory, increased reaction times
 Reay et al. (2005)46Ginseng; extract 200 mg or 400 mg, Panax ginseng G115Serial threes and serial sevens; rapid visual information processing taskGinseng increased number of subtractions in serial threes subtraction task and decreased false alarms in rapid visual information processing task
 Reay et al. (2006)43Ginseng; extract 200 mg, Panax ginseng G115Serial threes and serial sevens; rapid visual information processing taskGinseng enhanced performance of a mental arithmetic task, and improved performance on the rapid visual information processing task
 Scholey (2002)36Ginseng; extract 200 mg, 400 mg, or 600 mg, Panax ginseng G115Serial threes and serial sevensGinseng had no effect on serial threes, but there were significant time-dose interactions for series sevens
 Sørenson et al. (1996)47Ginseng; extract 400 mg, Panax ginseng G115Simple auditive reaction times test; simple visual reaction times test; finger-tapping test; D2 test; fluency test; selective reminding task; logical memory and reproduction test; Rey-Osterrieth complex figure test; Wisconsin card sorting testGinseng sped up performance on the simple auditive reaction times test and improved performance on the Wisconsin card sorting test
  • Abbreviations: CDR, cognitive drug research; PANAS, Positive Affect Negative Affect Schedule; POMS, Profile in Mood States; VAS, Visual Analog Scale.

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Table 4

Summary of studies on glucose and mental energy.

ReferenceTreatment descriptionOutcome measure(s)Results
Mood
 Green et al. (2001)48Glucose; 500 mL glucose. 4 groups: in 2 sessions (1 glucose and 1 aspartame), subjects were correctly informed of drink; in the other 2 sessions, they were told they received the other drink.VASNo effect
 Reay et al. (2006)43Glucose; 25 g drinkVASGlucose decreased mental fatigue
 Scholey et al. (2002)49Glucose; 25 g glucose plus 200 mL waterPOMSNo effect
 Winder et al. (1998)50Glucose; 250 mL beverage sweetened with 50 g glucose powder (Boots' “Glucose C”) balanced for taste and acidity with lemon drink concentrate (Boots' “Unsweetened Lemon”)POMSNo effect
Cognition
 Azari et al. (1991)51Glucose; 300 mL (water) beverage containing 30 or 100 g glucoseMemory recognition; memory recallNo effect
 Benton et al. (1993)52Glucose; experiment 1: glucose beverage: 50 gExperiment 1: word list; spatial memory testNo effect
 Benton et al. (1993)52Glucose; experiment 2: glucose beverage: 50 gExperiment 2: word list; WMSNo effect
 Craft et al. (1994)53Glucose; 50 g orangeflavored beverageModified CVLT; Stroop color task; PASAT; word-list generation; pattern recall and recognition; paragraph recall; serial reaction time taskGlucose enhanced performance on the declarative memory measure, paragraph recall, for both older males with good recovery and younger males with poor recovery. Younger males with good recovery showed impaired memory after glucose
 Donohoe et al. (1999)54Glucose; experiments 1 and 2: glucose drink: 50 g glucose powder added to 250 mL water, 2 tbsp Robinson's whole orange squash (sugar-free), 2 tsp lemon juiceEmbedded figures test; time taken to solve critical problems; water jars test; verbal fluency; block design test; Porteus maze; logical reasoning testGlucose increased verbal fluency. Higher initial blood glucose levels correlated to better performance on the water jars test; high blood glucose levels after beverage were associated with performance decrements on the block design test
 Flint, Jr., et al. (2003)55Glucose; drink: 10, 100, and 500 mg/kg, or 50 gContinuous performance taskSubjects given 100 mg/kg of glucose performed worse on the attention task
 Ford et al. (2002)56Glucose; 25 g glucose added to 150 mL of water, mixed with 20 mL of sugar-free orange drinkCDR computerized assessment batteryNo effect
 Foster et al. (1998)57Glucose; 25 g glucose added to 300 mL waterModified CVLT; forward and backward digit span; Rey-Osterrieth complex figure drawingGlucose improved long-term verbal free and cued recall, which correlated to blood glucose levels. No effects of glucose on short-term verbal memory or long-term non-verbal memory
 Gonder-Frederick et al. (1987)58Glucose; 50 g glucose, 16 oz sweetened beverageNarrative memory: WMS; digit span: WMS; visual memory: WMS; paired associate word list: WMSGlucose improved total score on the Wechsler memory scale and the narrative memory test
 Green et al. (2001)48Glucose; 500 mL glucose. 4 conditions (2 glucose and 2 aspartame). In 2 sessions (1 glucose and 1 aspartame) subjects were correctly informed about the drink, in the other 2 sessions they were told the oppositeVerbal recognition memory task; two-finger tapping verbal free-recall; Bakan vigilance taskGlucose improved recognition memory. Glucose improved vigilance, but only when subjects were told they were given glucose
 Hall et al. (1989)59Glucose; 50 g glucose, 16 oz lemon-flavored beverageVisual memory, WMS; logical memory, WMS; paired associates, WMS; digit span forward and backward, WMSGlucose enhanced memory in elderly and young subjects. Glucose tolerance predicted memory in elderly, but not in young adults
 Kaplan et al. (2000)60Glucose; 290 mL water, 10 mL lemon juice, 50 g glucoseParagraph recall; trails test part B; attention Rey auditory verbal learning testNo effect
 Kennedy et al. (2000)61Glucose; 25 g glucose added to 250 mL of water and 25 mL Robinson's low-calorie orange squashSerial sevens and serial threes; word retrievalGlucose consumption improved performance on serial sevens, but not serial threes
 Manning et al. (1990)62Glucose; 50 g glucose, lemon-flavored beverageDigit span forward and backward; logical memory, WMS; Rey-Osterreith complex figure drawing; Ammon's quick test; letter cancellation test; finger oscillation test; selective reminding testGlucose enhanced logical memory performance, but not short-term memory
 Manning et al. (1992)63Glucose; 50 g administered before or after acquisitionMemory recall; narrative passageBoth glucose groups improved recall
 Manning et al. (1997)64Glucose; 50 g drinkWord list recognition and recall; word-stem completionIn elderly subjects, glucose improved performance on the declarative test, but not non-declarative test. In young adult subjects glucose had no effect
 Manning et al. (1998)65Glucose; 50 g added to 8 oz (236.8 mL) lemon-flavored beverage given before or after acquisitionMemory recall; narrative passageSubjects had better recall performance when glucose was ingested. Recall was better when glucose was given before acquisition
 Martin & Benton (1999)66Glucose; 50 g glucose dissolved in 250 mL water flavored with 2 tbsp (29.5 mL) sugar-free Robinsons Whole Orange Squash, 2 tbsp (29.5 mL) and 2 tsp (9.8 mL) lemon juiceMemory; recall of trigramsGlucose drink improved memory in fasted subjects, but not in those who consumed breakfast
 Meikle et al. (2004)67Glucose; 25 or 50 g of glucose dissolved in 200 mL water flavored with 2 tbsp (29.5 mL) of sugar-free whole orange squash; and 5 mL of sugar-free whole lemonTrail making task A and B; letter cancellation task; verbal production; memory search; visual search; delayed free recall; visual span testGlucose improved memory search in older adults. Glucose improved recall in both age groups. No effect of dose
 Messier et al. (1997)68Glucose; 50 g plus 240 mL lemon-flavored beverageCancellation H test digit span backward and forward, WMS-R; logical memory, WMS-R; verbal paired associates, WMS-R; visual memory span, WMS-R; digit symbol substitution, WAIS-R; cognitive portion of Alzheimer's Disease Assessment ScaleGlucose ingestion improved memory in males with good glucoregulation for the first 7 items on the memory test, but decreased for those with poor glucoregulation
 Messier et al. (1999)69Glucose; 50 g plus 240 mL lemon-flavored beverageImmediate and delayed word recallBoth males and females with poor glucoregulation performed worse on a memory task during the saccharin condition, but not during glucose
 Metzger et al. (2000)70Glucose; lemonade (224 g) sweetened with glucose (50 g)Facial recognition; ComPhoto fit facial construction softwareGlucose enhanced performance on a facial recognition task
 Mohanty et al. (2001)71Glucose; 100 mg/kg or 50 g drinkSpatial memory retention, neutral and emotional; spatial memory acquisition, emotional and neutralBoth 100 mg/kg and 50 g glucose impaired performance for emotional stimuli on a spatial memory task; 100 mg/kg enhanced memory during neutral stimuli, 50 g showed no effect
 Owens et al. (1994)72Glucose; 50 g drinkReaction time; inspection timeIncreasing blood glucose levels resulted in faster decision times
 Parsons et al. (1992)73Glucose; 10 g + 38.8 mg saccharin, 25 g + 24.9 mg saccharin, or 50 g mixed with a 240 mL lemon-flavored beverageAmmon's quick test; logical memory; WMS25 g glucose enhanced logical memory
 Reay et al. (2006)43Glucose; 25 g drinkSerial threes and serial sevens; rapid visual information processing taskGlucose enhanced performance of a mental arithmetic task and the rapid visual information-processing task
 Scholey et al. (2001)74Glucose; 25 glucose powder, 250 mL water, and 25 mL flavoringVerbal fluency; word memory; serial sevensGlucose improved performance on serial sevens, but not word retrieval or word memory. Serial sevens task also significantly reduced blood glucose, indicating that high cognitive load enhances glucose utilization
 Scholey et al. (2002)49Glucose; 25 g glucose plus 200 mL waterKinesthetic memory; maze testGlucose improved kinesthetic memory performance
 Sünram-Lea et al. (2001)75Glucose; 25 g in 300 mL water; 3 food conditions: fasting, breakfast, and lunchRey-Osterrieth complex figure drawing; modified digit span; CVLTGlucose enhanced long-term spatial memory performance. No differences in time of day of glucose administration, or fasting condition
 Sünram-Lea et al. (2002)76Glucose; 25 g dissolved in 300 mL of waterRey-Osterrieth complex figure drawing; serial sevens; CVLTGlucose improved immediate recall performance and delayed recall performance
 Sünram-Lea et al. (2002)77Glucose; delayed anterograde: 25 g of glucose 15 min before; immediate anterograde: 25 g glucose immediately before testing; immediate retrograde: 25 g glucose given immediately after word listCVLT; Rey-Osterrieth complex figure drawing; serial sevensGlucose given before or after word list improved memory
 Sünram-Lea et al. (2004)78Glucose; 4 conditions: 25 g glucose plus full-fat yogurt (200 g); glucose plus fat-free yogurt (200 g); 0.2 g aspartame plus full-fat yogurt (200 g); 0.2 g aspartame plus fat-free yogurt (200 g)CVLT; Rey-Osterrieth complex figure drawing; serial sevensGlucose drink plus fat-free yogurt improved performance on short- and long-delay recall
 Winder et al. (1998)50Glucose; 250 mL beverage with 50 g glucose powder (Boots' “Glucose C”) plus lemon drink concentrate (Boots' “Unsweetened Lemon”)Name face association task; selective reminding taskNo effect
  • Abbreviations: CVLT, California Verbal Learning Test; PASAT, Paced Auditory Serial Addition Test; POMS, Profile in Mood States; VAS, Visual Analog Scale; WMS, Wechsler Memory Scale; WMS-R, Wechsler Memory Scale-Revised.

View this table:
Table 5

Summary of studies on omega-3 PUFAs and mental energy.

ReferenceTreatment descriptionOutcome measure(s)Results
Mood
 Fontani et al. (2005)79Omega-3; 4 g capsules, 2.8 g omega-3 PUFA, EPA + DHA ratio 2:1POMSOmega-3 supplements increased POMS index; vigor increased and anger decreased
 Fontani et al. (2005)80Omega-3; 4 g capsules, 2.8 g omega-3 PUFA, EPA + DHA ratio 2:1POMSOmega-3 increased vigor and reduced anger, anxiety, fatigue, confusion, and depression
 Johnson et al. (2008)81Omega-3; 800 mg DHANeurobehavioral evaluation system 2 Mood ScalesNo effect
 Rogers et al. (2008)82Omega-3; EPA (630 mg), DHA (850 mg), olive oil (870 mg), mixed tocopherols (7.5 mg), and orange oil (12 mg); 1.5 g EPA + DHA/dDepressed mood (primary outcome); depression and anxiety stress score, long form Beck Depression InventoryNo effect
Cognition
 Fontani et al. (2005)80Omega-3; 4 g capsules, 2.8 g omega-3 PUFA, EPA + DHA ratio 2:1Sustained attention; reaction time, alert; reaction time, choice; reaction time, go/no-goOmega-3 reduced reaction time in go/no go and sustained attention tasks
 Johnson et al. (2008)81Omega-3; 800 mg DHAVerbal fluency; digit span backward and forward; shopping list task; word list memory test; memory in reality apartment test; pattern comparison test; Stroop testOmega-3 improved verbal fluency
 Kalmijn et al. (1997)83Dietary recall; food intake estimated for omega-3 PUFAsand fish consumptionMMSEHigh fish consumption inversely associated with cognitive impairment
 Kalmijn et al. (2004)84Dietary recall; food intake estimated for omega-3 PUFAs and fish consumptionVisual verbal learning test; concept shifting test; abbreviated Stroop color word test; letter digit substitution test; category fluency testOmega-3 PUFA consumption was inversely associated with impaired overall cognitive function
 Morris et al. (2005)85Dietary recall; seafood intake and omega-3 PUFAMMSE; East Boston test of immediate and delayed recall; symbol digit modalities testFish intake (at least once per week) slowed cognitive decline. No effect of omega-3
 Nurk et al. (2007)86Dietary recall; fish intakeKendrick object learning test; trail making test part A; digit symbol test; block design; MMSE; and controlled word associationHigh fish intake improved mean test score and associated with a lower prevalence of poor cognitive performance
 Rogers et al. (2008)82Omega-3; EPA (630 mg), DHA (850 mg), olive oil (870 mg), mixed tocopherols (7.5 mg), and orange oil (12 mg); 1.5 g EPA + DHA/dSimple reaction time; lexical decision; digit symbol substitutionNo effect
 Van Gelder et al. (2007)87Dietary recall; fish intake omega-3 PUFAMMSEFish consumers had less cognitive decline
 Van de Rest et al. (2009)88Dietary recall; fish intake omega-3 PUFAMMSE; word list; backward digit span test, WAIS-R; pattern memory; verbal fluency; Boston naming test-short form, vocabulary, WAIS-R; pattern comparison; continuous performance test; spatial copying taskNo effect
 Velho et al. (2008)89Dietary recall; omega-3 PUFAMMSEOmega-3 dietary intake improved cognitive function
 Whalley et al. (2004)90Omega-3; self-selected fish-oil supplement or vitamin intakeBlock design subtest: WAIS-R; digit symbol subtest: WAIS-R; common objects test; Rey Auditory Verbal Learning Test; Raven's Standard Progressive MatricesFish oil supplement use was associated with better cognitive function
  • Abbreviations: DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; MMSE: Mini-Mental State Examination; POMS, Profile in Mood States; PUFA, polyunsaturated fatty acid; WAIS-R, Wechsler Adult Inventory Scale-Revised.

FOUR SPECIFIC DIETARY SUPPLEMENTS AND DIETARY CONSTITUENTS

Ginkgo biloba

Medicinal products derived from the maidenhair tree, Ginkgo biloba, are some of the most widely used of all plant-based products. The active components of Ginkgo biloba consist of flavonoids, terpenoids, and terpene lactones (i.e., ginkgolides and bilobalide). A well-defined extract, EGb 761, which is produced from ground-up leaves, contains 24% w/w flavone glycosides and 6% w/w terpene lactones. It is marketed as Tanakan, Tebonin, and Rokan. Kaveri (L1 1370) is similar but with 25% w/w flavone glycosides. Ginkgo biloba is available without prescription in the United Kingdom, Europe, Canada, China, and the United States, where it is marketed as a dietary supplement.

Ginkgo biloba has been used in China as a traditional medicine for a range of conditions for many centuries. The medicinal properties of Ginkgo biloba are likely due to several biological effects including increased cerebral blood flow, modification of neurotransmitter systems, reduced blood viscosity, and free radical scavenging.91 Single cases of bleeding (i.e., intracranial hemorrhaging) have been reported in relation to intake of Ginkgo biloba preparations.92 However, a review of controlled studies indicated EGb761 does not influence blood clotting for bleeding time and is unable to potentiate the effects of anticoagulant or antiplatelet drugs.93

The main use of Ginkgo biloba is in the treatment of cerebral dysfunction. Ginkgo biloba extract has been investigated for clinical efficacy in patients with age-related cognitive decline and dementia related to Alzheimer's disease. A 2007 Cochrane Collaboration Review found that evidence for the benefit of Ginkgo biloba on cognition in individuals with dementia was not convincing.91 The results of two recent randomized, placebo-controlled trials support the Cochrane conclusion2937; compared to placebo, 240 mg daily intake of Ginkgo biloba extract did not reduce the incidence of dementia or Alzheimer's disease, nor did it protect against cognitive decline in elderly populations. Fewer studies have evaluated whether Ginkgo biloba enhances cognitive function in younger healthy populations. The effects on mood and cognition in healthy adults administered Ginkgo biloba are discussed below.

Mood.  Several studies report that Ginkgo biloba improves overall mood (subjective intensity scale-mood, VAS),1428 alertness,21,25 and calmness.22 Four weeks of treatment with Ginkgo biloba (120 mg/d) in healthy older adults improved self-reported quality of life (VAS) and increased positive mood state (subjective intensity scale-mood) compared to placebo, but there were no differences between groups as measured by the POMS.14 Participants completed baseline mood measures in addition to weekly questionnaires. Although Cockle et al.15 and Trick et al.28 reached similar conclusions, neither of their studies employed placebo-controlled designs or determined baseline mood, thus weakening their findings.

Six hours after Ginkgo biloba (360 mg/d) administration to healthy young adults, participants reported greater alertness (VAS) compared to placebo.21 This study measured alertness at 1, 2.5, 5, and 6 h after Ginkgo biloba administration, and increased alertness was found at all time points compared to placebo. However, the sample size was small (n = 20), and a subsequent study by the same laboratory failed to replicate the findings over a range of doses (120–360 mg).20 A 6 h study of young adults by the same group demonstrated that 120 mg Ginkgo biloba extract was also associated with improved calmness.22 Rigney et al.25 administered a range of doses (120–300 mg) for 2 days to healthy adults. The participants reported increased alertness on day 1, but decreased arousal on day 2.

In contrast to the favorable effects of Ginkgo biloba on mood discussed above, 10 studies reported no appreciable effect.1327 In these negative studies, study duration varied from 1 h to 12 weeks of administration and wide-ranging doses of Ginkgo biloba (80–600 mg) were given to both young and elderly participants. A dose of 120 mg/d for 12 weeks had no effect on mood (POMS) in either older or younger adults.13 Three studies by the same laboratory reported no effect of 120 mg/d Ginkgo biloba on mood (VAS) given to either healthy young participants or older women for 6 weeks.1618Ginkgo biloba at a range of doses (120, 240, and 360 mg/d) given to healthy older women for 7 days had no effect on mood (VAS).19 Administration of a range of Ginkgo biloba doses (120, 240, or 360 mg) for just 6 h did not affect mood in healthy young adults, but this study had a very small sample size (n= 20).20 Two studies that administered 180 mg/d of Ginkgo biloba to healthy older adults reported no effect on mood after 6 weeks using an unvalidated self-report questionnaire created by the authors.23,24Ginkgo biloba (80 mg/d) given to healthy adults did not affect mood, as measured by the Medical Symptom Questionnaire, after 6 weeks of treatment.26 A range of Ginkgo biloba doses (120, 240, or 600 mg/d) administered to healthy adults did not affect mood after 1 h.27 Definitive conclusions cannot be drawn regarding the effects of Ginkgo biloba on mood due to a combination of poor study design elements and inconsistent findings.

Cognition.  Numerous studies have examined the relationship between Ginkgo biloba and cognition in healthy subjects, with variable results. Many studies focused on minor components of mental energy (i.e., learning and memory), although more relevant cognitive domains like attention and vigilance were also investigated. Improved speed of processing was reported in three studies that administered Ginkgo biloba at 40–180 mg/d for 14 d to 8 months to both young39 and older adults.2339 Stough et al.39 conducted a randomized, double-blind placebo-controlled clinical trial that lasted for 30 days. A neuropsychological test battery, including the digit symbol substitution test, was performed before and after treatment, adding validity to the results. Similar designs were used by Santos et al.35 and Mix et al.23 Cieza et al.14 also observed enhanced motor performance in older subjects (50–65 years) after 240 mg/d Ginkgo biloba extract for 4 weeks.

The relationship between Ginkgo biloba and attention has also been investigated. Ginkgo biloba improved attention in younger1631 and older participants18,35 in five studies, while one study of older women reported no effect.17,24 Elsabagh et al.16 measured sustained attention after 4 h and again after 6 weeks of treatment (120 mg/d). Improved attention was reported 4 h after intake of Ginkgo biloba (120 mg/d) by young subjects (18–26 years), but not after 6 weeks. A follow-up study in postmenopausal women (51–67 years) found no effect of Ginkgo biloba on attention.17 However, both studies lacked baseline data. Kennedy et al.20 reported improved speed of attention in young subjects (19–24 years) at 2.5 and 6 h after administration of either 240 or 360 mg Ginkgo biloba extract using the Cognitive Drug Research computerized assessment battery. A subsequent study by the same laboratory with a similar subject group31 demonstrated that a lower dose of Ginkgo biloba extract (120 mg) also improved speed of attention at 1 and 6 h after administration using the same assessment battery. Hartley et al.18 reported improved performance in healthy older females (53–65 years) on measures of frontal lobe function (rule shifting) and attention (Paced Auditory Serial Addition Test) after 7 days of Ginkgo biloba treatment (120 mg/d). Santos et al.35 reported improved attention and speed of information processing in healthy older men (60–70 years) taking 80 mg/d Ginkgo biloba extract for 8 months. These results suggest a potential effect of Ginkgo biloba extract on attention after short-term administration in both young and older subjects.

Several studies investigating the effects of Ginkgo biloba on memory suggest a favorable effect. In one study, Ginkgo biloba (120 mg/d) improved long-term memory in older participants after 12 weeks of treatment; however, no effect was found in younger participants.13 A well-designed 4-week study in healthy elderly subjects receiving 120 mg/d39 and an acute high-dose study in young adults receiving 600 mg/d27 reported improved working memory (digit span backwards, Sternberg memory scanning test) after administration of Ginkgo biloba. Mix et al.23 observed enhanced delayed free recall and delayed recognition of non-contextual auditory-verbal material in healthy older subjects (60 years or older; 127 treatment/122 controls) administered 180 mg/d Ginkgo biloba extract for 6 weeks. Polich et al.34 reported improved working memory when 40 mg/d Ginkgo biloba/vinpocetine compound was administered to a group (n = 24) of healthy subjects (22–59 years) for 14 days. Subhan and Hindmarch27 also reported improved working memory (Sternberg memory scanning test) after administering a range of doses (120–600 mg/d), but a poorly described product was used for a short duration (1 h) in a small subject group (n = 8), weakening these findings.

Three studies also evaluated concentration and memory using the Serial Threes and Serial Sevens tasks. Kennedy et al.21 administered 360 mg Ginkgo biloba extract to 20 healthy young participants (mean age, 21.2 years) and found improved performance on Serial Threes and Serial Sevens tests after 6 h. Scholey et al.36 found a dose-dependent improvement in speed of responding during Serial Threes in young subjects following Ginkgo biloba administration. However, in a subsequent study by the same group,22 a lower dose of Ginkgo biloba extract (120 mg) did not markedly improve performance on the Serial Subtraction tasks.

In contrast to the generally positive results discussed above, additional studies report no detectable effects of Ginkgo biloba on different aspects of memory (pattern recognition, working, spatial, and logical).1638 In a double-blind, placebo-controlled study, Nathan et al.33 found no effect 90 min after administration of 120 mg/d Ginkgo biloba to a small subject group (n = 11) using the Cognitive Drug Research battery in addition to tests of working memory. In another double-blind, placebo-controlled study, Moulton et al.32 found no effect on working memory in young subjects administered 120 mg/d Ginkgo biloba for 5 days using the Sternberg memory-scanning test. Solomon et al.38 found no changes in memory or learning in elderly participants administered 120 mg/d for 6 weeks using the California Verbal Learning Test, logical memory, visual reproduction, digit symbol subscales of the Wechsler Memory Scale-Revised, the Stroop test, or other tests. Elsabagh et al.16 measured episodic and working memory and pattern recognition in young subjects after 4 h and again after 6 weeks of Ginkgo biloba treatment (120 mg/d); improved pattern recognition memory was reported after 4 h, but no effect on episodic or working memory was reported after 6 weeks. These findings are weakened, however, by the absence of baseline testing. A follow-up study in older adult women found no effect of Ginkgo biloba on episodic memory.17 At this time, insufficient evidence is available to determine whether Ginkgo biloba improves memory, although memory is a minor component of mental energy.

Summary.  Several studies suggest Ginkgo biloba may improve aspects of mood1428 including alertness21,25 and calmness22 in healthy subjects. Aspects of cognition may also be affected; Ginkgo biloba extract consistently improved speed of processing in both younger and older adults2339 and appears to have favorable effects on attention after short-term administration.1635 However, conflicting evidence prohibits any clear association from being made between Ginkgo biloba and memory in healthy participants.

Ginseng

The root of Panax ginseng is commonly used either by itself or in combination with other herbal ingredients in Chinese medicine. Ginsenosides, the major active components of ginseng, are triterpene saponins that modulate platelet aggregation, blood pressure, immune function, and hypothalamic-pituitary-adrenal axis activity.94 Ginseng is unsafe in pregnant or breastfeeding women due to estrogenic activity,95 and in patients taking anticoagulants because it may reduce blood concentrations of these drugs.96

The quality and composition of ginsenosides are highly variable and are dependent on multiple factors including the species, age, and part of the plant, the cultivation method, preservation method, season of harvest, and extraction method.97 To avoid variability among preparations, researchers often use the standardized extract (G115) with total ginsenoside adjusted to 4% (Pharmaton SA, Switzerland).

Mood.  One study found that 2 months of supplementation with a multivitamin containing ginseng (40 mg) improved vigor (POMS).44 Two acute studies found that ginseng decreased fatigue (400 mg)43 and increased alertness (VAS) (200 or 400 mg).41 However, two additional studies found no effect of ginseng on mood.40,42 Kennedy42 conducted a 6-h crossover study that administered 3 doses of ginseng (200, 400, or 600 mg) and tested mood using a VAS. Cardinal and Engels40 conducted a double-blind, placebo-controlled, randomized clinical trial that administered 200 or 400 mg ginseng for 8 weeks and found no effect on mood as measured by the POMS or the Positive Affect–Negative Affect scale. Based on these studies, consistent evidence is lacking that ginseng affects mood in healthy subjects.

Cognition.  Two chronic studies of ginseng reported conflicting effects on mental energy. A well-designed 12-week study of ginseng (200 mg) improved mental arithmetic processing but had no effect on attention, recognition memory, or reaction time.45 In another study, 400 mg/d of ginseng improved abstract thinking and increased auditory reaction times but had no effect on learning and memory or speed of processing after 9 weeks.47

Several acute studies also report conflicting results. Three single doses of ginseng (200, 400, or 600 mg) were administered in a 6-h acute study,41 but only the 400 mg dose improved memory and both the 200 and 600 mg doses caused decrements in performance on an attention task. A 200 mg dose of ginseng improved attention and reaction time and enhanced memory 6 h after administration.42 The same group also reported that 400 mg of ginseng improved accuracy and a 200 mg dose slowed speed of processing on serial sevens but had no effect on serial threes.36 An acute dose of ginseng (200 or 400 mg) improved accuracy on a task of concentration (serial sevens) after 2 h, but it did not affect concentration (serial threes) or speed of processing.46 However, in a subsequent study from the same authors,43 the opposite effect was reported; the same dose of ginseng improved concentration (serial threes) and improved speed of processing but did not affect serial sevens. On the basis of these studies, no consistent evidence is available to substantiate the claim that ginseng affects cognition in healthy subjects.

Summary.  The literature is inconsistent regarding the effects of ginseng on mood and cognition. Although several studies report that it improves cognitive tasks, one study reports both positive and negative findings at different doses and time points41; the effect also varies between different studies from the same authors.46,43 Reay et al.43 postulated that possible differences in performance might stem from inconsistencies in ginsenosides in the extract.

Glucose

Glucose, a simple sugar, is the main energy source for the brain. It is required to perform cognitive tasks,98 but the potential benefit of supplementation beyond normal dietary intake is unclear. Although memory is a minor component of mental energy, a large body of data concerns the relationship between glucose and memory. Mood was occasionally included in these studies to ascertain differences in arousal and tension, which have indirect effects on memory. The effects of glucose on other cognitive functions, such as attention, are not as well documented.

Mood.  Several investigators have studied the relationship between glucose and mood. In one study, a glucose drink (25 g) decreased fatigue (VAS) in healthy young adults after 120 min.43 In another study, glucose (500 mL) enhanced vigilance (VAS) in healthy adults 30 min after administration, but this was only when subjects knew they were given glucose.48 Two studies found no effect of glucose on mood (POMS).49,50 All of the studies used similar dosing and timing. The differences in the reported effects of glucose on mood may be due to differing testing instruments; the two studies reporting positive mood effects used a VAS, while the two studies reporting no effects administered the POMS.

Cognition.  Glucose is an energy substrate for the brain and glucose supplementation may influence cognitive function. Raising blood glucose levels may increase acetylcholine synthesis and cholinergic drugs influence attention. Numerous studies have examined the relationship between glucose and cognitive function but have primarily focused on memory. Glucose has been reported to improve some aspects of memory (spatial, logical, word list recall, short- and long-term memory).4878 However, additional studies report that glucose does not enhance certain aspects of memory (recall, visual, short- and long-term memory).4875 Discrepancies in the reported findings may derive from the age of the subjects (young versus elderly), the type of memory tested (declarative versus short-term memory), testing instrument, glucose dose, time of testing, and duration of treatment. The available studies lack consistency in the type of memory-testing instrument used. These inconsistencies prohibit the formation of any conclusions regarding the memory effects of glucose.

Subject age may be particularly relevant in studies of glucose administration. Older adults are more likely to have poor blood glucoregulation; thus, glucose administration may be more likely to affect cognition in this population. Glucose increased performance on some aspects of declarative recall and logical memory in older participants,5367 but it had no effect in younger participants.64 A 50 g glucose beverage given to healthy elderly and young adult subjects improved logical memory in elderly adults and improved immediate recall (digit span forward) in young adults when subjects were tested immediately after administration.59 Additionally, the same authors replicated this finding of improved logical memory in older adults but found no effect of glucose on short-term memory.62 A 50 g glucose beverage resulted in greater improvements in memory when given before task acquisition than before memory retrieval task in elderly participants.63,65 Manning et al.62 also reported no effect of glucose in the elderly on other tests of cognition, such as attention (letter cancellation test). These studies all used the same glucose dose (50 g), but cognition was tested at different times after administration and had small sample sizes. These findings in the elderly seem limited to certain types of memory (i.e., logical and declarative) and do not extend to other cognitive functions, such as attention. Since the currently available evidence for the memory effect is from the same group of authors, replication by separate laboratories is needed to confirm the observed effects.

Blood glucose regulation might influence the efficacy of glucose supplementation in enhancing memory. Blood glucose levels after glucose supplementation were associated with better long-term verbal memory.57,75 Foster et al.57 administered 25 g of glucose to healthy young adults and measured short- and long-term verbal and nonverbal memory immediately after glucose administration; they found that blood glucose correlated with improved long-term verbal memory but not with short-term verbal memory or long-term nonverbal memory. Performance on a recall task was positively correlated with blood glucose levels.75 A correlation was observed 15 and 30 min after glucose administration (50 g) between blood glucose levels and improved short-term memory performance using a word recall task, but no effect on spatial memory was found.52 Owens et al.72 observed faster decision times in healthy young subjects (mean age, 21.2 years) 30 min after receiving 50 g of glucose. Reay et al.43 found that 25 g of glucose enhanced performance on the serial threes and sevens tasks 120 min after administration in young subjects (mean age, 21.9 years). In contrast, higher-than-baseline blood glucose levels measured 30 and 60 min after glucose administration were associated with poor performance on memory tasks measured by the Wechsler Memory Scale.58 At this time, no conclusions can be drawn regarding blood glucose levels and cognitive function; variation in time of blood draw and cognitive task testing may contribute to the disparate results. Blood glucose levels may impact long-term verbal memory, but more research is needed.

Summary.  At this time, little evidence links glucose intake to enhanced mood. A variety of studies have explored the relationship between glucose and memory, but the results are inconsistent. Contributing to this inconsistency are variations in timing, dosing, and study population. Other potentially relevant cognitive tasks, such as attention and vigilance, have not been substantially evaluated. Certain populations, such as the elderly or those with poor glucoregulation, are more likely to show improvements after glucose intake.99,100

Omega-3 polyunsaturated fatty acids

PUFAs are integral membrane lipids that serve to maintain both the structure and function of neuronal membranes, membrane-associated proteins, and protein complexes. Increased PUFA incorporation leads to increased membrane fluidity that can increase the number and affinity of receptors in the synapse and improve neurotransmission. Such fluidity is important for promoting synaptic plasticity that is essential for learning, memory, and other complex cognitive processes.101

Docosahexaenoic acid (DHA, 22:6 n-3) is considered to be an essential PUFA because it cannot be created de novo in humans.101α-linolenic acid (ALA, 18:3 n-3) and eicosapentaenoic acid (EPA, 20:5 n-3) are converted to DHA by some cell types and organs to a minor extent. DHA and EPA are initially produced by photosynthetic microalgae and are exclusively derived from marine animals. Little EPA or ALA is found in the brains of humans. In contrast, DHA is found predominantly in neuronal membranes in the gray matter and constitutes the major omega-3 PUFA in the brain. DHA may also play a key role in both the structure and function of brain regions involved in the formation of new memories. Hippocampal DHA levels have been associated with dietary intake in rats, and higher levels have been shown to enhance hippocampal-dependent learning processes.102 Omega-3 PUFAs may also act as mood stabilizers and have beneficial effects in several neuropsychiatric disorders, such as depression,103105 schizophrenia,106 and age-related cognitive decline.107 Chronic use of high-dose omega-3 PUFAs (>3 g/d) must be monitored because impaired blood coagulation and immune response depression may result.108

Mood.  Researchers have investigated associations between omega-3 PUFAs and mood because of their effects on neuropsychiatric disorders. Two similar studies by Fontani et al. found that 2.8 g/d of omega-3 PUFAs (EPA + DHA, 2:1, fish oil) increased vigor and decreased fatigue (POMS) in young participants at 5 weeks80 and at 10 weeks,79 but the results have not been replicated by other researchers. In contrast, another study reported that omega-3 supplementation (EPA + DHA, source not specified) had no effect on depressed mood.82 The different mood instruments used in the studies (i.e., POMS versus a depression inventory) may contribute to the conflicting results. At this time, there is not enough evidence to determine if omega-3 PUFAs alter mood in healthy adults.

Cognition.  Several observational studies of fish intake via dietary recall suggest an association exists between high fish intake (but not necessarily omega-3 intake) and reduced cognitive decline in older subjects. High dietary fish intake improved scores of global cognitive function on the Mini-Mental State Examination and prevented decline in older adults in three studies.8389 A study of 2,031 subjects aged 70–74 years in Norway reported that subjects whose mean daily intake of fish and fish products was ≥10 g/d had significantly better mean test scores and lower prevalence of poor cognitive performance than those whose intake was <10 g/d.86 The associations between seafood consumption and cognition were dose-dependent and the effect was more pronounced for consumption of nonprocessed lean fish and fatty fish. In a study of elderly subjects (65 years and older) participating in the Chicago Health and Aging Project, Morris et al.85 observed reduced cognitive decline in subjects consuming fish at least once per week, but the reduction was not associated with estimates of omega-3 PUFA intake.

Two prospective studies of fish consumption and cognitive decline in older subjects reached opposite conclusions. In the Zutphen Elderly Study, fish consumers (aged 70–80 years) had significantly lower 5-year subsequent cognitive decline than nonconsumers.87 In older men (mean age, 68 years) participating in the Veterans Affairs Normative Aging Study, no significant associations between fatty fish or omega-3 PUFA intake and cognitive performance or change were observed.88

Intervention studies of omega-3 PUFA supplementation reveal effects on differing cognitive outcomes. One 30-month observational study in older adults (each 64 years old) reported that fish-oil supplement use was associated with better speed of processing, as measured by the digit symbol subtest (Wechsler Adult Intelligence Scale-revised), but had no effect on verbal memory.90 However, a study administering omega-3 supplements to healthy adults (age range, 18–70 years) for 12 weeks reported no effect on speed of information processing or working memory.82 Verbal fluency scores improved significantly in older women (age range, 60–80 years) receiving 800 mg/d DHA for 4 months, but measures of mental processing speed and accuracy were not affected by supplementation.81 Omega-3 PUFA supplementation in young and middle-aged adults (age range, 22–51 years) for 5 weeks improved reaction times but had no effect on attention.80

Summary.  The available evidence suggests that fish consumption and omega-3 PUFAs might delay or reduce cognitive decline in the elderly. Despite the strength of much of these data, fish consumption patterns and the timing and duration of omega-3 PUFA supplementation have yet to be determined. Some data suggest that omega-3 supplementation is more beneficial if administered prior to the onset of cognitive decline. Lifelong dietary habits may also be necessary to observe a favorable effect of fish intake and/or omega-3 PUFA supplementation on age-related cognitive outcomes.101 Additional well-designed trials of omega-3 supplementation implementing a comprehensive battery of cognitive tests are required to clarify what cognitive tasks may be altered.

LIMITATIONS OF THE CURRENT DATA

The presently available literature suggests Ginkgo biloba affects certain aspects of mood and attention in healthy subjects, and associations exist between fish consumption/omega-3 PUFAs and reduced risk of age-related cognitive decline. However, additional studies are required to substantiate the existing data. The literature for glucose could also benefit from well-designed studies that evaluate cognitive tasks that are major components of mental energy, such as attention and vigilance.

For many foods, dietary constituents, and dietary supplements (including ginseng), little consistent evidence is available to confirm their effects on mental energy, even though claims are currently being made for consumer products. The usefulness of the existing data is limited by poor study designs with limitations that include varied populations, differing study durations, small sample sizes, inadequate accounting of baseline consumption, inadequate dosing and/or food intake information, and lack of accounting for natural product variation, as well as the lack of a uniform battery of tests to detect effects.

The composition of natural products may vary greatly between manufacturers and even batches of the same product. These variations often stem from variations in raw plant material (varietal factors and the parts of plant products derived), climate, growing season, soil, rainfall, and other growing conditions, method of preparation, and types of solvents used in the extraction process. Differing sources may also create variation among products. For example, different omega-3 PUFAs or combinations of omega-3 PUFAs can be sourced from fatty fish (EPA + DHA), algae (DHA), or seed oil (ALA). Additionally, observational studies cannot control for the wide variety of dietary sources of a particular nutrient, and dietary recall by participants may be inaccurate.

CONCLUSION

One of the greatest obstacles for interpreting the mental energy literature is the use of an immense variety of testing instruments, which makes it difficult (or impossible) to compare results across studies and to identify the reasons for inconsistent findings. A challenge for future research is, therefore, to promote the use of standardized methods with adequate sensitivity for measuring mental energy and to advocate the consistent use of those methods. Failure to find robust effects for many dietary constituents and supplements may partially result from a lack of method sensitivity, rather than a true absence of effect. Standardized methods would allow comparisons to be made of the relative potency of different supplements and foods and provide greater clarity regarding the nature of the observed effects. Ideally, experiments would use a post-training design with time-dependent effects measured; however, few of the current studies employ this design.

Double-blind and placebo-controlled studies with adequate numbers of subjects to provide sufficient statistical power are needed as are controls for circadian variation in performance and practice effects.109 Individual differences in response to dietary constituents and/or supplements may require larger sample sizes to increase the statistical power. Multiple doses/intakes should also be tested, when feasible, to obtain more complete dose-response data. Meal composition studies should include baseline tests and control for nutritional history (i.e., use of a within-subjects design). Subjects with a low baseline intake will likely show greater improvement than those who already consume the dietary constituent at adequate or high levels. Future cognitive research also needs to control for population effects due to demographic characteristics such as age, gender, socioeconomic status, and educational level.110

Motivation is an important aspect of any neuropsychological testing. A subject's willingness to engage in a task and complete all trials with the same level of engagement depends on many factors, including motivation. Differences in motivation can result in wide variations in task performance between subjects.110 Therefore, studies evaluating mood and cognition should also include measures of motivation.

At this time, the neurobiological mechanisms underlying mental energy are not clearly elucidated. Ideally, future research should measure biomarkers of exposure/intake (e.g., measure the amount of the dietary constituent in blood, saliva, or urine) and possibly of effect. A variety of techniques are used to study human brain metabolism, neurotransmission, and regional blood flow. Some of these techniques including functional magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography may allow investigation of the neurobiological mechanisms underlying changes in mood, motivation, and cognition.

Acknowledgments

HE Gorby and AM Brownawell contributed equally to the preparation of this manuscript.

Disclaimer.  This independent review was developed under a contract between the Life Sciences Research Organization (LSRO), Bethesda, MD, and the International Life Sciences Institute (ILSI) North America, Washington, DC. The conclusions drawn do not represent the official views of LSRO or ILSI. The mention of trade names, commercial products, or organizations does not imply endorsement by LSRO or ILSI North America. The opinions expressed herein are those of the authors and do not necessarily represent the views of the International Life Sciences Institute (ILSI).

Declaration of interest

HE Gorby, AM Brownawell, and MC Falk are employees of the Life Sciences Research Organization and received compensation for services performed in researching and writing this review. There are no other pending financial interests or conflicts of interest.

REFERENCES

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