Investigating the Effects of a Multinutrient Supplement on Cognition, Mood and Biochemical Markers in Middle-Aged Adults with 'Optimal' and 'Sub-Optimal' Diets: A Randomized Double Blind Placebo Controlled Trial.

Background: Previous randomized controlled trials examining cognitive and mood effects of combination multivitamin supplements in healthy, non-clinical adults have reported mixed results. One purported explanation for this is that the dietary status of participants at the start of supplement interventions may influence the magnitude of the effect of supplementation. Methods: In this study, we evaluated the effect of a multinutrient formula containing B group vitamins, Bacopa monniera and Ginkgo biloba on memory, attention, mood and biochemical markers of nutrient status in middle-aged adults (M = 52.84 years, n = 141) with 'optimal' and 'sub-optimal' diets over 12 weeks. We hypothesised that active supplementation would differentially improve memory and attention in those with a 'sub-optimal' diet. Results: Mixed model, repeated measures analysis revealed that, in comparison to placebo, active treatment was associated with significant increases in B vitamin status (B1, B6, B12). Regarding behavioural outcomes there was no significant benefit to memory (F(1, 113.51) = 0.53, p = 0.470) nor attention (F(1,113.77) = 1.89, p = 0.171) in the whole cohort. Contrary to our hypothesis, there was a significant beneficial effect of supplementation on attentional performance in individuals with an 'optimal' diet prior to supplementation (F(1,57.25) = 4.94, p = 0.030). In the absence of a main effect of supplementation across the entire cohort, there were also a number of significant three-way interactions (treatment by time by diet group) detected in secondary outcomes including lower state anxiety and mental fatigue in those with an 'optimal' diet. Conclusion: These findings suggest that the cognitive benefit of B vitamin and herbal supplementation may be dependent on diet quality, supporting the concepts of 'co-nutrient optimisation' and interdependency of nutrients. This warrants further investigation. This study advocates characterising the diet of participants prior to supplementation as it may influence the effect of a nutraceutical intervention.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (<75 mg) on sustained attention are limited and use short-term tests. Therefore, we investigated the acute effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

A randomised placebo-controlled trial to differentiate the acute cognitive and mood effects of chlorogenic acid from decaffeinated coffee.

UNLABELLED: In the current study, sixty healthy older adults aged 50 years or older, and who were light to moderate coffee drinkers, were administered 6g of a decaffeinated green coffee blend (NESCAFÉ Green Blend coffee; GB) or 540mg pure chlorogenic acids (CGA) or placebo in a double-blind acute cross-over design, with cognitive and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary outcome measure was accuracy in Rapid Visual Information Processing (RVIP). Secondary cognitive outcome measures included RVIP reaction time as well as Inspection time (IT), Jensen Box decision/reaction times, serial subtraction and N-Back working memory. Secondary mood measures included Bond-Lader and caffeine Research visual analogue scales (VAS). No significant treatment effects were found for the primary outcome measure, although significant effects were found amongst secondary measures. Overall, CGA in isolation was not found to significantly improve cognitive function relative to placebo whereas the GB was found to improve sustained attention as measured by the N-Back task in comparison to placebo overall (t=2.45,p=.05), as well as decision time on a 2-choice reaction time task (Jensen box) in comparison to placebo at 40 minutes post-dose (t=2.45,p=.05). Similarly, GB was found to improve alertness on both the Bond-Lader at 120 minutes relative to CGA (t=2.86, p=0.02) and the caffeine Research VAS relative to CGA (t=3.09, p=0.009) and placebo (t=2.75,p=0.02) at 120 minutes post-dose. Both the GB and CGA were also found to significantly improve symptoms of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04 respectively), whilst there was a trend towards a reduction in jitteriness with GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and t=2.20,p=0.06 respectively). These findings suggest that the improvements in mood observed with GB, but not the improvements in cognitive function, are likely to some extent to be attributable to CGAs. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000067976 www.anzctr.org.au.

The effect of d-methamphetamine on simulated driving performance.

OBJECTIVES: Methamphetamine is considered to be one of the most popularly abused drugs by drivers; however, its exact effect on driving and driving behaviour has yet to be thoroughly investigated. This being despite methamphetamine's increased prevalence in injured and deceased drivers. METHODS: Twenty healthy recreational illicit stimulant users (10 male and 10 female), aged between 21 and 32 years (mean = 25.4 years, SD = 3.3 years) attended two testing sessions involving oral consumption of 0.42 mg/kg d-methamphetamine or a matching placebo. The drug administration was counter-balanced, double-blind, and medically supervised. At each session driving, performance was assessed 2.5 h post drug administration. RESULTS: d-methamphetamine (0.42 mg/kg) did not significantly impair overall simulated driving performance 2.5 h post drug administration. At the individual driving variable level, participants in the d-methamphetamine condition were observed to be driving slower when an emergency situation occurred (T = 44, p < 0.05), but interestingly, participants in both conditions recorded average speeds in excess of the speed limit (100 km/h) when the emergency situations occurred. The d-methamphetamine condition did also produce four times more infringements where participants did not stop at red traffic light in comparison to the placebo, but this effect was only evident at a trend level (T = 7, p = 0.11). CONCLUSIONS: The findings presented herein suggest that d-methamphetamine administered at the levels supplied did not impair driving performance in a manner consistent with epidemiological evidence. Further research is certainly required to elucidate the effects of various doses of methamphetamine, alone and in combination with other legal and illicit substances.

Does coffee enriched with chlorogenic acids improve mood and cognition after acute administration in healthy elderly? A pilot study.

RATIONALE: Caffeine exerts positive effects on cognitive and behavioral processes, especially in sub-optimal conditions when arousal is low. Apart from caffeine, coffee contains other compounds including the phenolic compounds ferulic acid, caffeic acid, and the chlorogenic acids, which have purported antioxidant properties. The chlorogenic acids are the most abundant family of compounds found in coffee, yet their effects on cognition and mood have not been investigated. OBJECTIVES: This study aims to ascertain whether a coffee rich in chlorogenic acid modulates brain function. METHODS: The present pilot study examined the acute effects of decaffeinated coffee with regular chlorogenic acid content and decaffeinated coffee with high chlorogenic acid content on mood and cognitive processes, as measured by behavioral tasks and event-related potentials (ERPs). Performance and ERP responses to a battery of cognitive tasks were recorded at baseline and following the equivalent of three cups of coffee in a randomized, double-blind, crossover study of 39 healthy older participants. RESULTS: Compared with the decaffeinated coffee with regular chlorogenic acid and placebo, caffeinated coffee showed a robust positive effect on higher-level mood and attention processes. To a lesser extent, the decaffeinated coffee high in chlorogenic acid also improved some mood and behavioral measures, relative to regular decaffeinated coffee. CONCLUSIONS: Our pilot results suggest that non-caffeine compounds in coffee such as the chlorogenic acids may be capable of exerting some acute behavioral effects, thus warranting further investigation.

The effects of 90-day supplementation with the omega-3 essential fatty acid docosahexaenoic acid (DHA) on cognitive function and visual acuity in a healthy aging population.

The omega-3 fatty acid docosahexaenoic acid (DHA) is essential for nervous system and retinal development and there is evidence to suggest that DHA deficiencies increase with normal aging. A triple-blind placebo-controlled randomized repeated-measures trial was conducted with 74 healthy participants, aged 45-77 years. Cognitive and visual acuity measures and plasma levels of DHA were determined at baseline and after 90 days of administration of either HiDHA(®) (Clover Corp., Sydney, NSW, Australia: 1000 mg of tuna oil; comprising 252 mg DHA, 60 mg EPA and 10 mg vitamin E) or placebo (1000 mg soybean oil). Ninety days of DHA supplementation was found to significantly raise both plasma DHA and total ω-3 plasma levels in the treatment group, as well as significantly lower total ω-6 levels. However, no significant effects of DHA supplementation on cognitive functioning were found. For participants with corrected vision, the group receiving DHA were found to have significantly better right eye visual acuity posttreatment in comparison with the placebo group (F(1,22) = 7.651; p = 0.011; partial η(2) = 0.258).

The effect of d,l-methamphetamine on simulated driving performance.

RATIONALE: Illicit drugs such as methamphetamine are commonly abused drugs that have also been observed to be prevalent in drivers injured in road accidents. The exact effect of methamphetamine or its specific isomers on driving and driving behaviour have yet to be thoroughly investigated. METHODS: Twenty healthy recreational illicit stimulant users (ten males, ten females), aged between 21 and 34 years (mean = 24.3 years, SD = 3.4 years), attended two testing sessions involving oral consumption of 0.42 mg/kg d,l-methamphetamine or a matching placebo. The drug administration was counterbalanced, double-blind, and medically supervised. At each session, driving performance was assessed 2.5 h post-drug administration. RESULTS: Mean blood and saliva d,l-methamphetamine concentrations of approximately 90 and 400 ng/ml, respectively, at 2 h and 95 and 475 ng/ml at 3 h were observed. These levels of d,l-methamphetamine were found not to significantly impair, or improve, driving performance at the 2.5-h post-drug administration time point. CONCLUSIONS: The findings of this study illustrate that d,l-methamphetamine has no significant effect on simulated driving performance.

Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial.

While Ayurvedic medicine has touted the cognitive enhancing effects of Bacopa monniera for centuries, there is a need for double-blind placebo-controlled investigations. One hundred and seven healthy participants were recruited for this double-blind placebo-controlled independent group design investigation. Sixty-two participants completed the study with 80% treatment compliance. Neuropsychological testing using the Cognitive Drug Research cognitive assessment system was conducted at baseline and after 90 days of treatment with a special extract of Bacopa monniera (2 x 150 mg KeenMind) or placebo. The Bacopa monniera product significantly improved performance on the 'Working Memory' factor, more specifically spatial working memory accuracy. The number of false-positives recorded in the Rapid visual information processing task was also reduced for the Bacopa monniera group following the treatment period. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monniera extract. Further studies are required to ascertain the effective dosage range, the time required to attain therapeutic levels and the effects over a longer term of administration.

Subliminal display of action words interferes with motor planning: a combined EEG and kinematic study.

Recent evidence has shown that processing action-related language and motor action share common neural representations to a point that the two processes can interfere when performed concurrently. To support the assumption that language-induced motor activity contributes to action word understanding, the present study aimed at ruling out that this activity results from mental imagery of the movements depicted by the words. For this purpose, we examined cross-talk between action word processing and an arm reaching movement, using words that were presented too fast to be consciously perceived (subliminally). Encephalogram (EEG) and movement kinematics were recorded. EEG recordings of the "Readiness potential" ("RP", indicator of motor preparation) revealed that subliminal displays of action verbs during movement preparation reduced the RP and affected the subsequent reaching movement. The finding that motor processes were modulated by language processes despite the fact that words were not consciously perceived, suggests that cortical structures that serve the preparation and execution of motor actions are indeed part of the (action) language processing network.

Language-induced motor perturbations during the execution of a reaching movement.

In a recent study Boulenger et al. (2006) found that processing action verbs assisted reaching movement when the word was processed prior to movement onset and interfered with the movement when the word was processed at movement onset. The present study aimed to further corroborate the existence of such cross-talk between language processes and overt motor behaviour by demonstrating that the reaching movement can be disturbed by action words even when the words are presented delayed with respect to movement onset (50 ms and 200 ms). The results are compared to studies that show language-motor interaction in conditions where the word is presented prior to movement onset and are discussed within the context of embodied theories of language comprehension.

The acute effects of d-amphetamine and methamphetamine on attention and psychomotor performance.

RATIONALE: It is not clear how the deleterious effects of amphetamines on driving performance are mediated in terms of select cognitive processes. OBJECTIVES: The current three separate experiments assessed the acute effects of an oral dose of either 0.42-mg/kg d-amphetamine, d,l-methamphetamine and d-methamphetamine on driving-related cognitive functions in a total of 60 healthy non-fatigued adults. MATERIALS AND METHODS: Three separate repeated measures counterbalanced, double-blind, placebo-controlled designs were employed in which 20 volunteers completed two treatment conditions, either d-amphetamine, d,l-methamphetamine or d-methamphetamine and placebo. Performance was assessed on a range of attentional, psychomotor and perceptual speed tasks. RESULTS: Mean blood concentrations at 120-, 170- and 240-min postdrug administration were 83, 98 and 96 ng/ml, respectively, for d-amphetamine, 90, 95 and 105 ng/ml, respectively, for d,l-methamphetamine and 72, 67 and 59 ng/ml, respectively, for d-methamphetamine. The amphetamines, in general, improved various aspects of attention (Digit Vigilance, Digit Symbol Substitution Test and Movement Estimation Performance) with some evidence to suggest possible enhancement in psychomotor functioning (Tracking ability) and perceptual speed (Inspection Time). CONCLUSIONS: The current series of studies primarily provides evidence of low-level amphetamine-related enhancement of function; however, it also provides evidence of less conservative movement estimation that might contribute to amphetamine-related road fatalities.

An evaluation of the sensitivity of the standardised field sobriety tests to detect the presence of amphetamine.

RATIONALE: The Standardised Field Sobriety Tests (SFSTs), designed and validated to assess impairment associated with alcohol intoxication, are currently being employed by the Victoria Police (Australia) for the identification of driving impairment associated with drugs other than alcohol. OBJECTIVES: The aim of this study was to evaluate whether the SFSTs are a sensitive measure for identifying the presence of dexamphetamine and methamphetamine. METHODS: Three studies each employed a repeated-measures, counterbalanced, double-blind placebo-controlled design. In each study, 20 healthy volunteers completed two treatment conditions: either 0.42 mg/kg d,l-dexamphetamine and placebo, 0.42 mg/kg d,l-methamphetamine and placebo, or 0.42 mg/kg d-methamphetamine and placebo. Performance was assessed using the SFSTs, consisting of the Horizontal Gaze Nystagmus test, the Walk and Turn test, and the One Leg Stand test. Blood and saliva samples were obtained before and immediately after the administration of the SFSTs (120 and 170 min post drug administration). RESULTS: At 120 and 170 min post drug administration, d,l-dexamphetamine blood levels were 83.16 and 98.42 ng/ml, respectively; d,l-methamphetamine levels were 90 and 95 ng/ml, respectively; and d-methamphetamine blood levels were 72 and 67 ng/ml, respectively. None of the three amphetamine doses impaired performance on the SFSTs. Using the SFSTs, the presence of dexamphetamine was identified in 5% of cases, d-methamphetamine in 5%, and d,l-methamphetamine in 0% of cases. CONCLUSIONS: Under these conditions, the SFSTs are not a sensitive measure for detecting the presence of low levels of amphetamine.