Article

The effect of acute administration of 400mg of Panax ginseng on cognitive performance and mood in healthy young volunteers

Article

The effect of acute administration of 400mg of Panax ginseng on cognitive performance and mood in healthy young volunteers

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Abstract

Recent evidence suggests that single dose administration of ginseng can improve certain aspects of cognitive performance and mood in healthy young volunteers in a dose and time dependent manner. The aim of this study was to investigate the effect of acute administration of 400 mg of a standardised Panax ginseng extract (G115®, Pharmaton SA) on mood and cognitive performance. Following a double-blind, placebo controlled, balanced, cross-over design, thirty healthy young adult volunteers received 400 mg of ginseng, and a matching inert placebo, in a counterbalanced order, with a 7-day washout period between treatments. Following baseline evaluation of cognitive performance and mood measures, participants' cognitive performance and mood was assessed again 90 minutes after drug ingestion. Ginseng improved speed of attention, indicating a beneficial effect on participants' ability to allocate attentional processes to a particular task. No significant effect was observed on any other aspect of cognitive performance and on self-reported mood measures. Previous research demonstrated no improvement on attentional processes, but significant improvements on tasks associated with episodic memory performance following administration of 4OO mg of ginseng when participants were tested 1h, 2.5h, 4,h and 6h post ingestion. Consequently, it may be the ease that ginseng offers alternative windows of therapeutic opportunity on different aspects of cognitive performance at different time points.

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... In combination with ginkgo, ginseng has been shown to improve aspects of working memory and improved attention in younger adults [20]. Additionally, Sünram-Lea and colleagues found improvements in 15 participants regarding their processing speed and in episodic memory with an acute ingestion of 400 mg ginseng compared with a placebo group of the same sample size [24]. This outcome is of particular interest since episodic memory is a key deficit in adults with AD. ...
... In line with previous research examining individual constituents [1,14,[16][17][18][19][20][21][22][23][24][25], we hypothesise that a 6-month dose of Cognition Support Formula® will improve cognitive functioning with minimal adverse effects in older adults with SCI compared with placebo. Due to limited literature in this area, exploratory analyses will be conducted in the domains of mood, fatigue, and neurocognition. ...
... Each of the individual components of the formula has been found to increase cognition in older adults with cognitive impairment [1,14,[16][17][18][19][20][21][22][23][24][25]. If results are shown to be positive, this study will lend support to the use of the Cognition Support Formula® as a complementary treatment for SCI. ...
Article
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Background: Due to an ageing population in Australia there has been an increase in the number of older adults with subjective cognitive impairment (SCI), a self-reported decline in cognitive function associated with an increased risk of mild cognitive impairment and dementia. There is no current, recommended treatment for SCI; therefore, the effectiveness of a supplement approved by the Therapeutic Goods Association that has the potential to enhance cognitive function in an at-risk cohort should be tested. The primary aim of this proposed research is to determine the efficacy of 6 months of treatment with BioCeuticals Cognition Support Formula® (containing Bacopa monniera (brahmi), Ginkgo biloba, Panax ginseng and alpha-lipoic acid) on cognition in older adults with SCI (utilising the CogState® one card learning and identification tests as co-primary outcome measures of visual short-term memory and attention; mean speed (ms), accuracy (%), and total number of hits, misses, and anticipations) compared with placebo. The secondary aims are to assess an improvement in other cognitive domains (executive functioning, processing speed, and working memory), evaluate safety, adverse effects, and determine efficacy on mood, fatigue, and neurocognition. It is expected that improvements across the study timepoints in the co-primary outcomes in the active treatment group (compared with placebo) will be evident. Method: One-hundred and twenty participants will be recruited for the randomised, double-blind, placebo-controlled study. Participants will be randomly assigned to one of the treatment groups (active or placebo) at a 1:1 ratio, and will be required to complete a series of cognitive (using CogState®), mood (using the Depression, Anxiety, Stress Scale (DASS-42) and Short Health Anxiety Inventory (SHAI)), and fatigue (using the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F)) tasks at baseline (0 months), the midpoint (3 months), and the endpoint (6 months). These tasks will be evaluated between timepoints (baseline vs. midpoint, midpoint vs. endpoint, and baseline vs. endpoint). Neurocognition will be measured by electroencephalography at baseline and at the endpoint in half of the participants. Adverse effects will be documented over the 6-month trial period. Discussion: This is the first study to test the efficacy of Cognition Support Formula® on cognition in older adults with SCI. As people with SCI have an increased risk of dementia, and there are limited treatments options for this population, it is important to assess a supplement that has the potential to enhance cognitive function. Trial registration: Universal Trial Number (UTN), U1111-1196-9548. Australian New Zealand Clinical Trials Registry, ACTRN12617000945325 . Registered on 30 June 2017.
... However, results of studies testing the impact of Panax ginseng on cognitive performance are equivocal. 135,138 Overall, the studies conducted in the general population with young healthy adults suggest that a single dose of Panax ginseng can improve some aspects of cognitive performance, [139][140][141][142] especially memory, [139][140][141] but not others. 140,142,143 For instance,in a series of studies,Kennedy et al. [139][140][141] reported that various doses (200 mg or 400 mg) of Panax ginseng improved speed of performing a timed memory task, quality of memory, secondary memory, and accuracy of performing attention tasks. ...
... 135,138 Overall, the studies conducted in the general population with young healthy adults suggest that a single dose of Panax ginseng can improve some aspects of cognitive performance, [139][140][141][142] especially memory, [139][140][141] but not others. 140,142,143 For instance,in a series of studies,Kennedy et al. [139][140][141] reported that various doses (200 mg or 400 mg) of Panax ginseng improved speed of performing a timed memory task, quality of memory, secondary memory, and accuracy of performing attention tasks. Others 142 have reported that 400 mg of Panax ginseng improved speed of attention but had no effect on episodic memory. ...
Article
Performance in many sports is at least partially dependent on motor control, coordination, decision-making, and other cognitive tasks. This review summarizes available evidence about the ingestion of selected nutrients or isolated compounds (dietary constituents) and potential acute effects on motor skill and/or cognitive performance in athletes. Dietary constituents discussed include branched-chain amino acids, caffeine, carbohydrate, cocoa flavanols, Gingko biloba, ginseng, guarana, Rhodiola rosea, sage, L-theanine, theobromine, and tyrosine. Although this is not an exhaustive list, these are perhaps the most researched dietary constituents. Caffeine and carbohydrate have the greatest number of published reports supporting their ability to enhance acute motor skill and cognitive performance in athletes. At this time, there is insufficient published evidence to substantiate the use of any other dietary constituents to benefit sports-related motor skill or cognitive performance. The optimal dose and timing of caffeine and carbohydrate intake promoting enhanced motor skill and cognitive performance remain to be identified. Valid, reliable, and sensitive batteries of motor skills and cognitive tests should be developed for use in future efficacy studies.
... As well, 9 studies were performed in healthy adult volunteers, 1 study in patients diagnosed with noninsulin dependent diabetes (Sotaniemi et al., 1995), and 2 studies in AD patients . Of the studies investigating the effect of ginseng in healthy adult volunteers, 7 studies addressed the effect of acute treatment following a single dose (Kennedy et al., 2001Reay et al., 2005Reay et al., , 2006Scholey and Kennedy, 2002;Sunram-Lea et al., 2004), 1 subchronic study compared results after 8 days (Reay et al., 2010;Stupp et al., 2007), and 1 chronic study evaluated potential benefits after 12 weeks. These studies used oral ginseng supplements. ...
... Acute studies of ginseng were composed of participants with a mean age of 18-25 years (Kennedy et al., 2001Reay et al., 2005Reay et al., , 2006Scholey and Kennedy, 2002;Sunram-Lea et al., 2004). This reflects the demographic of Western consumers likely to use ginseng supplements (Gunther et al., 2004). ...
... In all, CDR battery tasks took approximately 20 min to complete. Detailed description of the tasks can be found in previous publications (Kennedy et al., 2000;2001a;2007;Pengelly et al., 2012;Wesnes et al., 2000;Sunram-Lea et al., 2005). ...
... 'Speed of Attention' and 'Accuracy of Attention' factors were described as 'Power of Attention' and 'Continuity of Attention' in the original factor analysis by Wesnes et al. (2000); however, description utilised in this research has been implemented in previous research on the effects of herbal extracts on cognition (e.g. Kennedy et al., 2002;Sunram-Lea et al., 2005;Haskell et al., 2007). ...
Article
A ginsenoside-rich extract of American ginseng (Panax quinquefolius L.), Cereboost(TM) , was previously shown to improve working memory and mood in healthy young individuals. The present study represented a partial replication investigating whether these effects extended to healthy middle-aged individuals. Fifty-two healthy volunteers (40-60 years old, mean age 51.63) received 200 mg of P. quinquefolius or a matching placebo according to a double-blind, placebo-controlled, balanced, crossover design. The Cognitive Drug Research battery and the Computerised Mental Performance Assessment System were used to evaluate cognitive performance at baseline then 1, 3 and 6 h following treatment. Blood glucose and mood were co-monitored. Compared with placebo, P. quinquefolius improved cognitive performance on 'Working Memory' factor at 3 h. Similar effects were observed in one of the two tasks making up this factor, spatial working memory. There were no significant effects on mood or blood glucose levels. These data confirm that P. quinquefolius can acutely benefit working memory and extend the age range of this effect to middle-aged individuals. These changes are unlikely to be underpinned by modulation of blood glucose in this population. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
... Rather than the physical performance, studies on psychomotor function which may effect the performance in certain athletic events have given more positive results (Ziemba et al., 1999;Kennedy et al., 2001;Scholey and Kennedy, 2002;Kennedy et al., 2002;Heo et al., 2008;Lee et al., 2008) comparing the negative results (Cardinal and Engels, 2001;Sunram-Lea et al., 2005). Although the widespread utilization in sports, ginseng was not shown to enhance physical performance with strong evidence and enhanced physical performance after ginseng administration in well-designed investigations remains to be demonstrated (Bahrke et al., 2009). ...
Article
Herbs have a long history of use as traditional medicines to enhance athletic performance. The following herbs are currently used to enhance athletic performance, mostly regardless of scientific evidence of effect: Ginsengs, ephedra, guarana, Tribulus terrestris, kava, St. John's wort, yhombine and ginkgo. Controlled studies for the potential ergogenic effects of herbs are limited and the results are controversial. Future research on ergogenic effects of herbs should consider identity and amount of substance or presumed active ingredients administered, dose, and duration of test period, proper experimental protocols, and measurement of psychological and physiological parameters and measurements of performance pertinent to intended uses. This review focuses mainly on most common herbs that are used to enhance athletic performance at present.
... In the last decade, Kennedy and co-workers [27][28][29][30][31][32] among other research groups [33,34] have published several papers on experimental evaluation of effects of acute administration of ginseng's extract G115 in humans [28,29]. For all experiments, a randomized, double-blind placebo-controlled, balanced crossover design, in which a small group of, and in almost all cases 20, volunteers received three different single doses of the extract or placebo on separate occasions. ...
Article
Full-text available
Neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) are currently incurable pathologies with huge social and economic impacts closely related to the increasing of life expectancy in modern times. Although the clinical and neuropathological aspects of these debilitating disorders are distinct, they share a pattern of neurodegeneration in anatomically or functionally related regions. For each disease, presently available treatments only address symptoms and do not alter the course or progression of the underlying diseases. In this context, the search for new effective chemical entities, capable of acting on diverse biochemical targets, with new mechanisms of action and low toxicity are genuine challenges to research groups and the pharmaceutical industry. This medical need has led to the reemerging of modern natural products chemistry that has yielded sophisticated and complex new lead molecules for drug discovery and development. In this review we discuss some of the main contributions of the natural products chemistry that covers multiple and varied plant species. Advances in the discovery of active constituents of plants, herbs, and extracts prescribed by traditional medicine practices for the treatment of senile neurodegenerative disorders, especially for PD, in the period after the 2000s is reviewed. The most important contributions from the 1990s are also discussed. The review also focuses on the pharmacological mechanisms of action that might underlie the purported beneficial improvements in memory and cognition, neurovascular function, and in neuroprotection. It is concluded that natural product chemistry brings tremendous diversity and historical precedent to a huge area of unmet medical need.
... The methodology of five of the studies was good, with a Jadad score of more than three points; the other studies scored two points. These studies yielded six positive [50,51,[53][54][55]57] and two negative findings [52,56], which indicated strong evidence (level 1) of efficacy. ...
Article
Full-text available
This systematic review aims to evaluate the available evidence from randomized clinical trials of the clinical efficacy and safety of ginseng. Systematic literature searches were performed in 13 databases up to March 2009 without language restriction. All randomized clinical trials evaluating the clinical effects or safety of the use of ginseng monopreparations (Panax ginseng or P. quinquefolium) were considered for inclusion. A total of 411 potentially relevant studies were identified and 57 randomized clinical trials were included. The main indications included glucose metabolism, physical performance, psychomotor function, sexual function, cardiac function, pulmonary disease, and cerebrovascular disease. We found strong evidence of a positive effect of ginseng on glucose metabolism, psychomotor function, and pulmonary disease, whereas evidence suggests that ginseng is not effective at enhancing physical performance. However, ginseng generally has a good safety profile and the incidence of adverse effects seems to be low. In conclusion, our review compiles the evidence on the use of ginseng, finding a strong positive potential for glucose metabolism, psychomotor function, and pulmonary disease, but not for physical performance enhancement.
... Ginseng improved attention speed, indicating a beneficial effect on a participant's ability to allocate attentional processes to a particular task. Ginseng also improved tasks associated with episodic memory performance at 1, 2.5, 4, and 6 h post-ingestion [37]. Over the last decade, Asian ginseng (P. ...
Article
Full-text available
Cognitive disorders can be associated with brain trauma, neurodegenerative disease or as a part of physiological aging. Aging in humans is generally associated with deterioration of cognitive performance and, in particular, learning and memory. Different therapeutic approaches are available to treat cognitive impairment during physiological aging and neurodegenerative or psychiatric disorders. Traditional herbal medicine and numerous plants, either directly as supplements or indirectly in the form of food, improve brain functions including memory and attention. More than a hundred herbal medicinal plants have been traditionally used for learning and memory improvement, but only a few have been tested in randomized clinical trials. Here, we will enumerate those medicinal plants that show positive effects on various cognitive functions in learning and memory clinical trials. Moreover, besides natural products that show promising effects in clinical trials, we briefly discuss medicinal plants that have promising experimental data or initial clinical data and might have potential to reach a clinical trial in the near future.
... declarative memory involving recollection) performance following extract G115 alone [10,36,37] and in combination with both Ginkgo biloba [37] and Paullinia cupana (guaraná) [36]. In addition, Panax ginseng (G115) has been shown to enhance aspects of working memory [38], to improve mental arithmetic performance (in a task that loads heavily on working memory resources) [11,12] and to speed attentional processes [39] in healthy volunteers. These benefits to reaction time occurred without a concomitant cost to accuracy, precluding the possibility of a treatment related shift in the speed/accuracy trade-off. ...
Article
AIMS: Over recent years there has been increasing research into both pharmaceutical and nutraceutical cognition enhancers. Here we aimed to calculate the effect sizes of positive cognitive effect of the pharmaceutical modafinil in order to benchmark the effect of two widely used nutraceuticals Ginseng and Bacopa (which have consistent acute and chronic cognitive effects respectively). METHODS: A search strategy was implemented to capture clinical studies into the neurocognitive effects of modafinil, Ginseng and Bacopa. Studies undertaken on healthy human subjects using a double-blind, placebo-controlled design were included. For each study where appropriate data were included, effect sizes (Cohen's d) were calculated for measures showing significant positive and negative effects of treatment over placebo. RESULTS: The highest effect sizes for cognitive outcomes were 0.77 for modafinil (visuospatial memory accuracy), 0.86 for Ginseng (simple reaction time) and 0.95 for Bacopa (delayed word recall). CONCLUSIONS: These data confirm that neurocognitive enhancement from well characterised nutraceuticals can produce cognition enhancing effects of similar magnitude to those from pharmaceutical interventions. Future research should compare these effects directly in clinical trials.
... Scores from individual measures were combined to form seven secondary out- come measures ('power of attention', continuity of attention', 'quality of working memory', 'quality of episodic secondary memory', 'quality of memory', 'speed of memory' and 'combined speed') derived from factor analysis of the Cognitive Drug Research computerised test battery ( Wesnes et al., 1999Wesnes et al., , 2000), and previously used (e.g. Wesnes et al., 1997Wesnes et al., , 1999Wesnes et al., , 2000Kennedy et al., 2001Kennedy et al., , 2002aSünram-Lea et al., 2004a,b); see Fig. 1. ...
... GK501 * Standardized extract of Ginkgo biloba Improvement in the speed of attention and tasks associated with episodic memory performance [142] 24. G115 * Standardized extract of Panax ginseng Improvement in speed of attention and tasks associated with episodic memory performance in healthy middle aged individuals [143] 25. ...
Article
Full-text available
Hanbang, the Traditional Korean Medicine (TKM), is an inseparable component of Korean culture both within the country, and further afield. Korean traditional herbs have been used medicinally to treat sickness and injury for thousands of years. Oriental medicine reflects our ancestor's wisdom and experience, and as the elderly population in Korea is rapidly increasing, so is the importance of their health problems. The proportion of the population who are over 65 years of age is expected to increase to 24.3% by 2031. Cognitive impairment is common with increasing age, and efforts are made to retain and restore the cognition ability of the elderly. Herbal materials have been considered for this purpose because of their low adverse effects and their cognitive-enhancing or anti-dementia activities. Herbal materials are reported to contain several active compounds that have effects on cognitive function. Here, we enumerate evidence linking TKMs which have shown benefits in memory improvements. Moreover, we have also listed Korean herbal formulations which have been the subject of scientific reports relating to memory improvement.
... In the studies deemed suitable for further analysis, 15 used extracts of P. ginseng, either alone or in combination with another ingredient, such that the effect of P. ginseng alone was measured. 50,52,[56][57][58][59][60][61][62][63][64][65][66][67] Of these, 12 studies directly measured components of cognition or neurological function. Nine studies were conducted in healthy volunteers, 1 study examined patients with noninsulindependent diabetes, 66 and 2 studies examined the effects of P. ginseng on clinical symptoms and cognition in Alzheimer's disease patients. ...
Article
Full-text available
Reviewed here is the existing evidence for the effects of ginseng extracts and isolated ginsenosides relevant to cognition in humans. Clinical studies in healthy volunteers and in patients with neurological disease or deficit, evidence from preclinical models of cognition, and pharmacokinetic data are considered. Conditions under which disease modification may indirectly benefit cognition but may not translate to cognitive benefits in healthy subjects are discussed. The number of chronic studies of ginseng effects in healthy individuals is limited, and the results from acute studies are inconsistent, making overall assessment of ginseng's efficacy as a cognitive enhancer premature. However, mechanistic results are encouraging; in particular, the ginsenosides Rg3 , Rh1 , Rh2 , Rb1 , Rd, Rg2 , and Rb3 , along with the aglycones protopanaxadiol and protopanaxatriol, warrant further attention. Compound K has a promising pharmacokinetic profile and can affect neurotransmission and neuroprotection. Properly conducted trials using standardized tests in healthy individuals reflecting the target population for ginseng supplementation are required to address inconsistencies in results from acute studies. The evidence summarized here suggests ginseng has potential, but unproven, benefits on cognition.
... The timing and strength of cognitive benefits following treatment with ginseng are likely to be strongly dependent on the metabolism, and thus subsequent bioavailability, of the ginsenosides present. Ginsenosides, such as Rb1, are known to be absorbed from the upper gastrointestinal tract [18]. A study investigating the oral administration of American ginseng in healthy adults (age not specified) found Rb1 to be present in plasma samples throughout a 2-12-h period after administration [19]. ...
Article
Full-text available
Purpose Cereboost®, an American ginseng extract, has shown improved short-term memory and attention/alertness in healthy young and middle-aged individuals, potentially via modulation of the gut microbiome and upregulation of neurotransmitters such as acetylcholine. Here, we explored the effects of Cereboost® on cognition and mood in the first 6 h post intervention (acute), after 2 weeks daily supplementation (chronic), and whether 2 weeks daily supplementation altered the response to a single acute dose (acute-on-chronic). A concurrent in vitro study evaluated effects of repeated Cereboost® administration on human gut microbiota. Methods Cognitive effects of Cereboost® were assessed using a double-blind, randomized, placebo-controlled clinical trial, with 61 healthy young adults. Modulation of the gut microbiome was concurrently modelled using the Simulator of the Human Microbial Ecosystem (SHIME®), using a young adult donor. Results Consistent with previous findings, Cereboost® improved working memory and attention during the immediate postprandial period; effects that were amplified following two weeks’ treatment (acute-on-chronic) compared to acute testing alone. Chronic supplementation improved cognition on an acetylcholine-sensitive attention task and improved mental fatigue and self-assurance aspects of mood. The parallel in vitro study revealed significantly increased acetate, propionate, and butyrate levels in simulated proximal and distal colon regions, linked with observed increases in Akkermansia muciniphila and Lactobacillus . Conclusion This study confirmed the promising effects of Cereboost® on cognitive function and mood, while suggesting a possible link to alterations of the gut microbiome and modulation of acetylcholine. Further studies will be required to unravel the underlying mechanisms that are involved. Registration The study was pre-registered at ClinicalTrials.gov on 6th July 2018 (Identifier: NCT03579095).
... Rather than the physical performance, studies on psychomotor functions which may effect the performance in certain athletic events have given more positive results (Ziemba et al., 1999;Kennedy et al., 2001;Scholey and Kennedy, 2002;Kennedy et al., 2002;Heo et al., 2008;Lee et al., 2008) comparing to negative results (Cardinal and Engels, 2001;Sunram-Lea et al., 2005). Although the widespread utilization in sports, ginseng was not shown to enhance physical performance with strong evidence and enhanced physical performance after ginseng administration in well-designed investigations remains to be demonstrated (Bahrke et al., 2009). ...
Article
Herbs have a long history of use as traditional medicines to enhance athletic performance. The following herbs are currently used to enhance athletic performance, mostly regardless of scientific evidence of effect: Ginsengs, ephedra, guarana, Tribulus terrestris, kava, St. John's wort, yhombine and ginkgo. Controlled studies for the potential ergogenic effects of herbs are limited and the results are controversial. Future research on ergogenic effects °f herbs should consider identity and amount of substance or presumed active ingredients administered, dose, and duration of test period, proper experimental protocols, and measurement of psychological and physiological parameters and measurements of performance pertinent to intended uses. This review focuses mainly on most common herbs that are used to enhance athletic performance at present.
... Neale et al [68] have recently reviewed some relevant clinical studies on the effects of G115 on cognitive functions, namely, studies by Reay et al [93], Reay et al [92], Reay et al [90], Sünram-Lea et al [111], Kennedy et al [112], Kennedy et al [113], Scholey and Kennedy [114], and Kennedy et al [115]. This review assessed that G115 enhances cognition effects comparable with those from modafinil therapy. ...
Article
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Ginseng products on the market show high variability in their composition and overall quality. This becomes a challenge for both consumers and health-care professionals who are in search of high-quality, reliable ginseng products that have a proven safety and efficacy profile. The botanical extract standardization is of crucial importance in this context as it determines the reproducibility of the quality of the product that is essential for the evaluation of effectiveness and safety. This review focuses on the well-characterized and standardized ginseng extract, G115, which represents an excellent example of an herbal drug preparation with constant safety and efficacy within the herbal medicinal products. Over the many decades, extensive preclinical and clinical research has been conducted to evaluate the efficacy and safety of G115. In vitro and in vivo studies of G115 have shown pharmacological effects on physical performance, cognitive function, metabolism, and the immune system. Furthermore, a significant number of G115 clinical studies, most of them double-blind placebo-controlled, have reinforced the findings of preclinical evidence and proved the efficacy of this extract on blood glucose and lipid regulation, chronic obstructive pulmonary disease, energy, physical performance, and immune and cognitive functions. Clinical trials and 50 years of presence on the market are proof of a good safety profile of G115. Keywords: Blood glucose and lipid regulation, Chronic obstructive pulmonary disease, Energy and physical performance, G115 standardized ginseng extract, Immune and cognitive functions
... In a non-sporting context a number of randomised, controlled, balanced-crossover, single-dose (200-400 mg) trials have demonstrated consistent improvements in the accuracy of memory tasks [198][199][200] and the speed of attention task performance [200,201]. Single doses have also decreased the latency of cerebro-electrical evoked potentials as measured by electroencephalography (EEG) [202], and improved the performance of difficult working memory/executive function tasks and concomitantly reduced mental fatigue [203,204]. A recent study [205] also showed that 7 days' supplementation increased 'calmness', following both doses investigated (200/400 mg), and improved performance of the '3-back' working memory task following the higher dose, but with slower performance following the lower dose. ...
Article
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Subjective alertness and optimal cognitive function, including in terms of attention, spatial/working memory and executive function, are intrinsic to peak performance in many sports. Consumption of a number of plant-derived ‘secondary metabolite’ phytochemicals can modulate these psychological parameters, although there is a paucity of evidence collected in a sporting context. The structural groups into which these phytochemicals fall—phenolics, terpenes and alkaloids—vary in terms of the ecological roles they play for the plant, their toxicity and the extent to which they exert direct effects on brain function. The phenolics, including polyphenols, play protective roles in the plant, and represent a natural, benign component of the human diet. Increased consumption has been shown to improve cardiovascular function and is associated with long-term brain health. However, whilst short-term supplementation with polyphenols has been shown to consistently modulate cerebral blood-flow parameters, evidence of direct effects on cognitive function and alertness/arousal is currently comparatively weak. Terpenes play both attractant and deterrent roles in the plant, and typically occur less frequently in the diet. Single doses of volatile monoterpenes derived from edible herbs such as sage (Salvia officinalis/lavandulaefolia) and peppermint (Mentha piperita), diterpene-rich Ginkgo biloba extracts and triterpene-containing extracts from plants such as ginseng (Panax ginseng/quinquefolius) and Bacopa monnieri have all been shown to enhance relevant aspects of cognitive function and alertness. The alkaloids play toxic defensive roles in the plant, including via interference with herbivore brain function. Whilst most alkaloids are inappropriate in a sporting context due to toxicity and legal status, evidence suggests that single doses of nicotine and caffeine may be able to enhance relevant aspects of cognitive function and/or alertness. However, their benefits may be confounded by habituation and withdrawal effects in the longer term. The efficacy of volatile terpenes, triterpene-rich extracts and products combining low doses of caffeine with other phytochemicals deserves more research attention.
... The evidence for a beneficial effect of ginseng on cognition is mixed. A review of studies that have adopted stringent clinical trial criteria such as double-blinding, randomization, placebo-controlled, and crossover designs show contrasting results in terms of ginseng effects on working memory, attention, concentration, speed of processing and reaction time [1][2][3][4][5]. Additionally, a research group found an effect of ginseng on concentration but not on speed of processing in one study [6], and reported opposite outcomes in a follow-up investigation [7]. ...
Article
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Background There is some evidence to suggest that ginseng and Ginkgo biloba can improve cognitive performance, however, very little is known about the mechanisms associated with such improvement. Here, we tested whether cardiovascular reactivity to a task is associated with cognitive improvement. Methodology/Principal findings Using a double-blind, placebo controlled, crossover design, participants (N = 24) received two doses of Panax Ginseng (500, 1000 mg) or Ginkgo Biloba (120, 240 mg) (N = 24), and underwent a series of cognitive tests while systolic, diastolic, and heart rate readings were taken. Ginkgo Biloba improved aspects of executive functioning (Stroop and Berg tasks) in females but not in males. Ginseng had no effect on cognition. Ginkgo biloba in females reversed the initial (i.e. placebo) increase in cardiovascular reactivity (systolic and diastolic readings increased compared to baseline) to cognitive tasks. This effect (reversal) was most notable after those tasks (Stroop and Iowa) that elicited the greatest cardiovascular reactivity during placebo. In males, although ginkgo also decreased cardiovascular readings, it did so from an initial (placebo) blunted response (i.e. decrease or no change from baseline) to cognitive tasks. Ginseng, on the contrary, increased cardiovascular readings compared to placebo. Conclusions/Significance These results suggest that cardiovascular reactivity may be a mechanism by which ginkgo but not ginseng, in females is associated with certain forms of cognitive improvement. Trial Registration ClinicalTrials.gov NCT02386852
Chapter
The chapter reviews the overall neuronal molecular mechanisms of Bacopa monnieri with respect to cognitive performance. It starts with defining cognition, and how interruption in signal transduction can cause cognitive impairment. Then the factors influencing signal transduction and regulation of those factors are briefed to give a glimpse on cascade involved in signal transduction and their importance in governing the cognitive performance. The drugs and nutraceuticals commonly used as cognition enhancers and their mechanisms of action are covered in brief before taking up details of B. monnieri. Later, effect of B. monnieri on various factors contributing to signal transduction like neurotransmitters, receptors, second messenger system, gene expression, neuronal structural factors, neuronal connections, cerebral blood flow and neuroprotection are detailed to understand the neuronal molecular mechanisms involved in improving cognitive performance. Summary of this review points toward strong scientific substantiation available in the literature to justify the use of B. monnieri in dietary and food supplements intended for cognitive health.
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Ginseng has been used to treat disease and to combat aging for thousands of years. Currently, ginseng occupies a prominent position in the herbal "best-sellers" list and is the most widely used herbal product throughout the world. This review aimed to identify all double-blind and single-blind randomized, placebo-controlled trials assessing the effects of ginseng on cognitive function. Five trials investigating the effects of ginseng on healthy participants had extractable information for efficacy and were included in the review. Ginseng appeared to have some beneficial effects on cognition, behavior and quality of life. More rigorously designed studies are needed on this important issue.
Chapter
Pharmaceutical cognitive enhancers tend to target single or classes of neurotransmitters. Given that most cognitive functions are the expression of multiple physiological processes, it is unsurprising that classic drug development has resulted in a few effective cognitive enhancers. At the same time there are well-characterised botanical extracts which appear to influence numerous neurotransmitter, neurohormonal and neurovascular processes involved in cognition. While many of these botanical extracts—e.g. cannabis, opiates and alcohol—are impairing, others can act as cognitive enhancers. This chapter will focus on acute cognitive enhancement from administration of select botanical extracts including Asian and American ginseng, sage and cocoa polyphenols. When benchmarked against pharmaceutical cognitive enhancers, these extracts enhance cognition with similar effect sizes to modafinil. The mechanisms of action appear to be different to those underlying pharmaceutical interventions, with positive effects on cerebral blood flow and central glucose utilisation complementing direct neurotransmitter effects. These mechanisms may be further elucidated through recently developed neuroimaging methodologies.
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The role of carbohydrates on mood and cognition is fairly well established, however research examining the behavioural effects of the other macronutrients is limited. The current study compared the effects of a 25 g glucose drink to energetically matched protein and fat drinks and an inert placebo. Following a blind, placebo-controlled, randomised crossover design, 18 healthy young adults consumed drinks containing fat, glucose, protein and placebo. Cognitive performance was examined at baseline and again 15- and 60 min post drink. Mood was assessed at baseline and then 10-, 35- and 80 min post drink. Attention and speed were enhanced 15 min following fat or glucose ingestion and working memory was enhanced 15 min following protein ingestion. Sixty minutes post drink memory enhancements were observed after protein and memory impairment was observed following glucose. All drinks increased ratings of alertness. The findings suggest that macronutrients: (i) have different windows of opportunity for effects (ii) target different cognitive domains.
Article
Objective: Lack of mental energy is one of the leading reasons adults turn to dietary supplements, with three out of ten supplement users hoping to improve their energy level; even more consume caffeine-containing products for the same reason. Despite this interest from consumers, there is no consensus scientific definition of mental energy or sole validated instrument for measuring it. We performed this review to summarize main findings from research regarding the influence of natural dietary compounds on three aspects of mental energy: cognition (vigilance), motivation (to do mental work), and mood (feelings of energy and/or absence of feelings of fatigue). Methods: A narrative review of key papers. Results: In addition to caffeine, a number of other compounds, including the polyphenols, which are found in all plant-derived products, and the phytochemicals in culinary herbs and herbal products such as Panax ginseng and Ginkgo biloba, have been shown in animal models to modulate neurotransmitter activity potentially relevant to mental energy. Inadequate intake of B vitamins could also potentially have a negative effect on mental energy due to their role in overall energy production, as precursors of key cofactors in the citric acid cycle, as well as their role in brain function and neurotransmitter synthesis. Consumption of some of these products may have direct or indirect effects on one or more elements of mental energy. Conclusion: Large, prospective clinical trials of these products using appropriate, validated instruments designed to measure mental energy may be worthwhile if sufficient evidence exists to justify such trials.
Article
Physicians are increasingly recommending the use of plant-derived products, partly because of a growing dissatisfaction among consumers with conventional medicines, but also because of the progress made in the chemical, pharmacological and clinical study of herbal medicinal products, the use of innovative galenical forms and the growing importance of self medication. Quality is a key issue in the development of herbal medicinal products that have consistent safety and efficacy, and quality can only be achieved if it is prioritized from the earliest stages of the development process. Problems in the development of herbal remedies include the frequent lack of standardized products (leading to a poor reproducibility of results and lack of batch-to-batch uniformity), a lack of toxicology, pharmacokinetic and pharmacodynamic data, as well as of dose-response and interaction studies. In addition, the placebo effect in trials with herbal remedies is often very high. Research involving herbal medicinal products must progress from the use of traditional evidence and/or open, observational trials to randomized, double-blind, placebo-controlled trials, the ‘gold standard’ of clinical and scientific research. Over time, the development process for herbal medicinal products should become more closely aligned with the development of new chemical entities. Pharmacovigilance is also slowly becoming a standard tool to monitor the safety of herbal medicinal products. Yet we should not discard the legacy of traditional wisdom because ethnopharmacology and knowledge provided by existing clinical trials (be they open, observational studies or small, double-blind investigations) is a source of invaluable insight into the safety and efficacy of herbal remedies. Ideally, a registration dossier for any herbal medicinal product should include both the results of appropriate preclinical and clinical studies, and the wealth of knowledge that has accumulated from the traditional use of the product.
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Panax ginseng C.A. Meyer is a common herb with many purported health benefits. However, there is no conclusive evidence supporting its use in the treatment of any particular disease. We conducted a systematic review to evaluate randomised controlled trials. Four English databases were searched with no publication date restriction. Included studies evaluated P. ginseng in patients with any type of disease or in healthy individuals. We assessed the quality of studies using the Cochrane risk of bias tool. Of the 475 potentially relevant studies, 65 met the inclusion criteria. These studies examined P. ginseng's effects on psychomotor performance (17 studies), physical performance (ten), circulatory system (eight), glucose metabolism (six), the respiratory system (five), erectile dysfunction (four), immunomodulation (four), quality of life/mood (four), antioxidant function (two), cancer (two), menopausal symptoms (two) and dry mouth (one). The risk of bias was unclear in most studies. Authors evaluated adverse events in 40 studies, with 135 minor events and no serious adverse events reported. P. ginseng shows promising results for improving glucose metabolism and moderating the immune response. This may have implications for several diseases including type 2 diabetes and chronic respiratory conditions. Further studies are needed to explore P. ginseng's potential as an effective treatment for these and other health conditions. Copyright © 2012 John Wiley & Sons, Ltd.
Article
Panax ginseng is one of the most frequently used herbs in the world. Numerous trials have evaluated its clinical benefits. However, the quality of these studies has not been comprehensively and systematically assessed. We reviewed randomized controlled trials (RCTs) of Panax ginseng to evaluate their quality and risk of bias. We searched four English databases, without publication date restriction. Two reviewers extracted details about the studies' methodological quality, guided by the Consolidated Standards of Reporting Trials (CONSORT) checklist and its extension for herbal interventions. Risk of bias was determined using the Cochrane Risk of Bias tool. Of 475 potentially relevant studies, 58 met our inclusion criteria. In these 58 studies, 48.3% of the suggested CONSORT checklist items and 35.9% of the extended herbal items were reported. The quality of RCTs published after the CONSORT checklist improved. Until 1995 (before CONSORT) (n = 4), 32.8% of the items were reported in studies. From 1996-2006 (CONSORT published and revised) (n = 30), 46.1% were reported, and from 2007 (n = 24), 53.5% were reported (p = 0.005). After the CONSORT extension for herbal interventions was published in 2006, RCT quality also improved, although not significantly. Until 2005 (n = 34), 35.2% of the extended herbal items were reported in studies; and from 2006 onwards (n = 24), 37.3% were reported (p = 0.64). Most studies classified risk of bias as "unclear". Overall, the quality of Panax ginseng RCT methodology has improved since the CONSORT checklist was introduced. However, more can be done to improve the methodological quality of, and reporting in, RCTs.
Chapter
With increasingly aging population there is an increase in the incidence of age-related neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. And despite the advent of many drugs that helped to ease the life of patients suffering from these disorders, there is yet no cure. In recent years, there has been a growing interest in the use of botanicals and dietary supplements to treat neurodegenerative diseases. Indeed, the use of herbal remedies in these patients is widespread and is on the rise. While the list of these botanicals is long, some of them, e.g., Panax ginseng, Ginkgo biloba, curcumin or their individual biologically active constituents, have been shown to exert neuroprotective effects in experimental animals. Data from epidemiological studies and clinical trials have also suggested clinical benefit of these herbal supplements in delaying or even modifying the neurodegenerative process. Likewise epidemiologic and experimental studies suggest therapeutic potential for such dietary components as tea catechins, coffee as well as dietary polyphenols This chapter discusses the clinical and experimental data suggesting a benefit from these commonly used herbal supplements and dietary components.
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Dietary nitrate supplementation has been shown to reduce the oxygen (O2) cost of exercise and enhance exercise tolerance in healthy individuals. This study assessed whether similar effects could be observed in individuals with type 2 diabetes (T2DM). In a randomized, double-blind, placebo-controlled crossover study, 48 participants with T2DM supplemented their diet for 4 days with either nitrate-rich beetroot juice (70 ml/day, 6.43 mmol nitrate/day) or nitrate-depleted beetroot juice as placebo (70 ml/day, 0.07 mmol nitrate/day). After each intervention period, resting plasma nitrate and nitrite concentrations were measured subsequent to participants completing moderate-paced walking. Pulmonary gas exchange was measured to assess the O2 cost of walking. After a rest period, participants performed the 6-min walk test (6MWT). Relative to placebo, beetroot juice resulted in a significant increase in plasma nitrate (placebo, 57±66 vs beetroot, 319±110 µM; P < 0.001) and plasma nitrite concentration (placebo, 680±256 vs beetroot, 1065±607 nM; P < 0.001). There were no differences between placebo juice and beetroot juice for the O2 cost of walking (946±221 vs 939±223 ml/min, respectively; P = 0.59) and distance covered in the 6MWT (550±83 vs 554±90 m, respectively; P = 0.17). Nitrate supplementation did not affect the O2 cost of moderate-paced walking or improve performance in the 6MWT. These findings indicate that dietary nitrate supplementation does not modulate the response to exercise in individuals with T2DM.
Article
Background: In this substudy of the effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes, we report the development of a novel nitrate depleted beetroot juice for use clinical trials and determine if dietary nitrate supplementation improved cognitive function in patients with type 2 diabetes mellitus. Methods: Beetroot juice was treated with the anion exchange resin Purolite A520e. UV-vis-spectrophotometry, and a blind taste test were performed along with determination of sugar content, measurement of ascorbate and dehydroascorbate, the ionic composition of juice and Proton NMR. Subsequently, 27 patients, age 67.2±4.9 years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order beetroot juice (nitrate content 7.5 mmol per 250 ml) or placebo (nitrate depleted beetroot juice nitrate content 0.002 mmol per 250 ml). At the end of each 2 week supplementation period cognitive function was assessed using E-prime, E-Studio software with 5 separate tests being performed. The tests utilised in the present study have been adapted from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results: The differences in the UV-vis spectra were comparable to the natural variation found in differing cultivars. There were no discernable differences in taste, sugar content, or Proton NMR. Ascorbate and dehydroascorbate were undetectable in either juice. After 2 weeks of beetroot juice simple reaction time was significantly quicker in the active arm at 327±40 ms versus 341.8±52.7 ms in the placebo arm, mean difference 13.9±25.6 ms (95% CI 3.8-24.0 ms), p=0.009. No other measures of cognitive function differed between treatment arms. Conclusion: We have developed an effective placebo beetroot juice for use in trials of supplementation of dietary nitrate. Two weeks supplementation of the diet with 7.5 mmol of nitrate per day caused a significant improvement in simple reaction time in individuals with T2DM.
Chapter
Nutraceuticals are foods, or compounds within foods, that provide health benefits beyond that of strict nutritional support. Common examples include Ephedra sinica to boost energy and promote weight loss, Ginkgo biloba to treat hypertension, and caffeine to stimulate the central nervous system. There are a number of nutraceuticals that claim to enhance cognitive function. Plants contain a large array of chemical compounds that have the potential to affect brain cell function. This chapter describes the cognitive-enhancing effects of several nutraceuticals, including G. biloba, Bacopa monnieri, ginseng (Panax ginseng), phosphatidylserine (PS), and caffeine. This chapter focuses on randomized, double-blind, placebo-controlled studies in humans to evaluate the potential efficacy of selected nutraceuticals for their cognitive enhancement. Findings from animal and in vitro studies are also covered to discuss their potential mechanisms of action. Based on our review of the literature, it can be concluded that there is insufficient evidence to consider G. biloba, B. monnieri, ginseng, or PS as bona fide cognitive enhancers. However, there is substantial evidence indicating that caffeine acutely enhances cognitive processing speed. Further, longitudinal studies associate a reduced risk of cognitive decline with drinking three to five cups of coffee per day.
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There is a lack of research into the cognitive and mood effects of repeated ginseng ingestion. The present study assessed the effects of Panax ginseng (G115) on subjective mood and aspects of 'working' memory processes, following a single dose and following sub-chronic (7 days) ingestion, in healthy volunteers. A placebo-controlled, double-blind, randomised, crossover was utilised. Thirty volunteers (mean age 22.87 years; SD 4.01) received each treatment (200 mg; 400 mg; placebo) for 8 days, in a counter balanced order, with a 6-day wash-out period. Testing was on days 1 and 8 of each treatment period, at pre-dose, 1, 2.5 and 4 h post-dose. Results revealed dose-related treatment effects (p < 0.05). Two hundred milligrams slowed a fall in mood at 2.5 and 4 h on day 1 and at 1 and 4 h on day 8, but slowed responding on a mental arithmetic task across day 1 and at 1 and 2.5 h on day 8. The 400 mg dose also improved calmness (restricted 2.5 and 4 h on day 1) and improved mental arithmetic across days 1 and 8. We found no evidence of additional benefits, nor attenuation of acute effects following repeated ingestion of Panax ginseng (G115).
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Despite numerous studies indicating that transient cerebral oxygen depletion has a detrimental effect on cognition, surprisingly little research has examined the possibility of cognitive enhancement following elevated oxygen levels in healthy adults. Here, we present evidence demonstrating that oxygen administration improves memory formation. Inhalation of oxygen immediately prior to learning a word list resulted in a significant increase in mean number of words recalled 10 min later, compared to subjects who inhaled oxygen immediately prior to recall or to controls who underwent no intervention. In a second experiment, the learning-test interval was increased to 24 h and, again, only pre-learning (but not pre-test) oxygen administration resulted in significant memory facilitation. In experiment 3, inhalation of oxygen prior to learning was compared to inhalation of compressed air, oxygen (but not compressed air) resulted in a significant increase in word recall 24 h later. In no experiment did oxygen have a significant effect on any mood item measured. We interpret these data as indicating that increased availability of cerebral oxygen facilitates cognition, including memory consolidation. The implications for the psychopharmacology of cognitive enhancement are considered in the context of cholinergic systems and neural metabolism.
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It was recently demonstrated that oxygen administration can improve performance on a simple word recall task in healthy young adults. This study was aimed at determining the impact of various durations of oxygen administration on a wider range of cognitive measures. This was achieved using the Cognitive Drug Research computerised test battery, and employing a double-blind, placebo-controlled crossover design. Over a period of 7 weeks, 20 participants were trained and subsequently assessed on the test battery under several durations of oxygen inhalation; air administered in an identical fashion served as a control. The results provided support for our earlier work in that increases were found in both immediate and delayed word recall. In addition, oxygen administration significantly improved performance on several measures of attention and vigilance. Simple reaction time, choice reaction time, digit vigilance reaction time and picture recognition reaction time were improved in a manner which depended on the duration of oxygen inspired. With the exception of word recall, no significant improvements were found for any measure of accuracy, nor were word recognition, digit memory scanning, or spatial memory improved. These results are discussed in the context of stages of information processing and are consistent with the hypothesis that cognitive performance is "fuel-limited" and can be differentially augmented by increasing the availability of the brain's metabolic resources.
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Oxygen administration coinciding with word presentation enhances word recall in humans, suggesting that elevated levels of circulating blood oxygen may be available to neural memory consolidation processes. This double-blind experiment examined the relationship between blood oxygen levels and cognitive performance when oxygen was inspired for 2 min at different times relative to a simple word recall task, forward digit span and backward digit span. Transient hyperoxia, measured by haemoglobin-bound oxygen, was evident following oxygen inspiration. Neither forward nor backward digit span was affected by oxygen administration. Word recall (12 min following word presentation) was enhanced when oxygen was administered 5 min prior to, immediately before or immediately following word presentation; but not 10 min prior to, 5 min following nor 10 min following, word presentation. These data suggest that oxygen administration can selectively enhance aspects of cognitive performance and support a hypothesis whereby supplemental blood oxygen is sequestered by neural mechanisms involved in memory consolidation.
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It is known that glucose administration is capable of improving performance on tests of declarative verbal memory and non-mnemonic tasks requiring high "mental effort". At the same time, cognitively demanding tasks are associated with elevated heart rate, a response that could feasibly be part of a physiological mechanism serving to increase the delivery of glucose to active brain substrates. The present placebo-controlled, double-blind, balanced, crossover study examined the interaction between glucose administration, cognitive performance and heart rate during three tasks of differing mental demand and somatically-matched control tasks. The effects of a glucose drink on participants' performance on two serial subtraction tasks (Serial Threes and Serial Sevens) and a Word Retrieval (Verbal Fluency) task were assessed. Heart rates were monitored throughout the experiment, and participants rated each task in terms of its perceived mental demand. Serial Sevens was rated as the most mentally demanding task, followed by Word Retrieval, then Serial Threes. Glucose consumption significantly improved performance on Serial Sevens, with a trend for improved performance on Word Retrieval. Both Serial Sevens and Serial Threes were associated with significant heart rate elevation above that seen in somatically matched control tasks (ruling out the possibility that accelerated heart rate was due to peripheral mechanisms alone). Unexpectedly, participants in the glucose condition had higher heart rates during cognitive processing. Additionally, individuals whose baseline heart rates were below the median performed better on Serial Threes and Serial Sevens. We suggest that supplemental glucose preferentially targets tasks with a relatively high cognitive load, which itself (through unknown mechanisms) mobilises physiological reserves as part of a natural response to such tasks. Furthermore, baseline heart rate and responses to cognitive demand and glucose administration may represent important physiological individual differences.
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The effects of capsules containing 60 mg of a standardised extract of Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) on various aspects of cognitive function were assessed in healthy middle-aged volunteers. A double blind, placebo controlled, 14 week, parallel group, repeated assessment, multi-centre trial of two dosing regimens, 160 mg b.i.d. and 320 mg o.d. was conducted. Two hundred and fifty-six healthy middle-aged volunteers successfully completed the study. On various study days (weeks 0, 4, 8, 12 and 14) the volunteers performed a selection of tests of attention and memory from the Cognitive Drug Research computerised cognitive assessment system prior to morning dosing and again, at 1, 3 and 6 h later. The volunteers also completed questionnaires about mood states, quality of life and sleep quality. The Ginkgo/ginseng combination was found significantly to improve an Index of Memory Quality, supporting a previous finding with the compound. This effect represented an average improvement of 7.5% and reflected improvements to a number of different aspects of memory, including working and long-term memory. This enhancement to memory was seen throughout the 12-week dosing period and also after a 2-week washout. This represents the first substantial demonstration of improvements to the memory of healthy middle-aged volunteers produced by a phytopharmaceutical.
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Previous investigations have demonstrated increased performance after the administration of a glucose-load on certain aspects of cognitive functioning in healthy young adults. Generally these studies have used a procedure where participants were tested in the morning after an overnight fast. The aim of the present study was, for the first time, to investigate the glucose cognitive facilitation effect under more natural testing times and with shorter duration of the previous fast. Measures of verbal and non-verbal memory performance were compared under different fasting intervals (2-h fast versus overnight fast), times (morning versus afternoon) and glycaemic conditions (glucose versus aspartame drinks) in healthy young participants. There was a significant glucose facilitation effect on long-term verbal memory performance. In addition, glucose significantly enhanced long-term spatial memory performance. The effect of glucose was essentially equivalent whether it was given after an overnight fast or a 2-h fast following breakfast or lunch. There was no effect of drink and time of day on working memory performance. The results of this study further support the hypothesis that glucose administration can enhance certain aspects of memory performance in healthy young adults. More significantly, the findings indicate that this cognitive facilitation effect persists under more naturalistic conditions of glucose administration and is not restricted to long fast durations or morning administration.
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Recent evidence suggests that chronic administration of Ginseng can improve cognitive performance in animals and in humans. No previous study has examined the possibility of cognitive effects following single doses of Ginseng in healthy adults. The present study investigated whether acute administration of Ginseng (G115, Pharmaton SA) had any consistent effect on mood and four aspects of cognitive performance ("Quality of Memory", "Speed of Memory", "Quality of Attention" and "Speed of Attention") that can be derived by factor analysis of the Cognitive Drug Research computerised assessment battery. The study followed a placebo-controlled, double-blind, balanced, crossover design. Twenty healthy young adult volunteers received 200, 400, and 600 mg of G115, and a matching placebo, in counterbalanced order, with a 7 day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4 and 6 h after the day's treatment. The most striking result was a significant improvement in "Quality of Memory" and the associated "Secondary Memory" factor at all time points following 400 mg of Ginseng. Both the 200 and 600 mg doses were associated with a significant decrement of the "Speed of Attention" factor at later testing times only. Subjective ratings of alertness were also reduced 6 h following the two lowest doses. To the best of our knowledge this represents the first demonstration of a modulation of mood and cognitive performance by acute administration of Ginseng.
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Memory for a list of 20 words can be enhanced by preceding learning with consumption of 25 g glucose rather than an equally sweet aspartame solution. In previous studies, participants performed a secondary hand-movement task during the list-learning phase. The present placebo-controlled, double-blind study examined whether the additional cognitive load created by a secondary task is a crucial feature of the glucose memory facilitation effect. The effect of glucose administration on word recall performance in healthy young participants was examined under conditions where the primary memory task and a secondary task were competing for cognitive resources (across a range of secondary tasks), and where task difficulty was increased but dual task-mediated competition for cognitive resources did not exist. Measures of non-verbal and working memory performance were also compared under the different glycaemic conditions (glucose versus aspartame drinks). In the present study, a beneficial effect of glucose on memory was detected after participants encoded a 20-word list while performing a secondary task, but not when participants encoded the list without a secondary task, nor when the 20 target words were intermixed with 20 non-target words (distinguished by gender of speaker). In addition, glucose significantly enhanced performance on spatial and working memory tasks. The data indicate that possible "depletion" of episodic memory capacity and/or glucose-mediated resources in the brain due to performing a concomitant cognitive task might be crucial to the demonstration of a glucose facilitation effect. Possible implications regarding underlying cognitive and physiological mechanisms are discussed in this article.
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Memory for a list of 20 words can be enhanced by preceding learning by consumption of 25 g of glucose, compared with consumption of an equally sweet aspartame solution (Psychopharmacology 137 (1998) 259; Psychopharmacology 157 (2001) 46). However, using this anterograde administration procedure, it is impossible to separate whether glucose affects encoding, consolidation, or retrieval. The present placebo-controlled, double-blind study investigated the effect of anterograde and retrograde administration on memory performance in healthy young participants. In order to evaluate whether post-acquisition administration of glucose can improve memory performance and to compare possible differences in the size of the effect, participants were administered 25 g of glucose immediately before or immediately after presentation of a word list. Moreover, in order to investigate whether the effect of glucose administration on memory performance is time-dependent, a third group received 25 g of glucose 15 min before learning the word list. Word- list recall was tested 30 min and 24 h after word list presentation. Measures of spatial memory performance and working memory were also evaluated. The results of this study showed that both pre- and post-acquisition oral glucose administration (25 g) can improve memory performance. However, as the time interval between anterograde glucose administration and memory encoding increased, the glucose memory facilitation effect decreased. This study provides evidence that glucose enhances memory performance in healthy young people even when it is given after learning has taken place, and that this effect is observed at least up to 24 h after glucose administration. Moreover, it provides evidence that the effect of glucose on memory performance may be time-dependent, as the enhancement of retention was decreased when the administration-learning interval was increased.
Article
The effects of a pure ginseng preparation on a variety of cognitive functions was compared with those of placebo in a double-masked, randomized, test-retest design. The subjects were healthy volunteers older than 40 years of age who were given the ginseng preparation or placebo for 8 to 9 weeks. Of the 112 subjects who completed the study, 55 received ginseng and 57 received placebo. The ginseng group showed a tendency to faster simple reactions and significantly better abstract thinking than the controls. However, there was no significant difference between the two groups in concentration, memory, or subjective experience.
Article
The present study was designed to investigate the possible neuroprotective activity of ginseng roots in 5-min ischemic gerbils using a step-down passive avoidance task and subsequent neuron and synapse counts in the hippocampal CA1 region. The following drugs were administered for 7 days before the induced ischemia: red ginseng powder (RGP), crude ginseng saponin (CGS), crude ginseng non-saponin (CGNS), and pure ginsenosides Rb1, Rg1 and Ro. Oral administration of RGP significantly prevented the ischemia-induced decrease in response latency, as determined by the passive avoidance test, and rescued a significant number of ischemic hippocampal CA1 pyramidal neurons in a dose-dependent manner. Intraperitoneal injections of CGS exhibited a similar neuroprotective effect. CGNS had a significant but less potent protective effect against impaired passive avoidance task and degeneration of hippocampal CA1 neurons. Ginsenoside Rb1 significantly prolonged the response latency of ischemic gerbils and rescued a significant number of ischemic CA1 pyramidal neurons, whereas ginisenosides Rg1 and Ro were ineffective. Postischemic treatment with RGP, CGS or ginsenoside Rb1 was ineffective. The neuroprotective activities of RGP, CGS and ginsenoside Rb1 were confirmed by electron microscopy counts of synapses in individual strata of the CA1 field of ischemic gerbils pretreated with the drugs. These findings suggest that RGP and CGS are effective in the prevention of delayed neuronal death, and that ginsenoside Rb1 is one of the neuroprotective molecules within ginseng root.
Article
Various tests of psychomotor performance were carried out in a group of 16 healthy male volunteers given a standardized preparation of Korean ginseng (G 115; 100 mg twice a day for 12 weeks) and in a similar group given identical placebo capsules under double-blind conditions. A favourable effect of G 115 relative to baseline performance was observed in attention (cancellation test), processing (mental arithmetic, logical deduction), integrated sensory-motor function (choice reaction time) and auditory reaction time. However, end performance of the G 115 group was superior statistically to the placebo group only in mental arithmetic. No difference between G 115 and placebo was found in tests of pure motor function (tapping test), recognition (digit symbol substitution) and visual reaction time. No adverse effects were reported. It is concluded that G 115 may be superior to placebo in improving certain psychomotor functions in healthy subjects.
Article
The pharmacokinetic charactor of ginsenoside Rg1, one of the main saponins of ginseng (Panax ginseng C.A. MEYER), was investigated in rats by using thin-layer chromatography (TLC) and a dual-wavelength TLC scanner. Ginsenoside Rg1 was absorbed rapidly from the upper parts of the digestive tract (accounting for 1.9-20.0% of the dose of Rg1 administered orally). The serum level of ginsenoside Rg1 reached its peak at 30 min, and the maximum levels of ginsenoside Rg1 in tissues were attained within 1.5 h. However, ginsenoside Rg1 was not found in the brain. Ginsenoside Rg1 was excreted into rat urine and bile in a 2 : 5 ratio. It was also proved that ginsenoside Rg1 was not significantly metabolized in the liver. However, the decomposition and/or metabolism of ginsenoside Rg1 in rat stomach and large intestine were confirmed.
Article
The pharmacokinetic character of ginsenoside Rb1 (Rb1), one of the main 20 (S)-protopanaxadiol group saponins of ginseng (Panax ginseng C.A. MEYER), was investigated in rats. First, quantitative analysis of Rb1 in biological samples was investigated and the most suitable assay procedure for each biological sample was established. Little Rb1 was absorbed from the digestive tract after oral administration (100mg/kg) to rats. The serum level of Rb1 in rats after intravenous injection (5 mg/kg) declined biexponentially, and the half-life of the β-phase was 14.5 h. The long persistence of Rb1 in serum and tissues in rats after intravenous administration was assumed to correlate with the high activity of plasma protein binding. Rb1 was gradually excreted into urine, but not bile. Unabsorbed Rb1 in the digestive tract was rapidly decomposed and/or metabolized mainly in the large intestine. These results are quite different from our results on ginsenoside Rg1 in rats.
Article
Some fractions extracted from ginseng radix (HAKUSAN) caused hypoglycemic effect on alloxan diabetic mice. The effect was abolished by the i.v. injection of antisera against bovine insulin. The same doses of the ginseng fraction (10--50 mg/kg) produced an increase in the blood insulin level in alloxan diabetic mice. Normal mice loaded i.p. with glucose (2 g/kg or more) showed also such an increase. Insulin release from perfused rat pancreases was stimulated by the ginseng fraction (0.2 mg/ml), but the potency was not stronger than that of the sulfonylureas. It was demonstrated that glucose-induced insulin release was marked in the presence of the ginseng fraction. Impaired insulin responses to glucose in alloxan diabetic rats were increased by the fraction (0.5 mg/ml) to or above the control responses in normal rats. The enhanced effect was observed also in the presence of 100 microgram/ml cycloheximide. These results indicate that some ginseng fractions stimulated insulin release, especially glucose-induced insulin release from pancreatic islets and thereby lowered the blood glucose level.
Article
The effects of Panax ginseng extract, ginseng saponins, and some other triterpenoid saponins on glucose uptake were examined by using sheep erythrocytes. Initial rates of glucose transport were determined by measurements of 2-deoxy-D-glucose (2-DG) uptake. From kinetic analysis apparent Km and Vmax values of facilitated glucose transport in sheep erythrocytes were calculated as 2.3 +/- 0.08 mM and 1.4 +/- 0.05 nmol/min/10(9) cells. The results showed that ginseng extract stimulated glucose uptake in sheep erythrocytes dose-dependently. Ginseng saponins, in general, also stimulated glucose transport. The maximum effect was observed at 1 microM of ginsenoside Rb1 showing an increase of 24 +/- 5% above basal activity. However, ginsenoside Rg3, chikusetsusaponin Ia, and glycyrrhetic acid induced significant inhibitory effects on glucose transport in sheep erythrocytes.
Article
The effects of Panax ginseng ethanol extract and its water (WSF)- and lipid-soluble (LSF) fractions on the scopolamine-induced disruption of radial maze performance in rats were examined. Ginseng root was refluxed with ethanol, and WSF and LSF were prepared from this ethanol extract. Scopolamine (0.075-0.3 mg/kg, i.p.) dose-dependently impaired the maze performance. However, the oral administration of Panax ginseng ethanol extract and WSF (2-8 g dried root/kg) 90 min before testing improved the maze performance disrupted by scopolamine (0.3 mg/kg) in a dose-dependent manner, but LSF failed to attenuate the disruption. These data suggest that ginseng extract possesses a beneficial effect regarding spatial cognitive impairment and that the water-soluble fraction of ginseng extract mainly contributes to the effect of the ethanol extract.
Article
To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients. In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. Ginseng may be a useful therapeutic adjunct in the management of NIDDM.
Article
The oral administration of the water extract of Ginseng Radix (GR) to normal and epinephrine-induced hyperglycemic mice caused a significant decrease in the blood glucose level 4 h after its administration. The hepatic content of facilitative glucose transporter isoform 2, liver type glucose transporter (GLUT2) protein content from mouse liver significantly increased in the orally GR-treated normal and epinephrine-induced hyperglycemic mice compared to that in the controls. These results suggest that the hypoglycemic activity of GR is presumably due, at least in part, to the increment of GLUT2 protein content.
Article
Panax ginseng is used in traditional Chinese medicine to enhance stamina and capacity to cope with fatigue and physical stress. Major active components are the ginsenosides, which are mainly triterpenoid dammarane derivatives. The mechanisms of ginseng actions remain unclear, although there is an extensive literature that deals with effects on the CNS (memory, learning, and behavior), neuroendocrine function, carbohydrate and lipid metabolism, immune function, and the cardiovascular system. Reports are often contradictory, perhaps because the ginsenoside content of ginseng root or root extracts can differ, depending on the method of extraction, subsequent treatment, or even the season of its collection. Therefore, use of standardized, authentic ginseng root both in research and by the public is to be advocated. Several recent studies have suggested that the antioxidant and organ-protective actions of ginseng are linked to enhanced nitric oxide (NO) synthesis in endothelium of lung, heart, and kidney and in the corpus cavernosum. Enhanced NO synthesis thus could contribute to ginseng-associated vasodilatation and perhaps also to an aphrodisiac action of the root. Ginseng is sold in the U.S. as a food additive and thus need not meet specific safety and efficacy requirements of the Food and Drug Administration. Currently, such sales amount to over $300 million annually. As public use of ginseng continues to grow, it is important for this industry and Federal regulatory authorities to encourage efforts to study the efficacy of ginseng in humans by means of appropriately designed double-blind clinical studies.
Article
We evaluated the effects of a Ginkgo biloba/ginseng combination on cognitive function in this 90-day, double-blind, placebo-controlled, parallel-group study. Sixty-four healthy volunteers (aged 40 to 65 years), selected on the basis of fulfilling the ICD-10 F48.0 criteria for neurasthenia, were assigned randomly to four equal dosing groups, receiving 80, 160, or 320 mg of the combination b.i.d. or placebo. Assessments were performed on the day before dosing, and again at Days 1, 30, and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose. The assessments included the Cognitive Drug Research (CDR) computerized assessment system, the Vienna Determination Unit, cycle ergometry, and various questionnaires. The treatments were well tolerated by all volunteers. On Day 90 at 1 hour post morning dosing, dose-related improvements were seen on the CDR tests, the 320 mg dose being significantly superior to placebo. These effects, however, were reversed 1 hour after the afternoon dose, possibly suggesting that a longer inter-dosing interval would be preferable. The 80-mg dose produced a significant benefit on the ergometry assessment of heart rate at maximum load. There were also several supporting changes from other assessments, including an advantage of 320 mg over placebo on the global score from the Symptom Checklist-90-revised (SCL-90-R) at Day 90.
Article
Ginseng is a highly valued herb in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the beneficial effects of ginseng and its constituents. The major active components of ginseng are ginsenosides, a diverse group of steroidal saponins, which demonstrate the ability to target a myriad of tissues, producing an array of pharmacological responses. However, many mechanisms of ginsenoside activity still remain unknown. Since ginsenosides and other constituents of ginseng produce effects that are different from one another, and a single ginsenoside initiates multiple actions in the same tissue, the overall pharmacology of ginseng is complex. The ability of ginsenosides to independently target multireceptor systems at the plasma membrane, as well as to activate intracellular steroid receptors, may explain some pharmacological effects. This commentary aims to review selected effects of ginseng and ginsenosides and describe their possible modes of action. Structural variability of ginsenosides, structural and functional relationship to steroids, and potential targets of action are discussed.
Article
Previous research has identified that glucose administration can enhance cognitive performance, especially during more intense cognitive processing. There appears to be a reciprocal relationship between falling glucose levels and cognitive performance, particularly under conditions of cognitive demand. The present placebo-controlled, double-blind, balanced, crossover study examined the possibility that a high cognitive load may produce changes in blood glucose levels. A secondary aim was to examine the effects of glucose on tasks of varying cognitive demand load. The effects of a glucose drink on participants' performance of a serial subtraction task (computerised Serial Sevens), a somatically matched control task (key-pressing), a short interval Word Memory task and a Word Retrieval (Verbal Fluency) task were assessed. The change in blood glucose during the demanding computerised Serial Sevens was compared to the change occurring during the key-pressing control. Glucose consumption significantly improved performance on Serial Sevens, with a trend for improved performance on Word Retrieval and no effect on the Word Memory task. Compared with the control task, Serial Sevens resulted in a significant reduction in blood glucose in both drink conditions. This accelerated decay was significantly greater following glucose than placebo. It is suggested that the amount of cognitive load associated with task performance is an index of its sensitivity to enhancement by glucose. Furthermore, a period of intense cognitive processing leads to a measurable decrease in levels of peripherally measured blood glucose, which may be linked to increased neural energy expenditure. However, the relative contribution of central and peripheral (e.g. cardiac) activity to this effect has yet to be determined.
Article
It has previously been demonstrated in separate studies that single doses of Ginkgo biloba, Panax ginseng, and a combination of the two extracts can improve different aspects of cognitive performance in healthy young volunteers. The present study directly compared the effects of single doses of G. biloba, ginseng, and a product combining the two on aspects of mood and cognitive performance in the same cohort of healthy, young adult volunteers. The study followed a randomised placebo-controlled, double-blind, balanced, cross-over design. Twenty participants received 360 mg of ginkgo, 400 mg of ginseng, 960 mg of a product combining the two extracts, and a matching placebo. Treatment order was dictated by random allocation to a Latin square, with a 7-day wash-out period between treatments. Cognitive testing comprised completion of the Cognitive Drug Research (CDR) computerised assessment battery and two serial subtraction mental arithmetic tasks. Mood was assessed with Bond-Lader visual analogue scales. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4, and 6 h after the day's treatment was taken. The results largely supported previous findings. All three treatments were associated with improved secondary memory performance on the CDR battery, with the ginseng condition evincing some improvement in the speed of performing memory tasks and in the accuracy of attentional tasks. Following ginkgo and the ginkgo/ginseng combination performance of both the Serial Threes and Serial Sevens, subtraction tasks was also improved at the later testing sessions. No modulation of the speed of performing attention tasks was evident. Improvements in self-rated mood was also found following ginkgo and to a lesser extent the combination product.
Article
The present paper describes three studies examining the acute effects of single doses of Ginkgo biloba (GK501), Ginseng (G115) and their combination (Ginkoba M/E, Pharmaton SA) on the performance of healthy young adults (mean age 21 years) during serial arithmetic tasks with differing cognitive load. In each double-blind, placebo-controlled study three different treatment doses and a placebo were administered, according to a balanced crossover design, with a 7-day washout period between each dose. Participants' scores on two computerised serial subtraction tasks (Serial Threes and Serial Sevens) were assessed pre-dosing and at 1, 2.5, 4 and 6 h thereafter. A number of significant time, dose and task-specific effects were associated with each treatment. There was a dose-dependent improvement in speed of responding during Serial Threes following Ginkgo biloba. Different doses of Ginseng improved accuracy and slowed responses during Serial Sevens. The most striking result, however, was a highly significant and sustained increase in the number of Serial Sevens responses following 320 mg of the Ginkgo–Ginseng combination at all post-treatment testing times. This was accompanied by improved accuracy during Serial Sevens and Serial Threes following the 640 mg and the 960 mg dose, respectively. The paper concludes with speculation into the possible mechanisms underlying these effects. Copyright
Article
Both Ginkgo biloba and Panax ginseng exert a number of physiological effects and have been shown to modulate aspects of cognitive performance. Whilst a number of studies have examined ginkgo's effects on electroencephalograph (EEG) recordings, to date, none have investigated the EEG effects of ginseng. In this double-blind, placebo-controlled, balanced crossover experiment, the effects of single doses of G. biloba (360 mg GK501), P. ginseng (200 mg G115), and an identical placebo, on auditory-evoked potentials, contingent negative variation (CNV), and resting power within the delta, theta, alpha, and beta wavebands, were assessed in 15 healthy volunteers. Each participant was assessed on three separate occasions 4 h after consuming that day's treatment. The order of presentation of the treatments was dictated by a Latin square with 7 days between testing sessions. The results showed that ginseng led to a significant shortening of the latency of the P300 component of the evoked potential. Both ginseng and ginkgo also led to significant reductions in frontal 'eyes closed' theta and beta activity, with additional reduction for ginseng in the alpha waveband. These findings demonstrate for the first time that P. ginseng can directly modulate cerebroelectrical activity, and that these effects are more pronounced than those following G. biloba.
Article
Ginseng has been used medicinally in the Far East for several millennia and is currently one of the most widely taken herbal products throughout the world. It has been attributed with a plethora of physiological effects that could potentially benefit cognitive performance or mood. Studies involving animals show that ginseng and its constituent ginsenosides can modulate indices of stress, fatigue, and learning. However, there is a lack of adequately controlled research showing behavioural effects following chronic administration to humans. Recent research has demonstrated that single doses of ginseng most notably engender cognitive benefits in terms of improved memory, but can also be associated with 'costs' in terms of attention task deficits following less mnemonically beneficial doses. A single dose of ginseng has also been shown to modulate cerebroelectrical (EEG) activity. It is suggested that ginseng would benefit from rigorous research further delineating its acute effects and exploring the relationship between acute effects and those seen during and following chronic administration regimens.
Article
This random double-blind trial compares psychological well-being and perceived quality of life in 60 subjects (18 M, 42 F), mean age 61 years, with age-associated memory impairment (AAMI), who were administered a standardised ginseng-containing vitamin complex or placebo for 9 months. We evaluated psychological well-being, in terms of affective status and memory functioning using the Symptom Rating Test [SRT] (depression, anxiety, somatisation, inadequacy) and Randt Memory Test [RMT] (memory index [MI]), respectively, and the quality of life, using the Life Satisfaction in the Elderly Scale [LSES]. At final evaluation, SRT did not differ in the drug and placebo groups, whereas MI and LSES were significantly higher in the drug-treated group. Moreover, the negative correlation between the affective (SRT) and cognitive (MI) component of psychological well-being waned in the drug-treated but not placebo group. In the drug-treated group, a positive correlation emerged between the cognitive index and social contacts, mood and self-concept factors of the LSES. In both groups, the initial negative correlations between quality of life (LSES) and affection (SRT) persisted at the end of the study. Drug-treated AAMI subjects differ from controls in part by improved scores on objective cognitive tests but even more so by modifications of the correlations among indexes of psychological well-being and quality of life.
The psychopharmacology of herbal medicine: plant drugs that alter mind, brain, and behavior
  • M Spinella
Spinella, M. (2001) The psychopharmacology of herbal medicine: plant drugs that alter mind, brain, and behavior, (Cambridge, Massachusetts: MIT Press)
Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats
  • Q F Xu
  • X L Fang
  • D F Chen
Xu, Q.F., Fang, X.L. and Chen, D.F. (2003) Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. Journal of Ethnopharmacology 84, 187-192.