Clinical Research

Dandelion Extract

1) Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons.

Neurobiology of Aging. Volume 33, Issue 1, January 2012, Pages 176–186. http://www.sciencedirect.com/science/article/pii/S0197458010000928

Relevant finding: Increased attention has been paid to the role of oxidant/antioxidant imbalance in neurodegenerative process and pharmaceutical neuroprotective interventions. Food-derived compound luteolin possesses multitarget actions including reactive oxygen species (ROS)- scavenging activity in cultured human endothelial cells or permanent immature rat oligodendrocytes. The results of the study shows that, luteolin functions by neuroprotection possibly through a rebalancing of pro-oxidant-antioxidant status. This agent points to possible interventions for preventing neurodegenerative diseases, as well as for improving brain aging.

2) Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long- lasting long-term potentiation and improves memory.

Proc Natl Acad Sci U S A. 1998 Dec 8; 95(25): 15020–15025. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC24568/

Relevant findings: High-dose rolipram, by generally raising cAMP concentration throughout the brain, may enhance memory by a different mechanism when given after training, perhaps by consolidating changes at recently stimulated synapses “tagged” by endogenous signaling mechanisms (32, 33).Our biochemical results indicate that it is possible to increase signaling in the cAMP pathway without significantly affecting basal cAMP concentrations. Targeting the degradative enzyme, in this case PDE, may be particularly fruitful because partial inhibition of degradation may be undetectable at basal levels of substrate, when the degradative enzyme is likely to be present in great excess, and homeostatic mechanisms may compensate for low levels of inhibition (34). Because rolipram is a competitive inhibitor with cAMP for PDE, Michaelis––Menton kinetics suggest that our results are most consistent with a model in which basal adenylyl cyclase activity is reduced to match that of the inhibited PDE [perhaps through phosphorylation by PKA (35, 36)], although retaining its normal potential for activation by forskolin. When signaling increases substrate concentration and stresses the capacity of the degradative enzyme, it uncovers the effect of the inhibitor and amplifies the size of the cAMP signal. Similar targeting of catabolic enzymes for low-level inhibition may be a fruitful means of amplifying other second-messenger signal to noise ratios for experimental and clinical purposes.

Forskolin

1) Forskolin: a unique diterpene activator of cyclic AMP-generating systems.

Journal of Cyclic Nucleotide Research [1981, 7(4):201-224] http://europepmc.org/abstract/MED/6278005/

Relevant finding: Forskolin, a diterpene of the labdane family, activates adenylate cyclase in broken cell preparations as well as in intact tissues. This activation does not require the guanine nucleotide regulatory subunit of the enzyme and probably occurs via an interaction with the catalytic subunit of adenylate cyclase. Activation of adenylate cyclase by forskolin results in marked increases in levels of intracellular cyclicAMP in a variety of eukaryotic cells. Low concentrations of forskolin which alone elicit small increases in intracellular cyclic AMP greatly potentiate hormonal activation of adenylate cyclase in a number of intact cells. Forskolin elicits cellular responses which have been proposed to be dependent on cyclicAMP as a second messenger. Forskolin, thus provides an invaluable tool for the investigation of the role of cyclic AMP in physiological responses to hormones, both through it direct activation of adenylate cyclase and through its ability to potentiate hormonal activation of adenylate cyclase.

2) Delayed memory dysfunction by transient hypoxia, and its prevention with forskolin.

Brain Research, Volume 405, Issue 2, 10 March 1987, Pages 371–374 http://www.sciencedirect.com/science/article/pii/0006899387903088

Relevant finding: Rats exposed to 40 min hypoxia 3 h before a one-trial learning passive avoidance task showed impaired memory retention 24 h later. This model was used to assess the ability of forskolin to restore the delayed memory dysfunction. Significant amelioration of memory retention was observed when forskolin (500 µg/kg, i.p.) was injected just after hypoxia.
Forskolin is suggested to enhance cerebral blood flow and to facilitate memory function through the action of increased cyclic adenosine monophosphate (cAMP).

3) Stimulation of Adenylyl Cyclase and Induction of Brain-Derived Neurotrophic Factor and TrkB mRNA by NKH477, a Novel and Potent Forskolin Derivative.

Journal of Neurochemistry, Volume 72, Issue 5, pages 2198–2205, May 1999 http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.1999.0722198.x/full

Relevant finding: The present study was undertaken to examine whether NKH477, a novel and potent water- soluble forskolin derivative, stimulates adenylyl cyclase and regulates brain- derived neurotrophic factor (BDNF) and TrkB expression in the rat brain. Administration of NKH477 at a dose of 1.0 mg/kg, but not 0.1 mg/kg, increased levels of cyclic AMP (cAMP) in a time-dependent manner in frontal cortex and hippocampus. Repeated administration of NKH477 (1.0 mg/kg) for 7 or 14 days also increased levels of cAMP in these two brain regions, indicating that the response does not desensitize with chronic treatment. In addition, administration of NKH477 at the 1 mg/kg dose increased the expression of BDNF and TrkB mRNA in frontal cortex and hippocampus. This effect was observed after single, as well as repeated (7 or 14 days), administration of NKH477. These results demonstrate that NKH477 administration rapidly increases cAMP levels in brain and provides evidence that stimulation of this second messenger system increases the expression of BDNF and TrkB mRNA.

4) Forskolin-induced LTP in the CA1 hippocampal region is NMDA receptor-dependent.

Articles in PresS. J Neurophysiol (December 31, 2003).10.1152/jn.00941.2003 http://jn.physiology.org/content/jn/early/2003/12/31/jn.00941.2003.full.pdf?origin=publication_detail

Relevant finding: Chemically induced long-term potentiation (cLTP) could potentially work by directly stimulating the biochemical machinery that underlies synaptic plasticity, bypassing the need for synaptic activation. Previous reports suggested that agents that raise cAMP concentration might have this capability. We examined the cLTP induced in acute slices by application of Sp-cAMPS or a combination of the adenylyl cyclase activator, Forskolin, and the phosphodiesterase inhibitor, Rolipram. Under our conditions, cLTP was induced, but only if inhibition was reduced. We found that this form of cLTP was blocked by an NMDAR antagonist and required the low-frequency test stimulation typically used to monitor the strength of synapses. Interestingly, similar LTP could be induced by lowering the Mg2+ concentration of the ACSF during Forskolin/Rolipram or Sp-cAMPS application or even by just lowering Mg2+ concentration alone. This LTP was also NMDAR-dependent and required only a few (around five) low frequency stimuli for its induction. The finding that even low frequency synaptic stimulation was sufficient for LTP induction indicates that a highly sensitized plasticity state was generated. The fact that some stimulation was required means that potentiation is probably restricted to the stimulated axons, limiting the usefulness of this form of cLTP. However, when similar experiments were conducted using slice cultures, potentiation occurred without test stimuli, probably because the CA3-CA1 connections are extensive and because presynaptic spontaneous activity is sufficient to fulfill the activity requirement. As in acute slices, the potentiation was blocked by an NMDAR antagonist. Our general conclusion is that the induction of LTP caused by elevating cAMP requires presynaptic activity and NMDA channel opening. The method of inducing cLTP in slice cultures will be useful when it is desirable to produce NMDAR-dependent LTP in a large fraction of synapses.

L–Theanine

1) Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats.

Neurochem Res. 1998. http://www.ncbi.nlm.nih.gov/pubmed/9566605

Relevant finding: Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (+/-)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.

2) The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial.

Altern Med Rev. 2011 Dec;16(4):348-54. http://www.ncbi.nlm.nih.gov/pubmed/22214254

Relevant finding: This study demonstrates that 400 mg daily of L-theanine is safe and effective in improving some aspects of sleep quality in boys diagnosed with ADHD. Since sleep problems are a common co-morbidity associated with ADHD, and because disturbed sleep may be linked etiologically to this disorder, L-theanine may represent: a safe and important adjunctive therapy in childhood ADHD. Larger, long-term studies looking at the wider therapeutic role of this agent in this population are warranted.

3) L-theanine, a natural constituent in tea, and its effect on mental state.

Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8. http://www.ncbi.nlm.nih.gov/pubmed/18296328

Relevant findings: These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.

Acetyl–L–Carnitine

1) Acetyl-L-carnitine (ALC) in attention-deficit/hyperactivity disorder: a multi-site, placebo- controlled pilot trial.

J Child Adolesc Psychopharmacol. 2007 Dec;17(6):791-802. doi: 10.1089/cap.2007.018. http://www.ncbi.nlm.nih.gov/pubmed/18315451

Relevant finding: Objective of this study was to determine whether acetyl-L-carnitine (ALC), a metabolite necessary for energy metabolism and essential fatty acid anabolism, might help attention-deficit/hyperactivity disorder (ADHD). Trials in Down's syndrome, migraine, and cognitive decline showed benefit for attention. A preliminary trial in ADHD using L-carnitine reported significant benefit. A multi-site 16-week pilot study randomized 112 children (83 boys, 29 girls) age 5-12 with systematically diagnosed ADHD to placebo or ALC in weight-based doses from 500 to 1500 mg b.i.d. The 2001 revisions of the Conners' parent and teacher scales (including DSM-IV ADHD symptoms) were administered at baseline, 8, 12, and 16 weeks. ALC appears safe, but with no effect on the overall ADHD population (especially combined type). It deserves further exploration for possible benefit specifically in the inattentive type.

2) Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild cognitive decline.

International Clinical Psychopharmacology: March 2003 - Volume 18 - Issue 2 - pp 61-71. http://journals.lww.com/intclinpsychopharm/Abstract/2003/03000/Meta_analysis_of_double_blind_randomized.1.aspx

Relevant findings: The efficacy of acetyl-L-carnitine (gamma-trimethyl-ß-acetylbutyrobetaine (Alcar) in mild cognitive impairment (MCI) and mild (early) cognitive decline was investigated with a meta-analysis of double-blind, placebo-controlled prospective, parallel group comparison studies of at least 3 months duration. The duration of the studies was 3, 6 or 12 months and the daily dose varied between studies from 1.5–3.0 g/day. An effect size was calculated to reflect the results of the variety of measures used in the studies grouped into the categories of clinical tests and psychometric tests. The effect sizes from the categories were integrated into an overall summary effect size. The effect size for the Clinical Global Impression of Change (CGI-CH) was calculated separately. Meta-analysis showed a significant advantage for Alcar compared to placebo for the integrated summary effect [ESall scales=0.201, 95% confidence interval (CI)=0.107–0.295] and CGI-CH (ESCGI-CH=0.32, 95% CI=0.18–0.47). The beneficial effects were seen on both the clinical scales and the psychometric tests. The advantage for Alcar was seen by the time of the first assessment at 3 months and increased over time. Alcar was well tolerated in all studies.

3) A double-blind, randomised, controlled clinical trial of acetyl-L-carnitine vs. amisulpride in the treatment of dysthymia.

Eur Neuropsychopharmacol. 2006. Department of Psychiatry, School of Medicine, Vita-Salute University San Raffaele, Milan, Italy. http://www.ncbi.nlm.nih.gov/pubmed/16316746

Relevant findings: Researchers evaluated the effect of acetyl-L-carnitine ( ALCAR ) vs. amisulpride measured by total Hamilton Depression Rating Scale score in patients with pure dysthymia. Two hundred and four patients were randomised and treated with ALCAR 500 mg twice a day or amisulpride 50 mg u.i.d. in a double-blind study, for 12 weeks. A solid improvement was observed in both treatment groups throughout the study. The results did not disclose statistically significant differences between treatments. The greater tolerability of ALCAR is of clinical relevance considering the chronicity of dysthymia, which often requires prolonged treatment.

Grape Seed Extract

1) Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract.

Neuroscience Letters, Volume 383, Issue 3, 5 August 2005, Pages 295–300. http://www.sciencedirect.com/science/article/pii/S0304394005004477

Relevant findings: Oxidative stress is considered as a major risk factor that contributes to age- related increase in lipid peroxidation and declined antioxidants in the central nervous system during aging. Grape seed extract, one of the bioflavonoid, is widely used for its medicinal properties. In the present study, we evaluated the role of grape seed extract on lipid peroxidation and antioxidant status in discrete regions of the central nervous system of young and aged rats. The findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in the central nervous system of aged rats.

2) Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats.

Exp Gerontol. 2011 Nov;46(11):958-64. doi: 10.1016/j.exger.2011.08.006. Epub 2011 Aug 16. http://www.ncbi.nlm.nih.gov/pubmed/21871550

Relevant findings: here is growing concern over the increasing instances of decline in cognitive abilities with aging in humans. The present study evaluated the benefits of the natural antioxidant, grape seed proanthocyanidin extract (GSPE) in treating the effects of age-related oxidative stress (OS) and accumulation of lipofuscin (LF) on the cognitive ability in rats. Female Wistar rats of 3- and 12-months of age received a daily oral supplement of GSPE until they attained 6- and 15-months of age. During this period, rats were tested for their cognitive ability. At the end of this period, blood glucose and markers of OS were assessed in the hippocampus. GSPE lowered blood glucose, lipid peroxidation, hydrogen peroxide level, and increased protein sulphydryl (P-SH) content in the hippocampus. In addition, GSPE significantly improved cognitive performance in the two age groups. These results demonstrate that the extent of OS- related LF accumulation is reducible by GSPE. They also suggest a critical role for GSPE as a neuroprotectant in the hippocampus and in preventing cognitive loss with aging.

3) Age-related oxidative protein damages in central nervous system of rats: modulatory role of grape seed extract.

Int J Dev Neurosci. 2005 Oct;23(6):501-7. http://www.ncbi.nlm.nih.gov/pubmed/16009524

Relevant findings: Oxidative stress has been shown to play a major role in aging and in neurodegenerative disorders. Protein modification is one of the important consequences of oxidative stress. In the present study, we evaluated the role of grape seed extract on memory, reactive oxygen species production, protein carbonyls (PCO), and thiol status in discrete regions of central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I--control young rats, Group II--young rats treated with grape seed extract (100 mg/kg BW) for 30 days, Group III--aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg BW) for 30 days. Memory loss was observed in the aged rats. Age associated increase in reactive oxygen species production and protein oxidation was observed in the spinal cord; cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). The levels of total thiol, non-protein thiol, protein thiols were found to be significantly decreased in spinal cord and all the brain regions studied in aged rats when compared to young rats. Supplementation of aged rats with grape seed extract showed increased memory performance and declined reactive oxygen species production, decreased protein carbonyl levels and improved thiol levels. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical induced protein oxidation in aged rats thereby protecting the central nervous system from the reactive oxygen species.

Brahmi (Bacopa Monnieri)

1) Bacopa monnieri and Bacoside-A for ameliorating epilepsy behavioral deficits.

Fitoterapia. Volume 81, Issue 5, July 2010, Pages 315–322. http://www.sciencedirect.com/science/article/pii/S0367326X09002731

Relevant finding: Bacopa monnieri is an outstanding nervine tonic used for raising the mental performance. It helps in concentration, comprehension, recall and alertness, Brahmi is particularly beneficial as it aids in categorizing information in brain and its subsequent expression. Bacopa is also called as a natural antioxidant which may give details its neuroprotective role seen in the memory centers of the brain.

2) An Acute, Double-Blind, Placebo-Controlled Cross-over Study of 320 mg and 640 mg Doses of Bacopa monnieri (CDRI 08) on Multitasking Stress Reactivity and Mood.

Phytotherapy Research. Volume 28, Issue 4, pages 551–559, April 2014. http://onlinelibrary.wiley.com/doi/10.1002/ptr.5029/abstract

Relevant findings: Indicated positive cognitive effects, notably at both 1 h post and 2 h post BM consumption on the Letter Search and Stroop tasks, suggesting an earlier nootropic effect of BM than previously investigated. There were also some positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction associated with BM consumption. It was concluded that acute BM supplementation produced some adaptogenic and nootropic effects that need to be replicated in a larger sample and in isolation from stressful cognitive tests in order to quantify the magnitude of these effects.

3) Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial.

The Journal of Alternative and Complementary Medicine. Volume: 14 Issue 6: August 6, 2008. http://online.liebertpub.com/doi/abs/10.1089/acm.2008.0018

Relevant findings: Controlling for baseline cognitive deficit using the Blessed Orientation– Memory–Concentration test, Bacopa participants had enhanced AVLT delayed word recall memory scores relative to placebo. Stroop results were similarly significant, with the Bacopa group improving and the placebo group unchanged. CESD-10 depression scores, combined state plus trait anxiety scores, and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated with few adverse events (Bacopa n = 9, placebo n = 10), primarily stomach upset. This study provides further evidence that B. monnieri has potential for safely enhancing cognitive performance in the aging.

Deanol (DMAE)

1) New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger.

Drug Metab Lett. 2012 Mar;6(1):54-9. http://www.ncbi.nlm.nih.gov/pubmed/22300295

Relevant findings: Recently, a number of synthetic drugs used in a variety of therapeutic indications have been reported to have antiaging effects. Among them, Dimethylaminoethanol (DMAE), an anologue of dietylaminoethanol, is a precursor of choline, which in turn allows the brain to optimize the production of acetylcholine that is a primary neurotransmitter involved in learning and memory. The data presented here includes new information on the ability of the compound to scavenge specific free radicals, assessed by Electron Spectroscopic Resonance (EPR), to further analyze the role of DMAE as an antioxidant. DMAE ability to directly react with hydroxyl, ascorbyl and lipid radicals was tested employing in vitro assays, and related to the supplemented dose of the compound.

2) Source density analysis of functional topographical EEG: monitoring of cognitive drug action.

Eur J Med Res. 1996 Mar 19;1(6):283-90. http://www.ncbi.nlm.nih.gov/pubmed/9367941

Relevant finding: In the light of the current hypothesis that high theta resting power and low increases at frontotemporal brain areas during mental work indicate mental impairment, treatment with the drug under investigation was seen to successfully reverse these changes. This drug effect was localized in the frontotemporal cortex in a statistically significant manner during both the memory and the symbol recognition tests. The observed effect is fully consistent with a previous study using Fourier transformed data from conventional EEG voltage recordings. It can be concluded that an analysis of EEG data by means of the charge mode provides an excellent tool to quantify drug effects especially in cognitive research. A second perspective arises from the fact that it should be possible to recognize mental impairments at a very early stage by using this method, thus providing the possibility of an early treatment.

3) Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies.

Psychopharmacology (Berl). 2009 Dec;207(2):201-12. doi: 10.1007/s00213-009-1648-7. Epub 2009 Sep 16. http://www.ncbi.nlm.nih.gov/pubmed/19756528

Relevant findings: Dimethylaminoethanol pyroglutamate (DMAE p-Glu) is a compound resulting from the reaction between dimethylaminoethanol (an indirect precursor of acetylcholine) and pyroglutamic acid (a cyclic derivative of glutamic acid having procholinergic properties and promnesic effects in both animals and man). These results indicate that DMAE p-Glu reduces the deleterious effect of scopolamine on long-term memory in healthy volunteers and suggest that DMAE p-Glu might be effective in reducing memory deficits in patients with cognitive impairment.

Vitamin B6

1) Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders.

Magnesium Research : Official Organ of the International Society for the Development of Research on Magnesium [2006, 19(1):46-52]. http://europepmc.org/abstract/MED/16846100

Relevant findings: Some previous studies have reported the involvement of magnesium (Mg) deficiency in children with ADHD syndrome. In this work, 40 children with clinical symptoms of ADHD were followed clinically and biologically during a magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6) which was set up for at least 8 weeks. Symptoms of ADHD (hyperactivity, hyperemotivity/ aggressiveness, lack of attention at school) were scored (0-4) at different times; in parallel, intraerythrocyte Mg2+ (Erc-Mg) and blood ionized Ca2+ (i-Ca) were measured. Children from the ADHD group showed significantly lower Erc-Mg values than control children (n = 36). In almost all cases of ADHD, Mg-B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg-B6 regimen led to a significant increase in Erc-Mg values. When the Mg-B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc-Mg values. This study brings additional information about the therapeutic role of a Mg-B6 regimen in children with ADHD symptoms.

2) Neurological aspect of clinical symptoms, pathophysiology and correction in attention deficit hyperactivity disorder.

Zh Nevrol Psikhiatr Im S S Korsakova. 2006;106(2):17-20. http://www.ncbi.nlm.nih.gov/pubmed/16548369

Relevant finding: We studied prevalence of attention deficit hyperactivity disorder (ADHD) in senior schoolchildren of Nefteyugansk (Khanty-Mansysky autonomic region) it was 8% (13% among boys and 3% among girls). Clinical examination of 122 children, aged 6-11 years, revealed that risk factors for ADHD were perinatal CNS injures, familial predisposition, unfavorable social and psychological influences. Neuropsychological, neurophysiologic (electroencephalography) and biochemical study showed mild neurological disturbances, some peculiarities of motor and emotional spheres and higher mental functions. Moreover, there were such biochemical alterations as a decrease of magnesium level in the plasma and erythrocytes and a reduction of Mg(2+)-ATPase activity. The use of MAGNE-B6 allowed us to correct many of the disturbances.

3) Neurological aspects of the clinical features, pathophysiology, and corrections of impairments in attention deficit hyperactivity disorder.

Neurosci Behav Physiol. 2007 Mar;37(3):199-202. http://www.ncbi.nlm.nih.gov/pubmed/17294093

Relevant finding: The prevalence of attention deficit hyperactivity disorder (ADHD) in young schoolchildren in Nefteyugansk (Khanty-Mansiiskii Autonomous Region) was found to be 8%, with rates of 13% amongst boys and 3% amongst girls. Clinical investigation of a cohort of 122 children aged 6-11 years identified risk factors for the formation of ADHD as perinatal CNS injuries, inherited predisposition, and unfavorable social-psychological influences. Neuropsychological, neurophysiological (electroencephalography), and biochemical studies identified minor neurological abnormalities, some characteristic features of the motor and emotional spheres, and changes in higher mental functions. In addition, biochemical changes consisting of decreases in plasma and erythrocyte magnesium levels and decreases in Mg(2+)- ATPase activity were identified. Treatment with MAGNE-B(6) allowed correction of many of these changes.

Ginkgo Biloba

1) Effect of the herbal extract combination Panax quinquefolium and Ginkgo biloba on attention- deficit hyperactivity disorder: a pilot study.

J Psychiatry Neurosci. May 2001; 26(3): 221–228. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1408291

Relevant finding: A combination herbal product containing American ginseng extract, Panax quinquefolium, (200 mg) and Ginkgo biloba extract (50 mg) was tested for its ability to improve the symptoms of attention-deficit hyperactivity disorder (ADHD). Five (14%) of 36 subjects reported adverse events -like more emotional, more impulsive, more hyperactive and more aggressive were product related and uncertain(may or may not related to this product) adverse events like sweating, headache, tiredness-, only 2 of which were considered related to the study medication. These preliminary results suggest that, this treatment may improve symptoms of ADHD and should encourage further research on the use of ginseng and Ginkgo biloba extracts to treat ADHD symptoms.

2) Ginkgo biloba treating patients with attention-deficit disorder.

Phytotherapy Research Volume 24, Issue 1, pages 26–27, January 2010. http://onlinelibrary.wiley.com/doi/10.1002/ptr.2854/abstract

Relevant finding: Various medications such as clonidine facilitate calming, enhance frustration tolerance and reduce aggression in attention-deficit disorder (ADD) patients. The use of Ginkgo biloba was studied as an herbal alternative. Six psychiatric outpatients diagnosed with ADD were rated at baseline and while taking Ginkgo biloba to determine its efficacy as a treatment for ADD. Comparisons of Wender Utah ratings within subject were used to measure behavioral changes in the subjects. During Ginkgo biloba treatment, the patients' mean scores improved significantly overall and in hyperactivity, inattention, and immaturity factors. This preliminary study indicates that Ginkgo biloba might be a beneficial and useful treatment of ADD, with minimal side effects.

3) Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory.

Hum Psychopharmacol. 2001 Jul;16(5):409- 416. http://www.ncbi.nlm.nih.gov/pubmed/12404561

Relevant findings: A computerized test battery was used in a double-blind design to assess the cognitive effects of a nutrient compound containing Ginkgo biloba in 24 normal adults. Ten tasks (perceptual, attention and short-term memory) were presented in a standardized manner designed to maximize performance, with substantial pre-test practice employed to minimize response variability. Subjects were given either placebo or Ginkgo biloba extract capsules to consume for 14 days, after which they performed all tasks twice. They then received the other condition, and after 14 days completed the final test session. Response time and error rate stabilized after pre-test practice. A 'working memory capacity' paradigm demonstrated a reliable 50 ms response time decrease between the placebo and Ginkgo biloba testing, suggesting that Ginkgo biloba speeds short-term working memory processing in normal adults.

Korean Red Ginseng

1) Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults.

2002 Apr 15;75(5):739-51. http://www.ncbi.nlm.nih.gov/pubmed/12020739

Relevant 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. Improvements in self-rated mood was also found following ginkgo and to a lesser extent the combination product.

2. Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand.

Hum Psychopharmacol. 2002 Jan;17(1):35-44. http://www.ncbi.nlm.nih.gov/pubmed/12404705

Relevant findings: 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.

3. Improvement of Cognitive Deficit in cognitive decline Patients by Long Term Treatment with Korean Red Ginseng.

J Ginseng Res. 2011 Nov; 35(4): 457–461. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659550

Relevant findings: In conclusion, the effect of KRG on cognitive functions was sustained for 2 yr follow-up, indicating feasible efficacies of long-term follow-up for cognitive decline. Ginsenoside Rb1 attenuated 1-42-induced neurotoxicity and tau hyperphosphorylation at multiple AD-related sites in a dose-dependent manner. In addition, it has been suggested that ginsenoside Rg1 and Rb1 potentiated the cholinergic pathways in the central nervous system. Thus, both Rg1 and Rb1 enhanced choline acetyltransferase activity and inhibited acetylcholine -esterase activity, thereby enhancing the function of cholinergic system. Administration of Rg1 and Rb1 in weaning mice increased the cortex thickness and density of synapses in the hippocampal CA3 region, which is suggested to modulate synaptic plasticity, regarded as one of the most essential mechanism in learning and memory. Nevertheless, our results suggest that KRG treatment is both safe and feasible, and is effective for the long-term management of AD patients.