Powering Your Potential
MIND MILQ was designed to boost and sustain energy levels while supporting healthy cognitive function. Whether you need extra focus at work, or a little extra push before the gym, MIND MILQ delivers the energy and cognitive support you need to maximize your potential!
Sensoril® is the Leading Clinically Tested Stress Neutralizer
Sensoril® is the industry leading, branded ingredient that is clinically tested to help relieve the negative effects of stress. That’s why Sensoril® is the mood-enhancing nutraceutical of choice for many of America’s leading dietary supplement brands. Sensoril® is a multi-patented, all natural, standardized extract of Ashwagandha (Withania somnifera) with the highest, most potent levels of stress-fighting, cognition-enhancing Ashwagandha bioactive constituents in the industry. Ashwagandha, a revered botanical with adaptogenic properties, has been one of the primary ingredients used in India’s Ayurvedic medicinal treatments for thousands of years. Adaptogens are a select group of botanicals that help provide resistance to stress and bring the body back into balance once it has been stressed.
Sensoril® Possesses Multiple Health Benefits
Sensoril® is protected by multiple United States patents and is clinically tested in a double-blind, placebo-controlled, human clinical trial. With its adaptogenic properties and clinical trial support, Sensoril® possesses multiple health benefits and has been substantiated in the following structure/function claim areas: Stress Reduction, Energy, Mental Acuity and Concentration, Healthy Cardiovascular Function, Blood Sugar Balance, and Healthy Weight Management. Sensoril® also helps promote more restful sleep.*
Sensoril® is Appropriate to Use 365 Days a Year
Sensoril® is the favored ingredient of choice for many dietary supplement marketers because it possesses an excellent safety and stability profile supported by extensive testing. Because Sensoril® is GRAS-affirmed (Generally Regarded as Safe), it can be taken as a daily tonic 365 days a year. Sensoril® can be found in foods and beverages under the tradename, Essentra®. In addition, Sensoril® can be utilized in many types of delivery systems due to its free flowing powder consistency and high degree of solubility in water. These include in a tablet, capsule, effervescent, or stick pack as well as in ready-to-drink beverages, shakes, strips, chews, and food bars.
Sensoril® Provides Many Health Benefits
Multi-patented, clinically tested Sensoril® is the ultimate all natural, stress-reducing, mood-enhancing dietary supplement ingredient with multiple health benefits you can really feel! Sensoril® contains the highest, most potent levels of stress-fighting, cognition-enhancing Ashwagandha bioactive constituents, which are extracted using a patented, pure water-based process without the use of any chemical solvents. That’s why Sensoril® is the specialty ingredient of choice for consumers, formulators, and leading dietary supplement brands. Taken daily to help shield the body against the negative effects of stress, Sensoril® helps promote emotional well-being, increased resistance to fatigue and tension while boosting energy levels, and enhanced mental clarity and concentration.* Sensoril® also helps promote healthy cardiovascular function, resistance to stress-induced overeating for healthy weight management, and more restful sleep.* In addition, Sensoril® helps support blood sugar levels which are already within the normal range.*
Sensoril® is Tested in Human Clinical Trials
Modern science has tested that the key to Sensoril Ashwagandha extract’s adaptogenic, stress-reducing properties, is its ability to reduce levels of cortisol. Cortisol, the “stress hormone”, is responsible for producing many of the negative effects of stress in the body. This was demonstrated in a randomized, double-blind, placebo-controlled, human clinical trial. This type of study is considered the “Gold Standard” by researchers to demonstrate an ingredient’s efficacy and associated health benefits.
Huperzine-A is a cognitive enhancer that inhibits an enzyme that degrades the learning neurotransmitter, acetylcholine; due to this, a relative increase occurs. It belongs to the cholinergic class of molecules, and may be useful in fighting cognitive decline in the elderly.
Huperzine-A is a compound extracted from the herbs of the Huperziceae family. It is known as an acetylcholinesterase inhibitor, which means that it stops an enzyme from breaking down acetylcholine which results in increases in acetylcholine.
Acetylcholine is known as the learning neurotransmitter, and is involved in muscle contraction as well. Increasing levels of acetylcholine is routinely used as a technique amongst weight-lifters and scholars.
Huperzine-A appears to be a relatively safe compound from animal studies of toxicity and studies in humans showing no side-effects at dosages routinely supplemented with. Huperzine-A is in preliminary trials for usage in fighting Alzheimer’s Disease as well.
Huperzine-A’s most renowned action is that of an acetylcholinesterase inhibitor. Specifically, it can inhibit the G4 isoform of acetylcholinesterase which is highly prevalent in mammalian brains. It is of greater or equal potency to other acetylcholinesterase inhibitors such as Tacrine or Rivastigmine. It has a high affinity for acetylcholinesterase as an inhibitor, and a slow dissociation constant which enables a long active half-life.
It may be preferable for usage as a cholinergic since it has been reported to have less cholinergic-related side-effects, possibly through its high affinity for brain G4 acetylcholine resulting in less availability for systemic butrylcholine inhibition, which leads to various systemic effects which may be seen as side effects.
In addition to acetylcholinesterase inhibition, it can also be seen as neuro-protective against glutamate, beta-amyloid pigmentation, and H2O2-induced toxicity.
Huperzine-A can also block the NDMA receptor ion channel without psycho-mimetic side-effects.
Huperzine-A is able to promote proliferation of hippocampal neural stem cells (NSCs) at a concentration of 1μM for 48 hours (which is more potent than 10-100μM) to 125% of control secondary to activating the ERK pathway, and this neurogenesis was confimed in vivo with injections of 0.2mg/kg of huperzine-A for 4 weeks (about a 25% increase in BrdU stained cells, affecting both newborn and adult mice).
L-Tyrosine is an amino acid that is used to produce noradrenaline and dopamine; supplemental appears to be anti-stress for acute stressors (which tend to deplete noradrenaline) and may preserve stress-induced memory deficits.
Most mechanisms related to L-Tyrosine are due to it being a precursor to catecholamine synthesis, and catecholamine synthesis being somewhat sensitive to a localized substrate pool.
L-Tyrosine (200-400mg/kg) can acutely increase noradrenaline (aka. norepinephrine or NE) concentrations in the hippocampus and prevent an acute stress-induced reduction of NE concentrations in rats subject to cold stress. This may precede the ability of L-Tyrosine administration to reverse losses of memory induced by cold stress in humans. This study (n=8) noted that 150mg/kg L-Tyrosine (dissolved in apple sauce that placebo ingested solely) taken before cognitive testing in a room where the temperature was reduced from 22°C to 4°C was able to reduce the time taken to answer a delayed Matching-to-Sample test and increase the amount of correct answers relative to cold placebo, but was unable to fully preserve performance seen in warm control periods (where L-Tyrosine did not appear to further improve performance).
Currently no evidence that L-Tyrosine supplementation can improve memory function from baseline, but may be able to attenuate a decrease in memory formation associated with acute stressors
One study in children with diagnosed ADHD given a combination supplement of Tyrosine and 5-HTP (doses being titrated, with the lowest reported dose being 1,500mg tyrosine and 150mg 5-HTP and the highest being 3,750mg and 425mg respectively) noted that supplementation was associated with a greater reduction in symptoms as assessed by ADHD-RS; this study is also confounded with the inclusion of other nutrients (1,000mg of Vitamin C, 220mg of calcium citrate, 75mg of vitamin B6 and 400μg of folate, 500mg of L-Lysine and 2,500-4,500mg L-cysteine, and 200-400μg of Selenium).
Although L-Tyrosine may have a contribution in promoting attention, it has not been tested in isolation at this moment in time and thus it is unsure what role it plays
One study has combined supplemental L-Tyrosine and ‘extended wakefulness’ and noted that 150mg/kg of L-Tyrosine was able to attenuate the decrease in cognitive performance that was associated with sleep deprivation.
May improve cognitive performance during sleep deprivation without significantly affecting sleep function
Acute uncontrollable stress is a phenomena that is able to deplete norepinephrine (NE) concentrations in neural tissue, particularly the hypothalamus and brainstem (containing the locus coeruleus) and behavioral alterations associated with NE depletion in research animals have been shown to be avoidance/escape, spontaneous motor activity, aggressive behaviors, and swimming. Ingestion of L-Tyrosine can attenuate the development of behavioral abnormalities associated with acute uncontrollable stressors in research animals in the range of 200-400mg/kg (oral or intravenous) 30-60 minutes prior to the acute stressor.
Appears to mitigate some overt symptoms of acute and uncontrollable stress (this is in contrast to the Adaptogen class of molecules, which may be effective against chronic and manageable stress); the two stress responses being mediated by different mechanisms
Some studies have been conducted specifically as it applies to cold stress (the goal of cold exposure therapy) have noted decrease immobility time in a dose-dependent manner in mice given 200-400mg/kg L-Tyrosine injections to a similar magnitude of 5-20mg/kg Phenylpropanolamine; Tyrosine appeared to synergistically reduce immobility time when paired with either Phenylpropanolamine or Amphetamines. These effects correlated with hippocampal noradrenaline concentrations, which were preserved with L-Tyrosine. These protective effects have been noted in human subjects, albeit a small sample size.
May reduce the adverse effects of cold stress, has some human evidence of doing so (as it pertains to memory function)
One study in humans subjected to high altitudes has noted protective effects against acute stress due to lessened symptoms of acute stress, where 100mg/kg L-tyrosine (divided into two doses taken an hour apart) was associated with less headaches, stress, fatigue, distress, sleepiness, muscular soreness, and coldness due to the acute stressor as assessed by the Environmental Symptoms Questionnaire. This study also noted improvements (relative to placebo) on global ratings of mood and happiness (assessed by Clyde Mood Scale and Profile of Mood states) and cognitive function (various cognitive tests). Similar results are noted with the same oral dose after acute noise stressor and some of these effects are noted after acute physical lower body stressors.
Protection against acute stress has also been noted during a week-long combat training session, where 42g of protein (of which 2g were Tyrosine) was compared to placebo and associated with a preservation of cognitive performance, although this study failed to find significant improvements in mood between groups.
Increasing levels of L-tyrosine in the brain is being looked at as a pharmaceutical method of alleviating neurological decline as catecholamines are typically decreased in states of dementia.
Surprisingly, catecholamines may act as anti-oxidants in the brain and be neuro-protective.
Bacopa monnieri is a Nootropic herb that has been used in traditional medicine for longevity and cognitive enhancement. Supplementation can reduce anxiety and improve memory formation
Bacopa monnieri, commonly known as water hyssop, is an herb often used in Ayurveda.
Supplementing Bacopa monnieri has been shown to improve Cognition, by means of reducing Anxiety. It is also reliable for improving Memory formation. Though effects of this nature are usually studied in the elderly, Bacopa monnieri appears to affect young people as well, making it a useful Nootropic.
Since Bacopa monnieri is also an Adaptogen, a relaxed person might experience a lack of motivation to work after supplementation. Theoretically, pairing Bacopa monnieri with a stimulant would ward off malaise, but this combination has not been tested.
Bacopa monnieri interacts with the dopamine and serotonergic systems, but its main mechanism concerns promoting neuron communication. It does this by enhancing the rate at which the nervous system can communicate by increasing the growth of nerve endings, also called dendrites. Bacopa monnieri is also an antioxidant.
Bacopa Monnieri extract may be able to increase memory formation by the enzyme Tryptophan Hydroxylase (TPH2) and increasing the expression of the serotonin transporter (SERT). Bacopa does appear to have some interactions with the serotonin system, and may have downstream effects on the cholinergic system through this.
Additionally, dendritic intersections and branching points in neurons have been noted to be proliferated with Bacopa Monnieri supplementation after 4 and 6 weeks, but failed to have any changes at 2 weeks. This neuronal growth effect occurs in adult rats and younger rats undergoing growth spurts, and occur in areas of the brain known to be involved with memory, such as the hippocampus and the basolateral amygdala. These changes coincide with memory enhancement seen in human studies, where usage for under 2 weeks is not associated with any cognitive enhancement but additional usage is; implicating dendritic enhancement as a probable explanation for memory enhancement.
Mechanism of memory enhancement has not been completely solidified, but appears to be related to either enhancing neuronal transmission (via enhancing dendritic proliferation) or through interactions with the serotonergic system (which then influence acetylcholinergic transmission). These effects do not appear to require cognitive decline or the elderly to work, and thus suggest Bacopa can benefit all ages
Enhancing neuronal transmission and proliferating dendrites may enhance memory map formation
Bacopa, in healthy persons, has been successful in beneficially affecting the retention of learned information. It may be able to reduce the rate of short term forgetting (ie. increase encoding of information) while increasing retention speeds. In addition to rate of learning, Bacopa Monnieri shows some promise at 300mg daily for improving memory, verbal learning and delayed recall. This has been repeated in healthy persons between 18 and 60 with two doses of 150mg daily.
In regards to persons with impaired memory, low dose Bacopa (125mg daily) appears to be somewhat effective. Bacopa has also been implicated in helping children aged 6-12 with ADHD, but this study used a blend of other herbs (Melissa officinalis, Centella Asiatica, Paeoniae Alba, Ashwagandha, and Spirulina Platensis) and causation cannot be placed on any in isolation. These two studies are less able to be extrapolated to healthy persons, but should still be noted.
Not all research is conclusively solid, as some studies do note no difference from placebo at therapeutically relevant dosages, although this study was critiqued on suggesting that the null results were due to ‘low doses’. The former study was conducted at 300mg Bacopa and 120mg Gingko for 2-4 weeks, which is shorter in time to other studies but at a similar dosage. Beyond this study, one other study has noted no effects with a single administration, suggesting that longer term supplementation is needed. Many of these studies have been subject to Meta-Analysis, where it was concluded that Bacopa shows preliminary efficacy in improving general memory (9 out of 17 measured parameters) with little influence on other parameters of cognition. In a study analyzing the comparative effect sizes of Bacopa, Panax ginseng, and Modafinil it was found that although Modafinil and Bacopa were both potent they were at different parameters; Modafinil increasing speed of information processing much better than Bacopa, which tended to reliably increase cognition after chronic dosing.
There is a surprising amount of human interventions on Bacopa Monnieri for being an Ayurvertic herb, and the majority of them note positive results. No longer term studies have been done, but the evidence at the time is very promising and is in line with the traditional claims of Bacopa Monnieri being a memory enhancer
Beyond enhancing memory, Bacopa has been implicated numerous times in reducing amnesia (memory loss due to stressor) via a collection of mechanisms.
In regards to cognition (not memory per se), Bacopa at 450mg daily for 3 months has failed to significantly improve performance on an Inspection Time Task (discrimination) and on a Stroop test (attention and interference).
450mg Bacopa daily for 3 months in otherwise healthy persons has failed to significantly influence performance on a Rapid Visual Information Processing task (RVIP).
Bacopa has some implications with serotonergic signalling in models of epilepsy (See Epilepsy subsection of Neurology) where receptor kinetics are normalized under the influence of 150mg/kg Bacopa Monnieri oral ingestion in pilocarpine-induced epilepsy.
Beyond that, Bacopa Monnieri has been found to increase serotonin levels in the hippocampus of treated animals as well as increasing the Serotonin Transporter (SERT). At 20-40mg/kg bodyweight Bacopa, Bacopa Monnieri appeared to increase SERT mRNA expression, but both the increases in SERT expression, Tryptophan Hydroxylase activity, and serotonin levels appear to decline with age, where rats that are 53 days postnatal do not experience increases in either, whereas 19 and 27 days postnatal still experience increases. In this study, memory was not tested across the age spans.
Appears to increase serotonin content and effects, may be related to memory formation, and its effects appear to be sensitive to age
Bacopa Monnieri has been investigated for its ability to reduce dopaminergic neuronal death seen in Parkinsons diseases, as evidenced by a genetically transfected C.Elegans line and mouse brains.
Treatment with Bacopa Monnieri at 40-80mg/kg bodyweight in rats subject to both acute and chronic stress (to assess Bacopa’s adaptogenic effects) found that the depletion of dopamine and serotonin associated with chronic stress did not occur with Bacopa supplementation, although the decrease in noradrenaline was unaffected. This preservation of dopamine levels has been seen with rotenone-induced neurotoxicity, which should normally deplete dopamine but doesn’t in the presence of Bacopa Monnieri. Through these studies, it is plausible to suggest that Bacopa reduces stress onto dopaminergic neurons that would otherwise then deplete dopamine, although the mechanism of protection is unknown.
Bacopa has also shown anti-dopaminergic effects in the striatum (location associated with Caffeine and morphine, and highly associated with dopamine induced locomotion) and prevented surges in dopamine when fed at a low dose of 5-15mg/kg bodyweight daily. This anti-dopaminergic effect may be useful in situations of drug dependence, Additionally, one study measuring levels of dopamine in the hindbrain noted statistically significant (91% of control).
Although no mechanisms have been found out yet, it appears Bacopa Monnieri may nicely regulate dopamine. Although theoretically it could work against compounds that induce a dopamine spike in the striatum such as Caffeine, this negation may reduce drug dependence and dopamine-induced locomotion (running in circles from caffeine)
Acetylcholine and Cholinergic Signalling
One study measuring hindbrain levels of acetylcholine noted an increase to 110% of the control rats. Bacopa Monnieri also appears to have anticholinesterase properties by inhibiting the acetylcholinesterase enzyme, but an IC50 value could not be calculated as 50% inhibition was not observed; thus these effects may be either weak or irrelevant.
It has been implicated in reversing amnesia induced by anti-cholinergic drugs (scopolamine) at 120mg/kg oral ingestion, both retrograde and anterograde amnesia, which is the first study to link previous literature on amnesia to cholinergic transmission. Interestingly, this study ran for 7 days only and did not note any benefit to normal acquisition or retrieval of memory (in line with previous reports suggesting up to 2-4 weeks are needed for effects), suggesting the mechanisms behind reversing amnesia are distinct from that of inducing memory promotion. Other protective effects, such as a decrease in neuronal death in an animal model of Alzheimer’s disease, have been noted.
Although Bacopa Monnieri technically does increase acetylcholine and protect from Alzheimer’s disease, there are not too many studies investigating these interactions and the observed interactions are fairly weak. Acetylcholine remains a possible expanation for some effects, but is not a promising avenue of research for Bacopa Monnieri. Protective effects seen may be secondary to anti-oxidant effects of Bacopa Monnieri
40mg/kg of bacopa monnieri ethanolic extract did not appear to significantly influence levels of glutamate (despite beneficially influencing memory formation). Furthermore, bacopa monnieri does not appear to protect neurons from glutamate-induced neurotoxicity at concentrations able to preserve the cell from beta-amyloid toxicity.
When looking at levels of glutamate itself, there does not appear to be any significant modifications relative to control
In a rat model of schizophrenia, administration of bacopa was able to increase concentrations of the vesicular glutamate transporter type 1 (VGLUT1) which was associated with improvements in the discrimination ratio and in epileptic rats the decrease in the metabotropic glutamate-8 receptor mRNA expression and NMDA R1 are nearly normalized to control.
There appear to be interactions with glutamate receptors and transporters, although due to all evidence currently taking place in models of cognitive ailments the interactions of Bacopa and glutaminergic neurotransmission in otherwise healthy persons is uncertain
Bacopa has been shown to have various benefits in the treatment of epilsepsy such as reducing convulsion occurrence (Brahmi Ghrithan is Bacopa Monnieri paired with Ghee).
It seems to exert these actions, in part, via changes in the GABA receptor subtypes in the hippocampus and striatum which may be due to the Bacoside-A content and are mediated through reducing the activity of the PNS.
Bacopa Monnieri has also been shown to upregulate expression of a certain type of presynaptic glutamate receptor, mGluR8, which is downregulated during epilepsy. mGlu receptors are believed to be a protective mechanism from excitotoxicity, and their downregulation is concurrent with hyperexcitation. Despite downregulation of mGluR8 in pilocarpine-induced epilepsy, Bacopa Monnieri at 150mg/kg daily for 15 days was able to upregulate mRNA transcription rates of mGluR8 to near control levels and this has been confirmed by other researchers.
Similar to downregulation of mGluR8 in epilepsy, Serotonin receptors (5-HT2C subset) are downregulated in the cerebellum during epilepsy and promptly reversed by Bacopa Monnieri, and upregulated in the hippocampus during epilepsy and also reversed by Bacopa Monneri. Both of these studies on serotonin receptor binding were done by the same research group and released within a month of each other, and using 150mg/kg dry weight Bacopa leaves. When Bacopa was fed to control rats without epilepsy, no effects were seen on 5-HT2C receptors.
As an Adaptogen, Bacopa Monnieri can reduce the effects of physiological stress when pre-loaded. It has been shown to reduce HSP70 expression (a biomarker of stress) in response to stress in all brain regions, but most significantly in the hippocampus; returning values in the hippocampus and cortex to near control levels, and the cerebellum about half-way to control. When 20mg/kg and 40mg/kg were tested, no significance dose-response occurred
Bacopa Monnieri, at 40mg/kg bodyweight in rats, has been noted to modulate the stress response rather than merely suppress it. When Bacopa was administered at 20-40mg/kg bodyweight, an increase in HSP70 was noted (15-17% in hippocampus, 44-51% in cortex, 65-83% in cerebellum) when the stress was not applied; these changes were not statistically significant, and were numerically about a third the HSP70 stress response invoked by perceived stresses without Bacopa Intervention. The authors hypothesized that Bacopa induced gene expression of stress, which prepared the rats for the perceived stress and minimized its potency.
When measuring PROD (7-pentoxyresoruﬁn-o-dealkylase) and EROD (7-ethoxyresoruﬁn-o-deethylase), Bacopa monnieri at 20 and 40mg/kg seem to elevate it to the same extent that stress does, but Bacopa ingested during stress appears to return PROD levels closer to baseline; reasons unknown. In looking at neurotransmitter levels, Bacopa Monneiri (40-80mg/kg) is able to reduce changes seen with dopamine and serotonin when a short-term stress is present, but is ineffective at preventing a rise in adrenaline; in chronic stress, Bacopa can prevent reductions in serotonin, dopamine, and adrenaline and was equally effective as was American ginseng (Panax quniquefolium) at 100mg/kg, similar to their comparisons on depression and anxiety.
Bacopa Monnieri appears to be effective at reducing the biochemical effects of a perceived stress, assuring its status as an Adaptogen. It seems to be protective against acute and chronic stress as well
At least one acute study using 320mg Bacopa Monneiri extract (CDRI 08) has noted that Bacopa acutely enhanced performance in a Cognitive Demand Battery (CDB) of tests. This study noted that while Bacopa failed to acutely influence fatigue or stress at this dose it attenuated the rate of performance decline associated with CDB (usually attributed to neural fatigue).
Bacopa has been noted to, in rats, reduce Superoxide Dismutase (SOD) levels by 2.4-fold in the hippocampus at 20mg/kg oral ingestion, without significantly affecting other areas of the brain. This study had measurements at day 7, yet it appears that testing later at 2-3 weeks (coinciding with when memory enhancement is seen in humans) SOD levels, as well as other anti-oxidant enzymes such as glutathione peroxidase and catalase, are increased in the hippocampus as well as other brain regions such as the frontal cortex and striatum.
Bacopa Monnieri supplementation can reduce oxidative damage from aluminum and prevent an increase in cognitive iron stores in cases of overload. These effects are also seen with mercury, in which Bacopa Monnieri appears to reduce oxidative damage from mercury on brain tissue in vivo where near pre-testing levels of damage were achieved with 40mg/kg bodyweight, although full protection was not seen. In general, Bacopa Monnieri appears to protect the brain from the damage induced by excessive mineral status.
There was a past contamination of mercury related to Bacopa Monnieri, but is atypical; Bacopa Monnieri supplements do not tend to have mercury contamination.
Effective in reducing the oxidative and adverse effects of minerals on the brain, specifically iron overload; there is a notion that Bacopa has mercury in it, and one crop in the past did. Irrelevant point now, as aside from it not being a common occurrence Bacopa also protects from mercury-induced neural damage
Bacopa Monnieri has been implicated in reducing neural inflammation associated with aging over a period of three months, and may exert a neurological anti-aging effect. Bacopa Monnieri at 200mg/kg (large dose) was associated with IL-1β and TNF-α being reduced in older age (22% and 25.7% less IL-1β and TNF-α, respectively, in the Bacopa treated groups) and having the elevation associated with aging suppressed in all experimental groups. IFN-γ was not significantly affected. These anti-inflammatory effects have been seen in vitro and is attributed to the steroidal saponins (the bacosides).
Additionally, Bacopa Monnieri is associated with preventing beta-amyloid pigmentation build-up and may be a therapeutic approach to Alzheimer’s. It may decrease beta-amyloid pigmentation through controlling oxidation (from lipids, metals, and ROS) and inhibiting lipoxygenase activity. It is dose dependent, and 100mcg ethanolic extract of Bacopa Monnieri is about as potent as 58mcg Vitamin E.
Anxiety and Depression
Despite the traditional usage for Anxiety and Depression, minimal human studies exist; persons over the age of 65 taking 300mg Bacopa Monnieri (55% Bacosides) experienced a decrease in both anxiety and depression in a double-blinded study although 450mg of Bacopa for 3 months in otherwise healthy males with no baseline anxiety failed to find a significant effect.
Bacopasides I and II, as well as bacopasaponin C, all show anti-depressant effects in mice. Depressive symptoms in epilepsy have been reversed with Bacopa Monnieri in research animals as well, as assessed by forced swim test.
Cerebral Blood Flow
Bacopa Monnieri has been implicated in increasing cerebral blood flow independent of overall blood pressure at a dose of 40mg/kg bodyweight in rats; it can also decrease blood pressure (both systolic and diastolic) independent of heart rate via vasodilation, and appear to be related to Bacoside A3 and Bacopaside II. It appears to be involved in releasing nitric oxide from the endothelium.
Bacopa Monnieri appears to have antinocioreceptive properties at high doses (80-160mg/kg bodyweight in rats, aqueous extract). These effects are inhibited by Yohimbine HCl, atenolol, and Cyproheptadine; showing that Bacopa’s antinocioreceptive effects at high doses seem to be mediated through a combination of opiodergic, serotonergic, and adrenergic mechanisms.
Bacopa Monnieri has traditionally been given to children to boost brain power, alongside Gotu Kola and mixed with some milk. Out of all the human evidence on Bacopa, the one study currently looking at children is too confounded with other herbs to answer research questions on Bacopa but did not show any signs of toxicity. Another study cited here yet not indexed in Medline suggests that 350mg crude bacopa daily improved reaction times, memory, and general cognition relative to placebo.
In studies on pre-pubertal animals, mice fed Bacopa at 0.5-1% of the diet (highest dose that mice would eat) for 4 weeks showed increases in anti-oxidant defense enzymes (Catalase by 26%, Glutathoine Peroxidase by 22%, SOD by 21%) and reduced levels of pro-oxidant compounds like MDA (15-21%) ROS (18-25%) and hydroperoxide (34-40%); these reductions in oxidants occurred in the cytosol and the mitochondria of tested neurons. The neurons were protected from toxic insult by 3-NPA, and no noticeable toxicity was noted in these mice. The memory-enhancing effects were also seen when orally administered to 10-day old rat pups at 20, 40, and 80mg/kg bodyweight with the extract at near 10% Bacosides A and B for 6 weeks were able to increase memorization of maze patterns and improve cognition more than controls, but 40mg/kg was needed at minimum as 20mg/kg was not statistically significant.
Limited studies on children and youth; the one human study really cannot answer any question on Bacopa itself due to confounds. It appears to be effective in children at the same oral dose, efficacy, and mechanisms as adults and the elderly; safety is understudied, but no adverse effects were reported in the one human study and it has traditionally been given to children at 300mg dry leaves daily
DMAE is a Choline molecule with one less methyl group, and has the ability to reduce build-up of the age pigmentation known as beta-amyloid. It is the active component of Centrophenoxine, or Lucidril, a pharmaceutical designed for cognitive health in the elderly.
DMAE is a compound that is known as a mind health compound. It does this by reducing buildup of what is known as the ‘age pigment’, which impairs cognitive function and is implicated in the cognitive decline with age. It can also increase levels of the compound involved with memory, acetylcholine.
It can also protect neurons and other cells from harmful effects of certain types of oxidation by embedding itself in the structure of the cell and acting as an anti-oxidant, as well as sustaining metabolic processes in the body through a process known as ‘methyl donation’.
DMAE (0.6% in vitro) appears to protect from iron-induced oxidation and subsequent protein cross-linking, thought to preserve membrane fluidity via anti-oxidative effects, either directly or by preventing formation of Nitroxyl radicals (hydroxyl radical binding with hydroxyproline) by non-oxidatively sequestering hydroxyl radicals.
V0191 (DMAE Pyroglutamate) in 55-90 year old persons (mean age 72.2) with mild cognitive impairment taking 1500mg of the supplement daily at breakfast over 24 weeks noted that although there was a trend to more response with treatment than placebo (defined as more than a 4 point improvement on the ADAS-cog rating scale), there were no statistically significant improvements nor improvement on global assessments.
DMAE supplementation has been shown in some studies to show an small albeit nonsignificant positive trend for symptoms in Tardive Dyskinesia, but typically it is seen as an ineffective treatment.
Cobalamin (Vitamin B12) is a water-soluble Essential Vitamin or Mineral that is known to play roles in neurology.
Vitamin B12 is known to be relatively deficient during the aging process, with the percentage of the population having suboptimal serum concentrations (less than 200pg/mL or 148pM) increasing from 23% in the 19-64yr age cohort to 62% above 65yrs of age (European data) although this is at the higher range of estimates; estimates for B12 deficiency in the older cohort range from 5-60% in general depending on the source consulted with studies assessing serum B12 at times measuring deficiency rates as low as 3.8% in the elderly (1.9% whole population).
A deficiency of vitamin B12 will ultimately lead to anemia (macrocytic), peripheral neuropathy, and cognitive impairment although a B12 deficiency does not necessarily manifest these symptoms (with 40% of elderly persons with B12 deficiency not having anemia). The leading conditions associated with a B12 deficiency are impairments in absorption (surgical resection, autoimmune pernicious anaemia, chronic pancreatitis, Celiac and Crohn’s disease) or gastric digestion (atrophic gastritis, achlorhydria or the consequences of gastrectomy), the latter being due to a lessened ability to dissociate B12 that is bound to meat products and the former impaired uptake.
Beyond complications in absorption, B12 deficiencies are also more prevalent in vegetarian populations than in omnivorous populations due to B12 being localized to animal products. It can be found in very few plant products of the algae class (Chlorella is a source of bioavailable B12, but Spirulina is not).
Vitamin B12 deficiency is known to predispose persons to neural complications (impairment of cognition and neuronal damage) and a form of anemia known as macrocytic which is unique to B12 deficiency. The actual rate of deficiency is quite variable and it isn’t fully known what it is, but elderly persons (above 65), vegetarians, or those with digestion or intestinal complications are almost always at a higher risk than otherwise healthy and omnivorous youth
Vitamin B12 can be measured in the blood by serum B12 concentrations, which is reproducible and reliable but may not accurately reflect bodily vitamin B12 stores (as low B12 concentrations in plasma or vitamin B12 deficiencies do not always coexist in a reliable manner) with a predictive value being reported to be as low as 22%. According to serum readings, a concentration less than 200pmol/L when paired with a homocysteine reading above 20mM is a clinically significant deficiency.
Other measurements include serum holotranscobalamin (holoTC) which reflects tissue uptake of B12, and is thought to be more reflective of B12 bioavailability (post absorption) rather than total bodily levels of B12 which is seen as more reliable in general but may have false positives in persons with renal impairment; it is thought to be the first significant alteration in the body and thus an acute marker of B12 deficiency. According to a holoTC reading, a deficiency of vitamin B12 is when holoTC drops below 32-37pmol/L (42-157pmol/L being the reference range) and taking a holoTC measurement in addition to a serum B12 measurement is no better than an holoTC measurement by itself and is more predictive of MMA (to be discussed) than is plasma B12.
Urinary or plasma methylmalonic acid (MMA, not to be confused with malondialdehyde or MDA which is a biomarker of lipid peroxidation) is also a biomarker for vitamin B12 deficiency, as reduced levels of B12 reduce the activity of the methylmalonyl CoA mutase enzyme which then causes an increase in MMA concentrations. Similar to holotranscobalamin, MMA concentrations are elevated in thyroid conditions and impaired renal function which may limit specificity (how reliably a reading indicates B12 deficiency and not something else) of this test.
Vitamin B12 can be measured in the body as either blood measurements (reproducable but not fully accurate), serum holotranscobalamin (more accurate in all cases except kidney conditions) and either serum or urinary methylmalonic acid (MMA; more accurate but also altered in kidney conditions)
One study using 10-500mcg of B12 (cyanocobalamin) for 8 weeks noted that while all dosages were able to increase plasma biomarkers of B12 status that there were still some persons who were deficiency, measuring at 8% (plasma B12), 12% (holoTC), or 15-25% (MMA).
Although 500mcg can normalize B12 deficiencies in most persons, there may be elderly persons who require a higher dose
It has been noted that both B12 as well as folate levels tend to be lower in depressed persons relative to undepressed controls at around a 17-31% and 15-38% prevalence (respectively) and that this depressed concentration of these two vitamins precedes higher plasma homocysteine concentrations. Interestingly, B12 has been associated with melancholic depressive symptoms but not non-melancholic when investigated (folate also linked, albeit weaker).
At least one study has noted that depressed serum concentrations of B12 (17% prevalence in mild depression and 27% in severe depression) were predictive of depression despite folate and homocysteine being normal and one study noting correlations with all three factors and depression noted that B12 had the strongest association, this suggests that B12 itself plays a causative role.
One study using antidepressant therapy noted that baseline B12 in serum was predictive of a successful outcome.
Although not unanimously affecting all depressed persons, the rates of B12 and folate deficiencies appear to be greater in depressed persons when compared to nondepressed controls. While homocysteine and folate are both implicated (and methylation in general), B12 itself appears to be implicated independently
Persons with lacunar stroke who suffer from depression and fatigue symptoms may be at a higher risk for B12 deficiency and a pilot study on 14 persons suffering from their first lacunar strokes noted that 3 months of 1,000mcg B12 (hydroxycobalamin) noted that while a portion of the sample (6/14) reported greater verbal learning than expected that there was no benefit to fatigue or depressive symptoms.
Vitamin B6 might be the most important of the B family of vitamins for brain function. This essential compound, also known as Pyridoxine, is utilized in energy metabolism processes in your cells as well as in the production of neurotransmitters. Low levels of Vitamin B6 in your diet can lead to decreased cognitive ability, lack of focus or energy, brain tissue shrinkage and even Alzheimer’s. Taking amounts of B6 above and beyond the typical recommended dietary intake may increase mental and physical energy levels, boost communication between brain cells and even prevent certain types of neuron damage due to aging.
The enzyme that converts L-DOPA into active dopamine, L-dopa decarboxylase, is a pyridoxine-5′-phosphate (PLP) dependent enzyme and due to the actions of pyridoxine infusion paralleling that of dopamine (in regards to prolactin and growth hormone) it is thought that additional pyridoxine increases the activity of this enzyme particularly in the hypothalamus. It is known that a deficiency of PLP hinders the activity of this enzyme in the brain.
Rats deficient in pyridoxine have significantly reduced hypothalamic levels of both pyridoxal phosphate (PLP) and serotonin, which seem to result in low plasma prolactin levels; since the plasma prolactin was remedied with a 5-HT1A agonist, it was thought that a deficiency in pyridoxine reduces activity of this serotonin receptor in the hypothalamus.
Hallucination and Euphoria
Pyridoxine has been suggested to be a contributor to inducing dreams due to its interaction with l-dopa decarboxylase crossing over into dopamine and serotonin production. Serotonin based drugs (such as SSRIs) have been noted to increase subjective dream intensity and it is hypothesized that increased arousal during REM sleep (when dreaming appears to occur most frequently) and subsequent waking may underlie the increases in dream intensity and frequency reported with pyridoxine.
When testing dream salience (subjective intensity of a dream) as self-reported after a night of sleep, 100mg and 250mg pyridoxine showed dose-dependent increases in dream salience relative to placebo.
Vitamin B9 is essential for human growth and development, encourages normal nerve and proper brain functioning, and may help reduce blood-levels of the amino acid homocysteine (elevated homocysteine levels have been implicated in increased risk of heart disease and stroke). Folic acid may also help protect against cancers of the lung, colon, and cervix, and may help slow memory decline associated with aging.