Bacopa Monnieri: About the OG of Nootropic Herbs

Bacopa has been a real staple herb in my personal nootropics practices, and is easily amongst the most popular nootropic herbs to exist. And for good reason, the research is in strong support.

To name a few, Bacopa monnieri supplements have been shown feature anti-oxidant, serotonergic, and also cholinergic mechanisms. So well past due, its is time dive into these mechanisms and the surrounding literature to demystify exactly how Bacopa is doing its great work for so many. 

A full video summary will be released soon, but for you keen readers... read on! Continue below for a full a detailed discussion and links to research resources for further reading. I hope everyone enjoys, and learns a lot from this Bacopa Monnieri walkthrough!

Bacopa monnieri is a well studied Ayurvedic herb grown and used for thousands of years in India. Reflecting this, and recognising it as a major export, the government of India has also produced a colossal amount of research into Bacopa monnieri over the last few decades. Exploring a diverse range of applications, dosages and mechanisms by which it works. If there is a potential mechanism you are considering, there's a good chance there's some research available on it.

But to keep this breakdown succinct (in relative terms haha), we'll just go over the main mechanisms of action and well supported research. We'll also have a quick discussion on the two popular proprietary extracts on the market currently. These being the Synapsa (aka. KeenMind) and Bacognize extracts. Onwards!


Main Mechanisms of Action

Neuroprotection by manipulation of Antioxidants 

A good number of studies have looked into the antioxidant activities of Bacopa Monnieri and a few of its key bioactive compounds.Of them all, the anitioxidant activity of Bacoside A (a mixture of four saponins) seems most profound. Bacoside A has been shown to increase cerebral levels of the potent antioxidants:

It has also been shown to increase the activity of the cerebral antioxidant enzymes:

  • Superoxide dismutase (SOD) - which catalyses the conversion of celld amaging superoxide anion free radicals (O2 - ) into Hydrogen Peroxide which can then converted into water by catalase and glutathione peroxidase.
  • Catalase (CAT) - As mentioned above, converts the cell damaging Hydrogen Peroxide into water to limit harm. See "Catalase, a Remarkable Enzyme..." 
  • Glutathione peroxidase (GPx) - As mentioned above, converts the cell damaging Hydrogen Peroxide into water to limit harm. See "Glutathione Peroxidase-1 in Health and Disease..."

As evidence that this influence has end results in neuroprotective success, researchers have shown that when Bacoside A is administered under high oxidative stress situations:

  • there is less creatine kinase leakage from cells into surrounding blood, indicating better cell wall structural integrity, which is in part weakened by oxidative damage;
  • there is less mitochondrial dysfunction, which is in part caused by oxidative damage;
  • there is less ATPase dysfunction, which is in part caused by oxidative damage;
  • lower concentrations of malondialdehyde, which is a chemical marker of oxidative damage.

Bacopaside I is the other saponin in notable concentration with some research. It too has been shown to increase ATP content and increase mitochondrial enzyme functions, indicating some similar protective functions against oxidative damage. It also showed decreased malondialdehyde content, further supporting its properties in preventing oxidative damage. This said, research investigating Bacopaside I is less in depth compared to Bacoside A, so their may be much more of the picture left to fill in.

TO EMPHASISE: Bacoside A and I's value in itself is not as a antioxidant or its own free radical scavenging, but rather its influence in increasing the concentration and activity of free radical scavengers in the brain. This is a line often blurred in mainstream media.

For references and further reading on bacopa's neuroprotective properties, see articles [1-6].

Serotonergic Activities

Bacopa Monnieri extracts have been shown to upregulate Trytophan hydroxylase and Serotonin Transporter (SERT) expression. 

Trytophan hydroxylase is the enzyme responsible for the first and rate limiting step toward serotonin synthesis. Tryptophan hydroxylase takes Tryptophan and through hydroxylation forms the amino acid 5-hydroxytryptophan (5-HTP).

Following this, when Tryptophan hydroxylase activity increases, so does the corresponding levels of 5-HTP, and hence serotonin synthesis as decarboxylation of 5-HTP to serotonin is not a rate limiting step (it will increase synthesis to meet supply). In rat studies, this pathway has been shown to successfully increase serotonin concentrations. 

The function of Serotonin Transporters is to transport serotonin released into the synaptic cleft, back into the presynaptic terminal, allowing for recycled use. ie. to be released again for synaptic transmission.

So by increased recycling, more serotonin is made available for its functions as a neurotransmitter to modulate stress response and mood. Serotonergic activity is often attributed to reducing impulsivity and aggression, reducing anxiety and stress, as well as improving cognition and learning via the neurogenisis and plasticity effects of activation of the 5-HT2A receptors. 

For references and further reading on bacopa's serotonergic properties, see articles [6-8].

Cholinergic Activities

A good number of clinical trials and investigations have demonstrated significant increases in free acetylcholine as well as reduction in acetylcholinesterase (the enzyme responsible for breaking down free acetylcholine). Probable indirect mechanisms responsible include:

  • activation of 5-HT receptors by increased serotonergic activity, resulting in increased acetylcholine release;
  • inhibition of acetylcholinesterase by unconfirmed, but likely indirect mechanisms via other neurotransmitters;

For references and further reading on bacopa's cholinergic properties, see articles [7, 9-13].


Other Potential Mechanisms:

Monoamine oxidase Inhibition

There are a select few studies which have investigated Monoamine oxidase (MAO) activity after use of Bacopa monnieri supplementation. Right now, it seems popular to attribute Bacopa monnieri to be an MAO inhibitor, however I would claim that this may be jumping the gun. 

Most commonly cited is a 2014 in vitro investigation on how a standardised Bacopa monnieri extract and a number of its individual components affect the activity of human MAO enzymes. This reported to show:

"Bacopaside I and bacoside A mixture inhibited the MAO-A and MAO-B enzymes." and "Bacopaside I is the major constituent of B. monniera, which inhibited the MAO-A enzyme selectively." [1]

However it is very worth mentioning for this case, that an "in vitro" study (ie. petri dish style, not in a living human) is very far from the complexity of interactions that occur in practical use. Hence we should be careful about extrapolating these findings to practical use.

Investigations with "in vivo" human clinical trials are limited. However one study investigating the effects in a healthy elderly group reported no significant changes in MAO activity. [2] Again, there are a number of factors to consider. However due to the limited and conflicting evidence it looks as if more research is required before we can make MAO related statements in the context of supplemental use.

For references and further reading on bacopa's monoaminergic properties, see articles [9, 14].

Vasodialation for increased blood flow

A number of animal studies have indicated vasodialation effects of Bacopa Monnieri extracts, and the main sapogenins Bacosides A and Bacopaside I. These appear to function by common Nitric Oxide release, as well as regulation of Ca2+ and K+ ion channels. [1] Human studies haven't shown Bacopa supplementation to affect blood pressure, however it should be acknowledged that animal studies have shown vasodialtion actions to be independant of blood pressure. [3][4]

Obviously human research is still required for this mechanism, however there is some promise.

For references and further reading on bacopa's vasodialation properties, see articles [2, 9, 15, 16].


Popular Extracts: Synapsa & Bacognize

Before we delve into the extracts specifically, I'd say these warrant a foreword.

These extracts aren't trusted or "good" just because they have a fancy logo or marketing team. It's because these products are standardised to a specified criteria, and have been tested time and time again by third parties, verifying its effects and consistency in quality and benefits. Because the outcomes have been positive, these companies have kept their products exactly the same for many years, allowing them to cash in on all the research money spent. Over time, more and more research and anecdotal reports have stacked up.

The resulting sum of this is that we have more known data on these products specifically than other unbranded or non-standardised products. And if you've read this far, you will probably agree that knowing things is more appealing than not.

So before we move onto these two extracts, to emphasise once more: A quality extract isn't proven by being branded, but rather by being tested and consistent. Synapsa and Bacognize are not the only options on the market, but they are good ones.

Also, if you are looking for a "which is better" type statement. You'd better read elsewhere. As you will discover, each has their unique place and purpose and I would highly recommend either as compared to a non-standardised extract.

Synapsa (aka. KeenMind)

 Synapsa, also branded as KeenMind, is a patented and standardised Bacopa monnieri extract developed by the Central Drug Research Institute in India as a result of over 35 years of research , much of which has contributed significantly to current understanding of Bacopa monnieri's mechanisms. The Synapsa extract has since been investigated with 6 double-blind, placebo-controlled human clinical studies, of which have shown positive outcomes. 

"healthy adults using Synapsa showed significantly improved performance in areas such as visual processing, learning rate, working memory, information retention and mental performance in cognitively demanding environments versus a placebo regimen."
                    - PLT Health Solutions, distributors of Synapsa.

Synapsa is a alcohol and water concentrated extract, derived from the roots, stems and leaves of Bacopa monnieri. It is a full spectrum extract standardised to 55%+-5% Bacosides, meaning that no specific bioactive component has been selected for. With these features and supporting evidence, it is no surprise that Synapsa is the most popular branded Bacopa monnieri extract. 

The Clinical Studies:

  1. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects (Stough, 2001).
    Outcomes: As compared to placebo, Bacopa monniera (300mg Synapsa) given chronically for 12 weeks improved early information processing, verbal learning, and memory consolidation. It also showed improvement in anxiety measures. (46 participants, both male and female, 18-60 years).

  2. Chronic Effects of Brahmi (Bacopa monnieri) on Human Memory (Roodenrys, 2002).
    Outcomes: As compared to placebo, Bacopa monniera (300-450mg Synapsa) given chronically for 12 weeks showed no significant improvement on short-term memory, working memory, attention, or the retrieval of information from long-term memory. No subjective measures of anxiety, stress or depression. There was a significant improvement on a task requiring the retention of new information, indicating that there appears to be a reduction in the amount of information lost from memory. (76 participants, both male and female, 40-65 years).

  3. Randomized controlled trial of standardized Bacopa monniera extract in age-associated memory impairment (Raghav, 2006).
    Outcomes: As compared to placebo, Bacopa monniera (125mg Synapsa) given chronically for 12 weeks, followed by 4 weeks of placebo, showed significant improvement on mental control, logical memory and paired associated learning for those with age-associated memory impairment (40 impaired participants, predominantly male, 55-70 years).

  4. Examining the Nootropic Effects of a special extract of Bacopa monniera on Human Cognitive Functioning: 90 day Double-Blind Placebo-Controlled Randomized Trial (Stough, 2008).
    Outcomes: As compared to placebo, Bacopa monniera (300mg Synapsa) given chronically for 12 weeks, showed significant improvement in working memory, visual information processing and accuracy in complex cognitive tasks. (62 participants, both male and female, 18-60 years).

  5. An acute, double-blind, placebo-controlled crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance (Downey, 2012) [No Open Access Report Available].
    Outcomes: As compared to placebo, Bacopa monniera (320 or 640mg Synapsa) given acutely showed significantly  improved performance was seen in faster information processing and improved decision-making time. (24 participants).

  6. An acute, double-blind, placebo controlled crossover study of 320mg and 640 mg doses of Bacopa monnieri (CDRI08) on multitasking stress reactivity and mood (Benson, 2014).
    Outcomes: As compared to placebo, Bacopa monniera (320 or 640mg Synapsa) given acutely showed significantly improved performance in reasoning and cognitive speed. Inconsistent mood and anxiety improvements. (17 participants, predominantly female, 18-44 years).

TLDR? In human trials of small to moderate sample size, Synaspa has been shown to have beneficial results in improving memory, reasoning, cognitive speed, mood and anxiety. Outcomes were not absolutely consistent, however a general trend as a valuable nootropic and adaptogen is evident. This is discussed well in the summary paper linked below.

Bacognize

Bacognize, produced by Vendure Sciences, brings a more targeted extract of Bacopa monnieri that has been selectively processed and standardised for the  serotonin-active bacopa glycosides (SABG). This should result in greater activation of the 5-HT1 and 5-HT2 receptors previously discussed, and their downstream effects.
Because Bacognize is focusing on the serotonin-active bacopa glycosides, it is often found to be more sedating or calmative than other extracts or Synapsa. Therefore its value is often better appreciated at the end of the day or evening.

Bacognize is usually standardised to 45% Bacosides and is extracted from the arial parts of the plant only. I say usually, because I have seen it in some products under different specifications, but those seem rare.

You can check out Vendure Science's promotional video below for an overview.

Worth noting, is that compared to Synapsa, Bacognize has notably less clinical studies investigating the effects of the standardised extract it provides. It has been around for a shorter period of time, and likely has less funding behind it. However, to some degree, general bacopa studies and Synapsa research is relevant due to overlapping chemical compounds.

The Clinical Studies:

  1. Effect of Bacopa monnieri on Cognitive functions in Alzheimer’s disease patients (Goswami, 2011). [Open Label Study]
    Outcomes: As compared to placebo, Bacopa monniera (300mg Bacognize twice daily) for 6 months showed significantly improved results on tests of orientation of time, place & person, attention and in their language component in terms of reading, writing & comprehension. (39 participants, male and female, 60-65 years, Alzheimer’s disease patients).

  2. Sustained cognitive effects and safety of HPLC-standardized Bacopa monnieri (Bacognize®) extract: A randomized, placebo controlled clinical trial. (Hingorani, 2012). [No Open Access Report Available].
    Outcomes: As compared to placebo, Bacopa monniera (300mg Bacognize once daily) for 12 weeks showed significantly improved results on short-term memory, processing speed, attention and depression. (20 participants, male and female, 60-75 years).
  3. Efficacy of Standardized Extract of Bacopa monnieri (Bacognize„) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial (Kumar, 2016).
    Outcomes: As compared to placebo, Bacopa monniera (150mg Bacognize twice daily) for 45 days showed significantly improved results on tests of working memory. (42 participants, male and female, 19-22 years, medical students).

TLDR? We do a few studies with very specific conditions to gains some insight from. More evidence is available for elderly individuals. Results are generally in line with that of full spectrum Bacopa monnieri extracts, so the unique value of the targeted serotonin-active extract of Bacognize is yet to be proven in practice. With consideration to the wider research, it is certainly still trending showing to be a valuable nootropic and adaptogen. 


Wrap Up

Well that's Bacopa monnieri for you! Certainly a time and investigation proven herbal supplement, with plenty of value to offer particularly in the space of supporting serotonergic activities and neuroprotection functions. Downstream of this we see plenty of cholinergic effects also, resulting in improved memory and other factors of working cognition and long term brain health.

In the debate to go for an unbranded extract, Synapsa, or Bacognize, it will really be up to your personal preference. That said, we do have a fair quantity of data on the effects of these specific branded extracts, and for that reason I would always recommend them over unknowns.

If you're keen to try out some Bacopa monnieri, just take a look around the store and you'll be sure to find a number of stacks with it included. If your keen on Synapsa in particular, you'd do well to check out the Neuratech Enhance Neurovitamin. Looking for a standalone extract? We don't stock any at VitaKea right now, but just shoot me an email and I'll happily make some outside sourcing reccomendations.

If this was just enough warm up your research brain, I highly recommend reading some of studies for yourself. Check them out below, boundless information is at your fingertips!  


Further Reading

[1] Insights into the Molecular Aspects of Neuroprotective Bacoside A and Bacopaside I (Sekhar, 2019);

[2] Neurocognitive Effect of Nootropic Drug Brahmi (Bacopa monnieri) in Alzheimer's Disease (Chaudhari, 2017);

[3]  Neuroprotective Effects of Bacopa monnieri in Experimental Model of Dementia (Saini, 2012);

[4] Neuroprotective effect of Bacopa monniera on memory deficits and ATPase system in Alzheimer’s disease (AD) induced mice (Bai Kunte, 2013);

[5] Bacopa monnieri, a Neuroprotective Lead in Alzheimer
Disease: A Review on Its Properties, Mechanisms of
Action, and Preclinical and Clinical Studies (Manap, 2019);

[6] The Molecular Links of Re-Emerging Therapy: A Review of Evidence of Brahmi (Bacopa monniera) (Mathur, 2016);

[7] Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: Implications in memory formation (Charles, 2011);

[8] Molecular and Functional Characterization of Bacopa monniera: A Retrospective Review (Rajan, 2015);

[9] Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers (Peth-Nui, 2012);

[10] Bacopa monniera Attenuates Scopolamine-Induced Impairment of Spatial Memory in Mice (Saraf, 2011);

[11] Antipsychotic activity of standardized Bacopa extract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems (Chatterjee, 2015);

[12] Activation of 5-HT2 Receptors Enhances the Release of Acetylcholine in the Prefrontal Cortex and Hippocampus of the Rat (Nair, 2014);

[13] Clozapine Increases Both Acetylcholine and Dopamine Release in Rat Ventral Hippocampus: Role of 5-HT1A Receptor Agonism (Chung, 2004);

[14] In Vitro Evaluation of Bacopa Monniera Extract and Individual Constituents on Human Recombinant Monoamine Oxidase Enzymes (Singh, 2014);

[15] Vasodilatory Effects and Mechanisms of Action of Bacopa monnieri Active Compounds on Rat Mesenteric Arteries (Kamkaew, 2019);

[16] Bacopa Monnieri Increases Cerebral Blood Flow in Rat Independent of Blood Pressure (Kamkaew, 2012);


Got Questions?

Any questions at all, just shoot me an email over at thomas@vitakea.co.nz and I'll gladly help out in anyway I can. Hopefully it is apparent from the content of this walkthrough that I could talk to the ends of the earth about this herb. The research and future potential goes on forever... and I would gladly direct you down a path into its expanse. :)


 

Key players in my current health regime include meditation, regular exercise (type depending on current fixation), early to bed, early to rise, packing in as many fungi leafy greens as possible. 
My 
supplementation varies as I test out new protocols. That considered, I prioritise anything that can be utilised for long-term benefits. Of course, for special cases I can definitely appreciate a good stimulant or perspective modifier.


Sincerely,

Your KeaLad, Thomas.


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