Bacopa

Bacopa Overview

bacopa

The Ayuvedic herb Bacopa monnieri

Bacopa monnieri is a herb that features prominently in Ayuvedic medicine and has been traditionally recommended for memory enhancement, epilepsy and asthma. Bacopa is classed as an adaptogen and thus helps to mitigate the effects of stress. A class of compounds known as bacosides are thought to be responsible for many of bacopa’s documented effects, the most studied of which is bacoside A.

As a nootropic, bacopa is frequently recommended as an anxiety reducing cognitive enhancer that enhances memory. In particular, research has found bacopa is able to:

  • Prevent drug induced amnesia in animal models.
  • Normalise neurotransmitter levels in various animal disease models.
  • Increase antioxidant levels (glutathione, catalase, SOD)  in rodent brains.
  • Enhance memory in humans.  Effective for all ages.
  • Reduce anxiety in various human trials.
  • Increase work capacity in patients with anxiety.
  • Reduce error rate and enhance performance time in various cognitive tasks.

Other Names:

Brahmi, Water Hyssop, WaterHyssop, Bacopa

Bacopa In a Nootropic Stack:

Bacopa seems a nice addition to most nootropic stacks and works to enhance both memory and reduce anxiety. It appears to do so through “adaptogenic” means and by supporting normal levels of neurotransmitters, so much so it reduces serotonin and dopamine spikes following morphine administration in rodents.

Give it’s rather unique mechanism of action, it could be stacked with most nootropics (save for adaptogens) without fear of “overcooking” a particular pathway (see our nootropic stack advice for more information). Bacopa appears to take weeks to kick into effect and shouldn’t be relied on as an acute anxiolytic (such as phenibut or picamilon).

Bacopa Dosing

Bacopa is fat soluble and should be taken with a meal. A dose of 150mg bacosides (from a greater amount of extract) taken twice per day seems to be a reasonable starting point.  Human trials noticing benefit have used 150mg bacosides (300mg @ 50% extract) (1)(2)(3).

Bacopa Structure

As with any herb there is typically a range of compounds (rather than just one molecule) that are responsible for the benefits provided. Bacopa contains a wide variety of unique compounds, the most studied of which are bacosides. Bacopa contains:

Bacoside A

Bacoside A

  • Bacosides (A and B) (4)
  • Bacosine (5)
  • Flavanoids – Luteolin (6), Apigenin (6) and Quercetin (6)

Research shows that under acidic conditions bacosides are further broken down into:

  • Jujubogenins (4) Bacoside A3, Bacopaside X, N1, IV, Bacopasaponin E, F
  • Pseudo-jujubogenins (Seriously) (4) Bacopaside I,II,,III,V, Bacopaside N2, Bacopasaponin C
Frankly the number of compounds and derivative compounds when discussing bacopa can seem a little overwhelming. Practically speaking, the take home point is that a high bacoside A and B extract (20-50%) is going to cover your bases.

Bacopa Absorption

Bacosides are fat soluble and should be taken with a meal. Traditionally bacopa is taken with ghee (clarified butter). Given the wide variety of compounds and derivative compounds formed when bacopa is consumed, it’s not easy to find direct data (like radiolabeling) on bacopa crossing the blood brain barrier or on half lives. That said, the vast number of changes in the brain such as upregulating antioxidants in the brain(7)(8), enhancing cerebral blood flow (9), protecting against neurotoxicity (10) clearly show that bacosides have activity and cross the BBB.

It’s clear that bacopa affects the brain and some compounds must cross the blood brain barrier, but there’s not enough research available to quantify the effects and tissue distribution of every compound and sub compound

Bacopa Benefits

Memory Enhancement

Bacopa has a traditional memory enhancer in Ayuvedic medicine and research has backed up this traditionally held belief. A study conducted rodents showed bacopa was able to alleviate scopolamine induced amnesia and protect against spacial memory impairment (11). Numerous human studies have also confirmed bacopa is able to improve memory performance in the over 55′s (1), improve recall and fight depression (again in the elderly)(2), and improve memory retention (3).

Perhaps most interesting, a 12 week study of 46 healthy participants (aged 18-60) concluded that bacopa improves verbal learning rate, speed of early information processing and memory consolidation. (12) A study of 40 children aged 6-8 years old (13) showed bacopa was able to;

  • Decrease reaction time, performance time and error rate in a visual motor performance task
  • Significantly increase digit span compared to placebo
  • Increase reaction time in a raven’s positive matrices
  • Improve test scores in bender-gestalt test – a visual motor test in which participants are shown a series of images and then asked to draw a copy on paper.
The (ref 12) found that the peak effects of bacopa on memory were after 12 weeks of administration. Similarly the study in children (ref 13) was conducted over 12 weeks. The research seems to point towards bacopa being a chronic memory enhancer rather than something that can acutely impact memory after a few days. Research into the acute effects of bacopa (15) showed no effect 2 hours following a single dose of 300mg, though the study only measured cognitive function rather than anxiety scores.


Anxiety Reducing

A study involving 35 participants diagnosed with anxiety showed bacopa was able to reduce mean anxiety score, improve behaviour such as social interactions, improve memory span and reduce mental fatigue. This study was conducted without a placebo group, and the 35 participants were split into 2 week or 4 week treatment times.  Both groups saw improvement, suggesting that bacopa doesn’t need a huge amount of time to take effect, however the largest benefits were seen in the 4 week treatment group.

The bacopa was administered as syrup which was equal to 12 grams of dried concentrated leaf. Given that dried bacopa is 10% bacosides by weight (14) this would equate to a 2.4 gram amount of 50% bacoside extract, which seems very high given the typical dose is 300mg of a 50% extract. I’m not sure if this abstract has a misprint (i.e. it was equal to 12 grams of fresh leaf), particularly as bacopa has been found helpful for anxiety at lower doses (below).

Research involving elderly patients (mean age 73.5 years) showed a daily 300mg tablet of bacopa (50% bacoside extract) was able to reduce anxiety scores following 12 weeks of supplementation (2). Similarly a study involving young healthy subjects showed bacopa was able to reduce anxiety after 12 weeks supplementation (12).

Bacopa Mechanism Of Action

Antioxidant Defence

Numerous studies show that bacopa is able to support brain antioxidant levels including glutathione, superoxide dismutase and catalase (7).  In rodent brains, bacopa has been shown to protect against both aluminum (15)(16) and mercury (17) induced neurotoxicity by reducing oxidative stress.

Bacopa has also been found to reduce HSP-70 expression (a biomarker of cellular stress) when given to rodents (18)

Protecting against oxidative stress induced neurodegeneration could be a potential mechanism of action for bacopa. Living up to it’s adaptogen title, bacopa seems to be able to mitigate the effects of oxidative stress.

Serotonin

Bacopa has been found to increase  both tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) levels (19) while the same study found no significant change in acetylcholine levels. Theoretically this change in serotonin metabolism could also be responsible for some of the anxiety reducing effects of bacopa.

serotonin

The serotonin molecule

In animal models of epilepsy, serotonin receptors have been found to be upregulated in the hippocampus and downregulated in the cerebellum, both of which bacopa seems to address (20)(21).

One rodent study involving morphine showed bacopa is able to prevent increased dopamine and serotonin turnover typically associated with morphine. The increased locomotive effect of morphine typically seen was also offset by bacopa (22). Interestingly the saline (placebo) group neurotransmitter levels were found to be unaffected.

Again suggesting bacopa has a “normalising” effect on the brain and supports a return to homoeostasis.


Dopamine

As mentioned above, bacopa prevents morphine induced dopamine surges and the associated increased movement when morphine is injected into rats, while control groups remain unchanged (22). In rodent models of Parkinson’s disease, bacopa has been shown to offset domapinergic neurodegeneration, though these effects appear to be more related to it’s neuroprotective role (perhaps through antioxidant effects) than it’s direct actions on dopamine (23) (24).

Bacopa Safety and Side Effects

LD50

In rodents the LD50 for bacopa was 17g/KG when taken orally, intraperitoneal toxicity was measured at 1g/kg for aqueous and 15g/kg for alcohol extracts (27).

Gastrointestinal Distress

A frequent theme in human trials with bacopa is some form of GI distress, be it nausea, cramping or increased stool frequency (1)(2)(12). It would be prudent to take bacopa with a fat source (as is traditionally recommended) to ensure maximum absorption. Splitting the daily dose up into 2-3 servings may also help to offset GI symptoms.

Possible Thyroid Hormone Elevation

In a rat study, 200mg/KG of bacopa extract (a considerable dose) was found to enhance T4 levels by 42%. T3 levels were unaffected (25).

Fertility

A dose of 250mg/KG for 28 and found to reduce spermatogenesis without impacting hormone or libido levels (26). This effect was reversed after cessation.

References Used

1. http://www.ncbi.nlm.nih.gov/pubmed/20590480
2. http://www.ncbi.nlm.nih.gov/pubmed/18611150
3. http://www.ncbi.nlm.nih.gov/pubmed/12093601
4. http://www.ncbi.nlm.nih.gov/pubmed/16755069
5. http://www.ncbi.nlm.nih.gov/pubmed/21154199
6. http://www.ncbi.nlm.nih.gov/pubmed/17654615
7. http://www.ncbi.nlm.nih.gov/pubmed/10815010
8. http://www.ncbi.nlm.nih.gov/pubmed/21783922
9. http://www.ncbi.nlm.nih.gov/pubmed/22447676
10. http://www.ncbi.nlm.nih.gov/pubmed/19744517
11. http://www.ncbi.nlm.nih.gov/pubmed/21607013
12. http://www.ncbi.nlm.nih.gov/pubmed/11498727
13. http://www.bacopin.com/funchtionchild.htm
14. http://www.ncbi.nlm.nih.gov/pubmed/20850955
15. http://www.ncbi.nlm.nih.gov/pubmed/17189676
16. http://www.ncbi.nlm.nih.gov/pubmed/16500707
17. http://www.ncbi.nlm.nih.gov/pubmed/22366895
18. http://www.ncbi.nlm.nih.gov/pubmed/12410544
19. http://www.ncbi.nlm.nih.gov/pubmed/21129470
20. http://www.ncbi.nlm.nih.gov/pubmed/19439326
21. http://www.ncbi.nlm.nih.gov/pubmed/19700373
22. http://www.ncbi.nlm.nih.gov/pubmed/22105846
23. http://www.ncbi.nlm.nih.gov/pubmed/21925152
24. http://www.ncbi.nlm.nih.gov/pubmed/22160863
25. http://www.sciencedirect.com/science/article/pii/S037887410200048X
26. http://www.ncbi.nlm.nih.gov/pubmed/19041444
27. http://www.thorne.com/altmedrev/.fulltext/9/1/79.pdf