Continuing Education Activity

Bacopa monnieri (often called brahmi) is a botanical frequently used in Ayurvedic medicine. The main indications for using Bacopa in Ayurvedic medicine are memory improvement, insomnia, epilepsy, and as an anxiolytic. Many clinical studies have demonstrated improvements in verbal learning, delayed word recall, memory acquisition, and anxiety reduction with using Bacopa. It has been described as a calming cognitive enhancer. The triterpenoid saponins are believed to be responsible for most of the herb's pharmacological actions. Bacopa has a high therapeutic index and is generally well-tolerated. The most common side effects are gastrointestinal, including increased stool frequency, nausea, and abdominal cramps. This activity reviews the indications, contraindications, activity, adverse events, and other key elements of the clinical use of the herb Bacopa monnieri in the care of patients with declining cognitive performance and anxiety.

Objectives:

• Describe the clinical indications for the use of the botanical Bacopa monnieri.
• Discuss possible mechanisms of action for Bacopa monnieri.
• Review adverse effects and contraindications for the use of Bacopa monnieri.
• Summarize the clinical studies on the effectiveness of Bacopa monnieri in improving cognitive performance, verbal learning, delayed word recall, memory acquisition, and decreasing anxiety.

Indications

Bacopa monnieri is a medicinal creeping perennial in the Scrophulariaceae family with small oblong leaves and white to purple flowers frequently used in ayurvedic medicine (see Image. Bacopa). Other names for this herb include brahmi, water hyssop, thyme-leaved gratiola, and the herb of grace.[1] Brahmi is derived from Hindu mythology meaning "Brahma," or the "supreme creator." [2] The term Brahmi has been used to describe Bacopa monnieri, Centella asiatica (Gotu kola), or a combination of the two botanicals.[2]

Bacopa is native to India, Indochina, Australia, and Sri Lanka. The leaves are used medicinally and contain triterpenoid saponins (Bacoside A, bacoside B, bacopasaponins, D-mannitol, acid A, monnierin), alkaloids (brahmine, nicotine, herpestine, hydrocotyline), flavonoids (luteolin, apigenin), glycosides (asiaticoside, thanakunicide), Phytochemicals (betulinic acid, betulic acid, wogonin, oroxindin, stigmasterol, beta-sitosterol), sapogenin (jujubacogenin, pseudojujubacogenin) and other compounds (Brahmic acid, brahamoside, brahminoside, isobrahmic acid.)[3] The saponins are believed to be responsible for most of the pharmacological actions.[4][5]

Its use has been documented in the Ayurvedic text "Caraka Samhita" as a treatment for various mental conditions.[4] Ayurvedic medicine describes Bacopa as a "medhya rasayana," meaning a class of herbs believed to improve mental health, memory, and intellect and promote rejuvenation and longevity.[3][2] The main indications for using Brahmi in Ayurvedic medicine are memory improvement, insomnia, epilepsy, and as an anxiolytic.[6] Many clinical studies demonstrate improvements in verbal learning, delayed word recall, memory acquisition, and anxiety reduction with Bacopa. It has been described as a calming cognitive enhancer.

Bacopa can be used on its own or in combination with other nootropic herbs such as Gotu Kola (Centella asiatica). Bacopa monnieri and Centella asiatica both possess neuroprotective properties and have nootropic activity with therapeutic uses for patients experiencing memory loss.[2] Gotu kola is used in Ayurvedic medicine and in combination with other herbs in traditional Chinese medicine to combat symptoms of anxiety and depression.[7] In human studies, Bacopa has demonstrated beneficial effects on cognitive performance, verbal learning, delayed word recall, memory acquisition, and decreasing anxiety. The FDA's position is that Bacopa monnieri products are not approved for any medical purposes, and in 2019 issued a warning to dietary supplement manufacturers who produce products containing Bacopa monnieri regarding making any therapeutic claims about the herb.

Human Studies

Bacopa monnieri functioning as a cognitive performance enhancer was demonstrated in a small (17 patient) randomized control trial published in 2014. They noted statistically significant improvement in cognitive performance (mental arithmetic, Stroop, letter search, visual tracking), improved mood, and a decreased cortisol response from stress after one dose of Bacopa (320 mg and 640 mg). A stronger effect was observed with the 640 mg dose.[8] In contrast, another small study (30 subjects) evaluated a daily dose of 450mg over a 12-week period in healthy adults, which demonstrated no significant change in cognitive testing scores (learning and memory, information processing), but a trend for decreased anxiety in the Bacopa group.[9]

A meta-analysis incorporating nine randomized controlled trials (437 subjects) demonstrated an improved speed of attention and cognition and decreased reaction time.[10] In a randomized, double-blinded, placebo-controlled study, patients (54 adults) were given a 300 mg standardized extract of either Bacopa or placebo. Measurements were obtained by evaluating tasks of attention, memory, and psychological state at baseline and following a 12-week trial. The treated group demonstrated enhanced delayed word recall memory scores and increased ability to ignore irrelevant information (Stroop's test) relative to placebo.[11]

In a study of memory acquisition, there was a randomized, double-blinded study (81 adults 55 years and older) that reported a 12-week cycle of Bacopa significantly improved memory acquisition and retention in healthy older Australians.[12] A meta-analysis incorporating results from six studies with 12 weeks or greater duration found that Bacopa improved memory-free recall but did not improve other aspects of cognition. These studies used a 300 to 450 mg dose of Bacopa extract standardized to 10 to 20% bacopa glycosides [13].

Bacopa has shown anxiolytic effects in people with cognitive decline. Bacopa, in combination with Gotu kola (Centella asiatica), has been shown in double-blind, randomized clinical trials to effectively reduce general anxiety symptoms.[14][15]

Animal Studies

In a study on male albino mice, Bacopa monniera extract was administered along with phenytoin in the second week of a two-week trial. There was a significant reversal of phenytoin-induced cognitive impairment with improved acquisition and retention of memory and no effect on the anticonvulsant activity.[16] Some animal studies suggest a benefit from Bacopa monnieri for Alzheimer disease,[3][17] epilepsy,[18][19] Parkinson disease,[20][21] and cerebral ischemia/infarct.[22][23][24] It has been shown to cure gastric ulcers in animals and have anti-Helicobacter pylori activity in human colonic tissue.[25][26]

Mechanism of Action

Bacopa monnieri has many pharmacological actions, including antioxidant, anti-inflammatory, anticonvulsant, cardiotonic, bronchodilator, and peptic ulcer protection.[27][28][25] The leaf powder of Bacopa has been shown to have antioxidant effects.[29] The cognitive-enhancing properties of Bacopa are likely from the presence of a group of saponins collectively referred to as bacosides. Purified bacosides A and B, as well as bacopa alcoholic extract, may facilitate learning ability, memory, and cognitive performance.[30]

Some possible mechanisms which may lead to cognitive improvement include modulation of acetylcholine release, muscarinic cholinergic receptor binding, and choline acetylase activity.[15][31] The saponins in Bacopa modulate hypothalamic-pituitary-adrenal (HPA) axis output and protect the hippocampus. Bacopa causes an anti-inflammatory effect on activated microglial cell cultures.[32] The microglial cells respond to any injury by transforming into either a neuroprotective or neurotoxic phenotype that releases pro-inflammatory cytokines.

In one study, tea, infusion, and alkaloid extracts of Bacopa, as well as bacoside A administration, was shown to significantly inhibit the release of TNF alpha and IL-6 from activated N9 microglial cells in vitro.[32] Other research demonstrates several mechanisms of action, including acetylcholinesterase inhibition, beta-amyloid reduction, choline acetyltransferase activation, increased cerebral blood flow, and monoamine potentiation.[1] Many neuroprotective aspects of Bacopa have been studied. 

Bacopa has been reported to protect against oxidative damage via decreased protein carbonyl levels in both cytosol and mitochondria in all brain regions.[33] There is evidence of the inhibitory activity of Bacopa in the prevention of lipid peroxidation in the prefrontal cortex, striatum, and hippocampus of rats.[34] In the presence of free radicals, the first line of defense is the antioxidant superoxide dismutase, which increases with oxidative stress. One study reported decreased superoxide dismutase activity to normal levels in treated diabetic rats. This suggested homeostasis between the oxidant and antioxidant species.[35] Reduced glutathione was significantly depleted in diabetic rats compared to non-diabetic rats due to oxidative stress.[36] Bacopa has been reported to increase the level of reduced glutathione.[37]

Catalase is a common antioxidant enzyme found in nearly all living organisms exposed to oxygen. The age-associated decline in the catalase activity in the lymphocytes of middle-aged and older male rats was significantly increased over those who received Bacopa treatment.[29] In animal tissue models, Bacopa was shown to increase the adaptation responses to stressors. It normalizes monoamine levels and corticosterone in experimental models of stress.[12]

The sedative actions of Bacopa lend an overall calming effect. Bacopa has been shown to support GABA production, which reduces neuron excitability, thereby improving rapid response decision-making.[2] Gamma-aminobutyric acid (GABA) is a neurotransmitter that provides a calming effect on the brain. Bacopa monnieri has been shown to increase GABA by enhancing the GABA A receptor subunit and up-regulating glutamate decarboxylase.[38]

Administration

The typical dose range of Bacopa monnieri used in traditional medicine, and modern clinical trials are crude herb (5 to 10 grams per day of herb, taken in 2 or 3 divided doses), 1:5 tincture (10 to 20 mL per day, taken in 2 or 3 divided doses, and extract (300 to 450 mg per day of extracts usually standardized to 24% to 55% bacosides for adults). Bacopa may be used for up to 6 months at a dose of 225 mg daily in children (6 to 12 years.)[39]

Adverse Effects

Bacopa monnieri has a high therapeutic index and is generally well-tolerated. The most common side effects are gastrointestinal, including increased stool frequency, nausea, and abdominal cramps. These are believed to be secondary to an upregulation of acetylcholine activity and/or a saponin-mediated gastrointestinal tract irritation.[12] One study reported that Bacopa extract could also decrease fertility in animals. Libido is unaltered; however, there was a decrease in sperm count, motility, and viability when a dose of 250 mg/kg/day was administered for 28 and 56 days.[40] Bacopa is mildly sedating, which may contribute to its anxiolytic activity.

Contraindications

Bacopa monnieri may inhibit the acetylcholinesterase enzyme, which may result in increased acetylcholine levels. As a result, Bacopa could counteract the effects of anticholinergic drugs and may worsen bradycardia and exacerbate conditions such as gastrointestinal obstruction, peptic ulcer disease, pulmonary conditions such as asthma, and chronic obstructive pulmonary disease or urogenital tract obstruction.[12]

Bacopa has been shown to inhibit human cytochrome P450 enzymes which could contribute to herb-drug interactions when co-administered orally with medications metabolized by CYP1A2, CYP2C9, CYP3A4, and CYP2C19.[41] Animal research suggests Bacopa may increase thyroxine levels (T4) in mice by about 40%. It should be used cautiously (or avoided) in those with a thyroid condition or who take thyroid hormone medications.[42]

Monitoring

Studies demonstrating adverse reactions to Bacopa monnieri are limited as of this writing. No significant documented adverse drug reactions or side effects have been demonstrated in clinical or biochemical measures in humans.[43] One study documented a decrease in appetite and mild elevation in albumin, aspartate aminotransferase, urea, nitrogen, globulin, and sodium in rats when they received a dose of 500 mg per kg, but there was no significant change in the weight of organs at the end of the 90-day study.[44] Another study found Bacopa monnieri causes reversible suppression of spermatogenesis and fertility in Parkes (P) strain mice without affecting libido or producing toxic effects.[40]

Toxicity

There has been no human toxicity demonstrated with the use of Bacopa monniera in humans. One study evaluated the effects of large doses (30, 60, 300, and 1,500 mg/kg) administered to Sprague-Dawley rats over a period of 270 days and did not produce any significant toxicity.[45]

Enhancing Healthcare Team Outcomes

Individuals should communicate to their primary care provider when taking Bacopa monniera. The provider may need to discuss this with a pharmacist regarding other medications the patient is taking. Bacopa has cholinergic properties and may increase the chance of side effects with cholinergic drugs (acetylcholine, methacholine, bethanechol) due to an additive effect. Bacopa may also decrease the effectiveness of anticholinergic medications such as atropine or belladonna alkaloids.

Bacopa is known to cause non-competitive inhibition of several cytochrome P450 enzymes (1A2 (CYP1A2), 2C19 (CYP2C19), 2C9 (CYP2C9), 3A4 (CYP3A4)).[41] This may cause increased accumulation of medications broken down by this enzyme and decreased rate of formation of active breakdown products. This may alter the effects and side effects of these medications. 

T4 concentration was increased with the use of Bacopa extract. Consuming Bacopa concomitantly with thyroid hormone may result in too much thyroid hormone and increase the potential for adverse effects.[42]

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Disclosure: Eric Walker declares no relevant financial relationships with ineligible companies.

Disclosure: Mark Pellegrini declares no relevant financial relationships with ineligible companies.