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Dr Des Corrigan looks at studies of varying quality into the potential benefits of the so-called ‘memory herb’

This month’s article was inspired by a recent visit to a branch of an Australian chain of DIY/gardening shops with an advertising jingle that is equally familiar to Irish people used to frequenting a very similar chain of shops here. I was there to buy chilli peppers on behalf of my son, who I am convinced is addicted to capsaicin, as my instructions were to ignore common or garden varieties and seek out exotics such as the Carolina Reaper, notorious for its zillions of those Scoville Units used to measure the fiery heat of chillies. While there, my eye was caught by a plant label that stated ‘Brahmi — the memory herb’. The plant in question turned out to be Bacopa monnieri, which further intrigued me, as I have up to this time associated the name Bacopa with a white flowering plant that I use as a window box plant at home. But what we call ‘Bacopa’ is in fact another totally unrelated South African plant named Sutera cordata. Genuine Bacopa has a long history of use in the Indian system of traditional medicine known as Ayurvedic Medicine, particularly in neurodegenerative diseases and memory loss. Because of this, Bacopa has attracted Western attention as a possible source of active molecules of value in such conditions.

In Ayurveda, three energies (Doshas), namely Vata, Pitta and Kapha, are believed to influence the body. A predominance of Vata results in neurodegenerative diseases, including memory loss. Ayurvedic formulations that balance Vata are of scientific interest as a basis for research into possible medicines targeting such diseases.

The sub-tropical creeper Brahmi, found growing in marshy conditions, is one of the main herbs in such formulations. The sheer number of papers on Brahmi that showed up on my usual PubMed search came as another surprise.

The main constituents believed to be responsible for the neuroprotective effect of Bacopa plants are the dammarane-type triterpene saponins Bacoside A and B. A review of the experimental evidence on neuroprotection with Bacopa monnieri appeared in Molecular Biology Reports in 2021. Among the effects relevant to neuroprotective activity noted were anti-oxidant activity, acetyl-cholinesterase inhibition, β-amyloid reduction, and increased cerebral blood flow. Extracts of the plant standardised on Bacoside content and the isolated bacosides have been shown, in a number of animal studies, to enhance aspects of mental function, learning ability and memory. A 2017 paper in the Annals of Neurosciences noted that an extract of Brahmi (EBM) promoted free radical scavenger mechanisms and protected cells in the prefrontal cortex, hippocampus and striatum against cytotoxicity and DNA damage implicated in Alzheimer’s. EBM also reduced anticholinesterase activity comparable to donepezil, rivastigmine and galantamine; reduced β-amyloid deposition in the hippocampus; improved cerebral vasodilation and also total memory score with the maximum effect on logical memory and paired associate learning in humans. There were no reported serious clinical, neurological or haematological complications, with only mild nausea and GIT upsets seen in humans.

A meta-analysis of RCTs on cognitive effects of EBM appeared in the Journal of Ethnopharmacology in 2014. A total of nine studies involving 437 subjects showed improved cognition as measured by the shortened Trail B test and decreased choice reaction time. The authors called for a large, well-designed “head to head” trial against an existing medication to provide definitive data on efficacy in healthy or dementia patients. A more recent meta-analysis was published in Nature Research Scientific Reports in January 20221. Eleven studies involving 645 participants were included in the meta-analysis. Those studies that involved healthy volunteers found one or two measures of memory to have statistically significant differences between the Brahmi treatment and placebo, but any such changes were small. Two trials reported significant improvements in memory in older people with memory loss but who did not suffer from Alzheimer’s. Here again, the effect was modest. The one study in Alzheimer’s patients used a polyherbal formulation, making it impossible to attribute any effect to the Bacopa component. That formulation did, however, appear to be equal to donepezil in those patients. This did not prevent the authors from concluding that there is no clinical evidence that Brahmi improves memory in healthy adults or in those with age-related memory complaints.

A 2022 systematic review of randomised controlled trials of Brahmi in the treatment of dementia due to Alzheimer’s has appeared online in the Interactive Journal of Medical Research. It found five RCTs eligible for inclusion. The authors concluded that very low-certainty evidence suggests that there is no difference between Bacopa and placebo or donepezil in the treatment of Alzheimer’s or mild cognitive impairment in such patients, which is hardly a ringing endorsement. The difficulties inherent in such trials is perhaps illustrated by a 2020 paper in the Annals of the Indian Academy of Neurology, titled ‘Efficacy of Bacopa monnieri (Brahmi) and donepezil in Alzheimer’s disease and mild cognitive impairment: A randomised double-blind parallel Phase 2B study’. The paper states that this study of Brahmi versus donepezil showed no significant difference between them after one year of treatment. On the surface this seems positive, until one reads further that the study was terminated after three years and nine months after recruiting just 34 patients because of slow recruitment and a high drop-out rate. On that basis, I wonder why they bothered publishing what is essentially a non-study.

There is also some evidence of an effect in epilepsy and in depression, according to a 2020 clinical study in patients with depression-linked anhedonia published in Phytotherapy Research. There was a statistically significant improvement in the Snaith-Hamilton Pleasure Scale (SHAPS) and in the HAM-D in patients given an extract of Brahmi containing 20 per cent Bacosides along with citalopram compared to a group given citalopram alone. Given the extent of the pre-clinical data, which is highly impressive, there is clearly potential for using Brahmi extracts and its constituents in these most distressing and intractable of neurodegenerative conditions. However, the quality of the clinical data does not yet match that of its pre-clinical counterpart. It may do so in the future but that, perhaps not surprisingly, has not stopped the supplement industry from marketing a wide range of Brahmi products over the Internet. If you were asked by patients or concerned family members about this herb, the best reply might be ‘perhaps, perhaps, perhaps’.

Dr Des Corrigan, Best Contribution in Pharmacy Award (winner), GSK Medical Media Awards 2014, is a former Director of the School of Pharmacy at TCD and won the Lifetime Achievement Award at the 2009 Pharmacist Awards. He was chair of the Government’s National Advisory Committee on Drugs from 2000 to 2011. He currently chairs the Advisory Subcommittee on Herbal Medicines and is a member of the Advisory Committee on Human Medicines at the IMB. He is a National Expert on Committee 13B (Phytochemistry) at the European Pharmacopoeia in Strasbourg and he is an editorial board member of the Journal of Herbal Medicine and of FACT — Focus on Alternative and Complementary Therapy.