Reviewed: Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Scholfield CN. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-535.

For more than 3,000 years, bacopa (Bacopa monnieri, Scrophulariaceae) has been used in Ayurvedic medicine to improve memory and brain function and to promote longevity. Many clinical studies have been conducted to evaluate the effect of bacopa on cognitive function; however, according to the authors, there have been no published meta-analyses.* Hence, the purpose of this study was to conduct a meta-analysis to evaluate the efficacy of bacopa for cognitive performance enhancement.

The following databases were searched from their inception through June 2013: MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central Register of Controlled Trials, WHO Registry Network, Thai Index Medicus, Index Medicus Siriraj Library, and www.clinicaltrials.gov. The following search terms, representing various current and previously used Latin and common nomenclature for the herb, were used in combination with “cognitive performance” or “memory”: Bacopa monnieri, Bacopa monniera, Herpestris monnieri, Herpestrismonniera, Monieraeuneifolia, Lysimachia monnieri, Brahmi, coastal water hyssop, water hyssop, thyme leafed gratiola, thyme leaved graticula, and thyme leafed graticula. In addition, reference lists were hand-searched.

Included studies were randomized, placebo-controlled studies that used neuropsychological tests for cognitive performance, had a treatment duration of at least 12 weeks, and in which subjects received a standardized extract of bacopa, the bacoside composition of which was measured or discoverable.** Studies that evaluated bacopa in combination with other treatments were excluded. Data were extracted from each article. The methodological quality of each study was evaluated with the Jadad scale (low-quality studies scored less than 3) and Cochrane’s risk of bias tool for assessing internal validity.

A total of 289 published studies were discovered, but only nine clinical trials met the inclusion/exclusion criteria. Of these nine studies, seven were conducted in healthy subjects, and two were conducted in patients with memory impairment. The most common dose evaluated was 300 mg/day (six studies), one study evaluated 250 mg/day, two studies evaluated 450 mg/day, and one study evaluated 600 mg/day (one study evaluated two doses). Six studies had a treatment duration of 12 weeks, one lasted 13 weeks, and two studies ran for 18 weeks. The Jadad scores for the nine studies were 3 (two studies), 4 (four studies), and 5 (three studies), which indicates that the included studies were well designed. Assessment using Cochrane’s tool indicated risk for bias was low or unclear in most areas; however, two studies were at high risk for selective outcome reporting, and one study was at high risk for “other sources of bias.”

Combining data from all nine studies, 231 subjects received bacopa, and 206 subjects received placebo. The outcome measures for the meta-analysis were the effects of bacopa on memory function and the effects of bacopa on attention. Six studies collected data on memory function (n=326 subjects) by evaluating the following parameters: picture recognition, numeric working memory, word recognition, spatial working memory, and auditory verbal learning. There was high heterogeneity in the results, and, on most, significant correlations between outcome measures and bacopa consumption and improved memory function could not be identified. The authors report that time taken to complete a task was decreased in subjects taking bacopa compared with placebo; however, this conclusion was drawn from only one study that examined this endpoint (further, it is difficult to assess the statistical significance of the time for completion of this task and its clinical significance).

Seven of the included studies evaluated attention (n=303 subjects). While the meta-analysis revealed no effect of bacopa extracts on choice reaction time, sub-group analyses of studies using only 300 mg/day bacopa extract showed a decreased choice reaction time of 10.6 milliseconds (comparative effects of 450 and 600 mg/day doses not reported).

Eight studies reported no serious adverse events (AEs). AEs commonly reported in the bacopa group were gastrointestinal related (increased stool frequency, nausea, abdominal cramps, and diarrhea). Other AEs reported in subjects taking bacopa were flu-like symptoms, dry mouth, and decrease in the number of dreams.

The authors conclude that bacopa may be beneficial in improving attention (choice reaction time). As one peer reviewer of this Research Review noted, “the authors interestingly indicate that ‘because attention was improved, the extract might be an appropriate treatment for young patients having attention deficit hyperactivity disorder (ADHD).’”

The heterogeneity in the results of the memory assessments could be attributed to the variety of doses and volunteer characteristics (healthy vs. memory impaired). The authors also note that there are many other measures of memory that the included studies did not evaluate. The data from this meta-analysis cannot be generalized to patients with cognitive impairment since the included population was mostly healthy subjects. “Also intriguing is that the standard tests, particularly for those used in patients with mild cognitive impairment (MCI), have low sensitivity,” another peer reviewer of this Research Review added. “The current treatments using licensed pharmaceutical drugs such as anticholinesterases, including donepezil, generally have little effect on MCI, while the improvements in more advanced disease are highly significant, but their clinical impacts are more questionable. Given that, the effects of bacopa reported here on MCI and non-impaired subjects, although small in absolute terms, suggest that bacopa could be clinically useful.”

More well-designed, randomized, placebo-controlled studies of bacopa extracts in patients with memory impairment are needed. Perhaps a meta-analysis might be more appropriate when more studies using similar designs are available.

—Heather S. Oliff, PhD

* A systematic review of 64 trials was published in 2012: Pase MP, Kean J, Sarris J, Neale C, Scholey AB, Stough C. The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. J Altern Complement Med. 2012;18(7):647-652.

** The paper notes that only in two studies are the concentrations of bacosides A and B described. The term “standardization” for bacopa extract usually refers to the amount of these two compounds. Thus, it is possible to compare the doses of the various bacopa extract preparations in mg terms only if such information on the standardization is present.