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Volume 23 • Issue 3 • 2011
A publication of the National Herbalists Association of Australia Australian Journal of Medical Herbalism 2011 23(3)
A clinical study to evaluate the effi cacy and safety
of Bacopa caplets in memory and learning ability:
a double blind placebo controlled study
Asim Kumar Mandal MDClinical Tutor, Institute of Post Graduation Medical Education & ResearchShyamadas Vaidya shashtra Pith Hospital, Kolkota-700009, India Suprabha Hedge MS (Ayu)Pralhad S Patki MDHead Medical Services & Clinical Trials, R & D Centre, The Himalaya Drug CompanyMakali, Bangalore 562 123, India. Ph 080 2271 9999 Fx 080 2371 4472 Bacopa has been used in the Ayurvedic system of medicine as a nervine tonic for centuries. The present study was carried out to evaluate the safety and effi cacy of Bacopa caplets to improve memory and learning ability in a double blind placebo controlled clinical study. Bacopa caplets were given in a dose of one caplet (750 mg) daily for sixteen weeks. Verbal span test, verbal working memory task test and text comprehension tests were used as clinical parameters to assess memory and learning ability in 84 subjects. Bacopa caplets signifi cantly improved these parameters at sixteen weeks of drug therapy. The drug was well tolerated without any serious adverse effects. It did not change any biochemical parameters. Bacopa caplets appear to be clinically effective in improving cognitive functions without any serious adverse effects.
Key words: Bacopa, cognitive function, effi cacy, safety.
Bacopa monnieri (BM), a well known memory booster Memory is an integral part of our existence, yet it is (Husain 2007). BM, also referred to as water hyssop, only vaguely understood. It is the ability to retain and brahmi or jalanimba in India, has been used for centuries utilise acquired information or knowledge.
in the Ayurvedic system of medicine, a holistic system Throughout the modern history of neuroscience, of medicine originally from India. The name brahmi is memory and attention have enjoyed centre stage as derived from the word ‘brahma' the mythical ‘creator' in a fundamental process of intellectual function. Both the Hindu pantheon. It is classifi ed as a medha rasayana, operate together, memory has a limited capacity and a drug used to improve memory and intellect (medhya) hence attention determines what will be encoded. (Mukheijee 1966). The plant has been used extensively Attention operates in a world that is relatively stable over as a nootropic and digestive and to improve learning and time and hence both memory and attention might refl ect memory (Nadkarni 1988). the same process. Attention helps to improve memory Compounds responsible for the pharmacological and encoding, but the details of this modulation remain effect of BM include alkaloids, saponins and sterols unsolved (Chun 2007, Roediger 1990).
(Bose 1931). Alkaloids such as brahmine, nicotine One of the most important conceptual developments and herpestine have been also reported to help in its in cognitive therapy is the subdivision of memory into pharmacology (Chopra 1956). A major chemical entity three separate processes, encoding, storage and retrieval. shown to be responsible for neuropharmocological Storage is diffi cult to study where the retrieval process effects is bacoside (Chatterji 1965). Bacoside is a is easiest to observe. A major question in many people's complex of bacoside A and bacoside B, probably optical minds is how to improve memory. Medications such as isomers. It is suggested that bacoside induces membrane modafanil, donepezil and racemic amphetamine have dephosphorylation, with a concomitant increase in been used to improve memory in humans. But most of protein and RNA turnover in specifi c brain areas (Singh them have serious adverse effects.
1988) and helps in motor learning (Aithal 1961). Recently interest in the use of herbal products Bacoside rich extracts of BM have been evaluated for has grown dramatically both in developing countries reversing depletion of acetylcholine in the frontal cortex and the Western world (Sparreboom 2004). It is now and hippocampus (Sairam 2001).
apparent those available psychotherapeutic agents are Recently Bacopa caplets have been introduced not suffi cient to meet the therapeutic requirements of into clinical practice. They contain extracts of Bacopa patients with mental illness. In the folklore of Indian monnieri 100 mg and powders of Bacopa monnieri medicine, several herbs have been traditionally used as 650 mg to be taken in a dose of 1 caplet daily. The present nerve tonics. One of the most popular of these herbs is study evaluated the clinical effi cacy and safety of Bacopa National Herbalists Association of Australia 2011 Australian Journal of Medical Herbalism 2011 23(3)
caplets in individuals with disturbances in concentration, and Ayurvedic criteria for desired quality were in memory and learning ability.
accordance with the guidelines of Pharmacopoeial Standards of Ayurvedic Formulations (1987) and were carried out by a qualifi ed chemist approved by the Food Ninety six subjects who were not taking any and Drug Administration.
medication or other herbal preparation and who reported Bacopa monnieri, a semi aquatic herb, grows no head injury, entered into the study. Before entry throughout India and is transplanted during September to each subject was given a detailed description of the November. Geographical source and harvest time for the investigational product, nature and duration of the study. herb was recorded. This formulation has been approved Twelve participants, seven from the placebo group and by regulatory authorities in India as a herbal formulation.
fi ve from the drug treated group withdrew from the study after the initial testing session for personal reasons. None of them withdrew because of any adverse effect due to Assessment was carried out initially and at monthly medication. Eighty four participants (52 females and 32 intervals until the end of the study. The assessment males) between the age of 30 and 42 (mean 36, SD 4) included a verbal memory battery designed for this study. completed the study.
All tasks proposed a reading input activity.
1. Verbal span test (Maria 2005) used to assess the general capacity of encoding verbal information. The study was designed as a double blind randomised Participants read three different series of frequent placebo control with two groups, a Bacopa monnieri words, which they were asked to recall randomly.The group (n=41) and a placebo group (n=43).
examiner recorded the number of words correctly recalled. The series was composed of phonologically The trial had a 3 week placebo run in with 12 weeks similar words [bangle (bala), garland (mala), of treatment with either Bacopa or placebo. Participants brother-in-law (sala)]. It also included long words were taken into the study as volunteers, living with family, such as current or running (cholito bhasha), name taking no medication, with no complaint of memory (pundarikaksha), guest (aaguntak), sweet (jolbhara problems and without any illness. They were educated sondesh), poem (shesher kovita). with adequate Bengal language skills and adequately 2. Verbal working memory task (Daneman 1980) corrected vision. They were asked to refrain from alcohol consists of reading several long sentences while for 24 hours prior to each visit and not to change life style retaining in memory the last word of each sentence. habits during the study period. They provided informed Participants were presented with three series of consent and the study was approved by the local ethics sentences and asked to recall the last word of each committee. They were free to withdraw from the study if they so desired.
3. Text comprehension test (logical memory) (Kintsch 1978). A story was presented to the participants and the subject was asked to recall the information in the The intervention was in the form of 12 weeks of a text with details after reading it once.
daily tablet comprising extract of Bacopa monnieri whole For each compiled task the subject received 1 point or plant 100 mg and powders of Bacopa monnieri whole a 0 score; in the repetitive tasks the maximum score was plant 650 mg. This extract was manufactured from the 2; the event based task was 4.
dried aerial plant of BM in India. The herb was extracted with water to produce 15% dry extract with a minimum Safety test
of 60% of total bacoside, the plant was identifi ed by a The subjects underwent hematological evaluation well qualifi ed botanist and a voucher copy of the plant on entry and at the end of the study. All adverse events is preserved in pharmacognosy laboratory. Placebo was either reported or observed by patients were recorded manufactured using excipient and replicated the active with information about severity, duration and action in appearance, odour and texture. Randomisation was taken regarding the study drug. The relationship of determined by a computer generated series. All study adverse events to the study medication was predefi ned as personnel were blinded to the assignment until analysis.
‘unrelated' (a reaction that does not follow a reasonable temporal sequence from the time of administration of the drug), ‘possible' (follows a known response pattern Each caplet contains: to the suspected drug but could have been produced • Extract Bacopa monnieri whole plant 100 mg by the patient's clinical state or other modes of therapy • Powder Bacopa minnieri whole plant 650 mg administered to the patient), and ‘probable' (follows a Good agricultural and collection practice (GACP) was known response pattern to the suspected drug that could followed during the collection and manufacture of the not be reasonably explained by the known characteristics herbal formulation (WHO 2003). Botanical identifi cation of the patient's clinical state). For patients recorded National Herbalists Association of Australia 2011 Australian Journal of Medical Herbalism 2011 23(3)
as withdrawing from the study, efforts were made to or education level. Mean score for tests of memory and ascertain the reason for the dropout. Non compliance learning are shown in Table 2. Bacopa drug therapy (defi ned as failure to take less than 80% of the medication) signifi cantly improved verbal span memory, verbal was not regarded as treatment failure and reasons for non working memory and logical memory at 16 weeks of compliance were recorded.
drug therapy; placebo group did not show any such change. Placebo run in period did not indicate any Primary and secondary outcome measures
signifi cant changes in any of the parameters. Similarly The predefi ned primary outcome measure was the no signifi cant effects were observed on blood pressure, effect of BM on memory and learning ability. The hematology, liver function tests, renal function test and predefi ned secondary outcome was incidence of adverse fasting blood sugar.
effects and patient compliance.
Table 1: Demographic data
Statistical analysis was carried out using Fisher's Exact test for presence or absence of various signs. Age (mean ± SD) years Repeated measures of ANOVA followed by Dunnett's Multiple comparison and Posthoc were used for analysis High school level of hematological parameters. Changes in memory and Mean blood pressure Systolic and diastolic learning ability were analysed using paired ‘t' test. Values were expressed mean ± SD. The minimal level of signifi cance was fi xed at p<0.05. Statistical analysis was The present study indicates that Bacopa caplets when carried out using GraphPad Prism version 4.03.
given for sixteen weeks are well tolerated in adults and help in improvement in cognitive function. Bacopa improved verbal span tests, verbal working memory task There were 96 subjects who were available for and text comprehension task where placebo recipients recruitment, 12 withdrew for personal reasons. The remained stable on these tasks. The benefi ts of Bacopa majority of the subjects were women of Asian origin. in cognitive functions have been reported in a number of Average age was 36.0±4 and educational level was high other studies (Stough 2001, Roodenrys 2002). school (Table 1). No difference existed between the The exact mechanism of action of Bacopa in groups for age, blood pressure, heart rate, temperature enhancing mental activity is unknown, however the Table 2: Mean score for memory and learning testslts
Bacopa (n = 41)
Placebo (n = 43)
Verbal span:Short words Table 3: Effect of drug therapy on hematological parameters
Haemoglobin (gm/dl) Total WBC count (cells/cu.mm3) National Herbalists Association of Australia 2011 Australian Journal of Medical Herbalism 2011 23(3)
triterpenide saponins and their bacosides are responsible Pharmacopoeial Standards of Ayurvedic Formulations. 1987. for the ability of Bacopa to enhance nerve impulse Central Council for Research in Ayurveda and Siddha. New transmission. The bacosides aid in repair of damaged Delhi: Government of India. neurons by enhancing kinase activity, neuronal synthesis Roediger HL. 1990. Implicit memory: retention without and restoration of synaptic activity (Singh 1997). Studies remembering. Am Psychologist 45;1043-56.
have also indicated that Bacopa extract modulates the Roodenrys S, Booth D, Bulzomi S et al. 2002. Chronic expression of certain enzymes involved in generation effects of Brahmi (Bacopa monniera) on human memory. and scavenging of reactive oxygen species in the brain (Chowdhuri 2002). Therapeutic doses of Bacopa are Sairam K, Rao CV, Babu MD, Goel RK. 2001. Prophylactic and curative effects of Bacopa monniera in gastric ulcer not associated with any known side effects and Bacopa models. Phytomed 8;423-30. has been used safely in Ayurvedic medicines for several Singh HK, Dhawan BN. 1997. Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn Further studies may be required to determine whether (Brahmi). Ind J Pharmacol 29;S359-65.
the advantageous effects of Bacopa are due to its direct Singh HK, Rastogi RP, Srimal RC, Dhawan BN. 1988. Effect of effect on brain chemistry to infl uence memory processes. bacosides A and B on avoidance responses in rats. Phytother A larger sample size will be useful for pharmacovigilance.
Res 2;70-5. Sparreboom A, Cox MC, Acharya MR, Figg WD. 2004. Herbal remedies in the United States: potential adverse interactions The present study indicates that Bacopa caplets are with anticancer agents. J Clin Oncol 22;2489-503.
safe and effi cacious in improving cognitive functions Stough C, Lloyd J, Clarke J et al. 2001.The chronic effects of an in human subjects. Bacopa drug therapy signifi cantly extract of Bacopa monniera (Brahmi) on cognitive function improved verbal span memory, verbal working memory in healthy human subjects. Psychopharmacol 156;481-4.
and logical memory at 16 weeks of drug therapy. The WHO. 2003. WHO Guidelines on Agricultural and Collection formulation is safe without any serious adverse effects. practices for medicinal plants. Geneva: World Health The drug is well tolerated. Disclosure of confl icting interest
Aithal HN, Sirsi M. 1961. Pharmacological investigation on Dr Pralhad S Patki and Dr Suprabha Hegde are full Herpestis monniera. Ind J Pharmacy 23;2-5. time employees of The Himalaya Drug Company. Dr Bose KC, Bose NK. 1931. Observations on the actions and uses Asim Kumar Mandal is a clinical tutor at Kolkata and of Herpestis monniera. J Ind Med Assoc 1;60. has no fi nancial interest in The Himalaya Drug Company.
Chatterji N, Rastogi RP, Dhar ML. 1965. Chemical examination of Bacopa monniera Wettst: part II isolation of chemical constituents. Ind J Chem 3;24-9. Chopra RN, Nayar L, Chopra IC. 1956. Glossary of Indian Medicinal Plants Vol 32. New Delhi: Council of Scientifi c & Industrial Research. Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC. 2002. Antistress effects of bacosides of B. monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytotherapy Research 16;639-45.
Chun MM, Turk-Browne NB. 2007. Interactions between attention and memory. Current Op Neurobiol 17;177-84.
Daneman M, Carpenter PA. 1980. Individual differences in working memory and reading. J Verbal Learning & Verbal Behav 19;450-66.
Husain GM, Mishra D, Singh PN, Rao ChV, Kumar V. 2007. Ethnopharmacological review of native traditional medicinal plants for brain disorders. Pharmacog Rev 1;20-8.
Kintsch W, Van Dick TA. 1978. Toward a model of text comprehension and production. Psychol Rev 85;363-94.
Mukheijee DG, Dey CD. 1966. Clinical trial on Brahmi. Int J Exp Med Sci 10;5-11. Nadkarni KM. 1988. The Indian Materia Medica. Columbia MO: South Asia Books. Parente MAMP, de Taussik IM, Ferreira ED, Kristensen CH. 2005. Different patterns of prospective, retrospective, and working memory decline across adulthood. InterAmerican J Psychol 39:2;231-8.
National Herbalists Association of Australia 2011
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