Brain HealtH

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activate yOur mind!The power of wild green oat extract

November/December 2008 Vol 4 No.6

trends in Brain HealtHInfluencing brain function has been a fixation for us humans since the beginning of civilization. The use of herbals to expand consciousness and alter the senses is only one side of the story, and the search for cognitive-enhancing potions has been a dream for generations of wizards, shamans, doctors and scientists. We now have the precise instruments to scientifically verify the extent to which herbs and nutrients can support and improve the functions of the most sophisticated organ of our body. Science has already helped the transformation of traditional remedies into therapeutics, Andrea Zangara reports.

at one end of the scale of brain function

is Alzheimer’s disease (AD). AD is

still as mysterious as the brain, the

organ targeted by dementias, but the

discovery of the role of natural cholinesterase

inhibitors such as Galantamine and Huperzine A is

already of great help for patients, and of inspiration

for the search for perhaps even more effective

synthetic medicines. At the other end of the scale

are healthy people: the elderly; students; business

executives; and stressed mums and dads

who are searching for an improvement in their

performance. Natural medicines and supplements

offer proven benefits for these people too. As our

brain is responsible for cognition and emotions,

we have a serious responsibility to support its

functions. A healthy lifestyle and diet, and a

sufficiently balanced and rich social and cultural

environment are the basis for brain health. This

underpins the normal development, maintenance

and protection of the whole nervous system.

However, we now have some scientific proof

that particular herbs and nutrients can promote

optimal cognitive functions and reduce age-related

cognitive decline.

Some clinical evidence confirms the importance

of consuming an antioxidant-rich diet to preserve

cognitive ability. Oxidative damage appears to

occur as one of the earliest pathophysiological

events in AD; thus, an increased intake of

antioxidants in patients with early signs of

cognitive deficits could be helpful in lowering

the rate of progression into dementia. Vitamins

A, C, E (particularly in the form of tocotrienols),

the vitamin-like compound coenzyme Q10

(CoQ10), anthocyanins from berries, curcumin

(derived from turmeric root), pycnogenol (from

pine bark) and the minerals selenium and zinc

all have produced promising results and various

degrees of evidence in terms of neuroprotection

and cognitive functions in a series of preclinical

and clinical studies. Also, the amount of evidence

associating polyunsaturated fatty acids (PUFAs)

with cognitive function is increasingly convincing.

The provision of adequate amounts of the long-

chain omega-3 fatty acid, docosahexaenoic acid

(DHA) to neural cell membranes is essential for

normal brain function. There is emerging evidence

that insufficient levels of polyunsaturated fatty

acids may play a role in a range of psychiatric

and neurological disorders in adults and children,

and there are currently several clinical trials

under way to investigate the role of omega-3 in

mood disorders, particularly with the ‘MEG-3’

product. Another fatty compound that is important

for cognitive health is the nutrient, choline, a

component of brain cell membrane phospholipids

and a precursor of acetylcholine (Ach), a

neurotransmitter involved in memory and learning.

Citicoline and phosphatidylserine (PS) are other

fatty compounds that have improved cognitive

functions in clinical trials. Acetyl-l-carnitine (ALC),

a transport molecule that occurs naturally in the

brain, liver and kidney, seems to be beneficial

to the ageing brain. A meta-analysis of double

blind randomized controlled clinical trials of ALC

versus a placebo in the treatment of mild cognitive

impairment and mild Alzheimer’s disease supports

a significant advantage for ALC compared

with the placebo on both clinical scales and in

psychometric tests. And finally glucose; this simple

sugar is increasingly the object of research as it

is directly related to the ability to sustain attention

and other aspects of cognition.

Psychopharmacology and the Importance of Product-Specific EvidenceThe concept of cognitive enhancement means

an improvement in basic aspects of the cognitive

functions that are essential to the conduct of

the activities of daily living. For healthy people,

this represents identifying an improvement on a

valid measure of cognitive function recognized

as important for everyday performance. The idea

that “natural equals safe” is irrational, given the

large number of poisonous substances in nature.

Also, that the therapeutic effects of any medicinal

product made from a particular herb are the same

as any other fails to recognize the complexity of

these products. Therefore, considering safety

and efficacy is vital when evaluating modern

natural products. A welcomed tightening of the

regulations on herbal and other food supplements

will help to protect the consumer and health

professional from products that present risks to

health or make misleading claims.

When considering evidence and how to apply

it to herbal medicines, we need to be careful.

The widely used claim for a number of herbal

products, that they improve cognitive abilities and

psychological well-being, often lacks evidence-

based data. The modern mass production of

herbal products has resulted in remedies that are

very different from the traditions of use that are the

basis for their safety and effectiveness (products

were not used as tablets in past centuries, for

example). Natural medicines are highly variable and

their active ingredients are often not fully known;

therefore, therapeutic results and safety issues

are very different from product to product. For

this reason, it is important to look for the specific

products that have been used in the clinical trials

as a guarantee of safety and efficacy. The use of

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Brain HealtH special

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computerized cognitive assessment like the

Cognitive Drug Research battery, commonly used

in dementia clinical trials, is increasingly employed in

the evaluation of natural products for the support of

brain functions, as it allows for a precise measure —

even in healthy volunteers.

“Generic” (untested) products and borrowed

science represent a threat to consumers

and the whole reputation of the market. The

goal for the century ahead is properly done

human clinical trials on specific products, with

validated tests and markers. Such “product-

specific evidence” will improve health outcomes

and the acceptance of natural medicines.

A growing trend will be that consumers will

ask manufacturers of herbal medicines, and

other natural remedies for brain health, for the

evidence to support their specific product.

Herbals for Cognitive Enhancement: Where’s the Evidence?Moving to botanicals, we have a plethora of

products that claim to be cognitive enhancers; but,

there are very few that have been clinically proven

to work. The herb Ginkgo biloba, in special forms

called EGb761 (Schwabe) and GK501 (Pharmaton),

has undergone significant research into its effects

on brain function. A patented combination of ginkgo

and ginseng (Gincosan) has been proven in one

of the largest clinical trials of its kind to be more

effective than a placebo for memory and attention in

healthy middle-aged volunteers, and extremely safe

(Wesnes, et al., 2000). It is important to recognize

that these results are not applicable to every ginkgo

or ginseng product on the market. In the case of

ginkgo, there is little traditional evidence for the

ginkgo leaf, from which EGb761 and GK501 are

made, further underlining the need to look for the

original clinically proven product. Other herbs at

various stages of clinical evaluation for the support

of cognitive functions are specific products made

from ginseng, green tea, sage, Rhodiola rosea,

lemon balm and aswaghanda, but a real rising star

in terms of scientific evidence is represented by a

particular product made from Bacopa monniera.

New evidence for an ancient Indian herbal

medicine: Since 3000 BC, the herb Bacopa

has been recorded as having anti-inflammatory,

analgesic, antipyretic, sedative and antiepileptic

effects, but its memory enhancing properties

have attracted most attention. Because of its

unique properties, the herb is known in India

as “Brahmi,” a name derived from the Lord

Brahma, the mythical creator of the world and

originator of Indian traditional medicine (Ayurveda).

Phytochemical studies have shown that Bacopa

monniera contains many active constituents,

including alkaloids, saponins, D-mannitol,

betulic acid, sitosteron and stigmasterols, and

the steroidal saponins, Bacosides A and B. As

with most herbal medicines, a complex mix of

constituents is needed for its therapeutic action.

The exact mechanism of action of Bacopa

monniera has not yet been determined. There is

evidence that it may be mediated by modulation of

the cholinergic system and/or antioxidant effects.

The scientific evidence for the memory

enhancing effects of Bacopa is based on

preclinical studies, and confirmed in clinical trials.

During the last 30 years, the Indian government

research institute, the Central Drug Research

Institute (CDRI), has investigated and developed

the modern use of Bacopa. In addition to a huge

number of scientific studies, this research includes

two single-blind clinical studies that have reported

the memory and learning enhancing effects of

chronic administration of a special extract of

Bacopa monniera in children (Sharma, et al.,

1987) and patients with anxiety neurosis (Singh

and Singh, 1980). This patented research has

led to the development of a special extract that

contains a complex of components including at

least 55% Bacosides A and B. This extract is

the major ingredient in the product, KeenMind,

which has been tested successfully in ‘gold

standard’ trials in Australia. Stough and colleagues

(2001) conducted the first double blind placebo-

controlled trial investigating the memory enhancing

effects of Bacopa monniera (KeenMind) in healthy

participants aged between 18 and 60 years.

Roodenrys and colleagues (2002) replicated the

memory enhancing effects of Bacopa monniera

(KeenMind) in 76 participants aged between 40

and 65 years. They reported a significant decrease

in the rate of forgetting newly acquired information

after 90 days of treatment with KeenMind in a

sample of older individuals than previously used by

Stough and colleagues (2001). These rigorously

designed trials have proven that KeenMind

improves memory and other measures of brain

function; therefore, this product is a newcomer

to be closely followed in the ongoing research of

evidence-based botanicals for brain health.

New Clinical Trial for BacopaA new trial on this patented extract of Bacopa

monniera has recently been published in the Journal

of Phytotherapy. The trial was conducted with 107

healthy participants at the Brain Sciences Institute

at Swinburne University in Melbourne, Australia.

About the AuthorApsychologistwithakeeninterestinthepsychopharmacologyofnaturalproducts,AndreaworkedatCognitiveDrugResearch(CDRLtd)asresearcherforanumberofyears.HethenhadtheroleofLaboratorymanagerfortheHumanCognitiveNeuroscienceUnit,thenBusinessDevelopmentManagerfortheBrainPerformanceandNutritionCentreandforNutrials,theFunctionalFoodsandNutraceuticalsResearchGroup,atNorthumbriaUniversity,UK.HeisalsomemberoftheMedicinalPlantResearchGroupatNewcastleUniversity,andworksasaprivateconsultantinareasrelatedtonutraceuticals(a.zangara@unn.ac.uk).

24 www.nutraceuticalmag.com

sectOr revieW

Cognitive function tests that are commonly used

in dementia trials (Cognitive Drug Research [CDR]

computerized assessment system) were used

to assess the effects. The effects of KeenMind

were compared with a placebo, in a randomized

double blind placebo controlled trial (the gold

standard in clinical research). After 90 days of

treatment with two capsules of KeenMind (www.

keenmind.com.au) the participants had significantly

improved performance on “working memory” (the

ability to hold information “online” in the brain and

do something with that information) and “visual

information processing” (a measure of the ability to

sustain attention). Professor Con Stough, principal

investigator of the study, said: “The results of this

trial substantiate the two other published trials in

non-elderly participants. That is, there is converging

evidence that chronic administration of KeenMind

improved cognitive processes (particularly memory

and speed of brain processing).”

He added: “KeenMind is not just another product

making claims about brain effects. It is the result of

30 years of intensive research worldwide and, now,

three clinical studies have confirmed the interesting

potential of this natural product. Interestingly, the

cognitive effects appear to have no side-effects,

even in elderly participants. Our current research

is examining the exact mechanism of action of

KeenMind on the brain. Early possibilities include

the removal of beta amyloid, anti-inflammatory,

antioxidant, increased blood flow to the brain and

direct neurotransmitter effects.” Flordis Natural

Medicines is currently seeking partners for the

global launch of KeenMind. For enquiries, e-mail

nigel@flordis.com.

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