2. 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.
A
t 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 Evidence
The 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
SECTOR REVIEW
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3. Brain HealtH special
23www.nutraceuticalmag.com
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 Bacopa
A 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 Author
A psychologist with a keen interest in the
psychopharmacology of natural products, Andrea
worked at Cognitive Drug Research (CDR Ltd) as
researcher for a number of years. He then had
the role of Laboratory manager for the Human
Cognitive Neuroscience Unit, then Business
Development Manager for the Brain Performance
and Nutrition Centre and for Nutrials, the
Functional Foods and Nutraceuticals Research
Group, at Northumbria University, UK. He is also
member of the Medicinal Plant Research Group
at Newcastle University, and works as a private
consultant in areas related to nutraceuticals
(a.zangara@unn.ac.uk).
4. 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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