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  • 1. Brain HealtH Omega-3 Fatty acids Taking brain health to another level activate yOur mind! The power of wild green oat extract November/December 2008 Vol 4 No.6
  • 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 22 www.nutraceuticalmag.com
  • 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. Bibliography • S.A. Montgomery, L.J. Thal and R. 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