Botanicals on the Brain

Originally Published NO June 2010

The process of normal aging contributes to a decline in several bodily systems and organs. While some of the effects of normal aging seem inevitable, one organ we all strive to keep in tip-top shape is our brain.

Recent statistics suggest an increased rate of cognitive decline in the overall population as a result of aging. Of even more concern is the fact that cognitive dysfunction seems to be occurring with increasing frequency earlier in life. Whether this includes normal declines in memory function associated with aging, or dementia associated with Alzheimer's disease, statistics show that the prevalence of these conditions is projected to increase significantly in the coming decades.

According to 2010 estimates published in the World Alzheimer Report released by Alzheimer's Disease International, 35.6 million people worldwide are living with some form of dementia. This prevalence is expected to nearly double by 2030, to 65.7 million people.,

Statistics published this year by the Alzheimer's Association estimate the U.S. prevalence of Alzheimer's disease to be 5.3 million people. Of these, the vast majority of individuals are over the age of 65. However, a half-million individuals in the United States under the age of 65 also suffer from some form of dementia, indicating a trend towards an increased development of cognitive deficiencies earlier in life.

These trends highlight the need for developing effective strategies designed to keep our brains healthier longer, with the hopes of preventing cognitive deficits occurring as a result of normal aging or various disease processes. A number of nutritional ingredients have been studied and found to have cognitive-supportive properties. Recent research has shown that several botanicals and compounds found within them can play an important part in supporting and correcting several fundamental aspects of health, which can ultimately lead to improved cognitive abilities. Some mechanisms employed by botanicals that are successfully used to support brain health include antioxidant and anti-inflammatory effects, improved circulation to brain tissues, and neural regenerative effects, which support the integrity of brain cells.

NEW SCIENCE FOR THOUGHT

Besides botanicals, research on other ingredients for cognitive health has been turning up promising results.

Citicoline

A study published this January in the International Journal of Eating Disorders studied the effects of Kyowa-Hakko's (New York City) Cognizin citicoline ingredient on appetite suppression. Citicoline is believed to increase dopamine levels in the brain and reduce food cravings.

Scientists at McLean Hospital and professors at Harvard Medical School performed the trial on eight men and eight women. For six weeks, subjects were given different doses of Cognizin (either 500 mg/day or 2000 mg/day). Subjects were monitored for changes in appetite ratings through questionnaires, weight, and brain responses to images of high-calorie foods using functional magnetic resonance imaging (fMRI).

The study found that appetite ratings declined significantly for the group given the highest dose of Cognizin. (There was no significant weight change in either group, although weight loss did occur.) High-dose participants showed the greatest activation in the three areas of the brain-the lateral orbitofrontal cortex, the insular cortex, and the amygdala-that are believed to be relevant in appetite control.

"The citicoline may have affected [the subjects'] appetite by stimulating regions of the brain used to normalize or regulate their response to the food images," said study researcher Deborah Yurgelun-Todd, PhD. "These three regions [of the brain] may help the participant see food as less rewarding, and therefore [the subjects] have a lesser desire to eat it."

Algal DHA

In May, a study published online in Alzheimer's & Dementia found that algal docosahexaenoic acid (DHA) omega-3 may improve memory and learning in older adults. The study, known as the Memory Improvement with Docosahexaenoic Acid Study, or MIDAS, was funded by Martek Biosciences (Columbia, MD), which markets Life'sDHA.

MIDAS is being called the first large, randomized, placebo-controlled study to demonstrate the benefits of algal DHA in maintaining and improving brain health in the elderly. The study was conducted on 485 people ages 55 and older, all of whom were considered to have age-related cognitive decline, such as problems remembering names or appointments, or difficulty solving complex problems. The participants took 900 mg/day of algal DHA or placebo over six months.

The study found that those supplementing with algal DHA had double the reduction in errors on a test (the CANTAB Paired Associates Learning test, which measures learning and memory performance) versus those taking placebo. Martek says that this improvement is "roughly equivalent to having the learning and memory skills of someone three years younger."

Chromium Picolinate

A new study published in the June edition of Nutritional Neuroscience says that chromium picolinate may improve memory function in elderly adults with early memory decline. The ingredient studied was Nutrition 21's (Purchase, NY) Chromax chromium picolinate.

The 12-week, double-blind, placebo-controlled study examined the effects of a 1000-µg daily dose, or placebo, on 26 older adults who had indications of early memory decline. Results of memory tests showed that Chromax-treated subjects made significantly fewer errors related to memory. In addition, 13 subjects (nine from the supplement group and four from the placebo group) also completed pre- and post-intervention fMRI scans while performing memory tasks. The researchers said that the supplemented group showed increased brain activation compared with the unchanged activation of the placebo subjects.

Turmeric

Turmeric (Curcuma longa) and the well-studied compound curcumin are renowned for antioxidant and anti-inflammatory benefits that are supportive to overall health and wellness. Recent studies suggest that this old stalwart, which has become a panacea of sorts, also promotes learning and memory abilities.

A Polish study in which aged rats were given an extract of turmeric found that pretreatment of the animals with this extract for two months increased learning ability and spatial memory compared to non-treated animals, as measured by performance on a standard water maze test. The authors reasoned that one possible mechanism of the extract's effect is that turmeric enhanced the ability of the animals to tolerate stress, and prevented degeneration of cells in the region of the brain known as the hippocampus. Animals in the groups treated with the extract also had significant differences in neurotransmitter levels compared to untreated animals, which indicates turmeric's ability to positively influence neurotransmitter production.

Because turmeric and its constituent curcumin seem to influence multiple pathways impacting brain health, it has been proposed as a potential treatment for Alzheimer's disease and other forms of dementia. Rahul Agrawal and colleagues at the Central Drug Research Institute in Lucknow, India, published a study in which curcumin was administered to a rat strain with drug-induced dementia. The researchers were investigating curcumin's ability to support the function of brain insulin receptors, which have recently been found to be defective in certain forms of dementia.

Untreated rats exhibited memory deficits as a result of dementia induction, as well as decreased functionality of insulin receptors in the hippocampus and cerebral cortex. Dementia induction also resulted in an increased breakdown of acetylcholine, while measures of oxidative stress were increased. Curcumin administration was found to restore the memory deficits in these animals, while brain insulin activity, acetylcholine levels, and oxidative stress were significantly improved.

These few studies serve to highlight curcumin's benefits and several unique modes of action for brain health, highlighting its importance as an effective supporter of cognitive function.

Sage

Sage (Salvia officinalis) is an herb with a traditional reputation for supporting memory function, and is also aptly named for its utility. Previously published controlled human studies have shown that sage extracts have cholinergic effects and can, therefore, improve cognitive ability in humans.

While earlier studies were conducted in young adults, a more recent study was undertaken in older adults at the Brain Sciences Institute of Swinburne University in Australia. In this double-blind study with a crossover design, 20 adults ages 65 or older received four different doses of sage extract or placebo treatment, with a seven-day washout phase between treatments. A baseline assessment was taken at each visit, followed by further assessments at four additional time points on the day of administration. The results of the study revealed significant improvements in memory performance and accuracy of attention with sage extract administration, indicating sage's acute benefits for memory and cognition.

Brahmi

In the Ayurvedic tradition of herbal medicine, one botanical in particular stands out for its cognitive benefits. That botanical is Brahmi (Bacopa monnieri). Its use as a memory and intelligence enhancer dates back thousands of years.

A recent investigation conducted in Thailand at Khon Kaen University and published in the January 2010 edition of the Journal of Ethnopharmacology studied the effect of Brahmi administration in a rat model of Alzheimer's disease. An alcoholic extract of Brahmi administered daily for two weeks resulted in significant improvements in memory function, as assessed using a standardized water maze test.

In addition, Brahmi administration led to a protective effect on neuron density, which was decreased as a result of Alzheimer's disease induction. Thus, Brahmi was able to support brain health and cognitive ability via its neuroprotective effects.

An earlier, double-blind, placebo-controlled study conducted by the Brain Sciences Institute in Australia focused on patients treated with 300 mg of a Bacopa monnieri extract for 90 days. Using the Cognitive Drug Research cognitive assessment system at baseline and again after 90 days of treatment, the researchers found that the Bacopa extract significantly improved spatial working memory accuracy, indicating its ability to enhance cognitive abilities.

Resveratrol

KRILL AND PS JOIN FORCES

AKER BIOMARINE (OSLO, NORWAY) and Lipogen (Haifa, Israel), respective producers of krill oil and phosphatidylserine (PS), announced the development of an innovative phospholipids ingredient in May. The new ingredient will combine Superba krill oil and Lipogen PS and is intended for the brain-health market.

"PS acts synergistically with omega-3 fatty acids to increase cognitive abilities," says Lipogen CEO Davis Rutenberg, noting memory support, mood, concentration, and other cognitive benefits from PS and krill oil.

Resveratrol has been in the news over the last several years for its potential benefits on cardiovascular health. It is known to have anti-inflammatory, antioxidant, and immune-modulating properties. More recently, resveratrol's ability to improve blood flow to the brain and impact cognitive performance was studied at the Brain Performance Nutrition Research Centre at Northumbria University in the United Kingdom.

Twenty-two healthy adults were administered placebo and two oral doses of trans-resveratrol (250 and 500 mg) on separate days. After 45 minutes, these adults performed a selection of cognitive tasks designed to activate the frontal cortex of the brain. Cerebral blood flow increased with resveratrol administration in a dose-related manner, indicating enhanced circulation as a result of resveratrol.

However, cognitive function was not affected in this study. Because this study only measured the effect of a one-time dose of resveratrol, longer-term studies are needed to show beneficial effects on cognitive function. Research in aged mice with neural inflammation related to infections has shown that resveratrol administration reduces cognitive decline associated with these dysfunctions. This is attributed to resveratrol's ability to decrease inflammation in brain tissue.

Promising Developments

Ginseng is known for its tonifying properties. However, the two major types of ginseng are thought of as having significantly different benefits in traditional Chinese medicine philosophy. Whereas Asian ginseng (Panax ginseng) promotes yang energy and is more stimulating, American ginseng (Panax quinquefolius) is thought of as calming, as it promotes yin energy. Due to its stress-reducing properties, American ginseng can have positive cognitive benefits.

Cereboost, an ingredient from Naturex (South Hackensack, NJ), is a patent-pending extract from American ginseng that has recently been studied for its cognitive effects. In fact, a recent, double-blind, placebo-controlled study with a crossover design assessed these benefits in 32 healthy young adults. The results of this study showed that Cereboost, administered as a single oral dose in three concentrations, significantly improved working memory performance in healthy young adults. Additional beneficial effects were seen on mood function, as noted by an increased sense of calmness with the lowest-administered, 100-mg dose.

Based on these results, Naturex is pursuing additional research on Cereboost, evaluating its immediate effects in older individuals. "We will be specifically looking at brain imaging in that study to evaluate any underlying neurophysiological substrates of cognitive enhancement associated with Cereboost," says Alvin Ibarra, strategic research programs manager for Naturex.

Cyvex Nutrition (Irvine, CA) is another company in the industry that is developing products specifically targeted to cognitive health. Cyvex Nutrition is partnering with the Salk Institute to study the impact that various flavonoids, including fisetin from strawberries, can have on cognitive health. Cognisetin is the brand name under which Cyvex Nutrition's fisetin product is marketed.

Initial studies on this and other flavonoids for improving cognitive health have been promising. According to Matt Phillips, president of Cyvex Nutrition, "Fisetin is highly efficacious in stimulating the signaling pathways that enhance long-term memory, as shown in previous studies conducted by the Salk Institute, but is unique to the industry."

Irfan Qureshi, ND, is vice president for technical and regulatory affairs for AIBMR Life Sciences (Puyallup, WA). AIBMR provides a complete range of natural-products consulting services.