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Preserving and Restoring Brain Function

October 2005

By Dale Kiefer

Grape Seed Counters Brain Cell Aging

Wine has always been popular, but its health benefits are now the subject of intense scientific scrutiny. Wine is an excellent source of beneficial polyphenol compounds. For those unwilling or unable to imbibe regularly, the remarkable benefits of grape polyphenols are available through grape seed extracts. Scientific studies have shown that the antioxidant power of these natural compounds—known as proanthocyanidins—is 20 times greater than vitamin E and 50 times greater than vitamin C.71

Recent research indicates that grape seed extract may play a specific role in protecting the brain by preventing the kind of neuronal toxicity experienced by Alzheimer’s disease patients. Korean scientists pre-treated rat brain cells with a grape seed extract in the laboratory before exposing the cells to beta-amyloid (Abeta), a toxic protein implicated in the formation of senile plaques in the brains of Alzheimer’s patients. Untreated cells exposed to Abeta accumulated damaging reactive oxygen species (free radicals) and underwent programmed cell death. However, rat brain cells pre-treated with the grape seed extract were significantly protected from the toxic effects of Abeta.72

New research from China suggests that grape seed polyphenols offer protection by preventing oxidative damage to cellular DNA.73 In the US, scientists analyzed the brain proteins of rats that were fed grape seed extract for six weeks, and identified 13 proteins that were positively altered by the supplement. The scientists stated that grape seed extract may confer “neuroprotective actions.”74

Vinpocetine Enhances Brain Circulation

Vinpocetine is a semi-synthetic derivative of the periwinkle (Vinca minor) plant. Developed more than three decades ago, vinpocetine has been hailed as an important neuroprotective agent with several key mechanisms of action.75 It has been widely used to treat symptoms of cognitive decline throughout Europe, where it is available only by prescription. Vinpocetine’s ability to increase blood circulation and enhance glucose utilization in the brain is one of its most powerful effects.76-79 This is particularly helpful to the aging brain, given that blood flow in the brain (and thus, oxygenation) tends to diminish with advancing age.

Vinpocetine’s therapeutic effects include its ability to enhance the electrical conductivity of cells composing the neural network. It protects the brain from damage caused by the excessive release of calcium ions intracellularly. Vinpocetine improves cerebral blood flow by inhibiting an enzyme that degrades cyclic GMP, a cellular metabolite. Degradation of cyclic GMP causes blood vessel constriction. Preventing degradation, therefore, allows cerebral arteries to relax, improving blood flow.76-78,80-82

Scientists have studied vinpocetine’s effects on human subjects under controlled conditions in various clinical trials. Three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease have shown that vinpocetine confers significantly more improvement than a placebo in performance on comprehensive cognitive tests reflecting attention, concentration, and memory.83 Vinpocetine has even been studied in newborn babies who suffered brain damage due to birth trauma. Vinpocetine significantly reduced or eradicated seizures and elicited a decrease in abnormally high pressure within the brain.84

These studies reveal that vinpocetine’s therapeutic effects compare favorably with acetylcholinesterase inhibitor drugs such as Aricept®, which is used extensively in the US and abroad to treat Alzheimer’s symptoms and vascular dementia. Human trials and others using rodent models reveal that vinpocetine is safe, effective, and well tolerated.81,85-87

There have been some reports that vinpocetine in combination with the prescription drug Coumadin® (warfarin) may slightly influence prothrombin time, a measure of the clotting time of blood plasma.88,89 Although vinpocetine is unlikely to have a clinically meaningful effect on prothrombin time in patients who are also taking Coumadin®, please consult with your doctor if you plan to use a vinpocetine-containing supplement concomitantly with Coumadin® (warfarin).

Pregnenolone Promotes Nerve Growth

Pregnenolone is a powerful natural hormone that is synthesized directly from cholesterol in the mitochondria, the “power plants” contained in all human cells. Pregnenolone for supplemental use is derived from a compound that occurs naturally in wild yams. In the body, pregnenolone is converted into other important hormones, including dehydroepiandrosterone (DHEA), estrogens, progesterone, and testosterone.90

Aging causes a sharp decline in pregnenolone production, and levels of the hormones for which it is a precursor tend to decline with age as well.91-93 Progesterone, for example, is synthesized in the brain, spinal cord, and peripheral nerves from its direct precursor, pregnenolone.94 Recent research suggests that progesterone plays a role in promoting the viability of nerve cells and in the formation of myelin sheaths, the fatty layers of “insulation” that allow electrochemical signals to propagate rapidly from one nerve to another. A recent clinical report summed up the potential implications of increasing progesterone: “Synthesis of progesterone in the brain, and the neuroprotective and promyelinating effects of this neurosteroid, offer interesting therapeutic possibilities for the prevention and treatment of neurodegenerative diseases, for accelerating regenerative processes, and for preserving cognitive functions during aging.”94

Researchers in France have documented a significant correlation between cognitive performance and levels of pregnenolone sulfate, a neurosteroid. The scientists recently established that pregnenolone directly influences acetylcholine release in several key brain areas involved in memory and learning, cognition, and the sleep-wakefulness cycle. The research team has also shown that pregnenolone reverses declining neurogenesis, or new nerve growth. Such declines are associated with disorders such as Alzheimer’s disease. “Our data demonstrate that [pregnenolone sulfate] central infusions dramatically increase neurogenesis . . . furthermore, our recent data suggest a critical role for neurosteroids in the modulation of cerebral plasticity, mainly on hippocampal neurogenesis.”95,96

Pregnenolone is not recommended for men with prostate cancer, as androgenizing hormones such as DHEA and testosterone may exacerbate this condition. Conversely, pregnenolone may confer some protection against other types of cancer by helping the body regulate estrogen levels. Pregnenolone has also been credited with alleviating symptoms of menopause, reducing the incidence of osteoporosis, and decreasing levels of LDL (low-density lipoprotein).

Rosemary (Rosmarinus officinalis)

Ginger and Rosemary: Natural Anti-inflammatories

The next time you need relief from pain or inflammation, consider heading for the spice rack rather than the medicine cabinet. Some of nature’s most potent anti-inflammatories are found in ginger and rosemary. Ginger has been used for thousands of years as a remedy for the pain and inflammation of arthritis,97 and research has confirmed its effects.97-103 A recent study conducted at Johns Hopkins University examined ginger’s ability to suppress inflammatory compounds in cells obtained from the joints of arthritis patients, which had been cultured in the laboratory. “We discovered that the ginger extract blocks activation of pro-inflammatory mediators and its transcriptional regulator . . . [ginger extract] offers a complementary and alternative approach to modulate the inflammatory process involved in arthritis,” the researchers concluded.101

Because inflammation is implicated in the development of certain degenerative neurological disorders such as Alzheimer’s disease, controlling it is crucial to preserving brain health. While ginger has demonstrated anti-inflammatory properties, especially in arthritis, it has also been shown to block activation of brain cells that are involved in the inflammatory cascade implicated in the development of Alzheimer’s.

Ginger (Zingiber officinale)

When brain cells are exposed to beta-amyloid peptides (Abeta), microglial cells surround the Abeta-containing neuritic plaques and produce proinflammatory cytokines, chemokines, and neurotoxic mediators. It is believed that when this inflammatory process continues unabated, nerve cells are destroyed, contributing to the development of Alzheimer’s.103,104 Scientists wondered whether ginger extract could suppress activation of these brain cells by proinflammatory substances. By incubating cells with ginger extract and various inflammation-provoking substances, they demonstrated that “ginger can inhibit activation of human monocytic THP-1 cells by different pro-inflammatory stimuli and reduce the expression of a wide range of inflammation-related genes in these microglial-like cells.” The scientists concluded that ginger extract “may be useful in delaying the onset and the progression of neurodegenerative disorders.103

Like ginger, rosemary has long enjoyed a reputation as a venerable healing herb. One of its chief active constituents, carnosol, functions as an antioxidant and anticarcinogen. Researchers in Taiwan reported recently that their findings suggest that carnosol inhibits nuclear factor-kappa beta activation, and provide possible mechanisms for its anti-inflammatory action.”105 Another rosemary constituent, ursolic acid, has also been shown to interrupt the pathway that leads to activation of pro-inflammatory nuclear factor- kappa beta.106

New Beginnings

While various factors threaten us with “brain drain” as we age, the good news is that modern science has identified nutrients that can slow or even reverse the progression of this once-inevitable decline. These supplements offer a smart option for maintaining brain health throughout life.

While various factors threaten us with “brain drain” as we age, the good news is that modern science has identified nutrients that can slow or even reverse the progression of this once-inevitable decline. These supplements offer a smart option for maintaining brain health throughout life.