From The February 2001 Issue of Nutrition Science News
by Jill Stansbury, N.D.
High on the aging populations' list of fears is losing one's mental faculties. With Alzheimer's disease and other forms of senile dementia affecting some 25 percent of all people older than 80, it certainly isn't an irrational fear. Hope lies in research that is revealing nutrition's role in both treating and preventing cognitive impairment.
Certain types of mental decline result from exposure to toxins and to both endogenous and exogenous oxidizing agentsall of which appear to contribute to brain inflammation, scarring and cognitive impairment. Brain inflammation may result from the presence of toxins and from allergies, stress or low nutrient levels in the tissues. The inflammatory process creates chemicals such as free radicals that cause oxidative damage. This oxidative damage may contribute to senile dementia. Exposure to free radicals can be especially damaging when brain tissues lack adequate levels of antioxidants and other nutrients to mitigate the consequences of chronic inflammation. The aging brain can have low levels of such nutrients for several reasons including a poor diet or inadequate nutrient absorption. Thus, antioxidants and B vitamins should top anyone's list of brain food.
Antioxidant nutrients such as beta-carotene, bioflavonoids, essential fatty acids, selenium, vitamins C and E, and zinc all reduce inflammation. Animal studies have shown antioxidant levels in the brain decline with age. The lowest levels are associated with the greatest neuronal impairment.
 Polyphenols in green tea, namely the catechins, have antioxidant properties that may help protect the central nervous system from oxidative damage. 
B Vitamins are also essential nutrients for mental health, with deficiencies potentially manifesting as psychosis and cognitive impairment.
The psychotic personality disorder known as Korsakoff's syndrome, for example, is a consequence of thiamin (vitamin B1) deficiency. Niacin (vitamin B3) deficiency is associated with delirium, dementia, and memory deficits. Vitamin B6 helps transform amino acids into monoamines, an important group of neurotransmitters. Hormone replacement therapy and birth control pills deplete vitamin B6, and many hormone-induced mental or emotional disturbances may be improved with B6 supplementation. Abnormally low levels of vitamin B12 are associated with Alzheimer's disease. Folic acid deficiency is associated with forgetfulness, psychosis, dementia, nd Alzheimer's disease. 
Clearly, B vitamins are essential for optimal mental function. Supplementation with these and antioxidant vitamins is useful for preventing, and possibly treating, cognitive impairment.
In addition to antioxidants and B vitamins, various nutrients and plant derivatives may help reduce inflammatory damage to the central nervous system as well as prevent and treat impaired brain function.
Acetyl-L-Carnitine (ALC), a transport molecule important to cellular energy production, has become a central focus in neurodegenerative disease research. Carnitine is a vitaminlike compound that plays a role in mitochondrial energy production. ALC is one form of carnitine and is structurally similar to the neurotransmitter acetylcholine. Acetylcholine plays a central role in basic nerve transmission, concentration, memory and learning. The leading pharmaceutical drugs used for senility are, in fact, aimed at elevating acetylcholine levels in the brain. Congenital conditions such as muscle and heart weakness and mental retardation are associated with maternal ALC deficiency.  Supplementing with ALC is said to improve general metabolism in many organ systems, including the nervous system. ALC is noted to protect and stabilize muscarinic receptors (mediators of the parasympathetic nervous system) and intracellular membranes, as well as support mitochondrial metabolism and general cholinergic (processes involving acetylcholine) neurotransmission.  By enhancing membrane stability, energy production, and neurotransmission, ALC may improve mental function.  In addition, it may also have anti-inflammatory effects that reduce free radical generation.
Several studies have explored ALC's usefulness for Alzheimer's disease patients. ALC may increase B-endorphin levels, which are frequently low in Alzheimer's patients.  B-endorphin is a naturally produced opiatelike compound associated with general mood and mental demeanor. ALC's ability to bind cortisol and increase nerve growth factor production within the hippocampal region may explain its positive effects on neurons.
In a double-blind Italian study, 236 elderly patients with mild senility were treated with either 1,500 mg ALC or placebo. The ALC group showed significant improvements in memory and cognition compared with controls.  Several smaller studies have also noted positive effects on cognitive function in Alzheimer's disease patients. The designers of one 40-patient study evaluated the efficacy and tolerability of ALC therapy. In the double-blind trial, senile patients were divided into two groups of 20 and treated for 40 days with either two 500 mg ALC tablets or placebo three times daily. Mental parameters were assessed at zero, 20, and 40 days of treatment. Researchers concluded that short-term, intensive 3,000 mg/day ALC treatment could improve the main mental parameters of senility without significant side effects. 
Alpha-Lipoic Acid (ALA) has been researched since the 1950s as a treatment for Alzheimer's and Parkinson's diseases. ALA (synonymous with thioctic acid) is an antioxidant produced endogenously; because it is both fat- and water-soluble, it travels throughout the body. ALA may protect the body from oxidative damage by enhancing detoxifying agents such as glutathione, which occurs in the brain and serves as an antioxidant in these tissues. 
Results of animal studies demonstrate that ALA can reduce damage to neurons caused by toxic substances that are by-products of inflammatory processes.
 Another animal study showed memory improvement in aged rats given ALA. 
ALA is also involved with numerous metabolic functions including energy production in muscles, glucose metabolism, liver function, and nervous system function, all of which ultimately have effects on the brain.  Clinical trials conducted in Germany have shown ALA to be valuable for treating diabetic polyneuropathy, a disease involving the peripheral nerves. Supplementation was shown to improve motor and sensory nerve conduction.  Doses ranging from 600 to 1,800 mg per day were used both orally and intravenously. Higher dosages administered intravenously reduced symptoms most quickly, but lower dosages taken orally for several months also provided relief.
Docosahexaenoic Acid (DHA), an omega-3 long-chain fatty acid, is one of the primary structural components of the brain. Adequate DHA levels are necessary for proper neurotransmissions, and deficiencies of this essential fat have been linked to memory loss and depression. In a 1995 multicenter European study, 494 elderly persons treated for six months with 90 mg per day DHA (contained in 300 mg bovine phosphatidylserine) showed marked improvement in apathy and social withdrawal symptoms. 
Huperzine A (HUPA), a purified alkaloid compound isolated from Chinese club moss (Huperzia serrata), may benefit memory and cognition in several ways, one of which is influencing cholinergic activity. Hyperzine's actions are very similar to that of cognitive drugs, because it is a highly purified single chemical.
Several studies indicate that HupA has a highly selective affinity for acetylcholinesterase (an enzyme that breaks down unused acetylcholine) and inhibits it primarily. By doing so, HupA inhibits the degeneration of the neurotransmitter acetylcholine, which is rapidly broken down in the brains of Alzheimer's patients. A shortage of the neurotransmitter also appears to contribute to memory loss. HupA has also been observed to bind to nicotinic receptors in the central nervous system,  an activity believed to improve mental function. Finally, HupA acts as a neuronal cell protector,
 which may be both therapeutic and preventive for Alzheimer's disease.
For these actions on the brain, HupA may be useful in cases of dementia and memory impairment. In animal tests, HupA is orally bioavailable and well absorbed.  HupA appears to act quickly and remain active for many hours.  Repeated doses do not appear to promote tolerance or unresponsiveness. Animal studies show it easily crosses the blood-brain barrier and enters all areas of the brain.  HupA trials have not shown significant toxicity or side effects.
Phosphatidylserine (PS), a phospholipid present in large amounts in brain tissue and a component of all cell membranes, is thought to be necessary for optimal cognitive function. Supplementing with PS is believed to improve membrane transport, which enhances communication between cells, as well as neurotransmitter release and membrane receptor activity.  PS supplements are produced from soy or animal brain phospholipids, but most research has been conducted on products derived from animal sources.
PS may reduce stress-induced cortisol response, which, when excessive, promotes brain inflammation. One placebo-controlled study of nine healthy men was conducted at the University of Naples in Italy. Patients received 800 mg/day PS derived from bovine brain cortex. The dose counteracted stress-induced cortisol release. 
Several other small research trials have been conducted in Italy, including a placebo-controlled test involving a 300 mg/ day PS dose administered to a group of depressed, elderly women. Researchers noted that PS improved depression, memory, and behavior. 
Results from other trials conducted at Italian medical universities have shown PS to produce in both healthy and senile patients predictable EEG changes suggestive of improved concentration and awareness. [25, 26]Both Alzheimer's and Parkinson's diseases produce characteristic EEG changes. EEG mapping is being used to help diagnose and monitor brain diseases, as well as to investigate the effects of therapies such as PS. One such study conducted at a psychiatric hospital in Munich, Germany, used EEG mapping to monitor the effects of PS in 33 patients with mild dementia. The eight-week, double-blind, placebo-controlled, crossover trial showed significant EEG changes and symptom improvement for patients taking 300 mg/day PS compared with patients receiving placebo. 
As positive as these findings may be, many people have concerns about using animal brain tissue until more studies can determine its safety. Some animal brain tissue may harbor contaminants such as prions, which are protein particles believed to cause various infectious nervous system diseases such as bovine spongiform encephalopathy, also known as Creutzfeldt-Jakob disease or mad cow disease (For more information on this, please see related news story). Because most studies involve brain-derived PS, many clinicians and physicians are waiting until more vegetable-based PS research is conducted before they seriously consider PS. Additionally, the therapeutic dose, which ranges from 50 to 100 mg several times a day, can be cost prohibitive.
Plant-Based Brain Boosters
"Why should anyone die who has sage in their garden", and "rosemary is for remembrance," as the old sayings go. Both of these herbs have been found to promote acetylcholine, the most versatile and common neurotransmitter. Rosemary (Rosmarinus officinalis) and sage (Salvia officinalis) have both been shown to enhance the actions of acetylcholine through cholinergic activity  and are listed as memory enhancers in old herbal compendiums. Lemon balm (Melissa officinalis), often called the gladdening herb, also has been found to improve cholinergic activity,  and is recommended in old herbals for improving mood and cognition. Two other herbs more commonly associated with memory enhancement are ginkgo and ginseng.
Ginkgo (Ginkgo biloba) has been well documented to improve cerebral blood flow and to have antioxidant activity on the nerves and vasculature. Ginkgo may also reduce the age-related decline of neurotransmitters and receptors. Through these actions ginkgo may improve cognitive function and reduce central nervous system degeneration. 
Ginkgo also may slow the progression of Alzheimer's by promoting cholinergic activity, which is known to be deficit in patients with Alzheimer's disease .
Ginkgolide-B, a terpene-based active constituent of ginkgo, has been shown to act as a platelet activity factor antagonist, which improves blood viscosity and reduces blood vessel inflammation. The herb's flavonoids, which are potent free radical scavengers, combined with the ginkgolides, provide neuroprotection. 
Ginseng (Panax ginseng) contains glucosides known as saponins, which have, in laboratory studies, improved learning and memory in rats.
 These saponins raise the levels of biogenic monoamines and promote hippocampal neuron function. Animal studies have shown ginseng to help prevent age-related cognitive decline.  One theory explaining how ginseng works suggests the herb may improve nitric oxide synthesis in the brain, heart, lung, and kidneys. Nitric oxide plays a role in vasodilation, and ginseng may improve the delivery of blood and oxygen to tissues.
Ginseng and ginkgo may also work synergistically, according to a small, double-blind study of 64 healthy patients previously diagnosed with neurasthenia, a condition of nervous debility derived from impaired spinal cord function. Subjects were divided into four groups and given either 80, 160, or 320 mg of the ginseng/ginkgo combination or placebo twice a day and evaluated at one, 30, and 90 days for cognitive and cardiac function. The different doses provided statistically significant improvements in several measures at various intervals compared with the control group. 
Results are far from conclusive about how certain supplements affect brain function and mental acuity. But the nutrients and botanicals mentioned here hold promise. With what's at stake, they deserve the attention of researchers and formulators.
Vinpocetine a Stroke of Good Luck
Jill Stansbury, N.D., maintains a private practice in Battleground,Wash., where she specializes in botanical and natural therapies.
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