Life Extension Magazine®
LE Magazine December 1998 Now A Dietary Supplement Vinpocetine is a medication used throughout the world to treat brain aging. It's now available to Americans, either as an individual supplement or as part of the Foundation's Cognitex formulation. The scientific literature provides persuasive evidence that this plant extract can improve memory and cognitive function. By William Faloon Vinpocetine was introduced into clinical practice 22 years ago in Hungary for the treatment of cerebrovascular disorders and symptoms related to senility. Since then, it has been increasingly used throughout the world in the treatment of cognitive deficits related to normal aging. Vinpocetine, a pharmaceutical extraction from the periwinkle plant, has become a popular "smart drug" that Americans import from Europe for personal use. A recent ruling in Federal court makes vinpocetine legally available in the United States as a low-cost dietary supplement. Vinpocetine is now sold in 5-mg tablets, and has been added as well to the new Cognitex formula. Vinpocetine functions via several important mechanisms to correct multiple known causes of brain aging. It is well-established that normal aging results in a reduction of blood flow to the brain and a decrease in the metabolic activity of brain cells. The biological actions of vinpocetine initially showed that it enhances circulation and oxygen utilization in the brain, increases tolerance of the brain toward diminished blood flow, and inhibits abnormal platelet aggregation that can interfere with circulation or cause a stroke. More recent studies demonstrate that vinpocetine offers significant and direct protection against neurological damage caused by aging. The molecular evidence indicates that the neuroprotective action of vinpocetine is related to its ability to maintain brain cell electrical conductivity and to protect against damage caused by excessive intracellular release of calcium. Vinpocetine enhances cyclic GMP levels in the vascular smooth muscle, leading to reduced resistance of cerebral vessels and increased cerebral blood flow. It is interesting to note that Viagra, the widely publicized sex drug, and vinpocetine both work in the same way to improve blood flow. Vinpocetine's improvement in blood flow is specific to the brain, but like Viagra, vinpocetine possesses a mechanism that improves blood flow by inhibiting a phosphodiesterase enzyme that degrades cyclic GMP. The degradation of cyclic GMP causes arterial constriction and reduced blood flow. By inhibiting a phosphodiesterase enzyme, vinpocetine increases blood flow to the brain just as Viagra increases blood flow to the genitals. In a double-blind clinical trial-that is, a medical study in which neither the subject nor the persons administering the treatment know which treatment a subject is receiving-vinpocetine was shown to effect significant improvement in elderly patients with chronic cerebral dysfunction. Forty-two patients received 10 mg of vinpocetine three times a day for 30 days, then 5 mg three times a day for 60 days. Placebo tablets were given to another 42 patients for the 90-day trial period. Patients on vinpocetine scored consistently better in all evaluations, including measurements on the Clinical Global Impression (CGI) scale, the Sandoz Clinical Assessment Geriatric (SCAG) scale, and the Mini-Mental Status Questionnaire (MMSQ). There were no serious side effects related to the treatment drug. In another double-blind study, 22 elderly patients with central nervous system degenerative disorders were treated with vinpocetine or placebo. Patients received 10 mg of vinpocetine three times a day for 30 days, then 5 mg three times a day for 60 days. Another 18 elderly patients were given matching placebo tablets. Vinpocetine-treated patients scored consistently better in all evaluations on the tests noted above. According to CGI assessments, the severity of illness decreased in 73 percent of the patients in the vinpocetine group at day 30 and 77 percent at day 90, and improvement was seen in 77 percent and 87 percent of the patients at days 30 and 90, respectively. Patients also showed statistically significant improvement for all SCAG items but one, at days 30 and 90. The physician rated the improvement in 59 percent of the vinpocetine-treated patients as good to excellent. Again, there were no serious side effects. The effect of vinpocetine on memory functions was studied in 50 patients with disturbances of cerebral circulation. Improvement of cerebral circulation was observed after intravenous and oral administration of vinpocetine. Blood flow was most markedly increased in the gray matter of the brain. Improvement of memory capacity evaluated by psychological tests was recorded after one month of vinpocetine treatment. Longer-term use was associated with alleviation or complete disappearance of symptoms of neurological deficit. No side effects attributable to the drug were observed. The doctors stated that vinpocetine is indicated in the treatment of ischemic disorders of cerebral circulation-that is, a deficiency of blood, usually due to a constriction or partial obstruction of a blood vessel-particularly in chronic vascular insufficiency. Vinpocetine's safety and efficacy were demonstrated in a study of infants who suffered severe brain damage caused by birth trauma. Vinpocetine caused a significant reduction or disappearance of seizures, and the vinpocetine group also showed a decrease of intracranial hypertension and normalization of the psychomotor development. In a study to ascertain how this compound boosts cognition in rats, vinpocetine produced a significant increase in the firing rate of neurons. The scientists noted that the dose of vinpocetine used to increase electrical firing corresponded to the dose range that produced memory- enhancing effects. These results provided direct electrophysiological evidence that vinpocetine increases the activity of ascending noradrenergic pathways, and that this effect may be related to the cognitive-enhancing characteristics of the compound. Life Extension readers learned about the damaging effects of glutamate-induced excitotoxicity earlier this year. A vitamin B12 metabolite called methylcobalamin has been shown to specifically protect against this type of neuronal injury. Vinpocetine also has been documented to partially protect against excitotoxicity induced by a wide range of glutamate related neurotoxins. The benefits of vinpocetine are not restricted to the brain. One study showed beneficial effects in protecting the retina against the hepatitis B virus. While hepatitis viruses primarily affect the liver, most people don't know that these viruses can also infect the heart muscle, retina and other parts of the body. Another study showed that vinpocetine administered to rats inhibited the development of gastric lesions induced by ethanol, indicating its potential value for humans who drink to excess. And, in fact, vinpocetine is a popular drug used by alcoholics in Russia to recover from gastric and neurological ethanol-induced toxicity. Space motion sickness has been a perplexing problem in both the Soviet/Russian and U.S. manned space programs. Both the sensory conflict theory (neuronal signal mismatch) and the cephalad fluid shift concept explain the mechanism. Whichever theory is correct, vinpocetine has been used successfully in offsetting space-motion sickness in experimental test subjects. Vinpocetine used to be an expensive European drug, but is now available as a low-cost dietary supplement. Health people need only 15 mg a day of vinpocetine, the amount contained in the recommended daily dose of the new Cognitex formula. Those with neurological impairment should take 10 mg three times a day for 30 days, then reduce the dose to 5 mg three times a day. Starting about the age of 30, we typically experience a progressive decline in cognitive function. By the time we're in our 60s or 70s, one can expect severe neurological impairment. The Foundation has sought out cerebral anti-aging compounds for two decades now, and has found several thousand scientific studies that show brain aging can be slowed, and impairment can be reversed. The recent availability of supplements like vinpocetine, that used to be restricted, appear to mitigage many of the degenerative processes involved in brain aging. Another European "Drug" To Boost Brain Function Another compound, phosphatidylserine (PS), has been shown in more than two-dozen controlled clinical trials to improve learning and memory among older adults with cognitive deficits, as well as normal healthy persons with age-associated cognitive deficiencies. In 1988, the Foundation published an article showing that PS dramatically slows the rate of brain aging in animals. PS restored mental function in older animals to levels exceeding those in some younger animals. Brain tissues are especially rich in PS, but aging causes a decline in cells throughout the body. The unique ability of PS to initiate, maintain, and enhance multiple aspects of brain-cell metabolism makes this lecithin extract one of the most promising anti-aging therapies available. PS also has been shown to help maintain brain cell-membrane integrity and youthful synaptic plasticity. This means that PS protects cells against the functional and structural deterioration that occurs with aging. In Europe, PS is approved and sold as an expensive "drug" to treat Alzheimer's and other forms of senile dementia. Americans can buy PS as a dietary supplement for a fraction of the cost that Europeans pay. In a new book called The Memory Cure, new studies are reported showing a multitude of neurological benefits associated with phosphatidylserine supplementation. Phosphatidylserine is available as a separate supplement, or in the Cognitex multi-nutrient formula. Since then, Cognitex has been improved on a regular basis as newly discovered agents become available that are shown to improve memory, boost cognitive performance and slow some effects of brain aging.
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STAYING MENTALLY SHARP
A New Study Preventing Mental Incapacity with Hydergine
Hydergine is approved by the Food and Drug Administration to treat individuals over the age of 60 who manifest signs or symptoms of mental incapacity. However, when one study showed that Hydergine was not effective in treating Alzheimer's disease, American physicians virtually stopped prescribing it, even though the drug was never approved as an Alzheimer's therapy.
Nevertheless, Hydergine remains a popular supplement among health-conscious people seeking to slow age-related mental decline. Recent studies reveal new mechanisms by which Hydergine protects against brain aging. The latest study, published in European Neuropsychopharmacology (1998, Vol. 8, Iss. 1, pages 13-16), showed that Hydergine causes an increase of superoxide dismutase (SOD) and catalase in the brain, the body's natural antioxidants and among the most effective free radical scavengers.
What was interesting about this study is that Hydergine was administered for only 20 days, but its effects in the brains of the lab rats were dramatic. Hydergine specifically increased catalase levels in the brain, as well as SOD in the hippocampus and in the corpus striatum regions. Those regions of the brain suffer severe oxidative damage from hydrogen peroxide and other free-radical generating agents. Orally ingested SOD and catalase have not proven efficacious because these antioxidant enzymes are broken down in the stomach, so scientists have concentrated on ways of prompting the body to produce its own cellular SOD and catalase. This study showed that Hydergine can increase brain levels of SOD and catalase after only short-term administration.
Hydergine also appears to safely inhibit toxic monoamine oxidase levels. Elevated MAO levels damage brain cells and are a specific cause of age-related neuronal deterioration. Too much MAO has also been shown to cause pathological disorders such as Parkinson's disease. Age-related depression has been linked to excessive production of MAO that occurs in the elderly. Drugs that inhibit MAO were widely used in the past to effectively treat depression. MAO-inhibiting drugs are seldom used today because of potential toxicity.
The scientists who conducted this study concluded, "Decreasing MAO levels and supporting the antioxidant enzymes may underlie the efficacy of Hydergine in the treatment of age-related cognitive decline."
In a study published in Life Sciences (Vol 58, No. 8, 1996), it was shown that Hydergine protects against brain aging and the development of Alzheimer's disease. This study identified a defect that occurs in brain cell membranes and showed that Hydergine could inhibit these degenerative changes.
The scientists who authored the Life Sciences study identified specific antibodies that bind to brain-cell membranes and then target the cell for destruction and removal by the immune system. (Young brains have significantly lower levels of these destructive antibodies compared with old brains.) Hydergine-treated mice showed a reduction in these destructive antibodies, thus suggesting that middle-aged people who take Hydergine could retard the development of senile dementia caused by programmed immune destruction.
The animals receiving Hydergine in middle-age maintained healthy brain cell-metabolic activities, compared with the control group who did not receive Hydergine. The scientists concluded that Hydergine therapy begun in middle age could protect against the initiation of the cascade that leads to Alzheimer's disease.
The scientists emphasized that once the Alzheimer's disease cascade begins, Hydergine would be of little value since the brain cells have already been inevitably marked and targeted for immune destruction.
The Life Extension Foundation has long advocated the use of Hydergine by people of all ages to prevent the degenerative changes that lead to brain cell aging and Alzheimer's disease. In addition, Hydergine appears frequently in the scientific literature as therapy for a wide range of diseases ranging from asthma to stroke. Earlier published studies showed that Hydergine can:
- Improve blood supply to the brain
- Increase the amount of oxygen delivered to the brain
- Increase oxygen use by the brain
- Enhance metabolism in brain cells
- Protect the brain from damage during periods of decreased and/or insufficient oxygen supply
- Lower the deposit of age pigment (lipofuscin) in the brain
- Prevent free radical damage in brain cells
- Increase intelligence, memory, learning, and recall
- Enhance the use of glucose by brain cells
- Increase ATP levels in the brain
- Stop blood from becoming sticky
- Raise the brain levels of serotonin
Brain Boosting: A Family Affair By Twig Mowatt Theresa Todoroff was a top-performing engineer with a sharp mind for detail until she had her first child in 1989. Six weeks later, when Todoroff returned to her job at a major regional power company, she began noticing a dramatic change in her memory capabilities and general acuity. She was highly concerned to find herself forgetting people's names and searching for words that wouldn't come. Her mind seemed suddenly dulled and she began making silly errors on the job that wouldn't have happened before. At first the culprit seemed to be the lack of sleep endured by all new parents. But Todoroff feared a darker reason for the lapses. A great uncle and aunt, both now deceased, suffered from Alzheimer's disease, and her grandfather from senile dementia. "I wasn't my former self, "she remembers. "My position at work demanded attention to detail, as did balancing work, home and family. I thought I was developing Alzheimer's and I was worried about not being able to take care of my family." That's when Todoroff got serious about taking care of her brain. Now 40, and mother to two sons, she insists on describing herself as an "ordinary mother staying home with the kids, doing everyday things." But her commitment to maintaining good health is anything but ordinary. To learn everything she could about cognitive enhancement and fighting Alzheimer's, she launched an all-out educational effort that included analyzing subscriptions to health newsletters, surfing the Internet, studying biological-aging textbooks and a wide range of research periodicals, and constantly revising her own personal regimen of supplements, diet and exercise in accordance with the latest science and how her body responds. This campaign, she reasons, is her best shot at taking care of herself, as well as her family. "I know I won't be young forever," she says. "I could develop Alzheimer's, or any other disease, as easily as the next person. But I'm trying to do everything I can now to make tomorrow better for myself and my children." To Todoroff and her kids, Byron, 9, and Kent, 5, this means being an effective, lucid parent for many years to come. It also means being a good role model and encouraging them, even at their tender ages, to adopt the kind of good habits that could keep them vital and healthy throughout their lives. To that end, Todoroff has started both boys on their own regimens. They each take multiple vitamins every day-approximately double the FDA-recommended amounts-and extra vitamin C twice a day. "When the kids are old enough to understand, and able to make their own decisions regarding supplementation, I'll guide them if they let me." Though Todoroff says she began her cognitive enhancement and anti-Alzheimer's regimen "full blast" in February 1997, she has a long-standing interest in health, describing herself as being a stereotypical health food nut throughout the 1970s and '80s. The release of Durk Pearson and Sandy Shaw's Life Extension: A Practical Approach, in 1982, sharpened her focus. Her current lifestyle includes plenty of exercise, though she's modified her routine a bit over the years, replacing high-impact exercise with a method easier on the joints. She takes power walks, for example, carrying three- pound weights to maintain upper-body strength and raise her heart beat more quickly. Doing chores, such as cutting the grass, she tries to exert herself enough to raise her heart-rate for at least 20 minutes. "Power vacuuming" is another favorite. Though Todoroff was a vegetarian for more than 10 years, she reintroduced meat into her diet at the suggestion of her husband when she was breast feeding. Still, meat isn't a focal point; she and her family have chicken or roast a turkey only on special occasions. The boys are just as happy with tofu with soy sauce, bean tacos, macaroni and cheese, and cheese pizza. In the summer, the family feasts on whatever is fresh from their own garden and winter finds them leaning toward breads, potatoes and pastas with tomato sauces. Fat-free dairy products are always good. To satisfy her kids' yearnings for sweets, Todoroff gives them low-fat cookies or dry, lightly sweetened boxed cereals, fruit roll-ups and frozen juice pops. Small meals and frequent snacks of crackers, nuts and popcorn are the norm throughout the day. Her avid reading and research have convinced her that fighting Alzheimer's also means avoiding aluminum in foods and in cooking utensils. She won't buy antacids, underarm antiperspirants or baking powders with aluminum, and usually cooks only in glass and stainless steel. If she does use her favorite ancient cast-aluminum pressure cooker, she's careful not to include acidic foods in order to avoid aluminum contamination. Then there is her list of daily vitamins and supplements. Trial and error has brought her to her current list of items and doses, and though she's pleased with the regimen at the moment, she's open to further revisions and changes as research suggests and as her body dictates. (Her background in chemistry helps in making these decisions.) For instance, she started out with 25 milligrams of DHEA, but later upped the dose to 50 mg, a move that she says made her feel dazed. "I actually backed my car through the garage door," she admits. "I wasn't feeling normal." She cut out the DHEA altogether for a couple of weeks, then introduced it again at 10 mg, working gradually back to 25 mg, which she takes first thing in the morning. She also starts the day with 60 mg of Ginkgo biloba, 125 mg of DMAE and 10 mg of pregnenolone for cognitive enhancement. Also on the list: 200 mg of chromium picolinate (to ward off another family disease, diabetes), calcium, magnesium and zinc. With her mid-morning meal or with lunch, Todoroff takes Life Extension Mix, 200 micrograms of selenium, 1,000 mg of vitamin C, 400 mg of vitamin E, fish oil, 400 mg of folic acid, 250 mg niacin, and a second round of calcium, magnesium and zinc. At this time she also uses 300 mg of aminoguanidine for anti-aging in general. Ten mg of vinpocetine, another cognitive enhancer, rounds out her lunchtime regimen. Later, with her afternoon or evening meal, Todoroff again reaches for Life Extension Mix, and another 10 mg of pregnenolone, calcium, magnesium and zinc. Two or three nights out of the week, and about one hour before going to bed, she will take 500 mg of niacin for growth-hormone enhancement, a final round of calcium, magnesium and zinc (for a total daily intake of 1,000 mg calcium, 400 mg magnesium and 15 mg zinc), and 3 mg of melatonin not for its sleep-enhancing properties but because it is a good antioxidant. Though the program is intended to fight Alzheimer's, Todoroff wouldn't mind improving her mental acuity in the process. "The smarter one is, the easier life is," she says. As for her boys, she adds, "Children have to be smart, because these days making foolish choices can kill. I hope for wisdom before I am old." Nowadays Todoroff feels much better than she did following the birth of her first son, but she still worries that she hasn't returned to her 25-year-old peak cognitive state. "I could remember where words were located on a page. My recall was phenomenal," she says. Rating her overall state of health on a scale of one to 10, she says she's a seven. "My goal is 10, of course. Then, when I reach 10, the scale will change." "But today, I don't have the murkiness of mind that once scared me," she says. "My thinking is clearer now, but there have been 20-some years of decline, so the climb back up will take time. But I don't think there is a ceiling on the clarity one can attain. The sky's the limit."
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