Naturalmemoryenhancer

Memories help shape our lives, and memory is one of our most valuable health assets. Without a normal memory, coping with daily life would be difficult. Previously, it was believed that memory loss was a normal part of aging, but many people now believe that this is not totally correct.

According to the US Census Bureau, there are about 291 million people in the United States today.1 In the year 2000, there were 35 million Americans 65 and older, and and it is expected that this number will grow to 54 million by 2020.2

While many elderly people are interested in improving their memories, they are not the only ones attempting to stave off memory loss. Many baby boomers and students are also trying out different strategies to ward off memory loss or to enhance memory.

Several treatments, including mental exercises, nutrition, and drug therapy, are being evaluated for their use in maintaining memory function over time. Mental exercises have been shown to improve memory in the elderly while good nutrition and drug therapy improve general health and increase blood flow to the brain.3,4

The old saying "use it or lose it" describes the aging memory. Some activities that are recommended for maintaining memory as one ages are crossword puzzles and word searches. Proper nutrition entails getting the correct amounts of vitamins, minerals, nutrients, and trace elements that the body needs as it ages. A good physical exercise program helps to maintain overall general health.3,4

Types of Herbal Supplements
There are several herbs that are purported to aid in body processes. Tonic herbs assist in maintaining the body's balance without affecting metabolism and include alfalfa, angelica root, and celery seeds. Adaptogenic herbs help the body adapt to a multitude of environmental and psychological stresses, maintain good health, and protect against disease. Examples of adaptogenic herbs are ashwaganda and the Asian, American, and Siberian varieties of ginseng. Nootropic herbs (nootropic is derived from Greek and means acting on the mind) and their isolated constituents—also referred to as smart drugs—include huperzine A (isolated from Chinese club moss), vincamine (isolated from Vinca minor), and vinpocetine (prepared from vincamine). Memory enhancer herbs, such as ginkgo, may enhance the memory and increase blood circulation in the brain.

According to a recent article in BusinessWeek, the herbal supplement industry is a $4-billion-a-year industry.5 With products on the market having brand names like Memory Booster, CerebroPlex, and Brain Lightning, it is no wonder that people want to try them. Because consumers obtain information from the Internet, friends, and infomercials, it is imperative that pharmacists have sufficient information to advise patients on herbal use. In a survey published in 1998, 18.4% of American adults reported concurrent use of at least one herbal product with a prescription medicine. Of this group, 61.5% did not disclose this information to their health care providers.6 This number has increased in the past few years as more people want to treat their various illnesses with natural products that they deem safe. Numerous articles discuss the lot-to-lot variability of products, the contamination of herbal supplements from Asia with heavy metals, and the adulteration with substances, such as antibiotics and steroids, that are not listed on the labels.7

This article will discuss four of the herbs reported to aid in both long- and short-term memory enhancement—ginkgo biloba, huperzine A, vincamine, and vinpocetine. It will also discuss information on herbal supplements that pharmacists should consider sharing with patients. Pregnant women and children should not use herbal supplements.

Ginkgo Biloba
The herbal supplement ginkgo biloba is obtained from the ginkgo tree, which is also known as maidenhair tree, kew tree, ginkyo, yinhsing, EGB-761 (extract ginkgo biloba), or GBE-761 (ginkgo biloba extract). These trees are dioecious and have fan-shaped leaves. The male tree produces blossoms, while the female produces a plum-like gray-tan fruit that has a fleshy pulp with a foul, offensive odor. The inner seeds of the fruit, resembling almonds, are edible when roasted.

The active compounds for memory enhancement are pr esent in the leaves and not in the seeds. The concentrations of these active compounds in the leaves vary with the seasons, with the highest amount present in autumn. These constituents include terpenoids (eg, bilobalide [FIGURE 1]) and ginkgolides A, B, C, J, and M [FIGURE 2]), flavonoids (eg, kaempferal, quercetin, isorhamnetin [FIGURE 3], and polymeric flavonoids proanthocyanidins), steroids (eg, sitosterol and stigmasterol), and organic acids (ascorbic, benzoic, shikimic, and vanillic).8 The flavonoids and terpenoids are believed to be responsible for the herb's pharmacologic actions, which include increasing blood flow, decreasing blood viscosity, antagonizing platelet-activating factor receptors, increasing tolerance to anoxia, inhibiting monoamine oxidase, protecting against infections, and preventing membrane damage by free radicals. The flavonoids are associated with the antioxidant and free radical scavenging properties of the herb, while the terpenoids are associated with the anti-infective properties and the antiplatelet-activating factor, which helps prevent membrane damage to vessels and decreases blood viscosity. Because ginkgo is believed to regulate the tone and elasticity of blood vessels, it could increase blood flow to the brain and improve the tolerance of the brain to hypoxia.9 Ginkgo is sold alone or in combination with other herbal and dietary supplements. Some ginkgo products include MemoRise, Super Memory Formula, Memory Boost, Ginkgo Plus, and Nature's Bounty Ginkgo Biloba

The data on ginkgo's efficacy in improving memory are encouraging but not fully convincing. Moulton et al found no significant improvement over placebo in memory performance when gingko was studied in young, healthy, male subjects. Study participants were given 120 mg/day of ginkgo for five days, which may not have been long enough to elicit an effect.10 Solomon et al performed a study in which subjects older than 60 were given 120 mg/ day of ginkgo for six weeks. The researchers did not observe a significant difference over placebo in memory improvement.11 However, an article published recently by Mix and Crews showed memory improvement in subjects older than 60 who were given 180 mg/day of ginkgo for six weeks.12 Many studies are poorly designed; they might include only a small number of patients, report only the positive effects of ginkgo over placebo, and study subjects for a short time period. Thus, ginkgo's long-term efficacy is not well understood.13 Since the parameters used to assess memory enhancement vary between studies, direct comparisons are not always possible.

Despite the lack of literature from well-conducted studies, the recommended dose of ginkgo is 40 mg three times a day of standardized extract made from ginkgo leaves. Quality extracts should contain 22% to 27% flavonoids and 5% to 7% terpenoids. Clinical effects usually appear after at least four weeks of treatment. There is no information on the long-term use of this herb or whether people taking ginkgo should have herb-free holidays.







There are relatively few drug interactions with ginkgo, but the herb can have serious interactions with antiplatelet drugs (increased risk of bleeding), thiazide diuretics (may increase blood pressure when used concurrently), and warfarin (increased anticoagulant effect of warfarin and risk of bleeding). Because of the increased risk of bleeding, patients should use caution when taking ginkgo with any herbs or dietary supplements that contain anticoagulant or antiplatelet constituents (eg, angelica, anise, capsicum, chamomile, garlic, ginseng, licorice).14 Pharmacists should consult appropriate references (eg, Natural Medicines Database, Micromedex, The Review of Natural Products) to answer questions regarding the use of ginkgo with other herbals or dietary supplements.

Reported adverse reactions to ginkgo include mild gastrointestinal complaints, headaches, dizziness, palpitations, and allergic skin reactions. Large doses have been associated with restlessness, diarrhea, nausea, vomiting, lack of muscle tone, and weakness. There are case reports of subdural hematoma resulting from ginkgo use, one report of a subarachnoid hemorrhage, and one report of a bleeding iris. Anecdotal evidence suggests that ginkgo may be associated with seizures. People with bleeding disorders and epilepsy should use ginkgo with caution.14 The fruit and pulp of the ginkgo tree are potent contact allergens and can cause severe allergic skin reactions and irritation of the mucous membranes and gastrointestinal tract. Ingestion of the pulp can cause redness around the mouth, rectal burning, and painful anal sphincter spasms. Properly prepared ginkgo extract, which is made from the roasted seeds of the ginkgo fruit, should not cause the adverse effects associated with ingested ginkgo's flesh and pulp. The fresh seeds, however, are toxic and potentially deadly.14

Huperzine A
Another herb that is purported to improve memory is huperzine A (FIGURE 4), which is also known as HupA, Huperzine-A, and selagine and is an alkaloid chemically isolated and purified from Chinese club moss, Huperzia serrata, or Lycopodium serratum. Huperzine A is a reversible inhibitor of acetylcholinesterase (AChE) and crosses the blood-brain barrier. It can inhibit AChE activity in the brain for up to three hours. It has been used for treating Alzheimer's disease, enhancing memory and learning, reversing age-related memory impairment, increasing alertness and energy, protecting against neurotoxic agents, and treating myasthenia gravis.14 Examples of products that contain huperzine A are Ginkgo/Ginseng, Huperzine A with Ginkgo, Huperzine A with Ginseng, and Huperzine A with Vitamin E.







Huperzine A may be effective in improving memory in healthy adolescents. Qing-Qi and colleagues studied huperzine A in 34 adolescents ages 14 and 15. The dose was 0.1 mg/day for four weeks; a significant improvement over placebo was noted in memory function using standard memory assessment tools.15 As with research on ginkgo, the studies of huperzine A have involved small numbers of patients and have compared the herb only to placebo. Thus, researchers do not know how huperzine A compares to the other memory enhancers.14

A few drug interactions must be kept in mind when counseling patients using huperzine A. Anticholinergic drugs (eg, scopolamine, atropine, benztropine, niperiden, procyclidine, and trihexyphenidyl) used concurrently with huperzine A may decrease the efficacy of either agent. Concurrent use of cholinergic drugs or AChE inhibitors (eg, bethanechol, donepezil, echothiophate, edrophonium, neostigimine, physostigimine, pyridostigmine, succinylcholine, and tacrine) with huperzine A may increase acetylcholine activity. There are no known interactions with other herbs or dietary supplements at this time.14

Adverse reactions reported when using huperzine A include nausea, sweating, blurred vision, hyperactivity, anorexia, decreased heart rate, and muscle twitching. Presumably, since huperzine is an AChE inhibitor, it may cause adverse effects similar to other AChE inhibitors (eg, vomiting, diarrhea, cramping, hypersalivation, increased urination/incontinence, and bradycardia). Huperzine may also exacerbate bradycardia, cardiovascular disease, and other heart conditions that are sensitive to a decreased heart rate; epilepsy and other seizure disorders; gastrointestinal tract obstruction; peptic ulcer disease; pulmonary conditions, including asthma and chronic obstructive pulmonary disease; and urogenital tract obstruction. The Cerebra brand of huperzine A has been confused with prescription drugs that have similar names (Celebrex, Celexa, and Cerbyx). Huperzine A, which is also known as selagine, should not be confused with selegiline.14

Vincamine
Vincamine (FIGURE 5), an alkaloid obtained from Vinca minor (periwinkle plant), is thought to increase cerebral circulation and the brain's use of oxygen. Aethroma, Centracetam, and Dipervina are products that contain vincamine.







There are insufficient data available to report on the clinical efficacy of vincamine for memory enhancement. Concomitant use of vincamine with antihypertensive agents may interfere with blood pressure control. There are insufficient reliable data concerning the use of vincamine with other herbal and dietary supplements. Possible adverse reactions to vincamine include stomach pressure, upper abdominal pain, nausea, facial flushing, slight reductions in both systolic and diastolic blood pressure, sleep disturbances, and headache. Patients who have hypertension or cardiac dysfunction should use vincamine cautiously.14

Vinpocetine
A chemically modified derivative of vincamine, vinpocetine (FIGURE 6), also known as AY-27255, cavinton, ethyl apovincaminate, RGH-4405, and TCV-3b, is thought to have some effect on memory. The mechanism of action of this compound is unclear. Some studies indicate that vinpocetine may enhance cerebral blood flow without affecting peripheral blood flow. It is believed that its actions upon the brain are due to indirect or direct cholinergic activity, augmented norepinephrine effects on cortical cyclic adenosine monophosphate, increased turnover of brain catecholamines, and inhibition of adenosine reuptake. It has been used orally for enhancing memory; improving cerebral blood flow, oxygen, and glucose use by the brain; and protecting against age-related cognitive impairment. It has also been used in the treatment of Alzheimer's disease, cerebrovascular disease, organic psychosyndromes, intractable tumoral calcinosis in hemodialysis patients, menopausal symptoms, and seizure disorders, as well as in the prevention of poststroke morbidity and mortality.14 Vinpocetine is sold alone or in combination with other products and is available as Vinpo-Zine, CerebroPlex, and Vipocem.







While vinpocetine may enhance memory, only a limited number of well-designed studies have been undertaken. One study, performed by Subhan and Hindmarch, evaluated three dosages of vinpocetine given to 12 women ages 25 to 40. The women took 10, 20, or 40 mg of vinpocetine or placebo three times daily for three days. Compared to placebo, the 40-mg dose showed significant reductions in response time but no significant changes in response rate.16 The recommended dosage of vinpocetine is 5 to 10 mg three times daily with food, which enhances its absorption.

Vinpocetine has been known to interact with antiplatelet drugs and warfarin by increasing bleeding risk and with blood-pressure­lowering agents by enhancing their effects. It is also known to interact with herbal and dietary supplements that have antiplatelet/anticoagulant activity, such as angelica, anise, capsicum, chamomile, garlic, ginkgo, ginseng, Panax, and licorice. When counseling patients, refer to the herbal references mentioned earlier to ensure that there are no interactions of note.14

The adverse reactions associated with vinpocetine include stomach pressure, upper abdominal pain, nausea, facial flushing, slight reductions in both systolic and diastolic blood pressure, sleep disturbances, and headache. Vinpocetine should not be used by patients who have blood-clotting disorders, since it may increase the risk of bleeding.14

Conclusion
As observed, there is a lack of data from well-designed clinical trials to show that any of these herbal agents will improve memory. Clearly, more clinical studies with larger numbers of patients and with longer durations than past studies are needed to better understand these agents. Pharmacists should proceed with caution and be aware of the potential hazards associated with herbal supplement use. Always check an appropriate reference before recommending these agents to patients to ensure that there are no drug, herbal/dietary supplement, or disease state interactions that would preclude their use. Encourage patients to inform their health care professionals that they use these agents. Because the FDA does not regulate these herbal supplements, it is recommended that patients use only products that are of high quality and from reputable suppliers. Pharmacists should recommend products that carry the USP certified logo, state on their packaging that they are standardized, and list a manufacturer's name and telephone number. Encourage patients to provide you with the information that they find on the Internet, so that you can assist them in evaluating accuracy and validity. Pharmacists are in a unique position to assist patients in this area of health care and need to become informed in order to provide the best care for their patients.

REFERENCES
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