Everybody probably knows the statistic that someone turns 50 every seven seconds in the U.S. And that the population of baby boomers will reach 70 billion by the year 2030. And that one third of our population will be 60 or over by mid-century. As our world's "older" inhabitants become an increasing portion of the population, companies are hard at work developing nutraceuticals to fight one of the most common diseases associated with aging-Alzheimer's disease.

According to the National Institutes of Health (NIH), the age-related disease of Alzheimer's is defined as a progressive degenerative disease of the brain and the most common form of dementia. According to the Alzheimer's Association, approximately four million Americans have Alzheimer's disease; however, by the middle of the next century 14 million are expected to suffer from the malady. On a global scale, more than 22 million individuals will have Alzheimer's by the year 2025. With the disease expected to reach epidemic proportions and the high cost of prescription drugs, the alternatives that supplement companies can provide are essential. In addition, as a result of rising healthcare costs and the probable loss of social security in the future, many elderly individuals are looking for alternatives to prescription drugs for Alzheimer's disease.

The only way to avoid the epidemic, according to the Alzheimer's Association, is to accelerate the search for a way to delay, prevent or cure the disease. This is where nutraceutical companies come in. So far the ingredients that have at least some science behind them, in terms of Alzheimer's disease, are acetyl L-carnitine (ALC), phosphatidylserine (PS), huperzine A and ginkgo biloba, with CoQ10 following close behind.


Ginkgo Biloba
Ginkgo biloba is best known for memory enhancement because it increases blood flow to the brain. Studies on ginkgo go as far back as 30 years, according to Michael Granville, president, Linnea, Locarno, Switzerland. In reference to Alzheimer's research he said, "I think ginkgo has a head start because it has already been established for memory enhancement and Alzheimer's is a condition not too far removed from that. I think moving to a specific condition such as Alzheimer's is a logical extension."

Due to its successful performance in studies involving memory enhancement, ginkgo has received recent attention from the NIH. Just last year the National Center for Complementary and Alternative Medicine (NCCAM) in collaboration with the National Institute on Aging (NIA), two components of NIH, awarded the University of Pittsburgh School of Medicine a six year cooperative agreement totaling $15 million to coordinate a multi-center effort to study the effectiveness of ginkgo biloba extract in preventing dementia in older individuals. The four clinical study centers include the Alzheimer's Disease Research Center (University of Pittsburgh School of Medicine), Johns Hopkins School of Medicine, Department of Radiology, University of California, Davis and Wake Forest University School of Medicine. The six year study will enroll a total of 2000 participants, who will be randomly assigned to one of two groups. Study participants will take 240 mg of ginkgo biloba and will be compared to a second group of individuals who will take a placebo. The primary outcome of this study will be the onset of any type of dementia. The secondary outcome will be measured by changes in cognitive function.

According to the NIH the first clinical study to examine ginkgo biloba and dementia in the U.S. was conducted by researchers at the New York Institute for Medical Research, Tarrytown, NY. The scientists studied how taking 120 mg a day of ginkgo biloba extract affected the rate of cognitive decline in older individuals with mild to moderately severe dementia due to Alzheimer's disease and vascular dementia. The results of this study, which suggested that a ginkgo biloba extract may be of some help in treating symptoms of Alzheimer's disease and vascular dementia, were published in the Journal of the American Medical Association (JAMA) in October 1997.

Phosphatidylserine (PS)
Phosphatidylserine (PS) is a phospholipid that is vital to brain cell structure and function as it is a key building block for the cells that make up the human brain. As we age, the amount of PS required increases and therefore supplementation is suggested.

Relating PS to Alzheimer's, Dr. Parris Kidd, industry consultant and nutrition educator based in El Cerrito, CA, explained, "All electrical activity in the brain passes along circuits that are held together via nerve cell connections called synapses. PS supports the brain's capacity to both generate electrical activity and maintain the synapses. In advanced Alzheimer's disease, as much as 80% of the synapses are gone. PS can benefit individuals with memory loss that does not involve such widespread synapse loss."

In relation to the science behind PS, Dr. Kidd offered, "Of all the nutrients that are available, PS is the best documented for stimulating regeneration of damaged circuits (synapses) in the brain. PS literally turns back the clock on aging of the brain."

To date PS has been the subject of several clinical trials, many of them double blind design. It has been around for more than 25 years, first in Europe and more recently in the U.S. Studies with PS were conducted in the early 1980's in which the PS was taken from bovine brain. However, when "mad cow disease" broke out around the mid 1980's it was taken off the market. A soy preparation arrived on the market about five years ago and although it is not structurally identical to bovine brain PS, it has been shown to be just as effective.

Dr. Kidd also noted that PS has an excellent benefit to risk profile. He said, "Probably because it has been an essential building block for all cells since the beginning of life, PS is extremely safe and well tolerated. In clinical trials PS was found to be compatible with drugs commonly prescribed to the elderly."

Acetyl L-carnitine (ALC)
A strong point of emphasis in this industry is having sufficient clinical evidence to back up an ingredient's effectiveness. In relation to acetyl L-carnitine (ALC), this is not a problem, as Alzheimer's disease has been the subject of a good portion of L-carnitine studies.

According to Ken Hassen, vp-sales and marketing, Biosint, Larchmont, NY, "The medical literature shows consistent evidence that metabolic stresses, such as suboptimal fat utilization, may contribute to the formation of paired helical filaments and amyloidal plaques in brain cells of the type seen in advanced age, cerebrovascular disease, stress and Alzheimer's disease." As a result, he said, "The nutritional use of ALC is actually suggested for two particular indications, mood improvement in cases of depression and memory enhancement and mental decline or Alzheimer's disease."

Paula Gaynor, PhD, manager of scientific affairs, Lonza, Fair Lawn, NJ, also commented on ALC and Alzheimer's disease. "The exact cause of Alzheimer's disease is not known but in the late 1970's it was determined that people with Alzheimer's were deficient in acetylcholine, which is a key neurotransmitter," she said, adding that ALC is very relevant in this case because it is structurally similar to acetylcholine and has the ability to activate the enzyme that produces acetylcholine. As a result, ALC has been shown in studies to slow down the progression of the disease. In addition, ALC is also neuroprotective because it has antioxidant properties, facilitates mitochondrial energy supply and enhances membrane stability.

As a result of the aging baby boomer population and the fact that four million people have the disease, Dr. Gaynor said that maintaining healthy brain function during the aging process is a major driver for business at Lonza. She said, "We have seen a definite increase in sales for ALC because it is positioned in the market as brain food for those people concerned with maintaining proper brain function with age." She continued, "People choose ALC because of the fact that there is so much research behind it. In addition, the research is ongoing on a global basis and has never come to a standstill."


Huperzine A
Huperzine A is a purified compound derived from the herb club moss (Huperzia serrata) and is found in China. According to Richard Sequeira, vice president of sales and marketing at huperzine A supplier Marco Hi-Tech JV Ltd., New York, NY, purified huperzine A has been safely and effectively used by over 100,000 people in China and has been the subject of over 30 studies.

Given that huperzine A acts as an acetylcholinesterase (AChE) inhibitor, it has potential in the area of Alzheimer's research. Carmine Covino, vice president, Kingchem, Oradell, NJ, explained huperzine A's role. He said, "Acetylcholinesterase is an enzyme that breaks down acetylcholine, which is a neurotransmitter essential for normal learning and memory abilities." He explained further, "There are gaps between cells in the brain and that is where everything happens. These gaps or synapses are also where things can go wrong as far as neurons not firing in the right direction. Huperzine A selectively inhibits acetylcholinesterase, preventing the breakdown of acetylcholine."

In terms of safety, there have been conflicting reports of its side effects. According to Mr. Sequeira, "Safety and efficacy studies were not conducted on the crude extract, huperzia serrata. Companies that unscrupulously market the crude extract under the purified compound's DSHEA filing violate the law and are selling a product that does not work and is potentially harmful." He went on, "Only purified huperzine A has been rigorously tested. We fully expect huperzine A to take over the memory enhancement market because, as opposed to ginkgo, researchers have identified how huperzine A works." He said as a site-specific acetylcholinesterase inhibitor, it is possible to positively enhance memory with a very small dose.

Also of great importance to manufacturers is price, which for huperzine A is high. However, Mr. Covino pointed out that although the price may seem high, the cost per pill is approximately $.04-.05. "This is because the typical finished dosage form only contains 50 micrograms, which has been found to be very effective," he said.

Huperzine A at this point is a baby in the U.S. market in terms of Alzheimer's but more research may further prove its effectiveness in this area. A recent review in Curr Med Chem (2000 Mar;7(3):355-74) noted that huperzine A could be considered as a potential treatment for Alzheimer's. The review said, "HupA is a potent, reversible and selective inhibitor of AChE with a rapid absorption and penetration into the brain in animal tests. It exhibits memory-enhancing activities in animal and clinical trials. Compared to 'Tacrine' and 'Donepezil,' (drugs for Alzheimer's treatment), HupA possesses a longer duration of action and higher therapeutic index and the peripheral cholinergic side effects are minimal at therapeutic doses...the dual bio-activities of HupA would further enhance its value and potentiality as the therapeutic agent for Alzheimer s disease."

As for huperzine A's future potential in Alzheimer's research, the Journal of the American Medical Association (JAMA) in March of 1997 said, "Huperzine A appears to be strongly specific for AChE, which suggests that it can be effective (for memory and function) without the adverse effects that have been caused by drugs used to treat memory loss and dementia."

Coenzyme Q-10
In terms of finding a place in Alzheimer's research, CoQ10's potential is still being explored. Dr. Hemmige Bhagavan, consultant for Tishcon Corporation, Westbury, NY, said, "Unfortunately, we don't have an answer yet in terms of clinical studies on Alzheimer's and CoQ10. For now, free radical damage and energy production is where CoQ10 plays a role in Alzheimer's disease."

He also suggested that a combination of ingredients such as CoQ10 and ALC may be the way to go. "Certainly, the biochemical evidence is there in addition to anecdotal evidence but we need more clinical substantiation for these products," he said. "Using one component alone cannot produce the beneficial effect because you have to make sure all ingredients are present in adequate amounts." For example, he said that carnitine brings the fuel to the mitochondria but no matter how much fuel is brought, it does not make a difference unless you have CoQ10 to make it burn. "An ideal situation would be to combine the two because they work synergistically," he said.

In the opinion of the Alzheimer's Association, however, "CoQ10, or ubiquinone, is an antioxidant that occurs naturally in the body and is needed for normal cell reactions to occur. This compound has not been researched to determine its effectiveness in treating Alzheimer's. A synthetic version of this compound, called idebenone, was tested for Alzheimer's disease but did not show favorable results. Little is known of about what dosage of CoQ10 is considered safe and there could be harmful effects if too much is taken."