TAMPA — Chuanhai Cao used to drink tea.
But that was before he and a colleague at the University of South Florida found that the caffeine in coffee could help prevent or delay the symptoms of Alzheimer's disease.
"Now I drink coffee, about two cups a day," says Cao, an assistant professor of molecular pharmacology and physiology at the USF Byrd Alzheimer's Institute, whose study on caffeine was published a few months ago in the Journal of Alzheimer's Disease.
But Cao and others recognize that despite such evidence, caffeine may never get the kind of attention needed to conduct a large-scale study that might offer more definitive evidence that it works.
Why? The answer lies with two things: mice and money.
Most of the research to date, including Cao's, has involved treating mice specially bred to develop Alzheimer's symptoms. And what works with mice frequently does not translate to humans.
But the bigger obstacle is money. Government funding for Alzheimer's research, already less than that for other deadly diseases, has been shrinking. And pharmaceutical companies — which fund most major clinical trials these days — can't make money off something like caffeine.
"Without a doubt there are things that are going to get ignored because you can't make money from it," said Dr. Amanda Smith, medical director of the Byrd Institute.
There are about 100 drugs that are being tested as possible treatments for Alzheimer's. Only five have been approved to date, yet none do anything to slow the progression of the memory-robbing disease that afflicts more than 5 million Americans.
Could the answer be in the piping hot beverage at your breakfast table?
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Caffeine is a natural stimulant found in more than 60 plants, including coffee beans and tea leaves, and added to various foods, drinks and medicines. The Food and Drug Administration estimates that more than 80 percent of U.S. adults consume an average of 200 milligrams of caffeine a day — the equivalent of two 5-ounce cups of coffee.
To most people, caffeine's main purpose is to keep you awake. But its health effects have been studied for years, both for its potential benefits to treat conditions such as liver disease, diabetes, and apnea in premature infants; and as a potential contributor to cardiac arrhythmia, atrial fibrillation and insomnia.
But lately, attention has focused on what it could mean for Alzheimer's disease.
In 2009, USF scientists found that heavy jolts of caffeine reinvigorated the brains of old, demented mice. And this year, Cao and then-USF colleague Gary Arendash found that caffeinated coffee specifically might help prevent or delay Alzheimer's symptoms.
Using the specially bred mice, their study found that caffeinated coffee caused an increase in blood levels of a growth factor called GCSF, or granulocyte colony-stimulating factor. GCSF is greatly decreased in patients with Alzheimer's, and it also has been demonstrated to improve memory in Alzheimer's mice.
But Cao said much work lies ahead. He'd like to test people, perhaps a group of 60. If results are positive, he'd want to expand to more than 300 subjects over a one- or two-year period.
He estimated a study of 60 people would cost $500,000, and the larger one at least $2.5 million, but he has funds for neither.
A major clinical trial would cost much more. An eight-year government-funded study on whether Ginkgo biloba was beneficial to Alzheimer's patients cost about $36.5 million (the dietary supplement was found to be ineffective).
In 2010, the government allotted $450 million for Alzheimer's research, down from $600 million three years earlier. That compares with $5.8 billion for cancer, $3 billion for HIV/AIDS and $1.3 billion for heart disease, according to the National Institutes of Health.
Alzheimer's research is "hideously underfunded," Smith said.
"It's extremely hard," Cao said of securing funding at a time when pharmaceutical companies are financing much of the research. "People normally don't want to invest in these kinds of therapeutics, where there's no intellectual property."
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There are some avenues for the study of natural substances like caffeine. One is the Alzheimer's Disease Cooperative Study, a government-funded research consortium.
Smith, who serves on its steering committee, said the group is studying therapies such as exercise, vitamins and supplements.
There's also the National Center for Complementary and Alternative Medicine, which was involved in the Ginkgo study.
Might either group fund major research into caffeine, or caffeinated coffee?
Dr. William Thies, chief medical and scientific officer of the national Alzheimer's Association, said what's working against caffeine is that most of the studies on it have been small.
"And, you'd have to have a pretty clear body of evidence that it works," he said. "I think at this point, it is virtually impossible to make a judgment on whether caffeine or coffee has a clinical benefit or harm in a human being."
Then there's the mouse issue. David Morgan, CEO of the Byrd Institute, said there are about 200 different agents that have shown benefits in the Alzheimer's mice. "But nothing has translated to humans," he said.
There are also some well-established side effects to excessive caffeine — jitters, insomnia, rapid heartbeat, elevated blood pressure, headaches, nervousness and/or dizziness.
"Many seniors find caffeine very difficult to tolerate," Morgan said.
Smith notes another caution: "Truth is, there are lots of people who consume lots of caffeine and still get Alzheimer's.''
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Cao plans to press on. He's working with a chemical engineer to identify a component in coffee that somehow interacts with the caffeine to achieve the Alzheimer's benefit. He's been in touch with a colleague in Tianjin, China, who is interested in a caffeinated coffee study there.
"Our initial study is encouraging," he said. "And we have people wanting to volunteer for a trial in China."
Morgan and Smith are less enthusiastic.
"I'm just very cautious in showing any enthusiasm about using caffeine, or even caffeinated coffee," Morgan said. "I'm a little concerned that people will start giving caffeine pills to relatives with Alzheimer's. People are desperate to try anything."
"It's not going to be the thing that changes the field in some sort of spectacular way," said Smith, who says she drinks her fair share of coffee.
"I think maybe this will help a little. Maybe I'll get (Alzheimer's) when I'm 85, instead of 80," she said. But mostly, "I drink it so I don't fall asleep at my desk."
Richard Martin can be reached at firstname.lastname@example.org or (813) 226-3322.