Heart Disease a Risk Factor for Alzheimer's

(HealthDay News) -- There's more evidence that cardiovascular problems help drive Alzheimer's disease, scientists say, and that treating the heart might help protect the brain.

The findings "represent hope that interventions with well-known drugs can interfere with the disease's progression," said lead investigator Yan Deschaintre, a neurologist and research fellow at the University Regional Hospital Center in Lille, France.

In fact, cognitive impairment, as measured by a standard test, stayed in the low end of the mild range over 36 months for Alzheimer's patients who got treatments for both the neurological disease and their cardiovascular problems, the researchers reported.

In contrast, Alzheimer's patients with vascular trouble who did not receive these medications experienced declines in cognition that approached the severe level, Deschaintre's team found.

They were slated to present the findings Sunday at the Alzheimer Association's International Conference on Prevention of Dementia, in Washington, D.C.

According to the National Institute on Aging, about 4.5 million Americans have Alzheimer's disease. Rates rise steadily with age, and experts estimate that "nearly half of those 85 and older may have the disease." One recent study from the World Health Organization, released this week, warned that Alzheimer's -- which currently has no cure -- could affect 100 million people worldwide by 2050.

The new study was based on chart reviews of 891 French patients diagnosed with either Alzheimer's disease, cardiovascular disease plus Alzheimer's disease, or vascular dementia. The cognitive risk factors included in the study were high blood pressure, diabetes, high cholesterol, atherosclerotic disease and tobacco smoking.

Treatment was defined as receiving an antihypertensive drug, insulin or drugs to lower blood sugar, a cholesterol-lowering statin, or anti-clotting medications. The patients with Alzheimer's disease typically received medications aimed at temporarily curbing their symptomsthat included Aricept, Exelon or Reminyl.

Deschaintre's findings represent "pretty exciting work," because cardiovascular risk factors are "something we can do something about," said Dr. Sam Gandy, director of Emory University's Center for Neurodegenerative Diseases. Gandy also is chairman of the Alzheimer's Association's National Medical and Scientific Advisory Council.

The work done by Deschaintre's team is consistent "with what we've been hearing over the past three to five years" about vascular risk factors increasing the risk for Alzheimer's, Gandy said. The new study, "really nails that down by looking at the other side of the coin by establishing that treating vascular risk factors slows the progression of cognitive decline," he added.

He suggested that physicians begin to take vascular risk factors seriously as they treat patients with Alzheimer's. The vascular risk factors for early Alzheimer's patients "certainly should be treated" because it "seems to slow progression," Gandy said.

Another expert agreed.

The Lille results "reinforce the treatment guidelines for these vascular conditions, such as hypertension and diabetes, and emphasize that Alzheimer's and demented patients should be treated, too," said Hugh C. Hendrie, a professor of psychiatry at the Indiana University Medical School and a scientist at its Center for Aging Research.

However, Deschaintre and Hendrie both noted that physicians at times may not treat vascular risk factors in Alzheimer's patients, for a variety of reasons. For example, Alzheimer's disease often leaves patients apathetic, so they may neglect to tell their physicians about vascular symptoms, Hendrie said.

And Deschaintre noted that, in the clinic where the research was done, patients with Alzheimer's were less likely than other patients to be treated for vascular risk factors. The reverse was true, as well -- patients with vascular dementia were more likely to be treated for heart risk factors, but not for Alzheimer's.

But, "since the majority of patients have both Alzheimer's disease and cerebrovascular disease, and since patients with pure Alzheimer's do seem to benefit from treatment of vascular risk factors, the message is to treat both conditions rather than to focus only on one," he said.

Hendrie remained cautious about the scientific impact of Deschaintre's study, however. He said results from a clinical epidemiological study, such as the Lille research, aren't as conclusive or compelling as those from randomized, controlled clinical trials.

Two other studies scheduled for release at the Alzheimer's conference on Sunday also emphasized the role of the brain-body connection in cognitive impairment and dementia.

Weight loss may signal the onset of Alzheimer's, and the rate of weight loss could be early warning of dementia severity, according to a new review of data from what's known as the Nun's Study. That effort followed health outcomes for a group of 537 non-demented Catholic sisters, aged 75 to 102, for 10 years.

In the study, a team led by Dr. James Mortimer, a professor of epidemiology and biostatistics at the University of South Florida, Tampa, found that unexplained weight loss late in life was often linked to Alzheimer's neuropathology in the brain and not to any change in eating habits linked to Alzheimer's.

Mortimer explained that, "early weight loss appears to result from the Alzheimer's disease process itself before that process leads to dementia. That's why it is a marker of impending dementia."

In a third study, a team from the Mayo Clinic in Rochester, Minn., found an increased risk of mild cognitive impairment (MCI) or dementia among 70- to 89-year-olds who have had a carotid endarterectomy (surgical clearance of the carotid artery, which brings blood to the brain) or a stroke or "mini-stroke," also known as a transient ischemic attack (TIA).

In the study, the team compared the medical histories of 295 people with MCI and 590 age and sex-matched controls. "Elderly subjects who have had a carotid endarterectomy or stroke or TIA are about two times more likely to have MCI," lead researcher Dr. Rosebud O. Roberts, a Mayo epidemiologist, said in a prepared statement.

More information
For more on Alzheimer's disease, visit the Alzheimer's Association.

End-of-Life Hospice Care Underused

(HealthDay News) -- Too few Americans entering life's final phase are availing themselves of high-quality hospice care, despite the fact that Medicare covers the expense, experts say.

The situation is only going to become more problematic as the nation's "baby boomers" reach the end of their expected life spans in coming decades, according to two articles in the July 26 New England Journal of Medicine.

"Hospice care is underutilized -- only a third of Americans die under the care of hospice, and hospice care is free," noted the author of one article, Dr. Gail Gazelle, assistant clinical professor at Harvard Medical School. "Far too often, patients end up in an ICU, rushed to the emergency room, and they end up dying there, when really they would much rather have died in their own home," she added.

According to Gazelle, many of these patients avoid hospice, because they -- and often their doctors -- believe end-of-life care means they have "failed" in the face of disease. "They often view it as, 'OK, someone is telling me to crawl into my bed and die,'" she said. In reality, many hospice patients lead full, mobile and high-quality lives for months, Gazelle said.

There's also the misperception that hospice is expensive. Too often, terminal patients don't realize that Medicare and private insurance cover the full cost of hospice care.

And yet those aren't the only factors keeping terminal patients from the pain management and emotional support that comes with hospice, say oncologists Dr. Ingrid Katz, of Beth Israel Deaconess Medical Center, and Dr. Alexi Wright, of the Dana-Farber Cancer Institute, both in Boston.

In a second journal article, they recounted the story of one Boston-area patient, Joanne Doolin, a 64-year-old mother of three with terminal colon cancer.

Doolin did not choose to enter hospice care. She understood that the service was covered by Medicare, but she also knew that coverage had its limits. As a prerequisite to enter hospice care, Doolin, who was unable to eat on her own, would have been forced to give up intravenous feeding, an expensive service for which she would not be reimbursed. "If she had gone on hospice care and not received [feeding], she would've died within a couple of days," said Wright, a fellow in hematology/oncology at Dana-Farber.

So, Doolin opted to stick with hospital-based chemotherapy and intravenous feeding instead. "Because she got this nutritional support, she lived for more than a month and got to see her daughter get married," said Wright.

Doolin's condition did deteriorate soon after, however. She and her family found themselves scrambling for some kind of dignified, palliative care in the woman's last days. "There shouldn't have been a single barrier to her receiving hospice care the night that she needed it," Wright said. Family and friends in the community worked together to help get Doolin the care she needed, "but her dying experience was a near-disaster," Wright said.

That's because gaps still exist when it comes to items that Medicare, as well as much private insurance, will reimburse for hospice patients. Intravenous nutrition is one such item, as are chemotherapy drugs that might extend -- but not save -- a cancer patient's life. Entering hospice care, "patients often have to give up medicines that are helping to support them, make them feel better, helping them live longer," Wright said.

She believes in an "open access" system where these needs are taken into account. Building such a system might mean the creation of larger hospice organizations, however, so that the cost of expensive therapies could be spread over a larger patient population, Wright said.

But Gazelle stressed that hospice continues to meet or exceed the expectations of terminally ill patients and the people who love them. In fact, one recent survey found that 98 percent of family members said they would strongly recommend hospice care to others in need.
And hospice isn't just focused on dying cancer patients. According to the National Hospice and Palliative Care Organization, about 40 percent of U.S. hospice admissions now involve patients with end-stage heart disease, dementia, lung disease or stroke.

Still, "people need to understand that hospice is about living," Gazelle said. "It's about living as well as you can when life has dealt you a bad deck of cards. Having your dignity, your quality of life, as little physical and emotional suffering as possible -- that's what hospice can do for people."

Hospice care focuses on the patient, of course, but also on those affected by his or her illness, Gazelle added. Counseling and support is made available to caregivers and can last for months after the patient's death. "To know that their family is going to be attended to is critically important for people near the end of life," said Gazelle, who is also president of the medical advocacy group MD Can Help.

But the fact remains that a full third of hospice patients enter the service only in the last week of their life -- even though Medicare covers six months of this type of care. "That's very, very sad," Gazelle said.

She and Wright believe things are about to change, however.

"Baby boomers are going to turn all of this around," Gazelle said. "They are so empowered around their health care and the health care of their loved ones -- they're going to push hard to make sure that their needs are met."

Wright agreed. "I think that we will see the reimbursement structure change dramatically over the next decade," she said. "Baby boomers have received the best medical care imaginable for their entire lives -- why should their death be any different?"

More information
Find out more about hospice and palliative care at the National Hospice and Palliative Care Organization.

Relaxed But Alert

The subjects in this study and many thousands of people who have taken Worry Free over the past six years have reported that it makes them feel relaxed, but also more alert.

"My job involves a tremendous amount of mental stress and sometimes I feel torn in several directions," says Molly Blackwell, a graphic designer. "Worry Free takes me to a whole new level of calm. It settles me down so I can focus, accomplish and not feel confused." says an ayurvedic expert from The Council of Maharishi Ayurveda Physicians says that people feel more alert even though calmer because of the factors already mentioned.

The medhya herbs enhance the capacity of dhi, dhriti, and smriti and improve coordination between them. Other herbs clear the channels. Winter Cherry increases overall alertness.Researchers were so intrigued with this effect that a whole new study is now being conducted to measure how much Worry Free increases the alertness of the mind.

We are confident that the new research will verify the experience of so many thousands of people who have benefited from this traditional Ayurvedic formula.

Natural Cancer-Fighting Protein May Also Slow Aging

(HealthDay News) -- There's no fountain of youth waiting around the corner, but a study of unusually old mice suggests a natural anticancer protein might also put the brakes on aging.

The protein, called p53, along with one of its cellular regulators, called Arf, may boost the body's antioxidant activity to keep cells younger longer, according to research in the July 19 issue of Nature.

In the study, a team of cancer investigators closely examined cells from mice genetically engineered to produce extra amounts of p53 and/or Arf.

"When we examined markers of aging in these mice, we observed that their aging is slower," said senior researcher Manuel Serrano of the Spanish National Cancer Research Centre in Madrid. This extended lifespan wasn't just due to p53's well-known anti-cancer activity, he said, since aging was slowed even when the researchers took cancer suppression into account.

Cancer researchers are certainly no strangers to the p53 protein, which is produced naturally by the body.

"P53 is the undisputed 'star' in cancer research -- scientists know more about p53 than about any other gene or protein," Serrano said. That's because the protein helps target and eliminate what he called "unhappy" cells -- cells with broken DNA, or cells poorly supplied in oxygen -- that have a higher risk of becoming malignant.

"P53 kills the unhappy cells by activating another complex cascade of events (only partly understood) that includes self-digestive proteins that basically destroy the cell," Serrano explained.

P53 is helped in this task by the regulatory chemical Arf, which lets p53 know that a particular cell is in trouble and marked for elimination.

Throughout their years of work with p53/Arf, Serrano's Spanish team has utilized a genetically engineered strain of lab mice that produces extra-high quantities of the two proteins. The Madrid researchers noted that these rodents lived longer than other mice, even when the scientists factored out reductions in cancer-related death.

While no one is sure just how p53 keeps cells young, Serrano believes the protein "delays aging for exactly the same reason that it prevents cancer."

"In the aging field, everyone agrees that aging is produced by the accumulation of faulty cells," he said. However, p53/Arf appears to be a kind of "quality control" manager in this regard, eliminating bad cells that cause cancer and speed up the aging process. Therefore, "the expectation is that by having more p53, mice will have more strict quality control for cells, hence less cancer and less aging," Serrano said.

In fact, p53 may be a key to explaining why cancer incidence rises near the end of any mammal's lifespan, the researchers said. This sharp rise in malignancy isn't dependent on how many years the animal lives (for example, mice live about three years, humans close to 80).

Instead, it always occurs near the end of a particular animal's expected lifespan.

So, "the fact that we have evolved to be such a long-lived species probably requires that we can fight cancer [longer]," and p53 probably helps humans do that, said Felipe Sierra, director of the Biology of Aging Program at the U.S. National Institute on Aging. He believes p53/Arf plays a key role in keeping cancer at bay throughout youth and middle-age, but this effect may wane in old age.

According to Sierra, the Spanish study helps answer the question of why aging and cancer are so closely intertwined, and p53's role in that relationship. "The fact that there was a connection was suspected for a long time, but it was difficult to prove," he said. "It's perfectly sensible that there's this correlation between these two things."

But don't look for any elixir of eternal life anytime soon, the experts said.

"There are a number of chemical compounds that have been developed by big pharmaceutical companies, and these compounds are able to boost p53 in the organism," Serrano noted. But testing of these compounds is still in its earliest stages and safely "fine-tuning" the p53 cascade will likely be a delicate process. "To achieve this fine-tuning with chemical drugs may not be that easy," he said.

Sierra was similarly cautious.

"We're not really talking here about anything that can manipulate the system," he said. "This is just about basic mechanisms, so we can start looking in different directions. There's no fountain of youth in the near future."

More information
Find out more about p53 at the National Center for Biotechnology Information.

No Danger Found in Blood Thinner-Statin Combination

(HealthDay News) -- A new study helps douse fears about possible harmful interactions when heart patients take both the anti-clotting drug clopidogrel and a cholesterol-lowering statin.

Those fears arose several years ago when researchers showed that the same enzyme metabolizes both clopidogrel and the various statins, explained Dr. Steven R. Steinhubl, an associate professor of medicine at the University of Kentucky, and a member of the team reporting the finding in the July 24 issue of the Journal of the American College of Cardiology.

"The original study made a lot of sense," Steinhubl said. "The mechanism of action was demonstrated very well. Since then, there have been a dozen other studies. About a third showed the same interaction, a third showed nothing, and a third showed the opposite -- a beneficial interaction."

Because of the results of the new study, "I tend to support the idea that this is not a clinically important interaction," Steinhubl said.

The new study used data from a trial called CHARISMA, which created a sensation last year when it showed that adding clopidogrel (Plavix) to aspirin for patients who had suffered a heart attack or stroke did not improve their survival. In this study, the researchers looked at just over 10,000 patients who got a statin as well as clopidogrel to see whether the combination therapy increased the incidence of heart attack, stroke or cardiovascular death over 28 months.

It didn't. The rate of such deadly interactions was 6.8 percent for those getting clopidogrel and a statin, and 7.3 percent for those getting a statin but not clopidogrel.

"It is potentially a big deal, because lots of patients who need to be on clopidogrel also need to be on a statin," said Dr. Deepak L. Bhatt, associate director of the Cleveland Clinic cardiovascular coordinating center and another member of the research team. "But if there is some kind of interaction, we didn't see it, although we didn't necessarily disprove it. It is below the level of natural drug variability."

Fears of the possible interaction have been fading, both Bhatt and Steinhubl said. "I don't know of any situation where people are changing their practice because of it," Steinhubl said.

"The bottom-line message to patients is that there was some concern about a possible interaction a couple of years ago," Bhatt said. "But, in a practical sense, there is nothing that patients now need to worry about."

Other findings unrelated to statins have emerged as researchers pore over data from the CHARISMA trial, which enrolled more than 15,000 patients, Bhatt said. One such finding, published last month, is that the aspirin-clopidogrel combination appears to have some benefit for people in the highest risk group -- those who have had a heart attack or stroke, or a history of rupture of an artery-blocking fatty deposit called a plaque, he said.

But the postulated dangers of the clopidogrel-statin combination appear not to have stood up to close examination, Bhatt said.

More information
Learn more about clopidogrel from the U.S. National Library of Medicine.

Skin Care

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Choose light, refreshing Lemongrass for dry skin; soothing, cooling Sandalwood for sensitive skin and fresh, lemony Citronella for oily skin. The neutral, fragrance-free herbal cleansing bar combines rose petals with herbs good for all skin types.

Patient's Own Body Fat Used in Breast Remodeling

(HealthDay News) -- Injecting a woman's own fat from her belly or thigh into the breast to reconstruct it after breast cancer lumpectomy shows real promise, the developers of the new technique say.

Called "Celution," the investigational procedure involves "supercharging" the fat cells so they will stay where they are injected, explained Dr. Eric Daniels, senior director of business development for Cytori Therapeutics in San Diego, which developed the approach.

Celution is not yet available in the United States. However, later this year, the company expects to launch a breast reconstruction study in Europe for women who had undergone partial mastectomy. The procedure is expected to be available in Europe in 2009.

The news sparked a story in the London-based industry publication Chemistry & Industry, headlined "Breast Boost in Your Lunch Hour."

That's misleading, said Daniels and Tom Baker, Cytori's director of investor relations, since the process takes at least two or three hours. And while breast augmentation with the procedure is a possibility in the future, the target patient right now is a woman with breast cancer who needs breast defects filled in after a partial mastectomy or "lumpectomy."

A plastic surgery expert not involved in the company said the approach might work if issues surrounding fat injections -- such as the likelihood of fat being absorbed by the body -- can be worked out.

In the technique, adipose (fat) tissue is taken from the patient, using a minor liposuction-like procedure. The tissue is then placed into the Celution system, and processing begins. An hour or so later, a dose of regenerative cells is delivered back to the patient, injected in the breast.

Fat tissue contains many types of cells, Baker said, but the stem cells and regenerative cells are the "stars" that make the reconstruction possible.

"We are trying to restore a defect," said Daniels. "We are trying to match the contralateral (opposite) breast." There are few reconstructive options to achieve that type of balance for these patients, Baker and Daniels said.

Fat injections have become common practice among plastic surgeons during the last 15 years or so, according to Dr. Brian Kinney, a Beverly Hills, Calif., plastic surgeon, and clinical assistant professor of plastic surgery at the University of Southern California Keck School of Medicine.

Kinney, who is also past president of the Plastic Surgery Educational Foundation of the American Society of Plastic Surgeons, said that, "It's become common practice for plastic surgeons to use [the patient's own] fat in filling in defects such as around the eyes, in the nasolabial (nose to mouth) folds, and in the body, especially after liposuction that leads to irregular contours."

"About 6 or 8 years ago, [some] doctors started talking about injecting fat into the breast," he said. Not many plastic surgeons do the procedure, he said. "The science is not worked out, and we don't encourage it," Kinney said.

Besides the issue of fat cell reabsorption, Kinney worried that injected fat that reabsorbs may look like breast cancer on a mammogram. "We've had some radiologists that come to our [plastic surgery] meetings and say, 'I can tell the difference,' and others say, 'I don't think so,' " Kinney said.

Because of these difficulties, any woman who did opt for a procedure such as Celution, "would need to seek out a radiologist experienced in reading mammograms on breasts with fat injected," Kinney added.

"Lumpiness could be a problem," he added. "We don't have good statistics on that."
However, if the fat absorption issue could be worked out, "It would not be surprising in the future -- with refinement in technique -- that this could be of benefit to women who need augmentation or reconstruction," Kinney said. "But it may be many years, and it's far too early to know before large, well-controlled case-control clinical trials are done and peer-reviewed by other experts," he added.

As for the lunch-hour time frame? "Just a few years ago, lots of attention focused on the weekend face lift," Kinney said. "A lunchtime breast augmentation is equally implausible."

More information
To learn more about cosmetic surgery procedures, visit the American Society of Plastic Surgeons

Cats Can Hamper Breathing Even in Non-Allergic

(HealthDay News) -- Adults plagued by allergies can be affected by cat dander even if they aren't specifically allergic to felines, a new European study shows.

"Exposure to cats is more of a problem than was thought," said study author, Susan Chinn, a professor of medical statistics at the Imperial College, London.

Chinn, along with colleagues at 20 European centers, expected to find higher bronchial (airway) responsiveness in research subjects who were sensitized to cats.

What they didn't expect to find -- but did -- was a similar increase in airway reaction among subjects who weren't allergic to cats but were sensitive to three other common allergens: dust mites, mold or timothy grass.

"Bronchial responsiveness is a measure of the propensity of the airways to constrict," Chinn explained. "Although it's not synonymous with asthma, it is an indicator of airways [that are] likely to show an asthmatic response," she said.

Consequently, the study found that "cat allergen exposure at moderate levels may be harmful" to all adults with allergies, regardless of what their allergy triggers might be, Chinn said. "The clinical implication is that it is insufficient to test patients with asthma for cat sensitization," she said, since all allergic people "might benefit from reduced cat exposure."

The findings are published in the first July issue of the American Journal of Respiratory and Critical Care Medicine.

Simply having a cat in the house is a good example of moderate exposure, Chinn said, but it's not necessary. That's because even the presence of cats kept by others in the nearby community was enough to leave cat allergens in mattress dust from homes tested by researchers, she said.

Still, the study's findings would have to be replicated before the researchers could make any strong recommendations about cat ownership, Chinn added.

But Dr. Jerry Shier, an allergist and an assistant clinical professor at George Washington University School of Medicine, in Washington, D.C., said that the European study is likely to spur additional research. That may lead allergic patients to lend more weight to their doctor's recommendations against pets -- even if "they aren't yet allergic to animals yet," he said.

Shier also suggested that schools and other public places where cat and other allergens are likely to be present should give more attention to cleaning hard surfaces and avoiding carpeting.

He noted that cat allergens are particularly widespread because they are "stickier," smaller and lighter than other allergens, which makes them easily airborne. As a result, a person could be exposed without being in the presence of cats. That's why Chinn's group found cat allergen to be ubiquitous in the mattress dust of both cat owners and non-owners.

What makes people with allergies who are not allergic to cats still sensitive to the animals' allergens? No one is quite sure.

The question deserves "a closer look," said Dr. Marc Riedl, an assistant professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. One reason cat allergens may have a wider impact is that these small airborne particles, which can be a quarter of the size of dust mites, "are much more likely to have access to the lung than other allergens," he said. Consequently, cat allergens could have wider effects that have nothing to do with allergic sensitivity per se.

Then there are substances called endotoxins. Endotoxins break down portions of bacteria that in turn stimulate the immune system, Shier explained.

The study raises the question of whether endotoxins -- which have been found at higher levels in cat owners' homes -- might be the cause of increased bronchial responsiveness observed in ostensibly non-cat-allergic people, he said. "There [also] may be some other unknown entity that comes from the cat that may be responsible for triggering the bronchial hyperactivity," he added.

The European study also pointed out gender differences in terms of who is most vulnerable to cat allergy. Among the almost 1,900 randomly selected participants included in the study, men and women turned out to be equally sensitive to cats. However, women had a higher exposure to cat allergens, were more likely currently to own a cat, and were more likely to allow the cat in the bedroom.

Cat ownership also varied by country, ranging from as low as 10 percent of participants in Spain to as high as 35 percent among the British.

More information
There's more on pet allergies at Asthma and Allergy Foundation of America.

Glucosamine Trials Show Little Benefit Against Arthritis

(HealthDay News) -- Although millions of arthritis sufferers buy glucosamine supplements to ease their joint pain, there's still no convincing proof the product works, according to a major new analysis.

In fact, the results of 15 trials of over-the-counter glucosamine vary so widely that industry bias may be a factor influencing the more positive outcomes, concludes a team writing in the July issue of Arthritis & Rheumatism.

"There's a big difference between trials, much more than you would expect by chance," explained lead investigator Dr. Steven Vlad, a fellow in rheumatology at Boston University Medical Center.

But an editorialist in the journal refutes those claims.

Dr. Jean-Yves Reginster, of the World Health Organization's Collaborating Center for Public Health Aspects of Rheumatic Disease, in Liege, Belgium, counters that industry trials are typically more stringent than independent academic research. He also believes that Vlad's group included trials in their analysis that were very unalike in terms of timeframes and methodology, confusing the results.

So, the years-long scientific debate on glucosamine continues. The popular supplement did take a major hit earlier this year, when a major U.S. study published in the New England Journal of Medicine found glucosamine hydrochloride to be of little help for knee osteoarthritis.

But Vlad also knew that other studies had found a real benefit to regular glucosamine use. Why the differences between trials?

To find out, he and his team combed through the available literature and selected 15 double-blind, placebo-controlled, randomized clinical trials that looked at the use of glucosamine for more than four weeks to help fight hip or knee osteoarthritis pain.

Trials involved either of the two major glucosamine preparations: glucosamine hydrochloride or glucosamine sulfate. Each delivers glucosamine bound to a different chemical salt.

First of all, the team determined one of the preparations to be useless.

"I think we have shown pretty conclusively that glucosamine hydrochloride doesn't work," Vlad said. "The data there is all consistent, it goes together -- there's just no evidence that it works."
But that wasn't the story with the other preparation, glucosamine sulfate.

In that case, results varied widely between the randomized trials. However, that variance went far beyond random chance. In fact, according to Vlad, the spread in results among various trials was four times that which would be normally expected.

No particular feature of the studies' design helped explain this disparity, except for differences among trials in what's known as "allocation concealment" -- the fact that some trials were more lax than others at concealing from the researchers involved which patients would get the drug and which would get a placebo.

One factor did appear to play a role in the variance between the glucosamine sulfate trial results: industry involvement.

"It's really hard to know just how big a factor that is," Vlad said, "whether it's manufacturing the whole effect or just exaggerating an effect that's there." He also stressed that, "If there is a bias from industry, I doubt very much that it is intentional. People want to sell their product, but I think that they rarely go into a study with the intention of twisting the results."

But Reginster, in his editorial, believes Vlad's own analysis is flawed. He agreed with the Boston group that industry involvement can, and often does, influence trial results. But he also notes that many of the industry studies included in the Boston analysis had to pass muster with the European League Against Rheumatism, the expert body which vouched for many of the trials' high quality.

That's important, he said, because -- unlike in the United States -- glucosamine sulfate is approved for sale as a prescription drug by regulatory agencies in Europe. To gain approval, industry-funded trials must conform to regulatory oversight and are often better designed than independent studies, he noted.

But Vlad doesn't buy that argument. "I would agree with [Reginster] that, in general, drug manufacturers do produce better trials," he said. "But I also believe it is too simplistic to say that academic researchers aren't as good at weeding out confounding factors and things that would influence the results. They can produce trials that are every bit as good."

Another expert weighed in on the issue.

"I have worked on both sides [industry and independent]," said Malachy McHugh, director of research at the Nicholas Institute of Sports Medicine and Athletic Trauma, at Lenox Hill Hospital, in New York City. He said one issue at play is the dire lack of quality independent studies.

"In the nutritional supplement area, the bigger problem is that there is a disincentive for companies to have their products tested," he said. "If they can convince people that their product works, why run the risk of proving otherwise? There are also many negative studies that never see the light of day."

Reginster lobbed another major criticism at the Vlad study. In his opinion, the Boston group mixed together trials with widely varying timeframes (four-week studies and three-year trials), glucosamine delivered in both injections and pills, and studies of greatly differing quality. This type of heterogeneity was bound to lead to variety in results, he wrote.

Vlad agreed that his team's analysis did cast a wide net, but he said that's the way meta-analyses are typically performed. "You try and capture all the trials that may be relevant to your question," he said. Select too few trials, he said, and you lose statistical power.

The system is "never going to be perfect," Vlad said.

He stressed that the new analysis does not close the book on glucosamine. And given the supplement's good safety profile, patients who really believe they are reaping a benefit from the glucosamine sulfate should feel free to continue to take it.

Vlad and McHugh remain dubious, however, that the pricey supplement does ease osteoarthritis pain.

"From my perspective," McHugh said, "the New England Journal of Medicine paper provides the most objective take on the efficacy. The bottom line is that there is limited efficacy."

In a related study in the same issue of the journal, U.S. researchers surveyed more than 6,000 people with rheumatoid arthritis and found that most are reluctant to switch to a new medication as long as their condition does not worsen.

The team from the National Data Bank for Rheumatic Diseases in Wichita, Kan., found three-quarters of respondents were happy with their current medications, and almost two-thirds (64 percent) said they wouldn't try a new drug unless their symptoms deteriorated. The findings may explain why many patients hold off trying promising new medications, the researchers said.

More information
There's more on osteoarthritis at the Arthritis Foundation.