Glucosamine Trials Show Little Benefit Against Arthritis

FRIDAY, June 29 (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.

Study to Assess Hormone Therapy Before Menopause

FRIDAY, June 22 (HealthDay News) -- Researchers at eight locations across the United States plan to examine the safety and effectiveness of estrogen therapy during perimenopause, the few years just prior to menopause.
The KEEPS (Kronos Early Estrogen Prevention Study), led by researchers at the University of Wisconsin (UW) School of Medicine and Public Health, will evaluate the effect that four years of estrogen therapy has on mood and cognition in 720 healthy perimenopausal women.
"There has been a tremendous amount of important and valuable research done on the positive and negative health effects of therapy using estrogen in menopausal women," study leader Sanjay Asthana, head of the UW Section of Geriatrics and Gerontology and director of the Geriatric Research, Education and Clinical Center, said in a prepared statement.
"It is my belief that this study will go a long way in helping us understand the complexity of estrogen and related hormones in humans. It is critical that we continue to systematically address all of the clinical issues concerning estrogen treatment and its effects on diseases like Alzheimer's," Asthana said.
The $3.4 million study will be funded by the U.S. National Institutes of Health.
Among its objectives, KEEPS will compare an arm patch that delivers a natural, human form of estrogen to the commonly used oral form of estrogen synthesized from animal sources.
Other goals include determining the best way to counteract the adverse effects of estrogen on the lining of the uterus and investigating which hormone therapy best mimics the menstrual cycle.

Girls Who Like Dad Favor Partners Who Look Like Him

The study, published in the July issue of the journal Evolution and Human Behavior by British and Polish psychologists, also found that women who had a negative/less positive childhood relationship with their father weren't attracted to men who looked like their father.
The researchers had 49 Polish women (eldest daughters) look at pictures of 15 faces and choose the one they found most attractive. Their selections were compared to their fathers' faces. The women were also asked to rate their childhood relationship with their father.
The findings offer new insight into how people select partners and the effect that parents have on the process, the researchers said. Until recently, it was believed that this parental influence was a passive process. But this study adds to growing evidence that it's actually an active process.
The results of this study "show for certain that the quality of a daughter's relationship with her father has an impact on whom she finds attractive. It shows our human brains don't simply build prototypes of the ideal face based on those we see around us, rather they build them based on those to whom we have a strongly positive relationship. We can now say that daughters who have very positive childhood relationships with their fathers choose men with similar facial characteristics to their fathers," study author Dr. Lynda Boothroyd of Durham University said in a prepared statement

Vitamin D Cuts Cancer Risk: Study

FRIDAY, June 8 (HealthDay News) -- Boosting your vitamin D intake can dramatically reduce your risk of breast and other cancers, a new study found.
The research adds to growing evidence that vitamin D can help protect against many forms of cancer as well as other diseases, Creighton University researchers said.
But an American Cancer Society spokeswoman urged caution in interpreting the findings, saying it was premature to recommend taking vitamins to reduce cancer risk.
Joan Lappe, a Creighton University professor of medicine and nursing and lead author of the study, said, "What we can say from our study is that 1,100 international units (IUs) a day of vitamin D definitely decreased the incidence of cancer."
That amount of the vitamin is nearly triple the recommended intake for the age group studied -- women who were 55 and older when the four-year study started.
Lappe's team followed 1,179 study participants who were all postmenopausal and lived in rural Nebraska. The women were free of known cancers for the 10 years before entering the study. They were assigned to one of three groups and followed for four years.
One group took 1,400 to 1,500 milligrams of supplementary calcium a day, another group took that same amount of calcium plus 1,100 IUs of vitamin D daily, while the third group took placebo pills every day.
After four years, those in the combination vitamin D and calcium group had a 60 percent lower risk of developing cancer, compared to the placebo group. The calcium-only group had a 47 percent reduced risk.
Then the researchers eliminated data from the first year of the study, figuring some women may have entered the study with cancer that had not yet been diagnosed. The results were more dramatic, Lappe said.
When the researchers looked at results from just the last three years of the trial, they found the combination calcium-and-vitamin D group had a 77 percent reduced risk of cancers, compared to the placebo group. The risk for the calcium-only group was essentially unchanged.
In all, a total of 50 women got non-skin cancers during the study, with breast cancer the most common. The other cancers included lung and colon tumors.
The findings are published in the June edition of the American Journal of Clinical Nutrition.
In May, Harvard Medical School researchers reported in the Archives of Internal Medicine that high intakes of vitamin D and calcium cut the risk of breast cancer by nearly one-third in premenopausal women, but not women past menopause.
Dr. Michael Holick, professor of medicine, physiology and biophysics at the Boston University School of Medicine and a long-time vitamin D researcher, said the Lappe study adds to growing evidence of the health and disease-fighting effects of vitamin D.
"It's very clear the data are significant," he said of the Lappe study.
Vitamin D is thought to act through the immune system to help prevent the formation of abnormal cells, Lappe said.
To date, both Lappe and Holick said, high intake of vitamin D has been found to reduce the risk of many forms of cancer as well as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and high blood pressure.
Both researchers think the current recommendations for daily vitamin D intake should be boosted. The U.S. Institute of Medicine, which makes recommendations on vitamin and mineral requirements, considers 200 IUs of vitamin D adequate for children and adults up to age 50; 400 IUs adequate for adults 51 to 70, and 600 for those 71 and older. The levels aren't Recommended Dietary Allowances, or RDAs, because the institute doesn't think there's enough evidence to establish an RDA for vitamin D.
"I think it's safe to say the current recommendations are much too low," Lappe said, adding that postmenopausal women should "probably be taking 1,100 IUs a day."
She recommends vitamin D3 supplements, the type used in the study, over D2, because D3 is more active, she said.
But Marji McCullough, strategic director of nutritional epidemiology for the American Cancer Society, who is familiar with the new study and other similar research, said in a prepared statement that the society doesn't currently recommend taking vitamin or mineral supplements to reduce cancer risk. But it has joined other health organization to weigh the evidence of vitamin D, and a joint panel recommends supplementation and small amounts of ultraviolet exposure "as the best way to achieve proper vitamin D status."
While she called the new study "intriguing,'' she said the number of participants was small and the research needs to be replicated before firmer conclusions can be drawn.
Discuss vitamin D intake with your doctor. And be aware that the Institute of Medicine has declared that 2,000 IUs is the upper tolerable, or safe, level for most people. For babies up to 1 year old, the limit is 1,000 IUs, McCullough said.
Vitamin D, which is important for strong bones, is found in salmon and other fish, and fortified milk and fortified cereals, among other foods.
Supplements aren't the only potential way to fight disease. In the same issue of the journal, another report found that a high intake of whole grain foods reduced the risk of atherosclerosis, or hardening of the blood vessels, which can lead to heart disease.
U.S. researchers tracked 1,178 men and women, from 40 to 69 years old at the start of the study, and found that eating more whole grains was associated with a lower risk of atherosclerosis.

Breakthrough Liver Cancer Treatment Found

MONDAY, June 4 (HealthDay News) -- Researchers have announced the first drug to make major inroads against liver cancer, one of the more voracious forms of the disease.
Nexavar, made by Bayer, gave patients with advanced liver cancer 44 percent more time to live, compared to patients who did not receive the drug, according to results presented Monday at the annual meeting of the American Society of Clinical Oncology, in Chicago.
Results of a major clinical trial with Nexavar (sorafenib) were, in fact, so successful that the trial was halted early, the researchers announced.
"This is the first systemic therapy to prolong survival in [liver cancer] patients," said Dr. Joseph Llovet, lead author of the study and director of research in liver cancer at Mount Sinai School of Medicine in New York City. "This is a new reference standard for systemic therapy of [liver cancer] patients after 30 years of research and more than 100 randomized controlled trials performed."
Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, added, "This is going to change the standard of practice."
Liver cancer is the third leading cause of cancer death in the world and often causes death within a year of diagnosis. About 40 percent of liver cancers (up to 80 percent in Asia and sub-Saharan Africa) are diagnosed at an advanced stage. Surgery is sometimes possible, and radiation and chemotherapy can also be options. But there is no systemic treatment, meaning a medication that enters the bloodstream.
"There is no established standard of care for liver cancer even though it is one of the leading causes of death," said Dr. A. William Blackstock, a Wake Forest University radiation oncology professor who moderated a Monday news conference to announce the study results.
Nexavar, which is taken in tablet form, is already approved in the United States for treating advanced kidney cancer. It is being studied for various other cancers; results of some of those studies are also being presented at ASCO annual meeting.
In this study, 602 patients with advanced liver cancer were randomly assigned to receive either 400 milligrams of Nexavar twice a day or a placebo for six months.
Patients receiving the drug lived a median of 10.7 months, compared with only 7.9 months for those on a placebo. Time to cancer progression was 5.5 months in the Nexavar group, versus only 2.8 months in the placebo group. The findings were so positive that the study was terminated early.
"We recommended ending the trial early because of survival advantages favoring the sorafenib group," said Llovet.
Side effects were similar in the two groups, the most common being diarrhea, skin reactions, fatigue and bleeding.
"Sorafenib was well tolerated with manageable side effects," Llovet said.
A second study presented Monday at the cancer meeting offered a bit of good news for colorectal cancer patients.
When chemotherapy was given both before and after surgery to remove liver metastases in colorectal cancer patients, the risk of the liver tumor recurring was reduced almost 30 percent.
"A few years ago, we had only palliation to offer these patients and survival lasted no longer than six months," said Dr. Bernard Nordlinger, lead author of the study and chairman of surgery and oncology at Ambroise Pare Hospital in Paris. "This treatment should be proposed as a new standard for these patients."
One million people are diagnosed with colorectal cancer each year; up to half will see their cancer spread to the liver. Liver tumors are removed when possible, but only 30 percent to 35 percent of patients who have liver metastases survive five years after surgery.
Adding the targeted therapy Erbitux (cetuximab) to chemotherapy reduced the risk of metastatic colorectal cancer spread by 15 percent. The drug is currently approved as a second-line or third-line therapy, not as the first option.
These new results indicate that Erbitux has promise as a first-line treatment, the researchers said.

TB Patient Apologizes to Fellow Passengers but Defends Actions

FRIDAY, June 1 (HealthDay News) -- The Georgia man infected with a dangerous form of tuberculosis insisted in a televised interview Friday that he was never told by health officials that he was contagious, and apologized to passengers who shared a series of airline flights with him last month.
"I've lived in this state of constant fear and anxiety and exhaustion for a week now, and to think that someone else is now feeling that, I wouldn't want anyone to feel that way. It's awful," Andrew Speaker told ABC's Diane Sawyer on Good Morning America from his room in a Denver hospital that specializes in infectious diseases.
Dressed in street clothes but wearing a face mask, Speaker, a 31-year-old personal injury lawyer from Atlanta, apologized repeatedly to the dozens of airline passengers and crew members now awaiting their own test results because they had been exposed to him, the Associated Press reported.
"I don't expect for people to ever forgive me. I just hope that they understand that I truly never meant to put them in harm," said Speaker, whose new father-in-law, Robert C. Cooksey, is a research microbiologist with the U.S. Centers for Disease Control and Prevention's division of tuberculosis elimination.
Speaker said he, his doctors and officials from the CDC all knew he had been diagnosed with "extensively drug-resistant" TB, also called XDR-TB, before he flew to Europe for his wedding and honeymoon last month. But he said he was told he wasn't infectious and did not pose a health risk to others. Health officials said they'd prefer he didn't fly, but no one ordered him not to, he said.
He said his father, also a lawyer, taped that meeting, the AP reported.
"My father said, 'OK, now are you saying, prefer not to go on the trip because he's a risk to anybody, or are you simply saying that to cover yourself?' And they said, we have to tell you that to cover ourself, but he's not a risk," Speaker said, the AP reported.
Dr. Steven Katkowsky, director of the Fulton County (Georgia) Department of Health and Wellness, said Speaker was told in early May not to travel to Europe.
"He was told traveling is against medical advice," agreed Dr. Martin Cetron, director of the CDC's division of global migration and quarantine. Once Speaker was in Europe, "He was told in no uncertain terms not to take a flight back," Cetron added.
Speaker said the CDC called him in Rome and informed him he had the drug-resistant form of TB and told him to cancel his commercial fight plans. But the CDC didn't offer him any help, he said, other than to meet with health officials in Italy. He contended in Friday's interview that the CDC was effectively abandoning him in Rome and eliminating his best chances for saving his life -- treatment at the TB facility at Denver's National Jewish Medical Center.
Meanwhile, Speaker continued to receive treatment Friday at the Denver hospital. He was flown to Denver from Atlanta, accompanied by federal marshals, on Thursday after being quarantined at Grady Memorial Hospital in Atlanta for two days.
Dr. Charles Daley, chief of the National Jewish Hospital's infectious-disease division, said he was optimistic Speaker could be cured because he appears to be in the early stages of the disease, the AP said.
Daley's colleague, Dr. Gwen Huitt, said Thursday that Speaker is "a young, healthy individual" who is "doing extremely well."
"By conventional methods that we traditionally use in the public health arena ... he would be considered low infectivity at this point in time," she said. "He is not coughing, he is healthy, he does not have a fever."
The hospital is testing other antibiotics and developing a drug regimen that could include as many as five antibiotics, Huitt said.
Speaker's new wife, Sarah, has tested negative for the respiratory disease.
Speaker had taken two trans-Atlantic flights last month for his wedding and honeymoon, possibly infecting fellow passengers in the process.
Speaker's father-in-law, Robert C. Cooksey, the CDC research microbiologist, issued a terse statement Thursday afternoon through the CDC, denying that he knew of his new son-in-law's travel plans.
"As part of my job, I am regularly tested for TB. I do not have TB, nor have I ever had TB. My son-in-law's TB did not originate from myself or the CDC's labs, which operate under the highest levels of biosecurity," said Cooksey, who has worked at the CDC for 32 years.
He added, "First and foremost, I am concerned about the health and well-being of my son-in-law and family, as well as the passengers on the affected flights."
Speaker flew on May 12 from Atlanta to Paris on Air France Flight 385, continued on to Prague, then took a return flight aboard Czech Air Flight 0104 to Montreal, Canada, on May 24, before driving back into the United States at Champlain, N.Y.
On Tuesday, CDC officials issued the first federal isolation order since 1963 to quarantine Speaker.
The agency has advised passengers who were on both flights to get tested for tuberculosis, although they are thought to be at low risk of infection from the disease, agency officials said Wednesday.
The CDC's Cetron noted that on the flight from Atlanta to Paris, some 40 to 50 passengers who sat near Speaker were those most likely at risk. Speaker probably sat in row 51. The same is true for the 30 passengers who sat near him on the flight from Prague to Montreal. On that flight, he sat in seat 12C.