Health
In a randomized trial that included nearly 15,000 male physicians, long-term daily multivitamin use resulted in a modest but statistically significant reduction in cancer after more than a decade of treatment and follow-up, according to a study appearing in JAMA.
The study is being published early online to coincide with its presentation at the Annual American Association for Cancer Research Frontiers in Cancer Prevention Research meeting.
“Multivitamins are the most common dietary supplement, regularly taken by at least one-third of U.S. adults. The traditional role of a daily multivitamin is to prevent nutritional deficiency. The combination of essential vitamins and minerals contained in multivitamins may mirror healthier dietary patterns such as fruit and vegetable intake, which have been modestly and inversely associated with cancer risk in some, but not all, epidemiologic studies. Observational studies of long-term multivitamin use and cancer end points have been inconsistent. To date, large-scale randomized trials testing single or small numbers of higher-dose individual vitamins and minerals for cancer have generally found a lack of effect,” according to background information in the article. “Despite the lack of definitive trial data regarding the benefits of multivitamins in the prevention of chronic disease, including cancer, many men and women take them for precisely this reason.”
J. Michael Gaziano, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, (and also Contributing Editor, JAMA), and colleagues analyzed data from the Physicians’ Health Study (PHS) II, the only large-scale, randomized, double-blind, placebo-controlled trial testing the long-term effects of a common multivitamin in the prevention of chronic disease.
The trial includes 14,641 male U.S. physicians, initially age 50 years or older, including 1,312 men with a history of cancer at randomization, who were enrolled in a multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011. Participants received a daily multivitamin or equivalent placebo.
The primary measured outcome for the study was total cancer (excluding nonmelanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points.
PHS II participants were followed for an average of 11.2 years. During multivitamin treatment, there were 2,669 confirmed cases of cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer, with some men experiencing multiple events. A total of 2,757 (18.8 percent) men died during follow-up, including 859 (5.9 percent) due to cancer.
Analysis of the data indicated that men taking a multivitamin had a modest 8 percent reduction in total cancer incidence. Men taking a multivitamin had a similar reduction in total epithelial cell cancer.
Approximately half of all incident cancers were prostate cancer, many of which were early stage. The researchers found no effect of a multivitamin on prostate cancer, whereas a multivitamin significantly reduced the risk of total cancer excluding prostate cancer.
There were no statistically significant reductions in individual site-specific cancers, including colorectal, lung, and bladder cancer, or in cancer mortality.
Daily multivitamin use was also associated with was a reduction in total cancer among the 1,312 men with a baseline history of cancer, but this result did not significantly differ from that observed among 13,329 men initially without cancer.
The researchers note that total cancer rates in their trial were likely influenced by the increased surveillance for prostate-specific antigen (PSA) and subsequent diagnoses of prostate cancer during PHS II follow-up starting in the late 1990s.
“Approximately half of all confirmed cancers in PHS II were prostate cancer, of which the vast majority were earlier stage, lower grade prostate cancer with high survival rates,” researchers said. “The significant reduction in total cancer minus prostate cancer suggests that daily multivitamin use may have a greater benefit on more clinically relevant cancer diagnoses.”
The authors add that although numerous individual vitamins and minerals contained in the PHS II multivitamin study have postulated chemopreventive roles, it is difficult to definitively identify any single mechanism of effect through which individual or multiple components of their tested multivitamin may have reduced cancer risk.
The study said, “The reduction in total cancer risk in PHS II argues that the broader combination of low-dose vitamins and minerals contained in the PHS II multivitamin, rather than an emphasis on previously tested high-dose vitamins and mineral trials, may be paramount for cancer prevention. … The role of a food-focused cancer prevention strategy such as targeted fruit and vegetable intake remains promising but unproven given the inconsistent epidemiologic evidence and lack of definitive trial data.”
“Although the main reason to take multivitamins is to prevent nutritional deficiency, these data provide support for the potential use of multivitamin supplements in the prevention of cancer in middle-aged and older men,” the researchers concluded.
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An inexpensive, five-minute eye scan can accurately assess the amount of brain damage in people with the debilitating autoimmune disorder multiple sclerosis (MS), and offer clues about how quickly the disease is progressing, according to results of two Johns Hopkins studies.
“The eye is the window into the brain and by measuring how healthy the eye is, we can determine how healthy the rest of the brain is,” said Peter A. Calabresi, M.D., a professor of neurology at the Johns Hopkins University School of Medicine, and leader of the studies described in recent issues of The Lancet Neurology and the Archives of Neurology.
“Eye scans are not that expensive, are really safe, and are widely used in ophthalmology, and now that we have evidence of their predictive value in MS, we think they are ready for prime time,” Calabresi said. “We should be using this new quantitative tool to learn more about disease progression, including nerve damage and brain atrophy.”
Calabresi and his colleagues used optical coherence tomography (OCT) to scan nerves deep in the back of the eye, applying special software they co-developed that is capable of assessing previously immeasurable layers of the light-sensitive retinal tissue.
The scan uses no harmful radiation and is one-tenth the cost of an MRI. The software will soon be widely available commercially.
In the Lancet paper, Calabresi and his team reported measuring thickness or swelling of the inner nuclear layer of the retina in 164 patients with MS and 60 healthy controls, following changes in these tissues over four years.
At the same time, they also used brain MRI to measure inflammation spots directly, and performed clinical tests to determine disability levels.
The more inflammation and swelling the researchers found in the retinas of the MS patients, the more inflammation showed up in their brain MRIs.
The correlation, they said, affirmed the value of the retinal scans as a stand-alone surrogate for brain damage. Having such information so easily available could allow physicians to accurately tell how far the disease has progressed, and to better advise patients about how they should proceed with their care.
The researchers also found microcystic macular edema in the central part of the retinas of 10 of the MS patients, tiny pockets of fluid typically found in older, usually diabetic people.
While Calabresi cautioned that eye scans do not as yet have primary diagnostic value for MS, he said finding a cyst like this on the eye of a young, healthy person might be reason to have her evaluated for the disorder.
In the United States, there are roughly 400,000 people living with MS. The disorder typically strikes between the ages of 20 and 50 and affects two-to-three times as many women as men.
In the paper published in the Archives of Neurology, Calabresi and colleagues looked at eye and brain scans of 84 MS patients and 24 healthy controls. This time, they focused on two other deep retinal layers, the ganglion cell layer + inner plexiform layer (GCL+IPL), and the peripapillary retinal nerve fiber layer (pRFNL).
Greater cell wasting in those areas was strongly correlated with more atrophy in the gray matter of the brain, signifying more nerve damage from MS.
Gray matter consists of the part of the brain where nerve cells live, and plays a role similar to a computer’s hard drive, in contrast to white matter that is more like the wiring that sends information out from the brain to the spinal cord and the rest of the body’s nerves.
Calabresi, director of the Johns Hopkins Multiple Sclerosis Center, said this finding is particularly important because neurodegeneration is so difficult to accurately gauge.
In a young person with MS, the brain may be atrophying but may cause no symptoms because the brain is able to compensate for what is being lost. Ultimately, though, the loss of brain cells becomes apparent and is irreversible.
Calabresi said that if he saw the kind of thickness on an eye scan indicating severe atrophy, he would consider a patient’s prognosis less encouraging than someone with a healthy retina, and this information may guide physicians to treat more aggressively.
For example, he said he would likely redouble efforts to enter a patient into a clinical trial for an experimental medication before too much permanent damage takes place.
Calabresi said his findings could also shift how researchers approach MS, long believed to be caused by an immune system that wrongly attacks the fatty protein called myelin that insulates nerves and helps them send electrical signals that control movement, speech and other functions.
The usefulness of the scans raises the possibility that there could be something else going on, as there is no myelin deep in the retina of the eye.
If the immune system is going after something else along with myelin, it could help researchers find new medications to target the incapacitating symptoms of MS, such as blurred vision, numbness and weakness.
“It is really important to know what the immune system is attacking,” he said. “The treatments we have right now are only moderately effective, so maybe we’re not blocking the right kinds of cells.”
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