Recent News Breast cancer risk falls as serum vitamin D levels rise May 12, 2008 By Fran Lowry SAN DIEGO (EGMN) – A serum 25-hydroxyvitamin D level of 30 ng/mL or higher was associated with at least a 50% lower risk of breast cancer, according to the findings of a meta-analysis of three observational studies. Together, the findings lend support for annually measuring serum vitamin D levels to better identify women at risk for breast cancer, according to the study’s lead author, Dr. Cedric F. Garland, professor of family and preventive medicine at the University of California, San Diego. Yet experts disagree that there is enough evidence to recommend any intervention that would inevitably result when a patient is found to have low levels of serum 25-hydroxyvitamin D (25[OH]D). “I don’t care how many observational studies there are,” they don’t establish causality, said Dr. Gary G. Schwartz of the departments of cancer biology and public health sciences at Wake Forest University, Winston-Salem, N.C. That said, “There are a lot of good reasons to be concerned about vitamin D,” said Dr. Schwartz. “Low levels of the vitamin probably are related to a number of outcomes that we care about.” The meta-analysis of data from 2,274 women with breast cancer and 2,268 controls without breast cancer indicated a linear dose-response gradient between serum 25(OH)D levels and the risk of breast cancer. “The higher the level of vitamin D metabolites in the serum, the lower the incidence rate of breast cancer,” Dr. Garland said in an interview while presenting his poster the annual meeting of the American Association for Cancer Research. Dr. Garland explained that four recent observational studies showed an inverse association between serum 25(OH)D and risk of breast cancer, but did not specify the 25(OH)D serum levels associated with specific levels of reduction in breast cancer incidence. The studies for his meta-analysis were chosen because they provided data on risk of breast cancer according to quintile of serum 25(OH)D. In the first study included in Dr. Garland’s analysis, researchers recruited 179 breast cancer patients and 179 controls and found that women with low levels of serum 25(OH)D and a polymorphism in the vitamin D receptor gene were 6.25 times more likely to have breast cancer, compared with women who had higher levels and no genetic polymorphism (Eur. J. Cancer 2005;41:1164-9). In the second study, blood samples were taken from 701 cases and 724 controls and women in the highest quintile of 25(OH)D had a relative risk of 0.73 for having breast cancer, compared with those in the lowest quintile (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991-7). In the third study, serum 25(OH)D levels were compared between 1,394 cases and 1,365 controls. Again, the researchers found that serum 25(OH)D concentrations were significantly inversely associated with postmenopausal breast cancer risk. The strongest inverse association was seen in women with levels below 50 nmol/L (20ng/mL) (Carcinogenesis 2008;29:93-9). When the data were combined, a sigmoid dose-response gradient was observed between serum 25(OH)D and risk of breast cancer and was consistent across all studies, Dr. Garland said. He and his colleagues concluded that more cohort studies would be worthwhile but, in the meantime, public health action to raise serum 25(OH)D to 30 ng/mL or more should be started. He commented that the pooled data from these trials add to the evidence for a link between low serum vitamin D and breast cancer, a link that he and his colleague, Dr. Edward D. Gorham, also of the University of California, San Diego, have long proposed. “We’re confident that we can prevent half the breast cancer in women in the United States, if we could raise serum vitamin D levels to 32 ng/mL,” he said. “We’re trying to get doctors, public health officials, and the women themselves involved, and we urge women to get their vitamin D tested. It’s as important, I would say even more important, than mammography,” Dr. Garland said. Women whose serum 25(OH)D levels fall below 32 ng/mL should take supplements until they reach that level. “This would be the best thing they could do for the prevention of breast cancer,” he said. How much vitamin D women should take depends on where they live and their routine sun exposure, he added. “If they live in New York, they need a minimum of 2,000 IU/day. If they’re in San Diego, they could get away with 1,000. Women in intermediate latitudes could take intermediate amounts.” Dr. Garland cited what he called a “landmark” study that supports his assertion that vitamin D reduces breast cancer risk. That study, funded by the National Institutes of Health and led by Joan Lappe, Ph.D, RN, of Creighton University, Omaha, Neb., showed that women who took 1,100 IU/day of vitamin D3 for 4 years--three times more than is currently recommended by the U.S. Recommended Daily Amount (RDA)--lowered their risk of cancer by more than 60%, compared with women who took placebo. (Am. J. Clin. Nutr. 2007;85:1586-91). Dr. Rowan T. Chlebowski, professor of medicine at the University of California, Los Angeles, countered, however, that it is too soon to claim that upping the intake of vitamin D can ward off breast cancer. In 2006, Dr. Chlebowski reported that a Women’s Health Initiative trial found no reduced breast cancer risk in 18,000 women randomized to 1,000 mg of calcium carbonate and 400 IU/day of vitamin D when compared with 18,000 women given a matching placebo. The results from Dr. Garland’s meta-analysis “require a much more cautious interpretation,” he added. This is a selective meta-analysis. It’s not comprehensive, and there are negative studies that were not included, he said. At best, Dr. Garland’s review shows an association, but it does not establish causality. Before public health policies are changed, “the lessons of combined hormone therapy and purported heart disease benefit should be remembered,” Dr. Chlebowski concluded. Studies uncover adverse reactions to probiotics May 6, 2008 By Robert Finn BEVERLY HILLS, Calif. (EGMN) – The jury may still be out on whether probiotics are beneficial, but at least they do no harm and can be safely recommended to patients, right? Not so, said Dr. David R. Mack at the International Probiotics Association World Congress. Several recent studies have uncovered some risks associated with probiotic use, in both children and adults. “We [physicians] are always looking for new things, but we’re a conservative, skeptical lot, and safety is a primary concern,” Dr. Mack said. One of the most concerning studies is also one of the newest, noted Dr. Mack of the University of Ottawa (Ont.). Investigators randomized 298 patients with predicted acute pancreatitis to receive probiotic prophylaxis or placebo. The probiotic preparation consisted of six live bacterial species: Lactobacillus acidophilus, L. casei, L. salivarius, Lactococcus lactis, Bifidobacterium bifidum, and B. lactis. Not only did the probiotic preparation fail to reduce the risk of infectious complications, but the mortality rate was 2.5 times higher among the patients receiving probiotics than among those receiving placebo. Twenty-four (16%) of the patients in the probiotics group died, compared with nine (6%) in the placebo group. v Furthermore, nine of the patients in the probiotics group developed bowel ischemia (eight with fatal outcomes), compared with none in the placebo group. The other deaths involved multiorgan failure (Lancet 2008;371:651-9). According to some studies, probiotics are associated with increased asthma and wheezing in children. In one study, for example, children exposed to L. rhamnosus GG at birth had 3.4 times the risk of having asthma at age 7 years as a control group had (J. Allergy Clin. Immunol. 2007;119:1019-21). In another study involving the use of L. rhamnosus GG to prevent atopic dermatitis, 26% of the children in the probiotic group versus 9% in the control group developed wheezing bronchitis (Pediatrics 2008;121:e850-6 [Epub doi:10.1542/peds.2007-1492]). And there is further evidence of possible allergic complications following probiotic use. One study in France demonstrated that two out of three common probiotic preparations contained cow’s milk proteins (J. Allergy Clin. Immunol. 2007;119:746-7), and a separate case report described a child who developed anaphylaxis after taking a probiotic containing cow’s milk proteins. Dr. Mack noted that one in five babies is allergic to cow’s milk (Allergy 006;61:507-8). Beyond these known adverse reactions, there are other reasons to be concerned about the possible long-term effects of probiotics in young children. When adults take probiotics, it’s rare to see extended colonization by the probiotic bacterial species, but outcomes appear to be different in young children: Some probiotic species have been detected in stool samples years later. The consequences of this extended exposure to probiotic organisms are unknown, Dr. Mack said. Speaking of these studies as a group, he added, “I think these are a little warning shot across the bow” and safety trials are needed. New guideline targets osteoporosis screening in men May 6, 2008 By Sherry Boschert Clinicians should assess older men for risk factors for osteoporosis and measure bone density by dual-energy x-ray absorptiometry if any risk factors are present, a new guideline from the American College of Physicians recommends. How old is “older” is left open to interpretation and is one point of difference between the new guideline and separate new guidelines issued by the National Osteoporosis Foundation (NOF) in February 2008. The American College of Physicians (ACP) recommendations–the first from the organization specifically on osteoporosis in men–will be published in the May 6, 2008, issue of the Annals of Internal Medicine (Ann. Intern. Med. 2008;148:680-4). The new NOF guidelines for the first time include screening and treatment in men as well as women, and recommend doing bone density testing in men aged 50-69 years who have risk factors for osteoporosis and in all men aged 70 years or older. The new ACP guideline focuses specifically on osteoporosis screening in men and notes that the appropriate age at which to start risk assessment is uncertain. The medical evidence in the literature shows that by age 65 years, at least 6% of men have osteoporosis proved by dual-energy x-ray absorptiometry (DXA), so “assessment of risk factors before this age is reasonable” for most men, Dr. Amir Qaseem said in an interview. The ACP plans to issue a separate new guideline for treating osteoporosis in men in the near future, added Dr. Qaseem, lead author of the guideline and a senior medical associate for the ACP. The main risk factors for osteoporosis in men that should prompt clinicians to consider ordering a DXA scan are age older than 70 years, low body weight (a body mass index of 25 kg/m2 or less), weight loss greater than 10% of what would be expected, physical inactivity (no regular walking, climbing stairs, carrying heavy objects, housework, or gardening), corticosteroid use, androgen deprivation therapy, or previous fracture related to fragility, the report states. If a man with risk factors declines a bone density test, the clinician should periodically revisit the topic with him and explain that the DXA scan is a painless, noninvasive test. The new ACP guideline is based on a systematic review of evidence published in 1990-2007 conducted by the federal Agency for Healthcare Research and Quality’s evidence-based practice center in Southern California. A separate article in the same issue as the new guideline describes the review of evidence (Ann. Intern. Med. 2008;148:685-701). The prevalence of osteoporosis is estimated to be 7% in white men, 5% in black men, and 3% in Hispanic men, Dr. Qaseem noted. “It’s always been viewed as a disease of women” and so is underdiagnosed and undertreated in men, causing substantial morbidity and mortality, he said. Over the next 15 years as the U.S. population ages, the rate of osteoporosis in men is expected to increase by half, with a doubling or tripling of hip fracture rates by 2040. The prevalence of osteoporosis in Asian American men and other ethnic groups is unknown because of a lack of data. More research is needed on multiple aspects of screening for osteoporosis in men, the guideline states. Shoe inserts may reduce anterior cruciate ligament injury risk in female athletes November 8, 2007 By Heidi Splete Wearing orthotics with a 5-degree medial post may reduce the risk of anterior cruciate ligament injury in female athletes, according to the results of a controlled laboratory study. Compared with men, women athletes experience 2-10 times more anterior cruciate ligament (ACL) tears. Excessive knee motion and womens’ knee valgus angle on landing from a jump may contribute to this difference, noted Michael Joseph, a physical therapist in the department of kinesiology at the University of Connecticut, Farmington, and his associates. Previous studies have shown that women have greater knee mobility than men, and controlling the excessive knee motion may reduce the risk of ACL tears, the researchers noted in the November issue of the American Journal of Sports Medicine. To determine whether a 5-degree wedge inside each shoe would stabilize the knees, Mr. Joseph and colleagues measured the knee and ankle motion of 10 female athletes during a drop jump exercise. The exercise involved dropping from a 31-cm-high box onto two force platforms (to gauge the movement of the knees and ankles on landing) and then performing a vertical jump (Am. J. Sports Med. Oct. 31 [Epub doi: 10.1177/0363546507308362]). The women were National Collegiate Athletic Association athletes with a mean age of 20 years without lower leg injuries or history of ACL tears or reconstructive surgery. The group included six basketball players, three volleyball players, and one soccer player. The uniform insert, a bilateral 5-degree full-length medial post (AliMed, Dedham, Mass.), was used to determine whether a standard insert would have an effect regardless of foot type or insert type. Each athlete performed three jumps while wearing the inserts and three jumps without them. None of the participants reported discomfort with the inserts. Overall, the outward twisting motion of the knee (valgus) was significantly reduced at initial contact on landing when each athlete wore a full-length orthotic insert with a 5-degree medial post, compared with motion during jumps when each athlete did not wear the insert. The knee motion decreased from an average of 3.03 degrees without the inserts to 1.79 degrees with the inserts. Similarly, the maximum knee movement at any point during the exercise averaged 9.30 degrees without the inserts, vs. 8.09 degrees with the inserts; this difference also was statistically significant. “The effect of the post at initial contact may be especially relevant, as ACL injuries during landing may occur near full knee extension,” the investigators wrote. Ankle pronation (as measured by the eversion angle), which is another factor in ACL injury, also was significantly reduced, from –3.25 degrees on initial contact without the insert to –4.03 degrees. The results support findings from previous studies in which a medial post orthotic device controlled knee motion during walking. The statistically significant reduction in sideways knee motion and foot pronation observed in this study with the use a 5-degree medial post may be enough to have a clinical impact by reducing the risk of ACL injury in athletes, the researchers said. Vitamin D inadequacy may play role in chronic pain November 5, 2007 By Sherry Boschert SAN FRANCISCO (EGMN) - In what may be the first study of the prevalence of vitamin D inadequacy in patients seeking treatment for chronic pain, those who were on opioids used significantly higher doses and had been taking opioids significantly longer if they had vitamin D inadequacy than if they had adequate vitamin D levels, Dr. W. Michael Hooten reported at the annual meeting of the American Society of Anesthesiologists. Inadequate levels of vitamin D were detected in 26% of 267 patients admitted to a multidisciplinary pain rehabilitation center at a tertiary referral medical center from February through December of 2006. Of the 140 patients who were using opioids, 27% had inadequate levels of vitamin D, Dr. Hooten of the Mayo Clinic, Rochester, Minn., and his associates reported in a poster presentation. “Vitamin D inadequacy may represent an underrecognized source of nociception and impaired neuromuscular functioning among patients with chronic pain,” he said. In previous studies, inadequate levels of vitamin D have been associated with medication-refractory musculoskeletal pain and neuromuscular dysfunction. In the current retrospective study, patients underwent vitamin D testing at admission, were questioned about opioid use, and completed the Short Form-36 Health Status Questionnaire (SF-36). Serum 25-hydroxyvitamin D levels of 20 ng/mL or higher were considered adequate, and levels below 20 ng/mL were considered inadequate. Both the adequate and inadequate vitamin D groups were nearly evenly split between opioid users and nonusers. Among 69 patients with vitamin D inadequacy, 38 were using opioids, and 31 were not. Among 198 patients with adequate vitamin D, 102 were using opioids and 96 were not. Patients taking opioids used a mean morphine equivalent dose of 134 mg/day in the subgroup with vitamin D inadequacy and 70 mg/day in the subgroup with adequate vitamin D. Opioid users with inadequate vitamin D had been taking the medications for a mean of 71 months, compared with 44 months for opioid users with sufficient vitamin D. Opioid users with inadequate vitamin D reported significantly worse health perceptions and physical functioning on the SF-36. Scores did not differ significantly between the vitamin D groups for “bodily pain” or “role emotional.” Prospective trials of vitamin D therapy are needed to assess effects on pain outcomes and physiological measures of neuromuscular functioning in patients with chronic pain and vitamin D inadequacy, Dr. Hooten said. Studies show exercise delays onset of dementia June 28, 2007 By Timothy F. Kirn SEATTLE (EGMN) – While it might not seem probable, evidence is starting to suggest that exercise can at least forestall Alzheimer’s disease, Dr. Eric B. Larson said at the annual scientific meeting of the American Geriatrics Society. “We now see association studies of physical activity showing a pretty convincing relationship with a delayed onset of dementia,” said Dr. Larson, the executive director of the Center for Health Studies of the Group Health Cooperative, Seattle. “I don’t think we are preventing this disease from ever happening,” he added. “What we’re doing is delaying it.” Four observational studies have now shown, with consistency, a 30%-40% reduction in the incidence of Alzheimer’s disease when people get regular exercise, noted Dr. Larson. Some might find it implausible that physical exercise could affect the brain, cognitive function, and decline, since it has been thought that the brain does not develop after a young age, Dr. Larson noted. But, it turns out that animal experiments show that new neurons do form in the adult brain. “Neurogenesis is possible at almost any phase of development, at least in animals,” he said. And then, there is the human study. In a study of individuals who used functional magnetic resonance imaging, the investigators found that aerobic physical fitness measured on a treadmill correlated with frontal, parietal, and temporal lobe tissue density, such that better fitness meant higher density, which indicates less age-related loss (J. Gerontol. A Biol. Sci. Med. Sci. 2003;58:176-80). In his own study, Dr. Larson looked at 2,581 individuals, who were aged 65 years or older, without dementia. They were tested for cognitive functioning and interviewed about exercise habits every 2 years, starting in 1994-1996. For the analysis, the investigators threw out those individuals who scored in the bottom quartile of subjects on the cognitive testing, on the grounds that they might be persons already showing some dementia-associated decline (Ann. Intern. Med. 2006;144:73-81). With an average follow-up of 6.2 years, during which time 158 subjects developed dementia, the researchers found that those subjects who exercised three or more times per week had a 40% reduction in the risk of developing dementia, compared with those who exercised less than three times per week. The incidence rates of dementia were 13/1,000 person-years for those who exercised three or more times per week, compared with 19.7/1,000 person-years for those who exercised less than three times per week. Exercise was defined as the number of days during the past year that the subjects had engaged in walking, hiking, bicycling, aerobics or calisthenics, swimming, water aerobics, weight training, stretching, or other exercise, for at least 15 minutes at a time. About 60% of those who developed dementia had developed Alzheimer’s disease. The interesting part of the findings was that those subjects who had the lowest physical performance benefited the most from exercise, Dr. Larson said. All of the prevention was in the people in the lowest third on physical performance measures. Weight lifting reduces pain in older adults June 11, 2007 By Kerri Wachter WASHINGTON (EGMN) – Older adults living in assisted-care facilities experienced overall reductions in pain following 8 weeks of weight-lifting exercise, reported Kelli F. Koltyn, Ph.D., of the University of Wisconsin, Madison, at the annual meeting of the American Pain Society. In a pilot study, Dr. Koltyn and her colleagues looked at the feasibility of a strength-training program to reduce pain in older women in assisted living. The researchers recruited 10 women (average age, 80 years) for the program, most of whom reported joint pain in multiple sites (three, on average) at the beginning of the study. They also reported moderate levels of both upper and lower body pain. “Many of these older adults have balance problems, so in initiating a strength-training program, we decided that we would do a combination of seated and standing exercises,” said Dr. Koltyn. In addition, whenever weight was increased for an exercise, the participant would start in the seated position and progress to standing. After 8 weeks of training, the women experienced a significant increase in upper and lower body strength, as assessed by the number of arm curls (upper body) and chair stands (lower body) they could perform. These measures were chosen from a functional fitness battery that has been validated in older adults. “By the end of the study, there was a significant decrease in pain,” said Dr. Koltyn. The average number of sites of joint pain decreased from three to one. However, there was no change in the use of pain medications. “We also found there were moderate to large decreases in pain for three specific activities,” said Dr. Koltyn. These activities were walking, climbing stairs, and lifting or lowering objects. Dr Koltyn started by contacting local assisted-living facilities to find out what exercise programs were offered and if they would participate in the pilot study. “I found there was a wide variability in the type of exercise programs that were being offered,” said Dr. Koltyn. Some facilities had daily scheduled walks, whereas other facilities had no exercise programs at all. The most common program was a chair-based exercise program offered twice a week. However, none of the facilities had a strength-training program in place. Notably, “most of the activity directors were reluctant for us to come in and do a free strength-training program ... because they were worried that it would exacerbate chronic pain conditions,” said Dr. Koltyn.