WUSTL.edu – High-dose vitamin D relieves joint pain and muscle pain for many breast cancer patients taking estrogen-lowering drugs, according to a new study from Washington University School of Medicine in St. Louis.

The medications, known as aromatase inhibitors, are commonly prescribed to shrink breast tumors fueled by the hormone estrogen and help prevent cancer recurrence. They are less toxic than chemotherapy, but for many patients, the drugs may cause severe musculoskeletal discomfort, including pain and stiffness in the hands, wrists, knees, hips, lower back, shoulders and feet.

“About half of patients can experience these symptoms,” says Antonella L. Rastelli, MD, assistant professor of medicine and first author of the study published online in the journal Breast Cancer Research and Treatment. “We don’t know exactly why the pain occurs, but it can be very debilitating – to the point that patients decide to stop taking aromatase inhibitors.”

Because the drugs reduce cancer recurrence, finding a way to help patients stay on them is important for long-term, relapse-free survival, according to Rastelli. Aromatase inhibitors are prescribed to post-menopausal women for at least five years and often longer after a breast cancer diagnosis. There is some evidence that patients who experience the drugs’ side effects are less likely to see their cancer return, providing even more incentive to help these patients continue taking them.

It was Rastelli’s colleague, Marie E. Taylor, MD, assistant professor of radiation oncology, who first noticed that patients on aromatase inhibitors who experienced this pain found some relief from high doses of vitamin D.

So Rastelli’s group recruited 60 patients who reported pain and discomfort associated with anastrozole, one of three FDA-approved aromatase inhibitors. The patients they studied also had low vitamin D levels. Half the group was randomly assigned to receive the recommended daily dose of vitamin D (400 international units) plus a 50,000-unit vitamin D capsule once a week. The other half received the daily dose of 400 units of vitamin D plus a weekly placebo. All subjects received 1,000 milligrams of calcium daily throughout the study.

Patients in the study reported any pain they experienced through three different questionnaires. They were asked to quantify their pain intensity, as well as report how much the pain altered their mood, affected their work and interfered with relationships and daily activities. The results show that patients receiving high-dose vitamin D every week reported significantly less musculoskeletal pain and also were less likely to experience pain that interfered with daily living.

“High-dose vitamin D seems to be really effective in reducing the musculoskeletal pain caused by aromatase inhibitors,” Rastelli says. “Patients who get the vitamin D weekly feel better because their pain is reduced and sometimes goes away completely. This makes the drugs much more tolerable. Millions of women worldwide take aromatase inhibitor therapy, and we may have another ‘tool’ to help them remain on it longer.”

Like anastrozole used in this study, the other two FDA-approved aromatase inhibitors, letrozole and exemestane, also cause musculoskeletal pain. Given the similar side effects, Rastelli says patients on these drugs may also benefit from high-dose vitamin D.

The vitamin used in this study is a plant-derived type called vitamin D2. Rastelli says it achieves the best results when given weekly because the body metabolizes it within seven to 10 days. Rastelli and her colleagues did not use high-dose vitamin D3 (cholecalciferol), which remains in the body longer. Vitamin D3 is the form made by the skin when exposed to sunlight.

“This was a very carefully conducted study, and the placebo control makes the findings quite compelling,” says Matthew J. Ellis, MD, PhD, the study’s senior author and director of the Breast Cancer Program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis. “We should follow up these findings further to determine the most efficacious and safe approach to vitamin D supplementation in our breast cancer patients.”

Since vitamin D helps the body absorb calcium, too much of it can cause high levels of calcium in the urine, which may increase the risk of kidney stones. Such possible side effects emphasize the importance of tracking patients’ urine calcium levels while taking high-dose vitamin D.

“It’s important to monitor the patients, but overall it appears to be very safe,” Rastelli says. “Because vitamin D2 is eliminated from the body so quickly, it’s very hard to overdose.”

In addition to relieving pain, the group wanted to examine whether vitamin D could protect against the bone loss often seen in patients taking aromatase inhibitors. The researchers measured each patient’s bone density at the beginning of the study and again after six months.

Perhaps because of its role in calcium absorption, high-dose vitamin D did appear to help maintain bone density at the neck of the femur, the top of the thighbone near the hip joint. Although the result did not reach statistical significance, Rastelli calls the result promising and worth further studies.

“It’s great that we have something as simple as vitamin D to help patients alleviate some of this pain,” Rastelli says. “It’s not toxic — it doesn’t cause major side effects. And if it is actually protecting against bone loss, that’s even better.”

Reference: Rastelli AL, et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. Online June 2011.

Thoracic.org – A traditional Chinese herbal paste known as Xiao Chuan, or XCP, may help reduce winter exacerbations of chronic obstructive pulmonary disease (COPD), according to a new study conducted by researchers in Beijing. The paste has been used to treat breathing difficulties in China for more than a thousand years.

The study results will be presented at the ATS 2011 International Conference in Denver.

“We had performed observational studies of XCP which had shown the paste decreased the frequency of COPD exacerbations, but this study is the first randomized controlled trial showing the effectiveness and safety of XCP in the prevention of COPD exacerbation,” said study author Yongjun Bian, MD, clinical researcher in the respiratory department of Gunag’anmen Hospital in Beijing. “These data confirmed the beneficial effect of XCP on the prevention of winter COPD exacerbations.”

Xiao Chuan paste has been used in China for centuries to aid in breathing disorders, including COPD and asthma. To treat winter exacerbations of COPD and other breathing problems, the paste is applied in the summer on specific acupuncture points on the back.

“The herbs contained in XCP and natural remedies may have some immune regulation properties, which in turn may aid in their ability to prevent COPD exacerbations,” Dr. Bian said.

The researchers enrolled 142 patients and randomized them to receive either XCP or a placebo paste. Both pastes were applied on the same back points four times during the eight-week period of July and August.

For the study, exacerbations were defined as either a worsening of respiratory symptoms resulting in the patient taking oral steroids or antibiotics, or a hospital admission for an acute respiratory complaint. Patients were monitored for exacerbations from November through February. Adverse events were evaluated using the Chinese Herb Skin Stimulation Classification.

“Treatment with XCP significantly reduced the frequency of winter exacerbation compared with patients treated with placebo,” Dr. Bian said. “XCP patients experienced statistically significant reductions in steroid use and episodes of shortness of breath, and XCP patients also reported an improved quality of life compared to those treated with placebo.”

The incidence of adverse events was two percent in treatment group, and all patients who experienced an adverse event recovered without intervention after stopping the medication. There were no adverse events in placebo group.

“Although this treatment has been used in China for thousands of years, no scientific studies had been performed on this conventional Chinese natural therapy,” Dr. Bian said. “This study results helped us standardize the treatment protocol and avoid adverse events in future clinical practice.”

The primary ingredients of Xiao Chuan (XCP) are Ephedra vulgaris, Asarum heterothropoides and Acorus gramineus Soland, all plants which are native to China.

Dr. Bian said future research should include longer follow-up times to evaluate the long-term efficacy of the paste in treating COPD exacerbations, and also should explore the mechanisms at play in reducing exacerbations.

Fish has long been considered in myriad cultures to be “brain food,” but only recently has bona fide science begun to support this deep-rooted belief. Researchers now know that the omega-3 fatty acids found in oily fish such as salmon and herring may play a critical role in both development and maintenance of the brain and nerves.

Although sufficient amounts of these long-chain omega-3 fats can be synthesized endogenously by most adults, experts recommend that pregnant women and infants get additional amounts of these compounds from their diets. This, combined with research suggesting that these fats play a critical role in cognitive and visual development during early life, has prompted much research and product development aimed at pregnant women and newborn infants. Studies have also suggested that higher consumption of certain omega-3 fatty acids may also benefit adult mental health as well – for instance, as it might relate to lower risk for depression.

Dr. Michelle Price Judge, a faculty member at the University of Connecticut School of Nursing, is keenly interested in how omega-3 fatty acids consumed during pregnancy impact both maternal and infant health. She has demonstrated previously that maternal consumption of docosahexaenoic acid (DHA; a prominent omega-3 fatty acid) during pregnancy gives infants a developmental advantage even 9 months after they are born. These findings prompted her to consider the benefits that DHA could holistically have on the maternal-infant dyad. Specifically, might greater omega-3 fatty acid intake during pregnancy lower risk for postpartum depression, a condition that leads to a multitude of problems including interruptions in maternal-infant attachment and subsequent impairments in later infant development? As part of the scientific program of the American Society for Nutrition, results from this study were presented April 12, 2011 at the Experimental Biology 2011 meeting in Washington, DC.

To answer this question, Dr. Judge oversaw a randomized, double-blind, placebo-controlled dietary intervention trial in which 52 pregnant women took either a placebo (corn oil) or a fish oil supplement containing 300 milligrams of DHA 5 days each week from 24-40 weeks of pregnancy. This is the amount a woman would consume if she ate about ½ serving of salmon. It is noteworthy that dietary DHA intake during pregnancy has been estimated to be 50-70 milligrams of DHA daily: a mere fraction of the 200 milligrams daily that is considered optimal during pregnancy by most experts. Using the Postpartum Depression Screening Scale developed by her colleague and coauthor Dr. Cheryl Beck, Judge was able to categorize postpartum women as having negligible depressive symptoms, significant symptoms of postpartum depression, or being “positive” for this condition. The Postpartum Depression Screening Scale also assisted the research team in discerning between several symptoms specific to the disorder including sleeping/eating disturbances, anxiety, emotional liability, confusion, loss of self, guilt, and thoughts of suicide.

Although the study did not have enough women to investigate if fish oil consumption resulted in a lower incidence of diagnosable postpartum depression, women in the treatment group had significantly lower total Postpartum Depression Screening Scale scores, with significantly fewer symptoms common to postpartum depression. For example, compared to those in the control group, women in the fish oil group were less likely to report symptoms related to anxiety and loss of self.

Judge and coworkers concluded “DHA consumption during pregnancy – at levels that are reasonably attained from foods – has the potential to decrease symptoms of postpartum depression.” Why is this important? For starters, some experts estimate that postpartum depression affects a whopping 25 percent of new mothers. And healthcare providers agree that this condition can have devastating consequences, not only for the women experiencing it but also for their children and family.

The bottom line? Although larger-scale intervention studies will be needed to better understand the mechanisms and magnitude by which fish oil consumption can improve postpartum mental health, women would be wise to eat at least a serving of high-omega-3 fish 2-3 days per week. Although fish oil supplements may be more acceptable to some women, the real thing is clearly the more nutritious option as a serving of fish is also protein- and mineral-rich. Clearly, fish as a “brain food” is gaining the nod from not only from the general public, but scientists as well (Courtesy of EurekAlert!, a service of AAAS).

UCLA.edu – It has been long known that stress plays a part not just in the graying of hair but in hair loss as well. Over the years, numerous hair growth or hair-restoration remedies have emerged, ranging from hucksters’ “miracle solvents” to legitimate medications such as minoxidil. But even the best of these have shown limited effectiveness.

Now, a NIH-funded team led by researchers from UCLA and the Veterans Administration that was investigating how stress affects gastrointestinal function may have found a chemical compound that induces hair regrowth by blocking a stress-related hormone associated with hair loss — entirely by accident.

The serendipitous discovery is described in an article published in the online journal PLoS One.

“Our findings show that a short-duration treatment with this compound causes an astounding long-term hair regrowth in chronically stressed mutant mice,” said Million Mulugeta, an adjunct professor of medicine in the division of digestive diseases at the David Geffen School of Medicine at UCLA and a corresponding author of the research. “This could open new venues to treat hair loss in humans through the modulation of the stress hormone receptors, particularly hair loss related to chronic stress and aging.”

The research team, which was originally studying brain–gut interactions, included Mulugeta, Lixin Wang, Noah Craft and Yvette Taché from UCLA; Jean Rivier and Catherine Rivier from the Salk Institute for Biological Studies in La Jolla, Calif.; and Mary Stenzel-Poore from the Oregon Health and Sciences University.

For their experiments, the researchers had been using mice that were genetically altered to overproduce a stress hormone called corticotrophin-releasing factor, or CRF. As these mice age, they lose hair and eventually become bald on their backs, making them visually distinct from their unaltered counterparts. The Salk Institute researchers had developed the chemical compound, a peptide called astressin-B, and described its ability to block the action of CRF. Stenzel-Poore had created an animal model of chronic stress by altering the mice to overproduce CRF.

UCLA and VA researchers injected the astressin-B into the bald mice to observe how its CRF-blocking ability affected gastrointestinal tract function. The initial single injection had no effect, so the investigators continued the injections over five days to give the peptide a better chance of blocking the CRF receptors. They measured the inhibitory effects of this regimen on the stress-induced response in the colons of the mice and placed the animals back in their cages with their hairy counterparts.

About three months later, the investigators returned to these mice to conduct further gastrointestinal studies and found they couldn’t distinguish them from their unaltered brethren. They had regrown hair on their previously bald backs.

“When we analyzed the identification number of the mice that had grown hair we found that, indeed, the astressin-B peptide was responsible for the remarkable hair growth in the bald mice,” Mulugeta said. “Subsequent studies confirmed this unequivocally.”

Of particular interest was the short duration of the treatments: Just one shot per day for five consecutive days maintained the effects (hair regrowth) for up to four months.

“This is a comparatively long time, considering that mice’s life span is less than two years,” Mulugeta said.

So far, this effect has been seen only in mice. Whether it also happens in humans remains to be seen, said the researchers, who also treated the bald mice with minoxidil alone, which resulted in mild hair growth, as it does in humans. This suggests that astressin-B could also translate for use in human hair growth. In fact, it is known that the stress-hormone CRF, its receptors and other peptides that modulate these receptors are found in human skin.

UCLA and the Salk Institute have applied for a patent on the use of the astressin-B peptide for hair growth.

The research article is available online free here:

New CRF blocker drug reverses hair loss, promotes hair re-growth

Reference: Wang L, Million M, Rivier J, Rivier C, Craft N, et al. (2011) CRF Receptor Antagonist Astressin-B Reverses and Prevents Alopecia in CRF Over-Expressing Mice. PLoS ONE 6(2): e16377. doi:10.1371/journal.pone.0016377