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Higher levels of melatonin, a hormone involved in the sleep-wake cycle, may suggest decreased risk for developing advanced prostate cancer, according to results presented here at the AACR-Prostate Cancer Foundation Conference on Advances in Prostate Cancer Research, held Jan. 18-21.
Melatonin is a hormone that is produced exclusively at night in the dark and is an important output of the circadian rhythm, or the body's inherent 24-hour clock. Many biological processes are regulated by the circadian rhythm, including the sleep-wake cycle. Melatonin may play a role in regulating a range of other hormones that influence certain cancers, including breast and prostate cancers.
"Sleep loss and other factors can influence the amount of melatonin secretion or block it altogether, and health problems associated with low melatonin, disrupted sleep, and/or disruption of the circadian rhythm are broad, including a potential risk factor for cancer," said Sarah C. Markt, M.P.H., doctoral candidate in the Department of Epidemiology at Harvard School of Public Health in Boston. "We found that men who had higher levels of melatonin had a 75 percent reduced risk for developing advanced prostate cancer compared with men who had lower levels of melatonin.
"Our results require replication, but support the public health implication of the importance of maintaining a stable light-dark and sleep-wake cycle," added Markt. "Because melatonin levels are potentially modifiable, further studies of melatonin and prostate cancer risk and progression are warranted."
To investigate the association between urine levels of the main breakdown product of melatonin, 6-sulfatoxymelatonin, and risk of prostate cancer, Markt and colleagues conducted a case-cohort study of 928 Icelandic men from the AGES-Reykjavik cohort between 2002 and 2009. They collected first morning void urine samples at recruitment, and asked the participants to answer a questionnaire about sleep patterns.
The median value of 6-sulfatoxymelatonin in the study participants was 17.14 nanograms per milliliter of urine. Men who reported taking medications for sleep, problems falling asleep, and problems staying asleep had significantly lower 6-sulfatoxymelatonin levels compared with men without sleep problems, according to Markt.
Of the study participants, 111 men were diagnosed with prostate cancer, including 24 with advanced disease. The researchers found that men whose 6-sulfatoxymelatonin levels were higher than the median value had a 75 percent decreased risk for advanced prostate cancer. A 31 percent decreased risk for prostate cancer overall was observed as well, but this finding was not statistically significant.
"Further prospective studies to investigate the interplay between sleep duration, sleep disturbance, and melatonin levels on risk for prostate cancer are needed," said Markt.
A common nutritional supplement may be part of the magic in improving the survival rates of babies born with heart defects, researchers report.
Carnitine, a compound that helps transport fat inside the cell powerhouse where it can be used for energy production, is currently used for purposes ranging from weight loss to chest pain.
New research shows it appears to normalize the blood vessel dysfunction that can accompany congenital heart defects and linger even after corrective surgery, said Dr. Stephen M. Black, cell and molecular physiologist at the Vascular Biology Center at the Medical College of Georgia at Georgia Regents University.
"My hope is this is going to have a major, major impact on survival of babies," Black said. About half the babies born with heart defects have excessive, continuous high pressure on their lungs from misdirected blood flow. Early surgery can prevent full-blown pulmonary vascular disease, but scientists are finding more subtle disruptions in the signaling inside blood vessels walls that can be problematic - even deadly - up to 72 hours after surgery.
The good news is the changes are reversible and that carnitine speeds recovery and can even prevent the damage in a lamb model of these human heart defects, according to studies published in the journal Pediatric Research.
Normally, most blood flow bypasses the lungs in utero when the placenta provides blood and oxygen for the baby. Baby's first breaths naturally expand the lungs and blood vessels, activating a process inside the lining of vessels that enables them to accommodate the initial blood surge, then reduce pressure quickly, dramatically and permanently.
This natural transition doesn't occur when heart defects misdirect blood flow. "It's kind of like a chronic fetal-to-newborn transition," said Black, the study's corresponding author. Lungs get pounded with about three times the normal flow and, even when surgeries are done as early as possible to repair the defect, correct blood flow and protect the lungs, the 20 percent death rates from acute pulmonary hypertension have remained unchanged for a decade. "That's 1 in 5 kid (with this condition)," Black said.
Left unchecked, the barrage thickens blood vessels, making them unresponsive, much like those of an elderly individual who has lived for years with uncontrolled high blood pressure. The comparatively brief periods of pounding these babies experience impairs the ability of the endothelial cells, which line blood vessels, to produce nitric oxide, a major dilator of blood vessels.
The shear force disrupts carnitine homeostasis, weakens the mitochondria (the cell powerhouse) and impairs nitric oxide production. To make bad matters worse, the precursor to nitric oxide instead makes more peroxynitrite, prompting endothelial cells to grow and thickening blood vessels. Black was also corresponding author of a recent study in the Journal of Biological Chemistry that showed peroxynitrite does this by turning on the cell survival protein kinase Akt1.
The new study indicates that even without fixing the heart defect, high daily doses of carnitine in the first four weeks of life can prevent endothelial dysfunction. In fact, the laboratory lambs' ability to make nitric oxide is preserved even without the benefit of heart surgery and the responses to the chemical activity that enables blood vessel dilation is normalized, Black said.
Death and serious complications more likely in patients with vitamin D deficiency, study suggests
Patients with low blood levels of vitamin D are at increased risk of death and serious complications after noncardiac surgery, suggests a study in Anesthesia & Analgesia.
"Vitamin D concentrations were associated with a composite of in-hospital death, serious infections, and serious cardiovascular events," according to the new research by Dr Alparslan Turan and colleagues of the Cleveland Clinic. They believe their results warrant further study to see if giving vitamin D supplementation before surgery can reduce the risk of these adverse outcomes.
Lower Vitamin D Levels Linked to Higher Surgical Risk
The researchers analyzed the relationship between vitamin D level and surgical outcomes in approximately 3,500 patients who underwent operations other than heart surgery between 2005 and 2011. Only patients who had available data on vitamin D levels around the time of surgery-from three months before to one month afterward-were included in the study.
The concentration of vitamin D (specifically, 25-hydroxyvitamin D) in blood samples was analyzed as a risk factor for death, cardiovascular events, or serious infections while in the hospital. The analysis included adjustment for other factors such as demographic characteristics, medical conditions, and type and duration of surgery.
Most patients did not meet the recommended 25-hydroxyvitamin D concentration of greater than 30 nanograms per milliliter (ng/mL). The median vitamin D level was 23.5 ng/mL-more than 60 percent of patients were in the range of vitamin D insufficiency (10 to 30 ng/mL). Nearly 20 percent had vitamin D deficiency (less than 10 ng/mL).
"Higher vitamin D concentrations were associated with decreased odds of in-hospital mortality/morbidity," the researchers write. For each 5 ng/mL increase in 25-hydroxyvitamin D level, the combined risk of death, cardiovascular events, or serious infections decreased by seven percent.
Further Study Needed to Determine Cause and Effect
"Vitamin D deficiency is a global health problem," according to Dr Turan and coauthors. In addition to protective cardiovascular and neurological effects, vitamin D plays an important role in the immune system.
The high rates of vitamin D insufficiency and deficiency in the surgical patients studied are consistent with previous findings in the general population. In recent years, studies have suggested that vitamin D levels may affect a wide range of health outcomes.
Patients undergoing surgery are at risk of cardiovascular and infectious complications, both of which may be aggravated by vitamin D deficiency. Previous studies found no increased risk of adverse outcomes related to vitamin D levels in patients undergoing cardiac surgery. It may be that the tissue injury and inflammation associated with heart surgery overwhelms any potential protective effect of vitamin D.
However, Dr Turan and colleagues note that their study had some important limitations of their study-especially the fact that it included only patients who had recent measurements of vitamin D levels. They may represent a less-healthy group, introducing a potential source of selection bias.
The study can't determine whether there is any cause-and-effect relationship between vitamin D levels and the risk of adverse outcomes. Dr Turan and colleagues suggest a formal randomized trial to evaluate whether preoperative vitamin D supplementation can reduce the risk of serious complications and death after surgery.
Diet experts urge move to poultry, fish and beans after results of long-term study.
Possible culprits in meat include iron, toxins formed during cooking and preservatives.
A diet packed with burgers, sausage and steak boosts the risk of developing colon or rectal cancer, a study confirms, lending weight to nutritionists' call for a switch to healthier alternatives.
A plethora of previous reports have connected red meat and colorectal cancer, which is the third most common cause of cancer-related deaths in the United States. But some of the results are inconsistent, and few studies have examined participants' diet over long periods, during which eating habits can change.
The new study is one of the most comprehensive so far. Michael Thun of the American Cancer Society (ACS) in Atlanta, Georgia, and his team collected information on the meat-eating behaviour of nearly 150,000 people in the United States in 1982 and in 1992. They divided them into three groups according to the amount of meat they ate, and noted which patients had developed colorectal cancers by 2001.
The group that ate the most processed meat had twice the risk of developing colon cancer compared with those who ate the least, the team found; and those who ate most red meat had a 40% higher risk of getting rectal cancer.
By contrast, those who ate the highest quantity of poultry or fish had a 20-30% lower risk of developing the diseases, the team reports in the Journal of the American Medical Association1. This applied even when the researchers took into account other risk factors, such as being overweight, not taking exercise and not eating fruit and vegetables.
“Substituting pistachio-encrusted salmon for roast beef is not a culinary sacrifice.”
Meaty study
The case against red meat still needs back-up from other studies. But for now, people would be well advised to cut back their consumption of red and processed meat, says Marjorie McCullough, an author of the paper, also at the ACS. This might involve removing red meat from a few meals per week, she suggests, or choosing smaller portions.
Members of the high risk group ate around 55-85 grams of red or processed meat each day, roughly equivalent to a medium sized burger. Red meat includes burgers, meatloaf, beef, liver and pork. Processed meat includes bacon, sausage, hot dogs, ham, salami and lunch meat.
Researchers are not yet clear which ingredient of meat might trigger cancer. Possible culprits include iron, toxins formed during cooking or the nitrates and nitrites used to preserve processed meats.
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Replacing red meat with some combination of fish, poultry, nuts and beans will probably help cut your risk of colorectal cancer, says nutritional expert Walter Willett of the Harvard School of Public Health in Boston. "It will have some beneficial effects for reducing heart disease as well," he adds.
"Fortunately, substituting pistachio-encrusted salmon and gingered brown basmati pilaf for roast beef with mashed potatoes and gravy is not a culinary sacrifice," Willett writes in an editorial that accompanies the study.
McGill researchers have shown that melatonin supplements may make bones stronger in old rats. This suggests a possible avenue for the prevention of osteoporosis. Bones are built up by certain cells known as osteoblasts during the daytime and broken down by others (osteoclasts) at night. As we age, we sleep less, and so the cells that break down the bones are more active. By giving old rats melatonin supplements to regulate their circadian rhythms, the McGill researchers have been able to make their bones denser, less brittle and more flexible. Next step is to explore whether melatonin supplements prevent bone breakdown or can actually repair damage.
Research on elderly rats suggests possible avenue for prevention of osteoporosis
Faleh Tamimi, a professor in McGill's School of Dentistry, is the leader of a research team that has just discovered that melatonin supplements make bones stronger in elderly rats and therefore, potentially, in elderly humans too. "Old rats are tedious to work with because they get sick a lot and that means they also cost a lot more. But if you're interested in diseases like osteoporosis, they're an essential part of the process."
Dem bones, dem bones, dem dry bones - sleep and bone regulation
The process of bone breakdown and buildup is affected by our circadian rhythms. The cells which break down our bones (known as osteoclasts) are more active at night, while those responsible for bone formation (osteoblasts) are more active during daylight hours. "As we age, we sleep less well, which means that the osteoclasts are more active," says Tamimi. "This tends to speed up the process of bone breakdown."
It is already well established that melatonin plays a role in regulating our body clocks and can potentially help us sleep better. So the researchers suspected that a melatonin supplement would help regulate the circadian rhythms of the elderly rats, thus reducing the activity of the osteoclasts and slowing down the process of bone breakdown. And that is exactly what they found.
The researchers found that there was a significant increase in both bone volume and density among the rats that had received melatonin supplements. As a result, it took much more force to break the bones of rats that had taken the melatonin supplements, a finding that suggests to the researchers that melatonin may prove a useful tool in combatting osteoporosis.
For Tamimi and his colleagues the next big question is whether melatonin is preventing or actually reversing the process of bone breakdown. "Until there is more research as well as clinical trials to determine how exactly the melatonin is working, we can't recommend that people with osteoporosis go ahead and simply take melatonin supplements," says Tamimi. "I am applying for funding to pursue the research and we hope to have answers soon."
A new study shows that vitamin B12 may protect against Alzheimer's disease, adding more evidence to the scientific debate about whether the vitamin is effective in reducing the risk of memory loss. The research will be published in the October 19, 2010, issue of Neurology®, the medical journal of the American Academy of Neurology.
"Our findings show the need for further research on the role of vitamin B12 as a marker for identifying people who are at increased risk of Alzheimer's disease," said study author Babak Hooshmand, MD, MSc, with Karolinska Institutet in Stockholm, Sweden. "Low levels of vitamin B12 are surprisingly common in the elderly. However, the few studies that have investigated the usefulness of vitamin B12 supplements to reduce the risk of memory loss have had mixed results."
For the seven-year study, researchers took blood samples from 271 Finnish people age 65 to 79 who did not have dementia at the start of the study. During that time, 17 people developed Alzheimer's disease. Blood samples were tested for levels for homocysteine, an amino acid associated with vitamin B12, and for levels of the active portion of the vitamin, called holotranscobalamin. Too much homocysteine in the blood has been linked to negative effects on the brain, such as stroke. However, higher levels of vitamin B12 can lower homocysteine.
The study found that for each micromolar increase in the concentration of homocysteine, the risk of Alzheimer's disease increased by 16 percent, whereas each picomolar increase in concentration of the active form of vitamin B12 reduced risk by two percent. The results stayed the same after taking into account other factors, such as age, gender, education, smoking status, blood pressure and body mass index. The addition of folate did not appear to raise or lower the risk of Alzheimer's disease.
"More research is needed to confirm these findings before vitamin B12 should be used solely as a supplement to help protect memory," said Hooshmand.
Vitamin B12 can be found in fish, poultry and other meat products.
With previous evidence suggesting that melatonin may have a role in glucose metabolism, researchers have found an independent association between decreased secretion of melatonin and an increased risk for the development of type 2 diabetes, according to a study in the April 3 issue of JAMA.
"Melatonin receptors have been found throughout the body in many tissues including pancreatic islet cells, reflecting the widespread effects of melatonin on physiological functions such as energy metabolism and the regulation of body weight," according to background information in the article. "Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance." A prospective association between melatonin secretion and type 2 diabetes has not been previously reported.
Ciaran J. McMullan, M.D., of Brigham and Women's Hospital, Boston, and colleagues conducted a study to investigate the association of melatonin secretion and the incidence of type 2 diabetes. The analysis consisted of a case-control study nested within the Nurses' Health Study cohort. Among participants without diabetes who provided urine and blood samples at baseline in 2000, the researchers identified 370 women who developed type 2 diabetes from 2000-2012 and matched 370 controls. Statistical analyses for determining associations between melatonin secretion at baseline and incidence of type 2 diabetes included controlling for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction.
retion of melatonin varied widely among participants in the study; the median (midpoint) urinary ratio of 6-sulfatoxymelatonin to creatinine was 67.0 ng/mg in the highest category compared with 14.4 ng/mg in the lowest category. The median ratio was significantly higher among controls (36.3 ng/mg) than among cases (28.2 ng/mg). Insulin sensitivity was higher among women with higher urinary ratios of 6-sulfatoxymelatonin to creatinine.
The researchers found that after controlling for body mass index and other lifestyle factors, menopausal status, family history of diabetes, history of hypertension, use of beta-blockers or non-steroidal anti-inflammatory drugs, region of the United States, and plasma biomarkers of diabetes risk, participants in the lowest category of urinary ratio of 6-sulfatoxymelatonin to creatinine had a 2.2 times higher odds of developing type 2 diabetes compared to participants in the highest category.
Women in the lowest category of melatonin secretion had an estimated diabetes incidence rate that was more than double that of women in the highest category (as measured by cases per 1,000 person-years).
"It is interesting to postulate from these data, in combination with prior literature, whether there is a causal role for reduced melatonin secretion in diabetes risk. Further studies are needed to determine whether increasing melatonin levels (endogenously via prolonged nighttime dark exposure or exogenously via supplementation) can increase insulin sensitivity and decrease the incidence of type 2 diabetes," the authors conclude.
Despite past safety concerns, the antioxidant supplement beta-carotene, is safe to use during radiation therapy treatments for prostate cancer and does not increase the risk of prostate cancer death or metastases, according to a study in the May issue of the International Journal of Radiation Oncology•Biology•Physics, the official scientific journal of the American Society for Radiation Oncology (ASTRO).
The use of vitamin supplements and antioxidants is common, but the safety of using antioxidant supplements during radiation treatments for prostate cancer is controversial. Radiation therapy relies on the pro-oxidant effects of DNA, which involves damaging tumor cells while leaving normal cells unharmed. However, some scientists have suggested that supplemental antioxidants may weaken the oxidizing effects of radiation and potentially lead to cancer recurrence.
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In the largest study to date of its kind, researchers followed 383 prostate cancer patients who were randomized to receive beta-carotene or placebo to determine if antioxidants could potentially counteract the pro-oxidant effects of radiation therapy and increase a patient's risk of death or metastases. The primary endpoint was prostate cancer death or bone metastases.
Researchers found no significant differences in lethal outcomes among the patients who took the antioxidant beta-carotene versus those who did not.
"This study shows that antioxidant supplementation with beta-carotene during radiation therapy does not appear to detract from the benefit of radiation therapy." Danielle Margalit, MD, MPH, lead author of the study and a radiation oncologist at the Dana-Farber Cancer Institute in Boston, said. "It also suggests that patients may continue to eat a well-balanced diet that contains foods with natural sources of antioxidants at the recommended daily amount.
A study conducted in more than 100 Mongolian schoolchildren found that daily treatment with a vitamin D supplement significantly reduced the symptoms of winter-related atopic dermatitis, a type of eczema. Led by a Massachusetts General Hospital (MGH) physician, the report in the October issue of the Journal of Allergy and Clinical Immunology supports the results of a preliminary study that showed similar results in a small group of children in Boston.
"While we don't know the exact proportion of patients with atopic dermatitis whose symptoms worsen in the winter, the problem is common," says Carlos Camargo, MD, DrPH, MGH Department of Emergency Medicine. "In this large group of patients, who probably had low levels of vitamin D, taking daily vitamin D supplements - which are inexpensive, safe and widely available - proved to be quite helpful." Camargo led both the earlier Boston pilot study and the current investigation, which was performed in collaboration with investigators from the Health Sciences University of Mongolia.
A chronic inflammatory disorder of the skin, atopic dermatitis is uncomfortable and makes patients more vulnerable to bacterial infection. Symptoms of the disorder - most commonly seen in children - often worsen during wintertime. While controlled administration of ultraviolet light, which can stimulate the production of vitamin D in the skin, is a common treatment for severe atopic dermatitis, the possibility that vitamin D deficiency contributes to the seasonal worsening of symptoms had received little consideration prior to the Boston study. That investigation involved only 11 children but provided preliminary support for the hypothesis.
The current study, conducted in collaboration with the National Dermatology Center in Mongolia, enrolled 107 children, ages 2 to 17, from nine outpatient clinics in the capital city of Ulaanbaatar. The participants - all of whom had a history of atopic dermatitis symptoms worsening either during cold weather or around the transition from autumn to winter - were randomly divided into two groups. One group received a daily vitamin D dose of 1000 IU while the other received a placebo - both delivered in odorless, colorless and tasteless drops. Neither the children's parents nor the study investigators knew to which group participants had been assigned.
Standard evaluations of atopic dermatitis symptoms were conducted at the outset of the trial and at the end of the month-long study period, and parents were also asked whether they saw any improvement in their child's condition. At the end of the month, children receiving the vitamin D supplement had an average 29 percent improvement on the primary assessment tool used, compared with 16 percent improvement in the placebo group. Additional assessments - including the report from parents - also showed significantly greater improvement among children receiving vitamin D.
While data gathered at the outset of the study could not determine whether or not participating children were deficient in vitamin D, the authors note that an even larger study of Ulaanbaatar children conducted at the same time found significant vitamin D deficiency in 98 percent of participants, supporting the probability that the children in this study were also deficient. While future studies are needed to assess the value of vitamin D treatment in adults and in children with year-round symptoms, Camargo - a professor of Medicine at Harvard Medical School - says that parents of children with symptoms that worsen in the winter should try a vitamin D supplement for a few weeks when symptoms flare to see if it helps. He encourages parents to discuss this study and their plan with their primary care provider.