N-acetylcysteine slows lung decline in pulmonary fibrosis
The November 24 2005 issue of the New England Journal of Medicine reported the findings of the Idiopathic Pulmonary Fibrosis International Group Exploring N-acetylcysteine I Annual (IFIGENIA) trial that acetylcysteine, a precursor of the antioxidant glutathione, slows the deterioration of lung function in patients being treated for idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis is a chronic progressive interstitial pneumonia whose cause is unknown, although an oxidant-antioxidant imbalance may contribute to the disease process.
In a double-blind placebo controlled trial, 182 pulmonary fibrosis patients were randomized to receive 600 milligrams N-acetylcysteine or a placebo three times per day for one year. Participants were also given prednisone and azathioprine, which are standard drugs prescribed for the disease. Vital capacity and and single-breath carbon monoxide diffusing capacity, which are measures of lung function, were measured at the beginning of the study, and at six and twelve months.
One hundred eight of the original participants completed the one-year study. Subjects who received N-acetylcysteine experienced a slower loss of vital capacity and single-breath carbon monoxide diffusing capacity than did those who received the placebo, and had greater values for both measurements at twelve months. Mortality was slightly lower among those who received N-acetylcysteine.
The authors concluded that adding 600 milligrams acetylcysteine three times daily to a regimen or prednisone and azathioprine helps preserve lung function in idiopathic pulmonary fibrosis patients better than drug therapy alone. "High-dose acetylcysteine in addition to standard therapy is," they write, "therefore, a rational treatment option for patients with idiopathic pulmonary fibrosis."
Aspirin: underprescribed and underused
Despite the fact that medical experts worldwide recommend that all cardiovascular patients considered to be at high risk of a second heart attack or stroke receive aspirin on a regular basis, many are still not receiving it. Even though aspirin is more cost effective, physicians are more likely to recommend statin drugs, which can lower cholesterol but may cause side effects.
For the study published in the open access journal PLoS (Public Library of Science) Medicine www.plosmedicine.org, Randall Stafford and colleagues at Stanford University School of Medicine evaluated information obtained by the 1993-2003 US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, which collected data on prescribing by private physicians and hospital outpatient departments. While it was found that the use of aspirin increased over the course of the survey, even at its highest use it was prescribed at just 32.8 percent of high risk visits. Prescriptions for statin drugs exceeded those for aspirin in 1997 and continued to increase throughout the period examined, which the authors attribute to widespread consumer drug advertising.
Although the American Diabetes Association has recommended aspirin to all diabetics over the age of 40, only 12 percent of diabetics were receiving aspirin in 2003. Women were less likely than men to receive the drug, and patients being cared for by physicians other than cardiologists were less likely to receive aspirin than those under a cardiologist's care.
The authors suggest that part of the reason for the underutilization of aspirin could be uncertainties concerning its risks. Aspirin has been associated with 2.5 to 4.5 percent of symptomatic ulcers and 1 to 1.5 percent of serious complications such as bleeding. These risks should be evaluated in light of the 15 to 40 percent decrease in cardiovascular events obtained when aspirin is used as a preventive.
Fasting protects animal hearts
Researchers at the National Institutes on Aging in Baltimore fed 60 two-month-old rats daily or every other day for three months before inducing myocardial infarction by ligation of the coronary artery. A subgroup of rats in each group received sham surgeries.
Predictably, rats on the every other day dietary regimen experienced significantly reduced weight gain over the three month period compared to the rats fed daily. Although a similar percentage of rats in each group died within 24 hours of coronary artery ligation, during the following ten weeks there were no deaths among the intermittently fasted rats while one-third of those who were allowed to eat every day failed to survive.
When heart tissue from animals who underwent coronary artery ligation was examined 24 hours after the surgery, the size of the damaged area was two and a half times smaller in the dietary restricted rats than in the group fed daily, and the number of apoptotic muscle cells were four times fewer. The inflammatory response in the intermittently fasted group was also significantly less than that observed in the non-fasted animals.
After ten weeks, during which time the animals continued on their specific regimens, the left ventricular remodeling and myocardial infarction expansion that occurred in the non-restricted group were not observed in the restricted group.
The authors write that calorie restriction may exert its benefits by oxidative stress reduction, while intermittent fasting may act via a stress resistance mechanism. Therefore both of these mechanisms may be responsible for the protective effects on the heart observed in this study.
Aspirin lowers deaths in women over a 6.5 year period
The findings of a study reported on November 14, 2005 at the annual scientific sessions of the American Heart Association showed that postmenopausal women with cardiovascular disease who take aspirin had a 17 percent reduction in all cause mortality as well as a 25 reduction in cardiovascular mortality during the 6 and a half year study period.
Duke University Medical Center cardiology fellow Jeffrey Berger, MD and colleagues analyzed data collected from 8,928 women with cardiovascular disease enrolled in the Women's Health Initiative Observational Study, which has been following 93,676 postmenopausal women since 1994. Forty-six percent of the participants in the current study were regular users of aspirin.
Over the 6.5 course of the study, 8.7 percent of the participants died. When the researchers compared subjects who were taking aspirin to those who weren’t, they found a 25 percent reduction in deaths associated with cardiovascular disease, a 17 percent reduction in all-cause mortality, and a slight reduction in cardiovascular events among those taking aspirin. There was no difference associated with taking a 325 milligram dose compared to the 81 milligram dose found in a baby aspirin. Dr Berger observed, “We know that aspirin can save the lives of postmenopausal women with cardiovascular disease, so the percentage of those women taking aspirin should be in the high 90 percent. The only reason for these women not to be taking aspirin is if they have an allergy or suffer severe side effects."
Dr Berger added, “When we looked at outcomes such as all-cause mortality or any other cardiovascular event, we found no significant difference between the two doses. For that reason, we not only encourage all postmenopausal women to talk with their doctors about taking aspirin, but if the doctor recommends aspirin, it should be taken at the lowest possible effective dose."
Calorie restriction could help reverse early-stage Parkinson's disease
The 35th annual meeting of the Society for Neuroscience held in Washington, D.C. was the site of a presentation on November 15 by Charles Meshul, PhD of Oregon Health & Science University (OHSU) of the findings that mice that consumed fewer calories showed some signs of reversal of early Parkinson's disease.
In the current study, Dr Meshul, who is an associate professor of behavioral neuroscience at the OHSU School of Medicine, and colleagues used mice who had a 60 to 70 percent loss of dopamine in the brain, which is characteristic of early Parkinson's disease. One group of animals had access to food on a daily basis and the other group was fed every other day for 21 days.
They found that the mice whose diets were restricted lost 10-15 percent of their body weight compared to the mice whose diets were not restricted, and glutamate levels in the restricted mice rose. Glutamate is a neurotransmitter involved in motor control and learning, which declines with Parkinson's disease. Dr Meshul explained, "Dietary restriction appears to be normalizing the levels of glutamate. The fact that we're getting the levels of glutamate back to, essentially, control levels may indicate there are certain synapse changes going on in the brain to counteract the effects of Parkinson's. In fact, what this may indicate is a reversal of locomotor deficits associated with the disease."
In addition, mice who received every other day feeding were found to have a reduction in the number of dopamine nerve terminals. Dr Meshul noted, "It could very well be that what dietary restriction is doing is trying to protect the system somehow. And one of the reasons dietary restriction is protective may be that it's reducing the activity of particular synapses.
Selenium deficiency linked with increased risk of knee osteoarthritis
In a study that is the first of its kind, researchers at the University of North Carolina (UNC) at Chapel Hill Thurston Arthritis Center discovered that having a deficiency of the mineral selenium is associated with arthritis of the knee. The finding will be presented at the annual meeting of the American College of Rheumatology in San Diego on November 15, 2005.
The current study involved 940 participants in the Johnston County Osteoarthritis Project, a long term study that enrolled 4,400 individuals with arthritis in Johnston County, North Carolina. Subjects' toenail clippings were analyzed for selenium levels, and x-ray films of the knee were evaluated to determine the extent of the disease.
The research team determined that for every additional tenth part per million selenium detected in the participants, there was a 15 to 20 percent reduction in the risk of knee osteoarthritis. Lead researcher Dr Joanne Jordan, who is associate professor of medicine and orthopedics at the UNC School of Medicine stated, "We are very excited about these findings because no one had ever measured body selenium in this way in relationship to osteoarthritis . . . We found that when we divided the participants into three groups, those with the highest selenium levels faced a 40 percent lower risk of knee osteoarthritis than those in the lowest-selenium group. Those in the highest selenium group had only about half the chance of severe osteoarthritis or disease in both knees. Some of the findings were even stronger in African-Americans and women.""The next step will be in the laboratory to see how selenium affects cartilage," Dr Jordan added. "It might act as a protective antioxidant. Later, we'll want to expand the study with larger samples and see whether selenium supplementation reduces pain or other symptoms."
Youth hormone increases oxidative stress resistance
An protein named Klotho after the Greek goddess who spins life's thread was recently discovered to exert youth-extending effects by acting as a hormone that suppresses insulin and insulin-like growth factor-1 signaling. (Inhibition of insulin-like signaling is a mechanism for extending life span.) Defects in the klotho gene were found to produce a syndrome in mice that resembles human aging, while an extension of life span was elicited by the gene's overexpression. In the "Paper of the Week," published in the November 11 2005 issue of the Journal of Biological Chemistry, Masaya Yamamoto and colleagues at the University of Texas Southwestern Medical Center in Dallas discovered that Klotho also increases the body's resistance to oxidative stress.
By studying cell cultures and mice, the researchers determined that by activating transcription factors negatively regulated by insulin and IGF-1 signaling, the Klotho protein induces manganese superoxide dismutase which hydrolyzes the damaging superoxide radical into a less harmful compound. Study coauthor Makoto Kuro-o, who is an assistant professor of pathology at the University of Texas Southwestern Medical Center, explained the findings: "Increased longevity is always associated with increased resistance to oxidative stress. Oxidative stress causes the accumulation of oxidative damage to important biological macromolecules such as DNA, lipids, and proteins that would result in functional deterioration of the cell, which eventually causes aging . . . In this study we propose that Klotho does its job by increasing the ability of the cell to detoxify harmful reactive oxygen species, thereby increasing resistance to oxidative stress of the body."
Dr Kuro-o added, "We showed that the antiaging hormone Klotho confers resistance to oxidative stress in cells and animals. This means that Klotho protein itself or small molecule mimetics may be potentially useful as antiaging medicines."
Adequate vitamin D could lower calcium requirement
Laufey Steingrimsdottir, PhD, at Landspitali-University Hospital in Reykjavik, Iceland, and colleagues studied 944 adults who were divided according to calcium intake and serum vitamin D levels. Food frequency questionnaires provided data on calcium and vitamin D intake and blood serum samples were analyzed for hydroxyvitamin D and parathyroid hormone (PTH) levels. Parathyroid hormone helps maintain normal concentrations of calcium and is regulated via levels of calcium and calcitriol, the biologically active form of vitamin D. Calcium and vitamin D insufficiency is associated with an increase in parathyroid hormone.
While participants in the high vitamin D group, whose vitamin D levels were over 18 nanograms per milliliter, had the lowest parathyroid levels, parathyroid levels were highest among those whose vitamin D levels were in the low group. Among those in the low vitamin D group, subjects whose calcium intake was also low at less than 800 milligrams per day had the highest parathyroid levels. Having a low calcium intake did not impact parathyroid levels in the group with high vitamin D, and having a high calcium intake but low vitamin D did not lower parathyroid levels below those measured in the high vitamin D group.
The authors concluded, "Our study suggests that vitamin D sufficiency may be more important than high calcium intake in maintaining desired values of serum PTH. Vitamin D may have a calcium sparing effect and as long as vitamin D status is ensured, calcium intake levels of more than 800 mg/d may be unnecessary for maintaining calcium metabolism. Vitamin D supplements are necessary to ensure adequate vitamin D status for most of the year in northern climates."
Cruciferous vegetables' protective effect against lung cancer is stronger in some individuals
A research letter published in the October 29 2005 issue of The Lancet stated that individuals whose GSTM1 and GSTT1 genes are inactive experience significantly greater protection against lung cancer from cruciferous vegetables than do those with active genes. Cruciferous vegetables such as cabbage, broccoli and Brussels sprouts have a high isothiocyanate content, which may be responsible for the protective effect against lung cancer found in some observational studies. GSTM1 and GSTT1 produce glutathione-S-transferase enzymes which eliminate isothiocyanates in the body. When one or both of the genes are inactive, isothiocyanate concentrations rise.
Paul Brennan of the International Agency for Cancer Research in Lyon, France and colleagues assessed the genetic status of 2,141 lung cancer patients and 2,168 age and gender matched controls. Food frequency questionnaires which included questions about cabbage, broccoli and Brussels sprouts consumption were completed by all participants.
High intake of cruciferous vegetables, defined as at least once per week consumption, was associated with a 22 percent reduced risk of developing lung cancer compared to low (less than once per month) consumption. The research team discovered that while weekly consumption of cruciferous vegetables was not associated with a protective effect against lung cancer in individuals in whom both genes were active, for those with an inactive GSTM1 there was a 33 percent lower risk of lung cancer among those with high compared to low intake, and in those with inactive form of the GSTT1 gene there was a 37 percent lower risk. Having both genes inactivated conferred a 72 percent lower risk of lung cancer for those whose intake of cruciferous vegetables was high compared to low.
Dr Brennan concluded, "These data provide strong evidence for a substantial protective effect of cruciferous vegetable consumption on lung cancer."
In one of several interesting presentations on October 31 2005 at the American Association for Cancer Research 4th International Conference on Frontiers in Cancer Prevention Research, it was reported that daily consumption of broccoli sprouts improves chronic bacterial gastritis (inflammation of the lining of the stomach) by fighting H pylori, the bacteria responsible for most cases of bacterial gastritis and stomach ulcers. Left untreated, the condition can predispose infected individuals to stomach cancer.
Akinori Yanaka, MD, PhD of the University of Tsukuba in Japan and colleagues randomized forty subjects infected with H pylori to receive 100 grams broccoli sprouts or alfalfa sprouts daily for two months. Broccoli sprouts are high in sulforaphane glucosinolate, a compound that converts to sulforaphane which protects cells from oxidative injury as well as acts as a bactericide against H pylori. Alfalfa sprouts, while high in other nutrients, contain no sulforaphane or sulforaphane glucosinolate. Gastric inflammation and H pylori colonization were measured before treatment, after one and two months of treatment, and two months following the end of the study.
Participants who consumed broccoli sprouts for two months were found to have lower markers of H pylori and gastritis while those who received alfalfa sprouts had no reduction. These values returned to their initial levels two months after the cessation of the treatment period.
"The indicators of bacterial infection and gastritis were significantly reduced in the group that ate broccoli sprouts," concluded study coauthor Jed Fahey, MD, ScD of Johns Hopkins University. He added, "H. pylori infection is especially prevalent in places with crowded living conditions and poor sanitation where it causes high rates of stomach cancers and other gastric disorders. In many developing regions with limited health care resources, an effective dietary change may be much more practical than prescribing a drug to reduce rates of certain illnesses."
Ginkgo use linked with lower incidence of most deadly female cancer
A presentation on October 31 2005 at the American Association for Cancer Research's 4th annual Frontiers in Cancer Prevention Research meeting in Baltimore revealed that consuming ginkgo biloba is associated with a 60 percent lower risk of developing ovarian cancer than that experienced by women who did not take the herb.
Massachusetts researchers, led by Drs. Bin Ye and Daniel Cramer of Brigham and Women's Hospital in Boston, examined data from 600 women with ovarian cancer and 640 healthy matched controls. Ten percent of the women with cancer reported the use of herbal supplements at least once per week for six months or longer prior to their diagnosis, which was comparable to the number of healthy women who reported herbal supplement use.
Of the most commonly used herbs, only ginkgo was found to be associated with a decreased risk of ovarian cancer. Over 4 percent of the healthy women compared to 1.6 percent of those with ovarian cancer reported using ginkgo. Among women who had nonmucinous ovarian cancers, ginkgo use was associated with a 65-70 percent risk reduction.
In vitro investigation found that specific compounds in ginkgo stopped the growth of ovarian cancer cells. Dr Ye explained: "Among the mixture of ginkgo chemicals we found laboratory evidence that ginkgolide A and B--terpene compounds--are the most active components contributing to this protective effect . . . While the detailed mechanism of ginkgo action on ovarian cancer cells is not yet well understood, from the existing literature it most likely that ginkgo and ginkgolides are involved in anti-inflammation and antiangiogenesis processes via many extra- and intra-cellular signal pathways. In the future, these findings could potentially offer a new strategy for ovarian cancer prevention and therapy, using the active forms of ginkgolides."