Drug that blocks inflammatory compound prevents type 1 diabetes in mice
In research presented at the 227 th national meeting of the American Chemical Society on March 30 2004, researchers from North Shore-Long Island Jewish Research Institute in Manhasset, New York discovered that a compound that blocks a chemical involved in inflammation prevents the development of type 1 diabetes in animals at risk of developing the disease.
Type 1 diabetes often appears in childhood, and is also known as juvenile-onset diabetes. The disease is characterized by a failure of the pancreas to produce adequate insulin, in contrast to type-2 diabetes, in which insulin may be produced adequately but is not efficiently utilized.
The drug, called ISO-1, was given to mice who had been given a compound that induces type 1 diabetes, while a control group received only the diabetes-inducing drug. The researchers found that the group that received ISO-1 was completely protected from developing diabetes, while all of the mice who did not receive it developed the disease. In a second experiment, when mice bred to develop diabetes were given ISO-1, only 10 percent became diabetic.
ISO-1 blocks the protein known as macrophage migration inhibitory factor which appears to be involved in the inflammatory events that lead to pancreatic beta cell destruction. Beta cells are the insulin-producing cells of the pancreas, and their loss causes the onset of diabetes type 1. Prediabetic individuals who have blood markers that are predictive of the disease would be ideal candidates to receive the drug.
Research team leader Yousef Al-Abed, PhD stated, "We believe this is the most promising compound to date for preventing type 1 diabetes. If it works, it will be especially beneficial for young people, who often have a difficult time managing their diabetes with daily insulin injections."
Vitamin E protects against bladder, prostate cancer
The 95th Annual Meeting of the American Association for Cancer Research was the site of the presentation of the results of two studies showing that vitamin E appears to have a protective effect against cancer of the bladder and prostate.
In the first study, researchers from the National Cancer Institute, the Fred Hutchinson Cancer Research Center in Seattle and the National Public Health Institute of Finland discovered an inverse association between serum alpha- tocopherol as well as gamma- tocopherol concentrations and prostate cancer risk A lpha- and gamma- tocopherol are two of eight fractions in which vitamin E occurs.
The study included 300 participants in the Alpha- Tocopherol , Beta-Carotene (ATBC) Cancer Prevention Study which involved 29,133 Finnish men. Previous findings demonstrated a 32 percent lower incidence of prostate cancer in men who took 50 mg alpha- tocopherol for five to eight years. One hundred participants in the current study had been diagnosed with prostate cancer. The researchers found higher levels of alpha- tocopherol associated with a 53 percent reduction in prostate cancer risk, and higher levels of gamma-tocopherol associated with a 39 percent reduction. Participants who had received a vitamin E supplement as part of the ATBC trial and whose serum levels of the vitamin were highest at the beginning of the study experienced the lowest rate of prostate cancer.
In the second study, researchers from the University of Texas M.D. Anderson Cancer Center and Texas Woman's University queried 468 individuals with bladder cancer and 534 cancer-free participants to determine the levels of alpha- and gamma- tocopherol from diet and supplements. Ladia M. Hernandez, RD of Texas Woman's University, reported, “High intake of vitamin E from dietary sources alone was associated with a 42 percent reduced risk of bladder cancer, whereas high intake of vitamin E from dietary sources and supplements combined reduced the risk by 44 percent.”
Supplements recommended over sun to obtain vitamin D
The American Academy of Dermatology, the Yale School of Dermatology and the Sun Safety Alliance have recommended that sun exposure not be relied upon to obtain one's vitamin D requirement. Recently some medical authorities have blamed sun avoidance and sunscreen use as the cause of widespread vitamin D deficiency. Yet Yale School of Medicine Department of Dermatology's Dr. David J. Leffell explained that the drop in vitamin D levels observed among northeastern residents in winter is a well-known process that is easily remedied by dietary supplementation. He stated that inadequate diet is the culprit in the portion of the population that is vitamin D deficient, and that vitamin D fortified milk or vitamin D supplements can correct the deficiency. "In my two decades of practice, I've never seen vitamin D deficiency caused by lack of sun exposure due to sunscreen use, yet the evidence that UV rays from the sun cause skin cancer is overwhelming," Dr Leffell said.
Vitamin D is essential for calcium absorption and proper muscular function, and recent research has revealed a role for the vitamin in the prevention of some cancers. Although evidence for this role for the vitamin is preliminary, the experts agree that if it proves to be true, they would not change their recommendation of supplementing over sunning.
Skin cancer is one of the few cancers where the cause is known, and every year one million new cases are diagnosed in the United States. The American Academy of Dermatology advises wearing a broad-spectrum sunscreen with a sun protection factor of at least 15, and re-applying it every two hours while in the sun. Director of the Sun Safety Alliance, Phil Schneider, recommended, “Enjoy the outdoors, and protect yourself. Block the sun but not the fun is proper advice.”
Zinc deficiency affects 20 percent of planet
A new report prepared by the International Zinc Nutrition Consultative Group (IZINCG), the United Nations University and the International Union of Nutrition Sciences has found that nearly one-fifth of the world's population is deficient in zinc, and up to one third live in countries that put them at risk of deficiency. The report, entitled, "Assessment of the Risk of Zinc Deficiency in Populations and Options for its Control" was presented at the UN Standing Committee on Nutrition on March 23, 2004. It cites several options for correcting zinc deficiency, including the administration of zinc supplements in the form of tablets or syrups, food fortification, and implementation of public education on good dietary sources of the mineral.
Zinc is an essential mineral for proper growth and development in children. Trials which provided at-risk children with zinc supplementation
have decreased diarrhea and acute lower respiratory infections—the most common causes of child mortality in developing countries—by 25 and 40 percent. Early evidence has found that the mortality rates in these children are cut in half by zinc supplementation. Commenting on these studies, Professor of international nutrition at the University of California, Davis, and cochair of IZINCG's Steering Committee, Ken Brown, MD, stated, "Knowledge of the occurrence of zinc deficiency and its importance to human health has increased greatly in recent years. These studies consistently show that the incidence of diarrhea and respiratory infections is reduced by providing additional zinc, and growth rates of previously stunted children are increased significantly. There is also some evidence that infants of mothers who received zinc supplements during pregnancy have less diarrhea during the first months of postnatal life. Interventions to improve zinc status show promise as a relatively low-cost means of improving children's health, and possibly their chances of survival, in poor countries."
Vitamin C treats neurologic condition
The April 2004 issue of the journal Nature Medicine published an article by French researchers who discussed the finding that vitamin C could help alleviate the symptoms of Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, which affects one out of every 25,000 individuals. Approximately half of CMT patients have the CMT-1A form which is characterized by abnormal peripheral nerve myelination, leading to nerve damage and muscle atrophy.
Michel Fontés and colleagues used a mouse model of the disease to determine the effects of ascorbic acid, which has been shown to be necessary for the promotion of myelination in vitro and, when deficient, has been linked with femoral neuropathies. In a series of experiments, the mice were fed the equivalent of approximately four grams ascorbic acid for a 70 kilogram adult male, which approaches the maximal amount approved for ascorbic acid deficiency treatment, or a placebo. The researchers found substantial improvements in movement in the mice treated with vitamin C after three months. The males were treated with the vitamin until their natural deaths. Males of this genetic strain who received placebos or no treatment lived an average of six months compared to male mice who received ascorbic acid who survived an average of 19.7 months, which approaches the lifespan of normal mice.
When the sciatic nerves of the experimental mice were examined, ascorbic acid was found to be associated with remyelination , demonstrating nerve repair.
A further finding was that the gene that is overexpressed in CMT-1A was inhibited by ascorbic acid to a level below that which is necessary to induce the disease's effects in the body. The authors propose that the effects of ascorbic acid are due not only to its antioxidant properties, but to a direct control of specific gene expression. They plan to initiate future trials in humans.
Glucosamine sulfate reduces arthritis progress in postmenopausal women
Glucosamine sulfate has been found in several studies to improve osteoarthritis (OA) symptoms and retard the structural degradation of the disease. Because knee osteoarthritis occurs more frequently in women than men after the age of 50, a possible role for hormone deficiency as a risk factor has been suggested, yet the current level of evidence does not recommend hormone replacement as a therapy for the disease.
In the current study, published in the March/April 2004 issue of the journal, Menopause, researchers evaluated a population of 319 postmenopausal women with knee osteoarthritis who had taken part in two three-year randomized, placebo controlled trials. Minimal knee joint space width, a measure of arthritis progression, was measured by radiographic imaging at the beginning of the studies and at three years. Additionally, symptoms such as joint pain severity, stiffness, and limitation of physical function, were evaluated at the beginning and end of the studies.
After three years it was found that 20.6 percent of the women who had received the placebo showed a clinically relevant narrowing of joint space width, compared to only 6.9 percent of those who received glucosamine sulfate. On average, there was a small increase in minimal joint space width among those who received glucosamine. Symptoms improved for those receiving glucosamine and tended to worsen for those in the placebo group, except for stiffness, which was the same between the two groups after three years.
The authors conclude that, “This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for osteoarthritis has a disease-modifying effect in this particular population, the most frequently affected by knee osteoarthritis.” ( Bruyer O et al, “ Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies,” Menopause, vol 11 no 2 2004)
Mechanism for choline in brain function identified
A report published in the April 2004 issue of the Journal of Neurochemistry revealed a mechanism of action for choline in brain development.
Researchers from the University of North Carolina at Chapel Hill reported five years ago that choline played a critical role in brain function by benefiting the brain's physical development. In the current University of North Carolina research, the effect of choline on human neuroblastoma tissue was studied to find out why the vitamin increases the reproduction of brain stem cells. It was found that choline inhibited cyclin-dependent kinase inhibitor 3 genes, which keep cells from dividing. Study coauthor and professor and chair of nutrition at the UNC schools of public health and medicine, Dr Steven H. Zeisel , explained: "We found that if we provided them with less choline , those nerve cells divided less and multiplied less. We then went on to try to explain why by looking at genes known to regulate cell division. We showed that choline donates a piece of its molecule called a methyl group and that gets put on the DNA for those genes. When the gene is methylated , its expression is shut down."
Conversely, the undermethylation of the gene which can occur in choline deficient conditions switches the gene on, retarding cell division. Dr Zeisel added, "Nature has built a remarkable switch into these genes something like the switches we have on the walls at home and at work. In this very complicated study, we've discovered that the diet during pregnancy turns on or turns off division of stem cells that form the memory areas of the brain. Once you have changed formation of the memory areas, we can see it later in how the babies perform on memory testing once they are born. And the deficits can last a lifetime."
New test can diagnose prostate cancer five years earlier than PSA
In the March 2004 issue of the Journal of Urology, researchers from the University of Pittsburgh suggest that testing for a protein called EPCA could detect prostate cancer up to five years in advance of the prostate specific antigen (PSA) test currently used to screen for the disease as well as other prostate conditions. Prostate specific antigen is a blood marker released by the prostate gland that is frequently elevated with prostate cancer, but an elevation in PSA does not always mean that the patient has cancer. The team believes that testing for EPCA could assist in diagnosing patients with elevated PSA levels who are frequently subjected to repeated needle biopsies.
Professor of urology, pathology and pharmacology at the University of Pittsburgh School of Medicine, Robert Getzenberg , PhD, and colleagues developed antibodies to EPCA so that its presence in tissue could be detected. When initial negative tissue biopsy samples from 29 prostate cancer patients were compared to 27 normal prostate tissue specimens, the tissue from the 29 who were eventually diagnosed with prostate cancer was found to express EPCA, while the normal tissue samples did not. EPCA was found to be expressed throughout the prostate, and not just in the tumor.
Dr Getzenberg commented, "One of the problems with testing for levels of PSA as an indicator of prostate cancer is that PSA levels often fluctuate up and down, making it difficult to know for certain whether a man has prostate cancer without performing multiple biopsies over time. By testing for EPCA in men with high levels of PSA, we may be able to detect the presence of prostate cancer earlier, before it is discoverable by biopsy, saving patients the fear and stress of repeat procedures and enabling us to treat the disease sooner."
Calorie restriction lowers breast cancer incidence in humans
A study published in the March 10 2004 issue of the Journal of the American Medical Association found that severe calorie restriction appears to have a protective effect against breast cancer. Numerous laboratory studies have found a lower incidence of cancer in calorie restricted animals. The current study examined 7303 Swedish women hospitalized for anorexia nervosa before the age of 40 from 1965 to 1998. Breast cancer incidence was found to be 53 percent lower in the anorexic women than the general population in Sweden. Anorexic women who had no children had a 23 percent lower incidence of the disease while those who had given birth experienced a 76 percent reduced risk.
The authors discuss a number of possible mechanisms for the findings including the beneficial effects of calorie restriction on oncogenes and tumor suppressor genes, a direct effect on breast cell growth and development, a reduction in estrogen caused by diminished body fat, and a reduction in IGF-1 due to restricted calories. Additionally, the disease is associated with lack of menstruation and a reduced number of ovulations which could be protective against breast cancer.
Having a high body mass index as well as being thinner than average during adolescence has been found to be protective against breast cancer. The reason for these seemingly contradictory findings could be that higher levels of estrogen may induce early differentiation of breast cells, offering protection against cancer later in life, while having low levels of estrogen and growth hormones due to decreased body fat is protective as well.
Although this study is not advocating the degree of calorie restriction adopted by anorexic patients, a moderately calorie restricted diet may be helpful in preventing breast cancer and other diseases.
Research finds drug free reduction of heart disease risk factors possible with TLC
A presentation at the American College of Cardiology's 53rd Scientific Sessions of the findings of a multicenter prospective study revealed that elevations in blood pressure, blood sugar and cholesterol—known risk factors for cardiovascular disease—can be controlled without drugs in many patients in a matter of months by the adoption of therapeutic lifestyles changes, or TLC. The study enrolled 2,390 patients who received 12 weeks of TLC, consisting of nutritional counseling, exercise training and other lifestyle interventions. Sixty-four percent of the participants experienced a reduction in systolic blood pressure to less than 140 mmHg, while the same percentage of diabetics and chronic renal disease patients met a lower goal of 130 mmHg. For diastolic blood pressure the goal was less than 90 mmHg and less than 80 mmHg for diabetics and kidney patients, which was met by 67 percent of the subjects. The goal of a fasting blood sugar level of less than 126 milligrams per deciliter was achieved by 37 percent of diabetics, and an equal number of nondiabetics met the goal of a fasting glucose level of under 110 mg/ dL . Twenty-three percent of the subjects met their LDL cholesterol goal.
Medical Director of the Center for Heart Disease Prevention at St. Joseph's/Candler Health System in Savannah, Neil F. Gordon MD, PHD, MPH, reported, "National clinical guidelines recommend TLC as a standard of care in the management of cardiovascular disease risk factors. But the value of TLC in actual contemporary medical practice is often discounted by clinicians and health insurers who instead frequently turn to widely available pharmacotherapeutic agents. This study was designed to evaluate the precise role of TLC in helping patients achieve goal risk factor levels – and our conclusions refute the notion that intensive lifestyle intervention is not worth the effort."
Friendly bacteria to be tried in intensive care patients
The Medical College of Georgia will be the site of a new study to test the effects of administering beneficial gastrointestinal bacteria called probiotics to patients in the intensive care unit, in hopes of preventing infections. Intensive care patients frequently receive antibiotic therapy, which destroys infectious bacteria as well as the healthy bacteria that exist in the intestinal tract, ironically rendering the intestinal lining more susceptible to invasion by abnormal bacteria such as E coli and salmonella. Lead researcher Robert G Martindale, MD, explained, “When people are admitted to intensive care on broad-spectrum antibiotics, we know that 25 to 40 percent of them will get an infection with a resistant bacteria during their stay. We kill all the normal bacteria in our GI tracts, allow these abnormal bacteria to grow and we are in trouble, we have upset the balance."
Dr Martindale first prescribes targeted antibiotic therapy, then provides his patients with beneficial bacteria such as lactobacillus plantarum , to help restore intestinal flora. This encourages macrophage activity which helps destroy infectious bacteria and prevents diarrhea. The proposed investigation will be the first to test the ability of the so- callled friendly bacteria to prevent infections in ICU patients in a large, randomized trial. Four hundred patients at three locations will be enrolled in the study.
Dr Martindale added, "We know very well that the source of sepsis in these patients, 50 to 70 percent of the time, is their own intestines. The question is, 'Why?' Why do bacteria from our own intestines that normally live with us in a nice, healthy relationship become aggressive and infective? Because we give these broad-spectrum antibiotics, we have big operations, GI bleeds … all these things destroy the normal lining of the intestines. Now these bacteria become aggressive."
Study finds low B12 levels linked with increased bone loss
A report published in the March 2004 issue of The Journal of Clinical Endocrinology & Metabolism revealed the findings of researchers at the University of California, San Francisco, that low levels of vitamin B12 in older women are associated with rapid bone loss.
The study involved 77 participants in the larger Study of Osteoporotic Fractures, which was initiated between 1986 and 1988 and involved 9,704 women aged sixty-five and older. The researchers analyzed blood samples taken during the study's initial examination for serum vitamin B12 levels and other factors. Bone mineral density of the heel was measured at the beginning of the study, and that of the hip was measured after two years. Follow up bone mineral density testing of the heel was obtained after nearly six years of follow-up, and that of the hip after three and one half years.
Following adjustment for age and other factors, it was discovered that women whose serum vitamin B12 levels were below 280 picograms per milliliter had much more rapid hip bone loss than women with higher levels.
Lead researcher Dr Katie Stone commented, "While deficiencies in vitamin B12 are uncommon among younger women, many older women suffer from vitamin B-12 deficiency. Our research shows that the women with the lowest levels of vitamin B12 are at an increased risk for bone loss in their hips, which could lead to fractures. We knew that vitamin B12 benefited the nervous system, but our findings suggest that it may also benefit bone health."
The authors conclude, “The results of this study raise the possibility that supplementation with vitamin B12, or, for some elderly women, dietary assessment and modification may slow rates of bone loss.”
High dietary folate associated with lower ovarian cancer risk
An article appearing in the March 3 2004 issue of the Journal of the National Cancer Institute has found a lower risk of ovarian cancer among women with a higher dietary intake of the B vitamin folate, especially if they consumed more than two alcoholic drinks per week. The researchers obtained their data from the Swedish Mammography cohort, a trial of 61,084 women between the ages of 38 and 76. The participants, who were free of cancer at the beginning of the study, completed food-frequency questionnaires from which the intake of folate and other nutrients intake was calculated.
From March 1987 through June 2003 there were 266 cases of invasive epithelial ovarian cancer diagnosed among the trial participants. Overall, a weak inverse association was found between dietary folate intake and ovarian cancer risk, however, this inverse association was significantly stronger among women who consumed more than two drinks per week. Women who drank more than 20 grams of alcohol per week who were in the top one fourth of folate consumption had a 74 percent lower risk of developing ovarian cancer than those in the lowest one fourth. This inverse relationship was even stronger for women who consumed over 40 grams of alcohol per week, yet no association between alcohol consumption and ovarian cancer risk was found.
In their discussion of a possible protective mechanism for folate in drinkers, the authors of the study suggest that alcohol may interefere with folate metabolism and increase the minimal amount needed for adequate intake. Previous studies have found an interaction between folate and alcohol intake in breast and colorectal cancers. A deficiency of folate reduces the regeneration of S-adenosylmethionine which plays a role in the methylation of DNA, that when lost, could promote cancer.
Nutrient formula improves resistance in older individuals
In one of the first studies to find a significant benefit for a complete nutritional formula on the immune systems of older individuals, research published in the January 2004 Journal of the American Geriatrics Society revealed that supplementing with a multinutrient formula decreased days spent sick with colds and improved immune response to flu vaccine.
Sixty-six individuals sixty-five years of age and older received a placebo or formula containing antioxidants, selenium, zinc, fermentable oligosaccharides and triacylgleryol for 183 days. On the day prior to the initiation of the supplementation, fasting blood samples were drawn and analyzed for various factors, including lymphocyte proliferation and antibody titers to influenza vaccine components. After two weeks, participants were vaccinated for influenza. Blood was redrawn and analyzed on or near the fifty-seventh day and on the last day of the study. Participants completed daily questionnaires which provided information on the occurrence of any symptoms of upper respiratory tract infection.
Of the individuals who completed the study, sixteen were in the group who received the nutritional supplement and eighteen in the placebo group. On the fifty-seventh day of the study, 87 percent of participants who received the nutritional supplement experienced at least a fourfold increase in serum antibody titer to one component of the influenza vaccine compared to 41 percent of those who received a placebo, demonstrating an improved immune response. Lymphocyte proliferation to flu vaccine components was also greater in the supplemented group. At the end of the study, the group who received the nutritional supplement reported a total of 78 days on which cold symptoms were reported, compared to a total of 156 for the placebo group.
The authors conclude that nutritional supplementation may improve immune function and reduce upper respiratory tract infection symptoms in an older population.