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Reduced vitamin D levels could account for over half of end stage renal disease cases in African Americans
Kidney failure disproportionately affects African Americans, which is largely attributable to the greater prevalence of high blood pressure and diabetes in this population. In the December, 2009 issue of the Journal of the American Society of Nephrology, Michal L. Melamed, MD, of Albert Einstein College of Medicine and his colleagues report a strong association between end stage renal disease (ESRD) in Africa Americans and reduced vitamin D levels, a condition that is also more common in this group compared to Caucasians due to increased skin pigmentation which results in reduced vitamin D synthesis from sun exposure.
The researchers evaluated data from Third National Health and Nutrition Examination Survey–linked Medicare claims files for 13,328 men and women which included information on serum levels of 25-hydroxyvitamin D (activated vitamin D). Medicare data identified those who eventually required hemodialysis for end stage renal disease.
Thirty-four percent of African Americans had deficient 25-hydroxyvitamin D levels of less than 15 nanograms per milliliter, compared to 5 percent of non-Hispanic Caucasians. "We found that the participants with the lowest 25(OH)D levels were 2.6 times as likely to end up on dialysis compared to those with higher levels," Dr Melamed stated. "We found that 25(OH)D deficiency was responsible for about 58 percent of the excess risk for ESRD experienced by African Americans."
"Our study adds to previous evidence linking vitamin D deficiency to the progression of kidney disease and the need for dialysis," he noted. “It also explains a fair amount of the increased risk of ESRD in African Americans.”
"We are currently in the process of enrolling for a clinical trial of vitamin D repletion in patients with chronic kidney disease to further test these hypotheses," he added.
Reduced mortality found among children whose mothers supplemented with folic acid and iron
In the November 1, 2009 issue of the American Journal of Epidemiology, Parul Christian, DrPH, MSc, and colleagues from Johns Hopkins Bloomberg School of Public Health report that children born to mothers who received folic acid and iron supplements during their pregnancies were less likely to die during childhood than children of mothers who did not supplement with these nutrients.
The current investigation was a follow-up to a randomized, double-blinded trial of micronutrient supplementation during pregnancy among women living in Sarlahi, Nepal. The trial compared the effects of supplementation with folic acid, folic acid with iron, folic acid, iron and zinc; or a supplement that contained folic acid, iron, zinc and 11 other nutrients. All participants were supplemented with vitamin A, and a control group received vitamin A alone. The combination of iron and folic acid was found to be protective against low infant birth weight as well as prenatal and postpartum maternal anemia.
The status of the 4,130 children who were born during the trial was ascertained when the children were approximately 7 years of age. Two hundred nine infants failed to survive during the first 3 months of the trial and 150 died between the ages of 3 months and 7 years. “In a setting where maternal iron deficiency and anemia are common, we found a 31 percent reduction in childhood mortality due to maternal antenatal and postnatal supplementation with iron-folic acid compared to a control,” Dr Christian stated. “A reduction in mortality resulting from an intervention, such as iron-folic acid supplementation during pregnancy, provides a new and previously unreported evidence of benefit to offspring during childhood.”
“To our knowledge this is the first time the long-term effects of maternal iron-folic acid supplementation on childhood survival have been examined,” he noted.
Ginkgo improves treatment of olfactory loss following viral infection
An article published in the October, 2009 issue of the American Medical Association Journal Archives of Otolaryngology--Head and Neck Surgery reports the finding of Korean researchers that the herb Ginkgo biloba improves the ability of glucocorticoid treatment for the restoration of sense of smell following upper respiratory viral infection. Loss of the olfactory sense, when it occurs, is generally reported three months following infection with the common cold. Although the genesis of the condition is not clearly understood, postviral olfactory loss is caused by neurodegeneration of olfactory neural system cells. The standard treatment is with glucocorticoid drugs, which are commonly used for neuroinflammatory disease.
The study included 71 patients diagnosed with postviral olfactory loss who had no current evidence of sinus inflammation. All participants were treated with prednisolone for 2 weeks. Forty-three participants also received 80 milligrams Ginkgo biloba three times per day for four weeks. The subjects received two olfactory function tests at the beginning of the study and at the end of the four week treatment period.
Scores on both olfactory tests increased significantly in both groups. According to the authors, “Although the treatment response was not statistically different between the monotherapy group and the combination therapy group, the addition of Ginkgo biloba showed a tendency of greater efficacy in the treatment of postviral olfactory loss.”
Possible mechanisms for ginkgo in restoration of the sense of smell involve an increase in blood flow or its antioxidant action. One animal study found that ginkgo had an action on central olfactory areas associated with activation of olfactory regeneration in mice that lacked the sense of smell.
The authors conclude that “More clinical trials are required to evaluate drugs shown to be effective against neurodegeneration for the future treatment of olfactory disorder.”
Scientists enhance neuroprotective progesterone compounds
Two presentations at the 2009 Society for Neuroscience meeting held this month in Chicago reveal new ways of enhancing the delivery and effectiveness of progesterone in the treatment of traumatic brain injury.
One abstract presented at the conference documented research conducted by Emory University Department of Emergency Medicine's Brain Research Laboratory director Donald Stein, PhD. The study, which was published on September 8, 2009 in the Journal of Medicinal Chemistry, evaluated the effects of analogs of progesterone that have greater water solubility and longer storage capacity. The compounds were shown to be as effective as progesterone at reducing brain swelling in an animal model of brain injury due to trauma.
In other research reported at the meeting, Dr Stein and his associates discovered that the addition of vitamin D enhances progesterone’s effects following excitotoxic injury to rat neurons. In an article describing the findings published in the September-October, 2009 issue of Molecular Medicine, Dr Stein and colleagues explain that 1,25-dihydroxyvitamin D3, like progesterone, is a neurosteroid that shares some of progesterone’s mechanisms of neuroprotection. They suggest that progesterone could help prevent the initial inflammatory cascade and brain swelling that follow injury, followed by administration with vitamin D to stimulate brain repair. “Because only a few studies have been done in this area, it is obvious that more preclinical research will be needed to determine the benefits of this combinatorial therapy in clinical trial for traumatic brain injury or other central nervous system injuries such as stroke,” they conclude.
The studies’ findings hold promise for improving progesterone’s effectiveness in human brain injury. Testing of the hormone in traumatic brain injury is currently being initiated at various U.S. sites.
Resveratrol acts on the brain to lower insulin
An article published online on October 9, 2009 in the journal Endocrinology reported the discovery of researchers from the University of Texas Southwestern Medical Center of an antidiabetic effect for resveratrol when infused into the brains of mice. Resveratrol, found in red grapes and other plants, has demonstrated benefits similar to those of calorie restriction in animal research, and has also been shown to have antidiabetic effects when administered orally in an animal model of type 2 diabetes. Because resveratrol activates a protein known as SIRT1 which is expressed in central nervous system neurons that control glucose and insulin homeostasis, the researchers sought to determine whether the compound’s antidiabetic effects are mediated by the brain.
University of Texas assistant professor of internal medicine Roberto Coppari and his injected resveratrol or saline directly into the brains of mice fed high fat diets. While insulin levels of animals given saline continued to increase until the end of the study, insulin levels in mice that received resveratrol significantly declined, glucose was normalized and brain sirtuins were activated after 5 weeks.
“Our study shows that the brain plays an important role in mediating resveratrol’s antidiabetic actions, and it does so independent of changes in food intake and body weight,” Dr Coppari stated. “These animals were overrun with fat and many of their organs were inflamed. But when we delivered resveratrol in the brain, it alleviated inflammation in the brain.”
“By knowing that the central nervous system is involved, pharmaceutical companies can begin to focus on developing drugs that selectively target sirtuins in the brain,” he added.
“Collectively, our results unveiled a previously unrecognized key role for the central nervous system in mediating the antidiabetic actions of resveratrol,” the authors conclude.
Reduced plasma EPA associated with greater all cause mortality following heart attack in women
An article published online on September 29, 2009 in Circulation Journal reported the discovery of researchers in Korea of an association between decreased levels of the omega-3 fatty acid eicosapentaenoic acid (EPA) in women and a greater risk of dying from all causes over in the period following a heart attack.
The current study included 365 men and 143 women enrolled in the Infarction Prognosis Study registry of acute myocardial infarction. Demographic and clinical information were obtained from participants at the time of their hospital admission for heart attack. Blood samples were analyzed for glucose, lipids, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and other factors. The subjects were followed for an average of 16.1 months.
Over the follow-up period, 29 patients died of cardiovascular causes and 7 from noncardiovascular causes. Those who died were older and tended to have a lower body mass index, a history of hypertension, lower total and LDL cholesterol levels and higher C-reactive protein levels. EPA levels in survivors comprised 1.49 percent of total plasma phospholipids, compared to 1.24 percent in nonsurvivors. Reduced EPA levels predicted death from all causes, however, when the subjects were examined by gender, low EPA levels were found to predict mortality only in women.
“This study is the first to show a difference in the prognostic value of blood EPA and DHA levels in acute myocardial infarction using a prospective design,” the authors announce. They attribute the benefit of EPA to its anti-inflammatory effect, which has been found to be greater than DHA in some studies. They note that “the capacity of sex hormones to modify plasma and tissue omega-3 PUFA content may partly explain the gender difference; however, the significance and magnitude of this difference need further investigation.”
Mediterranean diet associated with less depression
An article published in the in the October issue of the journal Archives of General Psychiatry revealed that consuming a Mediterranean diet is associated with a lower risk of depression. The diet been linked with a reduced risk of cardiovascular disease, Alzheimer’s disease and other disorders, as well as a greater life span.
Almudena Sánchez-Villegas, B Pharm, PhD, of University of Las Palmas de Gran Canaria and Clinic of the University of Navarra, Spain and colleagues evaluated data from 10,094 healthy participants in the Seguimiento Universidad de Navarra Follow-Up (SUN) Project, which included former students of the University of Navarra and other university graduates. Questionnaires completed upon enrollment were scored for adherence to the following Mediterranean diet components: high ratio of monounsaturated fats to saturated fats, moderate intake of alcohol and dairy products, low intake of meat, and high intake of legumes, fruit and nuts, cereals, vegetables and fish.
One hundred fifty-six men and 324 women were diagnosed with depression over a median of 4.4. years of follow-up. Subjects whose adherence to the diet was greatest were found to have a 31 percent lower adjusted risk of depression compared with those whose adherence was lowest.
“The specific mechanisms by which a better adherence to the Mediterranean dietary pattern could help to prevent the occurrence of depression are not well known,” the authors write. “However, the role of the overall dietary pattern may be more important than the effect of single components. It is plausible that the synergistic combination of a sufficient provision of omega-three fatty acids together with other natural unsaturated fatty acids and antioxidants from olive oil and nuts, flavonoids and other phytochemicals from fruit and other plant foods and large amounts of natural folates and other B vitamins in the overall Mediterranean dietary pattern may exert a fair degree of protection against depression.”
Soy compound dramatically reduces hot flashes
Postmenopausal women who consumed supplements containing a metabolic product of soy known as S-equol experienced a reduction of 59 percent in hot flashes after 12 weeks, according to research presented on October 2, 2009 at the North American Menopause Society’s 20th annual meeting. S-equol is metabolized from daidzein, a compound in soy, by specific bacteria residing in the digestive tract of some individuals. The ability to produce S-equol depends upon the type of bacteria present in the intestine and the amount of soy consumed. Half of all Asians and only 20 to 30 percent of those of European descent have the ability to produce S-equol.
Japanese researchers conducted a randomized, double-blind, placebo-controlled study of S-equol in 230 postmenopausal Japanese women who were not able to metabolize S-equol from soy and who experienced at least one hot flash per day. Half of the participants receive a placebo and the remainder received 10 milligrams of S-equol daily for 12 weeks.
While the placebo group reported a reduction in hot flash frequency of 34.5 percent, those who received S-equol experienced a 58.7 percent reduction. The treatment was also associated with improvements in other menopausal symptoms. These benefits may be the result of equol’s ability to act as a selective estrogen receptor modulator, which binds to the body’s estrogen receptors.
In another study of S-equol conducted in 12 postmenopausal women, S-equol showed high systemic bioavailability that was not dependent upon whether the subjects were S-equol producers.
"The compound appears to have a promising future role in the management of women's menopausal symptoms," stated study author Takashi Aso, MD, PhD, of the Department of Obstetrics and Gynecology, Faculty of Medicine, Tokyo Medical and Dental University "Safe and effective alternatives to hormone replacement therapy are needed to help women who suffer from menopause symptoms."
Higher dose vitamin D needed to help prevent falls
An analysis by American and Swiss researchers summarized online on October 1, 2009 in the British Medical Journal concluded that supplementing with more than 700 international units (IU) of vitamin D per day is necessary to help prevent falls among older men and women.
Eight double-blinded, randomized controlled trials evaluating the use of supplemental vitamin D with or without calcium in a total of 2426 participants aged 65 and older were selected for the analysis. Two trials that tested active forms of vitamin D in 624 individuals were additionally analyzed.
Pooled analysis of the data indicated that 700 to 1000 IU supplemental vitamin D2 or D3 reduced falls by 19 and up to 26 percent, respectively, independently of calcium supplementation. Lower doses of vitamin D or achieving serum 25-hydroxyvitamin D levels of less than 60 nanomoles per liter did not appear to be effective. Oral active forms of vitamin D, which included 1 alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3, were associated with a similar benefit but were more likely to elicit hypercalcaemia.
In their discussion of the findings, the authors remark that muscle weakness is associated with reduced vitamin D levels, and is a major risk factor in falls. “Doses of 700 IU to 1000 IU supplemental vitamin D a day could reduce falls by 19% or by up to 26% with vitamin D3,” they conclude. “This benefit may not depend on additional calcium supplementation, was significant within 2-5 months of treatment, and extended beyond 12 months of treatment. Conversely, our results do not support the clinical use of vitamin D doses below 700 IU a day for the prevention of falls among older individuals.”
Unstable coronary artery plaques have reduced omega-3 fatty acid levels
In an article published online on September 4, 2009 in Vascular Pharmacology, Hernan A. Bazan, MD and Dr Song Hong of Louisiana State University Health Sciences Center School of Medicine and their colleagues report their discovery that unstable carotid artery plaques found in patients with neurologic symptoms have more inflammation and lower levels of omega-3 fatty acids than stable plaques in asymptomatic patients.
Unstable plaques are at risk of rupturing, and inflammation has been hypothesized as a cause of rupture. Rupture of the fibrous cap of plaques in the carotid artery leading to the brain can result in transient ischemic attacks or stroke. Omega-3 fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory properties, and have been linked with a reduction in cardiovascular events when consumed in high amounts. Previous research has demonstrated that supplementation with fish oil thickens the plaques’ fibrous caps and may help stabilize them.
Dr Bazan and his associates examined plaques from 41 patients aged 44 to 84 who had undergone carotid endarterectomy. Seventeen patients had neurologic symptoms, and 24 were asymptomatic.
Symptomatic patients averaged 216.4 nanograms EPA per gram plaque and 270.7 nanograms DHA, while plaque from those without symptoms contained an average of 385.9 nanograms EPA and 545.8 nanograms DHA per gram. Plaques from symptomatic patients also showed more inflammation than those from patients without symptoms. No differences were observed in levels of arachidonic acid, an omega-6 fatty acid.
“In the future, a study to address whether supplementation with dietary omega-3 polyunsaturated fatty acids prevents carotid-related events in patients with moderate or high-grade carotid stenosis will help answer whether this is a formidable therapeutic target for the prevention of stroke,” Dr Bazan stated.
Olive oil compound could help prevent Alzheimer’s disease
The October 15, 2009 issue of Toxicology and Applied Pharmacology published the discovery of researchers from Northwestern University in Evanston, Illinois, and the Monell Chemical Senses Center in Philadelphia of a preventive effect against Alzheimer’s disease for oleocanthal, a phenolic compound that occurs in extra-virgin olive oil.
In their introduction to the article, William L. Klein, PhD, of Northwestern’s Department of Neurobiology and Physiology and his colleagues write that “It now appears likely that soluble oligomers of amyloid-beta peptide, rather than insoluble fibrils, act as the primary neurotoxin in Alzheimer's disease.” Dr Klein’s team discovered soluble oligomers of amyloid-beta peptide, otherwise known as amyloid-beta derived diffusible ligands (ADDLs), in 1998. ADDLs are structurally different from the amyloid-beta plaques that have long believed to be the cause of Alzheimer’s disease. ADDLs bind with nerve cell junctions known as synapses which facilitate the transmission of information from one nerve cell to the next. The consequent disruption in nerve cell function leads to functional deficits prior to plaque deposition and brain cell death, according to this model.
Dr Klein and his colleagues discovered that incubation of ADDLs with oleocanthal altered their structure which reduces their ability to bind to synapses in the brain’s hippocampus, one of the preliminary areas of the brain to be affected by Alzheimer’s disease. They also determined that oleocanthal protected the synapses from ADDLs’ damaging effects. "Binding of ADDLs to nerve cell synapses is thought to be a crucial first step in the initiation of Alzheimer's disease,” Dr Klein explained. “Oleocanthal alters ADDL structure in a way that deters their binding to synapses. Translational studies are needed to link these laboratory findings to clinical interventions."
Additionally, treatment with oleocanthal was found to improve the recognition and clearance of ADDLs by antibodies. "If antibody treatment of Alzheimer's is enhanced by oleocanthal, the collective anti-toxic and immunological effects of this compound may lead to a successful treatment for an incurable disease,” remarked study coleader Paul A. S. Breslin, PhD, of the Monell Center. “Only clinical trials will tell for sure."