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Research suggests prenatal carnitine supplementation could help prevent autism
January 29 2016. An article appearing online on January 28, 2016 in the journal Cell Reports reveals the finding of researchers at Texas A&M Health Science Center College of Medicine of a potential role for carnitine as a prenatal supplement to protect against a variety of autism in unborn children.
Carnitine, found in meat and other foods, is also manufactured in the body from the amino acid lysine. Research has shown that inherited mutations in a gene (TMLHE) required for carnitine synthesis are associated with development of autism spectrum disorders, yet the mechanism supporting the relationship had not been established.
By utilizing technology that allows tracking of individual neural stem cells in a developing brain, Zhigang Xie, PhD, and colleagues observed that cells that fail to produce carnitine are depleted; however, this phenomenon is prevented when the neural stem cells are supplied with carnitine. "We suggest that genetic screening of prospective parents for TMLHE mutations, coupled with inclusion of carnitine as a dietary supplement upon initial diagnosis of pregnancy, promises mental health benefits for newborns otherwise at significant risk for developmental brain disorders," the authors conclude.
"Here we have indications, at least for some types of autism risk, that a dietary carnitine prevention method might be effective," Dr Xie commented. "For some individuals, this simple nutritional supplement might really help reduce the risk of developing autism spectrum disorder. Any progress on the prevention front would be welcome given the number of people affected."
"While it could work in cases involving carnitine-deficiency, other pathways are also in play because as many as 1000 genes might ultimately be found to relate to autism risk," Dr Xie added. "Still, the potential impact of even such a limited preventive strategy could be significant as mutant TMLHE alleles are surprisingly common in the human population."
Higher serum magnesium levels linked with lower risk of heart disease and sudden cardiac death
January 27 2016. An article in the January 2016 issue of the Journal of the American Heart Association reports the finding of an association between higher magnesium levels and a decreased risk of coronary heart disease (CHD) and sudden cardiac death over a median follow-up of 8.7 years.
Researchers at Erasmus MC–University Medical Center in The Netherlands evaluated data from 9,820 participants in the Rotterdam Study of men and women aged 55 and older for whom serum magnesium levels were available. Among 2,303 deaths over follow-up, 780 were attributed to cardiovascular disease, of which 431 were classified as CHD deaths, including 187 sudden cardiac deaths.
For subjects whose serum magnesium was categorized as low, there was a 36% higher risk of coronary heart disease mortality and a 54% greater risk of sudden cardiac death in comparison with those who had levels in the middle range. When sudden cardiac death cases were excluded, having a high magnesium level was associated with a 31% lower risk of CHD. Each 0.1 micromole per liter magnesium was determined to be associated with an 18% lower risk of CHD mortality. Low magnesium was also associated with accelerated subclinical atherosclerosis, including increased carotid intima-media thickness and prolonged QT interval; however, according to the authors these factors do not explain the relationship between a higher risk of coronary heart disease mortality or sudden cardiac death with decreased magnesium levels.
"Low serum magnesium has been associated with inflammation and disturbances in the regulation of vascular tone and endothelial function," write Brenda C. T. Kieboom, MD, MSc, and colleagues.
"The results from this and previous studies may provide a rationale to design intervention studies to analyze whether magnesium supplementation could prove to be effective in lowering the burden of CHD mortality and sudden cardiac death," they conclude.
Fish oil, vitamin B12 supplementation associated with lower plasma homocysteine
January 25 2016. The September 2015 issue of Asia Pacific Journal of Clinical Nutrition published the finding of researchers at Zhejiang University in Hangzhou, China of a reduction in plasma homocysteine levels following supplementation with vitamin B12 and/or fish oil.
"No study has reported the effect of vitamin B12 in combination with fish oil on plasma homocysteine, ferritin, CRP and other cardiovascular disease risk factors in Chinese," announce Duo Li and colleagues in their introduction to the article.
Thirty men and women were randomly assigned to receive 1000 micrograms (mcg) vitamin B12, 2 grams fish oil, or 2 grams fish oil plus 1000 mcg vitamin B12. Plasma vitamin B12, lipids, ferritin (a biomarker of iron status), C-reactive protein (CRP), total homocysteine and other factors were measured before treatment and after four and eight weeks of supplementation.
Among those who received fish oil alone or fish oil plus vitamin B12, triglycerides, CRP and ferritin significantly decreased after four and eight weeks of supplementation. Homocysteine was lowered by 22% in the vitamin B12 group, 19% in the fish oil group and 39% among those who received both supplements for eight weeks.
"In summary, supplementation of fish oil alone or in combination with vitamin B12 decreased plasma concentrations of homocysteine, ferritin and CRP," Dr Li and associates conclude. "Oral supplementation with vitamin B12 in combination with fish oil had a synergistic effect on lowering plasma concentrations of homocysteine."
Aged garlic extract reduces arterial plaque burden
January 22 2016. A randomized, double-blind trial reported online on January 13, 2016 in the Journal of Nutrition found a reduction in vulnerable plaque in the arteries of metabolic syndrome patients who supplemented with aged garlic extract.
Fifty-five men and women between the ages of 40 and 75 years were given 2400 milligrams aged garlic extract or a placebo orally for a year. Cardiac computed tomography angiography screening was conducted at the beginning and end of the treatment period to assess coronary plaque volume, including total plaque volume, dense calcium, noncalcified plaque, and low-attenuation plaque, which is vulnerable to rupture.
At the end of the study, participants who received aged garlic were found to have experienced slower accumulation of total plaque compared to the placebo group, in addition to regression of low-attenuation plaque. "This study is another demonstration of the benefits of this supplement in reducing the accumulation of soft plaque and preventing the formation of new plaque in the arteries, which can cause heart disease," commented lead researcher Matthew J. Budoff, MD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, California. "We have completed four randomized studies, and they have led us to conclude that aged garlic extract can help slow the progression of atherosclerosis and reverse the early stages of heart disease."
"This study indicates that the percent low-attenuation plaque change was significantly greater in the aged garlic extract group than in the placebo group," the authors conclude. "Further studies are needed to evaluate whether aged garlic extract has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events."
Vitamin B12 deficiency common among long-term care patients
January 20 2016. An article published online on January 19, 2016 in Applied Physiology, Nutrition, and Metabolism reports a significant number of patients with deficient vitamin B12 levels in a sample of patients residing in Ontario long-term care facilities. The finding adds evidence to the benefit of blood testing for levels of B12, a vitamin that is less well absorbed with aging and necessary for healthy neurologic function.
Heather H. Keller and colleagues at Ontario's University of Waterloo examined the charts of 412 long-term care residents over the age of 65 who had blood testing conducted upon admission. They found that 13.8% of the patients had levels of vitamin B12 that were diagnostic of deficiency (below 156 pmol/L) and less than half of the residents had normal levels greater than 300 pmol/L. Another 4% of the residents developed deficiencies within a year of admission. More favorable vitamin B12 status was strongly associated with supplementation, with 84% of those with normal levels taking B12 supplements upon admission.
"The negative effects of a B12 deficiency are considerable," noted Dr Keller, who is a professor of kinesiology at the University of Waterloo and Schlegel Research Chair in Nutrition and Aging. "This is of particular importance in the context of our aging population with more Canadians requiring long-term care."
"In spending time in long-term care homes, you often see depression and loneliness," observed lead author Kaylen Pfisterer, who is an assistant research coordinator at the Schlegel-University of Waterloo Research Institute for Aging. "This is why we need to do everything in our power to enhance quality of life and quality of care in this setting. Screening for B12 deficiency is a first step to targeting B12 treatment to those who may benefit most."
How metformin inhibits pancreatic cancer progression
January 18 2016. A report published on December 7, 2015 in the journal PLOS One reveals the discovery of researchers at Massachusetts General Hospital of a mechanism supporting metformin's ability to reduce pancreatic cancer progression. Earlier research has documented a lower risk of pancreatic cancer in diabetics treated with metformin, as well as a reduced risk of mortality among those who develop the disease.
Dai Fukumura, MD, PhD, of Massachusetts General's Department of Radiation Oncology and colleagues examined the most common form of pancreatic cancer known as pancreatic ductal carcinoma, which is associated with type 2 diabetes and insulin resistance. Among inital findings was a 30% lower level of hyaluronan in the tumor extracellular matrix of pancreatic cancer tissue derived from overweight and obese patients treated with metformin in comparison with samples from those who had not been prescribed the drug. "We found that metformin alleviates desmoplasia - an accumulation of dense connective tissue and tumor-associated immune cells that is a hallmark of pancreatic cancer - by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation," Dr Fukumura explained. "We also found these effects only evident in tumors from overweight or obese individuals, who appear to have tumors with increased fibrosis."
"Nearly 200 clinical trials are currently underway investigating the effect of metformin on tumors in both diabetic and nondiabetic patients," noted co-senior author Rakesh K. Jain, PhD, who is the director of the Steele Laboratory of Tumor Biology at Massachusetts Generals' Radiation Oncology Department. "Understanding the mechanism behind metformin's effects on pancreatic and other cancers may help us identify biomarkers - such as patient body weight and increased tumor fibrosis - that can identify the patients for whom metformin treatment would be most beneficial."
Increased flavonoid intake linked with lower ED risk
January 15 2016. The February 2016 issue of the American Journal of Clinical Nutrition unveiled the finding of researchers at the University of East Anglia and Harvard of an association between greater intake of flavonoids and a lower risk of erectile dysfunction (ED).
"We already knew that intake of certain foods high in flavonoids may reduce the risk of conditions including diabetes and cardiovascular disease," commented lead researcher Aedín Cassidy. "This is the first study to look at the association between flavonoids and erectile dysfunction, which affects up to half of all middle-aged and older men."
For the current investigation, Dr Cassidy and colleagues utilized data from 25,096 men who participated in the Health Professionals Follow-Up Study. Dietary questionnaire responses collected every four years beginning in 1986 were analyzed to determine the intake of flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers/oligomers (including proanthocyanidins, theaflavins, and thearubigins). Erectile function was rated by participants during 2000, 2004 and 2008.
Over ten years of follow-up, erectile dysfunction was reported by 35.6% of subjects. Having an intake of flavones that was among the top 20% of participants was associated with a 9% lower adjusted risk of ED in comparison with the lowest 20%, and for those among the top 20% of flavanones and anthocyanins intake, the risk was 10% and 9% lower.
"Flavonoids are present in many plant-based foods and drinks including fruits, vegetables, tea, herbs and wine," Dr Cassidy observed. "We examined six main types of commonly consumed flavonoids and found that three in particular - anthocyanins, flavanones and flavones - are beneficial. Men who regularly consumed foods high in these flavonoids were 10 per cent less likely to suffer erectile dysfunction. In terms of quantities, we're talking just a few portions a week."
High dose vitamin D3 supplementation lowers inflammatory T cells in multiple sclerosis patients
January 13 2016. Results from a pilot study reported on December 30, 2015 in the journal Neurology suggest a benefit for treatment with high dose vitamin D for people diagnosed with the autoimmune disease multiple sclerosis (MS).
Peter A. Calabresi, MD, of Johns Hopkins University and colleagues tested the effects of vitamin D supplementation in a double-blind study involving 40 relapsing-remitting MS patients. Participants received 10,400 international units (IU) or 800 IU vitamin D for six months. Serum levels of 25-hydroxyvitamin D were measured at the beginning of the study and at three and six months.
While subjects who received the higher dose of vitamin D experienced an average 34.9 nanogram per milliliter (ng/mL) increase in serum 25-hydroxyvitamin D by the end of the study, levels increased by just 6.9 ng/mL in the low dose group. Relapse rate and reported minor adverse events were similar in both groups. Among those who received the higher dose, the proportion of pro-inflammatory interleukin-17+CD4+ T cells, CD161+CD4+ T cells and effector memory CD4+ T cells decreased, suggesting a reduction in disease severity.
"These results are exciting, as vitamin D has the potential to be an inexpensive, safe and convenient treatment for people with MS," stated Dr Calabresi, who is the director of the Johns Hopkins Multiple Sclerosis Center and professor neurology at John Hopkins School of Medicine. "More research is needed to confirm these findings with larger groups of people and to help us understand the mechanisms for these effects, but the results are promising."
"We hope that these changes in inflammatory T cell responses translate to a reduced severity of disease," he added. "Other clinical trials are underway to determine if that is the case."
Lower screening rates could delay early onset prostate cancer treatment
January 11 2016. The January 2016 issue of The Journal of Urology® published the results of study that provides a cautionary note to the recent U.S. Preventive Services Task Force (USPSTF) recommendation against regular prostate specific antigen (PSA) screening for prostate cancer. The investigation found a greater likeliness among men undergoing prostate needle biopsies (PNBs) to be diagnosed with high risk disease in comparison with the period prior to the establishment of the latest USPSTF guideline in 2012.
John M. Corman, MD, and colleagues examined data from 1,726 men who underwent needle biopsies of the prostate at Seattle's Virginia Mason Medical Center from 2004 to 2014. Among the 310 men whose biopsies were conducted after the USPSTF recommendation, PSA levels were greater and diagnosis with higher clinical state and high risk cancer more common compared to those whose biopsies were performed earlier.
"Results from our study support the argument that declining PSA screening may result in delayed diagnosis, potentially leading to avoidable cancer deaths," Dr Corman stated. "When compared to patients who underwent PNB in the 30 months prior to the USPSTF recommendation, those who underwent PNB in the 30 months after had a 33% higher relative risk of being diagnosed with high risk prostate cancer. The reduction in the number of potentially unnecessary biopsies appears to have occurred at the cost of detecting fewer intermediate risk prostate cancer tumors. Thus, the key concern is not only the increased risk of being diagnosed with high risk disease, but, more importantly, the missed opportunity to offer curative intervention for patients with intermediate risk prostate cancer."
"The importance of our study is not only the evolution in patient and tumor characteristics seen at PNB, but the rapidity by which statistically significant changes occurred following the release of the USPSTF recommendations," Dr Corman added. "The goal of prostate cancer screening is to maximize the benefit of screening tools such as PSA while minimizing the harm associated with over diagnosis and overtreatment. Rather than relegating PSA into oblivion, the balanced answer may be best found in the more intelligent use of available tools, implementation of shared decision making as recommended by the American Cancer Society, and development of more effective screening techniques."
Lower vitamin D levels may play a role in higher leukemia rates found at increased latitudes
January 8 2016. On December 4, 2015, the journal PLOS One reported the finding of an increased risk of leukemia in environments with a lower level of cloud cover-adjusted ultraviolet B (UVB) irradiance, which reduces the amount of vitamin D manufactured by the body. "This is a novel advance," announce authors Raphael E. Cuomo of the University of California San Diego and colleagues, "in that leukemia incidence has not previously been compared to UVB irradiance after adjustment for cloud cover using satellite data."
The researchers utilized leukemia incidence rates from the International Agency for Cancer Research and cloud cover data from the NASA International Satellite Cloud Climatology Project for 172 countries. They found a correspondence between higher leukemia rates and residence in countries closer to the poles, including Australia, the United States, Ireland, Canada and New Zealand, while equatorial countries, including Bolivia, Nigeria, Madagascar and Samoa had lower rates.
"These results suggest that much of the burden of leukemia worldwide is due to the epidemic of vitamin D deficiency we are experiencing in winter in populations distant from the equator," commented coauthor and vitamin D expert Cedric Garland, DrPH, who is an adjunct professor in the Department of Family Medicine and Public Health and member of Moores Cancer Center at UC San Diego Health. "People who live in areas with low solar ultraviolet B exposure tend to have low levels of vitamin D metabolites in their blood. These low levels place them at high risk of certain cancers, including leukemia."
"These studies do not necessarily provide final evidence," added Dr Garland, "but they have been helpful in the past in identifying associations that have helped minimize cancer risk."
Topical DHEA eases postmenopausal complaint
January 6 2016. An article in the March 2016 issue of Menopause reports a role for intravaginal dehydroepiandrosterone (DHEA) in relieving vaginal symptoms such as dryness and painful sex in postmenopausal women.
The phase III trial included 482 postmenopausal women, among whom 84% had moderate to severe vaginal dryness. Three hundred twenty-five women were provided with a daily intravaginal DHEA suppository and 157 women were given a placebo for twelve weeks. Vaginal symptoms were scored before and after treatment.
Among those who received DHEA, there was an 8.44% average increase in cells lining the vagina and a 27.7% decrease in immature precursors to these cells, indicating a reduction in thinning that occurs in the vaginal lining during menopause. Moderate to severe dryness also improved in the DHEA group. Vaginal secretions, tissue color, and vaginal lining integrity and thickness improved on average from 86% to 121% among women who received DHEA. The group also experienced a reduction in vaginal pH, indicating greater acidity. (A healthy vagina has an acidic pH.)
"Although this medication is considered 'hormonal,' the mechanism appears to be primarily local with minimal side effects beyond vaginal discharge from the suppository," explained JoAnn V. Pinkerton MD, NCMP, who is the Executive Director of the North American Menopause Society. "DHEA is transformed into estrogens within the parabasal cells, prompting the maturation process that ultimately transforms them into superficial cells. Its action seems to be entirely within the cells, and no significant amount of sex hormone gets released into the circulation."
"That means that intravaginal DHEA avoids the raised hormone levels that might stimulate breast tissue or the lining of the uterus," she noted. "Women who have been treated for these cancers often have severe vulvovaginal symptoms and need safe and effective treatment options."
Proton pump inhibitor drugs associated with varying cognitive side effects
January 4 2016. On December 27, 2015, Alzheimer's Research & Therapy published the results of a study which found varying adverse effects for five proton pump inhibitor (PPI) drugs among different cognitive domains. The administration of PPIs has been associated in rodent and cell culture studies with an increase in brain amyloid-beta (a protein found in the brain plaques that characterize Alzheimer's disease), as well as a deficiency of vitamin B12, which is necessary for healthy cognitive function.
For the current study, groups consisting of 10 men and women each received one of five classes of PPI for seven days. A sixth group received a placebo. Computerized neuropsychological tests of motor screening, paired associative learning, reaction time, rapid visual information processing and spatial working memory (which included a total of nine subtests) were completed by the subjects at the beginning and end of the study.
The researchers reported significant impairments in visual memory, attention, executive function and working and planning function among those who received PPIs. While all drugs tested in the study had adverse effects on cognition, omeprazole was associated with adverse effects in seven subtests, lansoprazole and pantoprazole in five, rabeprazole in four and esomeprazole in three.
"This study is probably the first of its kind to demonstrate the extent of impairment in different cognitive domains associated with use of different PPIs," authors Sanjida Akter of the University of Asia Pacific and colleagues announce. "In most of the cases, these negative effects may remain unnoticed, but in the long run they may take part in the development of Alzheimer's disease."
"However, to substantiate the robustness of the findings, studies with larger sample sizes and longer follow-up periods are required," they conclude.