184CNO27JUN2014
CNO Report 184
Release Date 27 JUN 2014
Draft Report Compiled by
Ralph Turchiano
http://www.clinicalnews.org
1. Omega (ω)-3 inhibits blood vessel growth in age-related macular degeneration in vivo
2. Lower isn’t necessarily better for people with high blood pressure
3. Broccoli Sprout Beverage Enhances Detoxification of Air Pollutants in Clinical Trial in China
4. Vitamin A derivative potentially treats type 2 diabetes and prevents its complications
5. Death by prescription painkiller
6. Raising low vitamin D levels lowers risk of prediabetes progressing to diabetes
7. Vitamin D can lower weight, blood sugar via the brain
8. Study finds association between maternal exposure to agricultural pesticides
9. Sharp rise in professional queries about harmful effects of ‘fat burning’ agent
10. Hormone-disrupting activity of fracking chemicals worse than initially found
11. Cocoa Extract May Counter Specific Mechanisms of Alzheimer’s Disease
Omega (ω)-3 inhibits blood vessel growth in age-related macular degeneration in vivo
Findings highlighted in PNAS Online Early Edition
Boston (June 16, 2014) – Age-related macular degeneration (AMD), which is characterized by choroidal neovascularization (CNV), or blood vessel growth, is the primary cause of blindness in elderly individuals of industrialized countries. The prevalence of the disease is projected to increase 50% by the year 2020. There is an urgent need for new pharmacological interventions for the treatment and prevention of AMD.
Researchers from Massachusetts Eye and Ear/Schepens Eye Research Institute, Harvard Medical School and other institutions have demonstrated for the first time that the omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs), DHA and EPA, and their specific bioactive products derived from the cytochrome P450 (CYP) pathway, can influence choroidal neovascularization (CNV) and vascular leakage by modulating micro-environmental immune cell recruitment to the site of these lesions. Their findings will be published in PNAS Online Early Edition the week of June 16-20, 2014.
“These are the first results showing that omega (ω)-3 LCPUFAs and their CYP derived metabolites can regulate choroidal angiogenesis in vivo. The fact that this can be accomplished with physiologically relevant naturally occurring lipid metabolites is of significant clinical interest as these molecules are readily available and considered to be safe. Our findings not only show promising therapeutic potential for resolution of neovascular AMD, but also for other conditions or diseases that involve pathologic angiogenesis and inflammation,” said Kip Connor, Ph.D., Assistant Professor in Ophthalmology at Harvard Medical School and senior author of the paper.
The omega (ω)-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFAs) are two classes of dietary lipids that are essential fatty acids and have opposing physiological effects. To evaluate the effect of LCPUFAs on CNV development, researchers fed mice one of three experimental diets beginning two weeks before CNV induction by laser photocoagulation. The experimental diets were enriched with either ω-3 or ω-6 LCPUFAs, or in the case of the control diet, devoid of the primary ω-3 or ω-6 LCPUFAs. The lesion size and vascular leakage were significantly smaller in animals fed with ω-3 LCPUFAs. To gain mechanistic insight into the effect of dietary ω-3 LCPUFAs on CNV regression, researchers analyzed the lipid profiles of these mice and identified endogenous CYP-generated metabolites. Specifically, 17,18-EEQ and 19,20-EDP, derived from the CYP-pathway were identified by liquid chromatography- mass spectrometry (LC–MS/MS) and found to confer protection. Systemic immune-cell recruitment and adhesion-molecule regulation were significantly dampened in mice receiving ω-3s, thereby suppressing inflammation that is thought to exacerbate this disease. These findings provide a unique mechanism whereby specific CYP derived lipid metabolites regulate angiogenesis in a mouse model of AMD,” said lead author Ryoji Yanai, M.D., Ph.D.
The researchers demonstrated that dietary supplementation of omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs) mediates choroidal neovessel regression in a well-characterized murine model of neovascular AMD. The cytochrome P450 (CYP) enzymes catalyze the epoxidation of these ω-3 LCPUFAs to form the eicosanoids 17,18-epoxyeicosatetraenoic acid (EEQ) and 19,20-epoxydocosapentaenoic acid (EDP), which were identified as key lipid mediators of disease resolution. Their findings show promising therapeutic potential in AMD disease resolution.
“Given the prevalence of neovascular eye disease, the potential impact of this study is highly significant. We have identified unique endogenous lipid biometabolites that are able to inhibit pathologic retinal angiogenesis, a major driver of vision loss worldwide. It is our hope that future studies will allow us to develop specific therapeutics that harness this knowledge resulting in a greater visual outcome and quality of life for patients suffering from these sight threatening diseases,” Dr. Connor said.
Lower isn’t necessarily better for people with high blood pressure
WINSTON-SALEM, N.C. – June 16, 2014 – For decades, common medical wisdom has been “the lower the better” in treating the approximately one in three people in this country who have high blood pressure. But does that approach result in reduced risk for dangerous heart events?
In a study published in the June 16 online edition of JAMA Internal Medicine, researchers at Wake Forest Baptist Medical Center found that lowering systolic blood pressure below 120 does not appear to provide additional benefit for patients. Systolic pressure is the top number in a standard blood pressure reading (e.g., 120/80).
“Frequently we treat patients’ blood pressure to the lowest it will go, thinking that is what’s best,” said Carlos J. Rodriguez, M.D., associate professor of public health sciences at Wake Forest Baptist and lead author of the study.
“Our observational study found that treating to low pressures doesn’t provide any benefit to patients with regard to reducing risk of dangerous heart events like heart attack, heart failure and stroke. This calls into question the notion that lower is better.”
Previous studies had documented a progressive increase in heart disease risk as systolic blood pressure (SBP) rose above 115, but it was not known whether SBP lower than 120 in patients with hypertension (HTN) lowered the risk of heart failure, stroke and heart attack.
In this study, a total of 4,480 participants from the Atherosclerosis Risk in Communities Study were followed for 21 years for development of a cardiovascular event. Measurements of SBP were taken at baseline and at three-year intervals. SBP was categorized as elevated (140 or greater), standard (120 -139) or low (less than 120). The study findings were independent of baseline age, gender, diabetes status, body mass index, cholesterol level, smoking status and alcohol intake. A cardiovascular event was defined as heart failure, ischemic stroke, heart attack or death related to coronary heart disease.
The researchers found that among people with high blood pressure, once SBP is below 140, lowering it below 120 did not further reduce the risk of cardiovascular events.
“Our study found that the optimal blood pressure range for people with hypertension is120-139, which significantly reduces the risk of stroke, heart attack or heart failure,” Rodriguez said. “These findings suggest that you don’t need to go lower than that to have the benefits.”
Rodriguez said that his study was not a clinical trial and its results need to be confirmed; noting that a large clinical trial under way called SPRINT should either confirm or refute the findings.
Broccoli Sprout Beverage Enhances Detoxification of Air Pollutants in Clinical Trial in China
Findings Could Pave Way for Inexpensive Food-Based Preventive Strategies
A clinical trial involving nearly 300 Chinese men and women residing in one of China’s most polluted regions found that daily consumption of a half cup of broccoli sprout beverage produced rapid, significant and sustained higher levels of excretion of benzene, a known human carcinogen, and acrolein, a lung irritant. Researchers from the Johns Hopkins Bloomberg School of Public Health, working with colleagues at several U.S. and Chinese institutions, used the broccoli sprout beverage to provide sulforaphane, a plant compound already demonstrated to have cancer preventive properties in animal studies. The study was published in the June 9 online edition of the journal Cancer Prevention Research.
“Air pollution is a complex and pervasive public health problem,” notes John Groopman, PhD, Anna M. Baetjer Professor of Environmental Health at the Johns Hopkins Bloomberg School of Public Health and one of the study’s co-authors. “To address this problem comprehensively, in addition to the engineering solutions to reduce regional pollution emissions, we need to translate our basic science into strategies to protect individuals from these exposures. This study supports the development of food-based strategies as part of this overall prevention effort.”
Air pollution, an increasing global problem, causes as many as seven million deaths a year worldwide, according to the World Health Organization, and has in recent years reached perilous levels in many parts of China. Last year, the International Agency for Research on Cancer classified air pollution and particulate matter (PM) from air pollution as carcinogenic to humans. Diets rich in cruciferous vegetables, of which broccoli is one, have been found to reduce risk of chronic degenerative diseases, including cancer. Broccoli sprouts are a source of glucoraphanin, a compound that generates sulforaphane when the plant is chewed or the beverage swallowed. It acts to increase enzymes that enhance the body’s capacity to expunge these types of the pollutants.
The 12-week trial included 291 participants who live in a rural farming community in Jiangsu Province, China, approximately 50 miles north of Shanghai, one of China’s more heavily industrialized regions. Participants in the control group drank a beverage made of sterilized water, pineapple and lime juice while the beverage for the treatment group additionally contained a dissolved freeze-dried powder made from broccoli sprouts that contained glucoraphanin and sulforaphane. Sixty-two men (21%) and 229 women (79%) with a median age of 53 (ranging from 21 to 65) years were enrolled in the study. Urine and blood samples were taken over the course of the trial to measure the fate of the inhaled air pollutants.
The research team found that among participants receiving the broccoli sprout beverage, the rate of excretion of the carcinogen benzene increased 61% beginning the first day and continuing throughout the 12-week period. In addition, the rate of excretion of the irritant acrolein, rapidly and durably increased 23% during the 12-week trial. Secondary analyses by the investigators indicated that the sulforaphane may be exerting its protective actions by activating a signaling molecule, NRF2, that elevates the capacity of cells to adapt to and survive a broad range of environmental toxins. This strategy may also be effective for some contaminants in water and food.
“This study points to a frugal, simple and safe means that can be taken by individuals to possibly reduce some of the long-term health risks associated with air pollution,” notes Thomas Kensler, PhD, professor at the Johns Hopkins Bloomberg School and one of the study’s co-authors. “This while government leaders and policy makers define and implement more effective regulatory policies to improve air quality.”
The clinical trial targeting prevention is notable in that it evaluated a possible means to reduce the body burden of toxins following unavoidable exposures to pollutants. The majority of clinical trials involve treatments of diseases that have already presented or advanced into later stages. Further clinical trials, to evaluate optimal dosage and frequency of the broccoli sprout beverage, are planned in the same general region of China.
“Rapid and Sustainable Detoxification of Airborne Pollutants by Broccoli Sprout Beverage: Results of a Randomized Clinical Trial in China” was written by Patricia A. Egner; Jian Guo Chen; Adam T Zarth; Derek Ng; Jinbing Wang; Kevin H Kensler; Lisa P Jacobson; Alvaro Munoz; Jamie L Johnson; John D Groopman; Jed W. Fahey; Paul Talalay; Jian Zhu; Tao-Yang Chen; Geng-Sun Qian; Steven G. Carmella; Stephen S. Hecht; and Thomas W. Kensler.
This work was supported by the National Institutes of Health (P01 ES006052 and P30 S003819). Safeway, Inc. donated the lime juice used in this study.
Vitamin A derivative potentially treats type 2 diabetes and prevents its complications
At a time when obesity, type 2 diabetes, and their complications are a veritable epidemic worldwide, researchers at the University of Montreal and CHUM Research Centre (CRCHUM) recently demonstrated the potential of retinoic acid (RA), a derivative of Vitamin A, in treating obesity and type 2 diabetes and preventing their cardiovascular complications. The findings were presented June 6, 2014 at the Annual Conference of the Canadian Nutrition Society in Saint John’s, Newfoundland.
“In obese and insulin resistant mice, retinoic acid reduces the risk of cardiac apoptosis, stimulates the expression of cardio-protective genes reduced by the disease, and protects against the accumulation of collagen in the cardiac muscle, thus avoiding the occurrence of fibrosis and possible associated future complications,” says the first author of the study, Daniel-Constantin Manolescu. Apoptosis is the process of programmed cell death. The discovery follows other research conducted by his team on the effects of RA on insulin resistance, diabetes, and obesity. “Blood glucose, insulin resistance, body weight, and adipocyte size were significantly decreased in treated animals, including abdominal fat, while dietary intake and physical activity were similar for treated or non-treated animals. This suggests an increase in basal energy expenditure,” says Manolescu.
White fat is an energy reserve formed by the accumulation of fat in the form of triglycerides to meet unexpected increases in energy costs, but it is also a hormonal tissue with a delicate balance. Overall, if energy intake is greater than expenditures over an extended period, obesity increases, while hormonal balance and energy metabolism are disturbed. In this context, resistance to type 2 diabetes develops over time.
Brown fat also stores triglycerides, but it has the ability to produce heat. Abundant in babies, brown fat does not disappear completely in adulthood. It is irrigated by blood vessels and has many mitochondria, the energy factories of cells. Vitamin A derivatives stimulate a mitochondrial uncoupling protein (UCP1) that allows uncoupling of the mitochondria pathway (oxidative phosphorylation ), which uses energy from the oxidation of nutrients for the production of adenosine triphosphate (ATP). For a period of time, they generate heat (thermogenesis) instead of ATP, which is traditionally the energy required for active metabolism. Exposure to cold leads to the stimulation of brown fat and white fat, promoting the conversion of triglycerides to free fatty acids and glycerol. However, in brown adipocytes, these fatty acids are rapidly oxidized in the mitochondria and produce heat (under the influence of the UCP1 protein). Brown fat thus helps to increase basal energy metabolism. As a result, hibernating mammals fatten in the fall without developing diabetes and lose weight without moving too much in the winter (while warming their den). They are also the animals that accumulate the most Vitamin A in their livers. Retinoic acid (a Vitamin A derivative) is recognized for its involvement in cell maturation and differentiation and may guide pre-adipocytes to become brown (or beige) instead of white. It is as if “boilers” were installed directly in reserves of white fat to melt it on the spot and prevent it from over-accumulating.
“Vitamine A is a bioactive nutrient. The originality of our project is in addressing obesity and type 2 diabetes through the involvement of retinoids. We have attracted international attention and were named among 12 teams in the world to bring conclusive data in this regard,” says Dr. Pangala V. Bhat.
“Our studies on animals show that retinoic acid induces normalization of blood glucose and reduction of obesity. It is an important contribution to understanding RA action on the liver, fat, muscles, and the heart, and on retinoid metabolism, energy metabolism, fatty acid oxidation, and insulin resistance. Our research identifies new metabolic effects of retinoids and may lead to anti-obesity and anti-diabetic medicines,” says Dr. Jean-Louis Chiasson.
Death by prescription painkiller
First major review provides evidence of sharp increase in deaths from painkillers in US and Canada and leading causes
The number of deaths involving commonly prescribed painkillers is higher than the number of deaths by overdose from heroin and cocaine combined, according to researchers at McGill University. In a first-of-its-kind review of existing research, the McGill team has put the spotlight on a major public health problem: the dramatic increase in deaths due to prescribed painkillers, which were involved in more than 16,000 deaths in 2010 in the U.S. alone. Currently, the US and Canada rank #1 and #2 in per capita opioid consumption.
“Prescription painkiller overdoses have received a lot of attention in editorials and the popular press, but we wanted to find out what solid evidence is out there,” says Nicholas King, of the Biomedical Ethics Unit in the Faculty of Medicine. In an effort to identify and summarize available evidence, King and his team conducted a systematic review of existing literature, comprehensively surveying the scientific literature and including only reports with quantitative evidence.
“We also wanted to find out why thousands of people in the U.S and Canada are dying from prescription painkillers every year, and why these rates have climbed steadily during the past two decades,” says Nicholas King, of the Biomedical Ethics Unit in the Faculty of Medicine. “We found evidence for at least 17 different determinants of increasing opioid-related mortality, mainly, dramatically increased prescription and sales of opioids; increased use of strong, long-acting opioids like Oxycontin and methadone; combined use of opioids and other (licit and illicit) drugs and alcohol; and social and demographic factors.”
“We found little evidence that Internet sales of pharmaceuticals and errors by doctors and patients–factors commonly cited in the media — have played a significant role,” Prof. King adds.
The findings point to a complicated “epidemic” in which physicians, users, the health care system, and the social environment all play a role, according to the researchers.
“Our work provides a reliable summary of the possible causes of the epidemic of opioid overdoses, which should be useful for clinicians and policy makers in North America in figuring out what further research needs to be done, and what strategies might or might not be useful in reducing future mortality,” says King. “And as efforts are made to increase access to prescription opioids outside of North America, our findings might be useful in preventing other countries from following the same path as the U.S. and Canada.”
Raising low vitamin D levels lowers risk of prediabetes progressing to diabetes
CHICAGO, IL—Vitamin D and calcium supplementation along with diet and exercise may prevent type 2 diabetes in prediabetic individuals who have insufficient vitamin D in their bodies, a study from India suggests. The results were presented Saturday at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago.
Vitamin D deficiency has been linked to prediabetes, which is a blood glucose, or sugar, level that is too high but not high enough to be considered diabetes. It is unclear, however, if bringing low vitamin D blood levels to normal through supplementation will affect progression to diabetes.
In the new study, every unit increase in vitamin D level after supplementation of the vitamin decreased the risk of progression to diabetes by 8 percent, the authors reported.
“Without healthy lifestyle changes, nothing works to prevent diabetes in at-risk individuals,” said the lead author, Deep Dutta, MD, DM, a research officer at the Institute of Postgraduate Medical Education & Research and Seth Sukhlal Karnani Memorial Hospital in Calcutta, India. “However, our results are encouraging because the addition of vitamin D and calcium supplements is easy and low in cost.”
“If our results are confirmed in a large multicenter trial,” Dutta said, “vitamin D supplementation would provide us with a new tool in the armamentarium of diabetes prevention strategies.”
The West Bengal chapter of the Research Society for the Study of Diabetes in India funded this study. Of 170 individuals with prediabetes who had not taken vitamin D supplements in the past six months, 125 had vitamin D deficiency or insufficiency, which the researchers defined as a vitamin D blood level (25-hydroxyvitamin D) of 30 nanograms per milliliter (ng/mL) or less. These 125 study subjects were randomly assigned to one of two treatment groups. In the first group, 68 subjects received ready-to-mix, powdered vitamin D3 (cholecalciferol, D-Rise sachets, USV Ltd., Mumbai, India) at a dose of 60,000 International Units (IU) once weekly for eight weeks and then monthly. They also received a daily 1,250-milligram calcium carbonate tablet.
The other group of 57 subjects received only calcium supplements. Both groups received advice to eat a healthy, calorie-appropriate diet and to engage in brisk exercise for 30 minutes each day.
The researchers analyzed results for subjects who had at least a year of follow-up tests. After an average of nearly two years and four months’ follow-up, only six of 55 subjects (10.9 percent) in the group that received vitamin D plus calcium supplementation had become diabetic, whereas diabetes developed in 13 of 49 individuals (26.5 percent) in the calcium-alone group. Blood sugar levels reportedly became normal in about twice as many people in the vitamin D group as in the group that did not get vitamin D supplementation: 23 of 55 subjects versus 10 of 49 subjects, respectively (41.8 percent versus 20.4 percent).
At the end of the study, those who received vitamin D supplementation had much higher vitamin D levels in the blood and lower fasting blood glucose levels compared with the other group. Every unit (1 ng/mL) increase in vitamin D in the body was associated with a 5.4 percent increased chance of reversal to normal blood sugar levels, Dutta reported.
He said the greater reversal to normal blood sugar in the vitamin D group presumably occurred through improvements in their insulin resistance and inflammation.
Vitamin D can lower weight, blood sugar via the brain
CHICAGO, IL—Vitamin D treatment acts in the brain to improve weight and blood glucose (sugar) control in obese rats, according to a new study presented Saturday at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago.
“Vitamin D deficiency occurs often in obese people and in patients with Type 2 diabetes, yet no one understands if it contributes to these diseases,” said Stephanie Sisley, MD, the study’s principal investigator and an assistant professor at Baylor College of Medicine, Houston. “Our results suggest that vitamin D may play a role in the onset of both obesity and Type 2 diabetes by its action in the brain.”
“The brain is the master regulator of weight,” Sisley said. A region of the brain called the hypothalamus controls both weight and glucose, and has vitamin D receptors there.
In this study funded by the National Institutes of Health, Sisley and partners at the University of Cincinnati delivered vitamin D directly to the hypothalamus. The investigators administered the active, potent form of vitamin D—called 1,25-dihydroxyvitamin D3—to obese male rats through a cannula (thin tube) surgically inserted using anesthesia into the brain’s third ventricle. This narrow cavity lies within the hypothalamus. Rats recovered their presurgery body weight, and the researchers verified the correct cannula placement.
The animals received nothing to eat for four hours, so they could have a fasting blood sugar measurement. Afterward, 12 rats received vitamin D dissolved in a solution acting as a vehicle for drug delivery. Another 14 rats, matched in body weight to the first group, received only the vehicle, thus serving as controls. One hour later, all rats had a glucose tolerance test, in which they received an injection of dextrose, a sugar, in their abdomen, followed by measurement of their blood sugar levels again.
Compared with the control rats, animals that received vitamin D had improved glucose tolerance, which is how the body responds to sugar. In a separate experiment, these treated rats also had greatly improved insulin sensitivity, the body’s ability to successfully respond to glucose. When this ability decreases—called insulin resistance—it eventually leads to high blood sugar levels. Two of insulin’s main effects are to clear glucose from the bloodstream and decrease glucose production in the liver. In this study, vitamin D in the brain decreased the glucose created by the liver.
In a separate experiment of long-term vitamin D treatment, the researchers gave three rats vitamin D and four rats vehicle alone for four weeks. They observed a large decrease in food intake and weight in rats receiving vitamin D compared with the group that did not get vitamin D. Over 28 days, the treated group ate nearly three times less food and lost 24 percent of their weight despite not changing the way they burned calories, study data showed. The control group did not lose any weight.
“Vitamin D is never going to be the silver bullet for weight loss, but it may work in combination with strategies we know work, like diet and exercise,” Sisley commented.
She said more research is necessary to determine if obesity alters vitamin D transport into the brain or its action in the brain.
Study finds association between maternal exposure to agricultural pesticides and autism
(SACRAMENTO, Calif.) — Pregnant women who lived in close proximity to fields and farms where chemical pesticides were applied experienced a two-thirds increased risk of having a child with autism spectrum disorder or other developmental delay, a study by researchers with the UC Davis MIND Institute has found. The associations were stronger when the exposures occurred during the second and third trimesters of the women’s pregnancies.
The large, multisite California-based study examined associations between specific classes of pesticides, including organophosphates, pyrethroids and carbamates, applied during the study participants’ pregnancies and later diagnoses of autism and developmental delay in their offspring. It is published online today in Environmental Health Perspectives.
“This study validates the results of earlier research that has reported associations between having a child with autism and prenatal exposure to agricultural chemicals in California,” said lead study author Janie F. Shelton, a UC Davis graduate student who now consults with the United Nations. “While we still must investigate whether certain sub-groups are more vulnerable to exposures to these compounds than others, the message is very clear: Women who are pregnant should take special care to avoid contact with agricultural chemicals whenever possible.”
California is the top agricultural producing state in the nation, grossing $38 billion in revenue from farm crops in 2010. Statewide, approximately 200 million pounds of active pesticides are applied each year, most of it in the Central Valley, north to the Sacramento Valley and south to the Imperial Valley on the California-Mexico border. While pesticides are critical for the modern agriculture industry, certain commonly used pesticides are neurotoxic and may pose threats to brain development during gestation, potentially resulting in developmental delay or autism.
The study was conducted by examining commercial pesticide application using the California Pesticide Use Report and linking the data to the residential addresses of approximately 1,000 participants in the Northern California-based Childhood Risk of Autism from Genetics and the Environment (CHARGE) Study. The study includes families with children between 2 and 5 diagnosed with autism or developmental delay or with typical development. It is led by principal investigator Irva Hertz-Picciotto, a MIND Institute researcher and professor and vice chair of the Department of Public Health Sciences at UC Davis. The majority of study participants live in the Sacramento Valley, Central Valley and the greater San Francisco Bay Area.
Twenty-one chemical compounds were identified in the organophosphate class, including chlorpyrifos, acephate and diazinon. The second most commonly applied class of pesticides was pyrethroids, one quarter of which was esfenvalerate, followed by lambda-cyhalothrin permethrin, cypermethrin and tau-fluvalinate. Eighty percent of the carbamates were methomyl and carbaryl.
For the study, researchers used questionnaires to obtain study participants’ residential addresses during the pre-conception and pregnancy periods. The addresses then were overlaid on maps with the locations of agricultural chemical application sites based on the pesticide-use reports to determine residential proximity. The study also examined which participants were exposed to which agricultural chemicals.
“We mapped where our study participants’ lived during pregnancy and around the time of birth. In California, pesticide applicators must report what they’re applying, where they’re applying it, dates when the applications were made and how much was applied,” Hertz-Picciotto said. “What we saw were several classes of pesticides more commonly applied near residences of mothers whose children developed autism or had delayed cognitive or other skills.”
The researchers found that during the study period approximately one-third of CHARGE Study participants lived in close proximity – within 1.25 to 1.75 kilometers – of commercial pesticide application sites. Some associations were greater among mothers living closer to application sites and lower as residential proximity to the application sites decreased, the researchers found.
Organophosphates applied over the course of pregnancy were associated with an elevated risk of autism spectrum disorder, particularly for chlorpyrifos applications in the second trimester. Pyrethroids were moderately associated with autism spectrum disorder immediately prior to conception and in the third trimester. Carbamates applied during pregnancy were associated with developmental delay.
Exposures to insecticides for those living near agricultural areas may be problematic, especially during gestation, because the developing fetal brain may be more vulnerable than it is in adults. Because these pesticides are neurotoxic, in utero exposures during early development may distort the complex processes of structural development and neuronal signaling, producing alterations to the excitation and inhibition mechanisms that govern mood, learning, social interactions and behavior.
“In that early developmental gestational period, the brain is developing synapses, the spaces between neurons, where electrical impulses are turned into neurotransmitting chemicals that leap from one neuron to another to pass messages along. The formation of these junctions is really important and may well be where these pesticides are operating and affecting neurotransmission,” Hertz-Picciotto said.
Research from the CHARGE Study has emphasized the importance of maternal nutrition during pregnancy, particularly the use of prenatal vitamins to reduce the risk of having a child with autism. While it’s impossible to entirely eliminate risks due to environmental exposures, Hertz-Picciotto said that finding ways to reduce exposures to chemical pesticides, particularly for the very young, is important.
“We need to open up a dialogue about how this can be done, at both a societal and individual level,” she said. “If it were my family, I wouldn’t want to live close to where heavy pesticides are being applied.”
Sharp rise in professional queries about harmful effects of ‘fat burning’ agent
2,4-Dinitrophenol, DNP, not licensed as medicine, but available on the internet
The number of professional enquiries made to the National Poisons Information Service about the harmful effects of a ‘fat burning’ agent used by body builders and dieters has risen sharply in the past three years, reveals research published online in Emergency Medicine Journal.
2,4-Dinitrophenol, or DNP for short, is a synthetic chemical originally used in the manufacture of dyes, wood preservatives, phototographic developers, explosives and insecticides.
It speeds up metabolism and the body’s use of fat and glucose stores, and was subsequently developed as a weight loss drug in the US in the 1930s.
But its side effects, which include very high fever and multi organ failure, especially at high doses, prompted US drugs regulator the FDA to ban it for human use in 1938. Although not licensed for medicinal use, it is available on the internet.
In a bid to gauge the prevalence of harm associated with DNP use in the UK, the researchers analysed the phone records of the National Poisons Information Service and online searches of its linked database, TOXBASE, for enquiries about DNP between 2007 and 2013.
The National Poisons Information Service is commissioned by Public Health England and provides phone and online information and clinical advice to healthcare professionals on all aspects of poisoning.
The phone records revealed that 39 enquiries had been made about 30 separate incidents involving 27 men and three women, ranging in age from 15 to 45.
Three cases occurred between 2007 and 2011; five in 2012; and 22 in 2013. A similarly sharp increase was seen in the number of online searches of TOXBASE. These rose from six in 2011 to 35 in 2012, and 331 in 2013.
The most commonly reported symptoms in the phone enquiries included fever (47% of cases), rapid heart rate or tachycardia in 43%, and sweating in 37% of cases.
But nausea or vomiting, skin discolouration or rash, breathing difficulties, abdominal pain, agitation, and headache were also reported.
Five people died, four of whom had taken very high doses of DNP. Three of the deaths occurred in 2013, with the others occurring in 2008 and 2012.
The researchers emphasise that the Poisons Service received more than 50,000 annual phone enquiries during the study period, with the total number of TOXBASE searches amounting to more than 550,000. So enquiries about DNP make up just a small fraction.
Nevertheless, the figures clearly show a sharp rise in the number of enquiries about DNP, they say, in spite of warnings about its harmful side effects, issued by the Food Standards Agency (FSA) in November 2012 and October 2013.
The FSA has been working with police and local authorities to crack down on sales of DNP, say the researchers, but additional steps may be necessary to curb the number of episodes of severe poisoning and associated deaths, they warn.
Hormone-disrupting activity of fracking chemicals worse than initially found
CHICAGO, IL—Many chemicals used in hydraulic fracturing, or fracking, can disrupt not only the human body’s reproductive hormones but also the glucocorticoid and thyroid hormone receptors, which are necessary to maintain good health, a new study finds. The results were presented Monday at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago.
“Among the chemicals that the fracking industry has reported using most often, all 24 that we have tested block the activity of one or more important hormone receptors,” said the study’s presenting author, Christopher Kassotis, a PhD student at the University of Missouri, Columbia. “The high levels of hormone disruption by endocrine-disrupting chemicals (EDCs) that we measured, have been associated with many poor health outcomes, such as infertility, cancer and birth defects.”
Hydraulic fracturing is the process of injecting numerous chemicals and millions of gallons of water deep underground under high pressure to fracture hard rock and release trapped natural gas and oil. Kassotis said spills of wastewater could contaminate surface and ground water.
In earlier research, this group found that water samples collected from sites with documented fracking spills in Garfield County, Colorado, had moderate to high levels of EDC activity that mimicked or blocked the effects of the female hormones (estrogens) and the male hormones (androgens) in human cells. However, water in areas away from these gas-drilling sites showed little EDC activity on these two reproductive hormones.
The new study extended the analysis to learn whether high-use fracking chemicals changed other key hormone receptors besides the estrogen and androgen receptors. (Receptors are proteins in cells that the hormone binds to in order to perform its function.) Specifically, the researchers also looked at the receptor for a female reproductive hormone, progesterone, as well as those for glucocorticoid—a hormone important to the immune system, which also plays a role in reproduction and fertility—and for thyroid hormone. The latter hormone helps control metabolism, normal brain development and other functions needed for good health.
Among 24 common fracking chemicals that Kassotis and his colleagues repeatedly tested for EDC activity in human cells, 20 blocked the estrogen receptor, preventing estrogen from binding to the receptor and being able to have its natural biological response, he reported. In addition, 17 chemicals inhibited the androgen receptor, 10 hindered the progesterone receptor, 10 blocked the glucocorticoid receptor and 7 inhibited the thyroid hormone receptor.
Kassotis cautioned that they have not measured these chemicals in local water samples, and it is likely that the high chemical concentrations tested would not show up in drinking water near drilling. However, he said mixtures of these chemicals act together to make their hormone-disrupting effects worse than any one chemical alone, and tested drinking water normally contains mixtures of EDCs.
“We don’t know what the adverse health consequences might be in humans and animals exposed to these chemicals,” Kassotis said, “but infants and children would be most vulnerable because they are smaller, and infants lack the ability to break down these chemicals.”
Cocoa Extract May Counter Specific Mechanisms of Alzheimer’s Disease
Insights into mechanisms behind cocoa’s benefit may lead to new treatments or dietary regimens
NEW YORK – June 23, 2014 /Press Release/ ––
A specific preparation of cocoa-extract called Lavado may reduce damage to nerve pathways seen in Alzheimer’s disease patients’ brains long before they develop symptoms, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published June 20 in the Journal of Alzheimer’s Disease (JAD).
Specifically, the study results, using mice genetically engineered to mimic Alzheimer’s disease, suggest that Lavado cocoa extract prevents the protein β-amyloid- (Aβ) from gradually forming sticky clumps in the brain, which are known to damage nerve cells as Alzheimer’s disease progresses.
Lavado cocoa is primarily composed of polyphenols, antioxidants also found in fruits and vegetables, with past studies suggesting that they prevent degenerative diseases of the brain.
The Mount Sinai study results revolve around synapses, the gaps between nerve cells. Within healthy nerve pathways, each nerve cell sends an electric pulse down itself until it reaches a synapse where it triggers the release of chemicals called neurotransmitters that float across the gap and cause the downstream nerve cell to “fire” and pass on the message.
The disease-causing formation of Aβ oligomers – groups of molecules loosely attracted to each other –build up around synapses. The theory is that these sticky clumps physically interfere with synaptic structures and disrupt mechanisms that maintain memory circuits’ fitness. In addition, Aβ triggers immune inflammatory responses, like an infection, bringing an on a rush of chemicals and cells meant to destroy invaders but that damage our own cells instead.
“Our data suggest that Lavado cocoa extract prevents the abnormal formation of Aβ into clumped oligomeric structures, to prevent synaptic insult and eventually cognitive decline,” says lead investigator Giulio Maria Pasinetti, MD, PhD, Saunders Family Chair and Professor of Neurology at the Icahn School of Medicine at Mount Sinai. “Given that cognitive decline in Alzheimer’s disease is thought to start decades before symptoms appear, we believe our results have broad implications for the prevention of Alzheimer’s disease and dementia.
Evidence in the current study is the first to suggest that adequate quantities of specific cocoa polyphenols in the diet over time may prevent the glomming together of Aβ into oligomers that damage the brain, as a means to prevent Alzheimer’s disease.
The research team led by Dr. Pasinetti tested the effects of extracts from Dutched, Natural, and Lavado cocoa, which contain different levels of polyphenols. Each cocoa type was evaluated for its ability to reduce the formation of Aβ oligomers and to rescue synaptic function. Lavado extract, which has the highest polyphenol content and anti-inflammatory activity among the three, was also the most effective in both reducing formation of Aβ oligomers and reversing damage to synapses in the study mice.
“There have been some inconsistencies in medical literature regarding the potential benefit of cocoa polyphenols on cognitive function,” says Dr. Pasinetti. “Our finding of protection against synaptic deficits by Lavado cocoa extract, but not Dutched cocoa extract, strongly suggests that polyphenols are the active component that rescue synaptic transmission, since much of the polyphenol content is lost by the high alkalinity in the Dutching process.”
Because loss of synaptic function may have a greater role in memory loss than the loss of nerve cells, rescue of synaptic function may serve as a more reliable target for an effective Alzheimer’s disease drug, said Dr. Pasinetti.
The new study provides experimental evidence that Lavado cocoa extract may influence Alzheimer’s disease mechanisms by modifying the physical structure of Aβ oligomers. It also strongly supports further studies to identify the metabolites of Lavado cocoa extract that are active in the brain and identify potential drug targets.
In addition, turning cocoa-based Lavado into a dietary supplement may provide a safe, inexpensive and easily accessible means to prevent Alzheimer’s disease, even in its earliest, asymptomatic stages.
Researchers from Kanazawa University in Japan contributed to the study and the cocoa used in the study was a gift from Dr. Jeffrey Hurst of the Hershey Company.