Health Research Report

#170

14 DEC 2013 /  White paper draft

Compiled by Ralph Turchiano

Detailed research references and further affiliations on each article are posted at www.healthreserachreport.me .

In this Issue:

14.   New study shows link between perfluorinated compounds and diabetes

Evidence suggests that “healthy and overweight” is a myth

A systematic review and meta-analysis of observational studies published from 1950 until 2013 suggests that there is no such thing as being healthy and overweight, according to an article published in Annals of Internal Medicine. Persons in the same BMI category can have varied metabolic features, such as lipid profile, glucose tolerance, blood pressure, and waist circumference. Some obese individuals have normal metabolic features, despite their increased body fat. This profile has been described as “benign obesity” or “metabolically healthy obesity.” Similarly, some normal-weight individuals may have adverse metabolic features, despite having a healthy BMI. Researchers reviewed published research to assess the association between metabolic status and all-cause mortality and cardiovascular events in normal-weight (BMI, 18.5 to 25 kg/m2), overweight (BMI, 25 to 30 kg/m2), and obese adults. The research showed that metabolically healthy obese individuals were at increased risk for death and cardiovascular events over the long term compared with metabolically healthy normal-weight persons, suggesting that increased BMI without metabolic abnormalities is not a benign condition. The research also showed that regardless of BMI category, metabolically unhealthy individuals had increased risk for events compared with healthy normal-weight individuals. The researchers conclude that both BMI and metabolic status should be considered when evaluating an individual’s health risks. The authors of an accompanying editorial write that recognizing that there is no level of healthy obesity is the first step. Next, physicians need to focus on treating obesity as any other chronic disease that requires long-term attention.

Vitamin D Decreases Pain in Women with Type 2 Diabetes and Depression

Loyola Health Sciences research demonstrates additional benefits of supplement

MAYWOOD, Ill. – Vitamin D decreases pain in women with type 2 diabetes and depression, according to a study conducted at Loyola University Chicago. These findings were presented at an Oct. 24, 2013 research conference at Loyola’s Health Sciences Campus.

Type 2 diabetes is associated with depression and pain, but few studies have looked at how pain may affect the treatment of depression in patients with type 2 diabetes and no studies have evaluated the role of vitamin D supplementation on this association.

Researchers in this study tested the efficacy of weekly vitamin D2 supplementation (50,000 IUs) for six months on depression in women with type 2 diabetes. Depression significantly improved following supplementation. In addition, 61 percent of patients reported shooting or burning pain in their legs and feet (neuropathic pain) and 74 percent reported numbness and tingling in their hands, fingers, and legs (sensory pain) at the beginning of the study. Researchers found a significant decrease in neuropathic and sensory pain at three and six months following vitamin D2 supplementation.

“Pain is a common and often serious problem for women with type 2 diabetes and depression,” said Todd Doyle, PhD, lead author and fellow, Department of Psychiatry & Behavioral Neurosciences, Loyola University Chicago Stritch School of Medicine (SSOM). “While further research is needed, D2 supplementation is a promising treatment for both pain and depression in type 2 diabetes.”

Loyola researchers have received funding from the National Institute of Nursing Research to conduct a trial comparing the effects of two different doses of vitamin D3 supplements on health outcomes in women with diabetes.

“Vitamin D has widespread benefits for our health and certain chronic diseases such as type 2 diabetes,” said Sue Penckofer, PhD, RN, study co-author and professor, Loyola University Chicago Marcella Niehoff School of Nursing. “This NIH grant will allow us to shed greater light on understanding the role that this nutrient plays in managing the health of women with diabetes.”

Estrogen: Not just produced by the ovaries

MADISON – A University of Wisconsin-Madison research team reports today that the brain can produce and release estrogen — a discovery that may lead to a better understanding of hormonal changes observed from before birth throughout the entire aging process.

The new research shows that the hypothalamus can directly control reproductive function in rhesus monkeys and very likely performs the same action in women.

Scientists have known for about 80 years that the hypothalamus, a region in the brain, is involved in regulating the menstrual cycle and reproduction. Within the past 40 years, they predicted the presence of neural estrogens, but they did not know whether the brain could actually make and release estrogen.

Most estrogens, such as estradiol, a primary hormone that controls the menstrual cycle, are produced in the ovaries. Estradiol circulates throughout the body, including the brain and pituitary gland, and influences reproduction, body weight, and learning and memory. As a result, many normal functions are compromised when the ovaries are removed or lose their function after menopause.

“Discovering that the hypothalamus can rapidly produce large amounts of estradiol and participate in control of gonadotropin-releasing hormone neurons surprised us,” says Ei Terasawa, professor of pediatrics at the UW School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. “These findings not only shift the concept of how reproductive function and behavior is regulated but have real implications for understanding and treating a number of diseases and disorders.”

For diseases that may be linked to estrogen imbalances, such as Alzheimer’s disease, stroke, depression, experimental autoimmune encephalomyelitis and other autoimmune disorders, the hypothalamus may become a novel area for drug targeting, Terasawa says. “Results such as these can point us in new research directions and find new diagnostic tools and treatments for neuroendocrine diseases.”

The study, published today in the Journal of Neuroscience, “opens up entirely new avenues of research into human reproduction and development, as well as the role of estrogen action as our bodies age,” reports the first author of the paper, Brian Kenealy, who earned his Ph.D. this summer in the Endocrinology and Reproductive Physiology Program at UW-Madison. Kenealy performed three studies. In the first experiment, a brief infusion of estradiol benzoate administered into the hypothalamus of rhesus monkeys that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large pulsing surges.

In the second experiment, mild electrical stimulation of the hypothalamus caused the release of both estrogen and GnRH (thus mimicking how estrogen could induce a neurotransmitter-like action). Third, the research team infused letrazole, an aromatase inhibitor that blocks the synthesis of estrogen, resulting in a lack of estrogen as well as GnRH release from the brain. Together, these methods demonstrated how local synthesis of estrogen in the brain is important in regulating reproductive function.

The reproductive, neurological and immune systems of rhesus macaques have proven to be excellent biomedical models for humans over several decades, says Terasawa, who focuses on the neural and endocrine mechanisms that control the initiation of puberty. “This work is further proof that these animals can teach us about so many basic functions we don’t fully understand in humans.”

Leading up to this discovery, Terasawa said, recent evidence had shown that estrogen acting as a neurotransmitter in the brain rapidly induced sexual behavior in quails and rats. Kenealy’s work is the first evidence of this local hypothalamic action in primates, and in those that don’t even have ovaries.

“The discovery that the primate brain can make estrogen is key to a better understanding of hormonal changes observed during every phase of development, from prenatal to puberty, and throughout adultActive component of grape seed extract effective against cancer cellshood, including aging,” Kenealy says.

Eating healthy vs. unhealthy diet costs about $1.50 more per day

Meta-analysis pinpoints the price difference of consuming a healthy diet, which could be burden for low-income families but is trivial compared with health costs of eating an unhealthy diet

Boston, MA – The healthiest diets cost about $1.50 more per day than the least healthy diets, according to new research from Harvard School of Public Health (HSPH). The finding is based on the most comprehensive examination to date comparing prices of healthy foods and diet patterns vs. less healthy ones.

The study will be published online December 5, 2013 in BMJ (British Medical Journal) Open.

“People often say that healthier foods are more expensive, and that such costs strongly limit better diet habits,” said lead author Mayuree Rao, a junior research fellow in the Department of Epidemiology at HSPH. “But, until now, the scientific evidence for this idea has not been systematically evaluated, nor have the actual differences in cost been characterized.”

To address this question, the HSPH researchers conducted a meta-analysis of 27 existing studies from 10 high-income countries that included price data for individual foods and for healthier vs. less healthy diets. They evaluated the differences in prices per serving and per 200 calories for particular types of foods, and prices per day and per 2,000 calories (the United States Department of Agriculture’s recommended average daily calorie intake for adults) for overall diet patterns. Both prices per serving and per calorie were assessed because prices can vary depending on the unit of comparison.

The researchers found that healthier diet patterns—for example, diets rich in fruits, vegetables, fish, and nuts—cost significantly more than unhealthy diets (for example, those rich in processed foods, meats, and refined grains). On average, a day’s worth of the most healthy diet patterns cost about $1.50 more per day than the least healthy ones.

The researchers suggested that unhealthy diets may cost less because food policies have focused on the production of “inexpensive, high volume” commodities, which has led to “a complex network of farming, storage, transportation, processing, manufacturing, and marketing capabilities that favor sales of highly processed food products for maximal industry profit.” Given this reality, they said that creating a similar infrastructure to support production of healthier foods might help increase availability—and reduce the prices—of more healthful diets.

“This research provides the most complete picture to-date on true cost differences of healthy diets,” said Dariush Mozaffarian, the study’s senior author and associate professor at HSPH and Harvard Medical School. “While healthier diets did cost more, the difference was smaller than many people might have expected. Over the course of a year, $1.50/day more for eating a healthy diet would increase food costs for one person by about $550 per year. This would represent a real burden for some families, and we need policies to help offset these costs. On the other hand, this price difference is very small in comparison to the economic costs of diet-related chronic diseases, which would be dramatically reduced by healthy diets.”

Progesterone changes may cause cognitive impairment of Alzheimer’s disease patients

Steroid hormones and their metabolites within the central nervous system are commonly defined as neuroactive steroids or neurosteroids. Although neuroactive steroids have been shown to improve learning and memory ability and protect against amyloid beta (Aβ) peptide-induced neurotoxicity, changes in their level during Alzheimer’s disease and their role in Aβ-mediated cognitive impairment remain elusive given the limitation in sample sizes and analysis methods. To gain a better understanding on the role of neuroactive steroids in the pathology of Alzheimer’s disease, Dr. Sha Liu and colleagues from Hebei Medical University, China investigated the effect of progesterone administration against Aβ25–35-induced impairment in vivo. In their study, intracerebral injection of aggregated Aβ25–35 into the bilateral hippocampal CA1 region impaired learning and memory abilities of rats, accompanied by reduced levels of progesterone. Treatment of these Alzheimer’s disease rats with exogenous progesterone could reverse cognitive impairment. Therefore, this study, published in the Neural Regeneration Research (Vol. 8, No. 30, 2013), provides a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.

Does zinc supplementation reduce aluminum-induced neurotoxicity?

Studies have shown that aluminum neurotoxicity can likely affect learning and memory function, and a diet containing 100–200 mg/kg zinc is adequate for maintaining learning and memory function in rats. Previous findings by Dr. Hao Lu and coworkers from Academy of Military Medical Sciences, China showed that male Wistar rats after treatment with aluminum chloride at a dose of 300 mg/kg daily for 7 weeks exhibited decreased acetylcholinesterase activity and enhanced lipid peroxidation in the cerebrum, appearing to have neurotoxic performance. A new study from these researchers further evaluated the effect of zinc supplementation on aluminum-induced neurotoxicity, and found zinc supplementation exhibited an antioxidant capacity. This study, published in the Neural Regeneration Research (Vol. 8, No. 29, 2013), can provide new targets and approaches for prevention and treatment of central nervous system diseases and open up new ideas for in-depth study of the relationship between zinc and brain function.

Researchers see added nutritional benefits in organic milk

Organic forage raises levels of beneficial fats

PULLMAN, Wash.—A team led by a Washington State University researcher has found that organic milk contains significantly higher concentrations of heart-healthy fatty acids compared to milk from cows on conventionally managed dairy farms. While all types of milk fat can help improve an individual’s fatty acid profile, the team concludes that organic whole milk does so even better.

The study is the first large-scale, U.S.-wide comparison of organic and conventional milk, testing nearly 400 samples of organic and conventional milk over an 18-month period. Conventional milk had an average omega-6 to omega-3 fatty acid ratio of 5.8, more than twice that of organic milk’s ratio of 2.3. The researchers say the far healthier ratio of fatty acids in organic milk is brought about by a greater reliance on pasture and forage-based feeds on organic dairy farms.

A large body of research has shown that grass and legume forages promote cow health and improve the fatty acid profile in organic dairy products. Still, said WSU researcher Dr. Charles Benbrook, the study’s lead author, “We were surprised by the magnitude of the nutritional quality differences we documented in this study.”

After fruits and vegetables, dairy products are the largest category of the growing, $29 billion organic food sector, according to the Organic Trade Association’s 2013 Organic Industry Survey. Organic milk and cream sales were worth $2.622 billion, the survey found. Overall, organic milk accounted for 4 percent of fluid milk sales last year, according to the Milk Processor Education Program.

The consumption of more omega-6 fatty acids than omega-3 fatty acids is a well-known risk factor for a variety of health problems, including cardiovascular disease, cancer, excessive inflammation, and autoimmune diseases. The higher the ratio of omega-6 to omega-3, the greater the associated health risk.

Western diets typically have a ratio of about 10-to-1 to 15-to-1, while a ratio of 2.3-to-1 is thought to maximize heart health. The team modeled a hypothetical diet for adult women with a baseline omega-6 to omega-3 ratio of 11.3, and looked at how far three interventions could go in reducing the ratio to 2.3.

They found that almost 40 percent of the needed nine-point drop could be achieved by switching from three daily servings of conventional dairy products to 4.5 daily servings of mostly full-fat organic dairy products. Women who also avoid a few foods each day that are high in omega-6 fatty acids can lower their fatty acid ratio to around 4, 80 percent of the way to the 2.3 goal.

“Surprisingly simple food choices can lead to much better levels of the healthier fats we see in organic milk,” says Benbrook.

The team also compared the fatty acids in dairy products to those in fish.

“We were surprised to find that recommended intakes of full-fat milk products supply far more of the major omega-3 fatty acid, ALA, than recommended servings of fish,” says co-author and WSU research associate Donald R. Davis. Conventional milk had about nine times more ALA than fish while organic milk had 14 times more, he says. Organic milk is also a significant source of two other omega-3 fatty acids, EPA and DPA, but not DHA.

You are what your father eats

McGill study suggests that a father’s diet before conception plays a crucial role in the health of his offspring

Mothers get all the attention. But a study led by McGill researcher Sarah Kimmins suggests that the father’s diet before conception may play an equally important role in the health of their offspring. It also raises concerns about the long-term effects of current Western diets and of food insecurity.

The research focused on vitamin B9, also called folate, which is found in a range of green leafy vegetables, cereals, fruit and meats. It is well known that in order to prevent miscarriages and birth defects mothers need to get adequate amounts of folate in their diet. But the way that a father’s diet can influence the health and development of their offspring has received almost no attention. Now research from the Kimmins group shows for the first time that the father’s folate levels may be just as important to the development and health of their offspring as are those of the mother. Indeed, the study suggests that fathers should pay as much attention to their lifestyle and diet before they set out to conceive a child as mothers do.

“Despite the fact that folic acid is now added to a variety of foods, fathers who are eating high-fat, fast food diets or who are obese may not be able to use or metabolize folate in the same way as those with adequate levels of the vitamin,” says Kimmins. “People who live in the Canadian North or in other parts of the world where there is food insecurity may also be particularly at risk for folate deficiency. And we now know that this information will be passed on from the father to the embryo with consequences that may be quite serious.”

The researchers arrived at this conclusion by working with mice, and comparing the offspring of fathers with insufficient folate in their diets with the offspring of fathers whose diets contained sufficient levels of the vitamin. They found that paternal folate deficiency was associated with an increase in birth defects of various kinds in the offspring, compared to the offspring of mice whose fathers were fed a diet with sufficient folate.

“We were very surprised to see that there was an almost 30 per cent increase in birth defects in the litters sired by fathers whose levels of folates were insufficient,” said Dr. Romain Lambrot, of McGill’s Dept. of Animal Science, one of the researchers who worked on the study. “We saw some pretty severe skeletal abnormalities that included both cranio-facial and spinal deformities.”

The research from the Kimmins’ group shows that there are regions of the sperm epigenome that are sensitive to life experience and particularly to diet. And that this information is in turn transferred to a so-called epigenomic map that influences development and may also influence metabolism and disease in the offspring in the long-term. (The epigenome is like a switch, which is affected by environmental cues, and is involved in many diseases including cancer and diabetes. The epigenome influences the way that genes are turned on or off, and hence how heritable information gets passed along).

Although it has been known for some time that there is a massive erasure and re-establishment that takes place in the epigenome as the sperm develops, this study now shows that along with the developmental map, the sperm also carries a memory of the father’s environment and possibly even of his diet and lifestyle choices.

“Our research suggests that fathers need to think about what they put in their mouths, what they smoke and what they drink and remember they are caretakers of generations to come,” said Kimmins. “If all goes as we hope, our next step will be to work with collaborators at a fertility clinic so that we can start assessing the links in men between diet, being overweight and how this information relates to the health of their children.”

Long-term use of common heartburn and ulcer medications linked to vitamin B12 deficiency

OAKLAND, Calif. — Long-term use of commonly prescribed heartburn and ulcer medications is linked to a higher risk of vitamin B12 deficiency, according to a new study published in the Journal of the American Medical Association.

Left untreated, vitamin B12 deficiency can increase the risk of dementia, nerve damage, anemia, and other medical complications, some of which may be irreversible. Stomach acid aids in vitamin B12 absorption; suppressing the acids can lead to the health-threatening vitamin deficiency.

Researchers examined the electronic health records (including diagnoses, pharmacy orders, and laboratory results) of 25,956 adult Kaiser Permanente patients diagnosed with vitamin B12 deficiency in Northern California between January 1997 and June 2011, and compared them with 184,199 patients without B12 deficiency during the same time period.

This is the first large, population-based study linking vitamin B12 deficiency to acid-suppressing medications, which are among the most commonly used pharmaceuticals in the United States. In 2012, about 15 million people received 157 million prescriptions for a class of anti-acid medications known as protein pump inhibitors (PPIs).

“Patients who took PPI medications for more than two years had a 65 percent increase in their risk of B12 deficiency,” said Douglas A. Corley, MD, PhD, a gastroenterologist and research scientist with the Kaiser Permanente Division of Research. “Higher doses also were associated with an increased risk, compared with lower doses. Kaiser Permanente’s electronic health records allowed us to look at what happens in the real world for these commonly used medications.”

While PPIs and a related class of anti-acid medications called histamine-2-receptor agonists (H2RAs) are usually prescribed by physicians, some are widely available over the counter without a prescription.

Among the 25,956 patients who had vitamin B12 deficiency, 12 percent used PPIs for at least two years, compared with 7.2 percent of the control patients. The impact of taking any daily dosage of H2RA medications was less pronounced but also significant: 4.2 percent of patients with B12 deficiency used these medications versus 3.2 percent of control patients.

“This research raises the question of whether people who are taking acid-depressing medications long term should be screened for vitamin B12 deficiency,” Dr. Corley said. “It’s a relatively simple blood test, and vitamin supplements are an effective way of managing the vitamin deficiency, if it is found.”

Kaiser Permanente can conduct transformational health research such as this study in part because it has the largest private patient-centered electronic health system in the world. The organization’s electronic health record system, Kaiser Permanente HealthConnect®, securely connects 9.1 million patients to 16,000 physicians in almost 600 medical offices and 38 hospitals. It also connects Kaiser Permanente’s research scientists to one of the most extensive collections of longitudinal medical data available, facilitating studies and important medical discoveries that shape the future of health and care delivery for patients and the medical community.

In addition to Dr. Corley, co-authors of the study were Jameson R. Lam, MPH, Jennifer L. Schneider, MPH, and Wei Zhao, MPH, all of the Kaiser Permanente Division of Research in Oakland, Calif.

Gut microbes affect MicroRNA response to bacterial infection

When it comes to fighting off pathogens like Listeria, your best allies may be the billions of microorganisms that line your gut, according to new research published in mBio®, the online open-access journal of the American Society for Microbiology. The study reveals that germ-free mice are more susceptible to infection with the foodborne pathogen Listeria monocytogenes than mice with conventional intestinal microbiota.

The authors were also able to show that expression of five intestinal microRNA (miRNA) molecules decreases in conventional mice upon Listeria infection while it did not in germ-free mice, indicating that the gut microbiota may determine, at least in part, how the mouse genome expression is reprogrammed in the gut and how the animal responds to an infection.

“We were surprised by the robustness of the intestinal miRNA signature in germ-free mice and conventional mice,” says corresponding author Pascale Cossart of the Institut Pasteur in Paris, France. “Our results show that even very small variations in miRNA expression can have important outcomes,” for the health of the animals, says Cossart.

In recent years, researchers have come to recognize that the gut microbiota is an indispensable partner in the development of an animal’s immune response and in maintaining its internal stability, but few studies have addressed the impact the microbiota has on miRNA expression during bacterial infections. Cossart and her colleagues approached the matter using the system they know best: Listeria infection. L. monocytogenes is a frequent contaminant of raw milk products, and a highly publicized outbreak traced to Listeria-contaminated cantaloupe left 30 people dead in the fall of 2011.

Previous studies in Cossart’s lab have shown that during infection with Listeria, the bacterium AND the host both reprogram their protein manufacturing using small non-coding RNA molecules like miRNA – pieces of genetic material that are used to selectively regulate the creation of proteins. Here, the researchers used conventional mice and germ-free mice to address the question of whether – and how – the gut microbiota has an effect on the course of infection and on the production of these regulatory miRNA molecules.

When it comes to susceptibility to infection, the results were unequivocal: 24 hours after infection, germ-free mice harbored 10,000 times more L. monocytogenes bacteria in their small intestines and about 1,000 times more Listeria in their mesenteric lymph nodes than did the conventional mice.

At the level of miRNA, however, the differences were not immediately evident: the most highly expressed miRNAs were produced at the same levels in both types of mice and they didn’t change much after infection. Nevertheless, the production of five miRNAs decreased after infection only in the conventional mice, indicating that the presence of the microbiota influences the level of miRNA expression.

“We found that even though the intestinal miRNA signature is globally stable, Listeria infection can affect the host miRNA response in a microbiota-dependent manner,” says Cossart. When paralleled with the lower susceptibility of the conventional mice to infection, these down-regulated regulatory molecules present an intriguing result, write the authors.

Cossart says that this study and others indicate that miRNA may be involved in protecting the host from infection, but their precise role isn’t yet clear. She notes that although this study was conducted in mice, miRNA and the protein coding gene targets they regulate may be very similar in mice and in humans. Cossart and her colleagues are planning to follow up on the work to try and figure out what impacts the changes in miRNA expression mean for the networks of protein-coding genes they regulate.

Low vitamin B12 levels increase the risk of fractures in older men

News: Nov 25, 2013

Older men who have low levels of vitamin B12 have a higher risk of having fractures. These are the findings of researchers at the Sahlgrenska Academy as a part of an international study of a total of 1000 older men.

Osteoporosis is one of the world’s most widespread diseases, and intensive research is under way worldwide to identify its causes and to be able to prevent fractures.

In an extensive study, researchers at the Sahlgrenska Academy at the University of Gothenburg can now show that low levels of vitamin B12 in the blood increases the risk of fractures in older men.

International research project

This study is a part of an international research project initiated by the National Institutes of Health (NIH) in the US and comprises 11,000 men in total. In their part of the study, the Gothenburg researchers studied 1,000 Swedish men, MrOS Sweden, with an average age of 75, and used various methods to analyze the blood concentrations of the B vitamins B12 and folate, which are found in our food naturally.

Higher fracture risk

The results show that the risk of suffering a fracture six years later was higher among men who had low B12 levels at the beginning of the study than men with normal B12 levels. In the quartile with the lowest B12 content, the risk was elevated by approximately 70 percent compared with the others. The risk increase pertained primarily to fractures in the lumbar region, where the risk increase was up to 120 percent.

“The higher risk also remains when we take other risk factors for fractures into consideration, such as age, smoking, BMI, BMD (bone mineral density), previous fractures, physical activity, the D-vitamin content in the blood and calcium intake,” says Catharina Lewerin, researcher at the Sahlgrenska Academy.

Does this mean that older men can prevent fractures by eating more vitamin B12?

“It has not been scientifically established, but such studies are under way, including one large Dutch study where older individuals over the age of 65 are treated with both vitamin B12, folic acid and vitamin D to investigate the occurrence of fractures.

“Right now, there is no reason to eat more vitamin B12, but rather treatment shall only be applied in confirmed cases of deficiencies and in some cases to prevent deficiencies. For anyone who wants to strengthen their bones and prevent fractures, physical activity 30 minutes a day and quitting smoking is good self care,” says Catharina Lewerin.

New method

In this study, the researchers used a relatively new method called holotranscobalamin, which measures the amount of vitamin that is taken up in the cells, which is considered to be a more sensitive test for B12 deficiency.

The article Low holotranscobalamin and cobalamins predict incident fractures in elderly men; The MrOS Sweden was published online in Osteoporosis International.

Dietary amino acids relieve sleep problems after traumatic brain injury in animals

In CHOP neuroscience lab, research suggests possible treatments for TBI in humans

Scientists who fed a cocktail of key amino acids to mice improved sleep disturbances caused by brain injuries in the animals. These new findings suggest a potential dietary treatment for millions of people affected by traumatic brain injury (TBI)—a condition that is currently untreatable.

“If this type of dietary treatment is proved to help patients recover function after traumatic brain injury, it could become an important public health benefit,” said study co-leader Akiva S. Cohen, Ph.D., a neuroscientist at The Children’s Hospital of Philadelphia (CHOP).

Cohen is the co-senior author of the animal TBI study appearing today in Science Translational Medicine. He collaborated with two experts in sleep medicine: co-senior author Allan I. Pack, M.D., Ph.D., director of the Center for Sleep and Circadian Neurobiology in the Perelman School of Medicine at the University of Pennsylvania; and first author Miranda M. Lim, M.D., Ph.D., formerly at the Penn Sleep Center, and now on faculty at the Portland VA Medical Center and Oregon Health and Science University.

Every year in the U.S., an estimated 2 million people suffer a TBI, accounting for a major cause of disability across all age groups. Although 75 percent of reported TBI cases are milder forms such as concussion, even concussion may cause chronic neurological impairments, including cognitive, motor and sleep problems.

“Sleep disturbances, such as excessive daytime sleepiness and nighttime insomnia, disrupt quality of life and can delay cognitive recovery in patients with TBI,” said Lim, a neurologist and sleep medicine specialist. Although physicians can relieve the dangerous swelling that occurs after a severe TBI, there are no existing treatments to address the underlying brain damage associated with neurobehavioral problems such as impaired memory, learning and sleep patterns.

Cohen and team investigate the use of selected branched chain amino acids (BCAA)—precursors of the neurotransmitters glutamate and GABA, which are involved in communication among neurons and help to maintain a normal balance in brain activity. His research team previously showed that a BCAA diet restored cognitive ability in brain-injured mice. The current study was the first to analyze sleep-wake patterns in an animal model.

Comparing mice with experimentally induced mild TBI to uninjured mice, the scientists found the injured mice were unable to stay awake for long periods of time. The injured mice had lower activity among orexin neurons, which help to maintain the animals’ wakefulness. This is similar to results in human studies showing decreased orexin levels in the spinal fluid after TBI.

In the current study, the dietary therapy restored the orexin neurons to a normal activity level and improved wakefulness in the brain-injured mice. EEG recordings also showed improved brain wave patterns among the mice that consumed the BCAA diet.

“These results in an animal model provide a proof-of-principle for investigating this dietary intervention as a treatment for TBI patients,” said Cohen. “If a dietary supplement can improve sleeping and waking patterns as well as cognitive problems, it could help brain-injured patients regain crucial functions.” Cohen cautioned that current evidence does not support TBI patients medicating themselves with commercially available amino acids.

Personal care products are possible sources of potentially harmful parabens for babies

Through lotions, shampoos and other personal care products (PCPs), infants and toddlers are likely becoming exposed to potentially harmful substances, called parabens, at an even higher level than adult women in the U.S., researchers have reported. They published their findings on parabens, which have been linked to reproductive and other health issues, in the ACS journal Environmental Science & Technology.

Kurunthachalam Kannan and Ying Guo point out that the substances called phthalates and parabens are used in a wide range of products, from medical devices to children’s toys, as well as PCPs. Phthalates hold in moisture; parabens are used as preservatives. Most people are exposed to them every day — for example, data from the U.S. Centers for Disease Control and Prevention suggests that more than 90 percent of the population is exposed to these substances. The body breaks them down quickly, but both have been detected in urine, breast milk and blood. Research suggests a link between these substances and health issues in animals and people, such as sperm damage, breast cancer and an increased risk for asthma. In previous studies, Kannan’s team found that food and indoor dust contributed to phthalate exposure to varying degrees, but paraben exposure was low. Now it was time for them to look at a third route of possible exposure — the use of PCPs.

They collected 170 samples of makeup, lotions, shampoos and other products, including 20 items for babies, and tested them for nine phthalates and six parabens. Both substances were found in PCPs. In baby products, phthalate concentrations were low, but parabens were common. When the researchers calculated possible exposure levels, they estimated that the potential daily skin exposure to parabens by infants and toddlers could be as much as two to three times higher than that for adult women.

New study shows link between perfluorinated compounds and diabetes

Press release Published 2013-12-12

Perfluorinated  compounds are environmental toxins that are found in fire extinguishing foam and water-repellent textiles and, for example. In a new study, a research team led from Uppsala University has seen links between high levels of perfluorinated compounds in the blood and diabetes.

The research group at Uppsala University has previously shown associations between high levels of environmental toxins, such as PCB, pesticides, and phthalates and diabetes. In the new study they have investigated whether elevated levels of another type of environmental toxin, so-called perfluorinated compounds, are related to diabetes. Perfluorinated compounds are used in a wide variety of industrial and consumer products, including fire fighting foam, non-stick cookware, and grease and water-repellent materials such as food contact material, ski wax and GoreTex, for example.

In a group of more than a thousand 70-year-old men and women from Uppsala, levels of seven different perfluorinated compounds were measured in the blood and related to whether the individuals had diabetes (114 persons) or not. These seven perfluorinated compounds was detectable in virtually all individuals in the study.

–   We saw that high levels, especially of one of the perfluorinated compounds, perfluorononanoic acid (PFNA), were linked to diabetes. Perfluorooctanoic acid (PFOA) was also associated with diabetes in this group. We also saw that PFOA was linked to disrupted secretion of insulin from the pancreas, explains Monica Lind, associate professor at the Division of Occupational and Environmental Medicine at Uppsala University.

The study raises the question of whether high levels of certain perfluorinated compounds, which were found in all individuals in this study, are linked to the development of diabetes.

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These reports are done with the appreciation of all the Doctors, Scientist, and other Medical Researchers who sacrificed their time and effort. In order to give people the ability to empower themselves. Without base aspirations of fame, or fortune. Just honorable people, doing honorable things.

Health Research Report

#170

14 DEC 2013 /  White paper draft

Compiled by Ralph Turchiano

Detailed research references and further affiliations on each article are posted at www.healthreserachreport.me .

In this Issue: