Researchers discover how polyphenols from grape seed extract block toxic Alzheimer’s plaque formation.

UCLA.edu - The so-called “French paradox” refers to French consumption of food high in cholesterol and saturated fat yet low death rates from heart disease. Research has suggested it is the red wine consumed with all that fatty food that may be beneficial - and not only for cardiovascular health but in warding off certain tumors and even Alzheimer’s disease.

Now, Alzheimer’s researchers at UCLA, in collaboration with Mt. Sinai School of Medicine in New York, have discovered how red wine may reduce the incidence of the disease. Reporting in the November 21, 2008 issue of the Journal of Biological Chemistry, David Teplow, a UCLA professor of neurology, and colleagues show how naturally occurring compounds in red wine called polyphenols block the formation of proteins that build the toxic plaques thought to destroy brain cells, and further, how they reduce the toxicity of existing plaques, thus reducing cognitive deterioration.

Polyphenols comprise a chemical class with more than 8,000 members, many of which are found in high concentrations in wine, tea, nuts, berries, cocoa and various plants. Past research has suggested that such polyphenols may inhibit or prevent the buildup of toxic fibers composed primarily of two proteins - Aß40 and Aß42 - that deposit in the brain and form the plaques which have long been associated with Alzheimer’s. Until now, however, no one understood the mechanics of how polyphenols worked in brain cells.

Teplow’s lab has been studying how amyloid beta (Aß) is involved in causing Alzheimer’s. In this work, researchers monitored how Aß40 and Aß42 proteins folded up and stuck to each other to produce aggregates that killed nerve cells in mice. They then treated the proteins with a polyphenol compound extracted from grape seeds. They discovered that polyphenols carried a one-two punch: They blocked the formation of the toxic aggregates of Aß and also decreased toxicity when they were combined with Aß before it was added to brain cells.

“What we found is pretty straightforward,” Teplow said. “If the Aß proteins can’t assemble, toxic aggregates can’t form, and thus there is no toxicity. Our work in the laboratory, and Mt. Sinai’s Dr. Giulio Pasinetti’s work in mice, suggest that administration of the compound to Alzheimer’s patients might block the development of these toxic aggregates, prevent disease development and also ameliorate existing disease.”

Human clinical trials of polyphenols are next.

“No disease-modifying treatments of Alzheimer’s now exist, and initial clinical trials of a number of different candidate drugs have been disappointing,” Teplow said. “So we believe that this is an important next step.” Grape seed extract and other dietary polyphenol extract supplements have been available over-the-counter for years in the United States - it will be good to finally have better data on which polyphenols (or which combinations of them) might have the most health benefits and anti-aging effects.

Ki.se - The so called bad cholesterol (LDL) inhibits the breakdown of fat in cells of peripheral deposits, according to a study from the Swedish medical university Karolinska Institutet. The discovery reveals a novel function of LDL as a regulator of fat turnover besides its well-established detrimental effects in promoting atherosclerosis.

The study, which is a collaboration of two research groups at Karolinska Institutet, is published in the open-access journal PLoS ONE. It shows that LDL cholesterol slows the rate of fat breakdown (i.e. lipolysis) in adipocytes, the peripheral cells responsible for fat storage. Previously, it has been known that release of free fatty acid from the peripheral fat to the blood stream increases the synthesis of LDL precursors in the liver.

“The results of our study provide evidence of a reciprocal link between the liver and peripheral fat regulating fat turnover”, says study-initiator Dr Johan Björkegren.

The discovery also opens up for new theories for the well-established association between blood lipids and the metabolic syndrome.

“If proven of general physiological importance, therapies lowering LDL, as for instances statins, may also affect the turnover of peripheral fat,” continues Dr Björkegren.

The study and has been performed on cell cultures and tissues from humans as well as mouse models with different levels of LDL. The inhibitory effect was also shown to be dependent on LDL receptors on the surface of the fat cells.

“The exact intracellular mechanism for how the binding of LDL to the surface of the fat cells inhibits the breakdown of intracellular fat remains to be revealed”, say project leader Dr Josefin Skogsberg

Reference: Skogsberg J, et al. “ApoB100-LDL Acts as a Metabolic Signal from Liver to Peripheral Fat Causing Inhibition of Lipolysis in Adipocytes” PLoS One, 2008;3(11):e3771. Epub 2008 Nov 20.

The abstract in PubMed can be found here:

LDL cholesterol slows down peripheral fat metabolism

Ehponline.org - Maternal on-the-job exposure to hair sprays, some of which contain chemicals known as phthalates, has been linked to hypospadias in newborn boys, according to a study accepted for publication today by the peer-reviewed journal, Environmental Health Perspectives (EHP). Hypospadias is a birth defect of the male urethra that results in an abnormally placed urinary opening. It is one of the most common urogenital congenital anomalies among baby boys.

Phthalates, predominantly diethyl phthalate (DEP) and dibutyl phthalate (DBP) are present in many cosmetics including deodorants, fragrances, and nail and hair products. Studies have linked the phthalates or their metabolites, including monoethyl phthalate (MEP) and mono-n-butyl phthalate (MBP), with androgen-lowering activities, abnormal Leydig cell function, a decrease in anogenital distance in male infants, and reproductive tract malformations including hypospadias.

The case–control study included 471 hypospadias cases referred to surgeons, and 490 randomly selected birth controls, born over a 21-month period in South East England. Sons of women working in industries where there is exposure to phthalates - including hairdressers, beauty therapists, research chemists, line operators, pharmaceutical operators, electrical assemblers, and factory assistants - had a 2- to 3-times greater risk for hypospadias. The results add to growing evidence that endocrine-disrupting chemicals (EDCs) such as phthalates may play a role in hypospadias.

However, folate supplementation in the first three months of pregnancy was associated with a 36% reduction in risk of hypospadias. Additionally, there was no observed association between hypospadias risk and eating a vegetarian or vegan diet, contrary to the findings of earlier studies.

Study author Gillian Ormond, of the Department of Epidemiology and Public Health, Imperial College London wrote, “Measurements of exposure to phthalates and/or biomonitoring may help to understand possible pathways of exposure and toxicology, and provide quantitative estimates.”

EHP editor-in-chief Hugh A. Tilson, PhD, said, “The findings in this study are the first showing an association between occupational exposure to endocrine-disrupting chemicals in hair sprays and the risk of birth defects in newborn babies.”

A free PDF copy of this study can be downloaded from this web page:

Hair spray, pregnancy, folate, hypospadias

Aecom.yu.edu - A team of researchers has determined that certain commonly-prescribed headache pain medications may have the unintended consequence of increasing the frequency of migraine attacks. This important finding by investigators at the Albert Einstein College of Medicine of Yeshiva University could alter the way doctors prescribe migraine medicines.

In a recent article published in the journal Headache, the Einstein-led study of more than 8,000 migraine sufferers nationwide, found that the use of medications containing barbiturates or narcotics – which relieve migraine short-term – may make migraine worse if these medications are overused. Treatment with these classes of medicines was associated with an increased risk of transformed migraine (TM) headaches, a form of migraine characterized by 15 or more days of headache per month.

The finding is significant because 35 million Americans suffer from migraine headaches and an additional 5 million suffer from transformed migraine. Migraine symptoms include throbbing head pain, most commonly on one side. The pain can worsen with physical activity. Attacks most commonly last from 4 to 72 hours, but may persist for longer. More severe attacks are overwhelming and hinder daily activities. In addition to personal suffering, lost labor costs in the U.S. due to migraine are in excess of $13 billion per year, according to an earlier study from the Einstein team.

Principal investigator and senior author of the study, Richard Lipton, M.D. noted, “This confirms the longstanding feeling among many doctors that certain medications used to treat migraine may increase the frequency of headaches if overused. These findings have important public health implications.” Dr. Lipton is professor and vice chair of neurology at Einstein and also directs the Montefiore Headache Center.

The objective of the study was to assess the role of specific classes of acute medications in the development of transformed or chronic migraine (TM) in people with episodic migraine (EM). In the study, 8,219 people with episodic migraine were followed for one year; 2.5% developed TM over the course of the year. The use of commonly prescribed medications, particularly narcotics (such as acetaminophen with codeine or Percocet), or barbiturates (such as Fiorinal, Fioricet and Esgic) were associated with a dose-dependent increased risk of new onset of TM. That means episodic or occasional migraine sufferers who took narcotics or barbiturates more frequently were more likely to develop TM.

Conversely, for those study participants that suffered less than 10 headaches per month (EM sufferers), a class of drugs called triptans – known to relieve migraine – did not increase the risk of transformed migraine. NSAIDs (ibuprofen and naproxen sodium, for example) were protective against transition to TM for those suffering less than 10 headache days per month, but were associated with increased risk of transition to TM for those with high levels of monthly headache days.

“Proper treatment with the appropriate medicines can bring relief to most people with migraine,” said Dr. Lipton. “Primary care practitioners and patients should try to avoid the use of narcotic or barbiturate medications that may exacerbate migraine; if these drugs are necessary, patients should be advised of the risks of medication overuse and dose limits should be applied.”

Aecom.yu.edu - A NIH-funded study of over 92,000 post-menopausal women strongly suggests that regular attendance at religious services reduces the risk of death by approximately 20 percent. The findings, published in Psychology and Health, were based on data drawn from participants who spanned numerous religious denominations. The research was conducted by Eliezer Schnall, Ph.D., clinical assistant professor of psychology at Yeshiva College of Yeshiva University, and co-authored by Sylvia Wassertheil-Smoller, Ph.D., professor of epidemiology and population health at Einstein, as an ancillary study of the Women’s Health Initiative (WHI). The WHI is a national, long-term study aimed at addressing women’s health issues and funded by the National Institutes of Health.

The researchers evaluated the religious practices of 92,395 post-menopausal women participating in the WHI. They examined the prospective association of religious affiliation, religious service attendance, and strength and comfort derived from religion with subsequent cardiovascular events and overall rates of mortality. Although the study showed as much as a 20 percent decrease in the overall risk of mortality for those attending religious services, it did not show any consistent change in rates of morbidity and death specifically related to cardiovascular disease, with no explanation readily evident.

The study adjusted for participation of individuals within communal organizations and group activities that promote a strong social life and enjoyable routines, behaviors known to lead to overall wellness. However, even after controlling for such behavior and other health-related factors, the improvements in morbidity and mortality rates exceeded expectations.

“Interestingly, the protection against mortality provided by religion cannot be entirely explained by expected factors that include enhanced social support of friends or family, lifestyle choices and reduced smoking and alcohol consumption,” said Dr. Schnall, who was lead author of the study. “There is something here that we don’t quite understand. It is always possible that some unknown or unmeasured factors confounded these results,” he added.

During WHI enrollment, study participants, aged 50 to 79, were recruited on a voluntary basis from a variety of sources, from all over the nation. The women answered questions about baseline health conditions and religiosity and were followed by WHI researchers for an average of 7.7 years, with potential study outcomes of cardiovascular events and mortality adjudicated by trained physicians.

To evaluate the impact of religiosity on mortality and morbidity, the investigators looked at variables including self-report of religious affiliation, frequency of religious service attendance, and religious strength as well as comfort, in relation to coronary heart disease (CHD) and death. It is important to note that the study did not attempt to measure spirituality; rather, it examined self-report religiosity measures (irrespective of the participant’s religion). Participants answered three key questions at registration, regarding:

1) religious affiliation (yes or no);
2) how often services were attended (never, less than once per week, once per week, or more than once per week);
3) if religion provided strength and comfort (none, a little, a great deal).

Those attending religious services at least once per week showed a 20 percent mortality risk reduction mark compared with those not attending services at all. These findings corroborate prior studies that have shown up to a 25 percent reduction in such risk.

The study investigators concluded that although religious behavior (as defined by the study’s criteria) is associated with a reduction in death rates among the study population, the physical relationships leading to that effect are not yet understood and require further investigation. “The next step is to figure out how the effect of religiosity is translated into biological mechanisms that affect rates of survival,” said Dr. Smoller. “However, we do not infer causation even from a prospective study, as that can only be done through a clinical trial.

She added, “There may be confounding factors that we can’t determine, such as a selection bias, which would lead people who are at reduced risk for an impending event to also be the ones who attend services.”

The investigators are considering doing an analysis of psychological profiles of women in the study to determine if such profiles can help to explain the apparent protective effects of attending religious services.

HBNS.org - Overweight teens who weigh themselves at least once a week are more likely to engage in other healthy weight control measures than teens who step on the scale less frequently, according to a new small study.

Self-weighing can be a successful tool for adults, but some concern exists that recommending the behavior could backfire with teens who struggle with obesity.

“The fear is that an excessive focus on weight from frequent self-weighing may place teens at greater risk for engaging in unhealthy weight control behaviors and for developing an eating disorder,” said Mary Alm, Ph.D., lead study author, with the University of Minnesota.

However, that was not the case for study participants.

The study, published online in the Journal of Adolescent Health, followed the behavior of 130 teens who were in the 85th percentile for body mass index (BMI) during the past two years. Of the teens, 43 percent weighed themselves frequently and 57 percent were infrequent self-weighers.

Frequent self-weighers had a lower average weight, 180.3 pounds, whereas the infrequent weighers averaged 187.6 pounds. Frequent weighers were more likely to have lost 10 pounds in the past two years. The study also suggests that frequent self-weighers tend to eat fewer calories, consume less fatty food and junk food, and are more likely to stick to a structured diet.

The study could not determine whether self-monitoring specifically caused weight loss behaviors or was simply part of an overall weight loss strategy.

“Our results suggest that self-weighing may be a beneficial tool, but more research is needed before recommending self-weighing to teens for weight control,” Alm said.

Jack Hollis, Ph.D., senior investigator at the Kaiser Permanente Center for Health Research, said, “Self-monitoring of weight - as well as caloric intake, exercise and other behaviors - is a powerful tool for change, so there is good reason to expect that those who self-monitor will benefit, and that would include teens” [who do not seem to be at risk of having an eating disorder].

Reference: Alm ME, et al. Self-weighing and weight control behaviors among adolescents with a history of overweight. J Adolesc Health online, 2008.