204 CNO Report 10 APR 2015


clip_image002CNO Report 204

Release Date 10 APR 2015

Draft Report Compiled by

Ralph Turchiano



In this issue:

1. UF study finds vitamin D can affect pain, movement in obese osteoarthritis patients

2. Study: Increased dietary magnesium intake associated with improved diabetes-related health outcomes

3. 1,000-year-old onion and garlic remedy kills antibiotic-resistant bugs

4. Folic acid may help elderly weather heat waves

5. Scientists reveal unique mechanism of natural product with powerful antimicrobial action

6. Study finds eyeliner application may cause eye problems

7. Common antidepressant increased coronary atherosclerosis in animal model

8. New report links frequency of diet soda use to waist increases

9. New study indicates that exercise improves non-alcoholic fatty liver disease

10. Microbes help produce serotonin in gut

11. Sellers of Fake Amazon Reviews Face Lawsuit


UF study finds vitamin D can affect pain, movement in obese osteoarthritis patients


GAINESVILLE, Fla. — Got milk? If you are overweight and have osteoarthritis, you may want to bone up on your dairy products that have vitamin D. According to a University of Florida study, higher levels of vitamin D may decrease pain and improve function in obese individuals with osteoarthritis.

Findings published in the January issue of The Clinical Journal of Pain indicate that obese individuals who suffer from osteoarthritis and have adequate vitamin D levels could walk, balance and rise from sitting to standing better than obese participants with insufficient vitamin D levels. The findings suggest an association between obesity and vitamin D status for tasks such as standing from a seated position.

“Adequate vitamin D may be significant to improving osteoarthritis pain because it affects bone quality and protects cell function to help reduce inflammation. Vitamin D maintains calcium and phosphate concentration levels to keep bones strong,” said lead author Toni L. Glover, an assistant professor in the UF College of Nursing, part of UF Health. “Increased pain due to osteoarthritis could limit physical activity, including outdoor activity, which would lead to both decreased vitamin D levels and increased obesity.”

Osteoarthritis is the most common form of arthritis, affecting millions of people worldwide. It occurs when the protective cartilage on the ends of bones wears down over time, causing pain, stiffness and loss of joint movement.

The researchers analyzed blood samples for vitamin D levels from a racially diverse group of 256 middle-aged and older adults. Participants also provided a self-report of knee osteoarthritis pain and completed functional performance tasks such as balance, walking and rising from sitting to standing. This study was part of a larger project that studies racial and ethnic differences in pain in individuals with osteoarthritis. Among the 126 obese participants, 68 were vitamin D-deficient while only 29 of the 130 non-obese participants were deficient, suggesting obesity is significantly associated with clinically relevant vitamin D deficiency.

Obesity is associated with vitamin D deficiency, knee osteoarthritis pain and poor functional performance. Vitamin D is stored in the liver and human fat cells, and previous research has shown that the larger fat amount in obese people can cause vitamin D to be stored instead of circulated in the body.

The Institute of Medicine recommends that adults ages 18-70 get 600 international units of vitamin D per day and adults over 71 get at least 800 international units of vitamin D per day. For context, an 8-ounce glass of fortified milk contains about 100 international units of calcium. Foods rich in vitamin D include salmon, tuna, sardines, shrimp, mushrooms, egg yolks and foods fortified with vitamin D, such as milk and some cereals, yogurts and orange juices. The body also produces vitamin D through sun exposure, although it can be hard to get enough from the sun alone from the winter sun in some climates and sunscreens block the vitamin’s production.

“Vitamin D is inexpensive, available over-the-counter and toxicity is fairly rare,” Glover said. Older obese patients with chronic pain should discuss their vitamin D status with their primary care provider. If it’s low, take a supplement and get judicious sun exposure.”


This research was supported by the National Institutes of Health/National Institute on Aging (grant number R01AG033906, Dr. Roger Fillingim, PI) and the University of Florida Clinical and Translational Science Institute (grant number UL1TR000064). Additionally, support came from the John A. Hartford Foundation (2011-2013) as a Building Academic Geriatric Nursing Capacity Scholar and a Mayday Fund grantee (grant number AAN 11-116).


Study: Increased dietary magnesium intake associated with improved diabetes-related health outcomes


Northridge, CA (March 30, 2015) – A recent analysis published in the Journal of Human Nutrition & Food Science reveals a beneficial relationship between dietary magnesium intake and diabetes-related outcomes including decreased risk for metabolic syndrome, obesity or overweight, elevated blood pressure, and reduced HDL (good) cholesterol(1).

This secondary analysis examined the relationship between dietary magnesium intake from food and food combined with supplements and diabetes and other related health factors in adults (? 20 years) using data from the National Health and Nutrition Examination Survey (NHANES), 2001-2010. NHANES is a program of studies designed to assess the health and nutritional status of adults and children in the United States, conducted by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC).

“Our analysis found that dietary intake of magnesium from foods or from food plus supplements was associated with improvements in many diabetes-related health outcomes. These results further demonstrate the importance of meeting magnesium intake recommendations and illustrate the usefulness of dietary magnesium supplementation when these recommendations cannot be met with diet alone.” said Yanni Papanikolaou, Vice President of Nutrition Research at Nutritional Strategies, Inc. and co-lead researcher of the analysis.

Magnesium, an essential micronutrient, assists in more than 300 metabolic reactions, helping support bone health, as well as nerve and muscle function. It also helps convert food to cellular energy. Sources of dietary magnesium include fruits, green leafy vegetables, whole grains, nuts and dairy products. The estimated average requirement (EAR) for magnesium is 330-350 mg/day for men and 225-265 mg/day for women. The 2010 Dietary Guidelines, and more recently the 2015 Dietary Guidelines Advisory Committee Report, indicate magnesium is commonly under-consumed relative to the estimated average requirements (EAR).

“Insufficiency of micronutrient intake is a global issue,” commented Dr. James Brooks, Vice President, Science, Technology and Quality, Pharmavite, and study author. “Dietary magnesium supplementation, coupled with appropriate food choices, offers an evidence-based option to meet the estimated average requirements.

The analysis funded by Pharmavite LLC, makers of Nature Made® brand dietary supplements, included data from more than 14,000 NHANES participants. Adults aged > 20 years with adequate intake (defined as meeting the EAR) of magnesium from food alone had significantly lower odds ratios for metabolic syndrome (0.88, p=0.0166), overweight or obesity (0.91, p=0.0305) elevated blood pressure (0.88, p=0.0205), elevated systolic blood pressure (0.87, p=0.0070) and reduced HDL (0.84, p=0.0039) compared to adults with inadequate intake of magnesium from food. Additionally, magnesium intake from food in combination with dietary supplements had significantly lower odds ratios for elevated glycohemoglobin (0.88, p=0.0046), obesity (0.92, p=0.85), overweight or obesity (0.86, p=0.0011), elevated waist circumference (0.88, p=0.0057) and reduced HDL (0.81, p=0.0034) compared to adults with inadequate intake of magnesium from food plus supplements.

Because this analysis is an examination of survey data, it does not indicate cause and effect, but rather demonstrates associations between dietary magnesium intake and health outcomes. Although results of this analysis may have been limited by errors in self-reported dietary intake and use of a 24-hour dietary recall, NHANES is recognized as a very credible source for dietary patterns and health outcomes data.


Access the full study, entitled “Dietary Magnesium Usual Intake is Associated with Favorable Diabetes-Related Physiological Outcomes and Reduced Risk of Metabolic Syndrome: An NHANES 2001-2010 Analysis,” at http://www.jscimedcentral.com/Nutrition/nutrition-2-1038.pdf. Study authors include Yanni Papanikolaou, Nutritional Strategies, Inc.; James Brooks, Pharmavite, LLC; Carroll Reider, Pharmavite, LLC; and Victor L. Fulgoni, III, Nutrition Impact, LLC.

About Pharmavite LLC:

For more than 40 years, Pharmavite LLC has earned and maintained the trust of healthcare professionals, consumers, and retailers by manufacturing high-quality vitamins, minerals and other dietary supplements, and all-natural foods under its Nature Made® andSOYJOY® brand names. Based in Northridge, California, Pharmavite LLC operates as a subsidiary of Otsuka Pharmaceutical Co., Ltd. For more information, please visitPharmavite.com.

(1) Papanikolaou Y, Brooks J, Reider C, Fulgoni VL (2014) Dietary Magnesium Usual Intake is Associated with Favorable Diabetes-Related Physiological Outcomes and Reduced Risk of Metabolic Syndrome: An NHANES 2001-2010 Analysis. J Hum Nutr Food Sci 2(4): 1044.

1,000-year-old onion and garlic remedy kills antibiotic-resistant bugs

The simple salve is more effective than modern antibiotics.


A 1,000-year-old Anglo-Saxon ‘eye salve’ made from onion, garlic, wine and part of a cow’s stomach has been shown to wipe out 90 percent of antibiotic-resistant Staphylococcus aureus, otherwise known as MRSA. And it works better than modern antibiotics in both lab and mouse models.

The 9th Century ‘eye salve’ recipe was originally found in Bald’s Leechbook – an old English manuscript held by the British Library.

It was translated from ancient Anglo-Saxon by researchers at the University of Nottingham in the UK, in the hopes of finding new solutions to the growing problem of antibiotic resistance – which a recent report has predicted will kill 300 million people by 2050. But the team wasn’t expecting to find something so potent.

“We did not see this coming at all,” said microbiologist Freya Harrison, the lead researcher, in the press video below.

“We thought that Bald’s eye salve might show a small amount of antibiotic activity. … But we were absolutely blown away by just how effective the combination of ingredients was,” she added in a press release.

To find out whether the ancient eye salve worked, they made the recipe as faithfully as possible – even using wine from a vineyard that existed back in the 9th Century – and then tested it against large MRSA cultures in the lab. They also tested each individual ingredient on its own against the superbugs, as well as a control solution.

Incredibly, they found that the eye salve killed up to 90 percent of MRSA bacteria, but only when all the ingredients were used together.

The team then went on to test the salve on biofilms of MRSA – sticky colonies of bacteria that are notoriously difficult for antibiotics to penetrate, and which pose a particular problem on hospital equipment. The results were the same.

The next step was to ship the eye salve off to the United States where it was tested on in vivo mouse wounds as a topical treatment. Again, it wiped out most of the MRSA cells after just 24 hours and was more efficient than modern antibiotics.

“I still can’t quite believe how well this 1,000-year-old antibiotic actually seems to be working,” said Harrison in the release. “We tested it in difficult conditions too.”

The team presented their findings at the Annual Conference of the Society for General Microbiology, in Birmingham, on Monday. However they’re still not sure exactly how the remedy works, and finding that out will be the next step.

Keen to try the Bald’s eye salve? You can make your own topical treatment by following the recipe, kindly translated by the BBC, below.

Bald’s eye salve

– Equal amounts of garlic and another allium (onion or leek), finely chopped and crushed in a mortar for two minutes.

– Add 25ml (0.87 fl oz) of English wine – in this case, taken from a historic vineyard near Glastonbury.

– Dissolve bovine salts in distilled water, add and then keep chilled for nine days at 4 degrees Celsius before straining through a cloth to remove particulates.

Public Release: 31-Mar-2015

Folic acid may help elderly weather heat waves

Penn State

Supplemental folic acid can enhance blood vessel dilation in older adults, according to Penn State researchers, suggesting that folic acid supplements may be an inexpensive alternative for helping older adults to increase skin blood flow during heat waves and reduce cardiovascular events.

“We know that when older adults are exposed to heat, their bodies are not able to increase skin blood flow to the same extent that young subjects do, and as a consequence, older adults are at a greater risk for cardiovascular events, such as heart attack and stroke, during environmental heat waves,” said Anna Stanhewicz, post-doctoral fellow in kinesiology.

Researchers know this is due, in part, to aged blood vessels that cannot produce enough nitric oxide, Stanhewicz said. “When young, healthy people are exposed to heat, their bodies increase blood flow to the skin and this increased flow, combined with sweating, helps to cool the body down.”

Nitric oxide is the molecule produced by the blood vessels using an enzyme that requires tetrahydrobiopterin — BH4. As people age, BH4 bioavailability decreases, Stanhewicz said.

In a previous study, Stanhewicz and researchers found that when they gave BH4 to older adults they were able to produce more nitric oxide. Folic acid increases the bioavailability of BH4 in the body, so in this study researchers believe that folic acid increased nitric oxide production by increasing BH4, Stanhewicz said. The researchers published their results online in the journal Clinical Science.

“The bottom line is that folic acid supplementation increased nitric oxide production in older blood vessels,” Stanhewicz said. “In the past, studies conducted in our lab showed that we can increase nitric oxide production, and then consequently reflex skin blood flow, in older adults by giving them an expensive pharmaceutical. So in this study, we wanted to test that again, but with an inexpensive treatment that might work the same way.”

Researchers tested very healthy older adults in order to isolate the affect of age without other cardiovascular diseases.

They conducted two sub-studies, localized heating and whole-body heating. For the local heating study, the researchers used two intradermal microdialysis fibers to deliver folic acid solution locally to the blood vessels in the skin.

“In this study we found that when we locally increased folic acid availability, those blood vessels produced more nitric oxide than the blood vessels at the control site,” Stanhewicz said.

Subjects received both folic acid and lactated ringer’s solution, a placebo, at randomized sites on their arms so subjects could serve as their own controls.

For the whole-body heating study, subjects took 5 milligrams of folic acid or a placebo once daily for six weeks. The researchers chose this treatment regimen because of previous reports and pilot testing. They performed all tests in a temperature-neutral laboratory with the subjects lying down and the experimental arm supported at heart level. They controlled skin temperature using a water-perfused suit that covered the entire body except for the head, hands, feet and forearms.

“In the future, it would be interesting to study whether folic acid can also improve vessel function in people with clinical cardiovascular disease, and to try to determine if people who have taken folic acid supplements throughout their life have better vascular health compared to people who do not,” Stanhewicz said.

Additional authors include Lacy M. Alexander, associate professor of kinesiology; and W. Larry Kenney, Marie Underhill Noll Chair in Human Performance and professor of physiology and kinesiology.

“In my opinion, this series of studies epitomizes translational research,” Kenney said. “Through systematic, stepwise advances in our knowledge Anna was able to identify a cost-effective way to potentially improve vascular health for a large number of individuals.”

Public Release: 31-Mar-2015

Scientists reveal unique mechanism of natural product with powerful antimicrobial action

Scripps Research Institute

IMAGE: Min Guo, Ph.D., is an associate professor at The Scripps Research Institute’s Florida campus. view more

Credit: Photo courtesy of The Scripps Research Institute.

JUPITER, FL, March 31, 2015 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have uncovered the unique mechanism of a powerful natural product with wide-ranging antifungal, antibacterial, anti-malaria and anti-cancer effects.

The new study, published online ahead of print by the journal Nature Communications, sheds light on the natural small molecule known as borrelidin.

“Our study may help the rational design of compounds similar to borrelidin with a range of useful applications, particularly in cancer,” said Min Guo, a TSRI associate professor who led the study.

Powerful Medicines

Guo and his colleagues were interested in borrelidin, because it inhibits a specific type of enzyme known as threonyl-tRNA synthetase (ThrRS), ultimately impeding protein synthesis.

Compounds similar to borrelidin have been used as treatments for microbial infections. For example, the natural product mupirocin is approved as a topical treatment for bacterial skin infections and febrifugine (the active component of the Chinese herb Chang Shan (Dichroa febrifuga Lour)) has been used for treating malaria-induced fever for nearly 2,000 years.

Previous studies from the collaborator Professor Christopher S. Francklyn of the University of Vermont College of Medicine and others have shown that borrelidin impedes angiogenesis, the growth of new blood vessels critical for the spread of malignant tumors, as well as increasing apoptosis in certain types of leukemia.

“It is probably the most potent tRNA synthetase inhibitor on Earth,”said Research Associate Pengfei Fang, co-first author of the study and member of the Guo lab at Scripps Florida. “It is also the earliest known tRNA synthetase inhibitor, discovered in 1966–just a few years after people learned the existence of tRNA synthetase and genetic code.”

Research Associate Xue Yu, also co-first author of the study and a member of the Guo lab, emphasized, “While little is known about how borrelidin works, the fairly widespread use of these types of inhibitors highlights their tremendous potential in a number of medical applications.”

Winning at Musical Chairs

In the new study, the scientists set out to conduct a detailed structural and functional analysis of the binding of borrelidin to both human and bacterial (E. coli) ThrRS in the hope of identifying its unique mechanism.

The researchers succeeded, and the new study shows for the first time that borrelidin occupies four distinct subsites on both the bacterial and human tRNA synthetase, including all three subsites for its normal binding substrates and an extra one that is created when the compound binds. In this way, borrelidin crowds out all natural partners that would otherwise bind those sites and fuel the process of protein synthesis.

In that sense, borrelidin more or less wins the game of molecular musical chairs by taking over everyone’s seat well before the music starts, even including the aisles.

Because each of the subsites is essential for its activity, the fact that borrelidin occupies four subsites within ThrRS, an apparent inhibitory overkill, was a quite surprise, and indeed accounts for its potency as validated by further experiments done in both in vitro and in cells.

“This has never been seen in any other tRNA synthetase inhibitors, including the ones sold as medicines,” said Guo. “This finding establishes a new inhibitor class and highlights the striking design of this natural compound that inhibits tRNA synthetases in two of the three kingdoms of life.”


In addition to Guo, Fang and Yu, other authors of the study, “Structural Basis for Full-Spectrum Inhibition of Translational Functions on a tRNA Synthetase,” are Kaige Chen and Xin Chen of TSRI; Seung Jae Jeong and Sunghoon Kim of Seoul National University, Korea; and Adam Mirando and Christopher S. Francklyn the University of Vermont College of Medicine.

The work was supported by the National Institutes of Health (grants NIEHS T32 ES007122-23, GM54899, GM100136 and GM106134), the Korean Global Frontier Project (NRF-M1AXA002-2010-0029785), and the PGA Women’s Cancer Awareness Foundation.

Public Release: 1-Apr-2015

Study finds eyeliner application may cause eye problems

University of Waterloo

People who apply eyeliner on the inner eyelid run the risk of contaminating the eye and causing vision trouble, according to research by a scientist at the University of Waterloo. This is the first study to prove that particles from pencil eyeliner move into the eye.

Dr. Alison Ng, at the Centre for Contact Lens Research at Waterloo, directed the study when she was at Cardiff University in Wales. The team’s findings appear in Eye and Contact Lens Science and Clinical Practice, the official peer-reviewed journal of the Contact Lens Association of Ophthalmologists.

Dr. Alison Ng and her colleagues used video recordings to observe and compare the amount of eyeliner particles that migrated into the tear film – the thin coating protecting the eye – after applying makeup in different styles.

“We noticed that the makeup migration happened quicker and was greater when eyeliner was put on the inner lid margin,” said Dr. Ng, also a post-doctoral fellow in the School of Optometry and Vision Science in the Faculty of Science at Waterloo.

Each participant wore glitter eyeliner outside the lash line, and then on the inner lid area closer to the eye, or along the waterline.

The vision scientists found that within five minutes, between 15 and 30 per cent more particles moved into the eye’s tear film when subjects applied eyeliner to the inside of the lash line, compared to outside it. The makeup also moved more quickly into the eye when eyeliner was applied inside the lash line.

As time passes, the amount of makeup entering the tear film steadily drops and by two hours, there was a negligible amount of eyeliner left. However, Dr. Ng and her colleagues say eyeliner can alter the tear film, adding to discomfort.

Eyeliner ingredients commonly include waxes, oils, silicones and natural gums to help eyeliner stick to eyelids and last for prolonged periods. It has to adhere through blinking, sweating and the secretion of natural oils.

Makeup that enters the tear film may cause discomfort for those with sensitive or dry eyes. But the eyeliner waxes and oils can also adhere to contact lenses and build up if used for more than one day. Resulting complications include irritation and redness, introduction of harmful bacteria from the eyeliner, and in some cases, eye infections or blurred vision.

“People who wear contact lenses are most likely to notice some problems,” said Dr. Ng. “If they have eyeliner stuck to their lenses, increasing deposits might cause vision disruption as the lens becomes cloudier.”

While this study didn’t examine the bacterial aspect of makeup contamination to the eye, Dr. Ng notes that previous studies do show that old eye makeup can harbour bacteria.

“If you thoroughly sharpen your pencil eyeliner before each application and get rid of the stuff that’s stuck to the end, you’ll have a fresh tip which can help prevent infection,” said Dr. Ng. “With twist-up eyeliner, cut some off the end before each use. And always make sure to fully remove eye makeup before bed.”


Alison Ng writes about cosmetics and eye care on ContactLensUpdate.com, an online resource for eye care practitioners, run by the Centre for Contact Lens Research. She and colleagues at the CCLR also produced handouts for the public to share makeup tips for contact lens wearers.

Public Release: 6-Apr-2015

Common antidepressant increased coronary atherosclerosis in animal model

Wake Forest Baptist Medical Center

WINSTON-SALEM, N.C. – April 6, 2015 – A commonly prescribed antidepressant caused up to a six-fold increase in atherosclerosis plaque in the coronary arteries of non-human primates, according to a study by researchers at Wake Forest Baptist Medical Center. Coronary artery atherosclerosis is the primary cause of heart attacks.

The study is published in the current online issue of the journal Psychosomatic Medicine.

“The medical community has known for years that depression is closely associated with heart disease, but we didn’t know if treating it would reduce the heart disease risk,” said Carol Shively, Ph.D., professor of pathology/comparative medicine at Wake Forest Baptist and lead author of the study.

In the study, 42 middle-aged female monkeys were fed a Western-like diet containing fat and cholesterol for 18 months. During this pre-treatment phase, depressive behavior in the animals was recorded.

Female animals were chosen for the study because coronary heart disease is the leading cause of death in women in the United States, and depressive disorders are twice as likely in women as in men.

The animals were then randomly assigned to receive a commonly prescribed antidepressant, a selective serotonin reuptake inhibitor (SSRI) marketed under the brand name Zoloft, or a placebo once a day for 18 months. The antidepressant was given in a dose comparable to that given to patients.

The monkeys that received the SSRI developed three times the amount of atherosclerosis in their coronary arteries as monkeys given the placebo. In the depressed animals, the amount was even higher – almost six times greater in the SSRI-treated animals than in those given the placebo.

“Our findings suggest that long-term treatment with this drug promotes coronary artery atherosclerosis in non-human primates,” Shively said. “This may be clinically significant for people because almost a quarter of middle-aged women in the United States take antidepressants, the most prescribed of which are SSRIs.”

Shively added that although more research is needed, doctors may want to keep these findings in mind when they are prescribing antidepressants. Previous studies have shown that exercise and counseling may be as effective as SSRIs in treating depression for many people.


The study was funded by the National Institutes of Health grant RO1HL087103.

Co-authors of the study are Thomas C. Register, Ph.D., Susan E. Appt, D.V.M., and Thomas B. Clarkson, D.V.M. of Wake Forest Baptist.

Public Release: 6-Apr-2015

New report links frequency of diet soda use to waist increases

University of Texas Health Science Center at San Antonio

SAN ANTONIO, Texas, U.S.A. (April 6, 2015) — Those who drink diet soda thinking it will help them shed unwanted belly fat may see their waistlines expand instead. New analyses from an observational study of San Antonio men and women age 65 and older seem to indicate this.

The San Antonio Longitudinal Study of Aging (SALSA), led by Helen P. Hazuda, Ph.D., professor of medicine in the School of Medicine at The University of Texas Health Science Center at San Antonio, gathered data on health status and lifestyles of 749 Mexican-American and European-American elders, then tracked the health outcomes in 466 survivors for more than nine years. The number of sodas they consumed – and whether they were diet or regular – was recorded by interviews at the beginning of the study and at each of three follow-up visits, where SALSA personnel measured participants’ waist circumferences and other parameters.


Among SALSA participants who reported that they did not consume any diet sodas, waist circumference increased less than 1 inch on average over the total follow-up period, said Sharon P. Fowler, M.P.H., adjunct faculty in the School of Medicine at the Health Science Center. Among participants who reported occasional use – drinking less than one diet soda a day – waist circumference increased almost 2 inches. And among those who consumed diet sodas every day, or more often than once a day, waist circumference increased over 3 inches. With senior author Dr. Hazuda and co-author Ken Williams, M.S., adjunct faculty in the School of Medicine, Fowler is lead author of a paper describing the data in the April issue of the Journal of the American Geriatrics Society.

These findings raise a red flag for seniors because fat around the waist – the proverbial tire around the middle – includes not only fat just under the skin but also fat that accumulates around internal organs, known as viscera. Many studies have linked visceral fat with increased inflammation and risk of metabolic disease, diabetes, heart attack, stroke, cancer and mortality. When waistlines expand in older age, visceral fat increases disproportionately, and risk rises.

“Because Dr. Hazuda’s study measured waist circumference as well as total weight, we were able to look at what happened to participants’ abdominal obesity,” Fowler said. “The increases in abdominal fat were more than three times as great in daily diet soda users as in non-users, during the very time in life when increasing waist circumference is associated with increased risk of these serious medical conditions, and mortality itself.”

Different from past research

The group’s previous related research, published in 2008, looked at the association between total consumption of artificially sweetened drinks – soda plus coffee plus tea – and long-term weight gain among participants in the San Antonio Heart Study, led by Michael Stern, M.D., emeritus professor in the School of Medicine. That study found that, among more than 3,600 25- to 65-year-old Mexican-Americans and European-Americans followed for seven to eight years, body mass index and risk of obesity rose consistently with increases in artificially sweetened beverage intake.

In the current SALSA report, the researchers adjusted statistically for a large number of variables that might have affected the findings, including initial waist size, exercise level and whether the participant had diabetes or smoked. “Even when you adjust for those things, you have this independent effect of diet soda consumption on waist circumference change over time,” Dr. Hazuda said.

“There is definitely debate about whether the association between diet soda intake and cardiometabolic risk, which has been detected in several large observational studies, is based on an actual causal relationship,” Fowler said. “We are simply reporting the statistical association we found: that, over almost a decade, waist circumference increased significantly, in a dose-response manner, with increasing diet soda intake in this group of older individuals. These results are consistent with findings from a number of other observational studies of increased long-term risk of diabetes, heart attack, stroke and other major medical problems among daily diet soda users.”

Although the study cohort is relatively small, with 466 individuals, the results were based on 3,706 person-years of follow-up. The findings were in people age 65 and older; whether they would apply to younger people is not known. The findings were also most pronounced among those who were already overweight or obese at the outset of SALSA. It is an observational study rather than a randomized, controlled trial design, which is the gold standard in clinical epidemiology.

“In spite of these limitations, however, the evidence, taken together with relevant findings from other studies in both humans and animals, is pretty compelling,” Dr. Hazuda said. “We’re trying to provide the evidence base for meaningful decision-making to improve both the health of individuals, and the public health.”


For current news from the UT Health Science Center San Antonio, please visit our news release website, like us on Facebook, follow us on Twitter or view us on YouTube.

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit http://www.uthscsa.edu.

Public Release: 8-Apr-2015

New study indicates that exercise improves non-alcoholic fatty liver disease

Improvements seen in obese and overweight adults regardless of amount and intensity of exercise, report researchers in the Journal of Hepatology

Elsevier Health Sciences


IMAGE: This graphic illustrates the effect of an aerobic exercise dose on intrahepatic lipid and visceral adiposity.

Credit: Journal of Hepatology

Amsterdam, The Netherlands, April 8, 2015 — Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the western world. A new study published in the Journal of Hepatology shows that exercise, regardless of frequency or intensity, benefits obese and overweight adults with NAFLD.

NAFLD is considered the hepatic manifestation of metabolic syndrome and is commonly associated with obesity and diabetes. There are no approved drug treatments for NAFLD, but lifestyle interventions such as diet, exercise, and the resulting weight loss have been shown to help improve NAFLD. In particular, these interventions can improve some features of non-alcoholic steatohepatitis (NASH), which is the progressive form of NAFLD.

Weight loss is the commonly recommended strategy for all obese and overweight patients with NAFLD. Both aerobic and resistance training-based exercise regimens reduce liver fat as well as visceral fat. However, the exact role of the amount and the intensity of aerobic exercise that would be needed to reverse or improve NAFLD (or NASH) had not been systematically assessed.

In the new study published in the Journal of Hepatology, investigators examined the effect of various aerobic exercise regimens in improving liver and visceral fat in overweight and obese people who had sedentary lifestyles. Using a randomized, placebo-controlled clinical trial (RCT) design, they randomized 48 participants into four equal groups of 12 people: low-to-moderate intensity, high-volume aerobic exercise (LO:HI); high-intensity, low-volume aerobic exercise (HI:LO); low-to-moderate intensity, low-volume aerobic exercise (LO:LO); and placebo (PLA) for an eight-week period. Change in liver fat was assessed by magnetic resonance spectroscopy (MRS).

All three groups, irrespective of the exercise regimen, showed improvement in liver fat of about 18-29% from the average baseline 7.5%, compared with the placebo group in which liver fat increased by an average of 14%. The improvement was independent of weight loss. There were no significant differences between the various aerobic exercise regimens in reducing liver fat over an eight-week period. However, the investigators conducted additional exploratory analyses and proposed that there was a trend towards greater reduction in liver fat and visceral fat in the two groups that utilized either high intensity with low volume (HI:LO) or low intensity with high volume (LO:HI) aerobic exercise.

“The results from our study show that all exercise doses, irrespective of volume or intensity, were efficacious in reducing liver fat and visceral fat by an amount that was clinically significant, in previously inactive, overweight, or obese adults compared with placebo. These changes were observed without clinically significant weight loss,” explained lead investigator Dr. Nathan Johnson, PhD, Senior Lecturer at the University of Sydney, Australia. “We found no difference between exercise regimens for these benefits,” added Jacob George, PhD, MBBS, Professor of Hepatic Medicine at the University of Sydney, Australia, and Head of the Department of Gastroenterology and Hepatology at Westmead Hospital and University of Sydney.

In an editorial in the same issue, Rohit Loomba, MD, MHSc, of the Division of Gastroenterology and Epidemiology at the University of California, San Diego, and Helena Cortez-Pinto, MD, PhD, of the Gastroenterology Service, Hospital de Santa Maria, Lisbon, Portugal, observed that “there is good quality evidence to support that regular exercise is beneficial in reducing the risk of NAFLD. In addition, both aerobic and resistance training regimens are equally effective in reducing liver fat in individuals with NAFLD even in the absence of weight loss.

They suggest that duration of exercise and intensity of exercise are both important and one could perhaps personalize the exercise regimen based upon a participant’s choice and still achieve similar results.

“There are, however, no data to support that exercise alone without weight loss can improve or reverse NASH. There is preliminary evidence that vigorous exercise may be associated with a decreased risk of having NASH,” added Dr. Loomba and Dr. Cortez-Pinto. “The individual and joint effect of dose and intensity of exercise and their association with improvement in liver fat and other histologic features that are associated with NASH are key research priorities. In our expert opinion, a more stringent exercise-regimen than the U.S. Department of Health and Human Services recommends, coupled with dietary interventions, may be needed to induce improvement in liver histologic features associated with NASH.”

Public Release: 9-Apr-2015

Microbes help produce serotonin in gut

California Institute of Technology

Although serotonin is well known as a brain neurotransmitter, it is estimated that 90 percent of the body’s serotonin is made in the digestive tract. In fact, altered levels of this peripheral serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis. New research at Caltech, published in the April 9 issue of the journal Cell, shows that certain bacteria in the gut are important for the production of peripheral serotonin.

“More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviors,” explains Elaine Hsiao, research assistant professor of biology and biological engineering and senior author of the study. “We are interested in how microbes communicate with the nervous system. To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.”

Peripheral serotonin is produced in the digestive tract by enterochromaffin (EC) cells and also by particular types of immune cells and neurons. Hsiao and her colleagues first wanted to know if gut microbes have any effect on serotonin production in the gut and, if so, in which types of cells. They began by measuring peripheral serotonin levels in mice with normal populations of gut bacteria and also in germ-free mice that lack these resident microbes.

The researchers found that the EC cells from germ-free mice produced approximately 60 percent less serotonin than did their peers with conventional bacterial colonies. When these germ-free mice were recolonized with normal gut microbes, the serotonin levels went back up–showing that the deficit in serotonin can be reversed.

“EC cells are rich sources of serotonin in the gut. What we saw in this experiment is that they appear to depend on microbes to make serotonin–or at least a large portion of it,” says Jessica Yano, first author on the paper and a research technician working with Hsiao.

The researchers next wanted to find out whether specific species of bacteria, out of the diverse pool of microbes that inhabit the gut, are interacting with EC cells to make serotonin.

After testing several different single species and groups of known gut microbes, Yano, Hsiao, and colleagues observed that one condition–the presence of a group of approximately 20 species of spore-forming bacteria–elevated serotonin levels in germ-free mice. The mice treated with this group also showed an increase in gastrointestinal motility compared to their germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting.

Wanting to home in on mechanisms that could be involved in this interesting collaboration between microbe and host, the researchers began looking for molecules that might be key. They identified several particular metabolites–products of the microbes’ metabolism–that were regulated by spore-forming bacteria and that elevated serotonin from EC cells in culture. Furthermore, increasing these metabolites in germ-free mice increased their serotonin levels.

Previous work in the field indicated that some bacteria can make serotonin all by themselves. However, this new study suggests that much of the body’s serotonin relies on particular bacteria that interact with the host to produce serotonin, says Yano. “Our work demonstrates that microbes normally present in the gut stimulate host intestinal cells to produce serotonin,” she explains.

“While the connections between the microbiome and the immune and metabolic systems are well appreciated, research into the role gut microbes play in shaping the nervous system is an exciting frontier in the biological sciences,” says Sarkis K. Mazmanian, Luis B. and Nelly Soux Professor of Microbiology and a coauthor on the study. “This work elegantly extends previous seminal research from Caltech in this emerging field”.

Additional coauthor Rustem Ismagilov, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering, adds, “This work illustrates both the richness of chemical interactions between the hosts and their microbial communities, and Dr. Hsiao’s scientific breadth and acumen in leading this work.”

Serotonin is important for many aspects of human health, but Hsiao cautions that much more research is needed before any of these findings can be translated to the clinic.

“We identified a group of bacteria that, aside from increasing serotonin, likely has other effects yet to be explored,” she says. “Also, there are conditions where an excess of peripheral serotonin appears to be detrimental.”

Although this study was limited to serotonin in the gut, Hsiao and her team are now investigating how this mechanism might also be important for the developing brain. “Serotonin is an important neurotransmitter and hormone that is involved in a variety of biological processes. The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology,” says Hsiao.


The work was published in an article titled “Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis.” In addition to Hsiao, Yano, Mazmanian, and Ismagilov, other Caltech coauthors include undergraduates Kristie Yu, Gauri Shastri, and Phoebe Ann; graduate student Gregory Donaldson; postdoctoral scholar Liang Ma. Additional coauthor Cathryn Nagler is from the University of Chicago.

This work was funded by an NIH Director’s Early Independence Award and a Caltech Center for Environmental Microbial Interactions Award, both to Hsiao. The study was also supported by NSF, NIDDK, and NIMH grants to Mazmanian, NSF EFRI and NHGRI grants to Ismagilov, and grants from the NIAID and Food Allergy Research and Education and University of Chicago Digestive Diseases Center Core to Nagler.

Sellers of Fake Amazon Reviews Face Lawsuit


SEATTLE (CN) – Leaving little to the imagination, four websites with names like “buyamazonreviews.com” are giving rave reviews on Amazon for a price, the online retail giant claims in court.

Amazon.com says in the April 8 complaint that the sites advise third-party sellers how to outsmart Amazon’s “verified purchaser” checks by mailing out empty boxes to the paid reviewers.

The complaint in King County Superior Court names Jay Gentile as the operator of buyazonreviews.com. Though it does not know who is operating buyamazonreviews,com, bayreviews.net and buyreviewsnow.com, Amazon wants the court to shut the John Does down as well for trademark infringement, unfair competition and violation of the Consumer Protection Act.

Amazon calls the practice of selling reviews an “unhealthy ecosystem” that threatens its brand.

“A very small minority of sellers and manufacturers attempts to gain unfair competitive advantages by creating false, misleading, and inauthentic customer reviews for their products on Amazon.com,” the complaint states. “While small in number, these reviews threaten to undermine the trust that customers, and the vast majority of sellers and manufacturers, place in Amazon, thereby tarnishing Amazon’s brand. Amazon strictly prohibits any attempt to manipulate customer reviews and actively polices its website to remove false, misleading, and inauthentic reviews. Despite substantial efforts to stamp out the practice, an unhealthy ecosystem is developing outside of Amazon to supply inauthentic reviews. Defendants’ businesses consist entirely of selling such reviews.”

The complaint accuses Gentile of offering customers unlimited fake five-star reviews, which he would “slow drip” onto product pages to avoid detection. Gentile also advised customers to ship empty boxes to reviewers so it appears they actually bought the products, Amazon claims.

“Gentile further explained that the reviewers at buyazonreviews.com do not actually need to receive the products they are reviewing, and the purchaser could simply ship empty packages in an effort to fool Amazon into believing the reviewer was a ‘verified purchaser,’ saying, ‘Note: You do not have to actually ship the item unless you want to. We suggest that for tracking purposes is that you just ship out an empty box or envelope, this will show [A]mazon that the item was actually shipped,'” the complaint states. “When a reviewer working for buyazonreviews.com complained to the customer that she had not actually received the product to review, Gentile promised to bring the reviewer in line: ‘All our reviewers know of the process and I am not sure as to why she sent this to you but I will ensure it does not happen in the future.'”

Amazon notes that it expressly prohibits paid reviews and suspends the sellers that purchase or post fake reviews.

“Defendants are misleading Amazon’s customers and tarnishing Amazon’s brand for their own profit and the profit of a handful of dishonest sellers and manufacturers,” the complaint states. “Amazon is bringing this action to protect its customers from this misconduct, by stopping Defendants and disrupting the marketplace in which they participate.”

In addition to damages for trademark infringement, unfair competition, violation of the Consumer Protection Act, Amazon wants an accounting of funds that the sites received from Amazon sellers.

It asks for an injunction to stop the practice of selling fake reviews, transfer of the domain names, and an order requiring the sites to identify each Amazon review created in exchange for payment, as well as the accounts and persons who paid for and created such reviews.

David Bateman of K & L Gates represents Amazon.

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