CNO Report 222
Release Date 14 JAN 2016
Draft Report Compiled by
In this Issue:
1. Early-life exercise alters gut microbes, promotes healthy brain and metabolism
2. Sugar in western diets increases risk for breast cancer tumors and metastasis
3. Saffron-based crocin prevents liver cancer: Preclinical studies and beyond!!
4. Taking vitamin D may benefit people with multiple sclerosis
5. Let hunger be your guide
6. Study details how good bacteria might help prevent middle ear infections and pneumonia
7. Magic mold: Food preservative kills cancer cells, superbugs
8. Sugar-sweetened drinks linked to increased visceral fat
9. Pre-pregnancy potato consumption may be linked to gestational diabetes risk
10. Blueberries, citrus fruits and red wine associated with reduced erectile dysfunction
11. High levels of urate in blood associated with lower risk of Parkinson’s disease
12. Low-fiber diet may cause irreversible depletion of gut bacteria over generations
Public Release: 29-Dec-2015
Early-life exercise alters gut microbes, promotes healthy brain and metabolism
University of Colorado at Boulder
The human gut harbors a teeming menagerie of over 100 trillion microorganisms, and researchers at the University of Colorado Boulder have discovered that exercising early in life can alter that microbial community for the better, promoting healthier brain and metabolic activity over the course of a lifetime.
The research, which was recently published in the journal Immunology and Cell Biology, indicates that there may be a window of opportunity during early human development to optimize the chances of better lifelong health.
“Exercise affects many aspects of health, both metabolic and mental, and people are only now starting to look at the plasticity of these gut microbes,” said Monika Fleshner, a professor in CU-Boulder’s Department of Integrative Physiology and the senior author of the new study. “That is one of the novel aspects of this research.”
Microbes take up residence within human intestines shortly after birth and are vital to the development of the immune system and various neural functions. These microbes can add as many 5 million genes to a person’s overall genetic profile and thus have tremendous power to influence aspects of human physiology.
While this diverse microbial community remains somewhat malleable throughout adult life and can be influenced by environmental factors such as diet and sleep patterns, the researchers found that gut microorganisms are especially ‘plastic’ at a young age.
The study found that juvenile rats who voluntarily exercised every day developed a more beneficial microbial structure, including the expansion of probiotic bacterial species in their gut compared to both their sedentary counterparts and adult rats, even when the adult rats exercised as well.
The researchers have not, as of yet, pinpointed an exact age range when the gut microbe community is likeliest to change, but the preliminary findings indicate that earlier is better.
A robust, healthy community of gut microbes also appears to promote healthy brain function and provide anti-depressant effects, Fleshner said. Previous research has shown that the human brain responds to microbial signals from the gut, though the exact communication methods are still under investigation.
“Future research on this microbial ecosystem will hone in on how these microbes influence brain function in a long-lasting way,” said Agniezka Mika, a graduate researcher in CU-Boulder’s Department of Integrative Physiology and the lead author of the new study.
Going forward, the researchers also plan to explore novel means of encouraging positive gut microbe plasticity in adults, who tend to have stable microbial communities that are more resistant to change.
The National Institutes of Health (NIH) supported this research.
Public Release: 1-Jan-2016
Sugar in western diets increases risk for breast cancer tumors and metastasis
MD Anderson study in mice points to sugar’s impact on inflammatory pathways as culprit
University of Texas M. D. Anderson Cancer Center
The high amounts of dietary sugar in the typical Western diet may increase the risk of breast cancer and metastasis to the lungs, according to a study at The University of Texas MD Anderson Cancer Center.
The findings, published in the Jan. 1, 2016 online issue of Cancer Research, demonstrated dietary sugar’s effect on an enzymatic signaling pathway known as 12-LOX (12-lipoxygenase).
“We found that sucrose intake in mice comparable to levels of Western diets led to increased tumor growth and metastasis, when compared to a non-sugar starch diet,” said Peiying Yang, Ph.D., assistant professor of Palliative, Rehabilitation, and Integrative Medicine. “This was due, in part, to increased expression of 12-LOX and a related fatty acid called 12-HETE.”
Previous epidemiological studies have shown that dietary sugar intake has an impact on breast cancer development, with inflammation thought to play a role.
“The current study investigated the impact of dietary sugar on mammary gland tumor development in multiple mouse models, along with mechanisms that may be involved,” said co-author Lorenzo Cohen, Ph.D., professor of Palliative, Rehabilitation, and Integrative Medicine. “We determined that it was specifically fructose, in table sugar and high-fructose corn syrup, ubiquitous within our food system, which was responsible for facilitating lung metastasis and 12-HETE production in breast tumors.”
Cohen added that the data suggested that dietary sugar induces 12-LOX signaling to increase risks for breast cancer development and metastasis.
Identifying risk factors for breast cancer is a public health priority, say the authors. The researchers state that moderate sugar consumption is critical, given that the per capita consumption of sugar in the U.S. has surged to over 100 lbs. per year and an increase in consumption of sugar-sweetened beverages has been identified as a significant contributor to an epidemic of obesity, heart disease and cancer worldwide.
“Prior research has examined the role of sugar, especially glucose, and energy-based metabolic pathways in cancer development,” said Yang. “However, the inflammatory cascade may be an alternative route of studying sugar-driven carcinogenesis that warrants further study.”
No previous studies have investigated the direct effect of sugar consumption on the development of breast cancer using breast cancer animal models or examined specific mechanisms, she added.
The MD Anderson team conducted four different studies in which mice were randomized to different diet groups and fed one of four diets. At six months of age, 30 percent of mice on a starch-control diet had measurable tumors, whereas 50 to 58 percent of the mice on sucrose-enriched diets had developed mammary tumors. The study also showed that numbers of lung metastases were significantly higher in mice on a sucrose- or a fructose-enriched diet, versus mice on a starch-control diet.
“This study suggests that dietary sucrose or fructose induced 12-LOX and 12-HETE production in breast tumor cells in vivo,” said Cohen. “This indicates a possible signaling pathway responsible for sugar-promoted tumor growth in mice. How dietary sucrose and fructose induces 12-HETE and whether it has a direct or indirect effect remains in question.”
The study team believes that the mechanism by which dietary sucrose or fructose affects breast tumor growth and metastasis, especially through the 12-LOX pathways, warrants further investigation.
MD Anderson research team members included Yan Jiang, Yong Pan, Patrea Rhea, and Lin Tan, all of Palliative, Rehabilitation and Integrative Medicine; Mihai Gagea, D.V.M., Ph.D., Veterinary Medicine & Surgery; and Susan Fischer, Epigenetics & Molecular Carcinogenesis.
The study was funded by the National Institutes of Health (P30CA0166672), Mr. and Mrs. H. Leighton Steward and EOG Resources, Inc.
Public Release: 31-Dec-2015
Saffron-based crocin prevents liver cancer: Preclinical studies and beyond!!
Biomolecule of the golden spice is good for your liver
Bentham Science Publishers
Liver cancer remains among the leading causes of cancer-related death worldwide. New study lead by UAE University Prof. Amr Amin unravels mechanisms by which saffron-based ‘crocin’ protects against liver cancer. The study entitled ‘Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In Vivo, In Vitro and Network Analyses’ is funded by Al-Jalila Foundation & Terry Fox Foundation and is published in Recent Patents on Anticancer Drug Discovery. Using murine model, human liver cancer cells, gene expression profiling and computer-assisted modeling analyses, Amin’s study identifies NF-kB as a regulatory hub and a candidate therapeutic drug target for liver cancer.
Public Release: 30-Dec-2015
Taking vitamin D may benefit people with multiple sclerosis
Johns Hopkins Medicine
Taking a high dose of vitamin D3 is safe for people with multiple sclerosis and may help regulate the body’s hyperactive immune response, according to a pilot study published by Johns Hopkins physicians in the Dec. 30 online issue of Neurology, the medical journal of the American Academy of Neurology.
“These results are exciting, as vitamin D has the potential to be an inexpensive, safe and convenient treatment for people with MS,” says study author Peter Calabresi, M.D., director of the Johns Hopkins Multiple Sclerosis Center and professor neurology at the Johns Hopkins University School of Medicine. “More research is needed to confirm these findings with larger groups of people and to help us understand the mechanisms for these effects, but the results are promising.”
Low levels of vitamin D in the blood are tied to an increased risk of developing MS. People who have MS and low levels of vitamin D are more likely to have greater disability and more disease activity.
For the study, 40 people with relapsing-remitting MS received either 10,400 international units or 800 international units of vitamin D3 supplements per day for six months. Patients with severe vitamin D deficiency were not included in the study. The current recommended daily allowance of vitamin D3 is 600 international units. Blood tests at the start of the study and again at three and six months measured the amount of vitamin D in the blood and the response in the immune system’s T cells, which play a key role in MS.
While researchers are still determining the optimal level of vitamin D in the blood for people with MS, a suggested range of 40 to 60 nanograms per milliliter (ng/ml) has been proposed as a target. Participants taking the high dose of vitamin D reached levels within the proposed target, whereas the group taking the low dose did not reach the target.
Side effects from the vitamin supplements were minor and were not different between the people taking the high dose and the people taking the low dose. One person in each group relapsed.
The people taking the high dose had a reduction in the percentage of inflammatory T cells related to MS severity, specifically IL-17+CD4+ and CD161+CD4+ cells. When the increase in vitamin D levels in the blood over base line levels was greater than 18 ng/ml, every additional 5 ng/ml increase in vitamin D led to a 1 percent decrease in the percentage of IL-17+CD4+ T cells in the blood. The people taking the low dose did not have any noticeable changes in the percentages of their T cell subsets.
“We hope that these changes in inflammatory T cell responses translate to a reduced severity of disease,” says Calabresi. “Other clinical trials are underway to determine if that is the case.”
Additional authors on the study include Elias Sotirchos, Pavan Bhargava, Moira Baynes, Achilles Ntranos, Anne Gocke and Ellen Mowry of Johns Hopkins Medicine; Christopher Eckstein of Duke University; and Keith Van Haren and Lawrence Steinman of Stanford University.
The study was supported by the Kenneth and Claudia Silverman Family Foundation, the Montel Williams Foundation, and the National Multiple Sclerosis Society.
–Modified from the press release issued by the journal Neurology
Public Release: 30-Dec-2015
Let hunger be your guide
Eating when we are not hungry is bad for our health
Cornell Food & Brand Lab
With the wide availability of convenient foods engineered for maximum tastiness– such as potato chips, chocolates, and bacon double cheeseburgers– in the modern food environment and with widespread advertising, the contemporary consumer is incessantly being bombarded with the temptation to eat. This means that, in contrast to people in traditional societies, people in contemporary societies often eat not on account of hunger but because tasty food is available and beckoning at all hours of the day. New research published in the Journal of the Association for Consumer Research, found that the tendency of today’s consumers to eat when they are not hungry might be less advantageous for health than eating when they are hungry.
The individuals participating in the study were 45 undergraduate students. The participants were first asked to rate their level of hunger and then to consume a meal rich in carbohydrates. To measure how the meal was impacting participants’ health, participants’ blood glucose levels were measured at regular intervals after they consumed the meal. Blood glucose levels tend to rise after a meal containing carbohydrates and it is generally healthier if blood glucose levels rise by a relatively small amount because elevated blood glucose is damaging to the body’s cells.
The results of the study showed that individuals who were moderately hungry before the meal tended to have lower blood glucose levels after consuming the meal than individuals who were not particularly hungry before consuming the meal. These findings suggest that it might be healthier for individuals to eat when they are moderately hungry than when they are not hungry.
This article is published in the inaugural issue of the Journal of the Association for Consumer Research entitled “The Behavioral Science of Eating.” This issue has been edited by Brian Wansink of Cornell University and Koert van Ittersum of the University of Groningen.
Public Release: 5-Jan-2016
Study details how good bacteria might help prevent middle ear infections and pneumonia
CAMBRIDGE, Mass., January 5, 2016 – A new study from the Forsyth Institute is helping to shed more light on the important connections among the diverse bacteria in our microbiome. According to research published in mBio, scientists at Forsyth, led by Dr. Katherine P. Lemon, along with their collaborator at Vanderbilt University, have demonstrated that a harmless bacterium found in the nose and on skin may negatively impact the growth of a pathogen that commonly causes middle ear infections in children and pneumonia in children and older adults.
This study provides the first evidence that Corynebacterium accolens, a harmless bacterial species that commonly colonizes the nose, can help inhibit Streptococcus pneumoniae (S. pneumoniae) — a major cause of pneumonia, meningitis, middle ear infection and sinusitis. According to the World Health Organization, S. pneumoniae leads to more than 1 million deaths each year, primarily in young children in developing countries. Although most people that host S. pneumoniae do not develop these infections, colonization greatly increases the risk of, and is a perquisite for, infection and transmission.
The study, titled, “Corynebacterium accolens (C. accolens) Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols,” is published on January 5, 2016 in mBio. In this study, first-author Dr. Lindsey Bomar and her colleagues show that C. accolens are overrepresented in the noses of children that are not colonized by S. pneumoniae, which is commonly found in children’s noses and can cause infection. In laboratory research, the team further found that C. accolens modifies its local habitat in a manner that inhibits the growth of S. pneumoniae by releasing antibacterial free fatty acids from representative host skin surface triacylglycerols. The team went on to identify the C. accolens enzyme needed for this. These results pave the way for potential future research to determine whether C. accolens might have role as a beneficial bacterium that could be used to control pathogen colonization. This research is authored by Lindsey Bomar, Silvio D. Brugger, Brian H. Yost, Sean S. Davies and Katherine P. Lemon.
Public Release: 11-Jan-2016
Magic mold: Food preservative kills cancer cells, superbugs
University of Michigan
ANN ARBOR–Nisin, a naturally occurring food preservative that grows on dairy products, delivers a one-two punch to two of medicine’s most lethal maladies: cancer and deadly, antibiotic-resistant bacteria.
A new University of Michigan study found that feeding rats a “nisin milkshake” killed 70-80 percent of head and neck tumor cells after nine weeks and extended survival, said Dr. Yvonne Kapila, a professor at the University of Michigan School of Dentistry.
Kapila has studied nisin in cancerous tumors and as an antimicrobial to combat diseases of the mouth. After nine weeks of nisin treatment, tumors were comparable to tumors at three weeks.
Kapila’s group has published positive results with less potent nisin, but the highly purified nisin ZP used in the present study nearly doubled its effectiveness. The dosage of 800 mg/kg given to mice would translate to a pill a little bigger than a third of an Advil per kilogram of body weight for people.
Nisin, a colorless, tasteless powder, is typically added to food at the rate of .25 to 37.5 mg/kg. Many foods contain nisin, but nowhere near the 800 mg/kg needed to kill cancer cells.
Several products available to consumers also contain nisin–creams and pharmaceuticals to fight infection and mastitis, and a sanitizer in lactating cows.
While promising, the results are small and in mice only, so it’s too early to say if nisin will act the same way in humans, Kapila said.
Nisin also fights deadly bacteria such as antibiotic-resistant MRSA. In a recent review paper, Kapila’s group looked at experimental uses of nisin to treat 30 different types of cancer; infections of the skin, respiratory system and abdomen; and oral health.
“To date, nobody had found bacteria from humans or living animals that is resistant to nisin,” Kapila said.
Nisin is lethal to bacteria for two reasons: 1) it binds to a static area of bacteria, which gives nisin the opportunity to work before bacteria changes into an antibiotic-resistant superbug, and 2) nisin kills biofilms–colonies of bacteria that group together into a fortress that thwarts antibiotics.
Another positive is that nisin has withstood the test of time, Kapila said.
“Mother Nature has done a lot of the research for us, it’s been tested for thousands of years,” she said.
The next step for Kapila’s lab will be to test nisin in a clinic setting.
“The application of nisin has advanced beyond its role as a food biopreservative,” Kapila said. “Current findings and other published data support nisin’s potential use to treat antibiotic resistant infections, periodontal disease and cancer.”
Related studies: myumi.ch/6nwdk and myumi.ch/6eKA4
Public Release: 11-Jan-2016
Sugar-sweetened drinks linked to increased visceral fat
American Heart Association rapid access journal report
American Heart Association
DALLAS, Jan. 11, 2016–Drinking sugar-sweetened beverages every day was associated with an increase in a particular type of body fat that may affect diabetes and heart disease risk, according to new research in the American Heart Association’s journal Circulation.
Data from the Framingham Heart Study — federally supported, ongoing research that has advanced the understanding of cardiovascular disease — showed that among middle-aged adults, there was a direct correlation between greater sweetened beverage consumption and increased visceral fat.
Visceral fat or “deep” fat wraps around a number of important internal organs such as the liver, pancreas and intestines. Visceral fat affects how our hormones function and is thought to play a larger role in insulin resistance – which may boost Type 2 diabetes and heart disease risk.
Researchers looked at both sugar-sweetened beverage and diet soda consumption. The researchers did not observe this association with diet soda, which is often promoted as low in calories and sugar.
“There is evidence linking sugar-sweetened beverages with cardiovascular disease and type 2 diabetes,” said Caroline S. Fox, M.D., M.P.H, lead study author and a former investigator with the Framingham Heart Study of the National Heart, Lung, and Blood Institute. She is currently a special volunteer with the National Institutes of Health (NIH). “Our message to consumers is to follow the current dietary guidelines and to be mindful of how much sugar-sweetened beverages they drink. To policy makers, this study adds another piece of evidence to the growing body of research suggesting sugar-sweetened beverages may be harmful to our health.”
A total of 1,003 study participants, average age 45 and nearly half women, answered food questionnaires and underwent CT scans at the start and the end of the study to measure body fat changes.
They were ranked into four categories: non-drinkers; occasional drinkers (sugar-sweetened beverages once a month or less than once a week); frequent drinkers (once a week or less than once a day); and those who drank at least one sugar sweetened beverage daily.
Over a six-year follow-up period, independent of the participants’ age, gender, physical activity, body mass index and other factors, they found visceral fat volume increased by:
· 658 centimeters cubed for non-drinkers;
· 649 centimeters cubed for occasional drinkers;
· 707 centimeters cubed for frequent drinkers; and
· 852 centimeters cubed for those who drank one beverage daily.
While the exact biological mechanism is unknown, Jiantao Ma, M.D., Ph.D., post-doctoral fellow at the NIH and co-leader of the study, said that it’s possible that added sugars may contribute to insulin resistance, a hormonal imbalance that increases the risk for Type 2 diabetes and heart disease.
Sugar-sweetened beverages are the largest contributor of added sugar intake in the United States. Sucrose or high fructose corn syrup are two of the most common sugars found in these popular drinks, which include caffeinated and de-caffeinated soda, carbonated and non-carbonated drinks with added sugar, fruit juice, and lemonade.
Daily consumption of added sugar, such as those found in sugar-sweetened beverages and processed foods, is high; in 2001 to 2004, the usual intake of added sugars for Americans was 22.2 teaspoons per day or an extra 355 calories. Growing evidence revealing the health risks associated with drinking sweetened beverages led the American Heart Association to provide added sugar recommendations in 2009; for most women, no more than 100 calories per day of added sugars, such as those found in sweetened beverages, and for most men, a limit of 150 calories per day.
“Our findings are in line with current dietary guidelines that suggest limiting the consumption of sugar-sweetened beverages,” Ma said.
Public Release: 12-Jan-2016
Pre-pregnancy potato consumption may be linked to gestational diabetes risk
NIH researchers suggest substituting vegetables, whole grain for potatoes
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development
Women who eat more potatoes before pregnancy may have higher rates of gestational diabetes–the form that occurs during pregnancy–compared to women who consume fewer potatoes, suggests a National Institutes of Health (NIH) study. The researchers propose that substituting potatoes with other vegetables, legumes or whole grains may help lower gestational diabetes risk. The findings appear in The BMJ (formerly the British Medical Journal).
Gestational diabetes is a common pregnancy complication that causes high blood sugar levels in the mother. The disorder can lead to future health problems for mother and child. Previous studies have linked foods with a high glycemic index, a measure of the ability to raise blood sugar levels, to a higher risk of gestational or type 2 diabetes. However, until the current study, the effect of potatoes, a common, high-glycemic food, on the development of gestational diabetes was unknown.
Researchers from NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Harvard University evaluated more than 15,000 women in the Nurses’ Health Study II. They analyzed records from 1991 to 2001 of women who had no history of illness before pregnancy and had not had gestational diabetes before. Every four years, the women filled out a questionnaire on the kinds of foods they had eaten during the previous year. For potatoes, the women were asked if they had consumed baked, boiled, or mashed potatoes, fries or potato chips, with possible responses ranging from “never” to “six or more times a day.”
The researchers found that women who ate more potatoes had a higher risk of gestational diabetes. They estimated reductions in gestational diabetes risk by substituting the following foods for two servings of potatoes per week:
· 9 percent for other vegetables
· 10 percent for legumes
· 12 percent for whole grain foods
The authors cautioned, however, that because their study was not designed to prove cause and effect, their results do not prove conclusively that potato consumption directly leads to gestational diabetes. They added that their results need to be confirmed by other studies.
Public Release: 13-Jan-2016
Blueberries, citrus fruits and red wine associated with reduced erectile dysfunction
University of East Anglia
Flavonoid-rich foods are associated with a reduced risk of erectile dysfunction – according to a new collaborative study from the University of East Anglia (UEA) and Harvard University.
Research published today in The American Journal of Clinical Nutrition reveals that eating foods rich in certain flavonoids is associated with a reduced risk of erectile dysfunction in men, with the greatest benefit in those under 70.
Of all the different flavonoids, Anthocyanins (found in blueberries, cherries, blackberries, radishes and blackcurrant), flavanones and flavones (found in citrus fruits) were found to offer the greatest benefits in preventing the condition.
It is already known that increased exercise can improve erectile function, but this research shows that eating a flavonoid-rich diet is as good for erectile function as briskly walking for up to five hours a week.
The study also showed that a higher total fruit intake was associated with a 14 per cent reduction in the risk of erectile dysfunction. And that a combination of consuming flavonoid-rich foods with exercise can reduce the risk by 21 per cent.
The study was carried out by nutrition departments at the Harvard TH Chan School of Public Health and UEA’s Norwich Medical School.
Lead researcher Prof Aedin Cassidy from UEA said: “We already knew that intake of certain foods high in flavonoids may reduce the risk of conditions including diabetes and cardiovascular disease. This is the first study to look at the association between flavonoids and erectile dysfunction, which affects up to half of all middle-aged and older men.
“Flavonoids are present in many plant-based foods and drinks including fruits, vegetables, tea, herbs and wine. We examined six main types of commonly consumed flavonoids and found that three in particular – anthocyanins, flavanones and flavones – are beneficial.
“Men who regularly consumed foods high in these flavonoids were 10 per cent less likely to suffer erectile dysfunction. In terms of quantities, we’re talking just a few portions a week.”
More than 50,000 middle aged men were included in this large population based study. They were asked about their ability to have and maintain an erection sufficient for intercourse – dating back to 1986. Data on dietary intake was also collected every four years.
The research team took into account a range of factors such as body weight, physical activity, amount of caffeine consumed, and whether the participants smoked. The research was also restricted to men who were otherwise in good health.
More than one third of the men surveyed reported suffering new onset erectile dysfunction. But those who consumed a diet rich in anthocyanins, flavones and flavanones were less likely to suffer the condition.
Prof Cassidy said: “The top sources of anthocyanins, flavones and flavanones consumed in the US are strawberries, blueberries, red wine, apples, pears, and citrus products.”
“We also found that the benefits were strongest among younger men,” she added.
The team also looked at other lifestyle factors and found that men who consumed a high intake of anthocyanins and flavanones and who were also physically active had the lowest risk of erectile dysfunction.
Dr Eric Rimm, senior author on the study and a Professor of Epidemiology and Nutrition at the Harvard TH Chan School of Public Health, said: “As well as improving sexual health for middle-aged men, there is another important benefit linked to heart health. Erectile dysfunction is often an early barometer of poor vascular function and offers a critical opportunity to intervene and prevent cardiovascular disease, heart attack and even death.
“Men with erectile dysfunction are likely to be highly motivated to make healthier lifestyle choices, such as exercising more and eating the right foods – which would greatly benefit their long-term cardiovascular health as well.”
‘Dietary flavonoid intake and incidence of erectile dysfunction’ is published in The American Journal of Clinical Nutrition on January 13, 2016.
Public Release: 13-Jan-2016
High levels of urate in blood associated with lower risk of Parkinson’s disease
American Academy of Neurology
MINNEAPOLIS – Men who have high levels of urate, also known as uric acid, in their blood may be less likely to develop Parkinson’s disease, according to a study published in the Jan. 13, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology.
Urate is formed when other chemicals, called purines, are broken down in the body. Purines are found in food, and some purines are the building blocks of DNA. Studies have suggested that urate may play a protective role with brain cells.
“These results suggest that urate could protect against Parkinson’s or slow the progression of the disease in its very early stages before symptoms are seen,” said study author Xiang Gao, MD, PhD, of Pennsylvania State University in University Park and a member of the American Academy of Neurology. “The findings support more research on whether raising the level of urate in people with early Parkinson’s may slow the disease down.”
Gao said the idea is exciting, as urate levels can be raised easily and inexpensively, but it must also be done cautiously, as excessively high levels of urate can cause kidney stones and gout.
The study looked at 90,214 participants in three large, ongoing studies. Blood tests measured the urate level of participants. A total of 388 people who developed Parkinson’s disease after the start of the studies were compared to 1,267 people who did not have the disease. The researchers also combined their results with the results from three previous studies on the topic for a meta-analysis.
The men with the lowest level of urate had levels of less than 4.9 milligrams per deciliter. Those with the highest levels had 6.3 to 9.0 mg/dL. Normal levels can range from 3.5 to 7.2 mg/dL. The men who had the highest levels of urate were nearly 40 percent less likely to develop Parkinson’s disease than those with the lowest levels. Among the men with Parkinson’s disease, 45 men had the highest level of urate and 58 men had the lowest level of urate. Among the healthy men, 111 were in the group with the highest level of urate; 107 were in the group with the lowest level. The researchers adjusted for other factors that could affect Parkinson’s disease risk, such as age, smoking and caffeine use. There was no relationship between the level of urate in women and whether they developed Parkinson’s disease.
Gao noted that the study does not prove that high levels of urate protect against Parkinson’s disease; it only shows an association consistent with a lower risk effect. He also notes more studies are needed to understand the sex differences in the relationship between urate and Parkinson’s disease.
Public Release: 13-Jan-2016
Low-fiber diet may cause irreversible depletion of gut bacteria over generations
Stanford University Medical Center
A study by Stanford University School of Medicine investigators raises concerns that the lower-fiber diets typical in industrialized societies may produce internal deficiencies that get passed along to future generations.
The study, conducted in mice, indicates that low-fiber diets not only deplete the complex microbial ecosystems residing in every mammalian gut, but can cause an irreversible loss of diversity within those ecosystems in as few as three or four generations.
Once an entire population has experienced the extinction of key bacterial species, simply “eating right” may no longer be enough to restore these lost species to the guts of individuals in that population, the study suggests. Those of us who live in advanced industrial societies may already be heading down that path.
The proliferation of nearly fiber-free, processed convenience foods since the mid-20th century has resulted in average per capita fiber consumption in industrialized societies of about 15 grams per day. That’s as little as one-tenth of the intake among the world’s dwindling hunter-gatherer and rural agrarian populations, whose living conditions and dietary intake presumably most closely resemble those of our common human ancestors, said Justin Sonnenburg, PhD, associate professor of microbiology and immunology and senior author of the study, to be published Jan. 13 in Nature.
Virtually all health experts agree that low-fiber diets are suboptimal. Probably the chief reason for this is that fiber, which can’t be digested by human enzymes, is the main food source for the commensal bacteria that colonize our colons, Sonnenburg said.
Thousands of distinct bacterial species inhabit every healthy individual’s large intestine. “We would have difficulty living without them,” he said. “They fend off pathogens, train our immune systems and even guide the development of our tissues.” While we pick up these microscopic passengers in the course of routine exposures throughout our lifetimes, one of the most significant sources of our intestinal bacterial populations is our immediate family, especially our mothers during childbirth and infancy.
Surveys of humans’ gut-dwelling microbes have shown that the diversity of bacterial species inhabiting the intestines of individual members of hunter-gatherer and rural agrarian populations greatly exceeds that of individuals living in modern industrialized societies, Sonnenburg said. In fact, these studies indicate the complete absence, throughout industrialized populations, of numerous bacterial species that are shared among many of the hunter-gatherer and rural agrarian populations surveyed, despite those groups’ being dispersed across vast geographic expanses ranging from Africa to South America to Papua New Guinea.
High- versus low-fiber diet
“Numerous factors including widespread antibiotic use, more-frequent cesarean sections and less-frequent breastfeeding have been proposed for why we see this depletion in industrialized populations,” said the study’s lead author, Erica Sonnenburg, PhD, a senior research scientist at Stanford (she and Justin Sonnenburg are married). “We asked ourselves whether the huge difference in dietary fiber intake between traditional and modern populations could, alone, account for it.”
The Stanford researchers employed young laboratory mice that had been specially bred and raised in aseptic environments so that, unlike ordinary mice (and ordinary humans), their intestines were devoid of any microbial inhabitants. After populating the mice’s guts with microbes from a human donor, the scientists divided them into two groups. One group was fed a diet rich in plant-derived fiber. The other group’s diet, equivalent to the first with respect to protein, fat and calories, was practically devoid of fiber content.
During the experimentation that followed, the researchers analyzed fecal samples from the animals. The two groups’ gut-bacteria profiles were initially indistinguishable but soon diverged. “Within a couple of weeks, we saw a massive change,” said Justin Sonnenburg. “The low-fiber-intake mice harbored fewer bacterial species in their gut.” More than half of these bacterial species’ numbers had dwindled by over 75 percent, and many species seemed to have disappeared altogether.
After seven weeks, the mice that had consumed a low-fiber diet were switched back to a high-fiber diet for four weeks. The mice’s gut-bacteria profiles partly recovered — probably due to an uptick in abundance of some bacteria whose ranks had declined to undetectable levels during the low-fiber-intake period. Still, this restoration was only partial: One-third of the original species never fully recovered despite their return to a high-fiber diet.
No such changes were seen in the control mice consistently fed a high-fiber diet.
The real surprise came after mice had been bred and maintained on low-fiber diets for a few generations. In their experimental confines, these mice were exposed to microbes only through contact with their parents. Each successive generation’s gut-bacterial ecosystem declined in diversity. By generation four, the depletion had reached a point where nearly three-quarters of the bacterial species resident in their great-grandparents’ guts appeared absent in their own. Even after these mice were put back on a high-fiber diet, more than two-thirds of the bacterial species identified in the guts of their first-generation ancestors proved irretrievable, indicating extinction of those species by the fourth generation of fiber deprivation.
On the other hand, a somewhat more aggressive measure — fecal transplantation — did result in these lost species’ retrieval, the study found. Introducing fecal contents of fourth-generation high-fiber-diet mice into the intestines of fourth-generation low-fiber mice, together with putting them on the high-fiber diet for two weeks, fully restored their bacterial profiles. Within 10 days of the procedure, the composition and diversity of the bacteria in the intestines of this group were indistinguishable from those of control mice.
These findings hold major implications for humans, said Erica Sonnenburg. “There are very few ecosystems where low species diversity is a good thing. There’s no reason to think our gut is any exception,” she said.
“The extremely low-fiber intake in industrialized countries has occurred relatively recently,” noted Justin Sonnenburg. “Is it possible that over the next few generations we’ll lose even more species in our gut? And what will the ramifications be for our health?”
Simple tweaks in our cultural practices — for example, not washing our hands after gardening or petting our dogs — could be a step in the right direction, and steering away from overuse of antibiotics certainly is, he said. More extreme measures, such as mass fecal transplants, would require large-scale testing to make sure they are both necessary and safe.