249 CNO REPORT 31 OCT 2017
CNO Report # 249
Release Date: 31 OCT 2017
Draft Report Compiled by
In This Issue:
1. Milk-alternative drinks do not replace the iodine in cows’ milk
2. Plant substance inhibits cancer stem cells
3. UTA study says zinc can halt the growth of cancer cells
4. Virginia Tech study finds that healthy bacteria in yogurt may reduce lupus symptoms in mice
5. Low consumption of vitamin K by adolescents associated with unhealthy enlargement of the heart’s major pumping chamber
6. One hour of exercise a week can prevent depression
7. Resistance training prevents age-related tendon damage
8. Black tea may help with weight loss, too
9. A need for bananas? Dietary potassium regulates calcification of arteries
10. Omega-6 fats may help prevent type 2 diabetes
11. A dietary supplement dampens the brain hyperexcitability seen in seizures or epilepsy
12. Scientists reveal the relationship between sugar and cancer
13. Most medical students overconfident, underprepared on nutrition guidelines
14. Common acid reflux medications promote chronic liver disease
15. Intake of pesticide residue from fruits, vegetables and infertility treatment outcomes
Public Release: 26-Sep-2017
University of Surrey
Consumers of milk-alternative drinks may be at of risk iodine deficiency, according to the findings of a new study in the British Journal of Nutrition.
In the first study of its kind in the United Kingdom, researchers from the University of Surrey examined the iodine content of 47 milk-alternative drinks (including soya, almond, coconut, oat, rice, hazelnut and hemp, but excluding those marketed specifically at infants and children) and compared it with that of cows’ milk.
Researchers discovered that the majority of milk-alternative drinks did not have adequate levels of iodine, with concentration levels found to be around 2% of that found in cows’ milk. Cows’ milk and dairy products are the main source of iodine in the UK diet however findings from the study show that most milk-alternative drinks are not an adequate substitute.
Iodine is required to make thyroid hormones, and is particularly important during pregnancy as it is essential for normal foetal brain development. Previous research in this area by the University of Surrey has shown that low iodine status in pregnant mothers is linked to lower IQ and reading scores in their children (up to 9 years of age).
Margaret Rayman, Professor of Nutritional Medicine at the University of Surrey, said: “Many people are unaware of the need for this vital dietary mineral and it is important that people who consume milk-alternative drinks realise that they will not be replacing the iodine from cows’ milk which is the main UK source of iodine. This is particularly important for pregnant women and those planning a pregnancy.
“A glass of a milk-alternative drink would only provide around 2 mcg of iodine which is a very small proportion of the adult recommended iodine intake of 150 mcg/day. In pregnancy, that recommendation goes up to 200 mcg/day”.
Dr Sarah Bath, Lecturer in Public Health Nutrition at the University of Surrey and registered dietitian, said: “Milk-alternative drinks are increasingly being used as a replacement for cows’ milk for a number of reasons that obviously include allergy or intolerance to cows’ milk.
“Worryingly, most milk-alternative drinks are not fortified with iodine and their iodine content is very low. If avoiding milk and dairy products, consumers need to ensure that they have iodine from other dietary sources, where possible. More information on good iodine sources such as white fish can be found in the British Dietetic Association Iodine Food Fact Sheet. If considering taking an iodine supplement, they should avoid kelp which can provide excessive amounts of iodine.”
The milk-alternative samples were analysed at LGC, the UK’s National Measurement Laboratory for chemical and bio-measurement. Dr Sarah Hill, Science Leader in Inorganic Analysis at LGC said: “Reliable methods to test food samples for minerals, such as iodine, are invaluable to nutrition research. As a metrology institute, one of our key missions is the provision of reference methods and materials that underpin validation of field laboratory measurements. This ensures that high quality data are generated to support researchers in these important studies”.
Public Release: 27-Sep-2017
The plant Ambrosia arborescens grows at a high elevation in large parts of South America, and is traditionally used as a medicinal plant. The researchers have isolated the sesquiterpene lactone damsin from the plant and studied its effect on cancer stem cells in three different breast cancer cell lines. They have also performed similar studies using what is known as an analogue called ambrosin – a substance similar to damsin, but produced synthetically. The results show that they both have an effect on cancer stem cells.
“Both the natural and the synthetic substances inhibit the growth and spread of cancer stem cells in breast cancer cell lines. This is the first time that it has been successfully proven by research”, says Stina Oredsson, professor at Lund University.
Already at low concentrations, the two substances inhibit the division and mobility of the cancer cells. This means that the tumour becomes smaller as cell proliferation decreases. In the present study, the researchers show that the actual number of cancer stem cells decreases.
Stina Oredsson emphasises that this is basic research and that the results are based on lab experiments involving cell cultures. However, she argues that the results are a breakthrough in cancer research as it may be the first step towards effective treatment of cancer stem cells, i.e. the cells believed to cause metastases.
“Different cancer cells have different abilities to survive chemotherapy. Cancer stem cells can be considered the most dangerous type of cancer cells, as they appear to have an inherent resistance to the chemotherapeutic drugs used today. Our results can contribute to the development of new drugs against cancer stem cells but, unfortunately, it takes a long time to get from basic research to usable drugs”, says Stina Oredsson.
She and her colleagues continue to study damsin and ambrosin. They have also developed other analogues that show very good inhibitory effects on cancer stem cells. These results have not yet been published.
The collaboration project between Lund University and the University Major of San Andrés in La Paz, Bolivia, is funded by the Swedish International Development Cooperation Agency (SIDA).
Public Release: 28-Sep-2017
Study may provide a road map for treatment and prevention
University of Texas at Arlington
Zinc supplements can significantly inhibit the proliferation of esophageal cancer cells, according to a new study co-authored by a University of Texas at Arlington researcher.
Previous studies had shown that zinc is essential for maintaining human health and protects the esophagus from cancer. However, it has never been fully understood why zinc has the ability to prevent cancer in the esophagus. In this study, a team led by Zui Pan, an associate professor of nursing at UTA’s College of Nursing and Health Innovation and a noted esophageal cancer researcher, discovered that zinc selectively halts the growth of cancer cells but not normal esophageal epithelial cells. The finding was published this month in The FASEB Journal, the official journal of the Federation of American Societies for Experimental Biology.
Esophageal cancer is the sixth leading cause of human cancer deaths around the world, according to the National Cancer Institute. The institute estimates that there were almost 16,000 esophageal cancer deaths in the United States in 2016. The average five-year survival rate is less than 20 percent.
Pan said this study could provide a pathway for better esophageal cancer prevention and treatment.
“Zinc deficiency has been found in many cancer patients,” said Pan, whose study was funded in part by a research grant from the National Institutes of Health – National Cancer Insitute. “Both clinical data and animal studies have shown that this mineral is very important for overall body health and for cancer prevention.”
Zinc is an important element in many proteins and many enzymes and the absence of zinc makes it impossible for cells to function, she added.
“But previously we didn’t know why the same physiological concentrations of zinc inhibit cancer cell growth but not normal cells. Our study, for the first time to our knowledge, reveals that zinc impedes overactive calcium signals in cancer cells, which is absent in normal cells, and thus zinc selectively inhibits cancer cell growth.” said Pan. “It now appears that zinc and calcium can have a cross talk, meaning that they can be linked.”
An insufficient amount of zinc can lead to the development of cancers and other diseases, Pan said.
“That’s why it is important to have a good diet,” she said.
Zinc enriched foods include spinach, flax seeds, beef, pumpkin seeds and seafood like shrimp and oysters.
Pan said that in the future they will study these two signals link, how they impact each other and how researchers can take advantage of what they know. Such a step will guide them in developing a better prevention and treatment strategy, she said.
Anne Bavier, dean of UTA’s College of Nursing and Health Innovation, called Pan’s study a classic example of UTA’s commitment to high impact research.
“It re-affirms UTA’s position as a major player in the global battle against cancer,” said Bavier. “Zui’s work on esophageal cancer gets straight to the heart our goal at the College of Nursing and Health Innovation to help solve health problems to build a healthier world.”
UTA’s Strategic Plan 2020 Bold Solutions | Global Impact includes a major focus on Health and the Human Condition.
Public Release: 2-Oct-2017
Researchers at the Virginia-Maryland College of Veterinary Medicine at Virginia Tech have released findings that explain how a type of healthy bacteria in yogurt and other dairy products might reduce disease symptoms in certain patients with lupus.
Xin Luo, assistant professor of immunology in the Department of Biomedical Sciences and Pathobiology, and her colleagues expanded upon earlier research linking a lack of Lactobacillus, which produces lactic acid and is an important part of gut microbiota in both humans and mice, and autoimmune diseases such as lupus. The new research describes the mechanism behind this association.
“In our 2014 paper, we found that mice with lupus had decreased amounts of Lactobacillus, which led to our hypothesis that adding this bacteria could ameliorate disease symptoms,” said Luo, who added that she and her colleagues also found that the mice had a “leaky gut,” a condition that affects the intestinal lining. “Probiotics, such as Lactobacillus, work by patching up and reversing the leaky gut.”
Lupus is an autoimmune disease that can cause chronic fatigue, joint pain, rash, fever, renal failure, and even death. It affects an estimated 3 million people in the United States. Luo’s recent study deals with lupus nephritis, or inflammation of the kidney that is caused by lupus.
According to the National Resource Center on Lupus, lupus nephritis usually develops within the first five years after lupus symptoms start, and as many as 40 percent of all people with lupus, and up to two-thirds of children with the disease, will develop kidney complications.
“In addition, we found that the addition of Lactobacillus to the diet only affected female mice and not males,” said Luo, who explained that lupus is 10 times more prevalent in females than in males. “We think that testosterone is suppressing the effect of the healthy bacteria. Before our study, researchers had never looked at male hormones suppressing the probiotic effect before.”
The research team included Qinghui Mu, a Ph.D. student in the biomedical and veterinary sciences program and recent recipient of a prestigious American Association of Immunologists Careers in Immunology Fellowship, and S. Ansar Ahmed, professor of immunology and associate dean of research and graduate studies at the veterinary college. Ahmed is also one of the leading authorities on the effect of hormones on lupus and other autoimmune disorders.
Although the research was limited to mice with lupus and kidney inflammation, and more work would need to be done to determine whether Lactobacillus has the same effect in humans, Luo emphasized that yogurt and probiotic supplements are considered safe.
“If a lupus patient is female and also has kidney inflammation, there would be no harm in adding yogurt or a probiotic supplement to the diet,” she said.
Now that researchers have identified the “good” bacteria that affects the severity of lupus, they hope to turn their attention to other areas of research.
“The next question is, ‘Are there bad bacteria that can be detrimental to the disease?’ ” Luo asked. “If that can be found, we can target the bad bacteria and remove them to ameliorate disease symptoms.”
The paper, “Control of lupus nephritis by changes of gut microbiota,” was published in the July issue of the journal Microbiome and is available online.
Public Release: 2-Oct-2017
A study of 766 otherwise healthy adolescents showed that those who consumed the least vitamin K1 were at 3.3 times greater risk for an unhealthy enlargement of the major pumping chamber of their heart
Medical College of Georgia at Augusta University
AUGUSTA, Ga. (Oct. 2, 2017) – Scientists have found another reason for children to eat their green leafy vegetables.
A study of 766 otherwise healthy adolescents showed that those who consumed the least vitamin K1- found in spinach, cabbage, iceberg lettuce and olive oil – were at 3.3 times greater risk for an unhealthy enlargement of the major pumping chamber of their heart, according to the study published in The Journal of Nutrition. Vitamin K1, or phylloquinone, is the predominant form of vitamin K in the U.S. diet.
“Those who consumed less had more risk,” says Dr. Norman Pollock, bone biologist at the Georgia Prevention Institute at the Medical College of Georgia at Augusta University and the study’s corresponding author.
Overall, about 10 percent of the teens had some degree of this left ventricular hypertrophy, Pollock and his colleagues report.
Left ventricular changes are more typically associated with adults whose hearts have been working too hard, too long to get blood out to the body because of sustained, elevated blood pressure. Unlike other muscles, a larger heart can become inefficient and ineffective.
The scientists believe theirs is the first study exploring associations between vitamin K and heart structure and function in young people. While more work is needed, their findings suggest that early interventions to ensure young people are getting adequate vitamin K1 could improve cardiovascular development and reduce future disease risk, they write.
In the 14-18 year olds who consumed the least vitamin K1, the study found the overall size and wall thickness of the left ventricle were already significantly greater and the amount of blood the heart pumped out significantly lower, Pollock says.
Changes were independent of other factors known to influence heart structure and function, including sex, race, body composition, physical activity and blood pressure, says Mary Ellen Fain, MCG second-year student and the study’s co-first author.
Only 25 percent of the teens in the study met current adequate intake levels of the Food and Nutrition Board of the Institute of Medicine, Pollock notes.
“They had higher levels relative to the other kids,” Fain said. “But even at that age, it seemed to make a difference in their hearts.” Fain and Pollock noted that it was clear than none of the participants consumed large amounts of the vitamin.
Vitamin K is known to be important to blood clotting and healthy bones. There is increasing evidence of its cardiovascular impact as well. For example, one direct, negative impact of low vitamin K intake on the heart may be reduced activity of matrix Gla protein, which helps prevent calcium deposits on blood vessel walls.
Pollock, who is also leading a novel study of the cardiovascular impact of a vitamin K supplement on obese children already showing signs of diabetes risk, has early evidence that the vitamin levels are lower in obese and overweight children.
Like matrix Gla protein, vitamin K is essential to increased production of osteocalcin, a protein hormone important to bone metabolism and insulin sensitivity. Those parallels – and the fact that osteocalcin can’t currently be given directly – led Pollock to pursue his ongoing clinical trial in obese children with higher-fasting glucose levels. Pollock’s lab and other investigators in the United States and Europe are also looking at the impact of vitamin K supplements on adults with heart disease, but adult findings to date have been inconclusive.
Further study is needed to clarify the importance of vitamin K1 intake to cardiovascular development and to better understand how vitamin K dependent proteins, like matrix Gla protein, aid cardiovascular development and health, the scientists note.
Participants wore activity monitors for seven days and completed between three and seven 24-hour periods of self-reports about what they ate. About 70 percent had a least six days of food records, which increases the accuracy of self-reports, Pollock says. Echocardiography was used to examine the left ventricle.
Fain received a plenary poster award for the research at the American Society for Bone and Mineral Research 2017 Annual Meeting Sept. 8-11 in Denver. The research was funded by the National Heart, Lung and Blood Institute, the American Heart Association and the Medical Scholars Program at MCG and AU.
The Framingham Offspring Cohort Study found an association between higher vitamin K1 levels and higher levels of the good LDL cholesterol and lower lipid levels in the blood, both associated with healthier hearts. Adult studies, like the Nurses’ Health Study and Prospective Army Coronary Calcium study, have provided conflicting evidence of its cardiovascular impact.
The short-acting vitamin is active only about six hours after it’s consumed.
Pollock is an associate professor in MCG’s newest department, the Department of Population Health Sciences.
Public Release: 3-Oct-2017
University of New South Wales
A landmark study led by the Black Dog Institute has revealed that regular exercise of any intensity can prevent future depression – and just one hour can help.
Published today in the American Journal of Psychiatry, the results show even small amounts of exercise can protect against depression, with mental health benefits seen regardless of age or gender.
In the largest and most extensive study of its kind, the analysis involved 33,908 Norwegian adults who had their levels of exercise and symptoms of depression and anxiety monitored over 11 years.
The international research team found that 12 percent of cases of depression could have been prevented if participants undertook just one hour of physical activity each week.
“We’ve known for some time that exercise has a role to play in treating symptoms of depression, but this is the first time we have been able to quantify the preventative potential of physical activity in terms of reducing future levels of depression,” said lead author Associate Professor Samuel Harvey from Black Dog Institute and UNSW.
“These findings are exciting because they show that even relatively small amounts of exercise – from one hour per week – can deliver significant protection against depression.
“We are still trying to determine exactly why exercise can have this protective effect, but we believe it is from the combined impact of the various physical and social benefits of physical activity.
“These results highlight the great potential to integrate exercise into individual mental health plans and broader public health campaigns. If we can find ways to increase the population’s level of physical activity even by a small amount, then this is likely to bring substantial physical and mental health benefits.”
The findings follow the Black Dog Institute’s recent Exercise Your Mood campaign, which ran throughout September and encouraged Australians to improve their physical and mental wellbeing through exercise.
Researchers used data from the Health Study of Nord-Trøndelag County (HUNT study) – one of the largest and most comprehensive population-based health surveys ever undertaken – which was conducted between January 1984 and June 1997.
A healthy cohort of participants was asked at baseline to report the frequency of exercise they participated in and at what intensity: without becoming breathless or sweating, becoming breathless and sweating, or exhausting themselves. At follow-up stage, they completed a self-report questionnaire (the Hospital Anxiety and Depression Scale) to indicate any emerging anxiety or depression.
The research team also accounted for variables which might impact the association between exercise and common mental illness. These include socio-economic and demographic factors, substance use, body mass index, new onset physical illness and perceived social support.
Results showed that people who reported doing no exercise at all at baseline had a 44% increased chance of developing depression compared to those who were exercising one to two hours a week.
However, these benefits did not carry through to protecting against anxiety, with no association identified between level and intensity of exercise and the chances of developing the disorder.
According to the Australian Health Survey, 20 percent of Australian adults do not undertake any regular physical activity, and more than a third spend less than 1.5 hours per week being physically active. At the same time, around 1 million Australians have depression, with one in five Australians aged 16-85 experiencing a mental illness in any year.
“Most of the mental health benefits of exercise are realised within the first hour undertaken each week,” said Associate Professor Harvey.
“With sedentary lifestyles becoming the norm worldwide, and rates of depression growing, these results are particularly pertinent as they highlight that even small lifestyle changes can reap significant mental health benefits.”
Public Release: 4-Oct-2017
New research in The FASEB Journal suggests resistance training can prevent age-related tendon disorders
Federation of American Societies for Experimental Biology
A study published online in The FASEB Journal suggests that resistance training may prevent age-related tendon problems, such as ruptures and tendinopathies. In the report, scientists used different groups of sedentary and resistance-trained rats to reveal that the tendons of trained rats showed fewer signs of age-related damage than their sedentary counterparts. If this proves true in humans, it would provide further evidence that resistance training can have beneficial effects throughout one’s lifespan.
“The relationship between aging and tendon disorders is not well documented,” said Rita de Cassia Marqueti Durigan, Ph.D., a researcher involved in the work from the Rehabilitation Science Program, University of Brasilia, in Brasilia, Brazil. “To restrain and revert the deleterious aging process, resistance training can be used as an important tool to prevent degeneration and even restore tendon functions.”
Durigan and colleagues used four groups of rats: 1) young sedentary, three months old; 2) young trained, three months old; 3) old sedentary, 21 months old; and 4) old trained, 21 months old. The sedentary rats did not perform the resistance training. The trained rats climbed a vertical ladder three times for 12 weeks, bearing progressive loads comprising 65, 85, 95, and 100 percent of their maximum carrying capacity. After the 12-week training period, the animals were euthanized for removal of the calcaneal tendon tissue. The researchers performed several assays (biochemical, histological, immunohistochemical, and molecular) to evaluate the effects of resistance training on the molecular and cellular aspects of the calcaneal tendon in young and old rats and their implications for tendon remodeling.
“It seems very plausible that the findings from this well-designed study are applicable to the comparable human situation, so the clinical potential is very signficiant,” said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal.
The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
Submit to The FASEB Journal by visiting http://fasebj.msubmit.net, and receive monthly highlights by signing up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is the world’s most cited biology journal according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.
FASEB is composed of 31 societies with more than 130,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.
Public Release: 4-Oct-2017
Benefits of green tea were already known; new UCLA study shows that polyphenols in both varieties alter gut bacteria
University of California – Los Angeles Health Sciences
UCLA researchers have demonstrated for the first time that black tea may promote weight loss and other health benefits by changing bacteria in the gut. In a study of mice, the scientists showed that black tea alters energy metabolism in the liver by changing gut metabolites.
The research is published in the European Journal of Nutrition.
The study found that both black and green tea changed the ratio of intestinal bacteria in the animals: The percentage of bacteria associated with obesity decreased, while bacteria associated with lean body mass increased.
Previous studies indicated that chemicals in green tea called polyphenols are absorbed and alter the energy metabolism in the liver. The new findings show that black tea polyphenols, which are too large to be absorbed in the small intestine, stimulate the growth of gut bacterium and the formation of short-chain fatty acids, a type of bacterial metabolites that has been shown to alter the energy metabolism in the liver.
“It was known that green tea polyphenols are more effective and offer more health benefits than black tea polyphenols since green tea chemicals are absorbed into the blood and tissue,” said Susanne Henning, the study’s lead author and an adjunct professor at the UCLA Center for Human Nutrition, which is part of the David Geffen School of Medicine at UCLA. “Our new findings suggest that black tea, through a specific mechanism through the gut microbiome, may also contribute to good health and weight loss in humans.”
“The results suggest that both green and black teas are prebiotics, substances that induce the growth of good microorganisms that contribute to a person’s well-being,” she said.
In the study, four groups of mice received different diets — two of which were supplemented with green tea or black tea extracts:
High-fat, high-sugar and green tea extract
High-fat, high-sugar and black tea extract
After four weeks, the weights of the mice that were given green or black tea extracts dropped to the same levels as those of the mice that received the low-fat diet throughout the study.
The researchers also collected samples from the mice’s large intestines (to measure bacteria content) and liver tissues (to measure fat deposits). In the mice that consumed either type of tea extract, there was less of the type of bacteria associated with obesity and more of the bacteria associated with lean body mass.
However, only the mice that consumed black tea extract had an increase in a type of bacteria called Pseudobutyrivibrio, which could help explain the difference between how black tea and green tea change energy metabolism.
Dr. Zhaoping Li, director of the UCLA Center for Human Nutrition, chief of the UCLA Division of Clinical Nutrition and the study’s senior author, said the findings suggest that the health benefits of both green tea and black tea go beyond their antioxidant benefits, and that both teas have a strong impact on the gut microbiome.
“For black tea lovers, there may be a new reason to keep drinking it,” she said.
The findings build on a 2015 UCLA study that demonstrated that both green tea and black tea helped prevent obesity in mice that consumed a high-fat, high-sugar diet.
The new study also concluded that both green tea and black tea have different effects on liver metabolism. According to Henning, the molecules in green tea are smaller and can more readily be absorbed into the body and reach the liver directly, while black tea molecules are larger and stay in the intestine rather than being absorbed. When black tea molecules stay in the intestinal tract, they enhance the growth of beneficial bacteria and the formation of microbial metabolites involved in the regulation of energy metabolism.
The study was funded by the National Institutes of Health and the UCLA Center for Human Nutrition.
Public Release: 5-Oct-2017
Low dietary potassium leads to calcified arteries and aortic stiffness, while increased dietary potassium alleviates that in a mouse model, suggesting dietary potassium may protect against heart disease and death from heart disease in humans
University of Alabama at Birmingham
BIRMINGHAM, Ala. – Bananas and avocados — foods that are rich in potassium — may help protect against pathogenic vascular calcification, also known as hardening of the arteries.
University of Alabama at Birmingham researchers have shown, for the first time, that reduced dietary potassium promotes elevated aortic stiffness in a mouse model, as compared with normal-potassium-fed mice. Such arterial stiffness in humans is predictive of heart disease and death from heart disease, and it represents an important health problem for the nation as a whole.
The UAB researchers also found that increased dietary potassium levels lessened vascular calcification and aortic stiffness. Furthermore, they unraveled the molecular mechanism underlying the effects of low or high dietary potassium.
Such knowledge of how vascular smooth muscle cells in the arteries regulate vascular calcification emphasizes the need to consider dietary intake of potassium in the prevention of vascular complications of atherosclerosis. It also provides new targets for potential therapies to prevent or treat atherosclerotic vascular calcification and arterial stiffness.
A UAB team led by Yabing Chen, Ph.D., UAB professor of pathology and a Research Career Scientist at the Birmingham VA Medical Center, explored this mechanism of vascular disease three ways: living mice fed diets that varied in potassium, mouse artery cross-sections studied in culture medium with varying concentrations of potassium, and mouse vascular smooth muscle cells grown in culture medium.
Working from living mice down to molecular events in cells in culture, the UAB researchers determined a causative link between reduced dietary potassium and vascular calcification in atherosclerosis, as well as uncovered the underlying pathogenic mechanisms.
The animal work was carried out in the atherosclerosis-prone mouse model, the apoliprotein E-deficient mice, a standard model that are prone to cardiovascular disease when fed a high-fat diet. Using low, normal or high levels of dietary potassium — 0.3 percent, 0.7 percent and 2.1 percent weight/weight, respectively, the UAB team found that the mice fed a low-potassium diet had a significant increase in vascular calcification. In contrast, the mice fed a high-potassium diet had markedly inhibited vascular calcification. Also, the low-potassium mice had increased stiffness of their aortas, and high-potassium mice had decreased stiffness, as indicated by the arterial stiffness indicator called pulse wave velocity, which is measured by echocardiography in live animals.
The different levels of dietary potassium were mirrored by different blood levels of potassium in the three groups of mice.
When researchers looked at arterial cross-sections in cultures that were exposed to three different concentrations of potassium, based on normal physiological levels of potassium in the blood, they found a direct effect for the potassium on arterial calcification within arterial rings. Arterial rings in low-potassium had markedly enhanced calcification, while high-potassium inhibited aortic calcification.
“The findings have important translational potential,” said Paul Sanders, M.D., professor of nephrology in the UAB Department of Medicine and a co-author, “since they demonstrate the benefit of adequate potassium supplementation on prevention of vascular calcification in atherosclerosis-prone mice, and the adverse effect of low potassium intake.”
In cell culture, low potassium levels in the culture media markedly enhanced calcification of vascular smooth muscle cells. Previous research by several labs including Chen’s group has shown that calcification of vascular smooth muscle cells resembles the differentiation of bone cells, which leads to the transformation of smooth muscle cells into bone-like cells.
So the UAB researchers tested the effect of growing vascular smooth muscle cells in low-potassium cell culture. They found that the low-potassium conditions promoted the expression of several gene markers that are hallmarks of bone cells, but decreased the expression of vascular smooth muscle cell markers, suggesting the transformation of the vascular smooth muscle cells into bone-like cells under low-potassium conditions.
Mechanistically, they found that low-potassium elevated intracellular calcium in the vascular smooth muscle cells, via a potassium transport channel called the inward rectifier potassium channel. This was accompanied by activation of several known downstream mediators, including protein kinase C and the calcium-activated cAMP response element-binding protein, or CREB.
In turn, CREB activation increased autophagy — the intracellular degradation system — in the low-potassium cells. Using autophagy inhibitors, the researchers showed that blocking autophagy blocked calcification. Thus, autophagy plays an important role in mediating calcification of vascular smooth muscle cells induced by the low-potassium condition.
The roles of the CREB activation and autophagy signals were then tested in the mouse artery cross-section and living-mouse models, with low, normal or high levels of potassium in the media or diet. Results in both of those systems supported the vital role for potassium to regulate vascular calcification through calcium signaling, CREB and autophagy.
Besides Chen and Sanders, co-authors of the paper, “Dietary potassium regulates vascular calcification and arterial stiffness,” published in JCI Insight, are Yong Sun, Chang Hyun Byon and Youfeng Yang, UAB Department of Pathology; Wayne E. Bradley, Louis J. Dell’Italia and Anupam Agarwal, UAB Department of Medicine; and Hui Wu, UAB Department of Pediatric Dentistry. Sanders, Agarwal and Chen are also members of the Research Department, Veterans Affairs Birmingham Medical Center.
The paper is also highlighted as an Editor’s Pick in the November issue of JCI This Month.
At UAB, Agarwal holds the Marie S. Ingalls Endowed Chair in Nephrology Leadership, Dell’Italia holds the Elmer and Glenda Harris Endowed Chair in Cardiovascular Disease, and Sanders holds the Thomas E. Andreoli Endowed Chair in Nephrology.
Funding for this work came from National Institutes of Health grants HL092215, HL136165 and DK100847, as well as Veterans Affairs Research Department awards BX000369, BX003617 and BX001591.
Public Release: 11-Oct-2017
George Institute for Global Health
The risk of developing type 2 diabetes could be significantly reduced by eating a diet rich in omega-6 polyunsaturated fats, a new study suggests.
These findings, published in The Lancet Diabetes & Endocrinology, shed new light on the potential health benefits of omega-6, which is found in bean and seed oils such as soybean and sunflower oils and in nuts, and support clinical recommendations to increase dietary intake of omega-6 rich foods.
Lead author Dr Jason Wu, of The George Institute for Global Health in Sydney, said: “Our findings suggest that a simple change in diet might protect people from developing type 2 diabetes which has reached alarming levels around the world.”
“This is striking evidence,” said senior author and Professor Dariush Mozaffarian, of the Friedman School of Nutrition Science and Policy at Tufts University in Massachusetts. “The people involved in the study were generally healthy and were not given specific guidance on what to eat. Yet those who had the highest levels of blood omega-6 markers had a much lower chance of developing type 2 diabetes.”
Recent studies have raised concerns that omega-6 may have negative health effects, such as inflammation leading to the increased risk of chronic diseases.
Yet, when the global collaboration led by The George Institute explored these concerns in studies from around the world, they found that individuals who had the highest blood level of linoleic acid, the major omega-6 fat, were 35 per cent less likely to develop type 2 diabetes in the future than those who had the least amount.
Researchers analysed data from 20 studies involving 39,740 adults from 10 countries, in whom 4,347 new cases of diabetes occurred over time. These included adults with a wide range of ages and without any diagnosis of type 2 diabetes at the onset of the studies, when they were laboratory tested for levels of two key omega-6 markers – linoleic acid and arachidonic acid. Linoleic acid was associated with lower risk, while levels of arachidonic acid were not significantly associated with either higher or lower risk of diabetes.
“Some scientists have theorized that omega-6 is harmful to health,” said Dr Wu. “But based on this large global study, we have demonstrated little evidence for harms, and indeed found that the major omega-6 fat is linked to lower risk of type 2 diabetes.”
Linoleic acid is not formed in the body and can only be obtained from the diet. US dietary guidelines recommend between 5-10 per cent of energy should be derived from polyunsaturated fats. “Based on concerns for harm, some countries recommend even lower intakes,” said Dr Wu. “Our results suggest that eating foods rich in linoleic acid may lower risk of type 2 diabetes.”
This research combined many large observational studies, and therefore it could not directly determine the effect of raising omega-6 fat levels in a trial. The study’s strengths include the use of objective blood or tissue biomarkers of fatty acids, that avoid memory errors associated with people’s own impressions of their diet; that researchers developed a pre-specified standardized analysis protocol, which increases consistency of the findings; and that data from many countries around the world was included, enhancing the relevance to different populations.
Public Release: 13-Oct-2017
These results, seen in animal models, represent a potentially novel therapeutic target for the treatment of seizure disorders
University of Alabama at Birmingham
BIRMINGHAM, Ala. – Seizure disorders — including epilepsy — are associated with pathological hyperexcitability in brain neurons. Unfortunately, there are limited available treatments that can prevent this hyperexcitability. However, University of Alabama at Birmingham researchers have found that inducing a biochemical alteration in brain proteins via the dietary supplement glucosamine was able to rapidly dampen that pathological hyperexcitability in rat and mouse models.
These results represent a potentially novel therapeutic target for the treatment of seizure disorders, and they show the need to better understand the physiology underlying these neural and brain circuit changes.
Proteins are the workhorses of living cells, and their activities are tightly and rapidly regulated in responses to changing conditions. Adding or removing a phosphoryl group to proteins is a well-known regulator for many proteins, and it is estimated that human proteins may have as many as 230,000 sites for phosphorylation.
A lesser-known regulation comes from the addition or removal of N-acetylglucosamine to proteins, which is usually controlled by glucose, the primary fuel for neurons. Several years ago, neuroscientist Lori McMahon, Ph.D., professor of cell, developmental and integrative biology at UAB, found out from her colleague John Chatham, D.Phil., a UAB professor of pathology and a cardiac physiologist, that brain cells had the second-highest amounts of proteins with N-acetylglucosamine, or O-GlcNAcylation, in the body.
At the time, very little was known about how O-GlcNAcylation might affect brain function, so McMahon and Chatham started working together. In 2014, McMahon and Chatham, in a study led by graduate student Erica Taylor and colleagues, reported that acute increases in protein O-GlcNAcylation caused long-term synaptic depression, a reduction in neuronal synaptic strength, in the hippocampus of the brain. This was the first time acute changes in O-GlcNAcylation of neuronal proteins were shown to directly change synaptic function.
Since neural excitability in the hippocampus is a key feature of seizures and epilepsy, they hypothesized that acutely increasing protein O-GlcNAcylation might dampen the pathological hyperexcitability associated with these brain disorders.
That turned out to be the case, as reported in the Journal of Neuroscience study, “Acute increases in protein O-GlcNAcylation dampen epileptiform activity in hippocampus.” The study was led by corresponding author McMahon and first author Luke Stewart, a doctoral student in the Neuroscience Theme of the Graduate Biomedical Sciences Program. Stewart is co-mentored by McMahon and Chatham.
“Our findings support the conclusion that protein O-GlcNAcylation is a regulator of neuronal excitability, and it represents a promising target for further research on seizure disorder therapeutics,” they wrote in their research significance statement. The researchers caution that the mechanism underlying the dampening is likely to be complex.
Glucose, the major fuel for neurons, also controls the levels of protein O-GlcNAcylation on proteins. However, high levels of the dietary supplement glucosamine, or an inhibitor of the enzyme that removes O-GlcNAcylation, leads to rapid increases in O-GlcNAc levels.
In experiments with hippocampal brain slices treated to induce a stable and ongoing hyperexcitability, UAB researchers found that an acute increase in protein O-GlcNAcylation significantly decreased the sudden bursts of electrical activity known as epileptiform activity in area CA1 of the hippocampus. An increased protein O-GlcNAcylation in normal cells also protected against a later induction of drug-induced hyperexcitability.
The effects were seen in slices treated with both glucosamine and an inhibitor of the enzyme that removes O-GlcNAc groups. They also found that treatment with glucosamine alone for as short a time as 10 minutes was able to dampen ongoing drug-induced hyperexcitability.
In common with the long-term synaptic depression provoked by increased O-GlcNAcylation, the dampening of hyperexcitability required the GluA2 subunit of the AMPA receptor, which is a glutamate-gated ion channel responsible for fast synaptic transmission in the brain. This finding suggested a conserved mechanism for the two changes provoked by increased O-GlcNAcylation — synaptic depression and dampening of hyperexcitability.
The researchers also found that the spontaneous firing of pyramidal neurons in another region of hippocampus, area CA3, was reduced by increased O-GlcNAcylation in normal brain slices and in slices with drug-induced hyperexcitability. This reduction in spontaneous firing of CA3 pyramidal neurons likely contributes to decreased hyperexcitability in area CA1 since the CA3 neurons directly excite those in CA1.
Similar to the findings for brain slices, mice that were treated to increase O-GlcNAcylation before getting drug-induced hyperexcitability had fewer of the brain activity spikes associated with epilepsy that are called interictal spikes. Several drug-induced hyperexcitable mice had convulsive seizures during the experiments — this occurred in both the increased O-GlcNAcylation mice and the control mice. Brain activity during the seizures differed between these two groups: The peak power of the brain activity for the mice with increased O-GlcNAcylation occurred at a lower frequency, as compared with the control mice.
Co-authors with McMahon, Chatham and Stewart in the Journal of Neuroscience study are Anas Khan, Kai Wang and Michelle Olsen, UAB Department of Cell, Developmental and Integrative Biology; Diana Pizarro and Sandip Pati, UAB Department of Neurology; and Sue Buckingham, UAB Department of Neurobiology.
Funding for the research came from the National Institutes of Health grant NS076312 and NIH pre-doctoral fellowship NS095568.
At UAB, McMahon holds the Jarman F. Lowder Endowed Professorship in Neuroscience.
Public Release: 13-Oct-2017
VIB (the Flanders Institute for Biotechnology)
A nine-year joint research project conducted by VIB, KU Leuven and VUB has led to a crucial breakthrough in cancer research. Scientists have clarified how the Warburg effect, a phenomenon in which cancer cells rapidly break down sugars, stimulates tumor growth. This discovery provides evidence for a positive correlation between sugar and cancer, which may have far-reaching impacts on tailor-made diets for cancer patients. The research has been published in the leading academic journal Nature Communications.
This project was started in 2008 under the leadership of Johan Thevelein (VIB-KU Leuven), Wim Versées (VIB-VUB) and Veerle Janssens (KU Leuven). Its main focus was the Warburg effect, or the observation that tumors convert significantly higher amounts of sugar into lactate compared to healthy tissues. As one of the most prominent features of cancer cells, this phenomenon has been extensively studied and even used to detect brain tumors, among other applications. But thus far, it has been unclear whether the effect is merely a symptom of cancer, or a cause.
Sugar awakens cancer cells
While earlier research into cancer cell metabolism focused on mapping out metabolic peculiarities, this study clarifies the link between metabolic deviation and oncogenic potency in cancerous cells.
Prof. Johan Thevelein (VIB-KU Leuven): “Our research reveals how the hyperactive sugar consumption of cancerous cells leads to a vicious cycle of continued stimulation of cancer development and growth. Thus, it is able to explain the correlation between the strength of the Warburg effect and tumor aggressiveness. This link between sugar and cancer has sweeping consequences. Our results provide a foundation for future research in this domain, which can now be performed with a much more precise and relevant focus.”
Yeast as an advantageous model organism
Yeast cell research was essential to the discovery, as these cells contain the same ‘Ras’ proteins commonly found in tumor cells, which can cause cancer in mutated form. Using yeast as a model organism, the research team examined the connection between Ras activity and the highly active sugar metabolism in yeast.
Prof. Johan Thevelein (VIB-KU Leuven): “We observed in yeast that sugar degradation is linked via the intermediate fructose 1,6-biophosphate to the activation of Ras proteins, which stimulate the multiplication of both yeast and cancer cells. It is striking that this mechanism has been conserved throughout the long evolution of yeast cell to human.
“The main advantage of using yeast was that our research was not affected by the additional regulatory mechanisms of mammalian cells, which conceal crucial underlying processes. We were thus able to target this process in yeast cells and confirm its presence in mammalian cells. However, the findings are not sufficient to identify the primary cause of the Warburg effect. Further research is needed to find out whether this primary cause is also conserved in yeast cells.”
Public Release: 16-Oct-2017
Research published in the Journal of the American Osteopathic Association examines gap between nutritional knowledge and attitudes in future physicians
American Osteopathic Association
CHICAGO — October 16, 2017–Ohio University researchers found medical students may be more confident than knowledgeable when it comes to nutrition. Of the 257 medical students studied, more than 55 percent were confident they could counsel patients on nutritional recommendations, but half did not achieve a passing score on a nutrition quiz, according to a study published in The Journal of the American Osteopathic Association.
Of particular note, only 12 percent were aware of Dietary Reference Intakes (DRIs), a key guide to differentiated nutrition requirements, although more than 68 percent agreed that primary care physicians should counsel patients about nutrition.
“There is a long-standing disconnect in medicine. Nutrition is understood to be integral to overall health, but it is not given serious attention in physician education,” said Elizabeth Beverly, PhD, the lead author of this study and assistant professor at Ohio University Heritage College of Osteopathic Medicine. “The lack of knowledge about dietary reference intakes, which tell physicians what kind of nutrient and energy intake their patients need, is concerning because the guidelines vary dramatically by age, sex, and other factors, like pregnancy and disease.”
Prior research has shown that physicians who are overly confident are less likely to seek additional resources and more likely to misdiagnose patients. Researchers expressed concern that overconfident medical students may not attempt to further understand or explore important nutritional recommendations when treating patients in the future.
The National Academy of Science recommends 25 hours of nutrition education for physicians. However, multiple studies have confirmed that most medical schools fall significantly short of that goal.
Beverly and her co-authors recommend developing nutrition-related competencies, as well as including nutrition questions on board certification examinations, to help ensure that schools adhere to the minimum number of hours of nutrition education.
“Medical schools are focused on preparing students to pass board certification exams. Currently, nutrition knowledge is not evaluated by most certification boards,” says Beverly. “If we can change that, schools will adjust their curriculum accordingly and we should ultimately see an improvement in patient education and care.”
The complete study can be found at jaoa.org.
About The Journal of the American Osteopathic Association
The Journal of the American Osteopathic Association (JAOA) is the official scientific publication of the American Osteopathic Association. Edited by Robert Orenstein, DO, it is the premier scholarly peer-reviewed publication of the osteopathic medical profession. The JAOA’s mission is to advance medicine through the publication of peer-reviewed osteopathic research.
Media Relations Manager
Public Release: 10-Oct-2017
University of California – San Diego
Credit: UC San Diego Health
Approximately 10 percent of the general population take a proton pump inhibitor (PPI) drug to block stomach acid secretions and relieve symptoms of frequent heartburn, acid reflux and gastroesophageal reflux disease. That percentage can be as much as seven times higher for people with chronic liver disease. Researchers at University of California San Diego School of Medicine have discovered evidence in mice and humans that stomach (gastric) acid suppression alters specific gut bacteria in a way that promotes liver injury and progression of three types of chronic liver disease.
The study is published October 10 in Nature Communications.
“Our stomachs produce gastric acid to kill ingested microbes, and taking a medication to suppress gastric acid secretion can change the composition of the gut microbiome,” said senior author Bernd Schnabl, MD, associate professor of gastroenterology at UC San Diego School of Medicine. “Since we found previously that the gut microbiome — the communities of bacteria and other microbes living there — can influence liver disease risk, we wondered what effect gastric acid suppression might have on the progression of chronic liver disease. We found that the absence of gastric acid promotes growth of Enterococcus bacteria in the intestines and translocation to the liver, where they exacerbate inflammation and worsen chronic liver disease.”
Liver cirrhosis is the 12th leading cause of death worldwide and the number of people with chronic liver disease is increasing rapidly in Western countries. The increase is partly due to the rising prevalence of obesity, which is associated with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Approximately half of all cirrhosis-associated deaths are related to alcohol.
PPIs, which include brand names such as Prilosec, Nexium and Prevacid, are among the most commonly prescribed medications in the world, particularly among people with chronic liver disease. They are also relatively inexpensive medications, retailing for approximately $7 for a recommended two-week course of generic, over-the-counter Prilosec (omeprazole). But the frequency of use adds up — one study estimates Americans spend $11 billion on PPIs each year.
To determine the effect of gastric acid suppression on the progression of chronic liver disease, Schnabl’s team looked at mouse models that mimic alcoholic liver disease, NAFLD and NASH in humans. In each, they blocked gastric acid production either by genetic engineering or with a PPI (omeprazole/Prilosec). They sequenced microbe-specific genes collected from the animals’ stool to determine the gut microbiome makeup of each mouse type, with or without blocked gastric acid production.
The researchers found that mice with gastric acid suppression developed alterations in their gut microbiomes. Specifically, they had more Enterococcus species of bacteria. These changes promoted liver inflammation and liver injury, increasing the progression of all three types of liver disease in the mice: alcohol-induced liver disease, NAFLD and NASH.
To confirm it was the increased Enterococcus that exacerbated chronic liver disease, Schnabl’s team also colonized mice with the common gut bacteria Enterococcus faecalis to mimic the overgrowth of intestinal enterococci they had observed following gastric acid suppression. They found that increased Enterococcus alone was sufficient to induce mild steatosis and increase alcohol-induced liver disease in mice.
The team also examined the link between PPI usage and alcoholic liver disease among people who abuse alcohol. They analyzed a cohort of 4,830 patients with a diagnosis of chronic alcohol abuse — 1,024 (21 percent) were active PPI users, 745 (15 percent) were previous users and 3061 (63 percent) had never used PPIs.
The researchers noted that PPI intake among these patients increased stool concentrations of Enterococcus. What’s more, the 10-year risk of a diagnosis of alcoholic liver disease was 20.7 percent for active users of PPIs, 16.1 percent for previous users and 12.4 percent for never users. In other words, the rate of liver disease in people who chronically abuse alcohol was 8.3 percent higher for those who actively use PPIs compared to those who never used the acid-blocking medications.
The researchers concluded that there is an association between PPI use among people who abuse alcohol and risk of liver disease. However, they can’t yet rule out the possibility that there could be other unidentified factors that differ between patients that do and do not take PPIs, which might confound the relationship between PPI use and liver disease.
While this study relies upon mouse models and a patient database, and a large, randomized, controlled clinical trial would be needed to definitively show causality between PPI usage and risk of chronic liver disease in humans, Schnabl said the initial data should at least get people thinking about reducing their use of PPIs in cases where they aren’t a necessity.
There are inexpensive and readily available alternatives to PPIs. However, even non-PPI-based antacids (e.g., Pepto-Bismol, Tums, or H2 blockers such as Tagamet and Zantac) still suppress gastric acid to a lesser degree. While these other types of antacids were not tested in this study, Schnabl said any medication that suppresses gastric acid effectively could cause changes in gut bacteria and thus potentially affect the progression of chronic liver disease. Alternatively, non-pharmacological methods for managing heartburn are an option for some patients, including losing weight and reducing intake of alcohol, caffeine, and fatty and spicy foods.
“Our findings indicate that the recent rise in use of gastric acid-suppressing medications might have contributed to the increased incidence of chronic liver disease,” Schnabl said. “Although obesity and alcohol use predispose a person to acid reflux requiring antacid medication, many patients with chronic liver disease take gastric acid suppressive medications without appropriate indication. We believe clinicians should consider withholding medications that suppress gastric acid unless there is a strong medical indication.”
This new information might also provide a new therapeutic avenue researchers could explore as a means to reduce risk of liver injury in some people.
“We might someday be able to manipulate the gut microbiome, and in particular Enterococcus faecalis, to attenuate alcohol-related liver disease associated with gastric acid suppression,” Schnabl said.
Co-authors of this study include: Cristina Llorente, Lirui Wang, Samuel B. Ho, UC San Diego and VA San Diego Healthcare System; Peter Jepsen, Henrik T. Sørensen, Hendrik Vilstrup, Aarhus University Hospital, Denmark; Tatsuo Inamine, UC San Diego and Nagasaki University; Sena Bluemel, Hui J. Wang,
Rohit Loomba, Jun Xu, Tatiana Kisseleva, Xin Du, David A. Brenner, UC San Diego; Jasmohan S. Bajaj, Mitchell L. Schubert, Virginia Commonwealth University and McGuire VA Medical Center; Masoumeh Sikaroodi, Patrick M. Gillevet, George Mason University; Jessica DePew, Karen E. Nelson, and Derrick E. Fouts, J. Craig Venter Institute.
Public Release: 30-Oct-2017
The JAMA Network Journals
Bottom Line: Eating more fruits and vegetables with high-pesticide residue was associated with a lower probability of pregnancy and live birth following infertility treatment for women using assisted reproductive technologies.
The Research Question: Is preconception intake of fruits and vegetables with pesticide residues associated with outcomes of assisted reproductive technologies?
Why The Question is Interesting: Animal studies suggest ingestion of pesticide mixtures in early pregnancy may be associated with decreased live-born offspring leading to concerns that levels of pesticide residues permitted in food by the U.S. Environmental Protection Agency may still be too high for pregnant women and infants.
Who: 325 women who completed a diet questionnaire and subsequently underwent cycles of assisted reproductive technologies as part of the Environment and Reproductive Health (EARTH) study at a fertility center at a teaching hospital in Boston.
When: Between 2007 and 2016
Study Measures: Researchers categorized fruits and vegetables as having high or low pesticide residues using a method based on surveillance data from the U.S. Department of Agriculture. They counted the number of confirmed pregnancies and live births per cycle of fertility treatment.
Design: This is an observational study. In observational studies, researchers observe exposures and outcomes for patients as they occur naturally in clinical care or real life. Because researchers are not intervening for purposes of the study they cannot control natural differences that could explain study findings so they cannot prove a cause-and-effect relationship.
Authors: Jorge E. Chavarro, M.D., Sc.D., of the Harvard T. H. Chan School of Public Health, Boston, and colleagues
Results: Eating more high-pesticide residue fruits and vegetables (for example, strawberries and raw spinach) was associated with a lower probability of pregnancy and live birth following infertility treatment. Eating more low-pesticide residue fruits and vegetables was not associated with worse pregnancy and live birth outcomes.
Study Limitations: The study estimated exposure to pesticides based on women’s self-reported intake combined with pesticide residue surveillance data rather than through direct measurement. The study also cannot link specific pesticides to adverse effects.
Study Conclusions: “In conclusion, intake of high-residue FVs [fruits and vegetables] was associated with lower probabilities of clinical pregnancy and live birth among women undergoing infertility treatment. Our findings are consistent with animal studies showing that low-dose pesticide ingestion may exert an adverse impact on sustaining pregnancy. Because, to our knowledge, this is the first report of this relationship to humans, confirmation of these findings is warranted.”