227 CNO REPORT 12 APR 2016

227CNO12APR2016

clip_image002

CNO Report 227

Release Date 12 APR 2016

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

 

 

In this issue:

1.       Are we what we eat?

2.       Are you what you sweat?

3.       Eating beans, peas, chickpeas or lentils may help lose weight and keep it off

4.       Large whey protein breakfast may help manage type 2 diabetes

5.       More dietary calcium may lower risk of cardiovascular disease

6.       Higher levels of vitamin D correspond to lower cancer risk, researchers say

7.       Is a popular painkiller hampering our ability to notice errors?

8.       Scientists discover how Chinese medicinal plant makes anti-cancer compound

 

 

Public Release: 29-Mar-2016

Are we what we eat?

Evidence of a vegetarian diet permanently shaping the human genome to change individual risk of cancer and heart disease

Molecular Biology and Evolution (Oxford University Press)

In a new evolutionary proof of the old adage, ‘we are what we eat’, Cornell University scientists have found tantalizing evidence that a vegetarian diet has led to a mutation that — if they stray from a balanced omega-6 to omega-3 diet — may make people more susceptible to inflammation, and by association, increased risk of heart disease and colon cancer.

The discovery, led by Drs. Tom Brenna, Kumar Kothapalli, and Alon Keinan provides the first evolutionary detective work that traces a higher frequency of a particular mutation to a primarily vegetarian population from Pune, India (about 70 percent), when compared to a traditional meat-eating American population, made up of mostly Kansans (less than 20 percent). It appears in the early online edition of the journal Molecular Biology and Evolution.

By using reference data from the 1000 Genomes Project, the research team provided evolutionary evidence that the vegetarian diet, over many generations, may have driven the higher frequency of a mutation in the Indian population. The mutation, called rs66698963 and found in the FADS2 gene, is an insertion or deletion of a sequence of DNA that regulates the expression of two genes, FADS1 and FADS2. These genes are key to making long chain polyunsaturated fats. Among these, arachidonic acid is a key target of the pharmaceutical industry because it is a central culprit for those at risk for heart disease, colon cancer, and many other inflammation-related conditions. Treating individuals according to whether they carry 0, 1, or 2 copies of the insertion, and their influence on fatty acid metabolites, can be an important consideration for precision medicine and nutrition.

The insertion mutation may be favored in populations subsisting primarily on vegetarian diets and possibly populations having limited access to diets rich in polyunsaturated fats, especially fatty fish. Very interestingly, the deletion of the same sequence might have been adaptive in populations which are based on marine diet, such as the Greenlandic Inuit. The authors will follow up the study with additional worldwide populations to better understand the mutations and these genes as a genetic marker for disease risk.

“With little animal food in the diet, the long chain polyunsaturated fatty acids must be made metabolically from plant PUFA precursors. The physiological demand for arachidonic acid, as well as omega-3 EPA and DHA, in vegetarians is likely to have favored genetics that support efficient synthesis of these key metabolites.” say Brenna and Kothapalli in a joint comment. “Changes in the dietary omega-6 to omega-3 balance may contribute to the increase in chronic disease seen in some developing countries.”

“This is the most unique scenario of local adaptation that I had the pleasure of helping uncover”, says Alon Keinan, a population geneticist who led the evolutionary study. “Several previous studies pointed to recent adaptation in this region of the genome. Our analysis points to both previous studies and our results being driven by the same insertion of an additional small piece of DNA, an insertion which has a known function. We showed this insertion to be adaptive, hence of high frequency, in Indian and some African populations, which are vegetarian. However, when it reached the Greenlandic Inuit, with their marine diet, it became maladaptive.” Kaixiong Ye, a postdoctoral research fellow at Keinan’s lab, further notes that “our results show a global frequency pattern of the insertion mutation adaptive to vegetarian diet (see figure), with highest frequency in Indians who traditionally relied heavily on a plant-based diet.”

Public Release: 30-Mar-2016

Are you what you sweat?

The importance of electrolyte concentration in perspiration

FECYT – Spanish Foundation for Science and Technology

Spanish researchers have analysed how the sodium lost through sweat during a marathon influences the maintenance of stable and physiologically sound conditions that allow the body to carry out its functions. Excessive electrolyte loss may lead to a medical problem known as hyponatraemia.

For years, scientists have emphasised the importance of staying properly hydrated during exercise. Maintaining the body’s sodium levels has become a key priority for the success of elite athletes and enthusiasts alike.

The amount of sweat that is lost during the majority of athletic activities (football, basketball, volleyball) is relatively low due to the duration of these sports.

However, in endurance and ultra-endurance events -such as marathon races that are increasingly more popular- several litres of sweat can be lost.

For this reason, experts from the Exercise Physiology Laboratory at Camilo José Cela University (UCJC) analysed the electrolytes present in the sweat of a group of marathon runners in addition to the concentration of electrolytes in their blood upon completing the race.

“We do not only lose fluids when we sweat -which can be replaced with beverages- but the levels of several electrolytes that are essential to fluid balance and neuromuscular functioning also decrease -especially sodium,” as explained to SINC by Beatriz Lara, the main author of the study and a researcher at UCJC.

This becomes a problem when that excessive loss of electrolytes through sweat is not properly recovered with food or beverages, a scenario that could lead to hyponatraemia (a sodium concentration in the blood of less than 135 mmol/L which, in severe cases, can cause decreased consciousness, hallucinations or coma, brain herniation and even death).

The study, now published in the Scandinavian Journal of Medicine & Science in Sports, demonstrates the importance of maintaining the correct serum electrolyte levels during the race in order to prevent decreased performance as well as the associated health complications.

What impact does this have on the marathon?

During the study, two patches specifically designed to collect sweat samples were placed on the skin of 51 marathon runners and were worn throughout the entire marathon. Immediately after completing the race, a blood sample was taken from each runner to analyse their electrolyte levels.

The first analysis allowed the runners to be classified into three groups depending on their sodium concentrations: runners with ‘low-salt’ sweat; ‘typical’ sweaters with a normal amount of sodium in their sweat, and ‘salty’ sweaters which are those runners who had an excessive amount of sodium in their sweat.

The data show that the marathon runners who had very high concentrations of electrolytes in their sweat (the ‘salty’ sweaters) had lower electrolyte levels in their blood despite having properly rehydrated and having eaten the same amount of food with salt as the rest of the runners.

These figures indicate that electrolyte levels in sweat can affect water and electrolyte homeostasis over the course of the marathon; in other words, sweat electrolyte levels can have an impact on the maintenance of stable and physiologically sound conditions that allow the body to carry out its functions.

“Electrolyte concentration in sweat is an essential factor for predicting sodium requirements during sports activities -especially endurance activities such as marathons. It is likely that individuals with very salty sweat would benefit from oral supplements, such as salt tablets for instance,” concludes Lara.

Public Release: 30-Mar-2016

Eating beans, peas, chickpeas or lentils may help lose weight and keep it off

United Nations and the Food and Agriculture Organization have designated 2016 as the International Year of Pulses

St. Michael’s Hospital

TORONTO, March 30, 2016–Eating one serving a day of beans, peas, chickpeas or lentils could contribute to modest weight loss, a new study suggests.

Eating about 3/4 cup (130 grams) each day of these foods known as pulses led to a weight loss of 0.34 kilograms (just over half a pound), in a systematic review and meta-analysis of all available clinical trials on the effects of eating pulses.

The paper, by lead author Dr. Russell de Souza, a researcher with the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, was published today in The American Journal of Clinical Nutrition.

The research builds on previous work by the hospital’s Clinical Nutrition and Risk Factor Modification Centre, that a daily serving of pulses makes people feel fuller than if they ate a control diet, and that eating pulses can significantly reduce “bad cholesterol.”

“Despite their known health benefits, only 13 per cent of Canadians eat pulses on any given day and most do not eat the full serving,” Dr. de Souza said. “So there is room for most of us to incorporate dietary pulses in our diet and realize potential weight management benefits.”

The United Nations and the Food and Agriculture Organization have designated 2016 as the International Year of Pulses.

The meta-analysis looked at 21 clinical trials involving 940 adult men and women, who lost an average of 0.34 kg (0.75 pounds) over six weeks with the addition of a single serving of pulses to the diet–and without making a particular effort to reduce other foods.

Pulses have a low glycemic index (meaning that they are foods that break down slowly) and can be used to reduce or displace animal protein as well as “bad” fats such as trans-fat in a dish or meal.

Dr. de Souza noted that 90 per cent of weight loss interventions fail, resulting in weight regain, which may be due in part to hunger and food cravings.

“This new study fits well with our previous work, which found that pulses increased the feeling of fullness by 31 per cent, which may indeed result in less food intake.” said Dr. de Souza.

Another recently published systematic review and meta-analysis found that eating on average one serving a day of beans, peas, chickpeas or lentils can also reduce “bad cholesterol” by five per cent and therefore lower the risk of cardiovascular disease.

Knowing which foods make people feel fuller longer may help them lose weight and keep it off.

“Though the weight loss was small, our findings suggest that simply including pulses in your diet may help you lose weight, and we think more importantly, prevent you from gaining it back after you lose it,” Dr. de Souza said.

He said another bonus from eating pulses is that they are Canadian crops.

“So eating more pulses means eating local, being more sustainable and receiving many health benefits,” he said.

Public Release: 2-Apr-2016

Large whey protein breakfast may help manage type 2 diabetes

The Endocrine Society

Boston, MA– A large breakfast containing whey protein may help manage Type 2 diabetes, new research from Israel reports. The study results will be presented Friday, April 1, at ENDO 2016, the annual meeting of the Endocrine Society, in Boston.

“A high-calorie protein breakfast, medium-sized lunch and small dinner is a proven successful strategy for weight loss, improved satiety and reduced glucose spikes throughout the day in people with obesity and Type 2 diabetes,” said lead study author Daniela Jakubowicz, MD, professor of medicine at Tel Aviv University.

“However, the benefits of high protein content at breakfast also depend on the protein source and quality,” Jakubowicz said. “Whey protein powder, which is a byproduct of milk during cheese production, induced greater satiety and reduction of glucose spikes after meals compared to other protein sources, such as eggs, soy or tuna.”

Jakubowicz and her colleagues investigated whether in overweight and obese people with Type 2 diabetes, whey protein for breakfast is more effective than other proteins for weight loss, satiety and reduction of glucose spikes and HbA1C (glycated hemoglobin) levels.

They randomly assigned 48 overweight and obese participants with Type 2 diabetes who were, on average, 59 years of age, to one of three diets that contained the same number of calories.

For 23 months, all participants ate a large breakfast, medium-sized lunch and small dinner, but the breakfast composition, amount and source of proteins differed among the groups.

One group ate breakfast containing mostly whey protein such as whey protein shakes, the second group ate breakfast containing other proteins including eggs, soy and tuna, and the third ate breakfast high in carbohydrates or starch.

After 12 weeks, the group on whey protein lost the most weight: 7.6 kg (16.7 pounds), compared to 6.1 kg (13.4 pounds) for those on the other proteins, and 3.1 kg (6.8 pounds) for those in the carbohydrate group.

Whey protein diet participants were more satiated and less hungry throughout the day, with lower glucose spikes after meals compared to the other two diets, and their HbA1C also decreased more than with the other two diets.

“The whey protein diet significantly suppresses the hunger hormone ‘ghrelin.’ A whey protein drink is easily prepared and provides the advantages of a high-protein breakfast on weight loss, reduction of hunger, glucose spikes and HbA1c,” Jakubowicz said.

Public Release: 2-Apr-2016

More dietary calcium may lower risk of cardiovascular disease

Diet change did not affect stroke or fracture risk

The Endocrine Society

Boston, MA – In older people, higher dietary calcium intake may lower the risk of cardiovascular disease, but not of stroke and fracture, new research from South Korea suggests. The results will be presented in a poster Saturday, April 2, at ENDO 2016, the annual meeting of the Endocrine Society, in Boston.

“The role of dietary calcium intake in cardiovascular disease, stroke and fracture is controversial. Moreover, participants in previous studies were from populations that had calcium-rich diets. We aimed to evaluate whether high dietary calcium intake increases the risk of CVD, stroke and fracture in a population with low calcium intake,” said lead author Sung Hye Kong, MD, resident physician in the Department of Internal Medicine of Seoul National University Hospital in Seoul, South Korea.

Kong and colleagues conducted their research among individuals in Korea’s ongoing prospective community-based Ansung and Ansan Cohort Study that began in 2001. Of the 4,589 men and 5,042 women in the cohort study’s database who were 40 years of age and above at baseline and were followed up for an average of 13 years, the authors performed their analyses in 2,199 men and 2,704 women over 50 years of age without previous cardiovascular disease and stroke.

The individuals in the study reported their dietary food intake in periodic food frequency questionnaires. Cardiovascular disease, stroke and fractures were recorded during interviews and examinations every two years. In their statistical analyses, the authors made adjustments for age, body mass index, vegetable and fruit intake, protein and sodium intake, physical activity, smoking and drinking, history of hypertension and diabetes, total energy from the diet, and additionally adjusted for menopausal status and hormone replacement therapy in women.

In older women in this population with low dietary calcium intake, higher dietary calcium intake was significantly associated with decreased risk of cardiovascular disease, but not significantly associated with risk of stroke and fracture.

Public Release: 6-Apr-2016

Higher levels of vitamin D correspond to lower cancer risk, researchers say

University of California – San Diego

Researchers at University of California, San Diego School of Medicine report that higher levels of vitamin D – specifically serum 25-hydroxyvitamin D – are associated with a correspondingly reduced risk of cancer. The findings are published in the April 6, online issue of PLOS ONE.

“We have quantitated the ability of adequate amounts of vitamin D to prevent all types of invasive cancer combined, which had been terra incognita until publication of this paper,” said Cedric Garland, DrPH, adjunct professor in the UC San Diego School of Medicine Department of Family Medicine and Public Health and member of Moores Cancer Center at UC San Diego Health.

Garland and his late brother, Frank, made the first connection between vitamin D deficiency and some cancers in 1980 when they noted populations at higher latitudes (with less available sunlight) were more likely to be deficient in vitamin D, which is produced by the body through exposure to sunshine, and experience higher rates of colon cancer. Subsequent studies by the Garlands and others found vitamin D links to other cancers, such as breast, lung and bladder.

The new PLOS ONE study sought to determine what blood level of vitamin D was required to effectively reduce cancer risk. The marker of vitamin D was 25-hydroxyvitamin D, the main form in the blood. The researchers employed a non-traditional approach, pooling analyses of two previous studies of different types: a randomized clinical trial of 1,169 women and a prospective cohort study of 1,135 women. A clinical trial focuses upon whether a specific test or treatment is safe and effective. A prospective study looks for outcomes during the study period, in this case incidence of cancer among participants.

By combining the two studies, the researchers obtained a larger sample size and a greater range of blood serum levels of 25-hydroxyvitamin D or 25(OH)D.

The only accurate measure of vitamin D levels in a person is a blood test. In the Lappe trial cohort, the median blood serum level of 25(OH)D was 30 nanograms per milliliter. In the GrassrootsHealth prospective cohort, it was higher: 48 ng/ml.

The researchers found that the age-adjusted cancer incidence was 1,020 cases per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort. Cancer incidence declined with increased 25(OH)D. Women with 25(OH)D concentrations of 40 ng/ml or greater had a 67 percent lower risk of cancer than women with levels of 20 ng/ml or less.

Recommended blood serum levels of vitamin D have been a source of vigorous debate in recent years. In 2010, the Institute of Medicine (IOM) concluded that levels lower than 12 ng/ml represented a vitamin D deficiency and recommended a target of 20 ng/ml, which could be met in most healthy adults (ages 19 to 70) with the equivalent of 600 International Units of vitamin D each day.

Subsequently, other groups have argued for higher blood serum levels: 50 ng/ml or more. Above 125 ng/ml, there may be side effects. Many vitamin D supporters now advocate 800 to 1,000 IUs daily; more for persons older than 70 and pregnant or lactating women.

Garland does not identify a singular, optimum daily intake of vitamin D or the manner of intake, which may be sunlight exposure, diet and/or supplementation. He said the current study simply clarifies that reduced cancer risk becomes measurable at 40 ng/ml, with additional benefit at higher levels.

“These findings support an inverse association between 25(OH)D and risk of cancer,” he said, “and highlight the importance for cancer prevention of achieving a vitamin D blood serum concentration above 20 ng/ml, the concentration recommended by the IOM for bone health.”

Garland said a broad effort to increase 25(OH)D concentrations to a minimum of 40 ng/ml in the general population would likely and substantially reduce cancer incidence and associated mortality.

“Primary prevention of cancer, rather than expanding early detection or improving treatment, will be essential to reversing the current upward trend of cancer incidence worldwide,” the researchers wrote. “This analysis suggests that improving vitamin D status is a key prevention tool.”

Public Release: 8-Apr-2016

Is a popular painkiller hampering our ability to notice errors?

University of Toronto

It’s been known for more than a century that acetaminophen is an effective painkiller, but according to a new U of T study it could also be impeding error-detection in the brain.

The research, authored by a team including postdoctoral fellow Dan Randles and researchers from the University of British Columbia, is the first neurological study to look at how acetaminophen could be inhibiting the brain response associated with making errors.

“Past research tells us physical pain and social rejection share a neural process that we experience as distress, and both have been traced to same part of the brain,” says Randles.

Recent research has begun to show how exactly acetaminophen inhibits pain, while behavioural studies suggest it may also inhibit evaluative responses more generally. Randles own past research has found that people are less reactive to uncertain situations when under the effect of acetaminophen.

“The core idea of our study is that we don’t fully understand how acetaminophen affects the brain,” says Randles. “While there’s been recent behavioural research on the effects of acetaminophen, we wanted to have a sense of what’s happening neurologically.”

To test the idea two groups of 30 were given a target-detection task called the Go or No Go. Participants were asked to hit a Go button every time the letter F flashed on a screen but refrain from hitting the button if an E flashed on the screen. “The trick is you’re supposed to move very quickly capturing all the GOs, but hold back when you see a No Go,” says Randles.

Each participant was hooked up to an electroencephalogram (EEG), which measures electrical activity in the brain. The researchers were looking for a particular wave called Error Related Negativity (ERN) and Error Related Positivity (Pe). Essentially what happens is that when people are hooked up to an EEG and make an error in the task there is a robust increase in ERN and Pe.

One group, which was given 1,000 mg of acetaminophen – the equivalent of a normal maximum dose – showed a smaller Pe when making mistakes than those who didn’t receive a dose, suggesting that acetaminophen inhibits our conscious awareness of the error.

“It looks like acetaminophen makes it harder to recognize an error, which may have implications for cognitive control in daily life,” says Randles.

Cognitive control is an important neurological function because people are constantly doing cognitive tasks that flow automatically like reading, walking or talking. These tasks require very little cognitive control because they are well mapped out neurological processes, notes Randles.

“Sometimes you need to interrupt your normal processes or they’ll lead to a mistake, like when you’re talking to a friend while crossing the street, you should still be ready to react to an erratic driver,” explains Randles.

“The task we designed is meant to capture that since most of the stimuli were Go, so you end up getting into a routine of automatically hitting the Go button. When you see a No Go, that requires cognitive control because you need to interrupt the process.”

The study was double blind, so neither the researcher running the study nor the participant knew whether they had been given a placebo or acetaminophen.

An unexpected and surprise finding that Randles plans to explore more closely is that those who received an acetaminophen dose appeared to miss more of the Go stimuli than they should have. He plans on expanding on the error detection aspect of the research to see whether acetaminophen is possibly causing people to “mind wander” and become distracted.

“An obvious question is if people aren’t detecting these errors, are they also making errors more often when taking acetaminophen? This is the first study to address this question, so we need more work and ideally with tasks more closely related to normal daily behaviour.”

The research is published in the current edition of the journal Social Cognitive and Affective Neuroscience.

Public Release: 8-Apr-2016

Scientists discover how Chinese medicinal plant makes anti-cancer compound

John Innes Centre

New research led by Professor Cathie Martin of the John Innes Centre has revealed how a plant used in traditional Chinese medicine produces compounds which may help to treat cancer and liver diseases.

The Chinese skullcap, Scutellaria baicalensis – otherwise known in Chinese medicine as Huang-Qin – is traditionally used as a treatment for fever, liver and lung complaints.

Previous research on cells cultured in the lab has shown that certain compounds called flavones, found in the roots of this plant, not only have beneficial anti-viral and anti-oxidant effects, but they can also kill human cancers while leaving healthy cells untouched. In live animal models, these flavones have also halted tumour growth, offering hope that they may one day lead to effective cancer treatments, or even cures.

As a group of compounds, the flavones are relatively well understood. But the beneficial flavones found in Huang-Qin roots, such as wogonin and baicalin, are different: a missing – OH (hydroxyl) group in their chemical structure left scientists scratching their heads as to how they were made in the plant.

Professor Cathie Martin, lead author of the paper published in Science Advances, explains: “Many flavones are synthesised using a compound called naringenin as a building block. But naringenin has this -OH group attached to it, and there is no known enzyme that will remove it to produce the flavones we find in Huang-Qin roots.”

Working in collaboration with Chinese scientists, Cathie and her team explored the possibility that Huang-Qin’s root-specific flavones (RSFs) were made via a different biochemical pathway. Step-by-step, the scientists unravelled the mechanism involving new enzymes that make RSFs using a different building block called chrysin.

“We believe that this biosynthetic pathway has evolved relatively recently in Scutellaria roots, diverging from the classical pathway that produces flavones in leaves and flowers, specifically to produce chrysin and its derived flavones,” said Professor Martin.

“Understanding the pathway should help us to produce these special flavones in large quantities, which will enable further research into their potential medicinal uses. It is wonderful to have collaborated with Chinese scientists on these traditional medicinal plants. Interest in traditional remedies has increased dramatically in China since Tu Youyou was awarded the Nobel Prize for Medicine in 2015 for her work on artemisinin. It’s exciting to consider that the plants which have been used as traditional Chinese remedies for thousands of years may lead to effective modern medicines.”