218CNO14NOV2015
Release Date 13 NOV 2015
Draft Report Compiled by
Ralph Turchiano
In this issue:
1. ‘Everything in moderation’ diet advice may lead to poor metabolic health in US adults
2. Vitamin D pill a day may improve exercise performance and lower risk of heart disease
3. Soybean foods may protect menopausal women against osteoporosis
4. Increasing vitamin D supplementation
5. Gut bacteria can dramatically amplify cancer immunotherapy
6. Vitamin C stresses and kills mutant cancer cells
7. Vanilla yogurt makes us feel happy, suggests research
8. First, do no harm: Hospital patients given anti-heartburn drugs have higher risk of dying
9. In new study, Illinois scientists trace activity of cancer-fighting tomato component
Public Release: 30-Oct-2015
‘Everything in moderation’ diet advice may lead to poor metabolic health in US adults
University of Texas Health Science Center at Houston
HOUSTON – (Oct. 30, 2015) – Diet diversity, as defined by less similarity among the foods people eat, may be linked to lower diet quality and worse metabolic health, according to researchers at The University of Texas Health Science Center at Houston (UTHealth) and the Friedman School of Nutrition Science and Policy at Tufts University. The study was published today in PLOS ONE.
“‘Eat everything in moderation’ has been a long-standing dietary recommendation, but without much empiric supporting evidence in populations. We wanted to characterize new metrics of diet diversity and evaluate their association with metabolic health,” said Marcia C. de Oliveira Otto, Ph.D., first author and assistant professor in the Department of Epidemiology, Human Genetics and Environmental Sciences at UTHealth School of Public Health.
Using data from 6,814 participants in the Multi-Ethnic Study of Atherosclerosis, a study of whites, blacks, Hispanic-Americans and Chinese-Americans in the United States, the authors measured diet diversity through different measures. These included the total count (number of different foods eaten in a week), evenness (the distribution of calories across different foods consumed), and dissimilarity (the differences in food attributes relevant to metabolic health, such as fiber, sodium or trans-fat content).
Researchers evaluated how diet diversity was associated with change in waist circumference five years after the beginning of the study and with onset of Type 2 diabetes 10 years later. Waist circumference is an important indicator of central fat and metabolic health.
When evaluating both food count and evenness, no associations were seen with either increase in waist circumference or incidence of diabetes. In other words, more diversity in the diet was not linked to better outcomes. Participants who had the greatest food dissimilarity actually experienced more central weight gain, with a 120 percent greater increase in waist circumference than participants with the lowest food dissimilarity.
To compare with the results seen for diet diversity, the researchers also examined how diet quality relates to metabolic health. Diet quality was measured using established scores such as the Dietary Approaches to Stop Hypertension (DASH) score and the Alternative Healthy Eating Index (AHEI) score. At five years, diet quality was not associated with change in waist circumference.
At ten years, higher diet quality was associated with about a 25 percent lower risk of developing Type 2 diabetes.
“An unexpected finding was that participants with greater diversity in their diets, as measured by dissimilarity, actually had worse diet quality. They were eating less healthy foods, such as fruits and vegetables, and more unhealthy foods, such as processed meats, desserts and soda,” said Otto. “This may help explain the relationship between greater food dissimilarity and increased waist circumference.”
Dietary diversity as measured by food count and evenness was also associated with higher intakes of both healthy and unhealthy foods.
“Americans with the healthiest diets actually eat a relatively small range of healthy foods,” said Dariush Mozaffarian, M.D., Dr.P.H., senior author and dean of the Friedman School of Nutrition Science and Policy at Tufts University in Boston. “These results suggest that in modern diets, eating ‘everything in moderation’ is actually worse than eating a smaller number of healthy foods.”
Public Release: 1-Nov-2015
Vitamin D pill a day may improve exercise performance and lower risk of heart disease
Society for Endocrinology
Taking vitamin D supplements can improve exercise performance and lower the risk of heart disease, according to the findings of a preliminary study presented today at the Society for Endocrinology annual conference in Edinburgh.
Vitamin D, which is both a vitamin and a hormone, helps control levels of calcium and phosphate in the blood and is essential for the formation of bones and teeth. Sources of Vitamin D include oily fish and eggs, but it can be difficult to get enough through diet alone. Most people generate vitamin D by exposing their skin to ultraviolet B rays in sunlight.
Previous studies suggest that vitamin D can block the action of enzyme 11-βHSD1, which is needed to make the “stress hormone” cortisol. High levels of cortisol may raise blood pressure by restricting arteries, narrowing blood vessels and stimulating the kidneys to retain water. As Vitamin D may reduce circulating levels of cortisol, it could theoretically improve exercise performance and lower cardiovascular risk factors.
In this study, researchers from Queen Margaret University in Edinburgh gave 13 healthy adults matched by age and weight 50μg of vitamin D per day or a placebo over a period of two weeks.
Adults supplementing with vitamin D had lower blood pressure compared to those given a placebo, as well as having lower levels of the stress hormone cortisol in their urine. A fitness test found that the group taking vitamin D could cycle 6.5km in 20 minutes, compared to just 5km at the start of the experiment. Despite cycling 30% further in the same time, the group taking vitamin D supplements also showed lower signs of physical exertion.
Around ten million people in England may have low vitamin D levels. On average, one in ten adults has low levels of vitamin D in summer, compared to two in five in winter. Because people with darker skin are less efficient at using sunlight to make vitamin D, up to three out of four adults with dark skin are deficient in winter.
“Our pilot study suggests that taking vitamin D supplements can improve fitness levels and lower cardiovascular risk factors such as blood pressure”, said Dr Raquel Revuelta Iniesta, co-author of the study. “Our next step is to perform a larger clinical trial for a longer period of time in both healthy individuals and large groups of athletes such as cyclists or long-distance runners”.
“Vitamin D deficiency is a silent syndrome linked to insulin resistance, diabetes, rheumatoid arthritis, and a higher risk for certain cancers”, said lead author of the study Dr Emad Al-Dujaili. “Our study adds to the body of evidence showing the importance of tackling this widespread problem”.
Public Release: 1-Nov-2015
Soybean foods may protect menopausal women against osteoporosis
Society for Endocrinology
Eating a diet rich in both soy protein and isoflavones can protect menopausal women from bone weakening and osteoporosis, according to the results of a preliminary study presented today at the Society for Endocrinology annual conference in Edinburgh.
Osteoporosis is a common condition where bones become brittle and fragile from tissue loss, causing 9 million fractures worldwide every year. In women, bone loss occurs most quickly in the years immediately after menopause because they produce less of the sex hormone oestrogen, which protects against bone loss.
Soybean foods contain chemicals known as isoflavones that are similar in structure to oestrogen and so could theoretically protect women against osteoporosis by mimicking the action of oestrogen.
In this study, researchers from the University of Hull gave two hundred women in early menopause a daily supplement containing soy protein with 66mg of isoflavones or a supplement with soy protein alone for six months. The researchers investigated changes in the women’s bone activity by measuring certain proteins (βCTX and P1NP) in their blood.
They found that the women on the soy diet with isoflavones had significantly lower levels of βCTX than the women on soy alone, suggesting that their rate of bone loss was slowing down and lowering their risk of developing osteoporosis. Women taking soy protein with isoflavones were also found to have decreased risk of cardiovascular disease than those taking soy alone.
Lead author of the study Thozhukat Sathyapalan said: “We found that soy protein and isoflavones are a safe and effective option for improving bone health in women during early menopause. The actions of soy appear to mimic that of conventional osteoporosis drugs.”
“The 66 mg of isoflavone that we use in this study is equivalent to eating an oriental diet, which is rich in soy foods. In contrast, we only get around 2-16 mg of isoflavone with the average western diet.”
“Supplementing our food with isoflavones could lead to a significant decrease in the number of women being diagnosed with osteoporosis.”
Researchers next aim to investigate the long-term health consequences of using soy protein and isoflavones supplements, and whether it may also have benefits beyond bone health.
Public Release: 2-Nov-2015
Increasing vitamin D supplementation
ETH Zurich
Osteoporosis is one of the chief reasons why the elderly often suffer broken bones from relatively minor injuries. Postmenopausal women in particular experience a relatively rapid loss in bone mass due to a reduced concentration of oestrogen, which is responsible for strong bone growth during youth. Maintaining bone mass requires physical exercise and vitamin D, which is mainly produced in the skin with the help of UVB radiation. This is why, especially in the wintertime, many elderly women are prescribed a vitamin D supplement by their doctor to maintain bone mass.
When it comes to determining the correct dosage, however, this supplement is the topic of more expert debate than any other nutrient. One camp believes that sunlight alone is enough to provide the body with sufficient vitamin D, and therefore only small quantities of supplements are necessary. The other asserts that it takes high doses of vitamin D supplements to prevent or slow down bone degeneration in elderly women.
How much is enough?
A group of researchers at ETH Zurich and the Universities of Zurich and Bern led by ETH Professor for Human Nutrition Michael B. Zimmermann took a closer look at this question. The team of scientists wanted to find out how much vitamin D there needs to be in the bloodstream to maintain bone strength.
Surprisingly, the results of their study have come out clearly in favour of higher supplement doses. Particularly in the wintertime, much higher dosages of vitamin D are necessary than previously assumed in order to maintain bone health. In the study, the researchers come to the conclusion that a vitamin D concentration of 40 micrograms per litre of serum in the bloodstream is ideal for slowing or preventing bone degeneration in postmenopausal women.
During the study, test participants were first given a single dose of calcium-41. This disperses like normal calcium throughout the body and into the bones and, given enough time, will mark the entire skeletal system evenly. “It’s after about six months that things get interesting, because from that point on we can trace the absorption and depletion of calcium in the bones,” says Zimmermann. However, highly sensitive measuring equipment is required to detect the minute quantities of calcium-41 present.
Researchers took urine samples from test participants at regular intervals and then used highly sensitive accelerator mass spectrometry equipment – which is found at ETH Zurich’s Laboratory for Ion Beam Physics and just a handful of other facilities worldwide – to measure the quantities of calcium-41 and calcium-40 and determine the ratio between them. To put it simply, a very low ratio means more calcium is being added to the bones than released; a high one means the bones are releasing more calcium than they are taking up.
Increased calcium absorption
Over a period of nine months beginning half a year after the calcium-41 marking of their bones, the women were given daily vitamin D supplements. The first dose was administered in early spring, when the vitamin D concentration in the blood is expected to be at its lowest, and the dosage was increased in step increments every three months. In addition, the scientists led by Zimmermann modelled the paths the calcium took through the various segments of the body in order to calculate an ideal vitamin D quantity.
At the beginning of the experiment, participants showed a concentration of 16 micrograms per litre of serum, which is to say they already had a deficiency. By the end of study, the average vitamin D concentration in their serum had risen to over 46 micrograms per litre thanks to the vitamin D supplementation – and to the sunshine, which increased over the course of the study to promote the body’s natural vitamin D production.
At the same time, the researchers noted that the ratio of calcium-41 to calcium-40 decreased abruptly following the start of the supplementation regimen – a sure sign that bone degeneration had been reduced.
Increasing vitamin D supplementation
“Experts are divided as to the ideal daily dose of vitamin D for maintaining bone mass,” says Zimmermann. This study has provided important new insights with respect to this topic.
For healthy postmenopausal women with sufficient calcium absorption and physical activity, a serum concentration of around 40 micrograms of vitamin D per litre of serum has the optimum effect on bone calcium absorption. “That the figure was so high was surprising,” says Zimmermann, “as previously I had tended to believe that a low dose of vitamin D was sufficient.”
In principle the body creates vitamin D in the form of cholecalciferol within the skin itself. But for this to occur, the body needs to be exposed to a sufficient amount of sunlight. In the winter months the sun is too low in the sky beyond the 40th latitude, which causes the body’s natural vitamin D production to be too low. Only a few food types, such as cod liver oil or saltwater fish, contain larger quantities of natural vitamin D; smaller quantities can be found in eggs, meats, milk and butter. Vegetables, nuts and fruits contain only very little if any vitamin D. Not only is this vital nutrient necessary for optimum uptake of calcium in the bones, it also controls countless important cellular and immune processes. One example of severe vitamin D deficiency is rickets, which causes skeletal deformation.
Public Release: 5-Nov-2015
Gut bacteria can dramatically amplify cancer immunotherapy
Manipulating microbes maximizes tumor immunity in mice
University of Chicago Medical Center
By introducing a particular strain of bacteria into the digestive tracts of mice with melanoma, researchers at the University of Chicago were able to boost the ability of the animal’s immune systems to attack tumor cells. The gains were comparable to treatment with anti-cancer drugs known as checkpoint inhibitors, such as anti-PD-L1 antibodies.
The combination of oral doses of the bacteria and injections with anti-PD-L1 antibody nearly abolished tumor outgrowth, the researchers report online Thursday in the journal Science.
“Our results clearly demonstrate a significant, although unexpected, role for specific gut bacteria in enhancing the immune system’s response to melanoma and possibly many other tumor types,” said study director Thomas Gajewski, MD, PhD, professor of medicine and pathology at the University of Chicago.
“The field has recently recognized close connections between the gut microbiome and the immune system,” he said. “This finding provides a novel way to exploit that connection, to improve immunotherapy by selectively modulating intestinal bacteria.”
Checkpoint inhibitors such as ipilimumab, nivolumab and pembrolizumab have had a dramatic impact on treatment of several tumor types, including melanoma, lung cancer, head and neck cancers and others. But only a minority of patients–one-third or less–have a vigorous response. Cancer researchers have wondered why so few benefit.
Gajewski and colleagues found a similar pattern in the mice they use for cancer research. They noticed that mice purchased from Jackson Laboratory (JAX) tended to have a robust spontaneous immune response to small melanoma tumors implanted under their skin. Mice from Taconic Biosciences (TAC) showed only a weak immune response.
But when the researchers put the mice from both sources in cages together for three weeks, they found that co-housing “completely abolished the differences in tumor growth,” Gajewski said. This made them suspect that by sharing exposure to various types of bacteria, the TAC mice had acquired microbes from JAX mice that somehow enhanced their immunity to tumors.
They confirmed their suspicion by collecting fecal matter from JAX mice and transferring it into the stomachs of TAC mice. It worked. Treated TAC mice were then able to mount a strong immune response and delay tumor growth. The reverse process, transferring fecal bacteria from TAC to JAX mice had no effect.
Next, they compared the effects of bacterial transfer against a checkpoint inhibitor, anti-PD-L1 antibodies. They found that introducing the bacteria was just as effective as treating them with anti-PD-L1 antibodies, resulting in significantly slower tumor growth. Combining the benefits associated with the bacteria with anti-PD-L1 treatment dramatically improved tumor control.
So they began searching for the specific bacteria that made the difference. They identified microbes from the digestive tracts of JAX and TAC mice by large-scale sequencing. Although there were significant differences in 254 taxonomic families of bacteria from the two sets of mice, three groups were prominent.
When they tested the effects of each group on the mice’s immune systems, one group, the Bifidobacterium, stood out. Within two weeks of oral administration, TAC mice that received just Bifidobacterium species had a marked increase in the anti-tumor T cell responses.
Mice treated just with Bifidobacterium, rather than the full fecal transfer, displayed tumor control comparable to those who received the full mixture. The effect was long-lasting. TAC mice exposed to tumors as late as six weeks after the Bifidobacterium transfer were still able to mount a robust immune response.
Additional tests showed that the Bifidobacterium did not leave the intestine. They appeared to trigger the immune response by interacting with roaming dendritic cells. These scavenger cells detect and process potential threats and present them to the T cells. The researchers suspect that Bifidobacterium colonize a compartment in the intestines. This enables them to interact with the cells that interact with dendritic cells, which activate tumor-killing T cells.
There may be other bacteria that also contribute to this process, the researchers note, either positively or negatively. They are investigating other bacteria that could influence other immune therapies, such at the CTLA-4 pathway, exploited by ipilimumab.
A second study–from the Institut Gustave Roussy in Paris, published in the same issue of Science–found that antibiotics could disrupt the antitumor effects of ipilimumab. Replenishing lost microbes in germ-free and antibiotic-treated mice restored the drug’s anti-cancer effects.
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The UChicago study was funded by a Team Science Award from the Melanoma Research Alliance and the National Institutes of Health. Additional authors include Ayelet Sivan, Leticia Corrales, Nathaniel Hubert, Jason Williams, Keston Aquino-Michaels, Zachary M. Earley, Franco W. Benyamin, Yuk Man Lei, Bana Jabri, Maria-Luisa Alegre, and Eugene B. Chang, all from the University of Chicago.
Public Release: 5-Nov-2015
Vitamin C stresses and kills mutant cancer cells
American Association for the Advancement of Science
Colorectal cancer cells with certain mutations “handle” vitamin C differently than other cells, and this difference ultimately kills them, a new study shows. The idea that vitamin C could be an effective therapy for human cancer holds great appeal, but its track record in this arena has been highly controversial, with clinical studies producing contradictory results. Several ongoing clinical studies are exploring whether a therapeutic effect may require a high plasma level of vitamin C that can be achieved only by intravenous, not oral, administration. In the meantime, the molecular mechanism by which vitamin C might selectively kill cancer cells remains unclear. In this study, Jihye Yun and colleagues studied human colorectal cancer (CRC) cells with certain mutations in genes known as KRAS and BRAF, which regulate cell growth. They show that these cells take up the oxidized form of vitamin C through a certain receptor that is specifically over-expressed in the mutant cells. This leads to oxidative stress, which in turn inactivates an enzyme required for growth of mutant but not normal cells. Consistent with the cell culture results, the authors found that administration of high-dose vitamin C to mice bearing intestinal tumors with the KRAS mutation inhibited tumor growth. Moving forward, scientists can begin to explore whether the selective toxicity of vitamin C to these cells could be exploited to create vitamin C-based therapies.
Public Release: 9-Nov-2015
Vanilla yogurt makes us feel happy, suggests research
Foods that are more — or less — delicious than we expect can also cause mood changes
Elsevier
Amsterdam, November 9, 2015 – We all know what it’s like to take a bite of something expecting one taste and getting another – it can be an enjoyable or disgusting experience. New research published in Food Research International reveals that being pleasantly surprised or disappointed with a food product can actually change a person’s mood.
Using different methods to measure people’s emotional responses, a team of researchers from Wageningen UR Food & Biobased Research, the Netherlands, University of Natural Resources and Life Sciences (BOKU), Austria and VTT Technical Research Centre of Finland Ltd., Finland looked at what emotional effects – if any – eating different yoghurts had on people.
They found that eating vanilla yoghurts made people feel happy, and that yoghurts with lower fat content gave people a stronger positive emotional response. Their results also showed that even if people reported differences in liking them, yoghurts with different fruits did not show much difference in their emotional effect.
“We were surprised to find that by measuring emotions, we could get information about products independent from whether people like them,” said lead author of the study, Dr. Jozina Mojet, from Food & Biobased Research, the Netherlands. “This kind of information could be very valuable to product manufacturers, giving them a glimpse into how we subconsciously respond to a product.”
The researchers used a new method called an emotive projection test to determine the effect of different yoghurts on people’s moods. The test involved showing study participants photographs of other people and asking them to rate the people in the photographs on six positive and six negative traits. The idea behind the test is that people project their emotions onto others, so their judgment of others could indicate their own mood.
Three groups of at least 24 participants were each given a pair of yoghurts to taste. The pairs of yoghurts were of the same brand and were marketed in the same way, but had different flavors or fat content. The team then tested their emotions using four methods, including the new emotive projection test.
The results revealed that liking or being familiar with a product had no effect on a person’s emotion. However, changes in whether they liked it after tasting the yoghurt did: being pleasantly surprised or disappointed about the food influenced people’s moods.
The team also looked at the sensory effect of the yoghurts. There was no difference in the emotional responses to strawberry versus pineapple yoghurts, but low-fat versions led to more positive emotional responses. Most strikingly, vanilla yoghurt elicited a strong positive emotional response, supporting previous evidence that a subtle vanilla scent in places like hospital waiting rooms can reduce aggression and encourage relationships among patients and between patients and staff.
The findings suggest that the new method could be an effective way to gather information about a product before taking it to market. Traditionally, products have been trialed using explicit methods – directly asking people how they feel. In contrast, the new method is implicit and therefore not controlled by people’s conscious thought.
“We were looking for a valid, quick and not too expensive and time-consuming method to measure the emotions or mood changes evoked by food,” said Dr. Mojet. “I strongly believe that sensory and consumer research should be conducted in an ecologically valid way. This sort of implicit method can reveal the complex interactions between the different factors involved in a situation, which, based on his or her memory and expectations, is given meaning by the person under investigation.”
Public Release: 10-Nov-2015
First, do no harm: Hospital patients given anti-heartburn drugs have higher risk of dying
U-M/VA computer model suggests that common use of acid-reducing medicine to prevent stomach bleeding increases mortality from infections
University of Michigan Health System
ANN ARBOR, Mich. — Right now, in any American hospital, about half of the patients have a prescription for an acid-reducing drug to reduce heartburn or prevent bleeding in their stomach and gut.
But that well-intentioned drug may actually boost their risk of dying during their hospital stay, a new study finds – by opening them up to infections that pose more risk than bleeding would.
In fact, according to a computer simulation based on real-world risk and benefit data, around 90 percent of hospital inpatients who were first prescribed these drugs in the hospital have a higher risk of dying when they’re taking them, compared with their risk if they hadn’t gotten the prescription.
And for around 80 percent of patients who were already on these common drugs, called proton-pump inhibitors or PPIs, when they arrived at the hospital, staying on them also may lead to a small increase in the risk of dying.
The extra risk of death comes from the fact that reducing acid in the stomach can increase the risk of infections – especially pneumonia and Clostridium difficile, both of which pose a serious risk to hospitalized patients who develop them.
The study, which uses a computer model to achieve a result that otherwise would require an impractically large clinical trial, is published in the Journal of General Internal Medicine by a team from the University of Michigan Medical School and VA Ann Arbor Healthcare System.
“Many patients who come into the hospital are on these medications, and we sometimes start them in the hospital to try to prevent gastrointestinal, or GI, bleeds,” says lead author Matthew Pappas, M.D., MPH.
“But other researchers have shown that these drugs seem to increase the risk of pneumonia and C. diff, two serious and potentially life-threatening infections that hospitalized patients are also at risk for,” he continues. “Our new model allows us to compare that increased risk with the risk of upper GI bleeding. In general, it shows us that we’re exposing many inpatients to higher risk of death than they would otherwise have – and though it’s not a big effect, it is a consistent effect.”
As a result of the new findings, he says, very few hospital patients should start taking or continue on PPIs as a preventive measure against gastrointestinal bleeding.
Pappas, a hospitalist physician at U-M with an engineering background and a VA Health Services Fellow, worked with Sandeep Vijan, M.D., MPH, who treats patients at the VAAHS and is a member of the VA Center for Clinical Management Research and U-M’s Institute for Healthcare Policy and Innovation. Pappas is a clinical lecturer, and Vijan a professor, in the U-M Medical School’s Division of General Medicine. The project’s only funding was Pappas’s fellowship support.
Cutting PPI use to cut infection risk
Pappas notes that nationally, some efforts have already shown ways to reduce the rate of new PPI prescriptions to hospitalized patients – about 20 percent of whom receive such orders right now.
But truly reducing PPI use in hospitals to the most appropriate patients – those with existing GI bleeding – will take more effort, Pappas predicts.
That’s because PPIs are built into many heuristics, or rules of thumb, that guide much hospital care. For instance, when a patient receives high-dose steroids in the hospital, the physician may automatically also prescribe a PPI to prevent the GI bleeding that steroids can cause.
“In fact, in running our simulation, we thought we would find some populations such as those on steroids or other medications often prescribed together with PPIs, who would not experience the increased mortality risk,” Pappas says. “But that turned out not to be the case.” GI bleeds are risky, it’s true. But hospital-acquired pneumonia and C. diff are much more common.
Although research is still needed on why PPI use increases a patient’s vulnerability to hospital-acquired pneumonia and C. diff infection, the effect of the acid-reducing drugs on gut bacteria likely has a direct impact. In the case of pneumonia, suppressing acid production may increase the amount of bacteria in the stomach and throat, which can then get into the lungs and cause pneumonia.
Model can be used for other risk-benefit balancing
Pappas notes that the model he developed with Vijan and recent U-M Ford School of Public Policy graduate Sanjay Jolly could be applied to many other situations where a common preventive or treatment measure in medicine also carries with it an increased risk of an unwanted effect.
Using such models, based on data from observational studies, could answer important questions in medicine without needing to carry out massive prospective clinical trials. To answer the question of whether the predicted increase in mortality risk caused by PPIs in inpatients is real, he says, would take a clinical trial of more than 64,000 patients randomly assigned to receive PPIs or not. Since PPIs are available as generic medications, the likelihood of such a study being funded and performed is nearly zero.
“Any time there are complex risk/benefit tradeoffs, without the possibility of a high-quality trial, this kind of simulation can help us come up with answers to inform clinical care,” he says.
For instance, he’s now studying the issue of “bridging” medication in patients who have been prescribed blood-thinning medications to prevent a stroke. Such patients often receive a prescription for an injected drug that will reduce stroke risk during the week or two before their regular oral drugs take effect. But that injection carries its own risk.
“Humans aren’t very good at recognizing very rare events, and reacting appropriately to things that are unlikely to happen,” says Pappas. “Physicians have an instinct to want to prevent very bad, though rare events – but everything we do carries risks. We need to be mindful of the things we are doing to prevent rare outcomes, and keep the risks in perspective. Computers can help.”
Public Release: 12-Nov-2015
In new study, Illinois scientists trace activity of cancer-fighting tomato component
University of Illinois College of Agricultural, Consumer and Environmental Sciences
· Plant biofactories can incorporate heavier carbon atoms into cancer-fighting phytochemicals, which can be used to trace their movement in the human body.
· Process allows Illinois researchers to study human metabolism of lycopene, the tomato component whose consumption is related to a lower risk of prostate cancer.
· When consumed, lycopene undergoes a change in its chemical structure that potentially influences health.
URBANA, Ill. – Years of research in University of Illinois scientist John Erdman’s laboratory have demonstrated that lycopene, the bioactive red pigment found in tomatoes, reduces growth of prostate tumors in a variety of animal models. Until now, though, he did not have a way to trace lycopene’s metabolism in the human body.
“Our team has learned to grow tomato plants in suspension culture that produce lycopene molecules with a heavier molecular weight. With this tool, we can trace lycopene’s absorption, biodistribution, and metabolism in the body of healthy adults. In the future, we will be able to conduct such studies in men who have prostate cancer and gain important information about this plant component’s anti-cancer activity,” said John W. Erdman Jr., a U of I emeritus professor of nutrition.
The U of I team began developing the tomato cultures that would yield heavier, traceable carbon molecules about 10 years ago. Erdman, doctoral student Nancy Engelmann, and “plant gurus” Randy Rogers and Mary Ann Lila first learned to optimize the production of lycopene in tomato cell cultures. They then grew the best lycopene producers with non-radioactive carbon-13 sugars, allowing carbon-13 to be incorporated into the lycopene molecules. Because most carbon in nature is carbon-12, the lycopene containing heavier carbon atoms is easy to follow in the body.
Soon after the carbon-13 technology was established, Engelmann, now Moran, took a postdoctoral research position at Ohio State University in the lab of medical oncologist Steven K. Clinton, and scientists at Illinois and Ohio State initiated human trials.
In this first study, the team followed lycopene activity in the blood of eight persons by feeding them lycopene labeled with the non-radioactive carbon-13. The researchers then drew blood hourly for 10 hours after dosing and followed with additional blood draws 1, 3, and 28 days later.
“The results provide novel information about absorption efficiency and how quickly lycopene is lost from the body. We determined its half-life in the body and now understand that the structural changes occur after the lycopene is absorbed,” Erdman explained.
“Most tomato lycopene that we eat exists as the all-trans isomer, a rigid and straight form, but in the bodies of regular tomato consumers, most lycopene exists as cis isomers, which tend to be bent and flexible. Because cis-lycopene is the form most often found in the body, some investigators think it may be the form responsible for disease risk reduction,” Moran explained.
“We wanted to understand why there is more cis-lycopene in the body, and by mathematically modeling our patients’ blood carbon-13 lycopene concentration data, we found that it is likely due to a conversion of all-trans to cis lycopene, which occurs soon after we absorb lycopene from our food,” she added.
The plant biofactories that produce the heavier, traceable lycopene are now being used to produce heavier versions of other bioactive food components. In another trial, phytoene, a second carbon-13 labeled tomato bioactive molecule, has been produced and tested in four human subjects.
“Our most recent project involves producing a heavy carbon version of lutein, found in green leafy vegetables and egg yolks. Lutein is known to be important for eye and brain health. In this case, we began with carrot suspension cultures and have already produced small quantities of ‘heavy-labeled’ lutein for animal trials,” Rogers said.
Right now, though, the Illinois-Ohio State team is excited about the new information the lycopene study has yielded. “In the future, these new techniques could help us to better understand how lycopene reduces prostate cancer risk and severity. We will be able to develop evidence-based dietary recommendations for prostate cancer prevention,” Erdman said.
This new journal article represents the most thorough study of lycopene metabolism that has been done to date, he added.