sign in sign up
<<
Home , Orthomolecular medicine

INSTITUTE OREGON STATE UNIVERSITY RESEARCH NEWSLETTER SPRING-SUMMER 2017

INSIDE: LPI Conference Announcement

THE HEALTHY YOUTH Food choices — healthy ones or not — IN THIS ISSUE develop early in life and become difficult to PROGRAM From the Director...... 2 change once we reach adulthood. Consistent Working to advance healthspan for nutrition education throughout the school and Optimum youth and families years provides children with the information Conference...... 5 and skills to make lasting, healthy food The foundation for a healthy lifespan is choices. A logical place to focus nutrition Stephen Lawson: 40 Years laid in childhood, as a balanced diet of Service to the LPI...... 6 education efforts is in schools, yet is this provides essential nutrients for healthy realistic? Nutrition education is not included IV C and : development and growth. As part of the in state standardized tests, so the average An Update...... 8 Linus Pauling Institute’s public outreach time devoted to teaching nutrition and mission, the Healthy Youth Program is dietary behavior in elementary school is Getting Enough dedicated to translating the scientific ?...... 10 only 4.6 hours over an entire school year. discoveries on , minerals, To gauge teachers’ perceptions on this Metabolomics in the phytochemicals, and healthy eating topic, we implemented a cross-sectional New Millennium...... 12 patterns into meaningful information for survey of Oregon elementary school class- the public. Working in the Corvallis LPI Graduate Students....14 room teachers about nutrition education community since 2009, we have developed programs. Overall, we were encouraged that Developments...... 15 several nutrition education programs that 97% of teachers rated nutrition education in are evidence-based, hands-on, and elementary school to be at least ‘somewhat community-centered — all promote healthy important,’ and more than half agreed that food choices for children and their families. Continued on page 4 FROM THE DIRECTOR

We are pleased to present this Nebraska, LPI investigators Drs. Fritz Spring/Summer edition of the Linus Gombart and Arup Indra won a subaward Pauling Institute’s Research Newsletter. on a four-year R01 grant from the We have many new developments to National Institutes of Health. Dr. Victoria share with you, such as the latest news Drake, Manager of the on our research findings, accomplishments Information Center (MIC), has received of our students, the activities of the a grant from a large nutraceutical Jan Frederik Stevens, Ph.D. Healthy Youth Program (on the cover), company, making it possible for her Professor and Interim Director and the program for this summer’s and her team to update several Linus Pauling Institute Diet and Optimum Health conference micronutrient articles and other in Corvallis, Oregon. materials to be published on the MIC As you may recall from our previous website. Congratulations to all! newsletter, we are moving forward Over the past several months, we in an ever-changing research have also begun reorganizing the LPI environment. While we stay on course Core Laboratories. These facilities with our mission and our research were established to meet the needs focus on vitamins, minerals, and of researchers over a decade ago. As phytochemicals, now more than ever research priorities have changed over it will take a multidisciplinary approach time, reorganization is needed to stay to reach our goals. We are now competitive. Although the original collaborating with colleagues throughout priorities of these labs remain intact, Oregon State University and academic we are expanding in the areas of institutions in the region to complement analytical chemistry (such as our expertise. metabolomics, see the article on page Today’s federal funding climate is the 12), new animal models, and human toughest I have seen in my 15 years at clinical research. The new core labs Oregon State University. The national will be named ‘Biological Models and competition for federal grants is fierce, Translational Research Core’ and the by some called ‘hypercompetition’ ‘Analytical Services Core.’ Most for the federal research budgets. Our importantly, they will have a broader strategy is not to simply wait for better scope and greater flexibility to assist times. To better position the Institute faculty and allocate resources where to face competition, I decided to give needs are most urgent. faculty who submit a grant application In this issue of the newsletter, we additional funds to generate proof-of- highlight news from the research and concept data requested by grant review outreach programs. Dr. Maret Traber panels or for professional grant-writing and her co-workers discovered that support. Most LPI faculty have already vitamin E pharmacokinetics is different taken advantage of this ‘submission between normal, healthy individuals premium’ to strengthen their proposals. and those with metabolic syndrome. Our approach is beginning to pay Please read the article on why that might off: Our faculty are submitting more just have an impact on your health. Dr. proposals than last year, and they are Claudia Maier, LPI adjunct faculty, and I receiving better scores with each new present an update on the metabolomics submission cycle. research at the LPI – a field pioneered Through a collaboration with by Dr. Linus Pauling himself. investigators from the University of If you have followed the news

2 The Biological Models and Translational Research Core in the Linus Pauling Institute includes the facilities and staff for conducting human clinical trials. Three such trials are currently underway, with more to come.

lately, you will have noticed that the years would fill this entire issue without losing the essence of the intravenously administered and beyond. In our article on page complexity. has reached the media headlines as a 6, we take a moment to celebrate We look forward to working with cancer therapeutic — we will update Steve’s many contributions over the Amanto and hope that you reach out to you on the research in this field. And, past 40 years with our Institute. On speak with him yourself sometime soon. as you have already seen on the cover, behalf of the entire LPI faculty, staff, Lastly, save the date, if you haven’t we will tell you about the efforts of the and students, I express my sincere done so already: The 2017 Diet and Institute’s Healthy Youth Program to gratitude to Steve for everything he Optimum Health conference will be held bring nutrition education to elementary has done for the Institute. We wish on September 13-16, 2017, at the CH2M school children, setting a trajectory for him all the best as a retiree! Hill Alumni Center in Corvallis, Oregon. a into adulthood. Now I would like to introduce LPI’s This year’s conference, chaired by Stephen Lawson decided to retire last new Director of Development, Dr. Maret Traber, will have a tribute to June. With the LPI since its inception Amanto Marcotulli, J.D., who joined Dr. Balz Frei, who directed the LPI from at OSU 20 years ago, he had worked the OSU Foundation in November 1997 to 2016. The scientific program has directly with Dr. Pauling at the Linus 2016. Amanto served in similar roles been set, and details can be found on Pauling Institute of Science and at the University of California, our website. If you are an LPI graduate Medicine in California. Steve enjoyed San Francisco, and at the University or lifelong friend of the Institute, don’t writing and editing the Research of California, Berkeley. Prior to forget to sign up for the LPI alumni Newsletter, corresponding with friends fundraising, he served as a public reception during the conference! of the LPI, introducing LPI research defender, solo practitioner, and and outreach activities to the public, recruiting manager. In the few assisting with the design of the new months I have worked with him, Linus Pauling Science Center and, at I have discovered that he has an long last, seeing its completion in 2011. amazing ability to explain complex Jan Frederik Stevens, Ph.D. But discussing his many activities over scientific topics in simple, clear terms Professor and Interim Director

3 Continued from cover — The Healthy Youth Program educational programs may improve As an established partner with level. Both courses meet once per students’ food choices at least in the Corvallis schools, the LPI’s Healthy week for two hours and include a short term and possibly in the long term. Youth Program has found that children nutrition lesson followed by 60 to However, as one might expect, are much more likely to eat healthfully 90 minutes of hands-on cooking in implementing nutrition education when they are involved in growing small teams of three-to-four programs in schools presents several and preparing the food. To this end, participants. Each team makes two challenges. Barriers noted by teachers nutrition messages presented in our or three healthy recipes each week, included competing academic programs are woven into cooking and importantly, time is spent expectations (52% of survey and garden-based activities where sharing the meal and talking about respondents), a lack of available time children, as active learners, become the experience. (48% of respondents), and a lack truly invested in the outcome of a Ingredients emphasize whole of suitable curricula (36% of meal or rewards of a harvest. Our grains, minimally added sugars, and respondents). Also, about half of these long-term goal is to set the stage for abundant fresh fruit and vegetables teachers thought that getting parents future generations to make lasting, that are often harvested on-site involved would be one key to healthy food choices; we accomplish from the school gardens. During the establishing an effective program. this by involving children in all off-season, you can find Master Chefs Not surprisingly, teachers also noted aspects of food preparation, from soil participants starting microgreen that unless the food environment in to seed to plate. seeds in the HYP-managed school school cafeterias reflects what is being Reinforcing nutrition messages greenhouse in week one of their taught, nutrition education will have provided during the school day, session. The kids harvest these greens a limited impact on students’ food Healthy Youth Program educators to use in a cooking competition, a choices. Following up on this, we sent work with K-12th graders in school much-anticipated activity in the final a second survey to Oregon elementary gardens managed by our staff. class of this six-week program. school foodservice personnel, also on Teachers involved in garden activities The goals of the cooking classes are the topic of nutriton education. All of appreciate the inherent links garden- to teach participants how to prepare those who responded thought that based education has to academic a variety of healthy, complete meals; nutrition education in elementary standards, and students appreciate expose participants to new and schools is at least somewhat important, the opportunity to learn outdoors. familiar healthy foods; teach and most thought that school cafeterias Harvests are taken directly to the participants basic kitchen safety skills should be involved for program success. school kitchens, where the colorful and nutrition knowledge; and, overall, Three-quarters of school foodservice and fresh fruit and vegetables enliven to promote healthy food choices for personnel were interested in nutrition cafeteria salad bars. Signs posted near children and their families by boosting education training, but, similar to these offerings boast messages like children’s confidence in the kitchen teachers, they noted barriers for “Grown by YOU!” or “From your school to make scratch cooking fun, tasty, and incorporating nutrition education garden!,” inspiring ownership, and rewarding. A preliminary evaluation programs into the school cafeteria. ultimately consumption. of both courses indicate that these These included cost, time, and the With constraints on teachers during course goals are being achieved. staff available to take on these roles. school hours, the Healthy Youth The changes go beyond our data, Program also offers after-school as we are witnessing changes in the cooking courses that combine food behaviors of children; it is not To learn more about the cooking/food preparation, kitchen uncommon to hear a child shout, Healthy Youth Program at the safety, tasting, and food/nutrition “I love kale!” at the end of a lesson. Linus Pauling Institute, visit: knowledge. Fresh Grown Cooking for lpi.oregonstate.edu/healthyyouth Kids and Master Chefs are two of our The Centers for Disease Control and Prevention (2014) cdc.gov/healthyschools or send us an email at courses designed for elementary and Perera et al. J Educ Pract. 6 (2015) [email protected] middle school students, respectively, Perera et al. J Health Edu Res Dev. 3 (2015) offered regardless of family income

4 Join the Linus Pauling Institute for the

Diet and Optimum Health Conference 2017

SeptemberJoin the Linus Pauling13–16 Institute for Corvallis, the OR

Diet and Optimum Health Conference 2017 Featuring September 13–16 Corvallis, OR

• A Tribute to Balz Frei • DietaryFeaturing Components and the Microbiome

• Update• A on Tribute Vitamin to Balz Frei E • Dietary Components • Bioactivesand the and Microbiome Cancer• UpdatePrev onention Vitamin E • Bioactives and •All-dayCancer Symposium Prevention on IV •AVitaminll-day Symposium C on IV Vitamin C • A Free•A Public Free Public Session Session on on Sat., September Sat., September 16th 16th

lpi.oregonstate.edu/DOH

5 STEPHEN LAWSON 40 years of service and an entire career dedicated to the Linus Pauling Institute

It is with mixed feelings that we In 1996 he organized the move announce that Stephen Lawson of the Institute to Oregon State has retired from the Linus Pauling University. “Dr. Pauling was aware Institute. Many who contacted the and supportive of our discussions Institute over the last few decades to move LPI to Oregon State knew something of Steve: He worked University and continue the mission at LPI for many years longer than of orthomolecular medicine,” says anyone else and was an integral part Lawson. “He would certainly be of its success over its history. pleased to know that important Stephen Lawson A graduate of Stanford University, research in metabolomics — a field he Steve joined the Linus Pauling Institute and colleagues pioneered in the late of Science and Medicine (LPISM) in 1960s — and on essential minerals like California in 1977. Initially, his work at zinc; phytochemicals; and vitamins C, the Institute with Linus Pauling focused D, and E has been conducted at LPI.” “Working at the on several projects with vitamin C, At the new Linus Pauling Institute, Linus Pauling Institute of including the role of vitamin C in the Steve served as our administrative prevention of cancer and potential officer and editor of the Research Science and Medicine and interactions between vitamin C and Newsletter, helping to preserve the Linus Pauling Institute cancer chemotherapeutic drugs. institutional memory. Steve also Later, as a co-director of the assisted in recruiting Balz Frei as the at Oregon State University Laboratory for Research in Gene new director of the LPI and served as has been an extraordinary Regulation in the late 1980s, Steve the director’s advisor until they both developed a technique for using retired in 2016. experience.” two-dimensional gel electrophoresis Steve was critically involved in to profile involved in cancer LPI’s fundraising and strategic, long- — STEPHEN LAWSON, 2017 metastasis. He also studied the effects term planning. He also served on the of phytic acid, a substance found in steering and art committees for OSU’s grain and plant seeds, on blood lipids Linus Pauling Science Center, the and tumor growth in rats, resulting current home of the Institute, and, for in a patent for its use in inhibiting many years, on the Campus Planning cancer growth. Committee and the Student Health From 1988 to 1991, Steve served as Advisory Board. executive assistant to the president, Over the years he has authored Emile Zuckerkandl — who developed or co-authored many papers, the concept of molecular evolution including those published in the with Pauling — and, in 1991, as Journal of Virology, Carcinogenesis, executive officer. Gynecologic Oncology, the Journal In 1993 he was appointed chief of Orthomolecular Medicine, the executive officer and grappled with Proceedings of the National Academy financial, legal, zoning, and other of Sciences, Nutrition Research, critical issues facing the Institute, the Journal of Applied Nutrition, the and successfully negotiated several American Journal of Clinical Nutrition, remunerative research and and the Journal of Anesthesia History, corporate contracts. among others.

6 Yet, all of these accomplishments summarizes recent research on only barely touch on Steve’s life at intravenous vitamin C as adjunctive the Institute. He often speaks of many therapy for cancer, to be published soon. happy afternoons in the LPISM spent Steve often gave lectures on identifying specimens and orthomolecular medicine or Linus crystals with Dr. Pauling and Zelek Pauling to graduate students in Herman, Pauling’s collaborator in nutrition or medicine; undergraduate theoretical chemistry. Or the occasions students in the School of History, when Pauling would ask him to take Philosophy, and Religion; other on special assignments, like writing student, professional, and civic a review of Vitamin C and Cancer: groups; and at scientific or medical Medicine or Politics? by Evelleen conferences. In late April, he was Richards for a journal publication. inducted into the Orthomolecular “Once,” he recollects, “Dr. Pauling Medicine Hall of Fame, joining stopped by my office to tell me scientists and physicians like Linus that he had an idea about a new Pauling, Ewan Cameron, Bruce Ames, method to fabricate superconductive Roger Williams, and . material… incredibly thin fibrils of Stephen Lawson (left) with Linus Pauling To conclude in Steve’s own words: conductive metal, such as tin, clad in (right) “I feel particularly fortunate to have nonconductive glass.” Pauling asked been so closely associated with Steve to help set up a small lab to everything he has accomplished over Linus Pauling and LPI for so long see if they could make this material, the years. He participated in many and cherish the time I spent learning hoping the licensing of a patent might film projects about Linus Pauling and about the critical contributions of provide a high revenue stream to fund orthomolecular medicine, including science to society and how science research in orthomolecular medicine the 2011 production “Linus Pauling” can be the source of so much fun and at the Institute. by Oregon Public Broadcasting for satisfaction.” Steve and Zelek bought a furnace, the Oregon Experience program. blowtorch, and supplies and started Steve also served on the Select Stephen Lawson currently holds a working away, melting and pulling the Advisory Committee for the Linus courtesy appointment at Oregon State tin and glass in the method outlined by Pauling Exhibition, an exhibit honoring University and can still be reached Dr. Pauling. “He joined us occasionally Pauling’s positive, long-term influence through the Linus Pauling Institute. in the lab and wielded the blowtorch,” on society, visited by millions of Lawson recalls, “When we finally people worldwide. Moreover, Steve succeeded, we rushed excitedly to has been an integral member of OSU’s his apartment and showed him the Pauling Heritage Committee, a group material. He was gleeful and gave organized to recognize the wide impact us each beautiful pyrite crystals in of Pauling’s life and work and how appreciation.” it is reflected on the Oregon State Most people are unaware that Steve University campus. set up the Institute’s first cell culture Steve annotated and added an laboratory. His recollections of these afterword to the 20th anniversary experiences provide a fascinating edition of Linus Pauling’s bestseller window into the LPISM, and how How to Live Longer and Feel Better, innovation triumphed in the days before published in 2006. He recently modern cell culture was the norm. contributed a preface discussing Steve’s commitment to the anticancer mechanisms to the new Institute and the memory of Linus 21st-Century Edition of Cancer and Pauling, as well as his advocacy for Vitamin C by Ewan Cameron and Linus orthomolecular medicine, is present in Pauling, as well as an appendix that

7 INTRAVENOUS VITAMIN C AND CANCER After nearly 40 years, where does the science stand on this therapy?

Linus Pauling was very interested vitamin C do indeed kill cancer cells current state of intravenous vitamin C in the value of vitamin C in treating in culture. Studies in animals show as a cancer therapy may be useful for cancer. Clinical research with his that vitamin C infusions can slow those who wish to know where the colleague Ewan Cameron in the 70s tumor growth. A number of studies science stands on this treatment: demonstrated that large doses of are now underway to characterize It is generally safe: Results from oral and intravenous (IV) vitamin C the molecular anticancer controlled clinical trials indicate that were helpful in increasing the survival mechanisms of vitamin C and IV vitamin C is generally safe and well time and improving the quality of life optimal protocols for administration. tolerated in most prescreened cancer of terminal cancer patients. When However, there is plenty of work patients. In fact, there are very few follow-up studies by the Mayo Clinic to be done before vitamin C can be contraindications for vitamin C in using only oral vitamin C did not show accepted as a mainstream therapy intravenous form. However, there is any benefit, many cancer researchers for cancer. still the potential for side effects: those doubted the value of vitamin C therapy, Yet, as clinical researchers try to with existing kidney disease, history and the research slipped out of the understand why and how much of kidney stones, or glucose-6-phos- mainstream. vitamin C can help fight against phate dehydrogenase deficiencies About 10 years ago, studies at the NIH cancer, thousands of people should take particular caution. with Dr. Mark Levine revitalized cancer worldwide are using it as a primary It is not the same as taking a research with vitamin C. His group treatment or adjunctive therapy. supplement: The therapeutic effect of confirmed that high concentrations of Therefore, we believe a review of the vitamin C in cancer patients has mainly

8 been demonstrated through IV thereby improving the quality of life administration or direct infusion, not of cancer patients. Some drugs have by taking supplements. Concentrations been shown to work better in of vitamin C in the blood are the key: combination with vitamin C. On the formulations of oral vitamin C — other hand, vitamin C may interact even those that claim to boost with other drugs to limit how well bioavailability — do not increase blood they work or even exacerbate side vitamin C levels to a point that would effects. Thus, it is extremely important produce the same anticancer effect. IV to talk to a physician before administration allows concentrations combining IV vitamin C with any of vitamin C in the blood to reach at drug. Of course, any administration least 100 times higher than taking of an injection or infusion of vitamin C oral supplements. should only be performed under Hydrogen peroxide is likely the direct supervision of a qualified important: Researchers have found health professional. that high concentrations of vitamin C IV vitamin C is not a miracle agent can produce hydrogen peroxide in the for all : Research has shown vicinity of a cancer cell. The hydrogen that some cancers are not affected peroxide interferes with functions in by the use of IV vitamin C, especially many cancer cells, leading to their cancer cells that are resistant to death. Cancer cell death cannot be hydrogen peroxide. Researchers are achieved by directly administering trying to find ways of overcoming hydrogen peroxide because enzymes those barriers, but progress in this in the blood would remove any area is slow and needs more funding hydrogen peroxide formed before to continue. it could reach tissues. Also, taking Bottom-line: Overall, vitamin C large amounts of hydrogen peroxide infusions are a promising approach by mouth is not safe and would not to fighting some types of cancer, target cancer cells. but much more work still needs to The working hypothesis is that high be done to determine how and when levels of vitamin C may reach the they should be used. It is still too spaces where removal enzymes are early for the Linus Pauling Institute absent, allowing a reaction with to make general recommendations oxygen, production of hydrogen about IV vitamin C to cancer patients. peroxide, and its transport into cells. Clinical trials are currently underway This causes a cascade of reactions that at centers around the world to provide ultimately can kill cancer cells. Other answers to important questions about mechanisms have also been proposed this therapy. regarding how vitamin C might slow tumor growth and cause cell death Chen et al. Proc Natl Acad Sci. USA 102 (2005) For those who want to know more that do not involve hydrogen Ma et al. Sci Transl Med. 6 (2014) about the subject, we recommend Schoenfeld et al. Cancer Cell. 31 (2017) peroxide, so it is possible that multiple the new edition of Cancer and mechanisms are at play. Vitamin C by Cameron and Pauling It can be combined with some that discusses anticancer cancer therapies; not with others: mechanisms and summarizes the Studies have found that intravenous vitamin C treatments can alleviate recent clinical research. Contact the fatigue or decrease other side effects Institute for more details. of some chemotherapeutic drugs,

9 GETTING ENOUGH VITAMIN E?

Studying metabolic syndrome may status. Her new studies show there Because of this distribution lead to new recommendations for might be a better way to tell if you system, measuring alpha- vitamin E are eating enough vitamin E. levels in the blood gives doctors and First, some background on how researchers a good understanding if Vitamin E, a fat-soluble , vitamin E moves through the body: someone is deficient. Under normal plays a supporting role in immune After you eat something containing circumstances, if vitamin E levels in function, wound healing, vision, and vitamin E — be it a handful of the blood are low, the person is not neurologic function. Estimates are almonds, some vegetable oil, a few consuming enough. If levels are high, that 90% of Americans do not eat cups of spinach, or a supplement — it probably means enough vitamin E enough vitamin E-rich foods to meet the vitamin E, along with the fat in is reaching the tissues where it needed published requirements. Despite your meal, gets absorbed and sent the most. its importance, people who don’t through the blood stream to the liver. However, this is not always the consume enough vitamin E still seem The liver is the guardian, picking out case. A problem arises when fat is to be healthy. Are the requirements those molecules needed for life and not taken up into tissues normally. wrong? sending those back into the blood This occurs in hyperlipidemia or Maret Traber, Ph.D., Ava Helen stream. It also sorts out and removes hypercholesterolemia, where Pauling Professor at the Linus Pauling the things you don’t need in your triglycerides and cholesterol particles Institute, believes that people are not body. Thus, the liver works as a circulate in the blood at abnormally getting enough vitamin E and are, in sorting facility, keeping the good and high levels. Where the fats go, the fact, not as healthy as they think. excreting the useless or potentially vitamin E follows. “It’s a micronutrient The extent of the problem, especially toxic. that’s going along for the ride,” says in people with underlying health Here, one form of vitamin E named Dr. Traber. conditions, may be worse than has alpha-tocopherol is special: A transfer To study this in more detail, Dr. been appreciated by most nutrition found in the liver rescues Traber, along with her collaborators professionals. Research from her alpha-tocopherol and sends it — along at The Ohio State University, decided laboratory has demonstrated that with dietary fats — back into the blood to look at persons with metabolic measuring the amount of vitamin E stream for delivery to tissues. Other syndrome (see sidebar). Although you consume, or even the amount forms of vitamin E, like tocotrienols, blood levels of vitamin E in these in your blood stream, might not give don’t get this special treatment. individuals are apparently normal, you a complete picture of vitamin E

10 Dr. Traber and her colleagues were showed that people with metabolic concerned. This syndrome is syndrome eliminated less CEHC than What is Metabolic Syndrome? associated with high levels of healthy people. inflammation and increased oxidative In other words, those with Metabolic syndrome is a combination of stress — could these problems metabolic syndrome were showing medical conditions that places you at increased risk for several chronic diseases. increase the amount of vitamin E signs that they weren’t getting the they need? vitamin E they needed. How is Metabolic Syndrome Diagnosed? The scientists gave volunteers Traber is now touting CEHC as a You have metabolic syndrome if you specially tagged alpha-tocopherol biomarker of vitamin E status — have three or more of the following to eat so that the vitamin E could be a way for researchers, and potentially risk factors, or are taking followed in the circulation. This physicians (if the future testing to control them: molecular tag let them follow the confirms the outcomes) to know if • Abdominal obesity (waist size vitamin E they provided and also the vitamin E levels in the body are ≥ 40 inches for men or ≥ 35 inches fate of that vitamin, such as vitamin E adequate. Traber hopes that future for women) catabolites that are excreted in support of this research will help • High serum triglycerides the urine. determine if this molecule can be (triglycerides greater than 150 mg/dL) In participants with metabolic clinically measured to validate a syndrome compared with healthy person’s low vitamin E levels in tissues. • High blood pressure (blood pressure individuals, the tagged vitamin E was The unfortunate conclusion to this of 130/85 mm Hg or higher) not only poorly absorbed but also set of experiments is that the people • High blood glucose ( blood disappeared from the blood stream with metabolic syndrome are glucose above 100 mg/dL) more slowly. Upon analysis, this odd showing signs of needing much more • Low HDL cholesterol (HDL levels behavior gave clues that something vitamin E. It is not yet clear if eating < 40 mg/dL for men or < 50 mg/dL peculiar was happening to this tagged more vitamin E-rich foods is the best for women) vitamin E in the body. solution for those with metabolic What is the Impact of Metabolic Traber explains: “In metabolic syndrome — but a balanced diet is Syndrome? syndrome, tissues are rejecting fat certainly a good start. Of course, because they already have enough. supplementation may be a good way Metabolic syndrome can increase your In the process, they also reject for many people to get enough risk for , type 2 vitamin E. So even though the tissues vitamin E, and the Linus Pauling diabetes, insulin resistance, Alzheimer’s are facing serious oxidative stress, Institute recommends taking a daily disease, and non-alcoholic fatty liver disease. Fatty liver can progress into the delivery of vitamin E to them is multivitamin supplement, which cirrhosis,hepatocellular carcinoma, being impaired. Our research shows usually contains close to the and potentially death. that people with metabolic syndrome recommended levels of vitamin E. need about 30-50 percent more The Traber lab is hoping to work with How is Metabolic Syndrome Prevented? vitamin E than those who are other research participants with lipid • Eat a healthy diet rich in fruit, generally healthy.” dysregulation in the future, to see if vegetables, fish, and whole grains When vitamin E intake is higher this problem may affect more people • Keep sugar intake low (less than than the body needs, the extra is than this small study would indicate. 10% of calories) eliminated. This is a catabolic process that starts by step-wise removal of Mah et al. Am J Clin Nutr. 102 (2015) • Get regular physical activity the carbons on the long tail found on Traber et al. Am J Clin Nutr. 105 (2017) • Achieve and maintain a Grundy et al. Circ. 112 (2005) a tocopherol molecule. The product of healthy body weight this elimination process is a molecule • Do not smoke called CEHC. The advanced laboratory • Get regular medical checkups tests conducted by Dr. Traber’s group For more information, see the Micronutrient Information Center: http://lpi.oregonstate.edu/mic

11 METABOLOMICS IN THE NEW MILLENNIUM Although ‘metabolomics’ or ‘metabolic profiling’ find their roots in the previous millennium, they are still in development to become mature techniques.

Claudia Maier, Ph.D. Is metabolomics really the latest electrospray mass spectrometry LPI Adjunct Faculty addition to the spectrum of ‘omics’ tools? greatly improved the ability to detect Linus Pauling and Arthur Robinson polar metabolites in plasma and urine. are credited by many sources, Since that time, high-resolution including Wikipedia, as pioneers in accurate mass detectors have found the field of metabolomics. In 1974, universal use in metabolome research. they published a paper in the journal, In the mid-2000s, several large Clinical Chemistry (vol. 20, pp. 961-5), metabolome databases were entitled “Techniques of Orthomolecular developed that can be accessed Medicine,” reporting on research they online, notably METLIN and the Human had been conducting since the late Metabolome Database (HMDB). sixties. They defined their term Yet, despite all of these technical and Jan Frederik Stevens, Ph.D. ‘orthomolecular diagnosis’ as ‘the Professor and Interim Director bioinformatics advancements, we are Linus Pauling Institute process of determining and evaluating still not able to identify the majority the concentrations of the substances of metabolites in a given biological normally present in the human body.’ sample. Most metabolomics laboratories Initially, they were trying to identify around the world have the ability to substances in urine that quantitatively identify hundreds of metabolites in a correlated with specific diseases or given sample; however, the mammalian What is physiological status. This is actually metabolome consists of an estimated Metabolomics? nearly identical to how metabolomics 2,500-3,500 metabolites. is used today (see sidebar). The Linus Pauling Institute has a Metabolites are small organic Pauling and Robinson hypothesized long history of being able to quantify molecules: intermediates in that information on the health status vitamins and markers of oxidative biochemical processes or of people can be derived from the stress. With funding from the National end-products of series of analysis of as many metabolites as Institutes of Health, Oregon State pathways of reactions that have possible. To support their case, they University, and generous gifts from occurred somewhere in the body. showed a pattern of amino acids found private donors, we have established First coined in the late 1990s, in the urine that was characteristic of a state-of-the-art infrastructure ‘metabolomics’ is the study of women taking birth control pills. In for metabolomics research over the these small molecules. another study, they failed to detect a past eight years. The Institute owns By analyzing metabolites in cells, urinary metabolomics pattern that a quadrupole time-of-flight mass correlated with the grade-point spectrometer — a device that allows us blood, urine, or other biological average in male Stanford students, to determine mass and abundance of fluids, researchers can monitor the as one might anticipate. metabolites with sufficient accuracy biochemical processes that are Dr. Pauling’s early exploratory work to calculate their chemical formula. The occurring. Certain molecules or suffered from many technological Biomolecular Mass Spectrometry Center patterns of metabolites may be limitations of the analytical equipment at OSU operates three additional mass indicators of health or disease. and the lack of databases to identify spectrometers that are also suitable for Other molecules may be produced metabolites. In the 1990s, the metabolomics research. Software tools in response to an intervention, widespread introduction of liquid have allowed us to build our own such as a . chromatography coupled to

12 in-house library that consists of more research focus on the use of than 650 metabolites commonly stable-isotope tracers. Functionally LPI/OSU Mass Spectrometry & found in mammals. We can identify identical to the naturally occurring Metabolomics Group tiny amounts of metabolites from molecules of interest, stable a variety of biological samples both isotope-labeled metabolites have From left-to-right: quickly and efficiently. heavier atoms, allowing them to be Back row: Fred Stevens, For additional support, we call distinguished from the naturally Joseph Beckman, Elizabeth Axton, upon OSU bioinformaticians and occurring metabolites by mass. Their biostatisticians, notably LPI Principal fate in a biological system can be Bayissi Bading Taika (Gabon), Investigator Gerd Bobe, Ph.D., to help followed with mass spectrometry by Jeff Morré, Claudia Maier, Liping us evaluate enormous amounts of monitoring what metabolites carry Yang, Fereshteh Zandkarimi (Iran), data generated by our metabolomics the additional mass. Ines Paraiso (France), Jaewoo platforms, the first step in interpreting Our faculty are using metabolic Choi, Cristobal Miranda; their functional meaning. With this tracers to study the dysregulation wealth of metabolomics data, of metabolic pathways in diverse Front row: David Yu, Armando we have already made several diseases and to examine the fate of Alcazar Magana (Mexico), discoveries of how vitamins and vitamins and dietary phytochemicals Johana Revel (France), Manual dietary phytochemicals work and in mammalian systems. García-Jaramillo (Spain), Supatcha how environmental stressors affect LPI investigators seek to determine Kubglomsong (Thailand). human ; see what dietary supplements and https://goo.gl/fV26XK for our functional foods are able to restore Foreign exchange students and current list of metabolomics distinct physiological pathways that postdoctoral researchers are identified publications. are disrupted in disease states or with their country of origin. The LPI is committed to invest altered by aging. LPI will continue to further in “new and emerging ‘omics’ conduct sophisticated metabolomics technologies” to advance research research with the most modern in human health and disease, technologies available to advance healthspan, and cancer prevention. micronutrient research aimed at New directions in metabolomics improving human health.

13 LPI GRADUATE STUDENTS

Graduate students are key to the success of the Linus Pauling Institute and research at Oregon State University. In this and future issues of the newsletter, we will highlight our students and their achievements at the Institute.

Melissa McDougall Bayissi Bading Taika Elizabeth Axton

Ph.D. Candidate in Nutrition in the Ph.D. Candidate in Pharmacy, Ph.D. Candidate in Pharmaceutical College of Public Health and Pharmacology and Postgraduate Sciences and Environmental and Human Sciences Medicine Molecular Toxicology

Melissa had the science bug at a very Bayissi is a visiting graduate student Elizabeth grew up in small rural young age. Eventually that developed and Ph.D. candidate at the University town in northern California, where into an interest in cellular biology. of Hertfordshire in London/UK, science careers were undervalued. After obtaining her bachelor’s degree in working in the laboratory of Dr. Fred Always interested in the natural world, molecular and cellular biology with an Stevens. Her project involves she developed a keen interest in emphasis in neuroscience, Melissa came bioactives from a shrub native to metabolomics (see p. 12) after her to Oregon State University to pursue a Gabon and Central Africa called undergraduate years at the University Ph.D. working with Dr. Maret Traber, Tabernanthe iboga. Alkaloid of California, Davis. This interest investigating the role of vitamin E in the compounds from this plant may be drove her to Oregon State University, body (see p. 10). Her focus is on vitamin E useful in treating obesity and type 2 specifically to work with Dr. Fred Stevens. in the brain, from beneficial functions in diabetes. Currently, she is using metabolomics early development to those found during With a background in molecular to explore the biological effects of old age. She is currently working to biology, cellular biology, biochemistry, nitrates, and she has followed the elucidate the effects of vitamin E deficiency and pharmacology from University interactions of vitamin C, nitroglycerin, on brain function using zebrafish. Paul Sabatier in France, Bayissi was and effects on the cardiovascular Melissa’s hard work has paid off in awarded a grant from the Gabon system. Elizabeth was recently multiple fellowships over the years, Oregon Center, which gave her the awarded first place at the annual and she is currently a Marion T. Tsefalas opportunity to work with Dr. Stevens’ Environmental and Molecular Toxicology Graduate Fellowship awardee. This lab and develop her mass spectrometry Research Day at Oregon State University generous financial support has helped skills, along with pharmacology for a presentation on her work. She propel her research forward in the last training. She is currently in the final also received a Science Communication few years at the LPI. Her research year of her Ph.D. program. Fellowship and a Food Science and projects have earned her several Nutrition Scholarship. Like Dr. Pauling, awards, including a Young Investigator she is committed to bringing Award from the Society for Free Radical communication and outreach into her Biology and Medicine, as well as a Travel science career. Award from the American Society for Biochemistry and Molecular Biology.

14 DEVELOPMENTS Dear Friends, Most of you who have read our These students have their own newsletter over the years are familiar accomplishments and awards, but with our wonderful faculty researchers. the size and number of funding However, did you know that the opportunities are limited. Many of Institute is also home to many student our brilliant students work their way researchers? In fact, we have 15 through school, and their families undergraduate researchers and 8 often make great sacrifices to help graduate researchers, many of whom them graduate. Sadly, there are times Amanto Marcotulli, J.D. are Ph.D. candidates. when research funding falls short and Director of Development In this issue, we feature some of our support for these students disappears student researchers so that you can — they simply can’t afford to pay for get a sense of the caliber of their work tuition, books, or living expenses and and the contributions they make work an unpaid position in the towards advancing the cutting-edge laboratory at the same time. When science taking place here at Linus this happens, our research gets held Pauling Institute. Our faculty takes back and students miss out on great pride in mentoring young important learning opportunities. researchers who are just starting their For these reasons, we have careers because educating the next established the Balz Frei Endowed generation of citizen scientists is an Fellowship Fund (in honor of our integral part of our mission. And make former director) to support graduate no mistake, these students play a vital students. I hope that you will consider role in advancing our research goals. making a gift to this fund. Your As a public institution, Oregon State generosity will support LPI’s research University is committed to offering and help hard-working students students access to a high-quality launch their careers. education regardless of their financial Please contact me to learn more background, and this commitment about the Balz Frei Endowed is shared by all of us at the Institute. Fellowship, or if you would like to set Many of our student researchers up your own named scholarship fund come from humble backgrounds — at LPI. Who knows, maybe one of the just like Dr. Pauling did — but once students that you help will become a they step into our labs, they become Nobel Laureate! integral members of a world-class Sincerely, research team. See us on Facebook Facebook.com/ LinusPaulingInstitute Amanto Marcotulli

Amanto is the new Director of Visit the LPI Blog Development for the Linus Pauling blogs.oregonstate.edu/ Institute at the OSU Foundation. LinusPaulingInstitute If you would like to know more about how to work with Amanto to support the LPI and its research goals, you can contact him at [email protected] or call at (503) 553-3400.

15 Non-Profit Org. U.S. Postage PAID Portland, OR Oregon State University Permit No. 1006 307 Linus Pauling Science Center Corvallis, Oregon 97331

phone: 541-737-5075 fax: 541-737-5077

email: [email protected] website: lpi.oregonstate.edu

New research updates from the Linus Pauling Institute. LOOK INSIDE

A LASTING LEGACY You can create a legacy of your own by providing opportunities for future researchers. Gifts in support of students or research projects at the Linus Pauling Institute can be made at any time. To learn the many ways you can help support the LPI, please contact the OSU Foundation at 1-800-354-7281, write to the Institute, or go online: osufoundation.org/GiveToLPI