LINUS
PAULINGINSTITUTE
OREGON STATE UNIVERSITYRESEARCH NEWSLETTERSPRING-SUMMER 2017

INSIDE: LPI Conference Announcement

THE HEALTHY YOUTHPROGRAM
Working to advance healthspan foryouth and families
The foundation for a healthy lifespan islaid in childhood, as a balanced dietprovides essential nutrients for healthy
development and growth. As part of theLinus Pauling Institute’s public outreachmission, the Healthy Youth Program isdedicated to translating the scientificdiscoveries on vitamins, minerals,
phytochemicals, and healthy eating
patterns into meaningful information forthe public. Working in the Corvallis
community since 2009, we have developed
several nutrition education programs thatare evidence-based, hands-on, andcommunity-centered — all promote healthy
food choices for children and their families.

Food choices — healthy ones or not —develop early in life and become difficult tochange once we reach adulthood. Consistentnutrition education throughout the school
years provides children with the informationand skills to make lasting, healthy foodchoices. A logical place to focus nutrition
education efforts is in schools, yet is thisrealistic? Nutrition education is not included
in state standardized tests, so the averagetime devoted to teaching nutrition anddietary behavior in elementary school is
only 4.6 hours over an entire school year.
To gauge teachers’ perceptions on this
topic, we implemented a cross-sectional
survey of Oregon elementary school classroom teachers about nutrition education
programs. Overall, we were encouraged that
97% of teachers rated nutrition education inelementary school to be at least ‘somewhat
important,’ and more than half agreed that
Continued on page 4

IN THIS ISSUE
From the Director............2
Diet and Optimum HealthConference......................5
Stephen Lawson: 40 Yearsof Service to the LPI........6
IV Vitamin C and Cancer:
An Update.......................8
Getting EnoughVitamin E?..................... 10
Metabolomics in the
New Millennium.............12
LPI Graduate Students....14
Developments................15

FROM THE DIRECTORJan Frederik Stevens, Ph.D.

Professor and Interim Director
Linus Pauling InstituteWe are pleased to present thisSpring/Summer edition of the Linus
Pauling Institute’s Research Newsletter.
We have many new developments toshare with you, such as the latest news
on our research findings, accomplishmentsof our students, the activities of the
Healthy Youth Program (on the cover),and the program for this summer’sDiet and Optimum Health conferencein Corvallis, Oregon.
As you may recall from our previous
newsletter, we are moving forward
in an ever-changing research
environment. While we stay on coursewith our mission and our research
focus on vitamins, minerals, andphytochemicals, now more than everit will take a multidisciplinary approachto reach our goals. We are now
collaborating with colleagues throughout
Oregon State University and academic
institutions in the region to complement
our expertise.
Today’s federal funding climate is thetoughest I have seen in my 15 years at
Oregon State University. The national
competition for federal grants is fierce,by some called ‘hypercompetition’for the federal research budgets. Our
strategy is not to simply wait for better
times. To better position the Instituteto face competition, I decided to give
faculty who submit a grant application
additional funds to generate proof-ofconcept data requested by grant review
panels or for professional grant-writing
support. Most LPI faculty have alreadytaken advantage of this ‘submission
premium’ to strengthen their proposals.
Our approach is beginning to pay
off: Our faculty are submitting more
proposals than last year, and they arereceiving better scores with each new
submission cycle.
Through a collaboration withinvestigators from the University of2

Nebraska, LPI investigators Drs. Fritz
Gombart and Arup Indra won a subaward
on a four-year R01 grant from the
National Institutes of Health. Dr. Victoria
Drake, Manager of the Micronutrient
Information Center (MIC), has received
a grant from a large nutraceuticalcompany, making it possible for her
and her team to update several
micronutrient articles and othermaterials to be published on the MIC
website. Congratulations to all!
Over the past several months, wehave also begun reorganizing the LPICore Laboratories. These facilities
were established to meet the needsof researchers over a decade ago. As
research priorities have changed overtime, reorganization is needed to staycompetitive. Although the originalpriorities of these labs remain intact,
we are expanding in the areas ofanalytical chemistry (such as
metabolomics, see the article on page12), new animal models, and humanclinical research. The new core labs
will be named ‘Biological Models andTranslational Research Core’ and the‘Analytical Services Core.’ Most
importantly, they will have a broader
scope and greater flexibility to assist
faculty and allocate resources whereneeds are most urgent.
In this issue of the newsletter, wehighlight news from the research andoutreach programs. Dr. Maret Traberand her co-workers discovered thatvitamin E pharmacokinetics is different
between normal, healthy individuals
and those with metabolic syndrome.
Please read the article on why that mightjust have an impact on your health. Dr.
Claudia Maier, LPI adjunct faculty, and I
present an update on the metabolomics
research at the LPI – a field pioneeredby Dr. Linus Pauling himself.
If you have followed the news

The Biological Models and Translational
Research Core in the Linus Pauling Instituteincludes 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
intravenously administered vitamin C
has reached the media headlines as acancer therapeutic — we will update
you on the research in this field. And,
as you have already seen on the cover,
we will tell you about the efforts of theInstitute’s Healthy Youth Program tobring nutrition education to elementary
school children, setting a trajectory fora healthy diet into adulthood.
Stephen Lawson decided to retire lastJune. With the LPI since its inception
at OSU 20 years ago, he had worked
directly with Dr. Pauling at the Linus
Pauling Institute of Science andMedicine in California. Steve enjoyedwriting and editing the ResearchNewsletter, corresponding with friendsof the LPI, introducing LPI researchand outreach activities to the public,
assisting with the design of the new
Linus Pauling Science Center and, atlong last, seeing its completion in 2011.
But discussing his many activities over

the years would fill this entire issue
and beyond. In our article on page6, we take a moment to celebrate
Steve’s many contributions over the
past 40 years with our Institute. On
behalf of the entire LPI faculty, staff,
and students, I express my sincere
gratitude to Steve for everything hehas done for the Institute. We wish
him all the best as a retiree!
Now I would like to introduce LPI’s
new Director of Development,
Amanto Marcotulli, J.D., who joined
the OSU Foundation in November
2016. Amanto served in similar rolesat the University of California,
San Francisco, and at the Universityof California, Berkeley. Prior to
fundraising, he served as a publicdefender, solo practitioner, andrecruiting manager. In the few
months I have worked with him,
I have discovered that he has anamazing ability to explain complex
scientific topics in simple, clear terms

3

without losing the essence of thecomplexity.
We look forward to working with
Amanto and hope that you reach out tospeak with him yourself sometime soon.
Lastly, save the date, if you haven’t
done so already: The 2017 Diet andOptimum Health conference will be held
on September 13-16, 2017, at the CH2M
Hill Alumni Center in Corvallis, Oregon.
This year’s conference, chaired by
Dr. Maret Traber, will have a tribute to
Dr. Balz Frei, who directed the LPI from1997 to 2016. The scientific program has
been set, and details can be found on
our website. If you are an LPI graduate
or lifelong friend of the Institute, don’t
forget to sign up for the LPI alumni
reception during the conference!

Jan Frederik Stevens, Ph.D.
Professor and Interim Director

Continued from cover — The Healthy Youth Programeducational programs may improvestudents’ food choices at least in the
short term and possibly in the long term.
However, as one might expect,
implementing nutrition education
programs in schools presents several
challenges. Barriers noted by teachers
included competing academic
expectations (52% of survey
respondents), a lack of available time
(48% of respondents), and a lackof suitable curricula (36% ofrespondents). Also, about half of theseteachers thought that getting parents
involved would be one key toestablishing an effective program.
Not surprisingly, teachers also notedthat unless the food environment inschool cafeterias reflects what is beingtaught, nutrition education will havea limited impact on students’ foodchoices. Following up on this, we senta second survey to Oregon elementary
school foodservice personnel, also on
the topic of nutriton education. All of
those who responded thought thatnutrition education in elementary
schools is at least somewhat important,and most thought that school cafeterias
should be involved for program success.
Three-quarters of school foodservice
personnel were interested in nutrition
education training, but, similar toteachers, they noted barriers forincorporating nutrition education
programs into the school cafeteria.
These included cost, time, and thestaff available to take on these roles.
To learn more about the
Healthy Youth Program at the
Linus Pauling Institute, visit:
lpi.oregonstate.edu/healthyyouth
or send us an email at
hyp@oregonstate.edu

As an established partner with
Corvallis schools, the LPI’s Healthy
Youth Program has found that children
are much more likely to eat healthfully
when they are involved in growing
and preparing the food. To this end,
nutrition messages presented in our
programs are woven into cooking
and garden-based activities wherechildren, as active learners, become
truly invested in the outcome of ameal or rewards of a harvest. Our
long-term goal is to set the stage for
future generations to make lasting,healthy food choices; we accomplish
this by involving children in all
aspects of food preparation, from soil
to seed to plate.
Reinforcing nutrition messages
provided during the school day,
Healthy Youth Program educators
work with K-12th graders in school
gardens managed by our staff.
Teachers involved in garden activities
appreciate the inherent links gardenbased education has to academic
standards, and students appreciate
the opportunity to learn outdoors.
Harvests are taken directly to theschool kitchens, where the colorfuland fresh fruit and vegetables enliven
cafeteria salad bars. Signs posted nearthese offerings boast messages like
“Grown by YOU!” or “From your school
garden!,” inspiring ownership, andultimately consumption.
With constraints on teachers during
school hours, the Healthy Youth
Program also offers after-school
cooking courses that combine
cooking/food preparation, kitchensafety, tasting, and food/nutrition
knowledge. Fresh Grown Cooking forKids and Master Chefs are two of ourcourses designed for elementary andmiddle school students, respectively,
offered regardless of family income

4level. Both courses meet once per
week for two hours and include anutrition lesson followed by 60 to
90 minutes of hands-on cooking insmall teams of three-to-fourparticipants. Each team makes twoor three healthy recipes each week,
and importantly, time is spentsharing the meal and talking about
the experience.
Ingredients emphasize wholegrains, minimally added sugars, andabundant fresh fruit and vegetables
that are often harvested on-sitefrom the school gardens. During theoff-season, you can find Master Chefs
participants starting microgreen
seeds in the HYP-managed school
greenhouse in week one of their
session. The kids harvest these greens
to use in a cooking competition, amuch-anticipated activity in the finalclass of this six-week program.
The goals of the cooking classes areto teach participants how to preparea variety of healthy, complete meals;
expose participants to new andfamiliar healthy foods; teachparticipants basic kitchen safety skills
and nutrition knowledge; and, overall,to promote healthy food choices forchildren and their families by boostingchildren’s confidence in the kitchen
to make scratch cooking fun, tasty, andrewarding. A preliminary evaluationof both courses indicate that thesecourse goals are being achieved.
The changes go beyond our data,
as we are witnessing changes in thefood behaviors of children; it is notuncommon to hear a child shout,“I love kale!” at the end of a lesson.
The Centers for Disease Control andPrevention (2014) cdc.gov/healthyschools
Perera et al. J Educ Pract. 6 (2015)
Perera et al. J Health Edu Res Dev. 3 (2015)

Join the Linus Pauling Institute for theDiet and Optimum HealthConference 2017
September
13–16
OR
Join the Linus Pauling
Institute forCorvallis,theDiet and Optimum HealthConference 2017

Featuring

September 13–16 Corvallis, OR• A Tribute to Balz Frei
• Dietary
Components
Featuringand the Microbiome• Update
VitaminE• Aon
Tributeto Balz Frei
• Dietary Components• Bioactives
andand theMicrobiome
CancerPrevention• Updateon Vitamin E• Bioactives and• All-day
Symposium
CancerPrevention
on IV •VitaminC
All-day Symposium
on IV Vitamin C

Session• A Free• Public
A Free Public
Session onon
Sat., September16th
16th
Sat., September

lpi.oregonstate.edu/DOH
5

STEPHEN LAWSON
40 years of service and an entire career dedicated to the Linus Pauling InstituteStephen Lawson“Working at the
Linus Pauling Institute of
Science and Medicine andthe Linus Pauling Instituteat Oregon State University
has been an extraordinary
experience.”— STEPHEN LAWSON, 2017

It is with mixed feelings that weannounce that Stephen Lawson
has retired from the Linus Pauling
Institute. Many who contacted theInstitute over the last few decades
knew something of Steve: He worked
at LPI for many years longer thananyone else and was an integral partof its success over its history.
A graduate of Stanford University,
Steve joined the Linus Pauling Instituteof Science and Medicine (LPISM) in
California in 1977. Initially, his work at
the Institute with Linus Pauling focusedon several projects with vitamin C,
including the role of vitamin C in theprevention of skin cancer and potential
interactions between vitamin C andcancer chemotherapeutic drugs.
Later, as a co-director of theLaboratory for Research in Gene
Regulation in the late 1980s, Stevedeveloped a technique for using
two-dimensional gel electrophoresis
to profile proteins involved in cancer
metastasis. He also studied the effectsof phytic acid, a substance found in
grain and plant seeds, on blood lipids
and tumor growth in rats, resulting
in a patent for its use in inhibiting
cancer growth.
From 1988 to 1991, Steve served as
executive assistant to the president,
Emile Zuckerkandl — who developed
the concept of molecular evolution
with Pauling — and, in 1991, as
executive officer.
In 1993 he was appointed chief
executive officer and grappled withfinancial, legal, zoning, and othercritical issues facing the Institute,and successfully negotiated several
remunerative research andcorporate contracts.

6

In 1996 he organized the moveof the Institute to Oregon State
University. “Dr. Pauling was awareand supportive of our discussions
to move LPI to Oregon State
University and continue the missionof orthomolecular medicine,” says
Lawson. “He would certainly bepleased to know that importantresearch in metabolomics — a field heand colleagues pioneered in the late1960s — and on essential minerals likezinc; phytochemicals; and vitamins C,
D, and E has been conducted at LPI.”
At the new Linus Pauling Institute,
Steve served as our administrative
officer and editor of the ResearchNewsletter, helping to preserve
institutional memory. Steve also
assisted in recruiting Balz Frei as the
new director of the LPI and served as
the director’s advisor until they both
retired in 2016.
Steve was critically involved in
LPI’s fundraising and strategic, longterm planning. He also served on thesteering and art committees for OSU’s
Linus Pauling Science Center, thecurrent home of the Institute, and, formany years, on the Campus Planning
Committee and the Student Health
Advisory Board.
Over the years he has authoredor co-authored many papers,
including those published in the
Journal of Virology, Carcinogenesis,
Gynecologic Oncology, the Journalof Orthomolecular Medicine, theProceedings of the National Academyof Sciences, Nutrition Research,
the Journal of Applied Nutrition, theAmerican Journal of Clinical Nutrition,and the Journal of Anesthesia History,
among others.

Yet, all of these accomplishments
only barely touch on Steve’s life at
the Institute. He often speaks of many
happy afternoons in the LPISM spent
identifying mineral specimens andcrystals with Dr. Pauling and Zelek
Herman, Pauling’s collaborator intheoretical chemistry. Or the occasions
when Pauling would ask him to takeon special assignments, like writing
a review of Vitamin C and Cancer:
Medicine or Politics? by Evelleen
Richards for a journal publication.
“Once,” he recollects, “Dr. Pauling
stopped by my office to tell methat he had an idea about a new
method to fabricate superconductive
material… incredibly thin fibrils of
conductive metal, such as tin, clad innonconductive glass.” Pauling asked
Steve to help set up a small lab tosee if they could make this material,
hoping the licensing of a patent mightprovide a high revenue stream to fundresearch in orthomolecular medicine
at the Institute.
Steve and Zelek bought a furnace,
blowtorch, and supplies and started
working away, melting and pulling thetin and glass in the method outlined by
Dr. Pauling. “He joined us occasionallyin the lab and wielded the blowtorch,”
Lawson recalls, “When we finallysucceeded, we rushed excitedly tohis apartment and showed him thematerial. He was gleeful and gave
us each beautiful pyrite crystals inappreciation.”
Most people are unaware that Steveset up the Institute’s first cell culture
laboratory. His recollections of theseexperiences provide a fascinating
window into the LPISM, and how
innovation triumphed in the days before
modern cell culture was the norm.
Steve’s commitment to theInstitute and the memory of Linus
Pauling, as well as his advocacy fororthomolecular medicine, is present in

Stephen Lawson (left) with Linus Pauling(right)everything he has accomplished over
the years. He participated in many
film projects about Linus Pauling andorthomolecular medicine, including
the 2011 production “Linus Pauling”
by Oregon Public Broadcasting for
the Oregon Experience program.
Steve also served on the SelectAdvisory Committee for the Linus
Pauling Exhibition, an exhibit honoring
Pauling’s positive, long-term influenceon society, visited by millions ofpeople worldwide. Moreover, Stevehas been an integral member of OSU’s
Pauling Heritage Committee, a grouporganized to recognize the wide impact
of Pauling’s life and work and how
it is reflected on the Oregon State
University campus.
Steve annotated and added anafterword to the 20th anniversary
edition of Linus Pauling’s bestseller
How to Live Longer and Feel Better,published in 2006. He recently
contributed a preface discussing
anticancer mechanisms to the new
21st-Century Edition of Cancer andVitamin C by Ewan Cameron and Linus
Pauling, as well as an appendix that7summarizes recent research on
intravenous vitamin C as adjunctive
therapy for cancer, to be published soon.
Steve often gave lectures on
orthomolecular medicine or Linus
Pauling to graduate students innutrition or medicine; undergraduate
students in the School of History,
Philosophy, and Religion; otherstudent, professional, and civic
groups; and at scientific or medical
conferences. In late April, he was
inducted into the Orthomolecular
Medicine Hall of Fame, joining
scientists and physicians like Linus
Pauling, Ewan Cameron, Bruce Ames,
Roger Williams, and Abram Hoffer.
To conclude in Steve’s own words:“I feel particularly fortunate to havebeen so closely associated with
Linus Pauling and LPI for so longand cherish the time I spent learning
about the critical contributions ofscience to society and how sciencecan be the source of so much fun andsatisfaction.”
Stephen Lawson currently holds a
courtesy appointment at Oregon State
University and can still be reachedthrough the Linus Pauling Institute.

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

Linus Pauling was very interested
in the value of vitamin C in treating
cancer. Clinical research with hiscolleague Ewan Cameron in the 70s
demonstrated that large doses oforal and intravenous (IV) vitamin C
were helpful in increasing the survival
time and improving the quality of lifeof terminal cancer patients. Whenfollow-up studies by the Mayo Clinic
using only oral vitamin C did not show
any benefit, many cancer researchers
doubted the value of vitamin C therapy,
and the research slipped out of themainstream.
About 10 years ago, studies at the NIH
with Dr. Mark Levine revitalized cancer
research with vitamin C. His groupconfirmed that high concentrations ofvitamin C do indeed kill cancer cells
in culture. Studies in animals showthat vitamin C infusions can slow
tumor growth. A number of studies
are now underway to characterize
the molecular anticancer
mechanisms of vitamin C andoptimal protocols for administration.
However, there is plenty of work
to be done before vitamin C can be
accepted as a mainstream therapy
for cancer.
Yet, as clinical researchers try tounderstand why and how much
vitamin C can help fight against
cancer, thousands of people
worldwide are using it as a primary
treatment or adjunctive therapy.
Therefore, we believe a review of the8current state of intravenous vitamin C
as a cancer therapy may be useful for
those who wish to know where thescience stands on this treatment:
It is generally safe: Results fromcontrolled clinical trials indicate thatIV vitamin C is generally safe and welltolerated in most prescreened cancer
patients. In fact, there are very few
contraindications for vitamin C in
intravenous form. However, there is
still the potential for side effects: thosewith existing kidney disease, historyof kidney stones, or glucose-6-phosphate dehydrogenase deficiencies
should take particular caution.
It is not the same as taking a
supplement: The therapeutic effect ofvitamin C in cancer patients has mainlybeen demonstrated through IV
administration or direct infusion, notby taking supplements. Concentrationsof vitamin C in the blood are the key:
formulations of oral vitamin C —even those that claim to boost
bioavailability — do not increase blood
vitamin C levels to a point that would
produce the same anticancer effect. IV
administration allows concentrationsof vitamin C in the blood to reach atleast 100 times higher than taking
oral supplements.
Hydrogen peroxide is likely
important: Researchers have foundthat high concentrations of vitamin C
can produce hydrogen peroxide in thevicinity of a cancer cell. The hydrogen
peroxide interferes with functions inmany cancer cells, leading to their
death. Cancer cell death cannot be
achieved by directly administeringhydrogen peroxide because enzymes
in the blood would remove anyhydrogen peroxide formed before
it could reach tissues. Also, taking
large amounts of hydrogen peroxideby mouth is not safe and would nottarget cancer cells.
The working hypothesis is that highlevels of vitamin C may reach thespaces where removal enzymes areabsent, allowing a reaction withoxygen, production of hydrogen
peroxide, and its transport into cells.
This causes a cascade of reactions that
ultimately can kill cancer cells. Other
mechanisms have also been proposed
regarding how vitamin C might slow
tumor growth and cause cell deaththat do not involve hydrogen
peroxide, so it is possible that multiple
mechanisms are at play.
It can be combined with somecancer therapies; not with others:
Studies have found that intravenous
vitamin C treatments can alleviate
fatigue or decrease other side effects
of some chemotherapeutic drugs,

thereby improving the quality of lifeof cancer patients. Some drugs havebeen shown to work better in
combination with vitamin C. On theother hand, vitamin C may interact
with other drugs to limit how wellthey work or even exacerbate side
effects. Thus, it is extremely importantto talk to a physician before
combining IV vitamin C with any
drug. Of course, any administrationof an injection or infusion of vitamin C
should only be performed under
the direct supervision of a qualified
health professional.
IV vitamin C is not a miracle agent
for all cancers: Research has shownthat some cancers are not affectedby the use of IV vitamin C, especiallycancer cells that are resistant tohydrogen peroxide. Researchers aretrying to find ways of overcoming
those barriers, but progress in thisarea is slow and needs more funding
to continue.
Bottom-line: Overall, vitamin C
infusions are a promising approach
to fighting some types of cancer,
but much more work still needs tobe done to determine how and when
they should be used. It is still too
early for the Linus Pauling Instituteto make general recommendations
about IV vitamin C to cancer patients.
Clinical trials are currently underway
at centers around the world to provide
answers to important questions about
this therapy.
Chen et al. Proc Natl Acad Sci. USA 102 (2005)
Ma et al. Sci Transl Med. 6 (2014)
Schoenfeld et al. Cancer Cell. 31 (2017)

For those who want to know more
about the subject, we recommend
the new edition of Cancer andVitamin C by Cameron and Paulingthat discusses anticancer
mechanisms and summarizes therecent clinical research. Contact theInstitute for more details.

9

GETTING
ENOUGH
VITAMIN E?

Studying metabolic syndrome maylead to new recommendations forvitamin E
Vitamin E, a fat-soluble antioxidant,
plays a supporting role in immune
function, wound healing, vision, andneurologic function. Estimates arethat 90% of Americans do not eat
enough vitamin E-rich foods to meet
published requirements. Despite
its importance, people who don’t
consume enough vitamin E still seemto be healthy. Are the requirements
wrong?
Maret Traber, Ph.D., Ava HelenPauling Professor at the Linus Pauling
Institute, believes that people are notgetting enough vitamin E and are, infact, not as healthy as they think.
The extent of the problem, especiallyin people with underlying healthconditions, may be worse than has
been appreciated by most nutrition
professionals. Research from herlaboratory has demonstrated thatmeasuring the amount of vitamin E
you consume, or even the amountin your blood stream, might not give
you a complete picture of vitamin E

status. Her new studies show there
might be a better way to tell if you
are eating enough vitamin E.
First, some background on how
vitamin E moves through the body:
After you eat something containing
vitamin E — be it a handful ofalmonds, some vegetable oil, a few
cups of spinach, or a supplement —the vitamin E, along with the fat inyour meal, gets absorbed and sent
through the blood stream to the liver.
The liver is the guardian, picking out
those molecules needed for life andsending those back into the bloodstream. It also sorts out and removes
the things you don’t need in yourbody. Thus, the liver works as asorting facility, keeping the good andexcreting the useless or potentially
toxic.
Here, one form of vitamin E named
alpha-tocopherol is special: A transfer
protein found in the liver rescues
alpha-tocopherol and sends it — alongwith dietary fats — back into the bloodstream for delivery to tissues. Other
forms of vitamin E, like tocotrienols,
don’t get this special treatment.

10

Because of this distribution
system, measuring alpha-tocopherollevels in the blood gives doctors andresearchers a good understanding if
someone is deficient. Under normal
circumstances, if vitamin E levels inthe blood are low, the person is notconsuming enough. If levels are high,it probably means enough vitamin E
is reaching the tissues where it needed
the most.
However, this is not always thecase. A problem arises when fat is
not taken up into tissues normally.
This occurs in hyperlipidemia or
hypercholesterolemia, where
triglycerides and cholesterol particles
circulate in the blood at abnormallyhigh levels. Where the fats go, thevitamin E follows. “It’s a micronutrient
that’s going along for the ride,” says
Dr. Traber.
To study this in more detail, Dr.
Traber, along with her collaborators
at The Ohio State University, decided
to look at persons with metabolic
syndrome (see sidebar). Althoughblood levels of vitamin E in these
individuals are apparently normal,

Dr. Traber and her colleagues wereconcerned. This syndrome isassociated with high levels of
inflammation and increased oxidative
stress — could these problems
increase the amount of vitamin E
they need?
The scientists gave volunteers
specially tagged alpha-tocopherol
to eat so that the vitamin E could be
followed in the circulation. This
molecular tag let them follow thevitamin E they provided and also thefate of that vitamin, such as vitamin E
catabolites that are excreted in
the urine.
In participants with metabolic
syndrome compared with healthy
individuals, the tagged vitamin E was
not only poorly absorbed but also
disappeared from the blood stream
more slowly. Upon analysis, this odd
behavior gave clues that something
peculiar was happening to this tagged
vitamin E in the body.
Traber explains: “In metabolic
syndrome, tissues are rejecting fat
because they already have enough.
In the process, they also rejectvitamin E. So even though the tissues
are facing serious oxidative stress,
the delivery of vitamin E to them isbeing impaired. Our research showsthat people with metabolic syndromeneed about 30-50 percent more
vitamin E than those who are
generally healthy.”
When vitamin E intake is higher
than the body needs, the extra iseliminated. This is a catabolic processthat starts by step-wise removal of
the carbons on the long tail found ona tocopherol molecule. The product of
this elimination process is a molecule
called CEHC. The advanced laboratory
tests conducted by Dr. Traber’s group

showed that people with metabolic
syndrome eliminated less CEHC thanhealthy people.
In other words, those withmetabolic syndrome were showing
signs that they weren’t getting thevitamin E they needed.
Traber is now touting CEHC as abiomarker of vitamin E status —a way for researchers, and potentially
physicians (if the future testing
confirms the outcomes) to know if
vitamin E levels in the body areadequate. Traber hopes that future
support of this research will help
determine if this molecule can beclinically measured to validate aperson’s low vitamin E levels in tissues.
The unfortunate conclusion to thisset of experiments is that the people
with metabolic syndrome areshowing signs of needing much more
vitamin E. It is not yet clear if eating
more vitamin E-rich foods is the bestsolution for those with metabolic
syndrome — but a balanced diet iscertainly a good start. Of course,
supplementation may be a good way
for many people to get enoughvitamin E, and the Linus Pauling
Institute recommends taking a daily
multivitamin supplement, whichusually contains close to therecommended levels of vitamin E.
The Traber lab is hoping to work withother research participants with lipid
dysregulation in the future, to see if
this problem may affect more people
than this small study would indicate.
Mah et al. Am J Clin Nutr. 102 (2015)
Traber et al. Am J Clin Nutr. 105 (2017)
Grundy et al. Circ. 112 (2005)

What is Metabolic Syndrome?
Metabolic syndrome is a combination of
medical conditions that places you atincreased risk for several chronic diseases.

How is Metabolic Syndrome Diagnosed?
You have metabolic syndrome if you
have three or more of the following
risk factors, or are taking medication
to control them:• Abdominal obesity (waist size
≥ 40 inches for men or ≥ 35 inches
for women)• High serum triglycerides(triglycerides greater than 150 mg/dL)• High blood pressure (blood pressureof 130/85 mm Hg or higher)• High blood glucose (fasting blood
glucose above 100 mg/dL)• Low HDL cholesterol (HDL levels< 40 mg/dL for men or < 50 mg/dL
for women)

What is the Impact of Metabolic
Syndrome?
Metabolic syndrome can increase yourrisk for cardiovascular disease, type 2
diabetes, insulin resistance, Alzheimer’s
disease, and non-alcoholic fatty liverdisease. Fatty liver can progress into
cirrhosis,hepatocellular carcinoma,
and potentially death.

How is Metabolic Syndrome Prevented?
• Eat a healthy diet rich in fruit,
vegetables, fish, and whole grains• Keep sugar intake low (less than
10% of calories)• Get regular physical activity• Achieve and maintain ahealthy body weight• Do not smoke• Get regular medical checkups
For more information, see theMicronutrient 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.
LPI Adjunct Faculty

Jan Frederik Stevens, Ph.D.
Professor and Interim Director
Linus Pauling Institute

What isMetabolomics?
Metabolites are small organic
molecules: intermediates inbiochemical processes or
end-products of series ofpathways of reactions that haveoccurred somewhere in the body.
First coined in the late 1990s,‘metabolomics’ is the study ofthese small molecules.
By analyzing metabolites in cells,
blood, urine, or other biologicalfluids, researchers can monitor thebiochemical processes that are
occurring. Certain molecules orpatterns of metabolites may be
indicators of health or disease.
Other molecules may be produced
in response to an intervention,such as a dietary supplement.

Is metabolomics really the latest
addition to the spectrum of ‘omics’ tools?
Linus Pauling and Arthur Robinson
are credited by many sources,
including Wikipedia, as pioneers in
the field of metabolomics. In 1974,
they published a paper in the journal,
Clinical Chemistry (vol. 20, pp. 961-5),
entitled “Techniques of Orthomolecular
Medicine,” reporting on research they
had been conducting since the latesixties. They defined their term‘orthomolecular diagnosis’ as ‘theprocess of determining and evaluating
the concentrations of the substances
normally present in the human body.’
Initially, they were trying to identify
substances in urine that quantitatively
correlated with specific diseases orphysiological status. This is actually
nearly identical to how metabolomics
is used today (see sidebar).
Pauling and Robinson hypothesizedthat information on the health statusof people can be derived from theanalysis of as many metabolites as
possible. To support their case, they
showed a pattern of amino acids foundin the urine that was characteristic ofwomen taking birth control pills. In
another study, they failed to detect aurinary metabolomics pattern that
correlated with the grade-point
average in male Stanford students,
as one might anticipate.
Dr. Pauling’s early exploratory work
suffered from many technologicallimitations of the analytical equipment
and the lack of databases to identify
metabolites. In the 1990s, thewidespread introduction of liquid
chromatography coupled to
12electrospray mass spectrometry
greatly improved the ability to detectpolar metabolites in plasma and urine.
Since that time, high-resolution
accurate mass detectors have founduniversal use in metabolome research.
In the mid-2000s, several large
metabolome databases weredeveloped that can be accessed
online, notably METLIN and the Human
Metabolome Database (HMDB).
Yet, despite all of these technical andbioinformatics advancements, we arestill not able to identify the majorityof metabolites in a given biologicalsample. Most metabolomics laboratories
around the world have the ability toidentify hundreds of metabolites in agiven sample; however, the mammalianmetabolome consists of an estimated2,500-3,500 metabolites.
The Linus Pauling Institute has along history of being able to quantify
vitamins and markers of oxidative
stress. With funding from the National
Institutes of Health, Oregon State
University, and generous gifts fromprivate donors, we have establisheda state-of-the-art infrastructure
for metabolomics research over the
past eight years. The Institute owns
a quadrupole time-of-flight mass
spectrometer — a device that allows us
to determine mass and abundance of
metabolites with sufficient accuracy
to calculate their chemical formula. The
Biomolecular Mass Spectrometry Centerat OSU operates three additional mass
spectrometers that are also suitable formetabolomics research. Software tools
have allowed us to build our own

in-house library that consists of morethan 650 metabolites commonly
found in mammals. We can identify
tiny amounts of metabolites froma variety of biological samples bothquickly and efficiently.
For additional support, we callupon OSU bioinformaticians andbiostatisticians, notably LPI Principal
Investigator Gerd Bobe, Ph.D., to help
us evaluate enormous amounts ofdata generated by our metabolomics
platforms, the first step in interpreting
their functional meaning. With thiswealth of metabolomics data,
we have already made several
discoveries of how vitamins anddietary phytochemicals work andhow environmental stressors affecthuman metabolism; see
https://goo.gl/fV26XK for ourcurrent list of metabolomics
publications.
The LPI is committed to invest
further in “new and emerging ‘omics’
technologies” to advance researchin human health and disease,healthspan, and cancer prevention.
New directions in metabolomics

research focus on the use of
stable-isotope tracers. Functionallyidentical to the naturally occurring
molecules of interest, stable
isotope-labeled metabolites haveheavier atoms, allowing them to be
distinguished from the naturally
occurring metabolites by mass. Theirfate in a biological system can befollowed with mass spectrometry bymonitoring what metabolites carry
the additional mass.
Our faculty are using metabolic
tracers to study the dysregulationof metabolic pathways in diverse
diseases and to examine the fate ofvitamins and dietary phytochemicals
in mammalian systems.
LPI investigators seek to determine
what dietary supplements andfunctional foods are able to restore
distinct physiological pathways thatare disrupted in disease states oraltered by aging. LPI will continue to
conduct sophisticated metabolomics
research with the most modern
technologies available to advancemicronutrient research aimed at
improving human health.
13

LPI/OSU Mass Spectrometry &Metabolomics Group
From left-to-right:
Back row: Fred Stevens,
Joseph Beckman, Elizabeth Axton,
Bayissi Bading Taika (Gabon),Jeff Morré, Claudia Maier, Liping
Yang, Fereshteh Zandkarimi (Iran),
Ines Paraiso (France), Jaewoo
Choi, Cristobal Miranda;
Front row: David Yu, Armando
Alcazar Magana (Mexico),
Johana Revel (France), Manual
García-Jaramillo (Spain), Supatcha
Kubglomsong (Thailand).
Foreign exchange students andpostdoctoral researchers are identified
with their country of origin.

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 theCollege of Public Health andHuman Sciences

Ph.D. Candidate in Pharmacy,
Pharmacology and Postgraduate
Medicine

Ph.D. Candidate in Pharmaceutical
Sciences and Environmental andMolecular Toxicology

Melissa had the science bug at a very
young age. Eventually that developed
into an interest in cellular biology.
After obtaining her bachelor’s degree inmolecular and cellular biology with anemphasis in neuroscience, Melissa cameto Oregon State University to pursue a
Ph.D. working with Dr. Maret Traber,investigating the role of vitamin E in the
body (see p. 10). Her focus is on vitamin E
in the brain, from beneficial functions inearly development to those found during
old age. She is currently working toelucidate the effects of vitamin E deficiency
on brain function using zebrafish.
Melissa’s hard work has paid off in
multiple fellowships over the years,
and she is currently a Marion T. Tsefalas
Graduate Fellowship awardee. This
generous financial support has helped
propel her research forward in the last
few years at the LPI. Her research
projects have earned her several
awards, including a Young InvestigatorAward from the Society for Free Radical
Biology and Medicine, as well as a TravelAward from the American Society for
Biochemistry and Molecular Biology.

Bayissi is a visiting graduate student
and Ph.D. candidate at the University
of Hertfordshire in London/UK,
working in the laboratory of Dr. Fred
Stevens. Her project involves
bioactives from a shrub native to
Gabon and Central Africa called
Tabernanthe iboga. Alkaloid
compounds from this plant may be
useful in treating obesity and type 2
diabetes.
With a background in molecularbiology, cellular biology, biochemistry,and pharmacology from University
Paul Sabatier in France, Bayissi wasawarded a grant from the Gabon
Oregon Center, which gave her theopportunity to work with Dr. Stevens’
lab and develop her mass spectrometry
skills, along with pharmacology
training. She is currently in the final
year of her Ph.D. program.

Elizabeth grew up in small rural
town in northern California, wherescience careers were undervalued.
Always interested in the natural world,she developed a keen interest in
metabolomics (see p. 12) after her
undergraduate years at the Universityof California, Davis. This interest
drove her to Oregon State University,
specifically to work with Dr. Fred Stevens.
Currently, she is using metabolomics
to explore the biological effects ofnitrates, and she has followed theinteractions of vitamin C, nitroglycerin,
and effects on the cardiovascularsystem. Elizabeth was recently
awarded first place at the annual
Environmental and Molecular Toxicology
Research Day at Oregon State University
for a presentation on her work. She
also received a Science Communication
Fellowship and a Food Science andNutrition Scholarship. Like Dr. Pauling,
she is committed to bringing
communication and outreach into herscience career.

14

DEVELOPMENTS
Dear Friends,
Most of you who have read our
newsletter over the years are familiar
with our wonderful faculty researchers.
However, did you know that theInstitute is also home to many student
researchers? In fact, we have 15
undergraduate researchers and 8
graduate researchers, many of whom
are Ph.D. candidates.
In this issue, we feature some of ourstudent researchers so that you can
get a sense of the caliber of their workand the contributions they maketowards advancing the cutting-edge
science taking place here at Linus
Pauling Institute. Our faculty takes
great pride in mentoring young
researchers who are just starting theircareers because educating the next
generation of citizen scientists is an
integral part of our mission. And makeno mistake, these students play a vitalrole in advancing our research goals.
As a public institution, Oregon State
University is committed to offering
students access to a high-quality
education regardless of their financial
background, and this commitment
is shared by all of us at the Institute.
Many of our student researchers
come from humble backgrounds —just like Dr. Pauling did — but once
they step into our labs, they become
integral members of a world-classresearch team.

These students have their own
accomplishments and awards, but
the size and number of funding
opportunities are limited. Many ofour brilliant students work their way
through school, and their families
often make great sacrifices to help
them graduate. Sadly, there are times
when research funding falls short andsupport for these students disappears— they simply can’t afford to pay fortuition, books, or living expenses andwork an unpaid position in thelaboratory at the same time. When
this happens, our research gets heldback and students miss out on
important learning opportunities.
For these reasons, we haveestablished the Balz Frei Endowed
Fellowship Fund (in honor of ourformer director) to support graduate
students. I hope that you will consider
making a gift to this fund. Your
generosity will support LPI’s researchand help hard-working students
launch their careers.
Please contact me to learn more
about the Balz Frei Endowed
Fellowship, or if you would like to set
up your own named scholarship fundat LPI. Who knows, maybe one of thestudents that you help will become aNobel Laureate!
Sincerely,

Amanto Marcotulli, J.D.
Director of Development

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Amanto Marcotulli
Amanto is the new Director ofDevelopment for the Linus Pauling
Institute at the OSU Foundation.
If you would like to know more
about how to work with Amanto
to support the LPI and its researchgoals, you can contact him at
Amanto.Marcotulli@osufoundation.org
or call at (503) 553-3400.

15

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New research updates fromthe Linus Pauling Institute. LOOK INSIDEA LASTING LEGACY
You can create a legacy of yourown by providing opportunities
for future researchers. Gifts insupport 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 OSUFoundation at 1-800-354-7281,
write to the Institute, or go online:
osufoundation.org/GiveToLPI