LINUS
PAULINGINSTITUTE
OREGON STATE UNIVERSITYRESEARCH NEWSLETTER
FALL–WINTER 2019

An In-depth Breakdown of the LPI Conference LOOK INSIDETIME FOR A GUT CHECKTHE GOMBART LAB GETS ITS HANDS DIRTY WITH THE GUT MICROBIOME
by Adrian Gombart, PhD
Adrian Gombart, PhD, professor in the Department of Biochemistry and Biophysics,
has been a principal investigator in the Linus Pauling Institute since coming toOregon State University in 2008. Typically, Dr. Gombart’s research focuses onvitamin D in immune responses, but with the help of his colleague, Dr. Fred Stevens,
his work took an unexpected turn to involve a compound from hops.
Scientific breakthroughs can come from themost unexpected places.
When I first arrived at the LPI, I joined the
Healthy Aging Program. This was a natural
fit since vitamin D is important for proper
immune function in older adults.
In 2011, with the move of LPI into the Linus
Pauling Science Center, conversations withmy colleagues began brewing around thecoffee pot in the new breakroom. As a result,
my good friend, Dr. Fred Stevens, invited me
to attend the informal scientific gatherings in
the LPI’s Cardio-Metabolic Disease group.

In these meetings, I learned about
xanthohumol, a phytochemical found in thehops plant, which you have likely read about
in previous LPI newsletters.
Realizing that there was significant overlap
in our scientific interests and expertise, mylab started working with Dr. Stevens and Dr.
Claudia Maier to determine what interactions
might occur between vitamin D andxanthohumol in cells.
I can honestly say that I was amazed by the
results of those studies.
Continued on page 4

IN THIS ISSUE
Time for a Gut
Check.....................1
From the Director...2
Taking the Fight
Against IBD to the
Next Level..............6
LPI Students...........9
An Interview with
Maret Traber..........10
The Linus
Pauling InstituteConference............12

FROM THE DIRECTOR
Over 50 years ago, two-time Nobel Prize winner Dr. Linus Paulingconcluded that dietary supplements play a significant role inenhancing health and preventing disease. The institution that hehelped establish, today known as the Linus Pauling Institute, isdedicated to making progress in this field.

Richard van Breemen, PhD
Endowed Chairand Director,
Linus Pauling Institute

A lot has happened since those days in Menlo Park, but the Linus Pauling
Institute of today still keeps a focus on dietary supplements. More so
now than ever before, we are focused on interdisciplinary research andeducating the next generation of experts.
Most recently, researching the health effects of botanical dietary
supplements has become essential to our mission.
One of my objectives as director of the LPI is to catalyze collaboration
among our expert faculty around researching the clinical applications ofbotanical dietary supplements. We have chosen to focus on combatingneurodegenerative diseases, like Alzheimer’s, Parkinson’s, or ALS,
because of the increasing prevalence and enormous public healthcareburden of these conditions.
Put simply, neurodegeneration is the progressive loss of neuronal
function and cognitive abilities. This often occurs in response to a stressto our nerve cells or tissues, which can come in a variety of forms. It also
occurs more frequently as we grow older, since our ability to resist or
recover from stress also declines.
In an effort to push back against the tide of aging in the field of
neurodegeneration, we have formed a multidisciplinary team of
LPI research faculty to conduct a new research project to enhancecognitive health. This team includes many experts in natural products
and neurobiology, all dedicated to understanding how botanical dietary
supplements can help improve our memory and cognitive flexibility as
we age.
We know that some botanical dietary supplements can boost cognitive
resilience, especially later in life. Through the application of state-ofthe-art scientific methodology, including innovative pharmacology andanalytical chemistry techniques, we will identify the most potent andpromising of these products.

What’s the scoop on curcumin?
Dr. van Breemen was recently featured in a webinar on thepharmacology of curcumin, which is one of the most abundantactive constituents of turmeric. Watch it online:
http://bit.ly/LPI-Curcumin

2

A comprehensive battery of tests for cognitive health and resilience will help
identify the active compounds from these products with the most promise.
With this application of our expert skill sets, we can prepare biologically andchemically standardized extracts for clinical trials. Therein lies the potential forthis project to help prevent or delay age-related neurodegeneration.

The staff and facultyof the Linus Pauling
Institute enjoying thefall colors of the OSU
campus.

Among the botanicals that we will be studying are those already showing promise
in cognitive health, such as hops, ginkgo, and turmeric. Both Dr. Stevens andI have extensively studied hops constituents, which include the compound
known as xanthohumol. See the cover article by Dr. Gombart and Dr. Stevens’
article on page six for more therapeutic applications of this molecule.
We hope that this project will be the first of many studies designed to elucidate
the roles of botanical extracts in health. This project is just one part of the larger
goal at the LPI: to push the boundaries of botanicals supplements and explore
new therapeutic applications.
Enjoy this issue of the newsletter. Stay healthy and happy this winter, and you
will hear from us again in the new year.
Sincerely,

Have a question?
As part of the ongoing evolution of
our Research Newsletter, we want
to hear from our readers.

Richard B. van Breemen

If you have questions, please send
them in – we plan on addressing
reader feedback in future editions.

3

Continued from cover — Gut HealthVitamin D and xanthohumol can work welltogether — and so could their investigators!
It was the start of mutually beneficial
scientific partnership.

Dr. Gombart is aprincipal investigatorat the Linus Pauling
Institute and is a
professor in the
Biochemistry andBiophysics department
at OSU.

The intestinal mucosa
is a single layer ofcells that forms a gut
barrier, keeping thingsin our digestive tract(like bacteria) out ofour bodies.

What I most appreciate about this instituteand our new building are the incredible
opportunities that occur when working inclose proximity with colleagues with diverse
scientific backgrounds and experiences.
New perspectives and collaborations cantake you in directions you never thoughtpossible.

Bad Bacteria Brewing
My lab is one of several at the LPI trying tocombat obesity and metabolic syndrome.
Since you have heard more about thiscondition in previous newsletters, I will
share our specific approach to tackle thehealth threat.
I am interested in the maintenance of gut
health. Members of my lab and others haveshown that poor gut health is a problem inmetabolic syndrome, particularly because
this condition reduces gut barrier function
and alters the microbiome – ramping up
inflammation.
This is where xanthohumol is important. In
research animals, Dr. Stevens has shownthat xanthohumol is a very promisingtreatment for metabolic syndrome. As wetry to take our work forward, I want to know
if xanthohumol is doing its job throughchanges in the gut.
More specifically, does taking xanthohumol
fix a gut microbiome that has gone bad?

Yang Zhang, a graduate student in mylaboratory, is examining the changes that
happen in mice that consume a high-fat
diet – one of the driving forces behindmetabolic syndrome. She discovered that
adding xanthohumol to the diet was enoughto change the composition of the gut
microbiota. These changes were associatedwith weight loss and reversal of metabolic
syndrome characteristics.
Recently published in Molecular Nutrition
and Food Research, our study found thattreatment with xanthohumol reduced
dysbiosis (microbial imbalance), altered bile
acid metabolism, and reduced inflammation.
In fact, some chemical derivatives ofxanthohumol were just as effective as
giving xanthohumol itself (For details onthese derivatives, see our Fall-Winter 2018
newsletter).
Apparently xanthohumol does some goodthings for the gut microbiome. Now we wantto find out exactly how it works.

Getting Better Germs
Food that passes through the intestine feeds
the microbes in our guts. When a diet is ofpoor quality, certain bacteria types start totake over, causing ripple effects throughout
the body.
Since most animals have a thriving gut
microbiome, it is not something that is easily
removed. To really understand the influenceof gut bacteria on metabolic syndrome, it
was necessary to raise animals that had nogut bacteria at all.
These are called ‘germ-free’ animals. They
live under very special conditions from birth
to prevent any bacteria (or other microbes)
from getting into their bodies from theoutside. Effectively these mice live in an
extraordinarily clean animal facility.
These mice are generally healthy, but they
are different from their conventionally raised
counterparts. Germ-free mice grow slower,
gain less weight, and are less prone toobesity. They also have an underdeveloped
immune system.

4

Xanthohumol canwork in several
ways to combat gut
inflammation andrestore a normal
healthy gut. Changing
gut bacteria is only one
piece of this puzzle.

Current research suggests that germ-freeanimals do not develop metabolic syndrome.
After all, no gut microbiome means nothing
to spoil with a bad diet, right? Wrong.
Isabelle Logan, another graduate student
in my lab, took a closer look. Working withdifferent animal strains, she found at least
one strain of germ-free mice that develops
several characteristics of metabolic
syndrome on a high-fat diet.
Just like their conventionally raised
counterparts, the germ-free mice gain
weight, are unable to clear glucose fromthe blood, and show elevated LDL (“bad”)
cholesterol.
Does this challenge the notion that badbacteria in the gut are the cause of metabolic
syndrome? Not entirely.
Although we induced something likemetabolic syndrome in these animals,
they did not develop all of the samecharacteristics. Conventionally raised miceon a high-fat diet are certainly less healthythan the germ-free mice, indicating thatcertain gut microbes could worsen the
disease.
Maybe there is something to be said for
fixing gut bacteria after all.
Since xanthohumol affects the compositionof the gut bacteria and this is associated withimproving metabolic syndrome, is it possiblethat changing the microbiome confers
xanthohumol’s benefits?

You will hear more from us on this topic soon.
At the moment I can only say that our early
results look very promising.

What about vitamin D?
In these studies, we took vitamin D out of
the equation to see what xanthohumol can
do alone. However, we do want to determine
what vitamin D can do for immunity and gut
health.
Vitamin D plays an important role inregulating the ‘gut barrier,’ important forkeeping the contents of our digestive tract
away from our tissues and bloodstream.
During the development of obesity andmetabolic syndrome, this barrier becomes‘leaky,’ allowing increased invasion of toxins
into our bodies and increasing systemic
inflammation.
It is important to keep our gut barrier healthy,
and we think that vitamin D is one way to dothat. Maybe, along with xanthohumol, we candevelop treatments that keep patients withmetabolic syndrome from cascading down
the path to serious chronic illness.
References
Zhang et al. Mol. Nutr Food Res. (2019) -In press.
doi: 10.1002/mnfr.201900789.
Paraiso et al. Mol Nutr Food Res. 63 (2019)
doi: 10.1002/mnfr.201800923
Miranda et al. Sci Rep. 8 (2018)
doi: 10.1038/s41598-017-18992-6

5

The multidisciplinary xanthohumol-IBD research team.
Dr. Fred Stevens is pictured in lower-left corner.

TAKING THE FIGHT AGAINST IBD TO THE NEXT LEVELSEED FUNDING SPARKS A COLLABORATIVE RESEARCH STUDY ON INFLAMMATORY BOWEL DISEASE

IBD is an umbrellaterm that describes
many disorders of thedigestive tract. These
include the more wellknown conditions like
Crohn’s disease andulcerative colitis.

In the Stevens laboratory and otherlaboratories at the LPI, studies on
xanthohumol have been a big success.
Using the momentum generated by small
grants, Dr. Fred Stevens leveraged thiswork to obtain a new federal grant on
inflammatory bowel diseases that involves
multiple research centers in the PacificNorthwest.

Treatment often includes steroids andother anti-inflammatory drugs that haveterrible side effects. Indeed, many of these
therapies do not address the changes in the
gut bacteria that can worsen the effects of
IBD over time.

Cases of inflammatory bowel disease (alsoknown as IBD) are on the rise. According
to the Centers for Disease Control andPrevention, over three million people in the
US have been diagnosed with this condition,
part of a trend of increased prevalence
worldwide.

“I have studied the chemistry and biologicalactivity of hop compounds for nearly 25
years,” Dr. Stevens explains. “In studies
conducted at the Linus Pauling Institute,we have found that xanthohumol targets
a nuclear receptor protein involved in
the pathogenesis of inflammatory bowel
disease.”One thing that inflammatory bowel diseases
have in common – as the name suggests –is chronic inflammation. Unfortunately, theroot cause of IBD is unclear, making current
therapies very limited.

6

Dr. Fred Stevens, principal investigator at
the Linus Pauling Institute, hopes to find abetter way to tackle IBD.

That nuclear receptor protein is the
Farnesoid X Receptor (FXR for short). FXR
is a one of the master control proteins in
the liver, responsible for regulating bile acid,glucose, and fatty acid metabolism.

Activation of FXR in the liver can improve
insulin sensitivity, lower blood lipids, andreduce inflammation.
FXR is also highly expressed in the small
intestine. It is there that we can see apossible link with IBD: Patients with these
diseases appear to have lower FXR activity
than healthy people.
Studies in animals have suggested that
xanthohumol can influence FXR. Recent
cell culture studies by the Stevens lab haverepeatedly demonstrated the ability ofxanthohumol to stimulate FXR activity.

“Seed funding was
the only thing thatmade it possible for
us to explore the antiinflammatory effectsof xanthohumol in
inflammatory bowel
disease”–Fred Stevens, PhD
Dr. Stevens’ research group has also shownthat xanthohumol reduces inflammation invarious preclinical models of disease. For
example, xanthohumol appears to influence
the composition of microbe species foundin the gut – a possible driving force ininflammatory response (see cover article
by Dr. Gombart).
The combined findings gave Dr. Stevens theidea to study the effects of xanthohumolin Crohn’s disease. So, he assembled amultidisciplinary team of OSU and LPI
scientists with researchers from nearby
research institutions. Now Dr. Stevens andhis colleagues have a $1.6 million grant tocontinue this work.
“Seed funding was the only thing thatmade it possible for us to explore the antiinflammatory effects of xanthohumol in
inflammatory bowel disease,” Dr. Stevens
added. “That leg-up resulted in this new, fouryear clinical research project.”

Currently in the process of recruiting
for a human clinical trial, this project isultimately designed to identify the effects ofxanthohumol in Crohn’s disease.
“We intend to identify a biological fingerprintof xanthohumol exposure in people andobserve a reliable effect on inflammation inthis disease,” Dr. Stevens said.

When out ofcontrol, intestinal
inflammation can leadto an increased risk ofserious complications.
For example, Crohn’sdisease can lead toan increased risk ofcolorectal cancer.

“Most importantly, stakeholder companies
Hopsteiner and Metagenics supported thiswork at the LPI,” he explained. ”That support
brought the metabolic, biochemical, and gut
microbial aspects of this project together,and was key to our success.”
This team also includes other scientists
from the Helfgott Research Institute at the
National University of Natural Medicine
and from the Pacific Northwest National
Laboratory in Richland, Washington.
Hopsteiner, Inc. and Metagenics, Inc. aredeveloping a pure xanthohumol supplement
suitable for human consumption.

Plant Your Own Seed – Support LPI Studies
With your support, the studies on xanthohumol have been a big
success. It is a shining example of how even small donations to the
LPI can be leveraged into something greater.
This large federal grant offers opportunities for LPI students andpostdoctoral researchers to participate in ground-breaking studies.
These experiences at LPI will help young investigators prepare forindependent careers in academia, government, or industry.

7

Interested inliving longer &feeling better?

SO ARE WE!
Here are a few ways you can support our mission:
1. Use your retirement accountDid you know that you can use retirement accounts (IRA, 401k, or similar) to make a gift while
potentially avoiding unwanted taxes?
You can pass 100% of these funds to the Linus Pauling Institute tax free.

2. Name the Linus Pauling Institute in your estate plan
Let’s chat! The OSU Foundation can help you make sure your generous contribution to the Linus
Pauling Institute matches your intentions.

3. Become a monthly donor
Regular support helps us expand research efforts and drive innovation.
Become a monthly donor today and support our healthy aging research, life-changing clinical trials,
and the training programs for next generation of scientists.

Don’t wait! Contact Andrew Norwood before December 31st

to learn more about these or other ways we can support the LPI mission together!
By phone: 503.936.0086
or by email at: Andrew.norwood@osufoundation.org

8

LPI STUDENTS
Luce Mattio
Visiting PhD Student, University of Milan“Answering questions about life.”
Luce Mattio fell in love with science at an early age. Seeing scientific discovery as ameans to find answers to her many questions about the world, she pursued education
in medicinal chemistry. Luce was fascinated with the study of molecular mechanisms
and how the creation of new molecules could affect biological processes.
Her Master’s degree work focused on the synthesis of natural compounds – producing
chemicals similar to those found in the natural world. Drawn further into natural
products chemistry, Luce enrolled in the doctoral program in Food Systems at
the University of Milan. Her research focuses on the identification, synthesis, andbiological studies of polyphenols from food or waste by-products.
For her study abroad component of her PhD program, Luce sought to work with anaccomplished and respected expert in natural products chemistry. She therefore
joined the laboratory of LPI investigator Dr. Fred Stevens, where she is learning various
analytical and biological approaches to study bioactive molecules. After graduation,
Luce would like to investigate natural products as the source of active molecules todiscover new drugs.

Alan Wong
PhD Student, van Breemen Laboratory“Exploring the wonders of nature.”
Alan Wong completed his undergraduate training in geology and biochemistry at
Northwestern University. As time went on, however, his passion gradually shifted fromstudying chemical signatures in fossils to studying plants. After an early job analyzing
products for the agrochemical, food, and botanical industries, he became interested in
exploring the health effects of botanical dietary supplements.
He thus joined the laboratory of Dr. Richard van Breemen, where he now focuses onconnecting basic research on botanicals to their use in a clinical setting. Using someof latest mass spectrometry technologies, Alan seeks to answer previously unsolvablequestions on the effects of these supplements in humans.
He is especially interested in understanding how natural products – when provided asa dietary supplement – affect hormone levels in the body. After graduation, Alan plansto take scientific tools like mass spectrometry into a clinical setting. His hope is to use
these cutting-edge techniques to develop powerful bioassays that will help advancethe treatment of disease.

Every student and postdoctoral trainee who studies with us furthers theimpact of the Linus Pauling Institute on a global scale. If you are interested
in contributing to a student’s success, please contact the LPI or the OSUFoundation today to explore your options.

9FOUR QUESTIONS WITH MARET TRABER
Dr. Maret Traber is one of the world’s foremost authorities on vitamin E – in fact,
at the LPI we call her the ‘Goddess of Vitamin E.’
The world is desperately in need for a more detailed look at vitamin E in people – a goal that
Dr. Traber has been reaching for since the 1980s. Recently, along with her collaborators at
the NIH, she established a new method for measuring vitamin E absorption.
Her study, published in the American Journal of Clinical Nutrition in November, takes a giant
leap forward in accomplishing that goal. What she and her colleagues found was amazing,and had far greater consequences than they initially expected.

In the year 2000,
Dr. Traber was amember of thecommittee that set
the dietary reference
intakes for vitamin E.

This is an amazing study with intricate
data sets in people. Before we get into
the nuances, let’s start with something
simple: What is one thing everybody
should know about your study?

We repeated the trial, this time with no fat.
We expected a big change in the rate ofabsorption. But it turns out there was nochange at all – vitamin E absorption was thesame as the previous trial.

“I think you can boil everything down
to one magic number. All the detailed
measurements, all of the logistics of getting
people to eat vitamin E in very defined ways,
and all of the complicated statistics say one
thing: you absorb a little over half (55%)
of the vitamin E from food that you eat, nomatter how you choose to eat it.

Suddenly this simple test was giving us asurprising and unexpected answer. How canthese people be absorbing the same amountwhether it was eaten with any amount of fat?
We know from previous studies that people

This study is the very first time that vitamin E
absorption has been accurately measured.
We need this number to estimate how much
vitamin E you need to eat every day – and
it is critically important for redefining the
dietary requirements for this vitamin in the
United States.”
Typically when people think of eating
something that dissolves in fat, likevitamin E, you need to eat fat with it – atleast to absorb it properly. Your study
challenges this idea?
“Based on our previous studies, we thought
the same way: you need fat in a meal toabsorb vitamin E. So we started with thatquestion: how much fat do you need?

“I call that a shake,”quips Traber, “But mycollaborator calls it a‘defined liquid meal.’”We started the study with people eating lotsof fat. The volunteers drank a beverage thatwas 40% fat. When these people drank thevitamin E, everything was going according toplan. As we expected, vitamin E appeared in
the blood, and over time distributed throughthe body.

10

who can’t absorb fat can’t absorb vitamin E.

Something more complex than fat absorption
had to be involved here.”
You really had no idea what was goingon? I am guessing there were somefundamental doubts about your study
design. What was the next step?
“My colleagues at the NIH started asking
tough questions. They noted that it took
a long time (9+ hours) after the person
consumed vitamin E for it to show up in the
blood. I had seen this in many, many studies
before this one, so it was not a surprise to me.
However, my collaborators expected it to beabsorbed in about three hours. Essentially,
they came to me and asked: ‘What’s wrong
with your vitamin?’As we started to re-examine everything, wethought about the influence of food. Even
though we had controlled the amount of fat andvitamin E in their lunches, it was still possiblethat eating was aiding vitamin E absorption.
In the end, the participants repeated the trial
but this time ate nothing after breakfast –they were fasting all day long.”

Chylomicrons areformed in the intestine
when fats from the dietneed to be transported
to other parts of the
body. Although mostly
comprised of lipids, theyalso carry fat-soluble
molecules like vitamin E
to the liver.

“It did turn out to be a problem, but not in
the way anyone expected. You see, during
this fasting period very little vitamin E
appeared in the blood – it trickled into thebloodstream very slowly.
Now comes the real kicker: When theparticipants ate their evening meal, thevitamin E was dumped into the plasma allat once. When we calculated how much theparticipants absorbed, we saw the sameanswer – high fat, no fat, or fasting madeno difference.
It took us a long time to understand what
was going on. Our best understanding isthat vitamin E is being absorbed into theintestinal cells and is ‘held’ in fat droplets.
There it waits, with small amounts of it being
released with chylomicrons into the blood.
It is almost as if the intestine is metering
how much fat is getting in the circulation
so it does not overwhelm the liver – leaving
the liver to deal with it at a reasonable pace.
When you eat again, however, that all goesout the window and it needs to clear out thefat and vitamin E to make room for the nextmeal.
It is exciting that this work uncovered theidea that the intestine is far smarter than weused to think and dedicated to a specific rolein the body.”

Is this phenomenon specific to vitamin E?
“Definitely not. In an editorial to our article,
Emmanuelle Reboul, a nutritionist from
Aix-Marseille Université, reviewed how betacarotene, a plant source of vitamin A, behavesin a similar fashion.
Our study is the first time this phenomenon
was characterized for vitamin E. It’s hard tosay right now how important this process will
be to understanding the absorption otherfat-soluble compounds.
After this study, we finally understand why alleight forms of vitamin E that plants makeget absorbed, even though the liver chooses
to retain only one of them: alpha-tocopherol.
The other forms are excreted.”

Plants make alpha, beta,
gamma, and delta formsof both tocopherols andtocotrienols, all of which
are considered part ofthe ‘vitamin E family.’This interview with Dr. Traber covered so much more than we cansummarize here. For example, did you know that vitamin E caneasily cross in to HDL (“good”) cholesterol after being absorbed?
Dr. Traber and her collaborators watched it happen.
If you want to see more from this conversation, then join us online
at: http://blogs.oregonstate.edu/linuspaulinginstituteOr if you want to read the full study, go to:
http://bit.ly/Traber2019

11

LPI 10th INTERNATIONAL CONFERENCE
In August 2019, the Linus Pauling Institute held its 10th International Conference “Botanicals, Bioactives, andRedox Mechanisms” in Corvallis, Oregon. In total, 161 people attended the conference, hailing from 55 different
institutions and nine different countries. By all measures, from the scientific sessions to the public open house,it was a huge success. For a complete conference program, see: lpi.oregonstate.edu/conference

LPIIC 2019
Overview.............12
Scientific
Sessions.............13
A Session For the
Public, Featuring
Nobel Laureate
Dr. Louis J
Ignarro................14
Top 5 Takeaways fromLPIIC 2019...........15

For LPIIC 2019, the conference chairs
were Dr. Richard van Breemen, Director of
the Linus Pauling Institute, and Dr. Maria
Clara Franco, from the Biochemistry andBiophysics department at Oregon State
University.
The purpose of this conference was unique:to bring professionals working in the fields
of dietary supplements and/or redox
biology together with world-renown expertson the treatment of chronic disease(in particular, neurodegenerative diseaseand cancer).

In only a few other places in the world
has such a fusion of research scientists,
clinicians, and industry representatives
existed, with the sole purpose of finding
new ways of working together.
The conference was divided into threedays of scientific presentations, eachwith dedicated themes for the individual
sessions. On the final day, an open housefeatured various scientific departments at
Oregon State University. This public event
culminated in a keynote presentation by
Nobel Laureate, Dr. Louis J. Ignarro.

Conference organizers
Jen Stotts, Dr. Alexander
Michels, and Caitlyn Reilley

12

SCIENTIFIC SESSIONSDay One: Botanical Dietary
Supplements

Day Two: Neurodegeneration and an
Update on Vitamins

This day began with presentations from Dr.
Wendy Weber from the National Institutesof Health and Dr. Chongwoo Yu from theFood and Drug Administration. They bothspoke about how botanical supplements
are viewed at the level of the federal
government, including how studies onthem are considered for federal funding.

This day began with a symposium
sponsored by the International Society
for Neurochemistry, chaired by Dr.
Alvaro Estevez. This session delved into
uncovering new targets for treatmentof neurodegenerative conditions like
Alzheimer’s disease and multiple sclerosis.

Other highlights from these sessions
included talks from Dr. Paula Brown and
Dr. Stefan Gafner. They both exposed an
important issue concerning botanicals:
identification. In short, it is often difficult
to know if a botanical supplement isauthentic, and there are many waysthat suppliers can fool existing testingprocedures.
Lastly, a series of provocative presentations
highlighted the therapeutic uses ofbotanicals. Dr. Edward Kennelly
summarized his two decades of researchon black cohosh – a supplement that isfrequently adulterated – and demonstrated
that the reported mechanism of action ofthis plant in women’s health is not correctand is need of revision.
Dr. Fred Stevens gave an overview of his
recent work with xanthohumol in metabolic
syndrome and inflammatory bowel disease(see page 6 for more).
Also, Dr. Tom Kensler gave a spectacular
update on the use of broccoli-based
interventions in the detoxificationof air pollutants. For instance, giving
sulforaphane (a compound from cruciferous
vegetables) may be a practical strategy todeal with the health risks of poor air quality.

Conference chair Dr. Maria
Clara Franco

Particularly fascinating were talks by
Drs. Larry Sherman, Jeremy Spencer,
and Tilman Grune, which revealed thebeneficial effects of polyphenols (withan emphasis on flavonoids) on cognitive
function. Later, Dr. Lee Martin presented
on appropriate cell models to study humanneurodegenerative disease.
The day also included an update on
vitamin research. This session began with
Dr. Douglas Feinstein speaking aboutvitamin K deficiency and how it can impact
the proper function of the nervous system.

Drs. Maret Traber andRichard Bruno

For an update on vitamin C, Dr. Jens
Lykkesfeldt explored the effects of thisvitamin on gene expression. Dr. Fiona
Harrison addressed the vital role thatvitamin C plays in the recovery fromsepsis.
Dr. Adrian Gombart spoke about
the results of a small clinical trial of
multivitamin supplementation andimmune function.
Dr. Maret Traber presented the details
about her work on vitamin E absorption inhuman participants (see page 10).

Drs. Jens Lykkesfeldt
and Fiona Harrison

Want More?
LPIIC2019 featured cutting-edge research from around the world. Much of the data at
the meeting was preliminary and could not be shared widely.
If you want more details on any study mentioned here, please let us know and we will
do our best to keep you informed.

Dr. Alvaro Estevez and LPI
graduate fellow, Isabelle Logan
13

SCIENTIFIC SESSIONS (CONTINUED)
Day Three: Redox Biology
Redox biology is the interplay of oxidants andantioxidants in the body, and understanding
how this affects health. These sessions
specifically focused on the impact of redox
biology on neurodegenerative diseases andcancer.

Dr. Enrique Cadenas

Drs. Enrique Cadenas and Allan
Butterfield started the day with discussions
about redox biology in Alzheimer’s disease.
Neurodegeneration is one area where theproduction of oxidants leads to lastingdamage – and represents a large opportunity
for future therapy.

Drs. Nadine Hempel, Rebecca OberleyDeegan, and Douglas Spitz each spoke ofways to exploit the vulnerabilities of cancer
cells, especially in their ability to fend off
oxidative damage.
Dr. Spitz gave a fascinating update on theuse of high-dose, intravenous ascorbic acidin the treatment of cancer. In a 21st century
update on Pauling’s work, he demonstrated
how high doses of vitamin C can turn fromantioxidant to pro-oxidant, creating reactive
oxygen molecules that can damage (andpossibly kill) cancer cells.

A SESSION FOR THE PUBLIC, FEATURING NOBELLAUREATE DR. LOUIS J. IGNARRO

Drs. Douglas Spitz(seated) and Allan
Butterfield

As Dr. Linus Pauling was a strong
advocate for bringing science to a generalaudience, we dedicate a portion of every
LPI conference to public outreach. This
year, we were honored to welcome Nobel
Laureate Dr. Louis J. Ignarro as our
keynote speaker for this session, which
was preceded by an open house thathighlighted various research programs at
Oregon State University.

Ignarro credits this meeting with Dr. Pauling
early in his formative years as contributing
to his later career success in chemistry.
Dr. Ignarro delved into his studies
surrounding nitric oxide, for which he
was awarded the 1998 Nobel Prize inPhysiology or Medicine. Dr. Ignarro andhis collaborators found that the body can
produce nitric oxide that causes bloodvessels to relax.

In his presentation, Dr. Ignarro highlighted
his early life as a driving force in his career.
Like Dr. Pauling, he had a hungry mind thatwas constantly exploring questions about
the world he lived in. Also like Dr. Pauling,
he was fascinated by chemistry from ayoung age.

Dr. Ignarro shared with us his fascinating(and often humorous) journey through thesciences. His discoveries are implicatedin many different aspects of health anddisease, especially concerning heart andarterial health.

This hunger for science served him well.
Indeed, when he questioned why his highschool did not have a functioning chemistrylab, his instructor brought in a friend – Dr.
Linus Pauling – to help set one up.

For a greater perspective on redox biology,
vascular function, and heart disease, we
encourage you to view the videos of Dr.
Ignarro’s lecture on our YouTube channel:
http://bit.ly/LPIVideos
LPI Director Dr. Richard van
Breemen and Dr. Louis Ignarro
visiting the OSU Library’s Special
Collections and Archives

14

Top 5 Takeaways from LPIIC 2019
1. Authenticity of botanical supplements is a big problem.
Identification, potency, and purity of botanicals plague research scientists, clinicians,
government agencies, and consumers alike. Suppliers often do not take time and effort to identify
their products correctly, or they try to sell inferior products. This needs to be fixed.

2. Botanicals are a promising field for therapeutics.
The science behind botanical supplements is advancing dramatically. Look for breakthroughsin neurodegenerative disease and cancer soon. However, many products are very potent (andpotentially dangerous), so the how, when, and why to use botanicals will be important questions
to address in the near future.

3. Many plants naturally contain chemicals that may protect the nervous system.
We are learning much more than ever before about the benefits of phytochemicals on thebrain and nervous system. Phytochemicals are non-nutrient compounds from plants, but they
may trigger cellular repair mechanisms and promote cell growth that may help slow
neurodegenerative diseases.

4. Redox biology is a normal part of life (but also disease).
Our everyday life involves the movement of electrons in our body. This is the field of redox
biology: understanding what electron reactions are normal and what parts can lead to disease
and dysfunction. Knowing the difference between these states informs what roles antioxidants(and other redox-active compounds) can have in human health.

5. Cancer has redox vulnerabilities.
Cancer cells maintain a delicate balance. In order to push their ability to divide and grow to thelimit, these cells sacrifice part of their natural defenses to oxidants. Therapies like high-dose,
intravenous vitamin C take advantage of that vulnerability, and might just be a promisingtreatment in combination with certain redox-active chemotherapies.

15

LINUS PAULING INSTITUTE
Alexander Michels, Newsletter Editor
Victoria Drake, Associate Editor
Caitlyn Reilley, Assistant Editor
Oregon State University
307 Linus Pauling Science Center
Corvallis, Oregon 97331
phone: 541-737-5075
fax: 541-737-5077
email: lpi@oregonstate.edu
website: lpi.oregonstate.edu

MARK YOURCALENDARSFEATURING• PUBLIC SEMINARS• ONLINE EVENTS• A BIRTHDAY
CELEBRATION

LINUS PAULING DAY
FEB 28, 2020