Oregon State University

The

Linus Pauling
Institute
FA L L / W I N T E R 2 0 14 R ES E A R C H N E WS L E T T E R

From the Director
Balz Frei, Ph.D.
LPI Director and Endowed Chair
Distinguished Professor of Biochemistry
and Biophysics
Joan H. Facey LPI ProfessorAs many of you know, our former Director ofDevelopment, Michele Erickson, left LPI earlier thisyear to become the Director of Development for OSU’s
College of Business. We are happy for her promotion andwish her success in her new position. I am very pleased toannounce that LPI has a new Director of Development,
Marlys Amundson, who was with OSU’s
College of Engineering for many years.
Marlys has a lot of passion for LPI’svision and mission and will work hard
to raise funds to help keep our researchand education enterprise in good shape.
As she discusses in her column on page15, federal funding for biomedical
Marlys Amundson
research has been stagnant for many
years, except for a brief stimulus period during the recent
recession. This has had the unfortunate consequence of
inhibiting bright, young scientists from entering academia,
where the expectations for constant grant funding are
high. It has also interrupted the research momentum ofscientists who lose grant funding. Many scientists compete
for extremely limited funding, and the probability of being
awarded grants, even for creative and important work, hassignificantly declined. Marlys is excited to be working
with you and LPI to help us advance our research into
achieving long and healthy lives for everybody.
To help increase our chances for successful grantapplications, Dr. Joe Beckman, one of LPI’s principal
investigators, has agreed to take on the new position of
Associate Director for Research at LPI. Many of you arefamiliar with Joe’s exciting and innovative research on
Lou Gehrig’s disease, also known as amyotrophic lateralsclerosis, or ALS. This research has been summarized inprevious newsletters, and you can read about Joe’s latest

continued on page 2

New Benefits ofVitamin E
An Interview with
Debbie J. Mustacich, Ph.D.
Associate Professor (Senior Research)

Q. Are you from the Pacific Northwest?
A. Yes, I am. I grew up mainly in Gig Harbor,

Washington. We lived on an island just outside the city.

Q. You earned your Ph.D. in biochemistry andbiophysics from Oregon State University (OSU).
What was your thesis about?
A. My thesis research was about the role of microtubules
and multi-drug resistant transporters in the secretionof alpha-tocopherol—vitamin E—in bile and thenreuptake in the gut.

Q. In 2004, you moved from the Arizona Cancer
Center at The University of Arizona to join the
Linus Pauling Institute (LPI) as a research
associate in Maret Traber’s lab. What motivated
you to come to LPI?
A. I was familiar with several of the LPI investigators

through scientific meetings, and I knew about thecollegial atmosphere here. That’s what I was looking
for, and that’s why I came here. I left a very high-paying
industry position to start over again in academia.

Q. Your academic appointment here at OSU is in
the Department of Biomedical Sciences in theCollege of Veterinary Medicine. Does that
stimulate collaborations between that collegeand LPI?
A. Yes, it does. There are several collaborations between

the vet school and myself, and other LPI investigators
have had collaborations, too. It’s part of the reason I
was invited to become part of the College of Veterinary
Medicine—in hopes to have more connections between
them and LPI.

continued on page 2

Continued from cover — New Benefits of Vitamin E
Continued from cover — From the Director

Q. Do a lot of the veterinary students get involved
in research?
A. Yes. The vet school has a program through the

Department of Biomedical Sciences. I usually have one
or two veterinary students every summer. They provide
fellowships for approximately 10 students every
summer to work in the various labs of Biomedical
Sciences faculty.

Q. At The University of Arizona, you worked on aprotein called thioredoxin. What important
cellular functions does thioredoxin have?
A. Thioredoxin has several functions. Thioredoxin protects
thiols—sulfur-containing compounds—within the cell.
It is part of the thioredoxin system and is involved inantioxidant defense. We were interested in cancer, so wewere looking at its role in cell signaling. Thioredoxin
is important in maintaining the reduced state of certain
cysteines within signaling proteins that induce cells to
proliferate. We found that when thioredoxin is overexpressed in human cells, there is increased cell growth
and resistance to apoptosis, or programmed cell death.

Dr. Joe Beckman

work in this area on page 10 of this newsletter.
As Associate Director for Research, Joe will help
me to coordinate LPI’s research program and assist
our principal investigators with individual andmulti-investigator grant applications. Joe will work
to integrate and expand our core laboratories inorder to develop screening assays for dietary factorsthat promote healthspan. He will also help toadvance our metabolomics efforts that will lead toa better understanding of the roles of metabolites
in health, coordinate the acquisition and use of
instruments, and, importantly, help LPI faculty
carry out studies with human subjects. Joe willassist with research contracts and work to increaseprivate support for LPI. I am very pleased to have
Joe’s expert help and guidance in managing ourresearch program.

Q. How is thioredoxin implicated in cancer?
A. Thioredoxin is expressed at high levels in a number ofhuman tumors, including lung, pancreas, colon, gastric,
and breast cancer. So that was the interest of our lab—does thioredoxin play a role in carcinogenesis andshould we target thioredoxin for cancer prevention
and/or treatment?

Q. How does thioredoxin promote cancer?
A. Although the presence of high levels of thioredoxin intumors has been linked to increased tumor proliferationand decreased patient survival, we demonstrated that
increased expression of thioredoxin by itself does notpromote cancer.

In my last two columns, I outlined our recently
concluded strategic planning process and the newgoals and key initiatives that emerged, including1) establishing LPI’s leadership in advancing healthspan through innovative research, 2) diversifying
and increasing funding for research and public
education, 3) effectively communicating ourmessage, and 4) improving public health throughcommunity engagement. We are in the initial phaseof implementing several of these objectives andhave been gaining some momentum and developing
a lot of enthusiasm. I will keep you informed of ourprogress through periodic emails and this column.
I’m glad that you are joining us on this adventure!

Q. Also in Tucson, you showed that transgenic miceexpressing increased levels of thioredoxin in theirskin cells developed more tumors when exposed toa topical carcinogen. How variable are thioredoxin
levels in human skin cells, and is there the same
correlation in humans with increased risk fortumorgenesis?
A. Thioredoxin is expressed at low levels in non-sun-

exposed human skin within hair follicles and sebaceous
glands but is not generally seen in the epidermis.
However, UVA and UVB exposure increases thioredoxin
in skin cells, and thioredoxin is significantly elevated insun-damaged human skin. In our mouse studies, miceexpressing elevated thioredoxin did not develop tumors
unless they were treated with both a carcinogen andpromoting agent. All of the mice treated with the
carcinogen and promoter developed tumors, but thosewith elevated skin thioredoxin developed more tumors,and the tumors tended to be more aggressive.

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FALL/WINTER 20142

Q. UV radiation increases thioredoxin levels inhuman skin, presumably to protect against DNA
damage. But could the increased levels also
contribute to cancer development?
A. Initially, the elevated levels would protect the cells

several months. That resulted in slight elevations of
one of the P450 enzymes that we saw induced with
injections. To date, we haven’t seen evidence of druginteractions due to altered P450s following oral
supplementation with vitamin E.

from damage and help them to repair themselves.
Nevertheless, some cells may get repeated DNA
damage from the sun, and the elevated thioredoxin
could protect a damaged cell that has not been repaired
from undergoing apoptosis. Thus, in normal cells,
thioredoxin will be protective. Elevated thioredoxin
by itself isn’t going to lead to cancer.

Q. More recently you worked on spinal cord
compression injuries in rats, showing that an
intravenous infusion of antioxidants andanti-inflammatory compounds after the injury
improved recovery of neurologic function,
decreased inflammation, increased vascularization,and increased survival. What was infused?
A. This was a collaborative project with a veterinary

Q. Can thioredoxin levels be affected by diet or drugs?
A. There are some drugs that may increase thioredoxin,

orthopedic surgeon, Dr. Wendy Baltzer, and was set
up to closely replicate a therapeutic treatment relevant
to both human and veterinary injuries. We usedcommercially available lipid emulsions. One emulsion
contained mainly long-chain fatty acids, the second
contained a mixture of long-chain and medium-chain
fatty acids, and the third contained long-chain, mediumchain, and omega-3 fatty acids—fish oil—as well as
elevated levels of vitamin E.

but I’m not aware of dietary agents that affect it.

Q. When you joined Maret Traber’s lab in LPI, youworked on vitamin E. One of your early studies
showed that rats metabolize excess vitamin E sothat it doesn’t accumulate. Do you know how
that’s accomplished? Why is that important?
A. It’s important because most lipid-soluble vitamins canaccumulate in your tissues, unlike the water-soluble
vitamins that tend not to accumulate and are readily
excreted in urine. When we injected rats with extremely
high levels of alpha-tocopherol—vitamin E—we foundthat metabolism and excretion of alpha-tocopherol
increased to eliminate the excess. This included increases
in some of the cytochrome P450 enzymes present in theliver that are known to metabolize foreign compounds.

Q. Which was the most effective emulsion?
A. The emulsion containing medium-chain and omega-3

fatty acids with elevated vitamin E was the mosteffective. We actually had a few rats that were able towalk normally three weeks following their injury.

Q. What explains those results?
A. We know that biochemical damage continues to occur

Q. Is that a case where the xenobiotic-metabolizing
enzymes recognize the very high level of vitamin
E and then metabolize it as if it were a foreign
substance?
A. Yes. Vitamin E, like any vitamin, is not made in theafter the initial mechanical injury. This is referred to as
secondary spinal cord injury. The mechanism for thisis undetermined, but we hypothesized that oxidative
stress, specifically lipid peroxidation, was playing a rolein this secondary injury. That’s why we chose to use
vitamin E in the treatments. Inflammatory responses
are also implicated in secondary injury, so we included
fish oil, which is anti-inflammatory. The emulsion
containing high levels of vitamin E andomega-3s helped decrease indices of both
lipid peroxidation and inflammationand significantly improved therecovery of our rats.

body. Technically, it is a xenobiotic—it’s a foreign
chemical as far as the body is concerned. If the levels
get too high, then mechanisms for metabolism
and excretion may be induced to rid the
body of the excess and prevent
possible toxic effects. This is the casefor excess vitamin E.

Q. You were injecting vitamin E
into the rats. Would you
expect the same thing tooccur when very large
amounts of vitamin E aretaken orally?
A. When vitamin E is taken

Q. Do you think that much
more work is needed
before that could be used
to treat people withcompression spinal cord
injuries?
A. I think that there’s moreorally the amount that may be
absorbed in the gut is low, so
you would not be able to reachthe liver concentrations that we
saw with our injection protocol.
There was one mouse study done
prior to my arrival at the Linus
Pauling Institute in which rats were fed
very high levels of vitamin E in the diet for

to be done to further improve
recoveries. That said, theseemulsions are commerciallyavailable in Europe and are
currently being used to improve
the recovery of surgical patients.

continued on page 4

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Continued from page 3 — New Benefits of Vitamin E

Q. Not spinal injuries?
A. No, they have not yet been used with spinal injuries tomy knowledge. They have been shown to improve thespeed of recovery—reducing time in the hospital—for
surgical patients.

Q.That’s very interesting because Nathens at the
University of Washington published a paper 12
years ago showing that surgical trauma patients
who got 1,000 mg of intravenous vitamin C and1,000 IU of oral vitamin E fared much better
than patients who did not get those antioxidants,
with lower organ failure rates and fewer days in
the ICU. It was a randomized controlled trial
with about 600 patients.
A. We see the same kind of data in small studies that havebeen done in Europe. Another reason we thought thatvitamin E would be beneficial is because injured rodents
that were supplemented with vitamin E prior toexperimental injury showed improved recovery
compared to non-supplemented rodents. However, since
we don’t know when we are going to get a spinal cord
injury, we did our study as a post-injury treatment. In
our pilot study, we merely gave a 24-hour intravenous
treatment following the injury. We did not give any oral
supplementation after that. I suspect that if we repeatedthe IV treatments at additional intervals after the injury
and/or gave oral supplements after the initial IV
treatment, the rats’ recoveries would be even better.

give female tumor-bearing rats high doses of vitamin
E the day before we give them cisplatin, we don’t see
decreases in the spinal cord vitamin E. In fact, we see
increased levels in tissues, sometimes elevated above
those in normal, healthy female rats.

Q. And there’s no effect on the anticancer efficacyof cisplatin?

Q. Cisplatin is a platinum compound used to treat
ovarian and lung cancer and lymphoma but hasserious toxic side effects, including neurotoxicity
and kidney damage. What do your studies withvitamin E show?
A. It’s known that cisplatin decreases plasma vitamin E

A. The great thing that we found in our study is thatvitamin E actually improves the anti-tumor efficacyof cisplatin. We observed a significant decrease in thenumber of rats with tumors in rats that received
cisplatin plus vitamin E compared to cisplatin alone.
In fact, some of the rats receiving the combination had
no evidence of tumors.

levels in cancer patients. We see similar decreases ofplasma vitamin E in rats given cisplatin, but because
we can look at all the tissues in the rats, we also see
significant decreases in organs. Importantly, we see
decreases of vitamin E in the various regions of the
spinal cord and ganglia.

Q. Do you have any idea how vitamin E prevents
the accumulation of platinum in normal tissues?
A. We don’t know exactly why platinum accumulates insome tissues more than others. Even the molecularmechanism of how it kills cancer cells has not been
fully determined, particularly its role in apoptosis.
We know that it incorporates into DNA and forms
adducts. The ability of a particular tissue to repair
those DNA adducts and remove the platinum may
determine whether a cell lives or dies. In our study
we saw a decreased accumulation of platinum in the
spinal cord, which is very important, but we don’t yet
know the mechanism. Equally important, vitamin
E does not alter the accumulation of platinum in theovarian tumors.

Q. Does that contribute to neuropathy?
A. The mechanism for cisplatin neuropathy is unknown.

However, the clinical features of cisplatin-induced
neuropathy are similar to those seen in vitamin E
deficiency neuropathy. Nervous tissue contains lots oflipids. Vitamin E protects lipids from oxidation but inthe process may be depleted from the tissues. We believe
platinum catalyzes the process of lipid peroxidation
within the nervous tissue, leading to depletion ofvitamin E and that this depletion of vitamin E plays acentral role in cisplatin-induced neuropathy. When we

FALL/WINTER 20144

Q. Does the vitamin E combined with cisplatin result
in decreased kidney damage?
A. That wasn’t a focus of the study. We did collect the

Q. Caitlin Crimp, one of your undergraduate
students in the Honors College at OSU, workedon the protection by vitamin E against polycyclicaromatic hydrocarbons—PAHs—that are
ubiquitous environmental carcinogens caused by
the incomplete combustion of carbon fuels.
What did she find?
A. She found that when we gave high levels of vitamin E

kidneys, and we didn’t see histologic differences,although there was an improved ability to concentrate
the urine in rats receiving vitamin E with the cisplatincompared to cisplatin alone. One of the signs of kidneydamage in rats given cisplatin is an increased volume ofvery dilute urine.

to our rats over a period of a few days with the purposeof inducing the P450s that we discussed earlier, we
actually altered the metabolism of the PAH, benzopyrene.
We pretreated the rats with vitamin E over a five- toseven-day period—sufficient to induce specific P450s—and then gave the rats a dose of benzopyrene.
I hypothesized that the PAH would be quickly
metabolized to non-toxic metabolites that would thenbe excreted. And that is exactly what we found.
We saw a shift in the metabolism of the PAH from thetoxic DNA–adducting metabolites to the non-toxic
non-DNA–adducting metabolites and elevated excretionof both the parent compound and the metabolites inurine and bile.

Q. What other animal studies need to be done?
A. We would like to look at the combination of vitamin

E and vitamin C plus cisplatin. We think that thiscombination would further improve the efficacy, as well
as further decrease side effects from the unwanted
damage in tissues outside the tumors. I don’t believethat the effect of vitamin C on neuropathy has been
investigated, and that would be very important as well.

Q. Can your results be extrapolated to otherchemotherapeutic drugs?
A. They could be extrapolated to other chemotherapeutic

drugs depending on the mechanism for the chemotherapeutic drug. Many chemotherapeutics cause theirside effects through various mechanisms of oxidative
stress, and some kill cancer cells by similar mechanisms.
Other cancer drugs, including cisplatin, cause oxidative
stress to both tumor and normal tissues but kill thecancer cells in a manner that does not require oxidative
stress. Those are the chemotherapeutics that might bebeneficially combined with antioxidants.

Q. Was the dose of PAH given by injection muchgreater than you would be exposed to in theenvironment?
A. Yes, it was more than the average person would be

exposed to environmentally. Our study used a high doseof PAH, the kind of occupational exposure to which
workers like forest fire fighters, roofers, first responders,
and road crews might be exposed. However, themechanism should be relevant for lower doses or
exposures. We would like to do further studies withlower, long-term doses to replicate additional exposure
scenarios.

Q. What are you working on now?
A. We are continuing to work on the cisplatin studies.

We need to further characterize the antioxidant levels
and tissue damage in the rat spinal cords. In addition,
we are examining the tumors histologically to look atmarkers of cell proliferation and apoptosis. Also, I amcollaborating with veterinarians in the veterinary school
on work with Lyprinol and osteoarthritis in dogs.

Q. Were there any gender differences in the responseof the rats to the treatment?
A. Yes. That was very interesting because the female rats
actually had a greater response. Other scientists
conducted a study in humans
who smoked. The smokers

Q. What is Lyprinol?
A. It comes from the green-lipped mussel. It’s a collectionof several different lipids (free fatty acids) and has
demonstrated anti-inflammatory properties. We
measured F2-isoprostane levels, which are markers ofoxidative stress, specifically lipid peroxidation, andfound they were significantly decreased in Lyprinolsupplemented dogs with osteoarthritis.

continued on page 6

Q. Was there any change in behavior in the dogs?
A. The veterinarians are still processing those outcomes.
Q. Is Lyprinol injected or given orally?
A. It’s taken orally.

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Continued from page 5 — New Benefits of Vitamin E
were given vitamin E orally, and the female smokers
responded—they had fewer DNA adducts in their
white blood cells than male smokers. Although thehuman findings didn’t reach statistical significance dueto the small sample size, we saw a similar trend in our
rat study.

Q. Is your work funded primarily by grants?
A. Yes. Currently, the cisplatin work is funded by theAmerican Cancer Society. The small veterinary studies,such as the Lyprinol studies, as well as the pilot study
in spinal cords, were funded by the Linus Pauling
Institute, the College of Veterinary Medicine, and theDivision of Health Sciences. The NIH funded thevitamin E and PAH studies.

Q. How do you like working in the new Linus
Pauling Science Center?
A. I love it. It’s spectacular to have such a nice facility

along with a nice group of researchers. We reallylike the open labs. I think they lead to increased
collaborations. My students like it, and it’s quite
popular with the veterinary students to work in my lab.

Q. Are you able to attract a lot of undergraduate
students or do you have some graduate students?
A. I do not have graduate students in my lab, but I haveno shortage of undergraduates. I turn undergraduatesaway on a regular basis because I don’t have room forthem. I prefer to keep a small group of students sothat I have time to work personally with each of themon their training. I generally have two veterinary
students in the summer. It’s good for me, and it’s goodfor them because we do animal studies that allow themto get some hands-on experience giving the injections,handling the animals, learning about care issues, andapplying scientific methods. They are very good atmonitoring animal health because they already havebeen trained for that. And I get excellent undergraduates—many have received awards for their work.
Most of my undergraduates and veterinary students
have presented their work at international scientificmeetings. They do great work, and I enjoy them.

Polycyclic aromatichydrocarbons (PAHs)
are ubiquitousenvironmental
carcinogens causedby the incomplete
combustion ofcarbon fuels.

Q. What do you like to do in your free time when
you are not working in the lab?
A. My main activity is golfing, and I usually do an annual
ski trip to visit my brother and family in Canada.
We recently went to France to visit my sister and herfamily, but mostly I golf and visit my nieces andnephews whenever possible. LPI

FALL/WINTER 2014

6

IN MEMORIAM:

Dr. George Bailey
1941-2014

Dcomprehensive database of carcinogen-DNA adducts
as early biomarkers for cancer chemoprotection byphytochemicals in any animal model.

r. George Bailey, OSU professor emeritus inenvironmental and molecular toxicology andformer LPI principal investigator, died on October 20th
after a serious illness. He retired in 2008 after a nearly30-year career at Oregon State University and over
five years as a principal investigator in LPI.

George and his colleagues showed that liver cancer
in trout induced by aflatoxin, a carcinogen formedby mold that grows on damp nuts and grain, could
be inhibited by chlorophyllin (a stable derivative ofchlorophyll) through a blocking mechanism. Aflatoxin
binds to chlorophyllin in the gut, and the complex isharmlessly excreted, preventing its absorption into
the blood stream and delivery to the liver. George
and his colleagues conducted a human trial in China
where people are unavoidably exposed to dietary
aflatoxin because of the improper storage of grainand, consequently, have a very high incidence of livercancer. The research team measured cancer biomarkers in the urine, which were decreased by about
half in people taking chlorophyllin supplements.
Those results suggested that a simple andinexpensive intervention may help protect people
from liver cancer caused by aflatoxin.

George earned a B.S. in chemistry at the Universityof Southern California, followed by a Ph.D. in biochemistry from the University of California-Berkeley.
He joined OSU in 1979 as an assistant professor in
the Department of Food Science and Technology andwas honored in 1998 with the title of Distinguished
Professor in the Department of Environmental andMolecular Toxicology. He served as the director of
OSU’s Marine and Freshwater Biomedical Sciences
Center from 1985 to 2002. George published over 150
papers in peer-reviewed scientific journals and won
several awards for outstanding research, including
the prestigious Prince Hitachi Prize for Comparative
Oncology in 2001. On November 12th, he was awarded
posthumously the Discovery Award by the Medical
Research Foundation of Oregon Health & Science
University, an honor previously bestowed on LPI’s
Drs. Balz Frei and Joe Beckman. Over the years, he
has also mentored many graduate students at OSU.

George is survived by Carol, his wife of 53 years,
son Kelly, daughter Leanne Collis, sister Patricia
Coffelt, and several grandchildren.

In 1995, George was one of several members of afaculty advisory committee established by Dr. Richard
Scanlan, OSU’s then-Dean of Research, to advise OSU’s
former President, Dr. John Byrne, on the possible
establishment of the Linus Pauling Institute at OSU.
Those deliberations were successful, and the Linus
Pauling Institute moved from Palo Alto, California, in
1996 to become a research institute at OSU.

The Linus Pauling Institute will honor George
through the establishment of the George Bailey
Graduate Student Fellowship in Cancer Research andhas set a goal of raising $250,000 to endow thisfellowship. “The students who receive this fellowship
will be doubly inspired,” said Balz Frei, LPI’s director,“by those who have invested in their future, and by
George’s deep commitment to education, improved
health, and rigorous scientific study.”

George was especially interested in how dietary
phytochemicals (plant-derived chemicals that may
affect health) inhibit cancer in animal models and theextrapolation of that research to humans. Using therainbow trout model, George and his colleagues wereable to achieve unprecedented statistical power using
the dose-dose matrix experimental design in which
various doses of carcinogens are tested against
various doses of phytochemicals that are expected toprotect against cancer. He also assembled the mostDonations to the endowed fellowship in honor ofGeorge Bailey can be made by sending a check to:
OSU Foundation, 850 SW 35th Street, Corvallis, OR
97333-4015; please write “George Bailey Fellowship”
in the memo line. Alternatively, to make a gift online,
please visit http://giving.campaignforosu.org, andselect “Make a Gift” at the bottom of the page; please
note “George Bailey Fellowship” in the box for “Area
you’d like to support.” LPI

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Vitamin C and the Common Cold: Current Status
Alexander Michels, Ph.D. — LPI Research AssociateV“the effectiveness of ascorbic acid in providing protection
against viral diseases results from its function… inpreventing the entry of virus particles into the cells.”

itamin C and the Common Cold by Linus Pauling
was first published in 1970. In this book, he outlined his own experience with vitamin C and the reasons
he believed gram doses of vitamin C would improve theimmune system. He also reviewed the few clinical trials
on vitamin C and the cold that had been published. The
response to this book was enormous and long-lasting.
Written at a time when natural therapies became
increasingly more popular alternatives to conventional
pharmaceuticals, the message resonated with the publicwith such intensity that vitamin C will forever be linked
with the prevention and treatment of the cold.

Even though more than 40 years have passed sincePauling wrote those lines, controlled laboratory trials withvitamin C and viral infection are exceedingly rare. As aconsequence, we still do not know what dose of vitamin C
might be effective at slowing or preventing many typesof viral transmission in cells. However, Pauling andcolleagues did identify some mechanisms by which vitamin
C protected against HIV infectivity and replication in cell
cultures, work that was published in the Proceedings of
the National Academy of Sciences in 1990.
The data collected to date suggest that
supplemental vitamin C most likely works bystrengthening the immune system, as outlinedin the Micronutrient Information Center on
the LPI website. However, these data arecontroversial as they are often conducted inanimal models that may poorly mimic thehuman immune system response.

From a scientific perspective, research studies
on vitamin C and colds have often been poorly
conducted and controversial. When Paulingwrote his book and advocated for the antiviral activity of vitamin C, there were only a
few clinical studies that could be evaluated.
Furthermore, scientific studies with ascorbic
acid at the time were still in their infancy
because the biological roles of ascorbic acid,such as its enzymatic functions and antioxidant activities, were poorly understood.
In the decades since Pauling’s initial reviewof the field, dozens of studies have been
conducted and published on the topic—many
inspired by Pauling’s claims—but many stilllack the level of sophistication needed todefinitively study vitamin C in human subjects. Indeed,without a radical change in the experimental design ofsuch studies and evidence from basic studies examining thepotential mechanisms of action of vitamin C, we will notsee scientific consensus on the effectiveness of vitamin C on
the prevention and treatment of colds.

Although Pauling advocated the use ofmultiple-gram doses of vitamin C per day
for health with increasing doses to battle acold infection, there are very few studies that
attempt to follow this regimen. Doses used inclinical trials on vitamin C vary greatly andare likely a reflection of the uncertainly surrounding thisfield. Vitamin C is obtained from the diet, and nutritional
status can play a large role in determining the amountof supplemental vitamin C that may have an influence.
Similarly, comparisons are difficult to make with individuals
who are deficient in vitamin C, insufficient (not yet
saturating the plasma), or saturated (taking vitamin C in
excess of that needed to saturate the plasma). Many studies
do not make this distinction, as it is a concept few
researchers fully understand.

One of the issues that plagues supplement trials on thecommon cold is fairly fundamental: What is a cold? There
are a whole host of viruses that cause symptoms associatedwith the cold, from rhinovirus and coronaviruses toparainfluenza. It is estimated that over 200 different typesof viral infections can cause cold symptoms. It is difficult
to detect an effect of vitamin C in clinical studies if it is
only most effective against a subset of these viral infections.
Furthermore, bacterial infections, especially of therespiratory tract, can induce symptoms that closely
mimic a viral infection. The effectiveness of vitamin C
supplementation in the prevention or treatment of bacterial
infections of the respiratory tract is currently unclear.

In 2013, 70 years of clinical research on vitamin C
and the cold were reviewed by Dr. Harri Hemilä for the
Cochrane Database of Systematic Reviews. The results,
which are summarized in the Linus Pauling Institute’s
Micronutrient Information Center, showed that regularsupplementation with 200 mg or more of vitamin C
reduced the duration of colds, with a greater benefit inchildren than in adults. In addition, regular vitamin C
supplementation with 250 mg to 2,000 mg/day reduced
the incidence of colds, but these results did not reachstatistical significance except in those individuals underheavy physical stress (e.g., marathon runners, skiers, or
soldiers in subarctic conditions).

In 1970, Pauling noted that “The mechanism of its[vitamin C] effectiveness against viral infection, such as acommon cold, is not yet known.” He speculated that
FALL/WINTER 20148

Dr. Hemilä concluded that regular daily supplementation
appears to be very important in reducing the severity andduration of colds. It is certainly possible that continuous
supplementation with vitamin C for long periods prior toa viral challenge is important to ensure optimal immune
system response, which takes time. A Japanese study,
published in 2006 in the European Journal of ClinicalNutrition, deserves special mention in this regard. This
study was a five-year trial designed to evaluate the effectof a daily dose of a low (50 mg) or high (500 mg) amountof vitamin C on the development of gastric cancer among
244 subjects. The researchers evaluated the effects of thevitamin C supplements on the common cold at thecompletion of the study and concluded that the risk ofcontracting three or more colds in the five-year period was
decreased by 66% by the daily intake of the high-dose
vitamin C supplement versus taking the lower dose ofvitamin C.

to have insufficient vitamin C status. During the eightweek trial, the vitamin C-supplemented individuals received
1,000 mg/day.
The vitamin C-supplemented subjects (but not thosereceiving placebo supplements) demonstrated elevatedplasma ascorbic acid levels to near saturation. By the endof the study, the researchers found that subjects taking
vitamin C supplements were 40% less likely to get a cold,
and the duration of colds was decreased nearly 60%.
In effect, this paper suggested that consuming a diet withinadequate vitamin C is possibly a factor in determining
cold susceptibility. A greater and more immediate benefit
on the common cold could be seen in individuals whocorrect inadequate vitamin C status with supplementation.
The Linus Pauling Institute recommends that all adults
consume at least 400 mg/day of vitamin C, which is a dosethat will likely achieve plasma saturation in the population.
It’s been proposed that vitamin C improves symptoms
due to its antihistamine effect. While Dr. Johnston has
conducted previous studies showing that vitamin C dosesof 2,000 mg/day decreased blood histamine levels by 60%,
doses of 1,000 mg/day in the recent study had no effect on
histamine levels in blood.

However, it is important to note that these individuals
in Japan were consuming a significant amount of vitamin C
in the diet before the study started. Plasma measurementsof ascorbic acid showed that these individuals were notdeficient in the vitamin, and many had likely achieved
vitamin C saturation of their blood. This could be why it
took approximately two to three years of supplementation
before the difference in cold incidence was apparent,
covering many cold seasons in which subjects were likely
exposed to repeated attacks by cold viruses. It is also
possible that the effect of vitamin C supplementation ismore effective against repeat infections, as it supports
an activated immune system, rather than the first cold
encountered after supplementation has begun.

It should be noted that supplementation taken only after
the cold symptoms have begun, such as consuming vitamin
C supplements at the first sign of a sore throat or runnynose, seems to have little appreciable effect. The beneficial
effects of vitamin C supplementation on the common cold
are more apparent when vitamin C is taken on a regularbasis, when a cold is present or not, as Linus Paulingadvocated. This is likely because of the amount of time
taken for vitamin C to have its full effect on the immune
system, as mentioned above.

The importance of plasma saturation wastouched upon earlier this year in a study
by Dr. Carol Johnston
published in the journal
Nutrients. This study
was not included
in Hemilä’s Cochranereview but deserves
special attention due
to its sophisticatedapproach to the subjectof vitamin C insufficiency.
Unlike the majority ofstudies on vitamin C
supplementation and thecold, including the Japanese
paper described above,
this study was limited
to men who all had plasma
vitamin C below 45 µM
and were considered

Despite some claims to the contrary, the clinical evidence
does support an effect of vitamin C supplements against thecommon cold, similar to Pauling’s assessment 44 years ago.
However, more rigorously-controlled studies are needed
to solidify this association. LPI

The Linus Pauling
Institute recommends
that all adults
consume at least
400 mg/day ofvitamin C, which isa dose that will likely
achieve plasma
saturation in
the population.

9

THE LINUS PAULING INSTITUTE

New
Discoveriesin ALS
Dr. Joe BeckmanDmodification involving peroxynitrite—called
nitration—to the amino acid tyrosine in the heatshock protein Hsp90 is sufficient to cause that
protein to change from a pro-survival protein to one
that causes motor neurons to die. This discovery
opened yet another perspective on ALS.

r. Joe Beckman has been working to understand
ALS (amyotrophic lateral sclerosis or Lou
Gehrig’s disease) for over 20 years. ALS ischaracterized by the progressive loss of motor
neurons, affecting all skeletal muscles and destroying
the ability to move. The patients become completely
paralyzed and usually die within one to five yearsof diagnosis.

Most recently, Dr. Beckman was part of a team thatfound that treating the mice that mimic ALS witha copper compound (copper ATSM) paradoxicallydelayed progression of the disease and improved
both their survival and locomotor function. This was
surprising because giving additional copper to micewith the mutant zinc-deficient superoxide dismutase
would be expected to increase the amount of themutant enzyme—which it did—and, therefore, might
be expected to increase motor neuron death andexacerbate the disease symptoms. In-depth
investigation revealed that the copper compound
was exquisitely targeted to cells in the spinal cord
where it stabilized SOD in its mature and protective
form. The researchers also found that much of thesuperoxide dismutase in the spinal
cord of the ALS mice was actuallycopper deficient. The key is that
copper ATSM can deliver the rightamount of copper to the rightplace in the spinal cord.

Dr. Beckman and colleagues previously discovered
the biological importance of an extremely reactive
compound called peroxynitrite, a powerful oxidant
and nitrating agent produced by immune cells thatcan kill pathogens but also damages biologicalmolecules. Peroxynitrite is formed by reactions
between superoxide and nitric oxide, which is
involved in arterial dilation. Peroxynitrite induces
motor neurons to die. Peroxynitrite also interacts
with the antioxidant enzyme copper-zinc superoxide
dismutase—an antioxidant protein that is sometimes
mutated in ALS. When the copper-zinc superoxide
dismutase loses zinc, the copper-containing enzyme
becomes very reactive, generating
peroxynitrite that can kill motor
neurons. This observation led Dr.
Beckman to try to compensate
by feeding extra zinc to mice thathave the defective superoxide
dismutase and mimic ALS inorder to normalize the zinccontent in copper-zinc superoxide
dismutase. That treatment slightly
modified the progression of thedisease, as did copper chelatorsthat bind copper and remove itfrom the body.

Copper ATSM has been usedclinically for many years in cancer
therapy to image tumors because
it concentrates copper in tumor
cells. The next steps are to more
fully understand the role ofcopper in ALS and to conductclinical studies to test safety andefficacy of copper ATSM
in patients. LPI

Dr. Beckman and his colleagues
also found that a type of chemical

FALL/WINTER 201410

Oxygen Club of California
Annual MeetingT

he Oxygen Club of California (OCC) held its annual
meeting, co-sponsored by LPI, in Davis, California, inearly May. Oxidants and Antioxidants in Biology convened
40 speakers from around the world to give presentations
on “Nutrition and Redox Biology in Development and
Health.” The conference was organized by LPI’s Maret
Traber, who is the President of OCC; Patricia Oteiza; andLester Packer.

• Mulchand Patel (The State University of New YorkBuffalo) reported that nutritional stress during the fetaland suckling stage, which overlaps with organogenesis,
can cause permanent changes in the structure and functionof organs. Breast-feeding enhances immunity and cognition
and reduces the probability of obesity later in life.
Excessive calories from carbohydrates during infancy
predisposes to obesity in adolescence and later.

The four sessions covered metabolic factors that
influence development from conception to two years ofage, flavonoids, redox signaling and systems biology, andvitamin E. Additionally, six posters were selected for oralpresentations on Thursday afternoon.

Flavonoids: From Metabolism toDietary Guidelines• Flavonoids from fruit and vegetables have attracted muchattention because of their in vitro antioxidant functions.
Alan Crozier (University of Glasgow, UK) researched thepharmacokinetics (absorption and excretion) of epicatechin,a type of flavonoid found in tea, chocolate, grapes, andberries. He found that the concentration of epicatechin inplasma peaked twice after consumption: one hour later(representing absorption in the small intestine) and about
seven hours later (representing absorption in the colon).
Epicatechin was metabolized in the colon by microorganisms, and those metabolites, rather than the parent
compound, were then absorbed. About 1.5% of theingested dose was detected in plasma, with a biologicalhalf-life of one to three hours. Over 80% of epicatechinmetabolites were excreted in urine within two days.

Some highlights that may be of special interest to ourreaders:

The First 1,000 Days: From Metabolic
Signal to Societal Impact• Mark Manary (Washington
University, St. Louis) noted that
infants are born without microorganisms in their intestines.
Each child develops an adult-like“microbiome”—the collectionof microorganisms like bacteria,
yeast, and viruses in the intestine—by the age of three. Everychild’s microbiome is unique anddepends on manner of birth, breast-feeding, diet, and otherenvironmental factors. The microbiota play an importantrole in immunity, food digestion, micronutrient synthesis,
and detoxification.

• Christian Heiss (University Düsseldorf, Germany)

reported the results of the European FLAVIOLA study,
designed to determine the impact of cocoa flavanols on
cardiovascular disease risk. FLAVIOLA found that cocoa
flavanol intake improved arterial flow-mediated dilation,
lowered blood pressure, and reduced arterial stiffness inboth genders across a broad age range. The beneficial
effects were both acute and long lasting.

• Audrie Lin (University of California-Berkeley) discussed

the widespread problem of environmental enteropathy(pathological problems in the intestine) in poor,
developing countries. Enteropathy—associated with
undernutrition and poor sanitation—results inpoor absorption of nutrients, the absorptionof substances ordinarily not absorbed,
and reduced efficacy of oral vaccines.

continued on page 12• The vital role of nutrition in early infancy
was addressed by Charles Stephensen(University of California-Davis). Breast-feeding
provides nutrients that ensure the developmentof immune-enhancing microbiotica. If pregnant
women are deficient in vitamin A, their infants will
have impaired adaptive and innate immunity and anincreased risk for death from infections.

11

THE LINUS PAULING INSTITUTE

called urolithins, which can be absorbed into the bloodstream. Differences in the microbiotica among people
affect the absorption of these compounds, illustrating thecomplexity of the process and difficulty in generalizing towhole populations.

Continued from page 11 — Oxygen Club of California• Anthocyanins are deeply pigmented flavonoids foundin red and blue food like prunes, blueberries, and grapes.
Aedin Cassidy (University of East Anglia, UK) informed usthat their bioavailability—about 12%—(absorption into
the blood stream) is greater than previously thought. The
ingestion of food rich in anthocyanins is associated with
reductions in blood pressure and reduced risk for heart
attack, stroke, type 2 diabetes, and cardiovascular disease.

Redox Signaling and Systems Biology
in Health• Twenty-five proteins that incorporate selenium have been
discovered. Their functions range from the metabolism of
thyroid hormones to the control of protein folding. Somehave antioxidant functions and offer protection against
cancer. Holger Steinbrenner (Heinrich-Heine-University,
Germany) emphasized that there is an optimum range ofselenium levels in blood; lower levels may not afford
disease protection, and very high levels may induce type 2
diabetes by affecting insulin secretion and signaling.
The role of selenium in diabetes remains controversial
because high glucose levels associated with diabetes may
stimulate selenoprotein synthesis in the liver, thus
explaining the association between high selenium levels inblood and diabetes.

• Jeremy Spencer (University of Reading, UK) discussed
the effect of flavonoids on cognitive performance. In one
study, 500 mg of cocoa flavanols improved “executive”
function—cognitive performance associated withattention—and memory processing. In another study,
supplemental blueberries improved spatial memory in oldrats. These effects are thought not to be due to antioxidant
functions but rather to the inhibition of neuroinflammationand improved cell signaling, synaptic plasticity, andcerebrovascular blood flow.
• According to Jiankang Liu (Xi’an Jiaotong University,
China) hydroxytyrosol, found in olives and olive oil,targets the mitochondria, resulting in improved functionthat affects aging and age-related disorders.

• Giuseppe Poli (University of Turin, Italy) discussed

the role of oxidized cholesterol in the development of
Alzheimer’s disease. Head trauma, high blood pressure,diabetes, age, gender, family history, and hypercholesterolemia affect the risk for Alzheimer’s disease.
While cholesterol itself does not cross the blood-brain
barrier, its oxidation products—called oxysterols—arefound in the brain. Oxysterols are very reactive andcontribute to beta-amyloid production (a hallmark of
Alzheimer’s disease) and inflammation. Another lipid
peroxidation product—4-hydroxynonenal—has neurotoxic
as well as pro-oxidant and pro-inflammatory properties.
High levels of oxysterols are found in the cerebrospinal
fluid of Alzheimer’s patients, and increasing levels ofhydroxynonenal in the frontal cortex correlate with theseverity of the disease. These findings may suggest
strategies to prevent the generation of these toxic molecules.

• Zhaoping Li (University of California-Los Angeles)
explained that the absorption of pomegranate flavonoids
called ellagitannins is highly complex. Ellagitannins are toolarge to be absorbed into the blood stream
from the intestine, so they are broken downin the intestine to ellagic acid, which isthen absorbed. Some ellagitannins arealso metabolized by intestinal
microorganisms tosmaller compounds

Grapes

The ingestion of foodrich in anthocyanins
is associated with
reductions in bloodpressure andreduced risk forheart attack, stroke,
type 2 diabetes, andcardiovascular disease.
FALL/WINTER 2014

• Roberta Brinton (University of Southern California,

Los Angeles) presented information on the role ofallopregnanolone, a neurosteroid synthesized from thehormone progesterone, in neurogenesis in the mousebrain. In cell culture and animal studies, allopregnanolone
improved mitochondrial function. In mice, allopregnanolone
decreased the amount of beta-amyloid in the brain,
prompting current human trials to determine if
allopregnanolone may
be beneficial in cases ofmild cognitive impairment
or Alzheimer’s disease.

Blueberries

Prunes12Vitamin E consists of eightantioxidants: four tocopherols
and four tocotrienols.

Vitamin E: Tocopherol andTocotrienols in Translational Medicine

important parameters (excluding fibrosis) and did not leadto the weight gain observed with drug therapy.

• Vitamin E consists of eight antioxidants: four tocopherols• Studies on the anti-inflammatory role of vitamin E have
had conflicting results. Joan Cook-Mills (Northwestern
University, Chicago) reported on studies in mice showingthat two isoforms of vitamin E—alpha-tocopherol andgamma-toocopherol—have opposing effects on inflammation.
Alpha-tocopherol inhibited, while gamma-tocopherol
increased allergic lung inflammation. An analysis of humandata obtained in research on cardiovascular disease risk
found that increasing levels of alpha-tocopherol in blood
were associated with better lung function, while increasinglevels of gamma-tocopherol were associated with worse
lung function.

and four tocotrienols. Chandan Sen (The Ohio State
University, Columbus) noted that orally ingested
tocotrienols are found in the brain in small concentrations
that may protect against stroke injury. Clinical trials areunder way to evaluate tocotrienols in secondary stroke
prevention.
• Arun Sanyal (Virginia Commonwealth University, VA)
noted that about 30% of Americans have steatosis—theabnormal accumulation of fat in the liver—that can leadto nonalcoholic fatty liver disease (NAFLD). Excessive fat
in the liver increases lipid peroxidation (oxidative stress),
inflammation, and mitochondrial dysfunction, and cancause liver fibrosis (scar tissue). In mice fed a high-fat dietto induce NAFLD, supplemental vitamin E favorably
affected lipid metabolism in the liver and exerted antiinflammatory effects. In a clinical trial with patients withfatty liver disease, supplemental vitamin E (800 IU of
d-alpha-tocopherol daily for 96 weeks) improved several

What is the
Oxygen Clubof California(OCC)?

• Vitamin E deficiency is associated with muscle weakness

and atrophy. Paul McNeil (Georgia Regents University,
Augusta) found that vitamin E deficiency caused the failureof muscle repair in exercised rats. Oxidants inhibit repair
mechanisms and thus contribute to the damage. Statins,
widely prescribed to lower cholesterol, lower vitamin E
levels in blood and may cause side effects, including
muscle weakness. LPI

OCC is a scientific organization dedicated to enhancing interactions and providing meetingsand discussion forums worldwide to those interested in free radicals in biological systems,oxidants and antioxidants in biology and medicine, micronutrients, nutrition, and health.
OCC Mission: The OCC seeks to promote scientific interactions to improve the understandingof the roles of micronutrients in oxygen biology and medicine as they pertain to redox andenergy metabolism, cell signaling and transcription, and epigenetics. An ultimate goal is totranslate these findings to benefit human life- and health-span. OCC sponsors are fromindustrial organizations, health and medical foundations, government, and academia. We arealso co-sponsored by the Linus Pauling Institute. With this wide support, conference organizers
bring together the world’s best researchers to address current scientific issues. The OCC
provides a forum—in the form of prizes and awards—for the recognition of scientificachievements by both promising scholars and established investigators.

13

THE LINUS PAULING INSTITUTE

The Essentiality ofVitamin E

Vitamin E is needed to protect the“embryo’s brain before a woman knows she ispregnant. The vitamin E in a multivitamin issufficient to meet the requirement.

”of frank vitamin E deficiency are extremely rare. People
with severely impaired fat absorption may be at risk for
deficiency symptoms because good absorption of
fat-soluble vitamin E requires it be consumed with fat.
Vitamin E inadequacy, defined as very low concentrations ofalpha-tocopherol in plasma, is associated with malnutritionin children. Inadequacy puts children at risk for infections,stunted growth, and anemia. Additionally, inadequacy during
the first few years after conception can impair neurologicaldevelopment. As Dr. Traber said, “Vitamin E is needed toprotect the embryo’s brain before a woman knows she ispregnant. The vitamin E in a multivitamin is sufficient to meetthe requirement.” High vitamin E concentrations in infants atbirth predict better cognitive function at two years of age.

A

recent review article on vitamin E inadequacy by LPI
principal investigator Dr. Maret Traber has attracted
a lot of attention. The supplemental
intake of vitamin E has been
controversial for many decades;
early observational studies found an
association between high vitamin E
intake and reduced risk for heartdisease, but subsequent studies
have yielded mixed results, withsome even claiming possible harmfrom supplemental vitamin E.
Dr. Maret Traber

Obese children are at increased risk for nonalcoholic
fatty liver disease, which can lead to liver cirrhosis andcancer. Vitamin E supplementation in obese children (andadults) has improved the histological profile observed infatty liver disease, probably due to reduced oxidative
stress. Adequate consumption of vitamin E may inhibit the
progression of fatty liver disease, which is dependent on
lipid oxidation.

The RDA of 15 mg (22.5 IU) of alpha-tocopherol, set by
the Food and Nutrition Board of the Institute of Medicine
in 2000, is based on the amount of vitamin E estimated toprevent the rupture of red blood cells, which could lead toanemia. This value was established for the intake ofalpha-tocopherol – the only form of vitamin E among theeight forms of tocopherols and tocotrienols that ismaintained in the body. Vitamin E is an important fatsoluble antioxidant that can be regenerated by vitamin Cfrom its oxidized form in the body, as previously shownby Dr. Traber and her colleagues. Dr. Traber has publishedother articles asserting that the main, and perhaps onlyrole of vitamin E in the body, is to prevent lipid oxidation.

In mice and fish, vitamin E has been found to play a
critical role in embryonic development, particularly thebrain and nervous system. There are abundant fatty acidsin the nervous system that are vulnerable to oxidationand dysfunction if vitamin E levels are inadequate. In older
adults, vitamin E has been found to slow the progressionof Alzheimer’s disease and to improve cognitive abilities,
presumably by inhibiting the oxidation of fatty acids inthe brain, especially DHA (docosahexaenoic acid)—anomega-3 fatty acid important in brain biochemistry andcognitive function.

While it is possible to consume 15 mg of alpha-tocopherol
from the diet alone, about 90% of men and 96% of
women do not meet this goal. Nuts and vegetable oils aregood sources of vitamin E but may not be consumed
daily in amounts sufficient to meet vitamin E adequacy.
Despite this failure to reach the RDA of vitamin E, cases
FALL/WINTER 2014

Dr. Traber makes a convincing argument that we should
be concerned about getting enough vitamin E, especially inthe first 1,000 days after conception and when elderly. LPI

14

DEVELOPMENTS
Gifts to LPI are an investment in your healthS

ince its founding in 1973, the Linus Pauling
Institute (at OSU since 1996) has been helping
people live longer, healthier lives, sharing informationon the critical role of diet, micronutrients, andsupplements in preventing and treating disease.
Researchers at the Institute receive support fromindividuals, corporations and foundations, andgrants from federal agencies, including the National
Institutes of Health.

National Institutes of Health grants decreasing from$5 million in 2009 to $1.5 million last year.
Fewer research dollars from NIH means that gifts
from individuals and corporate partners are having aneven greater impact on our research. This year, LPI
received significant gifts that are supporting a rangeof scientific studies: from better understanding of thecauses and possible treatment for ALS, to the role ofzinc in preventing inflammation, to the health benefitsof xanthohumol, a flavonoid found in hops.

Earlier this year, The New York Times highlighted
the role of philanthropy in advancing basic scientificresearch “Billionaires with Big Ideas Are Privatizing
American Science.” With continued declines in federal
funding, private donors are increasingly helping toshape science research through investment in areas of
personal interest.

Gifts from people like you also are helping sustain
the important research under way at the Institute.
Last year, the Linus Pauling Institute received morethan 1,300 gifts under $10,000—gifts that together
totaled more than $215,000. These gifts were used tosupport research in the Institute, as well as outreachand education through the Micronutrient Information
Center and the Healthy Youth Program.

In the article, the Times noted that “spending on
basic research has fallen by roughly a quarter, to $30
billion last year, one of the sharpest declines ever,”resulting in fewer grants and—in some cases—
research centers having to close their doors.

Many thanks to all of you who already support the
Linus Pauling Institute—your investment is making
a vital difference in people’s lives. I invite all of you
to consider a gift to the Institute and its mission ofresearch and outreach, helping everyone live longer,
healthier lives. LPI

Research at the Linus Pauling Institute has not been
exempt from the decline in federal spending, withMarlys Amundson
Director of Development
Photo by Jim Carroll Photography

LPI is grateful for the bequests wehave received from the following
friends this past year:

15

Angela A. Capsouras

Susan B. Shearer

Matilda Goodman

Mark R. Sponenburgh

Eugenie M. Hagerman

Roberta Tumbiolo

THE LINUS PAULING INSTITUTE

Linus Pauling InstituteStephen Lawson, Research Newsletter Editor
Oregon State University
307 Linus Pauling Science Center
Corvallis, Oregon 97331

Non-Profit Org.
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PAID
Portland, OR
Permit No. 1006

phone: 541-737-5075
fax: 541-737-5077
email: lpi@oregonstate.edu
website: lpi.oregonstate.edu

Printed on recyclable paper using soy inks

Look for these informative
articles inside!
Page 1 ....... From the Director
Page 1 ....... New Benefits of Vitamin E— An Interview with
Debbie J. Mustacich, Ph.D.
Page 7 ........In Memoriam: Dr. George Bailey
Page 8 ........Vitamin C and the Common Cold:
Current Status
Page 10 ......New Discoveries in ALS
Page 11 ......Oxygen Club of California
Annual Meeting
Page 14 ......The Essentiality of Vitamin E
Page 15 ......Developments

GIVING to theLinus Pauling InstituteGifts in support of research efforts can be madeat any time. Checks should be payable to OSUFoundation for Linus Pauling Institute. Information
on giving is available through the OSU Foundation,
1-800-354-7281, or by writing to the Institute.

Special thanks to Barbara McVicar for editorial assistance and photographs
and to authors of signed articles.