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Oregon State University

The

Linus Pauling
Institute

R E S E A R C H

From theDirector

LPI Diet andOptimum HealthConference

Balz Frei, Ph.D.
LPI Director and Endowed ChairOSU Distinguished Professor of
Biochemistry and Biophysics

To say we had a busy summer and fall at the Linus
Pauling Institute would be a vast understatement!
In the first week of September, the Institute moved into
our new home, the Linus Pauling Science Center. It is a
dream come true, 15 years after the Institute arrived on
the campus of Oregon State University. The new building,designed by the world-renowned architect firm Zimmer
Gunsul Frasca, headquartered in Portland, Oregon, is
simply magnificent. The Linus Pauling Institute’s top two
floors of the Center are connected by a two-story,“cathedralesque” atrium, which provides an independent
identity for the Institute. The continuous, open laboratory
space, housing the Institute’s 15 laboratories and threeresearch programs––Cancer Chemoprotection, Healthy
Aging, and Cardiovascular and Metabolic Diseases––
provides flexibility and facilitates collaborations in stateof-the-art facilities. The building maximizes functionality
and efficiency and is, at the same time, aesthetically very
pleasing with its modern design, ample natural light,
straight lines, extensive use of glass and natural

N E W S L E T T E R

Stephen Lawson
LPI Administrative OfficerThe sixth LPI Diet and Optimum Health Conference,co-sponsored by the Oxygen Club of California,
convened on the OSU campus in Corvallis from September
13 to 16. The conference featured 21 speakers from aroundthe world and was organized into five sessions:• Vitamin E: Biological Functions and Controversies• Micronutrients, Diet, and Immune Function• Diet and Cardiovascular Disease• Gut Microbes and Probiotics: Role in Health and Disease• Caloric Restriction Mimetics, Diet, and Healthy Aging

Forty-six posters depicting experimental projects weredisplayed beginning Wednesday afternoon. An additionaleight posters were selected for oral presentations on
Thursday afternoon.
The conference concluded on Thursday with thepresentation of the Linus Pauling Institute Prize for HealthResearch to Dr. Connie Weaver of Purdue University,
followed by her lecture on calcium and bone health.
For more details, please see the article on page six.

Vitamin E: Biological Functions andControversies
Chaired by Maret Traber (LPI)• Danny Manor (Case Western Reserve University)
discussed the role of the alpha-tocopherol transfer protein(TTP) in the regulation of vitamin E in the body. TTP issynthesized in the liver and distributes only the naturalor d-alpha-tocopherol form of vitamin E to the blood.
Mutations in TTP, therefore, affect vitamin E status.
Appropriate neuronal responses to stimuli are lacking in

Photo by Eckert & Eckert

continued on page 2

continued on page 3— DESIGNATED BY THE NATIONAL INSTITUTES OF HEALTH AS A —Center of Excellence for Research on Complementary and Alternative Medicine

Continued from cover — From the Director
wood, and some amazing art work. This, together withthe many formal and informal meeting places, provides
a first-rate working space that fosters cutting-edge
scientific research and development of new ideas andresearch projects, and greatly enhances the intellectual
environment of the Institute. We are truly privileged––and very happy––to be in such fabulous facilities!
In September, we also held our sixth Diet andOptimum Health conference on the OSU campus in
Corvallis, which allowed us to showcase the newCenter. The conference attracted 220 registrants andwas very successful, thanks to all the excellent talks
and poster presentations. The sixth Linus Pauling
Institute Prize for Health Research was awarded to
Dr. Connie Weaver, Distinguished Professor and Headof the Department of Foods and Nutrition at Purdue
University and an OSU alumna. Dr. Weaver washonored for her groundbreaking work in humancalcium metabolism and bone health, which
revolutionized our understanding of the importanceof building peak bone mass during adolescence, thefactors that contribute to bone loss in postmenopausal
women, and dietary and lifestyle factors that help
prevent osteoporosis. Summaries of Dr. Weaver’s
research and all the talks of the conference are provided
in this issue of the Newsletter.
We also recently filled
a new faculty position in
the Institute’s Healthy
Aging Program with an
outstanding candidate,
Dr. Viviana Perez, fromthe Institute for Longevity
and Aging Studies at the
University of Texas Health
Sciences Center at San
Antonio. In addition to
being a Principal
Dr. Viviana Perez
Investigator in theInstitute, Dr. Perez holds an Assistant Professor
position in OSU’s Department of Biochemistry andBiophysics. Her research focuses on the roles ofoxidative stress and protein homeostasis in the aging
process and how dietary restriction and rapamycin
extend life span, a topic which she addressed in her
talk at the Diet and Optimum Health conference(see inside). Dr. Perez brings with her a prestigious
New Scholar Award in Aging from the Ellison
Medical Foundation. She received her Ph.D. degreein Biomedical Sciences from the University ofChile, Santiago.
In addition, we hired a new Research Associate
to help maintain and expand the Institute’s
Micronutrient Information Center (MIC;

2

Fall/Winter 2011

http://lpi.oregonstate.edu/
infocenter). Dr. Giana
Angelo joined us from theFred Hutchinson Cancer
Research Center inSeattle, WA. She holds a
Ph.D. degree in Cellular
and Molecular Nutrition
from Tufts University in
Boston, MA, where she
did research on vitamin
D. Dr. Angelo will beworking with Dr. Victoria
Dr. Giana Angelo
Drake, MIC Manager, tocritically review and synthesize basic, clinical, andepidemiologic research literature in order to update
existing articles and write new ones for the MIC.
She will also respond to questions from donors,
health and nutrition
professionals, and the
media concerning topics
represented in the MIC.
Finally, thanks to a large
bequest LPI recently
received, we have beenable to establish two newendowed Professorships
in the Institute. Dr. Maret
Traber was selected as
the inaugural recipient of
Dr. Maret Traber
the “Helen P. Rumbel
Professorship in Micronutrient Research,” andDr. Rod Dashwood for the “Helen P. Rumbel
Professorship in Cancer Prevention.” A celebrationand public announcement took place at the grandopening of the Linus Pauling Science Center on
October 14, where Dr. Dashwood presented his
work on genetic and epigenetic aspects of cancer
development and the protective role of dietaryfactors, and Dr. Traber talked about the biological
functions and value ofvitamin E in protecting
against oxidative stress.
On behalf of everybody
in the Institute, I welcome
Drs. Perez and Angelo
and congratulate Drs.
Traber and Dashwood
for their well-deserved
recognition! LPI

Dr. Rod Dashwood

Continued from cover —LPI Diet and Optimum Health Conference
mice that have the gene for TTP deleted, illustratingthat vitamin E is important in normal brain function.
• Qing Jiang (Purdue University) showed that metabolites of gamma-tocopherol, a form of vitamin E foundin soybean and corn oils and the most commonly
consumed form of vitamin E in the American diet,possess anti-inflammatory activities greater than either
alpha- or gamma-tocopherol. • People born now havea 33% risk for diabetes, and cardiovascular disease is
the cause of death in 80% of diabetics. Andrew Levy
(Technion-Israel Institute of Technology) focused on
the influence of vitamin E on cardiovascular diseaserisk in people with variations in the haptoglobin gene.
Haptoglobin binds to hemoglobin released from red
blood cells and prevents oxidative damage. Diabetics
with the haptoglobin 2-2 gene (Hp 2-2) have an
increased risk for cardiovascular disease, which is
attenuated by supplemental vitamin E. Conversely,
vitamin E may be harmful in diabetics with the Hp 2-1
gene, so genotype screening may be valuable. • Etsuo
Nikki (National Institute of Advanced Industrial Scienceand Technology, Japan) addressed difficulties in assessing
the antioxidant role of vitamin E in vivo. He stated thatvitamin E reduces the risk for free radical-mediatedchronic diseases “if given to right subjects at righttiming.” Vitamin E may be more effective if given
early in disease development. Antibodies raised against
oxidatively damaged biomolecules may be good markers
for evaluating antioxidant interventions.

Micronutrients, Diet, and Immune
Function
Chaired by Adrian Gombart (LPI) and Emily Ho (LPI)• George Liu (UCLA) reported on the effect of nicotinamide,a derivative of nicotinic acid (collectively known as niacin or
vitamin B3), on enhancing immune function. Nicotinamide
amplifies the amount of a transcription factor, C/EBPε,needed for the mature function of immune system cells
called neutrophils and macrophages. Mice were infectedwith Staphylococcus aureus (MRSA), the most common
cause of soft tissue infections in people. Treatment with
nicotinamide dramatically killed the pathogen in the bloodby enhancing the production of antimicrobial compounds
in neutrophils. • Carlos Camargo (Harvard) noted that
supplementary vitamin D in people with low vitamin Dlevels decreased the risk for acute respiratory infections.
In a Boston study, vitamin D supplementation in pregnant
women reduced the incidence of wheezing in their children.
In a New Zealand study, vitamin D insufficiency in pregnant
women increased the risk of respiratory infections in theirchildren. In Afghanistan, vitamin D treatment prevented
subsequent pneumonia in children. An analysis of thetotality of evidence suggests that vitamin D may be more
effective in preventing rather than treating respiratory
infections. • Elizabeth Gardner (Michigan State University)
discussed the role of nutrition in influenza infection.

Although antibody response doesn’t seem to be affectedby nutritional status, the response of T cells needed tofight infection is influenced by nutrition. Specifically,
caloric restriction, a strategy observed to extend life spanin many animals, increases the susceptibility to influenza
infection in mice by adversely affecting the activity ofnatural killer cells, which are important in the early stageof infection. These data suggest that caloric restriction
can extend life span only in a germ-free environment.
• Sepsis is caused by overwhelming bacterial infection
and often results in death due to the collateral effects
of immune activity. Daren Knoell (The Ohio State
University) noted that zinc levels are low in septic andcritically ill patients. In mice, zinc deficiency decreases
survival from sepsis, and zinc restoration three days
before sepsis improves survival. After sepsis in mice,intraperitoneal injection of zinc—but not oral zinc—
improves survival. • Peter Hoffmann (University of
Hawaii) explained the relationship between selenium
and immune response. He found that high levels ofselenoprotein K are present in immune cells and that mice
without selenoprotein K are more susceptible to viral
infection. Selenoprotein K is important in the proper
function of T cells, neutrophils, and macrophages.
Strategies using nanotechnology may be developed totarget selenium to immune cells. • Robert Chapkin(Texas A&M University) studies the role of polyunsaturated fatty acids in immune function, especially as
it relates to inflammatory bowel disease. Omega-3 fatty
acids (n-3 fatty acids) like eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA) found in fish oil
suppress T-cell activation through effects on lipid “rafts”
in cell membranes. Therefore, supplementation may bebeneficial in people with hyperactive immune systems but
immunosuppressive in healthy people.

continued on page 4

Katie Lebold, Caitlin Crimp, and Sherry Farley

The Linus Pauling Institute3

Continued from page 3 —LPI Diet and Optimum Health Conference

olive oil, fish, and seafood but has little chicken, milk,or red meat. The diet also includes moderate intakes ofalcohol, usually as red wine. Dr. Estruch and colleagues
are conducting a clinical trial to evaluate the effects of aMediterranean diet on the risk of death from heartdisease, incidence of cardiovascular events like strokes
and heart attacks, incidence of cancer and diabetes, andmortality from all causes. To date, compliance to thediet has resulted in decreased oxidative stress andinflammation, lower BMI, decreased waist circumference,and decreased risk for metabolic syndrome.

Gut Microbes and Probiotics: Role in
Health and Disease
Maret and Biff Traber

Diet and Cardiovascular Disease
Chaired by Balz Frei (LPI)• Cooking food results in pleasant flavors andpalatability. However, Veronika Somoza (University of
Vienna, Austria) noted that high-temperature cooking
of processed food in the Western diet produces bothbeneficial and harmful compounds, including carcinogens
like heterocyclic amines (“cooked-meat mutagens”),
as well as advanced glycation end products (AGE) andlipid hydroperoxides associated with heart disease anddiabetes. Mild cooking, replacement of high-fructose
corn syrup with sucrose, and increasing the intake ofsubstances like vitamin C that counteract some of theharmful compounds are strategies to lower disease risk.
• Teresa Fung (Simmons College, Boston) discussed theepidemiological associations between diet and cardiovascular disease. Connections between diet and diseaserisk can be assessed in several ways: correlations between
actual food intake and disease or adherence to prudent
dietary recommendations. Many studies have found thatprudent patterns (i.e., plant-based, minimally processed
foods, Mediterranean diet) are associated with decreased
risk for heart disease, while the Western diet (refined
grains and meat) increased the risk for heart disease.
• Ramon Estruch (Barcelona University, Spain) focusedon the healthful effects of the Mediterranean diet, which
is rich in fruit, whole grains, vegetables, legumes, nuts,

Olga Vlasenko, Maret Traber, Lester Packer, and LeeCole Legette4

Fall/Winter 2011

Chaired by Sharon Krueger (LPI)• Cindy Davis (U.S. National Cancer Institute) discussed
the microbiome—the bacteria (“probiotics”) that populate
the gastrointestinal tract. Such organisms affect health,including cancer risk and, possibly, obesity. “Prebiotics”
include dietary factors like soy, fiber, and ellagitannins inberries that are metabolized by gut bacteria to compounds
like equol, butyrate, and ellagic acid, respectively, each ofwhich protects against cancer. Microbiotica also influenceenergy balance; lean people typically have populations ofgut bacteria different from those in obese people. •Bruce German (University of California-Davis) talked

Christine Merrill, Alan Taylor, Neil Mann, and Gary Merrill

about the evolutionary relationship between breast milk
and Bifidobacterium infantis, a bacterial strain thatcolonizes the infant’s gastrointestinal tract until weaning.
Complex oligosaccharides in breast milk are indigestible
in the infant’s gut but can be metabolized only by B.
infantis, releasing compounds that regulate metabolism,protect against pathogens, and educate the immune
system. • The role of probiotics in disease prevention
and treatment is gaining acceptance. Robert Martindale(Oregon Health & Science University) discussed a study
showing that probiotics routinely delivered via coateddrinking straws halved the number of sick days taken byworkers in a car factory. In other studies, probiotic use
decreased the incidence of ear infections in healthy
nursery school children, decreased gestational diabetes,and decreased mortality and pneumonia by 50% inpatients on ventilators. Vancomycin-resistant enterococci

(VRE), a common cause of hospital infections, can becleared by probiotics, further demonstrating theirclinical utility.

Alzheimer’s and amyotrophic lateral sclerosis (ALS) in
mouse models. Since there are differential effects of
dietary restriction and rapamycin on disease and because

Caloric Restriction
Mimetics, Diet,
and Healthy Aging
Chaired by Tory Hagen (LPI)and Viviana Perez (LPI)• Richard Miller (University ofMichigan) discussed several
strategies that increase life spanin mice, including rapamycin(an immunosuppressant drug
derived from bacteria); deletionof the gene for migration
inhibition factor, which is a
pro-inflammatory cytokine; alow-methionine diet, which
may provide resistance to stressand toxins; and food restriction
early in life. In contrast,
Front row: Kate Shay, Dove Keith, Drupadi Dillon, and Judy Butler; Standing: Nick Thomas, Liam Finlay, and Luis Gomez
resveratrol, simvastatin,
curcumin, and green tea extract
they work through different mechanisms, rapamycin
did not affect life span in mice. Additionally,
does not act as a dietary restriction mimetic.
calorically restricted mice are more susceptible toOral Abstracts
infections. • Resveratrol is a compound produced ingrapes in response to stress. According to Julie Mattison
Eight abstracts on a variety of topics were selected for(U.S. National Institute on Aging), its effects are speciesoral presentations:specific, although supplementation to mice and monkeys
Mark Levine (U.S. National Institute of Diabetes andfed high-fat or diabetes-inducing diets has resulted in
Digestive
and Kidney Diseases) discussed the cytotoxicity
health improvements. For example, monkeys kept onofhigh
concentrationsof vitamin C achieved bysuch diets and given very high doses of resveratrol
intravenous
infusionagainstcancer cells. Physician
exhibited less arterial stiffening and inflammation andsurveysshow
thathigh-dose
IV vitamin C has minimal
improved glucose control compared to control animals.
sideeffects.
Cell
culture,mouse
studies, and some
The mechanism responsible for those effects is unknown.
preliminary
studieswithcancerpatientssuggest that
• Jamie Barger (LifeGen Technologies, Madison, WI)
IV
vitaminC
combinedwithstandard
drug
therapypresented information on the identification of genes(gemcitabine)maybeespeciallyeffective
againstthat serve as biomarkers of caloric restriction. Suchpancreatic cancer.
biomarkers may be useful in determining the utility ofcompounds like resveratrol or quercetin—a flavonoid—
Margreet Vissers (University of Otago, New Zealand)on increasing life span. Of nearly 21,000 genes surveyed
noted that consuming kiwi fruit raises blood levels ofin mice, 11 served as markers of caloric restriction.
vitamin C more than vitamin C added to drinking water.
Low doses of resveratrol or quercetin slightly mimicked
Vitamin C inhibits hypoxia-inducible factor 1 (HIF-1),
caloric restriction, but the combination was synergistic.
a transcription factor induced by the low-oxygen• Gordon Lithgow (The Buck Institute for Age
environment in tumors. HIF-1 promotes the survival of
Research, California) discussed the importance ofcancer cells and enhances angiogenesis (blood vessel
protein homeostasis—dysfunctional proteins replacedformation), which is needed by rapidly growing tumors
with normal proteins—in longevity. Using small worms
to supply nutrients and remove waste.
(C. elegans), he has shown that curcumin, lithium, andSilvia Maggini (Bayer Consumer Care, Switzerland)
Thioflavin T, a dye that binds to aggregated andpresented David Kennedy’s (Northumbria University,
misfolded proteins, extend life span in worms. ChelatingUK) abstract on the effect of multivitamins/minerals on
metals in worms to maintain “metallostasis” also
cognitive performance and mood. In several studies
increased life span. • Viviana Perez (LPI) showed that
rapamycin and dietary restriction increased life span incontinued on page 7
mice, but only dietary restriction decreased fat mass,
resulting in improved glucose control and insulin
tolerance. Dietary restriction also delayed the onset of

The Linus Pauling Institute5The Linus Pauling InstitutePrize for Health ResearchDr. Connie Weaver of
Purdue University
was presented with the2011 Linus Pauling
Institute Prize for HealthResearch, consisting of a
medal and $25,000, for
her outstanding work on
calcium and bone health.
She pioneered the useof stable isotopes in
elucidating calcium
metabolism and has
been a very effective
advocate for science inthe public realm.
Dr. Weaver received her B.S. from Oregon State
University and a Ph.D. from Florida State University,where she held her first faculty appointment. She has
been a Professor of Foods and Nutrition at Purdue since
1988, Department Head since 1991, and Distinguished
Professor since 2000. Dr. Weaver has served as anadvisor to many organizations and in 1996 served on
the National Academy of Sciences’ Food and Nutrition
Board Dietary Reference Intakes Panel for Calcium andRelated Nutrients. She was elected to the Institute ofMedicine of the National Academies in 2010 and the
Food and Nutrition Board of the Institute of Medicine
in 2011. She has written over 160 peer-reviewed
research articles.

girls. There are also racial differences: AfricanAmerican girls absorb more calcium and deposit morecalcium in bones than Caucasian girls, and ChineseAmerican adolescents require less calcium intake for
maximal retention in bones. Transient low bone mineraldensity for body size may explain the increased risk for
fracture in teens, especially in the distal radius andamong obese children. Dr. Weaver noted that without
calcium supplementation, many Americans would be
deficient in calcium status.
Many recommendations for calcium intake haveemerged from research conducted at Purdue’s “CampCalcium,” a summer camp where scientists study
calcium metabolism in children, especially as affectedby gender and ethnicity. Camp Calcium was started by
Dr. Weaver 20 years ago to gather more information on
calcium metabolism and bone health in a controlledenvironment.
Nomination letters cited Dr. Weaver’s “strong
commitment to being actively engaged in public healthpolicy” and her work on calcium metabolism as “anelegant example of translational research, using uniqueand innovative technologies, that has had tremendous
impact on programs that aim to maximize peak bonemass and improve bone health.” LPI

Dr. Weaver’s lecture focused on the critical need foradequate calcium intake during skeletal development andduring the “fracture zone” period after 50 years of age.
About 50% of women over 50 have fractures, and there
is a linear relationship between bone mineral density
and the risk for fracture. Failure to reach optimal bonemineral density in adolescence predicts osteoporosis
later in life. About 99% of the body’s calcium is in bone,and over 30% of bone is calcium. Calcium is critical forthe structural strength of bones and to reduce bone
resorption by maintaining a positive calcium balance.
While environment and genes play a role in bonedevelopment and health, dietary calcium intake isexceedingly important early in life. For example, bone
accrual is most rapid during ages 12 to 15 for girls andboys, and peak bone mass is reached at age 20. A daily
calcium intake of 1,300 mg results in maximal retention
for bones, and boys more efficiently retain calcium thanDrs. Balz Frei and Connie Weaver

6

Fall/Winter 2011

Continued from page 5 —LPI Diet and Optimum Health Conference
conducted in labs or by mobile phone, subjects taking
multivitamin/minerals had improvements in stress,
mental health, mental vigor, and analytical performance.
Gene Bowman (Oregon Health & Science University)
noted that randomized controlled trials of the effect of
single nutrients in Alzheimer’s disease have been
disappointing. Studies that rely on food-frequency
questionnaires in these patients may be inaccurate
because even mild memory deficits attenuate theirvalidity. Higher blood levels of trans fat were associatedwith increased brain atrophy and poor memory andattention, whereas omega-3 fatty acids were associatedwith better executive function. Blood levels of B vitamins
and vitamins C, D, and E were associated with increased
brain volume.
Tetsuya Konishi (Niigata University of Pharmacy andApplied Life Sciences, Japan) discussed the biochemical
effects of Schisandrin B, a lignan from the Chinese vine
Fructus schisandrae. Schisandrin B lowers oxidative
stress and brain damage in mice induced by drugs likescopolamine and cisplatin, as well as protecting against
neurotoxicity, DNA damage, and cognitive impairment.
Katie Meyer (University of Minnesota) described along-term, observational diet study of about 5,000
adults in four U.S. cities. Based on food-frequency
questionnaires, the subjects’ diets were ranked according
to quality. Periodic measurements of F2-isoprostanes,
which are makers of oxidative stress, revealed that thehighest diet quality correlated with the lowest oxidative
stress. Diet quality was based on intake of 46 foodgroups scored as beneficial, neutral, or adverse for healthaccording to current science. The highest quality dietconsisted of whole grains, fruit, vegetables, fish, nuts
and seeds, and was low in red meat.

LPI’s Galen Miller and Dr. John Maguire of the Oxygen Club of California

Young Investigator Awards
Young Investigator Awards were presented to three
graduate students or post-doctoral fellows. Theirabstracts were selected as the most outstanding of thesubmissions.
The Linus Pauling Institute Young Investigator Awards
were given to Dr. Vijayasree V. Giridharan of the
Department of Functional and Analytical Food Sciences,
Niigata University of Pharmacy and Applied Life Sciences,in Niigata City, Japan (“Schisandrin B, a component of
medicinal herb Schisandra chinensis, attenuates β–amyloidinduced cognitive dysfunction and neuro-inflammation
by modulating NF-κB signaling”); and Dr. LeeCole
Legette of the Linus Pauling Institute (“Pharmacokinetics
of xanthohumol, a prenylflavonoid derived from hops”).
The Oxygen Club of California Young InvestigatorAward was given to Galen W. Miller, a graduate student
in the Linus Pauling Institute and OSU’s Molecular andCellular Biology Program (“Normal brain development
requires alpha-tocopherol delivery via the alpha-tocopherol transfer protein during zebrafish embryogenesis”).

Neil Mann (Royal Melbourne Institute of Technology
University, Australia) addressed dietary changes during
recent human evolution and the effect of a high-protein
diet similar to that consumed in the Paleolithic era on
body weight and glycemic control in type 2 diabetics.
Conventional recommendations for diabetics to consume
low-fat, high-carbohydrate diets result in elevated blood
glucose and triglycerides, whereas high-protein diets areassociated with weight loss, better glycemic control,
lower systolic blood pressure, and lowered dose of
medication like metformin.
Kate Shay (LPI) reported on newly characterized
pathways involved in lipoic acid activity. A transcription
factor called Nrf2 controls about 200 genes involved inoxidative/toxicological stress response. Nrf2 accumulates
in the nucleus of cells treated with lipoic acid, which
also attenuates the degradation of Nrf2. These effects
improve cellular response to various stressors.

LPI

Drs. Vijayasree V. Giridharan, LeeCole Legette, John Maguire, andLPI’s Adrian Gombart

The Linus Pauling Institute7

A dream come true — September 2011

The Linus Pauling Science Center

Photo by Eckert & Eckert

Photo by Karl Maasdam

8

Fall/Winter 2011

Photo by Barbara McVicar

Oregon’s “Percent for Art” program coordinated the selection of art for the Linus Pauling Science Center

Photo by Karl MaasdamWilliam Shumway’s Resonance,
a gift of Janet and Henry Nielsen

Photo by Barbara McVicar

Photo by Karl Maasdam

Photo by Karl Maasdam

Stephen Knapp’s lightpainting Structure, Spaceand Time (also below right)

Chris Dean’s Gold Will Stay andOpposite and Equal (far right)

Photo by Stephen Knapp

Photo by Barbara McVicar

Linus Pauling Institute lobby and atrium
Krysten Cunnigham’s Oloid sculpture, a gift from the Oxygen Club of California, is at left

Photo by Eckert & Eckert

The Linus Pauling Institute9Multivitamin/mineral
Supplements
Victoria J. Drake, Ph.D.
Manager, LPI Micronutrient
Information CenterAlthough there is no standardized definition, a multivitamin/mineral (MVM) supplement is generally
described as a dietary supplement that contains around100% of the Daily Value (DV) of most vitamins andnutritionally essential minerals. MVM supplements,
however, do not contain the DV for some of the essential
minerals (e.g., calcium and magnesium) because the resulting
pill would be too bulky to swallow. Notably, DVs listedon the supplement label are largely based on outdated
recommendations made in 1968 and therefore do not reflectcurrent dietary intake recommendations by the U.S.
government—the Recommended Dietary Allowance (RDA)or Adequate Intake (AI) for micronutrients. For a comparison
between the DVs and the current recommendations, see
the table at right. Although not typically the case,manufacturers may choose to include micronutrients at levels
equivalent to current recommendations in their products.
Additionally, many companies market gender- and agespecific formulations of MVM supplements.

but may also increase risk for chronic, age-related diseases,
such as cardiovascular disease, osteoporosis, and cancer.
Micronutrient deficiencies have further been linked tocognitive dysfunction. Given the fact that many people are
not meeting micronutrient intake recommendations, a daily
multivitamin/mineral supplement would offer insurance
that most micronutrient needs are met.
However, it is not known whether taking a MVM
supplement will decrease the risk of chronic disease.
A number of observational studies as well as randomized

Comparison between the
Daily Values (DV) and the Dietary
Reference Intakes (RDA or AI) for Adults
MicronutrientDV

RDA or AI for
Adult Males(amount/day)

RDA or AI for
Adult Females(amount/day)

Biotin

300 mcg

30 mcg30 mcg

Folate

400 mcg

400 mcga

400 mcga

Niacin20 mg

16 mgb14 mgb

Pantothenic Acid

10 mg

5 mg

5 mg

Riboflavin

1.7 mg

1.3 mg

1.1 mgThiamin

1.5 mg

1.2 mg

1.1 mgVitamin A

5,000 IU

3,000 IUc

2,333 IUc

Vitamin B6

2 mg

1.3-1.7 mg

1.3-1.5 mg
2.4 mcgd
75 mg

An estimated one-third of Americans aged one year andolder take MVMs—the most popular type of dietary
supplement in the United States. Studies have found that
MVM supplement use is more prevalent in certain subgroups, including females, non-Hispanic whites, older
adults, and individuals with higher education. Some otherstudies have associated MVM use with people who havegenerally healthier diets or rate their health as good or
excellent. Daily use of a MVM supplement can help fill
nutritional gaps and improve micronutrient status. Many
Americans are apparently eating sufficient (or excessive)
calories while, at the same time, not meeting daily intake
recommendations for vitamins and essential minerals. Indeed,
select micronutrient inadequacies are quite common in the
United States: a national survey (NHANES 2003-2006)
found that 60% of the U.S. population do not meet intake
recommendations from diet and supplement use for vitaminE, 45% for magnesium, 38% for calcium, 34% forvitamin A, 25% for vitamin C, 8% for vitamin B6, and
8% for zinc. Vitamin D insufficiency is also very common
among Americans.

Vitamin B12

6 mcg

2.4 mcgd

Vitamin C

60 mg

90 mg

Vitamin D

400 IU

600-800 IU

600-800 IU

Vitamin E

30 IU

22.5-33 IUe

22.5-33 IUeMoreover, micronutrient inadequacies have been
documented in other industrialized countries, and multiple
micronutrient deficiencies, especially of vitamin A, iodine,iron, and zinc, are widespread in the underdeveloped world.
Micronutrient deficiencies have been estimated to affectalmost two billion people worldwide. Such nutritional
deficiencies can increase susceptibility to infectious diseases

Cholinef

Vitamin K

80 mcg

120 mcg

90 mcgCalcium

1,000 mg

1,000-1,200 mg

1,000-1,200 mg

Chloride3,400 mg

1,800-2,300 mg

1,800-2,300 mg

Chromium

120 mcg

30-35 mcg

20-25 mcg

Copper2 mg

900 mcg

900 mcg

Iodine

150 mcg

150 mcg

150 mcg

Iron

18 mg

8 mg

8-18 mg

Magnesium

400 mg400-420 mg

310-320 mg

Manganese

2 mg

2.3 mg

1.8 mgMolybdenum

75 mcg45 mcg45 mcgPhosphorus

1,000 mg

700 mg

700 mgPotassium

3,500 mg

4,700 mg

4,700 mg

Selenium

70 mcg55 mcg55 mcg

Zinc

15 mg

11 mg

8 mg

None
established

550 mg425 mgaDietary Folate Equivalents
bNE, niacin equivalent: 1 mg NE = 60 mg tryptophan = 1 mg niacin
cRetinol Activity Equivalents
dIntake for adults >50 years should be from supplements or fortified foods due to the

age-related increase in food-bound malabsorption
e22.5 IU of natural-source alpha-tocopherol (d-alpha-tocopherol); 33 IU of syntheticalpha-tocopherol (dl-alpha-tocopherol)fConsidered an essential nutrient, although not strictly a micronutrient

10

Fall/Winter 2011

controlled trials (RCTs) have examined the effect of MVMs
on reducing the risk of various cancers, cardiovascularconditions, and other diseases, but results are largely
conflicting. Inconsistent findings among studies may bepartially attributed to variations in MVM supplement
composition, as well as dose and duration of use.
Additionally, both observational studies (studies in which agroup is simply observed over time with no experimental
intervention) and RCTs have inherent limitations thatmake it difficult to determine whether MVM use might
help prevent chronic disease. For example, people who
volunteer to be part of such studies are commonly
healthier than the average person, and some studies havefound that those who take MVM supplements have an
overall healthier diet and lifestyle than those who do nottake MVMs.
Observational studies may be subject to residual
confounding if all of the potential confounding variables
are not accounted for in the statistical model. Such studies
can only detect associations between MVM use and healthendpoints rather than establish cause-and-effect relationships. While RCTs are able to establish cause-and-effectassociations, they are ill-suited to study the effects of
micronutrients. In particular, the placebo group in RCTsof micronutrients is not a true placebo or non-exposedgroup because a micronutrient-free state does not exist in
the body without deficiency disease, and it is obviously
not ethical to deprive the control group of essential
micronutrients. Additionally, RCTs of MVM supplements
are conducted in generally healthy people (as opposed tothose with some disease) and thus would likely take years
or decades to observe a measurable effect; complianceduring such a long-term study is highly problematic.
Short-term RCTs that assess DNA damage, inflammation,
insulin sensitivity, lipid profile, blood pressure, immune
function, or other biomarkers of disease are more practicaland may be useful in determining whether MVMs help
prevent chronic disease.
While the health effects of MVM supplements are
difficult to determine, MVM supplement use is generally
considered safe for healthy people. U.S. government
regulations, called current good manufacturing practices(CGMPs), ensure that dietary supplements meet quality
standards for identity, purity, strength, and composition,
as long as supplement manufacturers comply. Although
excessive intakes of select micronutrients can be unsafe,
the amounts of micronutrients in MVM products
approximate the DVs. For most micronutrients, the DV
is considerably lower than the tolerable upper intake
level (UL)—the highest level of daily intake of a specificnutrient likely to pose no risk of adverse health effects inalmost all individuals of a specified age. The Food andNutrition Board of the Institute of Medicine recommends
that the total daily intake of micronutrients—from foods,
fortified foods, and supplements—should not exceed the
UL. The DV for vitamin A (5,000 IU) is considerably
higher than the current RDA (2,333 IU/day for womenand 3,000 IU/day for men), and excessive retinol(preformed vitamin A) intakes have been linked with bone
fractures in older adults. For these reasons, the Linus
Pauling Institute (LPI) recommends that adults take a
MVM supplement providing no more than 2,500 IU (750mcg) of preformed vitamin A, usually labeled as vitamin
A acetate or vitamin A palmitate, and no more than
2,500 IU of additional vitamin A as beta-carotene.
Additionally, because men and postmenopausal womenare not at risk for iron deficiency and excess iron can havedetrimental health effects, LPI recommends that men andpostmenopausal women take a MVM supplement withoutiron. MVM supplements formulated for men or older
adults generally do not contain iron, but one must examine
the supplement label. Although MVMs are safe for mostpeople, certain drug-nutrient interactions are possible;
thus, the use of all nutritional supplements should be
discussed with a competent healthcare provider.
According to national surveys, many Americans haveinadequate dietary intake of key micronutrients, possibly
increasing their risk for age-related diseases, such as
osteoporosis, cardiovascular disease, and some formsof cancer. Micronutrient inadequacies may also be
associated with impaired immune responses anduntoward effects on cognition. Many Americans areapparently consuming an energy-dense diet that islacking in essential micronutrients. Given the facts that
dietary habits are difficult to change and that many
people often cannot afford micronutrient-rich fruits
and vegetables, the Linus Pauling Institute recommendsa daily MVM supplement as nutritional insurance.
For information on healthy eating, see the LPI “Rx for
Health”: http://lpi.oregonstate.edu/lpirx2.html. Although
the specific consequences of chronic micronutrient
inadequacies are difficult to document, it is sensible toensure adequacy for health by taking a daily MVM
supplement at low cost and low risk. LPI

The Linus Pauling Institute11

Multivitamin/mineral Supplements and Mortality

A

recently published paper from the Iowa Women’s
Health Study (Arch. Intern. Med. 171:1625-1633,
2011) concluded that “In older women, several commonlyused dietary vitamin and mineral supplements may be
associated with increased total mortality risk; thisassociation isstrongest with
supplemental
iron.” For many,
this report isalarming,
especially sinceapproximately
half of the U.S.
population takes
at least one
dietary
supplement.
However, wefound insufficientevidence tosupport theclaims of theauthors that
dietary supplement
use is associatedwith increased
risk of mortality
in older women.

Pros and Cons of Observational Studies
First, it is important to note that the Iowa Women’s
Health Study is an observational study. In observational
studies, scientists examine associations between dietaryand lifestyle factors and the incidence of disease in the
study population, which is referred to as a “cohort.”
Although observational studies provide valuable ways
to generate hypotheses that can be further tested in
randomized, placebo-controlled trials, they cannot
establish cause and effect. Observational studies instead
establish associations between a given trait and disease
outcome, but they do this only after mathematicallyadjusting for multiple confounders—characteristics thatmight confound or confuse the association—such asage, gender, exercise habits, and body weight. Further,
despite the statisticians’ best efforts to take all of these
confounding factors into consideration, there are numerous
additional factors that haven’t been discovered yet orwere not measured in the study. This phenomenon iscalled “residual confounding” and is a major reason why
observational studies can only generate hypotheses.

In the Iowa Women’s Health Study, 38,772
postmenopausal women were asked to report their
supplement use at only three time points many years
apart (1986 at baseline, 1997, and 2004), and theirself-reported information was then related to theoccurrence of death during the corresponding interval.
The authors of the study emphasize that the mostconsistent findings were a dose-dependent increase inmortality risk with supplemental iron and a dose-dependent
decrease in mortality risk with supplemental calcium.

Study Limitations
After closer examination of the data, we note several
important limitations:
1. Healthy person or survivor bias
The supplement users were healthier and lived longer
overall. As a result, a higher percentage of them stayedin the study, while many non-users were lost to followup and their mortality data could not be assessed.
The authors report that supplement users were, in fact,“healthier” compared to non-users at baseline, characterized as having a lower prevalence of diabetes mellitus,
high blood pressure, and smoking status; having a lower
body mass index (BMI) and waist-to-hip ratio; being
more physically active; and being more likely to have
healthful dietary patterns. This differential retention
during the study period biases the results, contributing
to a spurious association between supplement use
and mortality.
2. Reverse causality
People may begin taking supplements as they age orwhen they are diagnosed with disease. As a result, death islikely due to old age or disease, not dietary supplementuse. In fact, the data reveal that self-reported supplement
use increased substantially at each study interval: 62.7%
in 1986, 75.1% in 1997, and 85.1% in 2004. As thestudy cohort aged, more women began taking dietary
supplements. Furthermore, subjects with cardiovasculardisease, diabetes mellitus, or cancer were excluded fromthe analysis at baseline but not afterwards. Consideringthat the follow-up period spanned 19 years and the mean
age at baseline was 60.1 years, it is likely that disease
emerged during the study period. The authors do notstate the cause of death; therefore, it is misleading toblame the supplement—rather than a serious chronic
disease—for mortality.
3. Recall bias
Self-reported use of dietary supplements is prone torecall error, and such data tend to be selective andinaccurate. Importantly, there is no information on

Continued on page 14

12

Fall/Winter 2011

Vitamin E and Prostate Cancer in Healthy MenApaper published recently from the Selenium andVitamin E Cancer Prevention Trial (SELECT) in
the Journal of the American Medical Association (JAMA
306:1549-1556, 2011) concluded that “dietary
supplementation with vitamin E significantly increased therisk of prostate cancer among healthy men.” This alarming
news spread fast, and many men are now wondering if itis prudent to take vitamin E supplements in light of thisnew information.
To date, two large randomized, placebo-controlled trials(RCTs) have been conducted in healthy men to investigate
the effect of vitamin E supplementation on prostatecancer: The Physicians’ Health Study (PHS) II and
SELECT. PHS II (JAMA 301:52-62, 2009) followed
14,641 healthy men, aged 50 years and older, given 400
International Units (IU) of synthetic vitamin E every otherday for eight years. In SELECT, 35,533 healthy men,
aged 50 and older, received 400 IU of synthetic vitamin E
every day for seven years. In both trials, there was nobenefit of taking vitamin E supplements on prostatecancer risk. After a median time of 5.5 years in SELECT,
vitamin E supplementation was discontinued, yet followup of the study participants continued for 1.5 years inorder to document additional events. Unexpectedly, the
SELECT updated analysis published recently in JAMA
found a 17% increased risk of being diagnosed withprostate cancer in men who had taken the vitamin E
supplement compared to those who had received placebo.
No biological mechanism was proposed to explain theincreased incidence of prostate cancer.

Why Did They Look at Vitamin E in theFirst Place?
Vitamin E functions as a powerful, fat-soluble antioxidant in our cells and tissues. Antioxidants neutralize
the effects of free radicals, highly reactive species thatoxidize DNA, proteins, and lipids inside our cells,
potentially causing damage and contributing to disease.
In particular, oxidative DNA damage may cause mutations
and, hence, increase the risk of certain cancers, including
prostate cancer. Free-radical exposure is an unavoidable
aspect of our lives, as these radicals are produced as anatural by-product of many biological processes, such as
cellular respiration and inflammation, in addition tocoming from our environment, particularly cigarettesmoke. Antioxidants produced in the body and ingested
in the diet are essential to reduce oxidative stress andcounteract the potentially harmful effects of free radicals.
Some studies support a beneficial role for vitamin E incancer and cardiovascular disease prevention. For example,
the Women’s Health Study (JAMA 294:56-65, 2005)
followed 39,876 women who took 600 IU natural vitamin
E every other day for ten years. The investigators foundthat supplemental vitamin E decreased cardiovascularrelated deaths by 24% but had no effect on cardiovascular

events, overall cancer incidence, or cancer-related deaths.
In general, studies have reported mixed results, and theimpact of vitamin E supplementation on chronic diseaserisk remains controversial.

Why Are the Results Different?
The Women’s Health Study (WHS), PHS II, and
SELECT are RCTs, also referred to as clinical trials orintervention studies. In RCTs, individuals are randomly
assigned to either treatment (vitamin E in this case) or
placebo, and the impact of the intervention on disease
incidence is evaluated after several years.
The important issues that emerge from these RCTs
are vitamin E dose (200-400 IU/day), vitamin E form
(natural vs. synthetic), and population studied. Synthetic
vitamin E (all-rac-alpha-tocopherol or dl-alphatocopherol) has half the bioactivity of naturally
occurring vitamin E (RRR-alpha-tocopherol or d-alphatocopherol)––hence, the “effective dose” in PHS II and
SELECT was only 100 and 200 IU/day, respectively,
and 300 IU/day in WHS. Higher doses may be needed toeffectively reduce oxidative stress. In one dose-response
study, significant reductions in plasma F2-isoprostanes(a marker of oxidative stress) occurred only at daily
doses of at least 1,600 IU of natural-source vitamin E.
Notably, this dose is above the tolerable upper intake
level (UL) of 1,500 IU/day set by the Food and Nutrition
Board of the Institute of Medicine.
The fact that the vitamin E doses used in the RCTs
appear insufficient to lower oxidative stress may explain
the lack of benefit with respect to cancer risk. It remains
unknown whether oxidative stress plays a causal role inprostate cancer. Furthermore, it remains unexplained

Continued on page 14

The Linus Pauling Institute13

Continued from page 12 — Multivitamin/mineral
Supplements and Mortality

Continued from page 13 — Vitamin E and
Prostate Cancer in Healthy Men

supplement dose (with the exception of calcium andiron), formulation, or frequency provided for the analysis.
Daily supplement habits can vary considerably over time,and multivitamin/mineral supplements are not uniformly
formulated. Many contain amounts of reactive metals
like iron that are not needed as supplements bypostmenopausal women (or men).

why vitamin E supplementation in SELECT was
associated with a 17% increased risk of prostate cancer,
whereas vitamin E supplementation in PHS II and WHS
was not associated with increased risk of any type ofcancer in men and women, respectively.

4. Generalizability issues
The cohort consisted of only white, postmenopausal
women with higher than average rates of supplementuse. This is not a representative population and theapplicability of the findings to premenopausal women,men, other ethnic groups, and the general population
is not appropriate.

LPI’s Recommendation
According to data from the National Health andNutrition Examination Survey (NHANES), many
Americans are not meeting current intake recommendations
for several micronutrients. Even when considering
micronutrient intake from fortified foods and dietary
supplements, an estimated 70% of the U.S. population
aged 2 years and older do not meet the estimated average
requirement (EAR) for vitamin D, 60% for vitamin E,
45% for magnesium, 38% for calcium, 34% for vitamin
A, and 25% for vitamin C. Multivitamin/mineral
supplements are a simple, inexpensive, and safe way
to help fill these nutritional gaps and improvemicronutrient status.
As part of its “Rx for Health” (http://lpi.oregonstate.edu/
lpirx2.html), LPI recommends a daily multivitamin/mineral supplement as nutritional insurance to meetmicronutrient needs. Some multivitamin/minerals may
provide excessive iron or vitamin A, which can haveuntoward health effects. Therefore, LPI recommends that
men and postmenopausal women take a multivitamin/mineral without iron and containing no more than 2,500
International Units (IU), or 750 mcg, of preformed
vitamin A (usually labeled vitamin A acetate or vitamin
A palmitate) and no more than 2,500 IU of additional
vitamin A in the form of beta-carotene. For more
information on multivitamin/mineral supplements, see
the article on page 10 of this Newsletter.
In summary, it would not be prudent to discourage theuse of all vitamin and mineral supplements based on asingle, flawed study. Each micronutrient fulfills one orseveral specific biological functions in normal metabolism
and good health. It is not sensible to discourage the useof micronutrient supplements when so many people in
the U.S. and around the world have insufficient dietaryintakes of many vitamins and minerals. LPI

Finally, the population studied in SELECT was healthy
males consuming a well-balanced diet, most of whom
likely were not vitamin E deficient or under increasedoxidative stress. Unfortunately, neither baseline vitamin
E levels in the study participants’ blood nor their oxidative
stress status was assessed. In situations of stress, disease,or deficiency, meeting an increased demand with vitamin
E supplementation may be warranted. However, in
healthy people, vitamin E supplementation shows noadded benefit on disease risk, as confirmed by the RCTs
discussed here. For example, a study on the effect of
supplemental vitamin E on cancer risk in 29,000 Finnish
male smokers (the Alpha-Tocopherol Beta-Carotene[ATBC] trial) reported in 1998 that daily supplements of
75 IU/day of synthetic vitamin E for five to eight years
were associated with a 32% and 41% reduction in
prostate cancer diagnosis and mortality, respectively,
compared to unsupplemented smokers. However, among
other limitations, the ATBC study was not designed toassess prostate cancer incidence as a primary endpoint.
Since oxidative stress was not measured in the study
subjects, the mechanism for the possible protective effectof low-dose vitamin E remains obscure. Factors otherthan oxidative stress play an important role in the
etiology of prostate cancer, such as endogenous
hormones, race, age, and dietary fat intake.
Based on the lack of conclusive evidence for a benefit ofvitamin E supplementation in cancer and cardiovasculardisease prevention in generally healthy adults and thepotential for harm in certain subpopulations, the Linus
Pauling Institute has revised its “Rx for Health”(http://lpi.oregonstate.edu/lpirx2.html) and no longer
includes a recommendation for supplemention with
200 IU/day of natural-source vitamin E.

What to Do?
Vitamin E is an important micronutrient, and meeting
daily recommendations is critical for optimum health.
The Recommended Dietary Allowance (RDA) of vitamin
E for adult men and women is 22.5 IU per day. Notably,
more than 90% of individuals aged 2 years and older in
the U.S. do not meet the daily requirement for vitamin E
from food sources alone. Major sources of vitamin E in
the American diet are vegetable oils, nuts, whole grains,and green leafy vegetables.
Taking all the issues discussed above into consideration,
LPI recommends that generally healthy adults take adaily multivitamin/mineral supplement, which usuallycontains 30 IU of synthetic vitamin E, or 90% of the RDA.
LPI

14

Fall/Winter 2011

Developments• Gifts from your IRA can fulfill your annual
required minimum distribution in part orin full.

Michele Erickson
LPI Director of Development• Gifts can only be made directly to publiccharities to be eligible for tax benefits. A gift
cannot be made to a charitable remainder trustor charitable gift annuity.

DON’T MISS this last chance
opportunity to make a tax-free gift
to the Linus Pauling Institute fromyour IRA!

The Next Step
Contact both your IRA administrator and yourtax professional if you are considering a gift under
this law. Feel free to call the OSU Foundation
Gift Planning Office at 1-800-336-8217 or
OSUFGiving@oregonstate.edu with any questions.

D

onors who are 701/2 or older can donate
up to $100,000 per year from their IRA
directly to a charity without paying income tax
on the money. This is a significant incentive thatremoves the tax penalty for some donors whowant to use their IRAs to fund a charitable gift.
The IRA Charitable Rollover Legislation is
only valid through December 2011.

LPI

bequests
LPI is grateful for thethe
we have received from
year:
st
pa
is
th
following friends• Gifts can only be made from an IRA.
Pension, 401k, profit sharing and other formsof retirement funds do not fall under thislegislation. However, donors can roll overnon-qualifying accounts (e.g., 401k) into thequalifying IRA account in order to make a gift.

Ella C. Brauch
Sally Wilson Fish
Donna Halter Hablitzel
Pauline Modica
Arnold E. Molzon
Alice Richards
Helen P. Rumbel

Photo by Karl Maasdam

Photo by Karl Maasdam• Gifts can be made to multiple charities inany combination that does not exceed the$100,000 per year per person limit.

Tammy Valley, Pat Reser, and Linus Pauling Jr.

Pat Reser, Dean of Science Sherm Bloomer, OSU President Ed Ray,LPI Director Balz Frei, and Tammy Valley

The Wayne and Gladys Valley Foundation and Al and Pat Reser made leadership gifts
to the fund-raising campaign for the Linus Pauling Science Center.

The Linus Pauling Institute15

Linus Pauling Institute

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307 Linus Pauling Science Center
Corvallis, Oregon 97331

Portland, OR
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phone: 541-737-5075
fax: 541-737-5077
email: lpi@oregonstate.edu
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to theLinus Pauling
Institute
Gifts in support of research
efforts can be made at any time.
Checks should be payable to
OSU Foundation for
Linus Pauling Institute.
Information on giving isavailable through the
OSU Foundation,
1-800-354-7281, or by
writing to the Institute.

Micronutrient
Research for
Optimum Health
Printed on recyclable paperusing soy inks

The Linus Pauling
Science Center
LPI and Chemistry
moved into our
new 105,000-squarefoot building in
September.

Photo by Karl Maasdam

Look for these informative articles inside!
Page 1 ....... From the Director
Page 1 ....... LPI Diet and Optimum
Health Conference
Page 6 ....... The Linus Pauling InstitutePrize for Health Research
Page 8 ....... The Linus Pauling Science Center
Page 10 ..... Multivitamin/mineral
Supplements

Page 12 .... Multivitamin/mineral Supplements
and Mortality
Page 13 .... Vitamin E and Prostate Cancer
in Healthy Men
Page 15 ..... Developments
Special thanks to Barbara McVicar for editorialassistance and photographs, authors of signed
articles, and Dick Willoughby for the logo
photograph of Linus Pauling.