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Oregon State University

The

Linus Pauling
Institute

R E S E A R C H

N E W S L E T T E R

From theDirector

Dairy, Beans,and HealthBalz Frei, Ph.D.
LPI Director and Endowed ChairOSU Distinguished Professor of
Biochemistry and Biophysics

An interview with Gerd Bobe, Ph.D.
Assistant Professor of Animal Sciences
LPI Principal InvestigatorIt is my pleasure to introduce the latest addition to theLinus Pauling Institute—Dr. Kathy Magnusson, whojoined the Institute’s Healthy Aging Program as a Principal
Investigator in March. She comes to us from the Departmentof Biomedical Sciences in the College of Veterinary Medicine
at Oregon State University, where she is a tenured professor.
Dr. Magnusson received both a Doctor of Veterinary
Medicine (D.V.M.) and a Ph.D. degree from the Universityof Minnesota, with a major degree in veterinary anatomy
and a minor degree in neuroscience. After holding faculty
positions at Colorado State University and the Universityof Idaho, she joined Oregon State University in 2005.

Dr. Magnusson calls herself an “aging
neuroscientist interested in how we canprevent or repair the declines that occur
during aging in learning and memory ability.”
She jokingly adds that she hopes “to figure
this out before I forget what the questionis.” Dr. Magnusson is particularly interested
Dr. Magnusson
in how aging affects specific proteins in thebrain called “N-methyl-D-aspartate (NMDA) receptors,”
which play a dominant role in memory function. She also
is investigating how dietary and lifestyle interventions may
slow age-related cognitive decline, memory loss, and brain
atrophy, the harbingers of Alzheimer’s disease.
A few years ago, she was the recipient of an LPI Pilot
Project grant—together with her colleague, Dr. Jane
Ishmael—to investigate how dietary zinc levels may
influence NMDA receptor properties in the elderly. She also
has collaborated with several LPI Principal Investigators,
including Dr. Tory Hagen, with whom she explored therole of lipoic acid in the aging brain. Since there is evidence

continued on page 2

Q. You were born and raised in Europe.
What brought you to the United States?
A. I was raised on a farm in western Germany. Originally,

I wanted to study abroad for one year. When I talked
to students who had studied abroad, they told me thatone year wouldn’t be enough to learn about American
culture and research. So I applied for a Master’s degree,
met my wife, earned my Ph.D., and stayed here.

Q. Is there much difference between the research
environment in Europe and in the United States?
A. There were many differences when I left Europe in theearly 1990s. For example, less funding was available forresearch in agriculture and animal science.

Q. You earned a Ph.D. in animal nutrition from
Iowa State University. Do you think that yourearly exposure to farm life stimulated yourinterest in animal nutrition?
A: Definitely. I have an older brother who did all theoutside work, while I helped with the animals. Taking
care of animals has always been very important to me.

Q. Your initial research concerned the fatty acid andprotein composition of milk in cows and dairy
products. What did you learn about that relationship?
A. In a series of studies, I showed that milk protein andfatty acid profiles can be altered by the cow’s dietand breeding.

Q. How does the cow’s diet affect the quality ofdairy products like milk and butter?
A. I demonstrated in a series of experiments that the cow’s
continued on page 2— 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
that elevated vitamin D levels in the elderly are correlatedwith improved cognitive function, Dr. Magnusson is
also collaborating with LPI’s Dr. Fritz Gombart toinvestigate how vitamin D deficiency and vitamin D
supplementation affect memory in young and old mice.
Coincidentally, Dr. Maret Traber and I were recently
involved in a related study looking at diet and brain
function in the elderly (summarized on page 6). In
collaboration with Dr. Gene Bowman of Oregon Health& Science University in Portland, we found that oldadults who had high plasma levels of B vitamins andvitamins C, D, and E performed better on memory andlearning tests and had less brain shrinkage than oldadults with lower plasma levels of these vitamins.
High plasma levels of B vitamins and C and E reflect a
Mediterranean-type diet rich in fruits and vegetables,
whole grains, nuts, and vegetable oils. Vitamin D is formedin the skin upon sun exposure, and only a few foods likefish and fortified milk provide vitamin D in the diet.
A similar association was observed between increased
plasma levels of omega-3 fatty acids and healthy brain
aging. These omega-3 fatty acids, often called EPA and
DHA, are primarily found in marine fish and fish oil
supplements. Our findings are consistent with previous
research suggesting that low DHA status is a risk factor
for Alzheimer’s disease and other types of dementia. In
addition, the study with Dr. Bowman found that oldpeople with high plasma levels of trans fats from highly
processed, nutrient-poor foods, such as packaged,
fried, or baked foods, were more likely to exhibit brain
shrinkage and score lower on the cognitive function tests
than old people with low plasma levels of trans fats.
Interestingly, all of these dietary patterns associatedwith poor or healthy brain aging are also associatedwith cardiovascular health. For example, people who
eat diets high in fruits and vegetables have about a 20%
lower risk of suffering a heart attack and a 30% lower
risk of a stroke, while high intake of trans fats is
associated with about a 20% increased risk of thesecardiovascular events. In addition, clinical trials haveshown that fish oil supplements significantly lower therisk of heart attacks and sudden cardiac death in people
with heart disease. These parallels between dietary
patterns and either brain or heart health suggest
common underlying causes, such as chronic
inflammation or high blood pressure. Indeed, it is
known that inflammation is counteracted by fish oils,
and a diet rich in low-fat dairy products and fruits
and vegetables, as well as vitamin C supplementation,
have beneficial effects on blood pressure.
While more studies are needed to demonstrate a
causal link between brain health in the elderly and thebeneficial or detrimental dietary patterns identified inour study with Dr. Bowman, these data certainly are
intriguing and, well, food for thought! LPI

2

Spring/Summer 2012

Continued from cover — Interview with Gerd Bobe
diet can improve the fatty acid profile and the texturalproperties of milk and dairy products.

Q. How does changing the cow’s diet by including
certain grains or nuts influence things like butter?
A: Feeding cows oil seeds that are rich in polyunsaturated
fatty acids increases the proportion of unsaturated
fatty acids and decreases the proportion of saturated
fatty acids in dairy products.

Q: Were you mainly interested in the health effectsof the dairy products, not their palatability?
A: The main focus was to improve the fatty acid profileand the nutritional properties of dairy products forhuman consumption.

Q: Do you think that the routine use of hormones indairy cows or cattle poses any serious threat tohuman health?
A: I’m not aware of any detrimental effects on human health.
Q: What about the use of antibiotics to spur growth
and to protect cows and cattle from infection?
Do you think that has any health consequence forpeople who consume those dairy or beef products?
A: Again, I’m not aware of any detrimental effects onhuman health when antibiotics are used according totheir labeled directions.

Q: Does cow’s milk contain partially hydrogenatedor trans fat and, if so, does that haveconsequences for human health?
A: The milk of dairy cows contains trans fatty acids; however,consumption of trans fatty acids from ruminant sources
has not been associated with detrimental effects onhuman health, unlike trans fatty acids from the industrial
partial hydrogenation of vegetable oils.

Q: What is conjugated linoleic acid, or CLA? Does it
have any special health benefit?
A: Conjugated linoleic acid is a group of isomers of linoleic

acid. Isomers are compounds that have the same chemical
makeup but different structures. Most research has been
done on cis-9, trans-11 linoleic acid and trans-10, cis-12
linoleic acid. I was involved in a study that examinedthe effect of these isomers on gene expression of the
corpus luteum in the ovaries of cows and reported thatboth isomers downregulated the gene expression of
cyclooxygenase 2 (COX-2). Inhibitors of COX-2 havebeen shown to inhibit inflammation and decrease therisk of many chronic diseases.

Q: How does CLA occur in dietary sources?
A: Cis-9, trans-11 linoleic acid is predominantly

synthesized in tissues from trans-11 linoleic acids bydelta-9 desaturases. Trans-10, cis-12 linoleic acid and theremaining proportion of cis-9, trans-11 are synthesized by
microorganisms in the cow’s rumen from linolenic acidand linoleic acid.

Q: You’ve also looked into the relationship between
selenium status and immune function in sheep.
Does that have relevance to people?
A: The objective of the studies has been to examine the effectof selenium source (inorganic sodium selenite versus
organic selenium yeast) and dosage (regular versus
supranutritional—higher than what is usually consumed
dietarily—dosage) on selenium status, performance, andhealth of ewes and their progeny. The studies arestill ongoing.

Q: A lot of your research has focused on the effectsof flavonoids, which are polyphenolic pigmentsfrom plants, on intestinal cancer in mice, the riskof pancreatic cancer in human smokers, and therecurrence of colorectal polyps in the PolypPrevention Trial. What led to your interestin flavonoids?
A: In cell culture and animal models for chronic diseases,

flavonoids exhibit biochemical properties beneficial for theprevention of multiple chronic diseases, including cancer.
Looking at the effect of flavonoids on cancer risk inepidemiological studies was the logical next step.

Q: What was the Polyp Prevention Trial?
A: The Polyp Prevention Trial (PPT) was a large, multicenter,randomized four-year nutritional intervention trial in theearly 1990s that evaluated the effects of promoting ahigh-fiber, high-fruit and -vegetable, low-fat diet on therecurrence of any or advanced colorectal adenoma.

Q: What was the main outcome of that study?
A: The main outcome was that the intervention and control

Q: Since absorption of flavonoids into the bloodstream is quite limited, and they are very quickly
metabolized once absorbed, is their beneficial
effect due, then, to a local effect in the colon?
A: This is an area of active research—we did not
examine that.

Q: What compounds are synthesized by gut
microbes that might have beneficial effects?
A: Butyrate is one compound that has been proposed

to have beneficial effects. There are probably many
more compounds that have beneficial effects—this is anew, rapidly growing research area. We still have a lot
to learn.

Q: What is butyrate?
A: Butyrate is a four-carbon, short-chain fatty acidproduced by intestinal microorganisms.

Q: How do flavonoids compare with other dietaryfactors in protecting against polyp formationor colon cancer?
A: In the PPT, a high-dry bean diet and a flavonol-richdiet were associated with decreased advanced adenoma
recurrence.

Q: Do different types of flavonoids have different
health effects?
A: Based on results from cell culture studies and animalmodels of chronic diseases, individual flavonoids differ
in their action on biochemical pathways. In the PPT,
only the consumption of the flavonoid subgroups
flavonols and, to a smaller extent, isoflavonoids
was associated with decreased advanced adenoma
recurrence.

continued on page 4group did not differ in recurrence of any or advanced
adenoma. However, strict adherence to a low-fat (≤ 20%of energy intake), high-fiber (≥ 18 grams per 1,000 kcal ofenergy), high-fruit and -vegetable diet (≥ 3.5 servings per
1,000 kcal) was associated with a 35% and 56% decreaseof any and advanced colorectal adenoma recurrence,
respectively.

Q: Did they measure oxidative stress or inflammationin those participants?
A: Several genetic and blood markers of metabolic syndrome
and inflammation were measured. We identified several
biomarkers that were modified by diet and/or predictedrisk of adenoma recurrence.

Q: Do we know that flavonoids in food help protect
against polyps or colon cancer?
A: In the PPT, a flavonol-rich diet was associated with adecreased risk of advanced colorectal adenoma recurrence.
Flavonols are a subclass of flavonoids.

The Linus Pauling Institute3

Continued from page 3 — Interview with Gerd Bobe

Q: Is it possible to estimate total flavonoid intake
from the diet?
A: It is difficult to accurately estimate flavonoid intake

from the diet because of limitations in flavonoid
databases from foods, variations in the food quantities
of recipes, and variability of flavonoid content due tothe climatic, growing, soil, and harvesting conditions ofplants, and storage conditions and preparation of foods.

Q: Why are flavonoids synthesized in plants?
What function do they perform?
A: Flavonoids have multiple functions in plants. It has

been proposed that flavonoids and their metabolites
have roles in UV protection and signaling in symbiosis,
as well as acting as chemical messengers to regulate
physiological processes, as pigments to attract pollinator
animals, and as defensive compounds against pathogens.

Q: Flavonoids in tea have been found to inhibit
lesions in the rat colon induced by dietary
mutagens. Do flavonoids also protect against
esophageal cancer?
A: There are two histological types of esophageal cancer—
esophageal adenocarcinoma (EAC) and esophageal
squamous cell carcinoma (ESCC)—that differ in their
etiology. EAC is associated strongly with gastroesophageal reflux disease and obesity, while ESCC isassociated strongly with tobacco and alcohol
consumption. I was involved in a population-based,case-control study of white and black men in the U.S.
that examined the effect of flavonoid consumption on
the risk of EAC and ESCC. Overall, consumption of
total flavonoids had little protective effect in thispopulation of heavy smokers and drinkers; however,there was some suggestion that foods rich in theflavonoid subgroup anthocyanidins may be protective
in EAC and that isoflavonoid-rich foods may beprotective in ESCC.

Q: You also investigated the role of lignans,legumes, beans, and sugar on colon cancer.
What did you find?
A: Lignans are diphenolic compounds present in the

structural portion of plants, which are partially or
fully converted by the intestinal microorganisms toenterolactone and enterodiol. In the PPT, individual
and total lignan intake was not associated withcolorectal adenoma recurrence; however,high-lignan intake was associated with
the increased risk of any adenoma
recurrence in women and inindividuals with saturated fat
intake below or equal to18.3 grams per day.

4

Spring/Summer 2012

Q: What about legumes and beans?
A: In the PPT, a high-dry bean diet was associated with adecreased risk of advanced colorectal adenoma
recurrence. The results from the PPT were followed upby the Legume Inflammation Feeding Experiment(LIFE), a randomized, crossover feeding study of alegume-enriched (250 grams per day) diet among men
under conditions of weight maintenance. The main
study was followed by a third, optional four-weekperiod, which encouraged weight loss. Participants loston average 4.4% of their body weight during theweight-loss phase and improved biomarkers of
metabolic syndrome and inflammation.

Q: What about sucrose intake?
A: Using a mouse model of colon cancer, we reported thatsucrose compared to cornstarch consumption increased
tumor number, serum glucose and insulin concentrations,and body weight in those mice.

Q: Does a low glycemic diet that emphasizes legumes
improve blood lipid profiles?
A: During the four weeks on the high-legume, high-fiber,and low-glycemic index diet in the LIFE Study, total andlow-density lipoprotein (LDL) cholesterol concentrations
during the weight-maintenance phase decreased by 10%
and 11%, respectively, and during the weight-loss phaseby 13% and 16%, respectively. In addition, total triglyceride concentrations decreased on the high-legume dietby 15% and 28% during the weight-maintenance phaseand the weight-loss phase, respectively.

Q: How does that diet affect insulin resistanceand inflammation?
A: During the four-week weight-loss phase, glucose andinsulin concentrations dropped by 6% and 14%,respectively. In addition, concentrations of theinflammatory markers, C-reactive protein and soluble
TNF receptor 1, decreased during the weightmaintenance phase and the weight-loss phase.

Q: What kinds of beans were used in that diet?
A: The high-legume diet contained approximately 250

grams or 1.5 cups of legumes a day. The legumes wereof the Phaseolus vulgaris species and included navy,
pinto, kidney, lima, and black beans.

Q: Based on your research in this area, would you
make any special dietary recommendations forpeople who are trying to manage weight and help
prevent age-related disease?
A: The results of the PPT and the LIFE study areencouraging. Further research needs to be done tovalidate those findings before dietary recommendations
can be made. Personally, I increased my consumption ofbeans, fiber, fruit, and vegetables over the last few years.

Q: What are you currently working on?
A: I work on identifying metabolic pathways and biomarkers
that are modifiable by legume and flavonol intake andcan predict cancer risk.

Q: And that, of course, has relevance not only tocancer but also to cardiovascular disease
and diabetes?
A: Yes.
Q: Where is your research headed?
A: My research is headed toward personalized cancer andgenomics, proteomics, metabolomics—to look at genes,
proteins, metabolites, and other substances in humanintervention trials to identify subpopulations that most
likely benefit from a particular diet.

Q: How do you like the Linus Pauling Institute’s
new building?
A: It is a dream come true!
Q: Does it meet all your research needs?
A: Definitely! It is great to work in close proximity to agroup of very talented and highly successful researchers,
which makes your own work so much better.

Q: Do you like living in Oregon?
A: Yes. We are close to the coast and to the mountains,

and the rain in the winter doesn’t bother me. Corvallis
reminds me of where I was raised in Germany.

Q: What do you like to do in your free time?
A: I love to spend time with my seven-year-old daughter.
Family is very important to me.

LPI

disease prevention. I will use an “omics” approach—

RECENT PUBLICATIONS BY LPI SCIENTISTS
SUMMARIES OF SELECTED PUBLICATIONS BY STEPHEN LAWSONLPI scientists are identified in boldface.

Healthy Aging Program
GOMBART AF. The vitamin D-antimicrobial peptide
pathway and its role in protection against infection. Future
Microbiol. 4:1151-1165, 2009
In the early 19th century, exposure to sunlight was foundto be beneficial for tuberculosis patients, although themechanism was unknown. Sunlight is required for theendogenous synthesis of vitamin D in the skin. Recent
research has found that vitamin D regulates the synthesisof antimicrobial peptides in the body, including cathelicidin
and defensin, involved in innate immunity. Cathelicidin anddefensin punch holes in bacterial membranes, leading totheir death. A study in hemodialysis patients by the author
showed that high cathelicidin levels in the blood wereassociated with decreased mortality from infections. Somephytochemicals and dietary fats, such as curcumin andpolyunsaturated fatty acids, may also stimulate antimicrobial peptide activity by binding to the vitamin D
receptor on cells. The quantitative relationship between
vitamin D and these antimicrobial peptides hasn’t yet
been worked out.
SHAY KP, MOREAU RF, SMITH EJ, SMITH AR, and
HAGEN TM. Alpha-lipoic acid as a dietary supplement:
Molecular mechanisms and therapeutic potential. Biochim.
Biophys. Acta 1790:1149-1160, 2009
In this review, the authors discuss the biochemical effectsof supplemental lipoic acid, which is usually found as aracemic mixture of the S and R forms. The R form has

greater bioavailability. About 20-40% of a dose of lipoic
acid is absorbed into the blood stream and then fairly
rapidly metabolized and excreted. It accumulates in theliver, heart, skeletal muscle, and, possibly, in the brain.
In humans, oral doses as high as 600 mg twice a day forsix months and intravenous infusions of 600 mg daily have
not resulted in any significant side effects or toxicity. Boththe oxidized and reduced forms of lipoic acid scavenge
reactive oxygen species and each selectively chelates reactive
metals like copper, iron, lead, and mercury. Lipoic acidinduces the synthesis of glutathione—an important
endogenous antioxidant—and may increase the absorptionof vitamin C into the blood stream. Lipoic acid influences thetranscription factor Nrf2, resulting in increased glutathione
synthesis and phase 2 detoxification enzyme levels. Lipoic
acid improves glucose handling, enhances vasodilation,
lowers blood pressure, and has anti-inflammatory
properties. Oral and intravenous lipoic acid have also
been used to significantly attenuate diabetic neuropathy.
LI L, SMITH A, HAGEN TM, and FREI B. Vascularoxidative stress and inflammation increase with age:
Ameliorating effects of alpha-lipoic acid supplementation.
Ann. N. Y. Acad. Sci. 1203:151-159, 2010
Age-related increases in oxidative stress and inflammation
have been implicated in the development of cardiovasculardiseases. In this study, the authors found that biomarkers ofcontinued on page 6

The Linus Pauling Institute5Continued from page 5 — Recent Publications

lived longer than unsupplemented mice, suggesting that leadinhibits neuroinflammation. Recent studies have also associated
low lead levels in ALS patients with longer survival.
MONETTE JS, GOMEZ LA, MOREAU RF, DUNN
KC, BUTLER JA, FINLAY LA, MICHELS AJ, SHAY KP,
SMITH EJ, and HAGEN TM. (R)-a-Lipoic acid treatment
restores ceramide balance in aging rat cardiac mitochondria.
Pharmacol. Res. 63:23-29, 2011
Ceramides are sphingolipids found in cell membranes thathave structural and signaling functions in cells. Ceramides arealso associated with oxidative stress and programmed cell
death (apoptosis) and accumulate upon exposure of cells to
inflammatory stimuli. Such accumulation may lead to alteredfunction of mitochondria—cellular organelles that generatechemical energy. The authors found that ceramides increasedby over 30% in the heart mitochondria from old rats compared to young rats. Supplementing old rats with lipoic acidfor two weeks lowered ceramide levels to those observed inyoung rats and restored mitochondrial energy metabolism.
BOWMAN GL, SILBERT LC, HOWIESON D, DODGE
HH, TRABER MG, FREI B, KAYE JA, SHANNON J, and
QUINN JF. Nutrient biomarker patterns, cognitive function,and MRI measures of brain aging. Neurology. 78:241-249,
2012

oxidative stress (e.g., superoxide radicals) and inflammation(e.g., NF-kB activation) were elevated in the aortas of old
rats compared to young rats. The levels of superoxide
dismutase—an important endogenous antioxidant
enzyme—were decreased in old rats. Supplementing thediets of old rats with lipoic acid for two weeks reduced
these biomarkers of oxidative stress and inflammation,
increased levels of superoxide dismutase, and alleviatedendothelial dysfunction.
BARBEITO AG, MARTINEZ-PALMA L, VARGAS MR,PEHAR M, MAÑAY N, BECKMAN JS, BARBEITO L,
and CASSINA P. Lead exposure stimulates VEGF
expression in the spinal cord and extends survival in amouse model of ALS. Neurobiol. Dis. 37:574-580, 2010
Amyotrophic lateral sclerosis (ALS), also known as Lou
Gehrig’s disease, is a neurological disease in which the deathof motor neurons leads inexorably to the patient’s death.
Functional mutations in the gene coding for the endogenous
antioxidant enzyme copper-zinc superoxide dismutase(SOD) are associated with a significant number of ALS
cases. Such mutations cause the enzyme to lose its affinity
for zinc, and the zinc-deficient SOD then becomes very
reactive—leading to the generation of reactive oxygen andnitrogen species in astrocytes that damage motor neurons—
and contributes to the development of ALS. Althoughenvironmental exposure to lead is a risk factor for ALS, theauthors found that, paradoxically, small amounts of lead
added to cultured astrocytes expressing the defective SOD
increased the amount of vascular endothelial growth factor,
which, in turn, protected motor neurons from death. Micewith the SOD mutation given low, non-toxic levels of lead

6

Spring/Summer 2012The Oregon Brain Aging Study began in 1989 with nearly
300 men and women aged 65 years and older to investigate
the link between diet and brain aging. Blood samples wereobtained and various nutrients were measured, including
vitamins, fatty acids, and carotenoids (beta-carotene, lycopene,lutein, etc.). Additionally, neuropsychological tests wereadministered, and the subjects’ brain volumes were assessedby MRI. Several nutrient biomarker patterns emerged fromthe analysis that were associated with cognitive function andbrain volume. In particular, those subjects who scoredhighest in plasma values for the B vitamins and vitamins C,
D, and E performed best on cognitive function tests and had
greater total cerebral brain volume. Subjects who had thehighest levels of plasma trans fats (partially hydrogenatedfats found in many processed foods) had worse cognitive
function and less total cerebral brain volume. Omega-3
fatty acids and higher lutein plus HDL cholesterol scores
were associated with better cognitive and memory function,
respectively.
GOMEZ LA, HEATH SH, and HAGEN TM. Acetyl-Lcarnitine supplementation reverses the age-related decline incarnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar
mitochondria without changing the L-carnitine content in the
rat heart. Mech. Ageing Dev. 133:99-106, 2012
Research has shown that supplementation with the nonprotein amino acid acetyl-L-carnitine (L-carnitine to which
an acetyl chemical group has been added) improves memory
performance and increases physical activity in old rats. In
this study, the authors investigated the specific biochemicalmechanisms that may explain these observations. There are
two subpopulations of mitochondria—the organelles that
produce chemical energy in cells. The authors found thatacetyl-L-carnitine increases the activity of the enzyme
carnitine palmitoyltransferase 1 (CPT1) in one mitochondrialsubpopulation in heart cells of old rats. CPT1 controls theoxidation of fatty acids, a crucial process in mitochondrialenergy metabolism, and declines with age. While these
relationships are complex and not fully understood, theauthors propose that age-related oxidative modificationsof CPT1 may be reversed by acetyl-L-carnitine
supplementation, leading to improved cardiac function
in old animals.

and do not accumulate in the body, unlike RRR-alpha-tocopherol, which does accumulate—but not excessively—due
to its slower metabolism. Results from the Women’s HealthStudy showing that vitamin E reduces the incidence ofvenous thromboembolism may be explained by vitamin E’s
interference with the conversion of active vitamin K, whichis critical in blood clotting.

Cardiovascular and Metabolic Diseases
MICHELS AJ, HAGEN TM, and FREI B. A new twist
on an old vitamin: Human polymorphisms in the geneencoding the sodium-dependent vitamin C transporter 1.
Am. J. Clin. Nutr. 92:271-272, 2010
In this commentary, the authors reflect on a paper by
Timpson et al. discussing variations among humans in thegene coding for one of the vitamin C transporters (SVCT1)
on cells. These transporters control the amount of vitamin C
that gets into the blood stream and into cells. Analysis of acohort of 15,000 people in the United Kingdom found thatpeople with a single nucleotide polymorphism (SNP) in the
SVCT1 gene have significantly reduced concentrations ofvitamin C in blood. SVCT1 is especially important in thereabsorption of vitamin C in the kidneys, and alterations in
its gene affect the level of vitamin C in the blood. The glucose
transporter may compensate for the inefficient SNP in theaffected SVCT1 gene since it takes up oxidized vitaminC, which may be increased by supplementation. Since theincidence of the SNP may be about 3% in Caucasians andover 9% in African-Americans, studies assessing the effectof vitamin C intake on health and disease outcomes shouldtake SNPs among subjects into account.
TRABER MG. Regulation of xenobiotic metabolism, theonly signaling function of alpha-tocopherol? Mol. Nutr.
Food Res. 54:1-8, 2010
Studies on vitamin E supplementation and mortality havebeen conflicting. Vitamin E is a family of eight isomers,
but only one—RRR-alpha-tocopherol (natural vitaminE)—is selectively recognized by transport mechanisms for
distribution to the body’s tissues. Vitamin E is metabolized
by cytochrome P450s, the same enzymes that metabolize
xenobiotics like drugs. Thus, the non-RRR-alpha-tocopherol
isoforms are metabolized for excretion in the urine or bile

KUIPER HC, BRUNO RS, TRABER MG, and STEVENS
JF. Vitamin C supplementation lowers urinary levels of
4-hydroperoxy-2-nonenal metabolites in humans. Free
Radic. Biol. Med. 50:848-853, 2011
Oxidative stress has been implicated in age-relateddiseases, but intervention trials with antioxidants have had
conflicting results for myriad reasons. It would be useful tovalidate biomarkers of oxidative stress that can help identify
people who might benefit from antioxidant supplementation.
The authors found that the levels of lipid peroxidation(LPO) products in urine can be affected by vitamin C intake.
LPO products are derived from polyunsaturated fatty acids
and can damage proteins and DNA; they are associated with
Alzheimer’s disease and cancer. Specifically, supplementation
with 500 mg of vitamin C twice per day for 17 days involunteers reduced levels of urinary LPO products by
20-30%. These LPO products may be more sensitive
biomarkers of oxidative stress than the commonly used F2isoprostanes, which are also products of lipid peroxidation.
JUMP DB. Fatty acid regulation of hepatic lipid metabolism.
Curr. Opin. Clin. Nutr. Metab. Care 14:115-120, 2011
In this review, the author summarizes findings from studies
on the role of dietary fatty acids in the metabolism of fatsin the liver. People with diabetes or metabolic syndrome
typically have low levels of polyunsaturated fatty acids(PUFA). In mice, high-fat diets lead to hyperglycemia,
insulin resistance, and fatty liver—conditions that areassociated with decreased levels of enzymes that synthesize
PUFA in the liver. Fatty acid elongase is a liver enzyme
involved in the synthesis of PUFA that regulates
carbohydrate metabolism and liver lipid content.

continued on page 8

The Linus Pauling Institute7

Continued from page 7 — Recent Publications
LOTITO SB, ZHANG WJ, YANG CS, CROZIER A, and
FREI B. Metabolic conversion of dietary flavonoids alters
their anti-inflammatory and antioxidant properties. Free
Radic. Biol. Med. 51:454-463, 2011
Flavonoids are pigmented compounds found in fruits,
vegetables, and tea that protect them from UV light andpathogens. They are believed to have health benefits inhumans, but their mode of action has been unclear because
they are poorly absorbed and then chemically modified
before being rapidly excreted. The authors studied theanti-inflammatory and antioxidant activity of two
flavonoids—quercetin (found in apples) and catechins(found in tea) and their metabolites—in human aortic
endothelial cells in culture. The antioxidant and antiinflammatory behavior of metabolites differed significantly
from the parent compounds depending on the type ofchemical modification, illustrating that the biological activityof metabolites of the dietary flavonoids cannot be predicted.
Cell culture studies have limited utility in evaluating theactivity of dietary flavonoids in the body.

LEGETTE L, MA L, REED RL, MIRANDA CL,
CHRISTENSEN JM, RODRIGUEZ-PROTEAU R, and
STEVENS JF. Pharmacokinetics of xanthohumol andmetabolites in rats after oral and intravenous
administration. Mol. Nutr. Food Res. 55:1-9, 2011
In vitro and rodent studies have shown that xanthohumol,
a flavonoid in hops used to make beer, has antioxidant,
anti-inflammatory, antimicrobial, and cancer chemoprotective properties. However, not much is known about
the uptake of xanthohumol into the blood stream fromthe gut, its distribution to tissues, or its metabolism in vivo.
The authors gave low, medium, and high doses ofxanthohumol to rats and determined that peak plasma
concentrations were achieved about four hours after
dosing and that half of the xanthohumol was gone fromthe plasma in 18-30 hours.

8

Spring/Summer 2012

Bioavailability correlated inversely with the dose; it was
highest for the low dose and lowest for the high dose. The
levels of metabolites peaked in plasma about 15-25 hours
after initial xanthohumol dosing. Scaling from rats tohumans on the basis of body weight suggests that the dietaryintake of xanthohumol by humans is insufficient to achieve
its postulated health benefits.
TRABER MG and STEVENS JF. Vitamins C and E:
Beneficial effects from a mechanistic perspective. Free Rad.
Biol. Med. 51:1000-1013, 2011
Vitamin C, required for collagen synthesis to prevent
scurvy, plays a number of other crucial biochemical roles inthe body. It regulates hypoxia-inducible factor-1 (HIF-1),
which is involved in cell growth, metal transport,
programmed cell death (apoptosis), blood vessel formation(angiogenesis), and energy metabolism. Vitamin C lowers
levels of the HIF-1alpha subunit, high levels of which havebeen associated with aggressive cancer. Vitamin C
accumulates in immune cells called neutrophils when they
attack bacteria, presumably to protect the neutrophils fromdamage by the reactive oxygen species they produce tokill pathogens. The suppression of HIF-1 by vitamin C also
regulates the death and removal of neutrophils when they
have completed their function. Importantly, vitamin C is
the premier water-soluble antioxidant in blood and protects
against damaging free radicals and, with vitamin E, theformation of oxidized lipids. In cultured cells, vitamin C
reacts with the lipid peroxidation product acrolein—a toxic
and potentially carcinogenic substance primarily formed byheating food—assisting in its metabolic degradation andelimination. Vitamin C also exerts beneficial effects
on blood pressure and vascular function by indirectly
improving nitric oxide activity.
Vitamin E is a family of eight fat-soluable antioxidant
molecules, only one of which, RRR-alpha-tocopherol, isselected for distribution to tissues. Deficiency of vitamin E
causes hemolysis (rupture of red blood cells) and peripheral
neuropathy. The degeneration of sensory neurons—leadingto ataxia—has been observed in infants deficient in vitamin
E due to fat malabsorption problems. There also seems to bea role for vitamin E in preserving proper immune function
in elderly people. Vitamin E terminates the chain reaction oflipid peroxidation and is regenerated from its oxidized formby vitamin C. In some populations studied, such as elderly
women, supplemental vitamin E decreased cardiovascularmortality, heart attacks, and strokes. While adequate vitamin
E intake over a lifetime may help protect against chronic
diseases, about 95% of Americans did not meet the Estimated
Average Requirement some years ago (12 mg/d [17.9 IU/d]
for adult men and women). Vitamin E may also ameliorate
abnormally high levels of oxidative stress. Furthermore,
vitamin E interferes with the synthesis of vitamin K, which is
involved in blood clotting, possibly preventing thrombosis.

Cancer Chemoprotection Program
HO E, CLARKE JD, and DASHWOOD RH. Dietary
sulforaphane, a histone deacetylase inhibitor for cancer
prevention. J. Nutr. 139:2393-2396, 2009
In the cell’s nucleus, DNA is wrapped around proteins
called histones. Acetylation (addition of acetyl chemicalgroups) of histones results in genes being turned on, andthe deacetylation of histones causes genes to be turned off.
Histone deacetylase (HDAC) inhibitors, therefore, keep
genes, including tumor suppressor genes, active. Cancer cells
seem to be especially sensitive to acetylation, which triggers
differentiation and apoptosis (programmed cell death).
Sulforaphane—found in cruciferous vegetables likebroccoli—is an isothiocyanate whose metabolites act as
HDAC inhibitors. Sulforaphane also induces Phase 2
enzymes that detoxify carcinogens, which is important in
the early stage of carcinogenesis. It has also been found to
induce cell-cycle arrest in cultured human prostate cancer
cells and to slow tumor growth in xenografts of humanprostate cancer cells in mice. In a mouse model of coloncancer, sulforaphane inhibited the development of polyps.
About 74% of sulforaphane from broccoli extracts areabsorbed in the intestine and have a biological half-life ofabout two hours.
HSU A, BRAY TM,
and HO E. Antiinflammatory activityof soy and tea inprostate cancer
prevention. Exp. Biol.
Med. (Maywood)
235:659-667, 2010
Chronic inflammation
has been implicated in
prostate cancer, whichis responsible for about
10% of cancer deaths
in men. In this review,
the authors focus on
the effects of diet on
prostate cancer, sinceenvironmental factors
play an important rolein cancer development. Historically, the incidence of
prostate cancer has been lower in Asian countries, wheresoy products and tea are commonly consumed, than inWestern countries. Inflammation, as indicated by activationof the transcription factor NF-kB, is associated with benign
prostatic hyperplasia, which often precedes prostate cancer.
Epigallocatechin-3-gallate (EGCG), a catechin in green tea,
attenuates NF-kB activity in vitro and inhibits carcinogenactivation and tumor growth in mice.
Isoflavones are found in soy and act as phytoestrogens.
Consumption of soy in Asia is associated with a low
incidence of prostate cancer, presumably due to its isoflavone
content. Through cell-signaling effects, isoflavones, especiallygenistein, inhibit angiogenesis (blood vessel formation)needed to support tumor growth and cancer cell proliferation. High dietary intakes of soy also inversely correlatewith testosterone levels in Japanese men, illustrating thehormone-like effects of soy. In the authors’ studies, only
supplementation with both green tea and soy—but notwith either alone—suppressed inflammation and inhibited
prostatic hyperplasia in hormone-treated rats. The authors
argue that a “whole foods” approach that relies on modest
concentrations of these compounds lacking toxicity may
be most effective against prostate cancer.
BOBE G, MURPHY G, ALBERT PS, SANSBURY LB,LANZA E, SCHATZKIN A, and CROSS AJ. Dietary lignan
and proanthocyanidin consumption and colorectal adenoma
recurrence in the Polyp Prevention Trial. Int. J. Cancer
130:1649-1659, 2012
Lignans and proanthocyanidins are polyphenols thathave attracted interest because of their anti-inflammatory
and anticancer properties. Lignans are found in the fibrous
portion of plants, especially whole grains and flax, andare metabolized by gut bacteria to compounds that have
estrogenic activity. Primary dietary sources ofproanthocyanidins are tea, chocolate, and apples.
The authors evaluated the association between lignan andproanthocyanidin intake—estimated from databases linked
to a food frequency questionnaire—and adenoma recurrence

continued on page 10

The Linus Pauling Institute9Continued from page 9 — Recent Publications
in 1,859 participants in a four-year, randomized, nutritional
intervention study that encouraged the consumption of ahigh-fiber, high-fruit, and vegetable-enriched diet. Overall,no association between lignan and proanthocyanidin intake
and adenoma recurrence was observed; however, lignan
intake was associated with adenoma recurrence in women,
indicating that high lignan intake may increase the risk of
adenoma recurrence in women.
CASTRO DJ, LÖHR CV, FISCHER KA, WATERS KM,
WEBB-ROBERTSON BJ, DASHWOOD RH, BAILEY GS,
and WILLIAMS DE. Identifying efficacious approaches tochemoprevention with chlorophyllin, purified chlorophylls,
and freeze-dried spinach in a mouse model of transplacental
carcinogenesis. Carcinogenesis 30:315-320, 2009
The authors previously reported that indole-3-carbinol—a phytochemical in cruciferous vegetables—green tea, or
caffeine fed to pregnant mice exposed to a carcinogenic
polycyclic aromatic hydrocarbon called dibenzo[a,l]pyrene (DBP) protected the offspring from mortality due tolymphomas and decreased the number of lung tumors per
mouse. Exposure to DBP is widespread because it is formed
from the combustion of coal, petroleum products, tobacco,and other organic material. The authors have also
demonstrated that chlorophyll or its derivative chlorophyllin protected trout from liver cancer caused by exposure
to aflatoxin B1 formed by molds on grain and nuts. In thepresent study, oral co-administration of chlorophyllin and
DBP to pregnant mice significantly protected their offspringfrom carcinogenesis, even though the offspring had no
direct exposure to either compound. This provides anotherexample of the utility of phytochemical chemoprotection
against transplacental carcinogenesis.
CLARKE JD, HSU A, RIEDL K, BELLA D, SCHWARTZ
SJ, STEVENS JF, and HO E. Bioavailability and interconversion of sulforaphane and erucin in human subjects
consuming broccoli sprouts or broccoli supplement in across-over study design. Pharmacol. Res. 64:456-463, 2011
It has long been known that consumption of cruciferous
vegetables like broccoli, Brussels sprouts, and cabbage
confers some protection against cancer. Glucosinolates inthese vegetables are converted by myrosinase—an enzyme
in the vegetables released by chopping or chewing—into
isothiocyanates like sulforaphane and erucin, as well asother compounds. Sulforaphane has demonstrated anticancer properties in cell culture and animal studies.
The authors examined the bioavailability of sulforaphanein humans consuming broccoli sprouts or broccoli
supplements by measuring sulforaphane and erucin in
the blood. Both compounds were measured because
sulforaphane can be converted to erucin and erucin tosulforaphane in the blood. The bioavailability ofsulforaphane and erucin in the broccoli supplement wasmuch lower than in fresh broccoli sprouts, probably
because the supplements lack the enzyme myrosinase.

10

Spring/Summer 2012MCQUISTAN TJ, SIMONICH MT, PRATT MM,PEREIRA CB, HENDRICKS JD, DASHWOOD RH,
WILLIAMS DE, and BAILEY GS. Cancer chemoprevention
by dietary chlorophylls: A 12,000-animal dose-dose matrix
biomarker and tumor study. Food Chem. Toxic.
50:341-352, 2012
Dibenzo(def,p)chrysene (DBC, formerly known as DBP), a
polycyclic aromatic hydrocarbon formed by the combustionof organic substances like coal, wood, and oil, is a potent
carcinogen in animals. Because people are unavoidably
exposed to DBC in urban areas, they may be at increased
risk for cancer. The authors exposed trout to DBC andobserved a linear dose-response increase in the incidence
and multiplicity of liver tumors up to the dose of maximum
effect. Co-treatment of the trout with chlorophyll-enrichedspinach extracts at human dietary intake levels significantly
inhibited the incidence and multiplicity of tumors, except at
the highest DBC doses. This suggests that chemoprevention
studies in animals conducted with very high carcinogendoses may not have much relevance to people.
Chlorophyll’s likely protective mechanism is its binding to
DBC in the gut, thereby preventing DBC uptake into theblood stream and delivery to target tissues.
WONG CP and HO E. Zinc and its role in age-related
inflammation and immune dysfunction. Mol. Nutr. Food
Res. 56:77-87, 2012
In this paper, the authors review the role of zinc deficiency
in age-related immune dysfunction—leading to increased
susceptibility to infections—and inflammation, which
contributes to chronic diseases like heart disease and certain
cancers. Over 40% of older Americans do not consume thedaily Estimated Average Requirement for zinc (9.4 mg/d
and 6.8 mg/d for men and women over 50, respectively),
and there is an unexplained age-related decline in zinc levels
that does not appear to be due to decreased dietary intake
or absorption. Zinc inhibits the activation of NF-kB, amolecule that regulates the inflammatory response. Zinc
supple- mentation has been shown to improve immune
response and to lower inflammation.
Epigenetics refers to changes in gene expression without
corresponding alterations in the underlying DNA. Zinc plays
an epigenetic role in the methylation of DNA required fornormal development and the suppression of carcinogenesis.
Additionally, rodent experiments have shown that maternalzinc deficiency impairs immune function and glucose
handling in offspring through epigenetic mechanisms. LPI

bequests
LPI is grateful for theceived from thewe have
LPIrepast year:
following friends thisMr. John F. Holterhoff
Mr. Gerald D. Carney
Ms. Zella E. Mack

LPI’s Healthy
Youth Program
Simone Frei, M.P.H., M.A.
Program Coordinator
Healthy Youth ProgramP

roviding public education to promote optimum healthand prevent disease has always been a major commitmentof the Linus Pauling Institute. Our educational efforts havebeen mainly focused on adults. We recently decided to reachout to our youth as well, to make an impact on their health.
Hence, we developed the Healthy Youth Program in 2009 in
response to the declining emphasis on nutrition and physicaleducation in our schools and the alarming increase ofchildhood weight problems in the United States. The goalsof the Healthy Youth Program are to provide educational
and activity programs to school children and their families toinstill healthful diet and lifestyle habits in our youth, thereby
helping them maintain a healthy body weight and preventthe chronic diseases of adulthood.

Micronutrient Intake
in Elementary SchoolChildrenOur micronutrient intake study
assesses the dietary intake levelsof all vitamins and essential
minerals, as well as the vitamin D
body status, in a cohort ofelementary school children in
Corvallis, Oregon. To date,
172 children have completed avalidated food questionnaire(Block Kids Food Questionnaire),and a subset of 71 children
completed a vitamin D blood spot
test from ZRT Laboratories in
Beaverton, Oregon. Preliminary
data indicate that 70% ofchildren had serum vitamin Dlevels between 21 and 30 ng/mL
and 13% had levels below 20 ng/
mL, considered insufficient anddeficient, respectively. None of thechildren met the recommended
intake levels for vitamin E and linoleic acid, and only one
child met the Adequate Intake (AI) for potassium. Very few
of the children met the AI for alpha-linolenic acid and therecommended intake level for fiber. Seventy-six percent ofchildren aged 5-8 years and 92% of children aged 9-11
years, respectively, did not meet the recommended intake
levels for calcium, 40% and 61% for magnesium, 40% and
54% for phosphorus, and 22% and 44% for vitamin A.
Most children met the recommended intake levels for the
B vitamins and vitamin C.
While we still need to collect and analyze more data, thesepreliminary results raise serious concerns about the nutrient

intake of children even in affluent and well-educatedcommunities. The low dietary intakes of calcium andmagnesium, together with low vitamin D status, may havedetrimental consequences for bone health, both in the shortterm (failure to mineralize growing bones and achieve peakbone mass) and long term (osteoporosis). There is a criticalneed for tools that help parents and health professionals
assess the nutritional status of children and provide guidance
to improve their nutrient intakes, including improved dietand use of dietary supplements.

Childhood Nutrition and Exercise in
Elementary Schools
Our study, Childhood Nutrition and Exercise in Elementary
Schools, examines elementary school teachers’ needs, knowledge, concerns, and barriers regarding nutrition educationand physical activity in elementary schools and also assesses
school cafeteria staff’s knowledge and attitudes towards
childhood nutrition. Confidential and anonymous surveys
have been administered to 227 elementary school teachersand 59 school cafeteria staff in public elementary schools in
Oregon. Results indicate that the
majority of Oregon’s classroom
teachers see a need to provide
nutrition education to elementary
school children, but they expressed
great concern about time and budget
restrictions. Competing academic
expectations and lack of a suitable
curriculum limit the time that teachers
can spend on nutrition education.
Parents and school cafeterias wereperceived as important to improvethe efficacy of a revised nutrition
curriculum. Most teachers wereinterested to learn a new nutrition
curriculum; however, money was apotential limiting factor for training.
Cafeteria staff also see a need to
improve the eating habits of thestudents and want to get involved
with nutrition education. However,time and training are limiting factors.
We also found that most teachers
would welcome more physical activity
breaks for children during the schoolday. The teachers are willing to bepart of the solution and want to learn more about ways
they can incorporate physical activity breaks into their dailyclassroom schedule.

K-5 Nutrition Curriculum
Based on the results of the above described study, we aredeveloping a K-5 nutrition curriculum, as well as an exercise
DVD. Our curriculum will reflect the core tenets of LPI
regarding healthful diet and lifestyle and will be divided into
three age-appropriate segments: a) kindergarten and 1st

continued on page 12

The Linus Pauling Institute11

grade, b) 2nd and 3rd
grades, and c) 4th and5th grades. We believethat a successful nutrition
curriculum needs to beengaging and tied toother academic areasin school, making its
content more meaningful
and applicable. This willallow the teachers toincorporate thecurriculum into theirlesson plan as an
academic enrichment.
Therefore, ourcurriculum will include
many hands-on activities
that relate to math,science, and English
language skills.

Exercise DVD
With the help of a group of exercise and sports science
students at Oregon State University, we are developing a
DVD with different segments of physical activities that canbe done in a classroom setting.
Since many classroom teachers are not trained in exercise
instruction or may be uncomfortable demonstrating
exercises to their students, they may prefer to use this DVD
to provide physical activity breaks. The exercises
demonstrated in the DVD will include stretching, yoga,
strengthening, flexibility, and aerobic moves, such as jumping
in place. Sports exercise students will demonstrate theexercises with music in an engaging and fun way, while
media students are responsible for producing the DVD.

Cooking Fun & PlayWe have partnered with KidSpirit to offer Cooking Fun& Play, an after school program for elementary and middle
school students. KidSpirit is a program in OSU’s College of
Public Health and Human Sciences aimed at improving theskills, lifestyle, and social development of children of allages, abilities, and cultural backgrounds.
The main objective of Cooking Fun & Play is to teachchildren the importance of a healthful diet, familiarize themwith preparing healthful meals, and increase their level ofphysical activity. Since many experts agree that healthrelated behaviors are developed during childhood, we
believe our program will have a lasting impact on thesechildren’s health into adulthood.
On two afternoons per week, students learn about theimportance of healthful eating, such as the benefits ofeating plenty of fruits and vegetables and substituting
whole-grain foods for refined-grain foods. Students also
learn to identify which foods are healthful and which foods
should be consumed in moderation or avoided, especiallyhighly processed, calorie-dense, nutrient-poor foods.

12

Spring/Summer 2012

Through hands-on teaching, the students learn tofollow a recipe and cook their own meal, develop cooking
skills, plan a menu, and put together a grocery shopping
list. We teach the children how to cook meals that are not
only affordable but also healthful and nutritious. Parents
and guardians are encouraged to participate in the cooking
sessions so that these skills can be implemented into thefamily’s daily routine to improve the dietary habits of theentire family.
On the other two afternoons per week, students participate
in physical activity games that are non-competitive, don’t
require athletic skills, and are designed to attract thosechildren who typically avoid competitive or recreational
sports. Students also participate in weekly swim lessons
and learn about water safety.

To Grow Box
We have partnered with the Corvallis Environmental
Center to expand their gardening education program for
low-income families, the To Grow Box, to include aninteractive and engaging nutrition education component.
Participation in this program is free. The expanded To
Grow Box will educate families on how to grow their own
vegetables, the importance of eating a healthful diet withplenty of fruits and vegetables, how to cook nutritious andhealthful meals with fresh produce, and how dietary habitsaffect health and well-being.
The To Grow Box is a six-week program that isoffered in the summer at the SAGE Community Gardenin Corvallis. The program will provide families with theknowledge and skills to plant their own vegetable garden
and to incorporate fresh produce into their meal planning.
Families will be provided with recipes that are not only
healthful and nutritious but also affordable and tasty. Every
week, families will take home a box full of fresh produce
harvested right from the garden. Childcare will be provided
and children will be encouraged to participate in thegardening and cooking. In each class, families will work in
the garden, harvest the produce, prepare and cook a meal,and end the day eating dinner together in the garden.
Nutrition education will be provided in an informal andinteractive way while the families are preparing dinner.
Families will be encouraged to ask questions and will begiven the opportunity to meet individually with our nutrition
educator to discuss theirfamily’s health behaviors.
Families will also receivea binder with nutrition
information, resources, andrecipes, including the ones
prepared in class. After thecompletion of the program,participants will be provided
with a box filled withgardening supplies to start
their own vegetable garden.
Follow-up for technicalgarden support will beavailable to participating
families for up to one year.

The Spartan
GardenCandace Russo, M.S.
Garden Manager
Healthy Youth Program

The Spartan Garden: Soil to Seed to Plate
The Healthy Youth Program (HYP) has partnered with
Corvallis High School (CHS) to develop a school garden(named the Spartan Garden, after the CHS mascot) that
includes an outdoor classroom, as well as produce
preparation and cooking spaces. The Spartan Garden
provides place-based learning, where students explore
where their food comes from, how to grow their own
food, the value of eating healthful foods, and the link
between a healthy environment and a healthy lifestyle.
Following a unique model, the Spartan Garden is
primarily student-run, as high-school youth are capable ofengaging in all aspects of the garden, from “soil to seed toplate.” Innovative design features allow multiple disciplines
to use the garden for science, health, nutrition, cooking,environmental sustainability, art, woodworking, and more.
The garden design includes a compost observatory, vegetablewashing station with water catchment, cooking tables, coboven, rain garden, living fence, and culinary herb spiral.
Students in each of the three horticulture classes at CHS
are committed to preparing and maintaining the garden
throughout the school year. This is a natural fit, as all garden
activities provide “real-world” experiences directly related tolearning objectives for this discipline. So far, students have
prepared the soil by removing debris, adding compost,
forming raised mounds, spreading leaves, and planting
cover-crops to protect the soil from winter rains. The
horticulture students have determined their garden’s soil
type, tested for earthworm abundance, measured soil pH
and nutrient levels, and started seeds for nutritious coolseason crops, including kale, greens, leeks, and broccoli.
Beyond the horticulture classes, many other disciplines
are incorporating the Spartan Garden into their curricula.
Foods and culinary arts students plan to harvest produce
to use in their spring cooking classes; they will also be
working with the Corvallis Environmental Center (CEC), a
community partner, to offer “tasting tables” for their peers
and teachers, as part of the Edible Corvallis Initiative.
Spearheaded by the CEC, the “Tasting Tables” projectencourages healthful eating by showcasing seasonal foodfrom local farms and provides tastings to schools throughout the Corvallis School District. “Tasting Tables” will be
brought to CHS (currently they are only offered at theelementary and middle schools), and the Spartan Garden
will become one of the highlighted “farms.”
Additionally, woodworking students have built a garden
tool shed, which will also serve as a canvas for art students tocreate a garden mural. Work has also started on the vegetablewashing station, which will allow food harvested from thegarden to be cleaned on-site and made available to the schoolcafeteria, as well as for students to cook and eat themselves.
Woodworking students are building the washing station, andceramics students plan to create tiles for the surface of thetable tops. Ceramics students will also create plates and bowls
for the cooking area, host a clothesline art show in the garden,
and make pots for “Thank You Herbs,” a donation project tobuild community support around the school.
The possibilities for curricular connections are endless, as
is evidenced by the diversity of teachers that have expressedinterest in the Spartan Garden project. I will be working
with these teachers to help deliver lessons and develop andimplement further ideas.

Chefs in the Garden
The HYP is offering Chefs in the Garden, a month ofsummer day camps in August. Third through fifth graders
will participate in gardening, nutrition, outdoor healthfulcooking, environmental science, and physical fitness activities,
using the Spartan Garden as the venue for these explorations.
Themes for each of the four weeks are “Secrets of the Soil,”“Garden Creatures,” “Backyard Science,” and “Adventurous
Artists.” Each day, camp goers will harvest food from thegarden to cook and eat lunch together, participate inengaging activities surrounding the weekly theme, and help
with fun garden tasks, which will, in turn, keep the Spartan
Garden vibrant throughout the summer. LPI
Special thanks to the following donors who made the
Healthy Youth Program possible:
Title Sponsor: USANA Health Sciences, Inc., Salt Lake City, UTOther Sponsors: Joan Facey, Atlanta, GA
Starker Forests, Corvallis, OR
Tim and Starleen Wood Foundation
Spartan Garden - Growing Side.
Proposed Plan

Spartan Garden - Gathering Side.
Proposed Plan

The Linus Pauling Institute13

Briefly. . .
Giana Angelo, Ph.D.
LPI Research Associate
Micronutrient Information Center

What’s Good About Chocolate?

M

ost of the health benefits ascribed to chocolate arelikely due to their flavonoids, dietary factors thatbelong to the general class of compounds known as
phytochemicals, or plant chemicals. More than 5,000
varieties of flavonoids have been identified, and hundredsof flavonoids can exist in a single food. All flavonoids
have the same basic polyphenol chemical ring structure,
hence the occasional reference to flavonoids as polyphenols.
Different flavonoids possess varying numbers of rings andchemical attachments, thus imparting different properties tothe specific compound.
Due to their unique chemical structures, flavonoids mayexert antioxidant, anti-inflammatory, and cytoprotective(cell protective) effects in humans. Consuming flavonoidrich foods has been associated with a reduced risk of certain
chronic diseases, particularly cardiovascular diseases (CVD).
Chocolate contains flavonoids belonging to the subclasscalled flavanols. The specific flavanols present in chocolate
are catechins and procyanidins. Catechins are also present
in tea, grapes, and berries; procyanidins are also present ingrapes, berries, and red wine.
Flavanols in chocolate come from the cocoa. Dark
chocolate contains approximately 43-63 mg flavanols per
100 grams (about 3 oz). However, differences in processing
can greatly affect the amount of flavanols present incommercial cocoa-containing products.
A common and early event in CVD occurs when theendothelium—the inner lining of blood vessels—isdamaged. Therefore, protecting endothelial function helps
minimize the risk for atherosclerosis, heart attack, andstroke. Several small-scale randomized, placebo-controlled
trials have been conducted to help determine what quantityof consumed flavanols benefits vascular health. Researchers
found that ingesting a cocoa powder drink (containing 375
mg flavanols) twice daily for 30 days improved endothelial
dysfunction and blood pressure in patients with coronary
artery disease. In healthy adults, ingestion of 46 grams ofdark chocolate (containing 250 mg flavanols) daily for
2 weeks improved endothelial function. Even as little as
6.3 grams of dark chocolate (containing approximately
30 mg of flavanols) consumed daily for 18 weeks lowered
blood pressure in healthy adults with above-optimal
blood pressure.
These studies demonstrate that the amount of flavanols
associated with beneficial effects is achievable throughdietary consumption of cocoa or cocoa-containing
products. It is important to note that flavanols in dark

14

Spring/Summer 2012

chocolate are found with other substances, such as fat,sugar, caffeine, and various additional phytochemicals.

Calcium and Cardiovascular Diseases
A recent meta-analysis reported in the British Medical
Journal has raised concern about the safety of calcium
supplements, either alone or with vitamin D, on the riskof cardiovascular events like strokes and heart attacks.
Specifically, the meta-analysis reported an increased risk
for myocardial infarction—heart attack—in women taking
calcium supplements. A “meta-analysis” is a statisticalmethod that combines the results from several randomized
controlled intervention trials that address similar questions.
Although the meta-analysis raises an issue that needs further
attention, there is insufficient evidence available at this time
to definitively refute or support the claims that calcium
supplementation increases the risk of cardiovasculardiseases (CVD).
CVD is a broad term that encompasses many diseases
affecting the heart and blood vessels. In the meta-analysis,
the slight negative effect of calcium supplementation wasseen with myocardial infarction in particular (approximately
25% increase in risk over five years of supplementation).
In an earlier intervention trial by the same researchers,
calcium supplementation had variable effects on othercardiovascular endpoints, including a beneficial effect onangina, which is chest pain caused by reduced blood flow
to the heart and a common symptom of coronary arterydisease. Why the authors removed angina from the recent
meta-analysis was not explained and raises concerns.
The risk of myocardial infarction was statisticallysignificant only at low to moderate calcium intakes, notat high levels of calcium intake. Moreover, those subjects
with the highest intakes of calcium (>1,000 mg/day) had
the lowest rates of death from all causes. This suggeststhat high calcium intake is protective overall. Why onlya moderate dose of calcium would increase the risk of
myocardial infarction is unknown.

CVD is a complicated disease with many risk factors.
There are other clinical markers of cardiovascular healththat can be measured in order to make the most informed
decision about your calcium needs. However, the potential
risk associated with calcium supplementation on
cardiovascular events requires further research.
The Recommended Dietary Allowance (RDA) for calcium
is 1,000 mg/day for women 19-50 years of age and 1,200
mg/day for women 51 years of age and older. It’s advisable
to meet this level of calcium intake from food sources. Gooddietary sources of calcium and the amount of calcium perserving can be found online on the LPI Micronutrient
Information Center in the section on calcium.

Calcium supplements may contain calcium in the form ofcalcium carbonate, calcium citrate, calcium citrate malate,calcium lactate, or calcium phosphate. Our intestines canabsorb the calcium from these supplemental forms with thesame efficiency as calcium from food, except for calcium
citrate malate (found in fortified juices), which is very slightly
more absorbable.
Importantly, our intestines can only absorb a maximumof 500 mg of calcium at a time. Therefore, if calcium is
supplemented, it’s best to consume it in small doses throughout the day and to take supplements with meals. LPI

Developments
Photo by Karl Maasdam

Michele Erickson
LPI Director of Development

Graduate Fellowships at LPI

Supporting knowledge, discovery, and apassion for learningT

hey are innovators and idea generators: men and womenfilled with passion and questions, eager to experiment,
ponder, and explore.

OSU student Caitlin Crimp (left) with LPI Research
Assistant Professor Dr. Debbie Mustacich (right)

Tomorrow they will be professors, principal investigators,
policy makers, and physicians. They will drive our society’s
future through scientific discovery, lending newunderstanding to the vital “protect and prevent” role ofmicronutrients and other dietary factors central to ourability to avert disease and improve human health.

“My colleagues and I really enjoy our graduate students. They are the heart and soul of our labs at OSU,
and it’s rewarding to see these bright, eager young
people develop their talents. Even as they help us makescientific discoveries today, they are becoming theleading scientists of tomorrow.”

Today they are graduate students. And with yoursupport, the most promising of these future researchers
will come to Oregon State University to study at the Linus
Pauling Institute.

— Dr. Balz Frei, Director and Endowed Chair,
Linus Pauling InstituteIn a fiercely competitive academic environment, fellowships
help LPI recruit the best and brightest graduate students.
These talented scholars power the Institute’s researchengine, performing much of the daily lab work and tacklingproblems with fresh energy and perspectives. As they work
closely with the Linus Pauling Institute’s world-class faculty,
they activate the kind of creative synergy that makes
breakthroughs happen. Graduate students also shape theexperience of many undergraduate students, whom they
mentor, guide in the lab, and teach in the classroom.
Supporting graduate students at the Linus Pauling Instituteis a meaningful way to invest in our research to determine
the role of vitamins and essential minerals, phytochemicals,
and dietary supplements in extending healthy lifespan andpreventing or treating age-associated diseases.

Even modest awards can make a great difference inenabling LPI to attract the finest students and to allow
them to focus on their research, teaching, and learning.
To recipients, your fellowship gift is extremely valuable
at a pivotal moment in their lives.
Your gift supporting graduate fellowships is aninvestment to build LPI’s future as a leading international
research institute working to improve human health andwellness, today and for decades to come.
To make a gift designated to support LPI graduate
students or to learn more, please contact:
Michele Erickson, Director of Development
Linus Pauling InstituteOregon State University Foundation(800) 354-7281, Michele.erickson@oregonstate.edu

The Linus Pauling Institute15

Linus Pauling Institute

Non-Profit Org.
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Stephen Lawson, Research Newsletter Editor
Oregon State University
307 Linus Pauling Science Center
Corvallis, Oregon 97331

Portland, OR
Permit No. 1006

phone: 541-737-5075
fax: 541-737-5077
email: lpi@oregonstate.edu
Internet Web site: http://lpi.oregonstate.edu

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

Photo by Karl Maasdam

GIVING
to theLinus Pauling
Institute

Look for these informative articles inside!
Page 1 ..... From the Director

Page 11 ..... LPI’s Healthy Youth Program

Page 1 .....Dairy, Beans, and HealthInterview with Gerd Bobe

Page 14 .... Briefly. . .
Page 15 ..... Developments

Page 5 .... Recent Publications by
LPI Scientists
Special thanks to Barbara McVicar for editorial assistance and photographs, authors of signed
articles, and Dick Willoughby for the logo photograph of Linus Pauling.