 |
LPI DIET AND OPTIMUM HEALTH CONFERENCE
Stephen Lawson
LPI Administrative Officer |
The 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 around
the 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 were
displayed beginning Wednesday afternoon. An additional
eight posters were selected for oral presentations on
Thursday afternoon.
The conference concluded on Thursday with the
presentation of the Linus Pauling Institute Prize for Health
Research to Dr. Connie Weaver of Purdue University,
followed by her lecture on calcium and bone health.
Vitamin E: Biological Functions and
Controversies
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 is
synthesized in the liver and distributes only the natural
or 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
mice that have the gene for TTP deleted, illustrating
that vitamin E is important in normal brain function.
Qing Jiang (Purdue University) showed that metabolites
of gamma-tocopherol, a form of vitamin E found
in 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 have
a 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 disease
risk 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 Science
and Technology, Japan) addressed difficulties in assessing
the antioxidant role of vitamin E in vivo. He stated that
vitamin E reduces the risk for free radical-mediated
chronic diseases "if given to right subjects at right
timing." 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 infected
with Staphylococcus aureus (MRSA), the most common
cause of soft tissue infections in people. Treatment with
nicotinamide dramatically killed the pathogen in the blood
by enhancing the production of antimicrobial compounds
in neutrophils.
Carlos Camargo (Harvard) noted that
supplementary vitamin D in people with low vitamin D
levels 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 their
children. In Afghanistan, vitamin D treatment prevented
subsequent pneumonia in children. An analysis of the
totality 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 affected
by nutritional status, the response of T cells needed to
fight infection is influenced by nutrition. Specifically,
caloric restriction, a strategy observed to extend life span
in many animals, increases the susceptibility to influenza
infection in mice by adversely affecting the activity of
natural killer cells, which are important in the early stage
of 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 and
critically 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 of
selenoprotein 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 to
target 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 be
beneficial in people with hyperactive immune systems but
immunosuppressive in healthy people.
Diet and Cardiovascular Disease
Chaired by Balz Frei (LPI)
Cooking food results in pleasant flavors and
palatability. However, Veronika Somoza (University of
Vienna, Austria) noted that high-temperature cooking
of processed food in the Western diet produces both
beneficial and harmful compounds, including carcinogens
like heterocyclic amines ("cooked-meat mutagens"),
as well as advanced glycation end products (AGE) and
lipid hydroperoxides associated with heart disease and
diabetes. Mild cooking, replacement of high-fructose
corn syrup with sucrose, and increasing the intake of
substances like vitamin C that counteract some of the
harmful compounds are strategies to lower disease risk.
Teresa Fung (Simmons College, Boston) discussed the
epidemiological associations between diet and cardiovascular
disease. Connections between diet and disease
risk can be assessed in several ways: correlations between
actual food intake and disease or adherence to prudent
dietary recommendations. Many studies have found that
prudent 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) focused
on the healthful effects of the Mediterranean diet, which
is rich in fruit, whole grains, vegetables, legumes, nuts,
olive oil, fish, and seafood but has little chicken, milk,
or red meat. The diet also includes moderate intakes of
alcohol, usually as red wine. Dr. Estruch and colleagues
are conducting a clinical trial to evaluate the effects of a
Mediterranean diet on the risk of death from heart
disease, incidence of cardiovascular events like strokes
and heart attacks, incidence of cancer and diabetes, and
mortality from all causes. To date, compliance to the
diet has resulted in decreased oxidative stress and
inflammation, lower BMI, decreased waist circumference,
and decreased risk for metabolic syndrome.
Gut Microbes and Probiotics: Role in
Health and Disease
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 in
berries that are metabolized by gut bacteria to compounds
like equol, butyrate, and ellagic acid, respectively, each of
which protects against cancer. Microbiotica also influence
energy balance; lean people typically have populations of
gut bacteria different from those in obese people.
Bruce German (University of California-Davis) talked
about the evolutionary relationship between breast milk
and Bifidobacterium infantis, a bacterial strain that
colonizes 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 coated
drinking straws halved the number of sick days taken by
workers 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% in
patients on ventilators. Vancomycin-resistant enterococci
(VRE), a common cause of hospital infections, can be
cleared by probiotics, further demonstrating their
clinical utility.
Caloric Restriction
Mimetics, Diet,
and Healthy Aging
Chaired by Tory Hagen (LPI) and Viviana Perez
(LPI)
Richard Miller (University of
Michigan) discussed several
strategies that increase life span
in mice, including rapamycin
(an immunosuppressant drug
derived from bacteria); deletion
of the gene for migration
inhibition factor, which is a
pro-inflammatory cytokine; a
low-methionine diet, which
may provide resistance to stress
and toxins; and food restriction
early in life. In contrast,
resveratrol, simvastatin,
curcumin, and green tea extract
did not affect life span in mice. Additionally,
calorically restricted mice are more susceptible to
infections.
Resveratrol is a compound produced in
grapes in response to stress. According to Julie Mattison
(U.S. National Institute on Aging), its effects are speciesspecific,
although supplementation to mice and monkeys
fed high-fat or diabetes-inducing diets has resulted in
health improvements. For example, monkeys kept on
such diets and given very high doses of resveratrol
exhibited less arterial stiffening and inflammation and
improved glucose control compared to control animals.
The mechanism responsible for those effects is unknown.
Jamie Barger (LifeGen Technologies, Madison, WI)
presented information on the identification of genes
that serve as biomarkers of caloric restriction. Such
biomarkers may be useful in determining the utility of
compounds like resveratrol or quercetin—a flavonoid—on
increasing life span. Of nearly 21,000 genes surveyed
in mice, 11 served as markers of caloric restriction.
Low doses of resveratrol or quercetin slightly mimicked
caloric restriction, but the combination was synergistic.
Gordon Lithgow (The Buck Institute for Age
Research, California) discussed the importance of
protein homeostasis—dysfunctional proteins replaced
with normal proteins—in longevity. Using small worms
(C. elegans), he has shown that curcumin, lithium, and
Thioflavin T, a dye that binds to aggregated and
misfolded proteins, extend life span in worms. Chelating
metals in worms to maintain "metallostasis" also
increased life span.
Viviana Perez (LPI) showed that
rapamycin and dietary restriction increased life span in
mice, but only dietary restriction decreased fat mass,
resulting in improved glucose control and insulin
tolerance. Dietary restriction also delayed the onset of
Alzheimer's and amyotrophic lateral sclerosis (ALS) in
mouse models. Since there are differential effects of
dietary restriction and rapamycin on disease and because
they work through different mechanisms, rapamycin
does not act as a dietary restriction mimetic.
Oral Abstracts
Eight abstracts on a variety of topics were selected for
oral presentations:
Mark Levine (U.S. National Institute of Diabetes and
Digestive and Kidney Diseases) discussed the cytotoxicity
of high concentrations of vitamin C achieved by
intravenous infusion against cancer cells. Physician
surveys show that high-dose IV vitamin C has minimal
side effects. Cell culture, mouse studies, and some
preliminary studies with cancer patients suggest that
IV vitamin C combined with standard drug therapy
(gemcitabine) may be especially effective against
pancreatic cancer.
Margreet Vissers (University of Otago, New Zealand)
noted that consuming kiwi fruit raises blood levels of
vitamin C more than vitamin C added to drinking water.
Vitamin C inhibits hypoxia-inducible factor 1 (HIF-1),
a transcription factor induced by the low-oxygen
environment in tumors. HIF-1 promotes the survival of
cancer cells and enhances angiogenesis (blood vessel
formation), which is needed by rapidly growing tumors
to supply nutrients and remove waste.
Silvia Maggini (Bayer Consumer Care, Switzerland)
presented David Kennedy’s (Northumbria University,
UK) abstract on the effect of multivitamins/minerals on
cognitive performance and mood. In several studies
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 their
validity. Higher blood levels of trans fat were associated
with increased brain atrophy and poor memory and
attention, whereas omega-3 fatty acids were associated
with 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 and
Applied 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 like
scopolamine and cisplatin, as well as protecting against
neurotoxicity, DNA damage, and cognitive impairment.
Katie Meyer (University of Minnesota) described a
long-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 the
highest diet quality correlated with the lowest oxidative
stress. Diet quality was based on intake of 46 food
groups scored as beneficial, neutral, or adverse for health
according to current science. The highest quality diet
consisted of whole grains, fruit, vegetables, fish, nuts
and seeds, and was low in red meat.
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 are
associated 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 in
oxidative/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.
Young Investigator Awards
Young Investigator Awards were presented to three
graduate students or post-doctoral fellows. Their
abstracts were selected as the most outstanding of the
submissions.
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–amyloid induced
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 Investigator
Award was given to Galen W. Miller, a graduate student
in the Linus Pauling Institute and OSU's Molecular and
Cellular Biology Program ("Normal brain development
requires alpha-tocopherol delivery via the alpha-tocopherol
transfer protein during zebrafish embryogenesis").
Last updated November 2011
