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DIET AND OPTIMUM HEALTH CONFERENCE
Stephen Lawson
LPI Administrative Officer |
The fifth biennial LPI Diet and Optimum Health Conference,
co-sponsored by the Oxygen Club of California and
Oregon Health & Science University, convened in Portland
from May 13th to 16th. The conference featured 22 speakers
from around the world and was organized into five sessions:
- Healthy Aging: Neurocognitive Disorders and
Molecular Mechanisms
- Micronutrients and Immune Function
- Vitamin K: New Functions and Mechanisms of Action
- Diet and Lifestyle in Metabolic Syndrome and
Cardiovascular Diseases
- Epigenetics, Diet, and Disease
The conference opened on Wednesday afternoon with a
special session of oral presentations selected from the many
abstracts submitted for posters. Additionally, finalists for the
Young Investigator Awards, sponsored jointly by LPI and
the Oxygen Club of California, gave short presentations.
Heather Kuiper, Alexander Michels, and Mansi Parasramka
were selected for Awards, which were presented by Rod
Dashwood of LPI and John Maguire of OCC at the banquet
on Friday evening.
Healthy Aging: Neurocognitive Disorders
and Molecular Mechanisms
Chaired by Tory Hagen (LPI) and Kathy Magnusson (Oregon
State University)
Kevin Pearson (University of Kentucky) discussed healthspan
extension by caloric restriction and resveratrol, a polyphenol
thought to mimic the effects of caloric restriction. In mice,
resveratrol did not extend lifespan but did produce some
health benefits, such as decreased inflammation, improved
aortic function, inhibition of cataracts, increased
bone mineral density, and improved glucose tolerance.
Tomas Prolla (University of Wisconsin) noted that low-dose
resveratrol mimics caloric restriction and retarded agerelated
decrements in mice. Mice fed resveratrol or calorically
restricted had similar changes in gene expression, which
were associated with protection against cardiac dysfunction
and skeletal muscle aging.
Craig Cooney (University of
Arkansas) has studied the epigenetic effects of diet on aging
and diabetes in mice. "Epigenetics" refers to changes in gene
expression without any changes to DNA. In a special mouse
strain, coat color is affected epigenetically through dietary
manipulation and is associated with glucose handling and
insulin sensitivity.
Carl Cotman (University of California-Irvine)
presented the results of a three-year study of cognition
in beagles fed alpha-lipoic acid, carnitine, and vitamins C
and E and/or environmentally enriched (exercise, play, social
interaction, and cognitive experience). Beagles fed antioxidants
and environmentally enriched scored best on
cognitive tests. Antioxidants also inhibited beta-amyloid
formation—associated with dementia—in the brain.
David Kennedy (Northumbria University) conducted
two supplement studies showing that 1) men given a
multivitamin/mineral supplement for five weeks reported
increased vigor and less mental fatigue than unsupplemented
men, and 2) working women taking a multivitamin/mineral
supplement for nine weeks reported better mood and had
increased cognitive performance and decreased homocysteine
levels, a marker for heart disease. Additionally, in a
small study, resveratrol increased cerebral blood flow and
oxygen use in a dose-dependent manner.
Oxidative stress
has been implicated in Alzheimer's disease (AD). D. Allan
Butterfield (University of Kentucky) uses proteomics to study
proteins in the brain that are oxidatively modified in AD.
The brain has high levels of oxygen and unsaturated fatty
acids, low levels of antioxidants, and iron, making brain
proteins vulnerable to oxidative modifications. Amyloid
beta-peptide, associated with AD, also causes oxidative
changes to brain proteins. Old beagles exhibit dementia
and amyloid beta plaque formation, but supplementation
with antioxidants and behavioral enrichment, including
exercise, attenuated plaque formation and oxidative stress,
leading to cognitive improvement.
Micronutrients and Immune Function
Chaired by Emily Ho (LPI)
Over one billion people worldwide are vitamin D
deficient, leaving them vulnerable to bone problems, heart
disease, autoimmune disorders, and infections. Adrian
Gombart (LPI) discussed how vitamin D boosts the innate
immune system, resulting in increased phagocytic activity
and decreased inflammation by stimulating the production of
an antimicrobial protein called cathelicidin. Low vitamin D
levels are insufficient for the cathelicidin gene to be expressed.
The development of a transgenic mouse model allows
further investigation of cathelicidin activity.
The RDA for
vitamin A is mainly based on its requirement for vision, but
Charles Stephensen (University of California-Davis) argued
that the role of vitamin A in immune function should be
more carefully evaluated. Vitamin A deficiency, due to low
intake, fat malabsorption problems, and frequent infections,
is associated with high childhood mortality from infections.
In clinical trials, supplementation decreased childhood
mortality from infections by 30%, including measles and
diarrheal diseases. However, very high vitamin A status in
infancy may pre-dispose to asthma.
Wafaie Fawzi (Harvard) discussed the association between multiple
micronutrient deficiencies and infectious diseases in Africa
and Asia. In various studies, vitamin A decreased mortality
from malaria, zinc decreased mortality from pneumonia and
diarrheal diseases, high
levels of maternal vitamin
A decreased transmission
of HIV to infants, multivitamins
improved child
growth and reduced the
risk of mortality from or
progression of HIV in
women by 30%, and iron
decreased the risk for
anemia and improved growth
and cognitive development in
children, although children
infected with malaria did
worse with iron supplements.
Vitamin K: New Functions and
Mechanisms of Action
Chaired by Maret Traber (LPI)
Vitamin K, a fat-soluble vitamin, is required for normal
blood clotting and bone growth and is found in vegetable
oils and green, leafy vegetables. Sarah Booth (Tufts) discussed
the variability in vitamin K status among people, partly
determined by estrogen status and genetic polymorphisms,
but also due to variations in diet and absorption and
antagonism with other fat-soluble vitamins. Since vitamin
K poorly crosses the placenta and is low in breast milk,
infants are at risk for vitamin K deficiency.
Leon Schurgers (University of Maastricht) addressed the
cardioprotective function of vitamin K2. Vitamin K refers
collectively to a group of related compounds: K1 is
synthesized in plants and K2 is synthesized in bacteria
and animals. A Dutch study found that high levels of
K2—but not K1—were associated with protection against
aortic calcification and a 50% lower risk for death from
cardiovascular disease, probably due to K2's role in
producing matrix Gla-protein, which may serve as a
biomarker for cardiovascular disease.
Kathleen Berkner (Cleveland Clinic Foundation) noted that vitamin K is
necessary for the carboxylation of the glutamate residue
in protein that takes place in the liver. Carboxylation of
proteins allows them to perform important physiological
functions involved in blood clotting and calcium homeostasis.
Studies of carboxylation have revealed that
mutations of critical molecules cause disease, including
pseudoxanthoma elasticum.
Diet and Lifestyle in Metabolic
Syndrome and Cardiovascular Diseases
Chaired by Donald Jump (LPI) and Jeffrey Blumberg (Tufts)
Christopher Newgard (Duke) studies metabolites to
understand mechanisms of human disease. In obese,
insulin-resistant people, metabolism of branched-chain
amino acids in proteins is altered, leading to increased
insulin resistance. Western-type diets typically provide an
excess of these amino acids, leading to high levels of their
detectable metabolites. In the context of a high-fat, highcalorie
diet, too much protein may cause insulin resistance,
associated with metabolic syndrome and diabetes.
Deborah Muoio (Duke) pondered the association
between weight gain, inactivity, and insulin resistance.
Lipids accumulate in muscle tissue in obese people and,
paradoxically, in athletes. In the sedentary obese, elevated
lipids are incompletely oxidized, leading to insulin resistance.
In athletes, these lipids provide the mitochondria in muscle
cells with extra fuel. In mice fed a high-fat diet, exercise
restored glucose tolerance (insulin sensitivity).
Jonathan
Purnell (Oregon Health & Science University) compared
various dietary regimens used to lose and control weight.
Abdominal obesity is associated with glucose intolerance,
hypertension, diabetes, and heart disease. Low-calorie diets
are successful in the short term but often fail long term.
Metabolic studies have shown that low-fat, high-protein
diets may be best for weight loss and that low-fat diets may
be more effective in the obese. Weight loss achieved through
dieting is usually modest, and the health benefits vary
substantially among individuals.
A certain heritable
phenotype of low-density lipoprotein (LDL-B) is a marker
for both atherogenesis and a metabolic profile associated
with altered triglyceride metabolism. Ronald Krauss
(Children's Hospital Oakland Research Institute) explained
how LDL-B is modified by various factors, including age,
gender, and diet. A low-fat, high-carbohydrate diet induces
LDL-B, and carbohydrate restriction in overweight people
improves the lipid-related risk for heart disease.
Ernst
Schaefer (Tufts) reviewed dietary intervention studies on
heart disease risk. Replacing animal fat with vegetable oil,
increasing the intake of fish or fish oil, decreasing caloric
intake (especially from sugar and corn syrup), and
increasing exercise all help lower the risk for heart disease.
Docosahexaenoic acid (DHA), an omega-3 fatty acid found
in fish, may reduce the risk for arrhythmia and Alzheimer's
disease. High-fructose corn syrup increases lipogenesis,
triglycerides, and the risk for heart disease.
The "antioxidant
conundrum"—why have clinical studies largely
failed to find the postulated benefits of antioxidants?—was
addressed by Jeffrey Blumberg (Tufts). Antioxidants may
merely serve as markers for other healthful compounds
identified in observational studies or may have real health
benefits that have not been discovered in randomized
clinical trials (RCT) because of methodological problems
concerning dose, duration, form, combination, timing of
the intervention, genetic polymorphisms, or inadequate
follow-up. Most RCTs have not determined plasma levels
of antioxidants or levels of oxidative stress in participants.
Despite these limitations, many studies have reported
benefits for antioxidants, such as reduced risks for stroke,
cancer, cognitive decline, and death from heart disease.
Epigenetics, Diet, and Disease
Chaired by Rod Dashwood (LPI) and Sharon Ross
(National Cancer Institute)
Rod Dashwood (LPI) discussed the anticancer mechanisms
of compounds in garlic (the metabolite allyl mercaptan) and
broccoli sprouts (sulforaphane). Both compounds act as
histone deacetylase (HDAC) inhibitors. When HDAC activity
is inhibited, tumor suppressor genes are turned on to block
tumor growth. Allyl mercaptan and sulforaphane caused
dose-dependent cell-cycle arrest and apoptosis (programmed
cell death) in cancer cells in culture, and sulforaphane
inhibited HDAC activity in mice, as did allyl mercaptan,
and in human blood cells. These are examples of epigenetics:
changes in gene activity without changes in the underlying
DNA.
Irfan Rahman (University of Rochester) explained
how curcumin, a polyphenol from the spice turmeric, and
resveratrol from red wine attenuate inflammation in the lung
caused by oxidative stress. Curcumin and resveratrol affect
cell-signaling pathways involved in chronic inflammation
associated with asthma and chronic obstructive pulmonary
disease (COPD) but have low bioavailability.
Using sheep
as a model, Lorraine Young (University of Nottingham)
investigated the effect of epigenetic modifications in the
maternal diet on offspring. Sheep were fed methyl-deficient
diets prior to and shortly after conception, resulting in
abnormal fetal development and predisposition to disease
in offspring. Sheep eggs cultivated in vitro and then
implanted were vulnerable to the chemical constituency of
the culture media, with some lambs exhibiting abnormally
large size. These effects were due to changes in DNA
methylation (the replacement of a hydrogen atom with a
hydrocarbon group, or CH3). Studies using human stem
cells found that methylation affected differentiation,
apoptosis, and proliferation, with ramifications for the
risk for adult diseases.
The Public Lecture
On Saturday morning in a free lecture open to the
public, Marion Nestle (New York University) discussed
the complex factors that influence what and how
Americans eat. She traced many of the problems affecting
our diet and obesity rates to government policies that
encourage the overproduction of certain foods through
subsidies and to corporate practices like the shareholder
value movement of the 1980s that require agricultural and
food companies to generate much higher financial returns
more frequently, resulting in more food availability to the
consumer. The ubiquitous "buffet syndrome" creates more
opportunities for people to eat—at low cost—more
non-nutritious food more often and in more places than
ever before. The food caloric availability has risen from
about 3,200 calories per person per day in the early 1980s
to 3,900 calories per person per day now.
Changes in labeling laws allowed companies to make
health claims on processed foods like cereal and also
contributed to the development of functional foods, which
is a big growth area. Corporate marketing practices foster
brand loyalty and develop kids' foods, resulting in the
"pester factor" that causes parents to acquiesce to
pestering and buy certain advertised products.
Dr. Nestle also addressed food safety, which has been an
alarming issue in recent years. Spinach, tomatoes, peanut
butter, pistachios, and meats have all been affected by
bacterial contamination and recalls. Intentional adulteration
of food produced in China with melamine to mislead about
protein content caused widespread health problems for
people and pets. Assurance of food safety is problematic
because of our global food supply, lack of adequate
testing, and oversight by multiple, competing agencies.
For example, the USDA is responsible for meat and
poultry safety, but the FDA has responsibility for other
foods. One new proposal calls for a single agency to
review risk-based food safety.
Dr. Nestle also
commented on food
as a social movement,
illustrated by the
popularity of local
farmers' markets,
popular books on
eating, and the
humane production
of animals. The "real
foods movement"
that originated
mainly in Berkeley,
California, in the
1970s emphasizes
minimal processing,
natural nutrients,
no additives, and
no hormones or
antibiotics used in
the production of
meat, poultry, and dairy products. Dr. Nestle distinguished
between personal responsibilities: eat food, not products;
eat smaller portions; support local farmers and grow and
eat food at home; and educate children about a healthful
diet, and social responsibilities: review marketing of food
in schools to children, insist on government oversight of
food safety, and reduce
government corruption
in which campaign
financing inhibits
reasonable corporate
regulation. Above all,
Dr. Nestle encouraged
people to eat less,
consume more fruit and
vegetables, move more,
and enjoy eating!
Last updated November 2009
