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DIET AND OPTIMUM HEALTH CONFERENCE
Stephen Lawson
LPI Administrative Officer |
The fourth LPI Diet and Optimum Health Conference,
co-sponsored by the Oxygen Club of California (OCC)
and Oregon Health & Science University, convened in Portland
from May 16th to 19th. The conference featured 22 speakers
from around the world and was organized into seven
sessions: Flavonoid Functions; New Discoveries of Vitamin C
in Health and Disease; Lipoic Acid: Biological Mechanisms
of Action; Neuroprotection by Antioxidants; Maternal Diet,
Genes, and Epigenetics; Cancer Chemoprevention; and
Obesity, Exercise, and Gene Regulation.
The conference opened on Wednesday evening with a
special session of oral presentations culled from the many
abstracts submitted for posters. Additionally, finalists for
the Young Investigator Awards, sponsored jointly by LPI
and OCC, gave short presentations. Anna Hsu, Jeff Monette,
and Keith Nylin were selected for Awards, which were
presented by Dr. Maret Traber of LPI and Dr. Lester Packer
of OCC at the banquet on Friday evening.
Flavonoid Functions
Chaired by Jeff Blumberg (Tufts)
Gary Williamson (Nestlé Research Center, Switzerland)
gave an overview of the role of flavonoids in human health.
Catechins—flavonoids from tea—affect energy metabolism,
and isoflavones from soy improve bone mineral density.
Sugars affect the activity and metabolism of ingested flavonoids,
which are poorly absorbed. Flavonoids may lower the risk of
chronic diseases, especially heart disease and inflammatory
diseases.
Augustin Scalbert (Centre de Recherche de
Clermont-Ferrand/Theix, France) discussed the comprehensive
database of flavonoids that his group is developing. The database
provides the flavonoid content of foods and analytical
methods. Using a "metabolomic" approach, metabolites of
flavonoids have been identified in urine that will be valuable
in nutritional epidemiological studies.
According to William Helferich (University of Illinois-Champaign/
Urbana), Americans are experiencing "isoflavone creep"
because many food products are supplemented with soy
isoflavones. Isolated isoflavones like genistein or genistin have
been found to stimulate breast cancer in animals and to inhibit
the effect of the breast cancer drug tamoxifen. On the other
hand, soy flour did not enhance tumor growth, suggesting
that the profile of components in soy is an important factor.
New Discoveries of Vitamin C in Health and Disease
Chaired by Brigitte Winklhofer-Roob (University of Graz,
Austria) and Enrique Cadenas (USC)
Fred Stevens (LPI) has been elucidating reactions
between oxidized fat and vitamin C. In test tube and cell
culture experiments, vitamin C (ascorbic acid) reacts with
oxidized lipids to ultimately form conjugates, a process that
presumably protects biomolecules like DNA from damage.
Ascorbylated acrolein (an aldehyde formed from oxidized
fat) has been detected in human urine, suggesting that
ascorbylation (reaction with vitamin C) of reactive aldehydes
may be important physiologically.
Over 35 years ago,
Cameron and Pauling began investigating the use of
high-dose vitamin C as cancer therapy. Mark Levine (NIH)
has contributed significantly to our understanding of how
vitamin C kills cancer cells. He found that high-dose
intravenous vitamin C produces hydrogen peroxide in the
extracellular milieu (but not in blood), which selectively kills
cancer cells in vitro through apoptosis (programmed cell
death) and necrosis.
James May (Vanderbilt) emphasized
the important role of vitamin C in neuronal function and
protection. The brain has among the highest concentrations
of vitamin C of any organ in the body. Oxidized vitamin C
can enter the brain through cellular glucose transporters,
but the sodium-dependent vitamin C transporter 2 in cell
membranes is responsible for vitamin C's access to neuronal
tissue, where vitamin C protects against oxidative damage
implicated in neurodegenerative diseases.
(left to right) Qi Chen, Mark Levine, Balz Frei, and Yao Hui Wang
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Lipoic Acid: Biological Mechanisms of Action
Chaired by Lester Packer (USC) and Kate Shay (LPI)
Tory Hagen (LPI) discussed work showing that feeding
old rats (R)-alpha-lipoic acid reversed the age-related decline in
glutathione levels in liver cells. Glutathione is an antioxidant
and plays an important role in detoxification, and its
increase in liver cells improved resistance to toxins in the
old rats. Lipoic acid affects the regulation of cell-signaling
molecules that control the expression of the Antioxidant
Response Element genes in DNA, which provide protection
against toxins, oxidants, and mutagens.
Erik Henriksen
(University of Arizona) noted that exercise and lipoic acid
improve insulin resistance in skeletal muscles of patients with
type 2 diabetes. Insulin resistance is characterized by increased
oxidative stress, which is attenuated by exercise and lipoic
acid. Lipoic acid also improves glucose tolerance, lowers
triglycerides, and reduces the amount of protein damage as
measured by protein carbonyls.
A mouse model of multiple
sclerosis (experimental autoimmune encephalomyelitis, EAE) has allowed investigators to study the therapeutic effect of
lipoic acid. Dennis Bourdette (Oregon Health & Science
University) explained that lipoic acid suppresses EAE in
mice—reducing paralysis and inhibiting inflammation.
In a short human trial, lipoic acid at high doses found to
be effective in the mouse model decreased a marker of
inflammation in MS patients, although the molecular
mechanisms for the effect remain obscure.
Neuroprotection by Antioxidants
Chaired by Joseph Quinn (OHSU) and Joe Beckman (LPI)
Raymond Burk (Vanderbilt) has studied the effect of
antioxidant vitamin deficiencies on the central nervous
system in guinea pigs.
Weanling guinea pigs
deprived of both
vitamins, but neither
singly, developed
severe neurological
problems, including
paralysis. F2 isoprostanes—markers of
lipid oxidation—were increased in the
vitamin-deprived animals. The brains of mice without a
selenium transport protein had low levels of selenium,
leading to severe neurological problems. Additionally,
combined selenium and vitamin E deficiency caused liver
damage in rats.
Chandan Sen (Ohio State University)
presented evidence that alpha-tocotrienol, one of the eight
members of the vitamin E family, protects neural cells in
culture from glutamate toxicity. He also discussed results
showing that orally supplemented alpha-tocotrienol
ameliorated brain damage in hypertensive rats induced by
strokes.
Alberto Ascherio (Harvard) discussed results
from epidemiological studies investigating the relationship
between dietary intake of antioxidants and the risk of
neurological disease. Two long-term, large-scale
epidemiological studies did not find any protective effect
of dietary or supplemental vitamins C and E in reducing
the risk of Parkinson's disease (PD), even though oxidative
stress plays a role in the disease. Several studies found
that urate, formed in the body from dietary precursors,
decreased the risk of PD, especially in men. Additionally,
the long-term use of vitamin E supplements was associated
with a reduced risk of ALS.
(left to right) Mark Levine, OSU President Ed Ray, and Tammy Bray
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Maternal Diet, Genes, and Epigenetics
Chaired by Carroll Cross (University of California-Davis)
and Tammy Bray (LPI)
Randy Jirtle (Duke) discussed how maternal nutrition
affects epigenetics and disease risk in offspring. Using mice,
he showed that maternal supplementation with B vitamins
or genistein from soy affected coat color and risk of
obesity, diabetes, and cancer in offspring. Nutrition did
not affect the genes in DNA, but rather influenced their
expression and chemical modifications of their protein
products. For example, many children born to mothers
who endured the Dutch famine of 1944-5 developed health and mental problems
as adults.
Dave
Williams (LPI) noted
that leukemia and
lymphoma are the
most common
childhood cancers.
In mice, maternal
exposure to a
carcinogenic
polycyclic aromatic
hydrocarbon called dibenzo[a,l]pyrene causes lymphoma in
offspring. The offspring are substantially protected against
cancer if indole-3-carbinol, a component of cruciferous
vegetables; caffeinated green tea; caffeine; or chlorophyllin,
a derivative of chlorophyll, is added to the maternal diet.
Choline is an essential nutrient that must be obtained
dietarily, primarily from milk, eggs, wheat germ, and liver in
the form of phosphatidylcholine, or lecithin. Steven Zeisel
(UNC) discussed how choline in the maternal diet affects
the development of brain structure and function in the fetus.
Fetal choline intake also affects adult memory, although
supplemental choline in adults does not significantly affect
memory function. Choline deficiency in adults can cause
muscle and liver damage.
Cancer Chemoprevention
Chaired by Rod Dashwood (LPI)
Emily Ho (LPI) described work with sulforaphane,
an isothiocyanate found in cruciferous vegetables, especially
broccoli. In human prostate cancer cells in culture and
implanted in mice, sulforaphane apparently acts as a histone
deacetylase (HDAC) inhibitor, which results in anticancer
effects by affecting how proteins called histones surround
DNA. HDACs are overexpressed in cancer cells, thereby
silencing tumor suppressor genes. In humans, sulforaphane
in broccoli sprouts inhibited HDAC activity in blood cells.
Glucuronidation is a metabolic process in which
compounds are chemically modified for excretion from the
body. Johanna Lampe (University of Washington) explained
that phytochemicals in cruciferous vegetables, soy, and citrus
fruit increase glucuronidation of carcinogens and, possibly,
some drugs. Most studies to date have been done using
animals; few human data are available.
Young-Soon Surh
(Seoul National University, Korea) discussed the role of
inflammation in cancer and how certain phytochemicals,
such as curcumin in tumeric, ginger, and sulforaphane in
cruciferous vegetables, may help protect against cancer by
influencing anti-inflammatory pathways. Dietary antioxidants
protect against cancer in part by activating cell signals that
affect detoxification genes.
Obesity, Exercise, and Gene Regulation
Chaired by Urszula Iwaniec (OSU)
Jacqueline Van Hoomissen (University of Portland,
Oregon) discussed the effect of physical exercise on mood and
neuronal function. Exercise improves cerebral blood volume,
which protects against damage caused by pathological events in the brain. It also results in neurogenesis, increased synthesis
of neuropeptides, and changes in brain morphology. Animal
experiments have shown that chronic exercise affects regions
of the brain different from those affected by acute exercise,
and research is under way to understand how those changes
affect behavior.
Kelvin Davies (USC) noted that endurance
training and sprint training result in different biochemical
adaptations. There is a much larger increase in muscle
mitochondria—cellular organelles responsible for energy
production—and endurance capacity after endurance training.
Intense exercise also generates free radicals, and vitamin E
deficiency during intense exercise causes damage to muscle
mitochondria.
Donald Ingram (Louisiana State University)
addressed the effects of caloric restriction (CR) on aging.
In rodents, CR reduces body fat, lowers body temperature,
inhibits tumor formation, reduces fasting glucose levels,
attenuates age-related decline, improves neuronal function,
and increases protection against toxins. CR has been shown
to extend lifespan in short-lived species, but this has not
yet been observed in higher primates, including humans.
Maria Luz Fernandez (University of Connecticut) presented
the results of several weight-loss studies. After ten weeks on a
low-calorie diet and with increased physical activity, overweight
women had reduced weight, abdominal fat, insulin
resistance, LDL cholesterol levels, and triglyceride levels.
Additionally, metabolic syndrome was significantly
attenuated. In another short study, overweight men were
given a carbohydraterestricted
diet
supplemented with
soluble fiber. After
twelve weeks, the
men had reductions
in weight, abdominal
fat, triglyceride levels
and blood pressure,
while HDL ("good")
cholesterol levels
increased.
(left to right) Barbara McVicar and Tracy Oddson
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Public Session
A session on Saturday, open to the public, featured
Washington Post columnist Sally Squires, whose presentation,
Secrets of the Lean Plate Club: Tales from the Waistline Wars,
focused on strategies for maintaining optimal weight. Ms.
Squires noted that about one billion people worldwide are
overweight and that by 2020, 75% of mortality from chronic
disease will be weight related. She discussed the alarming
trends in ever-enlarging portion size, or "calorie creep" that,
when combined with physical inactivity, result in unhealthy
weight gain. The Lean Plate Club has six goals: 1) eat smart,
2) move more, 3) add healthy habits, 4) reach a healthier
weight, 5) adopt a positive approach, and 6) ban the word
"don't". Ms. Squires emphasized the need for about 30
minutes of daily physical activity—not necessarily exercise—for health and 60-90 minutes of daily activity to lose weight.
She described a number of simple steps to attain better health:
eat a variety of foods, including fish, beans, whole grains,
fruit and vegetables; get enough sleep; eat breakfast; drink
plenty of water; take a calcium supplement with vitamin D;
if over 50, take a vitamin B12 supplement; and achieve
caloric balance between intake and expenditure.
Last updated December 2007
