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Research Newsletter-Fall/Winter 2011

Stephen Lawson


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.
  • Photo at the DOH 2011 Dinner
  • 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.
  • Photo of Maret and Biff Traber
  • 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.
  • Photo of Olga Vlasenko, Maret Traber, Lester Packer, and LeeCole Legette
  • 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.
  • Photo of Christine Merrill, Alan Taylor, Neil Mann, and Gary Merrill
  • 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.
  • Photo of Nick Thomas, Liam Finlay, Luis Gomez, Kate Shay, Dove Keith, Drupadi Dillon, and Judy Butler
  • 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.

    Photo of Drs. Vijayasree V. Giridharan, LeeCole Legette, John Maguire, and LPI's Adrian Gombart

    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").

    Photo of Galen Miller and John Maguire of the Oxygen Club of California

    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