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Research Newsletter-Fall/Winter 2009


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.
  • Joe Beckman presents the LPI Prize for Health Research to Michael Holick
  • 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)

    Conference Attendees
  • 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.
  • Conference Banquet

    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