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Research Newsletter-Fall/Winter 2007


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
    Photo from the Diet and Optimum Health Conference

    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
    Photo from the Diet and Optimum Health Conference

    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
    Photo from the Diet and Optimum Health Conference

    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