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Department

Experimental Biology 2008: Today’s Research, Tomorrow’s Health

Joseph M. Keenan, MD

July 2008

April 5-9, 2008, San Diego, CA The Experimental Biology (EB) meeting is a scientific conference that offers unique opportunities for basic science and clinical science researchers to mingle and exchange ideas. The EB meeting is actually a shared venue for the annual meetings of seven national societies:

The American Association of Anatomists (AAA),
The American Association of Immunologists (AAI),
The American Physiological Society (APS),
The American Society for Biochemistry and Molecular Biology (ASBMB),
The American Society for Investigative Pathology (ASIP),
The American Society for Nutrition (ASN), and the
American Society for Pharmacology and Experimental Therapeutics (ASPET).

This year, more than 13,000 scientists gathered under the umbrella organization of EB. The theme of the meeting, “Today’s Research, Tomorrow’s Health,” underscores the intent of this conference to bring together dozens of different disciplines to promote the development of knowledge and ideas from basic bench laboratory investigation to translational and clinical research. This report will include highlights from these sessions. Full proceedings from these meetings are available online, and individual abstracts can be searched by key words at www.eb2008.org.

Fish Oil: Food for Thought

One of the most interesting conference sessions was a symposium on the role of polyunsaturated fatty acids (PUFAs) in neuronal health. It has been known for some time that increased intake of omega-3 PUFAs (eg, marine oils) is associated with reduced risk of coronary disease and, more recently, with improvement of some inflammatory diseases such as arthritis. Omega-3 PUFAs have been shown to be important generally in the restorative and maintenance functions of cellular metabolism.

Recently, researchers at Louisiana State University Health Sciences Center (Bazan and colleagues) have shown that the omega-3 PUFA docosahexanoic acid (DHA) is an activator and inducer of an important neural mediator substance called neuroprotectin D1 (NPD1). DHA acts synergistically with another neurotrophin, pigment epithelium-derived factor, in the brain and retinal tissues to activate NPD1. NPD1 has three functions that are critical to retinal pigment health and neuronal health and longevity: (1) up-regulation of anti-apoptotic proteins; (2) down-regulation of pro-apoptotic proteins; and (3) protection against oxidative and inflammatory injury to neurons.

The interplay of DHA-derived neuroprotective signaling aims to counteract pro-inflammatory, cell-damaging events triggered by multiple converging cytokine and amyloid peptide factors, as in the case of Alzheimer’s disease. Generation of NPD1 from DHA thereby appears to redirect cellular fate toward successful preservation of retinal pigment epithelial (RPE)-photoreceptor cell integrity and counteracts brain cell aging. Tissue analysis from brain specimens of several degenerative neuronal diseases, in particular retinal degeneration and Alzheimer’s disease, show deficiencies of DHA and NPD1.

The researchers concluded that supplements or dietary regimens high in DHA may be useful as new preventive/therapeutic strategies for neurodegenerative diseases. Cautions were voiced about using fish oil that has not had heavy metal contaminants removed, since the high levels of mercury in some fish oils are neurotoxic and could offset the benefit of the DHA. In addition, DHA is easily oxidized, and supplements should be stored in a tightly-sealed container in the refrigerator or freezer.

Going Nuts

Multiple papers and presentations focused on the nutritional benefits of various nuts and their potential usefulness in preventing specific diseases. Findings included the following:

•Pistachios are an excellent dietary source of lutein and zeaxanthin (L/Z), both of which are thought to be protective against age-related macular degeneration. Serum levels of L/Z are related to levels in the macular tissues of the retina, and these substances are transported into the retina by high-density lipoprotein (HDL). In a pistachio feeding study, treatment subjects (N = 16) were able to raise their serum HDL-L/Z levels by 52% on a supplement of 68 grams of pistachios per day as compared to controls (N = 14) whose HDL-L/Z levels decreased 2% on their usual diet.

•Almonds may soon be renamed the “wonder nut.” There were more than a dozen studies reporting various beneficial effects of almond consumption including: decreased lipid peroxidation (LDL), improved serum lipids (decreased LDL, increased HDL), reduced post-prandial lipemia, decreased 24-hour insulin secretion, and a probiotic effect stimulating growth of beneficial intestinal bacteria.

•Both hazelnuts and macadamia nuts have been shown in studies to improve lipid profiles (increase HDL and decrease LDL), likely due to their favorable fat content (high in monounsaturated fatty acids).

•Brazil nuts are an excellent source of selenium, with one large nut or two smaller nuts supplying 100 mg of selenium. Adequate selenium levels are thought to be important in preventing some cancers, especially prostate cancer. However, in an animal study presented at this meeting, high levels as well as low levels of selenium were both associated with increased prostate cancer risk. Thus, researchers cautioned against oversupplementing with selenium, and perhaps measuring baseline levels in persons before starting supplementation. Brazil nut lovers should use moderation in consumption.

Nutrition, Physical Activity, and Cancer Prevention

The World Cancer Research Fund and the American Institute for Cancer Research held a symposium within the conference to present their second report, “Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective.” The first report was published in 1997 and has been considered the “bible” on cancer prevention for the past decade. The volumes of new evidence and additional scientific literature on the subject led these organizations to plan an updated second report that was released in November 2007. This report is part of a continuing review of the evidence (more than 7000 studies) on cancer risk and prevention, and uses an expert panel’s judgment based on this evidence to make and update recommendations. The report lists eight key recommendations:

1. Body Fatness Be as lean as possible within the normal range of body weight:

•Be sure that body weight through childhood projects toward the lower end of normal body mass index (BMI) range at age 21.
•Maintain weight within normal range from age 21.
•Avoid weight gain and waist circumference increases throughout adulthood.

2. Physical Activity Be physically active as part of your everyday life:

•Do at least the equivalent of brisk walking 30 minutes per day.
•As fitness improves, aim for 60 minutes or more per day of moderate exercise (eg, brisk walking) or 30 minutes per day of vigorous physical activity.

3. Foods and Drinks That Promote Weight Gain Limit consumption of energy-dense foods, and avoid sugary drinks:

•Consume energy-dense foods (225-275 kcal/100 g) sparingly, with a goal of overall diet energy density of 125 kcal/100 g.
•Consume fast foods sparingly, if at all.

4. Plant Foods Eat mostly foods of plant origin:

•Eat at least 5 servings (400 g or 14 oz) of a variety of non-starchy vegetables and fruits every day.
•Eat relatively unprocessed cereals (grains) and legumes with every meal.
•Limit refined starchy foods.

5. Animal Foods Limit intake of red meat, and avoid processed meat:

•Persons who eat red meat should consume less than 500 g per week, and very little, if any, processed meat.

6. Alcoholic Drinks If alcoholic drinks are consumed, limit consumption to no more than 2 drinks per day for men and 1 drink per day for women.

7. Preservation, Processing, Preparation

•Limit consumption of salt; avoid preserving foods with salt, and avoid salt-preserved and high-salt foods.
•Don’t eat grains or legumes that may be moldy; they may contain the carcinogen aflatoxin.

8. Dietary Supplements Aim to meet nutritional needs through diet alone:

•Dietary supplements are not recommended for cancer prevention.

The consensus panel developed a color-coded matrix that is a very useful display of the known cancer risk and protective factors. An enlargement of this chart would be a useful educational tool in clinical practice. The report may be viewed online at www.dietandcancerreport.org.

Seattle Area Dementia Study

The Group Health Cooperative in the Seattle area has been conducting a large study that is monitoring cognitive function in a cohort of volunteer members of their healthcare group. Group Health Cooperative members who reach the age of 65 and have normal cognitive ability are eligible to enter the Adult Changes in Thought (ACT) study. Study participants undergo cognitive, neurological, and psychological tests every two years until their death. Since its inception in 1994, the study has enrolled 3400 participants.

The overall goal of the study is to better understand dementia in the community, and the report at this meeting was focused on the brain findings at autopsy in the ACT participants who had developed dementia before death. Of the 221 brains that were studied, research pathologists found that 45% of the brains of persons with dementia had degenerative changes characteristic of Alzheimer’s disease, and another 10% had the pathological changes of Lewy body dementia. Perhaps the most important finding was that 33% of the persons with dementia had it on the basis of microvascular disease, such as that seen with hypertension or diabetes. They concluded that at least this group of dementia patients (33%) has a potentially preventable dementia with better management of their vascular diseases.