Medical Research Abstracts

Omega-3 Fatty Acid Diet Cuts Amyloid Burden in Murine Alzheimer's Model

Consuming a diet that is enriched with the omega-3 fatty acid docosahexanoic acid (DHA) reduces amyloid build-up in a murine model of Alzheimer's disease, according to a report in the March 30th issue of The Journal of Neuroscience.

"These results suggest that dietary DHA could be protective against beta-amyloid production, accumulation, and potential downstream toxicity," senior author Dr. Greg M. Cole, from the University of California at Los Angeles, and colleagues note.

There is epidemiologic evidence that increased intake of DHA may reduce the risk of Alzheimer's disease. Still, the effects of this fatty acid on Alzheimer's pathogenesis were unknown.

Further analysis showed that DHA altered the processing of amyloid precursor protein by decreasing both terminal fragment products as well as the full-length protein. By contrast, expression of ApoE was not affected by the high-DHA diet.

J Neurosci 2005;25

High Dietary Iron in Patients With Elevated Transferrin Saturation May Increase Cancer Risk

High intake of dietary iron in patients with elevated transferrin saturation increases the risk of cancer, according to the results of a cohort study published in the March/April issue of the Annals of Family Medicine.

"Transferrin saturation of more than 60% has been identified as a cancer risk factor," write Arch G. Mainous III, PhD, from the Medical University of South Carolina in Charleston, and colleagues. "It is unclear whether dietary iron intake increases the risk of cancer among individuals with transferrin saturation of less than 60%."

"Among persons with increased transferrin saturation, a daily intake of dietary iron more than 18 mg is associated with an increased risk of cancer," the authors write. "Future research might focus on the benefits of dietary changes in those individuals with increased serum transferrin saturation."

"The current evidence suggests that if a large proportion of the adult US population ingests high levels of dietary iron, then they have a significantly increased risk for deleterious consequences," the authors write. "Although severe iron deficiency causes serious adverse health effects, these data call into question the strategy of the addition of iron to food by manufacturers."

Ann Fam Med. 2005;3:131-137

Fish Oil Supplements May Increase Heart Rate

Fish oil supplements increase heart rate variability (HRV), according to the results of a randomized study published in the April issue of Chest. Soy oil was not as effective.

"Omega-3 fatty acid levels are associated with decreased risk for sudden death; however, the protective cardiovascular mechanisms of omega-3 are poorly understood," write Fernando Holguin, MD, from the Emory University School of Medicine in Atlanta, Georgia, and colleagues. "One of the proposed mechanisms by which omega-3 fatty acids may decrease the risk of arrhythmia is by increasing HRV, a measure of cardiac autonomic regulation."

After an initial control period of two months without supplementation, 58 elderly nursing home residents were randomized to receive a daily high dose of marine-derived omega-3 fatty acids (2 g/day of fish oil capsules) or a lower daily dose of a plant-derived omega-3 fatty acid (a-linolenic acid) in soy oil (2 g/day). Every other day for six months, patients had six-minute measurements of HRV while resting supine.

During the supplementation period, the average time-domain and frequency-domain parameters of HRV increased significantly in both groups. After adjusting for age and mean heart rate, supplementation with fish oil was associated with a significant increase in the high- and low-frequency components, and SD of normal R-R intervals (SDNN), whereas only SDNN increased significantly in the soy oil group.

"Supplementation with 2 g/d[ay] of fish oil was well tolerated and was associated with a significant increase in HRV," the authors write. "Therefore, a diet supplemented with omega-3 fatty acids derived from either soy oil or fish oil in conjunction with other factors known to increase HRV such as exercise, weight loss, stress reduction, and restoration of normal sleep could be part of an effective way to improve cardiac autonomic function."

"The American Heart Association has endorsed omega-3 fish oils as an important component of secondary prevention in patients with CHD [coronary heart disease"

Chest. 2005;127:1102-1107

High Intake of Processed Meat Increases Pancreatic Cancer Risk

A high intake of red meat and, particularly, processed meat, increases the risk of pancreatic cancer, suggest results of a large multiethnic study presented today, the last day of the 96th annual gathering of the American Association for Cancer Research.

The results hint that carcinogenic substances related to meat processing, such as heterocyclic amines or polycyclic aromatic hydrocarbons, rather than the inherent fat or cholesterol content, might be responsible for the association, Dr. Ute Nothlings from the Cancer Research Center of Hawaii in Honolulu told Reuters Health.

Meat consumption has been linked to pancreatic cancer in several case-control studies, but the results have been inconsistent and prospective data are lacking.

Dr. Nothlings and colleagues examined the relationship between diet and pancreatic cancer in 190,545 men and women in the Hawaii-Los Angeles Multiethnic Cohort Study of Diet and Cancer. The subjects included African Americans, Japanese Americans, Caucasians, Latinos and Native Hawaiians.

During an average follow up of 7 years, 482 subjects developed pancreatic cancer. In analyses adjusting for age, smoking status, history of diabetes, family history of pancreatic cancer and ethnicity, subjects with the highest intake of processed meat had a 67% increased risk of developing pancreatic cancer compared with those with the lowest intake of processed meat.

A high intake of pork and total red meat increased the risk of pancreatic cancer by about 50%. "In our study, red meat and processed meat intake were the most pronounced risk factors for exocrine pancreatic cancer, associated with a 50% to 70% increased risk for those consuming the largest amounts, respectively," Dr. Nothlings said.

Consumption of poultry, fish, dairy products, and eggs did not influence the overall risk of pancreatic cancer, nor did overall intake of total fat, saturated fat or cholesterol.

"An analysis of fat and saturated fat intakes showed a significant increase in risk for fats from meat, but not from dairy products, indicating that fat and saturated fat are not likely to contribute to the risk of pancreatic cancer," the team points out in a meeting abstract.

IBD Patients May Benefit From Folic Acid Supplementation

Homocysteine levels are increased in both the mucosa and blood of patients with Crohn's disease and ulcerative colitis, according to a new study, suggesting that this molecule may play a pathogenic role in intestinal inflammation. Further, the effect could be abolished by folate supplementation.

Elevated homocysteine "contributes to the pathophysiology" of several chronic inflammatory diseases, investigators note in the April issue of the American Journal of Gastroenterology. But whether homocysteine is involved in mucosal inflammation in patients with inflammatory bowel disease (IBD) has not been explored, until now.

In their study of 83 patients with Crohn's, 83 with ulcerative colitis, and 70 healthy controls, plasma and mucosal homocysteine levels were significantly higher in IBD patients relative to control subjects.

The team also observed low folate levels in the IBD patients. Folate levels were inversely correlated with homocysteine levels and, in in vitro studies, the addition of folic acid, a homocysteine scavenger, blocked the homocysteine-triggered inflammatory effects.

Therefore, Dr. Silvio Danese, from Catholic University in Rome, Italy and colleagues think it would be "reasonable to hypothesize a beneficial effect of folic acid supplementation in IBD patents to eliminate the homocysteine-mediated inflammatory events, especially mononuclear cell adhesion."

Am J Gastroenterol 2005;100:896-895

Low Levels of Zinc Linked to Esophageal Cancer

Low tissues levels of zinc appear to raise the risk esophageal squamous cell carcinoma, according to a report published in the Journal of the National Cancer Institute for February 16.

The findings support animal research showing that zinc deficiency potentiates the effects of certain nitrosamines, which are known esophageal carcinogens. Previous attempts to demonstrate an association in humans have been hampered by the inability to measure esophageal levels of zinc.

In the present study, Dr. Christian C. Abnet, from the National Cancer Institute in Bethesda, Maryland, and colleagues used x-ray fluorescence spectroscopy to assess esophageal zinc levels in biopsy specimens obtained from 132 residents of Linzhou, China in 1985. Of these subjects, 60 subsequently developed esophageal cancer and 72 did not.

The authors also found that esophageal cancer risk fell as tissue sulfur levels rose, although the association fell short of statistical significance (p = 0.08).

While the findings are interesting, their applicability to US or European populations is unclear. "We did this study in a population that is at extremely high risk for esophageal cancer," Dr. Abnet told Reuters Health. "Also, these subjects in China probably have fairly low zinc intake and tissue levels compared with a US population."

He said his group is interested in conducting a similar study in populations with a lower risk of esophageal cancer and higher zinc levels. "We don't have any data regarding an association with esophageal cancer in a zinc-sufficient population," Dr. Abnet commented. "It's possible that once you get above a certain threshold, tissue zinc levels are no longer associated with cancer risk."

J Natl Cancer Inst 2005;97:301-306.

Raw Food Vegetarian Diet May Cause Low BMD Without Evidence of Increased Bone Turnover

March 28, 2005 - People on a raw food (RF) vegetarian diet have low bone mineral density (BMD) but without evidence of increased bone turnover, according to the results of a small, cross-sectional study published in the March 28 issue of the Archives of Internal Medicine. The authors suggest that further study is needed to determine fracture risk.

"Because of their low calorie and low protein intake, RF vegetarians have a low body mass index (BMI) and a low total body fat content," write Luigi Fontana, MD, PhD, from Washington University School of Medicine in St. Louis, Missouri, and colleagues. "It is well documented that a low BMI and weight loss are strongly associated with low bone mass and increased fracture risk, while obesity protects against osteoporosis. However, the underlying mechanisms are not entirely clear."

The 18 volunteers studied included 11 men and seven women on an RF vegetarian diet for a mean of 3.6 years. Mean age was 54.2 ± 11.5 years. The authors compared body composition, bone mineral content and density, bone turnover markers (C-telopeptide of type I collagen and bone-specific alkaline phosphatase), C-reactive protein, 25-hydroxyvitamin D, insulin-like growth factor 1, and leptin in serum in these RF vegetarians with the same parameters in a comparison age- and sex-matched group eating typical American diets.

Mean BMI was 20.5 ± 2.3 kg/m2 in the RF vegetarians and 25.4 ± 3.3 kg/m2 in the control subjects. Compared with the control group, the RF vegetarians had lower mean bone mineral content (P = .003) and density of the lumbar spine (P < .001) and hip (P = .01 and P < .001, respectively). Both groups had similar serum C-telopeptide of type I collagen and bone-specific alkaline phosphatase levels. However, the RF group had higher mean 25-hydroxyvitamin D concentration (P < .001) and lower mean serum C-reactive protein (P = .03), insulin-like growth factor 1 (P = .002), and leptin (P = .005) than did the control group.

"A[n] RF vegetarian diet is associated with low bone mass at clinically important skeletal regions but is without evidence of increased bone turnover or impaired vitamin D status," the authors write. "Although low bone mass is a risk factor for fracture, bone quality also plays a role. It is therefore possible that RF vegetarians with a low bone mass may not have an increased incidence of fractures because of good bone quality."

Study limitations include small sample size, recruitment by advertisement, motivation of the RF vegetarians to confirm the beneficial effects of their diet, and inability to exclude the possibility that low bone mass could also be due to low peak bone mass rather than loss after institution of an RF diet.

"It will be necessary to follow up a large number of RF vegetarians for a sufficiently long period to determine whether they have an increased risk of developing fractures," the authors conclude.

The General Clinical Research Center, Diabetes Research and Training Center, and Clinical Nutrition Research Unit of the National Institutes of Health in Bethesda, Maryland, supported this study. The authors report no financial conflicts of interest.

Arch Intern Med. 2005;165:684-689

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