Archive for May, 2009

Protective Effect of Total Carotenoid and Lycopene Intake on the Risk of Hip Fracture: A 17-Year Follow-Up From the Framingham Osteoporosis Study.

Friday, May 8th, 2009
Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL
Abstract In vitro and in vivo studies suggest that carotenoids may inhibit bone resorption; yet no previous study has examined individual carotenoid intake (other than beta-carotene) and the risk of fracture. We evaluated associations of total and individual carotenoid intake (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein+zeaxanthin) with incident hip fracture and non-vertebral osteoporotic fracture. 370 men and 576 women (mean age 75 +/- 5 y) from the Framingham Osteoporosis Study completed a food frequency questionnaire (FFQ) in 1988-89 and were followed for hip fracture until 2005 and non-vertebral fracture until 2003. Tertiles of carotenoid intake were created from estimates obtained using the Willett FFQ adjusting for total energy (residual method). Hazard ratios (HR) were estimated using Cox-proportional hazards regression, adjusting for sex, age, body mass index, height, total energy, calcium and vitamin D intake, physical activity, alcohol, smoking, multivitamin use and current estrogen use. A total of 100 hip fractures occurred over 17-y of follow-up. Subjects in the highest tertile of total carotenoid intake had lower risk of hip fracture (P trend=0.02). Subjects with higher lycopene intake had lower risk of hip fracture (P trend=0.01), and non-vertebral fracture (P trend=0.02). A weak protective trend was observed for total beta-carotene for hip fracture alone but associations didnot reach statistical significance (P trend=0.10). No significant associations were observed with alpha-carotene, beta-cryptoxanthin or lutein plus zeaxanthin. These results suggest a protective role of several carotenoids for bone health in older adults.
J Bone Miner Res. 2009 Jan 12; [Epub ahead of print]

Posted in Bone Health | 2 Comments »

Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women’s Antioxidant and Folic Acid Cardiovascular Study.

Friday, May 8th, 2009

Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE.

Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Avenue E, Boston, MA 02215-1204, USA. wchristen@rics.bwh.harvard.edu

BACKGROUND: Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and the risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of therapy to lower homocysteine levels in AMD are lacking. Our objective was to examine the incidence of AMD in a trial of combined folic acid, pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)) therapy. METHODS: We conducted a randomized, double-blind, placebo-controlled trial including 5442 female health care professionals 40 years or older with preexisting cardiovascular disease or 3 or more cardiovascular disease risk factors. A total of 5205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), pyridoxine hydrochloride (50 mg/d), and cyanocobalamin (1 mg/d) or placebo. Our main outcome measures included total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. RESULTS: After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the combination treatment group and 82 in the placebo group (relative risk, 0.66; 95% confidence interval, 0.47-0.93 [P = .02]). For visually significant AMD, there were 26 cases in the combination treatment group and 44 in the placebo group (relative risk, 0.59; 95% confidence interval, 0.36-0.95 [P = .03]). CONCLUSIONS: These randomized trial data from a large cohort of women at high risk of cardiovascular disease indicate that daily supplementation with folic acid, pyridoxine, and cyanocobalamin may reduce the risk of AMD.

Arch Intern Med. 2009 Feb 23;169(4):335-41.Click here to read

Posted in Eye Health | 2 Comments »

Enteral Nutrition Enriched With Eicosapentaenoic Acid (EPA) Preserves Lean Body Mass Following Esophageal Cancer Surgery: Results of a Double-Blinded Randomized Controlled Trial

Friday, May 1st, 2009

Ryan, Aoife M. PhD; Reynolds, John V. MD; Healy, Laura BSc; Byrne, Miriam MD; Moore, Jennifer RN; Brannelly, Niamh BSc; McHugh, Aisling BSc; McCormack, Deirdre BSc; Flood, Philomena BSc

Collapse Box

Abstract

Background: Esophagectomy represents an exemplar of controlled major trauma, with marked metabolic, immunologic, and physiologic changes as well as an associated high incidence of complications. Eicosapentaenoic acid (EPA) enriched enteral nutrition (EN) modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the peri-operative period is unclear.

Objectives: To examine the effects of perioperative EPA enriched EN on the metabolic, nutritional, and immuno-inflammatory response to esophagectomy, and on postoperative complications.

Methods: In a double-blind design, patients were randomized to a standard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively (orally) and 21 days postoperatively (jejunostomy). Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21. Postoperative complications were monitored, as well as the acute phase response, coagulation markers, and serum cytokines.

Results: Fifty-three patients (28 EPA, 25 standard) completed the study, and both groups were well matched. Serum and peripheral blood mononuclear cell (PBMC) membrane EPA levels were significantly increased in the EPA group. There was no difference in the incidence of major complications. The EPA group maintained all aspects of body composition postoperatively, whereas patients in the standard EN group lost significant amounts of fat-free mass (1.9 kg, P = 0.030) compared with the EPA group [leg (0.3 kg, P = 0.05), arm (0.17 kg, P = 0.01), and trunk (1.44 kg, P = 0.03)]. The EPA group had a significantly (P < 0.05) attenuated stress response for TNFα, IL-10, and IL-8 compared with the standard group.

Conclusions: EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a standard EN. These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens.

Annals of Surgery:
March 2009 - Volume 249 - Issue 3 - pp 355-363

Posted in Cancer | 3 Comments »

Total and Cancer Mortality After Supplementation With Vitamins and Minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial

Friday, May 1st, 2009
You-Lin Qiao, Sanford M. Dawsey, Farin Kamangar, Jin-Hu Fan, Christian C. Abnet, Xiu-Di Sun, Laura Lee Johnson, Mitchell H. Gail, Zhi-Wei Dong, Binbing Yu, Steven D. Mark, Philip R. Taylor
Background: The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29 584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with “factor D,” a combination of 50 µg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention. Methods: Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models.

Results: Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .47). Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality.

Conclusion: The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.

For more information on custom supplementation go to Genewize.com

Posted in Cancer | 4 Comments »

Insulin, Insulin-Like Growth Factor-I, and Risk of Breast Cancer in Postmenopausal Women

Friday, May 1st, 2009
Marc J. Gunter, Donald R. Hoover, Herbert Yu, Sylvia Wassertheil-Smoller, Thomas E. Rohan, JoAnn E. Manson, Jixin Li, Gloria Y. F. Ho, Xiaonan Xue, Garnet L. Anderson, Robert C. Kaplan, Tiffany G. Harris, Barbara V. Howard, Judith Wylie-Rosett, Robert D. Burk, Howard D. Strickler

Background: The positive association between obesity and postmenopausal breast cancer has been attributed, in part, to the fact that estrogen, a risk factor for breast cancer, is synthesized in adipose tissue. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed associations between circulating levels of insulin and/or insulin-like growth factor (IGF)-I, a related hormone, and the risk of breast cancer independent of estrogen level.

Methods: We conducted a case–cohort study of incident breast cancer among nondiabetic women who were enrolled in the Women’s Health Initiative Observational Study (WHI-OS), a prospective cohort of 93 676 postmenopausal women. Fasting serum samples obtained at study entry from 835 incident breast cancer case subjects and from a subcohort of 816 randomly chosen WHI-OS subjects were tested for levels of insulin, glucose, total IGF-I, free IGF-I, insulin-like growth factor binding protein-3, and estradiol. Multivariable Cox proportional hazards models were used to estimate associations between levels of the serologic factors and baseline characteristics (including body mass index [BMI]) and the risk of breast cancer. All statistical tests were two-sided.

Results: Insulin levels were positively associated with the risk of breast cancer (hazard ratio [HR] for highest vs lowest quartile of insulin level = 1.46, 95% confidence interval [CI] = 1.00 to 2.13, Ptrend = .02); however, the association with insulin level varied by hormone therapy (HT) use (Pinteraction = .01). In a model that controlled for multiple breast cancer risk factors including estradiol, insulin level was associated with breast cancer only among nonusers of HT (HR for highest vs lowest quartile of insulin level = 2.40, 95% CI = 1.30 to 4.41, Ptrend < .001). Obesity (BMI ≥30 kg/m2) was also associated with the risk of breast cancer among nonusers of HT (HR for BMI ≥30 kg/m2 vs 18.5 to <25 kg/m2 = 2.12, 95% CI = 1.26 to 3.58, Ptrend = .003); however, this association was attenuated by adjustment for insulin (Ptrend = .40).

Conclusion: These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity–breast cancer relationship.

J Natl Cancer Inst 2009 101: 1. [Extract] [Full Text] [PDF]

Posted in Cancer | 3 Comments »

Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion.

Friday, May 1st, 2009

Butler JA, Hagen TM, Moreau R.

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.

Elevated blood triacylglycerol (TG) is a significant contributing factor to the current epidemic of obesity-related health disorders, including type-2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The observation that mice lacking the enzyme sn-glycerol-3-phosphate acyltransferase are protected from insulin resistance suggests the possibility that the regulation of TG synthesis be a target for therapy. Five-week-old Zucker Diabetic Fatty (ZDF) rats were fed a diet containing (R)-alpha-lipoic acid (LA, approximately 200mg/kg body weight per day) for 5 weeks. LA offset the rise in blood and liver TG by inhibiting liver lipogenic gene expression (e.g. sn-glycerol-3-phosphate acyltransferase-1 and diacylglycerol O-acyltransferase-2), lowering hepatic TG secretion, and stimulating clearance of TG-rich lipoproteins. LA-induced TG lowering was not due to the anorectic properties of LA, as pair-fed rats developed hypertriglyceridemia. Livers from LA-treated rats exhibited elevated glycogen content, suggesting dietary carbohydrates were stored as glycogen rather than becoming lipogenic substrate. Although AMP-activated protein kinase (AMPK) reportedly mediates the metabolic effects of LA in rodents, no change in AMPK activity was observed, suggesting LA acted independently of this kinase. The hepatic expression of peroxisome proliferator activated receptor alpha (PPARalpha) target genes involved in fatty acid beta-oxidation was either unchanged or decreased with LA, indicating a different mode of action than for fibrate drugs. Given its strong safety record, LA may have potential clinical applications for the treatment or prevention of hypertriglyceridemia and diabetic dyslipidemia.

Arch Biochem Biophys. 2009 May 1;485(1):63-71. Epub 2009 Feb 20.Click here to read

Posted in Cardiovascular | 3 Comments »

Determining the Effects of Lipophilic Drugs on Membrane Structure by Solid-State NMR Spectroscopy: The Case of the Antioxidant Curcumin

Friday, May 1st, 2009
Jeffrey Barry, Michelle Fritz, Jeffrey R. Brender, Pieter E. S. Smith, Dong-Kuk Lee† and Ayyalusamy Ramamoorthy*
Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055
J. Am. Chem. Soc., 2009, 131 (12), pp 4490–4498
DOI: 10.1021/ja809217u

Present address: Department of Fine Chemistry, Seoul National University of Technology, Seoul, Korea.

Abstract

Abstract Image

Curcumin is the active ingredient of turmeric powder, a natural spice used for generations in traditional medicines. Curcumin’s broad spectrum of antioxidant, anticarcinogenic, antimutagenic, and anti-inflammatory properties makes it particularly interesting for the development of pharmaceutical compounds. Because of curcumin’s various effects on the function of numerous unrelated membrane proteins, it has been suggested that it affects the properties of the bilayer itself. However, a detailed atomic-level study of the interaction of curcumin with membranes has not been attempted. A combination of solid-state NMR and differential scanning calorimetry experiments shows curcumin has a strong effect on membrane structure at low concentrations. Curcumin inserts deep into the membrane in a transbilayer orientation, anchored by hydrogen bonding to the phosphate group of lipids in a manner analogous to cholesterol. Like cholesterol, curcumin induces segmental ordering in the membrane. Analysis of the concentration dependence of the order parameter profile derived from NMR results suggests curcumin forms higher order oligomeric structures in the membrane that span and likely thin the bilayer. Curcumin promotes the formation of the highly curved inverted hexagonal phase, which may influence exocytotic and membrane fusion processes within the cell. The experiments outlined here show promise for understanding the action of other drugs such as capsaicin in which drug-induced alterations of membrane structure have strong pharmacological effects.

Posted in Antioxidants | 2 Comments »