¹ From the Departments of Human Nutrition (LEN, ALC, MLA, LFL, JRR, and MAB) and Statistics (JCH and DL), Department of Internal Medicine, Division of Endocrinology (KO and RDJ), The Ohio State University, Columbus, OH, and Nutrition and Health, Cognis, Monheim, Germany (DB).

² Cognis had no input into the design, interpretation, or dissemination of findings from the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

³ Supported, in part, by the National Center for Research Resources (UL1RR025755) and the Clinical Research Center at the Ohio State University (grant M01-RR00034) from the NIH, the Caroline S Kennedy Endowment. An unrestricted monetary gift and dietary oils were donated by Cognis (Monheim, Germany, and Cincinnati, OH).

⁴ Address correspondence to MA Belury, Department of Human Nutrition, The Ohio State University, 1787 Neil Avenue, Columbus, OH 43210. E-mail: mbelury@ehe.osu.edu.

ABSTRACT

Background: Weight loss may improve glucose control in persons with type 2 diabetes. The effects of fat quality, as opposed to quantity, on weight loss are not well understood.

Objective: We compared the effects of 2 dietary oils, conjugated linoleic acid (CLA) and safflower oil (SAF), on body weight and composition in obese postmenopausal women with type 2 diabetes.

Design: This was a 36-wk randomized, double-masked, crossover study. Fifty-five obese postmenopausal women with type 2 diabetes received SAF or CLA (8 g oil/d) during two 16-wk diet periods separated by a 4-wk washout period. Subjects met monthly with the study coordinator to receive new supplements and for assessment of energy balance, biochemical endpoints, or anthropometric variables.

Results: Thirty-five women completed the 36-wk intervention. Supplementation with CLA reduced body mass index (BMI) (P = 0.0022) and total adipose mass (P = 0.0187) without altering lean mass. The effect of CLA in lowering BMI was detected during the last 8 wk of each 16-wk diet period. In contrast, SAF had no effect on BMI or total adipose mass but reduced trunk adipose mass (P = 0.0422) and increased lean mass (P = 0.0432). SAF also significantly lowered fasting glucose (P = 0.0343) and increased adiponectin (P = 0.0051). No differences were observed in dietary energy intake, total fat intake, and fat quality in either diet period for either intervention.

Conclusions: Supplementation with CLA and SAF exerted different effects on BMI, total and trunk adipose mass, and lean tissue mass in obese postmenopausal women with type 2 diabetes. Supplementation with these dietary oils may be beneficial for weight loss, glycemic control, or both.

Am J Clin Nutr (June 17, 2009). doi:10.3945/ajcn.2008.27371

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© 2009 American Society for Clinical Nutrition

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.

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, P_trend = .02); however, the association with insulin level varied by hormone therapy (HT) use (P_interaction = .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, P_trend < .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, P_trend = .003); however, this association was attenuated by adjustment for insulin (P_trend = .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]

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.

Abstract

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.

After adjusting for age, sex, race/ethnicity, body mass index, socioeconomic status and physical activity, researchers found the adolescents with the lowest levels of vitamin D were:

• 2.36 times more likely to have high blood pressure;
• 2.54 times more likely to have high blood sugar; and
• 3.99 times more likely to have metabolic syndrome.

Metabolic syndrome is a cluster of cardiovascular disease and diabetes risk factors including elevated waist circumference, high blood pressure, elevated triglycerides, low levels of high-density lipoprotein (HDL or “good”) cholesterol and high fasting glucose levels. The presence of three or more of the factors increases a person’s risk of developing diabetes and cardiovascular disease.

“We showed strong associations between low levels of vitamin D and higher risk of high blood pressure, hyperglycemia and metabolic syndrome among adolescents, confirming the results of studies among adults,” said Jared P. Reis, Ph.D., the study’s lead author and post-doctoral research fellow at Johns Hopkins Bloomberg School of Public Health in Baltimore.

Researchers used a biomarker of vitamin D to measure levels in blood. The biomarker measures vitamin D obtained from food, vitamin supplementation and exposure to sunlight.

The ethnic breakdown was similar to the general U.S. population: 64.7 percent non-Hispanic whites; 13.5 percent non-Hispanic blacks; and 11 percent Mexican Americans.

The study highlights the association between high levels of vitamin D and lower risk of heart disease. The highest levels of vitamin D were found in whites, the lowest levels in blacks and intermediate levels in Mexican Americans. Whites had almost twice as high levels as blacks.

In whites, the average level of vitamin D was 28.0 nanograms per milliliter (ng/mL); in blacks, 15.5 ng/mL; and in Mexican Americans, 21.5 ng/mL.

“Although our study is important, we believe clinical trials designed to determine the effects of vitamin D supplementation on the risk of heart disease risk factors in adolescents should be conducted before recommendations can be made for vitamin D in the prevention of cardiovascular disease,” Reis said.

The Institute of Medicine recommends a daily intake of vitamin D of 200 International Units (IU) for those less than 50 years, which includes children and adolescents. More recent recommendations, however, from the American Academy of Pediatrics suggests a daily intake of 400 IU daily. While these intakes have been shown to be important in the prevention of skeletal conditions such as rickets in children and osteoporosis in adults, some specialists have suggested intakes of at least 1,000 IU daily may be needed for overall health.

Low levels of vitamin D are strongly associated with overweight and abdominal obesity. Since vitamin D is a fat-soluble vitamin, it may be sequestered within adipose tissue. This may explain why those who are obese are more likely to be vitamin D deficient, Reis said.

Vitamin D plays a useful role in general human health, particularly in bone health. Other roles are emerging, Reis said. “This is an exciting time; since we are just now beginning to understand the role that vitamin D may play in cardiovascular health.”

“These data on serum vitamin D levels in young people raise some concern about their food choices and even the amount of time they spend in the sunshine,” said Robert H. Eckel, M.D., American Heart Association past president. “The American Heart Association recommends an overall healthy diet and lifestyle, and that people get their nutrients primarily from food sources rather than supplements.”

Co-authors are: Denise von Muhlen, M.D., Ph.D.; Edgar R. Miller III, M.D., Ph.D.; Erin D. Michos, M.D., M.H.S.; and Lawrence J. Appel, M.D., M.P.H.

BACKGROUND: Milk thistle and its components are widely used as an alternative therapy for liver disease because of purported antioxidant, anti-inflammatory, and iron chelating properties.

STUDY: Thirty-seven patients with chronic hepatitis C and Batts-Ludwig fibrosis stage II, III, or IV were randomized to 1 of 3 doses of IdB 1016 for 12 weeks. Serum ferritin, serum iron, total iron binding capacity, and transferrin-iron saturation were measured at baseline, during treatment, and 4 weeks thereafter. Wilcoxon signed rank tests were used to compare baseline and posttreatment values.

RESULTS: There was a significant decrease in serum ferritin from baseline to end of treatment (mean, 244 vs. 215 mug/L; median, 178 vs. 148 mug/L; P=0.0005); 78% of subjects had a decrease in serum ferritin level. There was no significant change in serum iron or transferrin-iron saturation. Multivariate logistic regression analysis in a model that included dose, age, sex, HFE genotype, history of alcohol use, and elevated baseline ferritin levels demonstrated that stage III or IV fibrosis was independently associated with decreased posttreatment serum ferritin level.

CONCLUSIONS: Treatment with IdB 1016 is associated with reduced body iron stores, especially among patients with advanced fibrosis stage.

J Clin Gastroenterol. 2008 Sep;42(8):937-44.