Nutrition & Metabolism - Latest articles

Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes

Amanda M Gonzales and Robert A Orlando — 2008-06-12

Background: Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity. The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-κB signaling. In the present study, we examined if these natural products can inhibit NF-κB activation in adipocytes and in doing so reduce cytokine expression. Methods: Cytokine (TNF-α, IL-1β, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFα-stimulation. Cytokine protein and prostaglandin E2 (PGE2) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFα-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-κB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA. Results: Both preadipocytes and differentiated adipocytes express the genes for TNF-α, IL-6, and COX-2, key mediators of the inflammatory response. Preadipocytes were also found to express IL-1β; however, IL-1β expression was absent in differentiated adipocytes. TNF-α treatment activated NF-κB signaling in differentiated adipocytes by inducing IκB degradation and NF-κB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels. TNF-α also activated IL-1β gene expression in differentiated adipocytes, but had no effect on endogenous TNF-α mRNA levels. No detectable TNFα or IL-1β was secreted by adipocytes. Curcumin and resveratrol treatment inhibited NF-κB activation and resulted in a reduction of TNF-α, IL-1β, IL-6, and COX-2 gene expression (IC50 = 2 μM) and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 μM). Conclusion: Curcumin and resveratrol are able to inhibit TNFα-activated NF-κB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.

Physico-chemical modifications of conjugated linoleic acid for ruminal protection and oxidative stability

Hyun-Seuk Moon, Hong-Gu Lee, Chung-Soo Chung, Yun-Jaie Choi and Chong-Su Cho — 2008-06-01

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6]. Although ruminant milk and meat products represent the largest natural source of CLA and therefore, their concentration in ruminant lipids are of interest to human health, chemical or physical modifications of CLA should be needed as a means to enhance oxidative stability, to improve post-ruminal bioavailability, and to increase the clinical application. In fact, CLA are rapidly decomposed to form furan fatty acids when its are oxidized in air, and the effectiveness of dietary supplements of CLA may be related to the extent that their metabolisms by rumen bacteria are avoided. For these reasons, many scientists have examined the effect of manufacturing and protection on the stability of CLA in ruminants and food products. In this review, physico-chemical modifications of CLA for ruminal protection such as calcium salt (Ca), formaldehyde protection (FP), lipid encapsulation (LE), and amide linkage (AL), and for oxidative stability such as green tea catechin (GTC), cyclodextrin (CD), arginine (Arg), amylase, and PEGylation are proposed.

S100B concentration in colostrums of Burkinabe and Sicilian women

2008-05-22

The aim of this study is to determine the S100B concentration in colostrums of 51 Burkinabe and 30 Sicilian women, still living in their countries, and in case of a difference to search for its explanations, considering also ethnic differences.The concentration of S100B, in colostrums of the first three days from the delivery, was assessed with commercial immunoluminometric assay.The production of colostrums was significantly higher in Burkinabe women, where the colostrums S100B levels in the first day of lactation showed to be at 24 h higher than those of Sicilian mothers (672.21 ± 256.67 ng/ml vs 309.36 ± 65.28 ng/ml) and progressively decreased reaching the values of Sicilian mothers in the second and third day (204.31 ± 63.25 ng/ml and 199.42 ± 45.28 ng/ml, respectively). Correlation was found between the level of S100B and the length of stage II (duration of expulsive phase of delivery), but the correlation with pain was found only in Burkinabe women.The S100B level in colostrums of Burkinabe mothers differs from that of Sicilians only in the first day of lactation, and in consideration that Burkinabe women produce more colostrums, their newborns receive, during the first days of life, an higher amount of S100B. The elevated quantity of S100B ingested by Burkinabe newborn in the first days of life could promote the physiological postnatal brain adaptation and maturation in the precarious delivery condition of African infants.

Low-carbohydrate diet in type 2 diabetes: stable improvement of bodyweight and glycemic control during 44 months follow-up

Jörgen V Nielsen and Eva A Joensson — 2008-05-22

Background: Low-carbohydrate diets, due to their potent antihyperglycemic effect, are an intuitively attractive approach to the management of obese patients with type 2 diabetes. We previously reported that a 20% carbohydrate diet was significantly superior to a 55–60% carbohydrate diet with regard to bodyweight and glycemic control in 2 groups of obese diabetes patients observed closely over 6 months (intervention group, n = 16; controls, n = 15) and we reported maintenance of these gains after 22 months. The present study documents the degree to which these changes were preserved in the low-carbohydrate group after 44 months observation time, without close follow-up. In addition, we assessed the performance of the two thirds of control patients from the high-carbohydrate diet group that had changed to a low-carbohydrate diet after the initial 6 month observation period. We report cardiovascular outcome for the low-carbohydrate group as well as the control patients who did not change to a low-carbohydrate diet.MethodRetrospective follow-up of previously studied subjects on a low carbohydrate diet. Results: The mean bodyweight at the start of the initial study was 100.6 ± 14.7 kg. At six months it was 89.2 ± 14.3 kg. From 6 to 22 months, mean bodyweight had increased by 2.7 ± 4.2 kg to an average of 92.0 ± 14.0 kg. At 44 months average weight has increased from baseline g to 93.1 ± 14.5 kg. Of the sixteen patients, five have retained or reduced bodyweight since the 22 month point and all but one have lower weight at 44 months than at start. The initial mean HbA1c was 8.0 ± 1.5%. After 6, 12 and 22 months, HbA1c was 6.1 ± 1.0%, 7.0 ± 1.3% and 6.9 ± 1.1% respectively. After 44 months mean HbA1c is 6.8 ± 1.3%.Of the 23 patients who have used a low-carbohydrate diet and for whom we have long-term data, two have suffered a cardiovascular event while four of the six controls who never changed diet have suffered several cardiovascular events. Conclusion: Advice to obese patients with type 2 diabetes to follow a 20% carbohydrate diet with some caloric restriction has lasting effects on bodyweight and glycemic control.

Assessment of the bone quality of black male athletes using calcaneal ultrasound: a cross-sectional study

2008-05-20

Background: Lifestyle, genetics and environmental factors are established determinants of bone density. We aimed to describe the bone characteristics of competitive top-ranked Nigerian male athletes using calcaneal ultrasound and to assess whether intensive training promotes higher bone density in an environment with reportedly low calcium intake; to compare the bone characteristics of footballers with runners and other sportsmen; and to assess the correlation of stiffness index (SI) with activity level, since energy expenditure correlates with length of training and by extension, magnitude of skeletal loading. Methods: We recruited 102 male athletes: these included football (n = 68), running (n = 15), handball (n = 7), taekwando (n = 6), cycling (n = 2), judo (1), badminton (1) and high jump (1). Anthropometric data were first recorded on a structured form and energy expenditure was indirectly estimated with a validated questionnaire. Bone density was assessed using the Lunar Achilles+ calcaneal ultrasonometer. Results: The mean age of athletes was 25 ± 6 years. The means of BMI and energy expenditure were 21.9 ± 2.0 kg/m2 and 35.0 ± 13.7 kcal/kg/day, respectively. Footballers were younger (p < 0.001) and heavier (p < 0.001) than runners. Football was a significant determinant of BUA independent of age, BMI and energy expenditure (p = 0.001). Football was also a significant determinant of SOS independent of age, height, weight and BMI (p < 0.001). The mean SI was 127 ± 16 and the median T-score was 0.82 (-1.88, 3.35). The mean SI of footballers (130 ± 15), runners (130 ± 12) and other sportsmen (115 ± 18) differed significantly (p = 0.001). Multivariate analyses revealed that football (p < 0.001) and running (p < 0.001) were significant determinants of SI independent of age and BMI. Footballers when compared with other sportsmen had a higher mean SI independent of age and BMI (p < 0.001). Age was not correlated with SI. The median T-score of footballers, 0.94 (-1.0, 3.35) was higher than that of other sportsmen. Conclusion: Repetitive skeletal loading at the heel has the potential to improve bone density in black male athletes. The magnitude of increase may be higher in medium impact sports such as soccer and running compared with low or non-impact sports such as judo or taekwando, and is independent of age and BMI. However, future longitudinal data will be required to support our observations.

Down regulation by a low-zinc diet in gene expression of rat prostatic thymidylate synthase and thymidine kinase

2008-05-18

Background: Zinc has a wide spectrum of biological activities and its deficiency is related to various abnormalities of cell metabolism. Methods: Wistar male rats, at age of 4 weeks, were fed a low-zinc diet for six weeks. The levels of bromodeoxyuridine incorporated into the prostatic DNA and the mRNA expression levels of prostate thymidylate synthase and thymidine kinase were examined.ResultThe low-zinc diet caused a marked reduction in the body growth and organ weights, resulted in a low hematopoiesis, hypo-albuminemia and hypocholesterolemia. Although there were few differences in plasma biochemical markers, plasma levels of luteinizing hormone and testosterone were reduced by the low-zinc diet. Bromodeoxyuridine-immunoreactive (S-phase) cells and mRNA expression levels of thymidylate synthase and thymidine kinase in the prostate cells were markedly affected by the low-zinc diet. Conclusion: A low-zinc diet appears to reduce the body growth and organ weights including prostate, causing low plasma levels of luteinizing hormone and testosterone and reduction in prostate DNA replication in growing-rats.

Minimal nutrition intervention with high-protein/low-carbohydrate and low-fat, nutrient-dense food supplement improves body composition and exercise benefits in overweight adults: A randomized controlled trial

2008-04-21

Background: Exercise and high-protein/reduced-carbohydrate and -fat diets have each been shown separately, or in combination with an energy-restricted diet to improve body composition and health in sedentary, overweight (BMI > 25) adults. The current study, instead, examined the physiological response to 10 weeks of combined aerobic and resistance exercise (EX) versus exercise + minimal nutrition intervention designed to alter the macronutrient profile, in the absence of energy restriction, using a commercially available high-protein/low-carbohydrate and low-fat, nutrient-dense food supplement (EXFS); versus control (CON). Methods: Thirty-eight previously sedentary, overweight subjects (female = 19; male = 19) were randomly assigned to either CON (n = 10), EX (n = 14) or EXFS (n = 14). EX and EXFS participated in supervised resistance and endurance training (2× and 3×/wk, respectively); EXFS consumed 1 shake/d (weeks 1 and 2) and 2 shakes/d (weeks 3–10). Results: EXFS significantly decreased total energy, carbohydrate and fat intake (-14.4%, -27.2% and -26.7%, respectively; p < 0.017), and increased protein and fiber intake (+52.1% and +21.2%, respectively; p < 0.017). EX and EXFS significantly decreased fat mass (-4.6% and -9.3%, respectively; p < 0.017), with a greater (p < 0.05) decrease in EXFS than EX and CON. Muscle mass increase only reached significance in EXFS (+2.3%; p < 0.017), which was greater (p < 0.05) than CON but not EX (+1.1%). Relative VO2max improved in both exercise groups (EX = +5.0% and EXFS = +7.9%; p < 0.017); however, only EXFS significantly improved absolute VO2max (+6.2%; p = 0.001). Time-to-exhaustion during treadmill testing increased in EX (+9.8%) but was significantly less (p < 0.05) than in EXFS (+21.2%). Total cholesterol and LDL decreased only in the EXFS (-12.0% and -13.3%, respectively; p < 0.017). Total cholesterol-to-HDL ratio, however, decreased significantly (p < 0.017) in both exercise groups. Conclusion: Absent energy restriction or other dietary controls, provision of a high-protein/low-carbohydrate and -fat, nutrient-dense food supplement significantly, 1) modified ad libitum macronutrient and energy intake (behavior effect), 2) improved physiological adaptations to exercise (metabolic advantage), and 3) reduced the variability of individual responses for fat mass, muscle mass and time-to-exhaustion – all three variables improving in 100% of EXFS subjects.

Has carbohydrate-restriction been forgotten as a treatment for diabetes mellitus? A perspective on the ACCORD study design

Eric C Westman and Mary C Vernon — 2008-04-09

Prior to the discovery of medical treatment for diabetes, carbohydrate-restriction was the predominant treatment recommendation to treat diabetes mellitus. In this commentary we argue that carbohydrate-restriction should be reincorporated into contemporary treatment studies for diabetes mellitus.

Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal

2008-04-08

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.

A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study

2008-03-27

Background: This study evaluated a specialized whey fraction (Prolibra™, high in leucine, bioactive peptides and milk calcium) for use as a dietary supplement to enhance weight loss. Methods: This was a randomized, double-blind, parallel-arm, 12-week study. Caloric intake was reduced 500 calories per day. Subjects consumed Prolibra or an isocaloric ready-to-mix beverage 20 minutes before breakfast and 20 minutes before dinner. Body fat and lean muscle tissue were measured by dual-energy x-ray absorptiometry (DEXA). Body weight and anthropometric measurements were recorded every 4 weeks. Blood samples were taken at the beginning and end of the study. Statistical analyses were performed on all subjects that completed (completer analysis) and all subjects that lost at least 2.25 kg of body weight (responder analysis). Within group significance was determined at P < 0.05 using a two-tailed paired t-test and between group significance was determined using one way analysis of covariance with baseline data as a covariate. Results: Both groups lost a significant amount of weight and the Prolibra group tended to lose more weight than the control group; however the amount of weight loss was not significantly different between groups after 12 weeks. Prolibra subjects lost significantly more body fat compared to control subjects for both the completer (2.81 vs. 1.62 kg P = 0.03) and responder (3.63 vs. 2.11 kg, P = 0.01) groups. Prolibra subjects lost significantly less lean muscle mass in the responder group (1.07 vs. 2.41 kg, P = 0.02). The ratio of fat to lean loss (kg fat lost/kg lean lost) was much larger for Prolibra subjects for both completer (3.75 vs. 1.05) and responder (3.39 vs. 0.88) groups. Conclusion: Subjects in both the control and treatment group lost a significant amount of weight with a 500 calorie reduced diet. Subjects taking Prolibra lost significantly more body fat and showed a greater preservation of lean muscle compared to subjects consuming the control beverage. Because subjects taking Prolibra lost 6.1% of their body fat mass, and because a 5% reduction of body fat mass has been shown to reduce the risk of obesity related disease, the results have practical significance.