A. P. Nugent

The effect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects

Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of linoleic acid. Studies using animal models have shown that CLA reduces adiposity, improves plasma lipoprotein metabolism and insulin sensitivity and reduces arteriosclerosis. Whilst CLA may have therapeutic potential with regard to coronary artery disease risk factors in human subjects, there has been little investigation into its effects in human subjects. This current study investigated the effects of dietary supplementation using two isomeric blends of CLA on triacylglycerol (TAG)-rich lipoprotein metabolism and reverse cholesterol transport in human subjects and evaluates whether CLA modulated cardiovascular disease risk factors. Fifty-one normolipidaemic subjects participated in this randomised double-blind placebo-controlled intervention trial. Subjects were randomly assigned to receive 3 g cis-9,trans-11-trans-10,cis-12 isomeric blend (50 : 50) or a cis-9,trans-11-trans-10,cis-12 isomeric blend (80 : 20) CLA or linoleic acid (control)/d for 8 weeks. The 50 : 50 CLA isomer blend significantly reduced (P<or=0.005) fasting plasma TAG concentrations. The 80 : 20 CLA isomer blend significantly reduced (P<or=0.05) VLDL-cholesterol concentrations. CLA supplementation had no significant effect on LDL-cholesterol, HDL-lipid-protein composition or reverse cholesterol transport. CLA supplementation had no effect on body weight, plasma glucose and insulin concentrations. Fatty acid analysis revealed that the cis-9,trans-11 CLA isomer was incorporated into total plasma lipids following supplementation with both isomeric blends of CLA. The present study demonstrates that CLA supplementation significantly improves plasma TAG and VLDL metabolism in human subjects. The study confirms that some of the cardio-protective effects of CLA that were shown in animal studies are relevant to man.

Antidiabetic Effects of cis-9, trans-11–Conjugated Linoleic Acid May Be Mediated via Anti-Inflammatory Effects in White Adipose Tissue

Adipose tissue may be the source of insulin desensitizing proinflammatory molecules that predispose to insulin resistance. This study investigated whether dietary fatty acids could attenuate the proinflammatory insulin-resistant state in obese adipose tissue. The potential antidiabetic effect of cis-9, trans-11–conjugated linoleic acid (c9,t11-CLA) was determined, focusing on the molecular markers of insulin sensitivity and inflammation in adipose tissue of ob/ob C57BL-6 mice. Feeding a c9,t11-CLA–enriched diet reduced fasting glucose (P < 0.05), insulin (P < 0.05), and triacylglycerol concentrations (P < 0.01) and increased adipose tissue plasma membrane GLUT4 (P < 0.05) and insulin receptor (P < 0.05) expression compared with the control linoleic acid–enriched diet. Interestingly, after the c9,t11-CLA diet, adipose tissue macrophage infiltration was less, with marked downregulation of several inflammatory markers in adipose tissue, including reduced tumor necrosis factor-α and CD68 mRNA (P < 0.05), nuclear factor-κB (NF-κB) p65 expression (P < 0.01), NF-κB DNA binding (P < 0.01), and NF-κB p65, p50, c-Rel, p52, and RelB transcriptional activity (P < 0.01). To define whether these observations were direct effects of the nutrient intervention, complimentary cell culture studies showed that c9,t11-CLA inhibited tumor necrosis factor-α–induced downregulation of insulin receptor substrate 1 and GLUT4 mRNA expression and promoted insulin-stimulated glucose transport in 3T3-L1 adipocytes compared with linoleic acid. This study suggests that altering fatty acid composition may attenuate the proinflammatory state in adipose tissue that predisposes to obesity-induced insulin resistance.

Vitamin D status of Irish adults: findings from the National Adult Nutrition Survey

Previous national nutrition surveys in Irish adults did not include blood samples; thus, representative serum 25-hydroxyvitamin D (25(OH)D) data are lacking. In the present study, we characterised serum 25(OH)D concentrations in Irish adults from the recent National Adult Nutrition Survey, and determined the impact of vitamin D supplement use and season on serum 25(OH)D concentrations. Of the total representative sample (n 1500, aged 18+ years), blood samples were available for 1132 adults. Serum 25(OH)D was measured via immunoassay. Vitamin D-containing supplement use was assessed by questionnaire and food diary. Concentrations of serum 25(OH)D were compared by season and in supplement users and non-users. Year-round prevalence rates for serum 25(OH)D concentration < 30, < 40, < 50 and < 75 nmol/l were 6.7, 21.9, 40.1 and 75.6 %, respectively (11.1, 31.1, 55.0 and 84.0 % in winter, respectively). Supplement users had significantly higher serum 25(OH)D concentrations compared to non-users. However, 7.5 % of users had winter serum 25(OH)D < 30 nmol/l. Only 1.3 % had serum 25(OH)D concentrations >125 nmol/l. These first nationally representative serum 25(OH)D data for Irish adults show that while only 6.7 % had serum 25(OH)D < 30 nmol/l (vitamin D deficiency) throughout the year, 40.1 % had levels considered by the Institute of Medicine as being inadequate for bone health. These prevalence estimates were much higher during winter time. While vitamin D supplement use has benefits in terms of vitamin D status, at present rates of usage (17.5 % of Irish adults), it will have only very limited impact at a population level. Food-based strategies, including fortified foods, need to be explored.

The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers

Objective:To assess the effects of dietary supplementation using two isomeric blends of conjugated linoleic acid (CLA) on immune function in healthy human volunteers.Design:Double-blind, randomised, placebo-controlled intervention trial.Subjects and intervention:A total of 55 healthy volunteers (n=20 males, n=35 females) were randomised into one of three study groups who received 3 g/day of a fatty acid blend containing a 50:50 cis-9, trans-11: trans-10, cis-12 CLA isomer blend (2 g CLA), and 80:20 cis-9, trans-11: trans-10, cis-12 (80:20) CLA isomer blend (1.76 g CLA) or linoleic acid (control, 2 g linoleic acid) for 8 weeks.Results:Supplementation with the 80:20 CLA isomer blend significantly (P≤0.05) enhanced PHA-induced lymphocyte proliferation. CLA decreased basal interleukin (IL)-2 secretion (P≤0.01) and increased PHA-induced IL-2 and tumor necrosis factor α (TNFα) production (P≤0.01). However, these effects were not solely attributable to CLA as similar results were observed with linoleic acid. CLA supplementation had no significant effect on peripheral blood mononuclear cells IL-4 production, or on serum-soluble intercellular adhesion molecule-1 (sICAM-1) or plasma prostaglandin E2 (PGE2) or leukotreine B4 (LTB4) concentrations.Conclusions:This study shows that CLA supplementation had a minimal effect on the markers of human immune function. Furthermore, supplementation with CLA had no immunological benefit compared with linoleic acid.Sponsorship:CLA supplements were provided by Loders Croklaan.

The Potential Role of Vitamin D Enhanced Foods in Improving Vitamin D Status

Low vitamin D intake and status have been reported worldwide and many studies have suggested that this low status may be involved in the development of several chronic diseases. There are a limited number of natural dietary sources of vitamin D leading to a real need for alternatives to improve dietary intake. Enhancement of foods with vitamin D is a possible mode for ensuring increased consumption and thus improved vitamin D status. The present review examines studies investigating effects of vitamin D enhanced foods in humans and the feasibility of the approach is discussed.

Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men

Introduction:Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism in experimental animals and cells in culture, but there are limited human data available.Objective:To investigate the effect of CLA supplementation on biomarkers of calcium and bone metabolism in healthy adult males.Design:The study consisted of a double-blind, placebo-controlled trial in which 60 healthy adult males (aged 39–64 y) were randomly assigned to receive daily either 3.0 g CLA isomer blend (50:50% cis-9,trans-11:trans-10,cis-12 isomers) or a palm/bean oil blend (placebo) for 8 weeks. Urine and blood samples were collected at weeks 0 and 8 and were analysed for biomarkers of calcium and bone metabolism.Results:Supplementation with CLA or placebo for 8 weeks had no significant effects on markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) or bone resorption (serum C-telopeptide-related fraction of type 1 collagen degradation products, urinary N-telopeptide-related fraction of type 1 collagen degradation products, urinary pyridinoline and deoxypyridinoline), or on serum or urinary calcium levels. Baseline levels of these biochemical parameters were similar in both groups of subjects. While the placebo had no effect, CLA supplementation resulted in a three-fold increase (P<0.00001) in cis-9,trans-11 CLA isomer in total plasma lipids.Conclusion:Under the conditions tested in this double-blind, placebo-controlled trial in adult men, a CLA supplement of mixed isomers did not affect markers of calcium or bone metabolism. Further investigation of the effects of CLA on calcium and bone metabolism in other gender- and age-groups is warranted.Sponsorship:Irish Government.

The use of cluster analysis to derive dietary patterns: methodological considerations, reproducibility, validity and the effect of energy mis-reporting

Over the last three decades, dietary pattern analysis has come to the forefront of nutritional epidemiology, where the combined effects of total diet on health can be examined. Two analytical approaches are commonly used: a priori and a posteriori. Cluster analysis is a commonly used a posteriori approach, where dietary patterns are derived based on differences in mean dietary intake separating individuals into mutually exclusive, non-overlapping groups. This review examines the literature on dietary patterns derived by cluster analysis in adult population groups, focusing, in particular, on methodological considerations, reproducibility, validity and the effect of energy mis-reporting. There is a wealth of research suggesting that the human diet can be described in terms of a limited number of eating patterns in healthy population groups using cluster analysis, where studies have accounted for differences in sex, age, socio-economic status, geographical area and weight status. Furthermore, patterns have been used to explore relationships with health and chronic diseases and more recently with nutritional biomarkers, suggesting that these patterns are biologically meaningful. Overall, it is apparent that consistent trends emerge when using cluster analysis to derive dietary patterns; however, future studies should focus on the inconsistencies in methodology and the effect of energy mis-reporting.

Impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults

BACKGROUND Ireland has traditionally operated a liberal policy of voluntary fortification, but little is known about how this practice, along with supplement use, affects population intakes and status of folate and vitamin B-12. OBJECTIVE The aim was to examine the relative impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults. DESIGN Folic acid and vitamin B-12 from fortified foods and supplements were estimated by using brand information for participants from the cross-sectional National Adult Nutrition Survey 2008-2010. Dietary and biomarker values were compared between 6 mutually exclusive consumption groups formed on the basis of folic acid intake. RESULTS The consumption of folic acid through fortified foods at low, medium, and high levels of exposure [median (IQR) intakes of 22 (13, 32), 69 (56, 84), and 180 (137, 248) μg/d, respectively]; from supplements [203 (150, 400) μg/d]; or from both sources [287 (220, 438) μg/d] was associated with significantly higher folate intakes and status compared with nonconsumption of folic acid (18% of the population). Median (IQR) red blood cell (RBC) folate increased significantly from 699 (538, 934) nmol/L in nonconsumers to 1040 (83, 1390) nmol/L in consumers with a high intake of fortified foods (P < 0.001), with further nonsignificant increases in supplement users. Supplement use but not fortification was associated with significantly higher serum vitamin B-12 concentrations relative to nonconsumers (P < 0.001). Two-thirds of young women had suboptimal RBC folate for protection against neural tube defects (NTDs); among nonconsumers of folic acid, only 16% attained optimal RBC folate. CONCLUSIONS The consumption of voluntarily fortified foods and/or supplement use was associated with significantly higher dietary intakes and biomarker status of folate in Irish adults. Of concern, the majority of young women remain suboptimally protected against NTDs.

Pattern of intake of food additives associated with hyperactivity in Irish children and teenagers.

A double-blind randomized intervention study has previously shown that a significant relationship exists between the consumption of various mixes of seven target additives by children and the onset of hyperactive behaviour. The present study set out to ascertain the pattern of intake of two mixes (A and B) of these seven target additives in Irish children and teenagers using the Irish national food consumption databases for children (n = 594) and teenagers (n = 441) and the National Food Ingredient Database. The majority of additive-containing foods consumed by both the children and teenagers contained one of the target additives. No food consumed by either the children or teenagers contained all seven of the target food additives. For each additive intake, estimates for every individual were made assuming that the additive was present at the maximum legal permitted level in those foods identified as containing it. For both groups, mean intakes of the food additives among consumers only were far below the doses used in the previous study on hyperactivity. Intakes at the 97.5th percentile of all food colours fell below the doses used in Mix B, while intakes for four of the six food colours were also below the doses used in Mix A. However, in the case of the preservative sodium benzoate, it exceeded the previously used dose in both children and teenagers. No child or teenager achieved the overall intakes used in the study linking food additives with hyperactivity.

A metabolomics approach to the identification of biomarkers of sugar-sweetened beverage intake

BACKGROUND The association between sugar-sweetened beverages (SSBs) and health risks remains controversial. To clarify proposed links, reliable and accurate dietary assessment methods of food intakes are essential. OBJECTIVE The aim of this present work was to use a metabolomics approach to identify a panel of urinary biomarkers indicative of SSB consumption from a national food consumption survey and subsequently validate this panel in an acute intervention study. DESIGN Heat map analysis was performed to identify correlations between ¹H nuclear magnetic resonance (NMR) spectral regions and SSB intakes in participants of the National Adult Nutrition Survey (n = 565). Metabolites were identified and receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity of biomarkers. The panel of biomarkers was validated in an acute study (n = 10). A fasting first-void urine sample and postprandial samples (2, 4, 6 h) were collected after SSB consumption. After NMR spectroscopic profiling of the urine samples, multivariate data analysis was applied. RESULTS A panel of 4 biomarkers-formate, citrulline, taurine, and isocitrate-were identified as markers of SSB intake. This panel of biomarkers had an area under the curve of 0.8 for ROC analysis and a sensitivity and specificity of 0.7 and 0.8, respectively. All 4 biomarkers were identified in the SSB sample. After acute consumption of an SSB drink, all 4 metabolites increased in the urine. CONCLUSIONS The present metabolomics-based strategy proved to be successful in the identification of SSB biomarkers. Future work will ascertain how to translate this panel of markers for use in nutrition epidemiology.