Article

The effect of conjugated linoleic acid supplementation after weight loss on body weight regain, body composition, and resting metabolic rate in overweight subjects

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Abstract

To study the effects of 13 weeks conjugated linoleic acid (CLA) supplementation in overweight subjects after weight loss on weight regain, body composition, resting metabolic rate, substrate oxidation, and blood plasma parameters. This study had a double-blind, placebo-controlled randomized design. Subjects were first submitted to a very-low-calorie diet (VLCD 2.1 MJ/d) for 3 weeks after which they started with the 13-week intervention period. They either received 1.8 g CLA or placebo per day (low dosage, LD) or 3.6 g CLA or placebo per day (high dosage, HD). A total of 26 men and 28 women (age 37.8+/-7.7 y; body mass index (BMI) 27.8+/-1.5 kg/m(2)). Before VLCD (t=-3), after VLCD but before CLA or placebo intervention (t=0) and after 13-week CLA or placebo intervention (t=13), body weight, body composition (hydrodensitometry and deuterium dilution), resting metabolic rate, substrate oxidation, physical activity, and blood plasma parameters (glucose, insulin, triacylglycerol, free fatty acids, glycerol and beta-hydroxy butyrate) were measured. The VLCD significantly lowered body weight (6.9+/-1.7%), %body fat, fat mass, fat-free mass, resting metabolic rate, respiratory quotient and plasma glucose, insulin, and triacylglycerol concentrations, while free fatty acids, glycerol and beta-hydroxy butyrate concentrations were increased. Multiple regression analysis showed that at the end of the 13-week intervention, CLA did not affect %body weight regain (CLA LD 47.9+/-88.2%, CLA HD 27.4+/-29.8%, Placebo LD 32.0+/-42.8%, Placebo HD 22.5+/-37.9%). The regain of fat-free mass was increased by CLA (LD 6.2+/-3.9, HD 4.6+/-2.4%) compared to placebo (LD 2.8+/-3.2%, HD 3.4+/-3.6%), independent of %body weight regain and physical activity. As a consequence of an increased regain of fat-free mass by CLA, resting metabolic rate was increased by CLA (LD 12.0+/-11.4%, HD 13.7+/-14.4%) compared to placebo (LD 9.1+/-11.0%, HD 8.6+/-8.5%). Substrate oxidation and blood plasma parameters were not affected by CLA. In conclusion, the regain of fat-free mass was favorably, dose-independently affected by a 13-week consumption of 1.8 or 3.6 g CLA/day and consequently increased the resting metabolic rate. However, it did not result in improved body weight maintenance after weight loss.

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... 8 or 3 . 6 g CLA (as Tonalin)/d or a placebo for a 13-week intervention period during which they ate ad libitum (Kamphuis et al. 2003a). Subjects taking CLA (at either dose) were found to exhibit greater regain of fat-free mass relative to control subjects, accompanied by an increase in RMR (Kamphuis et al. 2003a). ...
... 6 g CLA (as Tonalin)/d or a placebo for a 13-week intervention period during which they ate ad libitum (Kamphuis et al. 2003a). Subjects taking CLA (at either dose) were found to exhibit greater regain of fat-free mass relative to control subjects, accompanied by an increase in RMR (Kamphuis et al. 2003a). However, CLA was not found to affect percentage body-weight regain (Kamphuis et al. 2003a). ...
... Subjects taking CLA (at either dose) were found to exhibit greater regain of fat-free mass relative to control subjects, accompanied by an increase in RMR (Kamphuis et al. 2003a). However, CLA was not found to affect percentage body-weight regain (Kamphuis et al. 2003a). Interestingly, measures of appetite (hunger, satiety and fullness) were also observed to be favourably and dosedependently affected by CLA ingestion (Kamphuis et al. 2003b). ...
... There is also a documented reduction in overall energy expenditure in these patients [52]. In examining the possible mechanisms of action for CLA treatment, there does not seem to be any reduction in food intake with CLA intake, either in this study or in other reports in both mice (e.g., [54]) and in overweight humans (e.g., [55]), although results are mixed (e.g., [56]). In the study by Kamphius and colleagues [55], feelings of fullness and satiety were increased and hunger was decreased with CLA supplementation. ...
... In examining the possible mechanisms of action for CLA treatment, there does not seem to be any reduction in food intake with CLA intake, either in this study or in other reports in both mice (e.g., [54]) and in overweight humans (e.g., [55]), although results are mixed (e.g., [56]). In the study by Kamphius and colleagues [55], feelings of fullness and satiety were increased and hunger was decreased with CLA supplementation. This could be an important consideration for patients, perhaps giving the ability to eat regularly, rather than diet, or could work in conjunction with a low-fat, low-calorie diet regimen. ...
Article
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Prader–Willi Syndrome (PWS) is a human genetic condition that affects up to 1 in 10,000 live births. Affected infants present with hypotonia and developmental delay. Hyperphagia and increasing body weight follow unless drastic calorie restriction is initiated. Recently, our laboratory showed that one of the genes in the deleted locus causative for PWS, Snord116, maintains increased expression of hypothalamic Nhlh2, a basic helix–loop–helix transcription factor. We have previously also shown that obese mice with a deletion of Nhlh2 respond to a conjugated linoleic acid (CLA) diet with weight and fat loss. In this study, we investigated whether mice with a paternal deletion of Snord116 (Snord116m+/p−) would respond similarly. We found that while Snord116m+/p− mice and mice with a deletion of both Snord116 alleles were not significantly obese on a high-fat diet, they did lose body weight and fat on a high-fat/CLA diet, suggesting that the genotype did not interfere with CLA actions. There were no changes in food intake or metabolic rate, and only moderate differences in exercise performance. RNA-seq and microbiome analyses identified hypothalamic mRNAs, and differentially populated gut bacteria, that support future mechanistic analyses. CLA may be useful as a food additive to reduce obesity in humans with PWS.
... Estudos têm demonstrado que o ácido linoleico conjugado (CLA) reduz a gordura corporal em animais (PARK et al., 1997, DELANY et al., 1999, MINER et al., 2001, SISK et al., 2001, TAKAHASHI et al. , 2002, BOTELHO et al. , 2005, MOURÃO et al., 2005 e em humanos sedentários (BLANKSON et al., 2000, RISÉRUS et al., 2001, KAMPHUIS et al., 2003 ou que praticam atividade física complementar (THOM, et al., 2001, PINKOSKI et al., 2006. A diminuição da gordura corporal em função de ingestão de CLA pode estar relacionada com alterações no metabolismo energético de tecido adiposo e de músculos esqueléticos (TAKAHASHI et al., 2002) e com aumento na taxa metabólica de repouso (KAMPHUIS et al. , 2003). ...
... Estudos têm demonstrado que o ácido linoleico conjugado (CLA) reduz a gordura corporal em animais (PARK et al., 1997, DELANY et al., 1999, MINER et al., 2001, SISK et al., 2001, TAKAHASHI et al. , 2002, BOTELHO et al. , 2005, MOURÃO et al., 2005 e em humanos sedentários (BLANKSON et al., 2000, RISÉRUS et al., 2001, KAMPHUIS et al., 2003 ou que praticam atividade física complementar (THOM, et al., 2001, PINKOSKI et al., 2006. A diminuição da gordura corporal em função de ingestão de CLA pode estar relacionada com alterações no metabolismo energético de tecido adiposo e de músculos esqueléticos (TAKAHASHI et al., 2002) e com aumento na taxa metabólica de repouso (KAMPHUIS et al. , 2003). Diferentes mecanismos têm sido propostos para explicar a diminuição da gordura corporal em decorrência da suplementação com CLA, incluindo apoptose em tecido adiposo (MINER et al., 2001), aumento da atividade das enzimas lípase e carnitina transferase, com conseqüente aumento de lipólise em tecido adiposo e de oxidação de ácidos graxos em músculos e tecido adiposo (MOURÃO et al., 2005) O ácido linoleico conjugado (CLA) corresponde a um conjunto de isômeros do ácido linoleico (ácido cis-9, cis-12 octadecadienóico = 18:2), que é um ácido graxo com dezoito carbonos e duas duplas ligações, uma entre os carbonos 9 e 10 e a outra, entre os carbonos 12 e 13. ...
Article
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Resumo A suplementação com ácido linoleico conjugado (CLA) tem sido relacionada com a perda de peso corporal, diminuição da massa gorda, efeitos no metabolismo de lipídeos e na taxa metabólica de repouso. O objetivo do trabalho foi avaliar a concentração de lipídeos, proteínas e glicogênio em tecidos de ratos Wistar mantidos com dieta suplementada com CLA e submetidos ao treinamento de natação. Os resultados indicaram redução de lipídeos e aumento de glicogênio no músculo esquelético. Não foram verificadas alterações nos outros parâmetros analisados em tecidos hepático, cardíaco e muscular. Palavras-Chave Ácido linoleico; Composição corporal; Lipídeo Abstract The supplementation with conjugated linoleic acid (CLA) has been related with the body weight loss, the fat mass reduction, effects on the metabolism of lipids and resting metabolic rate. The aim of this research was to evaluate the concentration of lipids, protein and glycogen in tissues of Wistar rats maintained on a diet supplemented with CLA and submitted to a swimming training. The results indicated reduction of lipids and increase of the skeletal muscle glycogen. No changes were observed in any other parameters examined in liver tissue, heart and muscle.
... Of the 21 included studies, eight studies (with a total of 12 intervention arms) (intervention n = 664, control n = 504) examined the effect of increasing protein intake on weight loss maintenance [12][13][14][15][16][17][18][19]. The other studies reported on other dietary strategies (lowering of glycemic index, three studies (intervention n = 254, control n = 223) [12,17,20]; green tea or its component epigallocatechin-3-gallate (EGCG) supplementation, three studies (intervention n = 93, control n = 93) [15,21,22]; whole grain enriched diet or fibre supplementation, two studies (intervention n = 101, control n = 99) [23,24]; conjugated linoleic acid (CLA) supplementation, two studies (intervention n = 78, control n = 77) [25,26]. The remainder of the studies reported on miscellaneous interventions: mono-unsaturated, fat-enriched diet, one study with short or long-term follow-up [27,28]; low-fat diet, one study with short or long-term follow-up [27,28]; acarbose supplementation, one study [29]; capsaicin supplementation, one study [30]; gamma-linoleic acid (GLA) supplementation, one study [31]; and CHO supplementation without or with a mixture of chromium picolinate, soluble fibre, and caffeine, one study [32] (intervention n = 274, control n = 177). ...
... Stimulation of lipolysis by capsaicin is not effective [30] (see above). There also does not seem to be a beneficial effect of CLA supplementation on weight regain [25,26]. CLA is derived from the metabolism of linoleic acid, a poly-unsaturated essential fatty acid, in the human gut, and is also present in animal products such as meat and dairy. ...
Article
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Weight regain after a successful weight loss intervention is very common. Most studies show that, on average, the weight loss attained during a weight loss intervention period is not or is not fully maintained during follow-up. We review what is currently known about dietary strategies for weight loss maintenance, focusing on nutrient composition by means of a systematic review and meta-analysis of studies and discuss other potential strategies that have not been studied so far. Twenty-one studies with 2875 participants who were overweight or obese are included in this systematic review and meta-analysis. Studies investigate increased protein intake (12 studies), lower dietary glycemic index (four studies), green tea (three studies), conjugated linoleic acid (three studies), higher fibre intake (three studies), and other miscellaneous interventions (six studies). The meta-analysis shows a significant beneficial effect of higher protein intake on the prevention of weight regain (SMD (standardized mean difference) −0.17 (95% CI −0.29, −0.05), z = 2.80, p = 0.005), without evidence for heterogeneity among the included studies. No significant effect of the other strategies is detected. Diets that combine higher protein intake with different other potentially beneficial strategies, such as anti-inflammatory or anti-insulinemic diets, may have more robust effects, but these have not been tested in randomized clinical trials yet.
... On the other hand, some studies have not found benefi cial effects with regards to body composition after the CLA supplement in adults (Zambell et al. 2000 ;Risérus et al. 2002 ;Whigham et al. 2004 ;Desroches et al. 2005 ;Taylor et al. 2006 ;Steck et al. 2007 ;Norris et al. 2009 ;Venkatramanan et al. 2010 ;Sluijs et al. 2010 ) . With respect to the lean mass, some investigations indicate a signifi cant increase in fatfree mass after the CLA supplementation (Kamphuis et al. 2003 ;Gaullier et al. 2004Gaullier et al. , 2007 , while in the majority of investigations, signifi cant effects have not been found (Blankson et al. 2000 ;Mougios et al. 2001 ;Tricon et al. 2004 ;Gaullier et al. 2005a, b ;Larsen et al. 2006 ;Syvertsen et al. 2007 ;Steck et al. 2007 ) . ...
... By contrast, other authors found no weight loss in the subjects who were given this fatty acid (Tricon et al. 2004 ) . In fact, in the study by Kamphuis et al. ( 2003 ) , which measured the recovered weight after a low-calorie diet, there was a greater weight gain in the group receiving CLA, compared with the control group. Daily CLA supplementation (3.4 g) for 1 year did not prevent weight or fat mass regain in a healthy obese population (Larsen et al. 2006 ) . ...
Chapter
The stability of body weight and fat composition depends on several components such as food intake, nutrient-associated turnover, thermogenesis, and physical activity. These elements underlie complex interrelated feedback mechanisms, which are affected by personal genetic traits. A number of investigations have evidence that not all calories count equal and that some specific biofactors occurring in foods may affect energy efficiency and fat deposition. Thus, the role of protein and specific amino acids, the glycemic load of different carbohydrates and foods, the type of fat, as well as the involvement of some food components with bioactive functions affecting the energy equation are being ascertained, since they can influence body composition and adiposity. Indeed, moderately high protein intake, carbohydrate with low glycemic index, n-3 fatty acids, calcium, and some thermogenic substances and antioxidants have been found to possibly contribute to reduce the body fat content. Many of these findings have been supported not only through epidemiological studies, but also by animal and cell investigations as well as through controlled nutritional interventions in humans. A better understanding of the putative involved mechanisms in the effects of individual fatty acids such as conjugated linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid in body composition maintenance, as well as the identification of new bioactive compounds affecting lipid turnover and energy metabolism will open the way for a better control and management of fat deposition in different stages of the life cycle, since some of them are able to control relevant metabolic pathways at the molecular level.
... 14,15 Thus, overweight subjects receiving dosages of 1.8 and 3.6 g/day showed regain of fat-free mass after weight loss. 16 This could be due to factors such as the much higher doses tested in humans than in animals, the metabolic differences associated among the species, or the protocol used in the study. It has to be noted that the considered effective dose of CLA in humans (3 g of CLA/day) was proposed after extrapolation of data obtained from animal studies focused on prevention of breast cancer. ...
Article
This study aimed to assess oral absorption and plasma kinetics of two main isomers contained in commercial CLA-rich oil (Tonalin TG-80), rumenic acid (RA) and C18:2 trans 10, cis 12. Isomer plasma disposition after single oral dose of 3000 mg Tonalin TG-80/kg, containing 1200 mg/kg of each isomer, was studied in rats. Isomer plasma concentrations were determined by GC-FID. Plasma kinetics showed rapid oral absorption of RA and C18:2 trans 10, cis 12 (t½a 0.34 ± 0.09 and 0.53 ± 0.01 h) and slow elimination (t½β 25.68 ± 3.29 and 18.12 ± 1.71 h); maximal isomer plasma concentrations (Cmax) of 8.48 ± 0.98 and 7.67 ± 0.80 µg mL-1, respectively, were estimated at 2.08 ± 0.14 and 2.26 ± 0.11 h. Our results from a pre-clinical kinetic study in rats help to design future studies in humans for evaluating CLA isomer dose-response
... It is hypothesized that certain doses of CLA (1.7-6.8 g/day) can help increase the fat-free mass and reduce fat mass (42,43). Currently, a number of dietary supplements, with CLA content for the purposes of weight loss, are being advertised, even though not all studies have reported positive results (44,45). ...
Article
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Obesity and its associated morbidities pose a major health hazard to the public. Despite a multiplex of available diet and exercise programs for losing and maintaining weight, over the past years, interest in the use of complementary and alternative medicine (CAM) for obesity treatment has greatly increased. We searched PubMed, Google scholar and the Cochrane databases for systemic reviews, review articles, meta-analysis and randomized clinical trials up to December 2013. In this review, the efficacy and safety of the more commonly used CAM methods for the treatment of obesity, namely herbal supplements, acupuncture, and non-invasive body-contouring, are briefly discussed. The evidence supporting the effectiveness and safety of these methods is either lacking or point to a negligible clinical benefit, barely surpassing that of the placebo. Furthermore, several limitations are observed in the available scientific literature. These shortcomings include, without being limited to, uncontrolled trial designs, non-random allocation of subjects to treatment arms, small number of patients enrolled, short durations of follow-up, and ambiguous clinical and laboratory endpoints. Further investigations are necessary to accurately determine the efficacy, safety, standard dosage/procedure, and potential side effects of the various CAM methods currently in use.
... Athletic, healthy women may want to reduce their body weight for personal or professional reasons, such as to achieve a specific weight class or to improve athletic performance through changes in body composition. Caloric restriction through low-calorie diets and very low-calorie diets has been used for rapid weight loss for decades, and the literature supports their effectiveness [1][2][3][4][5]. However, the duration of the low-calorie interventions in these studies varies from 1-3 months, and no studies have investigated rapid weight loss with an intervention lasting less than 1 month, which may be necessary in certain weight class sports. ...
Article
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Weight loss benefits of multi-ingredient supplements in conjunction with a low-calorie, highprotein diet in young women are unknown. Therefore, the purpose of this study was to investigate the effects of a three-week low-calorie diet with and without supplementation on body composition. Methods Thirty-seven recreationally-trained women (n = 37; age = 27.1 ± 4.2; height = 165.1 ± 6.4; weight = 68.5 ± 10.1; BMI = 25.1 ± 3.4) completed one of the following three-week interventions: no change in diet (CON); a high-protein, low-calorie diet supplemented with a thermogenic, conjugated linoleic acid (CLA), a protein gel, and a multi-vitamin (SUP); or the highprotein diet with isocaloric placebo supplements (PLA). Before and after the three-week intervention, body weight, %Fat via dual X-ray absorptiometry (DXA), segmental fat mass via DXA, %Fat via skinfolds, and skinfold thicknesses at seven sites were measured. Results SUP and PLA significantly decreased body weight (SUP: PRE, 70.47 ± 8.01 kg to POST, 67.51 ± 8.10 kg; PLA: PRE, 67.88 ± 12.28 kg vs. POST, 66.38 ± 11.94 kg; p 0.05) with a greater (p ≤ 0.05) decrease in SUP than PLA or CON. SUP and PLA significantly decreased %Fat according to DXA (SUP: PRE, 34.98 ± 7.05% to POST, 32.99 ± 6.89%; PLA: PRE, 34.22 ± 6.36% vs. POST, 32.69 ± 5.84%; p ≤ 0.05), whereas only SUP significantly decreased% Fat according to skinfolds (SUP: PRE, 27.40 ± 4.09% to POST, 24.08 ± 4.31%;p ≤ 0.05). SUP significantly (p ≤ 0.05) decreased thicknesses at five skinfolds (chest, waist, hip, subscapular, and tricep) compared to PLA, but not at two skinfolds (axilla and thigh). Conclusions The addition of a thermogenic, CLA, protein, and a multi-vitamin to a three-week low-calorie diet improved weight loss, total fat loss and subcutaneous fat loss, compared to diet alone.
... Based upon this background, a few clinical investigations were made on the effect of CLA on fat-mass regain after weight loss -with an assumption that CLA could block body fat gain. To check this, overweight adults were administered a very lowcalorie diet for 3 wk, followed by CLA supplementation at a dosage of either 1.8 or 3.6 g/d for an intervention period of 13 wk [37]. Subjects took CLA in either dose showed increased regain of fat-free mass and resting metabolic rate, thereby lowering the regain of body fat relative to the control subjects. ...
Article
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This comprehensive review critically evaluates whether supposed health benefits propounded upon human consumption of conjugated linoleic acids (CLAs) are clinically proven or not. With a general introduction on the chemistry of CLA, major clinical evidences pertaining to intervention strategies, body composition, cardio-vascular health, immunity, asthma, cancer and diabetes are evaluated. Supposed adverse effects such as oxidative stress, insulin resistance, irritation of intestinal tract and milk fat depression are also examined. It seems that no consistent result was observed even in similar studies conducted at different laboratories, this may be due to variations in age, gender, racial and geographical disparities, coupled with type and dose of CLA supplemented. Thus, supposed promising results reported in mechanistic and pre-clinical studies cannot be extrapolated with humans, mainly due to the lack of inconsistency in analyses, prolonged intervention studies, follow-up studies and international co-ordination of concerted studies. Briefly, clinical evidences accumulated thus far show that CLA is not eliciting significantly promising and consistent health effects so as to uphold it as neither a functional nor a medical food.
... There are many investigations to evaluate the influences of CLA on the energetic metabolism, promoting significant changes in the lipid metabolism and in body composition [9][10][11][17][18][19][20]. As a result, some effects can be cited such as: reduction of body fat, improved insulin resistance, antithrombogenic and anticarcinogenic effects, reduction of atherosclerosis, improved lipid profile, modulation of the immune system and stimulation of bone mineralization, and also reduced blood glucose. ...
Article
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Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation also could increase the lipolysis and reduce the accumulation of fatty acids on the adipose tissue; the putative mechanisms involved may be its action in reducing the lipase lipoprotein activity and to increase the carnitine-palmitoil-transferase-1 (CAT-1) activity, its interaction with PPARγ, and to raise the expression of UCP-1. Although studies made in human have shown some benefits of CLA supplementation as the weight loss, the results are still discordant. Moreover, some have shown adverse effects, such as negative effects on glucose metabolism and lipid profile. The purpose of this article is to review the available data regarding the benefits of CLA on the energetic metabolism and body composition, emphasizing action mechanisms.
... In fact, in a human study designed to analyze the effect of CLA on body weight gain after weight loss, CLA supplementation for 13 weeks did not affect the percentage of body weight regain, but favored the regain of lean body mass instead of fat mass. 210 In most human studies no safety problems have been described with the currently used daily doses of CLA (1.5-7 g/day). However, different reports by the Riserus and Vessby group have described signifi cant increases in lipid peroxidation parameters and insulin resistance, as well as in blood glucose 208,209,212 In one of these studies, the groups treated with CLA had higher values of lipoprotein(a), trombocytes and leucocytes, suggesting that CLA may increase cardiovascular disease risk and may promote an infl ammatory response, even though the observed changes were within the normal range and were not considered clinically relevant. ...
... Esta recomendación se ha establecido en virtud de estudios de seguridad y eficacia realizados en animales y humanos [22][23][24][25][26][27] . ...
... Además, al mismo tiempo contribuye a mantener la masa muscular, pues favorece la formación de la misma al actuar sobre la enzima carnitina palmitoiltransferasa, encargada de llevar ácidos grasos al interior de las mitocondrias para la obtención de energía. Como resultado, se obtiene una mejor actividad del tejido muscular y se consume la grasa acumulada (12)(13)(14) . ...
Article
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Background: Cellulite is defined as a localized metabolic disorder at the subcutaneous tissue which provokes an alteration in the female body shape. It is a complex problem involving the microcirculatory and lymphatic system, the extracellular matrix and the presence of an excess of subcutaneous fat that bulges into the dermis. Objective: The aim of this study was to determine wether the food supplement (In-Out Innovage® anticellulite lypo-reducer) reduces the cellulite, mobilizes localized fat and smooth bulging "orange peel" appearance. Methods: In this randomized, double-blinded and placebo-controlled study, 30 women (aged 20-55 years) with a clinically observable excess of subcutaneous fat and cellulite, were given either In-Out Innovage® or placebo during 3 months. Results were evaluated using anthropometric measurements, impedanciometry, echographic measurements of skin thickness, and standardized questionnaires. Results: An improvement in all measurements were observed in the treated group. There was a statistical reduction in the gluteal circumference, abdominal skinfold and also in thigh skinfold measurements comparing with placebo. Regarding the questionnaire, 75% of the treated group was satisfied or very satisfied with the efficacy of the product in reducing cellulite.
... The results of studies on lean mass in humans have produced conflicting results, similar to those results for fat mass (Salvado et al., 2006;Tricon and Yaqoob, 2006;). Although few human studies indicate an increase in lean mass with CLA supplementation (Kamphuis et al., 2003;Gaullier et al., 2004), the vast majority report no effect of CLA (Kreider et al., 2002;Riserus et al., 2002;Malpuech-Brugere et al., 2004;Whigham et al., 2004;Salas-Salvado et al., 2006). Again, these inconsistencies in the literature are likely due to differences in CLA dose and length of supplementation, differences in age, sex and physical condition of the subjects and differences in how leanBaumgard et al., In: ...
... That 10,12 CLA increases basal metabolic rate has been suggested previously in mice and humans [60,61], in which mixed CLA isomers were administered for 5 weeks (mice) and 13 weeks (humans), although subjects in those studies did not lose weight or gain lean mass. In our study mice fed only 10,12 CLA showed an increase in energy expenditure that was enhanced when adjusted for total body mass, in addition to significant total weight loss. ...
Article
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Background: Widely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance. Objective: We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism. Methods: Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured. Results: By design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT). Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation. Conclusions: These results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss.
... Sneddon et al. 23 reported that CLA plus n-3 long-chain polyunsaturated fatty acids n-3 LC-PUFA supplementation, 3 g/day CLA plus 3 g/day n-3 LC-PUFA for 12 weeks, has no effect on BMF in young lean male individuals age 30.5 4.9 years, BMI 23.6 1.5 kg/m 2 , body fat 16. 1 5.4 . And Macaluso et al. 24 reported that there were no significant differences in total body mass, BMF, and LBM by CLA supplementation, 6 g/day for Reduced body fat mass by CLA intake suggested that CLA causes reduction in lipid uptake by adipose cells because of an effect on lipoprotein lipase and stearoyl-CoA desaturase and carnitine palmitoyltransferase activity in muscle cells, which is the rate-limiting enzyme in β-oxidation, is increased 18 . On the other hand, increased muscle mass by CLA intake was suggested by increased serum testosterone level 15,24,27 . ...
Article
Conjugated linoleic acids (CLA) intake has been reported to reduce body fat mass or increase lean body mass and to improve exercise outcome by modulating testosterone in humans. These reports have studied mostly overweight subjects; few were athletes. Therefore, in this study, the effect of CLA intake on endurance performance and anti-fatigue in student athletes was investigated. A double-blind, crossover study was conducted with 10 male student athletes. Each subject was administered with either CLA (net 0.9 g/day) or a placebo for 14 days. They were subjected to an exercise tolerance test (steady loading) using a cycle ergometer on days 0 and 14. Peak VO2 was determined for each subject using a graded loading test. The steady loading test was performed with a pedaling exercise load of 50% peak VO2 for 40 min and then with a load of 70% peak VO2 until exhaustion. Blood sampling and measurement of critical flicker frequency (CFF) were performed before and after exercise. The rate of perceived exertion (RPE) was measured serially during exercise. In the results, amount of body weight variation significantly increased and amount of body fat percentage variation tended to decrease by CLA intake, it might have an effect by increase in muscle mass. In addition, amount of exercise time variation significantly increased, amount of variation of CFF before and after exercise tended to increase, that of RPE during exercise tended to decrease, and that of creatine phosphokinase before and after exercise tended to decrease in the CLA group. These results suggested that CLA intake for 14 days might have an effect on endurance performance and anti-fatigue in student athletes.
... In 2009, Gao et al. [128] reported that, in a mouse model of metabolic syndrome, oral supplementation of a high-fat diet with butyrate was able to attenuate the development of obesity and insulin resistance. Further studies demonstrated that, even in humans, diets that elevated fecal butyrate concentrations proved benefi cial [129,130]. Recently, Fernandes et al. [131] reported that fecal SCFA concentrations, including BA and PA, were significantly higher in overweight or obese patients than in lean subjects. This supports the hypothesis that colonic fermentation is altered in overweight or obese adults. ...
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With microbiome research being a fiercely contested playground in science, new data are being published at tremendous pace. The review at hand serves to critically revise four microbial metabolites widely applied in research: butyric acid, flagellin, lipoteichoic acid, and propionic acid. All four metabolites are physiologically present in healthy humans. Nevertheless, all four are likewise involved in pathologies ranging from cancer to mental retardation. Their inflammatory potential is equally friend and foe. The authors systematically analyze positive and negative attributes of the aforementioned substances, indicating chances and dangers with the use of pre- and probiotic therapeutics. Furthermore, the widespread actions of microbial metabolites on distinct organs and diseases are reconciled. Moreover, the review serves as critical discourse on scientific methods commonly employed in microbiome research and comparability as well as reproducibility issues arising thereof.
... A person's BMR is the energy utilized to maintain homeostasis at rest; excluding the influences of physical activity, diet induced thermogenesis, emotional stress, or any other stimulus resulting in an increase in sympathetic activity (15). BMR is a significant portion of total daily energy expenditure, but is dependent on a number of physiological factors such as total mass (18,27,29), body surface area (14), and age (21). BMR has also been found to be predictive of bone mineral density in older women (16). ...
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... Regarding the effects of CLA on body composition after following weight loss diets, CLA lowers regaining body fat by increasing regain of fat-free mass [83]. In prepubescent overweight and obese children, CLA is effective in reducing body fat accretion and percentage of body fat [84]. ...
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Obesity and its comorbidities, including type 2 diabetes and cardiovascular disease, are straining our healthcare system, necessitating the development of novel strategies for weight loss. Lifestyle modifications, such as exercise and caloric restriction, have proven effective against obesity in the short term, yet obesity persists because of the high predilection for weight regain. Therefore, alternative approaches to achieve long term sustainable weight loss are urgently needed. Conjugated linoleic acid (CLA), a fatty acid found naturally in ruminant animal food products, has been identified as a potential anti-obesogenic agent, with substantial efficacy in mice, and modest efficacy in obese human populations. Originally described as an anti-carcinogenic fatty acid, in addition to its anti-obesogenic effects, CLA has now been shown to possess anti-atherosclerotic properties. This review summarizes the pre-clinical and human studies conducted using CLA to date, which collectively suggest that CLA has efficacy against cancer, obesity, and atherosclerosis. In addition, the potential mechanisms for the many integrative physiological effects of CLA supplementation will be discussed in detail, including an introduction to the gut microbiota as a potential mediator of CLA effects on obesity and atherosclerosis.
Chapter
Naturally occurring conjugated fatty acids are reported to possess many health benefits. Among them, conjugated linoleic acids (CLA) have been extensively studied for the last three decades. This article provides a review of the known effects of CLA (anticancer, antiobesity, modulation of inflammation and immune responses, bone health effects, and lipid metabolism effects) followed by the potential adverse effects of CLA (oxidative stress, insulin resistance, milk fat depression, and hepatic dysfunctions). There are also other naturally occurring conjugated polyenes, including punicic, eleostearic, jacaric, catalpic, calendic, and parinaric acids. Although the research on these conjugated polyenes is limited, a summary is provided to summarize their health benefits.
Article
Conjugated Linoleic Acid [“CLA”] is a collective term for a mixture of positional and geometric isomers of linoleic acid in which the two double bonds are conjugated, that is, contiguous, unlike the double bonds in linoleic acid, which are separated by a methylene group. Although diet is the major source of CLA in humans, there is no systematic database for the CLA content of foods and limited data are available on the isomeric distribution of CLA isomers in food, owing to the difficulties in the chromatographic separation of the individual isomers. More controlled studies in specific populations with purified isomers of CLA are needed and should be used to define the beneficial and detrimental effects of each individual CLA isomer in humans. The development of dairy products naturally enriched with CLA should be considered with caution, given the associated increase in trans fatty acids, which might counteract any beneficial effects to health. Therefore, strategies to enrich milk with cis-9, trans-11 CLA without the accompanying increase in Trans Vaccenic Acid [“TVA”] are likely to be important for the future development of CLA-enriched dairy products.
Chapter
Conjugated linoleic acid (CLA) is a name given to a mixture of geometric and positional isomers of linoleic acid having conjugated double bonds. Depending on the position and cis‐trans‐configuration of conjugated double bonds, 54 isomers are possible, of which 14 isomers have been identified in commercial products. CLA was first produced in 1935 via alkali treatment of polyunsaturated fatty acid‐rich oils. The early research used CLA mainly as a marker for the study of fat metabolism because of its high UV absorbency compared with nonconjugated fat. From the 1980s, the research interest has increased in its biological properties, particularly its role in cancer, diabetes, and fat metabolism regulation. The present article discusses the metabolism, uses, method of production, and analysis of CLA.
Conference Paper
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Background: Although the effect of Conjugated Linoleic Acids (CLAs) on blood pressure and body composition is revealed in several in vitro and animal studies, the results of human studies are controversial. The purpose of the current clinical double blind trial was to determine the effect of 2 months CLA supplementation on blood pressure and body composition of non trained healthy young male students. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 66 non trained healthy male students. Before and after eight weeks supplementation with 4×0.8g.d-1 CLA or placebo (soybean oil), lean body mass and fat mass were measured with BIA, trunk and visceral fat and waist circumference were measured with ViScan. Physical activity amount and dietary intake of participants were similar together, because they lived in dorms. Statistical analyses were performed using the SPSS16 software, the statistical tests being analysis of covariance, Independent sample t test, paired-sample t-test and MannWhitney U tests. Results: CLA supplementation had no effect on blood pressure, lean body mass, body fat mass, trunk and visceral fat and waist circumference. Conclusions: These results show that CLA does not affect on body composition and blood pressure in non trained young male students. Keywords: Conjugated linoleic acids, Blood pressure, Body composition, Weight loss, Trunk fat
Chapter
The dietary treatment of the metabolic syndrome should target improving insulin sensitivity and preventing or correcting the associated metabolic and cardiovascular abnormalities. Although several nutrients seem to influence insulin sensitivity and other components of the metabolic syndrome, the main benefits are achievable with weight loss. A high simple-carbohydrates diet exerts hypertriglyceridemic effect in obese insulin-resistant individuals and also promotes small and dense LDL particles formation. A higher saturated fat and transfatty acids intake is associated with impaired insulin action, while the opposite is true for monounsaturated fatty acids. The total amount of fat can influence insulin sensitivity only when it exceeds a threshold level of 35-40% of the total energy intake. High carbohydrates-low fat diets induce significant weight losses and have been the most often proposed for metabolic syndrome and obesity. Nevertheless, high-carbohydrate diet with a high glycemic load has been associated with an impaired glucose response, decrease in insulin sensitivity, and hypertriglyceridemia. Low carb diets have recently been argued to significantly decrease triglyceride and increase HDL-cholesterol and insulin sensitivity but there are no evidences that low carbohydrate diets in the long term are superior to the energy-restricted low-fat diet. Our proposal of nutritional recommendations for the metabolic syndrome, besides a minimum weight loss of 5-10% which is enough to induce a clinically relevant effect, includes decreasing saturated fat (< 7%) and trans fatty acids (< 2% of energy intake) and increasing monounsaturated fatty acids intake as far as 20-25% of the energy intake, following a Mediterranean-diet style, so that the total amount of fat does not need to be drastically reduced and 35-40% of energy intake could be permitted. Regarding carbohydrates, less than 20% of the energy intake should be simple ones and sweetened soft drinks intake should be discouraged. Predominance of low glycemic index or glycemic load foods helps controlling insulin sensitivity and lipid levels and ensures a high fiber intake, together with higher satiation and lower energy intake. Monounsaturated fatty acids plus carbohydrate intake should be fit within 60-70% of total energy. Protein intake should be enough to retain lean body mass when following a hypocaloric diet. There are no available data regarding long term safety to recommend high-protein low-carb diets (ketogenics) in the treatment of obesity either associated or not to metabolic syndrome. Reducing salt intake (< 6 g of sodium chloride/day), limiting alcohol intake and following other dietary measures reflected in the recommendations by the NCEP-ATP-III expert panel will help in the management of metabolic syndrome.
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Reducing age-related degenerations and inflammatory pathologies by reducing excess adipose tissue may be a key to successful aging. Conjugated linoleic acid CLA's ability in selectively reducing body fat mass should receive more attention with the growing insight into the physiological and pathological functions of adipose tissue, and its role in inflammation and aging. Moreover, CLA might be a powerful ingredient to alleviate or counteract catabolic and degenerative processes, such as loss of skeletal muscle or bone mineral mass.
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This study investigated the effect of conjugated linoleic acid (CLA) on the aerobic capacity and anthropometric measurements of humans. Although this effect has been shown in animal studies, human studies have reported controversial results. In this double-blind, placebo-controlled, randomized clinical trial, 80 non-trained healthy young men received a 50:50 mixture of cis-9,trans-11 and trans-10 cis-12 CLA (CLA 4 × 0.8 g day(-1)) ora placebo (PLA; soybean oil) in an 8-week intervention. Maximal oxygen consumption (VO2 max), time to exhaustion, weight, body mass index (BMI) and waist circumference (WC) were measured. CLA had no effect on VO2 max (p = 0.5) also no change was seen in time to exhaustion (p = 0.51), weight (p = 0.7), BMI (p = 0.7) and WC (p = 0.8) vs PLA. Our results suggest that CLA has no significant effect on VO2 max, time to exhaustion and anthropometric measurements in untrained healthy young male students.
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Objective Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline-driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss. Methods A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively. Results Of the 20,504 citations retrieved in the database search, 1,743 full-text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3-4.93 kg). Conclusions Dietary supplements and alternative therapies for weight loss have a limited high-quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use.
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Article
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Conjugated linoleic acid (CLA) has garnered special attention as a food bioactive compound that prevents and attenuates obesity. Although most studies on the effects of CLA on obesity have focused on the reduction of body fat, a number of studies have demonstrated that CLA also increases lean body mass and enhances physical performances. It has been suggested that these effects may be due in part to physiological changes in the skeletal muscle, such as changes in the muscle fiber type transformation, alteration of the intracellular signaling pathways in muscle metabolism, or energy metabolism. However, the mode of action for CLA in muscle metabolism is not completely understood. The purpose of this review is to summarize the current knowledge of the effects of CLA on skeletal muscle metabolism. Given that CLA not only reduces body fat, but also improves lean mass, there is great potential for the use of CLA to improve muscle metabolism, which would have a significant health impact.
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Article
Clinical trials have indicated conflicting results on the effects of conjugated linoleic acid (CLA) on obesity. The present study aimed to systematically review controlled clinical trials examining the effects of CLA on anthropometric indices and body composition in overweight and obese subjects. Pubmed, Scopus, Web of science, and Cochrane databases were searched between 2000 and December 2017 with no language restriction. Placebo-controlled clinical trials that reported anthropometric indices and body composition in overweight and obese subjects were included. Random-effect model was used to pool the effect estimates. Of 4032 publications, 13 trials were included for the meta-analysis. Pooled effect sizes indicated that CLA significantly reduced body weight (WMD: -0.52 kg, 95% CI: -0.83, -0.21; I2: 48.0%, p=0.01), BMI (WMD: -0.23 kg/m2, 95% CI: -0.39, - 0.06; I2: 64.7%, p=0.0001), FM (WMD: -0.61 kg, 95% CI: -0.98, -0.24; I2: 53.8%, p=0.01) and increased LBM (WMD: 0.19 kg, 95% CI: 0.04, 0.34; I2: 81.4%, p=0.0001) compared to the placebo group. However, the effects of CLA on WC (WMD: 0.05 cm, 95% CI: -0.01, 0.1; I2: 0%, p=0.93) was not significant. Additionally, its impact on body weight in subjects older than 44 year (WMD: -1.05 kg, 95% CI: -1.75, -0.35; I2: 57.0%, p=0.01), with longer duration (more than 12 weeks) (WMD: -1.29 kg, 95% CI: -2.29, -0.29; I2: 70.3%, p=0.003) and dosage more than 3.4 g/day (WMD: -0.77 kg, 95% CI: -1.28, -0.25; I2: 62.7%, p=0.004) were greater than comparative groups. Supplementation with CLA can slightly reduce body weight and FM and increase LBM in overweight and obese subjects. However, its efficacy was not clinically relevant. Further studies with high methodological quality are needed to shed light on the effects of CLA on anthropometric indices in overweight and obese subjects.
Article
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Abstract Background: Although the effect of Conjugated Linoleic Acids (CLAs) on blood pressure and body composition is revealed in several in vitro and animal studies, the results of human studies are controversial. The purpose of the current clinical double blind trial was to determine the effect of 2 months CLA supplementation on blood pressure and body composition of non trained healthy young male students. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 66 non trained healthy male students. Before and after eight weeks supplementation with 4×0.8g.d-1 CLA or placebo (soybean oil), lean body mass and fat mass were measured with BIA, trunk and visceral fat and waist circumference were measured with ViScan. Physical activity amount and dietary intake of participants were similar together, because they lived in dorms. Statistical analyses were performed using the SPSS16 software, the statistical tests being analysis of covariance, Independent sample t test, paired-sample t-test and MannWhitney U tests. Results: CLA supplementation had no effect on blood pressure, lean body mass, body fat mass, trunk and visceral fat and waist circumference. Conclusions: These results show that CLA does not affect on body composition and blood pressure in non trained young male students. Keywords: Conjugated linoleic acids, Blood pressure, Body composition, Weight loss, Trunk fa
Article
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The dietary inclusion of feed additives to improve the carcass characteristics of the final product is of great importance for the pork production chain. The aim of our study was to evaluate the effects of the association of ractopamine ( RAC ) and conjugated linoleic acid ( CLA ) on the performance traits of finishing pigs during the last 26 days prior to slaughter. In total, 810 commercial hybrid barrows were used. Animals were distributed among treatments according to a randomised block design in a 3 × 3 factorial arrangement, with three RAC levels (0, 5 or 10 ppm) and three CLA levels (0, 0.3 or 0.6%). Pigs fed the diet with 5 ppm RAC had higher average daily feed intake ( ADFI ) (2.83 kg; P < 0.05) when compared with those fed 10 ppm RAC and the control diet (2.75 and 2.74 kg, respectively). Lower ADFI values ( P < 0.01) were observed with the diets containing CLA compared with the control diet with no CLA (2.73 and 2.75 v . 2.85 kg/day, respectively). The average daily weight gain of pigs fed 5 and 10 ppm RAC was +148 and +173 g/dayhigher ( P < 0.001), respectively, than those fed the control diet. Dietary RAC levels influenced ( P < 0.001) feed conversion ratio ( FCR ), which was reduced as RAC levels increased, with the pigs fed 10, 5 and 0 ppm RAC presenting FCR values of 2.57, 2.71 and 3.05, respectively. FCR also improved ( P < 0.05) with the inclusion of 0.6% CLA relative to the control diet (2.70 v . 2.84, respectively). There was a significant interaction between CLA × RAC levels ( P < 0.01) for final BW, loin eye area ( LEA ) ( P < 0.05 ) and backfat thickness ( BT ) ( P < 0.05 ). The treatments containing 10 ppm RAC + 0.6% or 0.3% CLA increased LEA and reduced BT. In conclusion, the level of 10 ppm inclusion of RAC increased the overall performance parameters of pigs and therefore improved production efficiency. The combined use of RAC and CLA promoted a lower feed conversion ratio as well as better quantitative carcass traits, as demonstrated by the higher LEA and lower BT. The dietary inclusion of CLA at 0.3% improved feed efficiency, however, without affecting LEA or BT yields.
Article
The mechanism of action of Clarinol™ conjugated linoleic acid (CLA), used as a safe and efficacious product for weight management, was investigated. The fat reduction observed in 'in vivo' studies caused by CLA treatment may be attributed to its inhibition of cell growth and differentiation of preadipocytes in animals. One of the mechanisms proposed to explain the effects of CLA on body composition is via the peroxisome proliferator-activated receptor (PPAR). The results show that Clarinol™ CLA has the highest concentration of the active isomers c-9,t-11 and t-10,c-12 CLA in approximately equal amounts.
Conference Paper
The amount of scientific literature on conjugated linoleic acid (CLA) is growing at a phenomenal rate. Animal studies and clinical trials indicate the possibility that CLA could be useful in improving human health in a number of areas, eg, controlling body fat gain and enhancing immunity while also reducing inflammation and other adverse effects typically associated with immune enhancement. The background of this growing research field and mechanistic insights from animal and cell culture experiments are briefly reviewed. Experimental and clinical data relating to the safety and effectiveness of CLA in humans are presented and discussed.
Chapter
In recent years, DNA sequencing and mass spectrometry technologies have advanced greatly, enabling the collection of more information on the gut microbiome and its metabolome in order to assess the influence of the gut microbiota on human health at a whole-system level. As the gut microbiota has been likened to a functional and measurable organ consisting of prokaryotic cells, which creates the unique gut ecosystem together with the host eukaryotic cells, metagenome and metabolome technologies have demonstrated that the gut microbiota contributes to host overall health status to a great extent. In this chapter, the detailed relationships between gut microbiota and its metabolites like choline, phenols, bile acids and short-chain fatty acids in host health and etiopathogenesis of various metabolic diseases such as obesity, diabetes, atherosclerosis, non-alcoholic fatty liver disease and extraintestinal diseases like multiple sclerosis, chronic kidney disease and autism will be discussed. In addition, therapeutic interventions like probiotic and prebiotic administrations and faecal microbiota transplantations which are recently used in dysbiosis restoration will be reviewed. This unique biology-wide approach of integrating metagenome and metabolome information would aid in the better understanding of the intricate interplay between gut microbiota and host metabolism. We believe that this novel integration of the microbiome, metatranscriptome and metabolome information will lay the way towards an improved holistic understanding of the complex mammalian superorganism. This modelling of the metabolic interactions between lifestyle, dietary habits and the gut microbiota, otherwise known as the “integrated omics-based understanding of the gut ecosystem”, will culminate in the comprehensive interpretation of the role and impact of microbial health potentials, thereby providing exciting novel therapeutic approaches for optimal host health.
Article
Background: Controversy persists regarding the effect of mixtures of conjugated linoleic acids (c9,t11- and t12,c10-CLA) in fasting blood glucose (FBG) and waist circumference (WC) in humans. Objective: The aim of this meta-analysis is to explore the effect of CLA on FBG and WC. Method: PubMed, Google Scholar, Cochrane Library, Science Direct, Pro-Quest and Ovid were searched up to January 2015. Studies that examined the effect of CLA supplementation or foods enriched with CLA on FBG and WC in healthy adults were included. Studies in animals or unhealthy individuals and studies other than clinical trials were excluded. Of the 3,095 articles initially retrieved, 32 eligible randomized clinical trials were included in this systematic review. The mean difference and standard deviation of changes in FBG and WC in the intervention and control groups were used as effect size measures for the meta-analysis. Results: Subgroup analysis showed that CLA supplement consumption did not significantly influence FBG (standardized mean differences [SMD] = 0.075 mg/dL; 95% confidence interval (CI) = -0.099 to 0.249; p = 0.399) or WC (SMD = -0.149 cm; 95% CI = -0.522 to 0.225; p = 0.435). Foods enriched in CLA also showed no significant effect on FBG (SMD = 0.126 mg/dL; 95% CI = -0.100 to 0.352; p = 0.274) or WC (SMD = -0.233 cm; 95% CI = -0.625 to 0.159; p = 0.244). Conclusion: We conclude that c9,t11- and t12,c10-CLA administered as a supplement or used to enrich foods does not affect FBG or WC in humans.
Article
Conjugated linoleic acid (CLA) has been reported to be a bioactive food component. However, there is limited knowledge on the sex‐dependent effects of CLA on energy metabolism. In the present study, Drosophila melanogaster was used to investigate the sex‐dependent effects of CLA with respect to body fat, muscle, locomotion, and a key metabolic regulator, AMP‐activated protein kinase α (AMPKα). Adult flies were fed a cornmeal‐based fly food with 0.5% of CLA oil (50:50 of cis‐9,trans‐11 and trans‐10,cis‐12 CLA isomers in triacylglycerol (TAG) form), 0.5% safflower oil (high in linoleic acid [LNA] as control), or 0.5% water (as blank) for 5 days. Accumulation of CLA in tissue was verified using gas chromatography–mass spectrometry. CLA‐fed flies had reduced TAG and increased locomotor activity when compared to LNA‐fed control flies. In addition, CLA increased the muscle content when compared to the blank. Moreover, following CLA supplementation, increased AMPKα activity was observed in females, but not in males. These sex‐dependent metabolic effects of CLA may be due to physiological differences in lipid metabolism and nutrient requirements. In conclusion, CLA promoted the body composition and locomotion behavior in D. melanogaster and regulated the sex‐specific metabolism in part via AMPKα. As key physiological processes are conserved between fly and human, information obtained from this research could provide valuable insights into sex‐dependent responses to CLA in humans.
Technical Report
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Cada vez mais, a prática médica vem sendo influenciada por notícias e direcionamentos a que estamos expostos por meio dos diversos canais de informação existentes. Entretanto, muitos dos conteúdos disponíveis não se baseiam em evidências científicas que possam ser utilizadas com segurança. Isto é particularmente verdadeiro na área da obesidade, onde ainda existem preconceitos, tabus, e visões distorcidas em relação ao paciente, ao médico e ao tratamento farmacológico. Diretrizes bem desenvolvidas têm o potencial de melhorar a adequação da prática médica, a qualidade do atendimento, a relação custo-eficácia promovendo um uso eficiente de recursos, identificar lacunas na base de evidência e áreas de novas necessidades de pesquisa. Além disso, diretrizes práticas bem estabelecidas minimizam dano e iatrogenia, reduzem práticas inadequadas, e ajudam na produção de um desfecho de saúde melhor para o paciente, e podem até mesmo ser usadas como base para a regulamentação de procedimentos e a tomada de decisão. O objetivo final é sempre a qualidade do cuidado, servindo o melhor interesse do paciente. As Diretrizes de Obesidade foram revisadas e atualizadas com o objetivo de fornecer dados contemporâneos sobre a etiologia, o diagnóstico e o tratamento dietético, cognitivo-comportamental, farmacológico em adultos e em crianças e adolescentes do sobrepeso e da obesidade, doença tão prevalente na população mundial. As diretrizes são formadas por declarações específicas com graus de recomendação baseados em forças de evidência de acordo com os estudos citados como referência ao longo do texto, que denotam a estimativa de certeza e precisão: evidências fortes, com estudos de alta qualidade e múltiplas populações avaliadas (grau A); intermediárias, como ensaios randomizados controlados (ERC) menores, estudos de corte e estudos caso-controle (grau B); fracas, como relatos ou séries de casos (grau C); e, por fim, desprovidas de evidências clínicas, são as derivadas da opinião de especialistas, os consensos, as opiniões e teorias, as revisões não sistemáticas, os estudos pré-clínicos em modelos animais, mecanísticos e in vitro (grau D). Eventualmente, pode ainda haver uma recomendação contra, se houver, pelo menos, moderada confiança com base em evidências de que não há nenhum benefício real ou que os riscos e malefícios superam os benefícios. É o caso de vários pontos do capítulo que aborda tratamentos heterodoxos e suplementos nutricionais. Além disso, a classificação das recomendações por nível de evidência prevê a avaliação da estimativa de certeza (precisão) do tratamento (desde o nível A, onde múltiplas populações foram avaliadas em muitos ERCs; passando pelo nível B, no qual um número limitado de pacientes em poucos ERCs de menor qualidade; até o nível C, em que muito poucos pacientes foram estudados em relatos de casos). O tamanho do efeito do tratamento também deve ser analisado e qualifica a recomendação em classes onde na classe I claramente o benefício é superior ao risco; na classe II pode haver condições para as quais há evidências conflitantes ou divergência de opinião sobre a utilidade ou eficácia de um procedimento ou tratamento (neste caso divide-se em IIa, quando a evidência ou opinião é a favor da utilidade ou da eficácia e em IIb quando a utilidade ou a eficácia não é bem estabelecida por divergência de opinião ou por divergência de evidências, quando, por exemplo, existem múltiplos ERC que chegam a divergentes conclusões) e na classe III ficam as condições para as quais há evidências ou concordância geral de que o procedimento ou tratamento não é útil e eficaz, pode ser prejudicial ou aumentar o custo. Declarações comparativas de eficácia em recomendações devem basear-se exclusivamente na eficácia comparativa de ERC de alta qualidade e podem ser feitas para a classe I e IIa para os níveis de evidência de recomendações A e B somente. As recomendações detalhadas baseadas em evidência permitem a tomada de decisão clínica nos múltiplos aspectos do tratamento da obesidade, estimulando tanto o cuidado médico como a prevenção da obesidade, uma doença envolvida em diversas complicações e comorbidades que elevam a morbidade, a mortalidade, e reduzem a expectativa de vida. O objetivo desta diretriz é englobar dados úteis para aplicação na prática clínica, objetivando auxiliar na conduta e facilitar o melhor cuidado dos pacientes, incluindo sua triagem, diagnóstico, avaliação, seleção da terapia não farmacológica, objetivo do tratamento e individualização de forma ética, com base em evidência racional e científica da melhor qualidade disponível para aperfeiçoar os desfechos de saúde e a segurança do paciente obeso. As recomendações são práticas, viáveis, clinicamente flexíveis, facilitando assim a divulgação e utilização. O presente resumo foi retirado do primeiro capítulo da diretriz, que é enriquecido com 3 Tabelas ilustrativas. Associação Brasileira para o Estudo da Obesidade e da Síndrome Metabólica (Abeso) Marcio C. Mancini (Editor-Coordenador) "A corpulência não é apenas uma enfermidade em si, mas o prenúncio de outras. A morte súbita é mais comum naqueles que são naturalmente gordos do que nos magros." -- Hipócrates (460 a.C.-370 a.C.)* * J. Chadwick, W.N. Mann. Medical Works of Hippocrates. Blackwell Scientific, Boston, MA (1950), p. 154.
Chapter
Body weight and fat content as well as enery metabolism depends on several factors such as food intake, nutrient-associated turnover, thermogenesis, and physical activity. These elements underlie complex interrelated feedback mechanisms, which are affected by personal genetic traits. A number of investigations have evidenced that not all calorie may count equal and that some specific biofactors occurring in foods may affect energy efficiency and fat deposition. Thus, the role of protein and specific amino acids, the glycemic load of different carbohydrates and foods, the type of fats, as well as the involvement of some food components with bioactive functions affecting the energy equation are being ascertained, since they can influence body composition and adiposity. Indeed, moderately high protein intake, carbohydrate with low glycemic index, n-3 fatty acids, calcium, and some thermogenic substances and antioxidants have been found to possibly contribute to reduce the body fat content. Many of these findings have been supported not only through epidemiological studies, but also by animal and cell investigations as well as through controlled nutritional interventions in humans. A better understanding of the putative involved mechanisms concerning the effects of individual fatty acids such as conjugated linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid in body composition maintenance, as well as the identification of new bioactive compounds affecting lipid turnover and energy metabolism will open the way for a better control and management of fat deposition in different stages of the life cycle, since some of them are able to control relevant metabolic pathways at the molecular level, which will contribute to precision nutrition.
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This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity.
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The specificity of linoleic acid isomerase from Butyrivibrio fibrisolvens for cis-9,cis-12-dienoic fatty acids with an ω chain length varying from 4 to 8 carbons has been examined. The enzyme was found to be highly specific for a straight chain fatty acid bearing an ω chain length of 6 carbon atoms. Stereospecific addition of hydrogen to carbon atom 13 of linoleic acid in the d configuration was demonstrated. It was deduced that the substrate was bound to the enzyme in the form of a loop and that the mechanism of isomerization involves either the protonation of an enzyme-bound carbanion or a concerted reaction. A tentative model with the carboxyl oxygens of the substrate participating in the isomerization reaction is proposed.
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Three parameters involved in the binding of substrate to linoleate isomerase of Butyrivibrio fibrisolvens have been identified from studies of inhibition by fatty acid isomers and analogues. They are (a) the π system of the substrate double bond, (b) hydrophobic interaction, and (c) hydrogen bonding of the substrate carboxyl group. Almost every unsaturated fatty acid tested inhibited the enzyme, regardless of configuration or double bond position between carbons 3 and 12. Superimposed on this contribution of unsaturation was the correlation of inhibition with chain length and with the presence of an active hydrogen on a C-1 substituent. Inhibition by unsaturated fatty acids or their derivatives in all cases examined was competitive. More restrictive requirements for isomerization were revealed by incubation of the enzyme with positional and configurational isomers and carboxyl derivatives of the substrate. An absolute requirement for a cis-9, cis-12-diene system and a free C-1 carboxyl group was shown. Two chelators, o-phenanthroline and EDTA, were identified as reversible inhibitors of the enzyme. Inhibition by o-phenanthroline was noncompetitive. The isomerase was also inhibited by the sulfhydryl reagents, p-hydroxymercuribenzoate, iodoacetamide, and N-ethylmaleimide.
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Deuterium or tritium labeled water traditionally has been used for the measurement of total body water by application of the dilution principle. However, these methods have not enjoyed wide clinical use. The use of deuterium is hampered by the tedious and time consuming nature of the analysis while the use of tritium involves a radiation hazard. In addition, exchange of the label with nonaqueous hydrogen in the body raises questions about the accuracy of total body water values. To determine if water labeled with the stable isotope 18O can yield faster and more accurate results, total body water was measured simultaneously using water labeled with both 18O and 2H. The 18O and 3H dilutions were measured by mass spectrometry. The relative precision of the body water value using the 18O method was 2% for both serum and breath analysis. The 18O was fully equilibrated within 2 to 3 hr after administration, and results from the analysis of breath CO2 could be readily obtained within 1 hr after sampling. The H2(18)O dilution space averaged 3.0% (SE = 0.4) less than the 2HHO dilution space, because the latter exchanges with nonaqueous hydrogen. For this reason, the H2(18)O dilution should be a more accurate measure of total body water than the 3HHO dilution.
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Deuterium dilution for the measurement of total body water (TBW) has been conducted using varying protocols for equilibration. We measured TBW from deuterium dilution in urine samples in twenty-eight subjects using three protocols: (1) early morning dosage without breakfast, measuring deuterium in a second voiding at 4 h and 6 h; (2) early morning dosage with breakfast with the same measurement times; (3) dosage as last consumption before overnight sleep, measuring deuterium in a second voiding at 10 h. Results were compared with TBW estimates from underwater weighing (UWW). Because UWW is an indirect measure of TBW, it is used as an independent reference method in order to compare only relative discrepancies between the two methods. TBW values in the fasted state were not significantly different from those obtained in the fed state. The urinary deuterium enrichment was higher at 4 h than at 6 h (resulting TBW differences: 0.6 (SD 0.4) l). At 4 h and 6 h, differences in TBW measurements from deuterium and densitometry were positively related to the amount of TBW, indicating incomplete equilibration in larger water compartments. At 10 h no such relationship existed, indicating complete mixing of deuterium. It is concluded that 10 h equilibration is preferable to the shorter 4 h and 6 h, for the determination of TBW.
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We investigated the basis for the reduction in fat pad size in rats fed conjugated linoleic acid (CLA). In the first study, growing female Sprague-Dawley rats (initial weight150 g) were fed diets containing 0, 0.25 and 0.5 g/100 g diet of a purified (97% CLA) and 0.5% of a feed-grade (55% CLA) source of CLA for 5 wk to determine the effects on growth performance and fat mass. There was no effect of CLA on growth rate or food intake. Dietary CLA reduced retroperitoneal fat pad weight 13, 25 and 32% in rats fed 0.25 and 0. 5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.05). Similar effects were observed in the parametrial fat pad. The reduced pad size was due to smaller adipocyte size rather than a reduced cell number. Relative to the control group, mean cell volume was 15, 28 and 29% lower in tissue from rats fed 0.25 and 0.5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.01). In the second study, rats were fed CLA (0 vs. 0.5%) for 7 or 49 d. Reductions in fat pad weight were observed within 7 d. In addition, the effects of CLA on energy metabolism were studied in the chronically fed rats. There were no significant effects of CLA on oxygen consumption, CO(2) or heat production. During wk 4 of feeding, but not at other times, there was a 5% lower respiratory quotient in CLA-fed rats (P < 0.05). There was a time-dependent accumulation of CLA in adipose tissue and a decrease in monounsaturated fatty acids. These results suggest that the reduction in fat mass in rats fed CLA can be accounted for by a reduction in cell size rather than a change in cell number.
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Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested. To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders. Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin. At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups. These results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.
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Supplementation with conjugated linoleic acid (CLA) induces a number of physiological effects in experimental animals, including reduced body fat content, decreased aortic lipid deposition, and improved serum lipid profile. Controlled trials on the effects of CLA in humans have hitherto been scarce. The aim of this study was to evaluate the effects of supplementation with CLA in healthy humans on anthropometric and metabolic variables and on the fatty acid composition of serum lipids and thrombocytes. Fifty-three healthy men and women, aged 23-63 yr, were randomly assigned to supplementation with CLA (4.2 g/d) or the same amount of olive oil during 12 wk in a double-blind fashion. The proportion of body fat decreased (-3.8%, P< 0.001) in the CLA-treated group, with a significant difference from the control group (P = 0.050). Body weight, body mass index, and sagittal abdominal diameter were unchanged. There were no major differences between the groups in serum lipoproteins, nonesterified fatty acids, plasma insulin, blood glucose, or plasminogen activator inhibitor 1 (PAI-1). In the CLA group the proportions of stearic, docosatetraenoic, and docosapentaenoic acids increased in serum lipids and thrombocytes, while proportions of palmitic, oleic, and dihomo-gamma-linolenic acids decreased, causing a decrease of the estimated delta-6 and delta-9 and an increase in the delta-5 desaturase activities. These results suggest that supplementation with CLA may reduce the proportion of body fat in humans and that CLA affects fatty acid metabolism. No effects on body weight, serum lipids, glucose metabolism, or PAI-1 were seen.
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Conjugated linoleic acid (CLA) is a natural component of meat and dairy products with anticarcinogenic, fat lowering, antiatherogenic and anticatabolic activity in animals. The purpose of this study was to examine the effect of CLA supplementation to humans on body fat, certain biochemical parameters of serum, and the CLA content of serum lipids. Twenty-two volunteers were divided into a study group and a control group in a doubly blind design. The study group received 0.7 g of CLA for four weeks and 1.4 g of CLA for the next four weeks, while the control group received placebo. Diet was controlled and no significant differences in energy or macronutrient intake were found between the two groups. Measurements were taken at baseline, four weeks, and eight weeks. The sum of the thickness of ten skinfolds, percentage body fat calculated from it and fat mass was significantly reduced in the CLA group during the second period (P < 0.004) but not overall during the study. Serum HDL-cholesterol decreased significantly (P < 0.001) and triacylglycerols as well as total cholesterol tended to decrease in the CLA group during the first period. The CLA content of serum non-esterified fatty acids, triacylglycerols, phospholipids, and cholesteryl esters increased gradually with supplementation; the CLA content of total serum lipids doubled at the end of the study compared to baseline. Phospholipids had the highest CLA content regardless of supplementation. These data indicate that supplementation with 0.7-1.4 g CLA daily for 4-8 weeks may modulate body fat and serum lipids, as well as increase the CLA content of serum lipids in humans.
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Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in the fat of beef and other ruminants. CLA is reported to have effects on both tumor development and body fat in animal models. To further characterize the metabolic effects of CLA, male AKR/J mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet with or without CLA (2.46 mg/kcal; 1.2 and 1.0% by weight in high- and low-fat diets, respectively) for 6 wk. CLA. significantly reduced energy intake, growth rate, adipose depot weight, and carcass lipid and protein content independent of diet composition. Overall, the reduction of adipose depot weight ranged from 43 to 88%, with the retroperitoneal depot most sensitive to CLA. CLA significantly increased metabolic rate and decreased the nighttime respiratory quotient. These findings demonstrate that CLA reduces body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.
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Objective: The objective of the study was to determine if consumption of conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue. Other objectives were to determine the influence of feeding mice CLA for 2 weeks on body fat, energy expenditure, and feed intake.Research Methods and Procedures: A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was included in the AIN-93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial 1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed intake was measured daily and energy expenditure was determined by direct calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for apoptosis by determination of DNA fragmentation.Results: Dietary CLA reduced feed intake by 10% to 12% (p < 0.01), but either did not influence or did not increase energy expenditure as indicated by heat loss. Body weight was not influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA consumption.Discussion: These results are interpreted to indicate that CLA consumption causes apoptosis in white adipose tissue. This effect occurs within 5 days of consuming a diet that contains CLA.Keywords: mouse, food intake, conjugated linoleic acid, apoptosis, body fat
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The main objective of the study was to investigate the safety of conjugated linoleic acid (CLA) in healthy volunteers. The effect of CLA on body composition was also investigated.The trial design was a randomized, double-blind placebo controlled study including 60 overweight or obese volunteers (body mass index (BMI) 27.5—39.0 kg/m2). The subjects were divided into two groups receiving 3.4 g CLA or placebo (4.5 g olive oil) daily for 12 weeks. The safety was evaluated by analysis of blood parameters and by clinical examinations at baseline and week 12. Vital signs and adverse events were registered at baseline, week 6, and week 12. Bio Impedance Assessment was applied for body composition measurements.55 subjects completed the study. Adverse events occurred in 10% of the subjects. No difference in adverse events or other safety parameters was found between the treatment groups. Small changes in the laboratory safety data were not regarded as clinically significant. Moreover, no clinically significant changes in vital signs were observed in any of the groups.In the CLA group, mean weight was reduced by 1.1 kg (paired t-test p = 0.005), while mean BMI was reduced by 0.4 kg/m2(p = 0.007). However, the overall treatment effect of CLA on body weight and BMI was not significant. There were no differences found between the groups with regard to efficacy parameters.The results indicate that CLA in the given dose is a safe substance in healthy populations with regard to the safety parameters investigated.
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This report describes the construction of a questionnaire to measure three dimensions of human eating behavior. The first step was a collation of items from two existing questionnaires that measure the related concepts of 'restrained eating' and 'latent obesity', to which were added items newly written to elucidate these concepts. This version was administered to several populations selected to include persons who exhibited the spectrum from extreme dietary restraint to extreme lack of restraint. The resulting responses were factor analyzed and the resulting factor structure was used to revise the questionnaire. This process was then repeated: administration of the revised questionnaire to groups representing extremes of dietary restraint, factor analysis of the results and questionnaire revision. Three stable factors emerged: (1) 'cognitive restraint of eating', (2) 'disinhibition' and (3) 'hunger'. The new 51-item questionnaire measuring these factors is presented.
Article
Three parameters involved in the binding of substrate to linoleate isomerase of Butyrivibrio fibrisolvens have been identified from studies of inhibition by fatty acid isomers and analogues. They are (a) the π system of the substrate double bond, (b) hydrophobic interaction, and (c) hydrogen bonding of the substrate carboxyl group. Almost every unsaturated fatty acid tested inhibited the enzyme, regardless of configuration or double bond position between carbons 3 and 12. Superimposed on this contribution of unsaturation was the correlation of inhibition with chain length and with the presence of an active hydrogen on a C-1 substituent. Inhibition by unsaturated fatty acids or their derivatives in all cases examined was competitive. More restrictive requirements for isomerization were revealed by incubation of the enzyme with positional and configurational isomers and carboxyl derivatives of the substrate. An absolute requirement for a cis-9, cis-12-diene system and a free C-1 carboxyl group was shown. Two chelators, o-phenanthroline and EDTA, were identified as reversible inhibitors of the enzyme. Inhibition by o-phenanthroline was noncompetitive. The isomerase was also inhibited by the sulfhydryl reagents, p-hydroxymercuribenzoate, iodoacetamide, and N-ethylmaleimide.
Article
The specificity of linoleic acid isomerase from Butyrivibrio fibrisolvens for cis-9,cis-12-dienoic fatty acids with an ω chain length varying from 4 to 8 carbons has been examined. The enzyme was found to be highly specific for a straight chain fatty acid bearing an ω chain length of 6 carbon atoms. Stereospecific addition of hydrogen to carbon atom 13 of linoleic acid in the d configuration was demonstrated. It was deduced that the substrate was bound to the enzyme in the form of a loop and that the mechanism of isomerization involves either the protonation of an enzyme-bound carbanion or a concerted reaction. A tentative model with the carboxyl oxygens of the substrate participating in the isomerization reaction is proposed.
Article
An enzymic rate method for measuring beta-hydroxybutyrate in plasma by use of beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30) was adapted to the Roche COBAS-BIO centrifugal analyzer. Optimum reagent composition and reaction conditions were determined, to provide increased sensitivity and accuracy. Use of magnesium ions increased sensitivity. Comparison of results with those of a manual enzymic endpoint method involving perchloric acid protein-free filtrates of whole blood showed excellent correlation (r = 0.996). The method has good within-run and day-to-day precision. Linearity of the standard curve extends to 5000 mumol of beta-hydroxybutyrate per liter. The assay can be completed in less than 5 min and requires 15 microL of plasma and minimal reagent volumes.
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Body composition was measured in twenty young females aged 19-27 years and eighteen elderly females, aged 65-78 years by densitometry (underwater weighing), deuterium oxide dilution and dual-energy X-ray absorptiometry (DXA). From body weight, bone-mineral content, total body water and body density, percentage body fat (BF%) was calculated using a four-compartment model. BF% obtained by this four-compartment model was regarded as a reference method and BF% obtained by the single methods were compared with this value. Differences in BF% from the four-compartment model minus the single methods were 2.1 (SD 1.2) for densitometry, 3.1 (SD 1.8) for DXA and -0.6 (SD 0.9) BF% for deuterium oxide dilution in the young women. In the elderly women these values were -0.6 (SD 2.3), 5.3 (SD 3.8) and 0.7 (SD 2.2) BF%. When a three-compartment model (calculated from body density and total body water) was compared with the four-compartment model, the bias was 0.4 (SD 0.3) BF% in the young and 0.0 (SD 0.3) BF% in the elderly women. From the mineral and water fractions in the fat-free mass the true density of the fat-free mass was calculated as 1.1070 (SD 0.0047) kg/l in the young females and 1.0970 (SD 0.0088) kg/l in the elderly women (P < 0.001). This study shows that the single methods have considerable mean and individual biases compared with the four-compartment model, but that a three-compartment model calculated from density and total body water offers an acceptable alternative. The difference in calculated density of the fat-free mass between the young and the elderly women shows the need to adapt Siri's formula for specific groups.
Article
The effects of conjugated linoleic acid (CLA) on body composition were investigated. ICR mice were fed a control diet containing 5.5% corn oil or a CLA-supplemented diet (5.0% corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet exhibited 57% and 60% lower body fat and 5% and 14% increased lean body mass relative to controls (P < 0.05). Total carnitine palmitoyltransferase activity was increased by dietary CLA supplementation in both fat pad and skeletal muscle; the differences were significant for fat pad of fed mice and skeletal muscle of fasted mice. In cultured 3T3-L1 adipocytes CLA treatment (1 x 10(-4)M) significantly reduced heparin-releasable lipoprotein lipase activity (-66%) and the intracellular concentrations of triacylglyceride (-8%) and glycerol (-15%), but significantly increased free glycerol in the culture medium (+22%) compared to control (P < 0.05). The effects of CLA on body composition appear to be due in part to reduced fat deposition and increased lipolysis in adipocytes, possibly coupled with enhanced fatty acid oxidation in both muscle cells and adipocytes.
Article
This study characterizes respiration chambers with fully automated calibration. The system consists of two 14-m3 pull-type chambers. Care was taken to provide a friendly environment for the subjects, with the possibility of social contact during the experiment. Gas analysis was automated to correct for analyzer drift and barometric pressure variations and to provide ease of use. Methods used for checking the system's performance are described. The gas-analysis repeatability was within 0.002%. Results of alcohol combustion (50-350 ml/min CO2) show an accuracy of 0.5 +/- 2.0 (SD) % for O2 consumption and -0.3 +/- 1.6% for CO2 production for 2- to 24-h experiments. It is concluded that response time is not the main factor with respect to the smallest practical measurement interval (duration); volume, mixing, gas-analysis accuracy, and levels of O2 consumption and CO2 production are at least equally important. The smallest practical interval was 15-25 min, as also found with most chamber systems described in the literature. We chose to standardize 0.5 h as the minimum measurement interval.
Article
Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in the fat of beef and other ruminants. CLA is reported to have effects on both tumor development and body fat in animal models. To further characterize the metabolic effects of CLA, male AKR/J mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet with or without CLA (2.46 mg/kcal; 1.2 and 1.0% by weight in high- and low-fat diets, respectively) for 6 wk. CLA significantly reduced energy intake, growth rate, adipose depot weight, and carcass lipid and protein content independent of diet composition. Overall, the reduction of adipose depot weight ranged from 43 to 88%, with the retroperitoneal depot most sensitive to CLA. CLA significantly increased metabolic rate and decreased the nighttime respiratory quotient. These findings demonstrate that CLA reduces body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.
Article
Epidemiologic studies have shown alcohol consumption to be inversely as well as positively related to body weight and body fat. Metabolic studies have shown an increase in energy intake as well as compensation after alcohol consumption. Our objective was to assess the effects on energy intake of an apéritif compared with those of a water appetizer and 3 fruit juice appetizers. Fifty-two men and women aged 20-45 y with a body mass index (in kg/m2) between 20 and 32 were randomly given 1 MJ (340 mL) alcohol (wine or beer), fat (cream fruit juice), protein (protein fruit juice), carbohydrate (grape juice), or water, or no preload 30 min before an ad libitum lunch consumed from the universal eating monitor. Energy intake (3.5+/-0.3 MJ compared with 2.7+/-0.2 MJ, P < 0.001) and eating rate were higher (44+/-3 g/min compared with 38+/-3 g/min, P < 0.01), meal duration was longer (14 min compared with 12.0 min, P < 0.01), satiation started to increase later (3.5 min compared with 1.5 min, P < 0.01), and eating was prolonged after maximum satiation (2.5 min compared with 0.6 min, P < 0.01) after an apéritif than after a fat, protein, or carbohydrate appetizer,. Twenty-four-hour energy intake was higher on a day that an apéritif was consumed than after water or no preload. Twenty-four-hour energy intake was elevated with a 1-MJ apéritif but not with a 1-MJ liquid carbohydrate, fat, or protein appetizer.
Article
Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects on body fat accumulation. In our previous work, CLA reduced body fat accumulation in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced energy intake, the results suggested that some of the metabolic effects were not a consequence of the reduced food intake. We therefore undertook a study to determine a dose of CLA that would have effects on body composition without affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by weight) were studied in AKR/J male mice (n = 12/group; age, 39 days) maintained on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups compared with controls. The retroperitoneal depot was most sensitive to the effects of CLA, whereas the epididymal depot was relatively resistant. Higher doses of CLA also significantly increased carcass protein content. A time-course study of the effects of 1% CLA on body composition showed reductions in fat pad weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion, CLA feeding produces a rapid, marked decrease in fat accumulation, and an increase in protein accumulation, at relatively low doses without any major effects on food intake.
Article
Two experiments were conducted. In Experiment 1, 8-wk-old mice were fed control diet or diet supplemented with 0.5% conjugated linoleic acid (CLA) to study the effect of CLA on body composition (CLA: 40.8-41.1% c-9,t-11 isomer, 43.5-44.9% t-10,c-12 isomer). The data for CLA-fed mice vs. controls described parallel but significantly distinct responses for both absolute and relative changes in body fat mass (reduced in CLA-fed mice) and for relative changes in whole body protein and whole body water (both of which were increased in CLA-fed mice). In the CLA-fed mice, the effect on whole body protein appeared to precede the reduction in body fat mass. In Experiment 2, weanling mice were fed control diet or diet supplemented with 0.5% CLA for 4 wk (test group), at which time all mice were fed control diet devoid of added CLA. The test group exhibited significantly reduced body fat and significantly enhanced whole body water relative to controls at the time of diet change. Time trends for changes in relative body composition were described by parallel lines where the test group exhibited significantly less body fat but significantly more whole body protein, whole body water, and whole body ash than controls. Tissue CLA levels declined following the withdrawal of CLA from the diet. In skeletal muscle of mice fed CLA-supplemented diet, the t-10,c-12 isomer was cleared significantly faster than the c-9,t-11 CLA isomer.
Article
We investigated the effects of conjugated linoleic acid (CLA) preparations, which were enriched for the cis-9,trans-11 CLA isomer or the trans-10,cis-12 CLA isomer, on body composition in mice. Body composition changes (reduced body fat, enhanced body water, enhanced body protein, and enhanced body ash) were associated with feeding the trans-10,cis-12 CLA isomer. In cultured 3T3-L1 adipocytes, the trans-10,cis-12 isomer reduced lipoprotein lipase activity, intracellular triacylglycerol and glycerol, and enhanced glycerol release into the medium. By contrast, the cis-9,trans-11 and trans-9,trans-11 CLA isomers did not affect these biochemical activities. We conclude that CLA-associated body composition change results from feeding the trans-10,cis-12 isomer.
Article
Conjugated linoleic acids (CLA) are a group of positional and geometric conjugated dienoic isomers of linoleic acid. The objective of this study was to determine the effects of the cis-9,trans-11 and trans-10,cis-12 isomers of conjugated linoleic acid on lipid composition and gene expression during the differentiation of mouse 3T3-L1 preadipocytes. Treatment of differentiating 3T3-L1 preadipocytes with trans-10,cis-12 conjugated linoleic acid (CLA) resulted in a dose-dependent decrease in the expression of the stearoyl-CoA desaturase 1 gene (SCD1). The expression of other adipocyte genes such as adipose P2 (aP2), fatty acid synthase (FAS), SCD2 and the key adipogenic transcription factors, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and CCAAT enhancer binding protein alpha (C/EBPalpha), remained elevated. Cells treated with trans-10,cis-12 CLA exhibited smaller lipid droplets, with reduced levels of the major monounsaturated fatty acids, palmitoleate and oleate. By contrast, the cis-9,trans-11 isomer did not alter adipocyte gene expression. Repression of the stearoyl-CoA desaturase gene expression in adipocytes by the trans-10,cis-12 isomer may contribute to the mechanisms by which CLA reduces body fat in mice.
Article
Recent animal studies have demonstrated that dietary conjugated linoleic acid (CLA) reduces body fat and that this decrease may be due to a change in energy expenditure. The present study examined the effect of CLA supplementation on body composition and energy expenditure in healthy, adult women. Seventeen women were fed either a CLA capsule (3 g/d) or a sunflower oil placebo for 64 d following a baseline period of 30 d. The subjects were confined to a metabolic suite for the entire 94 d study where diet and activity were controlled and held constant. Change in fat-free mass, fat mass, and percentage body fat were unaffected by CLA supplementation (0.18+/-0.43 vs. 0.09+/-0.35 kg; 0.01+/-0.64 vs. -0.19+/-0.53 kg; 0.05+/-0.62 vs. -0.67+/-0.51%, placebo vs. CLA, respectively). Likewise, body weight was not significantly different in the placebo vs. the CLA group (0.48+/-0.55 vs. -0.24+/-0.46 kg change). Energy expenditure (kcal/min), fat oxidation, and respiratory exchange ratio were measured once during the baseline period and during weeks 4 and 8 of the intervention period. At all three times, measurements were taken while resting and walking. CLA had no significant effect on energy expenditure, fat oxidation, or respiratory exchange ratio at rest or during exercise. When dietary intake was controlled, 64 d of CLA supplementation at 3 g/d had no significant effect on body composition or energy expenditure in adult women, which contrasts with previous findings in animals.
Article
AKR/J mice fed a high fat diet were treated with a 1% (1 g/100 g) admixture of conjugated linoleic acids (CLA) for 5 wk and compared with control mice. Body weights, energy intakes and energy expenditure (EE) determined by indirect calorimetry were measured weekly. CLA treatment reduced adipose depot weights by approximately 50% but had no significant effects on either body weight or energy intake. CLA increased EE persistently by an average of 7.7% throughout the 5-wk experiment. This greater EE, despite no difference in energy intake, was sufficient to account for the lower body fat stores in the CLA-treated mice. De novo fatty acid biosynthesis in adipose tissue, measured by incorporation of deuterium-labeled water, was not decreased by CLA treatment and therefore did not explain the lower adipose lipid in these mice. Expression of uncoupling protein (UCP) in skeletal muscle, white adipose tissue and kidney was not affected by CLA treatment. In brown adipose tissue, UCP1 expression was not affected by CLA treatment. However, UCP2 expression, although quite low, was significantly greater in CLA-fed mice. We conclude that CLA acts to reduce body fat stores by chronically increasing metabolic rate. This effect on metabolic rate is likely not due to increased UCP gene expression. Furthermore, the reduced body fat is not due to decreased de novo fatty acid synthesis in white adipose tissue.
Article
Conjugated linoleic acid (CLA) has been shown to reduce body fat mass (BFM) in animals. To investigate the dose-response relationships of conjugated linoleic acid with regard to BFM in humans, a randomized, double-blind study including 60 overweight or obese volunteers (body mass index 25-35 kg/m(2)) was performed. The subjects were divided into five groups receiving placebo (9 g olive oil), 1.7, 3.4, 5.1 or 6.8 g conjugated linoleic acid per day for 12 wk, respectively. Dual-energy X-ray absorptiometry was used to measure body composition [measurements at wk 0 (baseline), 6 and 12]. Of the 60 subjects, 47 completed the study. Eight subjects withdrew from the study due to adverse events; however, no differences among treatment groups were found regarding adverse events. Repeated-measures analysis showed that a significantly higher reduction in BFM was found in the conjugated linoleic acid groups compared with the placebo group (P: = 0.03). The reduction of body fat within the groups was significant for the 3.4 and 6.8 g CLA groups (P: = 0.05 and P: = 0.02, respectively). No significant differences among the groups were observed in lean body mass, body mass index, blood safety variables or blood lipids. The data suggest that conjugated linoleic acid may reduce BFM in humans and that no additional effect on BFM is achieved with doses > 3.4 g CLA/d.
Article
Recent studies have demonstrated a reduction in body fat in growing animals fed conjugated linoleic acid (CLA). Two experiments were conducted to extend these observations to obese rats so that the mechanism of the actions of CLA might be more easily elucidated. In experiment 1, male lean and obese Zucker rats were fed diets containing either 0 or 0.5% CLA for 5 wk. There was no effect of diet on growth rate or food intake. Dietary CLA reduced retroperitoneal and inguinal fat pad weights in the lean rats but increased fat pad weights in the obese genotype (diet x genotype interaction; P < 0.05). Determination of fat pad cellularity indicated that these changes in fat pad weight were due to a reduction or increase in average fat cell size for the lean and obese Zucker rats, respectively. In experiment 2, we sought to reproduce these effects on fat pad size, as well as to determine the effect of dietary CLA on the catabolic response to bacterial endotoxin injection in obese Zucker rats. Growing female lean and obese Zucker rats were fed diets containing 0 or 0.5% CLA for 8 wk. On d 28, each rat was injected intraperitoneally with lipopolysaccharide from Escherichia coli serotype 055:B5 (1 mg/kg body weight) and body weight was determined over the next 96 h. There was a diet x genotype interaction (P < 0.05) for the body weight response to lipopolysaccharide 24 h postinjection. Lean rats fed CLA lost less weight than did lean controls, but obese rats fed CLA lost more weight than did obese controls. As in the first experiment, there was a diet x genotype (P < 0.05) for the effect of treatment on retroperitoneal fat pad weights determined at the end of the experiment. Lean rats fed CLA had smaller RP fat pads than did lean controls, but obese rats fed CLA once again had heavier RP fat pads than did obese controls. These results indicate that CLA reduces body fat and catabolic response to endotoxin injection in lean Zucker rats but not in the obese genotype. The observed interaction between diet and genotype warrants additional investigation into the specific mechanism(s) of the biological activities of CLA.
Article
Numerous physiological effects are attributed to conjugated linoleic acid (CLA). The purpose of this presentation is to consider these effects with respect to the cis-9,trans-11 and trans-10,cis-12 CLA isomers. We review previously published data and present new findings that relate to underlying biochemical mechanisms of action. Both isomers are natural products. The cis-9,trans-11 isomer is the principal dietary form of CLA, but the concentrations of this isomer and the trans-10,cis-12 isomer in dairy products or beef vary depending on the diet fed to cows or steers, respectively. The trans-10,cis-12 CLA isomer exerts specific effects on adipocytes, in particular reducing the uptake of lipid by inhibiting the activities of lipoprotein lipase and stearoyl-CoA desaturase. The trans-10,cis-12 CLA isomer also affects lipid metabolism in cultured Hep-G2 human liver cells, whereas both the cis-9,trans-11 and trans-10,cis-12 CLA isomers appear to be active in inhibiting carcinogenesis in animal models. We present new findings indicating that the cis-9,trans-11 CLA isomer enhances growth and probably feed efficiency in young rodents. Accordingly, the effects of CLA on body composition (induced by trans-10,cis-12 CLA) and growth/feed efficiency (induced by cis-9,trans-11 CLA) appear to be due to separate biochemical mechanisms. We also show that a 19-carbon CLA cognate (conjugated nonadecadienoic acid, CNA) inhibits lipoprotein lipase activity as effectively as CLA in cultured 3T3-L1 adipocytes. Presumably, CNA is metabolized differently than the 18-carbon CLA isomers, so this finding indicates direct activity of the administered compound as opposed to acting via a metabolite.
Article
Dietary conjugated linoleic acid (CLA) in ruminant foods has potential health benefits. CLA content in dairy and meat products is known. However, CLA intake has not been documented from records of food intake in free-living Canadian subjects. Intake of the cis-9, trans-11-octadecadienoic acid (c9,t11 CLA) isomer was estimated for 22 free-living Canadians by analyzing two seven-day diet records taken six months apart. Intake of c9,t11 CLA did not differ between the two periods during which the food records were collected. Average intake was determined to be 94.9 +/- 40.6 mg/day ranging between 15-174 mg/day. Intake of the c9,t11 isomer of CLA when expressed as mg CLA per unit of energy consumed was significantly correlated to intake of saturated fat (r = 0.62, P < 0.002) and not significantly correlated to intake of total fat (r = 0.39, P < 0.08). Daily c9,t11 CLA intakes varied considerably with approximately 50% of the intakes falling below the 20th percentile for average level of intake per day.
Article
We investigated the effect of a single oral administration of conjugated linoleic acid (CLA) on energy metabolism in mice. Male Std ddY mice were orally administered CLA (5 mL/kg weight) or linoleic acid (5 mL/kg weight) (both solutions at concentrations of 73.5%) as a control. Oxygen consumption was significantly greater in the CLA-administered mice than in the control mice. Respiratory quotient was slightly lower in the CLA-adminis-tered mice than in the control mice. We calculated fat and carbohydrate oxidation from oxygen consumption and respiratory quotient. Fat oxidation in the CLA-administered mice was significantly higher than in the control mice, and there was no difference in carbohydrate oxidation. Serum concentrations of noradrenalin and adrenalin in the CLA administered mice were significantly higher than in the control mice. These results suggested that CLA enhanced sympathetic nervous activity and energy metabolism.
Conjugated linoleic acid (CLA) attenuates human preadipocyte triglyceride (TG) content and lipo-genesis. In: Obesity research, NAASO meeting An assessment of c9,t11 linoleic acid intake in a small group of young Canadians
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32 Halvorsen YD. Conjugated linoleic acid (CLA) attenuates human preadipocyte triglyceride (TG) content and lipo-genesis. In: Obesity research, NAASO meeting, Long Beach, USA; 2000. 33 Ens JG, Ma DW, Cole KS, Field CJ, Clandinin MT. An assessment of c9,t11 linoleic acid intake in a small group of young Canadians. Nutr. Res. 2001; 21: 955–960.
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29 Moore JJ, Marcus M, Sax SM. Kinetic assay of -hydroxybutyraat in plasma with cobas biocentrifugal analyzer. Clin Chem 1982; 73: 1334–1339.
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CI À1.0 to 0.4, NS), and gender (RC 0.7; CI À0.4 to 1.8, NS) (Table 1). Expressing body composition as absolute fat mass and fat-free mass, CLA (LD 1.5710.8%, HD À2.877.6%) compared to placebo (LD 0.275.3%, HD À1.574.5%) appeared not to affect fat mass, nor did dosage (RC À0.
Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure
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Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley DS, Nelson GJ. Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Lipids 2000; 35: 777–782.
Conjugated linoleic acid (CLA) attenuates human preadipocyte triglyceride (TG) content and lipogenesis
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Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure
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  • M D Van Loan
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  • D S Kelley
  • G J Nelson
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