Conjugated linoleic acid supplementation in humans: Effects on body composition and energy expenditure

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.     

Conjugated Linoleic Acid Isomers, t10c12 and c9t11, are Differentially Incorporated into Adipose Tissue and Skeletal Muscle in Humans

Conjugated linoleic acid (CLA) is a popular supplement believed to enhance immune function, body composition and insulin sensitivity, but results of scientific studies investigating its effects are conflicting. The isomer- and tissue-specific effects of CLA may explain these conflicting results. Therefore, this study quantified the incorporation of the c9t11 and t10c12 CLA isomers into adipose tissue and skeletal muscle in response to supplementation in healthy, regularly-exercising, non-obese persons. The CLA group (n = 14) ingested 3.9 g per day CLA (50:50 t9c11:c10t12) and the placebo group (n = 11) 3.9 g per day high-oleic-acid sunflower oil for 12 weeks. Following supplementation, the t10c12 isomer was incorporated into adipose tissue triacylglycerol (P < 0.001), and the c9t11 isomer tended to increase in skeletal muscle phospholipids (P = 0.056). Therefore, human adipose tissue and skeletal muscle are enriched with CLA in an isomer-specific manner.     

Supplementation with CLA: Isomer incorporation into serum lipids and effect on body fat of women

Animal studies have suggested that CLA, a natural component of meat and dairy products, may confer beneficial effects on health. However, human studies using supplementation with CLA have produced contradictory results. The aim of the present study was to further investigate the effect of CLA supplementation on human body fat, serum leptin, and serum lipids, as well as the incorporation of CLA isomers into serum lipids classes. Sixteen young healthy nonobese sedentary women received 2.1 g of CLA (divided equally between the cis,trans-9,11 and trans,cis-10,12 isomers) daily for 45 d and placebo for 45 d in a randomized double-blind crossover design. Body fat was estimated (by measurement of skinfold thickness at 10 sites), and blood was sampled at the beginning, middle, and end of the entire intervention period; an additional blood sample was obtained 2 wk thereafer. No significant differences in energy, carbohydrate, lipid, or protein intake existed between the CLA and placebo intake periods. No significant differences were found in body fat or serum leptin, TAG, total cholesterol, HDL-cholesterol, and alanine aminotransferase between CLA and placebo. The CLA isomer content of serum TAG, phospholipids, and total lipids increased 2–5 times with CLA supplementation (P<0.05). In contrast, the CLA content of cholesteryl esters did not change significantly. The period of 2 wk after the end of CLA supplementation was sufficient for its washout from serum lipids. These data indicate that supplementation with 2.1 g of CLA daily for 45 d increased its levels in blood but had no effect on body composition or the lipidemic profile of nonobese women.     

Conjugated linoleic acid supplementation modified the body composition and serum leptin levels in weaning rats

Dietary supplementation with conjugated linoleic acid (CLA) may reduce body fat mass and increase lean body mass in various species. The objective of this study was to study the effects of conjugated linoleic acid (CLA) supplementation on body composition, serum leptin and triacylglycerol levels in Wistar rats. Rats received linoleic acid (group C) or conjugated linoleic acid (group AE, supplemented with AdvantEdge CLA, and group CO, supplemented with CLA One) in the concentrations of 2% of daily feed consumption. Serum leptin and triacylglycerol levels of rats were measured by means of commercial kits. After 42 days of supplementation, rats in the control group exhibited body fat contents of 53.94 +/- 6.80 g, and those in groups AE and CO had 45.43 +/- 4.86 g and 43.75 +/- 1.93 g, respectively, corresponding to a mean body fat reduction of 18%. Water, whole body protein and ash contents of rats supplemented with CLA were statistically higher relative to control group content (corresponding to a mean increasing of 7.65%; 6.5% and 12.35%, respectively). Experimental groups AE and CO, which received CLA supplementation, had statistically lower serum leptin levels (3.45 +/- 0.46 ng/mL and 3.08 +/- 0.19 ng/mL, respectively) relative to the control group (4.21 +/- 0.22 ng/mL) which received linoleic acid. Triacylglycerol levels did not change after CLA supplementation (p > 0.05). Supplementation with conjugated linoleic acid in the concentration of 2% of mean daily feed consumption was able to change body composition of rats after 42 days of experimentation.     

Positional distribution of CLA in TAG of lamb tissues

The content and positional distribution of CLA in TAG fractions of lamb tissues was examined with either preformed CLA or the linoleic acid precursor of CLA in the diet as experimental treatments. The CLA content of phospholipid (PL) from these tissues was also examined. Thirteen lambs were randomized to the following dietary treatments: (i) control diet (no supplement); (ii) CLA supplementation (0.33 g d⁻¹ for 21 d prior to weaning) to milk-replacer of pre-ruminating lambs, or (iii) feeding linoleic acid-rich oil (6% safflower oil on a dry matter basis) to weaned ruminating lambs. At slaughter, tissue samples were procured from diaphragm, rib muscle, and subcutaneous (SC) adipose tissue. Safflower oil supplementation in the diet resulted in an increase in CLA content of the TAG from diaphragm, rib muscle, and SC adipose tissue by about threefold (P<0.05) on a mol% basis. CLA was localized to the sn-1/3 positions of TAG. Animals that received pre-formed CLA, however, had increased proportions of CLA at the sn-2 position of TAG from SC adipose tissue, suggesting that there were tissue-specific dietary effects and possible age-related effects on the mode of FA incorporation into TAG. Safflower oil supplementation in the diet had no effect on the CLA content of PL from diaphragm, rib muscle, and SC adipose tissue, suggesting that CLA was preferentially incorporated into the TAG of these tissues.     

Safety of dietary conjugated linoleic acid (CLA) in a 12-weeks trial in healthy overweight Japanese male volunteers

A study was conducted to investigate the short-term safety of dietary conjugated linoleic acid (CLA) in overweight Japanese male volunteers. The study design was a randomized, double-blind placebo-controlled trial including 60 healthy overweight volunteers (body mass index (BMI), 25 approximately 35 kg/m(2)). The subjects were randomly assigned to three groups: 5.4 g CLA-triacylglycerol (3.4 g as CLA), 10.8 g CLA-triacylglycerol (6.8 g as CLA) and placebo (10.8 g safflower oil) daily for 12 weeks. The CLA-triaclyglycerol contained 9c,11t- and 10t,12c-isomers at an equal proportion. The safety was evaluated by analyses of blood parameters and by clinical examinations at the baseline, and at 6 and 12 weeks, including vital signs and adverse effects. All subjects completed the study. The occurrence of adverse events tended to be higher in the CLA groups than in the placebo group, but all of the adverse events were mild to moderate, within normal ranges, and temporary. Serum aspartate aminotransferase (AST) activity did not differ significantly between the groups at 12 weeks, but in the high CLA group it was slightly increased from the baseline. Serum alanine aminotransferase (ALT) activity was higher in the high CLA group than in the placebo group after 12 weeks and was higher than at the baseline in both CLA groups. However, statistical analysis of the population of apparently healthy volunteers who had normal blood parameters at the baseline revealed that AST and ALT levels did not differ significantly among the 3 groups at 12 weeks. Moreover, no clinically significant changes in vital signs were observed in any of the groups. These results indicate that CLA at a dose of 3.4 g/day is a safe dietary level in healthy Japanese populations in terms of the parameters examined.     

The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans

Conjugated linoleic acid (CLA) has been suggested by some animal studies to possess antiatherogenic properties. To determine, in humans, the effect of dietary CLA on blood lipids, lipoproteins, and tissue fatty acid composition, we conducted a 93-d study with 17 healthy female volunteers at the Metabolic Research Unit of the Western Human Nutrition Research Center. Throughout the study, subjects were fed a low-fat diet [30 energy percent (en%) fat, 19 en% protein, and 51 en% carbohydrate] that consisted of natural foods with the recommended dietary allowances for all known nutrients. After a 30-d stabilization period, subjects were randomly assigned to either an intervention group (n=10) supplemented daily with capsules containing 3.9 g of CLA or a control group (n=7) that received an equivalent amount of sunflower oil. The CIA capsules (CLA 65%) contained four major cis/trans geometric isomers (11.4% 9 cis-,11 trans-18∶2; 10.8% 8 trans-,10 cis-18∶2; 15.3% 11 cis-,13 trans-18∶2; and 14.7% 10 trans-, 12 cis-18∶2) and their corresponding cis/cis (6.74% total) and trans/trans (5.99% total) varieties in smaller amounts. Fasting blood was drawn on study days 30 (end of the stabilization period), 60 (midpoint of the intervention period), and 93 (end of the intervention period). Adipose tissue samples were taken on days 30 and 93. CLA supplementation for 63 d did not change the levels of plasma cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. The weight percentage of CLA in plasma increased from 0.28±0.06 to 1.09±0.31 (n=10, P<0.05) after the supplementation. The 9 cis-,11 trans-isomer was the most prominent variety followed by the 11 cis-,13 trans- and 10 trans-,12 cis-isomers in lesser amounts. CLA in adipose tissue was not influenced by the supplementation (0.79±0.18 to 0.83±0.19 wt%) (n=10) and the 9 cis-,11 trans-variety was the only isomer present. Thus, contrary to findings from some animal studies, CLA does not seem to offer health benefits, in the short term, regarding the prevention of atherosclerosis in humans. CLA supplementation for 2 mon did not alter the blood cholesterol or lipoprotein levels of healthy, normolipidemic subjects. The supplementation did increase CLA in the plasma but only 4.23% of the ingested CLA was present in the plasma at any given time. No adverse effect of CLA supplementation was detected in this study.     

Maternal supplementation with CLA decreases milk fat in humans

CLA refers to isomers of octadecadienoic acid with conjugated double bonds. The most abundant form of CLA (rumenic acid (RA): c9,t11-18∶2) is found in milk and beef fat. Further, CLA supplements containing RA and t10,c12−18∶2 are now available. Consumption of commercially produced CLA has been shown to decrease adipose accretion in growing laboratory and production animals and cause milk fat depression in cows. We tested the hypothesis that CLA supplementation would increase milk CLA concentration and decrease milk fat content in humans. Breastfeeding women (n=9) participated in this double-blind, placebo-controlled, crossover study divided into three periods: intervention l (5 d), washout (7 d), and intervention II (5 d). Women were randomized to treatment order. During each intervention period, women consumed 1.5 g of CLA supplement or placebo (olive oil) daily; during the washout period, no supplements were consumed. Milk was collected by complete breast expression on the final day of each period; milk output was estimated by 24-h weighing on the penultimate day of each intervention period. Milk RA and t10,c12−18∶2 concentrations were greater (P<0.05) during the CLA treatment period as compared to the placebo period. Milk fat content was significantly lower during the CLA treatment, as compared to the placebo treatment (P<0.05). Data indicate no effect of treatment on milk output. Therefore, it would be prudent that lactating women not consume commercially available CLA supplements at this time. This paper was published in part in Masters, N., McGuire, M.A., and McGuire, M.K. (1999) Conjugated Linoleic Acid Supplementation and Milk Fat Content in Humans, FASEB J. 13, A697.     

Effect of fish oil supplementation on the excretion of the major metabolite of prostaglandin E in healthy male subjects

We investigated the effect of fish oil supplementation on the synthesis of prostaglandin E (PGE)in vivo by measuring the excretion of its catabolite, PGE-M, in 24-hr urine by gas chromatography/mass spectrometry. Forty healthy male volunteers (24–57 years of age) consumed a controlled basal diet providing 40% of energy from fat (P/S ratio about 0.8∶1), 130 mg/1000 kcal cholesterol, and a minimum of 22 mg/day of α-tocopherol (α-T), for three experimental periods lasting a total of 28 weeks. During period 1 (10 weeks) the diet was supplemented with placebo (PO) capsules (15×1 g/day) consisting of a blend of fats approaching the fatty acid profile of the basal diet. This was followed by a second 10-week period during which the subjects received 15×1 g/day capsules of fish oil concentrate (FOC). During period 3 (8 weeks) they continued the 15 g/day intake of FOC but received an additional 200 mg/day of α-T. PO and FOC capsules contained 1 mg α-T/g fat as antioxidant. A 14% reduction of PGE-M excretion was observed after 10 weeks of FOC supplementation (period 2), compared to an identical period of placebo supplementation (period 1), P=0.009. PGE-M excretion during the last week of period 3 was not significantly different from that at the end of period 2. The reduction in PGE synthesis in response to the relatively high marine oil supplementation was large in many subjects participating in this study.     

Conjugated linoleic acid supplementation in humans: Effects on circulating leptin concentrations and appetite

Conjugated linoleic acid (CLA) has been demonstrated to reduce body fat in animals. However, the mechanism by which this reduction occurs is unknown. Leptin may mediate the effect of CLA to decrease body fat. We assessed the effects of 64 d of CLA supplementation (3 g/d) on circulating leptin, insulin, glucose, and lactate concentrations in healthy women. Appetite was assessed as a physiological correlate of changes in circulating leptin levels. Analysis of plasma leptin concentrations adjusted for adiposity by using fat mass as a covariate showed that CLA supplementation significantly decreased circulating leptin concentrations in the absence of any changes of fat mass. Mean leptin levels decreased over the first 7 wk and then returned to baseline levels over the last 2 wk of the study in the CLA-treated group. Appetite parameters measured at around the time when the greatest decreases in leptin levels were observed showed no significant differences between supplementation and baseline determinations in the CLA-supplemented group or between the CLA and placebo-supplemented groups. There was a nonsignificant trend for mean insulin levels to increase toward the end of the supplementation period in CLA-treated subjects. CLA did not affect plasma glucose and lactate over the treatment period. Thus, 64 d of CLA supplementation in women produced a transient decrease in leptin levels but did not alter appetite. CLA did not affect these parameters in a manner that promoted decreases of adiposity.     

Conjugated Linoleic Acid Induces Uncoupling Protein 1 in White Adipose Tissue of <Emphasis Type="Italic">ob/ob</Emphasis> Mice

Conjugated linoleic acid (CLA) reduces body weight and adipose mass in a variety of species. The mechanisms by which CLA depletes adipose mass are unclear, but two independent microarray analyses indicate that in white adipose tissue (WAT), uncoupling protein 1 (UCP1) was among genes most changed by CLA. The objective of this study was to determine whether CLA induces ectopic expression of UCP1 in WAT, which may contribute to increased energy expenditure and weight loss. Six-week old, male ob/ob mice were fed either a control diet (CON) or a diet supplemented with 1.5% mixed isomer CLA (CLA) for 4 weeks. A third group of mice (LEPTIN) was fed the control diet and received daily injections of recombinant leptin as a positive control for adipose depletion in ob/ob mice. CLA did not alter several mRNA markers of lipid oxidation in epididymal white adipose tissue (eWAT) , but significantly increased carnitine palmitoyltransferase-1b (CPT1b) and PPAR gamma coactivator-1α (PGC1α) expression. Notably, CLA increased both mRNA and protein expression of uncoupling protein-1 (UCP1). β3-adrenoceptor mRNA and phosphorylated-p38 mitogen activated protein kinase (MAPK) protein levels were not affected by CLA, but were upregulated by LEPTIN. These data suggest the increased CPT1b, PGC1α, and UCP1, in WAT of CLA-fed mice may contribute to the depletion of adipose, and CLA does not appear to increase UCP1 through β3-adrenergic signaling. Future studies will focus on understanding how CLA increases mitochondrial oxidation and energy dissipation in white adipose tissue.     

Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice

Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes’ size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII.     

Interleukin-17A Gene Expression in Morbidly Obese Women

Data from recent studies conducted in rodent models and humans suggest that interleukin-17A (IL-17A) plays a role in the induction of inflammation in adipose tissue during obesity. The aim of this study was to assess the gene expression of IL-17A in adipose tissue of morbidly obese patients. We used RT-PCR to evaluate the expression of IL-17A and several adipo/cytokines in the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 10 normal-weight control women (BMI < 25 kg/m²) and 30 morbidly obese women (MO, BMI > 40 kg/m²). We measured serum levels of IL-17A and adipo/cytokines in MO and normal weight women. IL-17A expression was significantly higher in VAT than in SAT in MO patients (p = 0.0127). It was very low in normal-weight controls in both VAT and SAT tissues. We found positive correlations between IL-17A and IL-6, lipocalin-2 and resistin in VAT of MO patients. The circulating level of IL-17A was higher in the normal-weight group than the MO patients (p = 0.032), and it was significantly related to adiponectin and TNFRII levels. In conclusion, IL-17A expression in VAT is increased in morbidly obese women, which suggests a link between obesity and innate immunity in low-grade chronic inflammation in morbidly obese women.     

Conjugated linoleic acid supplementation in humans: effects on fatty acid and glycerol kinetics

Recent studies with mouse adipocytes have shown that dietary conjugated linoleic acid (CLA) may reduce body fat by increasing lipolysis. The present study examined the effect of CLA supplementation on fatty acid and glycerol kinetics in six healthy, adult women who were participating in a controlled metabolic ward study. These women were fed six CLA capsules per day (3.9 g/d) 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. The rate of appearance (Ra) of glycerol, which indicates lipolytic rates, was similar at baseline and after 4 wk of CLA supplementation at rest (1.87±0.21 and 2.00±0.39 μmol/kg/min, respectively) and during exercise (7.12±0.74 and 6.40±0.99 μmol/kg/min, respectively). Likewise, the Ra of free fatty acids (FFA) was not significantly different after 4 wk of dietary CLA at rest (2.72±0.06 and 2.74±0.12 μmol/kg/min, respectively) or during exercise (6.99±0.40 and 5.88±0.29 μmol/kg/min, respectively). CLA supplementation also had no effect on the percentage of FFA released from lipolysis that were re-esterified. The apparent rate of FFA re-esterification was 65.2±4.2% at rest and 32.1±3.44% during exercise. Four weeks of CLA supplementation had no significant effect on fatty acid or glycerol metabolism in healthy, weight-stable, adult women.     

Distinct Effects of Cannabidiol on Sphingolipid Metabolism in Subcutaneous and Visceral Adipose Tissues Derived from High-Fat-Diet-Fed Male Wistar Rats

Available data suggest that cannabidiol (CBD) may ameliorate symptoms of insulin resistance by modulating the sphingolipid concentrations in particular organs. However, it is not entirely clear whether its beneficial actions also involve adipose tissues in a state of overnutrition. The aim of the study was to evaluate the effect of CBD on sphingolipid metabolism pathways and, as a result, on the development of insulin resistance in subcutaneous (SAT) and visceral (VAT) adipose tissues of an animal model of HFD-induced insulin resistance. Our experiment was performed on Wistar rats that were fed with a high-fat diet and/or received intraperitoneal CBD injections. We showed that CBD significantly lowered the ceramide content in VAT by reducing its de novo synthesis and increasing its catabolism. However, in SAT, CBD decreased the ceramide level through the inhibition of salvage and de novo synthesis pathways. All of these changes restored adipose tissues’ sensitivity to insulin. Our study showed that CBD sensitized adipose tissue to insulin by influencing the metabolism of sphingolipids under the conditions of increased availability of fatty acids in the diet. Therefore, we believe that CBD use may be considered as a potential therapeutic strategy for treating or reducing insulin resistance, T2DM, and metabolic syndrome.     

CLA Supplementation and Aerobic Exercise Lower Blood Triacylglycerol,but Have No Effect on Peak Oxygen Uptake or Cardiorespiratory Fatigue Thresholds

This study examined the effects of 6 weeks of conjugated linoleic acid (CLA) supplementation and moderate aerobic exercise on peak oxygen uptake ( \(\dot{V}{\text{O}}_{ 2}\) peak), the gas exchange threshold (GET), the respiratory compensation point (RCP), and serum concentrations of cholesterol, triacylglycerol, and glucose in humans. Thirty-four untrained to moderately trained men (mean ± SD; age = 21.5 ± 2.8 years; mass = 77.2 ± 9.5 kg) completed this double-blind, placebo controlled study and were randomly assigned to either a CLA (Clarinol A-80; n = 18) or placebo (PLA; sunflower oil; n = 16) group. Prior to and following 6 weeks of aerobic training (50 % \(\dot{V}{\text{O}}_{ 2}\) peak for 30 min, twice per week) and supplementation (5.63 g of total CLA isomers [of which 2.67 g was c9, t11 and 2.67 g was t10, c12] or 7.35 g high oleic sunflower oil per day), each participant completed an incremental cycle ergometer test to exhaustion to determine their \(\dot{V}{\text{O}}_{ 2}\) peak, GET, and RCP and fasted blood draws were performed to measure serum concentrations of cholesterol, triacylglycerol, and glucose. Serum triacylglycerol concentrations were lower (p < 0.05) in the CLA than the PLA group. For \(\dot{V}{\text{O}}_{ 2}\) peak and glucose, there were group × time interactions (p < 0.05), however, post hoc statistical tests did not reveal any differences (p > 0.05) between the CLA and PLA groups. GET and RCP increased (p < 0.05) from pre- to post-training for both the CLA and PLA groups. Overall, these data suggested that CLA and aerobic exercise may have synergistic, blood triacylglycerol lowering effects, although CLA may be ineffective for enhancing aerobic exercise performance in conjunction with a 6-week aerobic exercise training program in college-age men.     

Effect of a new fermented soy milk product on serum lipid levels in normocholesterolemic adult men

This study was undertaken to verify the effect of a daily intake of a new fermented soy milk produced with Enterococcus faecium and Lactobacillus jugurti on the serum lipid levels in normocholesterolemic middle-aged men. The study was randomized, double-blind and placebo-controlled and was performed for a period of 6 weeks. Forty-four normocholesterolemic healthy, male volunteers, aged 40-55 years old were randomly separated in two groups: The F-group received 200 ml of the fermented product daily and the P-group received 200 ml of placebo (chemically fermented). The blood samples were drawn initially and after 3 and 6 weeks and serum values for total cholesterol, HDL-cholesterol and triglyceride were determined. The LDL-cholesterol value was estimated. No significant changes in the fermented group (F) were observed for total cholesterol, LDL-cholesterol or triglyceride levels, while the HDL-cholesterol level was significantly higher (p < or = 0.05) after 6 weeks. The total cholesterol and LDL-cholesterol levels were significantly higher (p < or = 0.05) in the placebo group (P), but no changes were found for the HDL-cholesterol and triglyceride levels during the experimental period. In conclusion, the intake of 200 ml/day of the fermented soy milk, produced with E. faecium and L. jugurti, for 6 weeks, did not affect the serum total cholesterol and LDL-cholesterol, and led an increase of 10% in the HDL-cholesterol level.     

Dietary supplementation with conjugated linoleic acid increased its concentration in human peripheral blood mononuclear cells, but did not alter their function

The purpose of this study was to examine if conjugated linoleic acid (CLA) supplementation of diets would alter fatty acid (FA) composition and function of peripheral blood mononuclear cells (PBMC). Seventeen women, 20–41 yr, participated in a 93-d study conducted at the Metabolic Research Unit. The same diet (19, 30, and 51% energy from protein, fat, and carbohydrate, respectively) was fed to all subjects throughout the study. Seven subjects (control group) supplemented their diet with six daily capsules (1 g each) of placebo oil (sunflower) for 93 d. For the other 10 subjects (CLA group), the supplement was changed to an equivalent amount of Tonalin capsules for the last 63 d of the study. Tonalin provided 3.9 g/d of a mixture of CLA isomers (trans-10,cis-12, 22.6%; cis-11,trans-13, 23.6%; cis-9,trans-11, 17.6%; trans-8,cis-10, 16.6%; other isomers 19.6%), and 2.1 g/d of other FA. PBMC isolated on study days 30 and 90 were used to assess intracellular cytokines by flow cytometry, secreted cytokines, and eicosanoid by enzyme-linked immonosorbent assay, and FA composition by gas-liquid chromatography. After supplementation, total CLA concentration increased from 0.012 to 0.97% (P<0.0001) in PBMC lipids, but it did not significantly alter the concentration of other FA. CLA supplementation did not alter the in vitro secretion of prostaglandin E₂, leukotriene B₄, interleukin-1β (IL-1β), or tumor necrosis factor α (TNFα) by PBMC simulated with lipopolysaccharide, and the secretion of IL-2 by PBMC stimulated with phytohemagglutinin. Nor did it alter the percentage T cells producing IL-2, interferon γ, and percentage of monocytes producing TNFα. The intracellular concentration of these cytokines was also not altered. None of the variables tested changed in the control group. Our results show that CLA supplementation increased its concentration in PBMC lipids, but did not alte their functions. Parts of data included here were published as abstracts for the Experimental Biology and AOCS 2001 meetings.     

Safety of conjugated linoleic acid (CLA) in overweight or obese human volunteers

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.     

Modulation of body composition and immune cell functions by conjugated linoleic acid in humans and animal models: Benefits vs. risks

We have reviewed the published literature regarding the effects of CLA on body composition and immune cell functions in humans and in animal models. Results from studies in mice, hamsters, rats, and pigs generally support the notion that CLA reduced depot fat in the normal or lean strains. However, in obese rats, it increased body fat or decreased it less than in the corresponding lean controls. These studies also indicate that t10,c12-CLA was the isomer that reduced adipose fat; however, it also increased the fat content of several other tissues and increased circulating insulin and the saturated FA content of adipose tissue and muscle. Four of the eight published human studies found small but significant reductions in body fat with CLA supplementation; however, the reductions were smaller than the prediction errors for the methods used. The other four human studies found no change in body fat with CLA supplementation. These studies also report that CLA supplementation increased the risk factors for diabetes and cardiovascular disease including increased blood glucose, insulin, insulin resistance, VLDL, C-reactive protein, lipid peroxidation, and decreased HDL. Most studies regarding the effects of CLA on immune cell functions have been conducted with a mixture of isomers, and the results have been variable. One study conducted in mice with the purified c9,t11-CLA and t10,c12-CLA isomers indicated that the two isomers have similar effects on immune cell functions. Some of the reasons for the discrepancies between the effects of CLA in published reports are discussed. Although significant benefit to humans from CLA supplementation is questionable, it may create several health risks in both humans and animals. On the basis of the published data, CLA supplementation of adult human diets to improve body composition or enhance immune functions cannot be recommended at this time.