Trans-10, cis-12 conjugated linoleic acid increases fatty acid oxidation in 3T3-L1 preadipocytes

The purpose of this study was to examine the effect of 0-50 micromol/L trans-10, cis-12 conjugated linoleic acid (CLA) and cis-9, trans-11 CLA isomers on lipid and glucose metabolism in cultures of differentiating 3T3-L1 preadipocytes. Specifically, we investigated the effects of 6 d of CLA treatment on the following: 1) (14)C-glucose and (14)C-oleic acid incorporation and esterification into lipid; 2) (14)C-glucose and (14)C-fatty acid oxidation; and 3) basal and isoproterenol-stimulated lipolysis. Trans-10, cis-12 CLA supplementation (25 and 50 micromol/L) increased both (14)C-glucose and (14)C-oleic acid incorporation into the cellular lipid fraction, which was primarily triglyceride (TG), compared with bovine serum albumin (BSA) controls. Although glucose oxidation ((14)C-glucose to (14)C-CO(2)) was unaffected by CLA supplementation, oleic acid oxidation ((14)C-oleic acid to (14)C-CO(2)) was increased by approximately 55% in the presence of 50 micromol/L trans-10, cis-12 CLA compared with BSA controls. In contrast, 50 micromol/L linoleic acid (LA) and cis-9, trans-11 CLA-treated cultures had approximately 50% lower CO(2) production from (14)C-oleic acid compared with control cultures after 6 d of fatty acid exposure. Finally, 50 micromol/L trans-10, cis-12 CLA modestly increased basal, but not isoproterenol-stimulated lipolysis compared with control cultures. Thus, the TG-lowering actions of trans-10, cis-12 CLA in cultures of 3T3-L1 preadipocytes may be via increased fatty acid oxidation, which exceeded its stimulatory effects on glucose and oleic acid incorporation into lipid.     

Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue

We have previously shown that both a commercially available mixture of conjugated linoleic acid (CLA) isomers and the trans-10, cis-12 isomer of CLA reduced the triglyceride (TG) content and induced apoptosis in differentiating cultures of murine 3T3-L1 preadipocytes. However, the influence of CLA isomers on differentiating human (pre)adipocytes is unknown. Therefore, we conducted a series of studies using primary cultures of stromal vascular cells isolated from human adipose tissue to determine: 1) the influence of seeding density and thiazolidinedione (TZD) concentration on TG content; 2) the chronic dose response of cis-9, trans-11 CLA vs. trans-10, cis-12 CLA on TG content; 3) whether chronic linoleic acid supplementation could rescue the TG content of CLA-treated cultures; and 4) whether trans-10, cis-12-mediated reduction in cellular TG was due to decreased lipogenesis and/or increased lipolysis. In expt. 1, the TG content [micromol/(L x 10(6) cells)] increased as both seeding density and TZD concentration increased. For example, cultures seeded at 4 x 10(4) cells/cm(2) and supplemented with 10 micromol/L BRL 49653 had 10-fold more TG than similarly seeded cultures without BRL 49653. In expt. 2, TG content decreased as the level of trans-10, cis-12 CLA increased from 1 to 10 micromol/L, whereas the TG content increased with increasing concentrations of either linoleic acid or cis-9, trans-11 CLA. In expt. 3, linoleic acid supplementation restored the TG content of cultures treated with trans-10, cis-12 CLA compared with cultures treated with CLA alone, suggesting that attenuation of TG content by CLA is reversible. In expt. 4, glucose incorporation into total lipid decreased with increasing levels of trans-10, cis-12 CLA, whereas neither CLA isomer acutely affected lipolysis. These data suggest that the reported antiobesity actions of a supplement containing a crude mixture of CLA isomers given to humans may be due to inhibition of lipogenesis by the trans-10, cis-12 isomer.     

Inhibition of phospholipase A<Subscript>2</Subscript> activity by conjugated linoleic acids in human macrophages

The objective of this study was to assess the effect of conjugated linoleic acid isomers (CLAs) on the expression and activity of phospholipases A₂ (PLA₂) in human macrophages. Macrophages were incubated with 30 μM cis-9, trans-11 and trans-10, cis-12 CLAs for 48 h. After incubation, the total activity of phospholipases as well as the expression of mRNA for cytosolic (cPLA₂) and secretory (sPLA₂) phospholipases and activity of sPLA₂ were measured. Both CLA isomers reduced the total activity of PLA₂ (by 30.2%, P < 0.01 for cis-9, trans-11 CLA and by 30%, P < 0.001 for trans-10, cis-12 CLA). Trans-10, cis-12 CLA isomer downregulated the expression of mRNA of sPLA₂ and decreased the enzymatic activity of this enzyme (by 23%, P = 0.02) in macrophages. Conjugated linoleic acid isomers can significantly reduce the activity of PLA₂ in macrophages and downregulate sPLA₂ expression. The consequence of this effect may be reduction of releasing the arachidonic acid (AA) from the cellular membranes of macrophages. Supported by grant No. 3 P05B 117 23 from the State Committee for Scientific Research, Poland.     

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

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

Adenoma growth stimulation by the trans-10, cis-12 isomer of conjugated linoleic acid (CLA) is associated with changes in mucosal NF-kappaB and cyclin D1 protein levels in the Min mouse

Conjugated linoleic acid (CLA) is a term used to describe the different conjugated isomers of linoleic acid. CLA has been found to be anticarcinogenic in mammary cancer, but its effects on colon carcinogenesis are still inconclusive. In this study, the isomer-specific effects of the cis-9, trans-11 and trans-10, cis-12 CLA isomers were investigated in the Min mouse model for intestinal carcinogenesis. The Min mice (n = 10/group) were fed either an AIN-93G control diet or a diet containing 1 g/100 g cis-9, trans-11 or trans-10, cis-12 CLA for 8 wk. The number and size of adenomas were measured and the proteins from the small intestinal tissues extracted for immunoblotting analysis. The number of adenomas did not differ, but the size of the adenomas was greater in the distal part of the small intestine in mice fed the trans-10, cis-12 isomer than in controls (1.19 +/- 0.16 vs. 0.94 +/- 0.21 mm, mean +/- SD, P < 0.01). The same isomer caused an increase in lipid peroxidation, measured as urinary 8-iso-prostaglandin (PG)F(2alpha). Nuclear p65 protein of the mucosal tissue was not detectable in the trans-10, cis-12 group, which differed (P < 0.05) from the control group. Cyclin D1, a target for the nuclear factor (NF)-kappaB pathway, was elevated in the trans-10, cis-12 group compared with the control group (P < 0.01), but cyclooxygenase-2 levels were not higher. There was no difference in beta-catenin protein levels between the groups. The results indicate that the trans-10, cis-12 isomer of CLA can act as a cancer promoter in colon carcinogenesis possibly through pathways affecting NF-kappaB and cyclin D1.     

Isomer-specific effect of conjugated linoleic acid on inflammatory adipokines associated with fat accumulation in 3T3-L1 adipocytes

The purpose of this study was to examine the isomer-specific effect of conjugated linoleic acid (CLA) on inflammatory markers associated with fat accumulation in cultures of differentiating 3T3-L1 adipocytes. trans-10,cis-12 CLA (t10c12 CLA) reduced leptin secretion and fat accumulation. Linoleic acid (LA) and cis-9,trans-11 CLA (c9t11 CLA) increased them, but not significantly. t10c12 CLA and LA showed similar effects on mRNA expression of inflammatory markers. t10c12 CLA and LA tended to up-regulate the mRNA levels of inflammatory cytokines such as interleukin (IL)-6 (not significantly), tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP) with no significant change in the secretion of adiponectin, an anti-inflammatory adipokine. However, c9t11 CLA induced no significant change in the mRNA expression of IL-6, TNF-alpha, or CRP, but significantly increased adiponectin secretion. In conclusion, CLA exerted isomer-specific effects on fat accumulation and mRNA expression of inflammatory markers in 3T3-L1 adipocytes. t10c12 CLA up-regulated inflammatory markers in spite of the decreased fat accumulation, and TNF-alpha might be one of the causal factors.     

Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity

Conjugated linoleic acid (CLA) isomers, a group of positional and geometric isomers of linoleic acid [18:2(n-6)], have been studied extensively due to their ability to modulate cancer, atherosclerosis, obesity, immune function and diabetes in a variety of experimental models. The purpose of this review was to examine CLA's isomer-specific regulation of adiposity and insulin sensitivity in humans and in cultures of human adipocytes. It has been clearly demonstrated that specific CLA isomers or a crude mixture of CLA isomers prevent the development of obesity in certain rodent and pig models. This has been attributed mainly to trans-10, cis-12 CLA, both in vivo and in vitro. However, CLA's ability to modulate human obesity remains controversial because data from clinical trials using mixed isomers are conflicting. In support of some studies in humans, our group demonstrated that trans-10, cis-12 CLA prevents triglyceride (TG) accumulation in primary cultures of differentiating human preadipocytes. In contrast, cis-9, trans-11 CLA increases TG content. Closer examination has revealed that CLA's antiadipogenic actions are due, at least in part, to regulation of glucose and fatty acid uptake and metabolism. This review presents our current understanding of potential isomer-specific mechanisms by which CLA reduces human adiposity and insulin sensitivity.     

Lipids in the diet and the fatty acid profile in beef: a review and recent patents on the topic

The objective of this review is to report how the use of lipid sources in diets for ruminants can affect the fatty acid profile of beef. In addition, recent patents that can be utilized to alter the fatty acid profile in the meat, or which concern the synthesis of conjugated fatty acids will be reviewed. The industrial production of conjugated linoleic acid (CLA) has already started and the commercial products present isomers cis-9, trans-11; trans-9, cis-11; and trans-10, cis-12. Patents on the biological synthesis of isomer C18:2 cis-9, trans-11 from the linoleic acid have also been published. However, the economic production of CLA in industrial scale is a difficult process. Most of the patents published for CLA production utilize bacteria of the genera Bifidobacterium sp. and Propionibacterium sp. Lipid supplementation, with the objective to improve the fatty acid profile of beef, can be done through the use of patented products, such as genetically modified oilseeds and calcium soaps of fatty acids.     

The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic triacylglycerol content without affecting lipogenic enzymes in hamsters

Conjugated linoleic acid (CLA) refers to the positional and geometric dienoic isomers of linoleic acid. The dietary intake of CLA has been associated with changes in lipid metabolism. The aim of the present work was to assess the effects of the two main isomers of CLA on sterol regulatory element binding protein (SREBP)-1a and SREBP-1c mRNA levels, as well as on mRNA levels and the activities of several lipogenic enzymes in liver. For this purpose hamsters were fed an atherogenic diet supplemented with 5 g linoleic acid, cis-9,trans-11 or trans-10,cis-12 CLA/kg diet for 6 weeks. The trans-10,cis-12 isomer intake produced significantly greater liver weight, but also significantly decreased liver fat accumulation. No changes in mRNA levels of SREBP-1a, SREBP-1c and lipogenic enzymes, or in the activities of these enzymes, were observed. There was no effect of feeding cis-9,trans-11 CLA. These results suggest that increased fat accumulation in liver does not occur on the basis of liver enlargement produced by feeding the trans-10,cis-12 isomer of CLA in hamsters. The reduction in hepatic triacylglycerol content induced by this isomer was not attributable to changes in lipogenesis.     

Biohydrogenation of linolenic acid to stearic acid by the rumen microbial population yields multiple intermediate conjugated diene isomers

The current literature suggests that linolenic acid biohydrogenation converts to stearic acid without the formation of CLA. However, a multitude of CLA were identified in the rumen that are generally attributed to linoleic acid biohydrogenation. This study used a stable isotope tracer to investigate the biohydrogenation intermediates of (13)C-linolenic acid, including CLA. A continuous culture fermenter was used to maintain a mixed microbial population obtained from the rumen of cattle at pH 6.5 for 6 d. The mixed fermenter contents were then transferred to batch cultures containing either (13)C-labeled or unlabeled linolenic acid, which were run in triplicate for 0, 3, 24, and 48 h. The (13)C enrichment was determined by GC-MS. After 48 h of incubation, 8 CLA isomers were significantly enriched, suggesting that these CLA isomers originated directly from linolenic acid. The cis-10, cis-12 CLA isomer exhibited the highest enrichment (21.7%), followed by cis-9, cis-11 and trans-8, trans-10 CLA. The enrichment of these 2 CLA isomers ranged from 20.1 to 21.1% and the remaining 5 CLA including cis-9, trans-11 CLA were <15.0%. A multitude of nonconjugated and partially conjugated 18:2 and 18:3 isomers was enriched during the 48 h of incubation. The results of this study confirm that mixed ruminal microbes are capable of the formation of several CLA and 18:3 isomers from linolenic acid, indicating that linolenic acid biohydrogenation pathways are more complex than previously reported.     

Trans10,cis12-18:2 is a more potent inhibitor of de novo fatty acid synthesis and desaturation than cis9,trans11-18:2 in the mammary gland of lactating mice

To investigate the effects of 2 conjugated linoleic acid (CLA) isomers and trans11-18:1 (TVA) on de novo lipogenesis and desaturation in liver and mammary gland, lactating mice were fed diets containing 3% canola oil (control) or 2% canola oil plus 1% stearic acid (SA), TVA, cis9,trans11 CLA (c9t11), or trans10,cis12 CLA (t10c12). In mammary tissue, TVA and CLA isomers reduced mRNA for acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) compared with control, but only c9t11 and t10c12 reduced mammary ACC activity. Of the 2 CLA isomers, t10c12 caused a greater reduction in mammary ACC activity. Hepatic ACC or FAS activity and mRNA abundance were not affected by dietary treatments. Feeding TVA, c9t11, or t10c12 reduced mammary stearoyl-CoA desaturase 1 (SCD) mRNA and activity. Reduction was greater due to feeding t10c12 compared with c9t11. Hepatic SCD mRNA was not affected by dietary treatments, but both CLA isomers depressed hepatic SCD activity. Results indicated that t10c12 is a more potent inhibitor of mammary lipogenesis and desaturation than is c9t11. A net gain of 77 and 1690 micro g of c9t11 in liver and mammary tissue, respectively, was found in the TVA-fed group over the control and SA-fed group. However, reduced mammary SCD mRNA or activity due to feeding TVA may indicate a limited capacity for desaturation of dietary TVA to c9t11 in vivo.     

Effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on immune cell function in healthy humans

BACKGROUND: Animal studies have suggested that conjugated linoleic acid (CLA), a natural component of ruminant meat and dairy products, may confer beneficial effects on health. However, little information on the effects of CLA on immune function is available, especially in humans. Furthermore, the effects of individual isomers of CLA have not been adequately investigated. OBJECTIVE: This study investigated the effects of supplementing the diet with 3 doses of highly enriched cis-9,trans-11 CLA (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 CLA (0.63, 1.26, and 2.52 g/d) on immune outcomes in healthy humans. DESIGN: The study had a randomized, double-blind, crossover design. Healthy men consumed 1, 2, and 4 capsules sequentially that contained 80% of either cis-9,trans-11 CLA or trans-10,cis-12 CLA for consecutive 8-wk periods. This regimen was followed by a 6-wk washout and a crossover to the other isomer. RESULTS: Both CLA isomers decreased mitogen-induced T lymphocyte activation in a dose-dependent manner. There was a significant negative correlation between mitogen-induced T lymphocyte activation and the proportions of both cis-9,trans-11 CLA and trans-10,cis-12 CLA in peripheral blood mononuclear cell lipids. However, CLA did not affect lymphocyte subpopulations or serum concentrations of C-reactive protein and did not have any consistent effects on ex vivo cytokine production. CONCLUSION: CLA supplementation results in a dose-dependent reduction in the mitogen-induced activation of T lymphocytes. The effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA were similar, and there was a negative correlation between mitogen-induced T lymphocyte activation and the cis-9,trans-11 CLA and trans-10,cis-12 CLA contents of mononuclear cells.     

Conjugated linoleic acid differentially modifies fatty acid composition in subcellular fractions of muscle and adipose tissue but not adiposity of postweaning pigs

This study examined the interaction between conjugated linoleic acid (CLA) and dietary fat type on the enrichment of subcellular fractions, the Delta(9) desaturase index and adiposity in pigs. Early weaned piglets (n = 6/group) were fed for 35 d diets supplemented with 15 g/100 g diet beef tallow or corn oil, or 12 g/100 g tallow or corn oil plus 3 g CLA. There were no effects of dietary fat or CLA on the mass of dissected skin, bone, muscle or adipose tissue of the 7th to 9th thoracic rib sections. Medial subcutaneous adipose tissue of pigs fed tallow had smaller adipocytes than that of pigs fed corn oil. The lateral subcutaneous site was unaffected by dietary fat type. Microsomes accumulated <50% the concentration of trans-10,cis-12, cis-11,trans-13, and cis-9,trans-11 CLA as membrane and nonmembrane fractions of adipose tissue and longissimus muscle. There was no evidence of preferential incorporation of any CLA isomer into any of the subcellular fractions. Addition of CLA to the diets reduced adipose tissue nonmembrane monounsaturated fatty acids (MUFA; g/100 g total fatty acids) by 15% in corn oil-fed pigs and by 19% in tallow-fed pigs. Total saturated fatty acids (SFA) were increased by CLA commensurately in this lipid fraction. This resulted in a reduced Delta(9) desaturase index [MUFA/(SFA + MUFA)] in the nonmembrane lipid fraction of pigs fed either the corn oil or tallow diets. Thus, in spite of marked effects on fatty acid composition and the Delta(9) desaturase index, CLA had no effect on adiposity in early weaned piglets fed high fat diets.     

Milk fat synthesis in dairy cows is progressively reduced by increasing supplemental amounts of trans-10, cis-12 conjugated linoleic acid (CLA)

Conjugated linoleic acid (CLA) supplements containing a variety of isomers reduce milk fat yield. We have recently identified trans-10, cis-12 CLA as the isomer responsible for inhibiting milk fat synthesis in dairy cows. Our objectives were to determine milk fat yield and fatty acid composition responses to different doses of trans-10, cis-12 CLA. Multiparous Holstein cows (n = 4) were used in a 4 x 4 Latin square design. Treatments consisted of a 5-d abomasal infusion of four doses of trans-10, cis-12 CLA, i.e., 0.0, 3.5, 7.0 and 14.0 g/d. Milk fat yield was decreased 25, 33, and 50%, and milk fat concentration was reduced 24, 37 and 46% when cows received 3.5, 7.0 and 14.0 g/d of trans-10, cis-12 CLA, respectively. Feed intake, milk yield, and milk protein content and yield were unaffected by treatment. Milk fatty acid composition revealed that de novo synthesized fatty acids (short and medium chain) were extensively reduced when cows received the two highest doses, but at the low dose (3.5 g/d), decreases in de novo synthesized fatty acids and preformed fatty acids were similar. Changes in milk fatty acid composition also demonstrated that (9)-desaturase activity was inhibited at the two high doses of trans-10, cis-12 CLA, but was unaffected by the low dose. Results indicate minimal quantities of trans-10, cis-12 CLA (0.016% of dietary dry matter) markedly inhibited milk fat synthesis (25% reduction) and that a curvilinear reduction in milk fat yield occurred with increasing quantities of trans-10, cis-12 CLA.     

Conjugated linoleic acid in diets for large-size rainbow trout (Oncorhynchus mykiss): effects on growth, chemical composition and sensory attributes

The effects of graded levels (0 %, 0.5 %, 0.75 and 1 %) of dietary conjugated linoleic acid (CLA) were assessed on 97 g rainbow trout. Fish were fed to satiation twice a day for 12 weeks. At the end of the experiment, all groups of fish weighed more than 250 g and no significant differences were detected in growth performance, feed conversion, nutrient or energy utilisation or body composition between treatments. A decrease in liver lipid content resulted from including CLA and was accompanied by a reduction in malic enzyme activity. The muscle saturated acid and PUFA content did not vary between dietary treatments, despite the increasing concentration of stearic acid and CLA. In the liver, however, both fractions increased significantly with dietary CLA. Moreover, the MUFA decreased significantly in both muscle and liver. CLA was incorporated into tissue lipids, with levels in flesh (2.1-4.2 %) being 2-fold higher than in liver (0.8-1.9 %). In muscle, the percentage of cis-9, trans-11 isomer ranged from 39.5 % to 41.8 % and that of trans-10, cis-12 isomer from 31.4 % to 33.4 % of total CLA. The incorporation of CLA isomers in the liver varied with dietary treatment, and the cis-9, trans-11 isomer seemed to be more efficiently incorporated than trans-10, cis-12. Sensory data indicated slight-to-moderate differences between the trout fed with and without CLA. The present results suggest that 250 g rainbow trout can incorporate CLA in both muscle and liver, contributing to the production of a functional food.     

Effect of dietary conjugated linoleic acid on body composition and energy balance in broiler chickens

The effect of dietary conjugated linoleic acid (CLA) on body composition and energy metabolism was investigated in broiler chickens. Male broiler chicks were assigned to receive either a control diet (1 % sunflower oil) or a diet containing CLA (1 % of a 1:1 mixture of trans-10, cis-12 and cis-9, trans-11 isomers of octadecadienoic acid). The diets were fed ad libitum for 3 weeks and there were eight replicates per diet, each replicate including four chickens so that each treatment had thirty-two animals. The proportion of body fat was lower in the control group than in the CLA group. No significant differences as to the proportions of body water, ash and protein were observed. Feed and energy intake were significantly lower in CLA-fed birds. The percentage of ingested energy lost in excreta was higher after CLA feeding and heat expenditure as a percentage of ingested energy was lower in the CLA-fed group. The CLA-fed group showed a higher percentage of SFA and lower percentages of MUFA and PUFA in carcass fat. It is concluded that CLA stimulated de novo fatty acid synthesis and lowered desaturase activity.     

Conjugated linoleic acid: a functional nutrient in the different pathophysiological components of the metabolic syndrome?

PURPOSE OF REVIEW: Much attention has focused on the therapeutic potential of conjugated linoleic acid with the most abundant isomers being cis-9,trans-11 conjugated linoleic acid and trans-10,cis-12 conjugated linoleic acid. Initial animal studies associated conjugated linoleic acid with beneficial health properties, such as reducing the risk of cancer, diabetes, atherosclerosis, inflammation and obesity. This review has appraised the evidence in relation to the effect of conjugated linoleic acid on components of the metabolic syndrome (clinically or experimentally), in particular, obesity, insulin resistance, atherosclerosis and inflammation. RECENT FINDINGS: More recent human conjugated linoleic acid supplementation studies have often shown conflicting and less convincing health benefits. The marked variation between studies may reflect the isomer-specific effect of the individual conjugated linoleic acid isomers, which can often have opposing effects. Detrimental effects have been observed in some studies, in particular after supplementation with the trans-10,cis-12 conjugated linoleic acid isomer. SUMMARY: Further studies and long-term clinical trials will be required to determine the efficacy and safety of conjugated linoleic acid isomers before conjugated linoleic acid could be considered as a functional nutrient in humans.