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Evaluation of conjugated linoleic acid and dietary antibiotics as growth promotants in weanling pigs.

An experiment was conducted to determine the efficacy of dietary conjugated linoleic acid (CLA) as a growth promotant in weanling swine. Weanling pigs (n = 192; 7.6 kg and 29 d of age) were randomly assigned to four treatments that were arranged as a 2 x 2 factorial. Concentrations of dietary CLA (0 or 0.6%) and antibiotics (+/-) constituted the main effect variables. Dietary CLA treatments consisted of a 1% addition of an oil containing 60% CLA isomers or 1% soybean oil, and dietary antibiotic treatments were antibiotics or no antibiotics. The experimental diets were fed for 9 wk in four phases (1, wk 1; 2, wk 2 and 3; 3, wk 4 through 6; and 4, wk 7 through 9), after which all pigs were fed identical medicated diets for the duration of the finishing phase. Live weights were recorded at wk 17 postweaning and at marketing to determine any residual effects of dietary treatments on finisher ADG and days to market. Medicated diets fed during phases 1 and 2 contained 55 mg carbadox/kg; during phase 3 contained 299 mg tilmicosin/kg; and during phase 4 contained 110 mg tylosin and 110 mg sulfamethazine/kg. Pigs fed medicated diets had higher overall ADG than pigs fed unmedicated diets for wk 0 through 9 (P < 0.03). Gain:feed (G:F) was greater for pigs fed medicated diets than for pigs fed unmedicated diets during phase 1 (P < 0.03) and for the duration of the nursery phase (P < 0.03). There were no effects of CLA on ADG, ADFI, or G:F. There were no residual effects of nursery CLA or antibiotics on finisher ADG and days to market. Blood samples collected from a subset of pigs (n = 72) at the completion of phases 2, 3, and 4 were assayed for serum IGF-I and antibody concentrations to porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae. There was a tendency for pigs fed medicated diets to have greater IGF-I concentrations than pigs fed unmedicated diets at the completion of phase 4 (P < 0.06). Pigs fed CLA had greater antibody titers (P < 0.02) to Mycoplasma hyopneumoniae at d 63 than pigs fed diets without CLA. These results indicate that feeding 0.6% dietary CLA did not enhance growth performance in weanling swine and that the use of dietary antibiotics can increase production efficiency in nursery pigs. Furthermore, there were no interactions between CLA and dietary antibiotics on the variables addressed in this study.

Animal Feed↗

Complete stereospecific determination of conjugated linoleic acids in triacylglycerol of milk-fat.

We analyzed two kinds of dairy fat differing in their contents of cis9, trans11-conjugated linoleic acid (cis9,trans 11-CLA or rumenic acid), and determined the positional distribution of this CLA-isomer within the three sn- positions of the triacylglycerol. In the high rumenic acid fat (HR), the CLA-isomers amounted to 2.1% of total fatty acids, and 0.8% in the low rumenic acid fat (LR). Over 90% of the total CLA-isomers were in the form of rumenic acid, with an identical isomeric CLA distribution in both fats. The two fats differed mainly with regards to their contents in palmitic acid, alpha-linolenic acid, and isomers of trans-C 18:1. Conversely, our stereospecific determination indicates that the positional distribution of rumenic acid is preserved among both types of fat, and is more specific for the sn-3 position of the triacylglycerol (54 to 64% of the total rumenic acid). Such a positional distribution is believed to be nutritionally relevant.

Animals↗

Conjugated linoleic acid content and organoleptic attributes of fermented milk products produced with probiotic bacteria.

The effect of probiotic bacteria on the formation of conjugated linoleic acid (CLA), microbial growth, and organoleptic attributes (acidity, texture, and flavor) of fermented milk products was determined. Four probiotic bacteria, Lactobacillus rhamnosus, Propionibacterium freudenreichii subsp. shermanii 56, P. freudenreichii subsp. shermanii 51, and P. freudenreichii subsp. freudenreichii 23, were evaluated individually or in coculture with traditional yogurt cultures (Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarius subsp. thermophilus). The lipid source was hydrolyzed soy oil. L. rhamnosus, in coculture with yogurt culture, resulted in the highest content of CLA. Growth and CLA formation of propionibacteria were enhanced in the presence of yogurt cultures. Texture and flavor attributes of fermented milks produced with propionibacteria were significantly different than the fermented milks processed with yogurt cultures. The fermented milks processed with probiotic bacteria in coculture with yogurt cultures demonstrated similar acidity, texture, and flavor as the fermented milk produced with yogurt cultures.

Caseins↗

Dietary intake of conjugated linoleic acids and risk of premenopausal and postmenopausal breast cancer, Western New York Exposures and Breast Cancer Study (WEB Study).

Specific fatty acids may have differential effects on breast cancer etiology. Animal studies have suggested that conjugated linoleic acids (CLA), a group of fatty acids found predominantly in dairy products and the meat of ruminants, have potent anticarcinogenic properties. We examined breast cancer risk and dietary CLA intake among 1,122 women with primary, incident, histologically confirmed breast cancer and 2,036 controls frequency matched to cases by age, race, and county of residence. Diet was assessed with a self-administered 104-item food frequency questionnaire and other relevant data were collected by detailed in-person interviews. We examined risk with intake of total CLAs and the 9c,11t-18:2 isomer of CLA (9,11 CLA). Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression, adjusting for age, the residual of fat adjusted for energy, and other breast cancer risk factors. No association was observed between intakes of total CLA or 9,11 CLA and overall risk of premenopausal or postmenopausal breast cancer. We observed little association between CLA intakes and risk of estrogen receptor (ER)-negative or ER-positive tumors, although, compared with premenopausal women in the lowest quartile of 9,11 CLA intake, those in the highest quartile had a marginally significant reduction in risk of having an ER-negative tumor (odds ratio, 0.40; 95% confidence interval, 0.16-1.01). Our findings suggest that, although CLA intake was not related to overall breast cancer risk, there may be associations with tumor biology at least among premenopausal women.

Adult↗

Detection of free radicals produced from the reaction of cytochrome P-450 with linoleic acid hydroperoxide.

The ESR spin-trapping technique was employed to investigate the reaction of rabbit cytochrome P-450 1A2 (P450) with linoleic acid hydroperoxide. This system was compared with chemical systems where FeSO4 or FeCl3 was used in place of P450. The spin trap 5, 5'-dimethyl-1-pyrroline N-oxide (DMPO) was employed to detect and identify radical species. The DMPO adducts of hydroxyl, O2-., peroxyl, methyl and acyl radicals were detected in the P450 system. The reaction did not require NADPH-cytochrome P-450 reductase or NADPH. The same DMPO-radical adducts were detected in the FeSO4 system. Only DMPO-.OH radical adduct and carbon-centred radical adducts were detected in the FeCl3 system. Peroxyl radical production was completely O2-dependent. We propose that polyunsaturated fatty acids are initially reduced to form alkoxyl radicals, which then undergo intramolecular rearrangement to form epoxyalkyl radicals. Each epoxyalkyl radical reacts with O2, forming a peroxyl radical. Subsequent unimolecular decomposition of this peroxyl radical eliminates O2-. radical.

Animals↗

Effect of linoleic acid hydroperoxide on endothelial cell calcium homeostasis and phospholipid hydrolysis.

The relationship between intracellular free calcium ion concentrations ([Ca2+]i) and release of arachidonic acid from membrane phospholipids following peroxidation was examined in rabbit aortic endothelial cells treated with linoleic acid hydroperoxide (LOOH). LOOH (0.1-0.4) mumol/10(6) cells) caused a rapid and dose-dependent transient increase in [Ca2+]i in the presence of extracellular Ca2+ that remained elevated over baseline for 15 to 30 s. In the absence of extracellular Ca2+, LOOH also evoked a transient increase in [Ca2+]i of lesser magnitude which immediately returned to basal (or below basal) levels. In this regard, the rise in intracellular Ca2+ after LOOH or vasopressin (AVP) treatments involved, at least in part, related intracellular pools that in each case was followed by influx of extracellular Ca2+. The intracellular membrane sources known to be affected by vasopressin were not directly involved. Most notably, the LOOH evoked rise in [Ca2+]i was not associated with release of IP3, suggesting that the source of intracellular Ca2+ is not IP3-sensitive pools. However, pretreatment with LOOH strongly inhibited the rise in [Ca2+]i upon subsequent addition of AVP or LOOH and the extent of such inhibition was dependent on the availability of free intracellular Ca2+ and presence of extracellular Ca2+. These findings suggest that reuptake of Ca2+ into intracellular membrane pools is reduced in the presence of LOOH and/or the availability of Ca2+ from agonist-sensitive sites is inhibited by LOOH. An increase in free 20:4 levels was found after LOOH treatment that was only partly prevented using intracellular Ca2+ chelators which maintained [Ca2+]i at basal levels after LOOH treatment. These findings suggest that LOOH induction of phospholipid hydrolysis proceeds following small transients in [Ca2+]i that are considerably less than that evoked by agents such as AVP, approximating basal Ca2+ concentrations. Inhibition of LOOH-induced lipid peroxidation by vitamin E also prevented the rise in [Ca2+]i and 20:4 release indicating that phospholipid hydrolysis is dependent, at least in part, on membrane lipid peroxidation. Inhibition of protein kinase C (PKC) completely blocked LOOH-induced release of 20:4 but had little effect on the LOOH-induced rise in [Ca2+]i, suggesting an indirect relationship between LOOH-induced membrane Ca2+ signalling events, with intervention via PKC-mediated induction of phospholipid hydrolysis. A rapid and progressive translocation of PKC to the membrane fraction was evident after LOOH addition over the time course corresponding to the maximal release of 20:4 which was also inhibited by vitamin E.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Dose-dependent effect of dietary conjugated linoleic acid on the growth of rat hepatoma dRLh-84 cells in vivo.

In this study, the effect of varying doses of conjugated linoleic acid (CLA) on the growth of transplanted hepatoma dRLh-84 cells and the relationship between tumor growth and prostaglandin (PG) E2 production or cyclooxygenase (COX)-2 expression were examined. Donryu rats were fed an experimental diet containing 0, 0.1, 0.5, or 2 wt.% CLA for 3 wk, and then dRLh-84 cells were transplanted into the liver. Results show that dietary CLA (0.5 and 2 wt.%) significantly enhanced the growth of the transplanted hepatoma cells compared to the non-CLA diet group at 20 d after cell transplantation. Tumor weight at 10 d after transplantation was also significantly higher in the 2 wt.% CLA group than in non-CLA fed rats. Ten days after transplantation, the PGE2 level in the tumor tissue was shown to be depressed in a CLA dose-dependent manner. Cyclooxygenase-2 (COX-2) mRNA expression in the tumor also tended to be lower in the CLA group than in the non-CLA diet group 10 d after transplantation. Dietary CLA did not affect the tumor phospholipid arachidonic acid level, which is a substrate for PG synthesis. These results indicate that dietary CLA of at least 0.5 wt.% enhances the growth of transplanted dRLh-84 cells in vivo. It is believed that growth promotion of dRLh-84 cells in vivo by CLA cannot be clarified by the PG synthesis dependent mechanism.

Animals↗

Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health.

Data from a number of studies and trials have shown that different conjugated linoleic acids (CLA's) may produce beneficial effects on cancer, atherosclerosis, hypertension, diabetes and changes in body composition. Despite the increasing knowledge about CLA's implications on health, the mechanism of action of these fatty acids is not completely understood. Moreover, human studies indicate that some of these beneficial effects are considerably less evident than anticipated from mice studies, while the efficacy and safety of dietary supplements containing CLA have been questioned in some intervention trials. Recently, it has been suggested that the anti-carcinogenic and anti-atherosclerosis effects of CLA's stem from its anti-inflammatory properties. Because inflammatory responses are associated with the pathophysiology of many diseases, including obesity and the metabolic syndrome, the investigation in this area is of growing interest in recent years.

Anti-Inflammatory Agents↗

Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men.

OBJECTIVES: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. DESIGN: Double-blind, randomized, parallel, reference-controlled intervention study. SUBJECTS AND INTERVENTION: Seventy-one healthy males aged 31-69 y received one of the following treatments: (1). mixture of 50% c9,t11 CLA and 50% t10,c12 CLA isomers (CLA 50:50); (2). mixture of 80% c9,t11 CLA and 20% t10,c12 CLA isomers (CLA 80:20); and (3). sunflower oil fatty acids (reference). The treatments were given as supplements in softgel capsules providing a total of 1.7 g (c9,t11+t10,c12) CLA fatty acids (50:50) or 1.6 g (c9,t11+t10,c12) CLA glycerides (80:20) per day in treatment groups for 12 weeks. RESULTS: Almost twice as many subjects reached protective antibody levels to hepatitis B when consuming CLA 50:50 fatty acids (15/24, 62%) compared with subjects consuming the reference substance (7/21, 33%, P=0.075). In subjects consuming CLA 80:20 glycerides this was 8/22 (36%). Other aspects of immune function, ie DTH responses, NK cell activity, lymphocyte proliferation and production of TNF-alpha, IL1-beta, IL6, IFN-gamma, IL2, IL4, and PGE(2), were not affected. CONCLUSION: This is the first study that suggests that CLA may beneficially affect the initiation of a specific response to a hepatitis B vaccination. This was seen in the CLA 50:50, but not in the CLA 80:20 group.

Adult↗

Glucuronidation of linoleic acid diols by human microsomal and recombinant UDP-glucuronosyltransferases: identification of UGT2B7 as the major isoform involved.

Recent reports suggest that linoleic acid (LA) epoxides and diols are associated with important physiological, pharmacological, and pathological events in vivo. We have shown recently that LA-diols are excellent substrates for human liver microsomal UDP-glucuronosyltransferases (UGTs); however, it is not known if other human tissues glucuronidate LA-diols or which UGT isozyme(s) is involved. The present studies with human intestinal microsomes indicate that glucuronidation of LA-diols occurs throughout the gastrointestinal tract, with the highest activity in the small intestine. LA-diols yielded exclusively hydroxyl-linked glucuronides, whereas LA yielded the carboxyl-linked glucuronide. Studies with human recombinant UGTs demonstrated that only UGT2B7 glucuronidated LA and LA-diols. Kinetic analysis with UGT2B7 yielded apparent K(m) values in the range of 40-70 microM and V(max) values from 4.5 to 5.4 nmol/mg x min. These studies indicate that LA and LA-diols are excellent substrates for intestinal UGTs and provide the first evidence for UGT2B7 being the major isoform involved.

Adolescent↗

Influence of feeding soybean oil on conjugated linoleic acid content in beef.

Forty-eight steers were used to study the influence of feeding soybean oil (SO) on the conjugated linoleic acid (CLA) content of beef. Steers were fed either a control diet containing 954 g/kg of dry matter (DM) corn-based concentrate (CTL) or a control diet supplemented with SO at 20 (SO2) or 40 g/kg (SO4) of diet DM for 105 days. Adipose tissue samples were collected from the M. longissimus dorsi (LD) and from the M. semitendinosus (ST) on days 0 and 63 of the experiment. Adipose and muscle tissue samples were collected from the LD and ST immediately after slaughter. Feeding 40 g/kg of DM as SO increased the proportions of trans-C(18:1) in beef lipid as compared to CTL and SO2 treatments. The C(18:2) cis-9, trans-11 isomer of CLA as a proportion of total fat was not different in adipose and muscle across treatments. Supplementing SO increased C(18:2) trans-10, cis-12 CLA in adipose tissue of the LD. Supplementing high-grain finishing diets with SO is not an effective strategy to enhance the C(18:2) cis-9, trans-11 isomer of CLA in beef.

Adipose Tissue↗

Structure-activity relationship of conjugated linoleic acid and its cognates in inhibiting heparin-releasable lipoprotein lipase and glycerol release from fully differentiated 3T3-L1 adipocytes.

Conjugated linoleic acid (CLA) reduces body fat in part by inhibiting the activity of heparin-releasable lipoprotein lipase (HR-LPL) activity in adipocytes, an effect that is induced by the trans-10,cis-12 CLA isomer. In this study we used a series of compounds that are structurally related to CLA (i.e., CLA cognates) to investigate the structural basis for this phenomenon. None of the 18:1 CLA cognates that were tested, nor trans-9,cis-12 18:2, cis-12-octadecen-10-ynoic acid (10y,cis-12) or 11-(2'-(n-pentyl)phenyl)-10-undecylenic acid (designated P-t10), exhibited any significant effect on HR-LPL activity. Among the CLA derivatives (alcohol, amide, and chloride) that were tested, only the alcohol form inhibited HR-LPL activity, although to a lesser extent than CLA itself. In addition, intracellular TG was reduced only by trans-10,cis-12 CLA and the alcohol form of CLA. Hence it appears that the trans-10,cis-12 conjugated double bond in conjunction with a carboxyl group at C-1 is required for inhibition of HR-LPL activity, and that an alcohol group can partially substitute for the carboxyl group. We also studied glycerol release from the cells, observing that this was enhanced by trans-10 18:1, trans-13 18:1, cis-12 18:1, cis-13 18:1, P-t10 but was reduced by cis-9 18:1, the alcohol and amide forms of CLA or 10y,cis-12. Accordingly the structural feature or features involved in regulating lipolysis appear to be more complex. Despite enhancing lipolysis in cultured 3T3-L1 adipocytes, trans-10 18:1 did not reduce body fat gain when fed to mice.

3T3-L1 Cells↗

Dietary conjugated linoleic acid affects morphofunctional and chemical aspects of subcutaneous adipose tissue in heavy pigs.

We investigated the in vivo effects of dietary conjugated linoleic acid (CLA) on subcutaneous adipose tissue from heavy pigs to clarify the involvement of possibly different causative effects in the established antiadipogenic effect of CLA. Pigs [n = 36; initial body weight, 106 kg live weight (LW)] were assigned to 1 of 2 LW-matched groups supplemented with either 0 or 0.75% of a CLA preparation containing 50% CLA isomers. The pigs were slaughtered at 155 kg LW and adipose tissue analyzed. CLA supplementation affected ash content, and decreased iodine values (P < 0.01) and adipocyte size (P < 0.05). The fat content of adipose tissue was lower (P < 0.05) in females than castrated males, and females had smaller (P < 0.01) adipocytes than castrated males. Neither CLA nor sex influenced adipocyte lipid droplet diameter or the extent of lipid peroxidation as determined by quantitation of Schiff's histochemical reaction. NADPH-diaphorase was not influenced by CLA treatment. Preadipocyte proliferation rates were lower in pigs fed CLA (P < 0.05), whereas the number of adipocyte apoptotic nuclei was greater (P < 0.05). Preadipocyte proliferation was also greater (P < 0.05) in females than castrated males. Neuronal and endothelial nitric oxide synthase activities did not differ between groups in adipose tissue vessels, but inducible nitric oxide synthase expression in adipocytes was lower in pigs fed CLA (P = 0.05). These findings suggest that the antiadipogenic effect of CLA in heavy pigs is not a direct effect but may occur by downregulation of a NO-mediated lipolytic pathway.

Adipocytes↗

Synergistic effects of conjugated linoleic acid and chromium picolinate improve vascular function and renal pathophysiology in the insulin-resistant JCR:LA-cp rat.

AIMS: Conjugated linoleic acid (CLA) is a natural constituent of dairy products, specific isomers of which have recently been found to have insulin sensitizing and possible antiobesity actions. Chromium is a micronutrient which, as the picolinate (CrP), has been shown to increase insulin sensitivity in animal models, including the JCR:LA-cp rat. We tested the hypothesis that these agents may have beneficial synergistic effects on the micro- and macrovasculopathy associated with hyperinsulinaemia and early type 2 diabetes. METHODS: Insulin-resistant cp/cp rats of the JCR:LA-cp strain were treated with mixed isomers of CLA (1.5% w/w in the chow) and/or CrP at 80 microg/kg/day (expressed as Cr) from 4 weeks of age to 12 weeks of age. Plasma insulin, lipid and adiponectin levels, aortic vascular function, renal function and glomerular sclerosis were assessed. RESULTS: CLA administration reduced food intake, body weight and fasting insulin in JCR:LA-cp rats. Plasma adiponectin levels were significantly elevated in rats treated with both CLA and CrP. Aortic hypercontractility was reduced and the relaxant response to the nitric oxide-releasing agent acetylcholine (Ach) was increased in CrP-treated rats. Striking reductions were also observed in the level of urinary albumin and the severity of glomerular sclerosis in rats treated specifically with CLA. CONCLUSIONS: CLA and CrP have beneficial effects ameliorating several of the pathophysiologic features of an insulin-resistant rat model. These supplements may be useful adjuncts in the management of patients with the metabolic syndrome and warrant further study.

Adiponectin↗

Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects.

OBJECTIVE: To study the effects of 13 weeks conjugated linoleic acid (CLA) supplementation in overweight subjects on body-weight maintenance, parameters of appetite and energy intake (EI) at breakfast after weight loss. DESIGN: This study had a double-blind, placebo-controlled randomized design. SUBJECTS: A total of 26 men and 28 women (age 37.8+/-7.7 y; body mass index 27.8+/-1.5 kg/m(2)). INTERVENTIONS: Subjects were first submitted to a very-low-calorie diet (VLCD; 2.1 MJ/day) for 3 weeks after which they started with the 13-week intervention period. They either received 1.8 g CLA or placebo per day or 3.6 g CLA or placebo per day. Additionally, subjects of the high dosage intervention replaced their habitual lunch by one meal of a protein-rich, low-energy supplement. EI was measured at breakfast and appetite profile after an overnight fast. RESULTS: The mean body weight loss was 6.9+/-1.7% of their original body weight. Multiple regression analysis showed that at the end of the 13-week intervention, CLA did not have an effect on body weight regain. Feelings of fullness and satiety were increased and feelings of hunger were decreased after 13 weeks intervention by CLA compared to placebo, independent of %body weight regain. However, EI measured at breakfast was not affected by CLA. CONCLUSION: Appetite (hunger, satiety and fullness) was favorably, dose-independently affected by a 13-week consumption of 1.8 or 3.6 g CLA/day. This did not result in a lower EI at breakfast or an improved body-weight maintenance after weight loss.

Adult↗

The linoleic acid derivative FR236924 facilitates hippocampal synaptic transmission by enhancing activity of presynaptic alpha7 acetylcholine receptors on the glutamatergic terminals.

The present study aimed at understanding the effect of FR236924, a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis-double bonds, on hippocampal synaptic transmission in both the in vitro and in vivo systems. FR236924 increased the rate of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated miniature excitatory postsynaptic currents, without affecting the amplitude, triggered by nicotine in CA1 pyramidal neurons of rat hippocampal slices, that is inhibited by GF109203X, a selective protein kinase C (PKC) inhibitor or alpha-bungarotoxin, an inhibitor of alpha7 acetylcholine (ACh) receptors. FR236924 stimulated glutamate release from rat hippocampal slices and in the hippocampus of freely behaving rats, and the effect was also inhibited by GF109203X or alpha-bungarotoxin. FR236924 induced a transient huge potentiation followed by a long-lasting potentiation in the slope of field excitatory postsynaptic potentials recorded from the CA1 region of rat hippocampal slices, and the latter effect was blocked by GF109203X or alpha-bungarotoxin. Likewise, the compound persistently facilitated hippocampal synaptic transmission in the CA1 region of the intact rat hippocampus. It is concluded from these results that FR236924 stimulates glutamate release by functionally targeting presynaptic alpha7 ACh receptors on the glutamatergic terminals under the influence of PKC, responsible for the facilitatory action on hippocampal synaptic transmission. This may provide evidence for a link between cis-unsaturated free fatty acids and presynaptic alpha7 ACh receptors in hippocampal synaptic plasticity.

Alkanes↗

Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus.

BACKGROUND: Some animal studies have suggested that conjugated linoleic acid (CLA) supplementation may have therapeutic potential with respect to insulin sensitivity and lipid metabolism, which are important cardiovascular disease (CVD) risk factors associated with type 2 diabetes mellitus. OBJECTIVE: We investigated the effect of CLA supplementation on markers of glucose and insulin metabolism, lipoprotein metabolism, and inflammatory markers of CVD in subjects with type 2 diabetes. DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Thirty-two subjects with stable, diet-controlled type 2 diabetes received CLA (3.0 g/d; 50:50 blend of cis-9,trans-11 CLA and trans-10,cis-12 CLA) or control for 8 wk. A 3-h 75-g oral-glucose-tolerance test was performed, and fasting plasma lipid concentrations and inflammatory markers were measured before and after the intervention. RESULTS: CLA supplementation significantly increased fasting glucose concentrations (6.3%; P < 0.05) and reduced insulin sensitivity as measured by homeostasis model assessment, oral glucose insulin sensitivity, and the insulin sensitivity index (composite) (P = 0.05). Total HDL-cholesterol concentrations increased by 8% (P < 0.05), which was due to a significant increase in HDL(2)-cholesterol concentrations (P < 0.05). The ratio of LDL to HDL cholesterol was significantly reduced (P < 0.01). CLA supplementation reduced fibrinogen concentrations (P < 0.01) but had no effect on the inflammatory markers of CVD (C-reactive protein and interleukin 6). CONCLUSIONS: CLA supplementation had an adverse effect on insulin and glucose metabolism. Whereas CLA had positive effects on HDL metabolism and fibrinogen, a therapeutic nutrient should not be associated with potentially adverse effects on other clinical markers of type 2 diabetes.

Analysis of Variance↗