Effects of dietary supplementation with conjugated linoleic acid on experimental human rhinovirus infection and illness.

BACKGROUND: Because studies suggest that the dietary supplement conjugated linoleic acid (CLA) has immunomodulatory activities that might benefit common colds, we performed two studies of CLA effects in experimental human rhinovirus (HRV) infection. METHODS: The first study explored whether CLA supplementation (Safflorin; Loders Croklaan, BV, Wormerveer, the Netherlands) altered the virological or clinical course of experimental HRV infection, and the second explored whether CLA affected the frequency and severity of HRV cold-associated sore throat and cough. The trials were randomized, double-blinded and placebo-controlled. In total, 50 healthy volunteers aged 18-45 years and susceptible to HRV type-39 (serum neutralizing antibody titre < or = 1:2) participated in study 1 and 80 similar volunteers susceptible to Hank's HRV participated in study 2. Participants ingested CLA 2 g/day or placebo for 4 weeks before and 4 days following intranasal HRV inoculation. The primary endpoint for study 1 was the frequency of colds and for study 2 was the symptom severity scores for sore throat and cough. RESULTS: In study 1, 10/24 (42%) placebo compared with 7/21 (33%) CLA participants developed colds (P = 0.53). CLA was associated with significant reductions in mean scores for cough (0 CLA versus 0.9 placebo) and sore throat (0.8 CLA versus 2.9 placebo). In study 2, clinical colds developed in 19/33 (58%) placebo and 27/43 (63%) CLA participants. Symptom scores for cough (0.9 CLA versus 1.0 placebo) and sore throat (2.6 CLA versus 3.2 placebo) were not significantly different. Similarly no differences in nasal viral titres or serological responses were found. CONCLUSIONS: CLA dietary supplementation had no consistent effects on the virological or clinical course of experimental HRV colds. A larger study would be required to detect more subtle effects of CLA on HRV cold-associated symptoms.

Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation.

BACKGROUND: Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-gamma (PPARgamma) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARgamma and PPARalpha reporter gene assays. RESULTS: Inclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lepob/lepob) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARgamma agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFalpha concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARgamma-mediated reporter gene activity; both isomers stimulated PPARalpha-mediated reporter gene activity. CONCLUSIONS: CLA initially decreased but subsequently increased insulin sensitivity in lepob/lepob mice. Activation of both PPARgamma and PPARalpha may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity.

Immunomodulatory properties of conjugated linoleic acid.

In vitro studies of the use of immune cells and animal models demonstrate that conjugated linoleic acid (CLA), a lipid, modulates immune function. In addition, recent publications demonstrate that 2 active CLA isomers (ie, cis-9,trans-11 CLA and trans-10,cis-12 CLA) modulate immune function in humans. Aspects of both the innate and adaptive immune responses are affected by dietary CLA supplementation. CLA consists of a mixture of isomers, which reduced immune-induced wasting and enhanced ex vivo lymphocyte proliferation in broilers and decreased tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production in rat models. In mice, ex vivo lymphocyte proliferation and IL-2 production were increased. Furthermore, evidence suggests that the cis-9,trans-11 and trans-10,cis-12 CLA isomers exert distinct effects on immune function. Specifically, these 2 isomers have differential effects on specific T cell populations and immunoglobulin subclasses in animal and human studies. Herein, a systematic review of the literature and relevant new data are presented with an aim to compare data and to present an overview covering the innate and adaptive components of the immune response that are regulated by CLA. In addition, potential mechanisms of action are discussed and the need for future studies on the immunomodulatory properties of CLA are outlined in detail. The understanding of the mechanism(s) by which CLA increases immune function will aid in the development of nutritionally based therapeutic applications to augment host resistance against infectious diseases and to treat immune imbalances, which result in inflammatory disorders, allergic reactions, or both.

Conjugated linoleic acid versus high-oleic acid sunflower oil: effects on energy metabolism, glucose tolerance, blood lipids, appetite and body composition in regularly exercising individuals.

The aim of this study was to measure the effects of 12 weeks of conjugated linoleic acid (CLA) supplementation on body composition, RER, RMR, blood lipid profiles, insulin sensitivity and appetite in exercising, normal-weight persons. In this double-blind, randomised, controlled trial, sixty-two non-obese subjects (twenty-five men, thirty-seven women) received either 3.9 g/d CLA or 3.9 g high-oleic acid sunflower oil for 12 weeks. Prior to and after 12 weeks of supplementation, oral glucose tolerance, blood lipid concentrations, body composition (dual-energy X-ray absorptiometry and computerised tomography scans), RMR, resting and exercising RER and appetite were measured. There were no significant effects of CLA on body composition or distribution, RMR, RER or appetite. During the oral glucose tolerance tests, mean plasma insulin concentrations (0, 30, 120 min) were significantly lower (P= 0.04) in women who supplemented with CLA (24.3 (SD 9.7) to 20.4 (SD 8.5) microU/ml) compared to high-oleic acid sunflower oil control (23.7 (SD 9.8) to 26.0 (SD 8.8) microU/ml). Serum NEFA levels in response to oral glucose were attenuated in both men and women in the CLA (P=0.001) compared to control group. However, serum total cholesterol and LDL-cholesterol concentrations decreased in both groups and HDL-cholesterol concentrations decreased in women over 12 weeks (P=0.001, P=0.02, P=0.02, respectively). In conclusion, mixed-isomer CLA supplementation had a favourable effect on serum insulin and NEFA response to oral glucose in non-obese, regularly exercising women, but there were no CLA-specific effects on body composition, energy expenditure or appetite.

Conjugated linoleic acid ameliorates viral infectivity in a pig model of virally induced immunosuppression.

We investigated the cellular and molecular immunoregulatory actions of conjugated linoleic acid (CLA) of relevance to viral disease pathogenesis and antiviral responses. To test the hypothesis that CLA ameliorates viral disease, we developed a viral challenge model by infecting pigs with type-2 porcine circovirus (PCV2). After 42 d of dietary supplementation with either soybean oil (n = 16) or CLA (n = 16), half of the pigs in each group were challenged with PCV2. We examined the effect of CLA on the development of lesions (i.e., lymphoid depletion and pneumonia) and observed the kinetics of the immune responses against PCV2. The viral infection depleted immature B cells (IgM+SWC3+) and favored proapoptotic mRNA expression profiles [i.e., suppressed B-cell leukemia/lymphoma-xl (Bcl-xl) and stimulated Bcl-2 homologous antagonist/killer (Bak)] in the external inguinal lymph nodes. B-cell depletion was more accentuated in pigs fed the control diet, whereas interleukin (IL)-2 mRNA expression was downregulated. Histopathological examination of the lungs revealed that the interstitial pneumonia tended to be more severe in infected pigs fed the control diet, which were also affected by growth retardation. CD8+ T cells were the primary cellular targets of CLA action in peripheral blood (CD8+CD29low and CD8+CD45RC+) and thymus (CD8+ and CD4+CD8+). CLA interacted with PCV2 to increase the proliferation of CD8+ T cells and to suppress PCV2-specific interferon (IFN)-gamma production in CD4+ T cells. At the molecular level, these cellular immunoregulatory properties were associated with differential patterns of peroxisome proliferator-activated receptor (alpha and gamma) mRNA expression between diets in virally infected pigs.