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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.

Animals↗

Trans-10, cis-12-conjugated linoleic acid increases phagocytosis of porcine peripheral blood polymorphonuclear cells in vitro.

Trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) has been shown to alter immune function. PPARgamma has been shown to potentially play an important role in regulating inflammatory and immune responses by modulating the activity of monocytes and macrophages. Previous studies have indicated that the phagocytic capacity of porcine peripheral blood polymorphonuclear cells (PMN) was enhanced by the culture supernatant fraction from t10c12-CL-stimulated porcine peripheral blood mononuclear cells (PBMC) but not by t10c12-CLA itself. In the present study, we examined the effects of t10c12-CLA on PPARgamma and TNF-alpha expression of porcine PBMC and the phagocytic capacity of PMN. t10c12-CLA increased TNF-alpha mRNA expression and production by PBMC. The phagocytic capacity of porcine PMN was enhanced by either culture supernatant fraction from PBMC treated with t10c12-CLA or recombinant porcine (rp) TNF-alpha. Anti-rpTNF-alpha polyclonal antibody inhibited the enhancement of PMN phagocytic capacity. t10c12-CLA also up regulated PPARgamma mRNA expression in porcine PBMC. Bisphenol A diglycidyl ether, a PPARgamma antagonist, not only completely negated the t10c12-CLA-stimulating effects on TNF-alpha expression and production by porcine PBMC, but also decreased the enhancement of PMN phagocytic capacity by the t10c12-CLA-stimulated porcine PBMC culture supernatant fraction. These results suggest that t10c12-CLA has an immunostimulating effect on porcine PMN phagocytic capacity, which is mediated by TNF-alpha from PBMC via a PPARgamma-dependent pathway.

Animals↗

Effect of a mixture of conjugated linoleic acid isomers on growth performance and antibody production in broiler chicks.

The effect of dietary conjugated linoleic acid (CLA) isomers mixture on antibody titres against sheep blood erythrocytes (SRBC) and immunoglobulin (Ig) G concentration in plasma was studied in broiler chickens. In experiment 1, male and female broiler chicks (11 d of age, Cobb strain) were fed a diet supplemented with 10 g CLA or 10 g safflower-seed oil/kg diet for 2 weeks. An SRBC suspension (5:100, v/v) in a phosphate buffer was intravenously injected at 18 d of age and a blood sample was taken from the wing vein at 25 d of age. Chicks fed the CLA-supplemented diet had enhanced first antibody titres in plasma to SRBC as compared with those fed the safflower-seed oil-supplemented diet, irrespective of sex differences. In experiment 2, male broiler chicks (8 d of age, Ross strain) were fed a basal diet or a diet containing 10 g CLA/kg diet for 3 weeks. CLA in the CLA diet partially replaced the soyabean oil in the basal diet. The SRBC suspension was intravenously injected at 15 and 25 d of age and a blood sample was obtained at 21 and 29 d of age. The first antibody titres against SRBC were higher in chicks fed the CLA diet than those in chicks fed the basal diet, but the second titres were not. Plasma IgG concentrations in chicks fed the CLA diet were higher than those in chicks fed the basal diet on both sampling days. The results showed that dietary CLA enhanced antibody production in broiler chickens.

Animal Nutritional Physiological Phenomena↗

Substituting dietary linoleic acid with alpha-linolenic acid improves insulin sensitivity in sucrose fed rats.

This study describes the effect of substituting dietary linoleic acid (18:2 n-6) with alpha-linolenic acid (18:3 n-3) on sucrose-induced insulin resistance (IR). Wistar NIN male weanling rats were fed casein based diet containing 22 energy percent (en%) fat with approximately 6, 9 and 7 en% saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) respectively for 3 months. IR was induced by replacing starch (ST) with sucrose (SU). Blends of groundnut, palmolein, and linseed oil in different proportions furnished the following levels of 18:3 n-3 (g/100 g diet) and 18:2 n-6/18:3 n-3 ratios respectively: ST-220 (0.014, 220), SU-220 (0.014, 220), SU-50 (0.06, 50), SU-10 (0.27, 10) and SU-2 (1.1, 2). The results showed IR in the sucrose fed group (SU-220) as evidenced by increase in fasting plasma insulin and area under the curve (AUC) of insulin in response to oral glucose load. In SU-220, the increase in adipocyte plasma membrane cholesterol/phospholipid ratio was associated with a decrease in fluidity, insulin stimulated glucose transport, antilipolytic effect of insulin and increase in basal and norepinephrine stimulated lipolysis in adipocytes. In SU-50, sucrose induced alterations in adipocyte lipolysis and antilipolysis were normalized. However, in SU-2, partial corrections in plasma insulin, AUC of insulin and adipocyte insulin stimulated glucose transport were observed. Further, plasma triglycerides and cholesterol decreased in SU-2. In diaphragm phospholipids, the observed dose dependent increase in long chain (LC) n-3 PUFA was associated with a decrease in LC-n-6 PUFA but insulin stimulated glucose transport increased only in SU-2. Thus, this study shows that the substitution of one-third of dietary 18:2 n-6 with 18:3 n-3 (SU-2) results in lowered blood lipid levels and increases peripheral insulin sensitivity, possibly due to the resulting high LCn-3 PUFA levels in target tissues of insulin action. These findings suggest a role for 18:3 n-3 in the prevention of insulin resistant states. The current recommendation to increase 18:3 n-3 intake for reducing cardiovascular risk may also be beneficial for preventing IR in humans.

Adipocytes↗

Morphological and biochemical status of the mammary gland as influenced by conjugated linoleic acid: implication for a reduction in mammary cancer risk.

Previous research showed that treatment with conjugated linoleic acid (CLA) during the period of active mammary gland morphogenesis was sufficient to confer a lasting protection against subsequent mammary tumorigenesis induced by methylnitrosourea. The present study was designed to characterize certain morphological and biochemical changes of the mammary gland that might potentially render it less susceptible to cancer induction. Female Sprague Dawley rats were fed a 1% CLA diet from weaning until about 50 days of age. The mammary gland parameters under investigation included (a) the deposition of neutral lipid, (b) the identification and quantification of CLA and its metabolites, (c) the density of the epithelium, and (d) the proliferative activity of various structural components. Our results showed that CLA treatment did not affect total fat deposition in the mammary tissue nor the extent of epithelial invasion into the surrounding fat pad but was able to cause a 20% reduction in the density of the ductal-lobular tree as determined by digitized image analysis of the whole mounts. This was accompanied by a suppression of bromodeoxyuridine labeling in the terminal end buds and lobuloalveolar buds. The recovery of desaturation and elongation products of CLA in the mammary gland confirmed our prior suggestion that the metabolism of CLA might be critical to risk modulation. The significance of the above findings was investigated in a mammary carcinogenesis bioassay with the use of the dimethylbenz[a]anthracene model. When CLA was started at weaning and continued for 6 months until the end of the experiment, this schedule of supplementation produced essentially the same magnitude of mammary tumor inhibition in the dimethylbenz[a]anthracene model as that produced by 1 month of CLA feeding from weaning. The observation is consistent with the hypothesis that exposure to CLA during the time of mammary gland maturation may modify the developmental potential of a subset of target cells that are normally susceptible to carcinogen-induced transformation.

9,10-Dimethyl-1,2-benzanthracene↗

Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich's ataxia-demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction.

Studies were undertaken to further characterize plasma lipids and lipoprotein abnormalities in Friedreich's ataxia. The high density lipoprotein (HDL) apo AI/AII ratio was quantitated by densitometry and found to be normal. The free to esterified cholesterol ratio in HDL was lower in Friedreich's ataxia because of a reduction in the amount of free cholesterol in this lipoprotein class. The fatty acid profile of the cholesteryl-ester (CE) fraction was markedly deficient in linoleic acid (18:2) in both total plasma and HDL. There was a compensatory increase in saturated acids. The HDL phospholipid (PL) fraction also showed a reduction in the proportion of 18:2 with a concomitant increase in stearic (18:0) and oleic acid (18:1) while the HDL triglyceride (TG) fraction showed only an increase in palmitoleic (16:1) and oleic acids. Feeding of soya lecithin rich in 18:2 failed to increase significantly the 18:2 content of HDL-CE and HDL-PL but lowered the percentage of 16:1 and 18:1 in all 3 lipid classes of HDL. Although the total plasma CE fatty acid profile was perturbed in Friedreich's Ataxia, total plasma PL and TG fatty acid patterns were unaffected. Among the plasma lipoprotein fatty acid profiles, that of the low density lipoprotein (LDL) was most affected, then that of the HDL. The very low density lipoprotein (VLDL) fatty acid composition showed an increase in 16:1 and a decrease in 18:2 which were entirely corrected by lecithin feeding. These results suggest the existence of a metabolic defect in the incorporation of 18:2 into chylomicron phospholipids within the intestinal mucosa.

Adolescent↗

Use of conjugated linoleic acid (CLA) enrichments to examine the effects of trans-8, cis-10 CLA, and cis-11, trans-13 CLA on milk-fat synthesis.

Conjugated linoleic acid (CLA) supplements have typically been comprised of 4 isomers (trans-8, cis-10; cis-9, trans-11; trans-10, cis-12; and cis-11, trans-13 CLA). Abomasal infusion of pure isomers has shown that trans-10, cis-12 CLA is a potent inhibitor of milk-fat synthesis, whereas cis-9, trans-11 CLA has no effect. However, there appear to be additional fatty acids that inhibit milk-fat synthesis, and the objective of this study was to investigate the effects of additional CLA isomers present in CLA supplements. Four rumen fistulated Holstein cows (141+/-8 DIM, mean+/-SE) were randomly assigned in a 4 x 4 Latin square experiment. Treatments were abomasal infusion of (1) skim milk (negative control), (2) trans-10, cis-12 CLA supplement (positive control), (3) trans-8, cis-10 CLA supplement, and (4) cis-11, trans-13 CLA supplement. Treatments 2 through 4 were targeted to provide 4 g/d of the CLA isomer of interest. The trans-8, cis-10 CLA supplement had no effect on milk-fat yield, whereas the trans-10, cis-12 CLA supplement reduced milk-fat yield by 35%. The cis-11, trans-13 CLA supplement contained some trans-10, cis-12 CLA, and when data were compared to the positive control treatment group, it was obvious that cis-11, trans-13 CLA also had no effect on milk-fat synthesis. Milk-fat content of specific CLA isomers was significantly elevated within respective treatment groups. Milk yield, DMI, and milk protein yield were unaffected by treatment. Overall, trans-10, cis-12 CLA reduced milk-fat synthesis, whereas the other major isomers present in CLA supplements (trans-8, cis-10 CLA and cis-11, trans-13 CLA) had no effect.

Abomasum↗

A new conjugated linoleic acid isomer, 7 trans, 9 cis-octadecadienoic acid, in cow milk, cheese, beef and human milk and adipose tissue.

The identity of a previously unrecognized conjugated linoleic acid (CLA) isomer, 7 trans, 9 cis-octadecadienoic acid (18:2) was confirmed in milk, cheese, beef, human milk, and human adipose tissue. The 7 trans, 9 cis-18:2 isomer was resolved chromatographically as the methyl ester by silver ion-high-performance liquid chromatography (Ag+-HPLC); it eluted after the major 9 cis, 11 trans-18:2 isomer (rumenic acid) in the natural products analyzed. In the biological matrices investigated by Ag+-HPLC, the 7 trans, 9 cis-18:2 peak was generally due to the most abundant minor CLA isomer, ranging in concentration from 3 to 16% of total CLA. By gas chromatography (GC) with long polar capillary columns, the methyl ester of 7 trans, 9 cis-18:2 was shown to elute near the leading edge of the major 9 cis, 11 trans-18:2 peak, while the 4,4-dimethyloxazoline (DMOX) derivative permitted partial resolution of these two CLA isomers. The DMOX derivative of this new CLA isomer was analyzed by gas chromatography-electron ionization mass spectrometry (GC-EIMS). The double bond positions were at delta7 and delta9 as indicated by the characteristic mass spectral fragment ions at m/z 168, 180, 194, and 206, and their allylic cleavages at m/z 154 and 234. The cis/trans double-bond configuration was established by GC-direct deposition-Fourier transform infrared as evidenced from the doublet at 988 and 949 cm(-1) and absorptions at 3020 and 3002 cm(-1). The 7 trans, 9 cis-18:2 configuration was established by GC-EIMS for the DMOX derivative of the natural products examined, and by comparison to a similar product obtained from treatment of a mixture of methyl 8-hydroxy- and 11-hydroxyoctadec-9 cis enoates with BF3 in methanol.

Adipose Tissue↗

The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells.

The antiproliferative effects of two commercial preparations of conjugated linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA, c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT-29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium. The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer.

Apoptosis↗

Isomer-specific effects of conjugated linoleic acid (CLA) on adiposity and lipid metabolism.

Isomers of conjugated linoleic acid (CLA), unsaturated fatty acids found in ruminant meats and dairy products, have been shown to reduce adiposity and alter lipid metabolism in animal, human, and cell culture studies. In particular, dietary CLA decreases body fat and increases lean body mass in certain rodents, chickens, and pigs, depending on the isomer, dose, and duration of treatment. However, the effects of CLA on human adiposity are conflicting because these studies have used different mixtures and levels of CLA isomers and diverse subject populations. Potential antiobesity mechanisms of CLA include decreased preadipocyte proliferation and differentiation into mature adipocytes, decreased fatty acid and triglyceride synthesis, and increased energy expenditure, lipolysis, and fatty acid oxidation. This review will address the current research on CLA's effects on human and animal adiposity and lipid metabolism as well as potential mechanism(s) responsible for CLA's antiobesity properties.

Journal Article↗

Effects of dietary conjugated linoleic acid and fish oil supplementation on performance and egg quality in laying hens.

1. Laying hen performance, yolk fat fatty acid concentrations and firmness of eggs were evaluated with respect to the inclusion in the diet of conjugated linoleic acid (CLA) and fish oil. 2. Nine diets were arranged factorially, with three levels of supplementation of CLA (1, 3 and 5 g/kg) and fish oil (0, 14 and 20 g/kg). 3. Type of diet did not affect egg production traits. 4. CLA addition increased yolk weight and yolk fat concentrations of CLA, saturated and total long-chain n-3 fatty acids, but decreased those of monounsaturated and total long-chain n-6 fatty acids. 5. Fish oil addition increased long-chain n-3 fatty acids yolk fat concentrations but decreased those of CLA, saturated and long-chain n-6 fatty acids. 6. Effects of CLA addition on yolk fat concentrations of C22:4 n-6 and C20:5 n-3 were greater when no fish oil was added to the diet. 7. CLA supplementation increased linearly yolk moisture and firmness and altered albumen and yolk pH.

Animal Feed↗

Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MB-231 breast cancer cell growth and apoptosis in nude mice.

Diets rich in linoleic acid (LA), an n-6 fatty acid, stimulate the progression of human breast cancer cell solid tumors in athymic nude mice, whereas docosahexaenoic acid (DHA) and eicosapentaenoic acid, long-chain n-3 fatty acids, exert suppressive effects. In the present study we used a novel source of DHA, in triglyceride form, to determine the effects of feeding low levels of the fatty acid on the growth of MDA-MB-231 cells injected into the thoracic mammary fat pads of female nude mice. Four different isocaloric diets were used, all of which provided 20% (wt/wt) total fat. The control diets contained 8% (20 mice) or 4% (50 mice) LA; the n-3 fatty acid-supplemented groups of 50 mice were fed 4% LA-containing diets plus 2% or 4% DHA. The tumor growth rates were reduced significantly in mice fed the 4% LA compared with the 8% LA diet; the addition of 4% DHA to the 4% LA-containing diet produced a further reduction in tumor growth rate (p < or = 0.003 at and after Week 6). The final tumor weights were also reduced in the DHA-fed mice compared with the 8% LA dietary group (2% DHA, p = 0.02; 4% DHA, p = 0.01) and in the 4% DHA-fed mice compared with the 4% LA control group (p = 0.02); a similar trend for mice fed the lower level of DHA did not achieve statistical significance. Tumor prostaglandin E2 concentrations were reduced by feeding the lower LA level; further dose-dependent decreases occurred in the DHA dietary groups and were accompanied by reduced levels of 12- and 15-hydroxyeicosatetraenoic acids. These changes in eicosanoid biosynthesis may have been responsible for the observed decreases in cell proliferation, indicated by suppressed Ki-67 expression, and increases in apoptotic activity, as reflected in TdT-mediated dUTP nick end labeling immunohistochemical staining.

Animals↗

Effects of conjugated linoleic acid on skeletal muscle triacylglycerol metabolism in hamsters.

OBJECTIVE: The present work evaluated the effects of conjugated linoleic acid (CLA) on various aspects of triacylglycerol metabolism in skeletal muscle to determine the potential involvement of this tissue in the effect of CLA to decrease body fat. METHODS: Animals were randomized to three groups that were fed atherogenic diets that provided different amounts of trans-10,cis-12 CLA (0%, 0.5%, or 1%) for 6 wk. Muscle triacylglycerol, protein, water, glycogen, and DNA contents and fatty acid profile in triacylglycerols were analyzed. Lipoprotein lipase and carnitine palmitoyltransferase-I (CPT-I) activities were assessed. Triacylglycerol, glucose, and insulin concentrations were evaluated in serum. RESULTS: The high dose of CLA increased food efficiency and gastrocnemius muscle weight. CLA feeding resulted in decreased muscle triacylglycerol content without changes in protein, water, glycogen, and DNA contents or in cell size (protein/DNA ratio) and produced decreased lipoprotein lipase activity and increased CPT-I activity. No differences were found between CLA doses. CLA feeding led to the saturation of stored triacylglycerols. CONCLUSIONS: Decreased fatty acid uptake and increased fatty acid oxidation can contribute to the decreased muscle triacylglycerol content observed in hamsters fed the CLA diets. The increase in muscle fatty acid beta-oxidation might ultimately prevent storage of triacylglycerols in adipose tissue. Nevertheless, the lack of matching of lipoprotein lipase and CPT-I modifications makes it difficult to ensure that skeletal muscle is responsible, at least in part, for the effect of CLA on decreasing body fat; thus, further research is needed.

Adipose Tissue↗

Comparison of silver-ion high-performance liquid chromatographic quantification of free and methylated conjugated linoleic acids.

Silver-ion high-performance liquid chromatography was used to fractionate a mixture of conjugated linoleic acid (CLA) isomers (as the free fatty acids, CLAFFA) in commercial CLA mixtures and biological samples. Due to the unchanged retention mechanism, it was assumed that the elution order of the isomers remained the same as that of methyl esters separated on the same column. The most abundant isomers, cis/trans 10, 12-18:2 and cis/trans 9,11-18:2, were separated better as free acids on a single column than in the methyl ester form. Quantification of the CLA standard was used as the reference profile to evaluate different methylation methods commonly used to prepare CLA methyl esters for quantitation. Acid-and base-catalyzed derivatization methods resulted in CLA intraisomerization and losses in total conjugated dienes content. Acid (HCl and BF3) methylations significantly elevated the level of trans,trans isomers and significantly reduced the cis/trans isomers. Base methylation, tetramethylguanidine/methanol, resulted in loss of trans,trans isomers, and a substantial loss of total underivatized conjugated dienes. Other catalysts such as the trimethylsilyldiazomethane produced additional peaks of unidentified artifacts. The analysis of CLAFFA appears to provide more accurate quantification of CLA isomers in commercial and biological samples.

Adipose Tissue↗

Changes in conjugated linoleic acid and palmitoleic acid are correlated to retinol levels in chronic renal failure in both hemodialysis and conservative treatment patients.

An increase in conjugated linoleic acid (CLA), a natural fatty acid present in our diet, which possesses anticarcinogenic and antiatherogenic activities in experimental models, has been found in both the plasma and adipose tissue of end-stage chronic renal failure (ESCRF) patients. Increased levels of retinol have also been found in those patients, due to a reduced excretion of the retinol-binding protein. Since retinol is known to influence lipid metabolism, we evaluated whether changes in retinol, CLA, and other fatty acids are correlated in the plasma of CRF patients. We measured CLA, retinol, and unsaturated fatty acids in the plasma of the following groups: (A) 35 ESCRF patients; (B) 20 hemodialysis (HD) patients; (C) 20 healthy controls. Subjects with total cholesterol and/or triglycerides higher than 250 mg/dL were excluded. We found a significant increase in CLA, retinol, palmitoleic (16:1), and oleic (18:1) acids in ESCRF patients. In HD patients we found a similar pattern, however, CLA increase was not significant. No changes were observed in the other fatty acids measured. In the groups of ESCRF and HD patients, a positive correlation between the levels of plasma retinol and CLA, and between retinol and 16:1 was found. These correlations were not detected in controls. The abnormal levels of plasma retinol in CRF patients might partly explain the changes in CLA and 16:1. The influence of retinol levels on these fatty acids might be due to an induction of delta 9 desaturase. In fact, 16:1 is known to be produced, partly, by delta 9 desaturation of palmitic acid. Moreover, the formation of CLA from delta 9 desaturation of vaccenic acid-a trans-monounsaturated fatty acid present in our diet-has recently been demonstrated in humans. Nevertheless, our data do not represent direct evidence supporting an increased delta 9 desaturase activity in CRF patients. Another possible explanation might be a variation in the exogenous intake.

Adipose Tissue↗

Dietary conjugated linoleic acid did not alter immune status in young healthy women.

The purpose of this study was to examine whether conjugated linoleic acid (CLA) supplementation in human diets would enhance indices of immune status as reported by others for animal models. Seventeen women, 20-41 yr, participated in a 93-d study conducted in two cohorts of 9 and 8 women at the Metabolic Research Unit of Western Human Nutrition Research Center. Seven subjects were fed the basal diet (19, 30, and 51% energy from protein, fat, and carbohydrate, respectively) throughout the study. The remaining 10 subjects were fed the basal diet for the first 30 d, followed by 3.9 g CLA (Tonalin)/d for the next 63 d. CLA made up 65% of the fatty acids in the Tonalin capsules, with the following isomeric composition: t10, c12, 22.6%; c11, t13, 23.6%; c9, t11, 17.6%; t8, c10, 16.6%; and other isomers 19.6%. Most indices of immune response were tested at weekly intervals, three times at the end of each period (stabilization/intervention); delayed-type hypersensitivity (DTH) to a panel of six recall antigens was tested on study day 30 and 90; all subjects were immunized on study day 65 with an influenza vaccine, and antibody titers were examined in the sera collected on day 65 and 92. None of the indices of immune status tested (number of circulating white blood cells, granulocytes, monocytes, lymphocytes, and their subsets, lymphocytes proliferation in response to phytohemagglutinin, and influenza vaccine, serum influenza antibody titers, and DTH response) were altered during the study in either dietary group. Thus, in contrast to the reports with animal models, CLA feeding to young healthy women did not alter any of the indices of immune status tested. These data suggest that short-term CLA supplementation in healthy volunteers is safe, but it does not have any added benefit to their immune status.

Adult↗

Linoleic acid derivative DCP-LA improves learning impairment in SAMP8.

In the water-maze test, the linoleic acid derivative, 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) (1 mg/kg, intraperitoneally), significantly shortened the prolonged latency for accelerated-senescence-prone mice 8 (SAMP8), reaching a level similar to the latency for accelerated-senescence-resistant mice 1 (SAMR1) as control. In the open-field test to assess motor activity, it was confirmed that the DCP-LA effect is not due to increased motor activity. In the passive avoidance test to assess fear memory, DCP-LA had no effect on the latency of acquisition and retention for SAMP8. The results of the present study, thus, suggest that DCP-LA could improve age-related learning impairment by enhancing cognitive functions.

Aging↗

Conjugated linoleic acid preserves muscle mass in mice bearing the Lewis lung carcinoma, but not the B16 melanoma.

Conjugated linoleic acid (CLA), which is found in dairy products, reduces synthesis of tumor necrosis factor-alpha (TNFa), a pro-inflammatory cytokine that plays a major role in tumor-induced skeletal muscle wasting (SMW). The B16 melanoma expresses TNFa mRNA, and induced SMW with no change in muscle levels of TNFa type 1 receptor (TNFR1) protein. A diet containing .5% CLA had no effect on SMW or TNFR1 in mice bearing B16 tumors. In contrast, the Lewis lung carcinoma expresses low levels of TNFa mRNA, induced SMW, and increased muscle levels of TNFR1. A diet containing .5% CLA reduced SMW, but had no effect on muscle levels of TNFR1. We conclude that that tumor-induced SMW can occur independent of muscle levels of TNFR1. Further study is needed before CLA can be tested in persons with cancer cachexia.

Analysis of Variance↗