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Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans
Abstract
Conjugated linoleic acid (CLA) is reported to have weight-reducing and antiatherogenic properties when fed to laboratory animals. However, the effects of CLA on human health and, in particular, the effects of individual CLA isomers are unclear.
This study investigated the effects of 3 doses of highly enriched cis-9,trans-11 (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 (0.63, 1.26, and 2.52 g/d) CLA preparations on body composition, blood lipid profile, and markers of insulin resistance in healthy men.
Healthy men consumed 1, 2, and 4 capsules sequentially, containing either 80% cis-9,trans-11 CLA or 80% trans-10,cis-12 CLA for consecutive 8-wk periods. This phase was followed by a 6-wk washout and a crossover to the other isomer.
Body composition was not significantly affected by either isomer of CLA. Mean plasma triacylglycerol concentration was higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA, although there was no influence of dose. There were significant effects of both isomer and dose on plasma total cholesterol and LDL-cholesterol concentrations but not on HDL-cholesterol concentration. The ratios of LDL to HDL cholesterol and of total to HDL cholesterol were higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA. CLA supplementation had no significant effect on plasma insulin concentration, homeostasis model for insulin resistance, or revised quantitative insulin sensitivity check index.
Divergent effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA appear on the blood lipid profile in healthy humans: trans-10,cis-12 CLA increases LDL:HDL cholesterol and total:HDL cholesterol, whereas cis-9,trans-11 CLA decreases them.
... As mentioned above, sheep and/or goat milk and their respective processed products may have many beneficial health impacts, which could appeal to modern consumers [38][39][40]. Sheep and goat milk, due to protein differences with cow milk, induce fewer allergy responses. The levels of minerals, vitamins, and essential fatty acids are also generally higher than in cow milk. ...
... CLA is claimed, for example, to prevent obesity [41] and reduce triglyceride levels. It should, therefore, help to prevent coronary heart disease and atherosclerosis [39]. ...
... Raw milk advocates argue that it is a complete, natural food containing more amino acids, antimicrobials, vitamins, minerals and fatty acids than pasteurized milk. Furthermore, raw sheep and goat milk is seen to be a better choice for those with lactose intolerance, asthma, and autoimmune and allergic conditions [38][39][40]. It is estimated that 35-60% of farm families and farm employees consume raw milk on a regular basis, whereas the consumption of raw milk by the urban community is more difficult to estimate [132]. ...
Listeria monocytogenes can cause severe foodborne infections in humans and invasive diseases in different animal species, especially in small ruminants. Infection of sheep and goats can occur via contaminated feed or through the teat canal. Both infection pathways result in direct (e.g., raw milk from an infected udder or fresh cheese produced from such milk) or indirect exposure of consumers. The majority of dairy farmers produces a high-risk product, namely fresh cheese made from raw ewe’s and goat’s milk. This, and the fact that L. monocytogenes has an extraordinary viability, poses a significant challenge to on-farm dairies. Yet, surprisingly, almost no scientific studies have been conducted dealing with the hygiene and food safety aspects of directly marketed dairy products. L. monocytogenes prevalence studies on small ruminant on-farm dairies are especially limited. Therefore, it was our aim to focus on three main transmission scenarios of this important major foodborne pathogen: (i) the impact of caprine and ovine listerial mastitis; (ii) the significance of clinical listeriosis and outbreak scenarios; and (iii) the impact of farm management and feeding practices.
... 25 Sheep milk is also recognized for its richness in beneficial fatty acids such as conjugated linoleic acid and ⊍-linolenic acid, potentially offering various health benefits such as osteoporosis prevention and improved cardiovascular health. [26][27][28][29][30] Additionally, sheep milk consumption may bolster immune function. 31 Bioactive peptides have been associated with the antihypertensive and antidiabetic activities of fermented milk in various studies. ...
... The addition of herbs minimally affected the protein pattern in matured cheeses. Furthermore, cheeses ripened from sheep milk predominantly featured low MW water-soluble peptides (14 kDa), whereas cow and goat ripened cheeses were mainly composed of water-soluble peptides (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). 56,72 The research highlighted that, during cheese ripening, native proteins undergo breakdown, resulting in the production of smaller peptides due to proteolysis. ...
BACKGROUND
The present study aimed to evaluate the anti‐hypertensive and anti‐diabetic activities from biologically active peptides produced by fermented sheep milk with Lacticaseibacillus paracasei M11 (MG027695), as well as to purify and characterize the angiotensin‐converting enzyme (ACE) inhibitory and anti‐diabetic peptides produced from fermented sheep milk.
RESULTS
After 48 h of fermentation at 37 °C, sheep milk demonstrated significant changes in anti‐diabetic effects and ACE‐I effects, with inhibition percentages observed for ACE inhibition (76.32%), α‐amylase (70.13%), α‐glucosidase (70.11%) and lipase inhibition (68.22%). The highest level of peptides (9.77 mg mL–1) was produced by optimizing the growth conditions, which included an inoculation rate of 2.5% and a 48 h of incubation period. The comparison of molecular weight distributions among protein fractions was conducted through sodium dodecyl‐sulfate polyacrylamide gel electrophoresis analysis, whereas spots were separated using 2D gel electrophoresis according to both the molecular weight and pH. Peptide characterization with ultra‐filtration membranes at 3 and 10 kDa allowed the study to assess molecular weight‐based separation. Nitric oxide generated by lipopolysaccharide and the secretion of pro‐inflammatory cytokines in RAW 264.7 immune cells were both inhibited by sheep milk fermented with M11. Fourier‐transform infrared spectroscopy was employed to assess changes in functional groups after fermentation, providing insights into the structural changes occurring during fermentation.
CONCLUSION
The present study demonstrates that fermentation with L. paracasei (M11) led to significant changes in fermented sheep milk, enhancing its bioactive properties, notably in terms of ACE inhibition and anti‐diabetic activities, and the generation of peptides with bioactive properties has potential health benefits. © 2024 Society of Chemical Industry.
... Evidence from clinical trials with healthy participants is also diverse. Here, CLAs have been reported to decrease plasma triglyceride and VLDL concentrations (mixed CLAs, 5.5 g/d for 5 weeks) [27] and to decrease the expression of intercellular adhesion molecule (ICAM)-1 by monocytes (CLA9,11 or CLA10,12, 2.5 g/day for 8 weeks), although CLA10,12 induced an increased ratio of LDL-to HDL-cholesterol and of total cholesterol to HDL-cholesterol in the same study [28] but had neutral effects in other studies [12,29]. Studies using CLA9,11-enriched dairy products also showed a reduction in inflammation markers in healthy participants [30,31]. ...
... Tricon et al. reported that supplementation with CLA9,11 or CLA10,12 in 49 healthy men had no effect on C-reactive protein levels, body composition or insulin concentration, but the higher dose of both CLAs (2.38 and 2.52 g/d, respectively) decreased the number of monocytes expressing ICAM-1. In the same study, CLA10,12 increased the LDL-to HDL-cholesterol ratio, whereas CLA9,11 decreased it [13,28]. In another study, 29 healthy adult volunteers underwent a CLA depletion followed by an 8 week period consuming 20 g of CLA9,11 enriched butter daily (1020 ± 167 mg CLA/day); when compared to the end of the depletion phase, the CLA repletion resulted in decreased NFκB protein in blood mononuclear cells, decreased serum levels of TNF-α, IL-2 and IL-8 and increased levels of the anti-inflammatory cytokine IL-10 [31]. ...
Conjugated linoleic acid (CLA) isomers may have a role in preventing atherosclerosis through the modulation of inflammation, particularly of the endothelium. However, whether low concentrations of CLAs are able to affect basal unstimulated endothelial cell (EC) responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the basal inflammatory responses by ECs. EA.hy926 cells (HUVEC lineage) were cultured under standard conditions and exposed to individual CLAs for 48 h. Both CLAs were incorporated into ECs in a dose-dependent manner. CLA9,11 (1 μM) significantly decreased concentrations of MCP-1 (p < 0.05), IL-6 (p < 0.05), IL-8 (p < 0.01) and RANTES (p < 0.05) in the culture medium. CLA10,12 (10 μM) decreased the concentrations of MCP-1 (p < 0.05) and RANTES (p < 0.05) but increased the concentration of IL-6 (p < 0.001). At 10 μM both CLAs increased the relative expression of the NFκβ subunit 1 gene (p < 0.01 and p < 0.05, respectively), while decreasing the relative expression of PPARα (p < 0.0001), COX-2 (p < 0.0001) and IL-6 (p < 0.0001) genes. CLA10,12 increased the relative expression of the gene encoding IκK-β at 10 μM compared with CLA9,11 (p < 0.05) and increased the relative expression of the gene encoding IκBα at 1 and 10 μM compared with linoleic acid (both p < 0.05). Neither CLA affected the adhesion of monocytes to ECs. These results suggest that low concentrations of both CLA9,11 and CLA10,12 have modest anti-inflammatory effects in ECs. Thus, CLAs may influence endothelial function and the risk of vascular disease. Nevertheless, at these low CLA concentrations some pro-inflammatory genes are upregulated while others are downregulated, suggesting complex effects of CLAs on inflammatory pathways.
... Nevertheless, the evidence for pro-inflammatory effects of CLA10,12 in humans is not consistent. A supplementation study in healthy young adults with CLA9,11 or CLA10,12 for 8 weeks showed that neither of the isomers affected lymphocyte subpopulations, serum concentrations of CRP or ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) in response to different inflammatory stimuli [31,32]. Only some differences in blood lipids and the expression of ICAM-1 on monocytes were observed [31,32]. ...
... A supplementation study in healthy young adults with CLA9,11 or CLA10,12 for 8 weeks showed that neither of the isomers affected lymphocyte subpopulations, serum concentrations of CRP or ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) in response to different inflammatory stimuli [31,32]. Only some differences in blood lipids and the expression of ICAM-1 on monocytes were observed [31,32]. In the latter study, there was a suggestion of fewer ICAM-positive monocytes in the blood after CLA10,12, which parallels the effects seen in the current study for CLA10,12 and EC ICAM-1. ...
Conjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways in different cell types, including endothelial cells (ECs). However, whether different CLA isomers have different actions is not entirely clear, with inconsistent reports to date. Furthermore, in cell culture studies, CLAs have often been used at fairly high concentrations. Whether lower concentrations of CLAs are able to affect EC responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the inflammatory responses of ECs. ECs (EA.hy926 cells) were cultured under standard conditions and exposed to CLAs (1 to 50 μM) for 48 h. Then, the cells were cultured for a further 6 or 24 h with tumour necrosis factor alpha (TNF-α, 1 ng/mL) as an inflammatory stimulant. ECs remained viable after treatments with 1 and 10 μM of each CLA, but not after treatment with 50 μM of CLA10,12. CLAs were incorporated into ECs in a concentration-dependent manner. CLA10,12 increased the levels of ICAM-1, IL-6, and RANTES in the culture medium, while CLA9,11 had null effects. Both CLAs (1 μM) decreased the appearance of NFκB1 mRNA, but only CLA9,11 maintained this downregulation at 10 μM. CLA10,12 had no effect on THP-1 cell adhesion to ECs while significantly decreasing the percentage of ECs expressing ICAM-1 and also levels of ICAM-1 expression per cell when used at 10 µM. Although CLA9,11 did not have any effect on ICAM-1 cell surface expression, it reduced THP-1 cell adhesion to the EA.hy926 cell monolayer at both concentrations. In summary, CLA10,12 showed some pro-inflammatory effects, while CLA9,11 exhibited null or anti-inflammatory effects. The results suggest that each CLA has different effects in ECs under a pro-inflammatory condition, highlighting the need to evaluate the effects of CLA isomers independently.
... On the other hand, results related to the protective effect of RA-rich dairies against breast cancer are still controversial [128,129]. Table 2. Summary of the main studies focused on the biological effects produced by the intake of RA-rich dairy products (data from [37,127,128,131,134,[142][143][144][145][146][147][148][149][150]). ...
... Female growing pigs RA-enriched butter Undetectable effects on blood lipoproteins [142] Wistar rats RA-enriched clarified butter ↑ Antioxidants [143] Wistar rats RA-enriched butter ↑ HDL, Triacylglycerol [144] Mice fed high fat diet Pasture dairy cream ↓ Inflammation, Triacylglycerol ↑ Protective cells in the gut [131] Wistar rats RA-enriched butter ↑ PLA2 [145] Mouse model of chemically -induced (DSS) colitis RA-enriched butter ↑ Nrf-2-mediated defenses ↓ Colitis signs [146] Wistar rats RA-enriched butter ↑ Mitochondrial function [37] Wistar rats RA-enriched butter ↓ Muscle inflammation, oxidative stress ↑ Mitochondrial function [128] Clinical studies Healthy middle-age subjects Naturally enriched dairy products Undetectable effects on blood lipoproteins [147] Healthy normal-weight and over-weight subjects Naturally enriched cheese ↓ IL-6, Tnf-α [148] Hypercholesterolemic subjects Naturally enriched cheese ↓ LDL [134] Healthy young subjects Naturally enriched cheese ↑ IL-10 ↓ NFkB, Tnf-α, IL-2, IL-8 [149] Meta-analyses CLA enriched food ↓ LDL, cholesterol [150] Healthy middle-age subjects RA enriched cheese ↑ Highly unsaturated fatty acids in blood plasma [127] RA, rumenic acid; HDL, high density lipoprotein; PLA2, phospholipase A2; DSS, dextran sulfate sodium; Nrf-2, nuclear factor E2-related factor 2; IL-6, interleukin-6; Tnf-α, tumor necrosis factor-α; LDL, low density lipoprotein; IL-10, interleukin-10; NFkB, nuclear factor kappa-beta; IL-2, interleukin-2; IL-8, interleukin-8; CLA, conjugated linoleic acid. ...
Milk contains several important nutrients that are beneficial for human health. This review considers the nutritional qualities of essential fatty acids (FAs), especially omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) present in milk from ruminant and non-ruminant species. In particular, the impact of milk fatty acids on metabolism is discussed, including its effects on the central nervous system. In addition, we presented data indicating how animal feeding—the main way to modify milk fat composition—may have a potential impact on human health, and how rearing and feeding systems strongly affect milk quality within the same animal species. Finally, we have presented the results of in vivo studies aimed at supporting the beneficial effects of milk FA intake in animal models, and the factors limiting their transferability to humans were discussed.
... Armonk, NY). Any effects of the order in which the oils were consumed were tested by students paired t test of the absolute changes in concentration during each period of supplementation (23) . If no order effects were found, data were pooled for each type of oil irrespective of the order in which the oil was consumed and the effects of the test oils on EPA and DHA concentrations were analysed using Student's paired t test (23) . ...
... Any effects of the order in which the oils were consumed were tested by students paired t test of the absolute changes in concentration during each period of supplementation (23) . If no order effects were found, data were pooled for each type of oil irrespective of the order in which the oil was consumed and the effects of the test oils on EPA and DHA concentrations were analysed using Student's paired t test (23) . Data which were not normally distributed were analysed using the Mann-Whitney U test. ...
EPA and DHA are required for normal cell function and can also induce health benefits. Oily fish are the main source of EPA and DHA for human consumption. However, food choices and concerns about the sustainability of marine fish stocks limit the effectiveness of dietary recommendations for EPA+DHA intakes. Seed oils from transgenic plants that contain EPA+DHA are a potential alternative source of EPA and DHA. The present study investigated whether dietary supplementation with transgenic Camelina sativa seed oil (CSO) that contained EPA and DHA was as effective as fish oil (FO) in increasing EPA and DHA concentrations when consumed as a dietary supplement in a blinded crossover study. Healthy men and women ( n 31; age 53 (20-74) yrs) were randomised to consume 450 mg/day EPA+DHA provided either as either CSO or FO for 8 weeks, followed by 6 weeks washout and then switched to consuming the other test oil. Fasting venous blood samples were collected at the start and end of each supplementation period. Consuming the test oils significantly (P < 0.05) increased EPA and DHA concentrations in plasma triacylglycerol, phosphatidylcholine and cholesteryl esters. There were no significant differences between test oils in the increments of EPA and DHA. There was no significant difference between test oils in the increase in the proportion of erythrocyte EPA+DHA (CSO, 12%; P < 0.0001 and FO, 8%; P = 0.02). Together these findings show that consuming CSO is as effective as FO for increasing EPA and DHA concentrations in humans.
... Chez les sujets non obèses, la majorité des études montre une absence d'effet de l'apport de CLA sur la réduction de la masse grasse [Zambell et al., 2001 ;Kreider et al., 2002, Petridou et al., 2003et Tricon et al., 2004 alors que trois études rapportent un effet modeste [Smedmann & Vessby, 2001 ;Thom et al., 2001 ;Mougios et al., 2001]. Toutefois, l'étude de Mougios et al., (2001), menée pendant 4 semaines, chez des volontaires sains recevant 0,7 ou 1,4 g/j de CLA montre une réduction de la masse grasse uniquement chez les volontaires supplémentés avec 1,4 g/j de CLA par rapport aux personnes ayant reçu 0,7 g/j, sans différence significative avec le groupe placebo (Tableau 8 Chez les sujets obèses ou en surpoids, les résultats sont aussi controversés (Tableau 8). ...
... ). D'autre part, afin d'explorer les effets spécifiques des isomères 9cis,11trans et 10trans,12cis de CLA,Tricon et al., (2004) ont conduit, pendant 3 périodes de 8 semaines consécutives, une étude d'intervention nutritionnelle chez l'homme sain recevant des préparations enrichies soit en isomère 9cis,11trans (0,59 à 2,38 g/j) soit en isomère 10trans,12cis (0,63 à 2,52 g/j). Aucun effet significatif des isomères de CLA sur le poids corporel, l'indice de masse corporelle et sa composition n'a été mis en évidence, quelque soit la dose étudiée montrant que, même à une dose élevée, l'isomère 10trans,12cis de CLA n'a pas d'effet sur la composition corporelle des sujets sains (Tableau 8). ...
... It is valuable to study the CLA isomers individually, as isomer-specific effects have been shown. For example, CLAt10c12 is antiadipogenic (Park et al., 1999) and atherogenic (Arbonés-Mainar et al., 2006;Tricon et al., 2004), while CLAc9t11 has no adipogenic effects (Park et al., 1999), and is antiatherogenic (Li et al., 2018;Tricon et al., 2004). ...
... It is valuable to study the CLA isomers individually, as isomer-specific effects have been shown. For example, CLAt10c12 is antiadipogenic (Park et al., 1999) and atherogenic (Arbonés-Mainar et al., 2006;Tricon et al., 2004), while CLAc9t11 has no adipogenic effects (Park et al., 1999), and is antiatherogenic (Li et al., 2018;Tricon et al., 2004). ...
... Badania przeprowadzone na królikach karmionych paszą z CLA pokazały, że obydwa izomery oraz ich mieszanina niemalże w jednakowym stopniu zapobiegają tworzeniu blaszki miażdżycowej w porównaniu do zwierząt karmionych paszą z dodatkiem cholesterolu [37]. Projekty badawcze z udziałem ludzi w kontekście aterogenności są niejednoznaczne [38]. ...
... Wyniki jednego z badań na chomikach wskazują izomer t10,c12 CLA jako ten, który zmniejszył kumulację lipidów w organizmie zwierząt a jednocześnie obniżył poziom cholesterolu w surowicy, izomer c9,t11 CLA nie miał znaczącego wpływu na metabolizm tłuszczy (w porównaniu do kwasu linolowego) [52]. Skutki działania CLA u ludzi w kontekście anty-i proaterogenności również są niejednoznaczne [38]. ...
Conjugated linoleic acids (CLA) are constitutional and geometric isomers of this acid. The most commonly consumed geometric isomers are cis-9,trans-11 (c9, t11) CLA and trans-10, cis-12 (t10,c12) CLA. These isomers together with trans-9,trans-11 CLA and trans-10,trans-12 CLA constitute about 90% of all CLA in natural products. Different structure of the isomers affects their functions in the body. Differences in the effects on organs and tissues are sometimes small and sometimes opposed, sometimes the isomers work synergistically. Diverse influence has been shown mainly in neoplastic processes and lipid metabolism. For example, differences in inhibition of proliferation of prostate cancer cells are explained by different pathways: t10,c12 CLA acts on apoptosis and cell cycle control genes, while c9,t11 CLA regulates genes involved in metabolism of arachidonic acid with subsequent impairment of eicosanoids synthesis. Other studies have shown that t10,c12 CLA, but not c9,t11 CLA, can induce fat reduction in adipose tissue and apoptosis of adipocytes in mice.
... A stimulated cells were treated with the Δ6 desaturase inhibitor SC26196 (200 nM) (20) or with DMSO as a vehicle control final concentration 0.02% (v/v). The proportion of activated T lymphocytes was determined by CD69 expression (21). 5 × 10 5 PBMCs were resuspended in 100 µl PBS. ...
... Fluorescein isothiocyanate-conjugated anti-human CD69 monoclonal antibody (Bio-Rad) (10 µl) was added and incubated for 30 min at 4°C in the dark. PBMCs were then processed for flow cytometry as described elsewhere (21). ...
Polyunsaturated fatty acids (PUFAs) are important for immune function. Limited evidence indicates that immune cell activation involves endogenous PUFA synthesis, but this has not been characterised. To address this, we measured metabolism of 18:3n-3 in quiescent and activated peripheral blood mononuclear cells (PBMCs), and in Jurkat T cell leukaemia. PBMCs from men and women (n = 34) were incubated with [1-¹³C]18:3n-3 with or without Concanavalin A (Con. A). 18:3n-3 conversion was undetectable in unstimulated PBMCs, but up-regulated when stimulated. The main products were 20:3n-3 and 20:4n-3, while 18:4n-3 was undetectable, suggesting initial elongation and Δ8 desaturation. PUFA synthesis was 17.4-fold greater in Jurkat cells than PBMCs. The major products of 18:3n-3 conversion in Jurkat cells were 20:4n-3, 20:5n-3, and 22:5n-3. ¹³C Enrichment of 18:4n-3 and 20:3n-3 suggests parallel initial elongation and Δ6 desaturation. The FADS2 inhibitor SC26196 reduced PBMC, but not Jurkat cell, proliferation suggesting PUFA synthesis is involved in regulating mitosis in PBMCs. Con. A stimulation increased FADS2, FADS1, ELOVL5 and ELOVL4 mRNA expression in PBMCs. A single transcript corresponding to the major isoform of FADS2, FADS20001, was detected in PBMCs and Jurkat cells. PBMC activation induced hypermethylation of a 470bp region in the FADS2 5′-regulatory sequence. This region was hypomethylated in Jurkat cells compared to quiescent PBMCs. These findings show that PUFA synthesis involving initial elongation and Δ8 desaturation is involved in regulating PBMC proliferation and is regulated via transcription possibly by altered DNA methylation. These processes were dysregulated in Jurkat cells. This has implications for understanding the regulation of mitosis in normal and transformed lymphocytes.
... Milk and dairy products are the main sources of CLAs in the human diet, mostly due to their high rumenic acid (cis-9, trans-11 C 18:2, representing 90% of CLA in cow milk) and trans-10, cis-12 C18:2 contents [67]. Beneficial effects attributed to CLAs include improved immune system function and weight regulation [68], although the final effect on the consumer could depend on the relative abundance of each isomer constituting the CLA mixture [69]. Besides CLAs, other PUFAs with a fundamental role in human health are n-6 and n-3 PUFAs. ...
Milk has become a staple food product globally. Traditionally, milk quality assessment has been primarily focused on hygiene and composition to ensure its safety for consumption and processing. However, in recent years, the concept of milk quality has expanded to encompass a broader range of factors. Consumers now also consider animal welfare, environmental impact, and the presence of additional beneficial components in milk when assessing its quality. This shifting consumer demand has led to increased attention on the overall production and sourcing practices of milk. Reflecting on this trend, this review critically explores such novel quality parameters, offering insights into how such practices meet the modern consumer’s holistic expectations. The multifaceted aspects of milk quality are examined, revealing the intertwined relationship between milk safety, compositional integrity, and the additional health benefits provided by milk’s bioactive properties. By embracing sustainable farming practices, dairy farmers and processors are encouraged not only to fulfill but to anticipate consumer standards for premium milk quality. This comprehensive approach to milk quality underscores the necessity of adapting dairy production to address the evolving nutritional landscape and consumption patterns.
... "CLA milk" is milk that contains conjugated linoleic acid (CLA), which is a fatty acid naturally present in some foods, including meat and dairy products (Parodi, 2004). CLA has been studied for its potential health benefits, such as reducing inflammation, improving body composition, and preventing certain cancers (Belury 2002;Tricon et al 2004). ...
... The presence of 9(Z),11(E)-conjugated linoleic acid (CLA), in corn silk extract is noteworthy as it encompasses various biological attributes including anticarcinogenic activity, inhibition of in vitro growth in human melanoma, colorectal, and breast cancer cells, and manifestation of anti-atherogenic activity [66]. It appears to enhance animal growth, inhibit osteoclast formation and activity in human cells [67], as well as reduce LDL: HDL and total HDL: cholesterol levels in humans [68]. Octadecanoic acid displays antibacterial, antifungal, and antitumor properties [69,70] and its inclusion in the corn silk extracts enhances its overall therapeutic potential. ...
Purpose
To analyse phytochemical composition, antioxidant potential, antimicrobial activity and α-amylase, α-glucosidase and xanthine oxidase inhibitory potential of corn silk extracts derived from the Syngenta 5414 corn variety.
Methods
Corn silk sample was lyophilized and extracted using 80% ethanol, methanol, water or acetone. Phytochemicals were qualitatively screened and bioactive compounds were identified through GCMS. Antimicrobial activities were evaluated using the agar well method for bacteria and fungal biomass method for fungi. The extracts were subjected to evaluation for their antidiabetic activity through α-amylase and α-glucosidase inhibitory assays, while their anti-gout potential was assessed through xanthine oxidase inhibitory assay, encompassing all four solvent extracts in the study.
Results
Phytochemical screening revealed the presence of phenols, flavonoids, tannins, alkaloids, sterols, protein xanthoproteic, and cardiac glycosides in the extracts. The Folin-Ciocalteu and AlCl3 assays demonstrated higher yields of phenolics and flavonoids in 80% ethanolic extract. Furthermore, the extracts remarkably scavenged reactive oxygen species like DPPH, ABTS and elicited considerable ferric ion reducing antioxidant power. GC–MS analysis identified 21 compounds in the 80% ethanolic extract, with 1,2,3-Propanetriol-1-acetate, n-Hexadecanoic acid, and 4H-Pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl- as major components. Antimicrobial assays demonstrated the ethanolic (80%) and methanolic extract's remarkable ability to inhibit the growth of Gram-positive bacteria and exhibit anti-fungal properties. The ethanolic (80%) extract exhibited an IC50 value of 0.70 ± 0.02 and 0.71 ± 0.01 mg against α-amylase and α-glucosidase, respectively, and 33.76 ± 0.43 mg against xanthine oxidase.
Conclusion
Corn silk exhibits potential as a valuable reservoir of natural bioactive compounds endowed with a wide array of health-promoting properties.
Graphical Abstract
... CLA may have an inhibitory e ect on the proliferation of colorectal, breast, and skin tumor cells in the studies of cell lines [20]. CLA has been shown to reduce the total plasma cholesterol concentration in humans [21]. e consumption of diets rich in trans fatty acids is associated with an increased risk of cardiovascular disease. ...
Bovine milk fat composition is substantially different from the proposed ideal milk fat composition regarding human health. The present paper discusses the current state of knowledge on various factors affecting bovine milk fat composition and proposes possible ways of altering milk fat profile in a desirable direction. Among the physiological factors, the stage of lactation seems to have a stronger impact on milk fat composition, probably due to varying energy balance across the lactation in dairy cows. Parity and age at calving may not significantly affect milk fat composition. Milk fat composition can be altered by changes in the feeding and/or production system, although change through forages seems to be less optimistic, and change by concentrate or dietary fat appears to be costly. Genetic selection, being permanent, cumulative, and multiplicative, for better milk fat composition may result in increased proportions of more desirable monounsaturated and polyunsaturated fatty acids and decreased proportions of less desirable saturated fatty acids in bovine milk fat. It is important for dairy farmers, nutritionists, and geneticists to consider the health aspects of milk and other dairy products while making any breeding and other management decisions.
... Indeed, this FA is directly derived from the trans-10 shifted BH pathway of C18:2 n-6 35 and has been associated with negative effects on lipid metabolism, specifically with milk fat depression in dairy cows. 36 The predominance of the t11 BH pathway with the inclusion of 40% sainfoin was confirmed with the increase in C18:1 t11 concentration, which was almost 6-fold higher in 40SF meat than that in 0SF or 20SF meat, and was mainly produced as a result of the t11 BH pathways of C18:3 n-3 and C18:2 n-6 after the hydrogenation of the C18:2 t11,c15 and CLA c9,t11 intermediates, respectively. 11,22 This result confirms the efficacy of increasing C18:1 t11 as the main isomer formed in the rumen of animals fed forage-rich diets. ...
The effects of sainfoin inclusion (Onobrychis viciifolia) in the finishing concentrate for light lambs on the fatty acid (FA) composition of the ruminal digesta, plasma, and meat were evaluated. Twenty-six weaned male lambs were divided into three groups and fed individually ad libitum for 40 days with one of three concentrates differing in the level of sainfoin inclusion: 0% (0SF), 20% (20SF), and 40% (40SF). The rumen digesta showed an increase in C18:3 n-3 concentration and a decrease in C18:1 t10 concentration when sainfoin was included in the concentrate regardless of the level of inclusion. However, the highest C18:1 t11 and the lowest C18:2 n-6 proportions were obtained only in the 40SF rumen, showing a stronger t11 biohydrogenation pathway. In plasma, most effects were associated with changes in the levels of polyunsaturated FA (PUFA) n-3. The meat FA profile of 40SF lambs presented higher percentages of PUFA n-3 and CLA c9,t11 and a lower PUFA n-6/PUFA n-3 ratio compared with those from 0SF and 20SF diets because of the potentiation of the ruminal t11 pathway. Inclusions of 20 and 40% sainfoin both showed beneficial effects on meat quality; furthermore, these effects were most marked in the 40% sainfoin diet.
... In human studies, supplementation with CLA for 8 weeks did not cause Fig. 4 Non-linear dose-response relations between CLA supplementation and absolute mean differences. Dose-response relations between dose (mg/day) and absolute mean differences in on A FBG (mg/dl); B Insulin (pmol/l); C HbA1c (%); D HOMA-IR; and E CRP (mg/l) a significant change in serum insulin and insulin resistance [52,53]. In some studies conducted on obese individuals or individuals with metabolic syndrome, CLA increased blood glucose and insulin resistance [54][55][56]. ...
Background
The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease.
Methods
Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods.
Results
A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group.
Conclusion
Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance.
Prospero registeration cod
CRD42023426374.
... The content of c9,t11-CLA in suckling lamb meat is in line with those reported in other studies on suckling [26] and weaned lambs [38]. Clinical and animal studies have suggested anti-inflammatory and immunomodulatory antiatherogenic activities of c9,t11-CLA [57][58][59], as well as lowering cholesterol [60][61][62] and hyperinsulinemia prevention [63,64] effects. The anticarcinogenic effect of c9,t11-CLA has been widely observed in several studies on cell cancer lines and laboratory animals [58], but these results need to be confirmed in humans. ...
The effects of the dams and suckling lamb feeding systems on the fatty acid (FA) profile of lamb meat are reviewed in this article. The suckling lamb can be considered a functional monogastric, and therefore, its meat FA composition is strongly influenced by the FA composition of maternal milk. The major source of variation for ewe milk FA composition is represented by pasture amount and type. In the traditional sheep breeding system of the Mediterranean area, the main lambing period occurs in late autumn–early winter, and ewes are able to exploit the seasonal availability of the natural pastures at their best. Therefore, lambs start suckling when maternal milk concentrations of vaccenic, rumenic, and n-3 long-chain polyunsaturated FA in maternal milk are the highest. When maternal diet is mainly based on hay and concentrates, the use of vegetable oils can be considered a good strategy to improve the meat FA profile of suckling lambs.
... In a human trial, 3 g of punicic acid per day for 28 days increased punicic acid from 0 to 0.47% of total FAs in plasma and from 0 to 0.37% of fatty acids in red blood cells [87]. Punicic acid also increased the proportion of cis-9, trans-11 conjugated linoleic acid in plasma and red blood cells; this FA can have benefits on human health including improving the blood lipid profile [88]. Feeding pomegranate seed oil to rats resulted in appearance of Table 8 Comparison of the anti-inflammatory effect of four omega-3 fatty acids and pinolenic acid (PLA) in cultured EA.hy296 cells. ...
Pine nut oil (PNO) is rich in a variety of unusual delta‐5‐non‐methylene‐interrupted fatty acids 2 (NMIFAs), including pinolenic acid (PLA; all cis‐5,‐9,‐12 18:3) which typically comprises 14 to 19% of total fatty acids. PLA has been shown to be metabolised to eicosatrienoic acid (ETA; all cis‐7,‐11,‐14 4 20:3) in various cells and tissues. Here we review the literature on PNO, PLA and its metabolite ETA in the context of human health applications. PNO and PLA have a range of favourable effects on body weight as well as fat deposition through increased energy expenditure (fatty acid oxidation) and decreased food energy intake (reduced appetite). PNO and PLA improve blood and hepatic lipids in animal models and insulin sensitivity in vitro and reduce inflammation and modulate immune function in vitro and in animal models. The few studies which have examined effects of ETA indicate it has antiinflammatory properties. Another NMIFA from PNO, sciadonic acid (all cis‐5,‐11,‐14 20:3), has generally similar properties to PLA where these have been investigated. There is potential for human health benefits from PNO, its constituent NMIFA PLA and the PLA derivative ETA. However further studies are needed to explore the effects in humans.
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... Numerous animal and human studies have shown also other positive effects of CLA in relation to human health. CLA has been reported to attenuate cardiovascular risk by reducing atherosclerotic lesions, lowering TAG, total cholesterol, LDLcholesterol and increasing HDL-cholesterol, respectively [ 183,201,202,203 ]. CLA, mainly through the isomer trans-10,cis-12, has been reported to improve body composition, by lowering body weight, subcutaneous fat mass and increasing lean body mass, respectively [ 204,205,206,207 ]. ...
... Supporting these results, an improvement in the lipid profile caused by CLA supplementation has been previously reported in animal [42] and human studies [43]. In fact, diverse lines of research indicate that the CLA effects on lipid metabolism are mediated by the modulation of eicosanoid formation [44], and these effect seems to be more favourably influenced by the c9,t11 isomers than others in both animals [45] and humans [46]. ...
Conjugated linoleic acid (CLA) is a dietary supplement that has been shown to improve obesity. However, some authors have associated high doses of CLA supplementation with liver impairment and insulin resistance. The aim of this study was to assess whether the consumption of low doses of CLA maintained the beneficial effects on the main metabolic disturbances associated with metabolic syndrome (MetS) but prevented the occurrence of non-desirable outcomes associated with its consumption. Male Wistar rats, fed standard or cafeteria (CAF) diet for 12 weeks, were supplemented with three different low doses of CLA in the last three weeks. Both biochemical and H1 NMR-based metabolomics profiles were analysed in serum and liver. The consumption of 100 mg/kg CLA, but not doses of 200 and 300 mg/kg, ameliorated the increase in body weight gain as well as the serum concentrations of glucose, insulin, cholesterol, triglyceride, diglyceride, and total phospholipid induced by a CAF diet. In turn, CLA reverted the increase in lactate, alanine, and glucose concentrations in the liver of these animals, but enhanced hepatic cholesterol accumulation without any detrimental effect on liver function. In conclusion, a low dose of CLA corrected the adverse effects associated with MetS without compromising other metabolic parameters.
... Fibrinogen ( [ 141,142] 42 overweight middle-aged adults Yogurt-like dairy product enriched with 3 g of high oleic acid oil (control group) or 3 g of CLA9,11 or 3 g of CLA10,12 instead of the oleic acid. ...
Endothelial dysfunction is a proinflammatory state characterized by chronic activation of the endothelium, which leads to atherosclerosis and cardiovascular disease (CVD). Intake of trans fatty acids (TFAs) is associated with an increased risk of CVD. This risk is usually associated with industrial TFAs (iTFAs) rather than ruminant TFAs (rTFAs); however it is not clear how specific TFA isomers differ in their biological activity and mechanisms of action with regard to inflammation. Here we review the literature on 18carbon TFAs, including the research associating their intake or levels with CVD and studies relating 18carbon TFA exposure to modulation of inflammatory processes. The evidence associating iTFAs with CVD risk factors is fairly consistent and studies in humans usually show a relation between iTFAs and higher levels of inflammatory markers. In contrast, studies in humans, animals and in vitro suggest that rTFAs have null or mildly beneficial effects in cardiovascular health, metabolic parameters and inflammatory markers, although the evidence is not always consistent. More studies are needed to better identify the beneficial and detrimental effects of the different TFAs, including those with 18 carbons.
... Sheep milk is the richest source of conjugated linoleic acid and αlinolenic acid (Markiewicz-Kęszycka et al., 2013). It is claimed to inhibit the occurrence and development of cancer (Parodi, 1999), in the prevention of coronary heart disease and atherosclerosis (Gavino et al., 2000;Tricon et al., 2004), inhibits the development of osteoporosis (Watkins and Seifert, 2000) and stimulates the immune system (O'Shea et al., 2004). The CLA has multiple functional properties. ...
... Additionally, CLA reduces the levels of triglycerides, total cholesterol, including LDL, and thus improves the ratio of LDL/HDL in plasma, therefore, it prevents coronary heart disease and atherosclerosis (GaviNo et al., 2000;Tricon et al., 2004). CLA also is said to inhibit the development of osteoporosis (Watkins and Seifert, 2000), to improve the metabolism of lipids, to reduce the blood glucose level, and to stimulate the immune system (O'Shea et al., 2004). ...
The main objective of the studies was to discuss situation in sheep milk market in the European Union. Specific objectives include presentation of the data related to dairy sheep’s population and commercial production of sheep's milk in separate EU countries, as well as indication of the main interdependent factors with milk production. Studies have been performed on a group that included all the countries which belonged to the EU as of 31.12.2013 and commercial produce a sheep's milk. There were 14 such countries. Data assumed for studies concerned years 2008-2017. The sources of materials were analysis of literature, EUROSTAT Database. For the purposes of the analysis of the materials, the authors used dynamic indicators on variable base, Gini coefficient, concentration analysis using the Lorenzo curve, and the Pearson linear correlation coefficient. For materials’ presentation the authors used descriptive, tabular and graphical methods. Studies carried out allowed to show changes in sheep's milk production. In 2008-2017, the production of sheep’s milk intended for processing in dairies increased, which could have been a result from the less internal consumption of farms. The level of concentration of sheep milk production in the EU was very high, but there were no changes in this regard. Commercial production of sheep's milk was concentred in several countries, like Greece, Spain, Italy and France. Commercial production of sheep's milk was more correlated with sheep population and lamb meat production, than population of dairy sheep and economy parameters.
... Additionally, CLA reduces the levels of triglycerides, total cholesterol, including LDL, and thus improves the ratio of LDL/HDL in plasma, which is a crucial factor in the prevention of coronary heart disease and (Tricon et al., 2004). CLA is also said to inhibit the development of osteoporosis (Watkins and Seifert, 2000), to improve the metabolism of lipids, to reduce the blood glucose level, and to stimulate the immune system (O'Shea et al., 2004). ...
The chapter provides information on nutritional importance of milk in human diets.
... In contrast, young adults with a sedentary lifestyle, supplemented with 4 g/day CLA (35.5% c9,t11; 36.8% t10,c12) for 8 weeks showed reduced fasting insulin concentrations and improved insulin sensitivity compared with placebo (173). The whole-body effects of CLA on insulin sensitivity appear to be isomer specific, and the human studies carried out would suggest that the effect of CLA supplementation may be dependent upon the age and background insulin sensitivity of the individual. ...
Metabolic syndrome and type 2 diabetes are two of the fastest growing public health problems in both developed and developing countries. The metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose that contributes to increased cardiovascular morbidity and mortality. The metabolic syndrome appears to have emerged from changes in our diet and sedentary. There has been much concern regarding the role of high fructose consumption in the development of metabolic diseases. Fructose has now become a major constituent of modern diet and an important causative factor in the development of metabolic syndrome. This concern arises from the continuous increase in fructose in recent decades, and from the increased use of high-fructose corn syrup as a sweetener. Despite the great strides that have been made in the understanding and management of metabolic syndrome, the disease and its complications are increasing unabated. Therefore, as the disease is progressing unabated, there is an urgent need for increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb the supplementation of packaged foods with high fructose additives. Parallel to this, recent developments in understanding the pathophysiology of the disease process have opened up several new avenues to identify and develop novel therapies to combat the metabolic syndrome. Lifestyle and diet modulate the metabolic syndrome. Concurrently, dietary bioactive lipids have been recognized as contributing factors in the treatment and the prevention of cardiovascular risk clustering. Dietary lipids act as sources of energy, cell structure, and signaling molecules, as well as regulators of nutrient metabolism and cell functions by the control of gene expression. Such regulatory lipids can be defined as "bioactive lipids" and attention must be paid to their molecular actions in the prevention and alleviation of the metabolic syndrome. The current review was undertaken to discuss the potential benefits of bioactive fatty acids such as omega-3 fatty acids and conjugated linoleic acid in the prevention and treatment of metabolic syndrome. Further, the authors studied the metabolic consequences of increased fructose intake, and the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia and the strength of the existing data linking dietary fructose feeding and metabolic syndrome.
... In contrast, young adults with a sedentary lifestyle, supplemented with 4 g/day CLA (35.5% c9,t11; 36.8% t10,c12) for 8 weeks showed reduced fasting insulin concentrations and improved insulin sensitivity compared with placebo (173). The whole-body effects of CLA on insulin sensitivity appear to be isomer specific, and the human studies carried out would suggest that the effect of CLA supplementation may be dependent upon the age and background insulin sensitivity of the individual. ...
Metabolic syndrome and type 2 diabetes are two of the fastest growing public health problems in both developed and
developing countries. The metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia,
hypertension and impaired fasting glucose that contributes to increased cardiovascular morbidity and mortality. The metabolic
syndrome appears to have emerged from changes in our diet and sedentary. There has been much concern regarding the role
of high fructose consumption in the development of metabolic diseases. Fructose has now become a major constituent of
modern diet and an important causative factor in the development of metabolic syndrome. This concern arises from the
continuous increase in fructose in recent decades, and from the increased use of high-fructose corn syrup as a sweetener.
Despite the great strides that have been made in the understanding and management of metabolic syndrome, the disease and
its complications are increasing unabated. Therefore, as the disease is progressing unabated, there is an urgent need for
increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb
the supplementation of packaged foods with high fructose additives. Parallel to this, recent developments in understanding the
pathophysiology of the disease process have opened up several new avenues to identify and develop novel therapies to combat
the metabolic syndrome. Lifestyle and diet modulate the metabolic syndrome. Concurrently, dietary bioactive lipids have been
recognized as contributing factors in the treatment and the prevention of cardiovascular risk clustering. Dietary lipids act as
sources of energy, cell structure, and signaling molecules, as well as regulators of nutrient metabolism and cell functions by the
control of gene expression. Such regulatory lipids can be defined as “bioactive lipids” and attention must be paid to their
molecular actions in the prevention and alleviation of the metabolic syndrome. The current review was undertaken to discuss
the potential benefits of bioactive fatty acids such as omega-3 fatty acids and conjugated linoleic acid in the prevention and
treatment of metabolic syndrome. Further, the authors studied the metabolic consequences of increased fructose intake, and
the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia and the
strength of the existing data linking dietary fructose feeding and metabolic syndrome.
KEY WORDS: fructose, metabolic syndrome, omega-3 fatty acids, conjugated linoleic acid.
... No impairment of endothelial function. [204] Healthy men (n = 49). Randomized, doubleblind, crossover for 8 weeks for each isomer dose consecutively (6 months per isomer), with a 6-week washout between isomers. ...
Obesity and its comorbidities, including type 2 diabetes and cardiovascular disease, are straining our healthcare system, necessitating the development of novel strategies for weight loss. Lifestyle modifications, such as exercise and caloric restriction, have proven effective against obesity in the short term, yet obesity persists because of the high predilection for weight regain. Therefore, alternative approaches to achieve long term sustainable weight loss are urgently needed. Conjugated linoleic acid (CLA), a fatty acid found naturally in ruminant animal food products, has been identified as a potential anti-obesogenic agent, with substantial efficacy in mice, and modest efficacy in obese human populations. Originally described as an anti-carcinogenic fatty acid, in addition to its anti-obesogenic effects, CLA has now been shown to possess anti-atherosclerotic properties. This review summarizes the pre-clinical and human studies conducted using CLA to date, which collectively suggest that CLA has efficacy against cancer, obesity, and atherosclerosis. In addition, the potential mechanisms for the many integrative physiological effects of CLA supplementation will be discussed in detail, including an introduction to the gut microbiota as a potential mediator of CLA effects on obesity and atherosclerosis.
... It has been reported that Cis-9, trans-11 conjugated linoleic acid and trans-11 oleic acid, derived from bacterial metabolism and existing in dairy products, have no adverse effects on lipoprotein levels [87]. Paradoxically, it has been reported that the intake of trans-10, cis-12 conjugated linoleic acid present in hydrogenated oils increases inflammatory markers in women [88], causes endothelial dysfunction [89], and adversely affects the plasma lipid profile by increasing LDL:HDL and total cholesterol (TC):HDL ratios in humans [90]. Although the exact role of trans fatty acids on the lipid profile and its mechanism of action is not yet clear, dietary recommendations in NAFLD suggest avoiding highly processed food products enriched with trans fatty acids [91]. ...
Non-alcoholic fatty liver disease (NAFLD) is an acquired metabolic disease characterized by triglycerides (TGs) deposition in liver induced by other factors rather than alcohol consumption. NAFLD significantly contributes to liver diseases in children and adults. NAFLD pathogenesis is associated with age, gender, race and ethnicity. Insulin resistance, hyperinsulinemia, elevated plasma free fatty acids (FFAs), fatty liver, hepatocyte injury, liver inflammation, oxidative stress, mitochondrial dysfunction, imbalanced pro-inflammatory cytokines, and fibrosis are the characteristics of NAFLD. Factors including genetic and epigenetic pathways, sedentary lifestyle, sleep, and diet composition affect NAFLD pathogenesis. In this review, we discuss the aetiology, risk factors and pathogenesis of NAFLD. Special focus is given to macro and micro nutrition as causing factors and their role in the prevention of NAFLD pathogenesis.
... The intake of CLA derives mainly from dairy and ruminant meat products, and the lower plasma proportions of cis-9,trans-11-CLA (which accounts for 90% of the CLA intake; 27) in the vegetarians and the vegans than in the meat-eaters largely reflect differences in dietary intake. Much smaller differences between the diet groups were seen for the trans-10,cis-12 isomer of CLA, which has gained increasing attention because of its possible body-fat-lowering effects (28) and its possible adverse effects on insulin sensitivity (29) and blood lipids (30). The increased proportions of plasma LA in the vegetarians and vegans are consistent with studies that showed that dietary intake of LA is higher in vegetarians and vegans than in omnivores (7,8). ...
Background: Plasma concentrations of long-chain n−3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans.
Objectives: We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n–3; EPA), docosapentaenoic acid (22:5n–3; DPA), and docosahexaenoic acid (22:6n–3; DHA) were related to the subjects’ duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n–6; LA) and α-linolenic acid (18:3n-3; ALA).
Design: The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured.
Results: The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from <1 y to >20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA.
Conclusions: The proportions of plasma long-chain n−3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.
... The improvement of milk quality by increasing the unsaturated fatty acid concentration is the answer to a higher demand for milk-derived bioactive components with special consideration of their effects on the human health. Although CLA is the best known for its anti-cancer properties, researchers have also found, among others, that the C18:2 c9 t11 form of CLA can reduce the risk of cardiovascular diseases and help fight inflammation (Tricon et al., 2004;Zulet et al., 2005). VA is a precursor of CLA synthesis in mammary gland, and hence dietary VA may contribute to the amount of CLA available to the human body. ...
The aim of our research was to evaluate whether rapeseed and linseed oils used as feed additives to ewe's diets allow to achieve the higher secretion of unsaturated fatty acids into milk with extended emphasis on the conjugated linoleic acid concentration. Two experiments were carried out on 6 lactating ewes in two independent 3 × 3 Latin square designs. In each feeding cycle the animals were subjected to one of the treatments: (1) without oil supplementation, (2) with 3.5% of rapeseed oil (RS) or linseed oil (LS), (3) with 7.0% of rapeseed oil or linseed oil. Feeding diets rich in mono- and polyunsaturated fatty acids to lactating ewes under our experimental conditions resulted in demanded changes in milk fatty acid content without causing milk fat depression or modification of other milk constituents. Milk fat was improved in unsaturated fatty acids including C18:2 c9 t11 CLA isomer without changing the milk fat concentration. The C18:2 c9 t11 concentration increased from 0.03 (FAME, %) in the control group to 0.21 and 0.12 (FAME, %) in groups receiving 3.5 and 7% RS, respectively. The diet with 7% LS also elevated the C18:2 c9 t11 level in milk from 0.04 (FAME, %) in the control group to 0.11 (FAME, %). Hence a conclusion is drawn that plant oils may be an important source of monoenic and also polyenic fatty acids in milk, however, our research and analysis of literature data indicate that results are strictly dietary and supplement-dependent.
... Some studies reported significant weight loss with CLA supplements (range, 0.59-6.8 g/day) and a fat-free mass increase , Smedman and Vessby 2001, Gaullier et al. 2004, Watras et al. 2007), while others found no effect (Berven et al. 2000, Zambell et al. 2000, Benito et al. 2001, Mougios et al. 2001, Kreider et al. 2002, Malpuech-Brugere et al. 2004, Moloney et al. 2004, Tricon et al. 2004, Whigham et al. 2004, Taylor et al. 2006, Joseph et al. 2011). WC was not significantly reduced in a meta-analysis of randomized control trials on CLA supplementation (including 534 subjects) over at least 6 months of treatment ( Onakpoya et al. 2012). ...
Milk and dairy products are known to have a significant role in human development and tissue maintenance due to their high nutritional value. With the higher incidence of obesity and metabolic diseases, nutrition and public health authorities have recommended the intake of fat‐free or low‐fat dairy due to the saturated fatty acid content of whole‐fat products and their effect on serum cholesterol levels. However, recent studies have questioned the association between milk fat consumption and cardiometabolic risk. This literature review aims to compile the scientific evidence of the metabolic effects of milk fatty acids in clinical and basic research studies, as well as their relationship with metabolic disorders and gut microbiota composition. Research shows that various milk fatty acids exert effects on metabolic alterations (obesity, type 2 diabetes and cardiovascular diseases) by modifying glucose homeostasis, inflammation and lipid profile‐related factors. Additionally, recent studies have associated the consumption of milk fatty acids with the production of metabolites and the promotion of healthy gut microbiota. From mainly observational studies, evidence suggests that milk and dairy fatty acids are not directly linked to cardiometabolic risk, but further controlled research is necessary to clarify such findings and to assess whether dietary recommendations to choose low‐fat dairy foods are necessary for the population for the prevention of obesity and cardiometabolic disease.
Nigella hispanica seed oil contains an abundance of conjugated linoleic (18:2) acid, thymoquinone, nigellone (dithymoquinone), melanthin, nigilline, damascenine, and tannins. In this study we identified the compounds in the seeds of Nigella hispanica and their anti oxident activity through insilico studies. Molecular modeling and flexible docking of Bcl2L10 has been studied in silico approach. Blast result was found to have similarity with Bcl2L10 of 48% identity with 2KUA. With the aid of Molecular dynamics and Molecular simulations studies it was identified that the generated structure was reliable. Active site of Bcl2L10 was identified by CASTP. Large potential drugs were designed for identifying molecules that can likely bind to protein target of interest. This structure was used to identify better inhibitor using docking studies. The drug derivatives were docked to the Bcl2L10 structure into the active site. The compounds were designed using chemsketch software and structure of the Cancer protein BCL-2 was collected from PDB databank. The active site was identified using Castp server. The results indicated that ASP-65, CYS-66, CYS-88 in BCL-2 were important determinant residues in binding as they have strong hydrogen bonding with compounds. These compunds were isolated using column chromatography based on the rate of separation. Then these extracts were used for antibacterial, antifungal, antioxidant, anti diabetic and anticancer activity. Keywords: Nigella hispanica, Docking, antidiabetic, antibacterial, anticancer activity and Bcl2l10 Protein. METHODOLOGY 3D model building Molecular modelling, also known as comparative modelling refers to constructing an atomic-resolution model of the "target" protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein (the "template"). Molecular modelling relies on the identification of one or more known protein structures likely to resemble the structure of the query sequence, and on the production of an alignment that maps residues in the query sequence to residues in the template sequence. The sequence alignment and template structure are then used to produce a structural model of the target. Because protein structures are more conserved than DNA sequences, detectable levels of sequence similarity usually imply significant structural similarity. Suppose you want to know the 3D structure of a target protein that has not been solved empirically by X-ray crystallography or NMR. You have only the sequence. If an empirically determined 3D structure is available for a sufficiently similar protein (50% or better sequence identity would be good), you can use software that arranges the backbone of your sequence identically to this template. This is called "homology modelling". It is, at best, moderately accurate for the positions of alpha carbons in the 3D structure, in regions where the sequence identity is high. It is inaccurate for the details of side chain positions, and for inserted loops with no matching sequence in the solved structure. The optimization procedure is a variable target function method that applies the conjugate gradients algorithm to positions of all non-hydrogen atoms. The query sequence from Homo sapiens was submitted to domain fishing server Signal transducer and activator of transcription 4 prediction. The predicted domain was searched to find out the related protein structure to be used as a template by the BLAST (Basic Local Alignment Search Tool) program against PDB (Protein Databank). Sequence that showed maximum identity with high score and less e-value was aligned and Bile salt
Key Words Nigella hispanica, Docking, antidiabetic, antibacterial,anticanceractivity and BCL Nigella hispanica leaves oil contains an abundance of conjugated linoleic (18:2) acid, thymoquinone, nigellone (dithymoquinone), melanthin, nigilline, damascenine, and tannins. In this study we identified the compounds in the leaves of Nigella hispanica and their anti oxident activity through insilico studies. Homology modeling and flexible docking of Bcl2L10 has been studied insilico approach. Blast result was found to have similarity with Bcl2L10 of 48% identity with 2KUA. With the aid of Molecular dynamics and Molecular simulations studies it was identified that the generated structure was reliable. Active site of Bcl2L10 was identified by CASTP. Large potential drugs were designed for identifying molecules that can likely bind to protein target of interest. This structure was used to identify better inhibitor using docking studies. The drug derivatives were docked to the Bcl2L10 structure into the active site. The compounds were designed using chemsketch software and structure of the Cancer protein BCL-2 was collected from PDB databank. The active site was identified using Castp server. The results indicated that ASP-65, CYS-66, CYS-88 in BCL-2 were important determinant residues in binding as they have strong hydrogen bonding with compounds. These compunds were isolated using column chromatography based on the rate of separation. Then these extracts were used for antibacterial, antifungal, antioxidant, anti diabeticand anticancer activity
Purpose
To analyse phytochemical composition, antioxidant potential, antimicrobial activity and α-amylase, α-glucosidase and xanthine oxidase inhibitory potential of corn silk extracts derived from the Syngenta 5414 corn variety.
Methods
Corn silk sample was lyophilized and extracted using 80% ethanol, methanol, water or acetone. Phytochemicals were qualitatively screened and bioactive compounds were identified through GCMS. Antimicrobial activities were evaluated using the agar well method for bacteria and fungal biomass method for fungi. The extracts were subjected to evaluation for their antidiabetic activity through α-amylase and α-glucosidase inhibitory assays, while their anti-gout potential was assessed through xanthine oxidase inhibitory assay, encompassing all four solvent extracts in the study.
Results
Phytochemical screening revealed the presence of phenols, flavonoids, tannins, alkaloids, sterols, protein xanthoproteic, and cardiac glycosides in the extracts. The Folin-Ciocalteu and AlCl3 assays demonstrated higher yields of phenolics and flavonoids in 80% ethanolic extract. Furthermore, the extracts remarkably scavenged reactive oxygen species like DPPH, ABTS and elicited considerable ferric ion reducing antioxidant power. GC-MS analysis identified 21 compounds in the 80% ethanolic extract, with 1,2,3-Propanetriol-1-acetate, n-Hexadecanoic acid, and 4H-Pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl- as major components. Antimicrobial assays demonstrated the ethanolic (80%) and methanolic extract's remarkable ability to inhibit the growth of Gram-positive bacteria and exhibit anti-fungal properties. The ethanolic (80%) extract exhibited an IC50 value of 0.70 ± 0.02 and 0.71 ± 0.01 mg against α-amylase and α-glucosidase, respectively, and 33.76 ± 0.43 mg against xanthine oxidase.
Conclusion
Corn silk exhibits potential as a valuable reservoir of natural bioactive compounds endowed with a wide array of health-promoting properties.
Whole milk products are of particular nutritional interest, although current dietary recommendations have focused on reducing saturated fat consumption as a means of improving the overall health of the population. However, this chapter provides new scientific evidence on the potential benefits of dairy fat consumption. The high presence of short-chain fatty acids and thus medium-chain triacylglycerols, which are not associated with an increased risk of cardiovascular disease or obesity, along with a large diversity of bioactive lipid components, such as the presence of conjugated linoleic acid, together with milk fat globule membrane components, and fat-soluble vitamins, suggest that these nutritional recommendations need to be reappraised.
Context
Conjugated linoleic acid (CLA) has been reported to have anti-obesity and antidiabetic effects. However, the benefits of CLA combined with exercise remain unclear, and studies report conflicting results.
Objective
A systematic review and meta-analysis were performed to investigate the synergistic effect of CLA and exercise on body composition, exercise-related indices, insulin resistance, and lipid profiles; and of the safety of CLA supplements.
Data sources
In October 2021, the PubMed, Embase, and Cochrane Library databases were searched for reports on clinical trials of the combined intervention of CLA and exercise.
Data extraction
A total of 18 randomized controlled trials and 2 crossover trials were included. The methodological quality assessment was performed using the revised Cochrane risk-of-bias tool. Pooled effect sizes were reported as standardized mean difference (SMD) for continuous data and risk ratio for dichotomous data with their corresponding 95% confidence intervals (CIs). Heterogeneity was tested using the I2 statistic.
Data analysis
The combination of CLA and exercise resulted in significantly decreased body fat (SMD, –0.42 [95%CI, –0.70, –0.14]; P = 0.003; I2 = 65) and insulin resistance (SMD, –0.25 [95%CI, –0.44, –0.06]; P = 0.01; I2 = 0) than did exercise alone. In subgroup analysis, the following factors were associated with significant outcomes: (1) body mass index ≥25 kg/m2; (2) female sex; (3) follow-up time >4 weeks; and (4) intervention duration >4 weeks. Nevertheless, supplementation with CLA during exercise programs was not effective for body-weight control, exercise performance enhancement, or lipid-profile improvement. CLA in combination with exercise did not result in a higher risk of adverse events (risk ratio, 1.32 [95%CI, 0.94–1.84]; P > 0.05; I2 = 0).
Conclusion
CLA combined with exercise is generally safe and can lower body fat and insulin resistance but does not reduce body weight, enhance exercise performance, or improve lipid profiles.
In this study, conjugated linoleic acid (CLA, 3.75%) enriched meatballs were cooked by sous vide (65°C and 95°C). It was determined that there was no significant change in oleic, linoleic, SFA, MUFA and PUFA values. While the amount of CLA isomers decreased significantly with the cooking process, it was determined that lower losses occurred in the sous vide method. The springiness, cohesiveness, resilience and chewiness values of the cooked meatballs with the sous vide method and containing CLA were higher than the other meatball samples. As a result of the study, it is thought that added CLA in foods can be preserved more by prepared with the sous vide method and thus the desired positive biological effects of CLA on human health can be observed.
This study aimed to evaluate the cardiovascular health-related effects of consuming ghee in the usual diet. Thirty healthy men and women were studied in a free-living outpatient regimen. The participants were instructed for the isocaloric inclusion of ghee or olive oil in their diets for 4 weeks using a randomized crossover design. At the end of run-in (baseline), 2-week wash-out, and interventions, fasting blood samples were drawn. In addition, 2-h postprandial blood samples were collected after ingestion of a meal containing olive oil or ghee at week 4 of each dietary intervention. Body weight was not different between the two interventions. Compared to the olive oil, the diet with ghee increased fasting plasma apolipoprotein-B (apo B) (0.09, 95% CI 0.02 to 0.17 g/L, p= 0.018) and non-high-density lipoprotein cholesterol (non-HDL-C) (0.53, 95% CI 0.01 to 1.05 mmol/L, p= 0.046) and low-density lipoprotein cholesterol did not differ significantly between diet groups (0.29, 95% CI –0.05 to 0.63 mmol/L, p= 0.092), but had no significant effect on total cholesterol/HDL-C ratio (0.75, 95% CI −0.24 to 1.74 mmol/L, p= 0.118). No significant difference was observed in fasting as well as 2-h postprandial plasma triacylglycerol, glucose, insulin, and plasminogen activator inhibitor-1 concentrations. This study showed that ghee which is predominantly saturated fats had an increasing effect on plasma apo B and non-HDL-C compared to olive oil, adding further evidence to the existing recommendations to replace dietary fats high in SFA with dietary fats high in unsaturated fats to reduce cardiovascular disease risk.
The term conjugated linoleic acid (CLA) refers to a mixture of positional and geometric isomers of linoleic acid with a conjugated double-bond system; milk fat can contain over 20 different isomers of CLA, which are produced as transient intermediates in the rumen biohydrogenation of dietary unsaturated fatty acids. cis-9, trans-11 CLA, known as rumenic acid (RA), is the predominant isomer (up to 90% of the total) because it is produced mainly by endogenous synthesis from vaccenic acid (VA). VA is typically the major biohydrogenation intermediate produced in the rumen and it is converted to RA by ∆9-desaturase in the mammary gland and other tissues. Biomedical studies with animal models have shown that RA and VA have anticarcinogenic and antiatherogenic properties. The RA and VA contents in milk fat are directly related and they can be markedly enhanced through the use of diet formulation and nutritional management of dairy cows. CLA isomers in milk fat and how they relate to both animal agriculture and human health are rapidly expanding fields. Milk and dairy products offer exciting opportunities in the area of functional foods, and the functional properties of VA and RA in milk further serve to illustrate the value of dairy products in the human diet.
In this study, a high fat diet induced obesity mouse model (DIO) was used to investigate the modulatory effect of high purity conjugated linoleic acid (CLA) on the intestinal microbiota. CLA was prepared by a simulated moving bed chromatography system and its influence on the gut microbes was analyzed by 16S amplicon V3–V4 region analysis. We observed a significant increase in the bacterial biodiversity and the abundance of genera of butyrate- and acetate-producing bacteria. After taking CLA for 6 weeks, the abundance of Bacteroides in the intestines of mice greatly increased, while the abundance of Firmicutes decreased. The corresponding decrease in the Firmicutes/Bacteroidetes ratio reflected a positive modulatory effect of CLA on the intestinal microbiota. In addition, KEGG pathways for the nucleotide metabolism, metabolism of terpenoids and polyketides and lipid metabolism were among the most differentially expressed genes after CLA intervention. The current study revealed that CLA can be used as a functional food component with potential therapeutic value to prevent obesity-related metabolic disorders by manipulating the intestinal microbiota.
The aim of this study was to utilize optimized processing conditions to obtain the highest conjugated linoleic acid (CLA) contents in semi-dry fermented sausages produced with L. plantarum AB20–961 and L. plantarum DSM 2601. Optimized conditions were 5.7 meat pH, 5% hydrolyzed safflower oil addition, 10⁸ CFU/g added starter culture, fermentation time of 73 h for L. plantarum DSM2601 and 79 h for L. plantarum AB20–961, 24 °C fermentation temperature, 65 °C internal cooking temperature and 90% relative humidity. Results indicated that CLA contents in sausages were increased 21% by L. plantarum AB20–961 and 121% by L. plantarum DSM2601 after fermentation compared to initial CLA level determined on manufacturing day (P < .05). After fermentation, an increased CLA content of sausages remained stable during heat processing and storage. Sausages incorporated with L. plantarum strains and hydrolyzed safflower oil had the highest TBARS and PUFA levels, and the lowest pH and moisture content (P < .05). Differences were not found in sensorial and other physicochemical properties among sausage treatment groups. This study demonstrated that high CLA content can be achieved in sausages by utilizing optimum processing conditions described above and starter cultures (L. plantarum AB20–961 and L. plantarum DSM2601) without any adverse effects on quality of the final product.
Fats and Oils: Structures and Functions
Background. Nutritional recommendations emphasize the need to limit consumption of saturated fatty acids and to increase the intake of polyunsaturated fatty acids in the prevention of non-communicable chronic diseases, particularly cardiovascular diseases. Among the fatty acids with health-related effects on the body, conjugated fatty acids are mentioned (i.e. CLA).
Objective. The current study was designed to determine the effects of conjugated linoleic acid (CLA) on serum lipid profile, glucose, liver enzymes activity (AST and ALT), malonic dialdehyde (MDA) as well as lipid hydroperoxide (LPO) concentrations in rats fed diet differing in type of dietary fat.
Material and methods. Male Wistar rats were divided into six groups and fed the following diets: control AIN-93G diet contained soybean oil (O) and diets with modification of fat source: butter (B) and margarine (M). The experimental diets were supplemented with 1% of conjugated linoleic acid (O+CLA, B+CLA, M+CLA). After 21 days the blood was collected and lipid profile, glucose, liver enzymes, MDA as well as LPO were analyzed.
Results. The dietary treatments had no significant effect on the body weight and liver weight of the animals. The concentrations of total cholesterol (TC) and LDL+VLDL cholesterol were unchanged. Both experimental factors (fat source and CLA) had a significant influence on the TAG and HDL levels. Margarine (M) significantly increased the TAG concentration, whereas CLA had a significant impact on the TAG reduction (M+CLA). Glucose level was significantly decreased in all groups fed diets supplemented with CLA. Serum ALT significantly increased in all CLA groups. Fat source had statistically significant influence on the MDA concentration. The LPO level was significantly elevated in all CLA groups. There was statistically significant interaction of experimental factors (fat source and CLA supplementation) on LPO level.
Conclusions. Margarine had an adverse effect on the rat’s lipid profile. However, in the group fed with margarine, the addition of CLA decreased the concentration of TAG. Regardless of the type of the dietary fat, CLA supplementation increased the level of LPO in the blood serum of animals.
Nitrated fatty acids (NO2‐FAs) exhibit a variety of important biological attributes, including a nitric oxide (˙NO) donor and a cell‐signaling molecule. We investigated the mechanisms of fatty‐acid nitration, and the release of ˙NO from NO2‐FAs. NO2‐FAs are formed effectively by the addition of ˙NO2, followed by either hydrogen abstraction or addition of a second NO2. The latter reaction results in a vicinal nitronitrite ester form of FA, which isomerizes into vicinal nitrohydroxy FA via hydronium ion catalysis. The nitrohydroxy FAs exist in equilibria with NO2‐FAs. Nitration of conjugated linoleic acid (cLA) was proved to be significantly more efficient than that of LA. In a nonaqueous environment, release of ˙NO from nitrite ester (ONO‐FA) was facilitated by ˙NO2. Furthermore, the release of ˙NO from NO2‐cLA is the most favorable in the nitrite ester mechanism. In an aqueous environment, the modified Nef reaction was shown to be feasible. In addition, the release of ˙NO from 10‐ and 12‐NO2‐LA involves a larger reaction barrier and is more endergonic than those from 9‐ and 13‐NO2‐LA. In an aqueous environment, modified Nef reaction was investigated. Proton transfer followed by hydration and dehydration of the nitrated fatty acid (NO2‐FA) results in the hydroxynitroso species. From which NO release is accomplished through breaking the C–N bond.
Animal studies have suggested that CLA, a natural component of meat and dairy products, may confer beneficial effects on health. However, human studies using supplementation with CLA have produced contradictory results. The aim of the present study was to further investigate the effect of CLA supplementation on human body fat, serum leptin, and serum lipids, as well as the incorporation of CLA isomers into serum lipids classes. Sixteen young healthy nonobese sedentary women received 2.1 g of CLA (divided equally between the cis,trans-9,11 and trans,cis-10,12 isomers) daily for 45 d and placebo for 45 d in a randomized double-blind crossover design. Body fat was estimated (by measurement of skinfold thickness at 10 sites), and blood was sampled at the beginning, middle, and end of the entire intervention period; an additional blood sample was obtained 2 wk thereafter. No significant differences in energy, carbohydrate, lipid, or protein intake existed between the CLA and placebo intake periods. No significant differences were found in body fat or serum leptin, TAG, total cholesterol, HDL-cholesterol, and alanine aminotransferase between CLA and placebo. The CLA isomer content of serum TAG, phospholipids, and total lipids increased 2-5 times with CLA supplementation (P < 0.05). In contrast, the CLA content of cholesteryl esters did not change significantly. The period of 2 wk after the end of CLA supplementation was sufficient for its washout from serum lipids. These data indicate that supplementation with 2.1 g of CLA daily for 45 d increased its levels in blood but had no effect on body composition or the lipidemic profile of nonobese women.
We report the effect of an atherogenic diet supplemented with cis-9, trans-11-octadecadienoic acid (c9t11), linoleic acid (LA) or an isomeric mixture of conjugated linoleic acids (CLA) on plasma lipids, weight gain and food intake of male Golden Syrian hamsters. Animals were assigned to three diet groups (n = 10), and fed nonpurified diet, supplemented with 10% hydrogenated coconut oil and 0.05% cholesterol for 6 wk. The first diet group was further supplemented with 1% CLA (CLA group), the second diet group with 0.2% c9t11 (c9t11 group) and the third group with 0.2% LA (LA group). The diets were designed to have equivalent levels of c9t11 in the CLA and c9t11 groups. At 2 and 6 wk of feeding, the CLA group had significantly lower plasma triglyceride and total cholesterol concentrations than either the c9t11 or the LA groups. HDL-cholesterol did not differ among diet groups. The CLA group had significantly lower weight gain but greater food intake than either the c9t11 or the LA groups. There were no significant differences between the c9t11 and the LA groups in any of the variables measured. We conclude that under our experimental conditions of short-term feeding, c9t11, thought to be the active compound in CLA, does not produce the same effect as the isomer mixture.
Conjugated linoleic acid (CLA) refers to a group of fatty acid isomers of linoleic acid. Recent research shows that CLA affects body composition, lipoprotein metabolism, inflammationand carcinogenesis. Therefore, CLA may have potential as a therapeutic nutrient with respect to many common diseases, including obesity, atherosclerosis, chronic inflammatory diseases and cancer. Animal studies show that CLA is a potent anti-adipogenic nutrient, reducing adipose tissue mass and increasing lean mass. However, the effect of CLA on body composition in human subjects has been less spectacular. Several studies have demonstrated that CLA significantly improves plasma cholesterol and triacylglycerol metabolism in a number of animal models. These studies also showed that CLA inhibits the progression and pathogenesis of atherosclerosis. Whilst CLA has also been shown to improve triacylglycerol metabolism in human subjects, it has not been determined whether CLA affects atherogenesis. Animal models show that CLA-rich diets modulate the inflammatory response and preliminary trials with human subjects show that CLA affects the cell-mediated immune response. The molecular basis of the health effects of CLA has not been elucidated, but it is probable that CLA mediates its effect in a number of ways including altered eicosanoid or cytokine metabolism and/orby a direct effect of dietary fats on gene transcription. Most of our knowledge is based on in vitro and animal studies; the challenge is to define the nature and molecular basis of any health effects of CLA in human subjects.
Conjugated dienoic derivative of linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is a naturally occurring substance in food and is present at higher concentrations in products from animal sources. The present study reports that synthetically prepared CLA is an effective agent in inhibiting the development of mammary tumors induced by dimethylbenz(a)anthracene. Rats were fed either the AIN-76A basal diet or the same diet supplemented with 0.5, 1, or 1.5% CLA by weight. These diets were started 2 weeks before carcinogen administration and continued until the end of the experiment. The total number of mammary adenocarcinomas in the 0.5, 1, and 1.5% CLA groups was reduced by 32, 56, and 60%, respectively. The final tumor incidence and cumulative tumor weight were similarly diminished in rats fed the CLA-containing diets. In general, there appeared to be a dose-dependent protection at levels of 1% CLA and below, but no further beneficial effect was evident at levels above 1%. Chronic feeding of up to 1.5% CLA produced no adverse consequences in the animals. Analysis of the phospholipid fraction from liver and mammary tumor extracts showed that only the c9,t11 isomer of CLA was incorporated and that the level of incorporation increased with dietary intake. An interesting property of CLA is its ability to suppress peroxide formation from unsaturated fatty acid in a test-tube model (Cancer Res., Ha et al. 50: 1097-1101, 1990). In view of this information, the amount of thiobarbituric acid-reactive substances (lipid peroxidation products) present endogenously in liver and mammary gland was quantitated. The feeding of CLA (for either 1 or 6 months) resulted in a decrease in the extent of lipid peroxidation in the mammary gland, but such a suppressive effect was not detected in the liver. It should be noted that maximal antioxidant activity was observed with only 0.25% CLA in the diet, whereas maximal tumor inhibition was achieved at about 1% CLA. Hence there is a discrepancy between the antioxidant efficacy of CLA and its anticarcinogenic potency, suggesting that some other mechanisms might be involved in cancer protection. Unlike the stimulatory effect of linoleic acid in carcinogenesis (Cancer Res., Ip et al., 45: 1997-2001, 1985), the reaction of CLA in cancer prevention is specific, and CLA is more powerful than any other fatty acid in modulating tumor development.
Conjugated linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is naturally occurring in meat and dairy products. We have previously reported (Ip, C., Chin, S. F., Scimeca, J. A., and Pariza, M. W. Cancer Res., 51: 6118-6124, 1991) that 1% CLA in the diet suppressed mammary carcinogenesis in rats given a high dose (10 mg) of 7,12-dimethylbenz(a)anthracene. In the present study, dietary CLA between 0.05 and 0.5% was found to produce a dose-dependent inhibition in mammary tumor yield when fed chronically to rats treated with a lower dose (5 mg) of 7,12-dimethylbenz(a)anthracene. Short-term CLA feeding for 5 weeks, from weaning to the time of carcinogen administration at 50 days of age, also offered significant protection against subsequent tumor occurrence. This period corresponds to maturation of the mammary gland to the adult stage in the rat. The inhibitory response to short-term CLA exposure was observed with the use of 2 different carcinogens: 7,12-dimethylbenz(a)anthracene and methylnitrosourea. The fact that CLA was protective in the methylnitrosourea model suggests that it may have a direct modulating effect on susceptibility of the target organ to neoplastic transformation. The proliferative activity of the mammary epithelium was assessed by the incorporation of bromodeoxyuridine. Immunohistochemical staining results showed that CLA reduced the labeling index of the lobuloalveolar compartment, but not that of the ductal compartment of the mammary tree. Since the lobuloalveolar structures are derived from the terminal end buds which are the sites of carcinogenic transformation, the above finding is consistent with the bioassay data of tumor inhibition. Thus, changes in gland development and morphogenesis may be a locus of action of CLA in modulating mammary carcinogenesis. CLA is a unique anticarcinogen because it is present in foods from animal sources. Furthermore, its efficacy in cancer protection is manifest at dietary concentrations which are close to the levels consumed by humans.
Conjugated linoleic acids (CLA) are positional isomers of linoleic acid which have been suggested by some to possess antiatherosclerotic properties. To test this hypothesis, three groups of twenty C57BL/6 mice were fed on atherogenic diets containing: 5 g CLA/kg, 2.5 g CLA + 2.5 g linoleic acid/kg or 5 g linoleic acid/kg. All diets were fed for 15 weeks and contained (g/kg): triacylglycerol 145, free fatty acids 5, cholesterol 10 and cholic acid 5. At the completion of the experimental period, when data from both groups fed on CLA were combined, dietary CLA did not produce significant differences in body weight, serum total cholesterol concentration or serum HDL-cholesterol concentration. However, mice receiving CLA developed a significantly higher serum HDL-cholesterol: total cholesterol ratio and a significantly lower serum triacylglycerol concentration than controls. Despite causing a serum lipoprotein profile considered to be less atherogenic, the addition of CLA to the atherogenic diet increased the development of aortic fatty streaks. Considering the increased atherogenesis associated with dietary CLA in the present study, and the failure to demonstrate a significant beneficial effect of CLA in other animal studies, there is currently no conclusive evidence to support the hypothesis that CLA protect against atherogenesis.
Conjugated linoleic acid (CLA) is a potent cancer preventive agent in animal models. To date, all of the in vivo work with CLA has been done with a commercial free fatty acid preparation containing a mixture of c9,t11-, t10,c12- and c11,t13-isomers, although CLA in food is predominantly (80-90%) the c9,t11-isomer present in triacylglycerols. The objective of this study was to determine whether a high CLA butter fat has biological activities similar to those of the mixture of free fatty acid CLA isomers. The following four different endpoints were evaluated in rat mammary gland: 1) digitized image analysis of epithelial mass in mammary whole mount; 2) terminal end bud (TEB) density; 3) proliferative activity of TEB cells as determined by proliferating cell nuclear antigen immunohistochemistry; and 4) mammary cancer prevention bioassay in the methylnitrosourea model. It should be noted that TEB cells are the target cells for mammary chemical carcinogenesis. Feeding butter fat CLA to rats during the time of pubescent mammary gland development reduced mammary epithelial mass by 22%, decreased the size of the TEB population by 30%, suppressed the proliferation of TEB cells by 30% and inhibited mammary tumor yield by 53% (P < 0.05). Furthermore, all of the above variables responded with the same magnitude of change to both butter fat CLA and the mixture of CLA isomers at the level of CLA (0.8%) present in the diet. Interestingly, there appeared to be some selectivity in the uptake or incorporation of c9,t11-CLA over t10,c12-CLA in the tissues of rats given the mixture of CLA isomers. Rats consuming the CLA-enriched butter fat also consistently accumulated more total CLA in the mammary gland and other tissues (four- to sixfold increases) compared with those consuming free fatty acid CLA (threefold increases) at the same dietary level of intake. We hypothesize that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction. Further studies will be conducted to investigate other attributes of this novel dairy product.
Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested.
To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders.
Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin.
At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups.
These results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.
Supplementation with conjugated linoleic acid (CLA) induces a number of physiological effects in experimental animals, including reduced body fat content, decreased aortic lipid deposition, and improved serum lipid profile. Controlled trials on the effects of CLA in humans have hitherto been scarce. The aim of this study was to evaluate the effects of supplementation with CLA in healthy humans on anthropometric and metabolic variables and on the fatty acid composition of serum lipids and thrombocytes. Fifty-three healthy men and women, aged 23-63 yr, were randomly assigned to supplementation with CLA (4.2 g/d) or the same amount of olive oil during 12 wk in a double-blind fashion. The proportion of body fat decreased (-3.8%, P< 0.001) in the CLA-treated group, with a significant difference from the control group (P = 0.050). Body weight, body mass index, and sagittal abdominal diameter were unchanged. There were no major differences between the groups in serum lipoproteins, nonesterified fatty acids, plasma insulin, blood glucose, or plasminogen activator inhibitor 1 (PAI-1). In the CLA group the proportions of stearic, docosatetraenoic, and docosapentaenoic acids increased in serum lipids and thrombocytes, while proportions of palmitic, oleic, and dihomo-gamma-linolenic acids decreased, causing a decrease of the estimated delta-6 and delta-9 and an increase in the delta-5 desaturase activities. These results suggest that supplementation with CLA may reduce the proportion of body fat in humans and that CLA affects fatty acid metabolism. No effects on body weight, serum lipids, glucose metabolism, or PAI-1 were seen.
Conjugated linoleic acid (CLA) is a natural component of meat and dairy products with anticarcinogenic, fat lowering, antiatherogenic and anticatabolic activity in animals. The purpose of this study was to examine the effect of CLA supplementation to humans on body fat, certain biochemical parameters of serum, and the CLA content of serum lipids. Twenty-two volunteers were divided into a study group and a control group in a doubly blind design. The study group received 0.7 g of CLA for four weeks and 1.4 g of CLA for the next four weeks, while the control group received placebo. Diet was controlled and no significant differences in energy or macronutrient intake were found between the two groups. Measurements were taken at baseline, four weeks, and eight weeks. The sum of the thickness of ten skinfolds, percentage body fat calculated from it and fat mass was significantly reduced in the CLA group during the second period (P < 0.004) but not overall during the study. Serum HDL-cholesterol decreased significantly (P < 0.001) and triacylglycerols as well as total cholesterol tended to decrease in the CLA group during the first period. The CLA content of serum non-esterified fatty acids, triacylglycerols, phospholipids, and cholesteryl esters increased gradually with supplementation; the CLA content of total serum lipids doubled at the end of the study compared to baseline. Phospholipids had the highest CLA content regardless of supplementation. These data indicate that supplementation with 0.7-1.4 g CLA daily for 4-8 weeks may modulate body fat and serum lipids, as well as increase the CLA content of serum lipids in humans.
Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in humans is unknown. The aim of this study was to investigate whether t10c12 CLA or a commercial CLA mixture could improve insulin sensitivity, lipid metabolism, or body composition in obese men with signs of the metabolic syndrome.
In a randomized, double-blind controlled trial, abdominally obese men (n = 60) were treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo. Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and anthropometry were assessed before and after 12 weeks of treatment.
Baseline metabolic status was similar between groups. Unexpectedly, t10c12 CLA increased insulin resistance (19%; P < 0.01) and glycemia (4%; P < 0.001) and reduced HDL cholesterol (-4%; P < 0.01) compared with placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but the difference was not significantly different from placebo. The CLA mixture did not change glucose metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (-2%; P < 0.05).
These results reveal important isomer-specific metabolic actions of CLA in abdominally obese humans. A CLA-induced insulin resistance has previously been described only in lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of these results, but they also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.
Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of linoleic acid. Studies using animal models have shown that CLA reduces adiposity, improves plasma lipoprotein metabolism and insulin sensitivity and reduces arteriosclerosis. Whilst CLA may have therapeutic potential with regard to coronary artery disease risk factors in human subjects, there has been little investigation into its effects in human subjects. This current study investigated the effects of dietary supplementation using two isomeric blends of CLA on triacylglycerol (TAG)-rich lipoprotein metabolism and reverse cholesterol transport in human subjects and evaluates whether CLA modulated cardiovascular disease risk factors. Fifty-one normolipidaemic subjects participated in this randomised double-blind placebo-controlled intervention trial. Subjects were randomly assigned to receive 3 g cis-9,trans-11-trans-10,cis-12 isomeric blend (50 : 50) or a cis-9,trans-11-trans-10,cis-12 isomeric blend (80 : 20) CLA or linoleic acid (control)/d for 8 weeks. The 50 : 50 CLA isomer blend significantly reduced (P<or=0.005) fasting plasma TAG concentrations. The 80 : 20 CLA isomer blend significantly reduced (P<or=0.05) VLDL-cholesterol concentrations. CLA supplementation had no significant effect on LDL-cholesterol, HDL-lipid-protein composition or reverse cholesterol transport. CLA supplementation had no effect on body weight, plasma glucose and insulin concentrations. Fatty acid analysis revealed that the cis-9,trans-11 CLA isomer was incorporated into total plasma lipids following supplementation with both isomeric blends of CLA. The present study demonstrates that CLA supplementation significantly improves plasma TAG and VLDL metabolism in human subjects. The study confirms that some of the cardio-protective effects of CLA that were shown in animal studies are relevant to man.
This study investigated the incorporation of cis-9,trans-11 conjugated linoleic acid (c9,t11 CLA) and trans-10,cis-12-CLA (t10,c12 CLA) into plasma and peripheral blood mononuclear cell (PBMC) lipids when consumed as supplements highly enriched in these isomers. Healthy men (n = 49, age 31 ± 8 years) consumed one, two, and four capsules containing ~600 mg of either c9,t11 CLA or t10,c12 CLA per capsule for sequential 8 week periods followed by a 6 week washout before consuming the alternative isomer. Both isomers were incorporated in a dose-dependent manner into plasma phosphatidylcholine (PC) (c9,t11 CLA r = 0.779, t10,c12 CLA r = 0.738; P < 0.0001) and cholesteryl ester (CE) (c9,t11 CLA r = 0.706, t10,c12 CLA r = 0.788; P < 0.0001). Only t10,c12 CLA was enriched in plasma nonesterified fatty acids. Both c9,t11 CLA and t10,c12 CLA were incorporated linearly into PBMC total lipids (r = 0.285 and r = 0.273, respectively; P < 0.0005). The highest concentrations of c9,t11 CLA and t10,c12 CLA in PBMC lipids were 3- to 4-fold lower than those in plasma PC and CE.
These data suggest that the level of intake is a major determinant of plasma and PBMC CLA content, although PBMCs appear to incorporate both CLA isomers less readily.
We report the effect of an atherogenic diet supplemented with cis-9,trans-11-octadecadienoic acid (c9t11), linoleic acid (LA) or an isomeric mixture of conjugated linoleic acids (CLA) on plasma lipids, weight gain and food intake of male Golden Syrian hamsters. Animals were assigned to three diet groups (n = 10), and fed nonpurified diet, supplemented with 10% hydrogenated coconut oil and 0.05% cholesterol for 6 wk. The first diet group was further supplemented with 1% CLA (CLA group), the second diet group with 0.2% c9t11 (c9t11 group) and the third group with 0.2% LA (LA group). The diets were designed to have equivalent levels of c9t11 in the CLA and c9t11 groups. At 2 and 6 wk of feeding, the CLA group had significantly lower plasma triglyceride and total cholesterol concentrations than either the c9t11 or the LA groups. HDL-cholesterol did not differ among diet groups. The CLA group had significantly lower weight gain but greater food intake than either the c9t11 or the LA groups. There were no significant differences between the c9t11 and the LA groups in any of the variables measured. We conclude that under our experimental conditions of short-term feeding, c9t11, thought to be the active compound in CLA, does not produce the same effect as the isomer mixture.
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Food products from ruminants are the major dietary source of conjugated linoleic acids (CLA) for humans. The uniqueness of CLA in ruminant fat relates to the biohydrogenation of dietary unsaturated fatty acids by rumen bacteria. The CLA are inter- mediates in the biohydrogenation, and a portion escape the rumen and are incorporated into milk fat and body fat. In addition, the animal itself synthesizes cis-9, trans-11 CLA from trans-11 octadecenoic acid, another intermediate in ruminal biohydroge- nation that is absorbed. This involves ∆9-desaturase, which is present in mammary tissue (lactation) and adipose tissue (growth). Investigations to alter the content of CLA have typically involved lactating cows (milk fat); fewer data from growing cattle (body fat) are available. Dietary factors that alter the content of CLA because of effects on the rumen biohydrogenation processes in- clude unsaturated fatty acid substrates and altered rumen environment. The cis-9, trans-11 CLA isomer is the major isomer found in ruminant fat; this isomer typically represents 80 to 90% of the total CLA in milk fat, but its proportion in beef fat is less. Under certain dietary conditions the proportion of the trans-10, cis-12 CLA isomer increases. Thus, dietary factors also alter the direction of the biohydrogenation pathways in the rumen. The CLA possess anticarcinogenic effects, which relates to the cis-9, trans-11 CLA isomer, as evident from results with mammary tumors in a rat model. Lipid accretion and nutrient partitioning are also altered by CLA in several species. Recent work demonstrates that this relates primarily to the trans-10, cis-12 CLA isomer, as evident by effects on milk fat synthesis in lactating cows and body fat accretion in growing mice. Overall, consideration of functional foods containing CLA represents an exciting area of potential importance in producing food products derived from ruminants.
The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
Conjugated linoleic acid (CLA) consists of a series of positional and geometric dienoic isomers of linoleic acid that occur naturally in foods. CLA exhibits antioxidant activity in vitro and in vivo. To assess the effect of CLA on atherosclerosis, 12 rabbits were fed a semi-synthetic diet containing 14% fat and 0.1% cholesterol for 22 weeks. For 6 of these rabbits, the diet was augmented with CLA (0.5 g CLA/rabbit per day). Blood samples were taken monthly for lipid analysis. By 12 weeks total and LDL cholesterol and triglycerides were markedly lower in the CLA-fed group. Interestingly, the LDL cholesterol to HDL cholesterol ratio and total cholesterol to HDL cholesterol ratio were significantly reduced in CLA-fed rabbits. Examination of the aortas of CLA-fed rabbits showed less atherosclerosis.
Conjugated linoleic acid (CLA) is a minor fatty acid found predominantly in the form of triglycerides in beef and dairy products. Previous work by Ip and co-workers showed that free fatty acid-CLA at < or = 1% in the diet is protective against mammary carcinogenesis in rats. The present study verified that the anticancer activities of free fatty acid-CLA and triglyceride-CLA are essentially identical. This is an important finding, because it rules out a nonspecific free fatty acid effect. In terms of practical implication, we can continue the in vivo research with the less-expensive free fatty acid-CLA without compromising the physiological relevance of the data. A primary objective of this report was to investigate how the timing and duration of CLA feeding might affect the development of mammary carcinogenesis in the methylnitrosourea (MNU) model. We found that exposure to 1% CLA during the early postweaning and pubertal period only (from 21 to 42 days of age) was sufficient to reduce subsequent tumorigenesis induced by a single dose of MNU given at 56 days of age. This period incidentally corresponds to a time of active morphological development of the mammary gland to the mature state. In contrast to the above observation, a continuous intake of CLA was required for maximal inhibition of tumorigenesis when CLA feeding was started after MNU administration, suggesting that some active metabolite(s) of CLA might be involved in suppressing the process of neoplastic promotion/progression.
Previous work by Ip and co-workers showed that mammary cancer prevention by conjugated linoleic acid (CLA) is independent of the level of fat in the diet. Because CLA is an isomer of linoleic acid, there is the question regarding whether the effect of CLA is due to a displacement of linoleic acid in cells. To further evaluate whether there might be an interaction between linoleic acid and CLA, the present study was designed to examine the dose response to CLA (at 0.5%, 1%, 1.5%, and 2%) in rats fed a 2% or a 12% linoleate diet (both basal diets contained 20% total fat by weight). The end points of investigation included the bioassay of mammary tumorigenesis in the rat dimethylbenz[a]anthracene model as well as the incorporation of CLA, linoleic acid, and arachidonic acid in mammary glands. The mammary carcinogenesis results showed that the efficacy of tumor suppression by CLA was not affected by linoleate intake. With either linoleate diet, no further protection was evident with levels of CLA > 1%. Analysis of neutral lipids and phospholipids of the mammary tissue indicated that 1) the accumulation of CLA in mammary tissue was dose dependent from 0.5% to 2%, 2) CLA concentration was 10 times higher in neutral lipids than in phospholipids, 3) the incorporation of CLA in either fraction was not affected by the availability of linoleic acid, and 4) CLA did not appear to displace linoleic acid or arachidonic acid in the mammary tissue. The above findings suggest that there may be distinctive mechanisms in the modulation of tumor development by linoleic acid and CLA.
Conjugated linoleic acid is a collective term used to designate a mixture of positional and geometric isomers of linoleic acid in which the double bonds are conjugated. Unlike linoleic acid, there is a paucity of information regarding the effect of dietary conjugated linoleic acid on plasma lipoproteins and aortic atherosclerosis. Therefore, fifty hamsters were divided into five groups of ten and fed 0 (Control), 0.06 (LOW), 0.11 (MEDIUM), and 1.1 (HIGH) en% conjugated linoleic acid or 1.1 en% linoleic acid. Blood samples were taken at 4, 8 and 11 weeks for plasma lipid analyses and for plasma tocopherol assay at sacrifice. Animals fed the conjugated linoleic acid-containing diets collectively had significantly reduced levels of plasma total cholesterol, non-high density lipoprotein cholesterol, (combined very low and low density lipoprotein) and triglycerides with no effect on high density lipoprotein cholesterol, as compared to CONTROLs. Linoleic acid-fed animals relative to CONTROLs also had reduced plasma total cholesterol, non-high density lipoprotein cholesterol and triglycerides, but only the latter was statistically significant. Compared to the CONTROL group, plasma tocopherol/total cholesterol ratios determined from plasma pools for the LOW, MEDIUM and HIGH conjugated linoleic acid and linoleic acid groups were increased by 48%, 48%, 86% and 29%, respectively, suggesting a tocopherol-sparing effect, at least for the conjugated linoleic acid treatment. Morphometric analysis of aortas revealed less early atherosclerosis in the conjugated linoleic acid and linoleic acid-fed hamsters compared to the CONTROL group.
We investigated the effects of conjugated linoleic acid (CLA) preparations, which were enriched for the cis-9,trans-11 CLA isomer or the trans-10,cis-12 CLA isomer, on body composition in mice. Body composition changes (reduced body fat, enhanced body water, enhanced body protein, and enhanced body ash) were associated with feeding the trans-10,cis-12 CLA isomer. In cultured 3T3-L1 adipocytes, the trans-10,cis-12 isomer reduced lipoprotein lipase activity, intracellular triacylglycerol and glycerol, and enhanced glycerol release into the medium. By contrast, the cis-9,trans-11 and trans-9,trans-11 CLA isomers did not affect these biochemical activities. We conclude that CLA-associated body composition change results from feeding the trans-10,cis-12 isomer.
Conjugated linoleic acid (CLA) has been demonstrated to reduce body fat in animals. However, the mechanism by which this reduction occurs is unknown. Leptin may mediate the effect of CLA to decrease body fat. We assessed the effects of 64 d of CLA supplementation (3 g/d) on circulating leptin, insulin, glucose, and lactate concentrations in healthy women. Appetite was assessed as a physiological correlate of changes in circulating leptin levels. Analysis of plasma leptin concentrations adjusted for adiposity by using fat mass as a covariate showed that CLA supplementation significantly decreased circulating leptin concentrations in the absence of any changes of fat mass. Mean leptin levels decreased over the first 7 wk and then returned to baseline levels over the last 2 wk of the study in the CLA-treated group. Appetite parameters measured at around the time when the greatest decreases in leptin levels were observed showed no significant differences between supplementation and baseline determinations in the CLA-supplemented group or between the CLA and placebo-supplemented groups. There was a nonsignificant trend for mean insulin levels to increase toward the end of the supplementation period in CLA-treated subjects. CLA did not affect plasma glucose and lactate over the treatment period. Thus, 64 d of CLA supplementation in women produced a transient decrease in leptin levels but did not alter appetite. CLA did not affect these parameters in a manner that promoted decreases of adiposity.
Recent animal studies have demonstrated that dietary conjugated linoleic acid (CLA) reduces body fat and that this decrease may be due to a change in energy expenditure. The present study examined the effect of CLA supplementation on body composition and energy expenditure in healthy, adult women. Seventeen women were fed either a CLA capsule (3 g/d) or a sunflower oil placebo for 64 d following a baseline period of 30 d. The subjects were confined to a metabolic suite for the entire 94 d study where diet and activity were controlled and held constant. Change in fat-free mass, fat mass, and percentage body fat were unaffected by CLA supplementation (0.18+/-0.43 vs. 0.09+/-0.35 kg; 0.01+/-0.64 vs. -0.19+/-0.53 kg; 0.05+/-0.62 vs. -0.67+/-0.51%, placebo vs. CLA, respectively). Likewise, body weight was not significantly different in the placebo vs. the CLA group (0.48+/-0.55 vs. -0.24+/-0.46 kg change). Energy expenditure (kcal/min), fat oxidation, and respiratory exchange ratio were measured once during the baseline period and during weeks 4 and 8 of the intervention period. At all three times, measurements were taken while resting and walking. CLA had no significant effect on energy expenditure, fat oxidation, or respiratory exchange ratio at rest or during exercise. When dietary intake was controlled, 64 d of CLA supplementation at 3 g/d had no significant effect on body composition or energy expenditure in adult women, which contrasts with previous findings in animals.
To determine effects of conjugated linoleic acid (CLA) on establishment and progression of experimentally-induced atherosclerosis in rabbits.
For establishment of atherosclerosis, New Zealand White rabbits were fed a semipurified diet containing 0.1% to 0.2% cholesterol for 90 days. Some groups were fed diet and CLA. For effects on progression of atherosclerosis, rabbits with established atherosclerosis were fed a semipurified diet +/- CLA for 90 days.
At dietary levels as low as 0.1%, CLA inhibited atherogenesis. At dietary levels of 1%, CLA caused substantial (30%) regression of established atherosclerosis. This is the first example of substantial regression of atherosclerosis being caused by diet alone.
Dietary CLA is an effective inhibitor of atherogenesis and also causes regression of established atherosclerosis.
Conjugated linoleic acid (CLA) has been shown to reduce body fat mass (BFM) in animals. To investigate the dose-response relationships of conjugated linoleic acid with regard to BFM in humans, a randomized, double-blind study including 60 overweight or obese volunteers (body mass index 25-35 kg/m(2)) was performed. The subjects were divided into five groups receiving placebo (9 g olive oil), 1.7, 3.4, 5.1 or 6.8 g conjugated linoleic acid per day for 12 wk, respectively. Dual-energy X-ray absorptiometry was used to measure body composition [measurements at wk 0 (baseline), 6 and 12]. Of the 60 subjects, 47 completed the study. Eight subjects withdrew from the study due to adverse events; however, no differences among treatment groups were found regarding adverse events. Repeated-measures analysis showed that a significantly higher reduction in BFM was found in the conjugated linoleic acid groups compared with the placebo group (P: = 0.03). The reduction of body fat within the groups was significant for the 3.4 and 6.8 g CLA groups (P: = 0.05 and P: = 0.02, respectively). No significant differences among the groups were observed in lean body mass, body mass index, blood safety variables or blood lipids. The data suggest that conjugated linoleic acid may reduce BFM in humans and that no additional effect on BFM is achieved with doses > 3.4 g CLA/d.
Conjugated linoleic acid (CLA) has been suggested by some animal studies to possess antiatherogenic properties. To determine, in humans, the effect of dietary CLA on blood lipids, lipoproteins, and tissue fatty acid composition, we conducted a 93-d study with 17 healthy female volunteers at the Metabolic Research Unit of the Western Human Nutrition Research Center. Throughout the study, subjects were fed a low-fat diet [30 energy percent (en%) fat, 19 en% protein, and 51 en% carbohydrate] that consisted of natural foods with the recommended dietary allowances for all known nutrients. After a 30-d stabilization period, subjects were randomly assigned to either an intervention group (n = 10) supplemented daily with capsules containing 3.9 g of CLA or a control group (n = 7) that received an equivalent amount of sunflower oil. The CLA capsules (CLA 65%) contained four major cis/trans geometric isomers (11.4% 9 cis-,11 trans-18:2; 10.8% 8 trans-,10 cis-18:2; 15.3% 11 cis-,13 trans-18:2; and 14.7% 10 trans-,12 cis-18:2) and their corresponding cis/cis (6.74% total) and trans/trans (5.99% total) varieties in smaller amounts. Fasting blood was drawn on study days 30 (end of the stabilization period), 60 (midpoint of the intervention period), and 93 (end of the intervention period). Adipose tissue samples were taken on days 30 and 93. CLA supplementation for 63 d did not change the levels of plasma cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. The weight percentage of CLA in plasma increased from 0.28 +/- 0.06 to 1.09 +/- 0.31 (n = 10, P < 0.05) after the supplementation. The 9 cis-,11 trans-isomer was the most prominent variety followed by the 11 cis-,13 trans- and 10 trans-,12 cis-isomers in lesser amounts. CLA in adipose tissue was not influenced by the supplementation (0.79 +/- 0.18 to 0.83 +/- 0.19 wt%) (n = 10) and the 9 cis-,11 trans-variety was the only isomer present. Thus, contrary to findings from some animal studies, CLA does not seem to offer health benefits, in the short term, regarding the prevention of atherosclerosis in humans. CLA supplementation for 2 mon did not alter the blood cholesterol or lipoprotein levels of healthy, normolipidemic subjects. The supplementation did increase CLA in the plasma but only 4.23% of the ingested CLA was present in the plasma at any given time. No adverse effect of CLA supplementation was detected in this study.
Numerous physiological effects are attributed to conjugated linoleic acid (CLA). The purpose of this presentation is to consider these effects with respect to the cis-9,trans-11 and trans-10,cis-12 CLA isomers. We review previously published data and present new findings that relate to underlying biochemical mechanisms of action. Both isomers are natural products. The cis-9,trans-11 isomer is the principal dietary form of CLA, but the concentrations of this isomer and the trans-10,cis-12 isomer in dairy products or beef vary depending on the diet fed to cows or steers, respectively. The trans-10,cis-12 CLA isomer exerts specific effects on adipocytes, in particular reducing the uptake of lipid by inhibiting the activities of lipoprotein lipase and stearoyl-CoA desaturase. The trans-10,cis-12 CLA isomer also affects lipid metabolism in cultured Hep-G2 human liver cells, whereas both the cis-9,trans-11 and trans-10,cis-12 CLA isomers appear to be active in inhibiting carcinogenesis in animal models. We present new findings indicating that the cis-9,trans-11 CLA isomer enhances growth and probably feed efficiency in young rodents. Accordingly, the effects of CLA on body composition (induced by trans-10,cis-12 CLA) and growth/feed efficiency (induced by cis-9,trans-11 CLA) appear to be due to separate biochemical mechanisms. We also show that a 19-carbon CLA cognate (conjugated nonadecadienoic acid, CNA) inhibits lipoprotein lipase activity as effectively as CLA in cultured 3T3-L1 adipocytes. Presumably, CNA is metabolized differently than the 18-carbon CLA isomers, so this finding indicates direct activity of the administered compound as opposed to acting via a metabolite.
Insulin resistance plays a major role in the pathophysiology of diabetes and is associated with obesity and cardiovascular disease. Excellent methods exist for the assessment of insulin sensitivity in the laboratory setting, such as the glucose clamp. However, these methods are not suitable for large population studies, and, thus, surrogate estimates of insulin sensitivity based on measurements in a single blood sample have been developed. Recently an index based on the logarithm and the reciprocal of the insulin-glucose product (QUICKI) has been proposed. QUICKI correlated with insulin sensitivity across the entire spectrum of glucose tolerance, but its performance was less satisfactory in normal subjects. Aim of this study was to ascertain whether the inclusion of fasting plasma free fatty acids concentration into QUICKI improves its association with insulin sensitivity in nonobese subjects. To test this hypothesis, we performed a euglycemic hyperinsulinemic clamp [40 mU/(m(2).min)] in 57 young, healthy, nonobese individuals with (n = 17) or without (n = 40) first-degree relatives affected by type 2 diabetes (the former group being an in vivo model of mild insulin resistance). We then compared the clamp-based index of insulin sensitivity with both QUICKI and a revised QUICKI, the latter index including the contribution of fasting free fatty acid concentration as well. The revised QUICKI considerably improved the relationship with the clamp-based index of insulin sensitivity (r = 0.51, P < 0.0001) with respect to QUICKI (r = 0.27, P < 0.05). In addition, the revised QUICKI revealed a reduction of insulin sensitivity in the offspring of type 2 diabetes (10%; P < 0.006) that QUICKI was unable to detect (3%; P = 0.28). In conclusion, this study suggests that the incorporation of fasting free fatty acid level into QUICKI is useful to improve its correlation with the clamp-based index of insulin sensitivity and its discriminatory power in case of mild insulin resistance. Further investigation is needed to ascertain its applicability to patients with obesity and type 2 diabetes.