The effect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects

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相似文献   

The effects of conjugated linoleic acid on human health-related outcomes

Conjugated linoleic acid (CLA) is a collective term for a mixture of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has received considerable attention as a result of animal experiments that report anti-carcinogenic, anti-atherogenic and anti-diabetic properties, and modulation of body composition and immune function. Several studies of CLA supplementation in human subjects have now been published, but in contrast to animal studies there has been marked variation between reports on the health-related outcomes. The consensus from seventeen published studies in human subjects is that CLA does not affect body weight or body composition. Some detrimental effects of the trans-10,cis-12 CLA isomer have also been reported in terms of altered blood lipid composition and impaired insulin sensitivity. Finally, CLA has only limited effects on immune functions in man. However, there have been reports of some interesting isomer-specific effects of CLA on the blood lipid profile, but not on immune function. These isomer-specific effects need further investigation. Until more is known, CLA supplementation in man should be considered with caution.     

Enrichment of n‐3 fatty acids and conjugated linoleic acid in beef: ProSafeBeef

ProSafeBeef is a 5‐year integrated project funded by the European Commission under the sixth Framework Programme. The overall aim is to advance beef safety and quality across Europe and the work programme spans seven integrated “pillars”. Pillar 3 is concerned with producing safe beef and beef products with enhanced nutritional and eating quality characteristics. A particular focus is on the development of strategies to enhance the concentrations in beef of those fatty acids considered to be of benefit to human health, without causing a detrimental effect on the appearance, shelf‐life or eating quality of the beef. There is accumulating evidence of the importance of long‐chain n‐3 (omega‐3) polyunsaturated fatty acids (PUFAs) for human health and disease prevention, and also evidence from experimental studies that has shown anticarcinogenic, antiatherogenic, and anti‐obesity effects of two isomers of conjugated linoleic acid (CLA). Based on this evidence, the major focus of research efforts to improve the nutritional value of beef has been on increasing the concentration of the n‐3 PUFAs and CLA. Considerable progress has been made within pillar 3 of ProSafeBeef to meet this aim, primarily by manipulating the diet of cattle. Fundamental information on ruminal lipid metabolism and on the control and/or prevention of ruminal hydrogenation of dietary lipids arising from research within ProSafeBeef will facilitate the production of beef with a ‘healthier’ fatty acid profile. Moreover, strategies will be defined for industry on how to optimise nutritional and sensory properties and oxidative quality of beef products, by combining the nutritional enhancement made in the live animal together with target levels of functional ingredients to be added during processing.     

Physiological properties of conjugated linoleic acid and implications for human health.

Conjugated linoleic acid (CLA) refers to a mixture of positional and geometric dienoic isomers of linoleic acid found naturally in animal products of ruminant sources. Recent interest in CLA research stems from the well-documented anticarcinogenic, antiatherogenic, antidiabetic, and antiobesity properties of CLA in rodents. However, there has been very little published human research on CLA. This review discusses the physiologic properties of CLA and their potential implications for human health.     

Conjugated linoleic acids: why the discrepancy between animal and human studies?

Conjugated linoleic acids (CLA) are positional and geometric isomers of linoleic acid. In animals, CLA consumption reduces body fat but results in humans are less conclusive. This review of the literature on CLA and loss of body fat or body weight in humans was conducted to explore the reasons for the discrepancy between animal and clinical trials. It indicates that the incongruity between human and animal data is largely related to methodological differences in the experimental design, including age and gender and, to a lesser extent, to CLA dose and isomers. The relatively unknown metabolic fate of CLA in humans may also be a contributing factor that helps explain the lack of consistency for CLA efficacy across studies.     

Conjugated linoleic acid blocks estrogen signaling in human breast cancer cells

Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid found in dairy products and meat from ruminants, has been widely shown to possess anticarcinogenic activity against breast cancer both in vitro and in animal models. However, little information is available concerning the mechanisms of the antitumor effects of these compounds. In this study, we investigated whether CLA has direct antiestrogenic activity in estrogen receptor positive (ER+) breast cancer cells. Treatment of the ER+ cell line, MCF-7, with 5 purified CLA isomers as well as "mixed" CLA showed a dose-dependent growth inhibition with the 9cis,11cis and 9cis,11trans being the most and least potent isomers, respectively. In assessing effects on a number of variables that play obligatory roles in the estrogen signaling pathway, we determined that CLA treatment downregulated ERalpha expression at both mRNA and protein levels and decreased binding activity of nuclear protein to a canonical estrogen response element (ERE(v)). Using a reporter gene construct (ERE(v)-tk-Luc) that was transiently transfected into MCF-7 cells, we also demonstrated inhibition of promoter activity by CLA that was directly mediated by blockage of activity through the ERE. The results indicated that the order of potency of the CLA isomers for inhibiting activation of ERE(v) was similar to that demonstrated for their antiproliferative activity on MCF-7 cells. Taken together, these findings demonstrate that CLA compounds possess potent antiestrogenic properties that may at least partly account for their antitumor activity on breast cancer cells.     

The change in conjugated linoleic acid concentration in blood of Japanese fed a conjugated linoleic acid diet

Conjugated linoleic acid (CLA) is a collective term used for fatty acids with a conjugated double bond that are geometrical and positional isomers of linoleic acid. Anti-obesity and anti-cancer properties, an immunopotentiation effect, and promotion of bone formation by CLA have been shown in cell culture and animal studies. A mixture of 9c11t- and 10t12c-CLA is now used as a health food supplement after testing in clinical trials. These trials focused on improvement of lipid metabolism by CLA, whereas few studies have examined absorption and metabolism of CLA in humans. In addition, there is no report concerning absorption and metabolism of CLA in Japanese. This study was designed to examine CLA concentration in blood, the elimination rate of CLA, and metabolic differences between 9c11t-CLA and 10t12c-CLA in blood in Japanese who ingested CLA (about 2 g/d, equal weights of 9c11t-CLA and 10t12c-CLA) for 3 wk. Blood samples were collected 1 wk before the 3-wk period, on the first and last days of the period, and 1 wk after the end of the period, and the CLA concentration and distribution in blood were investigated. The CLA concentration in blood was significantly increased by CLA ingestion and reached 36 μmol/L. The CLA concentration in blood one week after the intake period was significantly lower than that at the end of CLA intake. The 10t12c-CLA level in plasma decreased faster than that of 9c11t-CLA. This suggests faster metabolism (fatty acid β oxidation) of 10t12c-CLA compared with 9c11t-CLA.     

Conjugated linoleic acid and human health-related outcomes

Summary There has been increasing interest in health benefits of conjugated linoleic acid (CLA) based on findings with laboratory animals. Some human studies have also suggested health benefits of CLA, but because of the mixes used these could not be readily associated with a particular isomer of CLA. A recent study examined the separate effects of near‐pure cis‐9,trans‐11 CLA (c9,t11 CLA) or trans‐10,cis‐12 CLA (t10,c12 CLA) on health‐related outcomes in healthy young males. The CLA isomers were provided in capsules and at three doses (up to about 2.5 g/day) each for 8 weeks. Both c9,t11 and t10,c12 CLA were incorporated in a dose–response fashion into blood lipids and cells. At the doses and durations used, neither isomer of CLA affected bodyweight, body mass index or body composition, insulin sensitivity, immune function or markers of inflammation. However, at the doses and durations used, c9,t11 and t10,c12 CLA had opposing effects on blood lipid concentrations. Altered dairy cow‐feeding practices were used to produce c9,t11 CLA‐rich milk and, from this ultra heat‐treated milk, cheese and butter were produced. The milk and the dairy products made from it had ninefold higher contents of c9,t11 CLA, higher contents of n‐3 fatty acids and lower contents of total fat and of saturated fatty acids. They also contained much higher contents of trans‐vaccenic acid (tVA). The modified dairy products were used in a 6‐week controlled dietary intervention study in healthy middle‐aged males. c9,t11 CLA and tVA were incorporated from dairy products into blood lipids and cells. Consumption of the CLA‐rich (and tVA‐rich) dairy products did not affect bodyweight or body mass index, insulin sensitivity or inflammatory markers. However, there were some detrimental effects on blood lipids. These effects may be due to tVA rather than to c9,t11 CLA, as they are consistent with the effects of trans fatty acids and not consistent with the effects of c9,t11 CLA identified in the earlier study with c9,t11 CLA in capsules.     

Ruminant meat as a source of conjugated linoleic acid (CLA)

Summary Ruminant meat is a natural source of conjugated linoleic acid (CLA). Evidence has shown that CLA has many potential health benefits on cancer, coronary heart disease and diabetes. However, to date, all of the published research has been conducted in animals and there are few data in relation to the potential health benefits of CLA in humans. Lamb is the richest meat source of CLA. The main CLA isomer found in meat is c 9, t 11. Research has shown that cooking or storing meat does not alter its CLA content, but it can be changed by manipulating the diet of the animal. Little information is available that quantifies the contribution of meat to CLA intake. More research is required to further improve our knowledge on the role that meat can play as a vehicle that naturally supplies dietary CLA.     

Effect of conjugated linoleic acid on body composition and plasma lipids in humans: an overview of the literature

Studies in mice have indicated that feeding diets containing 0.5-1% conjugated linoleic acid (CLA) considerably reduces body fat. These findings have attracted much interest because of the potential use of CLA as a tool to promote weight loss in humans. Several CLA studies in humans have now been published, and the objective of the present review was to give an overview of these experiments. Most of the studies were done in free-living subjects and were not strictly controlled for nutrient and energy intakes. None of the studies found a significant reduction in body weight, and only 2 studies showed a significant but relatively small body fat-lowering effect. Some studies suggested that CLA may have a tendency to increase lean body mass. Furthermore, there are indications from animal studies that CLA may have effects on plasma lipids. However, only one study in humans showed a significant HDL-cholesterol-lowering effect of CLA; in all the other studies, there were no significant effects on plasma total, LDL-, and HDL-cholesterol concentrations or on plasma triacylglycerol concentrations. Thus, the results of the studies in humans indicate that the effect of CLA on body fat is considerably less than that anticipated from mice studies and that CLA has no major effect on plasma lipids.     

Inverse association between dietary and serum conjugated linoleic acid and risk of breast cancer in postmenopausal women

Conjugated linoleic acid (CLA) is anticarcinogenic in experimental animal studies. We studied dietary and serum CLA in Finnish patients with breast cancer in 1992-1995. Participants were consecutive women with breast cancer (68 premenopausal and 127 postmenopausal) and population-based control women (75 premenopausal and 133 postmenopausal), matched for age and area of residence. Diet was assessed by a validated food frequency questionnaire and the fatty acid composition of serum by gas-liquid chromatography. In postmenopausal women, dietary CLA, serum CLA, myristic acid, and trans-vaccenic acid were significantly lower in cases than in controls. The odds ratio for breast cancer in the highest quintile vs. the lowest was 0.4 [95% confidence interval (CI) = 0.2-0.9]for CLA, 0.3 (95% CI = 0.1-0.7) for myristic acid, and 0.3 (95% CI = 0.1-0.7) for trans-vaccenic acid in serum. The odds ratios remained similar after adjustment for known risk factors of breast cancer. A diet composed of CLA-rich foods, particularly cheese, may protect against breast cancer in postmenopausal women, but it is impossible to assess the independent effects of CLA in this study. The findings may be of relevance for food production, inasmuch as it is possible to increase CLA and its precursor trans-vaccenic acid in foods by modifying the feeding of ruminants.     

Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model.

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 modulation of risk factors associated with atherosclerosis

Conjugated linoleic acid (CLA) has been the subject of extensive investigation regarding its possible benefits on a variety of human diseases. In some animal studies, CLA has been shown to have a beneficial effect on sclerotic lesions associated with atherosclerosis, be a possible anti-carcinogen, increase feed efficiency, and act as a lean body mass supplement. However, the results have been inconsistent, and the effects of CLA on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific. Similarly, CLA trials in humans have resulted in conflicting findings. Both the human and animal study results may be attributed to contrasting doses of CLA, isomers, the coexistence of other dietary fatty acids, length of study, and inter-and/or intra-species diversities. Recent research advances have suggested the importance of CLA isomers in modulating gene expression involved in oxidative damage, fatty acid metabolism, immune/inflammatory responses, and ultimately atherosclerosis. Although the possible mechanisms of action of CLA have been suggested, they have yet to be determined.     

Estimation of conjugated linoleic acid intake by written dietary assessment methodologies underestimates actual intake evaluated by food duplicate methodology

Conjugated linoleic acids (CLA) are conjugated isomers of linoleic acid, which may promote health with regard to cancer, heart disease, diabetes, bone formation, growth modulation and immunity. The c9,t11 isomer of CLA, rumenic acid (RA), is the major isomer present in the diet. However, dietary intakes of CLA and RA by humans have not been examined rigorously, nor has the relationship between dietary CLA or RA and health (e.g., body composition). Three-day dietary records (DR) were collected from adult men (n = 46) and women (n = 47) and analyzed using a nutrient database modified to contain total CLA and RA. Simultaneously, 3-d food duplicates (FD) were collected to determine analytically individual fatty acid intakes, including those of total CLA and RA. Chronic total CLA and RA intakes were estimated using a semiquantitative food-frequency questionnaire (FFQ). Body composition was estimated using body mass index and percentage of body fat. Total CLA intake was estimated from FD to be 212 +/- 14 and 151 +/- 14 mg/d (mean +/- SEM) for men and women, respectively; RA intake was estimated to be 193 +/- 13 and 140 +/- 14 mg/d for men and women, respectively. In general, CLA and RA intakes estimated by DR and FFQ were significantly lower than those estimated by FD. Body composition was not significantly related to dietary total CLA or RA intake. In conclusion, results suggest that DR and FFQ methodologies are not reliable estimators of individual total CLA and RA intakes and may underestimate total CLA and RA intakes of groups. Intake of total CLA and RA was found to be significantly lower than that suggested previously by others.     

Impact of conjugated linoleic acid on bone physiology: proposed mechanism involving inhibition of adipogenesis

Conjugated linoleic acid (CLA) supplementation decreases adipose mass and increases bone mass in mice. Recent clinical studies demonstrate a beneficial effect of CLA on reducing weight and adipose mass in humans. This article reviews possible biological mechanisms of action of CLA on bone metabolism, focusing on modulation of nuclear receptor peroxisome proliferator-activated receptor gamma activity to steer mesenchymal stem cell differentiation toward an adipose and away from an osteoblast lineage. Clinical studies of the effects of CLA on bone mass and clinical implications of the effects of CLA on bone health in humans are summarized and discussed.     

Conjugated linoleic acid (CLA): Good or bad trans fat?

Even though trans fatty acids (TFAs) are present in natural sources such as foods from ruminant origins, the development of partially hydrogenated vegetable oil contributed to a significant increase in total TFAs consumption in humans. Currently, TFA consumption is considered to be a risk factor for coronary heart diseases. Researchers are now starting to discover that not all TFAs behave in a similar manner, that is, isomer specificity may be found. Among non-conjugated TFAs, plant originated TFAs (mainly elaidic and linolelaidic acids) are particularly linked to increased risk for coronary heart diseases, while animal originated TFAs (mainly vaccenic acid) are not. Among conjugated TFAs, two major isomers of conjugated linoleic acid (CLA), cis-9,trans-11 and trans-10,cis-12, show distinctive biological activities. A number of clinical trials of CLA with effects on body composition have been reported, but effects on coronary heart disease risk factors have been inconsistent. Meanwhile, safety concerns regarding CLA, in particular isomer specificity, have also been raised. Thus, it is critical to identify isomer specific effects of TFAs on particular risk factors, to determine their health impact.     

Colonic anti-inflammatory mechanisms of conjugated linoleic acid

Conjugated linoleic acid (CLA) is a mixture of positional (e.g. 7,9; 9,11; 10,12; 11,13) and geometric (cis or trans) isomers of octadecadienoic acid. This compound was first shown to prevent mammary carcinogenesis in murine models. Later investigations uncovered a number of additional health benefits, including decreasing atherosclerosis and inflammation while enhancing immune function. The mechanisms of action underlying these biological properties are not clearly understood. The aim of this review is to highlight recent advances in CLA research related to experimental inflammatory bowel disease. In addition, two possible mechanisms of action (i.e. endoplasmic and nuclear) were discussed in detail in the context of enteric inflammatory disorders. Conjugated linoleic acid was first implicated in down-regulating the generation of inducible eicosanoids (i.e. PGE(2) and LTB(4)) involved in early micro-inflammatory events (endoplasmic). More recently, CLA has been shown to modulate the expression of genes regulated by peroxisome proliferator-activated receptors (PPARs; nuclear). In pigs, prolonged dietary CLA treatment stimulated the expression of PPAR-gamma in the muscle. Thus, evidence supporting both mechanistic theories of CLA acting through eicosanoid synthesis and PPAR activity is available. The further understanding of the anti-inflammatory mechanisms of action of CLA may yield novel nutritional therapies for enteric inflammation.     

Conjugated linoleic acid alters matrix metalloproteinases of metastatic mouse mammary tumor cells

Conjugated linoleic acid (CLA) is a group of linoleic acid derivatives that has been implicated in animal studies to reduce a number of components of mammary tumorigenesis. Previously, we showed that CLA could alter the latency and metastasis of the highly metastatic transplantable line 4526 mouse mammary tumor. Several possible mechanisms have been proposed for the actions of CLA, but here we assessed how CLA may act to alter the expression and activity of matrix-modifying proteins within tumors from line 4526. In vitro, highly metastatic mouse mammary tumor cells had significantly decreased invasiveness after treatment with CLA, an indication that matrix-modifying proteins may have been altered. Using these same highly metastatic cells, primary tumors were grown in mice of separate groups fed 0, 0.1, 0.5, and 1% CLA (wt:wt) and evaluated for their levels and activities of matrix-modifying enzymes, enzyme inhibitors, and enzyme activators. The addition of CLA to the diet increased steady-state levels of messenger RNA (mRNA) of the matrix metalloproteinases (MMP) -2 and -9 in primary tumors removed from mice. However, western analysis revealed that although relative levels of the proform of MMP-9 were consistent with the mRNA observations, MMP-2 proform levels were actually decreased by dietary CLA. The activity of MMP-2 was barely detectable, but gelatin zymography and an in vitro activity assay showed that MMP-9 activity was significantly decreased by CLA. The steady-state mRNA and protein levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2, natural inhibitors of MMP, were increased at higher dietary CLA levels relative to low or no CLA. Suppression of MMP activity, therefore, may be 1 pathway through which CLA reduces tumor invasion and spread.     

Conjugated linoleic acid: health implications and effects on body composition

Conjugated linoleic acid (CLA) is attracting interest because of its purported effects on body composition, specifically a reduction in body fat mass and an increase in lean body mass. Other reported beneficial health-related effects of CLA include anticarcinogenic, antiatherogenic, antidiabetogenic, and immune modulating properties. Because research on CLA has been almost exclusively in animals and the mechanism(s) by which CLA exerts its effects remain largely unknown, scientists are extremely cautious about making definitive statements about CLA. Despite the limited research on CLA in human subjects, numerous Internet websites and health food stores sell CLA supplements or CLA-containing products as weight loss or ergogenic aids. The increasing popularity of CLA as a dietary supplement makes it important that dietitians and health professionals are aware of CLA and are able to provide the public with science-based information regarding CLA.