The Biologically Active Isomers of Conjugated Linoleic Acid

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) deals with the setting of Dietary Reference Values (DRVs) for fats. A lower bound of the reference intake range for total fat of 20 energy % (E%) and an upper bound of 35 E% are proposed. Fat intake in infants can gradually be reduced from 40 E% in the 6 12 month period to 35–40 E% in the 2nd and 3rd year of life. For specific fatty acids the following is proposed: saturated fatty acid (SFA) and trans fatty acid intake should be as low as possible; not to set any DRV for cis-monounsaturated fatty acids; not to formulate a DRV for the intake of total cis-polyunsaturated fatty acids (PUFA); not to set specific values for the n-3/n-6 ratio; to set an Adequate Intake (AI) of 4 E% for linolenic acid; not to set any DRV for arachidonic acid; not to set an UL for total or any of the n 6 PUFA; to set an AI for alpha-linilenic acid (ALA) of 0.5 E% not to set an UL for ALA; to set an AI of 250 mg for eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) for adults; to set an AI of 100 mg DHA for infants (>6 months) and young children <24 months; to increase by 100 200 mg preformed DHA in addition to the AI for adults as an adequate supply of n-3 long chain PUFA during pregnancy and lactation; not to set any DRV for conjugated linoleic acid. For cholesterol it was decided not to propose a reference value beside the limitation on the intake of SFA.

https://orbit.dtu.dk/files/6355881/prod11324452634179.Scientific.pdf

Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol

▪ Abstract Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty acids found in beef, lamb, and dairy products that exist as positional and stereo-isomers of octadecadienoate (18:2). Over the past two decades numerous health benefits have been attributed to CLA in experimental animal models including actions to reduce carcinogenesis, atherosclerosis, onset of diabetes, and body fat mass. The accumulation of CLA isomers and several elongated/desaturated and β-oxidation metabolites have been found in tissues of animals fed diets with CLA. Molecular mechanisms of action appear to include modulation of eicosanoid formation as well as regulation of the expression of genes coding for enzymes known to modulate macronutrient metabolism. This review focuses on health benefits, metabolism, and potential mechanisms of action of CLA and postulates the implications regarding dietary CLA for human health.

Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action.

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6] commonly found in beef, lamb and dairy products. The most abundant isomer of CLA in nature is the cis-9, trans-11 (c9t11) isomer. Commercially available CLA is usually a 1:1 mixture of c9t11 and trans-10, cis-12 (t10c12) isomers with other isomers as minor components. Conjugated LA isomer mixture and c9t11 and t10c12 isomers alone have been attributed to provide several health benefits that are largely based on animal and in vitro studies. Conjugated LA has been attributed many beneficial effects in prevention of atherosclerosis, different types of cancer, hypertension and also known to improve immune function. More recent literature with availability of purified c9t11 and t10c12 isomers suggests that t10c12 is the sole isomer involved in antiadipogenic role of CLA. Other studies in animals and cell lines suggest that the two isomers may act similarly or antagonistically to alter cellular function and metabolism, and may also act through different signaling pathways. The effect of CLA and individual isomers shows considerable variation between different strains (BALB/C mice vs. C57BL/6 mice) and species (e.g., rats vs. mice). The dramatic effects seen in animal studies have not been reflected in some clinical studies. This review comprehensively discusses the recent studies on the effects of CLA and individual isomers on body composition, cardiovascular disease, bone health, insulin resistance, mediators of inflammatory response and different types of cancer, obtained from both in vitro and animal studies. This review also discusses the latest available information from clinical studies in these areas of research.

Biological effects of conjugated linoleic acids in health and disease.

Functional foods can be considered to be those whole, fortified, enriched or enhanced foods that provide health benefits beyond the provision of essential nutrients (e.g., vitamins and minerals), when they are consumed at efficacious levels as part of a varied diet on a regular basis. Linking the consumption of functional foods or food ingredients with health claims should be based on sound scientific evidence, with the "gold standard" being replicated, randomized, placebo-controlled, intervention trials in human subjects. However, not all foods on the market today that are claimed to be functional foods are supported by enough solid data to merit such claims. This review categorizes a variety of functional foods according to the type of evidence supporting their functionality, the strength of that evidence and the recommended intakes. Functional foods represent one of the most intensively investigated and widely promoted areas in the food and nutrition sciences today. However, it must be emphasized that these foods and ingredients are not magic bullets or panaceas for poor health habits. Diet is only one aspect of a comprehensive approach to good health.

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Functional Foods: Benefits, Concerns and Challenges—A Position Paper from the American Council on Science and Health

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 Reduces Body Fat Mass in Overweight and Obese Humans

Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans

After 12 mo in a randomized, double-blind, placebo-controlled trial of conjugated linoleic acid (CLA) supplementation (2 groups received CLA as part of a triglyceride or as the free fatty acid, and 1 group received olive oil as placebo), 134 of the 157 participants who concluded the study were included in an open study for another 12 mo. The goals of the extension study were to evaluate the safety [with clinical chemistry analyses and reported adverse events (AEs)] and assess the effects of CLA on body composition [body fat mass (BFM), lean body mass (LBM), bone mineral mass (BMM)], body weight, and BMI. All subjects were supplemented with 3.4g CLA/d in the triglyceride form. Circulating lipoprotein(a) and thrombocytes increased in all groups. There was no change in fasting blood glucose. Aspartate amino transferase, but not alanine amino transferase, increased significantly. Plasma total cholesterol and LDL cholesterol were reduced, whereas HDL cholesterol and triglycerides were unchanged. The AE rate decreased compared with the first 12 mo of the study. Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo. LBM and BMM were not affected in any of the groups. Changes in body composition were not related to diet and/or training. In conclusion, this study shows that CLA supplementation for 24 mo in healthy, overweight adults was well tolerated. It confirms also that CLA decreases BFM in overweight humans, and may help maintain initial reductions in BFM and weight in the long term.

Supplementation with Conjugated Linoleic Acid for 24 Months Is Well Tolerated by and Reduces Body Fat Mass in Healthy, Overweight Humans

The main objective of the study was to investigate the safety of conjugated linoleic acid (CLA) in healthy volunteers. The effect of CLA on body composition was also investigated.



The trial design was a randomized, double-blind placebo controlled study including 60 overweight or obese volunteers (body mass index (BMI) 27.5—39.0 kg/m2). The subjects were divided into two groups receiving 3.4 g CLA or placebo (4.5 g olive oil) daily for 12 weeks. The safety was evaluated by analysis of blood parameters and by clinical examinations at baseline and week 12. Vital signs and adverse events were registered at baseline, week 6, and week 12. Bio Impedance Assessment was applied for body composition measurements.



55 subjects completed the study. Adverse events occurred in 10% of the subjects. No difference in adverse events or other safety parameters was found between the treatment groups. Small changes in the laboratory safety data were not regarded as clinically significant. Moreover, no clinically significant changes in vital signs were observed in any of the groups.



In the CLA group, mean weight was reduced by 1.1 kg (paired t-test p = 0.005), while mean BMI was reduced by 0.4 kg/m2(p = 0.007). However, the overall treatment effect of CLA on body weight and BMI was not significant. There were no differences found between the groups with regard to efficacy parameters.



The results indicate that CLA in the given dose is a safe substance in healthy populations with regard to the safety parameters investigated.

Safety of conjugated linoleic acid (CLA) in overweight or obese human volunteers

CLA mixtures are now commercially available. They differ from each other with respect to their content of CLA isomers and their degree of purification. As a group of natural FA, CLA have been widely assumed to be safe. However, the suspected presence of both impurities and particular isomers might induce undesirable side effects. Despite this potential health risk, only a few CLA preparations have been tested under rigorous conditions for clinical efficacy and safety. Based on the limited results available, it is possible to suggest that preparations enriched in c9,t11 and t10,c12 isomers are preferable for human consumption compared to preparations containing four isomers, in terms both of safety and efficacy.

Ola Gudmundsen

Papers

Conjugated Linoleic Acid Reduces Body Fat Mass in Overweight and Obese Humans

Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans

Supplementation with Conjugated Linoleic Acid for 24 Months Is Well Tolerated by and Reduces Body Fat Mass in Healthy, Overweight Humans

Safety of conjugated linoleic acid (CLA) in overweight or obese human volunteers

Clinical trial results support a preference for using CLA preparations enriched with two isomers rather than four isomers in human studies.