Rumenic acid

In the initial study by Ip et al. (1991), the authors fed rats a standard diet or that diet supplemented with 0.5, 1.0 or 1.5% CLA, 2 weeks prior to and following administration of the carcinogen 7, 12-dimethylbenz[a]anthracene (DMBA). At the end of the experiment, the total number of mammary adenocarcinomas in the groups fed 0.5, 1.0 and 1.5% CLA was reduced by 32, 56 and 60% compared to the control, respectively. Tumor incidence, tumor multiplicity (number of tumors per rat) and total tumor weight were reduced to a similar degree. This tumor inhibition by CLA is in contrast to linoleic acid, which promotes tumor development in this model. 

This group subsequently conducted numerous studies to explore mechanisms contributing to the anti-cancer action of CLA (reviewed in Ip et al., 2003). Notable findings were  

The age of the rat when CLA supplementation is commenced can influence outcome. When rats were fed CLA from weaning at 21 days of age until day 51 only, then administered a carcinogen at day 57, they were protected from subsequent tumor development. However, when CLA entered the diet for the same period of time after carcinogen administration and when the animals were older, there was no protection against tumor development. A continuous intake of CLA was then necessary to obtain equivalent protection. The period from 21 to 51 days of age corresponds to development of the mammary gland to adult stage morphology. 

Further studies showed that during the pubescent period, CLA reduced the development and branching of the expanding mammary ductal tree. There was also a reduction in the density and rate of proliferation of terminal end bud (TEB) cells. TEBs are the least differentiated and most actively growing glandular ductal structures, which are most abundant from weaning to puberty and are the site of chemically induced tumors (Ip et al., 2003). 

The early studies with CLA used a synthetic mixture of many isomers, but usually contained about 70-80% of near equal quantities of RA and trans-10, a. v-12-Cix 2- Recently, a number of studies have demonstrated that both isomers can inhibit mammary tumor development (Ip et al., 2003). 

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The term conjugated linoleic add (CLA) refers to a mixture of positional and geometric isomers of linoleic add with a conjugated double bond system milk fat can contain over 20 different isomers of CLA. CLA isomers are produced as transient intermediates in the rumen biohydrogenation of unsaturated fatty acids consumed in the diet. However, cis-9, trans-11 CLA, known as rumenic acid (RA), is the predominant isomer (up to 90% of 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 A9-desaturase in the mammary gland and other tissues. 

Figure 3.1. Chemical structures of linoleic acid (cis-9, cis-12 18 2 A), trans-10, cis-12 conjugated linoleic acid (B), rumenic acid (cis-9, trans-11 conjugated linoleic acid C) and vaccenic acid (trans-11 18 1 D).

Figure 3.2. Pathways for ruminal and endogenous synthesis of rumenic acid (cis-9, trans-11 CLA) in the lactating dairy cow. Pathways for biohydrogenation of linoleic and linolenic acids yielding vaccenic acid trans-11 18 1) are shown in the rumen box and endogenous synthesis by A9-desaturase is shown in the mammary gland box. Adapted from Bauman et at. (2003).

Rumenic acid A proposed common name for the major conjugated linoleic acid isomer found in natural products. Lipids. 33, 835. 

Palmquist, D.L., St Pierre, N., McClure, K.E. 2004. Tissue fatty acid profiles can be used to quantify endogenous rumenic acid synthesis in lambs. J. Nutr. 134, 2407-2414. 

Milk fat contains several compounds that have demonstrated anticancer activity in animal models. The more important ones are rumenic acid, a potent inhibitor of mammary tumorigenesis, sphingomyelin and other sphingolipids that prevent the development of intestinal tumors and butyric acid, which prevents colon and mammary tumor development. Emerging evidence suggests that milk fat can prevent intestinal infections, particularly in children, prevent allergic disorders, such as asthma and improve the level of long-chain co-3 polyunsaturated fatty acids in blood. 

Fatty acids with trans or non-methylene-interrupted unsaturation occur naturally or are formed during processing for example, vaccenic acid (18 1 Hr) and the conjugated linoleic acid (CLA) rumenic acid (18 2 9tllc) are found in dairy fats. Hydroxy, epoxy, cyclopropane, cyclopropene acetylenic, and methyl branched fatty acids are known, but only ricinoleic acid (12(/f)-hydroxy-9Z-octadecenoic acid) (2) from castor oil is used for oleochemical production. OUs containing vernolic acid (12(5),13(/ )-epoxy-9Z-octadecenoic acid) (3) have potential for industrial use. 

Kramer, J.K.G., Parodi, P.W., Jensen, R.G., Mossoba, M.M., Yurawecz, M.P., and Adlof, R.O. 1998. Rumenic acid A proposed common name for the major conjugated linoleic acid isomer found in natural products. Lipids 33, 835. 

Loor, J.J., Lin, X., and Herbein, J.H. 2002. Dietary /rajw-vaccenic acid trans 11-18 1) increases concentration of cis 9, trans 11-conjugated linoleic acid (rumenic acid) in tissues of lactating mice and suckling pups. Reprod. Nutr. Dev. 42, 85-99. 

As the result of feeding cows encapsulated fat, desirable milk fat modification can be obtained so that the PEFA in fat are limited. A conjugated linoleic acid (CLA), also referred to as rumen acid cis-9, trans-11 -octadecadienoic acid), is a nutritionally important fat component. If present in the human diet, this acid prevents obesity,... 

The first discovered CLA precursor is linoleic acid cis-9,cis- 2 18 2). The double bond of linoleic acid present further for the carboxyl group can be translocated by cis- 2,trans- isomerase (Kepler Tove, 1967) and the resulting rumenic acid cis-9,trans- CLA) is then hydrogenated by the reductase of Butyrivibrio fibrisol-vens to vaccenic acid (frans-W 18 1) (Hughes, Hunter, Tove, 1982). These steps occur relatively fast, whereas the hydrogenation of vaccenic add to stearic acid is... 

CLA can also be synthesised in the human colon. Some bacterial strains normally present in the human large intestine (Lactobacillus, Propionibacterium and Bifidobacterium species and some Clostridium-like bacteria) have been found to metabohse linoleic acid and form CLA that is converted further to trans-1118 1 in vitro. Vaccenic acid may be also a precursor of rumenic acid (cis-9,trans-ll CLA) in human tissues (Devillard, McIntosh, Duncan, Wallace, 2007). 

The anti-diabetic effect of CLA may depend on both species and types of isomer. Rumenic acid seemed to be inactive (Martin Valeille, 2002), but the role of Irans-10,cis-12 isomer is controversial some studies verified decreasing glucose levels and increased insulin sensitivity with increased intake of lrans-10,cis-l2 CLA (see the review by Khanal, 2004), while others reported opposite effects - that is, the promotion of insnlin resistance (Khanal, 2004 Moloney, Yeow, Mullen, Nolan, Roche, 2004 Wang Jones, 2004). 

Hennessy, A. A., Ross, R. P., Stanton, C., Devery, R., Murphy, J. J. (2007). Development of dairy based functional foods enriched in conjugated linoleic acid with special reference to rumenic acid. In M. Saarela (Ed.), Functional dairy products (pp. 443 94). New York, NY, USA CRC Press. 

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