Conjugated linoleic acid (CLA)

Bovine milk, milk products and bovine meat are the main dietary sources of the cis9, trans 11 isomer of conjugated linoleic acid (9c,11t-CLA) [63]. In most cases this isomer is the most abundant CLA-isomer in bovine milk [64]. Minor amounts of other geometrical and positional isomers of CLA also occur in milk (such as the 7t, c9 and 10t, 12c-CLA), with different biological effects [65,66]. Milk content of 9c,11t-CLA vary considerably (see later), but may constitute about 0,6 % of the fat fraction [67,68].

The health effects of CLA have been discussed [69]. Administration of 9c,11t CLA has shown to modulate plasma lipid concentration in both human and animal models [70,71]. Some studies [70-72] but not all [73] have shown that addition of CLA isomer mixtures (9c,11t and 10t,12c) to a diet affects plasma lipids. Studies have shown that especially 9c,11t-CLA can improve plasma cholesterol status [70,71]. In a study with healthy men Tricon et al. [70] found a significant reduction in plasma total cholesterol concentration by 9c,11t-CLA. The results concerning the effects of CLA on serum triglycerides are controversial [66,70,74,75]. Tricon et al. [70] observed a decrease in serum triglycerides by 9c,11t-CLA compared to 10t,12c-CLA in humans, and Roche et al. found serum triglycerides and unesterified FA to be decreased by 9c,11t-CLA in ob/ob-mice [66].

In experimental animals CLA has been shown to have anticarcinogenic effects [76]. Prospective data from a Swedish study suggest that high intakes of high-fat dairy foods and CLA may reduce the risk of colorectal cancer [77]. The knowledge of CLA's effects in metabolism and the reported anti-proliferative and pro-apoptotic effect of CLA on various types of cancer cells [78] makes CLA to an interesting, and possible therapeutic agent in nutritional cancer therapy. The mechanisms by which CLA might affect metabolism are many. It is suggested that CLA competes with arachidonic acid in the cyclooxygenase reaction, resulting in reduced concentration of prostaglandins and tromboxanes in the 2-series [79]. CLA may suppress the gene expression of cyclooxygenase [80], and reduce the release of pro-inflammatory cytokines such as TNF-alpha and interleukines in animals [79]. CLA also activates the PPARs transcription factors [63], and CLA may reduce the initial step in NF-kappa B activation and thereby reduce cytokines, adhesions molecules and other stress-induced molecules [81].

Trans vaccenic acid (VA)

The main trans 18:1 isomer in milk fat is vaccenic acid, (18:1, 11t, VA), but trans double bounds in position 4 to 16 is also observed in low concentrations in milk fat [82].

The amount of VA in milk fat may vary; constituting 1.7% [83], or 4–6 % of the total fatty acid content [84]. Typically, the concentration of VA may be about 2–4% when the cows are on fresh pasture and about 1–2 % on indoor feeding [67]. Normally, naturally increase in 9c,11t-CLA in milk also results in increased concentration of VA [85].

VA has a double role in metabolism as it is both a trans fatty acid and a precursor for 9c,11t-CLA. As demonstrated by Kay et al. [86] approximately 90 % of 9c,11t-CLA in milk fat was produced endogenously involving delta-9-desaturation of VA. Vaccenic acid can be converted to 9c,11t-CLA in rodents [87], pigs [88] and humans [89].

Trans fatty acids have been shown to increase blood lipids [90]. Industrially produced trans fat are shown to increase the risk of coronary heart disease as they have adverse influence on the ratio of LDL on HDL, and on Lp(a) [44,91]. It has been questioned if VA has these same adverse effects. In one study with hamster, Meijer et al. [92] found that VA was more detrimental to cardiovascular risk than elaidic acid (18:1, 9t) due to a more increasing effect on LDL/HDL cholesterol ratio. Furthermore, Clifton et al. [93] showed that VA was an independent predictor of a first myocardial infarction. In contrast to this, it has been shown by Willett et al. [28] that trans fat from animals did not give an increased risk for CHD. As recently demonstrated by Tricon et al [85], a combination of naturally increased concentration of VA and 9c,11t-CLA in milk fat did not result in detrimental effects on most cardiovascular disease risk parameters. However, it remains to clarify if VA has unhealthy effects on blood lipids.