Although limited, feeding studies in rodent models, with either induced or spontaneous dyslipidemia, do not support adverse health effects of VA on markers of CVD risk. Furthermore, findings suggest that VA supplementation may improve dyslipidemia by lowering circulating TG and/or cholesterol and attenuate atherosclerotic progression. Most studies with CLA have used mixtures of c9,t11-CLA and t10,c12-CLA; however, more recent studies suggest that these isomers may have divergent physiological effects. Some studies in various animal models have shown a beneficial effect of c9,t11-CLA on atherosclerotic lesions and risk factors of CVD. Inconsistencies in these data may be the result of differences in experimental models and species, base diet (chow vs. semipurified), and dose and isomer of CLA. It is important to note that although the estimated intake of c9,t11-CLA in humans varies considerably, the doses used in animal and cell culture studies (1.0% wt:wt on average, 3–5% energy) are typically high relative to intakes reported in epidemiological studies (~0.1% energy).
Results from epidemiological studies generally have shown an inverse or no association between rTFA intake and CHD across multiple geographical locations. However, a trend for a direct association was reported in 2 studies (10
). Inconsistencies in the data may be due in part to differences in the populations studied (i.e. gender) and in TFA intake. For example, in the Scottish Heart Health Study, intake of rTFA was relatively high (intake ranging from 1.2 to 4.9 g/d) compared with other studies (intake ranging up to 2.5 g/d). More epidemiologic data are needed to clarify the associations of rTFA intake and CHD risk. In particular, more information is needed to determine whether gender influences the cardiovascular effects of rTFA.
Results from clinical studies that have investigated the effects of VA and c9,t11-CLA on CVD risk factors remain unclear. There are multiple factors that may be contributing to the inconsistencies in the clinical data, including differences in dosage and isomer type, source of supplementation (capsules vs. diet), level of control of the overall diet, control diet used for comparison, duration of intervention, and study population (gender, age, and metabolic state of the participants, i.e. healthy vs. diseased). Some studies suggest that at lower doses, rTFA do not affect lipids and lipoproteins, but at higher doses, which are not attainable by diet, rTFA may have similar effects as iTFA.
Most of the studies that have investigated the effects of modified milk fat (resulting from dietary manipulation of dairy cows) have been conducted in animals. These studies have demonstrated a neutral or beneficial effect of VA/c9,t11-CLA on atherosclerosis and risk factors of CVD. It is important to note that modifying milk fat to increase VA/c9,t11-CLA also results in changes in other fatty acids, such as decreases in hypercholesterolemic SFA (lauric, myristic, and palmitic acids) and increases in neutral and hypocholesterolemic fatty acids (stearic acid, OA, and LA), thus making it difficult to distinguish which fatty acid modifications are responsible for any effects (i.e. decrease of SFA, increase of rTFA, increase of MUFA/PUFA, and/or increase of specific isomers of rTFA).
The anticarcinogenic properties of c9,t11-CLA have been studied in numerous experimental studies, various cell lines, and various animal models, both carcinogen induced and genetically modified. Animal studies generally show a benefit of c9,t11-CLA in mammary cancer and suggest that the anticarcinogenic effects of c9,t11-CLA may vary across species, with rats being more responsive than mice. Animal studies for gastrointestinal and prostate cancer are more limited and the data are inconclusive. Evidence from cell culture studies suggests that there may be isomer-specific effects of CLA, but results from different studies are very inconsistent. There are many factors that likely contribute to the discrepancies in the data from cell studies, including differences in tumor type, stage of development, treatment dose and isomer, and study duration. As mentioned above, it is important to keep in mind that the doses of CLA used in animal and cell culture studies are relatively high compared to the reported dietary intake in humans from epidemiological studies. There have been few animal studies with pure VA, largely due to high cost; however, the limited number of existing studies suggests that VA may inhibit tumor growth. Results from cell studies in human breast and colon adenocarcinoma cells generally show an inhibition of VA on cell growth. Although limited, the data suggest that dairy fat enriched with VA/c9,t11-CLA may reduce tumor development.
Epidemiological studies with VA and risk of cancer are very limited, although they generally do not support a benefit of VA intake. There are limitations to assessing dietary intake of rTFA isomers in epidemiological studies, because they are relatively minor lipids in the diet and are found in low concentrations in serum. Dietary questionnaires and databases may not accurately depict intake and food composition of VA and c9,t11-CLA. In some of the epidemiological studies, comparisons were made between groups (i.e. cases vs. controls) with very small or no significant differences in VA intake. Although results from some in vitro and in vivo studies suggest an anticarcinogenic effect of c9,t11-CLA, to date, there have been no clinical trials conducted to study the effects of VA or c9,t11-CLA on markers of cancer risk in humans; thus, it is difficult to draw conclusions regarding VA and c9,t11-CLA and various cancers.
In conclusion, although data from experimental models suggest that rTFA may beneficially affect risk of CVD and cancer, further research is needed to determine the effects of VA and c9,t11-CLA in humans as well as clarify the isomer-specific effects of CLA. Data from existing human studies do not consistently support the findings from experimental studies. Many of the clinical studies that have investigated the effects of rTFA on markers of cardiovascular risk have not been adequately powered; thus, the lack of detection of treatment effects reported in some studies may be due to insufficient statistical power. In addition, many studies have used doses of rTFA that are not realistically attainable via diet; the effect of rTFA in amounts that are commonly consumed in the diet remains unclear. Further clinical studies are warranted due to the limited number of studies and inconsistencies in the available data; specifically, adequately powered, controlled-feeding studies are needed to determine the effects of VA and c9,t11-CLA on markers of risk of CVD and cancer.