**4. Conclusions**

fed rabbit models, but it raised all lipid and lipoprotein profile and indices in cholesterol-fed rabbits. Moreover, no consensus for atherogenic diets was observed based on their cholesterol and fat contents and the types of their fat, including pure cholesterol, lard, egg yolk powder,

**ANOVA**

*Q* df *P Q* df *P*

*Q*M—model sum of squares compared to chi-square distribution with *p*– 1 df (*p* is number of predictors in the model); *Q*<sup>R</sup> —residual sum of squares compared to chi-square distribution with *k*– *p*– 1 df (*k* is the number of studies) [48].

The resulting funnel graphs and the associated statistics based on Egger et al. [46] revealed a significant asymmetry and publication bias among studies. Therefore, publication or other sources of bias could be relevant in evaluating an overall effect of the selected nutritional interventions in lipid and lipoprotein outcomes in the cholesterol-fed rabbit model of

**Regression of Cholesterol on Std diff in means**

**Cholesterol**

**Figure 4.** Fixed-effect model—regression of dietary cholesterol surplus on standardized mean difference of lipid and

**-0.03 0.41 0.85 1.29 1.73 2.17 2.61 3.05 3.49 3.93 4.37**

**Table 1.** Fixed- and mixed-effect models—analysis of variance (ANOVA) table for combined lipid and lipoprotein

profile regression.

10 Lipoproteins - From Bench to Bedside

(pre)atherosclerosis.

**0.40 -2.04 -4.48 -6.91 -9.35 -11.79 -14.23 -16.66 -19.10 -21.54 -23.98**

lipid profiles and indices in a rabbit model of atherosclerosis.

**Std diff in means**

*Q*<sup>M</sup> 44.51969 1 0.00000 5.30338 1 0.02128 *Q*<sup>R</sup> 287.66695 34 0.00000 43.61079 34 0.12506 *Q*TOTAL 332.18664 35 0.00000 48.91418 35 0.05934

**Fixed-effect regression Mixed effects regression**

coconut oil, and/or safflower oil as well as different nutritional interventions.

These systematic review and meta-analyses of RCTs initially assess the robustness of choles‐ terol-fed rabbit of atherosclerosis since the causal role of cholesterol intake in progression and induction of atherosclerosis is not supported in some clinical trials (e.g., see [49]). These systematic review and meta-analysis showed high levels of heterogeneity among studies that used the cholesterol-fed rabbit model of atherosclerosis, which may be due to the lack of consensus on the dietary ingredients and formulation, the amount of dietary cholesterol surplus, the duration of cholesterol intake, and the analytical methodology in lipid and lipoprotein determination. In sum, for the first time, this meta-analysis showed that dietary cholesterol surplus could not be a reliable determinant of dyslipidemic atherosclerosis in cholesterol-fed rabbits. Rabbits in fact are vegetarians, and plants actually do not contain cholesterol. Thus, by itself, the model for studying atherogenesis by cholesterol feeding is far from being ideal or relevant for the situation in humans.
