In our meta-analysis of randomized controlled trials, vitamin D supplementation provided a statistically significant increase in LDL-C (3.23 mg/dl). There was also a tendency towards an increase in TC (1.52 mg/dl) with supplementation of vitamin D, and the reductions in HDL-C (-0.14 mg/dl) and TG (-1.92 mg/dl) were both nonsignificant. The effect of vitamin D supplement on serum LDL-C levels seemed more significant in obese subjects and in studies with relatively shorter durations, while studies with longer durations only showed a significant reduction in HDL-C levels (-2.01 mg/dl). To our knowledge, this is the first meta-analysis looking at the effect of vitamin D supplement on lipid profiles. Two previous systematic reviews summarized the effect of vitamin D on serum lipid profiles [9, 32], however, no attempt to meta-analyze the data was made. By pooling information from all qualified randomized controlled studies, the results provided here are more precise and powerful than those from the individual studies.
Observational studies have shown that high serum 25(OH)D concentrations are associated with a favorable lipid profile . In the study by Jorde et al.  who included 8018 nonsmoking subjects in the cross-sectional study, there were highly significant positive associations between serum 25(OH)D and serum TC, HDL-C and LDL-C, and significant negative associations between serum 25(OH)D and both LDL-C/HDL-C ratio and TG after adjustment for gender, age, BMI and month of blood sampling. In consistent with this, an increase in serum 25(OH)D was associated with a significant decrease of serum TG in the longitudinal study involving 1762 nonsmoking subjects. Although these findings are provocative, it is important to understand the inherent limitations of observational studies. Associations found in cross-sectional studies are no proof of a causal relationship. Some common factors may be attributed to both the high serum 25(OH)D levels and favorable lipid profile. Individuals with habits of exercising outside frequently and eating nutritious food, which would elevate 25(OH)D levels, may have other healthy habits which could favorably affect lipid profiles. Therefore, intervention studies are needed to detect a causal relationship between 25(OH)D levels and lipids.
So far merely a few such intervention studies have been reported and the results provided by them are divergent. In addition, these studies are heterogeneous with respect to vitamin D dose, study duration, and the characteristics of subjects. In particular, the wide variation in the amount and formulation of supplemental vitamin D may be the most important contributor to the heterogeneity found in our results. To achieve 25(OH)D levels above 75 nmol/L, the recommended level for several health outcomes , the daily intake of at least 1000 IU (40 ug) vitamin D (cholecalciferol) would be required. Most of the studies included in this analysis used a high dosage of vitamin D (>/= 1000 IU) resulting in significantly elevated 25(OH)D levels after the treatment (Table 2). Notably, as the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-D) is considered to be more appropriate than 25(OH)D for assessing the links between vitamin D and lipids . It has been shown that 25(OH)D and 1,25-D had similar but independent biological effects. Unfortunately, few studies reported baseline 1,25-D levels and its changes after the intervention. As a result, it is not possible to evaluate the treatment effects of vitamin D on 1,25-D and the relationship between 1,25-D and lipids. Furthermore, not all included studies used vitamin D3 as supplementation. One study  used vitamin D2 and two other studies [22, 31] used alpha-calcidol. Vitamin D2 is less bioactive than vitamin D3, whereas alpha-calcidol is a direct precursor of 1,25-D. These differences make a direct comparison of study results difficult.
Subgroup analyses by duration of intervention revealed that vitamin D treatment has a more obvious effect on LDL-C in the shorter duration studies. This may be because longer duration studies are associated with poor compliance of the subjects. On the other hand, studies with longer durations showed a significant reduction in HDL-C levels. It is in agreement with the fact that in vitamin D receptor knockout mice, there are higher HDL-C levels and hepatic apoA-I mRNA expression relative to wild type mice . Experiments in cultured human hepatocytes also showed the metabolites of vitamin D had a potent inhibitory effect on apoA-I production and decreased both apoA-I secretion and apoA-I mRNA levels [37, 38].
It is reasonable to speculate that the treatment effects of vitamin D are influenced by its baseline levels and the increment in blood levels. However, it was not possible to assess the effect of baseline vitamin D status on lipids profile from this meta-analysis, as the populations among individual studies were heterogeneous. In addition, different geographical latitudes of the study sites might have further complicated the issue of baseline value of vitamin D, but the subgroup analysis by study sites revealed nonsignificant results.
Although we have excluded the studies that focused on patients in hemodialysis states, other confounders that may have an unexpected influence on lipids could not be eliminated. Among them, obesity is always associated with dyslipidemia which includes high levels of TG and LDL-C and low levels of HDL-C . Additionally, obesity may have an effect on vitamin D metabolism because adipose tissue in obese subjects preferentially uptakes vitamin D . Therefore, we conducted a subgroup analyses by the weight of subjects and it showed a greater increase in serum LDL-C concentrations in obese subjects. However, there was no significant effect in the normal weight subjects.
Our review has several limitations. First, we found few eligible studies and none of them were sufficiently powered because they had relatively small numbers of participants. Second, most participants included in our studies were non-Hispanic White and elderly which limits the applicability of our results to other groups in the whole population. Third, as with any meta-analysis, the potential for publication bias needs to be discussed. However, the visual inspection of funnel plots suggests that the presence of publication bias in this meta-analysis is less likely. Finally, none of the studies included in our analysis were specifically designed to evaluate the effect of vitamin D on serum lipids and none had hyperlipemia as an inclusion criterion. For all of these reasons, the results derived from this meta-analyses should be treated with considerable caution.