The results of this study indicated a significant association between serum 25(OH)D level and lipid profile, particularly TG level and TG/HDL-C ratio, in children and adolescents without obesity.
Although 1,25-dihydroxyvitamin D is recognized as the active form of vitamin D, 25(OH)D, the primary circulating form of vitamin D, it is considered the best indicator of serum vitamin D level and a sensitive measure of serum vitamin D status because of its long half-life. There exists no international definition for optimal vitamin D status in children. We divided subjects into two groups: Vitamin D-deficient group (25(OH)D <20 ng/mL) and the normal group (25(OH)D ≥20 ng/mL). In our study, the mean 25(OH)D level was 17.27 ng/mL, and there were more vitamin D-deficient children, which is similar to the result of the 2008 Korea National Health and Nutrition Examination Survey [24
Dyslipidemia, a cardiovascular risk factor, is characterized by elevated TG and LDL-C levels and reduced HDL-C levels. Small dense LDL (sdLDL) tends to rapidly deposit on the arterial wall, reducing LDL-C clearance. Hence, sdLDL is correlated to atherosclerosis and coronary artery disease. The atherogenic index of plasma (AIP), expressed as log[TG/HDL-C], could be an excellent predictor of sdLDL level. In the study of Wang et al., AIP > 0.15 was regarded as abnormal [25
]. Therefore, the TG/HDL-C ratio can be useful for predicting cardiovascular risk in the future. In our study, 113 (46.5%) out of 243 subjects had an abnormal TG/HDL-C ratio and thus had cardiovascular risk. Furthermore, 83 (49.1%) out of 169 vitamin D-deficient children had cardiovascular risk.
Previous studies have reported similar results for the adult population. Wang et al. investigated the effects of serum vitamin D status on lipids in Chinese adults and showed that serum 25(OH)D level was closely associated with lipids and AIP. In addition, Chaudhuri et al. reported that 25(OH)D deficiency was independently associated with dyslipidemia in Indian subjects [26
]. Numerous studies have confirmed the association between vitamin D level and lipid panel in children and adolescent with obesity. In the study of Lee et al., the mean 25(OH)D level was lower in children deemed obese. As the vitamin D level increased, TG and HDL-C levels became lower and higher, respectively [27
]. Rusconi et al. reported the association between low 25(OH)D level and unfavorable lipid patterns in a pediatric obese population [20
]. In our study, we also observed a relationship between vitamin D level and dyslipidemia even in non-obese children and adolescents.
The functions of vitamin D are linked to lipid values. First, vitamin D regulates calcium metabolism and increases intestinal calcium absorption, thereby reducing intestinal fatty acid absorption [25
]. Therefore, a reduction in intestinal fat absorption can lower the cholesterol level. Additionally, increasing the calcium concentration promotes the conversion of cholesterol into bile acids in the liver, resulting in reduced cholesterol level [28
Second, high vitamin D level inhibits the parathyroid hormone (PTH). When the vitamin D level is not high, vitamin D may not inhibit PTH [29
]. Increased PTH level enhances lipogenesis, promoting calcium influx into the adipocytes. Furthermore, a high PTH level decreases lipolytic activity, resulting in a high TG level. Therefore, in the presence of high vitamin D level, a low PTH level can reduce the TG level by increasing lipolytic activity and peripheral removal. In addition, a high PTH level increases bone turnover and induces calcium release from the bone. Increasing the calcium concentration can affect the cholesterol level, as explained above.
Third, vitamin D can affect lipoprotein metabolism and reduce TG synthesis and secretion in the liver, increasing very-low-density lipoprotein (VLDL-C) receptor expression. Consequently, a high vitamin D level induces a decrease in TG and VLDL-C levels and an increase in HDL-C level.
Our study showed that vitamin D could influence the lipid profile, even in non-obese children. Vitamin D-deficient children had a higher TG level and TG/HDL-C ratio and, therefore, they may progress to dyslipidemia or obesity. Dyslipidemia during childhood persists into adulthood; hence, maintaining the vitamin D level within the normal range seems important, even for non-obese children.
Lee et al. reported that hypertriglyceridemia and high TG/HDL-C ratio could increase the risk of nonalcoholic fatty liver disease (NAFLD) [31
]. Hence, it could be supposed that low vitamin D level could induce the progression to metabolic diseases, such as NAFLD. Therefore, a normal 25(OH)D level may be a marker of better lipid profile and reduced risk of adult diseases in non-obese children.
Our study limitation was that we did not consider diet differences and lifestyle habits, which may have influenced the relationship between vitamin D level and lipid profile. Future studies analyzing the association between vitamin D levels and lipid profile are warranted. Furthermore, the sample size of this investigation was small even though it was enough to conduct the study. Therefore, a large cohort study would be needed to support these results.
Whether dietary vitamin D supplementation plays a therapeutic or preventive role remains poorly explored. Data from epidemiologic studies [32
] do not support the finding that 25(OH)D supplementation could beneficially improve the lipid profile, thus leaving the role of 25(OH)D uncertain [34
]. A longitudinal follow-up study is required in order to verify whether vitamin D deficiency could lead to obesity or complications such as cardiovascular disease. Further studies on the potential positive effects of vitamin D supplementation on the lipid profile are warranted.