## 5 Effects of Micronutrient Supplementation on Weight Management and Metabolic Health in Obesity
### Effects of Micronutrient Supplementation on Lipid Homeostasis
Therefore, its role in maintaining lipid homeostasis  
is crucial, with recent animal research showing that when supplemented at high doses, it protects against the development of NAFLD [108]. The dose could be of importance for the effect of supplementation in humans, as a meta-analysis by [PERSON] (2022) found that administration of vitamin B1 only at 120 mg/day allowed for a statistically significant and greater reduction of TG levels in T2D patients (MD \(-\)97.4 mg/dL) [91]. Other micronutrients that showed dose-dependent performance in the regulation of lipid homeostasis were Ca (better effects at \(\geq\)1 g [94]), Se (at 200 mg/day [109]), Zn (at \(\geq\)50 mg/day for TG but <50 mg/day for TC, LDL and HDL [88]), Cr (at \(>\)500 mg/day [59]), vitamin D (at \(\geq\)4000 IU/day [89]), vitamin C (at \(<\)1000 mg/day [90]), and vitamin B9 (at \(\geq\)5 mg/day [92]). Not many studies looked at the effect of vitamins A, B6, and B12 on lipid homeostasis in humans. Therefore, for these micronutrients, Table 4 shows data from exemplary RCTs. Vitamin A was the only nutrient for which a significant negative outcome (decrease of HDL level; MD \(-\)3.1 mg/dL) on lipid homeostasis was reported [73]. In the cited study, supplementation with 25,000 IU/day retinyl palmit in women with obesity for 4 months, besides a mild decrease of HDL, resulted in a statistically significant increase of TG, TC, and LDL. These findings are difficult to interpret since two control groups (one, women with obesity receiving a placebo; two, women with normal weight supplementing retinyl palmit at the same dose) also exhibited negative changes in lipid homeostasis, similar to those in the treatment group. Other human studies on the association of vitamin A and carotenoids with weight loss and metabolic markers reported variable results, and currently, no clear recommendations for supplementing these substances in obesity are available [110,111]. Furthermore, due to the known dose-dependent, hepatotoxic effects of synthetic forms of this vitamin, recommending suitable doses poses a challenge [112]. On the other hand, maintaining adequate vitamin A levels may be crucial for the health of adipose tissue since this substance was shown to promote angiogenesis and de novo adipogenesis [113]. Healthy adipose tissue contains more abundant, well-vascularized adipocytes for fat storage [114]. Such a structure, to a certain extent, protects adipocytes from overgrowth and inflammation, which are risk factors contributing to the development of metabolic dysfunctions, especially insulin resistance [98]. Since the formation of adipocytes is most intense during fetal development and their number gets established in childhood and early adulthood, providing vitamin A adequacy might be especially crucial in early life [113]. Vitamin B6 supplementation at 80 mg/day in dieting women with excess weight for 8 weeks was shown to aid in the reduction of TG, TC, and LDL (see Table 4). A few of the mechanisms explaining the regulatory functions of vitamin B6 on lipid homeostasis are antioxidative properties, its role in enzymatic reactions, as well as its influence on calcium ion signaling associated with enhanced lipolysis and decreased synthesis of fatty acids [77]. In summary, the influence of the majority of micronutrients on lipid homeostasis is significant and supplementation may be recommended in mild cases of dyslipidemia or as an adjuvant to conventional treatments in more severe cases. In addition, research on the combinations of micronutrients at doses that were found to be effective would be of interest to determine whether additive or synergistic outcomes could be achieved.