**4. Own results**

We did some studies in obese children and adolescents (n = 41 and n = 48) and analytical evaluations were performed before and immediately after supplements were administrated. In one study we gave Sea-buckthorn pulp oil (800 mg/day for 60 days) and placebo, and in another study we gave Omega-3 fatty acids (DHA 130 mg and EPA 25 mg) associated with vitamins (A 200 µg, D 1.25 µg, E 2.5 mg, and C 30 mg). As a control, we enrolled 30 lean children. All the children under medications or those with chronic disease (endocrine, inflammatory, or hereditary diseases) or smokers were excluded. The participants were instructed not to change their lifestyle (dietary and drinking habits, physical activity) during the whole studies and not to take any additional medication including vitamin supplements.

The atherogenic indexes (calculated either as total cholesterol/HDL-c or apoB/apo-A1) were calculated in obese children. Higher values for atherogenic indexes have predictive values for atherosclerosis development. The atherogenic indexes were correlated with other cardiovas‐ cular risk factors such as: waist circumference (Figure 1), C reactive protein (CRP), GGT activity (Figure 2), diastolic blood pressure, and malondialdehyde (MDA)-marker of lipid peroxida‐ tion (Figure 3). The multiple associations of atherogenic index with dyslipidemia, antropo‐ metric, inflammatory, and oxidative stress markers underline that in obesity there is a cluster of patogenic mechanisms that contribute to atherosclerosis. Also, the atherogenic indexes were associated with subclinical atherosclerotic disease markers as carotid intima media thickness-CIMT (positive correlation) (Figure 4) and with brachial artery flow-mediated dilation-FMD (Flow Mediated Dilatation (negative correlation) (Figure 5) [104, 105].

**Figure 1.** Correlation between atherogenic index and waist circumference (r = 0.33). The atherogenic index was calcu‐ lated as the ratio between total cholesterol/HDL-c.

Obese Childhood Dyslipidemia Management Beyond Statins — MUFA, PUFA, and Sea-buckthorn Supplements http://dx.doi.org/10.5772/61001 71

**Figure 2.** Correlation between GGT activity with aterogenic index (r = 0.42). The atherogenic index was calculated as the ratio between total cholesterol/HDL-c.

By hydrolyzing the glutathione, the GGT has a pro-oxidant effect. Also, the products of the GGT reaction may themselves lead to increased free radical production, particularly in the presence of iron. High serum GGT activity was positively associated with the risk of coronary heart disease, type 2 diabetes mellitus, and stroke. We have demonstrated a positive correlation between GGT activity and the cholesterol/HDL-c ratio value [104] (Figure 2).

**Figure 3.** Correlation between MDA and apoB/apo A-1 (r = 0.39).

Pharmacotherapy for obesity has side effects (growth problems, lessened self-esteem, unheal‐ thy weight-control mechanisms) and frequently fails to be efficacious because obesity is a

We did some studies in obese children and adolescents (n = 41 and n = 48) and analytical evaluations were performed before and immediately after supplements were administrated. In one study we gave Sea-buckthorn pulp oil (800 mg/day for 60 days) and placebo, and in another study we gave Omega-3 fatty acids (DHA 130 mg and EPA 25 mg) associated with vitamins (A 200 µg, D 1.25 µg, E 2.5 mg, and C 30 mg). As a control, we enrolled 30 lean children. All the children under medications or those with chronic disease (endocrine, inflammatory, or hereditary diseases) or smokers were excluded. The participants were instructed not to change their lifestyle (dietary and drinking habits, physical activity) during the whole studies

The atherogenic indexes (calculated either as total cholesterol/HDL-c or apoB/apo-A1) were calculated in obese children. Higher values for atherogenic indexes have predictive values for atherosclerosis development. The atherogenic indexes were correlated with other cardiovas‐ cular risk factors such as: waist circumference (Figure 1), C reactive protein (CRP), GGT activity (Figure 2), diastolic blood pressure, and malondialdehyde (MDA)-marker of lipid peroxida‐ tion (Figure 3). The multiple associations of atherogenic index with dyslipidemia, antropo‐ metric, inflammatory, and oxidative stress markers underline that in obesity there is a cluster of patogenic mechanisms that contribute to atherosclerosis. Also, the atherogenic indexes were associated with subclinical atherosclerotic disease markers as carotid intima media thickness-CIMT (positive correlation) (Figure 4) and with brachial artery flow-mediated dilation-FMD

**Figure 1.** Correlation between atherogenic index and waist circumference (r = 0.33). The atherogenic index was calcu‐

and not to take any additional medication including vitamin supplements.

(Flow Mediated Dilatation (negative correlation) (Figure 5) [104, 105].

lated as the ratio between total cholesterol/HDL-c.

multifactorial, polygenic disease [102,103].

**4. Own results**

70 Lipoproteins - From Bench to Bedside

There is a paucity of studies on systemic oxidative stress in childhood obesity but almost all of them have demonstrated higher levels of serum malonyldialdehyde, a marker of lipid peroxidation. There is a direct relation between dyslipidemia and lipid peroxidation and both contribute to a pro-inflammatory phenotype in childhood obesity [105, 106, 107] (Figure 5). NADPH oxidase activity (respiratory burst) in monocytes is increased in childhood obesity and together with serum lipid peroxidation contributes to an increased systemic oxidative stress [105].

Our research team demonstrated that in obese children versus lean ones, plasma total cholesterol and triglycerides were higher, while HDL-c level was lower. LDL-c concentrations were similar in the studied groups. The treatment (800 mg/day, for 60 days) with Sea-buck‐ thorn pulp oil (obtained by cold pressing) reduced significantly the total plasma cholesterol, the apo B/apo A-I ratio and the plasma triglycerides. A weak improvement of HDL-c and LDLc levels was noticed [105]. We consider that the composition of the Sea-buckthorn pulp oil rich in MUFA and phytosterols is responsible for this effect [108].

**Figure 4.** Correlation between apo B/apo A-1 with CIMT (r = 0.38).

**Figure 5.** Correlation between apo B/apo A-1 with FMD (r = -0.36).

Dyslipidemia, inflammation, insulin resistance, and oxidative stress are important culprits for atherosclerosis in obesity. Hyperleptinemia and hypoadiponectinemia represent links between inflammation and vascular dysfunction in obese children. Atherosclerosis begins with endothelium dysfunction and insulin resistance is an important trigger. Puberty alerts some of the inflammatory markers associated with endothelial dysfunction in obese children and leptin concentration rises. Leptin is a biomarker of vascular dysfunction, while adiponectin improves endothelial cells function. In our study done on 48 obese children, the intake of Omega-3 fatty acids (DHA 130 mg and EPA 25 mg) associated with vita‐ mins (A 200 µg, D 1.25 µg, E 2.5 mg, and C 30 mg) for 3 months has resulted in im‐ proved lipid profile. The values for total cholesterol, LDL-c, and triglycerides were decreased, while the HDL-c level was increased [109]. We showed that in the obese children, supplements with Omega-3 fatty acids improved not only the lipid profile, but also the blood pressure values and inflammatory markers. By lowering leptin, increasing adiponec‐ tin, and by decreasing the HOMA-IR values, Omega-3 PUFA reduces the risk of cardiovas‐ cular disease development in adulthood [109].

Our research team demonstrated that in obese children versus lean ones, plasma total cholesterol and triglycerides were higher, while HDL-c level was lower. LDL-c concentrations were similar in the studied groups. The treatment (800 mg/day, for 60 days) with Sea-buck‐ thorn pulp oil (obtained by cold pressing) reduced significantly the total plasma cholesterol, the apo B/apo A-I ratio and the plasma triglycerides. A weak improvement of HDL-c and LDLc levels was noticed [105]. We consider that the composition of the Sea-buckthorn pulp oil rich

in MUFA and phytosterols is responsible for this effect [108].

72 Lipoproteins - From Bench to Bedside

**Figure 4.** Correlation between apo B/apo A-1 with CIMT (r = 0.38).

**Figure 5.** Correlation between apo B/apo A-1 with FMD (r = -0.36).

Dyslipidemia, inflammation, insulin resistance, and oxidative stress are important culprits for atherosclerosis in obesity. Hyperleptinemia and hypoadiponectinemia represent links between inflammation and vascular dysfunction in obese children. Atherosclerosis begins with endothelium dysfunction and insulin resistance is an important trigger. Puberty alerts According to the ATP III (adult treatment panel) modified criteria [110] in our studies, more than 55% of the obese children had triglyceridemia higher than 100 mg/dl and triglyceridemia was correlated with ALT (Alanine aminotransferase) activity. Our results are in accordance with others. In a study done on 700 overweight and obese children aged 7–18 years, ALT activity was correlated with BMI, waist circumference, blood pressure values, triglyceridemia, and insulin resistance [111]. Calcaterra et al. proposed the high value of ALT as a screening marker for metabolic syndrome in obese children [112].

In one of our studies, we divided the obese children in two groups: hypertriglyceridemic waist fenotype (n = 17) and obese nonhypertriglyceridemic (n = 24). Modified ATP III cut points for serum triglycerides (≥110 mg/dL) and waist circumference (≥90th percentile for age and sex) were used to divide obese children. Metabolic and inflammatory parameters were measured before and after Sea-buckthorn pulp oil intake (800 mg/day, 60 days) and the best improvement of the measured plasma variables was observed in hypertriglyceridemic waist phenotype obese children. We demonstrated that high serum values for triglycerides were associated with low values for HDL-C and the treatment reduced significantly the levels of triglycerides and improved the HDL-C concentration [113].

Hepatic de novo lipogenesis is augmented in hypertriglyceridemic waist phenotype obese children and this can be demonstrated by the high values of ALT. In our study, treatment with Sea-buckthorn pulp oil reduced ALT activity and triglyceridemia and improved blood pressure levels. By reducing triglyceridemia and by improving the blood pressure levels, Seabuckthorn pulp oil may prevent metabolic syndrome in obese children [105, 113]. The study underlines that treatment with Sea-buckthorn pulp oil should be recommended in hypertri‐ glyceridemic waist phenotype obese children. Also, in obese children, the intake of Omega-3 fatty acids (DHA 130 mg and EPA 25 mg per day) associated with vitamins (A 200 µg, D 1.25 µg, E 2.5 mg, and C 30 mg) for 3 months reduced the blood pressure values (systolic and diastolic) significantly [109].

Some of the most important effects for Omega-3 supplements and Sea-buckthorn pulp oil supplements are to prevent atherosclerosis and to reverse the CIMT values [105,109].

In a high-fat diet mouse model, we induced non-alcoholic fatty liver disease to NMRI mice and the treatment with normocaloric/normolipidic diet and Omega-3 fatty acids (DHA 130 mg and EPA 25 mg per day) had reversed liver histopatological results from steatohepatitis to normal aspect and improved the plasma lipid profile [114].
