Effects of cholecalciferol supplementation on serum angiogenic biomarkers in breast cancer patients treated with tamoxifen: A controlled randomized clinical trial.

OBJECTIVE: The aim of this study was to investigate the effects of cholecalciferol supplementation on serum levels of angiogenic parameters in patients with breast cancer (BC) who were treated with tamoxifen. METHODS: This was a pilot-based, randomized, triple-blind, placebo-controlled clinical trial with 52 patients with BC randomly assigned to either an intervention group receiving weekly 50 000 IU cholecalciferol or a placebo group for 8 wk. At baseline and at end of study, serum levels of angiogenic growth factors such as vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-2, hypoxia-inducible factor (Hif)-1, and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay. Every 4 wk, a completed 3-d, 24-h dietary record and daily sunlight exposure checklist were collected and anthropometric variables were measured. RESULTS: The ultimate number of participants in each arm was 22 for analyses. For premenopausal women, cholecalciferol supplementation resulted in a significant decrease in serum levels of Ang-2 and VEGF-A after 8 wk of treatment (P < 0.05). In the absence of vascular invasion, supplementation led to a significant decrease in Ang-2 levels compared with the placebo group (P < 0.05). Supplementation caused significant increases in Hif-1 in patients diagnosed with the infiltration of tumors into vascular or lymphatic vessels (P < 0.05). CONCLUSION: Cholecalciferol supplementation achieved sufficient efficacy among patients with BC taking tamoxifen and could be effective in the reduction of angiogenic biomarkers particularly dependent on the infiltration status of the tumor to vessels. Further studies with larger subgroups should be investigated.

Effects of EPA supplementation on plasma fatty acids composition in hypertriglyceridemic subjects with FABP2 and PPARα genotypes.

BACKGROUND: Fatty acid binding protein 2 (FABP2) and peroxisome proliferator-activated receptor α (PPARα) are involved in cellular uptake and metabolism of fatty acids. Polymorphism of FABP2 and PPARα may influence plasma levels of fatty acids in those who take supplemental eicosapentaenoic acid (EPA). The purpose of this study was to study the potential associations between the Ala54/Thr polymorphism in FABP2 protein and the Leu162/Val in exon 5 and G/C in intron 7 of PPARα with plasma fatty acids composition after EPA supplementation. METHODS: Twenty three FABP2 Ala54 and twenty three Thr54 carriers with hypertriglyceridemia were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wks. Plasma fatty acids composition was determined and changes from the baseline were measured. RESULTS: Although EPA supplementation increased the level of plasma EPA and ω-3 fatty acids in both carriers of FABP2 and PPARα genes, these effects were more pronounced in Thr54 and Val162 carriers. EPA supplementation decreased the level of some n-6 fatty acids such as arachidonic acid. CONCLUSION: EPA consumption has more favorable effects on blood n-3 fatty acids and can change the level of plasma n-3 fatty acids, particularly EPA. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for preventing cardiovascular diseases. Finally, diets and micronutrient recommendations should be individualized for high risk people.

Fatty acid-binding protein-2 genotype influences lipid and lipoprotein response to eicosapentaenoic acid supplementation in hypertriglyceridemic subjects.

OBJECTIVE: The blood lipid-lowering effects of eicosapentaenoic acid (EPA) on hypertriglyceridemic subjects with different fatty acid-binding protein-2 (FABP2) genotypes have not, to our knowledge, been previously studied. METHODS: Twenty-three FABP2 Ala54 and 23 Thr54 carriers with hypertriglyceridemia (triacylglycerol level >200mg/dL) were enrolled in this study. Participants took 2g of pure EPA daily for 8 wk. Fasting blood lipid and lipoprotein profiles were determined and changes from baseline were measured. RESULTS: Blood lipids and lipoprotein responses of the FABP2 genotypes differed after EPA supplementation. Changes from baseline for triacylglycerol (19.2% decrease for Ala54 and 60.5% for Thr54, P<0.001), very low-density lipoprotein (20.0% decrease for Ala54 and 60.5% for Thr54, P<0.001), apolipoprotein CIII (22.8% decrease for Ala54 and 36.4% for Thr54, P<0.01), and high-density lipoprotein cholesterol (17.6% increase for Ala54 and 30.7% for Thr54, P<0.01) differed significantly between the two carrier groups. However, changes in total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B were not significant. EPA supplementation increased plasma EPA in Ala54 and Thr54 carriers. Although EPA supplementation increased the level of plasma EPA in both carrier groups, this effect was more pronounced in the Thr54 carriers. CONCLUSION: Therefore, EPA consumption has more favorable effects on blood lipids of hypertriglyceridemics with Thr54 genotype rather than those with Ala54. The level of plasma EPA increases after EPA supplementation. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for reducing blood triacylglycerol concentration.

Effects of onion on serum uric acid levels and hepatic xanthine dehydrogenase/xanthine oxidase activities in hyperuricemic rats.

The aim of this study was to investigate the effects of onion on serum uric acid levels and hepatic Xanthine Dehydrogenase/Xanthine Oxidase activities in normal and hyperuricemic rats. Hyperuricemia was induced by intraperitoneal injection of 250 mg kg(-1) potassium oxonate in rats. Oral administration of onion at 3.5 and 7.0 mg kg(-1) day(-1) for 7 days was able to reduce serum uric acid levels in hyperuricemic rats with no significant effects on the level of this compound in the normal animals. In addition, onion when tested in vivo on rat liver homogeneities elicited significant inhibitory actions on the Xanthine Dehydrogenase (XDH) and Xanthine Oxidase (XO) activities. This effect resulted less potent than that of allopurinol. However, the hypouricemic effect observed in the experimental animal did not seem to parallel the change in XDH and XO activities, implying that the onion might be acting via other mechanisms apart from simple inhibition of enzyme activities. Such hypouricemic action and enzyme inhibitory activity of onion makes it a possible alternative for allopurinol, or at least in combination therapy to minimize the side-effects of allopurinol, in particular in long-term application.