Xanthophylls, Phytosterols and Pre‐β1‐HDL are Differentially Affected by Fenofibrate and Niacin HDL‐Raising in a Cross‐Over Study

Abstract

Fenofibrate and extended-release (ER) niacin similarly raise high-density lipoprotein cholesterol (HDL-C) concentration but their effects on levels of potent plasma antioxidant xanthophylls (lutein and zeaxanthin) and phytosterols obtained from dietary sources, and any relationship with plasma lipoproteins and pre-β1-HDL levels, have not been investigated. We studied these parameters in 66 dyslipidemic patients treated for 6 week with fenofibrate (160 mg/day) or ER-niacin (0.5 g/day for 3 week, then 1 g/day) in a cross-over study. Both treatments increased HDL-C (16 %) and apolipoprotein (apo) A-I (7 %) but only fenofibrate increased apoA-II (28 %). Lutein and zeaxanthin levels were unaffected by fenofibrate but inversely correlated with percentage change in apoB and low-density lipoprotein cholesterol and positively correlated with end of treatment apoA-II. ApoA-II in isolated HDL in vitro bound more lutein than apoA-I. Xanthophylls were increased by ER-niacin (each ~30 %) without any correlation to lipoprotein or apo levels. Only fenofibrate markedly decreased plasma markers of cholesterol absorption; pre-β1-HDL was significantly decreased by fenofibrate (-19 %, p < 0.0001), with little change (3.4 %) for ER-niacin. Although fenofibrate and ER-niacin similarly increased plasma HDL-C and apoA-I, effects on plasma xanthophylls, phytosterols and pre-β1-HDL differed markedly, suggesting differences in intestinal lipidation of HDL. In addition, the in vitro investigations suggest an important role of plasma apoA-II in xanthophyll metabolism.

Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice

“…In clinical conditions, FF could cause increases or decreases in HDL levels. 32 – 35 In the present study, FF supplementation decreased serum HDL levels, which may be related to the drug-induced lowering of serum TC levels. This is because HDL can pick up excessive cholesterol in the blood and take it back to the liver for degradation.…”

Effect of Compounds Affecting ABCA1 Expression and CETP Activity on the HDL Pathway Involved in Intestinal Absorption of Lutein and Zeaxanthin

“…Because anacetrapib is believed not to favor lipid-poor apoA1 particle formation, this result substantiates the view that the ABCA1/lipid-poor apoA1 pathway is implicated in the intestinal uptake of lutein and zeaxanthin [14]. The observed dissociation between increase in HDL-C and plasma lutein was also reported previously by our group in fenofibrate versus niacin-treated subjects in whom only niacin increased plasma lutein and zeaxanthin in spite of a similar increase in HDL-C [47].…”

Fenofibrate lowers atypical sphingolipids in plasma of dyslipidemic patients: A novel approach for treating diabetic neuropathy?

“…Sixty-six patients with primary hypercholesterolemia or mixed dyslipidemia were enrolled into a multi-center, open label, cross-over study to compare the effects of niacin and fenofibrate on the plasma lipid profile and the lipoproteins 22,23 (Fig. 1).…”