Effects of dietary sodium on reactive oxygen species formation and endothelial dysfunction in low-density lipoprotein receptor-deficient mice on high-fat diet.

Hypertension and high serum cholesterol level are important risk factors for atherosclerosis and coronary heart disease. In the present study we tested the hypothesis whether high sodium intake, when given in combination with Western type high-fat diet, induces endothelial dysfunction and promotes atherosclerosis. Furthermore, the role and enzyme sources of increased oxidative stress were examined. Low-density lipoprotein receptor-deficient mice (LDLR(-/-)) and control C57Bl/6 mice received either high-fat, normal-sodium diet (fat 18% and cholesterol 0.5%; NaCl 0.7%; w/w) or high-fat, high-sodium diet (7% NaCl w/w) for 12 weeks. Superoxide formation was assessed by lucigenin enhanced chemiluminescence, endothelial functions were examined ex vivo, and atherosclerotic lesions from the aorta were assessed by light microscopy. High-fat, high-sodium diet increased systolic blood pressure in LDLR(-/-) mice but not in C57Bl/6 mice, whereas it induced cardiac hypertrophy in both mouse strains. Dietary combination of fat and sodium induced endothelial dysfunction in LDLR(-/-) mice. Preincubation with a superoxide scavenger Tiron normalized endothelial dysfunction, whereas the hydrogen peroxide scavenger catalase did not alter endothelial function. High sodium intake induced superoxide formation in LDLR(-/-) mice on high-fat diet. Stimulation of muscarinic receptors in the endothelial cells by acetylcholine increased superoxide generation, whereas preincubation with the nitric oxide synthase (NOS) inhibitor L-arginine methyl ester or endothelium removal reduced superoxide production. Inhibition of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase by apocynin decreased vascular superoxide formation whereas the xanthine oxidase inhibitor oxypurinol did not significantly affect oxidative stress in LDLR(-/-) mice. In conclusion, the detrimental effects of dietary sodium on endothelial function and progression of atherosclerosis in LDLR(-/-) mice on high-fat diet are mediated by increased ROS formation mainly through uncoupled NOS and NADPH oxidase. The present study also underscores the importance of superoxide and endothelial NOS uncoupling in the pathogenesis of endothelial dysfunction.

Clinical inquiries: What is the dietary treatment for low HDL cholesterol?

Low-carbohydrate diets raise high-density lipoprotein (HDL) cholesterol levels by approximately 10%; soy protein with isoflavones raises HDL by 3% (strength of recommendation [SOR]: C, based on meta-analysis of physiologic parameters). The Dietary Approaches to Stop Hypertension (DASH) diet and multivitamin supplementation raise HDL 21% to 33% (SOR: C, based on single randomized trial each measuring physiologic parameters). No other dietary interventions studied raise HDL (SOR: C, based on meta-analysis of physiologic parameters).

Effectiveness of low-dose crystalline nicotinic acid in men with low high-density lipoprotein cholesterol levels.

BACKGROUND: Hypoalphalipoproteinemia (low serum concentration of high-density lipoprotein cholesterol [HDL-C]) is a common pattern of dyslipidemia associated with coronary heart disease. High doses of nicotinic acid effectively raise HDL-C levels in this condition, but they are commonly accompanied by side effects. The efficacy of low doses of nicotinic acid that may produce fewer side effects has not been adequately studied. OBJECTIVE: To determine the effects of low-dose nicotinic acid on HDL-C levels in patients with hypoalphalipoproteinemia. METHODS: Forty-four men with low HDL-C levels (< 1.03 mmol/L [< 40 mg/dL]) entered the study. Twenty-four patients otherwise had normal lipid levels, and 20 were moderately hypertriglyceridemic (range of plasma triglyceride levels, 2.82 to 5.64 mmol/L 250 to 500 mg/dL). The trial consisted of 3 phases; each phase lasted 8 weeks. The first phase was diet only (30% fat diet); in the second phase, crystalline nicotinic acid was added at 1.5 g/d; and in the third phase, the dose was increased to 3 g/d. RESULTS: Of the 44 patients who entered the study, 37 completed the low-dose phase (1.5 g/d); the remaining patients were withdrawn because of side effects to nicotinic acid. Four other patients who completed the low-dose phase were excluded from the higher dose phase because of side effects that developed when they were receiving the low dose. Ten other patients withdrew during the high-dose phase because of side effects. In both groups, responses to nicotinic acid therapy tended to be dose-dependent. For both groups, the higher dose generally produced a greater reduction in apolipoprotein B-containing lipoproteins and a greater rise in HDL-C levels. However, for both groups, the low dose of nicotinic acid gave an average 20% increase in HDL-C levels. CONCLUSIONS: A low dose (1.5 g/d) of crystalline nicotinic acid causes an average 20% increase in HDL-C levels and significantly lowers triglyceride levels in both normolipidemic and hyperlipidemic patients with low HDL-C levels. Although the changes induced by this dose are less than those that can be achieved by a higher dose, the lower dose is better tolerated. Nicotinic acid may be useful in combined drug therapy for secondary prevention of coronary heart disease, and if higher doses cannot be tolerated, use of a lower dose should still be useful for producing a moderate rise in HDL-C levels in patients with hypoalphalipoproteinemia.

Glucomannan and glucomannan plus spirulina added to pork significantly block dietary cholesterol effects on lipoproteinemia, arylesterase activity, and CYP7A1 expression in Zucker fa/fa rats.

Zucker fa/fa rats easily develop dyslipidemia and obesity. Restructured pork (RP) is a suitable matrix for including functional ingredients. The effects of glucomannan- RP or glucomannan plus spirulina-enriched RP on plasma lipid/lipoprotein levels, cytochrome P450 7A1 (CYP7A1) expression, and arylesterase activity in growing fa/fa rats fed high-energy, high-fat cholesterol-enriched diets were tested. Groups of six rats each received diet containing 15% control-RP (C), 15% glucomannan-RP diet (G), 15% glucomannan + spirulina-RP diet (GS), and same diets enriched with 2.4% cholesterol and 0.49% cholic acid (cholesterol-enriched control (HC), cholesterol-enriched glucomannan (HG), and cholesterol-enriched glucomannan + spirulina (HGS) diets) over a 7-week period. C diet induced obesity, severe hyperglycemia, moderate hypercholesterolemia, and hypertriglyceridemia. Those facts were not significantly modified by G or GS diets. G diet increased CYP7A1 expression but decreased the total cholesterol/high density lipoproteins (HDL)-cholesterol ratio (p < 0.05) vs. C diet. GS vs. G diet increased (p < 0.05) CYP7A1 expression. HC vs. C diet reduced food intake, body weight gain, and plasma glucose (p < 0.01) but increased cholesterolemia (p < 0.01), lipidemia (plasma cholesterol plus triglycerides) (p < 0.001), cholesterol/triglyceride ratio in very low density lipoproteins (VLDL), and HDL (p < 0.05), cholesterol transported by VLDL and intermediate density lipoproteins (IDL) + low density lipoproteins (LDL), total cholesterol/HDL-cholesterol ratio and CYP7A1 expression (at least p < 0.05). HG and HGS diets vs. HC noticeably reduced lipidemia (p < 0.001), normalized VLDL and IDL + LDL lipid composition, and increased CYP7A1 expression (p < 0.01) but did not modify the cholesterol/HDL-cholesterol ratio. HGS vs. HG decreased triglyceridemia, the triglyceride-glucose (TyG) index and increased arylesterase/HDL-cholesterol activity (p < 0.05). In conclusion, G- and GS-RP act as functional foods and notably blocked the dietary cholesterol effects. In addition, HGS-RP improved the glucomannan hypolipidemic effects, increased arylesterase/HDL-cholesterol activity, and decreased insulin resistance.

[Drug clinics. How I treat a patient with a low concentration of HDL cholesterol]. / Pharma-clinics. Comment je traite ... un sujet avec une concentration basse de cholestérol HDL.

The decision to treat an individual with low HDL cholesterol level depends on his overall cardiovascular risk profile and the therapeutic strategy is based upon the characteristics of the lipid profile (isolated abnormality, associated hypertriglyceridaemia or combined elevation of LDL cholesterol). The treatment must favour diet and exercise, before considering a possible pharmacological approach. Results are usually acceptable with better life habits and appropriate diet when low HDL cholesterol level is associated to hypertriglyceridaemia. From a pharmacological point of view, the best results are obtained with fibrates or nicotinic acid. However, results are often disappointing when low HDL cholesterol level is isolated.