A case in variant in cow's milk is atherogenic

Casein is a major protein in cow's milk that occurs in several variant forms, two of which are beta-casein A(1) and beta-casein A(2). The levels of these two proteins vary considerably in milk dependent on the breed of cow, and epidemiology studies suggest that there is a relationship between their consumption and the degree of atherosclerosis. In the present study, the direct effect of consumption of beta-casein A(1) vs beta-casein A(2) on atherosclerosis development was examined in a rabbit model. Sixty rabbits had their right carotid artery balloon de-endothelialised at t = 0, divided randomly into 10 groups (n = 6 per group), then for 6 weeks fed a diet containing 0, 5, 10 or 20% casein isolate, either beta-casein variant A(1) or A(2) made up to 20% milk protein with whey. Some groups had their diets supplemented with 0.5% cholesterol. Blood samples were collected at t = 0, 3 and 6 weeks and rabbits were sacrificed at t = 6 weeks. In the absence of dietary cholesterol, beta-casein A(1) produced significantly higher (P < 0.05) serum cholesterol, LDL, HDL and triglyceride levels than whey diet alone, which in turn produced higher levels than beta-casein A(2). Rabbits fed beta-casein A(1) had a higher percent surface area of aorta covered by fatty streaks than those fed beta-casein A(2) (5.2+/-0.81 vs 1.1+/-0.39, P < 0.05) and the thickness of the fatty streak lesions in the aortic arch was significantly higher (0.04+/-0.010 vs 0.00, P < 0.05). Similarly, the intima to media ratio (I:M) of the balloon injured carotid arteries in A(1) fed animals (0.77+/-0.07) was higher than in those that consumed A(2) (0.57+/-0.04) or whey (0.58+/-0.04), but this did not reach significance. In the presence of 0.5% dietary cholesterol, the thickness of the aortic arch lesions was higher (P < 0.05) in 5, 10 and 20% casein A(1) fed animals compared with their A(2) counterparts, while other parameters were not significantly different. It is concluded that beta-casein A(1)is atherogenic compared with beta-casein A(2). (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus

Objective: To compare the effects of a 4-month strength training (ST) versus aerobic endurance training (ET) program on metabolic control, muscle strength, and cardiovascular endurance in subjects with type 2 diabetes mellitus (T2D). Design: Randomized controlled trial. Setting: Large public tertiary hospital. Participants: Twenty-two T21) participants (I I men, I I women; mean age +/- standard error, 56.2 +/- 1.1 y; diabetes duration, 8.8 +/- 3.5y) were randomized into a 4-month ST program and 17 T2D participants (9 men, 8 women; mean age, 57.9 +/- 1.4y; diabetes duration, 9.2 +/- 1.7y) into a 4-month ET program. Interventions: ST (up to 6 sets per muscle group per week) and ET (with an intensity of maximal oxygen consumption of 60% and a volume beginning at 15min and advancing to a maximum of 30min 3X/wk) for 4 months. Main Outcome Measures: Laboratory tests included determinations of blood glucose, glycosylated hemoglobin (Hb A(1c)), insulin, and lipid assays. Results: A significant decline in Hb A, was only observed in the ST group (8.3% +/- 1.7% to 7.1% +/- 0.2%, P=.001). Blood glucose (204 +/- 16mg/dL to 147 +/- 8mg/dL, P <.001) and insulin resistance (9.11 +/- 1.51 to 7.15 +/- 1.15, P=.04) improved significantly in the ST group, whereas no significant changes were observed in the ET group. Baseline levels of total cholesterol (207 +/- 8mg/dL to 184 +/- 7mg/dL, P <.001), low-density lipoprotein cholesterol (120 +/- 8mg/dL to 106 +/- 8mg/dL, P=.001), and triglyceride levels (229 +/- 25mg/dL to 150 +/- 15mg/dL, P=.001) were significantly reduced and high-density lipoprotein cholesterol (43 +/- 3mg/dL to 48 +/- 2mg/dL, P=.004) was significantly increased in the ST group; in contrast, no such changes were seen in the ET group. Conclusions: ST was more effective than ET in improving glycemic control. With the added advantage of an improved lipid profile, we conclude that ST may play an important role in the treatment of T2D.

Berberine - a novel approach to cholesterol lowering

Although low-density lipoprotein (LDL)-cholesterol lowering with the statins reduces the mortality and morbidity associated with coronary artery disease, considerable mortality and morbidity remains. Berberine upregulates the LDL receptor (LDLR) by a mechanism distinct from that of the statins, which involves stabilising the LDLR mRNA. In hamsters fed a high-fat and high-cholesterol diet for 2 weeks, the oral administration of berberine 100 mg/kg for 10 days reduced total serum cholesterol from &SIM; 4.8 to 2.7 mmol/l, and LDL-cholesterol from &SIM; 2.5 to 1.4 mmol/l. In subjects with hypercholesterolaemia, berberine hydrochloride (0.5 g b.i.d. for 3 months) reduced LDL-cholesterol (from 3.2 to 2.4 mmol/l) without any effect on high-density lipoprotein-cholesterol. Berberine also caused a reduction in triglyceride levels from 2.3 to 1.5 mmol/l. As berberine and statins both upregulate LDLR, their lipid-lowering profiles are similar. Thus, this mechanism is unlikely to make berberine an attractive alternative to statins for lipid lowering in most circumstances. However, the other effects of berberine (anti hypertensive, inotropic and class III antiarrhythmic properties) may make it a useful agent in the treatment of cardiovascular disease.

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study

Aims Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density tipoprotein cholesterol (LDL-C) less than or equal to140 mg/dL (less than or equal to3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) less than or equal to40 mg/dL (less than or equal to1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with tow LDL-C and tow HDL-C. Methods and results Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C less than or equal to140 mg/dL (less than or equal to3.6 mmoL/L), HDL-C less than or equal to40 mg/dL (less than or equal to1.03 mmol/L), and triglyceride less than or equal to300 mg/dL (less than or equal to3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% Cl 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% Cl 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. Conclusions Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C. (C) 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology.