Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet.

BACKGROUND: The contemporary American diet figures centrally in the pathogenesis of numerous chronic diseases-'diseases of civilization'. We investigated in humans whether a diet similar to that consumed by our preagricultural hunter-gatherer ancestors (that is, a paleolithic type diet) confers health benefits. METHODS: We performed an outpatient, metabolically controlled study, in nine nonobese sedentary healthy volunteers, ensuring no weight loss by daily weight. We compared the findings when the participants consumed their usual diet with those when they consumed a paleolithic type diet. The participants consumed their usual diet for 3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a paleolithic type diet comprising lean meat, fruits, vegetables and nuts, and excluding nonpaleolithic type foods, such as cereal grains, dairy or legumes, for 10 days. Outcomes included arterial blood pressure (BP); 24-h urine sodium and potassium excretion; plasma glucose and insulin areas under the curve (AUC) during a 2 h oral glucose tolerance test (OGTT); insulin sensitivity; plasma lipid concentrations; and brachial artery reactivity in response to ischemia. RESULTS: Compared with the baseline (usual) diet, we observed (a) significant reductions in BP associated with improved arterial distensibility (-3.1+/-2.9, P=0.01 and +0.19+/-0.23, P=0.05);(b) significant reduction in plasma insulin vs time AUC, during the OGTT (P=0.006); and (c) large significant reductions in total cholesterol, low-density lipoproteins (LDL) and triglycerides (-0.8+/-0.6 (P=0.007), -0.7+/-0.5 (P=0.003) and -0.3+/-0.3 (P=0.01) mmol/l respectively). In all these measured variables, either eight or all nine participants had identical directional responses when switched to paleolithic type diet, that is, near consistently improved status of circulatory, carbohydrate and lipid metabolism/physiology. CONCLUSIONS: Even short-term consumption of a paleolithic type diet improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans.

Oxidized low density lipoproteins bind to the scavenger receptor expressed by rabbit smooth muscle cells and macrophages.

We have previously demonstrated that the acetylated low density lipoprotein (LDL), or scavenger, receptor expressed by rabbit smooth muscle cells (SMCs) is regulated. Phorbol ester treatment of the cells increased the number of scavenger receptors expressed and the metabolism of acetoacetylated (AcAc) LDL. The current studies examined the interaction of oxidized (Ox) LDL with the rabbit scavenger receptor. The internalization and degradation of both Ox-LDL and AcAc-LDL were increased to a similar extent by phorbol ester treatment of the SMCs. In cross-competition experiments, both Ox-LDL and AcAc-LDL competed equally for the degradation of 125I-Ox-LDL, suggesting that there is no independent receptor for Ox-LDL on these cells. In contrast, only AcAc-LDL competed totally for the degradation of 125I-AcAc-LDL. Similar results were obtained in cross-competition experiments with rabbit macrophages. To determine whether these data were consistent with the binding of both ligands to a single receptor, competition studies were conducted in Chinese hamster ovary fibroblasts transfected with the bovine scavenger receptor. After transfection, the metabolism of both AcAc-LDL and Ox-LDL was increased, in agreement with the previous data from other investigators, and cross-competition studies yielded essentially identical results to those obtained in the SMCs and macrophages. Northern blot analysis with an antisense rabbit scavenger receptor probe detected the same mRNA species in total RNA from rabbit macrophages and SMCs and showed that scavenger receptor mRNA increased dramatically after phorbol ester treatment of SMCs. The probe also detected bovine scavenger receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)