The effect of diets high in protein or carbohydrate on inflammatory markers in overweight subjects

AIM: Increased levels of inflammatory markers have been associated with weight gain and cardiovascular disease. The aim of the present study was to investigate the effect of diets high in either carbohydrate or protein on the inflammatory markers C-reactive protein (CRP), haptoglobin and transferrin in plasma after weight loss. METHODS: Fifty overweight subjects [age: 18-56 years, body mass index (BMI): 27-34] were randomly assigned to an ad libitum, fat-reduced diet (30% of energy, E%), either high in protein and low in carbohydrate (25 E and 45 E% respectively) or high in carbohydrate and low in protein (58 E and 12 E% respectively), during 6 months of strictly controlled dietary intervention with dietary counselling. RESULTS: An average reduction of 25% in CRP and an average increase of 20% in haptoglobin and transferrin were seen in both groups, however, these changes were not significant. In cross-sectional analyses after the intervention CRP was associated with fat mass (r = 0.323, p = 0.03), and the changes in CRP were associated with various indices of body fatness (Deltabody weight r = 0.346, p = 0.02). Changes in body fatness were positively associated with Deltatransferrin (r = 0.344, p = 0.02) and nearly significantly associated with Deltahaptoglobin (r = 0.271, p = 0.07) after 6 months. Multiple regression analysis showed no associations between dietary protein and carbohydrate content and serum CRP, haptoglobin or transferrin concentrations, and this remained unaltered after adjustment for weight change. CONCLUSION: Dietary carbohydrate/protein ratio has no effect on inflammatory markers, but the study confirmed that body fatness is positively associated with levels of serum CRP.     

Metabolic effects of carbohydrate in low-calorie diets

Fasting plasma glucose turnover, urinary 3-methylhistidine excretion, and fasting plasma protein profiles were compared in a 4-week randomized clinical trial of two very low-calorie weight-reduction diets. Diet A (360 kcal) provided 1.5 g egg protein per kg ideal body weight (IBW) but no carbohydrate. Diet B (340 kcal) provided 0.8 g egg protein per kg IBW plus 0.7 g carbohydrate per kg IBW. Eleven moderately obese healthy young women were studied. After 3 weeks of dieting, fasting plasma glucose appearance and oxidation decreased by equal amounts (20% and 30%, respectively) for both diets. 3-methylhistidine excretion remained at control rates for the first week on the diets, then fell by equal amounts (25% to 30%) with both diets. Similar declines were observed for both diets in serum prealbumin and retinol-binding protein concentrations. Mean serum transferrin declined with both diets, but the changes were not statistically significant. Serum albumin was unchanged by either diet. Thus, there were no significant differences between the two diets with regard to any of the measured parameters.     

Comparison of the effects on insulin sensitivity of high carbohydrate and high fat diets in normal subjects.

To examine whether achievable dietary changes influence insulin sensitivity, we performed euglycemic hyperinsulinemic glucose clamps in eight normal subjects who were prescribed high carbohydrate and high fat diets. The high carbohydrate diet was more than 50% (of energy intake) carbohydrate and less than 30% fat; the high fat diet was more than 45% fat (predominantly saturated) and less than 40% carbohydrate. The diets were consumed over consecutive 3-week periods in random sequence. The mean whole body glucose uptake during the glucose clamps was similar after the high carbohydrate (48.3 mumol/kg.min) and high fat diets (47.0 mumol/kg.min; P = 0.5; 95% confidence interval for the difference, -3.4 to 5.9 mumol/kg.min). Fasting blood glucose and serum insulin concentrations were also unchanged. In contrast, there were substantial effects on lipoprotein metabolism. During the high carbohydrate diet, fasting serum cholesterol decreased by 17% (P = 0.06), low density lipoprotein cholesterol decreased by 20% (P = 0.05), high density lipoprotein cholesterol decreased by 24% (P less than 0.005), and triglyceride increased by 33% (P = 0.06) compared with levels during the high fat diet. These results suggest that practically achievable high carbohydrate diets do not enhance insulin sensitivity in nondiabetic subjects and have net effects on lipoprotein metabolism that may be unfavorable.     

Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects

Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. CONCLUSION: A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet.     

Metabolism of apolipoproteins CII,CIII1, CIII2 and VLDL-B in human subjects consuming high carbohydrate diets

Simultaneous kinetics of apoproteins CII, CIII₁ and CIII₂ and VLDL-B were determined in six normal subjects initially while consuming a control diet and subsequently while consuming a high carbohydrate diet. Mean triglyceride levels in plasma and VLDL were significantly increased, from 110 to 173 mg/dl and 40 to 114 mg/dl respectively, by the high carbohydrate diet. Specific radioactivity of each C peptide was determined, following injection of ¹²⁵I-VLDL, in both VLDL and HDL from plasma samples taken over 48 hr using a technique involving analytical isoelectric focusing. Specific activity vs time curves for VLDL and HDL were almost superimposable on either diet, suggesting that CII, CIII₁ and CIII₂ were catabolized as a group. The high carbohydrate diet resulted in a significant increase in the mass of each C peptide which was brought about by an increase in production since no change in fractional removal rate (FRR) was observed. The pool size of VLDL apo B was also significantly increased and was a function of both increased production as well as decreased FRR. The proportion of CIII₂ mass relative to those of CII and CIII₁ was lower in both VLDL and HDL with the high carbohydrate diet. These observations indicate that the metabolism of the B and C apoproteins are independent of each other and do not respond in the same manner to changes in VLDL triglyceride and that increased triglyceride synthesis and secretion stimulates C apoprotein production.     

Short-term metabolic effects of prednisone administration in healthy subjects

Aims: Supraphysiologic glucocorticoid activity is well established to cause impaired glucose tolerance and insulin resistance, yet no study has evaluated dose‐dependent effects of low‐dose prednisone during short‐term oral administration. Methods: The objective of this study was to quantify the effects of daily 10 or 25 mg prednisone administration for one week on insulin sensitivity by employing a two‐step hyperinsulinemic euglycemic glucose clamp (Step 1: insulin infusion = 20 mU/m²/min; Step 2: insulin infusion = 80 mU/m²/min) in healthy, lean males. The amount of glucose infused at steady‐state to maintain stable blood glucose [90 mg/dl (4.95 mmol/l)] was used to calculate several indices of insulin sensitivity. Results: During Step 1 of the clamp, whole body glucose disposal (M) was reduced by 35% (p = 0.003) and M/I was reduced by 29% (p = 0.025) for 25 mg prednisone compared to placebo. No appreciable effect of 10 mg prednisone was observed. During Step 2, M was reduced by 33% (p = 0.001) and 15% (p = 0.006) for 25 and 10 mg prednisone compared to placebo; and M/I ratio was reduced by 31% (p < 0.001) and 13% (p = 0.026), respectively. The insulin sensitivity index, Si , calculated as the quotient of augmentation of M/I between Step 1 and 2, was reduced by 35.3% (p < 0.01) and 23.5% (p < 0.05) for 25 and 10 mg prednisone, respectively. Conclusion: Administration of relatively low pharmacological doses of prednisone for one week impaired insulin sensitivity in a dose‐dependent manner in healthy males. These observed changes in insulin sensitivity are likely to be clinically relevant, especially in individuals predisposed to develop glucose intolerance.     

Post-prandial effects of gemfibrozil vs simvastatin in hypercholesterolemic subjects with borderline hypertriglyceridemia

BACKGROUND AND AIM: Impaired triglyceride-rich lipoprotein metabolism is most probably related to an enhanced cardiovascular risk, and may be associated with a pro-coagulant state. A double-blind, randomized study was undertaken to evaluate two widely utilized hypolipidemic drugs in the post-prandial phase and their impact on lipid, coagulation and fibrinolytic parameters. METHODS AND RESULTS: Thirty middle-aged men selected according to their low density lipoprotein-cholesterol (LDL-C) > or = 160 and < or = 240 mg/dl and borderline hypertriglyceridemia (110-220 mg/dl) after at least one month of a lipid-lowering diet received gemfibrozil (600 mg bid) or simvastatin (20 mg qd) and the corresponding placebo. On enrollment and after 2 months of drug treatment, they were tested with a standard oral fat load (OFL) (35 g fat/m2 body surface). On both occasions plasma total-cholesterol, LDL-C, HDL-C, triglycerides, lipoprotein[a] (Lp[a]), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), antithrombin-III (AT-III), plasminogen and fibrinogen were determined just before the meal (t0) and at times 2 hours, 4 h, 6 h, 8 h after it (t2-t8). A two-factor (time and visit) multivariate analysis for repeated measurements was performed to evaluate the data. Total cholesterol, and LDL-C were significantly diminished 2 months after both gemfibrozil and simvastatin, the latter being more active. Plasma triglycerides showed a marked reduction with gemfibrozil at all times, while simvastatin regimen yielded only minor modifications. HDL-C was only slightly increased by simvastatin; Lp[a] plasma levels were almost unaffected. Small fibrinogen (t0, t2, t6, t8), PAI-1 (t6) and AT III (t0-t8) increases were observed after gemfibrozil, while simvastatin did not significantly modify these parameters. CONCLUSIONS: In the post-prandial phase, gemfibrozil and simvastatin induce different metabolic effects that beneficially influence the lipid pattern, whereas fibrinolytic and coagulative parameters display minor variations of undetermined significance.     

The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women.

Postmenopausal women are at an increased risk of developing coronary artery disease (CAD). This increase is due primarily to elevated cholesterol concentrations accompanying the loss of endogenous estrogen secretion. Recently, the consumption of soy foods has been shown to reduce serum cholesterol concentrations. Phytoestrogens (PE) have been proposed as the responsible agents of the hypocholesterolemic effect of soy foods. However, few studies have investigated the effect of PE supplementation on serum lipoproteins. The purpose of the present study is to investigate the effects of PE supplementation (150 mg) on serum lipids and lipoproteins in moderately hypercholesterolemic, elderly, postmenopausal women. Thirty-six subjects were randomized into two groups and received either a 150-mg PE supplement/d (n = 20) or a placebo (n = 16). Serum samples obtained at baseline and 2 months were analyzed for total triacylglycerol, total cholesterol, and high density lipoprotein cholesterol using standard Lipid Research Clinic procedures. In addition, total triacylglycerol and cholesterol were measured after 6 months of treatment. The t test and ANOVA were employed to compare the two groups. The results (mean +/- SEM) indicated no significant differences in total triacylglycerol (1.3 +/- 0.2 vs. 1.2 +/- 0.2 mmol/liter), total cholesterol (6.4 +/- 0.4 vs. 6.5 +/- 0.2 mmol/liter), or high density lipoprotein cholesterol (1.0 +/- 0.1 vs. 1.0 +/- 0.1 mmol/liter) between the placebo and the PE groups, respectively, after 2 months of treatment. Moreover, total triacylglycerol and cholesterol remained unchanged after 6 months. Our findings suggest that PE supplementation with 150 mg/d over a 6-month period does not significantly alter serum lipoproteins in postmenopausal women and, therefore, may not effectively reduce the risk of CAD in this population.     

Guar by-product improves carbohydrate tolerance in healthy human subjects

Guar gum possesses distinct hypoglycemic properties. The other fraction of the guar bean, guar by-product (GBP), was studied to determine if it possesses any hypoglycemic properties. When 25 g GBP or wheat bran were consumed with a carbohydrate test meal by 10 healthy subjects, at 15 and 30 min after the GBP test meal significantly lower normalized plasma glucose responses were measured. Postprandial plasma insulin responses were similar after both test meals. During the first 60 min postprandially, the mean integrated plasma glucose response area was significantly lower after the GBP test meal. These data indicate that GBP, like guar gum, possesses hypoglycemic properties; because of the different chemical characteristics of these 2 guar bean fractions, it seems that their hypoglycemic properties are due probably to different mechanisms.     

The effect of psyllium plantago in slightly to moderately hypercholesterolemic patients

The hypocholesterolemic effect of psyllium plantago (PP) was evaluated in 14 individuals with polygenic hypercholesterolemia. Subjects with secondary dyslipidemias were excluded. Since their admission until the end of the study all the patients had to follow an isocaloric diet, with less than 10% of the calories provided as saturated fats, P/S relation greater than 1 and daily intake of less than 300 mgr of cholesterol. The study was divided in two stages; the first one, from week -6 to 0 evaluated exclusively the response to diet, and the stage II, from week 0 to +12, evaluated the response to PP. The PP in envelopes with 3.4 grs each, was taken dissolved in water three times daily before meals. In the weeks -6, 0, +4, +8 and +12 were done lipid profiles that included; total cholesterol, triglycerides, and high density cholesterol. Cholesterol of the low density lipoproteins was obtained with the formula of Friedewald modified by De Long. The use of PP produced at week 12 a reduction of 8% in total cholesterol and 11% in LDL cholesterol. With non significant changes in triglycerides and HDL-C. We conclude that PP can be used as a complement of diet in the management of polygenic hypercholesterolemia.     

High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects

OBJECTIVE: To test the hypothesis that hyperinsulinemic obese subjects would respond differently to changes in the composition of hypoenergetic diets. DESIGN: A 4-week randomized dietary intervention trial. SUBJECTS: Thirteen male obese hyperinsulinemic normoglycemic subjects were divided into two groups and fed hypoenergetic diets providing 80% of their resting energy expenditure (REE). One group received a high-protein diet (HP; 45% protein, 25% carbohydrates, and 30% fat as percent of dietary energy) and the other a high-carbohydrate diet (HC; 12% protein, 58% carbohydrates and 30% fat). MEASUREMENTS: Anthropometry, body composition, fasting serum insulin and lipids, and REE were performed before and after the feeding period. RESULTS: Weight loss was higher in the HP than HC group (8.3+/-0.7 vs 6.0+/-0.6 kg, P<0. 05). There was a decrease in body fat in both groups, whereas body water decreased significantly more in the HP group. REE decreased more in the HC than the HP group (-384.3+/-84.6 vs -132.3+/-51.0 kcal, P<0.05). Serum total cholesterol, triglycerides and LDL cholesterol decreased significantly to a similar extent in both diet groups, while HDL cholesterol was decreased significantly only in the HP group. Mean fasting insulin decreased significantly in both diet groups and reached the normal range only in the HP group. CONCLUSION: A low-carbohydrate (LC), HP hypoenergetic diet could be the diet composition of choice for a weight-reducing regimen in obese hyperinsulinemic subjects.     

The thermogenic and metabolic effects of protein hydrolysate with or without a carbohydrate load in healthy male subjects

High-protein diets are beneficial in weight maintenance because of their satiating and thermogenic effects. These effects may be partly mediated by the hormonal effects of proteins. This study investigated the effect of soy protein hydrolysate (SPH) with and without a carbohydrate pre- and afterload on energy metabolism and hormonal secretion in 8 healthy nonobese subjects. In an additional trial, pea protein hydrolysate was compared to SPH, both with a carbohydrate afterload. The study had a single-blind crossover design. In all cases, 0.4 g protein and/or carbohydrate per kilogram of body weight was tested. Diet-induced thermogenesis (DIT) was measured by ventilated hood measurements, and postprandial blood samples were drawn over 3 hours. Soy protein hydrolysate consumption induced a higher DIT than a carbohydrate (CHO) load. Both conditions induced similar insulin responses. Soy protein hydrolysate induced a glucagon, but no glucose, response; whereas CHO induced a glucose, but no glucagon, response. Soy protein hydrolysate with a CHO pre- or afterload induced similar DIT and insulin responses. No glucose response was found when SPH preceded the CHO load. Total glucagon responses were similar with CHO as pre- and afterload, but time courses were different. Pea protein hydrolysate with a CHO afterload induced both higher insulin and glucagon responses (area under the curve) than SPH with CHO afterload, but DIT was similar in both conditions. In conclusion, this study shows that the larger DIT after protein than after CHO may be related to the glucagon response that is induced by protein but not by CHO; that the protein-induced DIT and glucagon response are not influenced by a CHO pre- or afterload; and that protein ingestion can fully prevent the plasma glucose increase associated with CHO when CHOs are ingested after proteins.     

Diet-induced thermogenesis in man: thermic effects of single protein and carbohydrate test meals in lean and obese subjects

Postprandial thermogenesis of 8 healthy males of normal body weight and 17 healthy obese subjects with a body weight gain of more than 10 kg per year was measured continuously by means of a respiratory chamber over 10 h after test meals of 1 and 2 MJ protein (casein) and 2 MJ carbohydrate (hydrolized starch). The total thermic response to all test meals was reduced by about 50% in the obese subjects. The thermic response was related to body weight, energy intake, resting metabolic rate and weight loss during restricted energy intake. The necessity for a careful characterization of the obese subjects in studies of thermogenesis and of efficiency of energy utilization in obesity is pointed out. It is suggested that thermic response to food can be considered as a suitable indicator for the distinction between people of different metabolic efficiency.     

Markedly elevated lipid transfer inhibitor protein in hypercholesterolemic subjects is mitigated by plasma triglyceride levels

Lipid transfer inhibitor protein (LTIP, apolipoprotein F) regulates the interaction of cholesteryl ester transfer protein (CETP) with lipoproteins and is postulated to enhance the ability of CETP to stimulate reverse cholesterol transport. The factors that regulate LTIP levels and control its biosynthesis are unknown. Here, we demonstrate that plasma LTIP is dramatically increased (3-fold) in hypercholesterolemic subjects with normal to mildly elevated plasma triglyceride (TG) levels compared with control subjects. LTIP in these subjects is not correlated with the extent of hypercholesterolemia or with low density lipoprotein (LDL), high density lipoprotein, or CETP levels. However, unlike CETP, LTIP levels correlate negatively with plasma TG levels. This association does not appear to reflect decreased LTIP synthesis, inasmuch as conditions that stimulate TG synthesis and secretion (200 micromol/L oleate) do not reduce LTIP secretion by SW872 or Caco-2 cells. In contrast, native or acetyl LDL stimulates LTIP secretion 2-fold. Importantly, although plasma LTIP typically resides on LDL, up to 25% of LTIP is bound to very low density lipoprotein when this lipoprotein is enriched in cholesteryl esters, as occurs in hypercholesterolemia. In summary, LTIP levels are markedly elevated by hypercholesterolemia; however, plasma TG levels attenuate this response. We hypothesize that this arises from an increased association of LTIP with very low density lipoprotein, leading to a more rapid clearance of the inhibitor from circulation.     

Short-term effects of low-dose atorvastatin on inflammatory status and lipid profiles in perimenopausal hypercholesterolemic, hypertriglyceridemic women

The short-term and small-dose pleiotropic effects of atorvastatin and influence on sex steroid production were investigated in 35 premenopausal and 71 postmenopausal hypercholesterolemic, hypertriglyceridemic women, as well as the temporal differences in these pleiotropic effects. Atorvastatin (10 mg daily) was given for 6 months and fasting lipid concentrations, high sensitive CRP, and coagulo-fibrinolytic parameters were measured at baseline and after 3 and 6 months of therapy. Atorvastatin reduced the low-density lipoprotein cholesterol, remnant-like particle lipoprotein cholesterol, and malondialdehyde-modified low-density lipoprotein cholesterol after 3 and 6 months in both pre- and postmenopausal women. Atorvastatin decreased significantly high-sensitivity C-reactive protein concentration (-47.6% and -58.0%, P<0.01) and tissue plasminogen activator/plasminogen activator inhibitor-1 ratio (-31.8% and -40.0%, P<0.001) after 6 months in pre- and postmenopausal women. There was no correlation between the pleiotropic effects and the improvement in the lipid profile. Furthermore, atorvastatin has no influence on sex steroid production in both pre- and postmenopausal period. The results indicate some short-term pleiotropic effects of small-dose atorvastatin therapy without influence of endocrinological status, which may be important with respect to the early benefits of statin therapy in the perimenopausal hyperlipidemic women.     

Soy protein reduces triglyceride levels and triglyceride fatty acid fractional synthesis rate in hypercholesterolemic subjects

To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g/1000 kcal), without or with isoflavones (49 mg/1000 kcal) and were each fed for 6 weeks. Blood samples from 20 hyperlipidemic subjects (6M, 14F, 62 +/- 9 years, BMI 26 +/- 3 kg/m(2), LDL cholesterol >160 mg/dl after feeding animal protein without isoflavones) were selected to measure TGFA fractional synthetic rate (TGFA-FSR) and free cholesterol fractional synthetic rate (FC-FSR) over 24h as deuterium oxide uptake into TGFA and free cholesterol. Soy protein reduced TG by 12.4% (P < 0.0001), total cholesterol by 4.4% (P < 0.001), and LDL cholesterol by 5.7% (P = 0.003) compared to animal protein. The TGFA-FSR was reduced by 13.3% (P = 0.018) and FC-FSR was increased by 7.6% (P = 0.017) after the soy protein relative to the animal protein. Isoflavones had no significant effect on TG and TGFA-FSR. Isoflavones reduced total cholesterol levels by 3.1% (P = 0.009) but had no significant effect on LDL, HDL cholesterol levels, or FC-FSR. These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms.