5-Year effects of a novel continuous remote care model with carbohydrate-restricted nutrition therapy including nutritional ketosis in type 2 diabetes: An extension study.

AIMS: This study assessed the five-year effects of a continuous care intervention (CCI) delivered via telemedicine, counseling people with type 2 diabetes (T2D) on a very low carbohydrate diet with nutritional ketosis. METHODS: Participants with T2D were enrolled in a 2-year, open-label, non-randomized study comparing CCI and usual care (UC). After 2 years, 194 of the 262 CCI participants were approached for a three-year extension. Of these, 169 consented, and 122 remained in the study for five years. Primary outcomes were changes in diabetes status assessed using McNemars' test, including remission and HbA1c < 6.5 % on no glucose lowering medication or only on metformin at 5 years. Changes in body mass, glycemia, and cardiometabolic markers from baseline to 5 years were assessed using linear mixed-effects models. RESULTS: Twenty percent (n = 24) of the five-year completers achieved remission, with sustained remission observed over three years in 15.8 % (n = 19) and four years in 12.5 % (n = 15). Reversal to HbA1c < 6.5 % without medication or only metformin was seen in 32.5 % (n = 39). Sustained improvements were noted in body mass (-7.6 %), HbA1c (-0.3 %), triglycerides (-18.4 %), HDL-C (+17.4 %), and inflammatory markers, with no significant changes in LDL-C and total cholesterol. CONCLUSIONS: Over five years, the very low carbohydrate intervention showed excellent retention and significant health benefits, including diabetes remission, weight loss, and improved cardiometabolic markers.

Impact of the COVID-19 Pandemic on the Effectiveness of a Metabolic Health Telemedicine Intervention for Weight Loss: A Propensity Score Matching Analysis.

Background: Coronavirus disease 2019 (COVID-19) pandemic public health measures such as stay-at-home and mandatory work-from-home orders have been associated with obesogenic lifestyle changes, increased risk of weight gain, and their metabolic sequelae. We sought to assess the impact of this pandemic on weight loss from a telemedicine-delivered very-low-carbohydrate intervention targeting nutritional ketosis (NKI). Methods: A total of 746 patients with a BMI ≥25kg/m2, enrolled between January and March 2020 and treated for at least 1 year with the NKI, were classified as pandemic cohort (PC). A separate cohort of 699 patients who received 1 year of the NKI in the preceding years, enrolled between January and March 2018, were identified as pre-pandemic cohort (Pre-PC). Demographic and clinical data were obtained from medical records to compare the cohorts and assess the outcomes. Using propensity score matching (PSM), balanced and matched groups of 407 patients in the Pre-PC and 407 patients in the PC were generated. Longitudinal change in absolute weight and percentage weight change from baseline to 1 year were assessed. Results: Weight significantly decreased in both PC and Pre-PC at 3, 6, 9, and 12 months. The weight loss trajectory was similar in both PC and Pre-PC with no significant weight differences between the two cohorts at 3, 6, 9, and 12 months. On an average, the PC lost 7.5% body weight while the Pre-PC lost 7.9% over 1 year, and the percent weight loss did not differ between the two cohorts (p = 0.50). Conclusion: A very-low-carbohydrate telemedicine intervention delivered comparable and medically significant weight loss independent of pandemic stress and lifestyle limitations.

Reduced COVID-19 severity elicited by weight loss from a medically supervised ketogenic diet in a geographically diverse ambulatory population with type 2 diabetes and obesity.

Objective: To investigate factors associated with COVID-19 severity in ambulatory individuals with type 2 diabetes mellitus (T2DM) and obesity treated with a medically supervised ketogenic diet (MSKD). Research design and methods: In this real-world, retrospective, exploratory analysis, multivariate modelling was used to assess clinical factors associated with hospitalisation for COVID-19 in a geographically diverse outpatient population with T2DM treated virtually. Results: Leading up to COVID-19 onset, non-hospitalised patients had higher average ketones (0.64 vs 0.52 mmol/L; p=0.016) and greater weight loss (6.8% vs 4.2%; p=0.009) compared with those hospitalised. Greater weight loss was significantly associated with lower likelihood of hospitalisation (adjusted OR=0.91, p=0.005), controlling for enrolment demographics and medical characteristics. Conclusions: Therapies such as MSKD, which elicit rapid, significant weight loss, may favourably impact COVID-19 hospitalisation rate and severity in individuals with T2DM and obesity.

Evidence of the Exercise-Hypogonadal Male Condition at the 2011 Kona Ironman World Championships.

PURPOSE: Prior research has illustrated that high volumes of aerobic exercise result in a reduction in basal concentrations of testosterone in men. Those studies were mostly conducted on recreational runners and identified reduced testosterone, but not concentrations low enough to be considered pathological. Therefore, the purpose of this study was to assess the basal concentrations of testosterone and cortisol in elite triathletes, as well as the impact of a World Championship race, on the acute responses of these hormones. METHODS: A total of 22 men (age 40.6 [11.5] y, height 179 [6] cm, weight 77.0 [7.0] kg) who participated in the 2011 Ironman World Championships served as subjects. Resting blood samples were taken 2-4 d prior to provide a baseline (BL), as well as immediately, 1 d, and 2 d after the event and were later analyzed for total testosterone and cortisol concentrations. RESULTS: At BL, 9 men had a normal testosterone concentration, whereas 9 men fell within a "gray zone" and 4 other men demonstrated concentrations suggestive of deficiency. Testosterone was significantly lower than BL at 1 d (95% confidence interval [CI] 0.10-0.34, P < .001, ES = 0.53) and 2 d (95% CI 0.01-0.21, P = .034, ES = 0.35) after the event. Cortisol was significantly different from BL at immediate post (95% CI 1.07-0.83, P < .001, ES = 8.0). There were significant correlations between time and age (R = .68, P = .001), as well as BL testosterone and cortisol (R = .51, P = .015). CONCLUSION: Elite ultraendurance athletes may demonstrate not only reduced testosterone but also sometimes clinically low concentrations that could be indicative of androgen deficiency.

Influence of cold-water immersion on recovery of elite triathletes following the ironman world championship.

OBJECTIVES: Cold water immersion (CWI) has been widely used for enhancing athlete recovery though its use following an Ironman triathlon has never been examined. The purpose of this paper is to determine the influence of CWI immediately following an Ironman triathlon on markers of muscle damage, inflammation and muscle soreness. DESIGN: Prospective cohort study. METHODS: Thirty three (22 male, 11 female), triathletes participating in the Ironman World Championships volunteered to participate (mean±SD: age=40±11years; height=174.5±9.1cm; body mass=70±11.8kg; percent body fat=11.4±4.1%, finish time=11:03.00±01:25.08). Post race, participants were randomly assigned to a 10-min bout of 10°C CWI or no-intervention control group. Data collection occurred pre-intervention (PRE), post-intervention (POST), 16h (16POST) and 40h (40POST) following the race. Linear mixed model ANOVA with Bonferroni corrections were performed to examine group by time differences for delayed onset muscle soreness (DOMS), hydration indices, myoglobin, creatine kinase (CK), cortisol, C-reactive protein (CRP), IL-6 and percent body mass loss (%BML). Pearson's bivariate correlations were used for comparisons with finishing time. Alpha level was set a priori at 0.05. RESULTS: No significant group by time interactions occurred. Significant differences occurred for POST BML (-1.7±0.9kg) vs. 16POST, and 40POST BML (0.9±1.4, -0.1±1.2kg, respectively; p<0.001). Compared to PRE, myoglobin, CRP and CK remained significantly elevated at 40POST. Cortisol returned to PRE values by 16POST and IL-6 returned to PRE values by 40POST. CONCLUSION: A single bout of CWI did not provide any physiological benefit during recovery from a triathlon within 40h post race. Effect of CWI beyond this time is unknown.

Author Correction: Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study.

The original version of this article unfortunately contained a mistake.

Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study.

INTRODUCTION: Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management. METHODS: We conducted an open-label, non-randomized, controlled, before-and-after 1-year study of this continuous care intervention (CCI) and usual care (UC). Primary outcomes were glycosylated hemoglobin (HbA1c), weight, and medication use. Secondary outcomes included fasting serum glucose and insulin, HOMA-IR, blood lipids and lipoproteins, liver and kidney function markers, and high-sensitivity C-reactive protein (hsCRP). RESULTS: 349 adults with T2D enrolled: CCI: n = 262 [mean (SD); 54 (8) years, 116.5 (25.9) kg, 40.4 (8.8) kg m2, 92% obese, 88% prescribed T2D medication]; UC: n = 87 (52 (10) years, 105.6 (22.15) kg, 36.72 (7.26) kg m2, 82% obese, 87% prescribed T2D medication]. 218 participants (83%) remained enrolled in the CCI at 1 year. Intention-to-treat analysis of the CCI (mean ± SE) revealed HbA1c declined from 59.6 ± 1.0 to 45.2 ± 0.8 mmol mol-1 (7.6 ± 0.09% to 6.3 ± 0.07%, P < 1.0 × 10-16), weight declined 13.8 ± 0.71 kg (P < 1.0 × 10-16), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (P < 1.0 × 10-16). Insulin therapy was reduced or eliminated in 94% of users; sulfonylureas were entirely eliminated in the CCI. No adverse events were attributed to the CCI. Additional CCI 1-year effects were HOMA-IR - 55% (P = 3.2 × 10-5), hsCRP - 39% (P < 1.0 × 10-16), triglycerides - 24% (P < 1.0 × 10-16), HDL-cholesterol + 18% (P < 1.0 × 10-16), and LDL-cholesterol + 10% (P = 5.1 × 10-5); serum creatinine and liver enzymes (ALT, AST, and ALP) declined (P ≤ 0.0001), and apolipoprotein B was unchanged (P = 0.37). UC participants had no significant changes in biomarkers or T2D medication prescription at 1 year. CONCLUSIONS: These results demonstrate that a novel metabolic and continuous remote care model can support adults with T2D to safely improve HbA1c, weight, and other biomarkers while reducing diabetes medication use. CLINICALTRIALS. GOV IDENTIFIER: NCT02519309. FUNDING: Virta Health Corp.

Treatments for type 2 diabetes (T2D) have improved, yet T2D and being overweight are still significant public health concerns. Blood sugar in patients with T2D can improve quickly when patients eat significantly fewer dietary carbohydrates. However, this demands careful medicine management by doctors, and patients need support and frequent contact with health providers to sustain this way of living. The purpose of this study was to evaluate if a new care model with very low dietary carbohydrate intake and continuous supervision by a health coach and doctor could safely lower HbA1c, weight and need for medicines after 1 year in adults with T2D. 262 adults with T2D volunteered to participate in this continuous care intervention (CCI) along with 87 adults with T2D receiving usual care (UC) from their doctors and diabetes education program. After 1 year, patients in the CCI, on average, lowered HbA1c from 7.6 to 6.3%, lost 12% of their body weight, and reduced diabetes medicine use. 94% of patients who were prescribed insulin reduced or stopped their insulin use, and sulfonylureas were eliminated in all patients. Participants in the UC group had no changes to HbA1c, weight or diabetes medicine use over the year. These changes in CCI participants happened safely while dyslipidemia and markers of inflammation and liver function improved. This suggests the novel care model studied here using dietary carbohydrate restriction and continuous remote care can safely support adults with T2D to lower HbA1c, weight, and medicine use.

A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes.

BACKGROUND: Type 2 diabetes (T2D) is typically managed with a reduced fat diet plus glucose-lowering medications, the latter often promoting weight gain. OBJECTIVE: We evaluated whether individuals with T2D could be taught by either on-site group or remote means to sustain adequate carbohydrate restriction to achieve nutritional ketosis as part of a comprehensive intervention, thereby improving glycemic control, decreasing medication use, and allowing clinically relevant weight loss. METHODS: This study was a nonrandomized, parallel arm, outpatient intervention. Adults with T2D (N=262; mean age 54, SD 8, years; mean body mass index 41, SD 8, kg·m-2; 66.8% (175/262) women) were enrolled in an outpatient protocol providing intensive nutrition and behavioral counseling, digital coaching and education platform, and physician-guided medication management. A total of 238 participants completed the first 10 weeks. Body weight, capillary blood glucose, and beta-hydroxybutyrate (BOHB) levels were recorded daily using a mobile interface. Hemoglobin A1c (HbA1c) and related biomarkers of T2D were evaluated at baseline and 10-week follow-up. RESULTS: Baseline HbA1c level was 7.6% (SD 1.5%) and only 52/262 (19.8%) participants had an HbA1c level of <6.5%. After 10 weeks, HbA1c level was reduced by 1.0% (SD 1.1%; 95% CI 0.9% to 1.1%, P<.001), and the percentage of individuals with an HbA1c level of <6.5% increased to 56.1% (147/262). The majority of participants (234/262, 89.3%) were taking at least one diabetes medication at baseline. By 10 weeks, 133/234 (56.8%) individuals had one or more diabetes medications reduced or eliminated. At follow-up, 47.7% of participants (125/262) achieved an HbA1c level of <6.5% while taking metformin only (n=86) or no diabetes medications (n=39). Mean body mass reduction was 7.2% (SD 3.7%; 95% CI 5.8% to 7.7%, P<.001) from baseline (117, SD 26, kg). Mean BOHB over 10 weeks was 0.6 (SD 0.6) mmol·L-1 indicating consistent carbohydrate restriction. Post hoc comparison of the remote versus on-site means of education revealed no effect of delivery method on change in HbA1c (F1,260=1.503, P=.22). CONCLUSIONS: These initial results indicate that an individualized program delivered and supported remotely that incorporates nutritional ketosis can be highly effective in improving glycemic control and weight loss in adults with T2D while significantly decreasing medication use.

Effects of step-wise increases in dietary carbohydrate on circulating saturated Fatty acids and palmitoleic Acid in adults with metabolic syndrome.

Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m2) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes.

Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins.

Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (<50 g carbohydrate/d) for 6 weeks would improve lipid profiles and insulin sensitivity, reduce blood pressure, decrease cellular adhesion and inflammatory biomarkers, and augment VEF (flow-mediated dilation and forearm blood flow) in statin users. Participants (n = 21; 59.3 ± 9.3 y, 29.5 ± 3.0 kg/m(2)) decreased total caloric intake by approximately 415 kcal at 6 weeks (P < .001). Daily nutrient intakes at baseline (46/36/17% carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P ≤ .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P < .01) from baseline at week 3, and this effect was maintained at week 6. In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules.

Triglyceride recrystallized phytosterols in fat-free milk improve lipoprotein profiles more than unmodified free phytosterols in hypercholesterolemic men and women.

OBJECTIVE: Foods incorporating plant sterols (PS) consistently decrease serum low-density lipoprotein cholesterol (LDL-C), although results vary depending on the PS form and food matrix. The objective was to study the effect of a novel triglyceride-recrystallized phystosterol (TRP) incorporated into fat-free milk on markers of cardiovascular risk compared to unmodified free sterols alone in the same fat-free milk. METHODS: Hypercholesterolemic men and women (n = 13 males/7 females; 56 ± 10 years; body mass index 27.3 ± 5.9 kg/m(2)) participated in 3 sequential 4-week phases of 480 mL milk consumption. During phase 1 (control) all subjects consumed 2% milk containing no PS, followed by phase 2 with fat-free milk containing free PS (2 g/d fPS) and phase 3 with fat-free milk with TRP (2 g/d). After each phase, determinations of lipoprotein cholesterol distribution, particle concentration via nuclear magnetic resonance (NMR), apolipoproteins, inflammatory markers, and fat-soluble dietary antioxidants were made. RESULTS: Body mass, body composition, dietary energy and macronutrients, and physical activity were unaffected throughout the study. Compared to the control 2% milk, LDL-C was significantly (p < 0.05) decreased by fPS (-9.1%) and was further decreased by TRP (-15.4%); reductions with TRP were significantly greater. Total LDL particle concentration was decreased to a greater extent after TRP (-8.8%) than fPS (-4.8%; p < 0.05). Only TRP significantly decreased serum levels of apolipoprotein B (apoB; -6%), interleukin-8 (IL-8; -11%) and monocyte chemotactic protein-1 (MCP-1; -19%). Plasma α- and γ-tocopherols and carotenoids, normalized to cholesterol, remained unchanged throughout the study with the exception that ß-carotene was lowered by 18%. CONCLUSION: In summary, TRP in fat-free milk may provide cardiovascular benefits beyond that of fPS by inducing more substantial decreases in LDL cholesterol and particle concentration, associated with declines in markers of vascular inflammation.

The effects of soy and whey protein supplementation on acute hormonal reponses to resistance exercise in men.

OBJECTIVE: For many resistance-trained men concerns exist regarding the production of estrogen with the consumption of soy protein when training for muscle strength and size. Thus, the purpose of this investigation was to examine the effects of soy and whey protein supplementation on sex hormones following an acute bout of heavy resistance exercise in resistance trained men. METHODS: Ten resistance-trained men (age 21.7 ± 2.8 [SD] years; height 175.0 ± 5.4 cm; weight 84.2 ± 9.1 kg) volunteered to participate in an investigation. Utilizing a within subject randomized crossover balanced placebo design, all subjects completed 3 experimental treatment conditions supplementing with whey protein isolate (WPI), soy protein isolate (SPI), and maltodextrin placebo control for 14 days with participants ingesting 20 g of their assigned supplement each morning at approximately the same time each day. Following supplementation, subjects performed an acute heavy resistance exercise test consisting of 6 sets of 10 repetitions in the squat exercise at 80% of the subject's one repetition maximum. RESULTS: This investigation observed lower testosterone responses following supplementation with soy protein in addition to a positive blunted cortisol response with the use of whey protein at some recovery time points. Although sex hormone binding globulin (SHBG) was proposed as a possible mechanism for understanding changes in androgen content, SHBG did not differ between experimental treatments. Importantly, there were no significant differences between groups in changes in estradiol concentrations. CONCLUSION: Our main findings demonstrate that 14 days of supplementation with soy protein does appear to partially blunt serum testosterone. In addition, whey influences the response of cortisol following an acute bout of resistance exercise by blunting its increase during recovery. Protein supplementation alters the physiological responses to a commonly used exercise modality with some differences due to the type of protein utilized.

Whey protein supplementation during resistance training augments lean body mass.

UNLABELLED: Compared to soy, whey protein is higher in leucine, absorbed quicker and results in a more pronounced increase in muscle protein synthesis. OBJECTIVE: To determine whether supplementation with whey promotes greater increases in muscle mass compared to soy or carbohydrate, we randomized non-resistance-trained men and women into groups who consumed daily isocaloric supplements containing carbohydrate (carb; n = 22), whey protein (whey; n = 19), or soy protein (soy; n = 22). METHODS: All subjects completed a supervised, whole-body periodized resistance training program consisting of 96 workouts (~9 months). Body composition was determined at baseline and after 3, 6, and 9 months. Plasma amino acid responses to resistance exercise followed by supplement ingestion were determined at baseline and 9 months. RESULTS: Daily protein intake (including the supplement) for carb, whey, and soy was 1.1, 1.4, and 1.4 g·kg body mass⁻¹, respectively. Lean body mass gains were significantly (p < 0.05) greater in whey (3.3 ± 1.5 kg) than carb (2.3 ± 1.7 kg) and soy (1.8 ± 1.6 kg). Fat mass decreased slightly but there were no differences between groups. Fasting concentrations of leucine were significantly elevated (20%) and postexercise plasma leucine increased more than 2-fold in whey. Fasting leucine concentrations were positively correlated with lean body mass responses. CONCLUSIONS: Despite consuming similar calories and protein during resistance training, daily supplementation with whey was more effective than soy protein or isocaloric carbohydrate control treatment conditions in promoting gains in lean body mass. These results highlight the importance of protein quality as an important determinant of lean body mass responses to resistance training.

Alterations in coagulatory and fibrinolytic systems following an ultra-marathon.

PURPOSE: The aim of this study was to examine coagulatory and fibrinolytic responses to the Western States Endurance Run (WSER, June 23 to 24, 2012). The WSER is a 161-km (100 mile) trail foot race through the Sierra Nevada Mountains that involves 6,030 m of climb and 7,001 m of descent. METHODS: We examined 12 men and 4 women [mean (95 % CI), age 44.6 years (38.7-50.6)] who completed the race (24.64 h; range 16.89-29.46). Blood samples were collected the morning before the race, immediately post-race, and 1 (D1) and 2 (D2) days post-race (corresponding to 51-54 h and 75-78 h from the start of the race, respectively). Hypercoagulable state was characterized by prothrombin fragment 1+2 (PTF 1+2) and thrombin-antithrombin complex (TAT). Fibrinolytic state was assessed by plasminogen activator inhibitor antigen (PAI-1 Ag), tissue plasminogen activator antigen (tPA Ag), and D-Dimer. Muscle damage was assessed by serum creatine kinase (CK) and myoglobin concentrations. RESULTS: Significant (P ≤ 0.05) increases were observed immediately post-race for thrombin generation markers, PTF 1+2 (3.9-fold) and TAT (2.4-fold); markers of fibrinolysis, tPA Ag (4.0-fold), PAI-1 Ag (4.5-fold), and D-Dimer (2.2-fold); and muscle damage markers, CK (154-fold) and myoglobin (114-fold). Most markers continued to be elevated at D1, as seen by PTF 1+2, TAT (1.5- and 1.3-fold increase at D1), and D-Dimer (2.5- and 2.1-fold increase at D1 and D2, respectively). Additionally, PTF 1+2:tPA and TAT:tPA ratios, which assessed balance between coagulation and fibrinolysis, were slightly, but significantly increased at D1 (69 and 36 %) and D2 (19 and 31 %). CK and myoglobin also remained elevated at D1 (54- and 7-fold) and D2 (25- and 2-fold) time points. CONCLUSION: The WSER produced extensive muscle damage and activated the coagulation and fibrinolytic systems. Since we observed a slight imbalance response between the two systems, a limited potential for thrombotic episodes is apparent in these highly trained athletes.

Influence of training on markers of platelet activation in response to a bout of heavy resistance exercise.

Recent connections between platelet activity and cardiovascular disease have raised questions of whether platelet function varies in exercising individuals. Resistance training has been linked to a possible reduction in hyper-aggregability of platelets, especially following acute strenuous exercise. The present investigation was designed to explore the effects of an acute resistance exercise test on the primary hemostatic system in both resistance-trained (RT) and untrained (UT) individuals. Ten RT (five men and five women; age, 26.0 ± 4.5 years; height, 175.12 ± 8.54 cm; weight, 79.56 ± 13.56 kg) and ten UT (five men and five women; age, 26.4 ± 6.2 years; height, 170.31 ± 7.45 cm; weight 67.88 ± 16.90 kg) individuals performed an Acute Exhaustive Resistance Exercise Test (AERET; six sets of ten repetitions of squats at 80 % of the 1-Repetition Maximum (RM)). Blood samples were obtained before, immediately after, and at 15, 60, and 120 min following the AERET. Blood samples were analyzed for platelet count, von Willebrand factor antigen (vWF:Ag), beta-thromboglobulin (ß-TG), and platelet factor 4 (PF4). B-TG showed significant differences (p < 0.05) between RT and UT at +15 and +60 min. Both groups showed a main effect for time in platelet count, vWF, and ß-TG following the AERET, whereas PF4 remained unchanged. All blood variables returned to baseline 120 min after exercise. Compared with UT, RT demonstrated reduced platelet activation in response to an acute bout of heavy resistance exercise. Reduced platelet activation may be attributed to training status, as shown by a reduction in plasma concentrations of B-TG in the RT group.

Beneficial effects of habitual resistance exercise training on coagulation and fibrinolytic responses.

BACKGROUND: A sedentary lifestyle is a major risk factor for cardiovascular and thrombotic complications. While habitual endurance activity will reduce the risk of these adverse events, the influence of habitual resistance exercise is less clear. This study examined coagulation and fibrinolytic responses to an acute exhaustive resistance exercise test (AERET) in both resistance-trained (RT, min 2 yr, 5 men and 5 women) and untrained (UT, 5 men and 5 women) subjects. METHODS: The AERET consisted of six sets of 10 repetitions of squats at 80% of 1-repetition maximum. Venous blood was collected pre-exercise, immediate post exercise (IP), and +15, +60, and +120 minutes post exercise. RESULTS: Compared to UT, RT exhibited a lower capacity to form a clot as seen by activated partial Thromboplastin time (aPTT) integrated area under the curve over time (iAUC) levels, lower pre-exercise and 120 min post-exercise plasminogen activator inhibitor -1 (PAI-1) activity, and higher tissue plasminogen activator (tPA) activity immediately post-exercise. There were no significant differences between RT and UT for fibrinogen, prothrombin fragment 1+2 (PTF 1+2), and thrombin-antithrombin complexes (TAT). CONCLUSION: These results suggest that habitual resistance exercise training may provide an enhanced fibrinolytic state.

Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women.

Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF. Brachial artery FMD, plasma amino acids, insulin, and endothelium-derived vasodilators and vasoconstrictors were measured for 2 h after ingestion of NOP-47 or placebo. Acute NOP-47 ingestion increased FMD at 30 min (4·6 (sem 0·5) %) and 120 min (5·1 (sem 0·5) %) post-ingestion (P< 0·05, time × trial interaction), and FMD responses at 120 min were significantly greater in the NOP-47 trial compared with placebo (4·3 (sem 0·5) %). Plasma amino acids increased at 30 min following NOP-47 ingestion (P< 0·05). Serum insulin increased at 15, 30 and 60 min (P< 0·001) following NOP-47 ingestion. No changes were observed between the trials for plasma NO∙ and prostacyclin metabolites or endothelin-1. Ingestion of a rapidly absorbed extract derived from whey protein improved endothelium-dependent dilation in older adults by a mechanism independent of changes in circulating vasoactive compounds. Future investigation is warranted in individuals at an increased CVD risk to further elucidate potential health benefits and the underlying mechanisms of extracts derived from whey.

Limited effect of dietary saturated fat on plasma saturated fat in the context of a low carbohydrate diet.

We recently showed that a hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA). Here we extend these findings in 8 weight stable men who were fed two 6-week CRD (12%en carbohydrate) varying in quality of fat. One CRD emphasized SFA (CRD-SFA, 86 g/d SFA) and the other, unsaturated fat (CRD-UFA, 47 g SFA/d). All foods were provided to subjects. Both CRD decreased serum triacylglycerol (TAG) and insulin, and increased LDL-C particle size. The CRD-UFA significantly decreased plasma TAG SFA (27.48 ± 2.89 mol%) compared to baseline (31.06 ± 4.26 mol%). Plasma TAG SFA, however, remained unchanged in the CRD-SFA (33.14 ± 3.49 mol%) despite a doubling in SFA intake. Both CRD significantly reduced plasma palmitoleic acid (16:1n-7) indicating decreased de novo lipogenesis. CRD-SFA significantly increased plasma phospholipid ARA content, while CRD-UFA significantly increased EPA and DHA. Urine 8-iso PGF(2α), a free radical-catalyzed product of ARA, was significantly lower than baseline following CRD-UFA (-32%). There was a significant inverse correlation between changes in urine 8-iso PGF(2α) and PL ARA on both CRD (r = -0.82 CRD-SFA; r = -0.62 CRD-UFA). These findings are consistent with the concept that dietary saturated fat is efficiently metabolized in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA.

Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial.

BACKGROUND: Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47) increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. METHODS: A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10) and women (n = 10) (25 +/- 5 y, BMI = 24.3 +/- 2.3 kg/m2) participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47) or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD) and venous occlusion strain gauge plethysmography. RESULTS: Baseline peak FMD was not different for Placebo (7.7%) and NOP-47 (7.8%). Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively) whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P < 0.0001 for time x trial interaction). Baseline reactive hyperemia forearm blood flow was not different for placebo (27.2 +/- 7.2%/min) and NOP-47 (27.3 +/- 7.6%/min). Hyperemia blood flow measured 120 min post-ingestion (27.2 +/- 7.8%/min) was unaffected by placebo whereas NOP-47 significantly increased hyperemia compared to baseline (29.9 +/- 7.8%/min; P = 0.008 for time x trial interaction). Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25%) compared to NOP-47 (-18%). CONCLUSION: These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.