Effects of Palm Stearin versus Butter in the Context of Low-Carbohydrate/High-Fat and High-Carbohydrate/Low-Fat Diets on Circulating Lipids in a Controlled Feeding Study in Healthy Humans.

BACKGROUND: Foods rich in saturated fatty acids (SFAs) have been discouraged by virtue of their cholesterol-raising potential, but this effect is modulated by the food source and background level of carbohydrate. OBJECTIVE: We aimed to compare the consumption of palm stearin (PS) versus butter on circulating cholesterol responses in the setting of both a low-carbohydrate/high-fat (LC/HF) and high-carbohydrate/low-fat (HC/LF) diet in healthy subjects. We also explored effects on plasma lipoprotein particle distribution and fatty acid composition. METHODS: We performed a randomized, controlled-feeding, cross-over study that compared a PS- versus a Butter-based diet in a group of normocholesterolemic, non-obese adults. A controlled canola oil-based 'Run-In' diet preceded the experimental PS and Butter diets. All diets were eucaloric, provided for 3-weeks, and had the same macronutrient distribution but varied in primary fat source (40% of the total fat). The same Run-In and cross-over experiments were done in two separate groups who self-selected to either a LC/HF (n = 12) or a HC/LF (n = 12) diet track. The primary outcomes were low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL)-C, triglycerides, and LDL particle distribution. RESULTS: Compared to PS, Butter resulted in higher LDL-C in both the LC/HF (13.4%, p = 0.003) and HC/LF (10.8%, p = 0.002) groups, which was primarily attributed to large LDL I and LDL IIa particles. There were no differences between PS and Butter in HDL-C, triglycerides, or small LDL particles. Oxidized LDL was lower after PS than Butter in LC/HF (p = 0.011), but not the HC/LF group. CONCLUSIONS: These results demonstrate that Butter raises LDL-C relative to PS in healthy normocholesterolemic adults regardless of background variations in carbohydrate and fat, an effect primarily attributed to larger cholesterol-rich LDL particles.

Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults.

Ketogenic diets (KDs) often contain high levels of saturated fat, which may increase liver fat, but the lower carbohydrate intake may have the opposite effect. Using a controlled feeding design, we compared liver fat responses to a hypocaloric KD with a placebo (PL) versus an energy-matched low-fat diet (LFD) in overweight adults. We also examined the added effect of a ketone supplement (KS). Overweight adults were randomized to a 6-week KD (KD + PL) or a KD with KS (KD + KS); an LFD group was recruited separately. All diets were estimated to provide 75% of energy expenditure. Weight loss was similar between groups (p > 0.05). Liver fat assessed by magnetic resonance imaging decreased after 6 week (p = 0.004) with no group differences (p > 0.05). A subset with nonalcoholic fatty liver disease (NAFLD) (liver fat > 5%, n = 12) showed a greater reduction in liver fat, but no group differences. In KD participants with NAFLD, 92% of the variability in change in liver fat was explained by baseline liver fat (p < 0.001). A short-term hypocaloric KD high in saturated fat does not adversely impact liver health and is not impacted by exogenous ketones. Hypocaloric low-fat and KDs can both be used in the short-term to significantly reduce liver fat in individuals with NAFLD.

A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health.

Animal data indicate that ketogenic diets are associated with improved mitochondrial function, but human data are lacking. We aimed to characterize skeletal muscle mitochondrial changes in response to a ketogenic diet combined with exercise training in healthy individuals. Twenty-nine physically active adults completed a 12-wk supervised exercise program after self-selection into a ketogenic diet (KD, n = 15) group or maintenance of their habitual mixed diet (MD, n = 14). Measures of metabolic health and muscle biopsies (vastus lateralis) were obtained before and after the intervention. Mitochondria were isolated from muscle and studied after exposure to carbohydrate (pyruvate), fat (palmitoyl-l-carnitine), and ketone (ß-hydroxybutyrate+acetoacetate) substrates. Compared with MD, the KD resulted in increased whole body resting fat oxidation (P < 0.001) and decreased fasting insulin (P = 0.019), insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), P = 0.022], and visceral fat (P < 0.001). The KD altered mitochondrial function as evidenced by increases in mitochondrial respiratory control ratio (19%, P = 0.009), ATP production (36%, P = 0.028), and ATP/H2O2 (36%, P = 0.033) with the fat-based substrate. ATP production with the ketone-based substrate was four to eight times lower than with other substrates, indicating minimal oxidation. The KD resulted in a small decrease in muscle glycogen (14%, P = 0.035) and an increase in muscle triglyceride (81%, P = 0.006). These results expand our understanding of human adaptation to a ketogenic diet combined with exercise. In conjunction with weight loss, we observed altered skeletal muscle mitochondrial function and efficiency, an effect that may contribute to the therapeutic use of ketogenic diets in various clinical conditions, especially those associated with insulin resistance.

A Pre-Workout Supplement of Ketone Salts, Caffeine, and Amino Acids Improves High-Intensity Exercise Performance in Keto-Naïve and Keto-Adapted Individuals.

Background: Acute ingestion of ketone supplements alters metabolism and potentially exercise performance. No studies to date have evaluated the impact of co-ingestion of ketone salts with caffeine and amino acids on high intensity exercise performance, and no data exists in Keto-Adapted individuals.Methods: We tested the performance and metabolic effects of a pre-workout supplement containing beta-hydroxybutyrate (BHB) salts, caffeine, and amino acids (KCA) in recreationally-active adults habitually consuming a mixed diet (Keto-Naïve; n = 12) or a ketogenic diet (Keto-Adapted; n = 12). In a randomized and balanced manner, subjects consumed either the KCA consisting of ∼7 g BHB (72% R-BHB and 28% S-BHB) with ∼100 mg of caffeine, and amino acids (leucine and taurine) or Water (control condition) 15 minutes prior to performing a staged cycle ergometer time to exhaustion test followed immediately by a 30 second Wingate test.Results: Circulating total BHB concentrations increased rapidly after KCA ingestion in KN (154 to 732 µM) and KA (848 to 1,973 µM) subjects and stayed elevated throughout recovery in both groups. Plasma S-BHB increased >20-fold 15 minutes after KCA ingestion in both groups and remained elevated throughout recovery. Compared to Water, KCA ingestion increased time to exhaustion 8.3% in Keto-Naïve and 9.8% in Keto-Adapted subjects (P < 0.001). There was no difference in power output during the Wingate test between trials. Peak lactate immediately after exercise was higher after KCA (∼14.9 vs 12.7 mM).Conclusion: These results indicate that pre-exercise ingestion of a moderate dose of R- and S-BHB salts combined with caffeine, leucine and taurine improves high-intensity exercise performance to a similar extent in both Keto-Adapted and Keto-Naïve individuals.

Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss.

BACKGROUNDMetabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.METHODSIndividuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.RESULTSDespite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.CONCLUSIONConsistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02918422.FUNDINGDairy Management Inc. and the Dutch Dairy Association.

Extended Ketogenic Diet and Physical Training Intervention in Military Personnel.

INTRODUCTION: Ketogenic diets (KDs) that elevate ketones into a range referred to as nutritional ketosis represent a possible nutrition approach to address the emerging physical readiness and obesity challenge in the military. An emerging body of evidence demonstrates broad-spectrum health benefits attributed to being in nutritional ketosis, but no studies have specifically explored the use of a KD in a military population using daily ketone monitoring to personalize the diet prescription. MATERIALS AND METHODS: To evaluate the feasibility, metabolic, and performance responses of an extended duration KD, healthy adults (n = 29) from various military branches participated in a supervised 12-wk exercise training program. Fifteen participants self-selected to an ad libitum KD guided by daily measures of capillary blood ketones and 14 continued their normal mixed diet (MD). A battery of tests were performed before and after the intervention to assess changes in body mass, body composition, visceral fat, liver fat, insulin sensitivity, resting energy metabolism, and physical performance. RESULTS: All KD subjects were in nutritional ketosis during the intervention as assessed by daily capillary beta-hydroxybutyrate (ßHB) (mean ßHB 1.2 mM reported 97% of all days) and showed higher rates of fat oxidation indicative of keto-adaptation. Despite no instruction regarding caloric intake, the KD group lost 7.7 kg body mass (range -3.5 to -13.6 kg), 5.1% whole-body percent fat (range -0.5 to -9.6%), 43.7% visceral fat (range 3.0 to -66.3%) (all p < 0.001), and had a 48% improvement in insulin sensitivity; there were no changes in the MD group. Adaptations in aerobic capacity, maximal strength, power, and military-specific obstacle course were similar between groups (p > 0.05). CONCLUSIONS: US military personnel demonstrated high adherence to a KD and showed remarkable weight loss and improvements in body composition, including loss of visceral fat, without compromising physical performance adaptations to exercise training. Implementation of a KD represents a credible strategy to enhance overall health and readiness of military service members who could benefit from weight loss and improved body composition.

Quantification of Human Central Adipose Tissue Depots: An Anatomically Matched Comparison Between DXA and MRI.

Excess visceral adipose tissue (VAT) and VAT volume relative to subcutaneous adipose tissue (SAT) are associated with elevated health risks. This study compares fat measurements by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). In total, 21 control subjects (Control) and 16 individuals with metabolic syndrome (MetSyn) were scanned by DXA and MRI. The region measured by MRI was matched to the android region defined by DXA, and MRI reproducibility was also evaluated. In addition, liver fat fraction was quantified via MRI and whole-body fat by DXA. VAT measurements are interchangeable between DXA and MRI in the Control (R = 0.946), MetSyn (R = 0.968), and combined cohort (R = 0.983). VAT/SAT ratio did not differ in the Control group (P = .10), but VAT/SAT ratio measured by DXA was significantly higher in the MetSyn group (P < .01) and the combined (P = .03) cohort. Intraobserver (ICC = 0.998) and interobserver (ICC = 0.977) reproducibility of MRI VAT measurements was excellent. Liver fat fraction by MRI was higher (P = .001) in MetSyn (12.4% ± 7.6%) than in controls (2.6% ± 2.2%), as was whole-body fat percentage by DXA (P = .001) between the MetSyn (42.0% ± 8.1%) and Control groups (26.7% ± 6.9%). DXA and MRI VAT are interchangeable when measured over an anatomically matched region of the abdomen, while SAT and VAT/SAT ratio differ between the 2 modalities.

Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes.

BACKGROUND: Low-carbohydrate diets have recently grown in popularity among endurance athletes, yet little is known about the long-term (>4wk) performance implications of consuming a low-carbohydrate high fat ketogenic diet (LCKD) in well-trained athletes. METHODS: Twenty male endurance-trained athletes (age 33±11y, body mass 80±11kg; BMI 24.7±3.1kg/m2) who habitually consumed a carbohydrate-based diet, self-selected into a high-carbohydrate (HC) group (n=11, %carbohydrate:protein:fat=65:14:20), or a LCKD group (n=9, 6:17:77). Both groups performed the same training intervention (endurance, strength and high intensity interval training (HIIT)). Prior to and following successful completion of 12-weeks of diet and training, participants had their body composition assessed, and completed a 100km time trial (TT), six second (SS) sprint, and a critical power test (CPT). During post-intervention testing the HC group consumed 30-60g/h carbohydrate, whereas the LCKD group consumed water, and electrolytes. RESULTS: The LCKD group experienced a significantly greater decrease in body mass (HC -0.8kg, LCKD -5.9kg; P=0.006, effect size (ES): 0.338) and percentage body fat percentage (HC -0.7%, LCKD -5.2%; P=0.008, ES: 0.346). Fasting serum beta-hydroxybutyrate (ßHB) significantly increased from 0.1 at baseline to 0.5mmol/L in the LCKD group (P=0.011, ES: 0.403) in week 12. There was no significant change in performance of the 100km TT between groups (HC -1.13min·s, LCKD -4.07min·s, P=0.057, ES: 0.196). SS sprint peak power increased by 0.8 watts per kilogram bodyweight (w/kg) in the LCKD group, versus a -0.1w/kg reduction in the HC group (P=0.025, ES: 0.263). CPT peak power decreased by -0.7w/kg in the HC group, and increased by 1.4w/kg in the LCKD group (P=0.047, ES: 0.212). Fat oxidation in the LCKD group was significantly greater throughout the 100km TT. CONCLUSIONS: Compared to a HC comparison group, a 12-week period of keto-adaptation and exercise training, enhanced body composition, fat oxidation during exercise, and specific measures of performance relevant to competitive endurance athletes.

Cardiopulmonary exercise testing in the MRI environment.

Maximal oxygen consumption ([Formula: see text]max) measured by cardiopulmonary exercise testing (CPX) is the gold standard for assessment of cardiorespiratory fitness. Likewise, cardiovascular magnetic resonance (CMR) is the gold standard for quantification of cardiac function. The combination of CPX and CMR may offer unique insights into cardiopulmonary pathophysiology; however, the MRI-compatible equipment needed to combine these tests has not been available to date. We sought to determine whether CPX testing in the MRI environment, using equipment modified for MRI yields results equivalent to those obtained in standard exercise physiology (EP) lab. Ten recreationally trained subjects completed [Formula: see text]max tests in different locations; an EP laboratory and an MRI laboratory, using site specific equipment. CMR cine images of the heart were acquired before and immediately after maximal exercise to measure cardiac function. Subjects in all tests met criteria indicating that peak exercise was achieved. Despite equipment modifications for the MRI environment, [Formula: see text]max was nearly identical between tests run in the different labs (95% lower confidence limit (LCL) = 0.8182). The mean difference in [Formula: see text]max was less than 3.40 ml (kg/min)(-1), within the variability expected for tests performed on different days, in different locations, using different metabolic carts. MRI performed at rest and following peak exercise stress indicated cardiac output increased from 5.1 ± 1.0 l min(-1) to 16.4 ± 5.6 l min(-1), LVEF increased from 65.2 ± 3.3% to 78.4 ± 4.8%, while RVEF increased from 52.8 ± 5.3% to 63.4 ± 5.3%. Regression analysis revealed a significant positive correlation between [Formula: see text]max and stroke volume (R = 0.788, P = 0.006), while the correlation with cardiac output did not reach statistical significance (R = 0.505, P = 0.137). [Formula: see text]max CPX testing can be effectively performed in the MRI environment, enabling direct combination of physiological data with advanced post-exercise imaging in the same test session.

Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.

Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of novel therapeutics.