Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial.

PURPOSE: Ketogenic diets may positively influence cancer through pleiotropic mechanisms, but only a few small and short-term studies have addressed feasibility and efficacy in cancer patients. The primary goals of this study were to evaluate the feasibility and the sustained metabolic effects of a personalized well-formulated ketogenic diet (WFKD) designed to achieve consistent blood beta-hydroxybutyrate (ßHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy. METHODS: Women (n = 20) were enrolled in a six month, two-phase, single-arm WFKD intervention (NCT03535701). Phase I was a highly-supervised, ad libitum, personalized WFKD, where women were provided with ketogenic-appropriate food daily for three months. Phase II transitioned women to a self-administered WFKD with ongoing coaching for an additional three months. Fasting capillary ßHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months. RESULTS: Capillary ßHB indicated women achieved nutritional ketosis (Phase I mean: 0.8 mM (n = 15); Phase II mean: 0.7 mM (n = 9)). Body weight decreased 10% after three months, primarily from body fat. Fasting plasma glucose, plasma insulin, and insulin resistance also decreased significantly after three months (p < 0.01), an effect that persisted at six months. CONCLUSIONS: Women diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six months.

Effect of a Telephone-Based Lifestyle Intervention on Weight, Body Composition, and Metabolic Biomarkers in Rural Ohio: Results from a Randomized Pilot Study.

Rural residents experience higher rates of obesity, obesity-related chronic diseases, and poorer lifestyle. Promoting physical activity and healthy eating are critical for rural residents; however, lack of resources and access barriers limit the feasibility of in-person lifestyle interventions. There is a need to design and deliver remotely accessible lifestyle interventions in this population. This pilot study examined the effect of a telephone-based lifestyle intervention on weight, body composition, lipids, and inflammatory biomarkers among rural Ohio residents. Rural Ohio adults with overweight/obesity (n = 40) were 2:1 randomized to a 15-week telephone-based lifestyle intervention (n = 27) or control group (n = 13). The lifestyle intervention group received weekly telephone counseling sessions emphasizing healthy eating and increasing physical activity. The control group received educational brochures describing physical activity and dietary recommendations. Weight, body composition, fasting blood lipids, and inflammatory biomarkers were objectively measured at baseline and 15 weeks at local community centers (trial registration#: NCT05040152 at ClinicalTrial.gov). Linear mixed models were used to examine change over time by group. Participants were mostly female, with an average age of 49 years. Over the 15-week trial, the lifestyle intervention showed superior improvements in total cholesterol (∆ = -18.7 ± 7.8 mg/dL, p = 0.02) and LDL (∆ = -17.1 ± 8.1 mg/dL, p = 0.04) vs. control, whereas no significant between-group differences in weight, body composition, or inflammation were observed. Our findings suggest that a 15-week telephone-based lifestyle intervention may offer metabolic benefits that reduce disease risk in rural adults with obesity. Future large-scale studies are needed to determine the efficacy of remotely accessible lifestyle interventions in rural populations, with the goal of reducing obesity-related disparities.

Metabolic and ruck performance effects of a novel, light-weight, energy-dense ketogenic bar.

NEW FINDINGS: What is the central question of the study? Can a novel, energy-dense and lightweight ketogenic bar (1000 kcal) consumed 3 h before exercise modulate steady-state incline rucksack march ('ruck') performance compared to isocaloric carbohydrate bars in recreationally active, college-aged men? What is the main finding and its importance? Acute ingestion of either nutritional bar sustained ∼1 h of exhaustive rucking with a 30% of body weight rucksack. This proof-of-concept study is the first to demonstrate that carbohydrate bars and lipid bars are equally feasible for preserving ruck performance. Novel ketogenic nutrition bars may have military-relevant applications to lessen carry load without compromising exercise capacity. ABSTRACT: Rucksack marches ('rucks') are strenuous, military-relevant exercises that may benefit from pre-event fuelling. The purpose of this investigation was to explore whether acute ingestion of carbohydrate- or lipid-based nutritional bars before rucking can elicit unique advantages that augment exercise performance. Recreationally active and healthy males (n = 29) were randomized and counterbalanced to consume 1000 kcal derived from a novel, energy-dense (percentage energy from carbohydrate/fat/protein: 5/83/12) ketogenic bar (KB), or isocaloric high-carbohydrate bars (CB; 61/23/16) 3 h before a time-to-exhaustion (TTE) ruck. Conditions were separated by a 1-week washout. The rucksack weight was standardized to 30% of bodyweight. Steady-state treadmill pace was set at 3.2 km/h (0.89 m/s) and 14% grade. TTE was the primary outcome; respiratory exchange ratio (RER), capillary ketones (R-ß-hydroxybutyrate), glucose and lactate, plus subjective thirst/hunger were the secondary outcomes. Mean TTE was similar between conditions (KB: 55 ± 25 vs. CB: 54 ± 22 min; P = 0.687). The RER and substrate oxidation rates revealed greater fat and carbohydrate oxidation after the KB and CB, respectively (all P < 0.0001). Capillary R-ßHB increased modestly after the KB ingestion (P < 0.0001). Neither bar influenced glycaemia. Lactate increased during the ruck independent of the condition (P < 0.0001). Thirst/fullness perceptions changed independent of the nutritional bar consumed. A novel KB nutritional bar produced equivalent TTE ruck results to the isocaloric CBs. The KB's energy density relative to CB (6.6 vs. 3.8 kcal/g) may provide a lightweight (-42% weight), pre-event fuelling alternative that does not compromise ruck physical performance.

Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts.

BACKGROUND: Single doses of exogenous ketone salts (KS) transiently increase circulating beta-hydroxybutyrate (BHB) (∼1 mM; 1-2 h) regardless of starting levels of ketosis; however, no studies have explored how sustained use of KS influences measures of ketonemia and glycemia. OBJECTIVES: To determine the response to a hypocaloric, well-formulated ketogenic diet (KD), with and without the inclusion of two daily racemic KS doses (6 g R-BHB + 6 g S-BHB per serving) on 1) daily fasting capillary R-BHB and glucose (R-BHB/GLUfast), 2) bi-weekly 13 h diurnal BHB and glucose (R-BHB/GLUdiur), 3) three-hours post-KS ingestion kinetics (R-BHBKS), and 4) bi-weekly fasting plasma enantiomer-specific BHB (R/S-BHBplasma). METHODS: Non-diabetic adults with overweight and obesity were randomized to receive a precisely measured hypocaloric KD (∼75 %en of maintenance) for six weeks, supplemented twice-daily with KS or placebo (PL). A non-randomized comparison group was provided an isonitrogenous/isoenergetic low-fat diet (LFD). All meals were provided to subjects. Capillary blood was collected daily to measure R-BHB/GLUfast and hourly for R-BHB/GLUdiur. Plasma was collected to measure R/S-BHBplasma, insulin, fasting glucose, and insulin resistance (HOMA-IR). Total AUC was calculated using the trapezoidal method. RESULTS: Mean R-BHBfast increased significantly during KD + PL (1.0 mM BHB), an effect enhanced 26% during KD + KS. GLUfast AUC was -6% lower during KD + KS versus LFD. Mean R-BHBdiur increased 40% in KD + KS versus KD + PL, whereas GLUdiur decreased 13% during both KDs versus LFD. R-BHBKS peaked (Δ: ∼1 mM) 1 h after the morning KS dose, but not following the afternoon dose. Both R/S-BHBplasma increased during KD independent of KS inclusion. R-BHBplasma was 50-times greater compared to S-BHBplasma, and the KS augmented S-BHBplasma 50% more than PL. Fasting insulin and HOMA-IR decreased after 14 days independent of diet. CONCLUSIONS: A hypocaloric KD was effective at reducing diurnal glucose compared to a LFD independent of weight loss, but twice-daily racemic KS ingestion during KD augmented ketonemia, both as R- and S-BHB, and decreased mean fasting glucose beyond a KD alone. The hypoglycemic effects of KD in combination with exogenous ketones merit further investigation.

Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin.

CONTEXT: Ketogenic diets (KDs) and low-fat diets (LFD) result in similar weight loss, but have differential cardiometabolic effects on lipids and insulin. Generally, weight loss decreases renin-angiotensin-aldosterone system (RAAS) activity. OBJECTIVE: Investigate the effects of KDs with varying sodium content vs LFD on RAAS in overweight and obese adults. METHODS: Twenty-eight participants were randomized 1:1 to a KD + ketone salt supplement (KD + KS) or a KD + placebo (KD + PL) arm with prepared hypocaloric meals. Twelve participants were enrolled in a post hoc LFD arm. Serum renin, aldosterone, and anthropometric and metabolic biomarkers were assessed at 0, 2, 4, and 6 weeks. Linear mixed models with random intercepts were used to compare between group differences controlling for sex and body mass index. RESULTS: Participants had a median age of 33 years, 51% female, weighed 91.3 kg, with body mass index 30.6 kg/m2. At 6 weeks, weight decreased by 6, 8, and 7 kg on average in the KD + KS, KD + PL, and LFD groups, respectively (P < .05). Aldosterone increased by 88% and 144% in the KD + PL and KD + KS groups, respectively, but did not change in the LFD after 6 weeks while renin decreased across groups. Systolic and diastolic blood pressure did not change in the KD + PL and KD + KS groups. Log ketones were positively associated with aldosterone (P < .001). Aldosterone was not associated with cardiovascular measures including blood pressure and ejection fraction (P > .05). CONCLUSION: KD reduced weight and increased aldosterone without worsening cardiometabolic risk factors. Future KD studies are needed to elucidate mechanistic connections between ketones and aldosterone.

Bis Hexanoyl (R)-1,3-Butanediol, a Novel Ketogenic Ester, Acutely Increases Circulating r- and s-ß-Hydroxybutyrate Concentrations in Healthy Adults.

BACKGROUND: Ketosis has been reported to benefit healthspan and resilience, which has driven considerable interest in development of exogenous ketones to induce ketosis without dietary changes. Bis hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone di-ester that can be used as a food ingredient that increases hepatic ketogenesis and blood beta-hydroxybutyrate (BHB) concentrations. METHODS: Here, we provide the first description of blood ketone and metabolite kinetics for up to five hours after consumption of a beverage containing BH-BD by healthy adults (n = 8) at rest in three randomized, cross-over conditions (25 g + Meal (FEDH); 12.5 g + Meal (FEDL) ; 25 g + Fasted (FASTH)). RESULTS: Consumption of BH-BD effectively raised plasma r-BHB concentrations to 0.8-1.7 mM in all conditions, and both peak r-BHB concentration and r-BHB area under the curve were greater with 25 g versus 12.5 g of BH-BD. Urinary excretion of r-BHB was <1 g. Plasma concentration of the non-physiological isoform s-BHB was increased to 20-60 µM in all conditions. BH-BD consumption decreased plasma glucose and free fatty acid concentrations; insulin was increased when BH-BD was consumed with a meal. CONCLUSIONS: These results demonstrate that consumption of BH-BD effectively induces exogenous ketosis in healthy adults at rest.

The Effects of Resistance Training on Physical Fitness and Neuromotor-Cognitive Functions in Adults With Down Syndrome.

Adults with Down syndrome are an underserved population at high risk for a host of different pathologies from aging and lack of activity. Purpose: To examine the effects of a 10-week resistance training program on measures of motor behavior, cognitive function, mood, and physical fitness. Methods: Participants (n = 11) were men and women clinically diagnosed with Down syndrome (age: 25.8 ± 6.4 years; height: 151.5 ± 8.3 cm; weight: 67.5 ± 13.0 kg; IQ: 58.3 ± 19.7 units). After familiarization of testing procedures, subjects performed The Arizona Cognitive Test Battery for Down Syndrome, TGMD-2, lower and upper body strength assessments, and body composition via DXA testing, while parental guardians completed cognitive and mood survey assessments (Cognitive Scale for Down Syndrome, Behavioral Rating Inventory of Executive Function, NiSonger Child Behavior Rating Form, Scales of Independent Behavior-Revised, Child Eating Behavior Questionnaire, Social Communication Questionnaire, and Mood and Feelings Questionnaire) at pre and post 10 weeks of periodized resistance training. Results: Significant (P ≤ 0.05) improvements in locomotor skills and object control skills were observed post-training. Both locomotor skills (e.g., sprint, gallop, leaping, broad jump) and object control skills (e.g., baseball catch, underhand roll, basketball dribble) were all significantly improved. Facets of cognitive performance significantly improved, specifically executive function and visuospatial working memory capacity, and frontal lobe activity. Mood disturbances significantly decrease. All aspects of physical strength and endurance were improved, i.e., leg press, bench press, sit-ups, push-ups, and chair sit-to-stand post-training. Lean tissue mass was significantly increased post-training. Conclusion: This study dramatically demonstrates that life enhancements for individuals with Down syndrome are achievable with a properly designed resistance training program.

The effects of a 6-week controlled, hypocaloric ketogenic diet, with and without exogenous ketone salts, on cognitive performance and mood states in overweight and obese adults.

Background: Ketogenic diets are a commonly used weight loss method, but little is known how variations in sodium content and ketones influence cognition and mood during the early keto-adaptation period. Objectives: To investigate the effects of an exogenous ketone salt (KS) as part of a hypocaloric KD on mood and cognitive outcomes in overweight and obese adults. A secondary objective was to evaluate changes in biochemical markers associated with inflammatory and cognitive responses. Materials and methods: Adults who were overweight or obese participated in a 6-week controlled-feeding intervention comparing hypocaloric diets (∼75% of energy expenditure). KD groups received twice daily ketone salt (KD + KS; n = 12) or a flavor-matched placebo, free of minerals (KD + PL; n = 13). A separate group of age and BMI matched adults were later assigned to an isoenergetic low-fat diet (LFD; n = 12) as comparison to KD. Mood was assessed by shortened Profile of Mood States and Visual Analog Mood Scale surveys. Cognitive function was determined by the Automated Neuropsychological Assessment Metrics mental test battery. Results: Both KD groups achieved nutritional ketosis. Fasting serum glucose decreased in both KD groups, whereas glucose was unaffected in the LFD. Insulin decreased at week 2 and remained lower in all groups. At week 2, depression scores in the KD + PL group were higher compared to KD + KS. Performance in the math processing and go/no-go cognitive tests were lower for KD + PL and LFD participants, respectively, compared to KD + KS. Serum leptin levels decreased for all groups throughout the study but were higher for KD + KS group at week 6. Serum TNF-α steadily increased for LFD participants, reaching significance at week 6. Conclusion: During a short-term hypocaloric diet, no indication of a consistent decline in mood or cognitive function were seen in participants following either KD, despite KD + PL being relatively low in sodium. WK2 scores of "anger" and "depression" were higher in the LFD and KD + PL groups, suggesting that KS may attenuate negative mood parameters during the early intervention stages.

Influence of Nutritional Ketosis Achieved through Various Methods on Plasma Concentrations of Brain Derived Neurotropic Factor.

Brain-Derived Neurotropic Factor (BDNF) expression is decreased in conditions associated with cognitive decline as well as metabolic diseases. One potential strategy to improve metabolic health and elevate BDNF is by increasing circulating ketones. Beta-Hydroxybutyrate (BHB) stimulates BDNF expression, but the association of circulating BHB and plasma BDNF in humans has not been widely studied. Here, we present results from three studies that evaluated how various methods of inducing ketosis influenced plasma BDNF in humans. Study 1 determined BDNF responses to a single bout of high-intensity cycling after ingestion of a dose of ketone salts in a group of healthy adults who were habitually consuming either a mixed diet or a ketogenic diet. Study 2 compared how a ketogenic diet versus a mixed diet impacts BDNF levels during a 12-week resistance training program in healthy adults. Study 3 examined the effects of a controlled hypocaloric ketogenic diet, with and without daily use of a ketone-salt, on BDNF levels in overweight/obese adults. We found that (1) fasting plasma BDNF concentrations were lower in keto-adapted versus non keto-adapted individuals, (2) intense cycling exercise was a strong stimulus to rapidly increase plasma BDNF independent of ketosis, and (3) clinically significant weight loss was a strong stimulus to decrease fasting plasma BDNF independent of diet composition or level of ketosis. These results highlight the plasticity of plasma BDNF in response to lifestyle factors but does not support a strong association with temporally matched BHB concentrations.

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.

The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketone Salts, on Body Composition Responses.

Background: Ketogenic diets (KDs) that elevate beta-hydroxybutyrate (BHB) promote weight and fat loss. Exogenous ketones, such as ketone salts (KS), also elevate BHB concentrations with the potential to protect against muscle loss during caloric restriction. Whether augmenting ketosis with KS impacts body composition responses to a well-formulated KD remains unknown. Purpose: To explore the effects of energy-matched, hypocaloric KD feeding (<50 g carbohydrates/day; 1.5 g/kg/day protein), with and without the inclusion of KS, on weight loss and body composition responses. Methods: Overweight and obese adults were provided a precisely defined hypocaloric KD (~75% of energy expenditure) for 6 weeks. In a double-blind manner, subjects were randomly assigned to receive ~24 g/day of a racemic BHB-salt (KD + KS; n = 12) or placebo (KD + PL; n = 13). A matched comparison group (n = 12) was separately assigned to an isoenergetic/isonitrogenous low-fat diet (LFD). Body composition parameters were assessed by dual x-ray absorptiometry and magnetic resonance imaging. Results: The KD induced nutritional ketosis (>1.0 mM capillary BHB) throughout the study (p < 0.001), with higher fasting concentrations observed in KD + KS than KD + PL for the first 2 weeks (p < 0.05). There were decreases in body mass, whole body fat and lean mass, mid-thigh muscle cross-sectional area, and both visceral and subcutaneous adipose tissues (p < 0.001), but no group differences between the two KDs or with the LFD. Urine nitrogen excretion was significantly higher in KD + PL than LFD (p < 0.01) and trended higher in KD + PL compared to KD + KS (p = 0.076), whereas the nitrogen excretion during KD + KS was similar to LFD (p > 0.05). Conclusion: Energy-matched hypocaloric ketogenic diets favorably affected body composition but were not further impacted by administration of an exogenous BHB-salt that augmented ketosis. The trend for less nitrogen loss with the BHB-salt, if manifested over a longer period of time, may contribute to preserved lean mass.

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.

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.