BACKGROUND:Exogenous ketone supplementation acutely elevates circulating beta-hydroxybutyrate (R-BHB), but the impact of chronic repeated dosing on exercise performance, cognition, mood, and cardiometabolic health remains unclear. PURPOSE:To evaluate the effects of 31 days of thrice-daily ketone monoester (KME) supplementation (90 g/day; high-dose) on exercise performance, executive function, mood, metabolism, body composition, blood pressure, and tolerability in recreational runners. METHODS:In a single-blind, randomized-controlled trial, 18 runners consumed either (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KME; 30 g/dose; n = 9) or an isocaloric, flavor-matched placebo (PLA; 30 g/dose; n = 9) three times daily for 31 days. Outcomes included 5-km time trial (5KTT) performance, cognitive function, mood, body composition, blood pressure, and tolerability. Metabolism and substrate oxidation (rest and graded exercise) were performed after 31-d supplementation was completed to assess metabolic responses following 31 days of repeated exogenous ketone exposure. RESULTS:31-day KME did not alter 5KTT performance, but improved cognitive function, as evidenced by faster Stroop Incongruent (p = 0.015) and Switching task responses (p = 0.038). Mood and quality of life scores were unchanged. Metabolically, the KME reliably elevated post-ingestion R-BHB (∼3.0 mM; p < 0.001) and lowered glycemia by 15% (p < 0.001). After the 31-day KME supplementation stopped, KME-treatment preserved mean absolute VO2 during graded exercise testing (p = 0.029), without accompanying improvements in running performance. CONCLUSION:High-dose KME administration for 31-days did not alter running performance, but increased cognitive function and oxygen uptake during maximal graded exercise even after ketone administration stopped, indicating that selected physiological measures differed between groups when assessed after the supplementation period.

ABSTRACT:Stoner, JT, Buga, A, Crabtree, CD, Robinson, BT, Decker, DD, Sapper, TN, Kackley, ML, Kraemer, WJ, and Volek, JS. Exogenous ketones preserve rate of force development in young adults. J Strength Cond Res XX(X): 000-000, 2026-Few studies have examined the relationship between ketones and anaerobic neuromuscular performance, especially maximal strength and explosive power. The purpose of this investigation was to determine whether exogenous ketone supplementation can enhance countermovement jump (CMJ) and isometric midthigh pull (IMTP) performance. Twenty, college-aged, active men and women (n = 10/10) were randomized and counterbalanced to consume 50 g of ketone precursors in the form of bis-octanoyl (R)-1,3-butanediol (BO-BD) or an isocaloric/flavor-matched placebo (PL) supplement during 2 experimental visits separated by a 3 to 7-day washout. Subjects completed 3 sets of 3 CMJ and IMTP repetitions at baseline, 60, and 120 minutes. Primary outcomes included CMJCMP, CMJPPP, CMJJH, and CMJPF, IMTPRFD, IMTPPF, IMTPRFD-FI, and IMTPPF-FI. Capillary beta-hydroxybutyrate (R-BHB), blood glucose, and heart rate were measured in 30-minute increments after supplement consumption. Capillary R-BHB concentrations rose incrementally post-BO-BD ingestion and peaked at 120-minutes (BO-BD vs. PL: 2.2 ± 0.7 vs. 0.3 ± 0.1 mM; p < 0.001), coinciding with lower blood glucose values (-24% vs. -3% mg·dl-1; p < 0.001), and elevated heart rate (13.3 vs. 3.6 bpm; p < 0.001). BO-BD preserved 8% higher RFD values 60-minutes post-ingestion relative to the PL (p = 0.022). CMJ performance was not influenced by either consuming condition. Consuming exogenous ketone precursors before peak strength attempts demonstrated a rate-of-force development preservation effect between sets, suggesting that nutritional ketosis may delay fatigue during repeated, high-intensity strength bouts.

Carbohydrate (CHO) ingestion during exercise has long been associated with improved performance. Early Scandinavian research proposed that CHO ingestion mitigates exercise-induced hypoglycemia (EIH) through a central neural mechanism, preventing glycopenic brain damage. Subsequent studies linked muscle glycogen depletion to fatigue during prolonged exercise, suggesting an obligatory reliance on glycogen, while overlooking the simultaneous presence of profound EIH at exhaustion. However, emerging evidence challenges this paradigm highlighting EIH role in fatigue. We comprehensively review more than 100 years of evidence from more than 160 studies looking at CHO ingestion, exercise metabolism, and physical performance that demonstrates the following key findings: (1) EIH correlates strongly with exercise termination, while muscle glycogen depletion alone does not induce rigor or whole-body fatigue; (2) CHO ingestion reduces liver glycogenolysis, preserves blood glucose, and paradoxically accelerates muscle glycogen breakdown through conserved neuroendocrine mechanisms; (3) high-fat-adapted athletes demonstrate exceptional fat oxidation, equivalent exercise performance, despite lower glycogen and CHO oxidation, challenging the belief that glycogen and CHO oxidation are central to exercise performance or that CHO is an obligatory fuel; and (4) CHO ingestion during exercise significantly enhances performance, even in glycogen-depleted states, by eliminating EIH. These data demonstrate that the main benefit of CHO ingestion before or during exercise is to prevent EIH, highlighted in prolonged efforts (>2-3 hours) and individuals with insufficient hepatic gluconeogenesis. This has important implications for sports dietary recommendations (ie, habitual high- or low-CHO diets) and the amount of CHOs athletes should be encouraged to ingest during exercise to maximize performance.

Background:An individual's metabolic state plays a critical role in breast cancer (BC) risk, influenced by factors such as obesity and insulin signaling. Hypocaloric diets induce metabolic changes that influence these metabolic factors, thereby potentially influencing BC risk. However, it remains unclear whether metabolic profiles like those induced by such beneficial diets are associated with BC risk. Methods:We compared the impact of a hypocaloric low-carbohydrate ketogenic diet (KD) and a low-fat diet (LFD) on BC risk in two stages. First, we developed metabolomics-based scores representing the metabolic states resulting from these two hypocaloric diets. Plasma metabolomics data of 43 individuals from two controlled dietary interventions were analyzed (N = 31 KD, N = 12 LFD) and a metabolite-based score was generated for both KD and LFD using diet-induced fold-changes. Second, these scores were applied to metabolomics data from a nested case-control study of participants from the Nurses' Health Study II (NHSII, 1,058 BC cases, 1,054 controls, predominantly premenopausal women). Using multivariable-adjusted models, we assessed the association between the metabolomic scores and BC risk. Results:KD and LFD had similar but distinct metabolic signatures. Both metabolomics scores were positively associated with breast cancer risk in NHSII. Women in the highest quartile of the KD metabolomic score had a 37% increased risk of BC compared to women in the lowest quartile (p=0.021). Similarly, women in the highest quartile of the LFD metabolomic score had a 32% increased BC risk compared to women in the lowest quartile (p=0.008). Similar increases in risk were seen when further adjusting for BMI at age 18 and weight change since age 18. Increased levels of cholesterol esters (CE), particularly CE 22:6, and long-chain polyunsaturated triglycerides were associated with higher risk in both diet scores, while increases in short-chain, more saturated triglycerides were associated with lower risk. Conclusion:Metabolomic profiles resembling those induced by hypocaloric ketogenic and low-fat diets were unexpectedly associated with an increased risk of breast cancer in a predominantly premenopausal cohort. These associations were independent of BMI, highlighting the complex relationship between metabolic states and cancer risk, independent of actual dietary interventions.

Increasing evidence suggests cardiac function improves in healthy and failing hearts alongside circulating ketones (1–4 mM). This study characterized cardiac function and blood flow responses to a ketogenic beverage compared to a volume/calorie matched placebo with repeated imaging over 120 min. This was a two‐group, placebo‐controlled, acute cardiac imaging study. Adults without cardiac abnormalities underwent baseline cardiac MRI including quantitative myocardial perfusion to measure myocardial blood flow (MBF). Subjects consumed 50 g of a ketogenic‐promoting beverage [bis‐hexanoyl R‐1‐3‐butanediol (BH‐BD)] (BH‐BD; n = 11) or a calorically/volume‐matched lipid‐based placebo (PL; n = 10) with cardiac MRI every 15–30 min. Following 120 min, subjects underwent a final scan including MBF measurement. R‐BHB and glucose were measured at every timepoint. 120 min following BH‐BD consumption, R‐BHB reached 2.1 mM. Cardiac output (CO) was elevated compared to PL ( p < 0.05) and increased +31% 120 min after BH‐BD ingestion ( p < 0.001). CO elevation was due to increased stroke volume (+11%; p = 0.02) and heart rate (+22%; p < 0.001). MBF increased 29% from baseline ( p < 0.001). PL did not induce differences in cardiac parameters. 50 g BH‐BD ingestion achieves exogenous ketosis and is associated with elevated MBF and CO providing evidence supporting their use as a therapeutic clinical agent.

Re-analysis results (Left) and takeaway messages (Right) are summarized above. RCOP, reverse crossover point. Figure created with Biorender.com.Reverse Crossover Point (RCOP) analysis showing a man on an exercise bike and running, indicating training intensity. A graph illustrates substrate oxidation levels over time, with fat oxidation surpassing carbohydrate oxidation. Key takeaways: Fat oxidation increased significantly despite carbohydrate intake, suggesting additional carbohydrate sources and reliance on lipids for energy.

Background/Objectives: Modifying standard foods to minimize postprandial glucose (PPG) and insulin excursions may benefit health. We conducted a randomized, double-blind, crossover study to compare postprandial responses to an isocaloric (~250 kcal) Standard Muffin (SM) containing refined flour and sugar versus a Modified Muffin (MM) consisting of wheat-free grains and low sugar levels in healthy individuals and individuals with type 2 diabetes (T2D). Subjects/Methods: Nineteen subjects (ten healthy, nine with T2D) participated in the trial. PPG responses were measured in capillary blood over 5 h to calculate the change in glucose from the baseline (ΔGLU), peak glucose (GLUPeak), peak–nadir glucose (GLUP-N), and 2 h incremental area under the curve (iAUC). Plasma insulin responses were quantified via assays. Results: Compared to the SM, the MM significantly reduced the GLUPeak (55%), GLUP-N (35%), and 2 h iAUC (80%). Within the cohort, the MM elicited a 68% reduction in the GLUPeak response compared to the SM in individuals with T2D. Insulin was lower following the MM (−62%). Participants reported similar subjective taste and mouthfeel ratings. Conclusion: A novel MM decreased PPG and insulin responses compared to a SM, without compromising taste, thus highlighting salient features for T2D nutrition management.

Very-low-carbohydrate diets (LCHF; <50 g/day) have been debated for their potential to lower pre-exercise muscle and liver glycogen stores and metabolic efficiency, risking premature fatigue. It is also hypothesized that carbohydrate ingestion during prolonged exercise delays fatigue by increasing carbohydrate oxidation, thereby sparing muscle glycogen. Leveraging a randomized crossover design, we evaluated performance during strenuous time-to-exhaustion (70% V̇o2max) tests in trained triathletes following 6-wk high-carbohydrate (HCLF, 380 g/day) or very-low-carbohydrate (LCHF, 40 g/day) diets to determine 1) if adoption of the LCHF diet impairs time-to-exhaustion performance, 2) whether carbohydrate ingestion (10 g/h) 6-12× lower than current CHO fueling recommendations during low glycogen availability (>15-h pre-exercise overnight fast and/or LCHF diet) improves time to exhaustion by preventing exercise-induced hypoglycemia (EIH; <3.9 mmol/L; <70 mg/dL), and 3) the "keto-adaptation" time course through continuous substrate monitoring while caloric intake, physical activity, and fat-free mass are maintained. Time-to-exhaustion performance was similar across both dietary interventions. Minimal carbohydrate supplementation prevented EIH and significantly increased time to exhaustion equivalently in LCHF and HCLF interventions (22%). The LCHF diet significantly lowered 24-h glucose concentrations, which normalized after 4 wk, at the same timepoint peak blood ketone (R-β-hydroxybutyrate) concentrations normalized. These findings 1) demonstrate that an LCHF diet sustains strenuous endurance performance, 2) establish that minimal carbohydrate supplementation was sufficient to enhance exercise performance on LCHF and HCLF diets by mitigating EIH, and 3) indicate that a minimum 4-wk adaptation period to an LCHF diet is required to ensure normalization of metabolic homeostasis, glycemic control, and exercise performance.NEW & NOTEWORTHY This study examines the belief that very-low-carbohydrate diets (LCHF) impair prolonged exercise performance during strenuous exercise by comparing it with high-carbohydrate diets in competitive triathletes. After 6-wk diet adaptation, time-to-exhaustion (TTE) performance was similar across both diets. Minimal carbohydrate supplementation (10 g/h) during exercise eliminated exercise-induced hypoglycemia and improved TTE by 22% on both diets. These findings suggest that LCHF diets do not impair exercise performance and require a 4-wk adaptation period for metabolic homeostasis.

Ballistic virtual reality (VR) can measure shooting performance reliably in trained and untrained subjects. The purpose of this investigation was to determine whether baseline traits such as age, habitual physical activity, and prior experience are correlated with VR decision-making and reaction time performance. Thirty participants completed a series of VR tests—Color Shapes and Steel Plates—while shooting a laser-guided and CO2-recoil fitted rifle at digitally-projected targets. The first test measured decision-making as a function of shooting a series of correct shapes (squares/triangles/circles) and colors (green/red/blue), twice, in under 2 s. The second test measured left-to-right target transition shooting skills on six, equidistant metal plates placed 7 m away from the shooting line. Age was correlated with (1) lower decision-making scores during the Color Shapes array identification test and (2) slower target transition time, smaller throughput (time/accuracy) and Hit Factor [(correct hits-misses)/time] on the Steel Plates test. Weekly physical activity had an inverse effect. A multiple regression model revealed that age and weekly activity combined predicted the Hit Factor, the most relevant shooting proficiency metric. Tactical populations scored significantly better than non-tactical in the decision-making task. Age and physical activity may plausibly predict ballistic performance, whereas tactical experience positively modulates better decision-making.

We provide an overview of cardiac metabolism, ketone physiology and terminology, methods of elevating ketones and their effect on cardiac function and disease. We discuss future research directions and speculate what ketogenic strategies may yield optimal effects on the heart and cardiovascular disease. Nutritional ketosis acutely elevates cardiac function (cardiac output, myocardial perfusion, etc.) in healthy people and those with cardiovascular disease in a dose-dependent manner between circulating ketones and cardiac function. Despite therapeutic potential, long-term studies have not been performed. This acute effect is rapid, dose-dependent, and has been seen to be durable for up to 14 days following intervention onset. There are numerous methods to elicit ketogenesis and promote nutritional ketosis. There is growing evidence to suggest that higher ketone levels may offer greater cardiac benefits. It is pertinent to consider what ketone levels to target, and the best methods to safely and feasibly reach those targets over sustained periods of time.

A ketogenic diet (KD) has shown promise as an adjunctive therapy for neurological and neuropsychiatric disorders, including bipolar disorder and major depressive disorder (MDD). We examined tolerance for a KD in young adults with MDD and assessed symptoms of depression and metabolic health. Students (n = 24) with a confirmed diagnosis of MDD at baseline receiving standard of care counseling and/or medication treatment were enrolled in a 10-12 week KD intervention that included partial provision of ketogenic-appropriate food items, frequent dietary counseling, and daily morning tracking of capillary R-beta-hydroxybutyrate (R-BHB). Primary outcome measures for mood symptoms included the Patient Health Questionnaire (PHQ-9) and Hamilton Rating Scale for Depression (HRSD). Additional outcomes included body composition, neurocognitive function, and blood hormonal and inflammatory markers. Sixteen students (10 women, 6 men, mean age 24 yr) completed the intervention. Nutritional ketosis (R-BHB > 0.5 mM) was achieved 73% of the time. Depressive symptoms decreased by 69% (PHQ-9) and 71% (HRSD) post-intervention (p < 0.001), with improvement occurring within 2-6 weeks. Global well-being increased nearly 3-fold (p < 0.001). Participants lost body mass (-6.2%; p = 0.002) and fat mass (-13.0%; p < 0.001). Serum leptin decreased (-52%; p = 0.009) and brain-derived neurotropic factor increased (+32%; p = 0.029). Performance improved on several cognitive tasks. In students with mild to moderate depression based on PHQ-9 and HRSD, implementation of a WFKD for 10-12 weeks is a feasible adjunctive therapy and may be associated with improvements in depression symptoms, well-being, body composition, and cognition.

Objective: Recent work has challenged the notion that preferred substrate oxidation is a key determinant of exercise performance. This investigation tested middle-distance running performance, in the fed state, to control for glycogen and exercise-induced hypoglycemia (EIH) confounders. Methods: In a randomized crossover fashion, all while controlling dietary intake, activity, and body weight, recreational distance runners completed either a 5K (n = 15; VO2max: 58.3 ± 6.2 mL/kg/min) or a 10K (n = 15; VO2max: 54.51 ± 5.9 mL/kg/min) middle-distance run after consuming isocaloric low-carbohydrate high-fat (LCHF) and high-carbohydrate low-fat (HCLF) pre-exercise meals. Time trial (TT) performance (sec), carbohydrate/fat substrate oxidation, blood metabolites, heart rate (HR), ratings of perceived exertion (RPE), and subjective fullness and thirst were measured throughout. Results: LCHF pre-exercise nutrition reliably altered substrate oxidation and metabolite profiles compared to HCLF, evidenced by significant increases in fat oxidation (77% higher) and reductions in RER (5% lower), with corresponding shifts in carbohydrate oxidation. Despite distinct preferred substrate oxidation profiles during exercise, the 5 and 10 km TT performances were similar between conditions (p = 0.646/p = 0.118). RER was significantly lower (p = 0.002) after the LCHF condition compared to HCLF. Capillary R-βHB increased modestly after LCHF, while blood glucose increased after HCLF only. The LCHF meal was 35% more filling than the HCLF meal. Preferred substrate oxidation did not significantly modulate middle-distance running performance. Conclusion: This work supports recent findings that substrate oxidation is not a primary determinant of aerobic performance, as previously conceived.

Nutritional ketosis achieved through various methods in animals and humans has been shown to augment cardiac efficiency and function. However, this response during exercise has not been well characterized. Recreationally active adults ( n = 12) completed a double blind, balanced, placebo‐controlled, crossover study to examine the effects of bis‐octanonyl ( R )‐1,3‐butanediol (BO‐BD) ingestion on cardiopulmonary function at rest and during a maximal oxygen consumption (V̇O 2max ) treadmill test (Bruce Protocol). Participants presented to the testing facility fasted. Capillary blood samples were obtained to measure glucose and beta‐hydroxybutyrate ( R ‐βHB) prior to consuming the BO‐BD or a calorically matched placebo (PL) beverage. Metabolic and cardiovascular measures were collected every 15–30 min following beverage consumption. Participants began the V̇O 2max test 120 min post‐beverage ingestion. At rest, capillary R ‐βHB elevated rapidly after BO‐BD ingestion and continued to steadily increase to 2.4 mM prior to the maximal exercise test. During the 120 min rest period, BO‐BD increased resting heart rate (HR) ( p = 0.001), ventilation ( p < 0.001), and V̇O 2 ( p = 0.002) relative to PL. Although the total time to exhaustion was similar between conditions, V̇O 2max was lower after BO‐BD ( p < 0.001). There were no differences in exercise lactate, RER, respiration, or rating of perceived exertion (RPE) between conditions. Compared to PL, BO‐BD rapidly achieves nutritional ketosis, increases resting cardio‐respiratory parameters, but somewhat paradoxically decreases peak aerobic exercise oxygen consumption despite achieving similar peak workloads.

ABSTRACT:Buga, A, Decker, DD, Robinson, BT, Crabtree, CD, Stoner, JT, Arce, LF, El-Shazly, X, Kackley, ML, Sapper, TN, Anders, JPV, Kraemer, WJ, and Volek, JS. The VirTra V-100 is a test-retest reliable shooting simulator for measuring accuracy/precision, decision-making, and reaction time in civilians, police/SWAT, and military personnel. J Strength Cond Res 38(10): 1714-1723, 2024-Law-enforcement agencies and the military have increasingly used virtual reality (VR) to augment job readiness. However, whether VR technology captures consistent data for shooting performance evaluation has never been explored. We enrolled 30 adults (24 M/6 F) to examine test-retest reliability of the VirTra shooting simulator. Approximately 30% of the sample had a tactical background (PD/SWAT and military). Trained research staff familiarized subjects with how to shoot the infrared-guided M4 rifle at digitally projected targets. Subjects then performed 3 identical experimental shooting sessions (consecutive or separated by 1-2 days) that assessed accuracy/precision, decision-making, and reaction time. Key metrics comprised projectile Cartesian position ( x , y ), score, time, and throughput (score or accuracy divided by time). Test-retest reliability was measured with intraclass correlation coefficients (ICC). After each visit, subjects completed a perceptual survey to self-evaluate their shooting performance and perceived VR realism. The simulator captured 21 ballistic variables with good to excellent test-retest agreement, producing a global ICC of 0.78. Notable metrics were the individual projectile distances to the center of the target (0.81), shot group radius (0.91), time-to-first decision (0.97), decision-making throughput (0.95), and target transition reaction time (0.91). Subjects had positive self-evaluations about their shooting performance, with "confidence" increasing from baseline to the end of the study ( p = 0.014). The VirTra V-100 virtual ballistic shooting simulator captures data with a high degree of test-retest reliability and is easy to familiarize regardless of starting expertise levels, making it appropriate for use as a method to objectively track progress or a tactical research testing tool.

Weight loss can positively alter female physiology; however, whether dietary carbohydrate- or fat- restriction confer unique effects is less studied. Precisely designed, hypocaloric well-formulated ketogenic diets (KD; ~75% energy for weight maintenance) were compared to isocaloric/isonitrogenous low-fat diet (LFD) on self-reported menses in pre-menopausal overweight and obese women (mean ± SD: 34 ± 10 years, BMI: 32.3 ± 2.7 kg/m2). Women received a precisely-weighed and formulated KD with either twice-daily with ketone salts (KS; n = 6) or a flavor-matched placebo (PL; n = 7) daily for six-weeks. An age and BMI-matched cohort (n = 6) was later assigned to the LFD and underwent the same testing procedures as the KD. Self-reported menses fluctuations were assessed bi-weekly along with measures of body weight, body composition, and fasting serum clinical chemistries using repeated measures ANOVA with Bonferroni post-hoc corrections. Both diets elicited clinically-significant weight-loss (Δ: -7.0 ± 0.5 kg; p < 0.001), primarily from fat-mass (Δ: -4.6 ± 0.3 kg; p < 0.001), and improved insulin-sensitivity and serum lipids (all p < 0.05). Fasting plasma glucose and inflammatory markers were not different between diets. Fasting capillary beta-hydroxybutyrate (R-βHB) increased significantly during the KD, independent of supplementation (Δ: 1.2 ± 0.3 mM R-βHB; p < 0.001). Women randomized to the KD+KS (30%) and KD+PL (43%) reported subjective increases in menses frequency and intensity after 14 days, whereas another third reported a regain of menses (>1 year since the last period) after 28 days. No LFD participants reported menses changes. Nutrient-dense, whole-food KDs and LFD improved weight, BMI, body composition, and blood parameters in pre-menopausal women after six-weeks. Changes in self-reported menses were described by most of the KD participants, but none of the LFD women suggesting there may be unique effects of nutritional ketosis, independent of weight loss.

Purpose of Review Considering the high prevalence of obesity and related metabolic impairments in the population, the unique role nutrition has in weight loss, reversing metabolic disorders, and maintaining health cannot be overstated. Normal weight and well-being are compatible with varying dietary patterns, but for the last half century there has been a strong emphasis on low-fat, low-saturated fat, high-carbohydrate based approaches. Whereas low-fat dietary patterns can be effective for a subset of individuals, we now have a population where the vast majority of adults have excess adiposity and some degree of metabolic impairment. We are also entering a new era with greater access to bariatric surgery and approval of anti-obesity medications (glucagon-like peptide-1 analogues) that produce substantial weight loss for many people, but there are concerns about disproportionate loss of lean mass and nutritional deficiencies.Recent Findings No matter the approach used to achieve major weight loss, careful attention to nutritional considerations is necessary. Here, we examine the recent findings regarding the importance of adequate protein to maintain lean mass, the rationale and evidence supporting low-carbohydrate and ketogenic dietary patterns, and the potential benefits of including exercise training in the context of major weight loss.Summary While losing and sustaining weight loss has proven challenging, we are optimistic that application of emerging nutrition science, particularly personalized well-formulated low-carbohydrate dietary patterns that contain adequate protein (1.2 to 2.0 g per kilogram reference weight) and achieve the beneficial metabolic state of euketonemia (circulating ketones 0.5 to 5 mM), is a promising path for many individuals with excess adiposity.Graphical Abstract Created with Biorender.com.

PurposeKetogenic 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 (βHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy.MethodsWomen (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 βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months.ResultsCapillary βHB 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.ConclusionsWomen diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six months.

Objectives: To explore whether an individualized well-formulated ketogenic diet (WFKD) or American Institute of Cancer Research (AICR) diet can be implemented in patients with brain metastases (BM) scheduled to receive stereotactic radiosurgery (SRS), and to test whether WFKD or AICR dietary approach can modulate the inflammatory markers. Methods: We are actively enrolling adults aged 18 to 75 years with BM who are scheduled to receive SRS as part of the standard-of-care clinical treatment to be randomized to a 16-week WFKD (n=4) or AICR (n=4) diet. Eight patients have completed the trial to date. Extensive dietary coaching was provided and daily tracking of capillary beta-hydroxybutyrate (BHB) and glucose levels was used to personalize the diet, measure adherence, and glycemic control. The following assessments were made at baseline and 16-wk: body mass and composition (dual-energy x-ray absorptiometry), MRI scans, and a blood collection for determination of serum IL-8. Results: Capillary βHB indicated the KD group achieved nutritional ketosis (Week 8 mean: 0.55 mM; Week 16 mean: 0.62 mM). Both diet groups lost weight (-7.1% ; p = 0.016) and body fat (-2.6%; p = 0.007), with no significant effect on lean body mass (4:1 fat:lean mass ratio loss). Serum IL-8 decreased over time for both diets (p=0.001), with a trend for a greater decrease in the KD group (p= 0.094, respectively). In the KD group, all patients had stable disease findings and no white matter changes on MRI. One patient in the AICR group experienced disease progression following SRS. A separate patient in the AICR group experienced white matter changes 6 months following SRS. All patients had follow-up imaging reviewed, and there were no significant increases in edema or radionecrosis findings. Conclusions: A WFKD may be a feasible adjunct therapy for adults diagnosed with BM receiving SRS treatment. Preliminary data indicate that body composition measures improved in both diet groups. Enrollment is ongoing which will allow for more robust comparisons between diets on metabolic and inflammatory responses as well as disease progression. Funding Sources: The funding organization for this study is Kroger.

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‐β‐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‐βHB 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.