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.

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.