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-week 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 (β-hydroxybutyrate+acetoacetate) substrates. Compared to MD, the KD resulted in increased whole-body resting fat oxidation (p<0.001) and decreased fasting insulin (p=0.019), 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 4 to 8 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.

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 ¼ 12) or a ketogenic diet (Keto-Adapted; n ¼ 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 lM) and KA (848 to 1,973 lM) 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.

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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 (&lt;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 (&gt;1.0 mM capillary BHB) throughout the study (p &lt; 0.001), with higher fasting concentrations observed in KD + KS than KD + PL for the first 2 weeks (p &lt; 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 &lt; 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 &lt; 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 &gt; 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.

Adults with Down syndrome are an underserved population at high risk for a host of different pathologies from aging and lack of activity.PurposeTo examine the effects of a 10-week resistance training program on measures of motor behavior, cognitive function, mood, and physical fitness.MethodsParticipants (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.ResultsSignificant (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.ConclusionThis study dramatically demonstrates that life enhancements for individuals with Down syndrome are achievable with a properly designed resistance training program.