Strategies to Augment Ketosis(STAK-OG)

STAK is a 6-week controlled feeding study designed to investigate the impact of exogenous ketones on indices of keto-adaptation in obese subjects on weight reducing diets. The primary objective of STAK sought to examine if supplementation with exogenous beta-hydroxybutyrate (BOHB) as part of a hypocaloric ketogenic diet subsequently affected metrics of renal function, changes in energy balance and body composition via DEXA and MRI, cognitive or behavioral adaptations, and cardio-metabolic risks observed in lipid panels.

39 participants were enrolled and randomly assigned to one of three groups: ketogenic diet + ketone supplement (KD+KS), ketogenic diet + placebo (KD+PL), or low-fat diet + placebo (LFD). Inclusion criteria for enrollment required a BMI between 27-35kg/m2, 21-65 years of age, no recent weight loss of >10% in six months, along with an eagerness to lose weight.

Feel free to view our published articles on this study

• Belany, P.*, Kackley, M.L*, Zhao, S., Kluwe B., Buga, A., Crabtree, C. D., Nedungadi, D., Kline, D., Brock, G., Volek, J.S, Joseph, J. J. The effects of a hypocaloric low-fat diet, ketogenic diet and ketogenic diet& ketone supplement on aldosterone and renin in overweight or obese participants. https://doi.org/10.1210/cliiinnem/dgad009
• Buga, A., Kackley, M. L., Crabtree, C. D., Sapper, T. N,  Robinson, B.T., Stoner, J.T., Decker, D.D., Hyde, P. N., LaFountain, R. A., Brownlow, M. L., O’Connor, A.,  Volek, J.S. Diurnal ketone and glucose pattern changes in a ketogenic diet, with and without a racemic ketone salt supplementation. https://doi.org/10.1016/j.clnesp.2023.01.030
• Kackley, M.L*, Brownlow, M.L*, Buga, A., Crabtree, C.D, Sapper, T.N., O’Connor, A. & Volek, J.S. The effects of a six-week controlled, hypocaloric ketogenic diet, with and without exogenous ketone salts, on cognitive performance and mood states in overweight and obese adults. https://doi.org/10.3389/fnins.2022.971144
• Kackley, M. L., Buga, A., Crabtree, C. D., Sapper, T. N., & Volek, J.S. Influence of Nutritional Ketosis Achieved through Various Methods on Plasma Concentrations of Brain Derived Neurotropic Factor. https://doi.org/10.3390/brainsci12091143
• Crabtree, C. D., Kackley, M. L.,;Buga, A., Fell, B., LaFountain, R. A., Hyde, P. N., Sapper, T. N., Kraemer, W. J., Scandling, D., Simonetti, O. P., & Volek, J. S. (2021). Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults. Nutrients, 13(3), 966. https://doi.org/10.3390/nu13030966
• Buga, A., Kackley, M., Crabtree, C. D., Sapper, T. N., Mccabe, L., Fell, B., LaFountain, R. A., Hyde, P. N., Martini, E. R., Bowman, J., Pan, Y., Scandling, D., Brownlow, M. L., O’Connor, A., Simonetti, O. P., Kraemer, W. J., & Volek, J.S. (2021). The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketoone Salts, on Body Composition Responses. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.618520

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Keto-CARE Trial

The Keto-CARE trial is designed to investigate the potential therapeutic impact of a carbohydrate restrictive diet on cancer-based outcomes. Keto-CARE is a 6-month dietary intervention. The first 3 months is a controlled feeding study, meaning we provide 100% of the food you are to consume. The second 3 months will transition to a “free-living”experiment to determine feasibility. Participants will undergo advanced imaging, blood testing, body composition assessments, blood testing, and are asked to complete questionnaires at baseline, midpoint (3 months) and post-testing (6 months). Daily monitoring of ketones and blood glucose via finger stick also occurs.

Currently there is very little information in the scientific field related to nutrition and advanced stage breast cancer. What we do know is the majority of cancer uses carbohydrate as its primary fuel source. Research in animal models has shown that ketogenic diets can reduce tumor burden and improve overall quality of life. On the contrary, very little research exists in humans, but what does exist has demonstrated positive results! When consuming a ketogenic diet your body produces ketones, and research has shown these ketones have the ability to combat inflammation at the genetic level.

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THE CHEESE STUDY

Completed in 2018, this body of work was recently published in The Journal of Clinical Investigation and featured in The Ohio State News here.

BACKGROUND. Metabolic 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.

METHODS. Individuals 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.

RESULTS. Despite 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.

CONCLUSION. Consistent 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.

The purpose of this study was to determine the unique effects of cheese while varying the quality and quantity of carbohydrate on various health markers. Participants had metabolic syndrome or a form of pre-diabetes as defined by having some of the following features: high blood pressure, high blood sugar, large waist circumference, and abnormal cholesterol levels. They underwent a baseline battery of tests including blood draws, body composition assessment to determine body fat percentage, measures of height and weight, collection of stool, urine and cheek cell samples and measurement of metabolic rate to determine how many calories were burnt at rest. Participants were placed on a 2-week controlled high carbohydrate run-in diet (HCD) to determine an appropriate caloric intake for weight maintenance. They then began a 5-round controlled feeding study. Each of the five feeding phases were 4 weeks in duration separated by a 2-week washout period, where no food was provided. The order of the feeding phases was randomized and balanced. The five feeding phases were as follows: a HCD with no cheese, a HCD with high cheese, a moderate carbohydrate diet (MCD) with high cheese, a low carbohydrate diet (LCD) with high cheese and a HCD high in resistant starch with high cheese. At the end of each diet phase the testing completed at baseline was repeated.

Feel free to view our published articles on this study:

• Hyde, P. N., Sapper, T. N., Crabtree, C. D., LaFountain, R. A., Kackley, M. L., Buga, A., Fell, B., McSwiney, F. T., Dickerson, R. M., Miller, V. J., Scandling, D., Simonetti, O. P., Phinney, S. D., Kraemer, W. J., King, S. A., Krauss, R. M., & Volek, J. S. (2019). Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss. JCI Insight, 4(12). https://doi.org/10.1172/jci.insight.128308

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THE TANK STUDY

Featured in The Ohio State News here, we showed that a group of people with military affiliation could accept a ketogenic diet and successfully lose weight, including visceral adipose tissue, a type of fat strongly associated with chronic disease. This could be the first step toward a bigger study looking at the potential benefits of ketogenic eating in the armed forces.

TANK in 2018 and recently published in Military Medicine, The Extended Ketogenic Diet and Physical Training Intervention in Military Personnel was a two-group prospective intervention study in a targeted group of individuals associated with the US military. Subjects self-selected into either a ketogenic (KD) or mixed (MD) diet group. We chose not to randomize participants because military personnel often have a choice in dietary preference when not deployed, and successful implementation of a KD requires considerable personal commitment. Therefore, we employed self-selection to increase compliance and translation of the findings. Both groups participated in an identical supervised training program that emphasized strength and power. Compliance to the KD was measured throughout the intervention by daily assessment of capillary βHB. A battery of tests were performed before and after the intervention.

This was the first study to successfully keto-adapt individuals representing a group affiliated with the US military, consisting mostly of Army ROTC. Our results demonstrate high adherence to a KD who made an informed choice to adopt such a diet during 12-weeks of concurrent physical training. High adherence was achieved through a combination of proper education on a KD, access to ketogenic-appropriate meals, and daily feedback regarding level of ketosis. The most striking result was consistent loss of body mass, fat mass, visceral fat, and enhanced insulin sensitivity in virtually all KD subjects despite no specific limitations in caloric intake. Physical performance was maintained across a broad range of tests despite the significant loss of mass (9% of body mass). These results are highly relevant considering the obesity problem affecting all branches of the military. Implementation of a KD guided by blood ketone measures represents a credible strategy for military service members who could benefit from weight loss and improved body composition.

• LaFountain, R. A., Miller, V. J., Barnhart, E. C., Hyde, P. N., Crabtree, C. D., McSwiney, F. T., Beeler, M. K., Buga, A., Sapper, T. N., Short, J. A.,Bowling, M. L, Kraemer, W. J., Simonetti, O. P., Maresh, C. M., & Volek, J. S. (2019). Extended Ketogenic Diet and Physical Training Intervention in Military Personnel. Military Medicine, 184(9–10), e538–e547. https://doi.org/10.1093/milmed/usz04
• Miller, V. J., LaFountain, R. A., Barnhart, E., Sapper, T. S., Short, J., Arnold, W. D., Hyde, P. N., Crabtree, C. D., Kackley, M. L., Kraemer, W. J., Villamena, F. A., & Volek, J. S. (2020). A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health. American journal of physiology. Endocrinology and metabolism, 319(6), E995–E1007. https://doi.org/10.1152/ajpendo.00305.2020

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