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Article: 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.

Kackley, Madison L / Brownlow, Milene L / Buga, Alex / Crabtree, Chris D / Sapper, Teryn N / O'Connor, Annalouise / Volek, Jeff S

Frontiers in neuroscience

2022 Volume 16, Page(s) 971144

Abstract: 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 ... ...

Abstract	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; 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.
Language	English
Publishing date	2022-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.971144
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 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.

Buga, Alex / Harper, David G / Sapper, Teryn N / Hyde, Parker N / Fell, Brandon / Dickerson, Ryan / Stoner, Justen T / Kackley, Madison L / Crabtree, Christopher D / Decker, Drew D / Robinson, Bradley T / Krystal, Gerald / Binzel, Katherine / Lustberg, Maryam B / Volek, Jeff S

PloS one

2024 Volume 19, Issue 1, Page(s) e0296523

Abstract: 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 ... ...

Abstract	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 (βHB) >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 βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months. Results: Capillary 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. 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.
MeSH term(s)	Humans ; Female ; Diet, Ketogenic ; Insulin Resistance ; Breast Neoplasms/drug therapy ; Feasibility Studies ; Ketosis ; 3-Hydroxybutyric Acid ; Insulins
Chemical Substances	3-Hydroxybutyric Acid (TZP1275679) ; Insulins
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0296523
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Article ; Online: Bis Hexanoyl (R)-1,3-Butanediol, a Novel Ketogenic Ester, Acutely Increases Circulating r- and s-ß-Hydroxybutyrate Concentrations in Healthy Adults

Crabtree, Christopher D. / Blade, Thanh / Hyde, Parker N. / Buga, Alex / Kackley, Madison L. / Sapper, Teryn N. / Panda, Oishika / Roa-Diaz, Stephanie / Anthony, Joshua C. / Newman, John C. / Volek, Jeff S. / Stubbs, Brianna J.

Journal of the American Nutrition Association. 2023 Feb. 17, v. 42, no. 2, p. 169-177

2023 , Page(s) 169–177

Abstract: 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 ... ...

Abstract	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. 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)). 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. These results demonstrate that consumption of BH-BD effectively induces exogenous ketosis in healthy adults at rest.
Keywords	3-hydroxybutyric acid ; beverages ; blood ; blood glucose ; excretion ; food composition ; free fatty acids ; insulin ; ketosis ; nutrition ; Ketones ; ketone ester ; ketone di-ester ; exogenous ketone ; beta-hydroxybutyrate
Language	English
Dates of publication	2023-0217
Size	p. 169-177
Publishing place	Taylor & Francis
Document type	Article ; Online
ISSN	2769-707X
DOI	10.1080/07315724.2021.2015476
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Article ; Online: Effect of a Telephone-Based Lifestyle Intervention on Weight, Body Composition, and Metabolic Biomarkers in Rural Ohio: Results from a Randomized Pilot Study.

Zhang, Xiaochen / DeScenza, Victoria R / Chaplow, Zachary L / Kilar, Megan / Bowman, Jessica / Buga, Alex / Kackley, Madison L / Shoben, Abigail B / Felix, Ashley S / Paskett, Electra D / Focht, Brian C

Nutrients

2023 Volume 15, Issue 18

Abstract: 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 ... ...

Abstract	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,
MeSH term(s)	Adult ; Humans ; Female ; Middle Aged ; Male ; Pilot Projects ; Rural Population ; Ohio ; Obesity/therapy ; Obesity/psychology ; Life Style ; Biomarkers ; Lipids ; Body Composition ; Telephone
Chemical Substances	Biomarkers ; Lipids
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15183998
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Article ; Online: Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin.

Belany, Paul / Kackley, Madison L / Zhao, Songzhu / Kluwe, Bjorn / Buga, Alex / Crabtree, Christopher D / Nedungadi, Divya / Kline, David / Brock, Guy / Simonetti, Orlando P / Volek, Jeff S / Joseph, Joshua J

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 7, Page(s) 1727–1739

Abstract: 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.: ... ...

Abstract	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.
MeSH term(s)	Adult ; Humans ; Female ; Male ; Ketones ; Renin ; Aldosterone ; Diet, Fat-Restricted ; Ketone Bodies ; Diet, Ketogenic/adverse effects ; Weight Loss/physiology
Chemical Substances	Ketones ; Renin (EC 3.4.23.15) ; Aldosterone (4964P6T9RB) ; Ketone Bodies
Language	English
Publishing date	2023-01-09
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad009
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Article ; Online: Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts.

Buga, Alex / Kackley, Madison L / Crabtree, Christopher D / Bedell, Teryn N / Robinson, Bradley T / Stoner, Justen T / Decker, Drew D / Hyde, Parker N / LaFountain, Rich A / Brownlow, Milene L / O'Connor, Annalouise / Krishnan, Deepa / McElroy, Craig A / Kraemer, William J / Volek, Jeff S

Clinical nutrition ESPEN

2023 Volume 54, Page(s) 277–287

Abstract: 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 ...

Abstract	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/GLU 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/GLU Results: Mean R-BHB 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.
MeSH term(s)	Adult ; Humans ; Diet, Ketogenic ; 3-Hydroxybutyric Acid ; Salts ; Ketone Bodies ; Ketosis ; Ketones ; Glucose ; Insulin ; Fasting
Chemical Substances	3-Hydroxybutyric Acid (TZP1275679) ; Salts ; Ketone Bodies ; Ketones ; Glucose (IY9XDZ35W2) ; Insulin
Language	English
Publishing date	2023-02-04
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2405-4577
ISSN (online)	2405-4577
DOI	10.1016/j.clnesp.2023.01.030
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Article: Influence of Nutritional Ketosis Achieved through Various Methods on Plasma Concentrations of Brain Derived Neurotropic Factor.

Kackley, Madison L / Buga, Alex / Crabtree, Chris D / Sapper, Teryn N / McElroy, Craig A / Focht, Brian C / Kraemer, William J / Volek, Jeff S

Brain sciences

2022 Volume 12, Issue 9

Abstract: 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- ... ...

Abstract	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.
Language	English
Publishing date	2022-08-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci12091143
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Article ; Online: Bis Hexanoyl (R)-1,3-Butanediol, a Novel Ketogenic Ester, Acutely Increases Circulating r- and s-ß-Hydroxybutyrate Concentrations in Healthy Adults.

Crabtree, Christopher D / Blade, Thanh / Hyde, Parker N / Buga, Alex / Kackley, Madison L / Sapper, Teryn N / Panda, Oishika / Roa-Diaz, Stephanie / Anthony, Joshua C / Newman, John C / Volek, Jeff S / Stubbs, Brianna J

Journal of the American Nutrition Association

2022 Volume 42, Issue 2, Page(s) 169–177

Abstract: 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 ... ...

Abstract	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 ( 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.
MeSH term(s)	Adult ; Humans ; 3-Hydroxybutyric Acid ; Esters ; Hydroxybutyrates ; Ketone Bodies ; Ketones ; Ketosis
Chemical Substances	3-Hydroxybutyric Acid (TZP1275679) ; bis hexanoyl (R)-1,3-butanediol ; Esters ; Hydroxybutyrates ; Ketone Bodies ; Ketones
Language	English
Publishing date	2022-03-25
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ISSN	2769-707X
ISSN (online)	2769-707X
DOI	10.1080/07315724.2021.2015476
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Article ; Online: The Effects of Resistance Training on Physical Fitness and Neuromotor-Cognitive Functions in Adults With Down Syndrome.

Post, Emily M / Kraemer, William J / Kackley, Madison L / Caldwell, Lydia K / Volek, Jeff S / Sanchez, Barbara N / Focht, Brian C / Newton, Robert U / Häkkinen, Keijo / Maresh, Carl M

Frontiers in rehabilitation sciences

2022 Volume 3, Page(s) 927629

Abstract: 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, ... ...

Abstract	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 ( Results: Significant ( Conclusion: This study dramatically demonstrates that life enhancements for individuals with Down syndrome are achievable with a properly designed resistance training program.
Language	English
Publishing date	2022-06-21
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-6861
ISSN (online)	2673-6861
DOI	10.3389/fresc.2022.927629
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Article ; Online: Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts

Buga, Alex / Kackley, Madison L. / Crabtree, Christopher D. / Bedell, Teryn N. / Robinson, Bradley T. / Stoner, Justen T. / Decker, Drew D. / Hyde, Parker N. / LaFountain, Rich A. / Brownlow, Milene L. / O'Connor, Annalouise / Krishnan, Deepa / McElroy, Craig A. / Kraemer, William J. / Volek, Jeff S.

European Society for Clinical Nutrition and Metabolism Clinical Nutrition ESPEN. 2023 Feb. 04,

2023

Abstract: 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 ... ...

Abstract	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. 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). 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. 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. 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.
Keywords	3-hydroxybutyric acid ; blood ; blood glucose ; clinical nutrition ; glucose ; ingestion ; insulin ; insulin resistance ; ketogenic diet ; ketonemia ; ketosis ; low fat diet ; obesity ; placebos ; weight loss ; Beta-hydroxybutyrate ; Low-fat diet ; Ketone salts
Language	English
Dates of publication	2023-0204
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ISSN	2405-4577
DOI	10.1016/j.clnesp.2023.01.030
Database	NAL-Catalogue (AGRICOLA)

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